Global Advances in Health and Medicine by Lee Dixson

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Improving Healthcare Outcomes Worldwide www.gahmj.com

MARCH 2012 • VOL. 1, NO. 1

Features

Case Reports • Chinese Scalp Acupuncture for Cerebral Palsy • Fever-inducing Mistletoe Treatment for Lymphoma • Ultradilute Medicines for Viral Hepatitis • Worst Case Reported to the NAFKAM International Registry of Exceptional Courses of Disease • A Patient-defined “Best Case” of Multiple Sclerosis

• Access to Medicines in Resource-limited Settings • The NAFKAM International Registry of Exceptional Courses of Disease • The Global Coherence Initiative • The Problem With Science—The Context and Process of Care

Research and Reviews • An Emotion Self-regulation Program for Preschool Children • Fever in Cancer Treatment • Horse Chestnut Seed Extract for Chronic Venous Insufficiency

Column • Cochrane Summary of Findings Tables: An Overview

Opinion • Global Advances in Health and Medicine • Why Medical Case Reports? • A Global and Historical Perspective on Integrative Medicine

• Review of Clinical Applications of Scalp Acupuncture for Paralysis

Abstracts published in Chinese and Spanish. 摘要刊登在中国和西班牙。Resúmenes publicados en Chino y Español.

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editorials

Global Advances in Health and Medicine

The Editors of Global Advances in Health and Medicine

Why Medical Case Reports?

Gunver Kienle, Dr med, Germany

Successful Treatment of Chronic Viral Hepatitis With High-dilution Medicine 《以高稀释药物成功治疗慢性病毒性肝炎》 Tratamiento exitoso de la hepatitis viral crónica con medicamentos de alta dilución

Barbara Sarter, RN, PhD, FAAN, United States; Prasanta Banerji, India; Pratip Banerji, India

Patient Case Reports

global perspectives

10 Systems Approaches: A Global and Historical Perspective

on Integrative Medicine

Patrick Hanaway, MD, United States

Worst Cases Reported to the NAFKAM International Registry of Exceptional Courses of Disease

Vinjar Fønnebø, PhD, Norway; Brit J. Drageset, BSc, Norway; Anita Salamonsen, MSc, Norway

Case Reports

A Patient-defined “Best Case” of Multiple Sclerosis From the NAFKAM International Registry of Exceptional Courses of Disease 《与补充和替代药物应用相关的多发性硬化的病人定义 “最佳案例”》 Una paciente fue catalogada como el “mejor caso” de esclerosis múltiple relacionado con el uso de medicina complementaria y alternativa

Anita Salamonsen, MSc, Norway; Brit J. Drageset, BSc, Norway; Vinjar Fønnebø, PhD, Norway

Changing landscapes

News From Around the World Suzanne Snyder, United States

Chinese Scalp Acupuncture for Cerebral Palsy in a Child Diagnosed With Stroke in Utero 《对患有脑瘫儿童的中医头皮针灸》 Técnica de acupuntura china en el cuero cabelludo para tratar la parálisis cerebral en un niño diagnosticado con derrame cerebral en el útero Jason Jishun Hao, DOM, MTCM, MBA, United States; Sun Zhongren, PhD,

China; Shi Xian, PhD, China; Yang Tiansong, doctoral candidate, China

18 Durable Regression of Primary Cutaneous B-Cell

Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports 《引起发热的槲寄生治疗之后原发性皮肤 B-细胞淋巴瘤持久性的复原：两份病历报告 Regresión duradera de linfomas cutáneos primarios de células B tras tratamiento pirógeno con muérdago: Dos casos clínicos

Maurice Orange, MSc, Switzerland; Aija Lace, United Kingdom; Maria P. Fonseca, United Kingdom; Broder H. von Laue, Dr med, Germany; Stefan Geider, Dr med, United Kingdom; Gunver S. Kienle, Dr med, Germany

Original research

36 Efficacy of an Emotion Self-regulation Program for

Promoting Development in Preschool Children 《为促进学龄前儿童发展的情绪自控计划之功效》 Eficacia de un programa de autorregulación emocional para promover el desarrollo en niños de edad preescolar

features

Access to Medicines in Resource-limited Settings: The End of a Golden Decade? 《在资源有限的环境下使用药物：黄金十年结束了？》 Acceso a los medicamentos en entornos con recursos limitados: ¿El final de la década dorada?

CONTENT ORIGINATION

Raymond Trevor Bradley, PhD, United States; Patrick Galvin, PhD, United States; Mike Atkinson, United States; Dana Tomasino, United States

Tido von Schoen-Angerer, MD, MSc, Switzerland; Nathan Ford, South Africa; James Arkinstall, Switzerland

CONTENT IDENTIFICATION

ON THE COVER

Symbols next to article titles identify the content with the following information:

These are honest and direct pictures; they bear a heavy silence, and are uncomplicated, singular ideas. These words invite a closer look uncompromised by time. They suggest a meditation that can bring to the surface what could otherwise have remained hidden—that opening in the sky beyond the child and his maze, and what it can mean. — Anthony Bannon, George Eastman House Director

Content designated as open access Online/Online ahead of print Audio/Video file available Online Supplemental content available Twitter account available

Volume 1, Number 1 • March 2012 • www.gahmj.com

Blue Lagoon, Iceland. Toned gelatin silver print, 6” W x 6” H, Hiroshi Watanabe. Mr Watanabe’s photographs can be found at www.hiroshiwatanabe.com.

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60 The NAFKAM International Registry of Exceptional

Courses of Disease

Vinjar Fønnebø, PhD, Norway; Brit J. Drageset, BSc, Norway; Anita Salamonsen, MSc, Norway

reviews

Fever in Cancer Treatment: Coley’s Therapy and Epidemiologic Observations

features

102 Review of Clinical Applications of Scalp Acupuncture

64 The Global Coherence Initiative: Creating a Coherent

Planetary Standing Wave 《全球一致性计划：创建连贯的行星驻波》 La Iniciativa de Coherencia Global: Creación de una onda estacionaria coherente en todo el mundo

Gunver Kienle, Dr med, Germany

Rollin McCraty, PhD, United States; Annette Deyhle, PhD, United States; Doc Childre, United States

78 The Problem With Science—The Context and Process of

Care: An Excerpt From Remodelling Medicine

Jeremy Swayne, BA(Oxon), BM, BCh, D(Obst)RCOG, MRCGP, FFHom, Scotland

for Paralysis: An Excerpt From Chinese Scalp Acupuncture

Jason Jishun Hao, DOM, MTCM, MBA, United States; Linda Lingzhi Hao, CA, PhD, United States

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Cochrane Summary of Findings: Horse Chestnut Seed Extract for Chronic Venous Insufficiency

Vigdis Underland, MS, Norway; Ingvil Sæterdal, PhD, Norway; Elin Strømme Nilsen, MS, Norway

Conference calendar

124 Events Around the World

COCHRANE COLUMN

90 Summary of Findings Tables: Presenting the Main

Findings of Cochrane Complementary and Alternative Medicine–related Reviews in a Transparent and Simple Tabular Format

Eric Manheimer, MS, United States

Suzanne Snyder, United States

book review

126 Chinese Scalp Acupuncture

Honora Lee Wolfe, United States

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Improving Healthcare Outcomes Worldwide

Cofounders, Managing Partners David Riley, MD; Michele Mittelman, RN, MPH Editor in Chief David Riley, MD Editors Gregory Plotnikoff, MD, MTS, FACP; Gunver Kienle, Dr med; Helmut Kiene, Dr med; Jason Jishun Hao, DOM, MTCM, MBA; Michele Mittelman, RN, MPH Methodology Editor Joel Gagnier, ND, MSc, PhD Columnists Eric Manheimer, MS; Linda L. Barnes, PhD, MTS, MA; Marianne van der Heijden, MSc Editorial Board Andrew Weil, MD, University of Arizona Barbara Dossey, PhD, RN, AHN-BC, FAAN, Nightingale Initiative for Global Health Bill Manahan, MD, University of Minnesota Academic Health Center Bradly Jacobs, MD, MPH, Sage Center for Healthy Living, Cavallo Point Lodge Brent Bauer, MD, Mayo Clinic Daniel A. Monti, MD, Thomas Jefferson University and Hospital David Jones, MD, Institute for Functional Medicine David Moher, PhD, University of Ottawa Dean Ornish, MD, Preventive Medicine Research Institute Elise Hewitt, DC, CST, DICCP, FICC, University of Western States Erminia Guarneri, MD, FACC, Scripps Center for Integrative Medicine Erqiang Li, PhD, LAc, China Acupuncture Center Ian Coulter, PhD, RAND Corporation Karen Lawson, MD, ABIHM, University of Minnesota, Center for Spirituality and Healing Kristi Hughes, ND, Institute for Functional Medicine Lawrence Rosen, MD, The Whole Child Center Linda L. Barnes, PhD, MTS, MA, Boston University School of Medicine Lori Knutson, RN, BSN, HN-BC, The Marsh: Center for Balance and Fitness Marietta Kaszkin-Bettag, PhD, Goethe University Frankfurt/Main Mary Jo Kreitzer, PhD, RN, University of Minnesota Menachem Oberbaum, MD, FFHom, The Center for Integrative Complementary Medicine, Shaare Zedek Medical Center Paolo Roberti di Sarsina, MD, University of Milano-Bicocca Patrick Hanaway, MD, Family to Family Robert Saper, MD, MPH, Boston University School of Medicine Roeland van Wijk, PhD, Sino-Dutch Centre for Preventive and Personalized Medicine Rollin McCraty, PhD, HeartMath Research Center Shi Xian, MD, PhD, General Hospital of the Chinese People’s Liberation Army Sidney M. Baker, MD, Autism360 Stacie Geller, PhD, University of Illinois, Chicago Stuart Sinoff, MD, Morton Plant Hospital Sun Zhongren, PhD, Heilongjiang University of Chinese Medicine Ted J. Kaptchuk, Harvard Medical School Thomas Schneider, PhD, Famna-Swedish Association for Non-Profit Health and Social Service Providers Tido von Schoen-Angerer, MD, MSc, Médecins Sans Frontières Vinjar Fønebbø, MD, MSc, PhD, University of Tromsø, Norway Xie Ning, PhD, Heilongjiang University of Chinese Medicine Yuxin He, LAc, MD, PhD, AOMA Graduate School of Integrative Medicine Zhu Min, MD, Guangzhou University of Chinese Medicine Global Advances in Health and Medicine Publisher: Nicholas Collatos Creative Director: Lee Dixson Managing Editor: Suzanne Snyder Director of Sales and Business Development: Greg Gorski Controller: Rebecca Cueto Operations Administrator: Alyshia Allaire

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editorial

Global Advances in Health and Medicine The Editors of Global Advances in Health and Medicine: David Riley, MD; Jason Jishun Hao, DOM, MTCM, MBA; Helmut Kiene, Dr med; Gunver Kienle, Dr med; Michele Mittelman, RN, MPH; Gregory A. Plotnikoff, MD, MTS, FACP

cience, technology, and medicine (STM) are not immune to the widespread and persistent crises that have defined the 21st century. We, the editors of Global Advances in Health and Medicine (GAHMJ), a new scholarly medical journal, believe that solutions in healthcare will be ones that accelerate the application of global advances in health and medicine, resulting in improved population-health management, healthcare delivery, and patient outcomes. The journal is focused on solutions in 3 main areas: (1) systems theory and medicine, (2) the global convergence of healthcare practices, and (3) evidence from the point of care (eg, medical case reports). And GAHMJ is more than a scholarly medical journal; it is a communication platform. The journal itself is cross-disciplinary and peer reviewed and offers innovative STM content for the worldwide community of healthcare professionals who actively participate in the healthcare debate. The content of the journal will highlight data from around the world with case reports, original research articles, opinion pieces, and hypotheses. GAHMJ has an experienced international editorial team: Jason Jishun Hao, DOM, MTCM, MBA; Helmut Kiene, Dr med; Gunver Kienle, Dr med; Michele Mittelman, RN, MPH; Gregory Plotnikoff, MD, MTS, FACP; and David Riley, MD. The journal will be published 10 times per year in print and digital formats with abstracts in multiple languages. The digital publication will offer additional features and information that take advantage of emergent digital technologies. A mobile application will be launched to better serve the needs of the journal’s readership. The website will offer additional features including blogs, topic forums, customizable eNews portals, searchable databases, collaboration tools, social-media functionality, international news, and conversations with key opinion leaders.

IN THIS ISSUE

We are honored to feature the following authors and articles, among others, in this inaugural issue of Global Advances in Health and Medicine.

Editorial

•• Tido von Schoen-Angerer, based in Switzerland and working with Medecins Sans Frontières (MSF), and coauthors Nathan Ford from South Africa and James Arkinstall from Switzerland write about access to medicine in areas of the world with limited resources and address the question of how this access is affected in times of economic uncertainty. •• Anita Salamonsen, Brit J. Drageset, and Vinjar Fønnebø from the University of Tromso in Norway based on their work with the Norwegian Registry of Exceptional Courses of Disease, contribute a selection of patient case reports as well as an overview of the registry. •• Maurice Orange et al provide 2 case reports on the successful treatment of primary cutaneous B-cell lymphoma with mistletoe. •• Gunver Kienle from Germany shares a review article—“Fever in Cancer Treatment: Coley’s Therapy and Epidemiologic Observations”—that is drawn largely from case reports. •• Jeremy Swayne from Scotland provides “The Problem With Science—The Context and Process of Care,” an excerpt from the recently published Remodelling Medicine. •• Jason Jishun Hao shares a “Review of Clinical Applications of Scalp Acupuncture in Paralysis,” an excerpt from Chinese Scalp Acupuncture. (This article is featured on our website, www.gahmj.com.) •• Rollin McCraty, Annette Deyhle, and Doc Childre from the Institute of HeartMath write about the convergence of several independent lines of evidence that support the existence of a global information field connecting all living systems.

For more information about GAHMJ’s editorial leadership, see page 7.

THE BIG PICTURE

We recognize that innovations are often disruptive, as cultures and traditions converge and compete with approaches built around “the way things have always been done.” We see a challenge and opportunity in healthcare today around the development of a new global taxonomy for healthcare—a taxonomy that accommodates the global convergence of healthcare practices, incorporates a systems approach to medicine, and uses data from the point of care in new and innovative ways. Sackett et al defined evidence-based medicine as the “conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. . . . Good doctors use both individual clinical expertise and the best available external evidence and neither alone is enough.”1

www.gahmj.com • Volume 1, Number 1 • March 2012

GLOBAL ADVANCES IN HEALTH AND MEDICINE

Case Reports

Around the world every day, doctors treat patients and these treatments produce outcomes—all generating practice-based evidence. In respect to individuality, we support endeavors that move healthcare toward an individualized approach documented through case reports. Case reports are at the convergence point of several disruptive trends in medicine and will be a particular focus of this journal. In this issue of the journal, our case reports editor, Gunver Kienle, has written an editorial featuring some of her perspectives on case reports. The editors believe that a process for the systematic collection and publication of case reports in accordance with quality-assurance guidelines will uncover important correlations among individual cases and allow for the comparison of strategies across healthcare systems for relevance, safety, and effectiveness. Data from the point of care, published as case reports, will inform the design and implementation of clinical trials. Practice-based evidence will enable realtime knowledge to leverage advances in health informatics to improve population health, healthcare delivery, and patient outcomes. To this end, we will offer Case Report Writing Workshops and develop guidelines for the publication of case reports. A Systems Approach

The editors of Global Advances in Health and Medicine also support a systems approach to healthcare and believe that this too is an important opportunity. In respect to system theory and medicine, the topics of systems biology, systems therapies, systems building, and systems analyses have priority. We recognize that reductionism in science has led to spectacular advances; we also believe this approach has limitations. For example, the systems biology approach has gained momentum for the past 40 years, and Leroy Hood and Jeff Bland in particular have made significant contributions. Systems biology offers the possibility of a healthcare system that is rooted in information science, costs less, and is individualized. We believe that the global convergence of healthcare practices and a systems approach combined with data from the point of care offer an opportunity to create a more effective approach to healthcare. Collaboration and Information Sharing

Following are some of the global questions that we will explore. We invite you, as readers and contributors, to join us in this exploration. How can we create a global community of healthcare professionals in a world with diverse healthcare traditions and cultures? What are the common threads in how we think, feel, and act that bind us together around the world? a

(1) eradicating extreme poverty and hunger; (2) achieving universal primary education; (3) promoting gender equality and empowering women; (4) reducing child mortality; (5) improving maternal health; (6) combating HIV/AIDS, malaria, and other communicable diseases; (7) ensuring environmental sustainability; and (8) developing global partnerships for development.

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How can the 8 primary health targets outlined by the World Health Organization be realized across cultures with different levels of economic development,a particularly when more than 11 million children under the age of 5 years and 500 000 pregnant women die every year2? Does the current population-based taxonomy for the classification and management of disease allow us to measure individual variations and responses, particularly across healthcare systems? What is the role of healthcare informatics in the evaluation of data from the point of care, and can this information be integrated with precise diagnoses? How will data from the point of care impact research models? Can we use a systems approach to integrate medical information from molecular biochemistry, genomics, lifestyle, diverse healthcare systems, and patient preferences? Can we understand and balance the interactions between global, environmental, and individual influences; the organism and the cell; and the tension between providing care for patients and the need for sustainability and profitability? How can healthcare professionals and patients engage in a therapeutic partnership across healthcare systems and cultures in a way that respects patients and their individuality? Will we invest in wellness and prevention in order to prevent tomorrow’s health problems that may not be visible today? How will the regulatory community change the evaluation process for new drugs, devices, and therapies in response to systematic data from the point of care? Global Advances in Health and Medicine is more than a scholarly medical journal; it is a communication platform to foster the dialogue among the different healthcare cultures and focus on the global convergence of these practices. How might this happen with Global Advances in Health and Medicine? Healthcare professionals who are interested in breakthroughs and best practices in one area will have the ability to query information by organizational source (eg, WHO), country (eg, Japan, India), culture (eg, Asian, Hispanic), system of medicine (eg, conventional medicine, Ayurveda), disciplinary credentials (eg, medical doctor, doctor of Oriental medicine), condition (eg, eating disorders, metabolic syndrome), or practices (eg, pharmacology, acupuncture). Users will be able to compare and contrast findings, exploring the implications of discoveries in one area or system vis-à-vis another. We welcome and invite your participation in the healthcare debate and the creation of a global healthcare community through the submission of case reports, other original manuscripts, and commentary to Global Advances in Health and Medicine. References 1. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson W. Evidence based medicine: what it is and what it isn’t. BMJ. 1996 Jan 13;312(7023):71-2. 2. World Health Organization. Engaging for health–eleventh general programme of work 2006-2015, a global health agenda [Internet]. Geneva, Switzerland: World Health Organization; 2006 [cited 2012 Feb 14]. Available from: http://whqlibdoc.who.int/publications/2006/GPW_eng.pdf.

Editorial

The editors of global advances in health and medicine

The Editors of Global Advances in Health and Medicine

David Riley, MD

Dr Riley is board-certified in internal medicine, served as the editor in chief for two indexed medical journals, Alternative Therapies in Health and Medicine and EXPLORE, from 1995 to 2010, and has written chapters for medical textbooks. He consults internationally on issues such as healthcare policy, regulatory issues, and models of clinical care. Dr Riley has received postgraduate training in a variety of healthcare disciplines, has conducted clinical research, and was a member of the CONSORT group.

Jason Jishun Hao, DOM,

Gunver Kienle, Dr med

Dr Kienle studied medicine at the University of Witten/Herdecke and Göttingen, Germany, and received methodological training at Harvard University. She worked in internal medicine and oncology before cofounding the Institute for Applied Epistemology and Medical Methodology in Freiburg, Germany, where she now serves as senior research scientist. Dr Kienle is a member of the Commission C for Anthroposophic Medicinal Products at the Federal Institute for Drugs and Medical Devices in Bonn, Germany, and a member of the German Network for Evidence based Medicine. She has authored 4 books and close to 100 articles, as well as book chapters and monographs.

MTCM, MBA

Dr Hao received his bachelor’s and master’s degrees from the Heilongjiang University of Chinese Medicine in China in 1982 and 1987, respectively, and earned his master’s of business administration from the University of Phoenix in 2004. Dr Hao has been teaching, practicing, and researching acupuncture and treatment with Chinese herbs for almost 30 years at academic centers in both the United States and China. He is president of the International Academy of Scalp Acupuncture, chairman of the Acupuncture Committee at the National Certification Commission for Acupuncture and Oriental Medicine, and vice president of the Southwest Acupuncture College Board in Santa Fe, New Mexico. His book, Chinese Scalp Acupuncture, was published in November 2011.

Helmut Kiene, Dr med

Dr Kiene studied medicine and philosophy at the University of Freiburg, Germany, and worked as a clinician in internal medicine and oncology. His scientific interests include epistemology, research methodology for complementary medicine, and clinical research. He has written 7 books and 150 articles on these topics. Dr Kiene is director of the Institute for Applied Epistemology and Medical Methodology in Freiburg, Germany.

The Editors of Global Advances in Health and Medicine

Michele Mittelman, RN, MPH

Ms Mittelman began her career in healthcare as a registered nurse, earned her master’s degree in public health from Columbia University, and served as a healthcare consultant for Ernst & Young. She served as an editor for Alternative Therapies in Health and Medicine and works on national and local nursing initiatives. Ms Mittelman also serves on the board of directors of the Bravewell Collaborative.

Gregory A. Plotnikoff, MD, MTS, FACP

Dr Plotnikoff is a graduate of Carleton College, Harvard Divinity School, and the University of Minnesota Medical School. He is a board-certified internist and pediatrician who is well known for his work in interventional nutrition, herbal medicines, and spirituality in clinical care. Dr Plotnikoff has received international honors for his work in cross-cultural and integrative medicine as well as the Early Career Distinguished Achievement Award from the University of Minnesota Medical School. He currently serves as an integrative medicine physician at the Penny George Institute for Health and Healing and as senior consultant at the Center for Health Care Innovation, Allina Health Care, Minneapolis, Minnesota.

www.gahmj.com • Volume 1, Number 1 • March 2012

editorial

Systems Approaches: A Global and Historical Perspective on Integrative Medicine Author Affiliation Gunver S. Kienle, Dr med, is senior research scientist at the Institute for Applied Epistemology and Medical Methodology at the University of Witten/Herdecke in Freiburg, Germany. Correspondence Gunver S. Kienle, Dr med gkienle@gahmj.com Citation Global Adv Health Med. 2012;1(1):##=##. Key words Cancer, fever, sarcoma, carcinoma, Coley, epidemiology, leukemia, remission, tumor,

edicine is built up of single cases. Individual patients—single cases—are the essence of what medicine deals with. Every patient is important, and every case can be a lesson. Clinician, researcher, and epidemiologist Alvan Feinstein said, “In caring for patients, clinicians constantly perform experiments. During a single week of active practice, a busy clinician conducts more experiments than most of his laboratory colleagues do in a year.”1 Medicine stretches between the intertwined poles of being developed in the laboratories of the pharmaceutical industry and in the clinical practice of the “clinical champions”—the innovative clinician, therapist, nurse, or midwife. While the laboratory testing route (pharmacology, quality assessment, phase I-IV trials) is well established, what about the significant clinical observations? How can they be presented scientifically? There is a wealth of case reports in medical journals and textbooks, and they range from groundbreaking to hardly noticeable. They are a colorful entity in the world of medical literature, but aren’t they notoriously biased? Haven’t they misled medicine for centuries? Don’t they inherently suffer from low methodological quality? Aren’t they just singularities and therefore always nonrepresentative? These questions reflect widespread convictions, but the issues have never been systematically investigated, so the answers remain unknown. Case reports, in fact, do have an important place in medicine. As “cornerstones of medical progress,”2 they often are the first presentation of discoveries: new conditions, novel therapies, new perspectives in pathogenesis, inventive diagnostic procedures. Their publication often provokes others to try to reproduce the observation and thus to either confirm or refute the initial hypothesis. A recent example is the discovery of beneficial effects of propranolol in severe hemangiomas of infancy, which found its way into routine application after the publication of just a few case reports. Another domain is side effects. The thalidomide tragedy was brought to light by a courageous pediatrician and geneticist, Widukind Lenz, who analyzed and presented numerous cases. About 40% of all side effects are uncovered by case reports.3 Many disciplines find themselves represented mainly in case reports. These include not only the legendary Sigmund Freud cases, which introduced the era of the intense and highly differentiated tradition of psychotherapy accounts that form the essence of this therapeutic artistry. Areas of medicine such as pediatric surgery and cardiologic guidelines rely heavily on case reports and case series. High-quality case reports

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Case Reports

A common thread in healthcare around the world is that patients receive treatments and these treatments produce outcomes. Reporting guidelines for case reports and their systematic documentation and publication are an important tool to share information across healthcare systems. The editors of Global Advances in Health and Medicine believe that high-quality, professional case reports focusing on a systems approach to medicine and the global convergence of conventional and traditional healthcare systems will inform the design and implementation of clinical trials and in turn improve the delivery of healthcare to patients everywhere.

Photographs reprinted with permission from AngelPHACE.com.

An Example of a High-Impact Case Report

Propranolol, a generic beta-blocker, was shown to effectively treat infantile hemangiomas (IH) in case reports published in The New England Journal of Medicinea in 2008 as a letter to the editor. This finding was confirmed in a case series published in 2010 in the Journal of the American Academy of Dermatology.b Propranolol is now recommended as a first-line therapy for ulcerating IH. The reasonable safety profile for this drug reduced the need for a randomized controlled trial (RCT), and the lack of compelling alternatives and propranolol’s availability as a generic drug further reduced the likelihood of an RCT. a

Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. b Hermans DJ, van Beynum IM, Schultze Kool LJ, van de Kerkhof PC, Wijnen MH, van der Vleuten CJ. Propranolol, a very promising treatment for ulceration in infantile hemangiomas: a study of 20 cases with matched historical controls. J Am Acad Dermatol. 2011 May;64(5):833-8.

Editorial

Why Medical Case Reports?

not only can be of great support in circumstances in which complex prospective trials cannot be conducted due to practical, ethical, or financial constraints, but they also provide important information for designing clinical trials. As they capture very different aspects of patient care and the course of disease, they can contribute valuable knowledge. Repeated case reports can also refute unrealistic claims if those claims are not replicated in comparable situations, a quality that can facilitate progress and prevent unnecessary trials. While experimental trials draw their elegance from a clear design with a homogeneous patient group and with highly standardized treatment and outcome measures, day-to-day healthcare often is confronted with enormous complexity: multimorbid patients, patients who do not fit into or do not respond to routine care, patients who show otherwise highly individualized treatment necessities. The current increase in popularity of individualized medicine is one approach to this challenge, mostly on the genetic level. But how do clinicians communicate about complex conditions? How do we exchange ideas about dealing with difficult and highly individualized situations? How do we acquire information and share ideas and existing clinical experiences? In these situations, the priority still lies in direct knowledge sharing by clinicians, especially in the form of personal stories or case reports, which then are melded with formal knowledge. Clinicians, physicians, therapists, nurses—all have a genuine interest in stories and reports that allow for knowledge sharing.4 In many situations, case reports are the best tool for obtaining information on a treatment, when and how to apply it, and its possible effects, both helpful and harmful. Medical education and the development of connoisseurship and expertise also depend on cases; even hazard ratios from randomized controlled trials and meta-analyses need to be hooked on stories in order to be memorable. Clinical judgment—the core competence in medicine that links the general formal knowledge to the uniqueness of patients and that is flexible and quickly adjustable to the individual situation— develops through the encounter with hundreds of single cases, one’s own and those of one’s colleagues, presented in conversation, at conferences, or in high-quality literature reports. Reliable clinical judgment is based on Gestalt principles, on pattern recognition, and not on unformed, premature, naïve statistical associations— and case reports can be as well.5 In this time of medical pluralism—the convergence of conventional and traditional medicine—the transparent information and insights about underlying pathophysiological concepts, diagnoses, decisions, treatments, outcomes, and harmful effects can be presented to others through the use of illustrative, comprehensible case reports. They can be the medium for the dialogue, preventing unfruitful hostility and serving patients who often search for help in different medical areas simultaneously. They can unveil the unseen needs

Editorial

of patients and provide suggestions for an improved experience in complex health situations. They can illustrate exceptional or exemplary treatment situations, healthcare in unusual settings, humanitarian work, and ethical challenges. They also can be a voice for patients when they themselves participate in case reporting. If a culture of high-quality case reporting can be established, if case reports can be published irrespective of outcome, and if these case reports can be made available in a searchable database, one could generate an information pool that would provide a complement to the realm of clinical trials and epidemiologic studies and that—though different in quality and the type of information it provides—would introduce valuable perspectives and ideas. A triangulation of different kinds of results could be an important research tool and could enhance the validity of clinical information, helping to approximate medical truth. Case reports and case studies will always be multicolored, stretching over the whole spectrum of case claims, anecdotes, detailed medical accounts, case study research, and randomized n-of-1 trials. They are, or can be, the primary instrument for all of the healthcare professionals who want to present their significant observations and share them with others. Case reports will definitely require elaborate guidelines for the systematic improvement of their quality. The reports would also benefit from systematic investigations of their role in medicine and innovation, the possibilities to reduce bias, and the issue of generalization. It is important, however, to resist the temptation of a strict and general formalization of case reports. What is needed is simply increased quality and efficiency in gathering and publishing the direct clinical observations of ambitious practitioners. To foster this process, we invite our readers who have a keen eye for the unusual, the interesting, the important to turn their observations into a case report and submit it for publication! References 1. Feinstein AR. Clinical judgment. Baltimore, MD: The Williams & Wilkins Company; 1967. 2. Vandenbroucke JP. In defense of case reports and case series. Ann Intern Med. 2001 Feb 20;134(4):330-4. 3. Aronson JK. Adverse drug reactions and the role of case reports. Paper presented at: Celebrating case reports and stories in healthcare; 2009 May 15; UK. 4. Gabbay J, Le May A. Practice-based evidence for healthcare: clinical mindlines. London, England: Routledge; 2010. 5. Kienle GS, Kiene H. Clinical judgement and the medical profession. J Eval Clin Pract. 2011 Aug;17(4):621-7.

www.gahmj.com • Volume 1, Number 1 • March 2012

global perspectives

Systems Approaches: A Global and Historical Perspective on Integrative Medicine Patrick Hanaway, MD

Author Affiliation Patrick Hanaway, MD, is the cofounder of Family to Family, Asheville, North Carolina; the chief medical officer of Genova Diagnostics, Asheville; and past president of the American Board of Integrative Holistic Medicine. Correspondence Patrick Hanaway, MD phanaway@gdx.net Citation Global Adv Health Med. 2012;1(1):10-11. Key Words Systems, medicine, integrative, Tibetan, traditional Chinese, TCM, Ayurveda, n-of-1, India, China

he globalization of healing systems is a dance of cultural awareness and cultural dominance that has arisen throughout history. With the development of greater communication and interest in wholesystems approaches to healing, the opportunity for the development of a global perspective on healing has emerged with new life force. The birth of integrative holistic healing systems in the West, such as naturopathic, homeopathic, anthroposophic, integral and functional medicine, and others, echoes the ocean of wisdom present in traditional healing systems, such as traditional Chinese medicine (TCM) and Ayurveda. In working to integrate the lessons from these systems, we see the inextricable link between man and the natural world, we work to understand the root cause of disease, we focus on the whole person to return balance, and we use empiric observation in large populations over time to grasp the interrelationships inherent in the whole-systems view of illness and wellness. Western medicine has progressed during the past 100 years with an emphasis on scientific method, allowing for incredible advances in pharmacology and acute care. During the past 50 years, there has been an increasing emphasis on evidence, as delineated through the randomized controlled trial (RCT)—an idea promoted by the US Food and Drug Administration Section 335(D) in 1964 as a means of evaluating a single therapeutic intervention. However, by definition, this approach does not allow for personalization. Multiple variables are controlled, but there is no ability to assess the clinical utility of an RCT in the “real world” of clinical practice. Compare this with the billions of people who have received diagnoses and treatment over thousands of years within the whole-systems approaches of TCM and Ayurveda—clearly another form of evidence, with an emphasis on “what works” clinically. Now that the spectrum of evidence begins with anecdotes and intuitive hunches based upon clinical experience, moving toward case studies, crosssectional reviews, prospective studies, and on to RCTs. All forms of evidence have value. An interesting phenomenon occurs when the rigors of Western reductionistic scientific methodology move us toward increased specialization, ie, knowing more and more about smaller and smaller phenomena. As the lens of investigation narrows its scope, so does the clinical value of the lessons learned. We have seen multiple examples over the past few years of drugs that have been approved and widely used for the treatment

Volume 1, Number 1 • March 2012 • www.gahmj.com

of “disease A” and then been implicated in increasing the risk of “disease B.” When there is a laser-like focus on a singular disease without evaluation of overall mortality and/or the effect of a therapeutic agent on the entire person, we lose the perspectives of a systemsbased, holistic approach to healing. TCM and Ayurveda intrinsically consider the entire person—indeed the entire community—when developing their approach to healing. Chinese medicine has long espoused the concept that macrocosm and microcosm recapitulate the same phenomenon—assimilation, transportation, energy production, detoxification/elimination, maintenance of structure, and other essential functions—whether at the level of the subcellular organelle, the organ, the person, the community, or the universe.1 This awareness may seem abstract to the practicing clinician until there is an understanding that the functions of the whole system must be understood in dynamic relationship with each other in order to facilitate appropriate diagnosis of the root cause and proper treatment of the individual person. This new order of thinking may constitute a barrier to entry for physicians who have developed their knowledge base through the linear, reductionist process of Western medicine. Very few doctors could discuss the difference between relative benefit, absolute benefit, and number needed to treat in a clinical trial. It is a clear understanding of these concepts that drives our clinical intuition that the current care paradigm does not effectively treat complex chronic disease with the standard pharmaceutical armamentarium. New systems-based approaches, including integrative medicine, metabolic medicine, and functional medicine, require us to change our mindset from one of disease as defined by an ICD-9 code toward a clinical passion to investigate the root cause of any given symptom complex, recognizing that the process becomes more difficult with increasing severity of illness, loss of reserve capacity, and a prolonged timeframe of disease. We assess imbalance and disease from the perspective of function and dysfunction. In clinical practice, we begin to ask a new set of questions. How is this person assimilating with their environment? Is this person effectively breathing in oxygen and, possibly, organic pollutants? Is this person effectively digesting and absorbing the 30 to 40 tons of macronutrients and micronutrients they eat in a lifetime? TCM evaluates the interrelationship between the functioning of the large intestine and the lungs, the yin and yang organs of the “metal” element. Ayurveda considers the

Global Perspectives

a global and historical perspective on integrative medicine

pre-eminent role of the lungs and large intestine as absorbing prana (life energy). These whole-systems perspectives are integrated into the framework of functional medicine, in which we investigate an imbalance in the process of assimilation when someone is not receiving the nourishment that they need. In order to understand the root cause of illness and effectively treat the whole person, we must gather, synthesize, integrate, and apply this information in clinical practice. Physicians, healers, sages, and politicians have sought to integrate the best forms of health and medicine for the past 2 millennia. Cultural information flow between India and China occurred nearly 2000 years ago, during the Buddhist era. The philosophical beliefs of each country contributed to its medical healing systems, Yoga in India and Taoism in China. Both healing systems include a theory of 5 elements, with Ayurveda applying them to physical structure and TCM seeing the 5 qualities of wood, fire, earth, metal, and water as representing the functional relationships between processes.2 Many have tried to overlay similar concepts onto different culture perspectives, thought patterns, and spiritual belief systems. The most informative and possibly the first real effort to develop an integrative medicine occurred in Tibet during the 7th century, when King Songtsen Gampo organized the first medical conference. During this time, doctors from India, China, Nepal, Greece, Persia, and other countries were invited to Tibet and brought with them medical texts that were later translated into Tibetan. Tibetan medical researchers were encouraged to incorporate Ayurvedic, Chinese, and Shangshung Bonpo medical principles into their work. This international conference developed into a complex system of healing that interweaves spiritual, shamanic, and rational healing practices based on the view of health as a harmonious balance between the physical, mental, emotional, spiritual, and natural worlds.3 It is easy to glorify the series of events in Tibet, but it should be clear that the acceptance of diversity through multiple streams of (sometimes conflicting) information provides a foundational framework of tolerance over standardization. Early in my career of studying different forms of healing, it seemed to me that the use of pulse diagnosis within TCM and Ayurveda could be used as a tool to standardize the diagnosis across healing systems. However, even with the use of pressure sensory electrodes, it was found that the pulse waveform varied depending upon who was taking the pulse. This clinical confirmation of the Heisenberg uncertainty principle tells us that the observer changes the field. Our perspective on healing has an influence on each patient we touch. We turn now to the emerging field of integrative medicine around the world. This globalization has varied implications for different cultures. Many physicians in China and India have eschewed their traditional healing systems because they are not perceived as having “status.” There have been precious few research

Global Perspectives

efforts that work to evaluate the efficacy of the wholesystems approach to healing within the peer reviewed medical literature. And Westerners have had little experience with integrating the philosophical framework of whole-systems healing approaches with the training they received in medical school and residency. The importance of systems-based research in healthcare cannot be overstated. The n-of-1 case report has the potential to expand to a case series, using an empiric, qualitative approach to classify phenomena as they occur in clinical practice. This includes the operational gathering of data on patients’ quality of life, diagnostic measures, treatment modalities, and followup data. The expansion of opportunities in this arena to monitor thousands, if not millions, of individuals will provide us with the statistical power we need to evaluate clinical utility. For example, one could assess the overall benefit to an individual who received standard medical care for irritable bowel syndrome (IBS) and compare that with an IBS patient who uses acupuncture and/or digestive enzymes in addition to standard medical care. The assessment of multiple different root causes for IBS as well as multiple treatment approaches can be evaluated over time with the participation of a sufficiently sized population. This new journal, Global Advances in Health and Medicine, begins to focus on this globalization through educational materials, including this journal, as well as strategies to gather data and report on systems-based healing research. The tools offered here will help us to see the inextricable link between man and the natural world, to understand the root cause of disease, to focus on the whole person returning to balance, and to use clinical observations over time to see the interrelationships inherent in the whole-systems view of illness and wellness. We cannot be content to simply deliver highquality personalized integrative medicine to one individual at a time. We are at the frontline of integrative, systems-based clinical research. As sages over time have asked, “If not you, who? If not now, when?” Join us. References 1. Jarrett LS. Nourishing destiny: the inner tradition of Chinese medicine. 2nd ed. Stockbridge (MA): Spirit Path Press; 1999. 2. Svoboda R, Lade A. Tao and dharma: Chinese medicine and Ayurveda. 1st ed. Silver Lake (WI): Lotus Press; 1995. 3. Gyatso DS. Mirror of Beryl: a historical introduction to Tibetan medicine. Kilty G, translator. 1st ed. Somerville (MA): Wisdom Publications. 2010.

www.gahmj.com • Volume 1, Number 1 • March 2012

GLOBAL ADVANCES IN HEALTH AND MEDICINE

changing landscapes

News From Around the World Suzanne Snyder

Mysterious Disease Devastates Pacific Coast of Central America

A mysterious epidemic has killed more than 24 000 people in El Salvador and Nicaragua since 2000 and stricken thousands of others with chronic kidney disease at rates unseen almost anywhere else. Some suggest that agricultural chemicals are the cause, but others contend that the grueling nature of the work and dehydration are to blame. Dr Richard J. Johnson, a kidney specialist at the University of Colorado, Denver, and other researchers who are working to discover the cause of the disease suspect chronic dehydration. To read the full article, click here. (Source: seattlepi.com)

Health Affairs Study Says Electronic Health Records May Not Cut Health Costs; Health IT Leaders Disagree

A study published this month in Health Affairs found that doctors using computers to track tests such as x-rays and magnetic resonance imaging ordered substantially more tests than doctors who relied on paper records. A number of experts have suggested that electronic health records (EHRs) will help reduce unnecessary and redundant tests by giving doctors more comprehensive and timely information when making diagnoses, but this study showed the opposite: doctors with computerized access to a patient’s previous image results ordered tests on 18% of the visits, whereas those using paper records ordered tests on 12.9% of visits. In other words, physicians using electronic technology ordered 40% more image testing than those without the tracking technology. Health information technology (IT) leaders are now voicing their disagreement with this contention. In a

blog post soon after the study’s results were featured on numerous websites, Dr Farzad Mostashari, national coordinator for health information technology, said that the study’s results “tell us little” about whether electronic health records will help to reduce costs. Dr Mostashari cites several problems with the study authors’ analysis, a major one of which is that reducing test orders is not the way in which EHRs are intended to reduce costs. Read the full article about the Health Affairs study here. (Source: The New York Times) Read Dr Mostashari’s blog post here. (Source: US Department of Health and Human Services’ HealthITBuzz)

Study: Malaria During Pregnancy Stunts Fetal Growth

The results of a large-scale study conducted along the Thai-Burmese border indicate that malaria infection during the early months of pregnancy stunts fetal growth even when the mothers do not have any symptoms of malaria. The study, conducted by the Shoklo Malaria Research Unit, tracked 3779 women’s pregnancies from 2001 to 2010. Pregnancy reduces a woman’s immunity, making pregnant women more vulnerable to malaria infections and increasing the risk of illness and death, according to the World Health Organization (WHO). Though the potential effects of malaria on later stages of pregnancy

Volume 1, Number 1 • March 2012 • www.gahmj.com

and birth weight—including spontaneous abortion, stillbirth, and premature delivery—are well documented, the study by SMRU is among the first to show the effects of malaria on early fetal growth, even in areas where malaria infections are not nearly as prevalent as they once were. Read more about the study’s results here. (Source: AsianScientist)

Urgent Humanitarian Aid Needed For 80 000 Sudanese Refugees

Only a short window of opportunity remains before the rainy season severely inhibits the urgent provision of humanitarian assistance to tens of thousands of Sudanese refugees in South Sudan, the international medical humanitarian organization Doctors Without Borders/ Médecins Sans Frontières (MSF) warned recently. Since November 2011, 80 000 refugees have fled violence in Sudan’s Blue Nile State, seeking shelter in the Doro and Jamam refugee camps. The camps are located in a remote and barren region of South Sudan, where humanitarian organizations confront massive logistic challenges to access and assist refugees. At the onset of rains in late April, the region will be even more inaccessible, likely becoming a vast swamp with small islands of dry ground. Over the coming weeks, all organizations providing assistance in the camps must transition to an emergency footing to ensure that refugees can survive the coming months, MSF said. Newly arriving refugees speak of ongoing bombing and fighting in Sudan’s Blue Nile State. While people have sought safety in the Doro and Jamam camps, they have encountered a harsh environment where their ability to survive is stretched to the breaking point.

Changing Landscapes

IMPROVING HEALTHCARE OUTCOMES WORLDWIDE

Serious gaps in assistance mean that the most basic needs are not adequately covered. Less than 8 liters of clean water per person per day is being provided, far below the recommended minimum standards of 15 to 20 liters per day in refugee camps. In its clinics, MSF witnesses the direct consequences of the lack of water; rising cases of diarrhea constitute 1 in 4 medical consultations. The full press release is available here. (Source: Médecins Sans Frontières)

Environmental Exposure to PCBs Linked to Infertility

Chemical structure of PCBs.

High levels of polychlorinated biphenyls (PCBs) and p,p’-DDE, a breakdown product of DDT, have been linked to an excessive number of sex chromosomes in sperm, according to a recent study published in Environmental Health Perspectives. Men with higher levels of PCBs and p,p’-DDE in their blood were more likely than those with lower levels to have a higher percentage of sperm sex-chromosome disomy, the greatest known cause of failed pregnancies. In the study of 341 men from subfertile couples, researchers found that exposure to p,p’-DDE may be associated with increased rates of XX, XY, and total sex-chromosome disomy, and exposure to PCBs may be associated with increased rates of YY, XY, and total sex chromosome disomy. Read the study here.

Camel Milk May Improve Autism Symptoms

Emerging reports suggest that camel milk, the drink of nomadic peoples from Mongolia to India, may have a healing effect on various diseases. Parents worldwide who have

Changing Landscapes

Photo: Kamran Jebreili/ASSOCIATED PRESS

been experimenting with camel milk in their children with autism spectrum disorder (ASD) are reporting reduced symptoms and increased skills in their children. Improvements cited in Internet posts include better sleep, increased motor planning abilities and spatial awareness, more eye contact, better language, and fewer gastrointestinal problems. Though autism is defined as a developmental disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM), studies have shown that inflammation, a condition common to many human diseases, may be a factor. Veteran Israeli camel expert Dr Reuven Yagil, who first described the use of camel milk to treat autism, contends that autism is an autoimmune disease afflicting primarily the intestines. American-Israeli scientist Dr Amnon Gonenne says that there is an active inflammatory component particularly in cases of autism that exhibit allergic symptoms. Eyal Lifshitz, manager of a camel milk research center and owner of Milk From Eden camel farm, and Dr Gonenne believe that one of camel milk’s beneficial effects is the calming of inflammation. Read the full article here. (Source: The Autism File)

USAID Launches New Gender Policy To Ensure Gender Equality and Female Empowerment

During a recent White House event, Dr Rajiv Shah, Administrator for the United States Agency for International Development (USAID), launched the Agency’s new Policy on Gender Equality and Female Empowerment. This policy comes at a critical

time as global efforts to reduce gender gaps have met only partial success. Across every development priority worldwide—from education to economic inclusion—gender inequality remains a significant challenge. For example, according to the United Nations Food and Agriculture Association, if women had equal access to the same productive resources as men, they could increase yields on their farms by 20% to 30%, which could reduce the number of hungry people in the world by up to 150 million people. The goal of the policy is to improve the lives of citizens around the world by advancing equality between females and males, and empowering women and girls to participate fully in and benefit from the development of their societies. More information, including the specific goals of the policy, is available here. (Source: USAID)

Millennium Development Goal Drinking Water Target Met

The world has met the Millennium Development Goal (MDG) target of halving the proportion of people without sustainable access to safe drinking water well in advance of the MDG’s 2015 deadline, according to a report issued recently by UNICEF and the World Health Organization (WHO). Between 1990 and 2010, more than 2 billion people gained access to improved drinking water sources, such as piped supplies and protected wells. The report, Progress on Drinking Water and Sanitation 2012, by the WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation, says that at the end of 2010, 89% of the world’s population, or 6.1 billion people, used improved drinking water sources. This is 1% more than the 88% MDG target. The report estimates that by 2015, 92% of the global population will have access to improved drinking water. But there is still considerable work to be done in this area. Read about it here. (Source: World Health Organization)

www.gahmj.com • Volume 1, Number 1 • March 2012

case report

Chinese Scalp Acupuncture for Cerebral Palsy in a Child Diagnosed With Stroke in Utero Jason Jishun Hao, DOM, MTCM, MBA; Sun Zhongren, PhD; Shi Xian, PhD; Yang Tiansong, doctoral candidate

Author Affiliations Jason Jishun Hao, DOM, MTCM, MBA, is president, International Academy of Scalp Acupuncture, Santa Fe, New Mexico. Sun Zhongren, PhD, is professor at Heilongjiang University of Chinese Medicine, Harbin, China. Shi Xian, PhD, is an associate professor at General Hospital of the Chinese People`s Liberation Army, Beijing, China. Yang Tiansong is a doctoral candidate at Heilongjiang University of Chinese Medicine. Correspondence Jason Jishun Hao, DOM, MTCM, MBA jasonhao888@yahoo.com Citation Global Adv Health Med. 2012;1(1):14-17.

Abstract

摘要

RESUMEN

A 6-year-old patient with cerebral palsy was treated with Chinese scalp acupuncture. The Speech I, Speech II, Motor, Foot motor and sensory, and Balance areas were stimulated once a week, then every other week for 15 sessions. His dysarthria, ataxia, and weakness of legs, arms, and hands showed significant improvement from each scalp acupuncture treatment, and after 15 sessions, the patient had recovered completely. This case report demonstrates that Chinese scalp acupuncture can satisfactorily treat a child with cerebral palsy. More research and clinical trials are needed so that the potential of scalp acupuncture to treat cerebral palsy can be fully explored and utilized.

用中医头针疗法对一名6岁脑瘫患儿进行治疗。每周对语言I区，语言II区，运动区域，足运动和感受区域以及平衡区域进行一次针灸，之后隔周进行一次针灸，共进行15次治疗。在每次头针治疗之后，患者的构音困难、运动失调，以及腿部、臂部和手部无力症状得到显著改善，15次治疗之后，患者完全康复。该病例证明，中医头针疗法在治疗儿童脑瘫方面能够取得令人满意的效果。当前仍需要进一步的研究和临床试验，对头针疗法在治疗脑瘫方面的潜在价值进行更充分的开发和利用。

Se aplicó acupuntura china en el cuero cabelludo para tratar a un paciente de 6 años de edad que sufría de parálisis cerebral. Una vez a la semana se estimularon el Habla I, Habla II, la función motora, la función motora del pie y funciones sensoriales, y las áreas que regulan el equilibrio. Luego, se repitió el procedimiento cada dos semanas durante 15 sesiones. La disartria, ataxia y debilidad en las piernas, brazos y manos que padecía el paciente mostró una mejoría considerable luego de recibir este tipo de tratamiento con acupuntura. Transcurridas las 15 sesiones, el paciente se había recuperado por completo. El análisis de este caso demuestra que esta técnica de acupuntura china puede ser efectiva en el tratamiento de los niños que sufren parálisis cerebral. Se necesitarán realizar más investigaciones y ensayos clínicos para que los beneficios potenciales de la acupuntura en el cuero cabelludo, como técnica de tratamiento de la parálisis cerebral, sea plenamente analizada y aplicada.

Key Words Chinese scalp acupuncture, cerebral palsy, dysarthria, ataxia, paralysis, stroke in utero

A chapter of Dr Hao’s book, Chinese Scalp Acupuncture, is available online exclusively at www.gahmj.com.

hinese scalp acupuncture is a contemporary acupuncture technique integrating traditional Chinese needling methods with Western medical knowledge of representative areas of the cerebral cortex (Figure 1). This modern system of acupuncture was first explored in the 1950s in China.1 Over the next 20 years, acupuncture practitioners developed a theoretical model integrating brain functions with the principles of Chinese medicine. Dr Jiao Shunfa, a neurosurgeon in Shanxi province in China, is the recognized founder of Chinese scalp acupuncture.2 He systematically undertook the scientific exploration and charting of scalp correspondences starting in 1971. Dr Jiao combined a modern understanding of neuroanatomy and neurophysiology with traditional techniques of Chinese acupuncture to develop a radical new tool for affecting the functions of the central nervous system. Acupuncture and moxibustion have been used to prevent and treat disease in China for thousands of years.

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Scalp acupuncture, however, is a modern technique with just 40 years of history. In the West, many healthcare practitioners are familiar with acupuncture for pain management. In contrast, scalp acupuncture is a new therapy to use as the primary tool for rehabilitation. It is still not easy for medical practitioners and the public to understand how scalp acupuncture may help in recovery from paralysis, aphasia, and ataxia, all conditions for which Western medicine has few effective treatments. Scalp acupuncture frequently is used to rehabilitate paralysis due to stroke, multiple sclerosis, automobile accident, and Parkinson’s disease. It is also often used in pain management, especially for pain caused by the central nervous system, such as phantom pain, complex regional pain, and residual limb pain.3 Scalp acupuncture has been used in the effective treatment of aphasia, loss of balance, loss of hearing, dizziness, and vertigo. The treatment is commonly given 2 to 3 times per week, and a basic therapeutic course consists of 10 treatments. Chinese

Case Report

chinese scalp acupuncture for cerebral palsy

Figure 1 Cerebral cortex, side view.

Figure 2 Stimulation areas, side view.

scalp acupuncture is helpful for children who are afraid of needles because the treatment requires few needles, they are not visible to the child, and the response is often rapid.

area (Figures 2-4). The needles were rotated at least 200 times per minute with thumb and index finger for several minutes.4 Foot motor and sensory area, Motor area, or Balance area was selected according to Michael’s symptoms. The ear point “Shenmen” was selected for the first needle in order to help Michael relax and reduce his sensitivity to scalp acupuncture. The needles were kept in place for 15 to 30 minutes. Although Michael was afraid of needles before beginning the treatment, he was quiet and cooperative and did not cry while the needles were inserted. He did not notice that there was a needle inserted in his ear and showed no negative reaction at all. Next, 4 needles were put on the Speech I area and the Foot motor and sensory area of his scalp. The needles were stimulated slightly.

Medical history and presenting condition

Michael, a 6-year-old with cerebral palsy, came from Amarillo, Texas, with his parents to our clinic in Albuquerque, New Mexico, on March 10, 2011. His mother reported that he had never spoken an understandable English sentence and had almost no coordination in his upper or lower extremities. For example, his hands were so weak that he could not make an observable mark on paper with a pencil. He had become passive and initiated little or no communication. His low functional level had resulted in his being diagnosed with mental retardation and learned helplessness. Multiple medical doctors, including neurologists and ear, nose, and throat specialists, evaluated Michael, and the diagnosis was stroke in utero. Michael had been receiving speech therapy and physical therapy for several years with no noticeable improvement and had been a passive participant in kindergarten for 2 years because of his inability to write, speak, or take part in physical activities. The examination at our clinic showed no abnormal findings of his physical development or hearing. It was hard to understand him when he said his name, age, and birthday or when he counted aloud. His coordination was severely impacted. He could not point to his nose, touch his index fingers together, or kick his legs. His tongue was red with a thin white coating, and his pulses were wiry and slippery. Treatment

Chinese scalp acupuncture and ear acupuncture were used to treat this patient. Primary scalp areas were Speech I and Speech III (Figure 2). The secondary scalp locations were Foot motor and sensory area, Motor area, and Balance Case Report

Outcome and Follow-up Treatments

Michael showed improvement in his speech during and at the end of his first treatment. It was easier to understand him when he said his name and age, and when he counted, most of the numbers were clearer after the treatment than they were before the treatment. During the second session, Michael was not afraid. The new toy his mother showed him as the last needle was inserted diminished any tension he may have experienced. He tried very hard to make clear sounds in order to get the new toy. Michael attempted to repeat the words and sentences the doctor and his parents were saying and continued to say many clear words that could be understood. He seemed very happy when he found he was able to kick his legs and stand on one leg without difficulty. Prior to the third session, his mother reported that Michael had started to talk in clearer sentences, some of which she could understand. She had found him already dressed when she went to wake him up to come to the acupuncture clinic. The fourth treatment was similar to the third, and 4 needles were inserted without any pain. During this treatment, Michael was able to speak like a www.gahmj.com • Volume 1, Number 1 • March 2012

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Figure 3 Stimulation areas, back view.

Figure 4 Stimulation areas, top view.

normal child, sing a song clearly, and laugh. By the fifth session, his parents said he was more physically active and had less trouble speaking. His fear and anxiety both at school and at home had diminished. Michael was playing with other children and based on his teacher’s report, had made some improvement in his schoolwork. Examination showed that he could speak more clearly and could write or paint like a normal child. His physical activities, such as jumping, kicking, running, and standing on one leg, showed no restriction at all. The redness of his tongue was now only on the tip. His treatments were extended to once every other week. After the 10th session, Michael’s speech and grades in school, as well as speech and physical activities at home, had significantly improved. He still had trouble saying some words, primarily those beginning with s or r. He improved so quickly that his treatments were extended from twice a month to once a month. After his 15th session, Michael had become a happy, communicative, and physically active boy who could say whatever he wanted, express his feelings with clear words, and move his body and limbs as he wished. He had no restriction of any of his mental and physical activities. His parents were happy to report that his math and reading scores had progressed by a grade level and he was moved to first grade. Our final examination at the clinic showed that his tongue was a little red with a thin white coating and his pulses were soft.

brain is not fully developed until about the age of 8 years and has the ability to reorganize, adapt, and reroute signals if it is stimulated properly.6 Brain cells not only can change in function and shape but also can take over the functions of nearby damaged cells.7 Based on these abilities, scalp acupuncture is geared toward stimulating and restoring affected brain tissue, as well as retraining unaffected brain tissue to compensate for the lost functions of damaged tissue. Cerebral palsy may occur in children in utero, during childbirth, or after birth up to about the age of 3 years.8 The majority of children with cerebral palsy are born with it, although it may not be detected until months or years later. The brain damage often is caused by genetic abnormalities, stroke, maternal infections and fevers, or fetal injury. In this case, the patient appeared to have a stroke in utero. The United Cerebral Palsy Foundation estimates that nearly 500 000 children and adults in the United States are living with one or more of the symptoms of cerebral palsy.9 According to the Centers for Disease Control and Prevention, about 10 000 babies born in the United States each year will develop cerebral palsy.10 Conventional Western medicine offers no cure for cerebral palsy, holding that the damage is not repairable and the disabilities that result are permanent.11 The diagnosis of cerebral palsy has historically relied upon the patient’s history and physical examination. Once a child is diagnosed with cerebral palsy, further diagnostic tests are optional. In Western medicine, treatment for cerebral palsy is a lifelong multidimensional process focused on overcoming developmental disabilities or learning new ways to accomplish challenging tasks.12 The incidence of dysarthria is estimated to range from 31% to 88%.13 To treat children with dysarthria, the needles are inserted bilaterally in Speech Areas I or III. The thinnest needles that can be inserted into the scalp should be selected. One needle should be inserted

Discussion

Chinese scalp acupuncture has been found to have good results in children with cerebral palsy including paralysis, ataxia, hypotonia or hypertonia, apraxia, dysarthria (trouble speaking), dysphasia, and mental retardation. With advanced brain research and imaging technology, scientists continue to understand better how the brain can adapt after damage and even regain its ability to function.5 It is now apparent that a child’s

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Case Report

chinese scalp acupuncture for cerebral palsy

on the “Shenmen” point on the ear to help young patients relax and to reduce sensitivity to needle insertion and stimulation of the scalp. The least number of needles possible should be used in the scalp in the initial treatment, and the needles should be rotated at least 200 times per minute with thumb and index finger for 1 minute. The needles should be twirled as gently as possible so that the child can tolerate the sensation, and the stimulation should be repeated every 10 minutes. The practitioner should select Foot motor and sensory area and Motor area or Balance areas accordingly to which symptoms and signs the child has. Verbal communication with children and their parents during treatment helps to reduce their fear and anxiety. At the same time, it can be important to encourage a child with aphasia to talk, count, or sing in order to exercise the power of speech. During treatment, some patients may have some or all of the following sensations: hot, cold, tingling, numbness, heaviness, distension, and the sensation of water or electricity moving along their spine, legs, or arms.14 The practitioner should tell the parents and child that those sensations are normal and that patients who experience some or all of these sensations usually respond and improve more quickly. However, those who do not have such sensations could still have immediate positive results. To treat motor dysfunction, the acupuncturist places the needles in Motor areas. Generally speaking, weakness of limbs or a paralyzed extremity is treated by choosing the opposite side of the Motor area on the scalp.15 For instance, for a patient with weakness in the right leg and foot, the left side of the Motor area on the scalp should be needled. The Upper one-fifth region is used to treat contralateral dysfunctional movement of the lower extremity, trunk, spinal cord, and neck. The Middle two-fifths region is used to treat contralateral dysfunctional movement of the upper extremity. The Lower two-fifths region is used to treat bilateral dysfunctional movement of the face and head.16 To treat patients with coordination and balance problems, the acupuncturist inserts and stimulates needles in the Balance area bilaterally. It is important to have patients move the affected limb actively as well as passively. Initially, the patient should be treated 2 to 3 times a week until major improvements are achieved. Then treatment is once weekly, then every 2 weeks, and then scheduled as indicated by the patient’s condition. A therapeutic course consists of 10 treatments. There are several different acupuncture techniques to treat weakness of limbs or paralysis. Although scalp acupuncture has the best and fastest response, other techniques are necessary for a fuller recovery. According to the individual’s condition, regular body acupuncture, electric acupuncture, and moxibustion, as well as physical therapy and massage, can be combined with scalp acupuncture to speed recovery. Electrical stimulation may be helpful if the practitioner has difficulty performing the rotation of the needles more than 200 times per minute. It is suggested that

Case Report

only 1 to 2 pairs of the scalp needles be stimulated at any one session or the brain can become too confused to respond. Moxibustion can enhance the therapeutic results of scalp acupuncture, especially in weaker patients. The timeframe for patients with cerebral palsy to be treated by scalp acupuncture is crucial. Parents should have their child receive acupuncture treatment as soon as his or her condition is diagnosed. The earlier the child receives treatment, the better the prognosis will be. Western medical science so far has not found a proven explanation for the success of Chinese scalp acupuncture in treating central nervous system disorders and specifically with treating cerebral palsy. There is a growing amount of clinical evidence that scalp acupuncture can improve or remove symptoms in patients with cerebral palsy. In China, there are many clinical and research studies showing the excellent results obtained from treating cerebral palsy with scalp acupuncture.17-19 Therefore, there is an urgent need for Chinese scalp acupuncture to be studied and perfected using modern Western science and technology. More case reports, case series, and clinical trials of Chinese scalp acupuncture in the treatment of cerebral palsy are needed so that its potential can be fully explored and utilized. References 1. Wang F. Scalp acupuncture therapy. Beijing: People’s Medical Publishing House; 2007. p. 5-6. 2. Jiao S. Head acupuncture. Bejiing: Foreign Languages Press; 1993. p. 8-22. 3. Hao JJ, Hao LL. Chinese scalp acupuncture. Boulder (CO): Blue Poppy Press; 2011. p. 7-8. 4. Chan HPY, Chan SSC, Conlon C, Lau P, Taylor JMR, Wong VK. Acupuncture for stroke rehabilitation: three decades of information from China. Boulder (CO): Blue Poppy Press; 2006. p. 18-9. 5. Ratey JJ. A user’s guide to the brain: Perception, attention, and the four theaters of the brain. New York: Pantheon Books; 2001. p. 30-43. 6. Schwartz JM, Begley S. The mind & the brain: neuroplasticity and the power of mental force. New York: HarperCollins Publishers; 2002. p. 212-35. 7. Doidge N. The brain that changes itself. New York: Penguin Group, Inc; 2007. p. xix-8. 8. WebMD.com [Internet]. Cerebral palsy – topic overview. Cited 6 Feb 20008. Available from: http://children.webmd.com/tc/cerebral-palsy-topic-overview. 9. Cerebralpalsysource.com [Internet]. Cerebral palsy quick facts. Cited 28 Jan 2012. Available from: http://www.cerebralpalsysource.com/cp_quickfacts/index.html. 10. Centers for Disease Control and Prevention. Cerebral palsy among children. Cited 28 Jan 2012. Available from: www.cdc.gov/NCBDDD/dd/documents/cp.pdf. 11. National Institute of Neurological Disorders and Stroke. Cerebral palsy: hope through research. Cited 29 Jan 2011. Available from: http://www.ninds.nih.gov/disorders/cerebral_palsy. 12. Cerebral Palsy World. Diagnosis. Cited 26 Jan 2012. Available from: http://cerebralpalsyworld.com/diagnosis.aspx. 13. Beukelman DR, Mirenda P. Augmentative and alternative communication: management of severe communication disorders in children and adults. 2nd ed. Baltimore: Paul H. Brookes Publishing Co; 1999. p. 246-99. 14. Jiao S. Scalp acupuncture and clinical cases. Bejiing: Foreign Languages Press; 1997. p. 32-5. 15. Zhu M, Kong R, Peng Z, Zhou M, Lu S. Zhu’s scalp acupuncture, China: Guangdong Technology and Science Press; 1992. p. 116-8. 16. O’Connor J, Bensky D. Acupuncture: a comprehensive text. Seattle: Eastland Press; 1981. p. 498-500. 17. Kong Y, Ren X, Lu S, editors. The acupuncture treatment for paralysis. Beijing: Science Press; 2000. p.143-5. 18. Ren X. The treatment of cerebral palsy by combining scalp acupuncture with rehabilitation. J Clin Acupunct Moxibustion, Harbin, China 2011, 27(1), p. 25-26. 19. Li H, Ma B. Clinical observation of scalp acupuncture for children’s dysarthria. Distal Education Chin Med. 2010;8(24):37-38.

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case report

Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports Maurice Orange, MSc; Aija Lace; Maria P. Fonseca; Broder H. von Laue, Dr med; Stefan Geider, Dr med; Gunver S. Kienle, Dr med

Author Affiliations Maurice Orange, MSc, is a general practitioner, formerly medical director at Park Attwood Clinic, United Kingdom, and currently senior hospital doctor integrative oncology at the Ita Wegman Klinik, Arlesheim. Maria P. Fonseca was formerly an assistant general practitioner at Park Attwood Clinic and currently is in private practice at Emerson College, United Kingdom. Broder H. von Laue, Dr med, is senior doctor, oncology focused practice, NiefernOeschelbronn, Germany. Stefan Geider, Dr med, is a general practitioner at Camphill Medical Practice NHS, St John’s, Aberdeen, United Kingdom. Gunver S. Kienle, Dr med, is senior research scientist at the Institute for Applied Epistemology and Medical Methodology at the University of Witten/ Herdecke in Freiburg, Germany. Correspondence Maurice Orange, MSc maurice.orange@ wegmanklinik.ch

abstract

摘要

RESUMEN

Background: Mistletoe is a complementary cancer treatment that is widely used, usually in addition to and alongside recommended conventional cancer therapy. However, little is known about its use, effectiveness, and safety in the treatment of cutaneous lymphoma. Case Report: Two patients with primary cutaneous B-cell lymphoma (pT2bcNxM0 follicle center and pT2acNxM0 marginal zone) either declined or postponed recommended conventional treatment and received highdose, fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous, and intravenous application was given; and one patient also underwent whole-body hyperthermia. The lymphoma regressed over a period of 12 and 8 months, respectively, and after administration of a cumulative dose of 12.98 g and 4.63 g mistletoe extract, respectively. The patients are in remission to date, 3.5 years after commencement of treatment. Neither patient received conventional cancer treatment during the entire observation period.

背景：槲寄生疗法是一种广泛使用的补充性癌症治疗方法，通常作为常规癌症治疗的补充疗法，或伴随常规疗法共同使用。然而，在皮肤淋巴瘤的治疗过程中，人们对该疗法的使用、有效性和安全性知之甚少。病例报告：两名原发性皮肤B-细胞淋巴瘤患者（pT2bcNxM0滤泡中心和pT2acNxM0边缘区域）取消或推迟推荐的常规治疗，并接受高剂量、可引起发热的槲寄生疗法；通过瘤内、皮下和静脉注射方式进行组合给药，其中一名患者还接受了全身过热疗法。这两名患者在分别接受12.98g和 4.63g累积剂量的槲寄生提取物治疗后，分别在12个月和8个月后淋巴瘤出现退化。迄今为止，即在开始治疗的3年半之后，患者病情正处于缓解期。在整个观察期期间，两名患者都未接受常规癌症治疗。

Antecedentes: El muérdago es una planta que se utiliza ampliamente como tratamiento oncológico complementario, por lo general, en forma concomitante con la terapia convencional recomendada. Sin embargo, no se sabe mucho sobre su uso, efectividad y seguridad en el tratamiento del linfoma cutáneo. Caso clínico: Dos pacientes diagnosticados con linfoma cutáneo primario de células B (centro folicular pT2bcNxM0 y zona marginal pT2acNxM0) habían rechazado o pospuesto el tratamiento convencional recomendado para estos casos, y recibieron dosis altas de tratamiento con muérdago, que provoca fiebre. Se administró una combinación de inyección intratumoral, subcutánea e intravenosa (IV), y uno de los pacientes también sufrió hipertermia en todo el cuerpo. Se registró un retroceso del linfoma en un período de 12 y 8 meses, respectivamente. Esto sucedió luego de que se administrara una dosis acumulativa de 12,98 g y 4,63 g de extracto de muérdago, respectivamente. A la fecha, los pacientes se encuentran en etapa de remisión, luego de transcurridos 3 años y medio desde el inicio del tratamiento. Ninguno de ellos recibió tratamiento oncológico convencional durante todo el período de observación.

Citation Global Adv Health Med. 2012;1(1):18-25. Key Words Mistletoe treatment, lymphoma, primary cutaneous B-cell lymphoma, fever, PCBCL, PCFCL, PCMZL, cancer, tumor Conflict of Interest The authors declare no competing interests.

ong-term remissions of lymphoma after feverinducing therapy with bacterial toxins have been documented since William Coley.1 Primary cutaneous lymphomas make up about 5% of all non-Hodgkin’s lymphoma (annual incidence, 1:100 000); 20% to 25% of these are primary cutaneous B-cell lymphomas (PCBCL).2-4 The most common subtypes are primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and diffuse large cell lymphoma. The follicle center and mar-

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ginal zone B-cell lymphomas tend to be indolent and have a 5-year survival of more than 95%5; although relapses are common, systemic progression is rare. Single lesions are treated with radiotherapy, intralesional steroids, surgical excision, or a “wait and see” strategy. Multifocal or relapsed systemic disease is usually treated with rituximab (R, anti-CD20 monoclonal antibody), single- or multi-agent chemotherapy (eg, chlorambucil or cyclophosphamide; vincristine; prednisolone; cyclophosphamide, vincristine, and predisolone [CVP]), or

Case Report

Fever-inducing Mistletoe Treatment for Lymphoma

immunotherapy with interferon-α.6, 7 PCBCL is associated with immune dysregulation and in some instances immunodeficiency with chronic inflammation (particularly PCMZL), eg, in rheumatoid arthritis or Sjögren’s syndrome and with Borrelia burgdorferi infection.8-12 They respond to immunological treatments like intralesional injections of interferon-α13 or adenovirus-encoding interferon-γ, which can even lead to remission in noninjected distant lesions.14 Survival in systemic lymphoma correlates with tumor-infiltrating immune cells,15 and for the occasionally observed spontaneous regressions of non-Hodgkin’s lymphoma, immunologic mechanisms have been proposed.16,17 Mistletoe extract (ME) is a whole plant remedy derived from Viscum album L, a hemi-parasitic shrub; it is widely used for complementary cancer treatment, especially in Europe, in conjunction with conventional therapy.18 A variety of biologically active compounds have been isolated from ME, including mistletoe lectins (MLs), viscotoxins, oligo- and polysaccharides, and others.19,20 ME has immunostimulatory activity (in vivo and in vitro activation of monocytes/macrophages, granulocytes, natural killer cells, T-cells, dendritic cells, induction of a variety of cytokines19,20), and several compounds (ML in particular) are cytotoxic with established apoptosis-inducing effects.19-21 ME is usually applied subcutaneously at a low starting dose, which is slowly titrated upwards and adjusted individually. This approach is associated with improvement of quality of life and probably also survival.22-24 Tumor remission has rarely been observed with low dosages, but mainly after high, fever-inducing ME dosage, often injected intratumorally or as an intravenous (IV) infusion.22-24 However, these observations have been reported only in case series and case reports.23-27 No randomized trials have yet investigated the role of ME in the treatment of lymphoma. Apart from dose-dependent flulike symptoms, fever, and inflammatory reactions at the injected sites, ME treatment is safe. Occasionally, hypersensitivity reactions are reported.28 Two patients with primary cutaneous lymphoma were treated at the Park Attwood Clinic (PAC, which closed in 2010), a British center specializing in complementary cancer care and particularly in high-dose and fever-inducing ME treatment. Informed consent for ME treatment was obtained from both patients with the understanding that this would not replace recommended therapies and there was good evidence that ME could improve tolerance of mainstream treatment when applied concurrently.

similar lesion developed over the mid shin of the same leg, and in the weeks leading up to presentation, a couple of much smaller satellite lesions appeared around the anterior lesion. Histopathology confirmed grade 1 follicular B-cell lymphoma (Figures 1 and 2). Staging computed tomography (CT) scan (chest, abdomen, pelvis) reported no intraabdominal or pelvic lymphadenopathy but showed one 2.7 x 1.7 inguinal lymph node, which was not biopsied. Stage was pT2bcNxM0.26 Hematology, biochemistry, and trephine bone marrow biopsy were essentially normal. IgH gene rearrangement analysis found clonality, confirming B-cell lymphoma; T-cell receptor (TCR)-β– ve; TCR-γ very weakly polyclonal. Cytogenetics: t(11;14) and t(14;18) translocations were not tested. The patient was generally well; she had no history of injury or infection and no B symptoms, such as fatigue, night sweats, weight loss, or pruritus. She had longstanding assumptive skin lipomas in different areas of the body but had been generally healthy, had a grown daughter, worked as a movement therapist, was a nonsmoker, drank no alcohol, took no regular medications, and reported no allergies. In view of the multicentric lesions, with satellites and possible regional node involvement indicative of advancement, it was recommended she undergo systemic immuno-chemotherapy with 6 cycles of cyclophosphamide,

Figure 1 Cellular lymphoid tumor. The pattern is largely diffuse with focal nodular areas (H&E x10). Image courtesy of Dr Ghada Bashat, Pathology, Aberdeen Royal Infirmary.

Case 1: primary cutaneous follicle centER B-cell lymphoma

A 51-year-old female presented with 2 lesions on the left lower leg in May 2008 at the oncology department of a large tertiary hospital (Aberdeen Royal Infirmary [ARI]). She had first noticed in the summer of 2007 a lesion in the left upper Achilles region, which increased in size and became red. In autumn 2007, a

Case Report

Figure 2 Cellular lymphoid tumor. The pattern is largely diffuse with focal nodular areas (H&E x20). Image courtesy of Dr Ghada Bashat, Pathology, Aberdeen Royal Infirmary.

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

vincristine, and prednisone plus rituximab (R-CVP) and involved-field radiotherapy on completion of the cycles. Although the patient was not opposed to this treatment in principle, she decided to keep it in reserve and improve her immunity with ME treatment first. On presentation for ME treatment in June 2008, the patient had a posterior lesion in the left proximal Achilles region measuring 5 cm x 4 cm (Figure 3) and an anterior mid shin tumor measuring 4 cm x 2 cm (Figure 4), with a number of surrounding satellites, each < 1.5 cm. The 2 large lesions were raised, red, and warm to the touch. The overlying skin was thinned but intact. There were no signs of deep tissue infiltration; she reported no pain, and no neurological deficits were ascertained. The left leg was well perfused, but there was pitting edema around the lesions and the ankle.

Table 1 Treatment Schedule (06/02/08-06/08/09) of Patient With PCBCLa ME Dosage (mg) Per Application Month 0

Treatment

Treatment with ME (using Abnobaviscum fraxini) comprised a combination of IV, intratumoral (IT), and subcutaneous (SC) applications over 12.3 months and IV and SC application over another 8 months. Details are shown in Table 1. Treatment was subdivided in an induction phase, wherein febrile reactions to ME are elicited, and a postinduction phase. ME treatment was combined with whole-body hyperthermia (WBHT)—a technique to increase core temperature to 39° to 39.5°C for 2 to 5 hours with water-filtered infrared A radiation

4 5 6

Figure 3 Primary cutaneous B-cell lymphoma in July 2008. Posterior lesion left lower leg.

Day or IV IT SC Treatment Interval Treatmentb Treatment (no. of sessions, if > 1) WBHT Induction phase 1 40 — — 2 80 — 1 3 160 1 10 4 — 4 20 8 160 10 30 11 160 20 20 15 160 — 40 Post-induction phase 16 — 40 40 18 160 — — c — — (3 x) 40 21-28 25 200 — — 29-35 — — (2 x) 40 32 200 — — 36-42 — — 40 36 200 80 — 37 — 40 — No. 1 42 200 120 — No. 2 43-49 — — (2 x) 40 46 200 — — 50-56 — — (2 x) 40 53 200 — 80 — 57 — 240d 58 200 — — No. 3 61 — — — 64-70 — — (2 x) 40 — 67 200 320d 71-77 — — (2 x) 40 74 200 — — 40 78 — 320d 79 200 — — No. 4 85-91 — — 40 d — 88 200 320 92-98 — — (2 x) 40 95 200 — — — 99 — 320d 100 200 — — No. 5 103-112 — — (2 x) 40 109 200 — — 113-119 — — (2 x) 40 116 200 — — 20 120 — 320d 127-140 — — (4 x) 40 135 200 — — No. 7 141-161 — — (5 x) 40 — 162 — 360d 163 200 — — No. 8 169-182 — — (3 x) 40 178 200 — — 183-189 — — (2 x) 40 d — 190 — 400 191 200 — — No. 9 197-210 — — (4 x) 40 204 200 — — 211-231 — — (6 x) 40 d — 233 — 400 234 200 — — No. 10 237-271 — — (12 x) 20 254 200 — — — 272 — 400d 279-369 — — (13 x) 40 338 200 — — — 370 — 240d 371 200 — — No. 12 372 End of IT treatment; subsequent IV and SC treatment and WBHT not shown.

Total No. of applications ME dosage

Figure 4 Primary cutaneous B-cell lymphoma in July 2008. Anterior lesion left lower leg; surrounding satellites not showing clearly.

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33 6120

19 3950

81 2901

12 x

Abbreviations: IT, intratumoral; IV, intravenous; ME, mistletoe extract; PCBCL, primary cutaneous B-cell lymphoma; SC, subcutaneous; WBHT, whole-body hyperthermia. a Month and day (interval) of treatment; mode, dose, and number of ME applications; application of WBHT. b Infused in 250 mL sodium chloride 0.9%, over 60-90 minutes. c Treatment periods of 1 or more weeks during which SC injections were given. d IT distributed over both lesions.

Case Report

Fever-inducing Mistletoe Treatment for Lymphoma

under controlled conditions. The skin lesions were not directly targeted. She had no other cancer treatments and was not taking any medications. During induction, the patient had 4 febrile responses of ≥38.5°C lasting < 24 hours with maximum readings of 38.5°C (after day 3); 38.7°C (after day 4); 39.1°C (after day 8); and 38.6°C (after day 11). For the IT approach, the lesions were injected from the healthy skin margins to avoid breaking the paper-thin skin overlying the bulging tumors. The volume of ME fluid often exceeded 20 mL (20 mg/mL/ampoule) and was injected evenly intraand perilesional while repositioning the needle during injection. After IT treatment, the lesions responded with immediate postinjection swelling and inflammation, followed by clinical resolution of inflammation, and over the course of treatment, the lesions successively appeared less inflamed. The rate of regression seemed slightly accelerated after starting WBHT (day 37), and after 4 months, there was a clear overall improvement. The lesions continued to show injection-associated fluctuations, and the posterior lesion resolved first. The lesions steadily decreased in volume, consistency, and redness. The remission was assessed by visual inspection and palpation and confirmed by 3 independent clinicians from 3 different clinical settings, including the ARI. The overall fitness and stamina of the patient improved. Re-scanning in May 2009 reflected “No significant supraclavicular, axillary or mediastinal . . . retroperitoneal or pelvic lymphadenopathy; as before, there are inguinal nodes the largest of which is on the left and measuring 1.3 x 1.8 cm. This node was documented as 2.7 x 1.7 cm on staging.” Routine full blood count and biochemistry were normal. Given the favorable clinical signs of control, the IT injections were discontinued at 12.3 months. Combined IV and SC ME treatment with WBHT continued for another 8 months, and the lesions continued to regress. The areas blanched eventually, leaving depressed (posterior, Figure 5) and level (anterior lesion, Figure 6) hyperpigmented areas. Conventional therapy was deferred indefinitely. At last review in December 2011, the patient was doing well and remained in remission; the appearances were similar to those from June 2011 (Figures 7 and 8).

Figure 5 Primary cutaneous B-cell lymphoma in May 2010. Posterior left lower leg; posttreatment pigmentation and depression.

Figure 6 Primary cutaneous B-cell lymphoma in May 2010. Anterior left lower leg showing pigmentation changes.

Figure 7 Primary cutaneous B-cell lymphoma in June 2011. Posterior left lower leg.

Tolerability

Fever was associated with sickness (grade 1) and grade 2 to 3 fatigue. The subsequent combined IV/IT administrations elicited fatigue (grade 1-2) for 1 to 3 days. No hypersensitivity was observed. SC injections elicited site responses of 4 cm to 5 cm erythema for < 2 days. The intralesional injections with concentrated ME were uncomfortable, with fluid pressure and pain for a few minutes, but did not require analgesia. Inflammatory responses (erythema, swelling, tenderness) and (transient) increase of edema of the lower leg lasted for < 2 days and were treated with cooling applications. The patient had no phlebitis at cannulation sites.

Case Report

Figure 8 Primary cutaneous B-cell lymphoma in June 2011. Anterior left lower leg.

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

Patient’s Description of Treatment

The patient in this case described the treatment experience as follows: With the initial fevers and fluctuating energy levels, my treatment was intense, exhausting and it was the only thing I could do during that time: but not a burden and a meaningful experience. During one of the high fevers an old traumatic experience became disentangled and I have felt freed up since; I now feel better than before my cancer, physically and emotionally. I also felt empowered by the working together with my doctors to develop the best treatment for me. I am very grateful for my new health! Case 2: primary cutaneous marginal zone B-cell lymphoma

A 52-year-old flight attendant was diagnosed at the same oncology department (ARI) with stage 2A, pT2acNxM0 primary cutaneous marginal zone B-cell lymphoma (PCMZL). In December 2007, 2 to 3 days after venapunction, he developed a lesion in the left antecubital fossa, which was excised in May 2008. The histopathology showed nodal marginal zone lymphoma (Figure 9). A staging CT scan of the neck, chest, abdomen, and pelvis showed no signs of systemic disease; trephine bone marrow biopsy, biochemistry, and hematology were normal. Shortly after excision, the patient developed a second lesion on the right anterior chest wall, medial to the right anterior axillary fold. The lesion was only palpable (no photographs). The patient was asymptomatic, had no recent weight loss or fatigue. Several treatment options were recommended: R-CVP, 10 fractions of involved-field radiotherapy of the 2 sites, or 6 months’ pulsed chlorambucil; he declined these options. The patient had a history of rosacea with keratitis; actinic keratoses of upper back (treated with occasional cryotherapy); 2 basal cell carcinomas—one of the upper back (excised 1999) and one of the left leg (excised early 2007)—and an uncertain diagnosis of facial cutaneous scleroderma with no visceral involve-

ment, but raised titres of antinuclear factor, which was unresponsive to azathioprine and oral prednisolone (2004). He used nicotine and alcohol moderately. Apart from emollients, he used no other regular conventional medications, reported no formal allergies, and was mistletoe-naïve. He had had no recent infections and no soft tissue trauma. On presentation at PAC in August 2008, the patient was in good general health, with a Karnofsky Performance Scale status of > 90%. There was one soft and mobile lymph node in the left axilla. The right upper thoracic lesion was 2 x 3 cm palpable and mobile. There were no other abnormal findings. Treatment

Combined IV, IT, and SC treatment with ME (Abnobaviscum fraxini) was provided over a period of 8.5 months. Details are shown in Table 2. During informed consent, it was explained to the patient that his underlying autoimmune condition theoretically could be aggravated. He received no other anticancer treatments. He had 6 febrile responses (38° to 39.2°C) between days 5 and 87. There were no signs of concomitant infection. After IT injections, the lymphoma lesion each time showed a similar response pattern of inflammatory swelling and erythema for up to 2 days, then resolution. The lesion increased in size over the first month to 4 x 5 cm, then remained unchanged for 3 months, and after the IT dose was increased to 100 mg ME, the lesion steadily diminished to become impalpable at 8.5 months (Table 2). This complete response (CR) was clinically verified by 3 clinicians in 2 separate institutions, including the ARI. The ITs were ceased in April 2009, and SC and IV treatment was continued until November 2010. A CT scan in March 2010 was unremarkable. The patient was last reviewed in December 2011 and was doing well and in remission; no new lesions had developed. Tolerability

During the first 3 months, treatment was challenging. The fever episodes in particular were accompanied by sickness and grade 1 to 2 fatigue. Once, grade 2 phlebitis developed at an IV cannulation site and resolved spontaneously; interestingly, no local relapse resulted from this. The SC and IT doses were followed by typical inflammatory site reactions that resolved without scarring or subcutaneous fibrosis. No hypersensitivity and no signs or symptoms of autoimmune reactivation were observed. After 6 months, the patient consistently reported improved vitality and well-being. Patient’s Description of Treatment

The patient in this case described the treatment experience as follows: Figure 9 Nodular marginal zone lymphoma. The architecture of the node is diffusely effaced by a population of lymphoid, plasmacytic, and histiocytic cells (H&E x10). Image courtesy of Dr Ghada Bashat, Pathology, Aberdeen Royal Infirmary.

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When I was offered chemo-/radiotherapy, this seemed aggressive to me like a sledge hammer [sic] to crack a nut. My understanding of mistletoe ther-

Case Report

Fever-inducing Mistletoe Treatment for Lymphoma

Table 2 Treatment Schedule (08/09/08-04/20/09) and Tumor Size of Patient With PCMZLa ME Dosage (mg) Per Application

Tumor Day or IT SC Treatment IV Size (cm) Month Interval Treatmentb Treatment (no. of sessions, if > 1) Palpation 0

1 2

6 7

1 2 3 4 5 7 10 13 22 26-47 52 54-64 66 71-85 87 93-107 109 114-128 130 132-149 151 153-170 172 176-191 193 195-219 221

Induction phase — — — 2 10 20 40 80 Post-induction phase — — — — 100 40 — — 140 40 — — 120 40 — — 160 40 — — 180 100 — — 180 100 — — 200 100 — — 160 80 — — 160 80 40 80 160 200 — 200 200 200

— 0.2 — 0.2 — — 2 4 12 (7 x) 20 — (3 x) 20 — (5 x) 20 — (4 x) 20 — (5 x) 20 — (6 x) 20 — (6 x) 20 — (5 x) 20 — (8 x) 20 —

3x2

5x4

Reducing

0.5 x 0.5 x 0.3

223-254 — — (10 x) 20 256 160 20 — Impalpable 257 End of IT treatment; subsequent IV and SC CR treatment not shown.

Total No. of applications ME dose

17 x 2 640

15 x 792

64 x 1 198.4

Abbreviations: CR, complete response; IT, intratumoral; IV, intravenous; ME, mistletoe extract; PCMZL, primary cutaneous marginal zone lymphoma; SC, subcutaneous. a

Month and day (interval) of treatment; mode, dose, and number of ME applications.

Infused in 250 mL sodium chloride 0.9% over 60-90 minutes.

apy felt gentler and simply like the right thing to do. The treatment itself, whilst challenging, confirmed my feeling that it was the bedrock, the main stay [sic] of being healed. Discussion

The primary cutaneous B-cell lymphoma of 2 patients regressed after administration of a combination of SC, IV, and IT applications of high-dose, feverinducing ME treatment. The rationale for the combination was to optimize immune responses as currently understood to elicit fever and to apply the principle of “in situ” vaccination with IT application. In one patient, WBHT was added to draw on the benefits of improved immune competence that is associated with fever-range hyperthermia.29 Three and a half years

Case Report

since commencement, the patients remain in clinical remission. With high dosage, especially local ME applications, tumor remissions have been reported repeatedly in a number of tumor types, including breast cancer, Merkel cell cancer, primary liver cancer, pancreatic cancer, and cutaneous squamous cell cancer.25-27 Still, high-dose and combined IT, IV, and SC administration that aims to elicit febrile induction is uncommon and underreported. The literature on ME treatment of lymphoma is limited compared to that of other tumor types. One retrospective study describes favorable outcomes, including a few remissions in a group of 61 patients with follicular non-Hodgkin’s lymphoma treated with a lowlectin ME (Iscador Pini) either alone or combined with or on completion of chemotherapy.30 Another retrospective study primarily investigated safety aspects of ME treatment in Hodgkin’s and non-Hodgkin’s lymphoma and found no risks.31 Some case reports describe remission of non-Hodgkin’s lymphoma under ME monotherapy,32-35 including 2 in cutaneous T-cell lymphoma in children.36,37 In these cases, the dosage was lower than in the cases reported here and applied mainly subcutaneously and only partly intravenously and intratumorally. At least one fever reaction was reported. Preclinical studies with lymphoma cells and murine lymphoma models treated with ME, isolated MLs, recombinant ML, and other ME peptides have consistently shown antitumoral effects with tumor inhibition, inhibition of metastases, and survival benefit.19,38-42 ME contain several cytotoxic ingredients, among them lectins and viscotoxins, which are particularly abundant in Abnobaviscum fraxini. When lectins are applied systemically, their cytotoxicity is moderated by serum proteins43 and later by the occurrence of anti-ML antibodies;44 hence, their cytotoxicity is to be expected, primarily with IT administration. However, a disease response could also be effected by an immunological mechanism, as has been demonstrated for ME repeatedly.19,20 Furthermore, fever seems to have a role in tumor defense.45 The impact of ME treatment cannot be easily ascertained when used concurrently with mainstream cancer therapy. Occasionally, however, patients postpone or decline recommended conventional treatment in favor of ME, and such cases allow evaluation of ME treatment alone. Two of these patients are described above; these are the only two cutaneous lymphoma cases treated at PAC with ME alone and are therefore unselected. The cases of 2 other patients from PAC who had cancer at other sites and were treated with ME monotherapy have been published previously.27 In lymphoma, spontaneous remission is estimated to occur in 5% to 20% of cases. It is sometimes of long duration16,17,46,47 and often is associated with reducing an immunosuppressive treatment or condition; following fever, viral or bacterial infections, or vaccination; or after biopsy and following eradication of helicobacter

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For more information on fever in cancer treatment, see page 92.

GLOBAL ADVANCES IN HEALTH AND MEDICINE

in gastric lymphoma.17 In a small follow-up study observing patients over many years, spontaneous remissions were reported in 4 of 16 patients with PCFCL (one of them complete) and in 4 of 8 patients with PCMZL (none of them complete), all of whom had a relapse.48 Although spontaneous remission could have played a role in the cases presented here, in the first of the cases presented , the lesions had grown progressively until commencement of ME treatment and then steadily decreased, with fluctuating treatment-related inflammatory responses. In the second case, the lesion resolved after initial treatment-related increase and with some delay, which is a known response pattern in ME-associated tumor remissions.26,30 Therefore, a mere coincidence is unlikely, especially as the 2 cases are unselected (meaning that they were not selected from a larger group of patients with cutaneous lymphomas treated with ME but were the only patients with cutaneous lymphonas treated in this way) and represent the only patients with PCBCL from PAC that had been treated with ME monotherapy. One also has to consider that the feverinduction ME treatment is likely to upregulate just those mechanisms implicated in the frequent spontaneous remission described for lymphoma. Two further case publications on ME treatment of a related entity, CD30+ T-cell lympho-proliferation, reported complete regression of multiple and active cutaneous and nodal disease.37,38 In one case, treatment consisted of low-dose IV (3 infusions of 0.02 mg, 0.2 mg, and 2 mg) and SC (up to 2 mg twice a week) without fever or site responses, with a noticeable disease response within 1 week and durable (30 months) complete response (CR) within 4 weeks. The second case was treated with primary fever intent (38°C), IT, and SC, and had a dose-dependent partial response and CR that relapsed with a lower-dose ME but regressed again with dose increase. A differentiated appreciation of the singular components of the combined ME treatment—the specific role of fever and each of the specific contributions of SC, IT, and IV—and of the synergies is not possible given the current knowledge and require further research. Although treatment was well tolerated and the safety observed is in accordance with other investigations on the safety of ME treatment in higher dosage,28 this treatment should be reserved for use by physicians who have experience with ME application in higher dosages and IT/IV until further investigations have explored the role of high-dose, fever-inducing ME in cancer and its safety in more detail. Conclusion

High-dose, fever-inducing mistletoe treatment seems to have beneficial effects in two cases of primary cutaneous B-cell lymphoma. Further research is needed to investigate antitumor effects, potential mechanisms

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of action, best mode of application, and the associated safety and efficacy. Consent

Written informed consent was obtained from both patients for publication of the report and the accompanying Figures. They both read the final version of the paper and confirmed its contents. References 1. Wiemann B, Starnes CO. Coley’s toxin, tumor necrosis factor and cancer research: a historical perspective. Pharmac Ther. 1994;64(3):529-64. 2. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005 May 15;105(10):3768-85. 3. Bradford PT, Devesa SS, Anderson WF, Toro JR. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases. Blood. 2009 May 21;113(21):5064-73. 4. Slater DN. The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants. Br J Dermatol. 2005 Nov;153(5):874-80. 5. Willemze R. Primary cutaneous B-cell lymphoma: classification and treatment. Curr Opin Oncol. 2006 Sep;18(5):425-31. 6. National Comprehensive Cancer Network. NCCN guidelinesTM version 4.2011: primary cutaneous B-cell lymphoma. Fort Washington: National Comprehensive Cancer Network; 2011. 7. Senff NJ, Noordijk EM, Kim YH, et al. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood. 2008 Sep 1;112(5):1600-9. 8. Zhao XF, Reitz M, Chen QC, Stass S. Pathogenesis of early leukemia and lymphoma. Cancer Biomark. 2011; 9(1-6):341-74. 9. Magro CM, Porcu P, Ahmad N, Klinger D, Crowson AN, Nuovo G. Cutaneous immunocytoma: a clinical, histologic, and phenotypic study of 11 cases. App Immunohistochem Mol Morphol. 2004 Sep;12(3):216-24. 10. Cho-Vega JH, Vega F, Rassidakis G, Medeiros LJ. Primary cutaneous marginal zone B-cell lymphoma. Am J Clin Pathol. 2006 Jun;125 Suppl:S38-49. 11. Takino H, Li C, Hu S, et al. Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathological study of cases from Asia, Germany, and the United States. Mod Pathol. 2008 Dec;21(12):1517-26. 12. Hoover RN. Lymphoma risks in populations with altered immunity—a search for mechanism. Cancer Res. 1992 Oct 1;52(19 Suppl):5477s-8s. 13. Cozzio A, Kempf W, Schmid-Meyer R, et al. Intra-lesional low-dose interferon alpha2a therapy for primary cutaneous marginal zone B-cell lymphoma. Leuk Lymphoma. 2006 May;47(5):865-69. 14. Dummer R, Eichmüller S, Gellrich S, et al. Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas. Mol Ther. 2010 Jun;18(6):1244-7. 15. Dave SS, Wright G, Tan B, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004 Nov 18;351(21):2159-69. 16. Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade Non-Hodgkin’s lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471-5. 17. Wiernik PH. Spontanremissionen bei lymphomen. In: Heim ME, Schwarz R, editors. Spontanremissionen in der onkologie. Stuttgart/New York: Schattauer Verlag; 1998. p. 193-199 18. Molassiotis A, Fernandez-Ortega P, Pud D, et al. Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol. 2005 Apr;16(4):655-63. 19. Kienle GS, Kiene H. Die Mistel in der Onkologie: Fakten und konzeptionelle Grundlagen. Stuttgart, New York: Schattauer Verlag; 2003. 20. Büssing A, editor. Mistletoe: the genus Viscum. Amsterdam: Hardwood Academic Publishers; 2000. 21. Büssing A, Schietzel M. Apoptosis-inducing properties of Viscum album L. extracts from different host trees, correlate with their content of toxic mistletoe lectins. Anticancer Res. 1999 Jan-Feb;19(1A):23-8. 22. Kienle GS, Kiene H. Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther. 2010 Jun;9(2):142-57. 23. Kienle GS, Glockmann A, Schink M, Kiene H. Viscum album L. extracts in breast and gynaecologic cancers: a systematic review of clinical and preclinical research. J Exp Clin Cancer Res. 2009 Jun 11;28:79. 24. Kienle GS, Kiene H. Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts. Eur J Med Res. 2007 Mar 26;12(3):103-19. 25. Matthes H, Schad F, Buchwald D, Schenk G. Endoscopic ultrasound-guided fineneedle injection of Viscum album L. (mistletoe; Helixor M) in the therapy of primary inoperable pancreas cancer: a pilot study. Gastroenterology. 2005;128(4 Suppl 2):433, T 988. 26. Mabed M, El-Helw L, Shamaa S. Phase II study of viscum fraxini-2 in patients with

Case Report

Fever-inducing Mistletoe Treatment for Lymphoma

advanced hepatocellular carcinoma. Br J Cancer. 2004 Jan 12;90(1):65-9. 27. Orange M, Fonseca M, Lace A, von Laue HB, Geider S. Durable tumour responses following primary high dose induction with mistletoe extracts: Two case reports. Eur J Integr Med. 2010 Jun;2(2):63-9. 28. Kienle GS, Grugel R, Kiene H. Safety of higher dosages of Viscum album L. in animals and humans–systematic review of immune changes and safety parameters. BMC Complement Altern Med. 2011 Aug 28;11:72. 29. Skitzki JJ, Repasky EA, Evans SS. Hyperthermia as an immunotherapy strategy for cancer. Curr Opin Investig Drugs. 2009 Jun;10(6):550-8. 30. Kuehn JJ. Treatment responses to viscum album pini (Iscador P) in non-Hodgkin´s lymphoma exploring a new therapeutic route. Medicina (B Aires). 2007; 67(Suppl II):107-14. 31. Stumpf C, Rosenberger A, Rieger S, Tröger W, Schietzel M. [Mistletoe extracts in the therapy of malignant, hematological and lymphatic diseases—a monocentric, retrospective analysis over 16 years]. Forsch Komplementarmed Klass Naturheilkd. 2000 Jun;7(3):139-46. German. 32. Wagner R. Eine Praxisbeobachtung 1993 - 1996. Iscador-Informationen, Verein für Krebsforschung e V. Ostfildern. 1996;(4):1-42. 33. Wolf P. Die mistel-infusionstherapie zur behandlung von tumorleiden. Naturamed. 1989;4:720-724. 34. Goyert A. Niedrig dosierte Misteltherapie bei niedrig malignem Non-HodgkinLymphom. Erfahrungsbericht. In: Scheer R, Becker H, Berg PA, editors. Grundlagen der Misteltherapie: Aktueller Stand der Forschung und klinische Anwendung. Stuttgart: Hippokrates Verlag GmbH; 1996. p. 362-5. 35. Kuehn JJ. [Favorable long-term outcome with mistletoe therapy in a patient with centroblastic-centrocytic non-Hodgkin lymphoma]. Dtsch Med Wochenschr. 1999 Nov 26;124(47):1414-8. German. 36. Kameda G, Kempf W, Oschlies I, Michael K, Seifert G, Längler A. [Nodal anaplastic large-cell lymphoma ALK-1- with CD30+ cutaneous lymphoproliferation treated with mistletoe: spontaneous remission or treatment response?] Klin Padiatr. 2011 Nov;223(6):364-7. German. 37. Seifert G, Tautz C, Seeger K, Henze G, Laengler A. Therapeutic use of mistletoe for CD30+ cutaneous lymphoproliferative disorder/lymphomatoid papulosis. J Eur Acad Dermatol Venereol. 2007 Apr;21(4):558-60. 38. Kovacs E, Link S, Toffol-Schmidt U. Comparison of Viscum album QuFrF extract with vincristine in an in vitro model of human B-cell lymphoma WSU-1. Arzneimittelforschung. 2008;58(11):592-7. 39. Kuttan G, Vasudevan DM, Kuttan R. Effect of a preparation from Viscum album on tumor development in vitro and in mice. J Ethnopharmacol. 1990 Apr;29(1):35-41. 40. Braun JM, Ko HL, Schierholz JM, Weir D, Blackwell CC, Beuth J. Application of standardized mistletoe extracts augment immune response and down regulates metastatic organ colonization in murine models. Cancer Lett. 2001 Sep 10;170(1):25-31. 41. Kuttan G, Vasudevan DM, Kuttan R. Tumour reducing activity of an isolated active ingredient from mistletoe extract and its possible mechanism of action. J Exp Clin Cancer Res. 1992;11(1):7-12. 42. Pryme IF, Bardocz S, Pusztai A, Ewen SW. Dietary mistletoe lectin supplementation and reduced growth of a murine non-Hodgkin lymphoma. Histol Histopathol. 2002 Jan;17(1):261-71. 43. Frantz M, Jung ML, Ribéreau-Gayon G, Anton R. Modulation of mistletoe (Viscum album L.) lectins cytotoxicity by carbohydrates and serum glycoproteins. Arzneimittelforschung. 2000 May;50(5):471-8. 44. Stettin A, Schultze JL, Stechemesser E, Berg PA. Anti-mistletoe lektin antibodies are produced in patients during therapy with an aqueous mistletoe extract derived from Viscum album L. and neutralize lectin-induced cytotoxicity in vitro. Klin Wochenschr. 1990 Sep 14;68(18):896-900. 45. Kienle GS. Fever in cancer treatment: Coley’s therapy and epidemiologic observations. Global Adv Health Med. 2012;1(1):92-100. 46. Gattiker HH, Wiltshaw E, Galton DA. Spontaneous regression in non-Hodgkin’s lymphoma. Cancer. 1980 May 15;45(10):2627-32. 47. Papac RJ. Spontaneous regression of cancer. Cancer Treat Rev. 1996 Nov;22(6):395-423. 48. Bekkenk MW, Vermeer MH, Geerts ML, et al. Treatment of multifocal primary cutaneous B-cell lymphoma: a clinical follow-up study of 29 patients. J Clin Oncol. 1999 Aug;17(8):2471-8.

Case Report

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case report

Successful Treatment of Chronic Viral Hepatitis With High-dilution Medicine Barbara Sarter, PhD, APRN, FNP-C, DiHom; Prasanta Banerji, FMIH; Pratip Banerji, MD(Hom)

Author Affiliations Barbara Sarter, PhD, APRN, FNP-C, DiHom, is an associate professor at Hahn School of Nursing and Health Sciences, University of San Diego, California. Prasanta Banerji, FMIH, is managing trustee and Pratip Banerji, MD(Hom), is deputy managing trustee at PBH Research Foundation, Kolkata, India. Correspondence Prasanta Banerji, FMIH info@pbhrfindia.org Citation Global Adv Health Med. 2012;1(1):26-29. Key Words Viral hepatitis, ultradilute medicines, homeopathy, liver disease, case reports, India

Abstract

摘要

RESUMEN

Introduction: Two cases of viral hepatitis that had failed conventional therapy are presented. Both were subsequently treated with protocols using homeopathic medicines as detailed below. Both patients sustained remissions for 2 years after taking ultradilute natural medicines after their conventional treatment had been discontinued. Methods: The treatment protocol included Chelidonium majus 6X and Thuja 30C as the main medicines. Other homeopathic medicines were used as detailed below. Cases were confirmed with standard hepatitis antibody and viral measurements. Patients were followed for more than 2 years with measurements of viral counts, liver enzymes, and other relevant biomarkers of liver disease. Results: Both patients are alive and functioning normally in their home environments more than 2 years after treatment initiation. Discussion: We review the literature related to the chief medicines used in these cases and find that they have known and demonstrated therapeutic effects suggesting plausible mechanisms of action in these cases. Conclusions: Clinical trials of this homeopathic treatment protocol should be conducted to explore the therapeutic potential of these medicines for treatment of viral hepatitis.

序言：常规治疗失败的两例病毒性肝炎病例。这两个病例后来都使用顺势疗法药物进行治疗，详见下文。在中断常规治疗，并服用过度稀释的自然药物之后，两名患者都经历了2年的持续缓解期。方法：白屈菜6X和金钟柏30C作为本治疗方案的主要药物。其他顺势疗法药物的使用，详见下文。通过标准肝炎抗体和病毒测量方法对两例病例的治疗效果进行确认。通过测量病毒计数、肝酶水平，以及肝病的其他相关生物标志物，对患者进行超过2年的后续跟踪。结果：在启动治疗2年多之后，两名患者都健在，而且在各自的家庭环境下官能正常。讨论：我们对这些病例中使用的主要药物的相关文献进行了审核，发现它们具有已知的、能够证明的疗效，因此可作出合理的推断，上述药物在这些病例中能够发挥积极作用。结论：应该对该顺势疗法进行临床试验，以发掘这些药物对病毒性肝炎的潜在疗效。

Introducción: Se presentan dos casos de hepatitis viral en los cuales la terapia convencional no fue efectiva. Ambos fueron tratados posteriormente según protocolos de uso de medicamentos homeopáticos, como se describe a continuación. Ambos pacientes registraron una remisión sostenida durante 2 años, luego de consumir medicamentos naturales ultradiluidos y de que se descontinuaran sus correspondientes tratamientos convencionales. Métodos: El protocolo de tratamiento incluyó como medicamentos principales Chelidonium majus (Celidonia mayor) 6X y Thuja (Tuya) 30C. Se utilizaron otros medicamentos homeopáticos, como se indica a continuación. Se confirmaron casos de desarrollo de anticuerpos estándares contra la hepatitis y mediciones de carga viral. Se realizó un seguimiento de los pacientes durante más de 2 años con mediciones de carga viral, enzimas hepáticas y otros marcadores biológicos relevantes de enfermedades hepáticas. Resultados: Ambos pacientes viven y se desenvuelven normalmente en sus hogares, luego de transcurridos más de 2 años desde el inicio del tratamiento. Discusión: Analizamos la información relacionada con los medicamentos principales empleados en estos casos y descubrimos que tienen efectos terapéuticos conocidos y demostrados que sugerían mecanismos de acción convincentes aplicables a estos casos. Conclusiones: Los ensayos clínicos de este protocolo de tratamiento homeopático se deben llevar a cabo para analizar los efectos terapéuticos potenciales de este tipo de medicamentos para el tratamiento de la hepatitis viral.

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Case Report

Ultradilute Medicines for Viral Hepatitis

ltradilute, serially agitated solutions behave quite differently than normal solutions; the principles of their behavior are being actively researched around the world.1 Meanwhile, ultradilute solutions in the form of homeopathic medicines are widely sought and used clinically throughout the world. In 1999, the US National Cancer Institute’s Office of Cancer Complementary and Alternative Medicine’s rigorous Best Case Series validated the effectiveness of cancer treatment protocols in 14 cases of different varieties of the disease using homeopathic medicinal protocols developed at the Prasanta Banerji Homeopathic Research Foundation (PBHRF) in Kolkata, India, and identified studies in collaboration with PBHRF as a funding priority.2 Published research reports also provide credible evidence of the mechanisms of action and effectiveness of some of the protocols used at PBHRF to treat cancer.3-7 In addition to cancer, virtually all diseases are treated at PBHRF with specific protocols using ultradilute medicines. In this article, we report on 2 well-documented cases of progressively worsening acute and chronic viral hepatitis that responded to treatment with these medicines per the Banerji Protocol. Case 1

On a routine health maintenance visit in 1994, a 37-year-old woman was found to have elevated liver enzymes. Her first liver biopsy in January 1998 showed grade 1 (of 4) inflammation and stage 1 to 2 (of 4) delicate bridging fibrosis. Subsequent hepatitis C antibody testing revealed chronic hepatitis C. Genotyping of the virus in 1998 revealed type 1b with a viral count of 33 000 000 IU/mL. She enrolled in a clinical trial of pegylated interferon (PEG-INF) subcutaneously 1.5 µg/kg once a week for 4 weeks followed by PEG-INF 0.5 µg/kg once a week for 44 weeks along with ribavirin 1000 mg orally daily, which was reduced to 600 mg daily due to anemia at treatment week 30. Serum levels of alanine aminotransferase reflected a response with relapse. Her virologic response using polymerase chain reaction (PCR)–based assay for hepatitis C virus RNA showed a temporary response. Posttreatment liver biopsy performed 6 months after completing treatment (in July 2000) was scored as grade 3 of 4 inflammation and stage 1 of 4 fibrosis with piecemeal necrosis consistent with relapse. Her viral count at that time was 16 000 000 IU/mL. A biopsy conducted in December 2003 showed inflammation grade 3 and fibrosis stage 3 of 4. She became increasingly symptomatic with nausea, fatigue, and loss of appetite. In April 2004, she started a second course of PEG-INF with ribavirin after undergoing whole-body hyperthermia. After 6 months, she was found to have no response to the interferon, and the drugs were discontinued. A biopsy in November 2005 showed stage 3 of 4 fibrosis and moderate (3 of 4) portal inflammation. Viral count in July 2006 was 14 250 000 IU/mL, and the patient was found to have persistent stage 3 of 4 fibrosis and grade 3 of 4 inflammation with bridging necrosis.

Case Report

In August 2006, the patient initiated treatment prescribed by the PBHRF. The following protocol was used: 1. Chelidonium 6X twice a day, 2. Thuja 30C twice a day, and 3. Kalium muriaticum 3X and Ferrum phosphoricum 3X twice a day. The 6X potency is the 6th decimal potency that is achieved by serial dilution and agitation of the mother tincture, or alcoholic extract, of the root of the plant Chelidonium majus. Thuja 30C is likewise the 30th centesimal serial dilution and agitated product; here, the alcoholic extract is from the fresh leaves and small twigs of the young Thuja occidentalis plant. The Kali muriaticum 3X and Ferrum phosphoricum 3X are triturations of the substances to the 3rd decimal potency. The medicine was procured from reputable homeopathic drug manufacturers and manufactured as per The Homeopathic Pharmacopoeia of India. Chelidonium 6X and Thuja 30C are our standard protocol for cases of chronic viral hepatitis. Chelidonium has a strong body of research supporting its use for liver disease, and Thuja is effective in treating a wide variety of viral infections (see Discussion section). The combination of Kali muriaticum and Ferrum phosphoricum is our standard protocol for treatment of anemia, which this patient experienced as a side effect of interferon/ ribavirin therapy. The patient adhered to this protocol for 2 years and was rebiopsied in the United States in December 2008. Her inflammation was reduced to stage 1 of 4, and her fibrosis had regressed to stage 0-1a of 4. She used no other treatments during this time period. She no longer experiences daily nausea and has regained her normal body weight. Her viral count in December 2009 was 7 IU/mL. As of June 2011, she remained in remission and continued treatment with Chelidonium 6X twice a day. Table 1 provides a summary of the relevant biomarkers. TABLE 1 Case 1: Chronic Active Hepatitis Ca Test

Reference Range

Date

Patient Value

HCV RNA

0-7 IU/mL

Jul 2006

14 250 000

Dec 2009

Liver biopsy

Stage 0 inflammation; Nov 2005 stage 0 fibrosis;

Stage 3 inflammation; stage 3 fibrosis; bridging necrosis

Dec 2008

Stage 1 inflammation; stage 0-1a fibrosis; no necrosis

Homeopathic treatment initiated August 2006; as of June 2011, patient remained in remission.

Abbreviations: HCV, hepatitis C virus; RNA, ribonucleic acid; PCR, polymerase chain reaction.

Case 2

In late November 2007, a 28-year-old male was admitted to the premier Indian medical institution, the All India Institute of Medical Science (AIIMS) in Delhi, for a case of hepatitis B virus (HBV)–related chronic

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

liver disease decompensated by acute hepatitis E virus (HEV) infection. He also had developed spontaneous bacterial peritonitis. His clinical history included a rapidly progressing jaundice followed by pedal edema, ascites, fever, and abdominal tenderness. Viral antibody testing revealed a positive Australia antigen (hepatitis B surface antigen), negative immunoglobulin M for hepatitis B core antigen, HBV DNA 1300 copies/mL, and positive immunoglobulin M antibody for HEV. At AIIMS, he was treated with intravenous glycyrrhizin (0.2%) 60 mL daily for 6 weeks, and then the dose was reduced to 3 times a week. Additionally, he received daily diuretic treatment with spironolactone/furosemide (Lasilactone, Sanofi-Aventis) 50 to 75 mg per day, 20% albumin 100 mL intravenously daily for the first 2 months of hospitalization, cefuroxime axetil (Ceftum, GlaxoSmithKline) 500 mg twice a day for 4 weeks, and lamivudine-HBV 100 mg daily. After 6 weeks of hospitalization and treatment at AIIMS, the patient’s serum bilirubin continued to be markedly elevated and alanine transaminase was continuously 75 times normal, indicating failure of conservative treatment. Endoscopy revealed esophageal varices. The cancer antigen 19-9 and carcinoembryonic antigen were negative. The patient and his parents were advised of the need for a liver transplant. They refused to have him placed on the transplant list, and he was discharged in January 2008 and returned to Kolkata. After repeated episodes of spontaneous bacterial peritonitis requiring multiple hospitalizations in Kolkata, he developed right hepatic hydrothorax. At this point, the patient sought treatment at PBHRF. On first presenting at PBHRF on August 22, 2008, he had severe ascites, dyspnea without exertion, abdominal pain, and 4+ pitting edema in the lower extremities. Treatment was initiated with the following protocol: 1. Chelidonium 6X 3 drops alternating 3 times a day with 2. Carduus marianus (milk thistle) mother tincture 10 drops, 3. Thuja 30C 2 pills once every evening, 4. Lycopodium clavatum 30C 3 drops 3 times a day, and 5. Belladonna 3C alternating with Carduus marianus mother tincture every 10 minutes as needed for pain. In addition to our first-line agent, Chelidonium, we added Carduus marianus, as it has a long history of use in traditional herbal medicine for support of liver problems. Thuja again was prescribed as an antiviral agent. Lycopodium is our first-line agent for treatment of edema or fluid retention of any kind. Belladonna is one of our firstline agents for pain, particularly pain of visceral origin. When the patient’s condition did not improve, on September 15, 2008, Myrica (bayberry) mother tincture was added, alternating every 3 hours with Chelidonium 6X, and Carduus was discontinued. On September 27, acetic acid 30C, another of our prime medicines for water retention and effusions, 3 drops 3 times a day replaced the Lycopodium for management of the ascites. By December

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13, 2008, the patient’s pleural effusion was clearing, ascites had decreased substantially, and urine output improved significantly. Clinic notes from January 7, 2009, reported worsening of the pleural effusion and ascites, and treatment exclusively by PBHRF continued with the expectation that improvement was likely to recur. By March 2009, the patient was reporting a sustained improvement in symptoms, and the pleural effusion and ascites had almost completely subsided. On June 3, 2009, the HBV DNA count was 5.82 copies, and the patient was feeling well. Blood work done on May 9, 2009, revealed liver function tests generally near the normal range, as indicated in Table 2. Table 2 also shows the continued improvement in liver function tests when retested in December 2009. As of June 2011, the patient continued to feel well, having been in remission for 2 years. Table 2 Case 2: Hepatitis B Virus and Hepatitis E Virusa Test

Reference Range

Date

INR

0.9-1.1

May 2009

tBili

<1.0 mg/dL

AST

ALT

Alk phos

10-60 IU/L

40-120 IU/L

0-60 IU/L

1.9

Dec 2009

1.2

Dec 2007

31.9

May 2009

1.37

Dec 2009

1.21

Dec 2007

324

May 2009

Dec 2009

Dec 2007

241

May 2009

Dec2009

May 2009

275

Dec 2009 GGT

Patient Value

N/A

May 2009

Dec 2009

Homeopathic treatment initiated August 2008; as of June 2011, the patient remained in remission.

Abbreviations: Alk phos, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; GGT, gamma-glutamyl transferase; INR, international normalized ratio; tBili, total bilirubin.

Discussion

The protocols used in these cases were developed based on the extensive experience of the physicians at PBHRF, which spans several generations, as well as the known actions of its specific component medicines. We will briefly review the research literature that is available on these medicinal substances. Chelidonium majus (greater celandine) is an herb with documented hepatotoxic properties in its undiluted tincture or herbal form,8-10 but it has also been shown to have hepatoprotective, antitumor, and immunostimulatory actions.11 Thuja occidentalis has been reported to have similar hepatoprotective and antitumor effects.4,12-17 Thuja and its related species also have been reported to have antiviral13,18 and antimetastatic4 properties. Myrica, or bayberry, is a common herb that is high in tannins; there is virtually no research documenting its effectiveness in treatment of liver disease, but standard

Case Report

Ultradilute Medicines for Viral Hepatitis

homeopathic references all list jaundice as one of its principle indications.19 Carduus marianus (milk thistle) was reviewed recently in the Cochrane database. The conclusion of this rigorous review was that milk thistle could potentially affect alcoholic and/ or hepatitis B or C virus liver diseases. Therefore, large-scale randomized clinical trials on milk thistle for alcoholic and/or hepatitis B or C liver diseases versus placebo are needed. 20 The larger issue is how ultradilute, serially agitated preparations of these biologically active substances are able to exert therapeutic effects even when the dilutions exceed Avogadro’s number, which is the case for the dilutions of 30C used in the Banerji Protocol for hepatitis. The preparations of Chelidonium are diluted to a factor of 1/1 000 000; this explains the lack of toxicity observed in the normally hepatotoxic Chelidonium when in its crude form but does not explain its effectiveness as a hepatoprotectant. The emerging disciplines of complexity, nanoscience, and materials science offer some hypotheses on how these ultradilute medicines may still maintain biological activity.21 One research team advocated the hypothesis based on available scientific evidence and logic that one major pathway of ultradilute homeopathic drugs could possibly be through regulation of expression of relevant genes.1 A recent study by Frenkel et al provided solid support for this hypothesis.3 The medicines used by PBHRF for treatment of breast cancer were tested in vitro at the University of Texas MD Anderson Cancer Center, Houston. The remedies exerted preferential cytotoxic effects against 2 breast cancer cell lines, causing cell cycle delay/arrest and apoptosis. The researchers demonstrated a clear biological activity of the tested natural products (Phytolacca, Carcinosin, Conium, and Thuja) when present at ultradiluted doses. Despite the lack of a proven explanation for how these ultradilute medicines exert their effects, there is significant laboratory evidence that highly dilute toxins can paradoxically protect the very tissues they harm in macrodoses. There are several reports of liver damage reversal in mice with ultradilutions of arsenic trioxide after exposure to toxic doses of the same substance.5,22 One randomized double-blind placebo-controlled human study documented favorable improvements in multiple markers of arsenic toxicity after 2 months of treatment with a serially agitated dilution (1:100 dilution 30 times) of arsenic,23 or the 30th centesimal potency. A recent review of the in vitro research on serially diluted and agitated solutions concluded that even the studies with high methodological standards demonstrated an effect of these solutions.24 A number of articles have been published in med ical journals denouncing categorically the use of homeopathic medicine, claiming that there is no evidence to support any further research into their therapeutic effects. Clearly, even in this very brief research

Case Report

review and in these case reports, there is enough to suggest that this is an area that should be further explored. The era of nanomedicine is upon us and requires a fresh look at medicines that are ultradiluted. A major advantage of treating disease with ultradilute solutions is that adverse effects are virtually eliminated. The case reports in this article will, hopefully, inspire a fresh interest and further research in this fascinating and controversial area of therapeutics. References 1. Khuda-Bukhsh AR. Towards understanding molecular mechanisms of action of homeopathic drugs: an overview. Mol Cell Biochem. 2003 Nov;253(1-2):339-45. 2. Banerji P, Campbell DR, Banerji P. Cancer patients treated with the Banerji protocols utilising homoeopathic medicine: a Best Case Series Program of the National Cancer Institute USA. Oncol Rep. 2008 Jul;20(1):69-74. 3. Frenkel M, Mishra BM, Sen S, et al. Cytotoxic effects of ultra-diluted remedies on breast cancer cells. Int J Oncol. 2010 Feb;36(2):395-403. 4. Es S, Kuttan G, Kc P, Kuttan R. Effect of homeopathic medicines on transplanted tumors in mice. Asian Pac J Cancer Prev. 2007 Jul-Sep;8(3):390-4. 5. Kundu SN, Mitra K, Khuda Bukhsh AR. Efficacy of a potentized homeopathic drug (Arsenicum-Aalbum-30) in reducing cytotoxic effects produced by arsenic trioxide in mice: IV. Pathological changes, protein profiles, and content of DNA and RNA. Complement Ther Med. 2000 Sep;8(3):157-65. 6. MacLaughlin BW, Gutsmuths B, Pretner E, et al. Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models. Integr Cancer Ther. 2006 Dec;5(4):362-72. 7. Pathak S, Multani AS, Banerji P, Banerji P. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer. Int J Oncol. 2003 Oct;23(4):975-82. 8. Hardeman E, Van Overbeke L, Ilegems S, Ferrante M. Acute hepatitis induced by greater celandine (Chelidonium majus). Acta Gastroenterol Belg. 2008 AprJun;71(2):281-2. 9. Rifai K, Flemming P, Manns MP, Trautwein C. [Severe drug hepatitis caused by Chelidonium]. Internist (Berl). 2006 Jul;47(7):749-51. German. 10. Stickel F, Pöschl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D. Acute hepatitis induced by Greater Celandine (Chelidonium majus). Scand J Gastroenterol. 2003 May;38(5):565-8. 11. Song JY, Yang HO, Pyo SN, Jung IS, Yi SY, Yun YS.Immunomodulatory activity of protein-bound polysaccharide extracted from Chelidonium majus. Arch Pharm Res. 2002 Apr;25(2):158-64. 12. Guleria S, Kumar A, Tiku AK. Chemical composition and fungitoxic activity of essential oil of Thuja orientalis L. grown in the north-western Himalaya. Z Naturforsch C. 2008 Mar-Apr;63(3-4):211-4. 13. Hassan HT, Drize NJ, Sadovinkova EYu, et al. TPSg, an anti-human immunodeficiency virus (HIV-1) agent, isolated from the Cupressaceae Thuja occidentale L. (Arborvitae) enhances in vivo hemopoietic progenitor cells recovery in sublethally irradiated mice. Immunol Lett. 1996 Apr;50(1-2):119-22. 14. Iwamoto M, Minami T, Tokuda H, Ohtsu H, Tanaka R. Potential antitumor promoting diterpenoids from the stem bark of Thuja standishii. Planta Med. 2003 Jan;69(1):69-72. 15. Katoh T, Tanaka R, Takeo M, Nishide K, Node M. A new synthesis of a potent cancer chemopreventive agent, 13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oic acid from trans-communic acid. Chem Pharm Bull (Tokyo). 2002 Dec;50(12):1625-9. 16. Naser B, Lund B, Henneicke-von Zepelin HH, Köhler G, Lehmacher W, Scaglione F. A randomized, double-blind, placebo-controlled, clinical dose-response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold. Phytomedicine. 2005 Nov;12(10):715-22. 17. Sunila ES, Kuttan G. A preliminary study on antimetastatic activity of Thuja occidentalis L. in mice model. Immunopharmacol Immunotoxicol. 2006;28(2):269-80. 18. Bodinet C, Mentel R, Wegner U, Lindequist U, Teuscher E, Freudenstein J. Effect of oral application of an immunomodulating plant extract on Influenza virus type A infection in mice.Planta Med. 2002 Oct;68(10):896-900. 19. Murphy R. Homeopathic clinical repertory. 3rd ed. Blacksburg (VA): Lotus Health Institute; 2005. 20. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003620. 21. Bellavite P, Signorini A, Fisher P. The emerging science of homeopathy: complexity, biodynamics, and nanopharmacology. 2nd ed. Berkeley (CA): North Atlantic Books; 2002. 22. Datta S, Mallick P, Bukhsh AR.Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing genotoxic effects produced by arsenic trioxide in mice: II. Comparative efficacy of an antibiotic, actinomycin D alone and in combination with either of two microdoses. Complement Ther Med. 1999 Sep;7(3):156-63. 23. Belon P, Banerjee A, Karmakar SR, et al. Homeopathic remedy for arsenic toxicity?: Evidence-based findings from a randomized placebo-controlled double blind human trial. Sci Total Environ. 2007 Oct 1;384(1-3):141-50. Epub 2007 Jul 12. 24. Witt CM, Bluth M, Albrecht H, Weisshuhn TE, Baumgartner S, Willich SN. The in vitro evidence for an effect of high homeopathic potencies—a systematic review of the literature. Complement Ther Med. 2007 Jun;15(2):128-38. Epub 2007 Mar 28.

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PATIENT CASE REPORT

Worst Cases Reported to the NAFKAM International Registry of Exceptional Courses of Disease Vinjar Fønnebø, PhD; Brit J. Drageset, BSc; Anita Salamonsen, MSc

Author Affiliations Vinjar Fønnebø, PhD, is professor of preventive medicine at and director of the National Research Center in Complementary and Alternative Medicine (NAFKAM), Department of Community Medicine, University of Tromsø, Norway. Brit J Drageset, BSc, is a consultant and Anita Salamonsen, MSc, is a researcher at NAFKAM. Correspondence Vinjar Fønnebø vinjar.fonnebo@uit.no Citation Global Adv Health Med. 2012;1(1):30. Key Words Registry, NAFKAM, Exceptional Courses of Disease, case reports, worst cases, Lightning Process, chronic fatigue syndrome, CFS, myalgic encephalomyelitis, ME, necrotizing vasculitis, homeopathy, sinusitis, prostatitis, hematologic cancer Supplemental Information For an overview of the National Research Center in Complementary and Alternative Medicine International Registry of Exceptional Courses of Disease, see page 60.

he National Research Center in Complementary and Alternative Medicine (NAFKAM) International Registry of Exceptional Courses of Disease (the Registry) related to the use of complementary and alternative medicine (CAM) has to date received 5 reports of exceptionally “worst” courses of disease from patients who have attributed their negative health experience to the use of CAM. The monitoring of unfavorable outcomes related to CAM treatment is seen by NAFKAM as important to ensure that treatments offered are associated with low risk of harm. This is particularly important when the conditions patients suffer from are not life threatening. If the Registry receives 3 negative reports of patients using the same treatment for the same condition, a “warning” is submitted to the health authorities. The same is done after only one report if the condition is life threatening. Three of the 5 patients had been diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and all of them have related their unfavorable outcomes to the treatment method called Lightning Process (LP), a 3-day training program designed by British osteopath Phil Parker.1 They had all followed the recommendation given by the LP instructors during the treatment to ignore what they sensed as their bodies’ symptoms of being pushed too hard. The patients had been diagnosed with CFS/ME 10, 2, and 7 years, respectively, before attending the LP treatment. Six to 12 months after the treatment, all 3 experienced a strong relapse of their CFS/ME symptoms. One patient expressed that “to follow the advice from the LP instructor eventually became a direct risk to my health.” The other 2 patients had both been treated with homeopathy. The first patient had sought homeopathic treatment for sinusitis problems and a desire to reduce her conventional medication. After using homeopathic treatment for 1 year, she was diagnosed with a necrotizing vasculitis, and she believes that she might have been diagnosed and treated earlier had she sought conventional treatment. The other patient had sought homeopathic treatment for prostatitis symptoms and used homeopathic remedies for this condition in combination with chemotherapy for hematologic cancer. He reports a number of symptoms (vision coordination problems, tinnitus, memory loss, and hiatal hernia) that he ascribes to an interaction between the homeopathic remedy and the chemotherapy.

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The 3 “worst” cases reported with regard to LP are consistent, and there is reason to suspect a causal relationship. The 2 other reports are less specific and will need to be supported by additional cases before any conclusions can be drawn. Reference 1. Parker P. The Lightning Process: the complete strategy for success. London: Nipton Publishing; 2007.

Patient Case Reports

Patient case report

A Patient-defined “Best Case” of Multiple Sclerosis Related to the Use of Complementary and Alternative Medicine Anita Salamonsen, MSc; Brit J. Drageset, BSc; Vinjar Fønnebø, PhD

Author Affiliations Anita Salamonsen, MSc, is a researcher, Brit J. Drageset, BSc, is a consultant, and Vinjar Fønnebø, PhD, is professor of preventive medicine and director of The National Research Center in Complementary and Alternative Medicine (NAFKAM), Department of Community Medicine, University of Tromsø, Norway. Correspondence Anita Salamonsen anita.salamonsen@uit.no Citation Global Adv Health Med. 2012;1(1):32-34. Funding This case report is based on the Registry of Exceptional Courses of Disease, which is 100% funded by NAFKAM, which in turn is funded by the Norwegian Ministry of Health and Care Services. Key Words Multiple sclerosis, MS, complementary and alternative medicine, CAM, case report, exceptional cases, Norway

Abstract

摘要

RESUMEN

Chronically ill people are frequent users of complementary and alternative medicine (CAM). Some patients experience great benefits from their use of CAM, like patient “XX” in this case report. XX was diagnosed with secondary progressive multiple sclerosis in 2004 and has reported a “best case” after the use of Dr Birgitta Brunes’ unconventional treatment. The patient reports that many of her symptoms that, according to her neurologist, were irreversible are gone or have been greatly reduced. Such patientdefined “best cases” related to the use of CAM should be further explored to optimize and safeguard patients’ treatment decisions and treatment outcomes.

慢性病患者经常使用补充和替代药物（CAM）。一些患者在CAM的使用过程中获益极大，比如本病例报告中的患者“XX”。2004 年，XX诊断患有继发进行性多发性硬化症，而在接受Birgitta Brunes医生的非常规治疗之后，该患者作为“最佳病例”进行报告。根据其神经科医生的意见，该患者报告称，她的许多症状永久性消失，或得到了极大的缓解。对这种与使用CAM相关的患者定义的“最佳病例”，应该进行进一步的探索，以优化并保护患者的治疗决策和治疗结果。

Las personas que padecen enfermedades crónicas son usuarios frecuentes de la medicina complementaria y alternativa (CMA, por sus siglas en inglés). Algunos pacientes experimentan grandes beneficios a partir del uso de CAM, como es el caso de la paciente “XX” que se analiza en este caso clínico. Dicha paciente fue diagnosticada con esclerosis múltiple secundaria progresiva en el año 2004 y fue registrada como el “mejor caso”, luego de recibir el tratamiento no convencional de la Dra. Birgitta Brunes. La paciente reconoció que muchos de sus síntomas, que según su neurólogo eran irreversibles, desaparecieron o se redujeron en gran medida. Dicha paciente, catalogada como el “mejor caso” relacionado con el uso de CAM, debe ser sujeta a análisis más profundos para optimizar y resguardar las decisiones que toman los pacientes sobre el tratamiento y los resultados del mismo.

ultiple sclerosis (MS) is an unpredictable condition both with respect to alternating exacerbation and remission of symptoms and variant symptom patterns.1,2 Studies show anxiety regarding what the future holds3 and high levels of depression and uncertainty in MS patients when they are compared to patients with other chronic diseases.4 MS-related depressive symptoms could be a function of prior disease-related impairment, life stress, and possible escape avoidance coping.5 Some MS patients experience conventional disease- and symptom-modifying drugs as having little influence on symptoms, functioning, or quality of life, while commonly experiencing adverse effects.6-8 Between 27% and 100%9 of MS patients use complementary and alternative medicine (CAM) to treat and live better with their symptoms. The Cochrane Collaboration defines CAM as a broad domain of healing resources that encompasses all health systems, modalities and practices, and their accompanying theories and beliefs,

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other than those intrinsic to the politically dominant health system of a particular society or culture in a given historical period. CAM includes all such practices and ideas self-defined by their users as preventing or treating illness or promoting health and well-being.10(p693) The Registry of Exceptional Courses of Disease

This case report was selected from the Registry of Exceptional Courses of Disease (hereafter referred to as “the Registry”). The Registry includes Scandinavian patient-defined, self-reported positive and negative exceptional courses of disease related to the use of CAM. To be included, the patients must have or have had a disease or health problem, must have experienced what they perceive to be exceptionally positive or exceptionally negative health effects, and must relate these health effects to the use of CAM. In a “best case,” the patient experiences reduced disease symptoms or full recovery.a,11-13 a

For more information on the Registry, see pages 70-75 of this issue.

Patient Case Report

A “Best Case” of MS Related to CAM Use

As of October 1, 2011, 72 patients diagnosed with MS were included in the Registry, all reporting “best cases.” Acupuncture, nutritional therapy, reflexology, herbs and food supplements, homeopathy, massage/ aromatherapy, and spiritual healing were the most frequently used CAM modalities among these patients. Case Presentation Context and Goal

We here present a self-defined “best case” of MS. The presentation is based on the Registry questionnaire, medical records, a medical assessment, and an in-depth interview. The goal is to describe a patientdefined “exceptionally positive” course of MS as seen from both a patient and medical perspective. Medical, Social, and Family History

“XX” is a 46-year-old married Norwegian woman with several children. She is a university graduate who had been working full time for some time after being diagnosed but is now on a 100%-disability pension. Approximately 28 years ago, she had a facial paralysis on her right side from which she fully recovered after 1 to 2 months. About 15 years ago, she experienced 2 episodes of herpes zoster (shingles). She has otherwise been healthy. Several of XX’s close relatives also have been diagnosed with MS. Presenting Condition

When she was in her 20s, XX was diagnosed with probable MS but was not herself informed of the diagnosis. A few years later, she experienced partial loss of sensation in her legs and was finally officially diagnosed with secondary progressive MS at the age of 41 years. Her main symptoms were fatigue, problems with leg coordination after experiencing strain for some time, periodical memory problems, and urge-characterized urination. Subsequently, XX experienced severe fatigue and reduced sensation in her feet, legs, and fingers. She even found brushing her teeth exhausting. She continued to have problems holding and emptying the bladder and also experienced depression. Treatment

No conventional treatment was provided by doctors within the conventional healthcare system. Within a year after being diagnosed, XX discovered the treatment given by Birgitta Brunes (BB), MD, and decided to participate in one of BB’s courses. BB is a Swedish medical doctor who herself suffers from MS and who has worked with treatment and rehabilitation of MS patients since 1994. She has developed a systematic approach to symptom alleviation, which she presented in a book14 published in the Scandinavian countries. With her colleagues, she gives courses for MS patients that usually last 4 days and focus on psychological factors (emotions, stress, etc), social factors, and medical treatment. These elements are combined in a treatment plan individually adapted for each patient.

Patient Case Report

BB does not consider her treatment as CAM per se.15 Her theory is based on conventional medical knowledge and practical experience from many years of working as a general practitioner. The treatment is only considered alternative in relation to the prevailing medical understanding of the cause and treatment of MS. The intention is not to heal MS but to alleviate MS symptoms. The treatment rests on 3 pillars: 1. Neurotransmitters (noradrenaline, dopamine, acetylcholine, serotonin), vitamin B 12, and amino acids adjusted according to individual need; 2. detoxification (for instance, removal of amalgam or elimination of toxic environmental factors)14,15; and 3. Psychotherapeutic treatment of basic psychological traits. XX’s Individualized Treatment

Use and Adjustment of Medication and Supplements. After careful self-testing, XX has found the

suitable dosage for the different medications, and she is making necessary adjustments as time passes. Her current intake of medication and supplements include lofepramine (a tricyclic antidepressant) plus tablets containing norepinephrine to prevent urge incontinence. She asserts that these drugs also give her energy. She also takes acetylcholine and anticholinesterase in addition to phosphatidylcholine and lecithin from the health food store, which she contends create “heat” and help her empty the bladder and intestines. The intake of serotonin tablets and 5-hydroxytryptophan (5-HTP) from the health food store help her keep a brighter outlook on life and to be positive, sleep well, and not worry about the future and her illness. At the same time, she takes specially adapted amino acids for MS patients that attend to the muscles while she is not using them. Detoxification. XX had her 8 amalgam fillings removed over a period of 2 years. To be able to tolerate the discomfort related to the removal of the fillings, she took large doses of cortisone for 3 weeks each time. Psychotherapeutic Treatment. For almost 4 years, XX has rested systematically. Meditation and rest in the form of mental control and relaxation have been important. This has gradually helped her get better because according to her, “the body has economized on the neurotransmitters which the nerves are supposed to bring to the muscles.” XX did not want to stop working, even though she understood that the job drained her of the little energy she had. The realization that she had to spend all her energy on herself in order to have a chance of getting better has been very important for her. Now she spends most of her time with her family. She is able to make herself and her own health a priority without feeling guilty. Other Measures. In consultation with BB, XX has changed her diet according to advice from the MS center at a Norwegian hospital. She first omitted red meat,

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

fat, and dairy products and later omitted sugar and yeast, artificial sweeteners, and natural sugars. Outcomes Medical Assessment

MS and cancer cases in the Registry are assessed by medical doctors. Medically exceptional courses of disease are defined as courses occurring with less than 1% probability after the given conventional treatment based on current medical knowledge. The assessment of this case concluded, “Interesting description of Dr. Brunes’ treatment and the experienced effects of this. This is, however, not a medically exceptional course of disease.” Patient’s Perspective

XX thinks that the CAM treatment consisting of vitamins and minerals from the health food store along with “mind control” in the form of meditation and positive thinking support the conventional medical treatment included in BBs’ treatment model. The patient writes, The supplements administer my immune system and the rest of my physical health, which again makes me stronger and helps me handle my MS better. . . . The reason why I experience my MS-course as exceptionally positive is that many of my symptoms that according to my neurologist were irreversible, now are gone or have been greatly reduced. I have a sense of touch in all fingers and toes and under the whole soles of my feet. Four years ago I was numb to my knees and sometimes all the way to my chest. I have more energy, can do more things myself, and I do not need to rest the whole day. I have much more control of the bladder. Going to the bathroom 13 to 16 times per 24 hours has now been reduced to about half of this. I have also learnt to handle the disease and to have a positive outlook on life. I am no longer melancholic. I actually feel that my life has never been as good as it is now, in spite of the many limitations caused by the disease. Follow-up Care

XX can contact BB by phone whenever she feels the need for follow-up care. Confidentiality and Informed Consent

The Regional Committee for Medical and Health Research Ethics and the Norwegian Data Inspectorate have approved the Registry. The patients have given their informed consent. Information that could identify the patient in this case report has been avoided. The patient has read and approved the case report. Discussion

BB and her treatment model have been criticized because the treatment is unconventional and expensive and the outcomes have not been validated through clinical studies.16 BB’s treatment model includes a holistic and psychosocial medical approach to MS treatment.

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Many arguments have been raised for a more patientcentered and biopsychosocial medicine to optimize and safeguard modern patients’ treatment decisions and treatment outcomes.17,18 A qualitative study of patients’ experiences and reflections with regard to their reported “best cases” of MS in the Registry found that these patients, independently of treatment systems, changed over time their position from passive recipients of conventional health care to explorers of healthcare. The concept of “explorer” implies action and entails all the social, cultural, and economical capital19 needed by the patients to take responsibility for and cope with their situations. As explorers, the patients, like XX in this case report, influence how an intervention is chosen and used. CAM facilitates the patients’ own efforts that patients believe are needed for improved health and well-being in their lives with MS.13 Conclusion

A holistic and psychosocial medical approach to MS treatment, including hope and the ability for the patient to cope, was of vital importance to XX’s positive outcome of the MS treatment presented in this case report. The patient-experienced benefits of CAM reported in “best cases” so far generate unexplored and complex questions worthy of further research. References 1. Kirkpatrick Pinson DM, Ottens AJ, Fisher TA. Women coping successfully with multiple sclerosis and the precursors of change. Qual Health Res. 2009 Feb;19(2):181-93. 2. Thorne S, Con A, McGuinness L, McPherson G, Harris SR. Health care communication issues in multiple sclerosis: an interpretive description. Qual Health Res. 2004 Jan;14(1):5-22. 3. Antonak RF, Livneh H. Psychosocial adaptation to disability and its investigation among persons with multiple sclerosis. Soc Sci Med. 1995 Apr;40(8):1099-108. 4. Rudick RA, Miller D, Clough JD, Gragg LA, Farmer RG. Quality of life in multiple sclerosis. Comparison with inflammatory bowel disease and rheumatoid arthritis. Arch Neurol. 1992 Dec;49(12):1237-42. 5. Aikens JE, Fischer JS, Namey M, Rudick RA. A replicated prospective investigation of life stress, coping, and depressive symptoms in multiple sclerosis. J Behav Med. 1997 Oct;20(5):433-45. 6. Apel A, Greim B, König N, Zettl UK. Frequency of current utilisation of complementary and alternative medicine by patients with multiple sclerosis. J Neurol. 2006 Oct;253(10):1331-6. 7. Nayak S, Matheis RJ, Schoenberger NE, Shiflett SC. Use of unconventional therapies by individuals with multiple sclerosis. Clin Rehabil. 2003 Mar;17(2):181-91. 8. Schwarz S, Knorr C, Geiger H, Flachenecker P. Complementary and alternative medicine for multiple sclerosis. Mult Scler. 2008 Sep;14(8):1113-9. 9. Olsen SA. A review of complementary and alternative medicine (CAM) by people with multiple sclerosis. Occup Ther Int. 2009;16(1):57-70. 10. Zollman C, Vickers A. What is complementary medicine? BMJ. 1999 Sep 11;319(7211):693-6. 11. Fønnebø V, Drageset BJ, Salamonsen A. The NAFKAM International Registry of Exceptional Courses of Disease related to the use of CAM. Global Adv Health Med. 2012;1(1):28. 12. Launsø L, Drageset B J, Fønnebø V, et al. Exceptional disease courses after the use of CAM: selection, registration, medical assessment, and research: an international perspective. J Altern Complement Med. 2006 Sep;12(7):607-13. 13. Salamonsen A, Launsø L, Kruse TE, Eriksen SH. Understanding unexpected courses of multiple sclerosis among patients using complementary and alternative medicine: A travel from recipient to explorer. Int J Qual Stud Health Well-being. 2010 Jul 2;5. doi: 10.3402/qhw.v5i2.5032. 14. Brunes B, Brunes C. Blurred signals. [Slørede signaler]. Copenhagen: Borgen; 2011. [Cited 2011 Sep 27.] Available from: http://brunes.se/. 15. Brunes Pharm AB. Treatment. [Behandling]. Copenhagen: Borgen; 2011. [Cited 2012 Feb 1]. Available from: http://brunes.se/behandlingar/. 16. Nissen M. Preface. In: Brunes B, Brunes C: Blurred signals. [Slørede signaler]. Copenhagen: Borgen; 2011:11-16. 17. Mead N, Bower P. Patient-centredness: a conceptual framework and review of the empirical literature. Soc Sci Med. 2000 Oct;51(7):1087-110. 18. White P, ed. Biopsychosocial medicine: an integrated approach to understanding illness. New York: Oxford University Press; 2005. 19. Bourdieu P. Outline of a theory of practice. Cambridge: Cambridge University Press; 1977.

Patient Case Report

original research

Efficacy of an Emotion Self-regulation Program for Promoting Development in Preschool Children Raymond Trevor Bradley, PhD; Patrick Galvin, PhD; Mike Atkinson; Dana Tomasino

Author Affiliations Raymond Trevor Bradley, PhD, is director of the Institute for Whole Social Science, Capitola, California. Patrick Galvin, PhD, is a research consultant and former director of research and evaluation, Salt Lake City School District, Salt Lake City, Utah. Mike Atkinson is laboratory manager at the Institute of HeartMath, Boulder Creek, California. Dana Tomasino is a research assistant at the Institute for Whole Social Science. Correspondence Mike Atkinson mike@heartmath.org Citation Global Adv Health Med. 2012;1(1):36-50. Key Words Early childhood development, emotion regulation, heart- brain interaction, intervention, preschool, self-regulation, social and emotional learning, neuropsychology, psychophysiology, psychosocial development

Abstract

摘要

RESUMEN

This work reports the results of an evaluation study to assess the efficacy of the Early HeartSmarts (EHS) program in schools of the Salt Lake City, Utah, School District. The EHS program is designed to guide teachers with methods that support young children (3-6 y old) in learning emotion self-regulation and key age-appropriate socioemotional competencies with the goal of facilitating their emotional, social, and cognitive development. The study was conducted over one school year using a quasiexperimental longitudinal field research design with 3 measurement points (baseline, preintervention, and postintervention) using The Creative Curriculum Assessment (TCCA), a teacher-scored, 50-item instrument measuring students growth in 4 areas of development: social/emotional, physical, cognitive, and language development. Children in 19 preschool classrooms in the Salt Lake City School District were divided into intervention and control group samples (n = 66 and n = 309, respectively; mean age = 3.6 y). The intervention classes were specifically selected to target children of lower socioeconomic and ethnic minority backgrounds. Overall, there is compelling evidence of the efficacy of the EHS program in increasing total psychosocial development and each of the 4 development areas measured by the TCCA: the results of a series of analyses of covariance found a strong, consistent pattern of large, significant differences on the development measures favoring preschool children who received the EHS program over those in the control group.

研究人员在犹他州盐湖城学区进行了一项名为Early HeartSmarts （EHS）的项目，本文对该项目有效性评估研究的结果进行了报告。EHS项目的目的是对教师进行方法指导，帮助幼儿（3~6岁）学习自我调节情绪以及关键的与年龄相适应的社会情绪能力，其目的是促进幼儿情感、社交能力和认识能力的发展。该研究采用半验证纵向研究设计，在一学年内实施，并设置了三个测量点（基线，干预前和干预后），使用创造性课程评估（TCCA）——教师计分，包含50道题的测量工具，对学生发展的4个方面进行测量：社交/情感，身体状况，认知能力以及语言能力开发。研究人员将盐湖城学区19个学前班教室的儿童划分为干预组和对照组样本（分别n=66和n=309；平均年龄=3.6 岁）。本研究特别选择针对具有较低的社会经济地位和少数民族背景的儿童进行干预。从整体上来说，有显著的证据能够证明，EHS项目在促进儿童的整体社会心理发展和TCCA测量的4个开发领域方面具有有效性：对两个组之间的差异进行的一系列分析结果发现，接受EHS项目的学前儿童组与对照组相比，在各项能力开发的测量指标上具有显著优势。

Este trabajo informa los resultados de un estudio de evaluación de la eficacia del programa Early Heartsmarts (EHS) en las escuelas del Distrito Escolar de Salt Lake City, Utah. El programa EHS está diseñado para orientar a los maestros respecto de métodos de asistencia a niños pequeños (entre 3 y 6 años de edad) en el aprendizaje de técnicas de autorregulación emocional y competencias socioemocionales fundamentales, adecuadas para su edad, con el fin de favorecer su desarrollo emocional, social y cognitivo. Este estudio se realizó durante un año escolar, conforme un diseño de investigación de campo cuasi experimental y longitudinal, diseñada con tres puntos de medición (punto de partida, intervención previa e intervención posterior), en la que se utilizó una Evaluación del Currículo Creativo (TCCA, por sus siglas en inglés), un instrumento calificado por el maestro de 50 puntos para medir el crecimiento de los estudiantes en 4 áreas del desarrollo: social y emocional, físico, cognitivo y desarrollo del lenguaje. Los niños de los 19 salones de clase de nivel preescolar en el Distrito Escolar de Salt Lake City, se analizaron de manera fraccionada según muestras de intervención y de control de grupo (n=66 y n=309, respectivamente; edad promedio=3 a 6 años). Las clases de intervención fueron seleccionadas específicamente para examinar a niños de bajo nivel socioeconómico y pertenecientes a minorías étnicas. En general, existen pruebas convincentes de la eficacia del programa EHS para fomentar el desarrollo psicosocial total. Respecto de cada una de las 4 áreas de desarrollo que fueron medidas por la TCCA: los resultados de una serie de análisis de la covarianza mostraron un patrón sólido y consistente de diferencias notorias y significativas en las medidas de desarrollo que favorecen a los niños de preescolar que recibieron el programa EHS, respecto de aquellos del grupo de control.

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Original Research

An Emotion Self-regulation Program for Preschool Children

umerous studies have found that people living in situations characterized by social disorganization, instability, isolation, or disconnectedness are at increased risk for acquiring many types of disease.1-5 The impact of education—or more specifically, academic failure—is not typically associated with communicative disorders and long-term health and wellness; however, James Lynch has provided some sobering statistics that show academic failure (defined by completing less than 10 years of schooling) produces a greater risk for heart disease than smoking, obesity, lack of exercise, and excessive alcohol consumption combined.6 He has shown that the link between academic failure and disease in later life is related to a lack of social and emotional competencies. The foundations of the competencies required for both academic and social success are developed in a child’s early years of development and are directly related to their ability to self-regulate. In essence, social competence is the ability to get along with others in a constructive manner and to build and maintain positive relationships with others.7 Young children who demonstrate this ability are more likely to have positive developmental outcomes, including higher intelligence quotient scores, positive self-worth, and better mental health.8-12 Social competence and positive social behavior are rooted in and built upon a child’s ability to self-regulate attention, emotion, and behavior.13 Self-regulation involves the ability to actively and flexibly direct one’s own behavior, emotions, and attention through effortful internal control and involves the ability to inhibit the expression of a behavior, emotion, or focus of attention when this is required.8,9 In their review of recent advances in neuroscience, Immordino-Yang and Damasio conclude that the “processes of emotion” also have a profound effect on the very elements of cognition targeted in education: Recent advances in neuroscience are highlighting connections between emotion, social functioning, and decision making that have the potential to revolutionize our understanding of the role of affect in education. In particular, the neurobiological evidence suggests that the aspects of cognition that we recruit most heavily in schools, namely learning, attention, memory, decision making, and social functioning, are both profoundly affected by and subsumed within the processes of emotion.14 Their conclusions mirror those found in research in psychophysiology that shows that learning effective emotion regulation techniques can significantly enhance attention, memory recall, comprehension, reasoning ability, creativity, and task performance in adults and children (see the review in McCraty et al, 2009).15 Schore’s16 syntheses of the research on the neurobiology of early childhood development also shows that learning how to process and self-regulate

Original Research

emotional experience is the earliest, most fundamental socioemotional skill that not only facilitates neurological growth but also determines the potential for subsequent psychosocial development. However, when the young child’s capacity for emotional self-regulation is lacking or the skills are seriously impaired, “affect dysregulation,” as Schore17 aptly labels it, is the result. The inability to appropriately self-regulate feelings and emotions has its origins in early childhood maltreatment and has enduring negative consequences for the developing frontal cortex, resulting in structurally defective neurobiological organization, which in turn impairs the young child’s cognitive development and produces disturbances in attachment formation.16,18 In addition to its implications for impeded neuropsychosocial development, this inability to appropriately self-regulate feelings and emotions results in impulsive and aggressive behavior, attentional and learning difficulties, an inability to engage in prosocial relationships, and difficulty in establishing stable social bonds.17 It is not surprising, therefore, that affect dysregulation has been highlighted in the research literature repeatedly with regard to its devastating effects on multiple domains of development, including cognition, language and literacy, and socioemotional skills.19-23 Yet as fundamental as emotion regulation is to all aspects of psychosocial development, the educational system remains woefully deficient in teaching children effective strategies for understanding and regulating their feelings and emotions.24-28 There is a predominant focus on teaching children purely “academic” skills without providing adequate education in the socioemotional foundations underlying the development of the very cognitive capacities required for academic performance.14 This is exacerbated by the disturbing number of children—20% to 30% by some estimates29-31—who start school lacking the basic social and motional skills needed to learn and get along with others.32,33 Moreover, children living in poverty, which disproportionately affects ethnic minorities, are at an increased risk for social, emotional, behavioral, and learning problems.31,34,35 Indeed, as many as 30% of elementary school children from low-income families and about the same proportion of preschoolers in Head Start programs do not have the necessary social and emotional skills for school.29 According to Boyd et al, Knowing the ABCs is not enough. To be prepared for school, children also must be excited and curious about learning and confident that they can succeed (motivational qualities). They must be able to understand the feelings of others, control their own feelings and behaviors, and get along with their peers and teachers (socioemotional skills). Indeed, kindergarten teachers rate these motivational and socio-emotional skills as more important to school success than

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

being able to hold a pencil or read. They want children to be ready for learning—able to cooperate, follow directions, demonstrate self-control, and “pay attention.”29 To help rectify this problem, the Institute of HeartMath (IHM) has developed a program specifically targeted to better equip children aged 3 to 6 years with the foundational emotional self-regulation and social competencies skills required for success in school and life. Called Early HeartSmarts (EHS),36 the program was designed to provide teachers with a curriculum to guide and support young children in learning several key age-appropriate emotion self-regulation techniques and social competencies, with the goal of facilitating the children’s emotional, cognitive, and psychosocial development. Based on almost 2 decades of research on the psychophysiology of emotions and heart-brain communication,37-42 the EHS program is the latest in a series of programs IHM has developed to teach schoolchildren emotion self-regulation techniques.43 Research has shown these programs to be effective in improving emotional stability, psychosocial functioning, learning, and academic performance at the elementary, middle school, high school, college, and graduate levels.43-46 This work reports the results of an initial evaluation study conducted to assess the efficacy of the EHS program in preschool classes in the Salt Lake City, Utah, School District. Early HeartSmarts Program

The EHS program was designed to facilitate emotional awareness and psychosocial development in young children 3 to 6 years of age. To achieve this goal, the EHS program provides teachers with a curriculum to guide and support young children in learning several key emotional and social competencies known to facilitate psychosocial development (Table 1): 1. how to recognize and better understand basic emotional states, 2. how to self-regulate emotions, 3. ways to strengthen the expression of positive feelings, 4. ways to improve peer relations, and 5. skills for developing problem-solving. Key among these competencies are two simple emotion shifting tools: “Shift and Shine” and “Heart Warmer.” These tools were specifically adapted from the HeartMath system of emotional management tools to facilitate young children’s learning of emotion selfregulation skills. Psychophysiology of Emotion Regulation

Research has shown that the positive emotion-focused tools and techniques that form the foundation of the EHS program can facilitate emotional self-regulation by teaching individuals, including children, the ability to make an intentional shift to a specific psychophysiological state,

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TABLE 1 Synopsis of the Early HeartSmarts Program The core of the Early HeartSmarts program (Institute of HeartMath, 2008) is teaching young children key social and emotional competencies known to facilitate their psychosocial growth and development: • How to recognize and better understand basic emotional states, • How to regulate emotions, • Ways to strengthen the expression of positive feeling, • Ways to improve peer relations, and • Skills for developing problem solving. How the Program Is Organized Each of these skills builds successively through the main sections of the program. 1. Connecting the physical and emotional aspects of the heart: Beginning with a model of a heart, children begin exploring the functions of the heart. The playing of different heartbeat sounds and the use of a stethoscope make this experience more real. Children move from the physical heart to the emotional heart through conversation led by the Bear Heart puppet. 2. Recognizing and understanding emotions: Children learn to recognize and better understand 5 basic emotions (happy, sad, angry, afraid, and peaceful) through a series of photo emotion cards. To help with emotional self-regulation, 2 simple techniques (described below) are taught by Bear Heart. The Shift and Shine technique strengthens children’s experience of positive feelings like love and care while Heart Warmer helps with impulse control and managing upsetting emotions. 3. Expressing love and care to family and friends: Playing Heart Ball and participating in a mini-unit around The Kissing Hand book supports the expression and experience of positive emotions. Dramatization further supports the developmental skill of learning to communicate what one is feeling. 4. Learning problem-solving skills: Using photo cards that portray typical age-related issues and a large instructional poster, children learn problem-solving and socialization skills with their peers. An album of songs is woven throughout the program to support the learning of key ideas and skills. 5. Emotional self-regulation Techniques: This segment of the program includes instructions for the Shift and Shine and Heart Warmer techniques, which are taught to help children develop skills for greater emotional self-control. Shift and Shine Technique • Begin by shifting your attention to the area around your heart. It helps to put your hand over your heart to begin with. • Now pretend to breathe in and out of your heart area. Take three slow breaths. • Think of someone or something that makes you feel happy. Feel that warm, happy feeling in your heart and then send or shine that love to someone special. • Teacher: Afterwards, ask the child if he or she sent that feeling to someone or something special. Then ask: How did it make you feel in your heart? Heart Warmer Technique • Begin by putting your attention on the area around your heart. It helps to put your hand over your heart to begin with. Teacher: Model by putting hand over your heart. • Now pretend to breathe in and out of your heart area. Take 3 slow breaths. • Imagine that your body feels nice from sitting in warm sunshine. Breathe in a feeling of warm sunshine.

Original Research

An Emotion Self-regulation Program for Preschool Children

termed psychophysiological coherence (described below). This state has been shown to be associated with optimal psychosocial growth, learning, and performance.39-41 The basis of this ability to make such a shift lies in the fundamental role the heart plays in the emotional system and the critical communication link between the heart and the brain. It is now known that heart’s pattern of rhythmic activity is directly responsive to changes in emotional states, as can be seen in the real-time example shown in Figure 1.40,41 During the experience of stress and negative emotions such as anger, frustration, and anxiety, heart rhythms become more erratic and disordered—incoherent. In such states, the corresponding patterns of afferent neurological signals sent from the heart to the brain produce an inhibition of higher cognitive functions (Figure 2), impeding brain processes necessary for functions such as attention, memory recall, abstract reasoning, problem solving, creativity, and the self-regulation of emotion and behavior. This cardiac neurological input also interacts with the brain’s emotional centers, where it acts to reinforce feelings of emotional stress and instability.47,48 Thus, when students come to school in a negative emotional state, the “inner noise” produced by such psychophysiological incoherence impairs the very cognitive resources needed for learning, academic performance, and prosocial behavior.43,45

Figure 1 Real-time heart rhythm patterns during different emotional states.

Conversely, the experience of positive emotions, such as love or appreciation, is associated with a highly ordered, smooth, sine wavelike pattern of heart rhythm activity—heart rhythm coherence (Figure 1). In such positive affective states, the heart transmits an ordered and harmonious signal to the higher brain centers (Figure 2), facilitating cognitive and emotion regulation abilities and typically producing increased emotional stability and enhanced attention, memory recall, comprehension, reasoning ability, creativity, and task performance (see research reviewed in McCraty et al, 2009).15 This is a particularly important point in understanding the operative mechanism of the HeartMath techniques taught in the EHS program.

Original Research

Figure 2 Afferent pathways by which heart activity affects brain function.

Furthermore, sustained positive emotions induce a system-wide shift to psychophysiological coherence,15,41 a state in which the brain, nervous system, and entire body operate with increased synchronization and harmony (Figure 3). Physiological correlates of the coherence state include increased synchronization between the 2 branches of the autonomic nervous system; a shift in autonomic balance toward increased parasympathetic activity; increased vascular system resonance; increased heart-brain synchronization (the brain’s α rhythms exhibit greater synchronicity with the heartbeat); and entrainment between the heart rhythm and other physiological oscillatory systems. The coherence state is also marked by reduced perceptions of emotional stress, enhanced positive emotional experience, and improved cognitive function and task performance.15,41 Moreover, studies have shown that psychophysiological states such as coherence that naturally enhance parasympathetic activity play an important role in facilitating children’s development of effective emotion regulation, prosocial behavior, and cognitive function.49,50 A pioneering discovery was that the psychophysiological coherence state can be intentionally generated. This shift to coherence can be achieved by using a positive emotion-based system of easy-to-use tools and techniques.51,52 (See Figure 1 for a real-time example of this shift.) Briefly, these techniques couple an intentional shift in attention to the physical area of the heart with the self-activation of a positive emotion like love or appreciation. This rapidly initiates a distinct shift to increased coherence in the heart’s pattern of rhythmic activity. In turn, this produces a change in the pattern of afferent cardiac signals sent to the brain, which reinforces the self-generated positive emotional

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shift and makes it easier to sustain. Typically, the shift to coherence induces enhancements in perception and cognition that enable more effective memory, reasoning, decision making, and action when confronted with stressful or challenging situations. Furthermore, with regular practice, these physiological, emotional, and cognitive patterns become increasingly familiar to the brain, ultimately establishing a new set point by which the system then strives to maintain these upgraded, healthier patterns of psychophysiological function. The occurrence of such a psychophysiological “repatterning” process facilitated by the HeartMath system of coherence-building techniques is supported by studies conducted in diverse populations, documenting enduring improvements in health, emotional well-being, attitudes, behaviors, and relationships in individuals who practiced these techniques over several months’ time.53-56

district and employed a quasi-experimental, longitudinal field research design with intervention and control groups. The Creative Curriculum Assessment instrument (TCCA) was administered by teachers, who evaluated each child on 50 items measuring student growth on 4 development dimensions—social/emotional, physical, cognitive, and language development58—at 3 measurement moments over the course of the school year. There were a total of 19 schools in the study, each with one preschool class. Students in the preschool classes were divided into intervention and control group samples, in which classes in the former were specifically selected to target children of lower socioeconomic and ethnic minority family backgrounds. Three preschool classes constituted the intervention group to which the EHS program was provided; the total student count for these classes was 66 preschoolers.a Sixteen preschool classes from the remaining schools constituted the control group, which had a total student count of 309. The study hypothesis was that, relative to the control group, children in the intervention group would exhibit an increased level of development along the 4 TCCA development dimensions of psychosocial growth—social and emotional, physical, cognitive, and language development—following exposure to the EHS program over the school year study period. Intervention

Figure 3 Entrainment of physiological systems during psychophysiological coherence. Abbreviations: AMP, amplitude; BPM, beats per minute; HRV, heart rate variability; PTT, pulse transit time.

Research also supports the efficacy of this approach in educational settings, where the introduction of programs incorporating coherence-building tools and techniques at the elementary, middle school, high school, college, and graduate levels has been demonstrated to improve emotional disposition, psychosocial functioning, learning, test anxiety management, and academic performance.43,45,46,53,57 Controlled laboratory experiments using electrophysiological measures have also shown that both middle school and high school students can acquire the ability to self-activate the coherence state by using the HeartMath emotion self-regulation tools and that they are able to effectively apply this skill during a stressful or challenging situation.46,53 Research Design and Methods

The study evolved informally as a research opportunity resulting from discussions between IHM’s education division staff and officials in the Salt Lake City, Utah, School District. The study was conducted in the 2006-2007 school year on all preschool classes in the

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In late January 2007, two members of IHM’s Education Division conducted a 1-day training for teachers selected to introduce the EHS program into their preschool classes. The goal of the training was to provide the teachers with a working familiarity with the scientific foundation of the HeartMath System as well as the EHS concepts, tools, techniques, and materials prior to their beginning classroom instruction. Teachers then delivered the EHS program (presented in summary form in Table 1) to their students throughout the rest of the school year through the end of May 2007. Measures

TCCA instrument has been psychometrically validated as an assessment instrument and is widely used in schools throughout the United States. It was adopted by the Salt Lake City School District as a standardized means of systematically assessing the psychosocial development of all preschool students in the 19 schools in the district. The TCCA is organized into 4 distinct dimensions a

The selection of intervention group schools was made by members of the Salt Lake City School District staff. b The rating process requires the teacher to identify the developmental level of each child for each item using a 4-point scale. The proficiency requirements for each item (Table 1) are phrased in terms of specific behaviors and functional areas (with exemplars) anchored to each level of the rating scale. The Forerunner level represents behaviors that may indicate a developmental delay or that a child has not previously been exposed to that skill and is scored to emphasize the child’s strengths upon which future development and instruction can build. While Step III represents complete mastery of a particular goal, Step I and Step II represent distinct successive phases of development a child moves through on the way to mastery.

Original Research

An Emotion Self-regulation Program for Preschool Children

covering the social/emotional, physical, cognitive, and language areas of a child’s development. Each dimension is divided into subcategories and then measurement items on which the teacher evaluates and scores each child. Altogether, there are 50 measurement items—13 in social/emotional development, 8 in physical development, 16 in cognitive development, and 13 in language development. For each item, the teachers assessed and scored each child’s development on a 4-point competency/proficiency rating scale: 0 = Forerunners; 1 = Step I; 2 = Step II; 3 = Step III.b Over the 2006-2007 school year, the teachers completed the TCCA 3 times: the first (baseline measurement) in October, 2006; the second (preintervention measurement) in early January, 2007; and the third (postintervention measurement) at the end of April, 2007. Results Sample Characteristics

Table 2 shows the breakdown of the study population in terms of sociodemographic characteristics. Aggregated across the 3 intervention and 16 control schools, there were a total of 375 children in the study’s sample population, ranging from 2.8 to 4.7 years of age. Of these, 66 (17.6%) were in the intervention group and 309 (82.4%) were in the control group. The 2 samples were comparable on both age and gender, with a mean age of 3.6 years each and with a nearly even division on gender: 48% male and 52% female for the intervention group and 49% male and 51% female for the control group. Reflecting sample selection, there is a difference Table 2 Sociodemographic Characteristics (Time 1) of the Whole Sample, Intervention Group, and Control Group Mean Age ± SD, y (Range 2.8 - 4.7)

All Students (n = 375)

Intervention Group (n = 66)

Control Group (n = 309)

3.6 ± 0.32

3.6 ± 0.31

3.6 ± 0.33

Gender, % male

Free lunch, %

Asian

Black

Hispanic

54%

65%

51%

Indian

Polynesian

White

29%

33%

Other

12%

19.7 (11-28)

19.3 (18-26)

22.0 (11-28)

Ethnicity

No. of classes Class size, mean (range)

Abbreviations: NA, not available; SD, standard deviation.

Original Research

in family socioeconomic status in that while almost two-thirds (64%) of the intervention group received a free lunch from the school district, only half (48%) of the children in the control group did so. Also, there are notable differences in ethnic composition: there was a greater proportion of Hispanic children in the intervention group (65% vs 51%) and a much lower proportion of white children (8% vs 33%, respectively). Finally, there was a greater range in class size in the control group (11-28 children vs 18-26, respectively), and the mean class size was slightly smaller in the intervention group (19.31 vs 22.00). Measurement Integrity

For each development dimension, a child’s scores on the items involved were aggregated to construct a scale score for that dimension and then aggregated again across all 50 items to construct a total development scale score. Students were scored on each of the 50 items using the values on the 4-point rating scale. Since the lowest point value on the rating scale was 0, the maximum score for any item was 3 points, which, summed over the 50 items, yields a total possible development scale score of 150 points. Using the whole sample, we conducted an item analysis and a validity and reliability of measurement analysis of the TCCA instrumentation—development scales, subcomponents, and individual items (results available in Bradley et al, 2009).59 Starting with the item analysis, the range of the point-biserial order correlation (pbs r) over the 50 items across the 3 measurement moments was 0.26 to 0.82. There were no items with a 0 or negative pbs r, so all items met the minimum criteria for technically acceptable measurement and indicate an adequate level of discrimination between high- and low-performing children on the assessment. The standard error of measurement (SEM) for the total development score was ±1.05, ±1.29, and ±1.20 points for time 1 (T1), time 2 (T2), and time 3 (T3), respectively, and ranged from ±0.15 to 0.44 for the 4 development dimensions over all 3 measurement moments—all well within psychometrically acceptable limits. Turning to the results of the validity and reliability of measurement for the total development score, the T1, T2, and T3 Cronbach’s α reliability coefficients were all high (0.97, 0.98, and 0.98, respectively). With the exception of somewhat lower α coefficients for physical development (0.80, 0.86, and 0.86), high α coefficients also were observed on the other 3 development dimensions (ranging from 0.92 to 0.95). Though lower α coefficients were observed for the subcomponents within each of the 4 development dimensions (ranging from 0.71 to 0.93), they were, with 3 exceptions (gross motor, T1, and fine motor, T1, and T2), all above 0.80. Overall, the results indicate a high degree of internal consistency. We also conducted a factor analysis with varimax rotation to evaluate the degree of convergent and

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discriminant validity in the EHS study data. Though there were some exceptions, the factors and loadings and item classifications are generally consistent with the results of the original validation study. In short, the results of these analyses indicate that the baseline, preintervention, and postintervention measures appear to have psychometric integrity as measurement constructs. The line graph in Figure 4 plots the results of these measurement procedures for the whole study population’s mean total development score and mean scores for the 4 development dimensions at the 3 moments of measurement. Clearly evident is a strong upward trend in development on all 5 measures over the 3 time points. Thus, the mean total development score rose from 47.71 at baseline to 90.71 at the preintervention moment to 124.15 at the postintervention measurement moment: a T1-to-T3 increase of 160.22%. For the development dimensions, the greatest increase in mean score observed was for cognitive development, 13.90 to 38.79 (an increase of 179.06%) whereas the lowest increase was for physical development (9.29 to 21.56, an increase of 132.08%). Baseline (Time 1) Results

Table 3 presents the results of a 1-way analysis of variance (ANOVA) of differences in mean score by intervention status on the 5 development scales at baseline broken down by gender, ethnicity, and socioeconomic status. Starting with the results for intervention status, significant differences on all 5 scales (P < .01) with a moderate or large effect size (ES,c 0.41- 0.66) were observed between the control group and the intervention group. Though there are no differences by gender, there are significant differences mostly in the moderate effect size range (0.30-49) favoring white children over

those with Hispanic or other ethnic affiliation on all development scales (P < .001) except physical development. A similar pattern is observed on the indicator of socioeconomic status: the non–free lunch children had significantly higher development scores than the freelunch children on all scales (P < .05) except that for physical development. Two points emerge from these results: first, that the intervention and control groups were not well matched at baseline on the 5 development scales; second, that in the analysis that follows, it was necessary to control for the effects of ethnicity and free-lunch status in the event that pre-to-postintervention differences in development are observed between the intervention and control groups. Preintervention-to-Postintervention Results

In the analysis of the effects of the EHS intervention, we conducted 2 analyses. The first—a withingroups analysis—was conducted on the intervention and control groups separately in order to investigate the degree of pre-post change in development within each group. The second—a between-groups analysis— was conducted to identify changes in development in the intervention group that could be attributed to any observed effects of the EHS intervention by comparing the differences in pre-post changes in development between the 2 groups. Within-Groups Analysis

For the within-groups analysis, we employed a within-subjects repeated measures procedure on the 5 development scales to investigate the changes in development in the 2 periods up to and then following the EHS intervention—T1 to T2 and T2 to T3, respectively. Though a lower rate of development in the preintervention period (T1 to T2) was expected in the intervention group relative to the control group, given the former’s disadvantaged status on the baseline measures, a higher rate was expected following exposure to the EHS intervention. However, as shown in Table 4, a different pattern of results was observed. Across all 5 development scales, though a significant increase in mean score (P < .001, on all measures) of an extremely large ES (ES ranges from 1.17-2.81 over all measures) was observed in both time periods for each group, the greatest increase in development occurred in the first period, T1 to T2. This pattern is typified by the total development data. Thus, the results for the intervention group show that the greatest increase in development occurred in the first period, before the EHS intervention (T1-T2 D mean score = 53.15 points, ES 2.73; T2-T3 D mean score = 38.69 points, ES 1.84). Although somewhat smaller in magnitude, a similar pattern was observed for the control group (T1-T2 D c

Figure 4 Line Graph of 5 Development Scales (Mean Score) for Entire Sample Population by Measurement Moment.

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Effect size (ES) was computed by dividing the mean difference by the pooled standard deviation. Following Cohen’s (1988) guidelines for interpreting the meaning of the ES coefficient’s magnitude: < 0.10 trivial effect; 0.10-0.29 small effect; 0.30-0.49 moderate effect; ≥ 0.50 large effect.

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Table 3 Baseline (Time 1) Analysis of Variance of Development Scales by Intervention Grouping and by Gender, Ethnicity, and Family Socioeconomic Statusa

Mean

SEM

Mean

SEM

Mean

ANOVA Between Groups

SEM

Mean Sq

Intervention Group (N=66) Control Group (N=309) Total Development Score

39.47

16.20

1.99

49.47

19.34

1.10

5434.40

15.33

0.56

.001

Social/Emotional Development Score

9.62

4.45

0.55

12.83

5.32

0.30

558.30

20.83

0.66

.001

Physical Development Score

8.33

2.19

0.27

9.49

2.93

0.17

73.00

9.23

0.45

.01

Cognitive Development Score

11.71

5.85

0.72

14.36

7.09

0.40

382.01

8.05

0.41

.01

Language Development Score

9.80

5.48

0.67

12.79

5.99

0.34

484.05

13.91

0.52

.001

Male (N=178)

Female (N=189)

Total Development Score

47.25

19.62

1.47

48.01

18.93

1.38

52.68

0.14

0.04

Social/Emotional Development Score

11.98

5.40

0.40

12.46

5.30

0.39

20.87

0.73

0.09

9.31

3.01

0.23

9.29

2.72

0.20

0.08

0.01

Cognitive Development Score

Physical Development Score

13.92

7.15

0.54

13.78

6.79

0.49

1.89

0.04

0.02

Language Development Score

12.03

6.17

0.46

12.48

5.86

0.43

18.84

0.52

0.08

Total Development Score

43.34

15.87

1.12

56.70

20.95

2.02

46.34

20.66 2.56

6360.78

18.94

0.47

.001

Social/Emotional Development Score

11.49

4.65

0.33

13.94

5.86

0.56

11.88

5.72 0.71

216.17

7.94

0.30

.001

9.13

2.46

0.17

9.78

3.20

0.31

8.97

3.25 0.40

18.82

2.35

0.18

12.25

5.70

0.40

17.28

7.84

0.75

13.38

7.03 0.87

898.88

20.54

0.49

.001

10.47

4.97

0.35

15.71

6.08

0.58

12.11

6.37 0.79

969.89

31.30

0.60

.001

10.82

0.34

.01

Hispanic (N=202)

Physical Development Score Cognitive Development Score Language Development Score

White (N=108)

Non–Free Lunch (N=184) Total Development Score

50.98

Social/Emotional Development Score

12.93 9.49

Physical Development Score

20.88

Other (N=65)

Free Lunch (N=191)

1.54

44.55

5.67

0.42

11.61

3.12

0.23

9.09

16.86

1.22

3879.50

4.88

0.35

163.84

5.88

0.25

.05

2.54

0.18

15.41

1.91

0.14

Cognitive Development Score

15.22

7.46

0.55

12.62

6.18

0.45

Language Development Score

13.33

6.47

0.48

11.23

5.33

0.39

635.98

13.60

0.38

.001

413.75

11.82

0.36

.001

Single-factor ANOVA.

Abbreviations: ANOVA, analysis of variance; ES, effect size; F, ANOVA test statistic; NS, not significant; SEM, standard error of measurement; Sq, square.

Table 4 Within-subjects Repeated Measures Analysis of Change in Development Scales (Mean Score) for Intervention and Control Groups

Time 1 Mean

Time 2

Mean

Time 3 Mean

Time 1 vs Time 2 Mean Sq

Time 2 vs Time 3 P<

Mean Sq

Within-Subjects Repeated Measures, Intervention Group Total Development

39.88 15.98

93.03 22.95 131.72 19.19 183646.54 620.87

2.73

.001

97311.15 411.63 1.84 .001

Social/Emotional Development 65

9.75

4.35

24.58

6.19 35.02 5.00

14296.86 413.81

2.81

.001

7072.06 197.48 1.86 .001

Physical Development

8.38

2.17

16.72

3.83 22.74 2.21

4519.45 503.43

2.78

.001

2352.02 248.00 1.99 .001

Cognitive Development

11.85

5.79

29.05

8.28 41.11 7.83

19229.60 439.16

2.44

.001

9456.25 292.12 1.5

Language Development

9.89

5.47

22.68

7.12 32.86 6.88

10624.02 399.73

2.03

.001

6742.22 333.52 1.45 .001

.001

Within-Subjects Repeated Measures, Control Group Total Development

301 49.57 19.23 90.21 23.38 122.63 22.12 497082.47 1920.83 1.91

.001 316405.59 1491.65 1.43 .001

Social/Emotional Development 301 12.88

5.25 23.62

6.91

31.88 6.55

34746.70 1199.91 1.77

.001

20532.21 1067.94 1.23 .001

Physical Development

301

9.51

2.92 16.13

3.37

21.32 2.85

13222.67 1389.75 2.11

.001

8105.79 1184.94 1.67 .001

Cognitive Development

301 14.39

7.08 27.61

8.24

38.30 7.95

52652.36 1462.75 1.73

.001

34382.36 998.26 1.32 .001

Language Development

301 12.80

5.98 22.84

7.18

31.12 7.00

30340.48 1525.28 1.53

.001

20664.57 815.77 1.17 .001

Abbreviations: ES, effect size; SD, standard deviation; Sq, square.

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mean score = 40.64 points, ES = 1.91; T2-T3 D mean score = 32.42 points, ES = 1.43). There are 2 points of interest here. One is that this pattern is similar in both groups. This suggests some underlying commonality, such as the initial novelty of children first entering a new, stimulating social environment, the preschool class. It could be expected that after the children experience an accelerated growth rate, they then adapt as the school environment becomes more familiar. The second point is that although the pattern is similar in both groups, there is a more elevated growth in the intervention group during the first period both in relation to the control group in the first period and also in relation to the intervention group’s rate of growth in the second period. A plausible explanation is that this pattern in the intervention group children may have resulted from an even more novel experience of a nurturing, growth-promoting teacher and the psychosocially stimulating preschool environment relative to the disadvantaged circumstances of an ethnic minority and/or lower socioeconomic family background characteristic of most children in this group. An alternative explanation for the pattern is the possibility of a Hawthorne effect: namely, that the intervention group teachers may have (consciously or unconsciously) inflated the ratings of their students in the preintervention period. Unfortunately, there were insufficient cases with the required combination of ethnosocioeconomic characteristics to investigate the first explanation posited above for the elevated rate of development observed. However, we were able to investigate the question of a potential Hawthorne effect, the results of which are presented below. Even with this pattern, the smaller degree of change in the second period was still very large (ES range 1.17-1.99) and highly significant (P < .001) across the 5 measures in both groups. Determining how much of this increase in development in the intervention group is attributable to the effects of the EHS program requires a between-groups comparison of the 2 groups, in which any differences in the measures of development at the baseline (T1) and preintervention (T2) moments are statistically controlled. We turn to this all-important question next. Between-Groups Analysis

The primary statistical analysis technique used to investigate pre-post changes in development was analysis of covariance (ANCOVA). An important advantage of ANCOVA is that the baseline (T1) and preintervention (T2) differences on the development measures between the intervention and control groups are statistically adjusted to make them comparable before the change effects are estimated. This is accomplished by treating them as covariates in the statistical model. We begin with the results by intervention status before moving to the breakdowns by gender, ethnicity, and family socioeconomic background.

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Figure 5 and Table 5 present the results for the 5 development scales and the 10 subcomponents by intervention status. Clearly evident is the strong consistent pattern of moderate to large, significant differences on all 15 measures of development, favoring the intervention group over the control group. On 10 of the 15 measures, including 4 of the 5 development scales, the magnitude of the difference was large and highly significant (ES > 0.60, P < .001). More specifically, from the adjusted means on the 5 development scales, a significant difference with a large ES was observed favoring the intervention group on the total development scale (130.96 vs 122.79, respectively; ES 0.81, P < .001) and on each of the social/emotional development (34.95 vs 31.90, ES 0.97, P < .001), physical development (22.59 vs 21.35, ES 0.79, P < .001), cognitive development (40.58 vs 38.41, ES 0.55, P < .01), and language development (33.74 vs 30.99, ES 0.73 P < .001) scales. At the subcomponent level, 6 of the 10 constructs had differences favoring the intervention group that were large in terms of ES and highly significant: sense of self, ES 1.05, P < .001; responsibility for self and others, ES 0.61, P < .001; prosocial behavior, ES 0.94, P < .001; fine motor, ES 0.68, P < .001; learning and problem solving, ES 0.65, P < .001; and reading and writing, ES 0.84, P < .001. Sociodemographic Effects

To investigate the degree to which these observed differences in development were not mediated by one or more intervening sociodemographic factors identified as significant at baseline, an ANOVA was conducted on the 5 development scales controlling for gender, ethnic status, and socioeconomic family background (free-lunch status). The results are presented in Table 6. Beginning with the results (adjusted means) for the total development scale, a consistent pattern of moderate to large, significant differences is observed favoring the intervention over the control group: for boys (128.10 vs 121.35, ES 0.47, P < .05), girls (133.876 vs 124.42, ES 0.65, P < .001), Hispanic children (129.60 vs 121.22, ES 0.63, P < .001), white children (130.62 vs 121.87, ES 0.44, P < .05), free-lunch recipients (131.61 vs 125.29, ES 0.56, P < .01), and non–free lunch recipients (130.09 vs 120.33, ES 0.57, P < .01). These results suggest a markedly greater level of development for children with these characteristics who were exposed to the EHS program than those who were not. Moving to the 4 development scales, for girls, Hispanic children, and free lunch students, there is a pattern of a significantly greater increase in development in the intervention group compared to the control group on all 4 scales. With the exception of the cognitive development scale, the same pattern is observed for boys and non–free lunch students. For white students, though, this difference is evident only on 2 dimensions—physical development and language development.

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Figure 5 Adjusted means showing results of analysis of covariance of intervention effects on development measures comparing intervention and control groups.

Table 5 Results of Analysis of Covariance of Intervention Effects on Development Measures Comparing Intervention and Control Groupsa Spring Post-study Between-Group Effects Intervention Group (n = 65)

Control Group (n = 301)

BetweenSubjects

Adj Mean

SEM

Lower 95% CI

Upper 95% CI

Adj Mean

SEM

Lower 95% CI

Upper 95% CI Mean Sq

130.96

1.72

127.57

134.35

122.79

0.77

121.27

124.31

3200.92

18.13 0.81

.001

Social/Emotional Development Score

34.95

0.54

33.89

36.02

31.90

0.24

31.42

32.38

446.46

25.69 0.97

.001

Physical Development Score

22.59

0.27

22.07

23.12

21.35

0.12

21.12

21.59

77.74

17.60 0.79

.001

Cognitive Development Score

40.58

0.68

39.25

41.92

38.41

0.31

37.81

39.02

235.35

8.33 0.55

.01

Total Development Score

Language Development Score

33.47

0.58

32.34

34.61

30.99

0.26

30.48

31.51

303.67

14.99 0.73

.001

Sense of Self

11.09

0.19

10.71

11.46

9.92

0.09

9.75

10.08

63.73

29.98 1.05

.001

Responsibility for Self and Others

13.24

0.26

12.72

13.75

12.29

0.12

12.06

12.53

43.52

10.40 0.61

.001

Prosocial Behavior

10.78

0.20

10.39

11.17

9.69

0.09

9.52

9.87

59.93

24.74 0.94

.001

Gross Motor

14.18

0.18

13.82

14.54

13.55

0.08

13.38

13.71

20.39

9.76 0.59

.01

8.41

0.15

8.12

8.69

7.82

0.07

7.68

7.95

18.03

13.20 0.68

.001

Learning and Problem Solving

12.45

0.27

11.92

12.97

11.42

0.12

11.18

11.66

53.38

12.00 0.65

.001

Logical Thinking

20.09

0.37

19.36

20.82

19.22

0.17

18.89

19.55

37.99

4.55 0.40

.05

Fine Motor

Representation and Symbolic Thinking

8.26

0.17

7.93

8.60

7.78

0.08

7.63

7.94

11.15

6.38 0.48

.05

Listening and Speaking

15.64

0.28

15.08

16.19

14.81

0.13

14.56

15.06

32.68

6.91 0.50

.01

Reading and Writing

17.89

0.33

17.24

18.55

16.25

0.15

15.95

16.55

138.65

20.23 0.84

.001

ANCOVA: covariates fall and winter baseline scores.

Abbreviations: Adj, adjusted; CI, confidence interval; ES, effect size; F, ANOVA test statistic; SEM, standard error of measurement; Sq, square.

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Table 6 Analysis of Covariance of Intervention Effects on Development Scales Comparing Intervention and Control Groups by Gender, Ethnicity, and Socioeconomic Statusa Spring Post-study Between-Group Effects

Intervention Group

Dependent Variable

Adj Mean

Lower Upper SEM 95% CI 95% CI

Control Group

Adj Lower Upper Mean SEM 95% CI 95% CI Mean Sq

Males Total Development

128.10

144 121.35

1.09 119.21 123.50

1021.06

6.14

0.47

.05

Social/Emotional Development 31

33.91

2.45 123.28 0.81

32.31

132.93 35.51

144

31.20

0.36

30.49

31.91

162.34

8.99

0.57

.01

Physical Development

22.56

0.37

21.82

23.30

144

21.14

0.17

20.81

21.48

47.82

11.58

0.64

.001

Cognitive Development

39.17

0.97

37.26

41.09

144

38.25

0.44

37.39

39.11

19.93

0.74

0.16

Language Development

32.83

0.73

31.39

34.28

144

30.68

0.33

30.03

31.34

109.70

7.03

0.50

.01

2.51 128.91

138.83

Females Total Development

133.87

152 124.42

1.11 122.22 126.61

2121.62

11.49

0.65

.001

Social/Emotional Development 32

35.70

0.76

34.20

37.21

152

32.54

0.34

31.86

33.21

241.88

13.97

0.71

.001

Physical Development

22.69

0.40

21.91

23.47

152

21.53

0.18

21.18

21.88

33.52

7.03

0.50

.01

Cognitive Development

42.12

0.95

40.24

43.99

152

38.76

0.43

37.92

39.60

278.85

10.20

0.60

.01

Language Development

34.39

0.91

32.59

36.19

152

31.38

0.41

30.58

32.18

215.84

8.84

0.57

.01

2.18 125.30

133.89

Ethnicity, Hispanic Total Development

129.60

157 121.22

1.10 119.04 123.40

2111.33

11.33

0.63

.001

Social/Emotional Development 43

34.95

0.68

33.61

36.29

157

31.79

0.35

31.10

32.47

302.41

16.55

0.76

.001

Physical Development

22.58

0.33

21.92

23.24

157

21.39

0.17

21.05

21.73

45.07

9.83

0.58

.01

Cognitive Development

40.07

0.83

38.42

41.71

157

37.94

0.43

37.09

38.78

142.24

5.05

0.42

.05

Language Development

32.60

0.78

31.07

34.13

157

29.94

0.39

29.17

30.72

215.16

9.01

0.56

.01

3.06 124.49

136.74

Ethnicity, White Total Development

130.62

42 121.87

1.87 118.12 125.62

768.54

5.55

0.44

.05

Social/Emotional Development 17

34.38

1.04

32.29

36.47

32.46

0.63

31.20

33.73

35.75

2.27

0.28

Physical Development

22.85

0.47

21.92

23.79

21.49

0.29

20.91

22.07

20.67

5.99

0.45

.05

Cognitive Development

40.19

1.32

37.54

42.84

37.09

0.81

35.47

38.71

97.69

3.74

0.36

Language Development

33.44

0.94

31.56

35.32

30.73

0.58

29.56

31.89

78.06

5.75

0.44

.05

1.89 127.88

135.34

Free Lunch Total Development

131.61

148 125.29

0.98 123.37 127.22

1168.07

8.48

0.55

.01

Social/Emotional Development 42

36.04

0.59

34.87

37.21

148

32.88

0.31

32.28

33.49

292.52

21.51

0.87

.001

Physical Development

22.94

0.27

22.40

23.48

148

21.85

0.14

21.57

22.13

37.29

12.28

0.65

.001

Cognitive Development

41.03

0.80

39.45

42.61

148

38.97

0.42

38.15

39.79

127.44

5.05

0.42

.05

Language Development

32.92

0.71

31.51

34.33

148

31.22

0.37

30.49

31.95

87.57

4.35

0.39

.05

3.10 123.98

136.20

Non–Free Lunch Total Development

130.09

153 120.33

1.15 118.06 122.59

1686.58

8.51

0.57

.01

Social/Emotional Development 23

33.57

0.98

31.64

35.50

153

30.86

0.37

30.14

31.58

132.80

6.59

0.50

.05

Physical Development

22.24

0.52

21.22

23.26

153

20.83

0.19

20.45

21.22

36.53

6.41

0.49

.05

Cognitive Development

39.88

1.17

37.57

42.18

153

37.86

0.44

36.99

38.72

74.61

2.58

0.31

Language Development

34.13

0.95

32.25

36.01

153

30.82

0.36

30.12

31.53

197.88

10.37

0.63

.01

ANCOVA: covariates fall and winter baseline scores.

Abbreviations: CI, confidence interval; F, ANOVA test statistic; ES, effect size; NS, not significant; SEM, standard error of measurement.

Matched-Groups Analysis

We conducted another ANCOVA to investigate the degree to which the observed differences between the 2 groups of children were not confounded by an underlying difference in class size (results not shown; available in Bradley et al, 2009).59 To conduct the study, we constructed a matched-group comparison by selecting classes from the control group sample that were close to or within the class size range (18-24 children) of the 3 classes in the intervention group. There were 4 classes in the control group (total n = 90)

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with a class size of between 17 and 26 children, and we selected these for the matched-group comparison. Coincidentally, these 7 classes also were within the same range on mean baseline total development score (35.78-42.71 points). This enabled us to simultaneously control for the effects of baseline differences between the intervention and control group on both class size and total development, providing for a somewhat more rigorous matched-groups analysis. As previously, to control for any differences in development between the 2 groups in the preintervention period,

Original Research

An Emotion Self-regulation Program for Preschool Children

development scores at T1 and T2 were deployed as covariates in the statistical model. A notable, significant difference in the pre-post increase in the mean total development score is observed for the intervention group over the matchedgroup sample from the control group (123.68 vs 115.93, respectively, ES 0.61, P < .001). A similar difference is evident for 3 of the 4 development dimensions: social/ emotional development (33.14 vs 29.53, ES 0.81, P < .001); physical development (21.86 vs 20.74, ES 0.55, P < .01), and language development (31.43 vs 28.60, ES 0.63 P < .001). In short, when baseline differences in class size and total development are controlled, there is still compelling evidence of markedly greater development in the children who participated in the EHS program than in those who did not. Split-half Sample Analysis

As the final step in the primary analysis, we conducted a split-half sample analysis (results not shown; available in Bradley et al, 2009).59 In a typical application, the procedure involves randomly dividing the study sample population into halves and then repeating the analysis separately on each half-sample. This enables a check on the statistical integrity of nonrandom samples and also provides some indication of the likely generalizability of results. To conduct this analysis, we randomly divided the intervention and control groups into 2 approximately equal subgroups each and then repeated the pre-post ANCOVA comparison on each of the two half-sample pairings, accordingly: viz, random split (RS) 1: first intervention subgroup vs 1st control subgroup; RS2: second intervention subgroup vs second control subgroup. As an extra precaution, we not only conducted the analysis on the 5 development scales and but also included the 10 subcomponents of the 4 development dimensions as well. Beginning with the 5 development scales, a comparison of the results for RS1 to those for RS2 found that, with one exception (cognitive development scale), a pattern of moderate to large, significant differences favoring the intervention group on the other 4 development measures was evident in both ANCOVAs. This suggests that the intervention results on the total development scale and the social/emotional, physical, and language development scales appear to be robust, are unlikely to be the result of sample bias, and are probably generalizable to children with similar characteristics. Discussion

To investigate the key question of a pre-postintervention effect, we used a rigorous multivariate procedure—ANCOVA—in order to be statistically confident that any observed pre-postintervention differences could not be the result of differences at baseline between the 2 groups. This procedure revealed a strong pattern of differences favoring the intervention

Original Research

group children on the 5 development dimension scales as well as on the 10 subcomponents. This intervention effect also was observed on the total development scale for each of the sociodemographic categories examinedd (male, female, Hispanic, white, free lunch, and non–free lunch) and also for female, Hispanic, and free-lunch on all 4 development dimension scales and for whites on the physical development and language development scales. These results are consistent with the findings of prior studies on the implementation of programs using similar emotion self-regulation techniques in elementary, middle, and high schools and tertiary education.43,45,46,53,57 The strong evidence of an EHS intervention effect appears robust. Both the matched-groups analysis (in which we controlled for baseline differences in class size and total development score) and the random splithalf sample analysis found essentially the same prepostintervention differences in development favoring the intervention group on the total development scale, and also on 3 of the 4 development dimension scales— social/emotional development, physical development, and language development. The random split-half sample results are noteworthy in that they suggest that on these development measures, it is unlikely that the differences between the 2 groups are due to sample bias and are probably generalizable to children with similar characteristics and in similar educational contexts as those in the intervention group. Overall, the strong, consistent pattern of positive pre-to-postintervention results provides compelling evidence of the efficacy of the EHS program in promoting greater development across the 5 primary measures—total development, social/emotional development, physical development, cognitive development, and language development. Limitations

The study evolved as an adjunct investigation to the research already being conducted on the development of preschoolers in all schools in the Salt Lake City School District. Some limitations came with this research strategy. One limitation concerns the generalizability of the study’s results. There are 2 potential issues: (1) the lack of randomization in sample selection and intervention/control group assignment and (2) the degree to which the study population is broadly representative of the population of preschoolers in the United States as a whole. Though the lack of randomization for sample selection is not an issue, because all 19 schools in the Salt Lake City School District were included, it is a limitation of the criterion-reference procedure used to assign intervention or control group status. Even so, the results from the random split-half sample analysis suggest, in broad terms, that the primary findings d There

were too few cases in the intervention group’s “Ethnicity-other” category (n = 5) for this analysis.

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Acknowledgments Development of the Early HeartSmarts (EHS) program was made possible by a generous grant from the Kalliopeia Foundation, San Rafael, California. We are grateful to the Salt Lake City School District personnel for their willingness to sponsor and implement the EHS evaluation, in particular Dr Patrick Galvin and Ms Donna Anderson for their roles in designing and carrying out data collection for the study. We also thank the teachers in the study, especially those who taught the classes included in the intervention group, and we extend our appreciation to all the children who participated in the study. Jeffrey Goelitz of Institute of HeartMath (IHM) coordinated all aspects of the study with the Salt Lake City School District. We are indebted to Drs Karl H. Pribram and Allan N. Schore for providing helpful comments on an earlier draft of this report. Finally, it should be noted that Dr Raymond Bradley and Dana Tomasino are independent research consultants to IHM, whose involvement in the EHS study began in 2009 after the data were collected.

appear to be generalizable to preschool children in similar sociogeographic contexts and with similar sociodemographic characteristics. Concerning the second issue, further research will be necessary on samples that are more representative of US preschool children as a whole in order to confirm the efficacy of the EHS program in promoting growth and development more broadly. Another limitation was that the teachers were not completely blinded to the study’s goals and desired outcomes and therefore could have consciously or unconsciously acted to affect the results. Although we found little evidence of scoring bias in the teachers’ ratings, we cannot definitively rule out such an artifact. A final limitation is that the children’s scores are all based on observation, evaluation, and rating from a single source: their teachers. Although we were mostly able to address the basic psychometric issues of rating consistency, measurement validity, reliability, and discrimination in the item analysis we performed, future studies should be conducted using at least 2 independent observers to rate each child’s development on the measurement items. Conclusion

Of the key socioemotional competencies in early childhood that lay the foundation for future development and the potential for adult psychosocial growth, well-being, and accomplishment, emotional self-regulation is core.16,17 Yet as noted at the outset, a disturbing proportion of preschool children, especially those from ethnic minority and low socioeconomic family backgrounds, lack the fundamental socioemotional skills needed to learn and function effectively at school. Although the EHS program was developed with the broader goal of enhancing the psychosocial development of all preschool children, it was expected that the program would have particular application in facilitating development in children from disadvantaged family backgrounds and circumstances. Despite the limitations noted above, the results are striking in that there is strong evidence of an intervention effect. First, across all of the analyses performed, a consistent pattern of large, significant differences in growth on the primary development constructs—total development scale, social/emotional development scale, physical development scale, cognitive development scale, and language development scale, plus their 10 subcomponents (all but 2 subcomponents had a large effect size)—is evident for the children receiving the EHS intervention relative to those in the control group who did not. The magnitude of development observed for the intervention-group children is particularly striking, as they started the study with a significant development handicap relative to their peers in the control group. Yet after participating in the EHS program, they had surpassed the latter’s development growth by the end of the study. A second important finding is the consistent pat-

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tern of pre-to-postintervention differences in total development score between the 2 groups for all of the sociodemographic categories investigated. Importantly, given the study’s targeting of ethnic-minority and low– socioeconomic status students, the evidence shows that the EHS program was effective in boosting the development of boys (with the exception of cognitive development), girls, Hispanic children, and free-lunch students in the intervention group on the 4 development dimensions—social/emotional, physical, cognitive, and language—beyond that of their peers in the control group. And it was effective for non–free lunch and white students in the intervention group, with the exception of cognitive development and language development scores, respectively. A series of additional analyses found that these differences do not appear to be mediated by classroom size or explained by baseline differences in development between the 2 groups of children. Further, the evidence from a random split-half sample analysis corroborates the results for the whole intervention and control group samples and indicates that the findings for all but 1 of the 5 development scales (cognitive development) are robust and likely generalizable to children of comparable sociodemographic characteristics. In sum, the strong, consistent pattern of positive results observed across all analyses is compelling evidence of the efficacy of the EHS program in significantly facilitating a marked growth in development in preschool children. An important point to emphasize is that these results are for very young preschool children, 96% of whom were between 3 and 4 years old. It is both striking and remarkable that children as young as 3 years can begin to learn and practice the emotion selfregulation skills they were taught in the EHS program, which appears to facilitate their psychosocial development. Given that the age range from 3 to 6 years is a period of accelerated neurological growth and psychosocial development, it is likely that the learning and sustained use of these competencies and skills during this important developmental period will readily instantiate a new set point in the young child’s nervous system for an optimal pattern of psychophysiological function and thereby significantly boost the development trajectory of future psychosocial growth. Establishing this key set point early in the child’s life, when neural connectivity is still highly malleable, and then sustaining it throughout the whole educational process with programs building on these foundational skills sets the child on a thriving life course of health, well-being, achievement, and social responsibility. Correspondingly, the integration of programs designed to foster socioemotional competence into educational curricula—beginning in preschool— should help prevent manifestation of much of the psychosocial dysfunction and pathology that not only robs individuals of a fulfilling life but also results in an enormous cost to our society.

Original Research

An Emotion Self-regulation Program for Preschool Children

Appendix Validity and Reliability of Measurement Analysis, Time 1 to Time 3

Items, no.

Cases, no.

Point Bi-serial Correlation Min

Max

Mean

SEM

Cronbach’s a

Fall Pre-study Score (Time 1) Total Development

274

0.26

0.77

51.57

17.43

1.05

0.97

Social/Emotional Development

340

0.57

0.71

12.85

5.01

0.27

0.92

345

0.43

0.62

9.45

2.79

0.15

0.80

Physical Development Cognitive Development

336

0.52

0.78

14.78

6.59

0.36

0.93

Language Development

340

0.47

0.77

12.87

5.73

0.31

0.92 0.82

Sense of Self

353

0.63

0.66

3.86

1.88

0.10

Responsibility for Self and Others

366

0.52

0.72

4.95

2.12

0.11

0.85

Prosocial Behavior

361

0.58

0.69

3.79

1.72

0.09

0.82

Gross Motor

351

0.51

0.66

5.92

1.87

0.10

0.79 0.71

Fine Motor

365

0.46

0.64

3.52

1.41

0.07

Learning and Problem Solving

365

0.63

0.77

4.26

2.25

0.12

0.87

Logical Thinking

342

0.56

0.71

7.27

3.76

0.20

0.88

Representation and Symbolic Thinking

367

0.63

0.70

2.93

1.35

0.07

0.81

Listening and Speaking

355

0.47

0.81

6.87

3.03

0.16

0.88

Reading and Writing

353

0.46

0.72

5.80

3.12

0.17

0.85

Winter Pre-study Score (Time 2) Total Development

326

0.47

0.78

91.54

23.33

1.29

0.98

Social/Emotional Development

356

0.65

0.78

23.90

6.74

0.36

0.94

354

0.42

0.68

16.39

3.32

0.18

0.86

Physical Development Cognitive Development

352

0.57

0.77

27.93

8.27

0.44

0.95

Language Development

356

0.51

0.82

22.85

7.17

0.38

0.94 0.87

Sense of Self

362

0.71

0.76

7.54

2.36

0.12

Responsibility for Self and Others

363

0.63

0.81

9.07

2.80

0.15

0.90

Prosocial Behavior

363

0.62

0.72

7.25

2.23

0.12

0.84

Gross Motor

359

0.62

0.73

10.00

2.22

0.12

0.87 0.77

Fine Motor

360

0.52

0.70

6.34

1.61

0.08

Learning and Problem Solving

362

0.72

0.79

8.33

2.79

0.15

0.90

Logical Thinking

359

0.55

0.78

13.94

4.60

0.24

0.92

Representation and Symbolic Thinking

362

0.65

0.77

5.68

1.72

0.09

0.84

Listening and Speaking

357

0.57

0.83

11.39

3.67

0.19

0.91

Reading and Writing

364

0.55

0.79

11.45

3.97

0.21

0.90

Spring Post-study Score (Time 3) Total Development

341

0.45

0.81

124.44

22.20

1.20

0.98

Social/Emotional Development

362

0.58

0.78

32.57

6.44

0.34

0.94

367

0.38

0.74

21.60

2.80

0.15

0.86

Physical Development Cognitive Development

364

0.53

0.81

38.80

7.99

0.42

0.95

Language Development

368

0.62

0.81

31.52

6.91

0.36

0.95

Sense of Self

365

0.61

0.76

10.20

2.02

0.11

0.84

Responsibility for Self and Others

372

0.65

0.82

12.46

2.84

0.15

0.91

Prosocial Behavior

374

0.59

0.76

9.85

2.17

0.11

0.86

Gross Motor

370

0.57

0.74

13.68

1.83

0.10

0.85

Fine Motor

372

0.59

0.78

7.95

1.40

0.07

0.83 0.91

Learning and Problem Solving

373

0.73

0.79

11.58

2.86

0.15

Logical Thinking

367

0.52

0.81

19.39

4.34

0.23

0.93

Representation and Symbolic Thinking

374

0.71

0.81

7.87

1.55

0.08

0.87

Listening and Speaking

371

0.62

0.83

15.01

3.19

0.17

0.90

Reading and Writing

371

0.64

0.83

16.53

4.05

0.21

0.92

Abbreviations: Min, minimum; max, maximum; SD, standard deviation; SEM, standard error of measurement.

Original Research

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35. Myers M, Popp P. (2003, Fall). What educators need to know about homelessness and special education. (Information Brief No. 7). Williamsburg, VA: Project HOPE. Cited February 6, 2012. Available from: http://www.wm.edu/hope/infobrief/personnel-complete.pdf 36. Institute of HeartMath. Early heartsmarts leaders guide: ages 3-6. Boulder Creek (CA): HeartMath LLC; 2008. 37. Armour JA. Peripheral autonomic neuronal interactions in cardiac regulation. In: Armour JA, Ardell JL, editors. Neurocardiology. New York: Oxford University Press; 1994. p. 219-44. 38. Lacey JI, Lacey BC. Some autonomic-central nervous system interrelationships. In: Black P, editor. Physiological correlates of emotion. New York: Academic Press; 1970. p. 205-27. 39. McCraty R, Atkinson M, Tiller WA, Rein G, Watkins AD. The effects of emotions on short-term power spectrum analysis of heart rate variability. Am J Cardiol. 1995 Nov 15;76(14):1089-93. 40. McCraty R, Atkinson M, Tomasino D, Bradley RT. The coherent heart: heart-brain interactions, psychophysiological coherence, and the emergence of system-wide order. 2006, Boulder Creek (CA): HeartMath Research Center; 2006. 41. Tiller WA, McCraty R, Atkinson M. Cardiac coherence: a new, noninvasive measure of autonomic nervous system order. Altern Ther Health Med. 1996 Jan;2(1):52-65. 42. van der Molen MW, Somsen RJ, Orlebeke JF. The rhythm of the heart beat in information processing. In: Ackles PK, Jennings JR, Coles MG, editors. Advances in psychophysiology. Vol. 1. London: JAI Press; 1985. p. 1-88. 43. Arguelles L, McCraty R, Rees RA. The heart in holistic education. Encounter Educ Meaning Soc Justice. 2003; 16(3): 13-21. 44. Bradley RT. The psychophysiology of intuition: a quantum-holographic theory of nonlocal communication. World Futures. 2007;63(2): 61-97. 45. McCraty R. Enhancing emotional, social, and academic learning with heart rhythm coherence feedback. Biofeedback. 2005;33(4):130-4. 46. McCraty R, Atkinson M, Tomasino D, Goelitz J, Mayrovitz HN. The impact of an emotional self-management skills course on psychosocial functioning and autonomic recovery to stress in middle school children. Integr Physiol Behav Sci. 1999;34(4):246-68. 47. McCraty R, Tomasino D. Emotional stress, positive emotions, and psychophysiological coherence. In: Arnetz BB, Ekman R, editors. Stress in health and disease. Weinheim: Wiley-VCH; 2006. p. 342-65. 48. McCraty R, Tomasino D. Coherence-building techniques and heart rhythm coherence feedback: new tools for stress reduction, disease prevention and rehabilitation. In: Molinari E, Compare A, Parati G, editors. Clinical psychology and heart disease. Milan: Springer-Verlag; 2006. p 487-509. 49. Porges SW. Vagal tone: A physiologic marker of stress vulnerability. Pediatrics, 1992 Sep;90(3 Pt 2):498-504. 50. Porges SW, Doussard-Roosevelt JA, Maiti AK. Vagal tone and the physiological regulation of emotion. In: Fox NA, editor. Emotion regulation: behavioral and biological considerations. Monographs of the society for research in child development. 1994. p. 167-186. 51. Childre D, Martin H. The heartmath solution. San Francisco: HarperSanFrancisco; 1999. 52. Childre D, Rozman D. Transforming stress: the heartmath solution to relieving worry, fatigue, and tension. Oakland: New Harbinger Publications; 2005. 53. Bradley RT, McCraty R, Atkinson M, Arguelles L, Rees RA, Tomasino D. Reducing test anxiety and improving test performance in America’s schools: results from the testedge national demonstration study. Boulder Creek (CA): HeartMath Research Center; 2007. 54. Luskin F, Reitz M, Newell K, Quinn TG, Haskell W. A controlled pilot study of stress management training of elderly patients with congestive heart failure. Prev Cardiol. 2002 Fall;5(4):168-72. 55. McCraty R, Atkinson M, Lipsenthal L, Arguelles L. New hope for correctional officers: an innovative program for reducing stress and health risks. Appl Psychophysiol Biofeedback. 2009 Dec;34(4):251-72. 56. McCraty R, Barrios-Choplin B, Rozman D, Atkinson M, Watkins AD. The impact of a new emotional self-management program on stress, emotions, heart rate variability, DHEA and cortisol. Integr Physiol Behav Sci. 1998 Apr-Jun; 33(2):151-70. 57. Hartnett-Edwards K. Stress matters: the social psychology and physiology of reading/language arts achievement. Saarbrücken: Verlag Dr Müller; 2008. 58. Dodge DT, Colker LJ, Heroman C. A teacher’s guide to using the creative curriulum developmental continuum assessment system. Washington: Teaching Strategies; 2001. 59. Bradley RT, Atkinson M, Tomasino D, Rees RA. Facilitating emotional self-regulation in preschool children: efficacy of the early heartsmarts program in promoting social, emotional and cognitive development. Boulder Creek (CA): HeartMath Research Center, Institute of HeartMath; 2009.

Original Research

feature

Access to Medicines in Resource-limited Settings: The End of a Golden Decade? Tido von Schoen-Angerer, MD, MSc; Nathan Ford, PhD, MPH; James Arkinstall, MA

Author Affiliations Tido von SchoenAngerer, MD, MSc, is the executive director of the Médecins Sans Frontières Access Campaign, Geneva, Switzerland. Nathan Ford, PhD, MPH, is the medical coordinator of the Médecins Sans Frontières Access Campaign and a research associate at the Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa. James Arkinstall, MA, is the head of communications at the Médecins Sans Frontières Access Campaign. Correspondence Tido von Schoen-Angerer Tido.von.schoenangerer@ geneva.msf.org Citation Global Adv Health Med. 2012;1(1):52-59. Key Words Medicines, access, innovation, resource- limited, global health, HIV/AIDS, tuberculosis, TB, malaria, HIV, public health, policy, World Health Organization, WHO, Global Fund to Fight AIDS, Tuberculosis and Malaria, GFATM, Doha Declaration, intellectual property, product development partnerships

Abstract

Strong international mobilization and political will drove a golden decade for global health. Key initiatives over the last decade include setting of health-related Millennium Development Goals; the Commission on Macroeconomics and Health; the creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria; the Doha Declaration on the TRIPS Agreement and Public Health affirming countries’ rights to protect public health when implementing patent rules; and the creation of product development partnerships to address neglected areas of research and development. Significant progress was made in reducing the incidence of and morbidity and mortality from human immunodeficiency virus (HIV), tuberculosis (TB), and malaria, with a major impact made through increased access to medicines. Antiretroviral treatment for HIV was expanded to 6.6 million people, and medication prices were reduced significantly through generic competition. However, donor support has started to decline at a time when many patients still wait for treatment and the prices of needed newer medicines are on the increase due to patent protection. TB incidence has started to decrease, but progress in diagnosis and treatment of multidrug-resistant TB has been slow due to complexity of treatment and high drug costs. Promising new TB drugs in development need to be introduced rapidly and appropriately while treatment is being expanded. The introduction of more affordable artemisinin combination therapies for malaria contributed to significantly reducing malaria incidence and mortality, but challenges remain in ensuring that the latest recommendations for treating severe malaria are implemented. Looking to the next decade, there is a worrisome

mismatch between additional health priorities accompanied by shifting burdens of disease that need to be addressed and dwindling political attention and financial support. Difficulties in producing and guaranteeing access to affordable medicines are expected from a changing pharmaceutical market where an appropriate balance between trade and health has not been found. Systematic changes through a global framework for research and development and access are needed to support increased innovation and access to the health tools of the next decade.

摘要

大的国际动员和政治引导，将催生出全球健康事业的一个黄金十年。在过去的十年中，主要的初步行动包括设立联合国千年发展目标；建立宏观经济学和卫生委员会；创建抗击艾滋病、肺结核与疟疾全球基金；TRIPS协定多哈宣言，确认在保护专利实施细则时，保护公共健康的国家权力；以及建立产品开发合作关系，促进被忽视的研发领域的发展。通过提高药物供应水平，在降低 HIV、肺结核和疟疾的发病率和死亡率方面取得了显著进展。HIV抗逆转录病毒疗法已经覆盖了660万人，并且通过非专利药品竞争，使得医疗价格显著降低。然而，随着更多的患者需要治疗，且患者所需的新药价格由于专利保护而上涨，捐赠者支持力度开始下降。肺结核的发病率已经开始下降，然而多药抗药性肺结核的诊断和治疗进展缓慢，其原因是治疗的复杂性和较高的药物花费。当前，随着治疗范围的扩大，需要在恰当时机迅速引入的新药物正在研发之中。青蒿素组合治疗是一种更廉价的疗法，该疗法的引入显著降低了疟疾的发病率和死亡率，但是在保证实施最新的治疗严重性疟疾的卫生计划方针方面，仍面临挑战。展望下一个

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十年，我们看到一个令人担忧的情况，那就是伴随着疾病负担转移的附加卫生工作重点，与政策注意力和资金支持减弱之间的矛盾。随着药物市场的变化，可以预见到在生产和保证廉价药物供应方面的困难，当前的市场贸易和卫生状况之间尚未建立起恰当的平衡。全球框架内药物研发和供应的系统变化，需要支持增加创新的要求，并为下一个十年提供健康工具。

RESUMEN

Una sólida movilización internacional y política generará una década dorada para la salud mundial. Las iniciativas fundamentales de la última década incluyen la propuesta de Objetivos de Desarrollo del Milenio relacionados con la salud; la Comisión sobre Macroeconomía y Salud; la creación de un Fondo mundial de lucha contra el SIDA, la tuberculosis y la malaria; la Declaración de Doha relativa al acuerdo sobre los ADPIC y la salud pública, en el que se reconocen los derechos de los países de proteger la salud pública cuando se implementen las leyes de patentes; y la creación de asociaciones para el desarrollo de productos con el fin de tratar las áreas descuidadas de investigación y desarrollo. Se logró un progreso importante en la reducción del índice de mortalidad causada por el VIH y su incidencia, la tuberculosis (TB) y la malaria, debido al aumento de las posibilidades de acceso a los medicamentos para tratar estas enfermedades. El tratamiento antirretroviral para el VIH fue tornó más accesible y benefició a 6,6 millones de personas. Además, los precios de los medicamentos se redujeron en forma significativa a raíz de la competencia con los genéricos. Sin embargo, el apoyo de los donantes comenzó a disminuir en el momento en que los pacientes más

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Access to Medicines in Resource-Limited Settings

necesitan el tratamiento y los precios de los nuevos medicamentos están en aumento a causa de la protección de patentes. La incidencia de la TB comenzó a disminuir, aunque el progreso en el diagnóstico y el tratamiento de pacientes con cepas de TB resistentes a una variedad de fármacos ha sido lento debido a la complejidad del mismo y al alto costo de los fármacos. Se están desarrollando nuevos fármacos con efectos prometedores que deben ser introducidos con rapidez, pero de manera adecuada, mientras se amplía el tratamien-

to. La introducción de terapias combinadas a base de artemisinina más asequibles para tratar la malaria contribuyó en la reducción significativa de la incidencia y tasa de mortalidad de esta enfermedad; no obstante, el desafío sigue siendo garantizar que se implementen las últimas recomendaciones para el tratamiento de la malaria grave. Para la próxima década, se prevé un desajuste preocupante entre las prioridades adicionales en materia de salud, así como un costo variable de la enfermedad que se debe tratar y la atención política y

he past 10 years have been hailed as the decade of health.1 The Millennium Development Goals, established in 2000, included health as a priority area for poverty alleviation.2 In December 2001, the World Health Organization (WHO) Commission on Macroeconomics and Health convincingly showed that investing in health boosts economic development.3 The Commission has been credited for helping to trigger a fivefold increase in funding for global health, from (US)$6 billion in 2000 to $30 billion in 2010.4 Financial commitments were solidified in January 2002 with the creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) following calls by then United Nations Secretary General Kofi Annan to establish “a war chest to fight the diseases of poverty.”5 It was also 10 years ago, in November 2001, that members of the World Trade Organization adopted the Doha Declaration on the TRIPS (Trade-Related Aspects of Intellectual Property Rights) Agreement and Public Health amid fierce debates about the negative impact of trade rules on access to medicines. The declaration affirmed countries’ sovereign right to protect public health when intellectual property stands in the way of access to medicines.6 Less noted but no less important was the founding roughly a decade ago of product development partnerships (PDPs) as not-for-profit entities to conduct and coordinate research and development into new drugs, diagnostics, or vaccines to address pressing health needs of resource-limited settings: the Medicines for Malaria Venture established in 1999, the Global Alliance for TB Drug Development (TB Alliance) in 2000, and the Drugs for Neglected Diseases initiative in 2003, to name a few. These new initiatives took drug development outside both industry and government.7,8 Three main factors lay behind these important, landscape-changing, political developments. First, the striking, unaddressed health needs for infectious diseases, and in particular human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome

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apoyo económico cada vez más escasos. Se prevén dificultades para producir y garantizar el acceso a medicamentos asequibles en un mercado farmacéutico cambiante, en el que se no se ha podido encontrar un equilibrio adecuado entre el comercio y la salud. Es necesario hacer cambios sistemáticos a partir de un marco global para la investigación, el desarrollo y el acceso a los medicamentos para sustentar la cantidad de innovaciones cada vez más alta y el acceso a las herramientas de salud de la próxima década.

(AIDS), sparked international civil society mobilization.9 The Pretoria court case, in which a consortium of 39 pharmaceutical companies took the South African government to court over a law to improve access to antiretroviral medicines (ARVs), particularly exemplified the crisis in access to medicines in developing countries. Civil society mobilization in South Africa and elsewhere in the South, linking up with activists in the North, helped bring global attention to the problem and ultimately resulted in the withdrawal of the pharmaceutical industry lawsuit.10 Second, an effective system of producing affordable medicines was coming under threat, as trade agreements increasingly required ever tighter patent protection, including in developing countries with large generic manufacturing industries. HIV again served to exemplify the problem, with the annual cost of treatment with patent-protected ARVs reaching $10 000.10 Third, political will emerged to challenge the systemic problem of neglected diseases research as the lack of a profitable market for diseases primarily affecting people in developing countries meant that research and development had come to a standstill in previous decades. An analysis found that only 1% of the new medications developed between 1975 and 1999 were treatments for tuberculosis (TB) and tropical diseases, despite these diseases causing 11% of the global disease burden.11 The most commonly used tools for tuberculosis diagnosis remained unchanged for more than a century, and the most recent treatments were developed from the 1940s to the 1960s.12 This article discusses key developments in improving access to medicines for the big 3 killer infectious diseases: HIV, TB, and malaria; the role the initiatives launched 10 years ago have played to address them; and the challenges that lie ahead. HIV/AIDS

Thirty-four million people are living with HIV today, more than ever before. But during the last decades, new infections were reduced from 3.1 to 2.7 million and AIDS deaths from 2 to 1.8 million per year.13

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Ten years ago, just a few thousand patients were on antiretroviral treatment (ART) in developing countries, a number that has now reached more than 6.6 million.13 Though this is a major achievement that seemed unthinkable 10 years ago, it still means that only half of those in need today have access to treatment. A decade ago, ART was considered too expensive and too complex for developing countries. The considerable decrease in the price of HIV medicines driven by generic competition—from $10 000 per patient per year a decade ago to $61 today14—the simplification of drug regimens and monitoring needs, and the elaboration of strategies to simplify treatment provision and overcome human resources shortages by shifting medical tasks away from doctors to other healthcare workers were all key to breaking the deadlock. Civil society mobilization played an essential role in each of these aspects.15 Substantial international political commitment and funding was necessary as countries suffering from the world’s highest burden of HIV could not have afforded the resources necessary to drive an appropriate response alone. The GFATM is widely recognized as one of two main funding mechanisms that have helped countries to increase prevention of HIV, TB, and malaria and expand treatment of and care for people with those diseases and is an example of what can be achieved through international solidarity with a clear focus on patients. GFATM ensured ART for 3.3 million people by the end of 2011 alone and aims to support 7.3 million by 2016.16 The US President’s Emergency Plan for AIDS Relief, launched in 2003, is the second important pillar of international support to AIDS prevention and treatment, supporting 3.9 million people on ART by the end of September 2011 and with a new target of 6 million people on treatment by the end of 2013.17 Until now, GFATM has been unique in adopting a “demand-driven” approach that relies on mobilizing sufficient resources to support all reasonable proposals for funding from affected countries. Proposals prepared at country level by Country Coordinating Mechanisms bringing together representatives from government, aid agencies, and non-governmental organizations, and people living with the diseases have promoted local ownership and participatory decision making in determining needs and overseeing implementation. Yet despite an impressive track record, the GFATM faces significant financial shortfalls, forcing it to cancel for the first time in its 10-year history its annual funding round.17 Affected countries now effectively have no new funding opportunities until 2014. Though a transition mechanism is being put in place to prevent interruption of programs, the funding crisis will significantly slow the expansion of life-saving treatment for the 3 diseases. It will also make it hard to make important improvements in the quality of care through, for example, earlier initiation of ART and better treatment regimens and monitoring.

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Decreased financial support for global health in general, and HIV/AIDS in particular, occurs despite political commitments to have 15 million people on treatment by 201519 and at a time when there is evidence that the epidemic can be reversed. A landmark study in 2011 showed that ART not only reduces mortality and morbidity but also can substantially reduce HIV transmission.20 This makes ART provision the most effective biomedical prevention tool for HIV/ AIDS we currently have21 and means that scaling up ART access makes good financial sense as well.22 With funding for AIDS decreasing,13 ensuring that medicines remain affordable is as important as ever. But all key generic-producing countries including India (which supplies more than 80% of ARVs in developing countries23), China, and Brazil protect patents, so generic production of new medicines generally is blocked. Newer ARVs, such as raltegravir and etravirine, to which patients will eventually need to switch, exist only as originator products and cost (US)$675 and (US)$913 per year, respectively (to which the price of 2 or more other drugs need to be added to form a complete treatment regimen).14 Unless these prices are reduced, treatment providers are effectively facing a treatment time bomb, as more and more patients will need to be switched to more expensive regimens.24 Tuberculosis

For most of the past decade, AIDS has been fuelling the TB epidemic in Africa, and TB remains the second leading cause of death from an infectious disease after HIV, with up to 1.5 million deaths per year. Progress in bringing TB under control has been slow, and global TB incidence only started decreasing modestly in 2006.25 The GFATM has played an important role, having funded 8.6 million TB treatments since its inception and providing about $0.5 billion per year, mainly to the poorest countries. With an affordable treatment regimen and the biggest health burden in some of the emerging economies like China and India, TB control may at first sight seem less vulnerable to dwindling international support than HIV, with 86% of financing coming from the high-burden countries themselves.25 Yet countries are struggling with the growing and costly challenge of multidrug-resistant (MDR) and extensively drug-resistant TB,26 as the usefulness of the WHO-recommended 6-month treatment regimen becomes increasingly limited. The number of MDR-TB cases is growing every year in Eastern Europe, Central Asia, and Africa, with Belarus currently topping the list with 26% of new TB cases and 60% of retreatment cases being MDR-TB.25 Considerable efforts by civil society organizations helped make MDR-TB a public health priority. As with HIV, it required challenging notions that MDR-TB was untreatable in resource-limited settings and that it would divert attention and resources from treating

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Access to Medicines in Resource-Limited Settings

drug-susceptible TB.27 Although MDR-TB is now an international priority with an agreed-upon global plan to universal access to treatment,28 too little practical progress has been made over the last decade. Only 46 000 people are diagnosed and treated out of an estimated 440 000 new cases every year.25 The cost of second-line drugs remains high at around $4500 on average per patient. Currently, the DR-TB drug market is too small and fragmented and barely attracts manufacturers. Price reductions from economies of scale will be realized only when more patients are put on treatment, but the vicious circle of high costs dissuading countries from addressing MDRTB—meaning limited patient numbers keep prices high—needs to be overcome.29 The complexity of treatment is an additional barrier to scale up. Diagnosis is complex and expensive and even in high-prevalence settings is not yet routinely offered. A new automated molecular test offers a much faster diagnosis but costs $17 per test. In addition, to obtain an individualized picture of drug resistance and determine treatment options, full culture and drug sensitivity testing are still required.30 MDR-TB treatment lasts for 18 to 24 months and is highly complex, with drugs inducing many side effects. As a result, treatment outcomes are poor (around 60% treatment success) and defaulter rates high.31 Nevertheless, it has been demonstrated that good outcomes can be achieved in resourcelimited settings supported by clinical or communitybased models.32,33 Despite the difficulties, treatment expansion is feasible. But the financial situation of the GFATM is threatening initiatives to expand treatment for MDR-TB. Some high-burden countries that finally recognize the severity of the problem may be able to finance at least part of the response with their own resources: India, which produces a quarter of the world’s MDR-TB cases, plans to diagnose and treat 30 000 new patients per year by 2014. Improving the treatment regimen to make it more efficacious, of shorter duration, and more affordable will be an essential part of the path toward rapid and large expansion of MDR-TB treatment. Though the problem of drug resistance has been driven by irrational drug use and prescribing, with over-the-counter availability of TB drugs in many countries (which remains unaddressed), it also has been a predictable crisis, as no new TB drugs have reached the market since the 1960s. Three PDPs were founded to address the research gaps in TB: the Global Alliance for TB drug development, the Foundation for Innovative New Diagnostics, and Aeras, for vaccines. In addition, some drug companies have restarted limited investment into TB drug development, often as a goodwill gesture. After decades of inactivity, there is again a pipeline of TB drugs in development, although this pipeline is not nearly as robust as those for more profitable diseases.12 Two new drugs, bedaquiline and delamanid, are the most advanced in clinical development. Both are

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being tested in MDR-TB patients, and approval by the US Food and Drug Administration is expected as early as 2012. However, additional studies will be needed not only to add these drugs to existing regimens but also to determine if a better and shorter regimen for MDR-TB can be defined, removing at least some of the old drugs. There is so far insufficient interest in and funding for such studies and few research sites with adequate capacity to carry them out. Market introduction of the new drugs is another challenge: they should be available to all those in need but only through appropriate programs and adequately skilled health workers in order to avoid the rapid development of resistance. Price should not be a barrier and should not be used as a way to restrict use. Ultimately, a completely new regimen, effective against both current drug-sensitive and drug-resistant TB, is needed. This still is some way off, at least for a universal regimen that will not require sophisticated tests before treatment can be started. Malaria

Progress in malaria control over the past decade has been significant. Global malaria incidence decreased by 17% and malaria-specific mortality by 26% since 2000. Yet malaria still takes a heavy toll, with an estimated 216 million episodes of malaria and 655 000 deaths occurring in 2010. Of these, 91%were in Africa, and 86% of global malaria deaths were in children under 5 years of age.34 More recent estimates suggest that the disease burden is even higher, putting the number of deaths from malaria in 2010 at 1.24 million.35 Three tools were the essential ingredients of progress during the past decade: artemisinin-based combination therapies (ACTs), impregnated bednets (including long-lasting insecticide-treated nets), and malaria rapid diagnostic tests (RDTs), which enable the confirmation of malaria even in the most remote areas where microscopy is not available.36 Artemisinin, a natural compound of Artemisia annua, an herb described as “a true gift from old Chinese medicine,” has been used as a traditional treatment for malaria and fever for more than 2 millennia and became more widely recognized and studied in the 1960s to 1990s.37 WHO first stated that ACTs should be introduced in 2001, after studies had long shown widespread and high-level resistance to the older drugs and in particular choloroquine, which has been in use since the 1940s.38 It took repeated, often redundant resistance studies in many countries and much mobilization over the following years to convince African governments to change national protocols.39 From the beginning, with ACTs being considerably more expensive than older, increasingly ineffective treatments such as chloroquine and sulfadoxine-pyrimethamine, cost was a major barrier. With international funding necessary for their large-scale introduction, the GFATM became the main funding source, supporting 230 million malaria treatments to date. Since 2005, the

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US President’s Malaria Initiative (PMI) has acted as a second pillar of international support to malaria control. In parallel, important price reductions were achieved thanks to generic competition. In 2001, WHO negotiated an agreement with Novartis (Basel, Switzerland), the manufacturer of one of the main ACT treatments, to lower the cost the company was charging the public sector from $4 to $2.40 per adult treatment. The company at the time claimed that $2.40 was its cost, implying it could go no lower. But competition from multiple producers has since lowered the price to under $1, illustrating again how market competition acts as a greater catalyst to price reductions than negotiated discounts with pharmaceutical companies.40 Reducing the price of ACTs until they reach a level similar to the average chloroquine price of less than $0.10 will not be feasible, as the production of the raw material through plant extraction is too costly. A semisynthetic artemisinin will reach the market in 2012 but with limited production capacity and only modest cost advantages initially.41 A scheme was developed in 2004 to subsidize the cost of ACTs in order to make the medicines more affordable in the private sector. This concept is currently being piloted through the Affordable Medicine Facility— malaria (AMFm) in 7 countries, starting in 2011.42 Many questions remain about the scheme. Mark-ups by middlemen add significantly to the end price, and some question whether scarce donor money shouldn’t be used to expand access to free care through the public sector rather than subsidizing the private sector, particularly given the funding crisis currently affecting global health. The AMFm got off to a troubled start as it allowed orders from wholesalers to increase so rapidly that they disrupted the global raw material market, contributing to a tripling of the raw material price in 2011.43 More recently, WHO also has changed its recommendations to countries for the treatment of severe malaria—from quinine injections to injectable artesunate. Severe malaria occurs less frequently than uncomplicated malaria but is often fatal. Injectable artesunate is safer and easier to use, and it reduces mortality by 39% in adults and 24% in children, compared to quinine.44 It is also more expensive, but a global treatment switch would only cost an additional $31.8 million per year—a small investment within the billion dollar budgets of the GFATM and PMI even in the current financial climate.45 After initial difficulties, the uptake of ACTs has been encouraging in the last 5 years, with annual sales of ACTs approximately matching the annual number of malaria cases. But the concern remains that malaria treatments are still widely used based on fever symptoms alone. As diagnosis is not always confirmed through microscopy or the use of RDTs, there is significant overtreatment. An increased use of RDTs to confirm malaria diagnosis is needed as is now recommended by WHO.46

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The emergence of drug resistance is a threat because of the continued availability of artesunate monotherapy, low-quality drugs and potentially because of overuse (as with chloroquine previously). Suspected resistance to artemisinin has now been identified in 4 countries in Southeast Asia.34 It would be a tragedy to lose “the gift of Chinese medicine” within a couple of decades of WHO’s recommending its introduction and after it has been used for millennia. It will also be very hard to replace. Malaria drug research has been revived through the product development partnership’s Medicines for Malaria Venture, but most of the drugs in the pipeline are artemisininlike molecules, and a different drug class is at least 5 years away. Ambitious targets have been set to eliminate malaria in a range of countries.36 This may be feasible in all but the countries with the highest transmission rates. It seems more urgent, therefore, to control malaria and reduce deaths in the 42 countries in Africa that are not ready yet for elimination. Looking to the next decade

The past decade has been a golden decade for global health, driven by strong international mobilization and political will to address priority health problems of the poorest. It has resulted in significant progress in expanding access to treatment and reducing mortality from and incidence of the main infectious diseases. Nevertheless, major needs remain, including those outlined below. Competing Health Priorities

The “vertical” approach to HIV, TB, and malaria is criticized by some as a distraction from the need to support health systems more broadly or by those who contend that the scope of the GFATM should be expanded; for example, to finance the health-related Millennium Development Goals.47,48 Other health challenges such as mother and child health received comparatively less investment. However, one of the strengths of the GFATM has been its clear focus on patients and its prioritization of 3 diseases. Whatever approach is adopted as a means to address a broader set of health priorities in an integrated way, it will need to build on, and not backpedal on, the progress being made for major infectious diseases. Shifting Burdens of Disease

Additional health challenges have increased in importance during the past decade: many developing countries now face the double burden of infectious diseases and noncommunicable diseases. Addressing noncommunicable diseases will require both a focus on prevention and basic interventions but also the access to treatment for complex diseases including cancers. Policy discussions have so far only focused on the first; lessons need to be learned from HIV, another chronic disease, from the past decade.49

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Dwindling Political Attention and Financial Shortfalls

Current financing is insufficient to even adequately address HIV, TB, and malaria, and there is a risk of backtracking on progress. International funding for global health has become more difficult to mobilize, and the time of large financial commitments made at annual G8 meetings is over. The financial crisis has made the leading economies more inward looking. Affected countries need to increase their investment in health, but the need for global solidarity will not go away. Major emerging countries like Brazil, Russia, India, China, and South Africa (collectively called the “BRICS”) do not appear ready to become significant international donors. The health challenges in BRICS countries are significant, and they are only just being weaned off international donor support. Least-developed countries have exceeded in total health expenditure the recommendations of the Macroeconomics and Health Commission (personal communication with Dr David Evans, World Health Organization, December 16, 2011). Significant additional and predictable funding for global health solidarity is therefore needed. An example of how innovative financing can benefit health already exists: a tax on airline tickets implemented by France and a number of other countries generates revenues that flow to UNITAID, a multilateral organization that funds medicines and diagnostics for HIV, TB, and malaria.50 Additional resources could be generated by creating a financial transaction tax (FTT), such as the one currently being debated in Europe, and dedicating a portion of the proceeds to healthcare.51 As the idea of a Eurozone FTT becomes a firmer political possibility, no leaders have yet committed a portion of the expected revenue to support global health. Increasing Difficulties in Producing and Providing Access to Affordable Medicines

Increased intellectual property protection that prevents production of newer medicines in key genericproducing countries such as India, Brazil, and China will continue to be fiercely debated in the coming decade. In the future, it should be assumed that all new medicines that are true innovations (and not minor modifications to existing drugs) will be widely patented. The need to ensure affordability will require political will to enforce strict patentability criteria, allow for patent opposition, routinely issue compulsory licenses, and resist pressure by rich countries to further increase monopoly protections. Although the Doha Declaration continues to play an important role, it is increasingly being eroded. Under international trade regulations, countries are free to determine patentability criteria or to issue compulsory licenses to overcome patents, but few countries have implemented these flexibilities into national legislation, and fewer still have made use of them—with the notable exception of India, Thailand and Brazil.52 This is a reflection of the considerable

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political pressure from industry and rich countries not to use them. A better balance between health and trade is needed as the importance of reining in drug costs becomes ever more acute. Increasingly, use of these flexibilities has been constrained through bilateral trade agreements. Both the European Union–India Free Trade Agreement and the European Free Trade Association-India deal currently being negotiated pose a threat to access to medicines by introducing, for example, intellectual property enforcement measures. The United States is negotiating the Transpacific Partnership Agreement with a number of Asian and Latin American countries, which it considers the blueprint for future US-led free trade agreements where significant threats to access to medicines exist.53 The overall trend is that a system of affordable medicine production for resource-limited countries is continuously eroding and nothing adequate is being proposed to replace it. Though health groups have been fighting a defensive battle to maintain the possibility of generic production for as long as possible, it may now be time to call for revision of the TRIPS Agreement itself to ensure that it is consistent with access to medicine as a key aspect of the right to health. Evolving Strategies From Drug Companies

Pharmaceutical companies continue to affirm that concerns around the price of medicines can be resolved through tiered pricing policies—where developing countries are offered price discounts, with the leastdeveloped countries paying the least. There is evidence, however, that lower-middle income countries are squeezed out of standardized price discounts and face increasing prices.23 While tiered pricing reduces the cost burden, it is in most cases significantly less efficient than generic competition in reducing prices.54 Some patent-holding pharmaceutical companies have entered into voluntary license agreements to authorize generic manufacturers to produce generic versions of their medications. The terms of such licenses are typically secret and have many restrictions, on geographical scope in particular. Voluntary licenses can be part of the solution if they are used in a way that responds to medical needs, as pioneered by the recently created Medicines Patent Pool.10 Experience with voluntary licenses to date is that companies will need to be under greater pressure before they allow access in all countries; the inherent limitation lies in the voluntary nature of this approach. In addition, the decade ahead will see changes in the pharmaceutical industry—including Indian generic companies being bought by multinational companies and generic companies entering into research and development—that are of concern for the future capacity of generic competition for newer drugs. Profit expectations on one hand and access challenges on the other for noncommunicable diseases will likely crystallize the fight for access to medicines.

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

A Global Framework for Research and Development

A decade after the establishment of PDPs, there is today a range of products in the pipeline that can be expected to reach patients in the coming years. This is significant progress. But at the same time, PDPs are only a very limited effort to address large research and development needs not comparable to investments made into more profitable areas like cardiovascular diseases or even hepatitis C. The TB Alliance’s goal to develop a completely new treatment regimen that works for all TB patients, for example, remains many years away. Beyond HIV, TB, and malaria and certain neglected tropical diseases, significant innovation needs remain unaddressed. The PDPs also face considerable funding challenges, with public funding having decreased since onset of the financial crises and philanthropic funding, on which the PDPs are still heavily dependent, not being easily expanded.55 Intense policy discussions have taken place at the intergovernmental level during the past decade recognizing that more systematic changes to the current research and development system are needed to ensure that research and development is driven toward major public health needs and the specific requirements of resourcelimited settings and that its fruits are affordable.56,57 A key concept that has emerged is a need to separate the cost of research and development from the price of products. This means that research and development should be funded with grants or innovation rewards (or prizes)58 rather than relying on high prices protected by drug monopolies to recoup investments made into medical research and drug development. This separation would allow research and development to be steered toward areas of greatest medical need, and not only as in the current patent-driven model, toward areas of high commercial return. At the same time, such an approach would overcome the problem of high product prices that leads to the exclusion of patients who cannot afford them. A WHO Consultative Expert Working Group on Research and Development: Financing and Coordination has further examined the available options and recommends to the World Health Assembly in May 2012 to start negotiation of a research and development convention as a binding legal instrument to ensure adequate funding toward agreed health priorities and access to the fruits of this research.59 This is the type of long-term solution that countries need to support to ensure that future innovation is driven in a way that it meets health needs, products are priced affordably, and the access to medicine struggles of the past decade are not condemned to be repeated. References 1. Global health in 2012: development to sustainability. Lancet. 2012 Jan 21;379(9812):193. 2. United Nations General Assembly. United Nations Millennium Declaration. Resolution A/RES/55/2. New York: United Nations General Assembly, September 18, 2000. Cited February 2, 2012. Available from: http://www.un.org/millennium/ declaration/ares552e.pdf. 3. Sachs J. Macroeconomics and Health: Investing in Health for Economic Development. Report of the Commission on Macroeconomics and Health. World Health Organization. Geneva.

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4. Das P, Samarasekera U. The Commission on Macroeconomics and Health: 10 years on. Lancet. 2011; 378(9807): 1907-8. 5. Annan K. Ten-year fight for world health A war chest Le Monde Diplomatique January 2012 http://mondediplocom/2012/01/16warchest [accessed 26 January 2012]. 6. Declaration on the TRIPS agreement and public health: adopted on 14 November 2001. World Trade Organization. http://www.wto.org/english/thewto_e/minist_e/ min01_e/mindecl_trips_e.htm. Accessed January 28, 2012. 7. Ridley RG, Lob-Levyt J, Sachs J, Johns D, Evans T, Bale HE, et al. Round table. A role for public-private partnerships in controlling neglected diseases? Bull World Health Organ. 2001; 79(8): 771-7. 8. Moran M RA, Guzman J, Diaz J, Garrison C. The new landscape of neglected disease drug development. London School of Economics and The Wellcome Trust. London, 2005. 9. von Schoen Angerer T, Wilson D, Ford N, Kasper T. Access and activism: the ethics of providing antiretroviral therapy in developing countries. Aids. 2001;15 Suppl 5: S81-90. 10. Hoen E, Berger J, Calmy A, Moon S. Driving a decade of change: HIV/AIDS, patents and access to medicines for all. J Int AIDS Soc. 2011 Mar 27;14:15. 11. Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet. 2002 Jun 22;359(9324):2188-94. 12. Ma Z, Lienhardt C, McIlleron H, Nunn AJ, Wang X. Global tuberculosis drug development pipeline: the need and the reality. Lancet. 2010 Jun 12;375(9731):2100-9. 13. World Health Organization. Global HIV/AIDS response: epidemic update and health sector progress towards universal access: Progress report 2011. Geneva: World Health Organization; 2011. Cited January 26, 2012. Available from: http:// whqlibdoc.who.int/publications/2011/9789241502986_eng.pdf. 14. Médecins Sans Frontières. Untangling the web of anti-retroviral price reduction. 14th ed. Geneva: Médecins Sans Frontières; 2011. 15. Ford N, Calmy A, Mills EJ. The first decade of antiretroviral therapy in Africa. Global Health. 2011 Sep 29;7:33. 16. The Global Fund. Our strategy: the global fund strategy 2012-2016: investing for impact. http://www.theglobalfund.org/en/about/strategy/. Accessed January 28, 2012. 17. Remarks by the president on world AIDS day [news release]. Washington, DC: The White House Office of the Press Secretary; December 1, 2011. http://www.whitehouse.gov/the-press-office/2011/12/01/remarks-president-world-aids-day. Accessed January 28, 2012. 18. Hurst A. The global fund adopts new strategy to save 10 million lives by 2016. November 23, 2011. http://www.theglobalfund.org/en/mediacenter/pressreleases/2011-11-23_The_Global_Fund_adopts_new_strategy_to_save_10_million_ lives_by_2016/. Accessed January 28, 2012. 19. United Nations General Assembly. Political declaration on HIV/AIDS: intensifying our efforts to eliminate HIV/AIDS. Resolution A/RES/65/277. New York: United Nations General Assembly; 2011, 20. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. 21. Karim SS, Karim QA. Antiretroviral prophylaxis: a defining moment in HIV control. Lancet. 2011 Dec 17;378(9809):e23-5. 22. Schwartländer B, Stover J, Hallett T, et al. Towards an improved investment approach for an effective response to HIV/AIDS. Lancet. 2011 Jun 11;377(9782):2031-41. 23. Waning B, Diedrichsen E, Moon S. A lifeline to treatment: the role of Indian generic manufacturers in supplying antiretroviral medicines to developing countries. J Int AIDS Soc. 2010 Sep 14;13:35. 24. All Parliamentary Group on AIDS. The treatment timebomb. London: All Parliamentary Group on AIDS; 2009. 25. World Health Organization. Global tuberculosis control 2011. Geneva: World Health Organization; 2011. 26. Keshavjee S, Farmer PE. Picking up the pace—scale-up of MDR tuberculosis treatment programs. N Engl J Med. 2010 Nov 4;363(19):1781-4. 27. Farmer P. Infections and inequalities: the modern plagues. Berkeley: University of California Press; 1999. 28. Nathanson E, Nunn P, Uplekar M, et al. MDR tuberculosis—critical steps for prevention and control. N Engl J Med. 2010 Sep 9;363(11):1050-8. 29. Médecins Sans Frontières. DR-TB drugs under the microscope: the sources and prices for drug resistant tuberculosis medicines. Geneva: Médecins Sans Frontières, International Union Against TB and Lung Disease; 2011. 30. Vassall A, van Kampen S, Sohn H, et al. Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis. PLoS Med. 2 2011 Nov;8(11):e1001120. 31. Orenstein EW, Basu S, Shah NS, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009 Mar;9(3):153-61. 32. Shin S, Furin J, Bayona J, Mate K, Kim JY, Farmer P. Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience. Soc Sci Med. 2004 Oct;59(7):1529-39. 33. Malla P, Kanitz EE, Akhtar M, F et al. Ambulatory-based standardized therapy for multi-drug resistant tuberculosis: experience from Nepal, 2005-2006. PLoS One. 2009 Dec 23;4(12):e8313. 34. World Health Organization. World malaria report 2011. Geneva: World Health O4ganization; 2011. 35. Murray CJ, Rosenfeld LC, Lim SS, et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012 Feb 4;379(9814):413-31. 36. Roll Back Malaria Partnership. Eliminating malaria: learning from the past, looking ahead. Geneva: World Health Organization; 2011.

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Access to Medicines in Resource-Limited Settings

37. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011 Oct 11;17(10):1217-20. 38. Roll Back Malaria Partnership, World Health Organization. The use of antimalarial drugs: report of a WHO informal consultation: 13-17 November 2000. Geneva: Roll Back Malaria/World Health Organization; 2001. 39. Guthmann JP, Checchi F, van den Broek I, et al. Assessing antimalarial efficacy in a time of change to artemisinin-based combination therapies: the role of Médecins Sans Frontières. PLoS Med. 2008 Aug 5;5(8):e169. 40. Moon S, Pérez Casas C, Kindermans JM, de Smet M, von Schoen-Angerer T. Focusing on quality patient care in the new global subsidy for malaria medicines. PLoS Med. 2009 Jul 21;6(7):e1000106. 41. Barbacka K, Baer-Dubowska W. Searching for artemisinin production improvement in plants and microorganisms. Curr Pharm Biotechnol. 2011 Nov 1;12(11):1743-51. 42. Matowe L, Adeyi O. The quest for universal access to effective malaria treatment: how can the AMFm contribute? Malar J. 2010 Oct 8;9:274. 43. Roll Back Malaria Partnership, World Health Organization. RBM-WHO round table on ACT supply. Geneva: Roll Back Malaria Partnership, World Health Organization; 2011. 44. Dondorp AM, Fanello CI, Hendriksen IC, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an openlabel, randomised trial. Lancet. 2010 Nov 13;376(9753):1647-57. 45. Ford NP, de Smet M, Kolappa K, White NJ. Responding to the evidence for the management of severe malaria. Trop Med Int Health. 2011 Sep;16(9):1085-6. 46. World Health Organization. Universal access to malaria diagnostic testing: an operational manual 2011. Geneva: World Health Organization; 2011. 47. Balabanova D, McKee M, Mills A, Walt G, Haines A. What can global health institutions do to help strengthen health systems in low income countries? Health Res Policy Syst. 2010 Jun 29;8:22. 48. Cometto G, Ooms G, Starrs A, Zeitz P. Towards a global fund for the health MDGs? Lancet. 2009 Oct 3;374(9696):1146. 49. Beaglehole R, Bonita R, Alleyne G, et al. UN High-Level Meeting on NonCommunicable Diseases: addressing four questions. Lancet. 2011 Jul

30;378(9789):449-55. 50. Simon C, de Lemos G. [UNITAID: an innovative and collective financing system for the fight against malaria, AIDS and tuberculosis]. Med Trop (Mars). 2006 Dec;66(6):583-4. French. 51. McColl K. Bill Gates is to urge G20 nations to adopt a financial transaction tax to fund development. BMJ. 2011 Oct 26;343:d6963. 52. Ford N, Wilson D, Costa Chaves G, Lotrowska M, Kijtiwatchakul K. Sustaining access to antiretroviral therapy in the less-developed world: lessons from Brazil and Thailand. AIDS. 2007 Jul;21 Suppl 4:S21-9. 53. How the Trans-Pacific Partnership Agreement threatens access to medicines. Doctors Without Borders/Médecins Sans Frontières (MSF) Campaign for Access to Essential Medicines TPP Issue Brief, September 2011. Cited January 26, 2012. Available from: http://www.doctorswithoutborders.org/press/2011/MSF-TPPIssue-Brief.pdf. 54. Moon S, Jambert E, Childs M, von Schoen-Angerer T. A win-win solution?: A critical analysis of tiered pricing to improve access to medicines in developing countries. Global Health. 2011 Oct 12;7(1):39. 55. Moran M, Guzamn J, Abela-Oversteegen L, et al. Neglected disease research and development: is innovation under threat? Sydney: Policy Cures; 2011. Cited January 26, 2012. Available from: http://policycures.org/downloads/g-finder_2011.pdf. 56. ‘t Hoen E. Report of the Commission on Intellectual Property Rights, Innovation and Public Health: a call to governments. Bull World Health Organ. 2006 May;84(5):421-3. 57. Sixty-first World Health Assembly. Global strategy and plan of action for public health, innovation and intellectual property. Resolution A61.21. Geneva: World Health Assembly; 2008. 58. Love J, Hubbard T. Prizes for innovation of new medicines and vaccines. Ann Health Law. 2009;18(2):155-86, 8 p. preceding i. 59. World Health Organization Consultative Expert Working Group on Research and Development. Report of the third meeting of the consultative expert working group on research and development: financing and coordination. Geneva: World Health Organization; 2011.

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The NAFKAM International Registry of Exceptional Courses of Disease Related to the Use of Complementary and Alternative Medicine Vinjar Fønnebø, PhD; Brit J. Drageset, BSc; Anita Salamonsen, MSc

Author Affiliations Vinjar Fønnebø, PhD, is professor of preventive medicine at and director of the National Research Center in Complementary and Alternative Medicine (NAFKAM), Department of Community Medicine, University of Tromsø, Norway. Brit J Drageset, BSc, is a consultant and Anita Salamonsen, MSc, is a researcher at NAFKAM. Correspondence Vinjar Fønnebø, PhD vinjar.fonnebo@uit.no Citation Global Adv Health Med. 2012;1(1):60-62. Funding The Registry is 100% funded by NAFKAM, which in turn is funded by the Norwegian Ministry of Health and Care Services. Key Words Norway, patient registry, NAFKAM, case reports, exceptional courses of disease, complementary and alternative medicine, CAM, medical assessments, safety

he increasing use of complementary and alternative medicine (CAM) represents a continuing demand for treatment approaches in parallel with, or as an alternative to, conventional healthcare delivery.1,2 Some patients report considerable health improvements related to their use of CAM,3-6 and others report no effect or possibly harm.7 Limited efforts have been made so far to systematically collect patients’ personal experiences with various CAM therapies. Methods to collect “best cases” after the use of CAM in cancer patients have been initiated in the United States and Germany.5,8,9 The focus of these projects has been to assess treatment response on outcomes measured independently of the patients’ awareness of, experience with, and reflections on things such as tumor size or survival.6 They have either concentrated on one condition or have constituted a one-time limited research project. The National Research Center in Complementary and Alternative Medicine (NAFKAM) in Norway believes it is important to monitor positive as well as negative patient experiences after the use of CAM, and in 2002, the first international registry for long-term collection of exceptional “best” and “worst” cases was established. In the beginning, only severe and chronic diseases such as cancer, multiple sclerosis (MS), asthma and allergy, migraine, and chronic fatigue syndrome were included, but the registry has since been expanded to include all health conditions. The Registry of Exceptional Courses of Disease (hereafter referred to as “the Registry”) serves as a basis for research on questionnaire data, medical assessments, and interview data from “exceptional” patients’ experiences and reflections.3,6 The purposes of the Registry are to (1) collect patient-reported experiences from courses of illness/ disease that have followed a different course than expected; (2) make these patient experiences accessible to researchers in a searchable format; and (3) monitor the collected experiences and refer series of similar experiences to researchers and health authorities.

a representative from a national patient organization), and a 50% administrative position has been allocated to the day-to-day running of the Registry. The Registry is 100% funded by NAFKAM, which in turn is funded by the Norwegian Ministry of Health and Care Services. Information about the Registry is available through the websites of NAFKAM and the Norwegian Information Center on Complementary and Alternative Medicine as well as the websites of a number of cooperating patient organizations throughout Scandinavia. Doctors, alternative practitioners, and the media also provide patients with information about the Registry. So far, no paid advertising has been used. Data to be included in the Registry can only be submitted by the patient him- or herself or by close family (if the patient is a child or has passed away). The data are collected through a self-administered questionnaire (on paper) with both open and closed questions. Topics include demographic information, history of diseases, CAM and conventional treatments used, and reasons for the “exceptional” classification of the disease course. A request is made for informed consent for the use of the collected data for research purposes and consent for access to medical records from hospitals, general practitioners, and CAM providers. Some patients have attached letters, notes, books, etc. Core information from the questionnaire is entered into a database at NAFKAM, and the whole questionnaire and the informed consent form are physically stored, along with medical records collected for some cases, in fireproof, locked filing cabinets at NAFKAM. The documents are also stored in portable document format for future retrieval. The database is placed as a part of EUTRO (an information technology solution designed to protect and manage biologic material, metadata, data, and projects for major health surveys) at the Department of Community Medicine. An overview of all available Registry variables can be found online (http://www2.uit.no/ikbViewer/page/ ansatte/organisasjon/hjem?p_dimension_ id=88112&p_menu=42374&p_lang=1).

Infrastructure

Eligible Patients

The Registry is located at NAFKAM’s offices in Tromsø, Norway. NAFKAM is part of the Department of Community Medicine at the Faculty of Health Sciences, University of Tromsø. A steering committee has been established (2 researchers from NAFKAM and

To be included in the Registry, a patient must have (1) had a disease/health problem, (2) experienced unexpected improvement or worsening of the course of disease, and (3) related this improvement or worsening to the use of CAM. In the Registry, “exceptional courses

Goals

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International Registry Related to CAM Use

of disease” refers to both best and worst courses related to the use of CAM. In best courses of disease, patients report disease remission, cure, symptom relief, or improved survival. In worst courses of disease, patients report severe adverse reactions. In best courses of disease, the patients do not define improvement of their courses of disease related to the use of CAM as miracles or spontaneous remissions, although their exceptional courses of disease can include spiritual or religious experiences or practices.3 Medical Assessments

Some reported exceptional courses of disease are medically assessed by physicians at NAFKAM and external specialists according to a predefined procedure. The assessment is performed on the basis of patient records that we have collected with the patient’s consent from hospitals and primary care. The purpose of this assessment is to determine whether a reported course of disease is likely to happen in a similar patient undergoing conventional treatment alone. These assessments are currently limited to conditions where a patient-independent evaluation is possible. A patientindependent evaluation is an evaluation where there is no need for verbal or nonverbal input from the patient to achieve a disease status description. The only condition in the Registry fulfilling this requirement at the present time is cancer. The Registry is, however, also piloting whether a similar assessment procedure can be followed for patients with MS. The medical assessment makes a conclusion at 3 possible levels. 1. Not medically exceptional: a physician would most likely see this course of disease in at least 10% of similar patients. 2. Possibly medically exceptional: a physician would most likely see this course of disease in less than 10% but more than 1% of similar patients. 3. Medically exceptional: a physician would most likely see this course of disease in 1% or less of similar patients. Research Opportunities

Research based on data from the Registry can be initiated in 2 ways. 1. Researcher-initiated research: Information about the collected data is available on the website of the Registry (http://www2.uit.no/ ikbViewer/page/ansatte/organisasjon/hjem?p_ dimension_id=88112&p_menu=42374&p_ lang=1). Any researcher can apply to the Registry steering group for access to the data. If the necessary formalities (ethics, etc) are in place, a data set will be submitted to the researcher. After ethics approval, a researcher is also allowed to contact the patient(s), initially via NAFKAM, for further information collection by interview, questionnaire, etc.

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2. Registry-initiated research: When the Registry has received 5 positive courses of similar chronic disease and the same treatment, a pseudonymous report of these 5 cases will be transferred to the NAFKAM researchers for possible efficacy/effectiveness research. The same is done after 3 courses of serious/life-threatening diseases. Safety Warnings

When the Registry has received 3 negative courses of similar chronic disease and same treatment, a pseudonymous report of these 3 cases will be sent to the Directorate of Health in Norway as a warning of a potentially harmful treatment. The same is done after one negative course of serious/life-threatening disease.   Results So Far

The Registry has received and registered a total number of 322 patient-reported exceptional courses of disease (by December 31, 2011), 317 positive and 5 negative. Of the cancer and MS courses that have been medically assessed, one has been classified as medically exceptional and 14 have been classified as possibly exceptional. The most common conditions the patients have been suffering from are cancer, MS, asthma/allergies, chronic fatigue syndrome/myalgic encephalomyelitis, conditions patients ascribe to dental-filling materials, migraine, ulcerous colitis, diabetes, and rheumatic conditions. The most commonly used CAM treatments have been massage, acupuncture, reflexology, dietary supplements, healing, and homeopathy. Published Research

Four scientific articles based on data from the Registry have been published to date.3,6,10,11 The first and second publications are a general description of the Registry and a comparative study of the procedures used internationally to register and assess exceptional courses of disease. Findings from the other 2 publications are as follows: 1. MS patients change from passive recipients of care to active explorers of healthcare independently of treatment systems. CAM facilitates the patients’ own efforts that are needed for improved health and well-being in their lives with MS. 2. Patients reporting their disease courses as exceptionally positive most often also take responsibility for developing the condition in the first place. This creates a basis for handling their disease now and in the future, often involving major changes in lifestyle and attitude toward the conventional healthcare system. Four additional scientific manuscripts based on data from the Registry are under review for publication, and one doctoral thesis will be completed in 2012.

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

Discussion

Internationally, NAFKAM is, as far as we know, the first research institution to establish a registry for patients having experienced exceptional courses of disease related to CAM treatment(s). Previously, somewhat similar approaches have been limited to positive (best) cases after cancer patients’ use of CAM and were initiated in the United States and in Germany.5,6,8,9,12 Characteristics of the NAFKAM Registry that differentiate it from previous efforts/projects are as follows: 1. It is a long-term, ongoing registry. 2. Both positive and negative courses of disease are collected. 3. Disease courses are always patient-reported and patient-defined. 4. Medical assessments are based solely on patients’ medical records. The exceptional courses of disease submitted to the Registry constitute a self-selected sample of patients from Scandinavia. It is therefore important to emphasize that based on the Registry, it is impossible to establish incidence or prevalence of being an exceptional patient. It may, however, be possible to identify some common patterns among patients reporting their disease courses as exceptional. The Registry is not intended to be a collection of miracles and spontaneous remissions. The term miracle implies a relationship to the divine and thereby to issues of faith.13,14 Spontaneous means something that occurs naturally and not as a consequence of an intervention. Thus, spontaneous remissions are defined as recoveries without reason or cause15 and are recognized in many health disorders.16 Spontaneous events could also be seen as events without “known” cause, and miracles as events where the cause is thought to be “divine.” In that understanding, both events could be interesting for the Registry. Based consistently on patient reports, the Registry has the unique opportunity of being an important basis for research on the patients’ body of knowledge. This body of knowledge can include numerous aspects of understanding that are normally not included in medical records. This body of knowledge has already resulted in valuable insight into perspectives that are important for patients to understand their diseases and change their behavior. These research results are fundamental in building an understanding of the context of patients’ CAM use, the first step in the NAFKAM research strategy.17 With medical assessments available for patients with cancer and MS, the Registry also can provide insight into patient-experienced exceptional disease courses from a strictly conventional medicine perspective. The medical and patient perspectives can be perceived as complementary perspectives underpinning different aspects of a chronic disease and living with a chronic disease. Our experience so far has shown that some of the discrepancies in these 2 perspectives are

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caused partly by a misunderstanding on the patient’s part with regard to his or her exact diagnosis. There also seems to be an interesting discrepancy between “objectively” measured symptoms and signs of disease on the one hand and reported symptom load on the other hand. Patients report feeling better even though the “measured” symptoms and signs may remain unchanged. This knowledge can become an important foundation for research based on the patients’ experiences. References 1. Bodeker G, Kronenberg F, Burford G. Policy and public health perspectives in traditional, complementary and alternative medicine: an overview. In: Bodeker G, Burford G, editors. Traditional, complementary and alternative medicine: policy and public health perspectives. London: Imperial College Press; 2007. p. 9-38. 2. Kessler RC, Davis RB, Foster DF, et al. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med. 2001 Aug 21;135(4):262-8. 3. Salamonsen A, Launsø L, Kruse TE, Eriksen SH. Understanding unexpected courses of multiple sclerosis among patients using complementary and alternative medicine: a travel from recipient to explorer. Int J Qual Stud Health Well-being. 2010 Jul 2;5. doi: 10.3402/qhw.v5i2.5032. 4. Hök J, Tishelman C, Ploner A, Forss A, Falkenberg T. Mapping patterns of complementary and alternative medicine use in cancer: an explorative cross-sectional study of individuals with reported positive “exceptional” experiences. BMC Complement Altern Med. 2008 Aug 8;8:48. 5. Jacobson JS, Grann VR, Gnatt MA, et al. Cancer outcomes at the Hufeland (Complementary/Alternative Medicine) Klinik: a best-case series review. Integr Cancer Ther. 2005 Jun;4(2):156-67. 6. Launsø L, Drageset B J, Fønnebø V, et al. Exceptional disease courses after the use of CAM: selection, registration, medical assessment, and research. An international perspective. J Altern Complement Med. 2006;12(7):607-13. 7. Markman M. Safety issues in using complementary and alternative medicine. J Clin Oncol. 2002 Sep 15;20(Suppl 1):39s-41s. 8. Nahin R. Use of the best case series to evaluate complementary and alternative therapies for cancer: a systematic review. Semin Oncol. 2002 Dec;29(6):552-62. 9. Vanchieri C. Alternative therapies getting notice through best case series program. J Natl Cancer Inst. 2000 Oct 4;92(19):1558-60. 10. Launsø L, Salamonsen A. Registry of exceptional courses of disease. [In Danish: Register for Exceptionelle Sygdomsforløb.] OMSORG, nordisk tidsskrift for palliativ medisin 2006;3:77-81. 11. Kruse T. Interpretation of illness and use of history. A patient perspective on causes of disease and roads to healing. [In Danish: Sygdomsfortolkning og historiebrug. Et patientperspektiv på årsager til sygdom og veje til helbredelse.] Bibliotek for Læger, 2009;201:432-459. 12. Büschel G, Kaiser G, Weigner M, Weigang K, Birkmann J, Gallmeier WM. Bestfallanalysen zu 4 aktuellen unkonventionellen Behandlungsverfahren in der Onkologie. Forsch Komplementärmed. 1998;5 Supp S1:68-71. 13. Pawlikowski J. The history of thinking about miracles in the west. South Med J. 2007 Dec;100(12):1229-35. 14. Stempsey WE. Miracles and the limits of medical knowledge. Med Health Care Philos. 2002;5(1):1-9. 15. Bakal DA. Minding the body: clinical use of somatic awareness. New York: Guilford; 2001. 16. Ledingham JG, Warrell DA. Concise Oxford textbook of medicine. Oxford: Oxford University Press; 2000. 17. Fønnebø V, Grimsgaard S, Walach H, et al. Researching complementary and alternative treatments—the gatekeepers are not at home. BMC Med Res Methodol. 2007 Feb 11;7:7.

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The Global Coherence Initiative: Creating a Coherent Planetary Standing Wave Rollin McCraty, PhD; Annette Deyhle, PhD; Doc Childre

Author Affiliations Rollin McCraty, PhD, is director of research at the Institute of HeartMath (IHM), Boulder Creek, California. Annette Deyhle, PhD, is a geologist, marine geochemist, and a researcher at the Global Coherence Initiative (GCI) and IHM. Doc Childre is chairman of the GCI Steering Committee and founder of IHM. Correspondence Rollin McCraty, PhD rollin@heartmath.org Citation Global Adv Health Med. 2012;1(1):64-77. Key Words Global Coherence Initiative, geomagnetic, Schumann resonances, coherence, heart-based living, global health

Abstract

The much anticipated year of 2012 is now here. Amidst the predictions and cosmic alignments that many are aware of, one thing is for sure: it will be an interesting and exciting year as the speed of change continues to increase, bringing both chaos and great opportunity. One benchmark of these times is a shift in many people from a paradigm of competition to one of greater cooperation. All across the planet, increasing numbers of people are practicing heart-based living, and more groups are forming activities that support positive change and creative solutions for manifesting a better world. The Global Coherence Initiative (GCI) is a science-based, co-creative project to unite people in heart-focused care and intention. GCI is working in concert with other initiatives to realize the increased power of collective intention and consciousness. The convergence of several independent lines of evidence provides strong support for the existence of a global information field that connects all living systems and consciousness. Every cell in our bodies is bathed in an external and internal environment of fluctuating invisible magnetic forces that can affect virtually every cell and circuit in biological systems. Therefore, it should not be surprising that numerous physiological rhythms in humans and global collective behaviors are not only synchronized with solar and geomagnetic activity, but disruptions in these fields can create adverse effects on human health and behavior. The most likely mechanism for explaining how solar and geomagnetic influences affect human health and behavior are a coupling between the human nervous system and resonating geomagnetic frequencies, called Schumann resonances, which

occur in the earth-ionosphere resonant cavity and Alfvén waves. It is well established that these resonant frequencies directly overlap with those of the human brain and cardiovascular system. If all living systems are indeed interconnected and communicate with each other via biological, electromagnetic, and nonlocal fields, it stands to reason that humans can work together in a co-creative relationship to consciously increase the coherence in the global field environment, which in turn distributes this information to all living systems within the field. GCI was established to help facilitate the shift in global consciousness from instability and discord to balance, cooperation, and enduring peace. A primary goal of GCI is to test the hypothesis that large numbers of people when in a heart-coherent state and holding a shared intention can encode information on the earth’s energetic and geomagnetic fields, which act as carrier waves of this physiologically patterned and relevant information. In order to conduct this research, a global network of 12 to 14 ultrasensitive magnetic field detectors specifically designed to measure the earth’s magnetic resonances is being installed strategically around the planet. More important is GCI’s primary goal to motivate as many people as possible to work together in a more coherent and collaborative manner to increase the collective human consciousness. If we are persuaded that not only external fields of solar and cosmic origins but also human attention and emotion can directly affect the physical world and the mental and emotional states of others (consciousness), it broadens our view of what interconnectedness means and how it can be intentionally utilized to shape the future of the world we live

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in. It implies that our attitudes, emotions, and intentions matter and that coherent, cooperative intent can have positive effects. GCI hypothesizes that when enough individuals and social groups increase their coherence baseline and utilize that increased coherence to intentionally create a more coherent standing reference wave in the global field, it will help increase global consciousness. This can be achieved when an increasing number of people move towards more balanced and selfregulated emotions and responses. This in turn can help facilitate cooperation and collaboration in innovative problem solving and intuitive discernment for addressing society’s significant social, environmental, and economic problems. In time, as more individuals stabilize the global field and families, workplaces, and communities move to increased social coherence, it will lead to increased global coherence. This will be indicated by countries adopting a more coherent planetary view so that social and economic oppression, warfare, cultural intolerance, crime, and disregard for the environment can be addressed meaningfully and successfully.

摘要

令人期待的2012年已经到来。在诸多的预言和宇宙调整运动之中，许多人确信有一件事是肯定的：这将是有趣和激动人心的一年，变化速度持续增长，在制造混乱的同时，也带来了巨大的机遇。这个伟大时代的一个标志，就是人们需要从成熟的竞争者转变为更加伟大的合作者。在这个世界上，越来越多的人正在尝试基于内心的生活方式，越来越多的团体正在为改善世界而提倡支持积极的改变和创造性的解决方案。全球相干性启动计划（GCI）是一个立足于科学的合作创造性

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The Global Coherence Initiative

项目，其目的是联合关注心脏领域和有此方面意图的人。GCI与其他机构协同工作，以实现集体力量和意识的增强。多条独立的证据线呈现出收敛性，能够有力地支持通用信息场的存在，该通用信息场能够连接所有有生命的系统和意识。我们身体内的每一个细胞都沐浴在外部和内部环境的无形的磁力波内，这种磁力波能够影响几乎每个细胞，并对生物系统内的电路产生影响。因此，我们不应感到奇怪，人类大量的生理节律和全球集体行为不仅仅与太阳活动和地磁活动同步，而且当这些场被破坏时，会对人类健康和行为产生不利影响。能够解释太阳和地磁场如何影响人类健康的一个最好的机制，是建立人类神经系统和地磁场频率的共振，这种机制称为舒曼共振，出现在地球电离层共振腔和 Alfvén波中。这些共振频率能够直接与人类大脑和心血管系统重叠，这一点已经得到公认。如果所有有生命的系统都是相互联系的，并且通过生物、电磁和非本地场进行彼此交流，则我们有理由相信人类能够以一种共同创造性的关系共同工作，不断增加通用场环境的相干性，该环境反过来将这些信息分布到该场内的所有的生命系统。 GCI致力于促进全球意识从不稳定和不调和状态转变为平衡、合作和持久的和平状态。GCI的一个主要目标，是检验处于心脏相干态并持有同一个意图的大量人群能够对地球的能量和地磁场进行编码的假说，而地球能量和地磁场是这一生理-成像和相关信息的载体波。为了能够实施这一研究，有12到14台特别设计的用于测量地球磁共振的超灵敏磁场探测仪被有计划性地安装到地球的不同位置。GCI更重要的一个目标，是鼓励尽可能多的人以更具相干性和合作的方式共同工作，以提高人类集体意识。如果我们相信，除了太阳的外源场和宇宙起源之外，甚至人类注意力和情感也能够直接影响物理世界以及其他人的精神和情感状态（意识），这将有助于开拓我们对交互连通性的认识，以及如何主动地利用其来塑造我们将来所生活的世界。这意味着我们的态度、情感和注意力都很重

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要，而且相干、合作的意图能够产生积极的影响。 GCI的假说认为，当足够多的个体和社会团体提高他们的相干性基础水平，并利用升高后的相干性在通用场中有意地创造一个相干性更高的参考驻波，则将有助于提高全球意识。当越来越多的人向着更加平衡和情感、反应自我调节的方向努力时，该假说就可以实现。反过来，这也将有助于促进人类在解决创新性问题领域的合作，提高解决重大社会、环境和经济问题的直觉洞察力。随着更多的个体对通用场的稳定作用，以及家庭、工作场所和社区形成更牢固的社会相干性，迟早会形成更高的全球相干性。国家采用更具相干性的全球视野，则社会和经济压迫、战争、文化偏狭、犯罪以及无视环境的问题都将得到积极和成功的解决，通过这种方式能够对该假说进行证明。

RESUMEN

Finalmente llegó el tan anticipado año 2012. Entre las predicciones y alineamientos cósmicos que muchos conocemos, una cosa es segura: será un año interesante y fascinante a medida que la velocidad de los cambios que se suscitan siga en aumento, ocasionando caos y grandes oportunidades. Un punto de referencia de estos tiempos es el cambio de actitud que se produce en muchas personas, desde un paradigma de competencia a uno de mayor colaboración. En todo el mundo, una creciente cantidad de personas practican una existencia basada en el corazón y más grupos participan en actividades que apoyan los cambios positivos y soluciones creativas para tener un mundo mejor. La Iniciativa de Coherencia Global (GCI, por sus siglas en inglés) es un proyecto científico y cocreativo, orientado a unir a las personas a partir de atenciones e intenciones centradas en el corazón. La GCI trabaja en conjunto con otras iniciativas para poner de manifiesto el creciente poder de la intención y conciencia colectiva. La convergencia de varias líneas independientes de evidencia brinda un sólido sustento a la existencia de un campo de información global que

conecte todos los sistemas vivos y la conciencia. Cada célula de nuestro cuerpo circula en un ambiente externo e interno de fuerzas magnéticas fluctuantes e invisibles que pueden afectar prácticamente cada célula y circuito presente en los sistemas biológicos. Por esta causa, no debería sorprender que una gran cantidad de ritmos fisiológicos en los humanos y los comportamientos colectivos a nivel mundial no sólo estén sincronizados con la actividad solar y geomagnética, sino que los trastornos que se producen en estos campos pueden crear efectos adversos en la salud y el comportamiento de los humanos. Los mecanismos con más posibilidades de explicar cómo la influencia solar y geomagnética afectan la salud y el comportamiento de los humanos son una combinación del sistema nervioso humano y las frecuencias resonantes geomagnéticas, denominadas resonancias Schumann, las cuales se producen en la cavidad resonante terrestre, en la capa de la ionosfera, y las ondas de Alfvén. Es bien sabido que estas frecuencias resonantes se superponen directamente con las que se producen en el cerebro y el sistema cardiovascular. Si, de hecho, todos los sistemas vivos estuvieran interconectados y se comunicaran entre sí a través de campos biológicos, electromagnéticos y no locales, sería razonable pensar que los humanos pueden trabajar juntos en una relación cocreativa, para aumentar de manera conciente la coherencia en el campo del ambiente mundial, el cual a su vez distribuye esta información a todos los sistemas vivos dentro del campo. La GCI fue creada para ayudar a facilitar el cambio en la conciencia global, desde la inestabilidad y la discordia al equilibrio, la colaboración y la paz duradera. El objetivo principal de la GCI es poner a prueba la hipótesis de que una gran cantidad de personas, cuando se encuentran en un estado de coherencia cardíaca y comparten una misma intención, pueden codificar la información de los campos energéticos y geomagnéticos de la tierra, los cuales actúan como ondas portadoras de esta información fisiológicamente diseñada y relevante.

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

Con el fin de llevar a cabo esta investigación, una red mundial de 12 a 14 detectores de campos magnéticos ultrasensitivos, diseñados específicamente para medir las resonancias magnéticas de la tierra, se están instalando estratégicamente en el planeta. Pero más importante es la meta fundamental de la GCI de motivar a la mayor cantidad de personas a trabajar en conjunto, de manera más coherente y conjunta para estimular la conciencia colectiva. Si nos convencemos de que no sólo los campos externos de los orígenes solares y cósmicos, sino también la atención y emoción humana pueden afectar directamente el mundo físico y los estados mentales y emocionales de los demás (conciencia), esto nos permite ampliar nuestra visión de lo que significa la

interrelación y cómo se puede utilizar en forma intencional para moldear el futuro del mundo en que vivimos. Esto implica que nuestras actitudes, emociones e intenciones tienen importancia y que la intención coherente y conjunta puede tener efectos positivos. La GCI plantea la hipótesis de que cuando suficientes individuos y grupos sociales incrementan sus puntos de partida de coherencia y utilizan dicho aumento para crear deliberadamente una onda de referencia permanente más coherente en el campo mundial, esto ayudará a incrementar la conciencia global. Tales efectos se pueden lograr cuando una creciente cantidad de personas se orienta hacia emociones y respuestas más equilibradas y autorreguladas. Esto a su vez, puede ayudar a facilitar la cooper-

any people perceive that humanity has reached a critical juncture in these early years of the 21st century. We are on the threshold of a new stage of social, spiritual, and cultural evolution. We are evolving out of nationally based industrial societies toward an interconnected, information-based social, economic, and cultural system that spans the entire planet. The path of this transition is not certain; it is proving to be filled with numerous shocks and surprises. Worldwide, people are experiencing mounting concerns about climate change, terrorism, energy and water shortages, food and product safety, and economic instability. Such concerns are justified with the extreme volatility in global financial markets and the increase in frequency of record-breaking destructive weather, fires, and floods, as well as earthquakes, tsunamis, and volcanic eruptions. There is also an increase in social unrest and the number of revolutions, insurrections, and uprisings. This accelerating pace of change in the world is contributing to a momentum of global incoherence, stress, and instability. All too often, this results in stress, confusion, lack of focus, a narrowing field of perception, frustration, anxiety, and depression—all of which negatively impact relationships, health, productivity, and the global energetic field environment. When multiplied by the number of people who are affected, the growing insecurity has become a global paradigm that permeates our political, financial, social, educational, and natural environments. We are at a choice point, and it is arguably the most important ever faced. It is defined by technological sophistication that is not matched by an evolution in consciousness and social development. We see the social and environmental devastation that has been brought by the application of science and engineering

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ación y colaboración en métodos innovadores de resolución de problemas y de discernimiento intuitivo, para hacer frente a los problemas sociales, ambientales y económicos importantes que aquejan a la sociedad. Con el tiempo, a medida que más personas logren estabilidad en el campo global y sus familias, en sus lugares de trabajo y las comunidades se dirijan hacia una creciente coherencia social, esto conducirá a una coherencia global creciente. Los países indicarán esta tendencia mediante la adopción de una visión del mundo más coherente, de modo que la opresión social y la económica, la guerra, la intolerancia cultural, los delitos y la falta de preocupación por el medio ambiente sean cuestiones que se puedan abordar en forma significativa y exitosa.

to conquer the natural world. At the same time, there is an increase in the number of individuals, groups, and organizations around the world who are longing and working for peace, environmental improvement, and social change. We are on the verge of a shift in human consciousness, one in which we are co-creators and more in control of our own evolution. As a shift is instated, it brings new models for living together on the earth in cooperative and collaborative union, but increasing stress makes it more difficult for individuals, groups, and organizations to carry out their intentions and actualize their missions. While practices to increase balance and peace through personal and collective efforts, such as prayer, meditation, affirmations, focused intention, and other methods can positively add to the field environment, due to the stress of the current times, people often still find it difficult to calm down, focus, and quiet the mind, thereby compromising the effectiveness of their efforts. Coherence

One of the scientific understandings that emerged from the last century is that the universe is wholly and enduringly coherent.1-3 The phenomenon of coherence is well known. It indicates a quasi-instant connection among the parts or elements of things, whether an atom, an organism, or a galaxy. This kind of coherence is observed in fields as diverse as quantum physics, biology, cosmology, and brain and consciousness research. The new picture that has emerged is that all living systems are interconnected at a deep fundamental level and communicate with one another via biological fields and nonlocal mechanisms.4,5 Although the nature of these interconnecting fields is not yet Feature

The Global Coherence Initiative

fully understood, there is considerable scientific data that substantiate their existence through observation of their effects.6,7 It also has become increasingly clear that invisible magnetic influences emanating from the sun and earth profoundly affect life on earth from birth to death. It has been reliably shown that solar and geomagnetic cycles not only correlate with human health indicators, but also with such major societal conflicts as violence, crime, terrorism, and war.8-11 The concepts and understanding of coherence in physics is not new. It is our increasing understanding of how coherence functions in the human system that is relatively new, as well as scientific studies on how we can increase it. The Institute of HeartMath (IHM) has identified a psychophysiological state that is the underpinning of optimal function they termed heart coherence.5,12-14 This has led to the development of practical techniques, tools, and technologies that help empower people to better manage stress, increase performance, and connect with a deeper intelligence and intuitive awareness.15-17 Numerous studies have shown that learning how to shift into this psychophysiological state quickly improves cognitive performance, focus and effectiveness, self-responsibility, and social cohesion.5,12,18-21 Although people are able to achieve and increase heart coherence in a variety of ways—breathing exercises, heart-focused meditation, and listening to uplifting music among others—studies at IHM and elsewhere have shown one of the quickest and most effective ways is through emotional self-regulation and generating positive emotions, such as compassion, love, appreciation, and care.13 At the individual level, a person’s level of heart coherence can be assessed by monitoring the rhythmic patterns that are reflected in their heart-rate variability (HRV), the beat-to-beat changes in heart rate. Positive emotions such as love, appreciation, and compassion generate a heart-rhythm pattern that is more ordered and coherent, whereas negative emotions such as anxiety, anger, and fear generate a disordered, incoherent heart-rhythm pattern.12 Ongoing feelings of impatience, frustration, irritation, worry, or blame throw our inner rhythms out of sync and have a negative carryover effect on our hormonal and nervous systems. Studies have found that the combination of emotional self-regulation techniques with heart rhythm coherence monitoring technology (emWave) has proven to be highly successful for reducing stress, anxiety, anger, chronic pain, fatigue, and burnout, as well as many other stress-related conditions.5,12,18-21 By practicing the heart-focused self-regulation techniques and using heart rhythm coherence monitoring devices, people can learn how to quickly reset their emotions and shift into a balanced inner rhythm that the rest of the body will harmonize to, allowing more ease and flow. The inner rhythm and state of heart coherence is what many meditation techniques are trying to achieve. The emWave helps people quickly get into a meditative state and provides feedback when they lose

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focus. It also signals when they return to a coherent state. The emWave helps to slow the mental/emotional vibratory rate and increase the heart coherence baseline (ie, when the heart, brain and nervous system operate more in sync and with increased efficiency). As a person’s heart coherence baseline increases, he or she will experience more mental clarity, creativity, and focus during the day. The carryover effect helps users to be more conscious and intuitive at choice points, allowing them to choose their actions and reactions rather than automatically responding in the same old stress-producing behavior patterns. The Global Coherence Initiative

IHM, a nonprofit research and education organization, established the Global Coherence Initiative (GCI) as a science-based, co-creative initiative to unite people in heart-focused care and intention and to facilitate the shift in global consciousness from instability and discord to balance, cooperation, and enduring peace. A primary goal of GCI is to determine the effects of collective emotional responses that are reflected in the earth’s energetic fields (ionosphere and geomagnetic field). The first overarching hypothesis of GCI is that all living systems are interconnected at an energetic level and communicate with one another via biological fields, including nonlocal fields, when certain conditions are met. From this general hypothesis, the second overarching hypothesis is that not only are humans affected by planetary energetic fields, but conversely the earth’s energetic systems are also influenced by and act as a carrier wave for collective human emotions and consciousness (positively or negatively). Thus, much of the planetary “information field environment” is made up of the collective consciousness of the inhabitants. The third hypothesis is that large numbers of people intentionally generating heart-coherent positive emotional states of care, compassion, love, and appreciation will generate a coherent standing wave that can help offset present and future planetary-wide standing waves of stress, fear, discord, and incoherence. Embedded within the above overarching hypotheses is a related hypothesis that human emotions and consciousness interact with and encode information in planetary energetic fields, including the geomagnetic field, thereby communicating information between people at a subconscious level, which in effect, links all living systems and gives rise to a form of collective consciousness. Thus, a feedback loop exists between all human beings and the earth’s energetic systems. It is further proposed that when coherently aligned individuals are intentionally creating physiologically coherent waves, they encode information in the planetary scale energetic fields, which act as a carrier wave, thereby positively impacting all living systems contained within the field environment and the collective consciousness. This in turn will create a mutually beneficial feedback loop between human beings and the earth’s energetic systems. The intention

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

of GCI is to be a catalyst that will instigate, facilitate, and support the maintenance of an upward spiral of this feedback loop for the mutual benefit of human beings and the planet we call home. To support these efforts, GCI has established an international web-based membership of individuals which as of early 2012 has more than 37 000 members (see glcoherence.org). GCI is also working with various partner groups and organizations committed to increasing planetary coherence. The current focus of the initiative is the deployment of the Global Coherence Monitoring System to measure and explore fluctuations and resonances in the earth’s magnetic field and in the earth-ionosphere resonant cavity in order to 1. conduct research on the mechanisms of how the earth’s fields affect human mental and emotional processes, health outcomes, and collective human behavior; 2. explore how collective human emotional states and intentions are reflected in the earth’s electromagnetic and energetic fields; 3. determine if changes in the earth’s energetic fields occur prior to natural catastrophes such as earthquakes, volcanic eruptions, floods, storms, and human-made events such as social upheaval, unrest, and terrorist attacks; and 4. monitor global events to determine where GCI members’ collective heart-coherent prayers, meditations, affirmations, and intentions can be directed.

els, increased occurrence of cancer, balance of hormonal system, reproductive system, cardiac and neurological disease, and death.2,6,15-19 An important finding is that of all the bodily systems studied thus far, changes in geomagnetic conditions most strongly affect the rhythms of the heart.7,9,16,20 Historically, many cultures believed that their collective behavior could be influenced by the sun and other external cycles and influences. This belief has proven to be true. On a larger societal scale, increased violence, crime rate, social unrest, revolutions, and frequency of terrorist attacks have been linked to the solar cycle and the resulting disturbances in the geomagnetic field.25-31 The first scientific evidence of this belief was provided by Alexander Tchijevsky, a Russian scientist who noticed that more severe battles during World War I occurred during peak sunspot periods.31 He conducted a thorough study of global human history and constructed an index of Mass Human Excitability dating back to 1749, which he then compared to the solar cycles over the same time period until 1926. Figure 1, constructed from Tchijevsky’s original data, plots the number of significant human events compared to the solar cycle from 1749 to 1926.31

It is anticipated that by investigating how individual and collective emotional energy affects the earth’s fields that, it will facilitate a growing awareness of humanity’s interdependence with the earth and with each other. Earth’s Energetic Systems and Human Health and Behavior

Every cell in our bodies is bathed in an external and internal environment of fluctuating invisible magnetic forces.9 It has become increasingly apparent that fluctuations in magnetic fields can affect virtually every circuit in biological systems to a greater or lesser degree, depending on the particular biological system and the properties of the magnetic fluctuations.9,12,22 Therefore, it should not be surprising that human physiological rhythms and global behaviors are not only synchronized with solar and geomagnetic activity, but disruptions in these fields can create adverse effects on human health and behavior.23-25 Changes in geomagnetic activity are correlated with hospital admissions and mortality from heart attacks and strokes, as well as numerous other adverse health effects such as depression, fatigue, mental confusion, and number of traffic accidents that occur. There is a voluminous scientific literature indicating important biological processes take place such as altered blood pressure, heart rate, HRV, melatonin lev-

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Figure 1 Tchijevsky’s original data. The blue line plots the yearly number of important political and social events such as the start of a war, social revolutions, etc, while the red line plots the solar activity as indicated by the number of sunspots from 1749 to 1922. The histories of 72 countries were compiled, and it was found that 80% of the most significant events occurred during the solar maximum, which correlates with highest periods of geomagnetic activity.

In Figure 2, the last 2 solar cycles (22 and 23) are plotted, along with the beginnings of solar cycle 24 where it can be seen that Iraq invaded Kuwait during the peak of the solar cycle 22. The 9/11 terrorist attacks on the World Trade Center occurred during the peak of the solar cycle 23. Solar cycle 24 started in early 2011, and increased social unrest (especially in the Middle East, Tunisia, Egypt, and Libya) started to occur in synchronicity with

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The Global Coherence Initiative

Figure 2 The last 2 solar cycles and the onset of the current solar cycle. Events during the last 2 solar peaks had a profound impact on the world. The occurrence of the recent social unrest in the Middle East can be associated with the increase in solar activity and geomagnetic disturbance.

the increased solar activity. Solar cycle 24 will continue to pick up in activity and reach its peak sometimes in 2013 or 2014. It follows then that social activity, increased mass excitement, and social unrest will also continue in the years to come. Energetic Influxes and Human Flourishing

Solar activity has not only has been associated with social unrest; it has also been related to the periods of greatest human flourishing with clear spurts in architecture, arts and science, and positive social change.32 When old structures that do not serve humanity collapse, an opportunity opens for them to be replaced with more suitable and sustainable models. Such positive change can affect the political, economic, medical, and educational systems, as well as relationships of individuals at work and home and in communities. At times of such pertinent energy influx, we have the greatest opportunity to instate positive change in our world. We can learn from past mistakes and consciously choose new ways of navigating energy influxes to create periods of human flourishing and humanitarian advances. The most likely mechanism for explaining how solar and geomagnetic influences affect human behavior and health are a coupling between the human nervous system and the resonant frequencies generated by geomagnetic field line resonances and the globally propagating magnetic waves called Schumann resonances (SR) that occur in the earth-ionosphere resonant cavity. It is well established that the earth and ionosphere generate a symphony of resonant frequen-

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cies that directly overlap with those of the human brain and cardiovascular system. Figures 3 and 4 provide examples of the earth’s resonant frequencies. The central hypothesis is that changes in these resonances can in turn influence the function of the human autonomic nervous system, brain, and cardiovascular system. It has not been possible to test this central hypothesis scientifically until now due to the unavailability of reliable, continuous measures of ionospheric and field line resonances in combination with monitoring of peoples’ HRV as a measure of nervous system activity along with health and social indicators. Fortunately, this limitation has recently been resolved with the installation of the first 3 of 12 to 14 planned GCI monitoring sites designed to measure these resonances. The Global Coherence Initiative Monitoring System

When completed, the global coherence monitoring system will have a network of 12 to 14 sensor sites placed strategically around the planet. Each site will include ultrasensitive magnetic field detectors specifically designed to measure the magnetic resonances in the earth/ionosphere cavity, resonances that are generated by the vibrations of the earth’s geomagnetic field lines, and ultra-low frequencies that occur in the earth’s magnetic field, all of which have been shown to impact human health, mental and emotional processes and behaviors. Although there are several networks of ground-based fluxgate magnetometers which measure the strength of the earth magnetic field and geomagnetic disturbances (Kp), as well as several space weather satellites, there has

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

Figure 3 Schumann resonance data recorded From the Global Coherence Initiative sensor site in Boulder Creek, California. Note that all the resonant frequencies directly overlap human brainwave frequencies.

and transmits the data to a common server. In addition, each site has a random number generator (RNG) that is part of the Global Consciousness Project (GCP) network (described below). The monitoring system will track changes in geomagnetic activity due to solar storms, changes in solar wind speed, disruption of SRs, and, potentially, the signatures of major global events that have a strong emotional component. A growing body of data also suggests that changes occur in ionospheric activity prior to earthquake activity. We make our data freely available to other research groups who wish to explore how it may be utilized to predict earthquakes and related events. Thus, the network will provide a significant research tool to further understand how solar and earth-generated fields and rhythms affect human health, emotions, behaviors, and consciousness and vice versa. Global Coherence Initiative Interconnectedness Study

In 2010, we conducted a study in which 1643 GCI members from 51 countries completed a biweekly survey at random times 6 days each week over a 6-month period. The survey contained 6 valid scales: positive affect, wellbeing, anxiety, confusion, fatigue, and physical symptoms.

Figure 4 Geomagnetic field line resonance data recorded from the Global Coherence Initiative sensor site in Boulder Creek, California. Note that all the resonant frequencies directly overlap human cardiovascular system frequencies and that the there is a clear standing wave frequency at 0.1 Hz, which is the same resonant frequency of the cardiovascular systems and thus coherent heart rhythms in humans and many animals.

not been a global network of detectors that continuously measure the time varying signals such as the SR and other signals that occur in the same range as human physiological frequencies such as the brain and cardiovascular systems. The monitoring system adds the missing component required to better understand how we are affected by the earth’s fields as well as enabling us and other researchers to better understand the interconnections between solar and other external forces on the planetary field environment. Figure 5 shows the relative positions of monitoring sites, and Figure 6 illustrates the actual setup of a monitoring site. As of the beginning of 2012, 3 sites—one at the HeartMath Research Center in northern California, one in the eastern province of Saudi Arabia, and another in southern England—are operational. Three additional sites will be installed in 2012: one each in New Zealand, Canada, and South Africa. Each monitoring site will detect and send the local alternating magnetic field strengths in 3 dimensions over a relatively wide frequency range (0.01-300 Hz) while maintaining a flat frequency response. The data acquisition the infrastructure captures, stamps with time and global positioning data,

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Figure 5 Proposed locations for the global network of monitoring sites. These sites will be specifically designed to measure the magnetic resonances in the earth/ionosphere cavity, resonances that are generated by the vibrations of the earth’s geomagnetic field lines, and ultra-low frequencies that occur in the earth’s magnetic field.

Figure 6 The monitoring site located at the HeartMath Research Center in Boulder Creek, California.

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The Global Coherence Initiative

Table Global Coherence Initiative Interconnectedness Results Physical Symptoms

Fatigue

Anxiety

Confusion

Positive Affect

Well-being

Dreams

.17b

.30a

-.22a

-.17b

-0.14

.20b

-.25a

-.21a

-0.04

0.15

-.24a

-.20b

-0.05

-0.15

.28a

.20b

-.32a

-.24a

Solar wind speed

-0.01

.32a

Kp-indexc

-0.05

.28a

-0.05

.27a

Solar radio flux (F 10.7index)

0.09

-.34a

-.17b

Polar Cap Magnetic Activity

-0.06

.32a

.19b

Ap-indexd

0.11 0.10

.24a

.21b -0.01

Correlation is significant at the 0.01 level (2-tailed).

Correlation is significant at the 0.05 level (2-tailed).

The Kp-index is a “planetary” index derived by calculating a weighted average of K indices from a network of magnetometer readings. K is a code letter related to a magnetometer horizontal component.

The Ap-index is an averaged planetary A index based on data from a set of specific Kp stations. The A index is a 3-hourly “equivalent amplitude” index of local geomagnetic activity (a). In short, Ap-index

is a geomagnetic “planetary activity” index.

The survey data were subjected to correlation analysis with a number of planetary and solar activity variables such as solar wind speed, magnetic field and plasma data, measures of energetic protons, solar flux, and geomagnetic activity indices. The Table shows the results of the correlation analysis. A positive correlation coefficient represents positive linear correlations, and a negative correlation coefficient (indicated with a minus sign) represents negative correlations. Positive affect was negatively correlated to the solar wind speed, Kp, Ap index, and polar cap magnetic activity. (The Ap index is a mean, 3-hourly ”equivalent amplitude” of magnetic activity based on K index data from a planetary network of 11 northern and 2 southern hemisphere magnetic observatories between the geomagnetic latitudes of 46° and 6° by the lnstitut fur Geophysik at Gottingen, Germany; Ap values are given in units of 2 nT.) In other words, when solar wind speed, Kp, Ap, and polar cap activity increased, positive affect among the participants decreased. As expected, well-being scores were also negatively correlated with solar wind speed, Kp, Ap-index, and polar cap magnetic activity. Thus, when solar wind speed increased and the geomagnetic field was disturbed, the levels of fatigue, anxiety, and mental confusion increased. The study also uncovered some unexpected findings. For example, the solar radio flux index was correlated with reduced fatigue and improved positive affect, indicating that there are mechanisms affecting human wellbeing that are not fully understood and additional research needs to be conducted in order to understand the effects of the various variables and the time sequence of their effects.33 Another study performed at the Prince Sultan Cardiac Hospital in Saudi Arabia, entitled “Effects of Changes in Geomagnetic and Ionospheric Fields on Human Heart Rate Variability” recently began to more rigorously test the hypothesis that SRs and field line resonances are primary mechanisms mediating the interactions between geomagnetic activity and the human nervous system. This study has 2 major components. First, sequential, 24-hour HRV recordings will be obtained each day over a 1-year period. Changes in the participants HRV data will be correlated with variations in planetary and solar activity, including solar

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wind speed, magnetic field, plasma data, protons, geomagnetic activity indices like AE, Dst, Kp, solar radio flux (F 10.7 index), locally recoded SRs, and geomagnetic field line resonances. It is expected that we will find strong correlations between increased solar activity, geomagnetic activity, and SR intensities and disturbances. It is also expected that we will find that the SR intensities and disturbances have strong correlations with changes in the participants HRV indices, especially with changes in the VLF rhythms of HRV. The longest time frame of any study so far has been a 6-week period.34 The second aspect of this study involves studying the impact of solar and geomagnetic activity on a societal level. We will map the time structures of the solar and magnetic variables listed above along with indicators of the larger, local population’s social and physical health indicators such as social unrest, mood disorders, fatigue, depression, hospital admissions, and traffic accidents. If the hypothesis can be validated, it will significantly increase our understanding of the mechanisms by which geomagnetic disturbances affect human health and behavior and thus significantly increase our ability to predict and take steps to counteract the impact of energetic disturbances on individuals and society. Creating Positive Change in the Planetary Field Environment

The evidence that human health and behaviors are globally influenced by geomagnetic activity is quite strong and convincing. However, there is experimental evidence that human bioemotional energy can have a subtle but significant (scientifically measurable) nonlocal effect on people, events, and organic matter. It is becoming clear that a bioelectromagnetic field such as the ones radiated by each human heart and brain can affect other individuals and the “global information field environment.” For example, research conducted in our laboratory has confirmed the hypothesis that when an individual is in a state of heart coherence, the heart radiates a more coherent electromagnetic signal into the environment that can be detected by nearby animals or the nervous systems of other people.35 Of all the organs, the heart generates the largest rhythmic electromagnetic field, one that is approximately 100

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

times stronger than that produced by the brain. This field can be detected several feet from the body with sensitive magnetometers. This magnetic field provides a plausible mechanism for how we can “feel” or sense another person’s presence and emotional state independent of body language or other factors. We have also found that there is a direct relationship between the heart rhythm patterns and the spectral information encoded in the frequency spectra of the magnetic field radiated by the heart. Thus, information about a person’s emotional state is encoded in the heart’s magnetic field, which is communicated throughout the body and into the external environment. Further support for this hypothesis was provided in a study examining the possibility that people trained in achieving high states of heart coherence could facilitate coherence in other people in close proximity. The results showed that the coherence of untrained participants was indeed facilitated by others who were in a coherent state. In addition, evidence of heart rhythm synchronization among group participants was revealed through several evaluation methods, and higher levels of coherence correlated to higher levels of synchronization among participants. Also, there was a statistical relationship between this synchronization and relational measures (bonding) among the participants. The authors concluded that “evidence of heartto-heart synchronization across subjects was found which lends credence to the possibility of heart-toheart bio-communications.”36 In another study, Kathi Kemper at Wake Forest University, Winston-Salem, North Carolina, conducted a blinded study to evaluate the direct psychophysiological benefits of the nonverbal communication of loving kindness and compassion to others. The study participants were unaware of the true purpose of the study and did not know that the practitioner was at the time practicing being in a more heart coherent state of loving kindness and compassion. After the periods the practitioner was in this state, the participants had significantly reduced stress and increased feelings of relaxation and peacefulness. The participants also had significant improvements in their measures of HRV, which was used as an objective measure of autonomic activity. The study concluded that extending compassion to others has measurable affects and is “good medicine.”37

pable “team energy” that affects a team or a group’s performance. A growing body of evidence suggests that an energetic field is formed among individuals in groups through which communication among all the group members occurs simultaneously. In other words, there is a literal group “field” that connects all the members.5 Sociologist Raymond Bradley in collaboration with neuroscientist Karl Pribram developed a general theory of social communication to explain the patterns of social organization common to most groups independent of size, culture, degree of formal organization, length of existence, or member characteristics. They found that most groups have a global organization and a coherent network of emotional energetic relations interconnecting virtually all members into a single, multilevel hierarchy. They found a direct relationship between the number and structure of reciprocated positive emotional bonds among the members that predicted group stability and performance 2 years later. The only model that best fit and explained the data was one based on a field concept where information about the group as a whole was distributed to all members in such a way that information about the group’s global organization could be obtained from any member within the field—ie, a collective consciousness or a “social hologram.”38 It requires energy to shift a system into a more coherent mode, and the key to creating stable, coherent groups is related to establishing positive emotions and dissipating negative emotional tensions, interpersonal conflicts, and other stressors among the individuals in that group. Michael Persinger, a well-known neuroscientist at Laurentian University, Sudbury, Ontario, has conducted numerous studies examining the effects of magnetic fields with the same magnitude as the geomagnetic field on brain functions.39,40 Not only has he shown that by applying external fields similar to the SRs that can induce altered states of consciousness, he has also suggested in a detailed theory that the space occupied by the geomagnetic field can store information related to brain activity and that this information can be accessed by the human brain.41 Furthermore, Persinger suggests that the earth’s magnetic field can act as a carrier of information between individuals and that information rather than the signal intensity is important for interaction with neural networks.42

Group Coherence

Interconnection Between Collective Human Emotions and Random Number Generators

Anyone who has watched a championship sports team or experienced an exceptional concert knows that something special can happen in groups that transcends their normal performance. It seems as though the players are in sync and communicating on an unseen energetic level. Many teams, including Olympic and professional sports teams and Special Forces military units, understand the importance of team coherence. While they may refer to coherence as “team spirit” or “bonding,” they instinctively know there is a pal-

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There is also a substantial body of evidence indicating an interaction between human emotions and global fields when large numbers of people have similar emotional responses to events or organized global peace meditations. Research conducted by the GCP, which maintains a worldwide network of RNGs, has found that human emotionality affects the randomness of these electronic devices in a globally correlated manner. Roger Nelson, director of the GCP states,

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The Global Coherence Initiative

The GCP is a long-term experiment that asks fundamental questions about human consciousness. It provides evidence for effects of synchronized collective attention—operationally defined global consciousness—on a world-spanning network of physical devices. There are multiple indicators of anomalous data structure which are correlated specifically with moments of importance to humans. The findings suggest that some aspect of consciousness may directly create effects in the material world. This is a provocative notion, but it is the most viable of several alternative explanations.43(p16)

Figure 7 The shift in correlated output of a global network of random number generators during the terrorist attacks on September 11, 2001.

Figure 8 Global Consciousness Project vs level of emotion. Level of emotion determined by categorizing the events significantly affects the network variance effect size.

Figure 9 Effect of compassion. The degree of love and compassion evoked or embodied in an event significantly affects the network variance effect size.

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The research conducted by GCP has found that there is a significant correlation between global events that elicit a high level of emotionality from a large part of the world’s population and periods of nonrandom order generated by the RNGs.44 For example, multiple independent analyses of the network during the terrorist attacks that took place in the United States on the morning of September 11, 2001 (Figure 7), correlate with a large and significant shift in the output of the global network of RNGs.45 The mechanisms for why human emotions create more coherence in the randomness of this global network are not yet fully understood; the data, however, clearly show that they do have such affects and data now have an odds-against chance ratio of over a billion to one.46 Dr Nelson also found clear evidence that larger events defined by the number of people engaged and their level of “importance” produces larger effects on the global network. Figure 8 shows large differences depending on the level of emotion associated with events. Figure 9 shows that when an event is characterized by deep and widespread compassion, the GCP effects are stronger.43 This makes sense as compassion is related to interconnection and positive emotional engagement. As demonstrated, when we experience true feelings of compassion, we tend to shift into a more coherent physiological state12 and are thus radiating more coherent magnetic waves into the environment.47 Compassion by definition is an emotional state that brings us together and makes us coherent; we invest a small part of our individual being to connect with others and, as the GCP data indicate, with the global field environment. The CGP group has investigated a number of theoretical models that could potentially explain the global effect they are detecting with the network. Most have been rejected and the following statement provides a summary of their analysis. The picture is more promising when we look at field-type models associated with human consciousness. A simple version is similar to ordinary physical models of fields generated by a distribution of sources. In this case the field sources are associated with individual conscious humans,

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

while the field dynamics that might explain the random number generators correlations derive from the coherence of human activity during events. This proposal can accommodate all the inter-node correlations and structure seen in the data, but it remains phenomenological since it does not explain how the field arises in terms of underlying principles. Finally, a non-linear dynamic field model proposes that individual minds are mutually interactive, and that the interactions are responsible for an emergent field which depends on individual consciousness but is not reducible to it. The model implies that the dynamic and interactive qualities of consciousness also involve subtle interactions with the physical world and that these are responsible for certain anomalous phenomena such as are found in the GCP experiment. The proposal can be construed as embodying in a formal way the ideas of such thinkers as Teilhard de Chardin, describing a “noosphere” of intelligence for the earth, (1961) or Arthur Eddington, conceiving a “great mind.”43(p12) In a study that examined GCP data between 1998 and 2008, matched satellite-based interplanetary magnetic field (IMF) polarity with GCP defined world events such as meditations, celebrations, natural catastrophes, or violence. He found that such RNG deviations may depend on a positive IMF polarity coinciding with emotionally significant conditions and/or entropy changes.48 Since we are still in the infancy in the field of consciousness research modulated by solar activity, sun/ earth distance, and mass human emotionality, an important line of research is to develop a better understanding of processes influencing RNG data in comparison with solar and magnetic field data. Mass Emotional Responses and the Geomagnetic Field

Another line of evidence for human emotional energy interacting with earth’s energetic fields was provided from measures of the earth’s geomagnetic field during the September 11, 2001, terrorist attacks. Figure 10 shows data recorded from 2 separate space weather satellites in geosynchronous orbit in the days before and after the attacks. The data from the magnetometers on these two satellites, which are positioned over the east and west coasts of the United States, reveal that a large shift occurred in the earth’s geomagnetic field at the same time as the attacks. Note the difference in the fields in the days before and after the attacks. The incoherence and discord in the fields during the days after the attacks may reflect the mass emotional turmoil that occurred as news of the attacks spread around the globe. The same patterns were also observed in ground-based magnetometers. Although the data shown in Figure 10 does not prove that human emotion modulated the earth’s geomagnetic field, combined with the GCP and other

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data, they support the overarching hypothesis that the earth’s energetic systems are coupled with and exchange information in a bidirectional manor with the collective emotional energy of humanity. One of our goals at GCI is to test the hypothesis that large numbers of people in a heart-coherent state and holding a shared intention can encode information on the earth’s energetic and geomagnetic fields that act as carrier waves of this physiologically-patterned and relevant information. If living systems are indeed interconnected and communicate with each other via such biological and electromagnetic fields, it stands to reason that humans can work together in a co-creative relationship to consciously increase the coherence in the global field environment which in turn distributes this information to all living systems within the field. Of course, the idea is not new that shared intentions can influence others at a distance; such ideas have been the subject of numerous studies that have looked at the effects of prayer, meditations, and groups sending intentions in various experimental contexts.6,49-51 Quantum physicist John Hagelin has conducted research on the “Power of the Collective” and concluded that ”Since meditation provides an effective, scientifically proven way to dissolve individual stress, and if society is composed of individuals, then it seems like common sense to use meditation to similarly diffuse societal stress.”52 A study conducted in 1993 in Washington, DC, showed a 25% drop in crime rate with 2500 meditators,53 which means that a relatively small group of a few thousand was influencing a much larger group, a million and a half. The question posed itself that if crime rates could be decreased, could a group of meditators also influence social conflicts and wars? A similar experiment was done during the peak of the Israel-Lebanon war in the 1980s. Drs Charles Alexander and John Davies at Harvard University organized groups of experienced meditators in Jerusalem, Yugoslavia, and the United States to mediate on the area at various intervals over a 27-month period. After controlling statistically for weather changes; Lebanese, Muslim, Christian, and Jewish holidays; police activity; fluctuation in group sizes; and other variant influences during the course of the study, the levels of violence in Lebanon decreased between 40% to 80% each time a meditating group was in place, with the largest reductions occurring when the numbers of meditators were largest. During these periods, the average number of people killed during the war per day dropped from 12 to 3, a decrease of more than 70%; war-related injuries fell by 68%, and the intensity level of conflict decreased by 48%.54 How can we have such an influence on each other at a distance? There are no clear answers yet; however, we hypothesize, that there is a unified field and universal consciousness that allows individually coherent waves to be coupled to the larger collective field environment. The GCI theory of change states that as

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The Global Coherence Initiative

Figure 10 The data recorded from the Geostationary Operational Environmental Satellite 8 and 10 weather satellites in geosynchronous orbit over the east and west coasts of the United States in the days before, during, and after the September 11, 2001, terrorist attacks.

enough individuals increase their personal coherence, it can lead to increased social coherence (family, teams, organizations), and as increasing numbers of social units (families, schools, communities, etc) become more coherently aligned, it can in turn lead to increased global coherence, all of which is facilitated through self-reinforcing feedback loops between humanity and the global field environment (Figure 11). As more and more people increase their personal coherence, it strengthens and stabilizes the standing waves and coherent information in the planetary information field. Once a coherent standing wave is established, reinforced, and amplified through collective coherent intention, it in turn facilitates the amplification of the collective heart, mind, and consciousness, making it easier for more and more people to increase their coherence and expand their consciousness. Every individual contributes to the global field environment, and each person’s attitudes, intentions, and emotional experiences count. This is empowering for many individuals who often feel overwhelmed by the current negative predictions and conflicts on the planet. They come to realize that their actions can make a difference and that by increasing their own coherence, they can make a contribution that can help facilitate the shift that many now perceive to be occurring.

Figure 11 Global Coherence Initiative theory of change.

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The personal benefits of better emotional self-regulation, enhanced well-being, more self-responsibility, better health, and improved relationships people experience are powerful motivators that reinforce the process for the individual. As more and more individuals become increasingly self-regulated and grow in conscious awareness, the increased individual coherence in turn increases social coherence, which is reflected in increased cooperation and effective co-creative initiatives for the benefit of society and the planet. It is our perspective that a shift in consciousness is necessary in order for a significant shift to occur that enables new levels of cooperation and collaboration in innovative problem solving and intuitive discernment for addressing our social, environmental, and economic problems. In time, global coherence will be indicated by more communities, states, and countries adopting a more coherent planetary view. Conclusions

GCI is a science-based, co-creative project to unite people in heart-focused care and intention and to facilitate the shift in global consciousness from instability and discord to balance, cooperation, and enduring peace. A primary goal is further study the interconnectedness between humanity and the earth’s energetic systems. There is a substantial body of evidence that humans are affected by planetary energetic fields. GCI hypothesizes that human emotions and consciousness interact with and encode information in planetary energetic fields, including the geomagnetic field, thereby communicating information between people at a subconscious level, which, in effect, links all living systems and gives rise to a form of collective consciousness. Thus, a feedback loop exists among all human beings and the earth’s energetic systems. Our basic hypothesis is that when enough individuals and social groups increase their coherence and utilize that increased coherence to intentionally create a more coherent standing reference wave in the global field, it will help increase the global consciousness. This can be achieved when an increasing ratio of people move towards more balanced and self-regulated www.gahmj.com • Volume 1, Number 1 • March 2012

GLOBAL ADVANCES IN HEALTH AND MEDICINE

emotions and responses. This in turn can help facilitate cooperation and collaboration in innovative problem solving and intuitive discernment for addressing society’s significant social, environmental, and economic problems. In time, as more individuals stabilize the global field and families, workplaces, and communities move to increased social coherence, it will lead to increased global coherence. This will be indicated by countries adopting a more coherent planetary view so that social and economic oppression, warfare, cultural intolerance, crime, and disregard for the environment can be addressed meaningfully and successfully. In order to conduct research on the mechanisms of how the earth’s fields affect human mental and emotional processes, health outcomes, and collective human behavior and explore how collective human emotions and intentions may be reflected in the earth’s electromagnetic and energetic fields, a global network of ultrasensitive magnetic field detectors specifically designed to measure the magnetic resonances in the earth/ionosphere cavity and resonances and earth’s geomagnetic field lines resonances are being installed at strategic locations around the earth. The monitoring system and the research studies it will make possible are only one aspect of a much larger goal, which is bringing people together for the purposes of improving their lives and creating a new more coherent standing wave in the planetary field environment. The studies demonstrating that a relatively small number of the population who are intentionally meditating to create positive benefits supports the hypothesis that humanity is connected via a global field. Hence, we believe that the scientific research investigating how we are both impacted by the earth’s energetic fields and the potential for detecting effects of collective human emotion and intention in the field environment is an important aspect of the GCIs goals. However, even if we are not able to prove the encoding of human intention in the global fields in the next few years, we are confident that we can facilitate a deeper understanding of the mechanisms by which human health and behaviors are modulated by the earth’s fields and further clarify which aspects of the field environment mediate the varied and specific effects. More important is GCI’s primary goal, which is to motivate more people to work together in a more coherent and collaborative manner to increase harmony in the collective consciousness to alleviate social conflicts and to improve the environmental impact we have on the planet and assist in planetary evolution. REFERENCES 1. Bohm D, Hiley BJ. The undivided universe: an ontological interpretation of quantum theory. London: Routledge; 1993. 2. Laszlo E. The interconnected universe: conceptual foundations of transdiciplinary unified theory. Singapore: World Scientific; 1995. 3. Laszlo E. Quantum shift in the global brain: how the new scientific reality can change us and our world. Rochester (VT): Inner Traditions; 2008. 4. Ho MW. The rainbow and the worm: the physics of organisms. Singapore: World Scientific Publishing Co; 2005. 5. McCraty R, Childre D. Coherence: bridging personal, social and global health. Altern Ther Health Med. 2010;16(4):10-24.

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6. Radin D. The conscious universe: the scientific truth of psychic phenomena. San Francisco: HarperEdge; 1997. 7. Tart C. The end of materialism: how evidence of the paranormal is bringing science and spirit together. Oakland: New Harbinger Publications Inc; 2009. 8. Halberg F, Cornelissen G, McCraty R, Czaplicki J, Al-Abdulgader AA. Time structures (chronomes) of the blood circulation, populations’ health, human affairs and space weather. World Heart J. 2011;3(1):1-40. 9. Halberg F, Cornélissen G, Otsuka K, et al. Cross-spectrally coherent ~10.5- and 21-year biological and physical cycles, magnetic storms and myocardial infarctions. Neuro Endocrinol Lett. 2000;21(3):233-58. 10. Halberg F, Cornélissen G, Sothernet RB, et al. Cycles tipping the scale between death and survival (=”life”). Progress Theoret Phys Suppl. 2008;173:153-81. 11. Halaris A, editor. Chronobiology and psychiatric disorders. New York: Elsevier; 1987. 12. McCraty R, Atkinson M, Tomasino D, Bradley RT. The coherent heart: heart-brain interactions, psychophysiological coherence, and the emergence of system-wide order. Integral Rev. 2009 Dec;5(2):10-115. 13. McCraty R, Childre D. The grateful heart: the psychophysiology of appreciation. In: Emmons RA, McCullough ME, editors. The psychology of gratitude. New York: Oxford University Press; 2004. p. 230-55. 14. Tiller WA, McCraty R, Atkinson M. Cardiac coherence: a new, noninvasive measure of autonomic nervous system order. Altern Ther Health Med. 1996 Jan;2(1):52-65. 15. Bradley RT, Gillin M, McCraty R, Atkinson M. Non-local intuition in entrepreneurs and non-entrepreneurs: results of two experiments using electrophysiological measures. Int J Entrepren Small Bus. 2011;12(3):343-72. 16. McCraty R, Atkinson M, Bradley RT. Electrophysiological evidence of intuition: part 1. The surprising role of the heart. J Altern Complement Med. 2004 Feb;10(1):133-43. 17. McCraty R, Atkinson M, Bradley RT. Electrophysiological evidence of intuition: part 2. A system-wide process? J Altern Complement Med. 2004 Apr;10(2):325-36. 18. Bradley RT, McCraty R, Atkinson M, Tomasino D, Daugherty A, Arguelles L. Emotion self-regulation, psychophysiological coherence, and test anxiety: results from an experiment using electrophysiological measures. Appl Psychophysiol Biofeedback. 2010 Dec;35(4):261-83. 19. Ginsberg JP, Berry ME, Powell DA. Cardiac coherence and PTSD in combat veterans. Altern Ther Health Med. 2010 Jul-Aug;16(4):52-60. Erratum in: Altern Ther Health Med. 2010 Sep-Oct;16(5):11. 20. Lloyd A, Brett D, Wesnes K. Coherence training improves cognitive functions and behavior in children with attention-deficit hyperactivity disorder: cognitive functions and behavioral changes. Altern Ther Health Med. 2010 Jul-Aug;16(4):34-42. 21. McCraty R, Atkinson M, Lipsenthal L, Arguelles L. New hope for correctional officers: an innovative program for reducing stress and health risks. Appl Psychophysiol Biofeedback. 2009 Dec;34(4):251-72. 22. Cornelissen G, et al. Chronomes, time structures, for chronobioengineering for “a full life.” Biomed Instrumentation Technol. 1999;33:152-87. 23. Doronin VN, Parfentĕv VA, Tleulin SZh,et al. [Effect of variations of the geomagnetic field and solar activity on human physiological indicators]. Biofizika. 1998 Jul-Aug;43(4):647-53. Russian. 24. Kay RW. Geomagnetic storms: association with incidence of depression as measured by hospital admission. Br J Psychiatry. 1994 Mar;164(3):403-9. 25. Mikulecký M. Solar activity, revolutions and cultural prime in the history of mankind. Neuro Endocrinol Lett. 2007 Dec;28(6):749-56. 26. Cornélissen G, Hillman D, Halberg F. Public health systems as central components of international security and personalized health care. The Lancet. Forthcoming. 27. Gordon C, Berk M. The effect of geomagnetic storms on suicide. S Afr Psychiatr Rev. 2003;6:24-7. 28. Grigoryev P, Rozanov V, Vaiserman A, Vladimirskiy B. Heliogeophysical factors as possible triggers of suicide terroristic acts. Health. 2009;1(4):294-7. 29. Perry FS, Reichmanis M, Marino AA, Becker RO. Environmental power-frequency magnetic fields and suicide. Health Phys. 1981 Aug;41(2):267-77. 30. Smelyakov SV. Tchijevsky’s disclosure: how the solar cycles modulate the history; 2006 [cited 2012 Feb 10]. Available from: http://www.astrotheos.com/Page5.htm. 31. Tchijevsky AL (de Smitt VP, translator). Physical factors of the historical process. Cycles. 1971 Jan;22:11-27. 32. Ertel S. [Cosmophysical correlations of creative activity in cultural history]. Biofizika. 1998 Jul-Aug;43(4):736-41. Russian. 33. McCraty R. The global coherence initiative: measuring human-earth energetic interactions in 3rd heart. King of Organs Conference; 28 Oct 2010; Hufuf, Saudi Arabia. 34. Pobachenko SV, Kolesnik AG, Borodin AS, Kalyuzhin VV. The contigency of parameters of human encephalograms and schumann resonance electromagnetic fields revealed in monitoring studies. Complex Syst Biophys. 2006;51(3):480-3. 35. McCraty R. The energetic heart: bioelectromagnetic interactions within and between people. Boulder Creek (CA): HeartMath Research Center, Institute of HeartMath; 2002. 36. Morris SM. Achieving collective coherence: group effects on heart rate variability, coherence and heart rhythm synchronization. Altern Ther Health Med. 2010;16(4):epub only. 37. Kemper KJ, Shaltout HA. Non-verbal communication of compassion: measuring psychophysiologic effects. BMC Complement Altern Med. 2011 Dec 20;11:132. 38. Bradley RT, Roberts NC. Network structure from relational data: measurement and inference in four operational models. Soc Network. 1989 Jun;11(2):89-134. 39. Persinger MA. Geopsychology and geopsychopathology: mental processes and disorders associated with geochemical and geophysical factors. Experientia. 1987 Jan 15;43(1):92-104. 40. Persinger MA, Psych C. Sudden unexpected death in epileptics following sudden,

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intense, increases in geomagnetic activity: prevalence of effect and potential mechanisms. Int J Biometeorol. 1995 Dec;38(4):180-7. 41. Persinger M. On the possible representation of the electromagnetic equivalents of all human memory within the earth’s magnetic filed: implications of theoretical biology. Theoret Biol Insights. 2008 Sep;1:3-11. 42. Persinger MA. On the possibility of directly accessing every human brain by electromagnetic induction of the fundamental alogorithms. Percept Mot Skills. 1995 Jun;80(3 Pt 1):791-9. 43. Nelson R. Scientific evidence for the existence of a true noosphere: foundation for a noo-constitution. Paper presented at: World Forum of Spiritual Culture; October 18-20, 2010; Astana, Kazakhstan. 44. Bancel P, Nelson R. The GCP event experiment: Design, analytical methods, results. J Sci Exploration. 2008;22:309-33. 45. Nelson R D, Dobyns YH, Dunne BJ, Jahn RG. Analysis of variance of REG experiments: operator intention, secondary parameters, database structure (Technical Note PEAR 9 1004). Princeton Engineering Anomalies Research, Princeton University, School of Engineering/Applied Science, 1991. 46. Nelson R. Detecting mass consciousness: effects of globally shared attention and emotion. J Cosmol. 2011;14. 47. McCraty R. The energetic heart: bioelectromagnetic communication within and between people. In: Rosch PJ, Markov MS, editors. Bioelectromagnetic Medicine. Marcel Dekker: New York; 2001. p. 541-62. 48. Wendt HW. Mass emotions apparently affect nominally random quantum processes: interplanetary magnetic field polarity found critical, but how is causal path? St. Paul; Halberg Chronobiology Center, University of Minnesota; 2002. 49. Ameling A. Prayer: an ancient healing practice becomes new again. Holist Nurs Pract. 2000 Apr;14(3):40-8. 50. Gillum F, Griffith DM. Prayer and spiritual practices for health reasons among American adults: the role of race and ethnicity. J Relig Health. 2010 Sep;49(3):283-95. 51. Schwartz SA, Dossey L. Nonlocality, intention, and observer effects in healing studies: laying a foundation for the future. Explore (NY). 2010 SepOct;6(5):295-307. 52. Hagelin J. The power of the collective. Shift. 2007 Jun-Aug;15:16-20. 53. Hagelin JS, Rainforth MV, Cavanaugh KL, et al. Effects of group practice of the transcendental meditation program on preventing violent crime in Washington, D.C.: results of the National Demonstration Project, June-July 1993. Soc Indicat Res.1999 June;47(2):153-201. 54. Davies JL. Alleviating political violence through enhancing coherence in collective consciousness: impact assessment analysis of the Lebanon war [dissertation]. Fairfield (IA): Maharishi University of Management; 1988.

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The Problem With Science—The Context and Process of Care: An Excerpt From Remodelling Medicine Jeremy Swayne, BA(Oxon), BM, BCh, D(Obst)RCOG, MRCGP, FFHom

Copyright 2012 Saltire Books Limited. Glasgow, Scotland. This chapter is excerpted from Jeremy Swayne’s new book, Remodelling Medicine, and is reprinted with the permission of the publishers. Citation Global Adv Health Med. 2012;1(1):78-87. Key Words Scientificism, science, truth, illness, treatment, research, integrative medicine, healing, policy, whole person

Summary

•• The goal of science is truth through knowledge. But medicine’s truth is not altogether the same as science’s truth. •• Science works with ideas, imagination and intuition, but essentially has to do with facts. Medicine has also to deal with meaning. •• This is not an argument for less science in medicine, but for more and better science; better in the sense of better attuned to ‘the rest of life’. •• Truthfulness is a core principle of medical practice and medical science. •• But a kind of untruthfulness is common in day-to-day clinical practice. •• The fundamental untruth is the illusion of certainty. •• The inexcusable untruth is to reduce the patient’s problem to it to its narrow biomedical parameters and to allow the patient as a person to vanish from our gaze. •• Science fails medicine by the narrowness of the scope of things it is willing to investigate. Important areas of medicine have been neglected as a consequence. •• The medical research culture must change if it is to promote science for understanding alongside science for manipulation. We need to be unsparingly critical of the distinction between useful science and wasteful science. •• “Medical knowledge is not knowledge acquired primarily for its own sake (but) for a specific purpose—the care of the sick.”1 Scientificism

William James (1842–1910) was an American psychologist and philosopher best known for the series of Gifford lectures delivered in Edinburgh in 1901 and later published as The Varieties of Religious Experience. His work was reviewed in the BBC Radio 4 programme ‘In our time’ on the 13th of May 2010, when he was judged by one expert to have been the greatest philosopher ever! He did not draw any firm conclusions about the existence of God from his research, whose purpose was psychological rather than theological, and he was open to the possibility that some or all of those varieties of experience might be eruptions from the individual’s subconscious. But he was insistent that they should be taken seriously, and was critical of the scientific attitude towards such phenomena, though he was primarily a Darwinian scientist himself who turned to philosophy in later life. One of his criticisms is particularly pertinent to the problem of science in relation to medicine. He said that the worst thing about science is ‘the religion of scientificism’—which induces a kind of fear. He said his fellow scientists crippled themselves by the fear of doing something that might be regarded as unscientific, and so they closed their minds. This is reflected in quotations from Kuhn and Polanyi in Chapter 11. James’s view, consistent with Darwin’s open-minded scientific attitude, was that we have to be open to the thought that what seems intellectually absolutely unavoidable today may seem really stupid to us tomorrow. So we

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should never close down on any intellectual possibilities whatsoever. The quotation from George Engel that introduces Chapter 6 that the scientific attitude can permit no restrictions as to the category of natural phenomena investigated echoes the same conviction. The discussion on the radio went on to reflect on the ascendancy of Bertrand Russell’s philosophy, and the triumph of what James would have regarded as an overinvestment in logic and a lack of interest in the diversity of human experience. This sentiment is echoed in the quotation from Mary Midgeley at the end of Chapter 6, which concludes, “We do not need to esteem science less. What we need is to esteem it in the right way. Especially we need to stop isolating it from the rest of life”.2 One of the speakers on the radio suggested that James’ continuing importance is that he represents a struggle in his period and our own to reconcile naturalism, the understanding that human beings are the product of nature, with humanism; the struggle to find a place for human values in a world of nature. Which today might be represented as the question—in a world of particles, what place is there for values? Scientific truth in medicine

The good internal to the practice of research is truth, an understanding of what is really real about some aspect of the world we inhabit.1 The goal of science is truth through knowledge. Thus, the role of science in medicine is to get at the

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truth. But medicine’s truth is not altogether the same as science’s truth. Science works with ideas, imagination and intuition, but essentially has to do with facts. Medicine has also to deal with meaning. In this, medicine comes close to theology. Science and theology are both exploring reality; different but inseparable aspects of reality. Medicine somehow has to accommodate the patient’s whole reality. The truth we seek is “to understand things as they really are, knowing that in its fullness it will always be beyond us”.3 But if we abandon it we abandon our patient. And medicine’s truth has to accommodate the diversity of human experience that an over-investment in logic may disregard. It has to accommodate ‘the rest of life’ of which our biomedical condition is only a part and a reflection. It has to accommodate the values that give meaning to the particles. Medicine’s problem with science has been a recurring theme throughout this book—a problem born out of success. The programme on William James also touched upon the fate of movements, of the spirit or of the mind, that become codified and institutionalised and suffer a loss of the life that inspired and motivated them. This is true of medical science to the extent that it has become increasingly concerned with manipulation rather than understanding; increasingly focused on the particles, and less on the rest of life. Our gratitude for the success of medical science in what it has been able to do for us need not be diminished by suggesting that it is seeking increasingly sophisticated answers to the wrong questions. Or rather that it is failing to address the right questions with the same degree of sophistication and commitment. This is not an argument for less science. On the contrary, it is the same argument that David Horrobin made 30 years ago for more and better science.4 That does not mean ‘better’ in the sense of more skilled or sophisticated, but in the sense of better attuned to ‘the rest of life’. In Horrobin’s terms it means making science more humane; more concerned, as he puts it, with the extraordinary potency of the control mechanisms that maintain the constancy of our physico-chemical equilibrium, without which we would never remain well. He is highlighting medical science’s surprising lack of interest in this ‘evolutionary imperative’; its preoccupation with learning to control the processes that go wrong at the expense of learning to enable the processes that help to put things right. And its lack of interest in learning to exploit them; even though they are integral and indispensable to every therapeutic process. This is an argument that medical science needs to be better directed; better attuned to the humanistic rather than the mechanistic goals of medicine. It is a huge challenge to the culture of medical science; and to the culture of medicine in general. And to the culture of the society that medicine serves and helps to shape, and in turn is shaped by. The wider cultural implications, such as medicine’s role in creating the kinder, more imaginative, more generous world’, ‘the more just and sustainable

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world’ envisioned in the quotations in Chapter 4, are employed in Chapter 17. The essential cultural reorientation that is required of medical science is that it should ‘frame its understanding of the world to understand the world truly rather than in order to control the world easily and cheaply.’ That is a crude paraphrase of a quotation from an essay on medical knowledge by HT Engelhardt that is used by David Greaves in his analysis of the problem with science in Mystery in Western Medicine, which I warmly recommend.5 The quotation is crude not only in the way I have rephrased it, but in the aspersion it casts on the goals of medical science; whose application in the real world is in any case seldom easy or cheap. But it makes the point yet again that the role of science is to understand the world truly. Truthfulness, I have suggested, is a core principle of medical practice and medical science, and I outline my reasons in Chapter 10. But in fact, untruthfulness is common in day-to-day clinical practice.6 It arises when medicine only acknowledges part of ‘the story of sickness’. A diagnosis, for example, is only part of the story; a description of what is going on, rarely an explanation of why a thing is as it is, but often presented as if it defines the whole problem.7 Untruthfulness arises when a doctor gives an antibiotic for a self-limiting illness, or another inappropriate prescription (though possibly with significant ‘placebo’ effect); or offers a diagnosis when the truth is ‘I don’t know’; or tells an ill patient there is nothing wrong because the tests are all normal. Untruth is introduced when “the dogma of technological medicine ignores the therapeutic effect of the doctor and the self-healing powers of the patient”8 when “doctors expect to find an answer to every problem if only they look hard enough with the right instruments.”9 It happens because although technology allows us to practise with ever greater precision and is a powerful tool for understanding, it also creates powerful misunderstanding when unwisely applied.10 In a great deal of medical practice, often with the best of intentions and to good effect, there is an element of deceit. This inherent untruthfulness is not necessarily to be condemned so much as to be acknowledged and reflected upon; sometimes to be corrected, sometimes to be accepted when there are mitigating circumstances.11 Deceit and consent to deceit are inevitable in medical practice whenever we imply, and quite possibly believe, that we know the truth of the matter when all we really know are some of the facts of the matter. We are victims of the success of biomedicine because of the expectation it encourages that we have the answers; whereas we are always dealing with a high degree of complexity and uncertainty. The inherent truth of the patient’s experience will often be beyond us. But that does not absolve us from the responsibility to be open to it, and faithful to it—as best we can be and as fully as the patient invites us to be. The fundamental untruth is the illusion of certainty. The inexcusable untruth is to reduce the problem and our response to it to its narrow biomedical

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parameters and to allow the patient as a person to vanish from our gaze. We can have no certainty about all that determines the course of illness and healing in any individual. We have to explore constantly and courageously that penumbra of uncertainty that surrounds our presumed certainties. This attitude does not displace, but assumes and comprehends proper respect for evidence and scientific method, clinical knowledge and skill. But it leaves room for the flexibility of mind that is essential if we are to know the world truly; especially if we are to open to the inherent truth of the patient’s experience. This flexibility is not scientific laissez-fair but an honest acknowledgement that, to paraphrase John Polkinghorne, on the one hand the physical world is too surprising to allow any a priori concept of what is reasonable, and on the other, the actual character of our encounter with reality must be allowed to shape our knowledge and our thought.12 The limitations of science

Science fails medicine not through lack of competence—it is able to do and to discover amazing things, but through lack of vision. Not for want of curiosity, but for the limit of things it is curious about. Not for any lack of the ability to investigate, but for the narrowness of the scope of things it is willing to investigate. The weaknesses of science are its strengths: its preoccupation with the things it does well and with the tools it knows how to use best. The opportunities of science to explore novel conceptions that do not sit comfortably with its contemporary paradigm seem to be regarded almost as threats; stifled by the fear that once a new framework is accepted it will lead to conclusions that have been hitherto, rightly or wrongly, abhorred (to paraphrase the quotation from Polanyi in Chapter 11); stifled by the quasi-religious fear of William James’s ‘scientificism’. In short, science must be true to its traditional vocation to the systematic pursuit of knowledge that permits no restriction as to the category of natural phenomena investigated. The cultural and structural problems that contribute to this loss of vision are explored in the Introduction and in Chapters 10 and 11. The areas of medicine that have been neglected as a consequence, though not quite ignored, include the following: Healing processes

We know a great deal about the causes of disease and the mechanism of the body’s response to insult and disorder of various kinds; causes as precise as our genetic susceptibility; mechanisms analysed down to the cellular and intracellular level. We know a great deal about the detailed mechanics of bodily self-regulation. We know a certain amount about the influence of psychological and environmental factors on these processes. We can describe the healing of a wound by first and second ‘intention’, the restoration of biochemical measurements to ‘the normal range’, the change in certain pathognomonic symptoms (symptoms charac-

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teristic of a specific disease). But our understanding of the correlation of these factors with the well-being of the person as a whole is more uncertain. Remember the quotation from Roy Porter: In myriad ways, medicine continues to advance, new treatments appear, surgery works marvels, and (partly as a result) people live longer. Yet few people today feel confident, either about their personal health or about doctors, healthcare delivery and the medical profession in general.13 For example, we know perfectly well that the ‘placebo’ effect and contextual healing happen. We know that various factors can promote these effects. And we know that they account for a significant part of even the specific efficacy of treatments demonstrated in controlled trials, as well as their actual effectiveness in practice. But we have a very poor understanding of these fundamental dynamics of healing processes; let alone how to make best use of them. We know very little about the natural history of these effects in the person as a whole. We know that placebo can induce relief of presenting symptoms, measurable physiological changes, and changes in brain chemistry. But the more general effect of these reactions in the person as a whole, and the effects over time are not known. We do not know anything much about the time scale of onset or duration of placebo responses, or their permanence or transience. We do not know to what extent they are usually limited to the target symptom or condition. We do not know whether and to what extent they have incidental effects on aspects of wellbeing other than the presenting problem. Bearing in mind that ‘placebo’ responses ‘work’ by mobilising resources for self-regulation and self-healing, we do not know whether these resources are thereafter enhanced to the benefit of longer term healthfulness. The only context I know, and to which I can find reference, in which detailed observations of this kind are made is the homeopathic method that I describe in Chapter 14 and Appendix 14.1. A piece of research begging to be attempted, for example, is suggested by the short notes on ‘Healing processes’ in that chapter. The detailed observation of changes in response to treatment by the homeopathic method provides a well documented account of the dynamics of self-regulation and self-healing across a wide range of morbidity. These clinical observations, described in the appendix, are valid whether the agent of the healing process is the contextual or ‘placebo’ effect of the method, or the homeopathic prescription itself, or a combination of the two. A similarly detailed and documented account of placebo responses, in conventional trial situations perhaps, would permit comparison between the two sets of observations. Firstly, both would be descriptions of ‘natural healing’, providing invaluable insight into that process, because whatever they do homeopathic medicines cannot have

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pharmacological effects. And secondly the comparison would cast light on the similarity or difference of the process in the two clinical situations, allowing us to draw inferences about the similarities or differences between the effect of the homeopathic medicines and the inert placebo agents used in trials. Illness

We know a great deal about disease processes, but we do not know much about the poorly defined state that we call illness, and out of which disease arises; or from which medicine has to ‘create’ a disease in order to explain it. Actually, that is not quite true. It is more accurate to say that we do know a fair amount about the things that make us ill, but we can’t do much about it, unless and until it becomes a disease, or unless we can turn it into a disease we do know how to treat, or at least how to control. We know, for example, that exams, bereavement and moving house, and other critical or traumatic situations in life affect our immune system and our adrenal function. We know that poverty and social deprivation make us ill; not only when there is actual lack of essential food, accommodation, hygiene, education, etc., but also where there is relative lack of material well-being compared to wealthier sections of society. And the medical and social sciences do develop or advocate the means to remedy or mitigate such problems. But there is an inevitable element of mystery to personal illness, and to the challenge of meeting the needs of a particular individual who is ill. It may be beyond the scope of science to analyse every facet of the mystery of personal illness. But at least it must not encourage us to neglect the mysterious in favour of the measurable—the McNamara fallacy again (Chapter 10). The science that permits us to define illness in terms of precise biological disorder must not distract us from the importance of the biographical diagnosis, the story of the sickness. But more importantly it must take account of that broader diagnostic perspective, explore it, and help us to understand and manage it. However, there are questions that may shed light on aspects of the mystery that medical science can, and to a limited extent does answer: •• ‘Why me?’ Why do/did I become ill when others in similar circumstances did not? •• ‘Why this?’ Why did I develop this illness/disease? Why do I react to anxiety/hot weather/a virus with headache, when X gets diarrhoea and Y gets eczema? •• ‘Why now/then?’ Why did it happen when it did—not six months ago, or next week? What were the factors/ circumstances that determined the time of onset? The limited extent of medical science’s exploration of these questions is illustrated by contrast with the particularly detailed case taking necessarily employed by doctors using the homeopathic method.

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This is a clinical process of a wholly conventional if unusually comprehensive kind that yields an unusually versatile and comprehensive synthesis of biological and biographical data from which, by contrast with a more conventional approach, a more complete understanding both of the evolution of the illness in that person (the story of sickness), and of what needs to be healed as well as treated can emerge.14 This not only facilitates the therapeutic process, but also reveals the possible scope of detailed epidemiological enquiry. Treatment—The Black Box

For a period during my GP career my surgery was in our home. My consulting room was our sitting room out of hours. Patients would often sit on the sofa. The waiting room was a small room immediately adjacent where the receptionist sat with the patients, and the atmosphere was intimate, welcoming and cheerful. The sound of laughter filtering through the door into the consulting room, unusual in the average doctors’ waiting room, was not uncommon. I provided routine fifteen minute appointments, but the patients were often and evidently feeling better by the time they came in to me because of the warmth of their ‘reception’. They did then get the benefit of my repertoire of clinical skills, and whatever personal qualities I brought to the relationship. This, at the time, was my therapeutic ‘black box’. It would be quite difficult to itemise all of its component parts. And impossible to be sure which component made what contribution to the patient’s subsequent well-being and clinical outcome. A GP colleague of mine identified 35 separate components of the therapeutic encounter. All treatment, every medical encounter is a therapeutic black box. The workings of the black box in conventional practice, we like to think, are less of a mystery because we know what the specific component, the drug or procedure is meant to do. The workings of the black box in complementary medicine are often represented as a sort of confidence trick because we are sceptical that it has a specific component that does anything at all. In either case the result may be effective or ineffective, safe or unsafe. But the medical model justifies the use of the black box only if it has a specific component whose efficacy can be ‘proved’. One approach to the black box is to unpack it, isolate that specific component, and submit it to ‘destructive analysis’. Another approach is to say that we must not attempt to unpack the black box because to try may destroy it, and deprive it of its practical effectiveness. Science has a dual responsibility towards the understanding of human wholeness and the healing vocation that is expressed beautifully in an essay by George Orwell on The Meaning of a Poem: I have tried to analyse this poem as well as I can in a short period, but nothing I have said can explain, or explain away, the pleasure I take in it. That is finally in explicable, and it is just because

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it is inexplicable that detailed criticism is worthwhile. Men of science can study the life-processes of a flower, or they can split it up into its component elements, but any scientist will tell you that a flower does not become less wonderful, it becomes more wonderful, if you know all about it.15 Science must combine a humility and sense of awe in the face of the wonderful and inexplicable, and in the face of irreducible uncertainty, with a scientific passion and insatiable curiosity to know all about it. It will never fully explain, and must never seek to explain away, the mystery of life, but the mystery itself makes critical analysis worthwhile. Medical science must accept that there is always a black box that operates between every practitioner and every patient in every therapeutic encounter. It has many components and many dimensions, and the permutation of these will vary from one encounter to another. The complete and precise operation of the black box, the outcome of its operation, its effectiveness, the human consequences, will always, ultimately defy analysis. That finally is inexplicable, and it is just because it is inexplicable that detailed criticism is worthwhile. Medical science must not make the mistake of confusing the question whether the black box ‘works’, with the question how it does it. Both are valid questions, and both have valid answers. Both are worth exploring. But the answer to one does not depend upon the answer to the other. We would like to know how our black boxes ‘work’, and we will try to find out. But what matters more is that they do work. If we are honest, and admit, as research into placebo effects increasingly reveals, that all our therapeutic activities are effectively black box operations; and if we were to abandon all treatments in which we do not fully understand how the black box works, we would give up medical practice altogether. Useful science and wasteful science

Useful science enables us to do things that are really worth doing. The question of what is really worth doing is an ethical and cultural question that is profoundly important to our conception of the goals of medicine and the model we devise to serve those goals. But we have seen in Chapter 9, when exploring the crisis of cost in the health service, that when challenged to reduce cost there is a considerable number of activities that clinicians consider are not worth doing. Medical science has made it possible to do them and provided the technology to do them. This bears out Lyng’s suggestion quoted in the earlier discussion of the problems of technology in Chapter 11, that technology encourages ‘the interventionist thrust’ of modern medicine. This appetite for and tacit dependence on the necessary ‘instrumentation’ is fed by medical science, and rather than serving the goals of medicine simply ‘creates the space for possible medical events.’16 David Horrobin characterised this over-use of technol-

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ogy as “The application of a technique to a situation, without any critical consideration of whether the outcome is likely to be favourable or not”.4 We might restate David Haslam’s observation that “We use the medical model because the medical is what we use, even though it may not be appropriate”,17 as ‘We use medical technology because medical technology is what we use, even though it may not be appropriate.’ Science wastefully applied, because it is not really useful, is of course science harmfully applied. Every intervention carries some risk; is potentially iatrogenic. An intervention that is not really useful is one kind of medical untruth. And a wasteful intervention costs money that could be better spent. In May 2010 the British Medical Journal published a ‘head to head’ debate, ‘Is modern genetics a blind alley?’18 “Yes”, says James le Fanu. “Modern genetics has become the largest single research field in the history of biology, driven forward by the expectation that ‘like a mechanical army (it will) destroy ignorance . . . promising unprecedented opportunities for science and medicine’. And yet for all this cornucopia of new facts and knowledge, its influence on everyday medical practice remains scarcely detectable.” He quotes the chief executive of Genentech as saying that all this effort amounts to “the largest money losing industry in the history of mankind.” He speculates that the complexities of those methodologies might explain in part the paucity of original ideas in medicine, diverting attention and resources from more fruitful forms of clinical research. Le Fanu regards it as “highly improbable that the future of medicine might lie in understanding disease at (this) most fundamental reductionist level.” D.J. Weatherall argues that on the contrary genetic research promises real benefits and is already delivering some. He points out that genetic research is a young discipline and that it would be short sighted to view it as a blind alley, considering the complexity of the subject it has to explore. But his contribution to the debate does not inspire confidence. He acknowledges the extraordinary complexity of biological function in health and disease that modern genetics continues to unearth. He compares this phase of its exploration to the endless, and some might argue similarly fruitless search in modern physics for a grand unifying theory. He acknowledges that most common diseases “seem to reflect the action of many different genes with small effects, presumably combined with environmental factors and the biology of ageing.” Research like this is presumably driven by scientific passion, and does increase our wonder at the beautiful intricacy of life, even if ultimately what makes us tick remains inexplicable. But having read this debate, I wonder to what extent the research will prove to be practically useful. Nevertheless, it is reassuring that this debate, and the ethical debates about embryo research and the like, are happening. But science has a huge responsibility to be sure that its passion and the seductive power of what it can do, do

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not lead us up blind alleys, at the end of which nothing really useful is achieved; particularly if our essential humanity and wholeness is diminished in the process. Research

Perhaps the most serious revolution that remodelling medicine requires is in medical research. There are many challenges (see Box 18.1). The predominant thrust of research programmes is to isolate a problem from its ‘confounding variables’ (all the other things in life that bear upon the health and well-being of the afflicted person), and then to reduce the problem to its most fundamental biological component (genetic, biochemical, functional, anatomical) so that this can be managed or manipulated. The test of the ability of any treatment that results from this process to do what is expected of it (its efficacy) requires that the measurement of this outcome is similarly isolated from the effect of confounding variables. BOX 18.1 Research Challenges

•• The dynamics of illness. •• Healing processes. •• Enabling self-regulation. •• Context and meaning. •• ‘Subtle’ therapeutic effects. •• The therapeutic ‘black box.

This is a generalisation that is not true of all research methods, but it does represent the principal focus and predominant thrust of medical research. It is brilliantly successful in what it sets out to do. It does make it possible to manage or manipulate particular components of disease processes. But it provides a very partial solution to the whole complex spectrum of illness-disease-sickness. I have hyphenated the three words to emphasise that medicine is concerned with a complex phenomenon of which the pathology, which is what we usually mean by disease, is only a part. The illness-disease-sickness triad, whose various meanings are discussed at the beginning of Chapter 8, involves the person as a whole and is contingent upon a multiplicity of circumstances in the person’s life. What is more any medical intervention affects the person as a whole, not just the part that it acts directly upon, and has consequences for the circumstances of the person’s life. And lastly, no actual medical intervention is simple or circumscribed. As we have seen it is always a ‘black box’ procedure. The narrow focus of biomedical research, for all its achievements, cannot do justice to this complexity. In fact it really has nothing to say about it. This is not to disparage biomedical science. It is not an argument to esteem science less, but ‘to esteem it in the right way’, in Mary Midgeley’s words; ‘especially to stop isolating it from the rest of life’. As Iris Bell and colleagues put it in a discussion of the research relevant to a new

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model for primary health care: “The reductionist approach to science is valuable (but) it fails to reflect the way the real world operates”.19 Which is perhaps why as Roy Porter reflected in the quotation in Chapter 3, despite the myriad ways in which science continues to advance, “Few people today feel confident, either about their personal health or about doctors, healthcare delivery and the medical profession in general”.13 The medical research culture must change if it is to promote science for understanding alongside science for manipulation. Medical scientists might argue that the myriad advances in science do allow us to understand; to understand what goes wrong when disease affects us, and what to do about it. But it is probably fair, and more accurate to say that science allows us to describe what goes wrong so that we may do something about it, but not necessarily to understand it. It allows us to know what to do to correct the fault, but it does not help us to understand the mixed dynamics of the illness-diseasesickness process, nor of the healing process. A change in the medical research culture that promotes this level of understanding and the health care practices that it permits will not come easily. The biomedical paradigm is so powerful and the model so successful that it is almost impervious to change. The plausibility construct or world view that sustains them is not conducive to change. Its materialist perspective encourages mechanistic solutions. “World views and the values placed on different health outcomes are closely related. Thus the values that underlie medical care shape the scientific questions that researchers ask, the health outcomes they measure, and the interpretation of the results”—Iris Bell and colleagues again, reflecting the discussion in Chapters 10 and 11. To develop research methods that study healthcare processes that are holistic and integrative is even more difficult than studying diseases and treatments that are isolated from the rest of life. This is because, by definition they concern illness-disease-sickness that has multiple determinants (predisposing and causative factors), that affects the person as a whole (all aspects of their well-being), that has multiple outcomes (physical, psychological and social), and that involves a number of interventions (either as ingredients of the ‘black box’ or as separate and distinctive processes), which are individualised to the needs of the patient. It is obvious from this scenario that research of this kind is asking far more profound questions than ‘what is wrong?’, and ‘what works?’ It is asking questions about the whole phenomenon of illness-disease-sickness within the narrative of human experience, of life. It is exploring new ways of thinking about disease and therapeutics. This may sound idealistic and impossibly challenging. It is challenging, but it is not impossible. And to a limited extent the challenge is being met, the methods are being explored, and it is beginning to happen. This is too big a subject for me to do more than offer a few examples to illustrate it. General readers who do not have an interest in research may find the

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next few pages heavy going, and may prefer to skip to the Conclusion at the end of the chapter. 1. Research policy

Based on work by Trisha Greenhalgh, Professor of Primary Care Research, University College, London, writing in the British Medical Journal20: The narrow focus of research policy and research commissioning is manifestly inadequate and inappropriate to health care in the real world: “Research policy is currently powerfully shaped and constrained by talk of the knowledge based economy and the contribution of high technology innovation to UK plc. This discourse has repositioned the core business of primary care research as running a ‘population laboratory’ for large scale epidemiological studies, preferably with a pharmacological component. Such studies are important but they are not the whole story.” Research initiative in general practice (which might reveal more of the story) is burdened by “the creeping institutionalisation and regulation of research. Epidemiology’s unanswered questions demand large scale collaborative studies that can be undertaken only within a complex research infrastructure. Non-epidemiological questions relevant to primary care (for example, on the humanistic and social dimensions of illness and healing) are currently defined as a lesser form of science for which only B-list funding and publication outlets are available.” 2. Exploring illness: interpretive medicine

These quotations are taken from a paper by Joanne Reeve proposing ‘interpretive medicine’ as a better framework for the generalist care that must be the foundation of good clinical practice. It is “the critical, thoughtful, professional use of an appropriate range of knowledge in the dynamic, shared exploration and interpretation of individual illness experience, in order to support the creative capacity of individuals in maintaining their daily lives.”21 The holistic and integrative ideal in medicine is best, if imperfectly, represented by general practice. Other disciplines, such as geriatric medicine and palliative care and some aspects of mental health care, also represent this generalist ideal. But it is threatened by the evidence based approach which has strayed from its founders’ intention that evidence should be submitted to the judgement of clinical relevance, and become focused on “hierarchies of evidence (that) privilege knowledge from what some consider to be a narrow methodological perspective.” The effect of this is to narrow the scope of the generalist’s perception of the patient. “The disadvantages of constrained protocoldriven care are recognised by the profession; but still form a new formative normative framework for clinical practice.” This militates against generalism, which “is more than disease-focused care delivered in a community setting. It is a different approach to understanding and addressing health and illness. (It) describes a

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philosophy of practice which is person, not disease, centred; continuous, not episodic; integrates biotechnical and biographical perspectives; and views health as a resource for living and not an end in itself.” The generalist approach is essential to address growing concerns about the inefficiency, ineffectiveness and inequity of fragmented health care, and to promote an understanding of “specific events in their broader context, integrating biomedical evidence with a reflexive and interpretive approach that acknowledges, the complexity of individual human experience.” 3. Setting research priorities: a layman’s experience

This is a personal view published in the British Medical Journal.22 The author, Lester Firkins, is a former banker who became involved in the world of medical research, specifically clinical trials, because of his role in a patients’ charity concerned with Creutzfeldt-Jakob Disease (CJD) which had claimed the life of his son. When he attended a consumer workshop on clinical trials for CJD he “assumed that this was what always happened in planning clinical research; it seemed natural and made sense.” He was surprised to discover however, that “the views of patients, their families and even clinicians are rarely sought when research priorities are being decided,” and that his later involvement as co-chairman on the steering committee for a CJD research project was “an example of ‘cutting edge’ involvement of lay people in clinical research.” Whereas to him it had seemed “a normal and sensible thing to do: who else other than someone closely involved with the disease could help with some important elements in the design of the trial?” In banking an attempt would automatically be made to research customers’ needs before packaging a new product. His experience taught him that unpleasant competition for academic status and fiefdoms must not be allowed to override patients’ interests in research planning and funding: and that involvement of patients and their professional and lay carers should be normal and welcome in the shaping of clinical research, and knowledge about and participation in good clinical trials should be a normal feature of citizenship. 4. A circular model for research

Presumably the kind of participation described above would be a component of the circular model of evaluation of complex interventions recommended by Harald Walach and colleagues.23 This is proposed as an alternative to, and an improvement upon the ‘hierarchical’ method for evaluating complex interventions. All medical interventions when they are applied in the real world are in effect, as we have seen, complex interventions; if only because they inevitably include contextual and placebo effects, even when they involve only one specific procedure, which is seldom the case anyway. The hierarchical research model has at its base

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descriptive case studies, but at its apex, and as the final arbiter of efficacy, the blinded randomised controlled trial. This depends upon the assumption that only the specific effects of a treatment or procedure, attributable to an understandable mechanism are of clinical value. This we know to be a false assumption. The circular model described in that paper is derived from the evolution of evaluation methodology in the social sciences “which has reached the consensus that only a multiplicity of methods used in a complementary fashion will eventually give a realistic estimate of the effectiveness and safety of an intervention. Rather than postulating a single ‘best method’ this view acknowledges that there are optimal methods for answering specific questions, and that a composite of all methods constitutes best scientific evidence. Experimental methods that test specifically for efficacy have to be complemented by observational, non-experimental methods that are more descriptive in nature and describe real-life effects and applicability.” The authors quote the synthesis of different ways of knowing described by Gabbay and le May as the ‘mindlines’ used in decision making by general practitioners, as an empirical example and justification for this model.24 (See Chapter 10, ‘Ways of knowing’.) “Many patients recover because of complex, synergistic or idiosyncratic reasons that cannot be isolated in controlled environments (trials). . . . By conceptualising evidence as circular we can highlight the fact that sometimes the ‘best’ evidence may not be attributional, objective, additive or even clinical.” 5. Evaluating large scale and complex interventions

In fact it is not unusual that large scale healthcare interventions are introduced without clear evidence that benefits outweigh costs and harms. This was pointed out in a debate about the merits or otherwise of such a process in the British Medical Journal.25 Bernard Crump argues that it can be appropriate to do so when explicit evidence is hard to come by; particularly in complex interventions that involve the behaviour of people and systems and that are just not susceptible to evaluation by the yardsticks that have been developed for narrower biomedical interventions. He, too, argues, as do Walach and colleagues vis-à-vis the social sciences, “We need to learn from other scientific sectors to broaden our understanding of evidence.” He is not suggesting an uncritical approach to such interventions, far from it, but a process for developing programmes of improvement that “builds on feedback on intermediate outcomes and will allow for adjustment of the intervention as the implementation takes place.” He recommends combining this with the ‘generative’ approach that takes account of the mixed dynamics of the therapeutic process and requires a deep appreciation of contextual factors, using a combination of qualitative methods (descriptive, observational, narrative) and quantitative methods (measur-

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ing what it is possible and appropriate to measure). The other protagonist to this debate, Seth Landefeld, argues that on the contrary the evidence should be compelling if well intended interventions are not to fail, perhaps cause harm, and cost dearly. He is doubtful that observational studies provide sufficient justification. But he warns that evidence should only be accepted, and interventions put into practice “carefully, because the effects of interventions may vary among patients, providers, and medical care environments, which often differ from those in studies that establish efficacy.” Which actually seems like an argument for the circular, iterative and generative approaches that others recommend. 6. Multi-disciplinary integrative care

In a study from Denmark five conventional practitioners (neurologist, occupational therapist, physical therapist, psychologist and nurse) and five complementary practitioners (acupuncture, nutritional therapy, classical homeopathy, craniosacral therapy and reflexology) explored the possibilities of collaboration in the care of patients with multiple sclerosis (MS).26 The project’s core question was—‘Is it possible to improve treatment outcomes in people with MS by developing a model for bridge-building between conventional and alternative practitioners, and thereby facilitate and integrative treatment process at the patient level?’ The study is particularly interesting, and ambitious, because it brings together practitioners with, effectively, ten different theoretical and practical approaches to patient care. The basis for the dialogue (IMCO) was the four parameters—Intervention (what does the practitioner do together with the patient?), Mechanism (how do the process and context of treatment achieve the outcome?), Context (the motivation, attitudes, personal resources, insights and expectations that the patient brings to the process), and Outcomes (what physical, emotional, psychological and social benefits are expected and achieved by the intervention?). The definitions in parenthesis are my paraphrase. The study did not set out to evaluate the outcome of multidisciplinary integrative care of this kind, but to explore its feasibility and the means by which it can be achieved. The study process (four seminars with preparatory work) was not easy, and common objectives in terms of outcomes were very difficult to agree. But eventually the ten practitioners “developed a mutual understanding of the different treatment models; began to think as a team; developed a mutual communication platform based on trust; and developed a platform for collaboration with the researchers.” The authors conclude, “Creating bridges between fundamentally different ways of conceptualising diseases, curing and healing, simply takes time. However, collaboration is possible when focusing less on singular treatments and more on the primary target of optimising the treatment of each unique individual.”

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

7. Investigating ‘whole person’ approaches

Iris Bell and colleagues emphasise as I have done that Integrative Medicine is not the same thing as complementary medicine (CAM) but “a comprehensive primary care system that emphasises wellness and healing of the whole person”.19 Nevertheless, they go on to say that, “As it evolves, truly integrative medicine also depends for its philosophical foundation and patient-centred approach on systems of CAM that emphasise healing the person as a whole (e.g., Traditional Chinese Medicine, Ayurvedic Medicine, and classical homeopathy). These CAM systems diverge the most in philosophy, diagnosis and treatment from conventional medicine, and thus remain marginalised. As a result, clinicians and researchers often break off parts of these CAM systems from their original contexts to fit a few of the smaller pieces into the dominant model of conventional care and medical research. For example, numerous studies have investigated the efficacy of acupuncture for various Western disorders, but virtually no studies examine the effectiveness of the sum total of Chinese medicine as practiced. It is a testable hypothesis that the effect sizes of the full treatment program could be much larger and more clinically significant if the entire Chinese medicine treatment program were studied as used.”

care. It would require consortia: •• Get to know the complementary practices in their area. •• Understand and appraise their potential contribution to patient care—but not to learn their therapeutic methods (example 6). •• Learn from patients’ experience of using complementary medicine (example 3). •• Select therapists (Chapter 19). •• Learn to collaborate (Chapter 19). •• Negotiate payment. •• Establish proper communication and continuity. •• Audit the process and its outcomes. •• Apply all appropriate ways of knowing (Chapter 10) to inform and develop their practice ‘mindlines’. •• Incorporate research from formal trials with these other sources of knowledge in a circular process of evaluation (example 4) that comprehends the effectiveness of the complementary approaches as a whole rather than isolated bits of their respective black box (example 7). This need not actually be a hugely time consuming or demanding task. It might even be enjoyable and liberating. Conclusion

A thought experiment

Only two of these examples of lateral thinking around the subject of research are directly related to complementary medicine (CAM), but they are all relevant to the particular challenge that is presented by the role of CAM, and any expanded role for CAM, within integrative health care. Here is a thought experiment that supposes the large scale introduction of a potential health care improvement for which there is not compelling evidence (example 5), but which could generate, or of course fail to generate such evidence. The 2010 UK coalition government proposed that an £80 billion (€94 billion, $124 billion) budget should be entrusted to general practitioners to commission services from other health care providers. Suppose that all 500 of the GP consortia expected to manage this budget, if it is equally distributed, were required to commit 0.1% of their share of the budget to integrating complementary medicine into primary and secondary care. Or if that seems too extreme, suppose that 0.0002% of the total budget is allocated to a 20% cohort of consortia, 100 of them, for that purpose. In either case each consortium committed to the task would have £160 000 (€187 000, $247 000) to spend per year. The object of the exercise is to improve the health and well-being of their patients and to reduce the burden (of time, cost and stress) on themselves and their practices and the other services they would normally commission by the informed and discriminating use of complementary medicine; a similar exercise to that undertaken in the Glastonbury Project (Chapter 16). It would be a new exercise in interprofessional

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Medical knowledge is not knowledge acquired primarily for its own sake (but) for a specific purpose – the care of the sick.1 Medical science and the study of health care delivery are already developing methods of enquiry and suggesting outcomes that justify a radical reappraisal of medical thought and practice. Subtle therapeutic methods that stimulate self-regulation and self-healing, and the contextual and ‘meta-organic’ factors that contribute to these have already achieved significance and importance in our understanding of the dynamics of health care. And their application is a widespread and insistent reality of contemporary medicine. Wider and more formal and systematic adoption and integration of these methods and of the precepts they exemplify promise health gains and economic benefits that are too great to ignore. If the promise is to be fulfilled, and it must certainly be tested to be sure that it can be, medical science must redirect its biomedical gaze towards these more holistic horizons. And that redirection of its gaze will require that it is more willing to adopt ways of looking at illness-disease-sickness, and at health care and healing that are far more flexible and versatile than the ‘hierarchy’ of evidence has hitherto permitted. Medical science must acknowledge that there are ways of knowing and things to be known that exceed the scope of its presently dominant paradigm. The examples given in these pages point the way. Science, the systematically organised expression of our desire to know the world truly, admits to no

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Remodelling medicine

boundaries. But medical science is an applied science. As a doctor I am guided in my practice as much by an awareness of what I should not do as of what I should do. There are questions that I must ask, and questions that I must not ask unless the patient invites them, at least implicitly. There are insights that I must not offer unless and until the patient is ready to receive them; things I must not say because they would be inappropriate, impertinent or unkind. There are procedures I must not perform without the patient’s consent; prescriptions I must not make unless they are really needed and will be tolerated. This often requires great sensitivity, discretion and restraint. In other words I have a repertoire of knowledge and skills, and personal attributes, which must always be subordinated to my compassionate understanding of the person in my care and the context of that particular therapeutic encounter. It must be appropriately applied. The application of science in medicine must be similarly discriminating, and always have a person in its gaze, even when it is a molecule that is the precise focus of attention. This is a shared responsibility between the clinician and the scientist. Scientists must fully understand the implications that the application of their science will have for the therapeutic process, the healing relationship. They must not promote its application simply out of their scientific enthusiasm for its possibilities, just as I must not impose some treatment on a patient simply because of my enthusiasm for that particular drug or procedure, or therapeutic theory. And the clinician must not adopt a scientific advance just because it becomes available. It must never be true, to misquote David Haslam again, that we use the medical science because the medical science is what we use. We must never be tempted to use a laboratory test just because it has become a cheaper and easier way of managing a patient if it does not help us to understand that patient’s predicament truly; particularly if it becomes a substitute for listening to the patient carefully. And I mean carefully. Clinicians must never succumb to the lust described by D.H. Lawrence and quoted by David Horrobin4:

References 1. Pellegrino E, Thomasma D. The Virtues in Medical Practice. Oxford: Oxford University Press; 1963. 2. Midgeley M. Science as Salvation. London: Routledge; 1992. 3. Ward K. In Defence of the Soul. Oxford: Oneworld; 1998. 4. Horrobin D. Medical Hubris – A reply to Ivan Illich. Edinburgh: Churchill Livingstone; 1978. 5. Greaves D. Mystery in Western Medicine. Aldershot: Avebury; 1996. 6. Swayne J. The truth the whole truth or anything but the truth. Consent and deceit in pain medicine The British Pain Society: Special interest group for philosophy and ethics. London: British Pain Society; 2009. pp28–43. 7. Rosenberg C. The Tyranny of Diagnosis: Specific Entities and Individual Experience. The Millbank Quarterly 2002; 80(2):237–260. 8. Dixon M. Sweeney K. The Human Effect in Medicine. Oxford: Radcliffe; 2000. 9. Spiro H. The Power of Hope. New Haven & London: Yale University Press; 1998. 10. Engel G. The need for a new medical model. Science 1977; 196:4286;129–136. 11. Sokol D. The Humane Lie: Acceptable deceptions in the doctor–patient relationship. Consent and deceit in pain medicine British Pain Society; Special interest group for philosophy and ethics. London: British Pain Society; 2009. pp5–15. 12. Polkinghorne J. Theology in the Context of Science. London: SPCK; 2008. 13. Porter R. The greatest benefit to mankind. London: Fontana; 1997. 14. Swayne J. Homeopathic Method: Implications for Clinical Practice and Medical Science. Edinburgh: Churchill Livingstone; 1998. 15. Orwell G. The Collected Essays Journalism and Letters of George Orwell. Volume II: My Country Right or Left 1940–1943. London: Harmondsworth-Penguin; 1970. 16. Lyng S. Holistic Health and Biomedical Medicine. New York: State University of New York Press; 1990. 17. Haslam D. Who cares? Br J Gen Pract. 2007; 57(545):987–993. 18. le Fanu J, Weatherall DJ. Is modern genetics a blind alley? Br Med J. 2010; 340 c1008:1008–9. 19. Bell IR, Caspi O, Schwartz G et al. Integrative medicine and systemic outcomes research. Arch Intern Med. 2002; 162:133–140. 20. Greenhalgh T. Not all those who wander are lost. Br Med J. 2010; 340 c4611:229. 21. Reeve J. Protecting generalism: moving on from evidence-based medicine? Br J Gen Pract. 2010; 60:576;521–523. 22. Firkins L. Setting research priorities: a layman’s experience. Br Med J. 2008; 337 a212:114. 23. Walach H, Falkenberg T, Fønnebø V et al. Circular instead of hierarchical: methodological principles for the evaluation of complex interventions. BMC Med Res Methodol. 2006; 6:29. 24. Gabbay J, le May A. Evidence based guidelines or collectively constructed “mindlines”? Ethnographic study of knowledge management in primary care. Br Med J. 2004; 329;1013–17. 25. Crump B, Landefeld S. Should we use large scale healthcare interventions without clear evidence that benefits outweigh costs and harms. Br Med J. 2008; 336:1267–1277. 26. Launsø L, Skovgaard L. The IMCO scheme as a tool in developing team-based treatment for people with Multiple sclerosis. J Altern Complement Med. 2008; 14(1):69–77.

When I went to the scientific doctor I realised what lust there was in him to wreak his so-called science on me and reduce me to the level of a thing. So I said: Good morning! And left him. There must be a dialogue between clinicians and scientists that ensures that what clinicians really need to know, or really need to have available to them, is translated into an agenda for the scientists. And that what scientists have to offer can be really usefully applied in clinical practice. The same principle applies to other fields of applied science, of course. And it begs the question—When should this dialogue begin? I suspect that to be truly fruitful it must begin at quite an early stage in a common educational pathway.

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www.gahmj.com • Volume 1, Number 1 • March 2012

cochrane column

Summary of Findings Tables: Presenting the Main Findings of Cochrane Complementary and Alternative Medicine–related Reviews in a Transparent and Simple Tabular Format Eric Manheimer, MS

Author Affiliation Eric Manheimer, MS, is a research associate at the University of Maryland School of Medicine and an administrator and methodologist in the Cochrane Collaboration Complementary Medicine Field, University of Maryland School of Medicine, Baltimore. Correspondence Eric Manheimer emanheimer@ compmed.umm.edu Citation Global Adv Health Med. 2012;1(1):90-91. Key Words Summary of Findings, Cochrane, Collaboration, CAM, complementary and alternative medicine, systematic review, RCT, GRADE, randomized controlled trial

For more information about the Cochrane CAM Field, visit http://www. compmed.umm.edu/ cochrane_about.asp

he systematic review is widely accepted as the most reliable and objective method for evaluating the effects of healthcare interventions, including complementary and alternative medicine (CAM) therapies. Systematic reviews use explicit, transparent, and well-documented methods to find, evaluate, and synthesize the best available research studies related to a specific research question. Systematic reviews of healthcare treatment typically have focused on randomized controlled trials (RCTs) because RCTs are widely regarded as the study design providing the most reliable estimates of a healthcare treatment’s effects. Systematic reviewers aim to evaluate and appraise relevant RCTs using objective and reproducible methods to provide an unbiased assessment of the evidence for a given therapy. Systematic reviews sometimes include a meta-analysis, the quantitative combining (pooling) of results from similar but separate RCTs to obtain an overall effect estimate. Up-to-date systematic reviews are of critical importance to researchers, healthcare providers, and policymakers. Systematic reviews can help researchers pinpoint where knowledge gaps exist and thereby help in the design and conduct of new RCTs. The systematic review serves to ensure that a proposed new RCT is relevant, necessary, and guided by earlier RCTs. Indeed, to ensure that future RCTs are optimally designed based on what has been learned from previous RCTs,1,2 some funding agencies such as the Canadian Institutes of Health Research3 and the UK Medical Research Council4 and medical journals including the Lancet5 now require evidence from a recent systematic review before funding or publishing a new RCT. Amidst the vast, almost limitless number of research questions that remain to be addressed in CAM and the limited financial support available to study CAM therapies, which unlike pharmaceuticals and medical devices typically cannot be patented by industry, it is particularly important that CAM investigators plan RCTs in the context of what is already known on a topic as summarized in a systematic review. Healthcare providers must also keep current with research findings or they risk adverse consequences for patient care, including the continued recommendation and use of therapies proven ineffective or even harmful by RCTs, as well as a delay in the uptake of treatments proven to be effec-

Volume 1, Number 1 • March 2012 • www.gahmj.com

tive.6 Similarly, policymakers need access to such reviews (and their summaries) as a way of summarizing evidence for the development of guidelines and as a factor in decision making.7 The Cochrane Collaboration, founded in 1992, is an internationally renowned nonprofit initiative dedicated to preparing, maintaining, and promoting the accessibility of systematic reviews to improve healthcare for the world’s population. The Cochrane Collaboration currently involves more than 28 000 contributors from 110 countries,8 most of whom are volunteer researchers who prepare the rigorous and high-impact Cochrane reviews as part of their academic responsibilities. As of Issue 10, 2011, the Cochrane Database of Systematic Reviews includes 4791 Cochrane systematic reviews, 488 of which relate to CAM. Cochrane reviews often are considered the gold standard of systematic reviews because they undergo a strict and meticulous peer review process, are regularly updated, and are largely free from commercial conflicts of interest. Indeed, the reputation of the Cochrane Collaboration as an unbiased source of evidence rests upon organizational policies forbidding sponsorship of Cochrane reviews and their derivative products, Cochrane review authors, and Cochrane entities by any commercial source, particularly the pharmaceutical industry and medical device manufacturers.9 The full Cochrane reviews, however, are sometimes not accessible to healthcare providers, consumers, and policymakers because of the length and complexity of the full reviews. Shorter summaries of Cochrane reviews are therefore necessary to bridge the gap in stakeholders’ accessibility to evidence-based information about CAM. To address this need, the Cochrane Collaboration has developed an innovative way to disseminate the overall findings of Cochrane reviews as Summary of Findings (SoF) tables and Plain Language Summaries. SoF tables focus on the major comparison from a Cochrane review (eg, acupuncture vs sham acupuncture) and display in a tabular format the findings for each outcome (eg, pain, function) for this comparison, as well as an evaluation of the overall strength and quality of the evidence for each outcome. Plain Language Summaries are prepared based on the data from the SoF tables. The development and refinement of an approach

Cochrane Column

Summary of Findings Tables: An Overview

for disseminating the bottom-line findings of Cochrane Reviews have been underway within the Cochrane Collaboration since 2000. The final SoF format that has now been endorsed by the Cochrane Collaboration is based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for rating the quality of evidence. In addition to its endorsement by the Cochrane Collaboration, the GRADE approach has been adopted by more than 20 other organizations, including the World Health Organization, the American College of Physicians, the UK National Institute for Health and Clinical Excellence, UpToDate, and the British Medical Journal. The CAM researchers and providers who read Global Advances in Health and Medicine may find it helpful to become familiar with the GRADE approach and the resultant SoF tables. In GRADEing the quality of RCT evidence for the SoF tables, Cochrane reviewers consider several factors, including within-study risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates, and risk of publication bias.10 To prepare the SoF tables and Plain Language Summaries of CAM-related Cochrane reviews, the Cochrane CAM Field has collaborated with the Nordic Cochrane Centre. The preparation of each SoF table is time and labor intensive and generally requires 3 to 4 days of an experienced methodologist’s time. Some of the work involves deciding which outcomes to present for which time points and evaluating the strength and quality of the evidence for the outcomes. For each SoF table, the authors of the Cochrane Review are contacted to request clarification on any points that are not understood in the Cochrane Review and also to request their review of the SoF table. Beginning with this issue, Global Advances in Health and Medicine and the Cochrane CAM Field launch the first in a series of columns called “Cochrane CAM Reviews: Summary of Findings.” The first column, on page 100 of this issue, summarizes the Cochrane review “Horse chestnut seed extract for chronic venous insufficiency.” In that column, Underland et al present the Plain Language Summary, which provides a general introduction to the treatment—in this case, horse chestnut seed extract (HCSE)—and the condition, chronic venous insufficiency, as well as a narrative review of the effectiveness of HCSE for chronic venous insufficiency. The narrative summary is followed by an SoF table that quantitatively documents the effects of HCSE relative to a placebo on 6 different health outcomes relevant to chronic venous insufficiency, as well as the number of participants/studies and a GRADEing of the quality of the evidence for each of the 6 outcomes. The summary in this first column suggests that the inexpensive and relatively safe HCSE has the potential to improve chronic venous insufficiency while also pointing out limitations in the quality of the existing RCT evidence.

Cochrane Column

REFERENCES 1. Clarke M, Alderson P, Chalmers I. Discussion sections in reports of controlled trials published in general medical journals. JAMA. 2002 Jun 5;287(21):2799-801. 2. Clarke M, Hopewell S, Chalmers I. Clinical trials should begin and end with systematic reviews of relevant evidence: 12 years and waiting. Lancet. 2010 Jul 3;376(9734):20-1. 3. Straus S, Moher D. Registering systematic reviews. CMAJ. 2010 Jan 12;182(1):13-4. 4. Chalmers I. Using systematic reviews and registers of ongoing trials for scientific and ethical trial design, monitoring, and reporting. In: Egger M, Davey SG, Altman DG, editors. Systematic reviews in health care: meta-analysis in context. London: BMJ Books; 2001. p. 429-43. 5. Young C, Horton R. Putting clinical trials into context. Lancet. 2005 Jul 9-15;366(9480):107-8. 6. Lau J, Antman EM, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med. 1992 Jul 23;327(4):248-54. 7. Dickersin K, Manheimer E. The Cochrane Collaboration: evaluation of health care and services using systematic reviews of the results of randomized controlled trials. Clin Obstet Gynecol. 1998 Jun;41(2):315-31. 8. Allen C, Richmond K. The Cochrane Collaboration: International activity within Cochrane Review Groups in the first decade of the twenty-first century. J Evid Based Med. 2011 January 27 [Epub ahead of print]. 9. Commercial sponsorship and the Cochrane Collaboration. The Cochrane Collaboration website. http://www.cochrane.org/about-us/commercial-sponsorship. Accessed January 13, 2012. 10. Schünemann HJ, Oxman AD, Vist GE, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JP, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011; cited 2012 Jan 13]. Available from: http://www.cochrane-handbook.org/.

For more information about Global Advances in Health and Medicine, please visit our website: www.gahmj.com. 如需获得关于《全球健康与医疗进展》的更多信息，请访问我们的网站：www.gahmjcom. Para obtener más información sobre Global Advances in Health and Medicine, visite nuestra página Web: www.GAHMJ.com.

www.gahmj.com • Volume 1, Number 1 • March 2012

Review

Fever in Cancer Treatment: Coley’s Therapy and Epidemiologic Observations Gunver S. Kienle, Dr med

Author Affiliation Gunver S. Kienle, Dr med, is senior research scientist at the Institute for Applied Epistemology and Medical Methodology at the University of Witten/Herdecke in Freiburg, Germany. Correspondence Gunver S. Kienle, Dr med gkienle@gahmj.com Citation Global Adv Health Med. 2012;1(1):92-100. Key Words Cancer, fever, sarcoma, carcinoma, Coley, epidemiology, leukemia, remission, tumor, vaccine, MBV, infectious disease

n the fall of 1890, an athletic, self-possessed, and thoughtful 17-year-old girl, who had just returned from an adventurous trip to Alaska where she had hurt her hand in a trivial accident, went to see a young, innovative surgeon in his new practice in New York City. Barely out of Harvard Medical School, he was a rising star in New York surgical circles, and the young woman asked him for help with her poorly healing, swollen, and naggingly painful injury. This visit had a far-reaching effect on cancer research, American philanthropy, and the career of the young man, William Coley, MD (1862-1936, Figure 1). The patient, Elisabeth Dashiell, confidant and close friend of John D. Rockefeller, Jr, was diagnosed by Coley with a highly aggressive round cell sarcoma, and despite radical surgery and in spite of Coley’s undoubtedly fine surgical skills and intensive care, a rapid progression of the cancer, immense suffering, and Elisabeth’s death a few months later could not be prevented. The experience of the swift, fatal course and of the insufficiency of surgery in even the finest and most modern American hospital left Coley deeply shaken— and determined to find a treatment for this dreadful disease. It also was the starting point of Coley’s lifelong friendship with Rockefeller, whose philanthropic work was inspired by Elisabeth’s death, leading to the foundation of the Rockefeller University.1 Coley went on to develop the first immunological cancer treatment, attempting to cure cancer with fever, and thereby founded the field of tumor immunology. He began with an investigation of all case histories of sarcoma at the New York Cancer Hospital (later Memorial Sloan-Kettering). He stumbled on the record of 31-year-old Fred K. Stein, who was afflicted with a round cell sarcoma on the neck that had recurred 5 times after surgical removal until it was considered inoperable; the case had been declared hopeless when the man contracted a severe erysipelas infection (caused by Streptococcus pyogenes) that spread rapidly over the neck and face and was accompanied by a raging fever. A second attack followed 2 weeks later. In the course of these attacks, the sarcoma disappeared entirely. Seven years later, Coley tracked Stein down on the Lower East Side, where he still enjoyed excellent health and had only a scar below his ear left to show where the “inoperable” sarcoma had been.1,2 Feverish Infections and Spontaneous Remission

Since the 18th century, spontaneous remissions of cancer—altogether a very rare event—have been

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Figure 1 William Coley, circa 1888, at the start of his medical career. Reprinted with permission from the Cancer Research Institute.

observed repeatedly in connection with febrile infectious diseases, especially those of bacterial origin.1,3-5 In 1866, Busch described complete remissions occurring under erysipelas covering the tumor.3 In 1882, Fehleisen induced tumor remission with the inoculation of streptococci causing erysipelas.6 The French physician Dussosoy dressed an ulcerated breast carcinoma with charpie soaked with gangrenous discharge and inoculated gangrenous matter; the tumor was said to have disappeared.4 In the 1950s, Huth described 24 remissions of leukemia after bacterial infections.7 Of a total of 224 spontaneous remissions of cancer reviewed by Stephenson, 62 had occurred under infection or persistent fever and 77 under “reticuloendothelial stimulants.”8 Of 68 spontaneous remissions of metastatic melanoma, 21 occurred concurrent to infections and 11 to immunoactive interventions (eg, vaccination, application of antibodies, tumor cells, Bacillus CalmetteGuérin [BCG]).9 Of 86 spontaneous remissions of lymphoma, 3 occurred after bacterial or viral infections and 12 after termination of immunosuppressive treatment.10 Of 98 children with Hodgkin’s lymphoma, 3 contracted measles that led to tumor remission.11 Among 21 patients with spontaneous regression of colorectal cancer, 6 occurred under septic complications or febrile

Review

Fever in Cancer Treatment

pneumonia.12 A profound and comprehensive documentation included 449 cases of spontaneous or induced bacterial or viral infections in cancer patients that led to remission in most cases. For instance, of 163 patients with inoperable carcinoma or sarcoma who had pyogenic infections, a complete regression had occurred in 37 who were followed for 5 to 46 years; in 54 patients, the tumor had regressed completely but was followed for less than 5 years or diagnosed only clinically; 13 patients had shown no response; the remaining patients had a tumor remission with an unknown longterm outcome or had died.13 Coley thoroughly reviewed the literature available at that time and found 38 reports of cancer patients with accidental or iatrogenic feverish erysipelas. In 12 patients, the sarcoma or carcinoma had completely disappeared; the others had substantially improved. Coley decided to attempt the therapeutic use of iatrogenic erysipelas when the next patient with an infaust and hopeless condition was referred to him: Signor Zola, a 35-year-old Italian, had a recurrent and now inoperable sarcoma of the neck and the tonsil (Figure 2). The size of a hen’s egg, it almost completely blocked the pharynx. The patient was in a bad condition—cachectic, with liquids regurgitated through the nose—and was expected to live only a few weeks. Coley inoculated Streptococcus pyogenes every 3 to 4 days for months but only induced slight local and systemic reactions, leading to some tumor shrinkage and improvement of the general condition but not to erysipelas or to disappearance of the tumor. When the inoculations were paused, the tumor continued to grow and shrank again during the next inoculations. Dissatisfied with this course, Coley managed to get bacteria from Robert Koch’s laboratory in Germany. Within 1 hour of the bacteria being injected directly into the neck tumor, the patient developed chills, pain, nausea, vomiting, and a high fever (105º), and after 12 hours, a typical erysipelas stretched over the tumor of the neck, extended over the face and head, and met on the other side. The attack lasted 10 days. The neck tumor changed promptly, got paler and softer, began to break down on the second day, discharged a caseous material until the last day, and had disappeared after 2 weeks. The tonsil tumor regressed but never disappeared completely and remained as a hard, fibrous mass. The patient rapidly gained strength and appetite and became perfectly well again for 8 years. The tumor then recurred, and he died of the disease.2,14 Coley treated with living bacteria 10 patients who had inoperable sarcoma (n = 6) or carcinoma (n = 4) and infaust prognoses. Repeatedly, the condition temporarily improved and the tumor partly regressed, but no erysipelas could be induced. Just 4 patients developed a full erysipelas, followed by a remission of the tumor.2 However, 2 additional patients died due to erysipelas infections that raged out of control.1,2 Mixed Bacterial Vaccine

Different lessons were learned: A fulminant attack

Review

Figure 2 Signor Zola, who survived another 8 years after being treated by Coley in 1891. Reprinted with permission from the Cancer Research Institute.

of erysipelas can induce dramatic and complete tumor remission; a mere injection of Streptococcus pyogenes without a full erysipelas can improve the disease and induce some tumor shrinkage but does not lead to complete, durable tumor remission; it is not easy to induce a full erysipelas attack by streptococci; and erysipelas is a severe, life-threatening disease. These difficulties led Coley to try cultures sterilized by heating or filtration, which produced little effect. Inspired by the animal experiments of Rogers, he mixed them with toxins of gram-negative Serratia marcescens and thus created the mixed bacterial vaccine (MBV). The first patient treated with MBV was a 16-year-old German with an inoperable spindle cell sarcoma on the abdominal wall, 6.5 x 5.25 x 5 inches, attached to the pelvis, and infiltrating the bladder. The patient was in bad condition when the MBV treatment was started. The intratumoral injections were followed by a temperature increase of 0.5° to 6°, with tachycardia, chill, extreme trembling, and severe headache. At times, the tumor was enlarged on the days following the injection but then gradually decreased over the next months and finally disappeared. The man regained good health and stayed healthy without a recurrence until he suddenly died of myocarditis 26 years later in a subway station.15 Coley, who meanwhile became a staff member and later chief of the Bone Cancer Department of the New York Cancer Hospital—the second in the world dedicated to the treatment of cancer and supported by wealthy families16—successively developed and improved MBV treatment, the first official immunotherapy for cancer. Especially in sarcomas but also in other cancer types, long-term remissions could be

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

TABLE 1 Patients With Inoperable Cancer Treated With Mixed Bacterial Vaccine Alone Before 1940a Type of Cancer

Total

Patients With Complete Tumor Remission

No Tumor Response

Follow-up > 20 y

5-10 y

< 5 yb

Soft tissue sarcomas

Lymphosarcomas (lymphomas)

Osteosarcoma

Ewing’s tumor/reticulum cell sarcoma

Ovarian carcinoma

Cervical carcinoma

Renal tumor

Multiple myeloma

Colorectal carcinoma

Testicular tumor

Breast carcinoma Melanoma

Values indicate number of patients with or without tumor response, duration of follow-up with no indication of relapse.17

Or relapse within 5 years.

achieved with MBV alone, without surgery or radiotherapy (Table 1).17 The patients were tracked down, and their longterm outcomes were carefully documented over years and decades, up to 88 years in one case. The documentation was done for the most part by William Coley’s daughter, Helen Coley-Nauts (1907-2000), founder of the New York Cancer Research Institute. She conscientiously and comprehensively documented all the patients treated with MBV by her father and colleagues and tried to keep track of all of them. In 1953, she published her first detailed analysis, which attracted worldwide attention. She had collected 1200 cases treated with MBV and reported more than 270 patients with inoperable cancer achieving a complete remission with MBV; the follow-up time stretched up to 45 years. Cases were classified into “successes” (ie, complete remission with no recurrence during later years) and “failures”: those cases that also included complete remissions but in which cancer recurred later. In 1959, a survey was published on all MBV-treated cases with soft tissue sarcoma (except lymphosarcoma) known to the New York Cancer Institute. Of 186 patients, in 105 (57%), the treatment was regarded as successful (of these, 35 tumors were operable and 70 tumors were primarily inoperable, 2 of which were treated with apparent success with radiotherapy), with a follow-up of 4 to 62 years (one of the patients was pregnant; she later gave birth to a healthy baby). Eighty-one (43%) patients were treated “unsuccessfully,” which included patients with complete tumor remissions that later relapsed.18,19 Other surveys assessed and described MBV treatment in reticulum cell sarcoma of the bone20; Hodgkin’s lymphoma21; osteogenic sarcoma22,23; ovarian, uterine, and cervical carcinoma24; breast cancer25; neuroblastoma26; renal cancer27; melanoma28; testicular cancer29; sarcoma

10-20 y

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of the soft tissues30; colorectal cancer31; Ewing’s sarcoma32; and multiple myeloma33 with similar results. MBV was usually injected intramuscularly and locally intra- or peritumorally; intravenous application was not generally recommended due to safety concerns. Patients developed shaking chills followed by fever (102105º F) lasting up to 12 to 24 hours. The injections were repeated first every day and then on alternate days with increasing dosage. High and consistent fever plus the local inflammation at the tumor site were regarded as essential for therapeutic success. Treatment success was obvious within a few days: the tumors became paler, softer, and movable, then regressed or opened and discharged a caseous secretion or just regressed. If these reactions did not occur within 1 to 4 weeks, MBV was regarded as ineffective; nevertheless, it often still improved the patient’s general condition, reduced pain, or improved appetite. To achieve a durable remission and prevent relapses, the treatment was continued for a long time (usually months).34,35 Patients were treated according to their individual constitution and reaction in order to increase the effectiveness and to minimize the risks.34,35 The recurrent chills and the induced fever over weeks and months were strenuous for the patients, many of whom were severely ill. In 1000 treated patients, 6 fatal complications were observed due to embolism, acute nephritis, hemorrhage (if the tumor had grown into a blood vessel), or the injection of too large initial dosages by inexperienced physicians.34,36,37 Otherwise, MBV was largely safe.18,19,38-40 Up to 15 different preparations of MBV existed, but not all were potent enough to induce high fever and durable remissions.30,41 This was particularly the case with the commercial preparations used mostly outside of New York. In one instance, Coley was contacted by a colleague who had treated a lymphosarco-

Review

Fever in Cancer Treatment

ma patient with high doses of a commercial product without any response. When Coley provided him with vaccines from his own supply, the patient reacted to the very first injection with high fever, chills, and subsequent tumor remission and was disease-free until he died of heart disease 33 years later.30 After Coley’s death in 1936, MBV treatment was continued but clinical interest diminished in favor of radiotherapy and chemotherapy, which promised a breakthrough in cancer treatment comparable to antibacterial treatment. In 1961, the thalidomide tragedy occurred and gave rise in the United States to the Kefauver Harris Amendment, which applied strict requirements to preclinical and clinical investigations of new treatments. Although it had been used for 70 years, MBV was at that time classified as a new treatment, necessitating expensive investigations for drug licensing. As MBV is a natural substance and was therefore not patentable, the investment of millions of dollars for testing was unattractive for any drug company. As for academic institutions, other topics were more appealing than an old bacterial treatment dealing essentially with “dirt.” Still, some small prospective studies were conducted; MBV treatment was, however, increasingly standardized, applied less aggressively, and the vaccines less potent (Helen Coley-Nauts, oral communication, December 1996). Furthermore, the included patients were often pretreated with chemotherapy or radiotherapy, which substantially alters the immune system and therefore modifies the response to an immunomodulating treatment.17 In one randomized controlled trial (RCT), MBVtreated patients with advanced, metastatic cancer (n = 34) showed 7 subjective and 9 objective responses, 3 of which were complete remissions (partly verified by later autopsy); in the control group (n = 37), which was administered typhoid vaccines, one improvement was reported.38 Of 93 patients with advanced cancer in a single-arm MBV study, 30 had a tumor remission (partly verified by later autopsy), 20 reported subjective improvements, and the remaining 43 had no change.39 In a study of 7 patients with inoperable cancer, no remissions were found.42 In a small RCT, patients with advanced non-Hodgkin’s lymphoma who were treated with MBV in addition to chemotherapy showed higher response rates than control patients without MBV (complete remissions 85% vs 44%, respectively), and survival was significantly longer.43-45 Patients with liver cancer showed better survival (trend) in an RCT when chemotherapy (partly also radiotherapy) was combined with MBV.46 In a study on metastatic melanoma, of 15 patients receiving MBV, 3 had a complete remission (20%) lasting at least 15, 21, and 32 months.39 Other studies on MBV primarily investigated immunomodulation and tolerability.47,48 Recently, 128 cases treated with MBV between 1890 and 1960 were matched with 1675 control patients from the Surveillance Epidemiology End Results (SEER) cancer

Review

registry who received a cancer diagnosis in 1983. The survival rates were not significantly different, despite the tremendous advances in surgical techniques and modern medicine with which patients in the SEER group were treated (Table 2).49 TABLE 2 Survival of Patients Treated (1890-1960) With Mixed Bacterial Vaccine (MBV) Matched With Patients From Surveillance Epidemiology End Results (SEER) Diagnosed in 1981a Median Survival, y Tumor type

MBV

Kidney cancer

Breast cancer Soft-tissue sarcoma a

MBV

SEER

33.3%

23.1%

55.6%

29.8%

25.0%

38.1%

50.6%

38.9%

6.5

Ovarian cancer

10-y Survival Rate

SEER

Matching criteria: site, stage, treatment status (ie, no radiotherapy), age, sex, ethnicity.49

Infectious Diseases and Subsequent Cancer

Clinicians frequently have claimed that the anamnesis of cancer patients revealed fewer feverish infections compared to other patients. This gave rise to numerous epidemiological investigations,50 which predominantly show an inverse association between various acute infectious diseases or fever and cancer risk (Table 3).51-88 The risk is further reduced with increased frequency of infections and if fever is involved. Somehow, these events affect cancer immune surveillance, which seems to be—conversely—negatively affected by the risk factors supporting cancer growth.89 Often, a better outcome is also reported in cancer patients who had postoperative infections. However, the corresponding studies usually refer to very small sample sizes, limiting their validity. Potential confounders prevalent especially after postoperative infectious complications are another reason for these altogether conflicting results. For instance, several studies reported longer survival in patients with empyema after lung cancer surgery.90-93 These observations prompted an RCT in which BCG was applied intrapleurally after resection of lung cancer, which led to a substantial reduction of recurrences in early stages but no difference in advanced stages of the cancer.94 Two studies found no difference in survival after empyema,95,96 and one study showed a slightly negative effect.97 In colon cancer (stage I), one study found better survival in patients with postoperative infections,98 another study found no difference,99 and a third study found increased recurrences (with, however, an altogether high prevalence of infections).100 In melanoma, after local wound infection, decreased recurrences were reported, but there was no difference in survival.101 Survival also was increased in osteosarcoma patients after postoperative infection.102 In patients with breast and head and neck cancer, however, rates of recurrence were higher and survival partly reduced after a postoperative increase in temperature or wound infection.103-105 Interestingly, in contrast to acute inflammation,

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TABLE 3 Epidemiologic Studies (One Meta-analysis) Investigating the Association Between Infectious Diseases and Subsequent Cancer51-88,a Infectious Disease or Condition

Case/Control Cancer Site

Year

Reference No.

Childhood disease, infectious diseases

241/—

Gastrointestinal

No infectious disease as child in 180 patients, as child and 1910 as adult in 99 patients

Childhood disease, infectious diseases

300/300

Multiple

No infectious disease in 113 cancer patients vs 16 control patients

1934

Childhood disease, infectious diseases

232/2444

Multiple

Fewer infectious diseases, especially childhood diseases

1936

Tonsillectomya

831/9990

Upper aerodigestive tract Fewer tonsillectomies

1960

Tonsillectomya

542/5020

Upper aerodigestive tract Fewer tonsillectomies

1963

Mumps, measles, rubella

97/97

Ovarian

Less mumps and rubella

1966

Mumps

36/150

Ovarian

No association

1969

Typhoid fever

5460b/

Multiple

Lower cancer mortality in survivors of typhoid fever 1945-1947

1970

Viennese population

History of Infectious Diseases in Cancer Patients/ Cancer Risk After Infectious Diseases

Multiple (febrile disease, other diseases)

150/150

Multiple

Less fever (1% vs 13%), fewer doctor visits (15% vs 45%), 1970 less hospitalization (5% vs 12%)

Pneumonia, influenza

399/395

Ovarian

Less pneumonia and influenza

1974

Tonsillectomya

305/305

Leukemia (in children)

Fewer tonsillectomies

1975

Tonsillectomya

752/752

Leukemia

Fewer tonsillectomies

1976

Mumps, measles, chicken pox, rubella

300/600

Ovarian

Fewer infections (reduced risk of ovarian cancer in history 1977 of infections: RR 0.47-0.86)

Tonsillectomya

1415/1415

Lung

Fewer tonsillectomies

1978

Rubella, measles, mumps

197/197

Ovarian

Overall, no difference; more peripubertal rubella and measles (12-18 y), less during childhood years

1979

Immunizations, infectious diseases

33/99

Rhabdomyosarcoma (in children)

Fewer immunizations, more preventable (with immunization) infectious diseases

1982

Multiple, fever

110/126

Multiple

Less fever, fewer colds and organic infections

1983

Measles

252/230c

Multiple

More tumors in people with no measles rash despite immunoglobulin G measles antibody

1985

Multiple

492/480

Leukemia (in children)

Reduced risk of leukemia after serious infectious diseases: RR 0.6

1986

Common cold

120/239

Multiple

No association

1986

Fever >3 days, herpes

204/1353d

Multiple

Reduced cancer risk after febrile diseases

1987

Multiple

255/485

Multiple

Reduced cancer risk after cold/influenza (OR 0.18-0.23) or febrile abdominal influenza (OR 0.15-0.23) but not after childhood diseases

1991

Childhood disease, febrile infectious diseases

139/271

Melanoma

Reduced risk of melanoma after chronic infectious diseases 1992 (OR 0.32), febrile abscesses, wound infections (OR 0.21), influence/cold (OR 0.32), trivial febrile diseases (OR 0.34). No association with childhood disease

Chicken pox, shingles

462/443

Glioma

Fewer chicken pox (OR 0.4) and shingles (OR 0.5)

1997

Febrile childhood disease

379/379

Multiple

Reduced cancer risk after febrile childhood diseases 1998 (non–breast cancer OR 0.27, especially rubella, chicken pox)

Infectious diseases

Italian population

Multiple

Decreased mortality from infectious diseases (1895-1947) paralleled and followed by increased mortality from cancer (1895-1990)

1998

Multiple (severe or less severe, fever)

603/627

Melanoma

Reduced risk of melanoma after febrile infections: tuberculosis (OR 0.16), Staphylococcus aureus (OR 0.54), sepsis (OR 0.23), flu (OR 0.65), pneumonia (OR 0.45); dose-response relationship

1999

Infectious diseases

1509/2493

Glioma, meningioma

Reduced risk of glioma and meningioma after infectious diseases (RR 0.72 and 0.73)

1999

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Review

Fever in Cancer Treatment

TABLE 3 Epidemiologic Studies (One Meta-analysis) Investigating the Association Between Infectious Diseases and Subsequent Cancer51-88,a (cont) Infectious Disease or Condition

Case/Control Cancer Site

History of Infectious Diseases in Cancer Patients/ Cancer Risk After Infectious Diseases

Year

Reference No.

Childhood disease, febrile infections

111/109

Multiple

Increased risk of cancer after mumps, whooping cough, decreased risk after cold

2002

Childhood disease, ear infection

538/504

Neuroblastoma (children)

Reduced risk of neuroblastoma after childhood diseases (OR 0.60), increased risk after ear infections (OR 1.76)

2004

Infections

455/1031

ALL (children)

More infectious episodes in leukemia than control patients (3.6 vs 3.1)

2007

Infections

162/2125

Leukemia (children)

No association

2008

Vaccination, childhood disease

399/399

Leukemia (children)

No association

2008

Multiple

Less mumps, rubella, chicken pox. Never fever in 83% of cancer vs 57% of control patients

2009

Fever during infections, child- 355/244 hood disease Day-care attendancee

6108/19910f ALL (children)

Reduced risk for ALL (OR 0.76) after day-care attendance

2010

Common infections, day-care attendancee

720/1494

ALL, acute myeloblastic leukemia (children)

Reduced risk for ALL after repeated common infections (OR 0.7) and day-care attendance (OR 0.8)

2010

Tonsillitis, tonsillectomya,g

2988/h

Hodgkin’s lymphoma

Increased risk (RR 1.4) of lymphoma after tonsillitis

2010

Common infections, day-care attendancee

669/977

ALL (children)

Reduced risk of ALL after day-care attendance and ear infections

2011

Abbreviations: ALL, acute lymphoblastic leukemia; OR, odds ratio; RR, relative risk. a

Tonsillectomy as indicator for tonsillitis.

Exposed to typhoid fever.

Negative vs positive history of measles.

Total patient group (prospective study).

Day-care attendance as indicator for early exposure to various infectious diseases.

f Meta-analysis

of 14 studies.

Studies on tonsillectomy only partly included.

124 million person years.

chronic inflammation increases cancer risk and can affect every aspect of tumor development.106 Many chronic viral, bacterial, and parasitic infections are a risk factor for developing cancer: Helicobacter pylori in mucosa-associated lymphoid tissue lymphomas, Epstein-Barr virus in lymphoma or nasopharyngeal cancer, hepatitis B and C virus in liver cancer, herpes virus type 8 in Kaposi sarcoma, human papillomavirus in cervix or anogenital cancer, Schistosoma in bladder cancer, and others.50 About 15% to 20% of cancers worldwide are attributed to these infectious agents.107 Noninfectious chronic inflammatory diseases also are a major risk factor for cancer. Examples include inflammatory bowel disease and colon cancer, bronchitis and lung carcinoma, reflux esophagitis and esophageal cancer.106,108 Sustained inflammation seems to be the result of an individual’s inability to eliminate infection and restore immune homeostasis.50,109 Immune and inflammatory cells as well as cytokines can have antitumor- and tumor-promoting functions, depending on the context.106,110,111 Initiation of Cancer Immunotherapy

In Coley’s era, the scientific and medical community lacked the prerequisite knowledge to understand his treatment. The intellectual environment was incapable of making scientific sense of tumor remissions after application of bacterial toxins. Hardly anything was known about the immune system. The notion of cellular immunity was completely out of favor.

Review

Regarding inflammation, almost everybody agreed that this was a deleterious reaction of no benefit for the host, a purely passive response to the insulted organism.112 So it is not surprising that Coley—a respected surgeon but not a trained scientist—received harsh opposition.1 For decades after Coley’s death, fighting cancer with a host response was regarded as impossible; for a long time, investigating tumor immunity was considered a scientific red-light district, “a seedy intellectual neighborhood of fantasy and wishful thinking, a landscape littered with the hulks of abandoned hypotheses and charred reputations.” It was a biological minefield, capable of ruining careers.1 Even in the 1980s, the concept of clinical tumor immunity was regarded as consisting of laboratory artifacts.113-115 Still, Coley’s work substantially inspired research, and his observations were a main impulse for later tumor immunology. Shortly after Coley’s death, Shear discovered lipopolysaccharides (LPS), a component from the membrane of Serratia that induced necrosis of sarcoma in mice.116 Later, Old and Carswell isolated tumor necrosis factor (TNF) as an active mediator in LPS- or BCG-induced tumor necrosis.117,118 These and other discoveries restored Coley’s reputation. They were considered to provide a satisfactory answer to his observations,118,119 but despite all expectations, the cures obtained with MBV could not be replicated with isolated TNF-α or other cytokines. Nevertheless, these discoveries marked the beginning of an immunological

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GLOBAL ADVANCES IN HEALTH AND MEDICINE

renaissance in cancer research and assured Coley a permanent place in history.120 Today, a far more comprehensive understanding of the human immune system and tumor immunology is present,121 as is a conceptual extension beyond the simple self-nonself model,122 permitting a better understanding of Coley’s results. Obviously, MBVs stimulated a complex cascade, a “perfect storm” of cytokines— among these, interleukin (IL)-2, interferon-α,120 TNFα,118,119 and IL-12119 are seen as critical—and of tolllike receptors and other pattern recognition receptor agonists, each of which plays a unique and vital role in the orchestration of the immune response.120 Both the innate and the adaptive immunity are decisive, and the tumor vasculature is involved.17,120 Critical in the mediation of MBV effects is probably the activation of resting dendritic cells—via induction of cytokines and inflammatory factors with co-stimulatory activity. This leads to an activation of anergic T-cells, paralleled by a possible direct damage of cancer cells, inducing an improved supply of tumor antigens.123 A growing body of literature shows the complex modifying and orchestrating effects of fever and elevated temperature on the host response, immune cells, cytokines, antimicrobial defense, antitumor activity, and immune surveillance.124-127 For instance, fever and hyperthermia activate the heat-shock response, inducing heat-shock proteins; these can then activate dendritic cells and transform them into mature antigenpresenting cells, which then potentiate the immune recognition of antigens. Furthermore, hyperthermia improves immune surveillance by activating NK-cells and T-cells and increasing trafficking of dendritic cells into lymph nodes.127 Hyperthermia also directly induces tumor cell necrosis and apoptosis.128 In patients with sarcoma, hyperthermia increases the antitumoral efficacy of chemotherapy and radiotherapy.129,130 It is notable that erysipelas in particular is connected with spontaneous or induced tumor remission. Heat-killed, however, these gram-positive bacteria are hardly effective at all. In MBV, the gram-negative Serratia far outweigh the streptococci by an estimated factor of 7300:1, and in animal experiments, the curative and toxic effects are connected to Serratia whereas heat-killed streptococci alone are neither therapeutic nor toxic. Additionally, further research centered on endotoxins that are not present in gram-positive streptococci. During a fulminant erysipelas attack, possibly, a translocation of endotoxins of the gastrointestinal tract is induced, which then initiates a cytokine cascade.17 A further influence might be that during erysipelas attack, toxins are released continuously and fever may last for 1 to 2 weeks whereas the bacterial toxins were applied as a bolus. For the tumor responses obtained with living streptococci, a plasminogen activator also may have played a role, particularly streptokinase, which is produced by virulent streptococci.131 It is remarkable that tumor remissions by MBV required continuous and aggressive administration of

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bacterial vaccines, eliciting a cascade of cytokines over an extended period of time—days and weeks. The full therapeutic effects achieved with these vaccines may not be reproducible when applying just 1 or 2 recombinant cytokines.17 Though Coley’s cures involved the same immune mediators as modern stand-alone immune therapies, they used all of them in concert over an extended time and in the relevant part of the body.120 One should also bear in mind that a century ago, high exposure to tuberculosis was omnipresent and may have substantially contributed to higher effectiveness of the toxins.17 The question arises whether sarcomas respond better and more dramatically to erysipelas and MBV than carcinomas. They are overrepresented in erysipelas-induced tumor remissions. Mostly sarcomas were treated with MBV, especially soft-tissue sarcoma. Perhaps Coley, being the head of the New York Cancer Hospital’s Bone Cancer Department, had greater access to sarcoma patients and was not often consulted by carcinoma patients. His own comments on this issue are inconsistent. There are, in fact, a variety of reports of complete remissions of carcinomas as well, mainly from other physicians.24,25,31 Still, the hypothesis was raised that the mesodermal (mesenchymal) embryonic origin of sarcoma tissue might make these tumors more immunogenic.17 Conclusion

Altogether, the responses to fever therapy, spontaneous remissions in the course of infectious diseases, and the observation of the inverse correlation of acute febrile infections and incidence of cancer are remarkable. Still, deciphering the optimal tuning of host response and immune surveillance is far from being solved. A systemic concept is probably needed to understand the orchestrated cytokine and cellular storm resulting in the cures; otherwise, we might forever be left perplexed by the multitude of different kinds of cellular and molecular interactions.132-134 What is remarkable is that Coley developed the treatment not as we are used to—via “research and development” by the laboratories of biotech industry— but quite differently: through careful clinical observation of hundreds of patients and thorough knowledge of medical and scientific literature combined with critical reflection. Coley was the epitome of a clinician scientist, one of those pioneering individual physicians who made the seminal discoveries, especially in the golden age between 1930 and 1965, that irrevocably changed medicine by bringing us, for instance, sulphonamides, penicillin, cephalosporins, neuroleptics, antidepressants, and steroids.135,136 Since then, clinical drug research has moved into the laboratories and the pharmaceutical industry and is presently experiencing an insufficiency crisis.137-139 The strengths of those clinical champions are today remembered and called for again, and so are their virtues. Like Coley, they were proficient in their clinical work, guided by practical scientific thinking, open to the unexpected, and driven by the desire to cure patients.135,136,140,141

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Fever in Cancer Treatment

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Surg Gynecol Obstet. 1971 Oct;133(4):649-55. 9. Maurer S, Kölmel KF. Spontaneous regression of malignant melanoma. New York: Cancer Research Institute; 1997. 10. Wiernik PH. Spontaneous regression of lymphoma. 1-14. 1997. Albert Einstein Cancer Center and Montefiore Medical Center. Ref Type: Report. 11. Zygiert Z. Hodgkin’s disease: remissions after measles. Lancet. 1971 Mar 20;1(7699):593. 12. Abdelrazeq AS. Spontaneous regression of colorectal cancer: a review of cases from 1900 to 2005. Int J Colorectal Dis. 2007 Jul;22(7):727-36. 13. Nauts HC. The beneficial effects of bacterial infections on host resistance to cancer. End results in 449 cases. 2nd ed. New York: Cancer Research Institute; 1980. 14. Coley WB. Late results of the treatment in inoperable sarcoma by the mixed toxins of erysipelas and bacillus prodigiosus. Am J Med Sci. 1906;131(3):375-430. 15. Nauts HC, Fowler A, Bogatko FH. A review of the influence of bacterial infection and of bacterial products (Coley’s toxins) on malignant tumors in man; a critical analysis of 30 inoperable cases treated by Coley’s mixed toxins, in which diagnosis was confirmed by microscopic examination selected for special study. Acta Med Scand Suppl. 1953;276:1-103. 16. Levine DB. The Hospital for the Ruptured and Crippled: William Bradley Coley, third Surgeon-in-Chief 1925-1933. HSS J. 2008 Feb;4(1):1-9. 17. Wiemann B, Starnes CO. Coley’s toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther. 1994;64(3):529-64. 18. Pelner L, Fowler A. Host-tumor antagonism. XIII. Sarcoma of the soft tissues treated by bacterial toxins: successful series. J Am Geriatr Soc. 1959 Aug;7(8):624-47. 19. Pelner L, Fowler A. Host-tumor antagonisms. XIV. Sarcoma of the soft tissues treated by bacterial toxins: unsuccessful series. J Am Geriatr Soc. 1959 Sep;7:698-729. 20. Miller TR, Nicholson JT. End results in reticulum cell sarcoma of bone treated by bacterial toxin therapy alone or combined with surgery and/or radiotherapy (47 cases) or with concurrent injection (5 cases). Cancer. 1971 Mar;27(3):524-48. 21. Coley WB. Primary neoplasms of the lymphatic glands including Hodgkin’s disease. Ann Surg. 1916 Jan;63(1):35-70. 22. Coley WB, Coley BL. Primary malignant tumors of the long bones: end results in 170 operable cases, including a small group of malignant central sarcoma. Arch Surg. 1926 Dec;13(6):779-836. 23. Nauts HC. Osteogenic sarcoma: End results following immunotherapy with bacterial vaccines 165 cases, or concurrent infections, inflammation or fever, 41 cases. New York: Cancer Research Institute; 1975. 24. Nauts HC. Beneficial effects of acute concurrent infection, inflammation, fever or immunotherapy (bacterial toxins) on ovarian and uterine cancer. New York: Cancer Research Institute; 1977. 25. Nauts HC. Breast cancer: immunological factors affecting incidence, prognosis and survival (Part I-III). New York: Cancer Research Institute; 1984. 26. Fowler GA, Nauts HC. The apparently beneficial effects of concurrent infections, inflammation or fever and of bacterial toxin therapy on neuroblastoma. New York: Cancer Research Institute; 1970. 27. Nauts HC. Enhancement of natural resistance to renal cancer: beneficial effects of concurrent infections and immunotherapy with bacterial vaccines. New York: Cancer Research Institute; 1973. 28. Fowler GA. Enhancement of natural resistance to malignant melanoma with special reference to the beneficial effects of concurrent infections and bacterial toxin therapy. New York: Cancer Research Institute; 1969. 29. Fowler GA. Testicular cancer treated by bacterial toxin therapy as a means of enhancing host resistance. New York: Cancer Research Institute; 1968. 30. Nauts HC. Beneficial effects of immunotherapy (bacterial toxins) on sarcoma of the soft tissues, other than lymphosarcoma. New York: Cancer Research Institute; 1975. 31. Fowler GA. Beneficial effects of acute bacterial infections or bacterial toxin therapy on cancer of the colon or rectum. New York: Cancer Research Institute; 1969. 32. Nauts HC. Ewing’s sarcoma of bone: end results following immunotherapy (bacterial toxins) combined with surgery and/or radiation. New York: Cancer Research Institute; 1974. 33. Nauts HC. Multiple myeloma: beneficial effects of acute infections or immunotherapy (bacterial vaccines). New York: Cancer Research Institute; 1975. 34. Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the streptococcus of erysipelas and the bacillus prodigiosus). The Practitioner. 1909; 83:589-613. 35. Coley WB. The treatment of sarcoma with the mixed toxins of erysipelas and bacillus prodigiosus. Boston Med Surg J. 1908;158(6):175-82. 36. Coley WB. The treatment of inoperable sarcoma with the mixed toxins of erysipelas and bacillus prodigiosus. Med Record. 1917;91:965-6.

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37. Coley WB. Erysipelas toxins and erysipelas serum in the treatment of inoperable malignant tumors: further observations. Med Record. 1895;47(20):609-12. 38. Johnston BJ. Clinical effect of Coley’s toxin. I. A controlled study. Cancer Chemother Rep. 1962 Aug;21:19-41. 39. Johnston BJ, Novales ET. Clinical effect of Coley’s toxin. II. A seven-year study. Cancer Chemoth Rep. 1962 Aug;21:43-68. 40. Kölmel KF, Vehmeyer K, Göhring E, Kuhn B, Wieding JU. Treatment of advanced malignant melanoma by a pyrogenic bacterial lysate. a pilot study. Onkologie. 1991;14(5):411-7. 41. Nauts HC. Pyrogen therapy of cancer: a historical overview and current activities. In: National Cancer Institute and American College of Radiology, editor. Proceedings of the International Symposium on Cancer Therapy by Hyperthermia and Radiation, Apr 28-30, 1975:239-50. 42. Chandler JJ, Stark DB, Allen CV, Fletcher WS. Treatment of cancer by bacterial toxins. Am Surg. 1965 Jul;31:443-9. 43. Kempin S, Cirrencione C, Myers J, et al. Combined modality therapy of advanced nodular lymphomas (NL): The role of nonspecific immunotherapy (MBV) as an important determinant of responses and survival. Proc Am Soc Clin Oncol. 1983;24:56. 44. Kempin S, Cirrincione C, Straus DS, et al. Improved remission rate and duration in Nodular Non-Hodgkin Lymphoma (NNHL) with the use of mixed bacterial vaccine (MBV). Proc Am Assoc Cancer Res. 1981;22:514. 45. Oettgen HF, Old LJ, Hoffmann MK, Moore MA. Antitumor effects of endotoxin: possible mechanisms of action. In: Homma JY, editor. Bacterial endotoxin: chemical, biological and clinical aspects. Weinheim: Verlag Chemie; 1984. p. 205-22. 46. Tang ZY, Zhou HY, Zhao G, et al. Preliminary result of mixed bacterial vaccine as adjuvant treatment of hepatocellular carcinoma. Med Oncol Tumor Pharmacother. 1991;8(1):23-8. 47. Axelrod RS, Havas HF, Murasko DM, Bushnell B, Guan CF. Effect of the mixed bacterial vaccine on the immune response of patients with non-small cell lung cancer and refractory malignancies. Cancer. 1988 Jun 1;61(11):2219-30. 48. Havas HF, Axelrod RS, Burns MM, Murasko DM, Goonewardene M. Clinical results and immunologic effects of a mixed bacterial vaccine in cancer patients. Med Oncol Tumor Pharmacother. 1993;10(4):145-58. 49. Richardson MA, Ramirez T, Russell NC, Moye LA. Coley toxins immunotherapy: a retrospective review. Altern Ther Health Med. 1999 May;5(3):42-7. 50. Hoption Cann SA, van Netten JP, Van Netten C. Acute infections as a means of cancer prevention: opposing effects to chronic infections? Cancer Detect Prev. 2006;30(1):83-93. 51. Schmidt R. Krebs und Infektionskrankheiten. Med Klin. 1910;(43):1690-3. 52. Engel P. Über den Infektionsindex der Krebskrankheiten. Wien Klin Wochenschr. 1934;(37):1118-9. 53. Sinek F. Versuch einer statistischen Erfassung endogener Faktoren bei Carcinomkranken. Z Krebsforsch. 1936;44:492-527. 54. Güttich H. [Are tonsillectomized patients less subject to carcinoma of the upper respiratory and gastrointestinal tract?] HNO. 1960 Nov;9:47-9. German 55. Matzker J, Schmidt P. [On the problem of the relation between the tonsils and carcinoma of the respiratory and digestive tracts]. Z Laryngol Rhinol Otol. 1963 May;42:363-71. German. 56. West RO. Epidemiologic study of malignancies of the ovaries. Cancer. 1966 Jul;19(7):1001-7. 57. Wynder EL, Dodo H, Barber HR. Epidemiology of cancer of the ovary. Cancer. 1969 Feb;22(2):352-70. 58. Denk W, Karber K. [Studies on the possibility of immunoprophylaxis of carcinoma]. Österr Z Erforsch Bekampf Krebskr. 1970;25(1):30-9. German. 59. Witzel L. [History and other diseases in patients with malignant neoplasms]. Med Klin. 1970 May;65(18):876-9. German. 60. Joly DJ, Lilienfeld AM, Diamond EL, Bross ID. An epidemiologic study of the relationship of reproductive experience to cancer of the ovary. Am J Epidemiol. 1974 Mar;99(3):190-209. 61. Matzker J, Klasen HP. Tonsillektomie und Leukämie im Kindesalter. Laryngol Rhinol Otol (Stuttg). 1975;54(12):991-7. 62. Matzker J, Steinberg A. [Tonsillectomy and leukemia in adults (author’s transl)]. Laryng Rhinol Otol (Stuttg). 1976 Sep;55(9):721-5. German. 63. Newhouse ML, Pearson RM, Fullerton JM, Boesen EAM, Shannon HS. A case control study of carcinoma of the ovary. Br J Prev Soc Med. 1977 Sep;31(3):148-53. 64. Jentgens H, Matzker J, Steinhaus C. [Frequency of tonsillectomy in bronchial cancer patients (author’s transl)]. Laryng Rhinol Otol (Stuttg). 1978 Mar;57(3):190-3. German. 65. McGowan L, Parent L, Lednar W, Norris HJ. The woman at risk for developing ovarian cancer. Gynecol Oncol. 1979 Jun;7(3):325-4. 66. Grufferman S, Wang HH, DeLong ER, Kimm SYS, Delzell ES, Falletta JM. Environmental factors in the etiology of rhabdomyosarcoma in childhood. J Natl Cancer Inst. 1982 Jan;68(1):107-13. 67. Remy W, Hammerschmid K, Zänker KS et al. Tumorträger haben selten Infekte in der Anamnese. Med Klin. 1983;78(3):95-8. 68. Ronne T. Measles virus infection without rash in childhood is related to disease in adult life. Lancet. 1985 Jan 5;1(8419):1-5. 69. van Steensel-Moll HA, Valkenburg HA, van Zanen GE. Childhood leukemia and infectious diseases in the first year of life: a register-based case-control study. Am J Epidemiol. 1986 Oct;124(4):590-4. 70. Chilvers C, Johnson B, Leach S, Taylor C, Vigar E. The common cold, allergy and cancer. Br J Cancer. 1986 Jul;54(1):123-6. 71. Grossarth-Maticek R, Frentzel-Beyme R, Kanazir D, Jankovic M, Vetter H. Reported herpes-virus-infection, fever and cancer incidence in a prospective study. J Chronic Dis. 1987;40(10):967-76.

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72. Abel U, Becker N, Angerer R, et al. Common infections in the history of cancer patients and controls. J Cancer Res Clin Oncol. 1991;(117):339-44. 73. Kölmel KF, Gefeller O, Haferkamp B. Febrile infections and malignant melanoma: results of a case-control study. Melanoma Res. 1992 Sep;2(3):207-11. 74. Wrensch M, Weinberg A, Wiencke J, et al. Does prior infection with varicella-zoster virus influence risk of adult glioma? Am J Epidemiol. 1997 Apr 1;145(7):594-7. 75. Albonico HU, Bräker HU, Hüsler J. Febrile infectious childhood diseases in the history of cancer patients and matched controls. Med Hypotheses. 1998 Oct;51(4):315-20. 76. Mastrangelo G, Fadda E, Milan G. Cancer increased after a reduction of infections in the first half of this century in Italy: etiologic and preventive implications. Eur J Epidemiol. 1998 Dec;14(8):749-54. 77. Kölmel KF, Pfahlberg A, Mastrangelo G, et al. Infections and melanoma risk: results of a multicentre EORTC case-control study. Melanoma Res. 1999 Oct;9(5):511-9. 78. Schlehofer B, Blettner M, Preston-Martin S, et al. Role of medical history in brain tumour development. Results from the international adult brain tumour study. Int J Cancer. 1999 Jul 19;82(2):155-60. 79. Hoffmann C, Rosenberger A, Troger W, Buhring M. [Childhood diseases, infectious diseases, and fever as potential risk factors for cancer?] Forsch Komplementarmed Klass Naturheilkd. 2002 Dec;9(6):324-30; discussion 323. German. 80. Menegaux F, Olshan AF, Neglia JP, Pollock BH, Bondy ML. Day care, childhood infections, and risk of neuroblastoma. Am J Epidemiol. 2004 May 1;159(9):843-51. 81. Roman E, Simpson J, Ansell P, et al. Childhood acute lymphoblastic leukemia and infections in the first year of life: a report from the United Kingdom Childhood Cancer Study. Am J Epidemiol. 2007 Mar 1;165(5):496-504. 82. Cardwell CR, McKinney PA, Patterson CC, Murray LJ. Infections in early life and childhood leukaemia risk: a UK case-control study of general practitioner records. Br J Cancer. 2008 Nov 4;99(9):1529-33. 83. MacArthur AC, McBride ML, Spinelli JJ, Tamaro S, Gallagher RP, Theriault GP. Risk of childhood leukemia associated with vaccination, infection, and medication use in childhood: the Cross-Canada Childhood Leukemia Study. Am J Epidemiol. 2008 Mar 1;167(5):598-606. 84. Wrotek S, Kamecki K, Kwiatkowski S, Kozak W. Cancer patients report a history of fewer fevers during infections than healthy controls. J Preclin Clin Res. 2009;3(1):031-5. 85. Urayama KY, Buffler PA, Gallagher ER, Ayoob JM, Ma X. A meta-analysis of the association between day-care attendance and childhood acute lymphoblastic leukaemia. Int J Epidemiol. 2010 Jun;39(3):718-32. 86. Rudant J, Orsi L, Menegaux F, et al. Childhood acute leukemia, early common infections, and allergy: the ESCALE Study. Am J Epidemiol. 2010 Nov 1;172(9):1015-27. 87. Vestergaard H, Westergaard T, Wohlfahrt J, Hjalgrim H, Melbye M. Tonsillitis, tonsillectomy and Hodgkin’s lymphoma. Int J Cancer. 2010 Aug 1;127(3):633-7. 88. Urayama KY, Ma X, Selvin S, et al. Early life exposure to infections and risk of childhood acute lymphoblastic leukemia. Int J Cancer. 2011 Apr 1;128(7):1632-43. 89. Cramer DW, Finn OJ. Epidemiologic perspective on immune-surveillance in cancer. Curr Opin Immunol. 2011 Apr;23(2):265-71. 90. Takita H. Effect of postoperative empyema on survival of patients with bronchogenic carcinoma. J Thorac Cardiovasc Surg. 1970 May;59(5):642-4. 91. LeRoux BT. Empyema thoracis. Br J Surg. 1965 Feb;52:89-99. 92. Sensenig DM, Rossi NP, Ehrenhaft JL. Results of the surgical treatment of bronchogenic carcinoma. Surg Gynecol Obstet. 1963 Mar;116:279-84. 93. Ruckdeschel JC, Codish SD, Stranaham A, McKneally MF. Postoperative empyema improves survival in lung cancer. Documentation and analysis of a natural experiment. N Engl J Med. 1972 Nov 16;287(20):1013-7. 94. McKneally MF, Maver C, Kausel HW. Regional immunotherapy of lung cancer with intrapleural B. C. G. Lancet. 1976 Feb 21;1(7956):377-9. 95. Cady B, Cliffton EE. Empyema and survival following surgery for bronchogenic carcinoma. J Thorac Cardiovasc Surg. 1967 Jan;53(1):102-8. 96. Minasian H, Lewis CT, Evans SJ. Influence of postoperative empyema on survival after pulmonary resection for bronchogenic carcinoma. Br Med J. 1978 Nov 11;2(6148):1329-31. 97. Brohee D, Vanderhoeft P, Smets P. Lung cancer and postoperative empyema. Eur J Cancer. 1977 Dec;13(12):1429-36. 98. Müller W, Regazzoni P. [Does a local postoperative infection improve the prognosis in colonic carcinoma?] Helv Chir Acta. 1975 Mar;42(1-2):205-8. German. 99. Fucini C, Bandettini L, D’Elia M, Filipponi F, Herd-Smith A. Are postoperative fever and/or septic complications prognostic factors in colorectal cancer resected for cure? Dis Colon Rectum. 1985 Feb;28(2):94-5. 100. Nowacki MP, Szymendera JJ. The strongest prognostic factors in colorectal carcinoma. Surgicopathologic stage of disease and postoperative fever. Dis Colon Rectum. 1983 Apr;26(4):263-8. 101. Papachristou DN, Fortner JG. Effect of postoperative wound infection on the course of stage II melanoma. Cancer. 1979 Mar;43(3):1106-11. 102. Jeys LM, Grimer RJ, Carter SR, Tillman RM, Abudu A. Post operative infection and increased survival in osteosarcoma patients: are they associated? Ann Surg Oncol. 2007 Oct;14(10):2887-95. 103. Teucher G, Schindler AE. [Postoperative fever and prognosis in breast cancer]. Arch Geschwulstforsch. 1987;57(4):309-17. German. 104. Jackson RM, Rice DH. Wound infections and recurrence in head and neck cancer. Otolaryngol Head Neck Surg. 1990 Apr;102(4):331-3. 105. Grandis JR, Snyderman CH, Johnson JT, Yu VL, D’Amico F. Postoperative wound infections. A poor prognostic sign for patients with head and neck cancer. Cancer. 1992 Oct 15;70(8):2166-70. 106. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010 Mar 19;140(6):883-99.

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107. Boyle P, Levin B, International Agency for Research on Cancer. World cancer report 2008. Lyon: International Agency for Research on Cancer; 2008. 108. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7. 109. Ryan SO, Gantt KR, Finn OJ. Tumor antigen-based immunotherapy and immunoprevention of cancer. Int Arch Allergy Immunol. 2007;142(3):179-89. 110. Sporn MB, Roberts AB. Peptide growth factors are multifunctional. Nature. 1988 Mar 17;332(6161):217-9. 111. Nathan C, Sporn MB. Cytokines in context. J Cell Biol. 1991 Jun;113(5):981-6. 112. Silverstein AM. A history of immunology. San Diego, New York, Boston, London, Sydney, Tokyo, Toronto: Academic Press; 1989. 113. Hewitt HB. Animal tumor models and their relevance to human tumor immunology. J Biol Response Modif. 1982;1(2):107-19. 114. Nossal GJ. The case history of Mr. T.I. Terminal patient or still curable? Immunol Today. 1980 Jul;1(1):5-9. 115. Hewitt HB, Blake ER, Walder AS. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneus origin. Br J Cancer. 1976 Mar;33(3):241-59. 116. Shear MJ, Turner FC, Perrault A, Shovelton T. Chemical treatment of tumors. V. Isolation of the hemorrhage-producing fraction from Serratia marcescens (Bacillus prodigiosus) culture filtrate. J Natl Cancer Inst. 1943;4:81-97. 117. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxininduced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666-70. 118. Old LJ. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630-2. 119. Tsung K, Norton JA. Lessons from Coley’s toxin. Surg Oncol. 2006 Jul;15(1):25-8. 120. Decker WK, Safdar A. Bioimmunoadjuvants for the treatment of neoplastic and infectious disease: Coley’s legacy revisited. Cytokine Growth Factor Rev. 2009 Aug;20(4):271-81. 121. Finn OJ. Cancer immunology. N Engl J Med. 2008 Jun 19;358(25):2704-15. 122. Matzinger P. The danger model: a renewed sense of self. Science. 2002 Apr 12;296(5566):301-5. 123. Hobohm U. Fever and cancer in perspective. Cancer Immunol Immunother. 2001 Oct;50(8):391-6. 124. Baronzio G, Gramaglia A, Fiorentini G. Hyperthermia and immunity. A brief overview. In Vivo. 2006 Nov-Dec;20(6A):689-95. 125. Fisher DT, Vardam TD, Muhitch JB, Evans SS. Fine-tuning immune surveillance by fever-range thermal stress. Immunol Res. 2010 Mar;46(1-3):177-88. 126. Hasday JD, Singh IS. Fever and the heat shock response: distinct, partially overlapping processes. Cell Stress Chaperones. 2000 Nov;5(5):471-80. 127. Skitzki JJ, Repasky EA, Evans SS. Hyperthermia as an immunotherapy strategy for cancer. Curr Opin Investig Drugs. 2009 Jun;10(6):550-8. 128. Roti Roti JL. Cellular responses to hyperthermia (40-46 degrees C): Cell killing and molecular events. Int J Hyperthermia. 2008 Feb;24(1):3-15. 129. Wust P, Hildebrandt B, Sreenivasa G, et al. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002 Aug;3(8):487-97. 130. Issels RD, Lindner LH, Verweij J, et al. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. 131. Zacharski LR, Sukhatme VP. Coley’s toxin revisited: immunotherapy or plasminogen activator therapy of cancer? J Thromb Haemost. 2005 Mar;3(3):424-7. 132. Bonn D. Biocomplexity: look at the whole, not the parts. Lancet. 2001 Jan 27;357(9252):288. 133. Orosz CG. An introduction to immuno-ecology and immuno-informatics. In: Segel LA, Cohen IR, editors. Design principles for the immune system and other distributed autonomous systems. Oxford, New York: Oxford University Press; 2001. p. 125-49. 134. Kienle GS, Kiene H. “Beyond reductionism”—zur Notwendigkeit komplexer, organismischer Ansätze in der Tumorimmunologie und Onkologie. In: Kienle GS, Kiene H, editors. Die Mistel in der Onkologie. Fakten und konzeptionelle Grundlagen. Stuttgart, New York: Schattauer Verlag; 2003:333-432. 135. Horrobin DF. Effective clinical innovation: an ethical imperative. Lancet. 2002 May 25;359(9320):1857-8. 136. Horrobin DF. Are large clinical trials in rapidly lethal diseases usually unethical? Lancet. 2003 Feb 22;361(9358):695-7. 137. Horrobin DF. Innovation in the pharmaceutical industry. J R Soc Med. 2000 Jul;93(7):341-5. 138. Drews J. In quest of tomorrow’s medicines. Berlin, Heidelberg, New York: Springer; 2003. 139. Angell M. The truth about drug companies. New York: Random House; 2004. 140. Shaywitz DA, Ausiello DA. Preserving creativity in medicine. PLoS Med. 2004 Dec;1(3):e34. 141. Kienle GS, Kiene H. Clinical judgement and the medical profession. J Eval Clin Pract. 2011 Aug;17(4):621-7.

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review

Review of Clinical Applications of Scalp Acupuncture for Paralysis: An Excerpt From Chinese Scalp Acupuncture Jason Jishun Hao, DOM, MTCM, MBA, United States; Linda Lingzhi Hao, CA, PhD, United States

The following is an excerpt from Chinese Scalp Acupuncture, by Jason Jishun Hao, DOM, MTCM, MBA, and Linda Lingzhi Hao, CA, PhD. It is reprinted here with permission from Blue Poppy Press, Boulder, Colorado. Correspondence Jason Jishun Hao, DOM, MTCM, MBA jasonhao888@yahoo.com Citation Global Adv Health Med. 2012;1(1):102-121. Key Words Chinese scalp acupuncture, paralysis, multiple sclerosis, stroke, dysphagia, brain injury, Bell’s palsy

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Introduction

Chinese scalp acupuncture is a contemporary acupuncture technique integrating traditional Chinese needling methods with Western medical knowledge of representative areas of the cerebral cortex. It has been proven to be a most effective technique for treating acute and chronic central nervous system disorders. Scalp acupuncture often produces remarkable results with just a few needles and usually brings about immediate improvement, sometimes taking only several seconds to a minute. History

Acupuncture, a therapeutic technique of Oriental Medicine, can be traced back more than 2500 years. Throughout its long history, acupuncture has evolved as its own unique traditional medicine. By embracing newly developed knowledge and technology, the profession continues to create additional methods of treatment. Techniques such as electrical and laser acupuncture and even new acupuncture points are currently being developed. We believe scalp acupuncture, which integrates Western medicine with Traditional Chinese Medicine, to be the most significant development that Chinese acupuncture has made in the past 60 years. Scalp acupuncture is a well-researched natural science and incorporates extensive knowledge of both the past and present. Years of clinical experience have contributed to its recent discoveries and developments, but treatment of disorders by needling the scalp can also be traced back to early civilizations. In 100 BCE, the first Chinese acupuncture text, Huang Di Nei Jing (The Yellow Emperor’s Classic of Internal Medicine) described the relationship between the brain and the body in physiology, pathology, and treatment as it was understood at that time, and citations of acupuncture treatments on the head can be found throughout classical Chinese literature. The modern system of scalp acupuncture in China has been explored and developed since the 1950s. Various famous physicians introduced Western neurophysiology into the field of acupuncture and explored correlations between the brain and human body. In these early years of its development, there were several hypotheses for mapping stimulation areas. For example, Fan Yunpeng mapped the scalp area as a prone homunculus with the head toward the forehead and the legs toward the occipital area.1 Taking a dividing line that connects the

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left ear to the vertex to the right ear, Tang Song-yan proposed two homunculi on the scalp, one in prone position and another in supine position.2 Zhang Ming-jiu’s and Yu Zhi-shun’s scalp locations are formulated by penetrating regular head points, and Zhu Ming-qing created several special therapeutic bands on the scalp.3,4 It took acupuncture practitioners in China roughly 20 years before they accepted a central theory that incorporated brain functions into Chinese medicine principles. Dr. Jiao Shun-fa, a neurosurgeon in Shan Xi province, is the recognized founder of Chinese scalp acupuncture. He systematically undertook the scientific exploration and charting of scalp correspondences starting in 1971. Dr. Jiao combined a modern understanding of neuroanatomy and neurophysiology with traditional techniques of Chinese acupuncture to develop a radical new tool for affecting the functions of the central nervous system. Dr. Jiao’s discovery was investigated, acknowledged, and formally recognized by the acupuncture profession in a national acupuncture textbook, Acupuncture and Moxibustion, in 1977.5 Ten years later, at the First International Acupuncture and Moxibustion Conference held in Beijing, China, scalp acupuncture began to gain international recognition. At the time, scalp acupuncture was primarily used to treat paralysis and aphasia due to stroke. Since then, the techniques and applications of this science have been expanded and standardized through further research and experience. Many studies on scalp acupuncture have shown positive results in treating various disorders of the central nervous system. The most outstanding results are with paralysis and pain management in very difficult neurological disorders. Characteristics

Scalp acupuncture, sometimes also called head acupuncture, is a modern innovation and development. Just like any new technology and science, the discovery, development, and clinical application of scalp acupuncture has undergone a period of challenge because it falls outside some fundamental theories of Chinese medicine as well as being a new concept in the Western world. As a contemporary acupuncture technique, many of the specific treatments put forward in this book are also new, at least for a work that discusses Western medical concepts along with Chinese ones. There are three new principles in this presentation of scalp acupuncture, however, which are of central

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importance and which depart considerably from traditional Chinese medicine. The first of these principles is the location of scalp acupuncture areas based on the reflex somatotopic system organized on the surface of the scalp in Western medicine. These do not relate to the theory of channels in Chinese medicine and are an essentially new type of conception. Second, because the technological innovation and invention of scalp acupuncture is fairly new, positive results can only reasonably be achieved by practitioners who have studied it; even an established doctor in China cannot perform it without at least seeing a demonstration of it. Third, scalp acupuncture consists of needling areas rather than points on the skull according to the brain’s neuroanatomy and neurophysiology. Unlike traditional acupuncture, where one needle is inserted into a single point, in scalp acupuncture needles are subcutaneously inserted into whole sections of various zones. These zones are the specific areas through which the functions of the central nervous system, endocrine system, and channels are transported to and from the surface of the scalp. From a Western perspective, these zones correspond to the cortical areas of the cerebrum and cerebellum responsible for central nervous system functions such as motor activity, sensory input, vision, speech, hearing, and balance. In clinical practice, acupuncture treatments are typically based not just on a systematic or rigidly applied system, but also on highly individualized philosophical constructs and intuitive impressions. The practitioner has a wide amount of discretion on the use of points and techniques. Therefore, even when treating the same complaint, the method of treatment chosen by one practitioner can vary significantly from another. Scalp acupuncture, on the other hand, applies more of a Western medicine approach, where patients with the same diagnosis usually receive the same or very similar treatment. The scalp somatotopic system seems to operate as a miniature transmitter-receiver in direct contact with the central nervous system and endocrine system. By stimulating those reflex areas, acupuncture can have direct effects on the cerebral cortex, cerebellum, thalamo-cortical circuits, thalamus, hypothalamus, and pineal body. The scalp’s unique neurological and endocrinal composition makes it an ideal external stimulating field for internal activities of the brain. Scalp acupuncture treats and prevents disease through the proper insertion of needles into scalp areas. It is accompanied by special manipulations to regulate and harmonize the functional activities of the brain and body, as well as to restore and strengthen the functions of the body, organs, and tissues. Scalp acupuncture successfully integrates the essence of ancient Chinese needling techniques with the essence of neurology in Western medicine. Studying its results in clinical practice can also add clarity to ambiguities found in the practice of neurophysiology and pathology. In terms of Western medicine, it contributes significantly to the treatment of central nervous system disorders. In complementary and alterna-

Review

tive medicine, it contributes new understanding to both theory and practice. Scalp acupuncture can successfully treat many problems of the central nervous system such as paralysis and aphasia, for which Western medicine has little to offer. Applications

Scalp acupuncture areas are frequently used in the rehabilitation of paralysis due to stroke, multiple sclerosis, automobile accident, and Parkinson’s disease. These areas may also be effectively employed for pain management, especially that caused by the central nervous system such as phantom pain, complex regional pain, and residual limb pain. It has been proven to have very effective results in treating aphasia, loss of balance, loss of hearing, dizziness and vertigo. The disorders covered in this book are commonly found in Western clinics. This book will show the scope of scalp acupuncture in treating many kinds of disorders and diseases, based on years of clinical experience. Scalp acupuncture not only treats disorders, but also can prevent illness and help to build the immune system. It can help increase energy, preserve youth, and promote longevity. The technique of scalp acupuncture is systematic, logical, easy to understand, and easy to practice. The techniques introduced in this book can be easily mastered and performed even by people with minimal acupuncture experience. Scalp acupuncture is more easily accessible, less expensive, entails less risk, can yield quicker responses, and causes fewer side effects than many Western treatments. Practitioners should consider scalp acupuncture as either the primary approach or a complementary approach when treating disorders of the central nervous system and endocrine system. Although acupuncture and moxibustion have been used to prevent and treat disease in China for thousands of years, scalp acupuncture is a modern technique with a short history. In the West, many healthcare practitioners are familiar with acupuncture for pain management, while scalp acupuncture as a main tool for rehabilitation is a relatively new concept. It is still not easy for medical practitioners and the public to accept the reality that acupuncture can help in the recovery of paralysis, aphasia, and ataxia, while Western medical technology does not so far have effective treatments for those conditions. It is not surprising for a Western physician to claim that it is a coincidence if a patient recovers from paralysis after acupuncture. Therefore, there is an urgent need for Chinese scalp acupuncture to be studied and perfected, and extensive research done to fully explore its potential and utility. Chinese scalp acupuncture has been taught and used sparingly in the West and there are few books published on the subject. With such little information available, it has been almost impossible to apply this technique widely and with confidence. This book supplies all the needed information to practice scalp acupuncture.

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In addition to more than 29 years of clinical practice of scalp acupuncture, we have taught scores of seminars for both practitioners of Chinese medicine and Western physicians practicing acupuncture in the USA and Europe, including eight years of seminars sponsored by UCLA and Stanford University. This book contains many amazing case reports from our years of clinical practice and teaching as examples of what is possible using these techniques. While it is not our intention to assert that scalp acupuncture is always effective with every patient, these clinical reports make a compelling case for its wider use. For example, in a report about the scalp acupuncture treatment of seven veterans with phantom limb pain at Walter Reed Army Medical Center in 2006, the results were as follows. After only one treatment per patient, three of the seven veterans instantly felt no further phantom pain, three others reported having very little pain, and only one patient showed no improvement. Such results warrant continued research into other possible uses for scalp acupuncture to alleviate human suffering. During our lectures around the world, we are often asked why, if it is so effective in treating disorders of the central nervous system, has scalp acupuncture not spread to the whole world and been applied widely in practice? First, up to now there has been no authoritative and practical text for scalp acupuncture in English. Second, there is a very limited number of highly experienced teachers. Third, manual manipulation is very difficult to learn and master without detailed description and demonstration. And fourth, the names of stimulation areas are different from the standardized names given by the Standard International Acupuncture Nomenclature of the World Health Organization, Section 3.6 on Scalp Acupuncture, in Geneva in 1989. Furthermore, there have been few reports or articles published on treatment by scalp acupuncture. Most existing textbooks either lack detailed information or only introduce some new research on the topic. From their teachers and textbooks, students can learn only general information about scalp acupuncture and its locations and clinical applications. Therefore, many practitioners in both the West and the East are only mildly aware of this new technique, and few apply it in their practices. There is a high demand for a book that can provide teachers and students with useful knowledge and offer proper references to experienced practitioners. We feel confident that this book will meet these requirements. Part One of this book is designed to give practitioners fundamental knowledge of neuroanatomy, neurophysiology, and pathology in Western medicine. Chapter One provides a review for practitioners with a Western medical background and an adequate introduction for practitioners new to this material. The next chapter is a review of essential theories of Chinese medicine related to scalp acupuncture including the

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Four Seas theory and the Four Qi Street theory that provide readers with a systematic explanation of function and indication based on Chinese medicine. Chapter Three describes in detail locations and techniques of scalp acupuncture in order to offer a wide range of useful information for teachers, experienced or new practitioners, and students. Readers may notice that the indications for treatment for each scalp area are many in order to demonstrate the variety of disorders that can benefit from scalp acupuncture therapy. Finally, Chapter Four presents a large number of treatment strategies and techniques with color figures clearly illustrating the location of stimulation areas. In Part Two of our book, we discuss in detail many common central nervous disorders. All of these have proven to respond well to scalp acupuncture treatment. Forty-five successful case histories are given from our clinical experience. In these case descriptions, we explain in practical detail how to apply the needling techniques in order to obtain optimal results. These cases demonstrate practical application of the principles of scalp acupuncture. Each one reflects our experience, thought processes, strategies, and special techniques for treating patients suffering from disorders of the central nervous system. Wherever possible or useful, other modalities or techniques to enhance the scalp acupuncture treatments are included with the case histories, which demonstrates the integration of Chinese medical theory and application into the clinical practice of scalp acupuncture. A few “miracle” cases are presented in this book, such as the woman who was completely cured of quadriplegia after only two scalp acupuncture treatments and a man who was cured of aphasia after just five. While more the exception than the rule, such cases demonstrate not only how remarkable these new techniques are, but also provide the readers with examples of real clinical practice using them. The information presented in the book is primarily a synthesis of two components of knowledge of scalp acupuncture. First, we were among an early group of people who studied these techniques and were very fortunate to have opportunities to learn it directly from famous scalp acupuncture specialists including Jiao Shun-fa, the brilliant founder of Chinese scalp acupuncture, Yu Zhi-shun, a well-known professor in scalp acupuncture development, and Sun Shentian, an outstanding professor in scalp acupuncture research. Second, we have been teaching, practicing, and researching it for 29 years, both in China and in the US and Europe, and have accumulated extensive and valuable experience, which has given us insight into the needs and questions of acupuncture practitioners in Western clinical settings. Through this book, we hope to contribute this knowledge and experience to current and future students, practitioners, and teachers, and that it will serve as a stepping stone for further teaching, practice, research, and development of Chinese scalp acupuncture.

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Part Two Common Clinical Applications of Scalp Acupuncture

Types Of Paralysis Classified By Region • monoplegia is impairment in the motor function of only one limb

CHAPTER FIVE Paralysis

• diplegia affects the same body region on both sides of the body (both arms, for example)

Paralysis refers to complete or partial loss of muscle strength and voluntary movement for one or more muscles. Paralysis can be localized, generalized, or it may follow a certain pattern. Paralysis is most often caused by damage to the nervous system, especially the brain and spinal cord. Such damage may be due to stroke, trauma with nerve injury, poliomyelitis, amyotrophic lateral sclerosis, botulism, spinal bifida, and multiple sclerosis. Paralysis due to stroke, multiple sclerosis, and traumatic injury of the brain or spinal cord are the most commonly seen problems in our practice. Most paralyses caused by nervous system damage are constant in nature. There are forms of periodic paralysis, including sleep paralysis, which are caused by other factors. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory nerve damage as well. The chain of nerve cells that runs from the brain through the spinal cord out to the muscles is called the motor pathway. Normal muscle function requires intact connections all along this motor pathway. Damage at any level often interrupts the brain’s ability to control muscle movements resulting in paralysis. Paralysis almost always causes a change in muscle tone. Paralyzed muscles may be flaccid, flabby, and without appreciable tone, or may be spastic, tight, and with abnormally high tone that increases when the muscle is moved. Paralysis may affect an individual muscle but it usually affects an entire body region. The distribution of weakness is an important clue to locate the level of nerve damage that caused the paralysis. The types of paralysis are classified by region. Monoplegia is impairment in the motor function of only one limb. Diplegia affects the same body region on both sides of the body (both arms, for example). Hemiplegia, affects one side of the body. Paraplegia is impairment in motor function of both legs and the trunk. Quadriplegia, also known as tetraplegia, is paralysis with partial or total loss of use of all limbs and the torso. Paralysis is also divided into four types in neurological practice, namely upper motor neuron paralysis, lower motor neuron paralysis, paralysis due to neuromuscular transmission diseases, and the paralysis caused by muscular diseases. To test the strength of each muscle group and record it in a systematic fashion is important before and after scalp acupuncture treatment for paralyzed patients. It can help localize a lesion to a particular cortical region and spinal cord level, evaluate scalp acupuncture treatment, and give the patient encouragement when there is subtle improvement that the patient might not notice. When evaluating a patient with paralysis, the practitioner should follow a systematic approach that includes inspection of muscle, palpation and percussion of mus-

• hemiplegia affects one side of the body

Editor’s note: The references in this article have been renumbered for continuity.

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• paraplegia is impairment in motor function of both legs and the trunk • quadriplegia, also known as tetraplegia, is paralysis with partial or total loss of use of all limbs and the torso

cle, manual muscle strength testing, and assessment of motor function. It is useful to pair the testing of each muscle group immediately with the testing of its contralateral counterpart to enhance detection of any asymmetries and record detailed information of any changes. Muscle strength is often rated at six levels on a scale of 0 out of 5 to 5 out of 5.6,a The level of 0 out of 5 shows no muscular contraction, which means complete paralysis; the level of 1 out of 5 shows some muscular contraction, but no limb or body movement; the level of 2 out of 5 shows limb movement is possible but not against gravity, which means the limb can only move in its horizontal plane; the level of 3 out of 5 shows limb movement is possible against gravity but not against resistance by the examiner; the level of 4 out of 5 shows limb movement is possible against some resistance by the examiner but it is still weak compared to a normal limb; and the level of 5 out of 5 shows normal muscular strength, which means complete recovery from paralysis. Scalp acupuncture is frequently used in rehabilitation of paralysis due to stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. It has been proven effective in treating any type of paralysis, sometimes taking only one to two treatments for an amazing amount of recovery. We have treated hundreds of paralyzed patients with remarkable results in the US, China, and Europe, allowing many patients to leave their wheelchairs, walkers, crutches, and canes behind.7-12 Since scalp acupuncture is a modern technique with just 39 years of history, much more research needs to be done so that its potential can be fully explored and utilized and more paralyzed patients helped to regain a normal life. Stroke

Stroke is an acute neurological disease in which the blood supply to the brain is interrupted causing brain cells to die or be seriously damaged, thus impairing brain functions. Stroke is classified into two major categories, ischemic and hemorrhagic. In an ischemic stroke, a blood vessel becomes occluded and the blood supply to part of the brain is blocked. Ischemic stroke is divided into thrombosis stroke, embolic stroke, systemic hypoperfusion, and venous thrombosis. A hemorrhagic stroke occurs when a blood vessel in the brain ruptures and bleeds. The bleeding vessel can no longer carry the blood to its target tissue and interrupts the brain’s blood supply. Hemorrhagic stroke is commonly divided into two types, intracerebral and subarachnoid.

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The symptoms of stroke depend on the type of stroke and the area of the brain affected. These include weakness, paralysis or abnormal sensations in limbs or face, aphasia, apraxia, altered vision, problems with hearing, taste, or smell, vertigo, disequilibrium, altered coordination, difficulty swallowing, and mental and emotional changes. Some stroke patients may have loss of consciousness, headache, and vomiting at the onset. If the symptoms disappear within several minutes up to a maximum of 24 hours, the diagnosis is transient ischemic attack (TIA), which is a mini or brief stroke. Those symptoms are warning signs and a large proportion of patients with TIA may develop full strokes in the future. Stroke is the third leading cause of death in the United States after heart attack and cancer and it is a leading cause of adult disability. It is necessary for stroke patients to receive emergency treatment with Western medicine and it is important to identify a stroke as early as possible because patients who are treated earlier are more likely to survive and become less disabled. Stroke survivors usually have some degree of sequelae of symptoms depending primarily on the location in the brain involved and the amount of brain tissue damaged. Disability affects about 75% of stroke survivors and it can affect patients physically, mentally, emotionally, or a combination of all three. Because each side of the brain controls the opposite side of the body, a stroke affecting one side of the brain results in neurological symptoms on the other side of the body. For example, if stroke occurs in the motor area of the right side of the brain, the left side of the body may show weakness or paralysis. Although there is no cure for stroke, most stroke patients now have a good chance for survival and recovery. When stroke patients pass the acute stage they should start rehabilitation as soon as possible. Stroke rehabilitation therapy helps patients return to normal life as much as possible by regaining and relearning skills of everyday living such as speaking or walking. Treatment may include acupuncture, physical therapy, occupational therapy, speech and language therapy, and massage. In Chinese medicine, the stroke itself is thought to involve several interpromoting disease mechanisms, possibly including qi stagnation, heat, phlegm, blood stasis and, of course, wind. Hence the common name for stroke in Chinese medicine is wind stroke. Many of these same patterns will be present in cases involving post-stroke symptomology discussed in this book such as paralysis, dysphagia, and aphasia.

CASE HISTORY #1

At a workshop conducted at Tri-State Acupuncture College in New York City in 1998, a patient named Tom volunteered for scalp acupuncture. The manager at the college told us that the patient had had a stroke from cerebral thrombosis only 11 months before and was a good candidate for the class demonstration. While interviewing Tom, we were shocked to find that his right arm

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and hand had actually been paralyzed for 11 years. Although we were not at all certain that we could help this patient, it had taken several hours for the family member to give him a ride here and we did not want to turn him away. His tongue was a little purple with a normal coating and his pulses were bilaterally fine and wiry. As an additional source of concern, we had only a few hours earlier told the students that any patient with paralysis enduring for more than three years was unlikely to respond to scalp acupuncture therapy. Unsure how to proceed, we considered simply demonstrating the location and technique of scalp acupuncture on this patient and not immediately showing the results to the students. After demonstrating two needles in his scalp, we moved Tom to another room to rest, inserted more needles, and then continued with the lecture. Chinese medical pattern discrimination: Qi stagnation and blood stasis in the channels and network vessels

Scalp acupuncture treatment Area selection

Primary area: Upper 1/5 and middle 2/5 of the Motor Area Secondary area: Upper 1/5 and middle 2/5 of the Sensory Area Manipulation

For treating motor dysfunction, place the needles and rotate them at least 200 revolutions per minute for 1-3 minutes every 10 minutes for a total of 30-60 minutes. The worse the symptoms or longer the duration of disease, the longer the duration of each treatment should be. As stated above in Chapter Four, unless the paralysis is due to the removal of damaged tissue by brain surgery, a paralyzed extremity is generally treated by choosing the opposite side of the Motor Area on the scalp. The upper 1/5 region is used to treat contralateral dysfunctional movement of

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the lower extremity, trunk, spinal cord, and neck. The doctor should twirl the needle as vigorously as the patient can tolerate and have the patient move the affected limb actively and passively. It is helpful to have the patient exercise the affected limbs with or without assistance as indicated, between needle stimulations.13 During treatment, some patients may have sensations of heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving along their affected limbs. Those patients usually respond and show improvement quickly. However, those who don’t have such sensations could still have immediate effects. Initially, treatment should be two to three times a week until major improvements are achieved, then once weekly, then every two weeks, and then spaced out as indicated by the patient’s condition. A therapeutic course consists of 10 treatments. Results of Case #1

Tom was instructed to do some passive exercise while the needles were in place, having his wife move his hand and raise his arm. While we were continuing our lecture, we heard screaming from the other room. The patient’s wife rushed back into the lecture room saying repeatedly, “He can move his arm and hand now” in a loud, excited voice. Tom was able to move his arm, hand, and even his fingers in any way or direction that he was asked by the audience. This patient’s experience has caused us to change the information we give students about whether treatment could be successful after a specific number of years. It is now our opinion that a patient with paralysis should be treated no matter how long ago a stroke has occurred as long as the limb shows no muscular atrophy. One student at this class offered the conclusion, “It’s never too late to treat a paralyzed patient with scalp acupuncture.”

Discussion

Scalp acupuncture has been found to have very good effects on the sequelae of stroke including hemiplegia, aphasia, and abnormal sensations in the limbs. Thanks to advanced stroke research and brain imaging technology, doctors are continuing to gain new understanding of how the brain can adapt after stroke in order to regain its ability to function. New research suggests that normal brain cells are highly adaptable. They can undergo changes not only in function and shape but also can take over the functions of nearby damaged cells. Because of these abilities, scalp acupuncture is geared toward stimulating and restoring affected brain tissue or retraining unaffected brain tissue to compensate for the lost functions of damaged brain tissue. In Tom’s case, the hemiplegia was caused by cerebral thrombosis, which has the best prognosis for recovery from stroke compared to cerebral embolism and cerebral hemorrhage. It is necessary to point out, however, how unusual it is that a patient gets only one scalp acupuncture treatment and recovers completely. In our

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normal practice it often takes from several weeks to several months for stroke patients to improve and recover. Also, the time frame for patients with stroke to be treated by scalp acupuncture is crucial; the earlier the treatment the better the prognosis. When treating stroke from thrombosis or embolism, scalp acupuncture treatment should begin as soon as feasible. When treating a hemorrhagic stroke, however, scalp acupuncture should not be performed until the patient’s condition is stable, probably one month after a stroke. As we discovered with Tom, a patient with any duration of stroke disabilities can be treated, but treatment within a year brings about the greatest response in our experience. The longer the duration of the impairment, the more gradual will be the improvement. With long-term conditions expectations need to be realistic, although occasionally a patient will surprise practitioners. It is hardest to achieve improvement for a patient with paralysis for a long time, especially if there is also muscular atrophy and rigid, inflexible joints. There are several different acupuncture techniques to treat paralysis. Although scalp acupuncture has the best and fastest response, other techniques are necessary for a fuller recovery. According to the individual’s condition, regular body acupuncture, electrical acupuncture, and moxibustion, as well as physical therapy and massage can combine with scalp acupuncture to speed up the time of recovery. Regular acupuncture treatment has been found to have positive therapeutic effects on the recovery of movement in the hands, fingers, feet, and toes. In treating unilateral paralysis of the limbs, traditionally more points from yang ming channels are selected because yang corresponds to movement and agility, and foot yang ming stomach channel controls muscle functions. Commonly used points are He Gu (LI 4), Wai Guan (TB 5), Qu Chi (LI 11), Bi Nao (LI 14), and Jian Yu (LI 15) for upper limb paralysis, and Kun Lun (Bl 60), Cheng Shan (Bl 57), Yang Ling Quan (GB 34), Zu San Li (St 36), and Huan Tiao (GB 30) for lower limb paralysis. Although more yang ming points are used for paralysis, points from yin channels, especially tai yin and jue yin channels should not be ignored. Yin corresponds to nourishing muscles and tendons and points from yin channels have positive results for pronounced stiffness and contraction of the limbs. Commonly used points are Chi Ze (Lu 5) and Nei Guan (Per 6) for upper limbs and San Yin Jiao (Sp 6), Yin Ling Quan (Sp 9), Xue Hai (Sp 10), and Qu Quan (Liv 8) for lower limbs. Hand or foot paralysis is relatively difficult to recover and often requires a longer process, especially for a contracted hand and foot. To relax contractures of the hand, thread a two-inch needle from He Gu (LI 4) under the palm toward Lao Gong (Per 8) and Hou Xi (SI 3). Stimulate this needle with vigorous thrusting, lifting, and twirling. Thread another needle deeply from Wai Guan (TB 5) toward Nei Guan (Per 6) and stimulate in a similar fashion. To relax the upper arm and shoulder, thread a needle from Jian Yu (LI 15) to Bi Nao (LI 14) and stimulate vigorously. To relax contractures of the foot and ankle, thread a two-inch needle from Jie Xi

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(St 41) toward Qiu Xu (GB 40) and Sheng Mai (Bl 62). Thread a second needle from Jie Xi (St 41) toward Zhong Feng (Liv 4) and Zhao Hai (Ki 6). Thread a third needle from Tai Chong (Liv 3) through the foot to Yong Quan (Ki 1) on the sole of the foot. Stimulate all needles with vigorous thrusting, lifting, and twirling. For additional effect, thread a long needle from Yang Ling Quan (GB 34) through to Yin Ling Quan (Sp 9) and from Kun Lun (Bl 60) through to Tai Xi (Ki 3). Electrical stimulation is very helpful if the practitioner has difficulty performing needle rotation of more than 200 times per minute. It is suggested that only one to two pairs of the scalp needles be stimulated at any one session or the brain can become too confused to respond. For electrical stimulation in body acupuncture, fewer than four needles should be stimulated in each limb. Best results are achieved by applying low frequency (for example, 3 hertz) with high intensity (for instance, when visible muscle contraction is observed). Moxibustion can enhance the therapeutic results of scalp acupuncture, especially for older or weaker patients. Research on the effect of scalp acupuncture for stroke

There are considerable clinical studies and experimental research showing the excellent results obtained from scalp acupuncture on paralysis due to stroke. •• Jiao Shun-fa, the founder of scalp acupuncture, collected and analyzed 20,923 cases of paralysis caused by stroke from 1970 to 1992. After treatment on the Motor Area of the scalp, 7,637 cases were cured (36.5%), 7,117 cases showed marked improvement (34%), and 5,196 cases showed some improvement (24.8%), yielding a total effective rate of 95.13%.14 •• Jia Huai-yu reported on 1,800 cases of paralysis due to stroke treated on the Motor Area by scalp acupuncture in 1992. The result were as follows: 462 cases fully recovered (25.67%), 950 cases markedly improved (52.78%), 292 cases somewhat improved (16.22%), 96 cases failure (5.33%), yielding a total effective rate of 94.67%. Findings in these two studies are very similar.15 •• Liu Jian-hao and colleagues reported on the treatment of 60 cases of paralysis due to stroke using scalp acupuncture in 2010. The duration of the paralysis was from one day to 14 days. The patients were randomly divided into a body acupuncture group and a scalp acupuncture group, 30 in each group. The body acupuncture group was treated with needling from Bai Hui (GV 20) penetrating to Tai Yang (extra point) and the scalp acupuncture group was treated at the Motor Area. Treatments were given once a day and 14 treatments comprised a course. The neurological deficit scores (NDS) and the therapeutic effects were compared before and after treatment and the contents of plasma endothelins (ET) and calcitonin gene related peptide (CGRP) were tested on the second and four-

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teenth days respectively after initial treatment. The results showed that the effective rate was 86.7% (26/30) in the body acupuncture group and 80.0% (24/30) in the scalp acupuncture group. The NDS of both groups were statistically decreased (P < 0.01). The ET level was also decreased and the CGRP level was effectively increased in both groups (P< 0.01).16 Dysphagia

Dysphagia is the medical term for the symptom of difficulty in swallowing. The signs and symptoms of dysphagia include difficulty controlling food in the mouth, inability to control food or saliva in the mouth, difficulty initiating a swallow, coughing, choking, frequent pneumonia, unexplained weight loss, gurgly or wet voice after swallowing, nasal regurgitation, and swallowing difficulty. When asked where the food is getting stuck, patients will often point to the cervical region. The actual site of obstruction is always at or below the level at which patients perceive the obstruction. The most common symptom of esophageal dysphagia is the inability to swallow solid food, which the patient often describes as “becoming stuck” or “held up” before it either passes into the stomach or is regurgitated. Some people present with “silent aspiration” and do not cough or show outward signs of aspiration. When the airway is unprotected and foreign material is aspirated into the lungs, the person is at risk for development of pulmonary infection and aspiration pneumonia. A swallowing disorder can occur in people of all age groups but it is more likely in the elderly, patients who have had strokes, and in patients who are admitted to acute care hospitals or chronic care facilities. Dysphagia is classified into two major types, oropharyngeal dysphagia and esophageal dysphagia. Oropharyngeal dysphagia is often caused by stroke, multiple sclerosis, myasthenia gravis, Parkinson’s disease, amyotrophic lateral sclerosis, and Bell’s palsy. Esophageal dysphagia can be subdivided into mechanical and functional causes. Functional causes include achalasia, myasthenia gravis, and bulbar or pseudobulbar palsy. Mechanical causes usually comprise peptic esophagitis, carcinoma of the esophagus or gastric cardia, candida esophagitis, and pharyngeal pouch. Medicines can help some people, while others may need surgery. Treatment with a speech-language pathologist can help. Patients may find it helpful to change their diet or hold their heads or necks in a certain way when they eat. In very serious cases, patients may need feeding tubes.

CASE HISTORY #2

Fred, a 62-year-old male in a wheelchair, was brought to our clinic in Santa Fe, NM. His wife gave a brief medical history because of his aphasia. One month before, Fred had severe headache, slurred speech, and the right side of his body became paralyzed. A local hospital diagnosed stroke caused by cerebral hemorrhage in his left hemisphere. He initially was totally paralyzed on the

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right side and had lost his speech. He had been receiving physical therapy and speech therapy since he was admitted to the hospital. Although his aphasia gradually improved, his speech was not clear. His voice was low and it was very difficult to understand him. He had severe dysphagia and could not swallow any food or water at all, which was his primary complaint at our clinic. He felt depressed, irritable, angry, and severely fatigued. A nasogastric tube was inserted to provide nonoral feeding. Examination showed he was unable to move his right leg and foot at all with muscular tone at 0 out of 5. He could move his right arm slightly with muscular tone at 2 out of 5. He could not elevate the hyoid bone, indicating a probable swallow reflex problem. Maximum phonation duration of seven seconds indicated reduced breath support, likely resulting from vocal cord paralysis. He had a weak cough and diminished throat-clearing ability. His aphasia, dysphasia, and paralysis on the right side had shown no further improvement for the past two weeks. A hospital physician recommended that Fred try acupuncture treatment. Upon examination he looked very tired and depressed, his tongue was red with a dry, thick, yellow coating, and his pulses were wiry and slippery.b Chinese medical pattern discrimination: Liver depression qi stagnation, spleen qi deficiency, blood stasis in the channels, liver-gallbladder damp heat Scalp acupuncture treatment Area selection

Primary area: Upper 1/5, middle 2/5 and lower 2/5 Motor Area Secondary area: Speech I Area (same as lower 2/5 Motor Area), Neck point, (a new extra point for dysphagia, located at 1 inch below Feng Chi (GB 20) Manipulation

The entire Motor Area should be needled and stimulated on the opposite side of the paralyzed limbs. Always put one needle in the ear point Shen Men to help a depressed and angry patient relax and to reduce the sensitivity of needle insertion and stimulation of the scalp. Use the fewest number of needles possible in the scalp and rotate the needles at least 200 times per minute with the thumb and index finger for 2-3 minutes, twirling as gently as possible so that the depressed patient can tolerate the sensation and repeating the stimulation every 10 minutes. Select the Speech I Area or some local points in the neck accordingly if the patient has aphasia or difficulty swallowing. Retain the needles in place for 30-45 minutes. The treatment is given two to three times per week and a therapeutic course consists of 10 treatments. Communicate with the patient and any relatives often in order to gain their confidence, to encourage them, and reduce their fear and anxiety. During the treatment, some patients may experience sensations of heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving

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along their spine, legs, or arms. Telling the patient that those are normal and that people who experience some or all of these sensations usually respond and improve more quickly encourages them to come back for additional treatments. However, those who do not have such sensations could still have immediate positive results. Results of Case #2

Fred was very negative and showed no interest in treatment by scalp acupuncture at the initial visit. He was reluctant to do any active exercise when being instructed. Even after showing some improvement of his aphasia and the paralyzed arm and leg, he demonstrated no excitement and simply said, “I do not notice any difference about my throat and swallowing.” At the second treatment, Fred presented with severe depression and no motivation. He did not like to perform speech, swallowing, and body exercises. His treatment strategy was modified to take care of depression. The ear points Heart, Liver, and Shen Men along with the Head Area and Chest Area on the scalp were needled. At the beginning of the third visit, his wife reported that Fred’s mood and attitude were much better after the last treatment. He talked a little more and was easier to understand. To her surprise he reminded her what time he had the acupuncture appointment that day. Since the patient’s attitude was relatively more positive toward acupuncture therapy, we were able to perform stronger stimulation after inserting needles at the same locations as for the initial treatment. Fred was able to follow instructions to practice his speech and do oral and pharyngeal exercises. He started to smile after hearing himself count from one to 10 very clearly. He refused to try drinking a little bit of water to test his swallowing function and said he was afraid that it could induce severe coughing and choking and cause aspiration. With continued encouragement Fred finally agreed to try. To his astonishment he did not choke at all when he took a first sip of water. He drank more and more and finished a whole cup of water without a problem. The patient thrived on this program. He began to tolerate a soft/semi-solid diet and the nasogastric feeding was gradually tapered down to overnight only as his oral intake improved. At this point his weight increased and his stamina was markedly improved. Fred started to eat more solid food and add more kinds of food gradually. With every treatment, Fred showed dramatic improvements in speech, eating and drinking, and movement of his right arm, hand, leg, and foot. By the fifth treatment, Fred wanted to add more foods and soon could eat and drink anything like a normal person. The nasogastric tube was removed and he had no problem with talking or depression after his sixth treatment. His subsequent treatments were focused on his paralyzed arm and leg. He was treated by combined scalp acupuncture and body acupuncture. For body acub

Publisher’s note: We are choosing to use the authors’ translation for the xian mai (弦脉). In A Practical Dictionary of Chinese Medicine, Wiseman and Feng translate this pulse image as the “string-like” pulse, but “wiry” is the more common usage.

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puncture, Qu Chi (LI 11), Wai Guan (TB 5), and He Gu (LI 4) on the right upper limb and Zu San Li (St 36), Kun Lun (Bl 60), and Jie Xi (St 41) on the right lower limb were needled. Sometimes those points were stimulated with electrical acupuncture. Fred could move his right arm up and down more and he was able to start walking to our clinic on his own. After the sixteenth treatment he had gained more mobility and use of his right hand and gained more muscular strength in that hand. At the end of 20 treatments his walking appeared almost normal. At his last visit, Fred said, “Thank you very much for giving me back my normal life.” Discussion

Scalp acupuncture offers great rehabilitation tools for dysphagia. Most patients with dysphagia whom we have treated showed some improvement after three treatments and some of them appear better right way. However, to treat dysphagia patients who have depression is very challenging because patients are not always willing to participate in the treatment. It requires very good needle technique as well as good communication skills. Sometimes it is necessary to treat the depression first and then address the difficulty in swallowing. Compared to other patients, in general depressed patients should receive fewer needles, milder stimulation, and a shorter time of needle retention. Whether you are treating a child or adult with depression, it is important to observe the response and reaction while inserting, stimulating, or withdrawing needles, and adjust the techniques accordingly. Although each part of the cerebral cortex has its own functions, some variation is possible. When one area is impaired, this area can recover to a certain extent or can be compensated somewhat by other areas with proper scalp stimulation. This may be the mechanism by which scalp acupuncture is successful in treating dysphagia. Correct food consistency, texture, and temperature are important for the dysphagia patient’s success during acupuncture treatment. All three factors are important as they act to heighten lingual control, reduce oral muscle fatigue, minimize the patient’s fear of choking, and provide a cohesive bolus to stimulate a swallow reflex. A dysphagia diet uses foods that stimulate swallowing and minimize mucus build-up around the larynx. Dysphagia may lead to malnutrition and dehydration and at the most severe stages can cause choking, aspiration, and airway obstruction. Therefore it is imperative to deal with the dangers of dysphagia through dietary management once acupuncture has been instituted. Overall, our patient Fred had a very successful recovery, progressing from dysphagia to total normal eating within just a few weeks. This case study followed the patient as his poststroke swallowing status changed and various acupuncture decisions were made. In addition to scalp acupuncture, the ear and body acupuncture were very helpful in the patient’s progress and recovery. This case illustrates that scalp acupuncture could be the primary approach to manage swallowing disorder.

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Research on the effect of scalp acupuncture for dysphagia •• Li Min and colleagues reported the treatment of 60 cases of dysphagia due to stroke using scalp acupuncture in 2009. The duration of the condition was from 30-360 days. The 60 cases were randomly divided into a five-needle-in-nape (FNN) group and a routine acupuncture (RA) group, 30 cases in each group. The FNN group was treated with needling Ya Men (GV 15), Tian Zhu (Bl 10), and Zhi Qiang Xue (new extra point). The RA group was treated with needling at Lian Quan (CV 23), Tong Li (Ht 5) and Zhao Hai (Ki 6). Treatment was given six times a week and 16 treatments made a course. Results showed seven cases fully recovered, 13 cases markedly improved, eight cases some improvement and two cases failure in FNN group. Five cases fully recovered, eight cases markedly improved, 11 cases some improvement, and six cases failure in the RA group. The effective rate was 93.3% in the FNN group, better than that of 80.8% in RA group (P< 0.05).17 Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease of the central nervous system in which communication between the brain and other parts of the body is disrupted. Its effects can range from relatively benign in most cases, to somewhat disabling, to devastating for some people. During an MS attack, inflammation occurs in areas of the white matter of the central nervous system in random patches. These are called plaques. This is followed by the destruction of myelin. Myelin allows for the smooth, high-speed transmission of electrochemical messages between the brain, the spinal cord, and the rest of the body. When myelin is damaged, neurological transmission of messages may be slowed or blocked completely resulting in some body functions being diminished or lost. Approximately 300,000 people in the US and 2.5 million people worldwide suffer from MS. It primarily affects adults, with age of onset typically between 20 and 40 years, and is twice as common in women compared to men. Symptoms and signs of multiple sclerosis vary widely depending on the location of affected myelin sheaths. Common symptoms include numbness, tingling or weakness in one or more limbs, partial or complete loss of vision, double or blurred vision, tremor, unsteady gait, fatigue, cognitive impairment, and dizziness. Some patients may also develop muscle stiffness or spasticity, paralysis, slurred speech, dysfunction of urine or bowels, and depression. In the worst cases, people with MS may be unable to write, speak, or walk. Multiple sclerosis is unpredictable and varies in severity. In some patients it is a mild disease but it can lead to permanent disability in others. Multiple sclerosis may occur either in discrete attacks or slowly over time. Although symptoms may resolve completely between the episodes, permanent neurological problems usually

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persist, especially as the disease progresses.18 Many risk factors for multiple sclerosis have been identified, but no definitive cause has been found. It likely occurs as a result of some combination of environmental and genetic factors. Currently, multiple sclerosis does not have a cure in terms of conventional treatments. However, a number of therapies including acupuncture can be used to treat the disease symptomatically and convert MS into remission. In Chinese medicine, there are at least six or more patterns of disharmony that can account for the signs and symptoms of multiple sclerosis. The common denominators in most cases are external invasion or internal engenderment of damp heat, which damages qi and consumes yin and blood, thus giving rise to internal stirring of wind. Former heaven or prenatal natural endowment insufficiency may also play a role.

and spasms in her legs accompanied by incontinence of urine and severe fatigue. The examination revealed she had paraparesis of the left lower extremity that was more affected than the right. Her tongue was purple with a thin white coating. Her pulses were wiry and fine overall, with especially weak pulses in the cubit (chi) positions bilaterally.

CASE HISTORY #3

Manipulation

Denise, a 79-year-old female in a wheelchair, was brought to our clinic in Santa Fe, New Mexico, in 1994. She had suffered from multiple sclerosis for more than 25 years. Her initial symptoms were an onset of numbness in the right arm followed by subsequent numbness descending down both her legs. Over the past 25 years, Denise had multiple relapses and remissions with episodes of lower extremity weakness, stiffness and muscle spasm, incontinence of urine, loss of balance, and fatigue. Those symptoms typically lasted a few weeks to several months. Five years ago she had a dramatic neurological decline during which she was unable to stand up and lost strength and sensation in her lower extremities. For the last three years and currently, she could not stand or walk by herself due to weakness in her legs and loss of balance. Denise also complained of numbness, tingling,

Insert needles in the Motor Area, Sensory Area, and Foot Motor and Sensory Area and stimulate unilaterally or bilaterally according to the patient’s symptoms. Rotate the needles at least 200 times per minute with the thumb and index finger for 1-3 minutes, twirling them as vigorously as the patient can tolerate and repeating the stimulation every 10 minutes. During treatment, some patients may have all or some of the following sensations: increasing tingling or numbness, heat, cold, heaviness, distention, or the sensation of water or electricity moving along their spine, legs or arms. Patients with some or all of these sensations usually respond and improve more quickly. However, those who do not have such sensations could still have immediate positive results. If balance, dizziness, or vertigo is present, select the Balance Area or the Vertigo and Hearing Area. The Chorea and Tremor Area should be chosen if the patient has tremor or limb spasms. Keep the needles in for 25-30 minutes. Treatment is given two to three times per week and a therapeutic course consists of 10 treatments.

Chinese medical pattern discrimination: Liver blood deficiency with internal stirring of liver wind, kidney qi deficiency, liver depression qi stagnation, blood stasis Scalp acupuncture treatment Area selection

Primary area: Motor Area, Sensory Area, Foot Motor and Sensory Area Secondary area: Balance Area, Chorea and Tremor Area, and Vertigo and Hearing Area

Results of Case #3

Denise had a very positive response to her initial scalp acupuncture treatment. She was amazed to feel the spasms and numbness in her legs improve just minutes after a few needles were inserted. Although she was nervous when the doctor asked her to stand up, her family was thrilled to see her not only stand up with improved stability, but also start to walk a few steps. At the second treatment, Denise reported that the incontinence of urine had improved remarkably after the first treatment and the numbness, spasms, and weakness of both legs showed some improvement as well. She continued to get better with each additional treatment and by the sixth treatment, Denise was able to enter our clinic with a walker instead of in a wheelchair. She also had more energy and started to do some housework again. By the fifteenth treatment, Denise reported that she

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was able to walk around her home by herself and walk much longer distances. The numbness and tingling in her limbs did not bother her as much, she had more energy, and had not experienced incontinence of urine for several weeks. However, her right foot was still weak and was sometimes difficult to pick up and she had to drag it to walk. During each treatment, however, her right foot was getting stronger and she could pick it up more easily. This ability would last for several days after treatment, so Denise liked to get a tune-up treatment every other week. At each session, a few needles would be inserted in her scalp and she would go out for a walk and come back later for withdrawal of the needles. Discussion

When compared to other acupuncture modalities including acupuncture on the ear, body, and hand, scalp acupuncture has proven to have the most success in treating MS and other central nervous system damage. Not only can it improve symptoms, the patient’s quality of life, and slow the progression of physical disability, but it can also reduce the number of relapses. The patient should get treatment as soon as possible as the earlier the treatment, the better the prognosis. Scalp acupuncture treatment for MS has had much success in reducing numbness and pain, decreasing spasms, improving weakness and paralysis of limbs, and improving balance. Many patients also have reported that their bladder and bowel control, fatigue, and overall sense of well-being significantly improved after treatment. Recent studies have shown that scalp acupuncture can be a very effective modality in controlling MS, often producing remarkable results after just a few needles are inserted. It usually relieves symptoms immediately and may take only a few minutes to achieve significant improvement. Although scalp acupuncture areas may be chosen according to the patient’s particular symptoms, primary areas for patients with motor problems such as paralysis, weakness of limbs, or abnormal sensations in limbs including tingling, numbness, or pain, are the Motor Area and the Sensory and Foot Motor Areas. Those areas should be stimulated unilaterally or bilaterally, according to the patient’s manifestations. Select the Balance Area or Vertigo and Hearing Area of the scalp, respectively, depending on the symptoms. The Chorea and Tremor Area should be chosen if patients have limb spasm. Many patients have a very quick and positive response in controlling urine and bowel functions when the Foot Motor and Sensory Area is stimulated. There are many different acupuncture techniques for treating MS. Although scalp acupuncture has the fastest track record for improving symptoms, other techniques are also necessary for further improvement. Regular body acupuncture, electrical acupuncture, and moxibustion as well as physical therapy and massage can be combined with scalp acupuncture to speed up recovery. Regular acupuncture treatment has been found to have a positive therapeutic effect on the recovery of movement and reducing abnormal sensa-

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tions of the hands, fingers, feet and toes. Commonly used points are Feng Chi (GB 20), Yu Zhen (Bl 9), Nao Kong (GB 19), Huan Tiao (GB 30), Yang Ling Quan (GB 34), Tai Chong (Liv 3), and Tai Xi (Ki 3) for lower limbs, and Qu Chi (LI 11), He Gu (LI 4), and Wai Guan (TB 5) for upper limbs.19 Electrical stimulation is very helpful if the practitioner has difficulty performing needle rotation more than 200 times per minute. It is suggested that no more than two of the scalp needles be stimulated at any session so the brain does not become too confused to respond. Moxibustion can enhance the therapeutic results of scalp acupuncture, especially for older or weak patients. Recommended points are Zu San Li (St 36), San Yin Jiao (Sp 6), Guan Yuan (CV 4), Yong Quan (Ki 1) and Shen Shu (Bl 23). When treating chronic progressive diseases like multiple sclerosis, Parkinsonism, and amyotrophic lateral sclerosis (ALS), the effects are sometimes temporary. Improvement may last for hours, days, weeks, or months, but follow-up treatments will be necessary on an ongoing basis. When treating paralysis, whether from stroke or trauma, improvements in movement are often permanent. The practitioner should consider scalp acupuncture as the primary approach rather than as a complementary approach for the patient with multiple sclerosis. Although other acupuncture techniques can be effective, scalp acupuncture seems to bring about quicker and often immediate improvement. In a recent investigation, scalp acupuncture was applied to 16 patients with multiple sclerosis at our National Healthcare Center in Albuquerque, NM. After only one treatment per patient, eight of the 16 patients instantly showed significant improvement, six patients showed some improvement, and only two patients showed no improvement, thus yielding a total effective rate of 87%.

CASE HISTORY #4

Michael, a 52-year-old patient referred by his primary care physician, walked with the aid of a cane. He sought treatment from us during a conference in Phoenix, Arizona, in 2006. He had suffered from multiple sclerosis since 1982 and had received many kinds of treatments with no positive results. Five years before, his medical team had noted his condition “has been slowly going downhill.” Because his legs were very stiff and weak, Michael had to drag both legs in a shuffling manner when he walked. Other symptoms included an inability to lift his feet or wiggle his toes. His fatigue was so great he could only walk 2-3 minutes at a time. Further examination showed that he could not stand with stability due to losing his balance when standing on both legs, and it was impossible for him to stand on one leg. He could neither utilize a normal gait from heel to toe nor walk backwards. His tongue was red and slightly purple with a thick, white coating and his pulses were wiry and slippery. Chinese medical pattern discrimination: Spleen qi and kidney essence deficiency, liver depression with depressive

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heat leading to the internal stirring of liver wind Results of Case #4

While needles were being inserted in Michael’s scalp the audience was quiet, waiting to see how he would respond to his first treatment. Michael showed remarkable improvement right away. When told that it was time for him to “show off,” he stood up straight with great stability and even stood on one leg for several seconds without losing his balance. The audience reported that he was taking much larger steps, was lifting up his legs rather than dragging them, and was turning around without hesitation. During the break, Michael went outside for a bit more exercise. He walked back into the conference room without using his cane and his face glowed with pleasure as he told the audience, “I walked for about 30 minutes without any rest and without my cane except for security. I am so overjoyed with these unexpected wonderful results. I can walk solidly from heel to toe and walk backwards with no difficulty.”

Discussion

Although multiple sclerosis (MS) remains an incurable disease of the central nervous system, scalp acupuncture provides an important complementary/alternative treatment approach for improving many symptoms and the patient’s quality of life by slowing or reversing the progression of physical disability and reducing the number of relapses. By directly stimulating affected areas of the central nervous system, scalp acupuncture has shown more effective results compared to other acupuncture techniques. Our studies showed that 87% of patients had instant improvement after only one treatment. Scalp acupuncture for MS is accessible, less expensive, safer, more effective, and causes fewer side effects than Western medical treatments. It not only benefits MS patients, but also significantly helps us to better understand the mechanisms that cause the condition. It may lead to the discovery of new effective treatments and hopefully to a cure for this disease in the future. Spinal Cord Injury

Often caused by a car or sporting accident, spinal cord injury is extremely serious. When cervical discs are injured, compression fractures may cause permanent disability. Also hernias or bulges of intervertebral discs may cause spinal cord compression. Common symptoms of spinal injuries include arm and leg paralysis or weakness, difficulty breathing, tingling, numbness, or pain in affected limbs, and incontinence of both bowel and urine. Modern medicine has not yet found a cure for spinal cord injury. The majority of treatments available in Western medicine involve drugs or surgery and are often ineffective. Acupuncture treats the patient as a whole entity and helps patients with spinal cord injury to recover function more effectively than Western medical treatment. If the spinal cord injury is not total, it is

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possible for some people to recover all bodily functions including touch and pain sensations, bladder and bowel functions, and motor control. Through acupuncture treatment, some patients can be cured and many others witness a variety of significant improvements.

CASE HISTORY #5

Julia, a 49-year-old female in a wheelchair, was brought to our clinic in Santa Fe, NM, in 1992. Four months prior to the first visit, this patient was injured in a car accident. Her neck was severely damaged at the level of C-5 and C-6. Upon examination, it was found that she had paralysis of all four extremities. Below the level of injury on the neck there was minimal contraction and movement of arm muscles, which indicated that the muscular tone of her arm was a 2 out of 5. Her hand, legs, and feet were completely paralyzed, which meant that muscular tones were 0 out of 5. Julia had incontinence of urine and was experiencing muscle spasms throughout her entire body. Her tongue was purplish with a thin, sticky, yellow coating. The pulse reading showed lack of force in the inch (cun) and bar (guan) positions, with faint pulses in the cubit (chi) position. Chinese medical pattern discrimination: Qi stagnation and blood stasis in the channels, kidney qi deficiency Scalp acupuncture treatment Area selection

Primary area: Upper 1/5 Motor Area and middle 2/5 Motor Area Secondary area: Foot Motor and Sensory Area, Chorea and Tremor Area Manipulation

Needles should be inserted in both upper 1/5 Motor Area and middle 2/5 Motor Area and stimulated bilaterally. Rotate the needles at least 200 times per minute with the thumb and index finger for 1-3 minutes, twirling them as vigorously as the patient can tolerate and repeating the stimulation every 10 minutes. During the treatment, some patients may experience sensations of heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving along their spine, legs, or arms. Patients with some or all of these sensations usually respond and improve more quickly. However, those who do not have such sensations could still have immediate, positive results. Select the Chorea and Tremor Area or Foot Motor and Sensory Area according to whether the patient has muscular spasms or other abnormal sensations such as pain or burning. Retain the needles for 25-30 minutes. Treatment is given two to three times per week and a therapeutic course consists of 10 treatments. Results of Case #5

During the first treatment, Julia experienced

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immediate relief from the muscle spasms. She also experienced a sensation like electricity shooting downward through her spine, radiating to her feet. With more stimulation of the needles on her head, she started to feel a hot sensation in her hands and feet. She felt so excited about these improvements that she began to cry. While Julia was starting to wiggle her paralyzed toes, we told her that her responses were a good prognosis for significant improvement in the near future. During the third treatment she was able to stand on her feet with someone holding her knees and could lift her arms much higher. The incontinence of urine also showed some improvement. After each treatment from the third to the fifth visit there were gradual improvements in all her limbs. During the sixth treatment, Julia was able to kick her legs with some strength and she could bend her legs at the knee and hold this position for a few minutes. This was a signal that she could possibly stand and walk. With strong encouragement, she struggled up and stood by herself for one minute, two minutes, and then three minutes. After resting for a while, she stood up again and started to walk, managing 20 halting steps before needing to sit down, exhausted. Julia was also in much better control of urination, now holding her urine for six hours at night. After the eighth treatment she was able to walk with the assistance of a walker, experienced much more mobility in her hand movements, and her body spasms were almost entirely gone. With the increase in hand functions she was able to hold a knife with both hands and cut vegetables. To be able to cook again brought her such tremendous joy and gratitude that she laughed and cried at the same time. Though she continued to improve with each treatment, the most dramatic changes occurred in the twentieth treatment. At that time her leg and arm muscles were so much stronger that she was able to write and make phone calls. She called the Western medicine physician who had told her she would be paralyzed for the rest of her life and gave him the wonderful news. Not believing that she was once again able to walk, he went to her house in person to see this miraculous change. Though shocked and stunned watching her walk up to greet him, her doctor was thrilled with her progress and hoped for more excellent results. After 39 treatments, she had gained back all movement of her hands and arms, was able to walk with a cane, and began living without the aid of personal assistants. After 48 treatments, Julia felt well enough to end treatment and start a new life in San Francisco where her son was living. Discussion

Scalp acupuncture is the best therapy for spinal cord injury. Having proven effective through clinical results recorded over the last 35 years, it can effectively stimulate the paralyzed area in order to restore the body’s energy flow to a normal state so that the body

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can heal itself. In other words, scalp acupuncture is able to treat the cause and thus heal the injury. It is also the most useful technique for the patient to improve quickly in the initial visits. In our practice, the combination of scalp acupuncture and regular body acupuncture ensures the best results, especially for the further recovery of paralyzed fingers and toes. Common acupuncture points include Qu Chi (LI 11), He Gu (LI 4), Jian Yu (LI 15), and Wai Guan (TB 5) for upper limb paralysis and Yang Ling Quan (GB 34), Huan Tiao (GB 30), Feng Shi (GB 31), Zu San Li (St 36), and Kun Lun (Bl 60) for lower limb paralysis. Electrical acupuncture is very helpful for speeding up recovery and can be applied on the above points as well as at the Hua Tou Jia Ji points on the back. When choosing Hua Tou Jia Ji points, the pair of points for stimulation should be one above and one below the site of injury level. The electrical stimulation usually lasts 10-20 minutes. Exercise is very important for the recovery of affected limbs. Regular exercise helps the blood circulation and keeps muscles active, and this also accelerates the results from ongoing acupuncture treatments. Traumatic Brain Injury

Traumatic brain injury is a serious condition that may lead to permanent or temporary impairment of the brain’s functions. Brain damage is often related to quick acceleration and deceleration of the brain, which results in injury to the area of impact and its opposite area. The symptoms of brain injury depend on the area of the brain affected. When the speech and motor areas are damaged, body dysfunctions appear such as aphasia and paralysis. According to Chinese medicine, trauma to the head (or anywhere else in the body) causes the blood to extravasate outside its normal vessels, obstructing the flow of fresh new blood to the area. Any tissue of the body requires nourishment by blood to perform its proper function. Blood stasis must be resolved for the tissue to once again receive the nourishment of healthy blood.

CASE HISTORY #6

Lisa, a 10-year-old girl in a wheelchair, was brought by her mother to our clinic in Santa Fe, New Mexico, in 1993. Four months before, Lisa fell off her bicycle and hit her head on the left side, above and behind her ear. She had had a concussion on the left side of the brain in the internal capsule and initially was totally paralyzed on her right side and lost the ability to speak. She had been receiving rehabilitation treatment including physical therapy, osteopathic therapy, and speech therapy starting two weeks after her injury. Her aphasia gradually improved and she was able to drag her right leg while walking and move her right arm slightly but the paralysis had shown no further improvement for the past eight weeks. Her primary doctor recommended that she try acupuncture treatment. Upon examination, her tongue

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was red with a thin white coating and her pulse was slippery and wiry. Chinese medical pattern discrimination: Qi stagnation and blood stasis in the channels

Scalp acupuncture treatment Area selection

Primary area: Upper 1/5 Motor Area and middle 2/5 Motor Area Secondary area: Foot Motor and Sensory Area, Chorea and Tremor Area Manipulation

Needles should be inserted in both upper 1/5 Motor Area and middle 2/5 Motor Area and stimulated on the opposite side of the paralyzed limbs. With children, select the thinnest needles that you can insert into the scalp. Always put one needle in the ear point Shen Men to help a young patient relax and to reduce the sensitivity of needle insertion and stimulation of the scalp. Use the fewest number of needles possible in the scalp and rotate them at least 200 times per minute with the thumb and index finger for one minute, twirling as gently as possible so that the child patient can tolerate the sensation and repeating the stimulation every 10 minutes. Communicate with children and their parents more often than with adult patients in order to reduce their fear and anxiety. During the treatment, some patients may experience sensations of heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving along their spine, legs, or arms. Tell the child that those are normal and are a good sign for improving more quickly. Select the Chorea and Tremor Area or Foot Motor and Sensory Area according to whether the patient has muscular spasms or other abnormal sensations such as pain or burn-

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ing. Retain the needles in place for 10-20 minutes. Treatment is given two to three times per week and a therapeutic course consists of 10 treatments. Results of Case #6

Lisa was afraid of needles and started to cry and refuse the treatment before the first needle was inserted. She agreed to allow the needle insertion only after her mother told her that she might ride a bike again if these treatments worked. The insertion of two needles on the left side of her scalp did not seem to bother her at all. Two minutes after the treatment began, Lisa announced that she felt “a lot of blood move to my head.” After that, the child was able to lift her right arm with much more ease. Her walking also showed some improvement as she was able to lift her right leg more easily. Lisa experienced dramatic improvements of her right arm, hand, leg, and foot with every visit. By the sixth treatment, Lisa could move her right arm up and down very quickly and was able to start writing with that hand again. After the fifteenth treatment, she had gained more mobility and use of her right hand as well as more muscle strength in that hand, which was now as strong as her left hand. Her walking appeared almost normal, and she was again able to run, at least slowly. At the end of the twenty-second treatment her right hand was completely back to normal and all paralysis was gone. She had participated in running a race and did very well.

Discussion

Scalp acupuncture can be an excellent rehabilitation tool for traumatic brain injury patients. However, while treating children with body acupuncture can be challenging, it can be even harder with scalp acupuncture. Children and their parents might not be willing to participate in needling as a therapeutic method. It requires the doctor to have very good techniques of insertion and manipulation of needles as well as good communication skills. Sometimes it is necessary to show a patient how tiny the needles are or demonstrate the insertion of a needle in the practitioner’s own body. This helps to reduce fear and anxiety for both patient and parents. It is very helpful to play or chat with young patients as if they are friends or family members before the treatment. It is also a good strategy to ask the parents to talk, play with, or feed young patients during the insertion and stimulation of needles, which acts as a diversion to turn the child’s attention away from the needles and makes them less sensitive to the procedure. For a child who is extremely sensitive to needles, stimulation by twirling should be avoided during the first one or two visits. For children less than two years old, an effective technique is to hide each needle from their sight while inserting and stimulating. Compared to adult patients, generally speaking, young patients should receive fewer needles, milder stimulation, and shorter time of needle

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retention. Whether you are treating a child or adult, it is important to observe responses and reactions while inserting, stimulating, or withdrawing needles, and adjust the techniques accordingly. Monoplegia

CASE HISTORY #7

David, a 52-year-old man, was vacationing with his wife in Santa Fe, NM, in 1993. A waitress who noticed that he was paralyzed told him that he should come to our clinic, which specialized in treating that affliction. The man had developed paralysis in the right arm and hand after an operation on the left side of his brain to remove a tumor. Following the surgery, the left front side of his head no longer contained any scalp and there was a depression where the tumor and surrounding tissue had been removed. Because he was feeling very frustrated with his condition, David took the advice of the waitress and made an appointment at our clinic for a free consultation the same day. In addition to the paralysis on the right side, his tongue was purple with teeth marks and a thin, white coating. His pulses were wiry and fine. Chinese medical pattern discrimination: Qi stagnation and blood stasis in the channels Scalp acupuncture treatment Area selection

Primary area: Upper 1/5 Motor Area and middle 2/5 Motor Area Manipulation

Needles should be inserted in the upper 1/5 Motor Area and the middle 2/5 Motor Area on the unaffected side of the scalp for patients who develop paralysis from brain surgery. Always put one needle in the ear point Shen Men to help nervous patients relax and reduce the sensitivity of needle insertion and stimulation of the scalp. Rotate the needles at least 200 times per minute with the thumb and index finger for 1-3 minutes, twirling them as vigorously as the patient can tolerate and repeat the stimulation every 10 minutes. During treatment, some patients may experience sensations of heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving along their spine, legs, or arms. As mentioned previously, those patients with some or all of these sensations usually respond and improve more quickly. One may also choose the Chorea and Tremor Area or Foot Motor and Sensory Area accordingly if the patient has muscular spasms there. Retain the needles for 25-30 minutes. Treatment is given two to three times per week and a therapeutic course consists of 10 treatments. Results of Case #7

During the initial consultation, David and his wife asked many questions because they were doubtful that

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scalp acupuncture could help him. They asked, “How quickly could he notice any improvement?” David decided to try the treatment but was still skeptical after being told that some patients had immediate improvement and others did not. Examination showed that the sensations in his right arm and hand were still normal. There was a little twitching in the muscles of his arm but no movement at all in his right arm or hand and the hand appeared puffy and swollen. After two needles were inserted on the right side of his scalp, David immediately noticed tingling sensations in his right arm and hand. A few minutes later he was able to move his paralyzed arm and hand, amazed as he raised it over his head. The following day he returned to the clinic for another treatment. David appeared to be very tired because, he said, “Everyone at the hotel came to our room for hours to shake my recovering hand.” By the end of his fifth treatment David had full use of his right hand and arm and the edema in his hand was completely gone.

Bell’s Palsy

Bell’s palsy is a paralysis and weakness of the muscles that control expression on one side of the face. The disorder results from damage or trauma to one of a pair of facial nerves (Cranial Nerve VII) that controls the muscles of the face. Symptoms of Bell’s palsy usually appear suddenly and reach their peak within 48 hours. Symptoms range in severity from mild weakness to total paralysis of the face, and Bell’s palsy can often cause significant facial distortion. Until recently, in most cases its cause was unknown. Most scientists believe that a viral infection causes the disorder and that the facial nerve swells and becomes inflamed in reaction to the infection. Signs and symptoms of Bell’s palsy may include sudden onset of weakness or paralysis on one side of the face making it difficult to smile or close the eye on the affected side, and deviation and droop of the corner of the mouth making facial expressions difficult. Other symptoms include pain behind or in front of the ear on the affected side, sounds that seem louder on the affected side, and changes in the amount of tears and saliva the body produces. Babies can be born with facial palsy and they exhibit many of the same symptoms as adults with Bell’s palsy. This is often due to a traumatic birth that causes irreparable damage to the facial nerve resulting in acute facial nerve paralysis. Patients with facial paralysis for which an underlying cause can be readily found are not generally considered to have Bell’s palsy. These underlying problems include tumor, stroke, diabetes, meningitis, head trauma, and inflammatory diseases of the cranial nerves. However, the neurological findings are rarely restricted to the facial nerve in these conditions. There is no cure or specific treatment for Bell’s palsy, although three in four patients’ symptoms may subside on their own within two to three weeks. Others may be left with deficits of varying degrees, and some patients have permanent damage. Major complications of the condition include

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chronic loss of taste (ageusia), chronic facial spasm, and corneal infections. To treat loss of taste, the lower 2/5 Sensory Area in the scalp should be stimulated. It is not advisable to use electrical stimulation on the needles in the face because it may cause facial muscle spasm. To treat facial muscle spasm the Chorea and Tremor Area and the lower 2/5 Motor Area should be stimulated. To prevent corneal infections, the eyes may be protected by covers or taped shut during sleep and for rest periods. Tear-like eyedrops or eye ointments may be recommended, especially in cases of complete paralysis. Facial paralysis, according to Chinese medicine, involves both disregulation of qi and blood causing malnourishment of the channels in the facial region, as well as invasion by pathogenic wind-cold or phlegm.

CASE HISTORY # 8

Jimmy, a 52-year-old male, came to our clinic in Santa Fe, NM, in 2000. He had been diagnosed with Bell’s palsy two weeks prior and was suffering from cold-like symptoms. He was experiencing moderate pain running along the line of his jaw and behind his left ear. As well, he could not close his left eye, raise his left eyebrow, show his upper teeth, frown, or puff out his left cheek. If this was not enough, the corner of his mouth on the affected side drooped and his mouth deviated to the right side, which was aggravated when he smiled. Because of all these symptoms, he was extremely agitated, angry, and fearful that his face would never look normal again. He had a red tongue with a thin, yellow coating. His pulses were wiry and slippery. Chinese medical pattern discrimination: Damp heat obstructing the channels and network vessels Scalp acupuncture treatment Area selection

Primary area: Lower 2/5 Motor Area Secondary area: Lower 2/5 Sensory Area Manipulation

Needles should be inserted on both lower 2/5 Motor Area and lower 2/5 Sensory Area on the contralateral side. Select the finest gauge needles that you can insert into the scalp for the initial treatments. Always put one needle in the ear point Shen Men to help the patient relax and reduce sensitivity to needle insertion and stimulation of the scalp. For two minutes, rotate the needles at least 200 times per minute with the thumb and index finger, twirling them as gently as possible at the beginning of treatment and repeating stimulation every 10 minutes so that the patient can tolerate the sensations better. During treatment, some patients may have all or some of the following sensations: heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving in the affected side of the face. Retain the needles in place for 20-30 minutes and request the patient to exercise the affected side of his

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facial muscles during scalp acupuncture treatments, especially if there are no needles in his face. The treatment is first given two times per week and then gradually reduced to fewer sessions after patients have experienced major improvement. A therapeutic course consists of 10 treatments. Results of Case #8

Jimmy had a very good response to his first scalp acupuncture treatment. He was immediately able to close his left eye better and the pain around his ear and jaw significantly reduced just a few minutes after two needles were inserted. After the third treatment, the deviation and drooped corner of his mouth showed remarkable improvement, especially after more needles were inserted into his face, hands, and feet. He was able to raise his left eyebrow, reveal his upper teeth, and puff out his left cheek after only six visits. However, he still could not squeeze his left eye completely closed and his smile was a little crooked. After nine scalp acupuncture treatments, he regained all functions of expression in his face and was very pleased with the outcome.

Discussion

Scalp acupuncture is an effective treatment for Bell’s palsy. It can repair damaged nerves and restore full use and strength to injured areas. Most patients can recover completely after five to 15 treatments. The sooner patients get treatment, the quicker their recovery. However, facial paralysis may continue to develop and get worse for seven to 10 days after initial symptoms occur. If treating a patient with Bell’s palsy within seven days of its onset, it is wise to inform patients that their condition is not yet stable and more or worse symptoms can continue to develop. Otherwise, patients may conclude that acupuncture made their symptoms worse. Although scalp acupuncture has been successful in the treatment of Bell’s palsy, body acupuncture with threaded techniques is very effective for this disorder as well. Common points are Si Bai (St 2) threaded toward Di Cang (St 4), Di Cang (St 4) threaded toward Jia Che (St 6), Yu Yao (extra point) threaded toward Tai Yang (extra point), Yang Bai (GB 14) threaded toward Yu Yao (extra point), and Xia Guan (St 7), He Gu (LI 4), and Tai Chong (Liv 3). Research on the effects of scalp acupuncture for Bell’s palsy

There are several clinical studies showing the excellent results obtained from scalp acupuncture and regular body acupuncture on facial paralysis. •• Wu Jian-min reported on treating 80 cases of facial paralysis using scalp acupuncture in 1989. The duration of the ailment was from four days to two years. Scalp acupuncture treatments were given once a day and 10 treatments made a course. The results showed Bell’s palsy fully resolved in 72 cases (90%) and markedly improved in 8 cases (10%) with zero

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failure, yielding an effective rate of 100%.20 •• Based on Liu Fang-shi’s report of research done in 1994, 48 cases of facial paralysis were treated by scalp acupuncture on the Motor Area. The results were 25 cases fully recovered (52%), 18 cases markedly improved (38%), and 5 cases failed to improve at all (10%), yielding a total effective rate of 90%.21 Motor Neuron Diseases

The motor neuron diseases (MNDs) refer to a group of progressive neurological disorders that affect motor neurons associated with controlling voluntary muscle activity including speaking, walking, breathing, swallowing, and general movement of the body. They commonly have distinctive differences in their origin and causation but a similar result in their outcome for the patient, which is severe muscle weakness. Common MNDs include amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy, and poliomyelitis. Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a disorder that generally involves either the lower or upper motor systems of the body. In advanced stages, both regions of the body are affected. It is caused by sclerosis in the corticospinal tracts. Primary lateral sclerosis is a rare motor neuron disease that resembles ALS but there is no evidence of the degeneration of spinal motor neurons or muscle wasting that occurs in ALS. Progressive muscular atrophies are a wide group of genetic disorders characterized by primary degeneration of the anterior horn cells of the spinal cord, resulting in progressive muscle weakness. Poliomyelitis, also called polio or infantile paralysis, is a highly infectious viral disease that may attack the central nervous system and is characterized by symptoms that range from a mild nonparalytic infection to total paralysis. Common symptoms and signs include progressive weakness, muscle wasting, muscle fasciculations, spasticity or stiffness in the arms and legs, and overactive tendon reflexes. Patients may present dragging foot, unilateral muscle wasting in one or the other hand, or slurred speech. Causes of many motor neuron diseases are unknown and others have varying causes according to the specific motor neuron disease. There is no cure or standard treatment for motor neuron diseases and treatment focuses on reducing the symptoms of muscle spasm and pain while maintaining the highest practical level of overall health. Diseases such as progressive muscular atrophy, poliomyelitis, and ALS are categorized as wei zheng (痿证) or wilting conditions in Chinese medicine. The patterns presenting in these diseases usually include a complex combination of liver blood, kidney yin, and spleen qi deficiencies along with damp heat further consuming the blood and damaging the qi, and thus depriving the limbs of strength and the flesh and muscles of nourishment. The damp heat may become congested in the network vessels causing the sinews and muscles to

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further lose their nourishment. Other patterns based on the patient’s constitutional tendencies may also present or arise as the disease progresses.

CASE HISTORY #9

Sherry, a 38-year-old female, came to our clinic in 2007. It was difficult for her to walk even with her mother’s support and because of Sherry’s aphasia, her mother gave the medical history. Sherry fell frequently, lost her balance easily, and had had difficulty walking since the age of 19. Her slurred speech sometimes even her mother could not understand. She could not control her urine, choked when eating, and always felt fatigued. Her left ovary hurt and the pain was worse during menses. She often had a migraine headache and premenstrual syndrome (PMS), and she had considerable mucous in her nose and throat much of the time. Sherry had been to several famous hospitals but there was no clear diagnosis. Several doctors thought she suffered from a motor neuron disorder or ALS. Her mental activity presented as normal and she was then in graduate school for a master’s degree. Examination showed she was unable to stand and walk straight by herself. Her gait was wide-based and unsteady and she had to hold on to someone to walk in order to maintain her balance. Her ataxia was even more apparent when she tried to turn and her whole body was stiff and rigid, but worse on the left side. She had lost her fine motor skills. Her legs had severe tremors when she put her toes on the ground and she could not stand on one leg. She counted the numbers from one to 20 with a slow, slurred, weak voice. She could hardly be understood when she said her home phone number. Her tongue had a red tip, a peeled coating on the right side, was purple in the center, had major teeth marks along the sides, a severe tremor, and a thick, white coating. Her pulses were fine

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and wiry, and were faint in both cubit (chi) positions. Chinese medical pattern discrimination: Liver wind stirring internally, kidney qi deficiency Scalp acupuncture treatment Area selection

Primary area: Upper 1/5 Motor Area and Speech I Area Secondary area: Foot Motor and Sensory Area, Chorea and Tremor Area, and Praxis Area Manipulation

Insert needles in the upper 1/5 Motor Area, Speech I Area, Foot Motor and Sensory Area, Chorea and Tremor Area, and Praxis Area and stimulate bilaterally. Rotate the needles at least 200 times per minute with the thumb and index finger for 1-3 minutes, twirling them as vigorously as the patient can tolerate and having the patient move her affected limbs actively and passively. Repeat the stimulation every 10 minutes. During treatment, some patients experience sensations of heat, cold, tingling, numbness, heaviness, distention, or the sensation of water or electricity moving in the affected limbs. Those patients usually respond and improve more quickly. However, those who don’t have such sensations could still experience immediate and positive effects. Retain the needles for 30-45 minutes and treat two or three times a week. A therapeutic course consists of 10 treatments. Results of Case #9

A few minutes after being needled on her head, Sherry felt a whole-body hot sensation, which then moved from her hips to her feet, stronger on the left side. Afterwards, her speech was so much clearer, faster, and stronger that even she was surprised. Her walking was much more stable and she was able to lift both legs much higher. She could stand on either leg alone and had to look down to check if it was true. She returned for the second treatment a day later, having had traveled across the country for these treatments. Sherry reported without her mother’s help that her body was less stiff and that she could walk and move better. Her speech was clearer, she didn’t feel that her tongue was thick when talking, and very little choking had occurred. Her fatigue and bladder control were improved but she still had a lot of mucous and leg tremor. Her bowel movements were a little loose and she had experienced some nausea and gas after taking the prescribed Chinese herbs. Examination showed that the tremor as well as teeth marks in her tongue were less, the thick, white coating was less, and it was peeled more on the front part of her tongue. Her pulses remained unchanged. During the second treatment, Sherry experienced a hot sensation again, more so on the left side of the body. She was able to count from one to 20 without breathing. She felt that her legs were not as heavy when walking. For scalp acupuncture, the Chorea and Tremor Area replaced the Foot Motor and Sensory

Review

Area in this second treatment. Body acupuncture was added 15 minutes after scalp acupuncture began. The points were Tai Chong (Liv 3), Tai Xi (Ki 3), Yang Ling Quan (GB 34), Feng Long (St 40), Wai Guan (TB 5), and Lian Quan (CV 23). During the third treatment the next day, the patient reported that she walked better with more control of her left leg and that it felt less heavy. Her speech continued improving with less of a heavy sensation in her tongue. She was able to eat better because of less choking. She had less mucous in her nose and throat and no nausea since the last visit. Although the tremor in both legs was better, she still had some fine movement problems such as difficulty with buttons and writing and still had some stiffness in her legs. Examination showed that her tongue was less red with fewer teeth marks and tremor only on the left side. The thick, white coating was less. Her pulses remained unchanged and were still fine and wiry. The treatment strategy was modified. While the same scalp areas of upper 1/5 Motor Area and Speech I Area were still used, the Praxis Area and Chorea and Tremor Area were added to address her secondary complaints. The manipulation and retaining of needles remained the same. She could pick up pennies on a table with either hand during the treatment. Two days later, Sherry arrived for her fourth session and reported very positive reactions to the last treatment. Eating was easier because she could swallow without choking and had less mucous in the throat. Her breathing was less labored when she was active, and friends noticed major improvement in her speech during phone conversations. Sherry’s fine motor movement showed some improvement such as turning on a light switch. Unfortunately, that morning she had lost her balance and fallen backward, but with no severe injury. Her tongue showed a red tip, only a thin, white coating, and a peeling coating at the front. There were almost no teeth marks remaining. Her fine pulses had become a little larger and stronger, were still slightly wiry, and showed more strength in the cubit (chi) positions. She received more aggressive treatment that day because it was her last treatment for this trip. The upper 1/5 Motor Area and Speech I Area were still considered primary according to her condition. The Speech III Area, Balance Area, and Foot Motor and Sensory Area were added to assist and consolidate her improved clinical signs. She responded immediately after the needles were inserted, her voice sounding much clearer and stronger. She reported that her balance was improving and her legs felt lighter during the walking exercises. She watched and listened to herself on the video screen while she walked and talked like a normal person. At the end of her final treatment she was both laughing and crying. Discussion

Scalp acupuncture has been found to have very a significant positive impact on hemiplegic aphasia due to

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various central nerve disorders, even during the initial few treatments. In Sherry’s case, the hemiplegia was caused by a motor neuron disorder. For patients such as Sherry who present with multiple symptoms and signs, it is, in our experience, more effective to treat major complaints first with a few needles. Secondary symptoms can be addressed after patients have significant improvements in their major complaints. As the above case study demonstrated, doctors should modify the treatment strategy and stimulate areas according to changes in a patient’s condition. In our practice, the combination of scalp acupuncture and regular body acupuncture ensures the best results, especially for the further recovery of paralyzed fingers or toes. Common acupuncture points include He Gu (LI 4), Qu Chi (LI 11), Jian Yu (LI 15), and Wai Guan (TB 5) for upper limb paralysis and Yang Ling Quan (GB 34), Feng Shi (GB 31), Huan Tiao (GB 30) Zu San Li (St 36), and Kun Lun (Bl 60) for lower limb paralysis. Electrical acupuncture is very helpful for speeding up recovery. The electrical stimulation usually lasts 10 to 20 minutes. Exercise is also important for the recovery of affected limbs. Active and passive exercise during scalp acupuncture treatment is very important for improvement. It helps the blood circulation and keeps muscles active, accelerating the results from ongoing acupuncture treatments.

her body below the neck and had paralysis of all four limbs. As a result, she had incontinence of bowel and urine. After trying many kinds of therapies that brought no improvement, she became depressed. Examination showed that all four extremities were very tight and had occasional spasms. The muscular tone of her right arm ranked 2 out of 5 degrees, and her left arm and both legs were 0 out of 5 degrees, or completely paralyzed. Her tongue was red with a thin, white coating; her pulses were fine and wiry. Chinese medical pattern discrimination: Qi stagnation and blood stasis in the channels, kidney qi deficiency, liver blood deficiency and liver depression qi stagnation

Quadriplegia

Quadriplegia means paralysis of all four limbs or of the entire body below the neck. When the arms, legs, and torso are paralyzed, this is commonly caused by damage to the brain, injury of the cervical spinal cord, polyneuritis, myasthenia gravis, progressive myodystrophy, multiple myositis, or acute infective multiple radiculoneuritis. The severity of quadriplegia depends on both the level at which the spinal cord is injured and the extent of the injury. Although the most obvious symptom is impairment to the limbs, function is also impaired in the torso. That results in loss or impairment of bowel and bladder control, sexual function, digestion, breathing, and other autonomic functions. Because sensation is usually impaired in affected areas, this can manifest as numbness, reduced sensation, or burning sensation and pain. Quadriplegics are often vulnerable to pressure sores, osteoporosis and fractures, frozen joints, spasticity, respiratory complications and infections, poor autonomic reflexes, deep vein thrombosis, and cardiovascular disease because of depressed functioning and immobility.

CASE HISTORY #10

Barbara was in a wheelchair when she was brought to our 2006 scalp acupuncture seminar in Phoenix, Arizona. She had little hope that our treatment would help her condition. Infected by West Nile virus, she had immediately developed quadriplegia. She lost control of

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Scalp acupuncture treatment Area selection

Primary area: Upper 1/5 and middle 2/5 of Motor Area Secondary area: Foot Motor and Sensory Area Manipulation

Needles should be inserted in both upper 1/5 Motor Area and middle 2/5 Motor Area and stimulated bilaterally. Rotate the needles at least 200 times per minute with the thumb and index finger for 1-3 minutes, twirling them as vigorously as the patient can tolerate and repeating the stimulation every 10 minutes. During treatment, some patients feel heat, cold, tingling, numbness, heaviness, distention, and/or the sensation of water or electricity moving along their spine, legs, or arms. Patients who experience some or all of these sensations usually respond and improve more quickly. As stated previously, however, those who do not have such sensations could still have immediate, positive results. It is important to instruct patients to move their affected limbs actively and passively, if possible. Select either the Chorea and Tremor Area or the Foot Motor and Sensory

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IMPROVING HEALTHCARE OUTCOMES WORLDWIDE

Area, depending whether the patient has muscular spasms or other abnormal sensations such as pain or burning. Retain the needles for 30-45 minutes. Treatment is given two to three times per week and a therapeutic course consists of 10 treatments. Results of Case #10

Barbara had very positive responses to scalp acupuncture treatment. As soon as we inserted two needles in her scalp at the Chorea and Tremor Area, the tightness in all four limbs loosened up and the spasms were gone. Soon after that, both of her arms began to move and lift. When we told Barbara that some similar patients were able to walk again, her eyes filled with tears. After inserting four more needles in her scalp, we encouraged Barbara to stand up. She was very surprised to find that she had regained the ability to control her legs again. Although she felt nervous and was assisted by two people, she stood up. She couldn’t believe it when we encouraged her to start walking. With much excitement and audience applause, she followed our instruction and started to move: one step, then two, three, and four steps. She walked as much as she could, turning about every 30 steps, walking with confidence and a smile on her face. At another scalp acupuncture seminar in Phoenix, Arizona, later the same year, the audience was waiting to see Barbara, whom we had treated several months before. We were astonished and barely able to recognize her when she walked into the conference room by herself. Barbara reported that she had not received further acupuncture treatment after the last two scalp acupuncture treatments because neither her insurance nor her own money could cover further sessions. Instead, she did intensive exercise as we had instructed seven months before and had recovered completely. For the benefit of the seminar audience, Barbara demonstrated many different kinds of movement of her four extremities such as jumping, running, and easily raising her arms, which brought audience applause. She had gotten married and returned to work. The only remaining problem was urgent, frequent urination and some incontinence of urine. That was one of the reasons that she returned to this second seminar half a year later. We put two needles in the Foot Motor and Sensory Area and two needles in the Reproductive Area. Barbara had constantly felt pressure and a “strange feeling” there, but she left the seminar very happy. She no longer had that urgent feeling in her bladder and was able to hold her urine for two hours.

Discussion

We need to emphasize that this patient received only three scalp acupuncture treatments and had recovered completely. That is highly unusual and by no means the norm. Treating quadriplegia by acupuncture is very challenging. Normally it takes several months or even as much as one to two years for this treatment to be effective. Even then, only 50% of patients have a chance

Review

of improving. Quadriplegia can be treated after any duration, but less than three months from the date of injury or illness shows the greatest improvement. The longer the duration of impairment, the more gradual the improvement occurs. With long-term conditions expectations need to be realistic, although some patients will occasionally surprise practitioners. There are many different acupuncture techniques to treat paralysis. Although scalp acupuncture has the best and fastest response, other techniques are necessary for a more complete recovery. Regular body acupuncture treatment has been found to have a positive therapeutic effect on the recovery of movement of hands, fingers, feet, and toes. Electrical stimulation is very helpful if the practitioner has difficulty rotating the needle more than 200 times per minute. Only two of the scalp needles should be stimulated at any one session, or the brain can become too confused to respond. For electrical stimulation in body acupuncture, fewer than four needles should be stimulated in each limb. The best results are usually achieved by applying low frequency (for example, 3 hertz) with high intensity (for instance, when visible muscle contraction is observed). Electrical stimulation can be applied above and below the damaged level at Hua Tuo Jia Ji points on the back, which is another important technique for treating quadriplegia in addition to scalp acupuncture. References 1. Feng Cun-xiang et al., Practical Handbook of Scalp Acupuncture, Chinese Medicine and Science Publishing House, 1999, p. 30–36 2. Wang Fu-chun, Yu Xian-mei, Deng Yu, Scalp Acupuncture Therapy, People’s Medical Publishing House, Beijing, 2003, p. 61–68 3. Wu Bo-li et al., “Yu Zhi-shun’s Experience on Head Points for Paralysis,” Chinese Acupuncture & Moxibustion, 1997, Vol.17 No. 3, p. 153–154 4. Zhu Ming-qing et al., Scalp Acupuncture, Guangdong Technology and Science Press, 1992, p. 8–11 5. Jiao Shun-fa, Head Acupuncture, Foreign Languages Press, Beijing, 1993, p.17–22 6. Blumenfeld, op.cit., p. 64 7. Olmstead, Donna, “Acupuncture: The Medicine Is Powerful,” Albuquerque Journal, February 19, 1996, p. A1 8. Chang, Richard, “Fertile Ground for Alternative Medicine,” The New Mexican, June 1, 1997, p. E2–4 9. Chang, Richard, “Acupuncture Rehab,” The New Mexican, April 3, 1998, p. C-3 10. McMillan, Brett B., “Easing the Pain, Acupuncture Program Looks to Help Relieve Discomfort of Troops,” Stripe, February 17, 2006, p. 1 11. Zhou Ying, “He Teaches and Popularizes Chinese Medicine in USA,” China News On Traditional Chinese Medicine, April 5, 2006, p. 8 12. Lampe, Frank, and Snyder, Suzanne, “Jason Hao, DOM: Pioneering the Use of Scalp Acupuncture to Transform Healing,” Alternative Therapies, March/April 2009, Vol.15 No. 2, p. 62–71 13. Kong Yao-qi et al., The Acupuncture Treatment for Paralysis, Science Press, Beijing, 2000, p. 23 14. Jiao, op.cit., p. 47 15. Jia, op.cit., p. 74 16. Liu Jian-hao et al., “Observation on Specificity of Acupuncture Location in Treatment of Acute Apoplexy by Scalp Penetration Needling,” Chinese Acupuncture & Moxibustion, April 2010, Vol. 30 No. 4, p. 275–278 17. Li Min et al., “Observation on Therapeutic Effect of Five-Needle-in-Nape Acupuncture for Treatment of Post-stroke Pseudobulbar Paralysis Dysphagia,” Chinese Acupuncture & Moxibustion, November 2009, Vol. 29 No. 11, p. 873–875 18. Hao, Jason and Hao, Linda, “Treatment of Multiple Sclerosis by Scalp Acupuncture,” Acupuncture Today, April 2008, Vol. 9 No. 4, p. 12–13 19. Gao Wei-bin and Gao Jing-li, Acupuncture and Moxibustion Six Unique Skills, Chinese Medical Science Publishing House, 1998, p. 243–244 20. Wu Jian-min, “Clinical Observation of 80 Cases of Facial Paralysis by Scalp Acupuncture,” Shanxi Journal of Traditional Chinese Medicine, 1989, Vol. 10 No. 2, p. 81 21. Liu Fang-shi et al., “Clinical Observation of 48 Cases of Facial Paralysis by Scalp Acupuncture,” Shanghai Journal of Acupuncture and Moxibustion, 1994, Vol. 13 No. 4, p. 166

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Review

Cochrane Summary of Findings: Horse Chestnut Seed Extract for Chronic Venous Insufficiency Vigdis Underland, MS; Ingvil Sæterdal, PhD; Elin Strømme Nilsen, MS

Author Affiliations Vigdis Underland, MS; Ingvil Sæterdal, PhD; and Elin Strømme Nilsen, MS, are researchers at the Nordic Cochrane Centre’s Norwegian branch, Norwegian Knowledge Centre for Health Services, Oslo, Norway. Correspondence Elin Strømme Nilsen, MS esn@nokc.no Citation Global Adv Health Med. 2012;1(1):122-123. Key Words Summary of findings, Cochrane, CAM, review, horse chestnut seed extract, HCSE, chronic venous insufficiency, CVI, collaboration, GRADE Acknowledgment This article was prepared on behalf of the Cochrane Complementary and Alternative Medicine Field and with funding from the US National Center for Complementary and Alternative Medicine of the US National Institutes of Health (grant number R24 AT001293).

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s part of its efforts to disseminate the results of Cochrane reviews to a wider audience, the Cochrane Complementary and Alternative Medicine (CAM) Field develops Summary of Findings (SoF) tables and then uses these tables as a basis for its Plain Language Summaries. In each SoF table, the most important outcomes of the review, the effect of the intervention on each outcome, and the quality of the evidence for each outcome are presented. The process of developing the SoF table involves deciding which outcomes to present for which time points and evaluating the strength and quality of the evidence for the outcomes. The Cochrane CAM Field contacted the authors of this review to request clarification on any points that are not understood in the Cochrane review and also to request their review of the SoF. In this article, review authors in the Cochrane Collaboration reviewed the effects of horse chestnut seed extract for chronic venous insufficiency. CHRONIC VENOUS INSUFFICIENCY AND HORSE CHESTNUT SEED EXTRACT

Chronic venous insufficiency (CVI) is characterized by a chronic inability of veins in the lower leg to transport blood back toward the heart due to damage to the one-way valves within the leg veins. This damage is caused by blood clots (deep vein thromboses) or other factors, such as congenital disorders. This results in venous hypertension, an increase in pressure within the veins in the leg. The signs of CVI include swelling of the leg, feelings of tired and painful legs, dry scaly skin, varicose veins, hardening of the skin, and leg ulcers (open wounds on the lower legs that do not heal after 6 weeks). CVI severity is often graded into 3 categories: stage I, swelling (edema); stage II, swelling (edema) plus skin changes; stage III, the presence of open or healed leg ulcers. Stage III is considered the most severe stage of CVI. About 10% to 15% of adult men and 20% to 25% of adult women present signs and symptoms consistent with a diagnosis of CVI, and the prevalence increases with age. The horse chestnut (Aesculus hippocastanum L) is a large tree growing to about 25 to 30 m in height. The seed of the horse chestnut is a small brown nut. Unprocessed horse chestnut seeds contain a toxin called esculin (also spelled aesculin). This toxin may increase the risk of bleeding due to its ability to pre-

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vent blood clots from forming. The unprocessed seeds are poisonous, and symptoms associated with horse chestnut seed poisoning include vomiting, diarrhea, headache, confusion, weakness, muscle twitching, poor coordination, coma, and paralysis. Horse chestnut seeds are therefore processed to remove the toxic component, resulting in purified horse chestnut seed extract (HCSE). The active component of HCSE is called escin (also spelled aescin). Escin appears to promote blood circulation through the veins and thereby reduce swelling and inflammation of the legs. It is not exactly clear how escin works, but theories include that it works by “sealing” leaking capillaries, improving the elastic strength of veins, preventing the release of enzymes that damage the blood vessels, and blocking other various physiological events that lead to vein damage. The most common dosage of horse chestnut is 300 mg HCSE twice daily, standardized to contain 50 mg escin per dose, for a total daily dose of 100 mg escin. In theory, horse chestnut may increase the risk of bleeding. In addition, animal studies suggest that HCSE may cause lowered blood sugar. WHAT DOES THE RESEARCH SAY?

Not all research provides the same quality of evidence. The higher the quality, the more certain we are about what the research says about an effect. The words will (high-quality evidence), probably (moderate-quality evidence), and may (low-quality evidence) describe how certain we are about the effect. After searching for all relevant studies, the review authors found 17 studies that they included in the review. Ten of these studies were placebo-controlled trials. The trials showed that for people with chronic venous insufficiency, horse chestnut seed extract •• probably reduces lower-leg volume, •• may reduce circumference at ankle, and •• may reduce circumference at calf. We are uncertain of the effect of HCSE on leg pain and edema because the quality of the evidence is very low. In general, side effects are poorly documented, and it is difficult to provide precise information. In these trials, some participants experienced gastrointestinal complaints, dizziness, nausea, headache, and itching.

Review

Horse Chestnut Seed Extract for Chronic Venous Insufficiency

TABLE Summary of Findings: Horse Chestnut Seed Extract Compared to Placebo for Chronic Venous Insufficiency Patient or population: Patients with chronic venous insufficiency Intervention: Horse chestnut seed extract Comparison: Placebo Illustrative Comparative Risks (95% Confidence Interval)

Outcomes Mean reduction of lower leg volume (mL)

Assumed risk

Corresponding risk

Placebo

Horse chestnut seed extract

The mean reduction of lower leg volume in the control groups was –45.65

The mean reduction of lower leg volume in the intervention groups was 32.10 higher (13.49-50.72 higher)

Mean reduction of The mean reduction of circumference at circumference at ankle (mm) ankle in the control groups was –1.3

The mean reduction of circumference at ankle in the intervention groups was 4.71 higher (1.13-8.28 higher)

Mean reduction of circumference at calf (mm)

The mean reduction of circumference at calf The mean reduction of circumference at calf in the control groups was –1.23 in the intervention groups was 3.51 higher (0.58-6.45 higher)

Improvement in leg pain

44 per 100

63 per 100 (52-76 per 100)

Reduction of leg pain (VAS 0-100)

The mean reduction of leg pain in the control groups was 0.2

The mean reduction of leg pain in the intervention groups was 42.40 higher (34.9-49.9 higher)

Improvement of edema

41 per 100

66 per 100 (53-81)

No. of Participants (Studies)

Quality of the Evidence (GRADE)

502 (6)

⊕⊕⊕ Moderatea

80 (3)

⊕⊕ Lowb,c

80 (3)

⊕⊕ Lowb,c

418 (1)

⊕ Very lowd,e,f

30 (1)

⊕ Very lowb,g

346 (1)

⊕ Very lowd,e,f

Abbreviations: GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; VAS, visual analog scale. GRADE Working Group grades of evidence: High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. a

All studies have uncertainty of randomization procedure and allocation concealment. One trial has a large number of dropouts. Randomization procedures not reported, with an uncertainty of allocation concealment. Only 3 small studies with a total of 80 participants, with a consequent imprecision of results and wide confidence intervals. d Randomization procedure not reported, with no information on allocation concealment. From the analyses, there appears to be a large number of dropouts during the trial. e The crossover design was considered a reason to downgrade on directness because of the risk of carryover effects. f Only 1 trial with uncertainty about the number of participants in each group according to table of included studies and analysis. g Only 1 small study with a total of 30 participants. b c

WHERE DOES THIS INFORMATION COME FROM?

The Cochrane Collaboration is an independent global network of volunteers dedicated to summarizing research about healthcare. This information is taken from this Cochrane Review: Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003230.

A new search for studies and updated content was published in Issue 9, 2010 (no change to conclusions).

Review

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conference calendAr: EVENTS AROUND THE WORLD Compiled by Suzanne Snyder Conference listing locations are indicated on the map

For more listings and to have your event included in GAHM’s calendar of events in print and online, please visit www.gahmj.com.

May 15-18, 2012—2012 International Research Congress on Integrative Medicine and Health

July 18-21, 2012—The 39th Annual International Conference on Global Health

July 13-15, 2012—Functional Nutrition Course

Portland Marriott Downtown Waterfront,

Omni Shoreham Hotel, Washington, DC,

Portland, OR, United States

United States

This Congress will showcase original scientific research through 8 keynote and plenary sessions, oral and poster presentations, and innovative sessions. Areas of integrative medicine and health research presented and discussed at the Congress will include basic science, clinical trials, lifestyle and prevention, methodology, health services, cost effectiveness, and education. http://imconsortium-congress2012.org/

In the context of competing agendas, restricted budgets and increased calls for positive results, global health is more challenging than ever. How can global health stakeholders define their priorities and harness linkages to maximize outcomes? http://www.globalhealth.org/ Conference.html

In response to the epidemic of lifestylerelated chronic illnesses—now classified as lifestyle syndromes—The Institute for Functional Medicine developed the Functional Nutrition Course (FNC) to provide nutrition assessment and clinical management skills for primary care and nutrition professionals. http://www.functionalmedicine.org/conference.aspx?id=2598&cid=35&section=t97

Hilton New York, NY, United States

September 10-14, 2012—Applying Functional Medicine in Clinical Practice (AFMCP) Ritz Carlton, Marina Del Rey, CA, United States

The Institute for Functional Medicine’s AFMCP teaches healthcare practitioners to more effectively integrate science, research, and clinical insights to treat and prevent disease and maintain health. It is a well-orchestrated, comprehensive, patient-centered education program that helps you deepen your clinical understanding and practical application of the Functional Medicine Matrix Model. http:// www.functionalmedicine.org/conference. aspx?id=2565&cid=0&section=t77

May 31-June 3, 2012—The Institute for Functional Medicine’s Annual International Conference: A New Era in Preventing, Managing, and Reversing Cardiovascular and Metabolic Dysfunction The Westin Kierland Resort & Spa, Scottsdale, AZ, United States

This conference presents a more inclusive understanding of cardiometabolic disease initiation and progression, emphasizing recognition of the opportunities for early intervention and best outcomes, for improved risk assessment, and for individualized care. It will stimulate the critical thinking of clinicians from a variety of disciplines who seek a more systematic, effective, and integrated approach to preventing, managing, and reversing cardiovascular and metabolic dysfunction. http:// www.functionalmedicine.org/conference. aspx?id=2561&cid=35&section=t86

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April 16-18, 2012—The 9th Annual World Healthcare Congress Gaylord National Resort and Convention Center, Washington, DC, United States

The 9th Annual World Health Care Congress will gather more than 1600 global healthcare, pharmaceutical, and employer executives and leaders to engage in keynote presentations, debates, co- located summits, case studies, and emerging trend forums on the latest solutions to the issues facing the healthcare industry. http:// www.worldcongress.com/events/HR12000/ index.cfm?confCode=HR12000

April 30-May 4, 2012—Applying Functional Medicine in Clinical Practice (AFMCP) London Hilton Metropole, United Kingdom

The Institute for Functional Medicine, in conjunction with its UK Lead Sponsor, Nutri-Link Ltd, will bring its foundational course, AFMCP to London again. As in 2011, AFMCP London will adhere to the same rigorous standards as in the United States, with minor adjustments in topics such as laboratory profiles, tests, etc, to make it directly relevant to UK and EU practitioners. http://www.functionalmedicine.org/conference.aspx?id=2620&cid=35&section=t139

May 16-20, 2012—8th Metabolic Syndrome, Type II Diabetes, and Atherosclerosis Conference Palmeraie Golf Palace, Marrakech, Morocco

Since its creation, this meeting welcomes a wide number of participants from all over the world who are involved in the atherosclerosis and cardiovascular diseases fields. It covers every item from evolution to definition, from basic research to the latest therapeutic managements and prevention. http://www.msdacongress.com/ congress_2012/index.html#

Conference Calendar

IMPROVING HEALTHCARE OUTCOMES WORLDWIDE

September 21-22, 2012—5th European Congress for Integrative Medicine (ECIM) Firenze Fiera, Florence, Italy

The 5th EICM is on “The future of comprehensive patient care: promoting health and developing integrated and sustainable treatment for acute and chronic diseases.” This is the main European and international event for physicians, healthcare and wellness professionals, researchers, and sponsors about the efficacy of complementary/ unconventional medicines and practices and their integration with orthodox medicine. http://www.ecim-congress.org/ general-information.html

September 9-13, 2012—17th International Conference on Cancer Nursing (ICCN)

May 13-15, 2012—The Jerusalem International Conference on Integrative Medicine

Hilton Prague Hotel, Czech Republic

The 17th ICCN will offer the unique opportunity to meet with international cancer nursing leaders from all over the world in one place at one time. The ISNCC Scientific Planning Committee is pleased to announce that the theme of the 17th ICCN will be “Enhancing patient safety through quality cancer nursing practice.” http:// www.isncc.org/conference/17th_ICCN/

ICC Jerusalem International Convention Center, Jerusalem

The International Conference on Integrative Medicine brings together physicians and therapists from all over the world for a scientific meeting and dialog on the methods, techniques, and progress of integrative medicine. http://www.mediconvention.com/

June 7-9, 2012—6th Congress of Asian Society of Cardiovascular Imaging (ASCI) Centara Grand at Central World, Bangkok, Thailand

ASCI 2012 will focus on imaging innovation for cardiovascular practice, which will be presented in a plenary session and symposia by renowned international speakers to disseminate scientific knowledge and information and to exchange ideas and explore possible collaboration opportunities in academics and for professionals in the region. More than 100 abstracts from researchers in cardiac imaging field are expected to be presented in oral and poster presentations. http://www.asci2012.org/

May 9-11, 2012—Pan-African Orthopaedics Conference 2012

Centre Convencions International

Johannesburg Expo Centre, Nasrec,

This congress will offer outstanding plenary lectures complemented by focused symposia across 18 topics. There will be opportunities for participants to attend educational sessions as well as invitations to “meet the expert.” Posters will be displayed for review and “defense” in the Exhibition Hall, and all participants will be invited to assist in their evaluation. http://www.ecco-org.eu/eacr

The conference will offer delegates a 1-day review and update that will cover pressing clinical issues in the management of musculoskeletal trauma, sports injuries, degenerative diseases, and congenital disorders. http://www.africahealthexhibition.com/ Site-Root/Conference-Centre/ Conferences1/Complementary-Medicine/

Conference Calendar

Hotel Fort Canning, Singapore

Funding for health and medical facilities are vital to the health and well-being of the public. But most importantly, health and medical researchers and developers serve the task of advancing health care and medical science through the study and proper dissemination of information in order to improve the state of health care service of any country. That is the purpose of this conference. http://www.globalhc-conf.org/

August 13-15, 2012—22nd Annual Australian Cardiovascular Health and Rehabilitation Association (ACRA) Conference

July 7-10, 2012—22nd Biennial European Association for Cancer Research (EACR) Congress

South Africa

August 27-28, 2012—Annual Global Healthcare Conference (GHC 2012)

Brisbane Convention Centre, Queensland,

Barcelona, Spain

Australia

The theme of the meeting: Crisis. Recover. Rehabilitate. This conference encompasses the life-changing effect cardiovascular disease has, particularly the psychological, physiological, and often geographical journey that patients go through. This conference aims to recognize the challenges patients face in dealing with cardiovascular disease and the implications this has on services and clinicians caring for these patients. http://www.cdesign.com.au/acra2012/

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book review • Chinese Scalp Acupuncture for Cerebral Palsy • Fever-inducing Mistletoe Treatment for Lymphoma • Ultradilute Medicines for Viral Hepatitis • Worst Case Reported to the NAFKAM International

hinese Scalp Acupuncture, though written primarily as a clinic manual for practitioners of acupuncture, would be very interesting reading for neurologists, physical therapists, occupational therapists, veterans hospital administrators, and any other specialists who work in any capacity with patients suffering from brain injuries, neurological diseases, chronic debilitating pain, or neuropsychological disorders such as posttraumatic stress disorder (PTSD). The authors are passionate about acupuncture and wish not only to train as many practitioners as possible in its uses and techniques but also to increase both public and professional awareness of the power of scalp acupuncture in treating conditions that many medical practitioners consider to have few if any treatment options. Their enthusiasm for their work and caring for their patients is palpable throughout the book.

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In the first section, Drs Hao and Hao provide readers with information about the history, development, fundamental theory, and full details of the practice of scalp acupuncture. However, the meat of the book, where it shines brightest for this reader, is in the 45 case history presentations. Together, these provide the clinical details on a wide variety of patients, and each explains how the patient was treated from the first visit to his or her discharge from care. This material is compelling, and the treatment specifics could be applied in an acupuncture practice immediately. The book has two potential shortcomings. First, the authors’ presentation of only positive results in their case studies may be beyond some Western readers’ level of credulity. Still, they do give their general amelioration rates in the first part of the book, which may balance this to some extent. Second, Western researchers and some clinicians will likely call the case studies anecdotal. The material presented has not been subjected to randomized controlled trials, and there are no systematic standards for case report data collection. This evidence does not meet the conventional standards of proof that the techniques will work in a specific percentage of cases. Still, if one has a patient who cannot walk or talk, who has tried everything

Volume 1, Number 1 • March 2012 • www.gahmj.com

Western medicine currently has to offer, and who might gain some immediate improved functionality from a few acupuncture treatments, perhaps that is a good reason for larger studies on these techniques to be pursued. For example, the veterans who are currently suffering from PTSD and phantom limb pain might agree that these techniques are certainly worth a try in their cases, given that the technology is low-tech, inexpensive, and without side effects. All in all, this book is an important addition to the literature on acupuncture and compelling food for thought for the groups of possible readers listed above. About the Reviewer

Honora Lee Wolfe was founding director at the Boulder College of Massage Therapy in Colorado from 1976 to 1980. She studied Chinese therapeutic massage at the Shanghai College of Traditional Chinese Medicine from 1984 to 1986 and completed her acupuncture training in 1988. Ms Wolfe has taught at many national and regional acupuncture colleges and conferences in North America and Europe and is the author or coauthor of several books, including Managing Menopause Naturally with Chinese Medicine (1998), Points for Profit: The Essential Guide to Practice Success for Acupuncturists (2004), and The Successful Chinese Herbalist (2005). She most recently coauthored Western Physical Exam Skills for Practitioners of Asian Medicine (2009).

Book Review