Greenville Health System Preceedings vol 1. issue 1

May 2016 | Volume 1 | Issue 1

University of South Carolina School of Medicine Greenville, Greenville, SC

Cancer Institute: Making Lives Longer On the national stage, GHS’ Cancer Institute is making breakthroughs in cancer research and treatment—and making innovative, comprehensive care available close to home for upstate patients: • In 2014, 34 programs were lauded by the National Cancer Institute as a leader in community-site care delivery and research: GHS’ Cancer Institute is the only community-based program originating in S.C. to attain this distinction • GHS’ Institute for Translational Oncology Research includes a Phase I clinical research unit, a biorepository services platform, and proteomics and genomics capabilities: Thus far, it has enrolled 939 patients in 131 studies, including 15 first-in-human trials, with 12+ drugs moving to FDA approval and 40+ articles published • GHS’ Blood and Marrow Transplant Program, the first in S.C. to receive accreditation for autologous transplantation, provides both autologous and allogeneic transplants from matched related, unrelated and haplotype donor sources • GHS’ Center for Integrative Oncology and Survivorship, one of the first programs of its kind in the nation, offers evidence-based complementary therapies in addition to conventional cancer treatment and research studies For more information, please call (864) 455-7070.

ghs.org/cancer

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May 2016 Volume 1 | Issue 1

The peer-reviewed journal of Greenville Health System

Vision To transform healthcare through the publication of relevant, innovative, and multidisciplinary scholarship concerning advancements in clinical, academic, and translational research

Editor-in-Chief

Managing Editor

William D. Bolton, MD wbolton@ghs.org

Ally Hale, BA ahale@ghs.org

Associate Editors A. Michael Devane, MD Haytham H. Dimashkieh, MD Jeffrey W. Elder, MD

Timothy P. McHenry, MD Naveen N. Parti, MD Jeremy A. Warren, MD

Editorial Board Jagannadha R. Avasarla, MD, PhD Susan Bethel, MSN, RN, NE-BC Matthew D. Bitner, MD, MEd, FACEP Christopher Campen, PharmD, BCOP Joni Canter, MBA, ATC Christopher G. Carsten III, MD Anna L. Cass, MPH, PhD Catherine M. Chang, MD Patricia L. Cheek, MD Patrick J. Culumovic, MD Kacey Y. Eichelberger, MD J. Alexander Ewing, MS Sagar S. Gandhi, MD Steven B. Holsten Jr, MD, FACS William W. Hope, MD, FACS Sandip Jain, MD Esther M. Johnstone, MSN, DNPc, RN, CNOR Lindsay H. Jones, CRNA Laura H. Leduc, MD Bruce A. Lessey, MD, PhD Editorial Services: Jeanine Halva-Neubauer, MA Produced By: GHS Creative Services

Tina Lindsey, CCP Perfusion Ervin L. Lowther, MD Charles G. Marguet, MD Paul B. Miller, MD Ryan Miller, Sr Embryologist Phillip Moschella, MD, PhD M. Jason Palmer, MD Nirav T. Patil, MBBS, MPH Robert A. Saul, MD Antine E. Stenbit, MD, PhD Jeremy Stuart, PhD, MPH Thomas L. Wheeler, MD Yuliya Yurko, MD Christopher C. Wright, MD

Greenville Health System Proceedings (GHS Proceedings) is a peerreviewed medical journal that represents the top academic and clinical research activities happening at GHS and throughout the world.

GHS Proceedings is published twice a year (May and November) and is a primarily online journal constructed of original research, review articles, case reports, editorials, book reviews, and more. GHS Proceedings mission is to provide quality publications on healthcare innovation and delivery (university.

GHS.org/Proceedings).

All statements and opinions expressed in GHS Proceedings are those of the authors and not necessarily those of Greenville Health System, its boards, or any of its affiliates.

Guidelines for authors are available at university.ghs.org/ proceedings/authors.

Completed manuscripts may be submitted online (university.ghs.org/ proceedings/submit) or by mail (POSTMASTER: GHS Proceedings, Health Sciences Administration Building, 701 Grove Rd, Greenville, SC 29605) To receive upcoming issues by email, contact Ally Hale at AHale@ghs.org.

Copyright © 2016 Greenville Health System.

All rights reserved.

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GHS Women’s Hospital: Making Lives Better GHS Women’s Hospital is recognized for its outstanding patient-centered care, advancements in education and technology, and ongoing research to promote the health of women in the Upstate and beyond. It offers …

• • • • • • • • • • •

The largest OB/GYN service provider in the state with more than 7,100 deliveries in 2015 Baby-Friendly designation stemming from a World Health Organization initiative Family-centered Maternity Care designation Partnership as an affiliate member with MFMU (Maternal-Fetal Medicine Units) research network A novel drug for ovarian cancer developed in collaboration with MD Anderson Cancer Center and Clemson University; a therapeutic vaccine for ovarian cancer created here Research partnerships with UNC and Michigan State University studying implantation failure and infertility NIH-funded research in CenteringPregnancy (group prenatal care) and its decrease in preterm birth NIH-funded research on endometriosis and its effects on infertility and pregnancy loss The only pediatric and adolescent gynecology practice in the Upstate Ultrasound telemedicine serving Greenwood, Easley and Laurens The only facility in the Southeast offering laparoscopic creation of a neovagina to women born without a vagina

For more information, please call (864) 455-1600.

ghs.org/womens

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Children’s Hospital: Caring for the Whole Child At GHS Children’s Hospital, we offer more comprehensive “whole child” care than many of the country’s major medical centers. GHS Children’s Hospital is the Upstate’s only pediatric program recognized by the Children’s Hospital Association as a Center of Excellence. It offers …

• A Pediatric Residency Program in the nation’s top 5 in academic achievement • An endowed fellowship in Developmental-Behavioral Pediatrics and a federally funded inter- professional leadership training program in neurodevelopmental disabilities • Leading-edge autism research with an endowed research chair (an international leader in the field) • Centers of Excellence in clinical treatment and research in diabetes, pediatric neuro-oncology, esophagitis, asthma, cystic fibrosis, obesity, autism and more • The area’s largest group of pediatric specialists and an extensive network

of primary care pediatricians

Buddies Bear Together!

ghschildrens.org 16-0328

Table of Contents From the Editor

Case Studies

7 Changing the Culture by William D. Bolton

47 Yolk Sac Diameter in Multiple Gestations

by Chelsea Fox, Karenne Fru, and Bruce A. Lessey

Special Article 9 Launching a New Kind of Medical School— The University of South Carolina School of Medicine Greenville by Allyson L. Hale and William D. Bolton

Original Research 13 Contemporary Indications for Vascular Surgery Fail to Achieve Desired Patient-Centered Outcomes When Applied to Critical Limb Ischemia by Matthew F. Hudson, John J. McLeod, Kaitlyn M. Dunphy, William M. Bristow Jr, Gabrielle S. Genal, Yonge R. Jones, Brent L. Johnson, Peggy J. Wagner, David L. Cull, and Spence M. Taylor 22 Medicare Shared Savings Program Second-Year Results: Predictors of Success by Susan E. Sutherland, Brent M. Egan, Douglas O. Fleming, George A. Helmrich, Robert A. Davis, Valinda Rutledge, and Angelo Sinopoli 28 A Retrospective Data Analysis of Levetiracetam as Initial Monotherapy in Pediatric Epilepsy Patients by Addie S. Hunnicutt, Augusto Morales, Randall R. Blouin, Emily T. Foster, Anna L. Cass, and Mansi Patel 32 Discharge mEdication reconciliation by Pharmacists to improve Transitions following Hospitalization (DEPTH) by Rebecca T. Sawyer, Jessica M. Odom, Jasmine Jennings, Julianne Orr, and Anna L. Cass

Review Article 38 Modern Management of Abdominal Wall Hernias by Jeremy A. Warren, William S. Cobb IV, and Alfredo M. Carbonell II

49 Complex Perirectal Abscess Extending to the Preperitoneum and Space of Retzius by Caleb J. Mentzer, James R. Yon, Ray King, and Jeremy A. Warren 52 A Revertant of the Pathogenic Germline Mutation in BRCA1 as a Possible Cause of Breast Cancer Chemoresistance by Phillip Callihan, Anatole Ghazalpour, and W. Jeffery Edenfield 56 Fatal Clostridium difficile Enteritis as a Delayed Complication of Loop Ileostomy for Fulminant C difficile Colitis by Summer N. Rochester, Robert Farrar, R. Jared Sanders, Megan K. Straughan, and Meghann L. Kaiser 60 Outcomes of Treatment with Radiation Therapy for Residual Soft Tissue Sarcoma of the Hand Following “Unplanned” Initial Resection by Drew Ratner, S. John Millon, and Scott E. Porter 64 Diagnostic Management of Urinary Retention: Why Multiple Sclerosis Should Be Included as a Differential Diagnosis by Amanda Raines, Samantha C. Ward, and W. Patrick Springhart

Value Vignette and Editorial 68 Choosing High-Value Medications by Misty L. McDowell and Lauren D. Demosthenes 70 Mercy by Robert A. Saul

Miscellany 71 2016 Graduates of Greenville Health System and University of South Carolina School of Medicine Greenville 72 2015 Publications of Greenville Health System’s Medical and Scientific Staff

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GHS Proc. May 2016; 1 (1)

From the Editor

Changing the Culture

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n 2013, I became the director of Research for the Department of Surgery at Greenville Health System (GHS). With this role came the task of changing the research culture in the department.

In an attempt to enhance our research efforts and truly change the culture, I decided to start at the grassroots with the more pliable residents. A team of us subsequently developed a resident research program that included the requirement for all interns to publish a case report. Although the residents followed through on their part, we soon discovered that publication of these reports wasn’t easy, as many journals either no longer accepted case reports or required payment for publication.

Following this realization, a small group from the department discussed some possible solutions, which culminated in the idea of developing our own journal of surgical case reports. Over the next several weeks, however, this concept steadily grew in scale as it advanced up the chain of command. Within 2 months, the idea for a specialized, surgical case report journal had been transformed into the concept of an institution-wide, peer-reviewed academic journal.

An ad hoc committee, chaired by Dr Spence Taylor, chief academic officer at GHS, was formed to determine the feasibility of starting a scholarly journal at GHS. After concluding that the concept was consistent with GHS’ overall mission and that a sufficient pipeline of academic content existed, the committee named the journal GHS Proceedings and then defined its mission, vision, and goals. This committee also determined that GHS Proceedings would be a primarily online, peer-reviewed journal consisting of original research, review articles, case reports, and a miscellany category. In its final act, the ad hoc committee elected me, Dr William Bolton, as editor-in-chief and Ally Hale as managing editor.

With the desire for this journal to truly represent the abundant “proceedings” happening at GHS, as well as with our academic partners, we

started a system-wide search for associate editors, from which 6 were established: A. Michael Devane, MD; Haytham H. Dimashkieh, MD; Jeffrey W. Elder, MD; Timothy P. McHenry, MD; Naveen N. Parti, MD; and Jeremy A. Warren, MD. Next we distributed our first “call for manuscripts” and began recruiting peer reviewers from GHS, as well as from outside institutions. The number of manuscript submissions we received for this inaugural issue reaffirmed the ad hoc committee’s findings regarding the amount of research happening at GHS and the potential pipeline of content for future issues.

Throughout this journey, several people have asked the question, “Why have an academic journal?” For me, the answer is simple—we want others to see GHS how we see GHS. When we look at our academic health center, we see a world-class institution that’s leading the medical community in many areas. So for me, the question isn’t why have a scholarly journal, the real question is, “How do we show people throughout our institution, as well as those outside, the care we’re providing and the research we’re performing that makes us a first-class medical center?”

Acknowledgments Thank you to the ad hoc committee for your time, effort, and support of GHS Proceedings. Members of this committee were David L. Cull, MD; Cortney O. Easterling, BA; W. Larry Gluck, MD; Bruce H. Gray, DO; Allyson L. Hale, BA; Eli Hestermann, PhD; Desmond P. Kelly, MD; Bruce A. Lessey, MD, PhD; Windsor W. Sherrill, PhD; Spence M. Taylor, MD; Brenda Thames, EdD; Peter L. Tilkemeier, MD; Thomas L. Wheeler II, MD; and Cindy Youssef, MA.

We believe GHS Proceedings can accomplish many things. First, it can educate our own researchers and practitioners, as well as advance the academic careers of our faculty. Second, it can assist our young trainees in the publication of their works by teaching them how to do research and then providing them with an avenue for early success.

Last, it can help cultivate a better sense of family by providing a connection back to GHS when our trainees graduate and embark on the next phase in their medical careers. It is our belief that GHS Proceedings can accomplish all of these things and more as it seeks to transform health care through publication of the relevant, innovative, and multidisciplinary scholarship being conducted by our students, physicians, clinicians, allied health professionals, population health scientists, and alumni.

William D. Bolton, MD Editor-in-Chief

GHS Proc. May 2016; 1 (1): 7

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Congratulations to Our Charter Class Class of 2016 Residency Placements Greenville Health System/ University of South Carolina Palmetto Health Richland Medical College of Georgia University of Alabama Medical Center Naval Medical Center San Diego University of Arizona College of Medicine Naval Medical Center Portsmouth Beth Israel Deaconess Medical Center Vanderbilt University Medical Center University of Virginia Spartanburg Regional Healthcare Carolinas Medical Center Bayfront Medical Center Medical College of Wisconsin Affiliated Hospitals Tripler Army Medical Center

greenvillemed.sc.edu

Wright State University/88th Medical Group, Wright Patterson Air Force Base Utah Healthcare Institute Albany Medical Center Self Regional Healthcare National Capital Consortium-Walter Reed National Military Medical Center University of Louisville School of Medicine Louisiana State University School of Medicine Anderson Area Medical Center University of Florida Health/Sacred Heart Hospital Wake Forest Baptist Medical Center Georgetown University Hospital University of Wisconsin Hospital and Clinics University of South Florida Morsani College of Medicine Medical University of South Carolina

Special Article

Launching a New Kind of Medical School—The University of South Carolina School of Medicine Greenville Allyson L. Hale, BA, and William D. Bolton, MD

T

he United States (US) population is increasing by approximately 25 million people each decade. However, between 1980 and 2002, no new medical schools were opened following the 1980 Graduate Medical Education National Advisory Committee (GMENAC) report that warned of an “impending doctor glut.”1 While the cautionary account was arguably justified as the number of US medical schools had doubled between 1965 and 1979, our nation failed to anticipate that the baby boom generation would require more complex care and live longer, while at the same time making up a substantial demographic of the physician population. Because 25% of actively practicing physicians are currently over the age of 65 years, approximately one-third of the nation’s physicians are anticipated to retire during the next decade, resulting in an estimated shortage of more than 90 000 physicians by 2020 and 130 000 physicians by 2025.2

In response to this looming crisis, in 2006 the Association of American Medical Colleges (AAMC) called for a 30% increase in medical school enrollment.3 Until recently, the state of South Carolina (SC) had 2 medical schools: the University of South Carolina School of Medicine (USCSOM), located in Columbia, SC, and the Medical University of South Carolina (MUSC), located in Charleston, SC. Combined, these schools receive more than 7500 applications annually, with only 275 students matriculating.4 Starting in 1991, Greenville Health System (GHS), a large, not-for-profit academic health center located approximately 90 miles northwest of Columbia, established a partnership with USCSOM to become a regional, clinical teaching site for roughly 15%−30% of the USCSOM medical students, providing the entire M3 and M4 years for those students who relocated to Greenville following their M2 year. GHS currently encompasses 7 regional medical facilities, 1660 beds, 1200

GHS Proc. May 2016; 1 (1): 9-12

healthcare providers, over 200 residents and fellows, a Level I Trauma Center, a Level III neonatal Intensive Care Unit (ICU), and is the largest cardiovascular, obstetrical, and specialty children’s service provider in the region.

In 2009, Dr Jerry Youkey, executive vice president of Medical and Academic Affairs at GHS, named Dr Spence Taylor, chair of the Department of Surgery at that time, the new assistant dean for Academic Affairs. Aware of the AAMC’s recent plea for an increase in medical school enrollment, Dr Taylor unofficially began looking into opportunities for GHS to expand its undergraduate medical education. Following several conversations with knowledgeable advisors, Dr Taylor presented the concept of expansion of the Greenville site to a second full M1-M4 separately accredited USC medical school campus to GHS President Michael Riordan and University of South Carolina (USC) President Harris Pastides. With both parties interested, a feasibility committee was formed and over a period of 3 months it affirmed 2 things: 1) GHS had the capacity to support a 4-year medical school campus and 2) SC had a qualified medical school applicant pool large enough to support an additional campus. During that time, GHS also worked with the Greenville Chamber of Commerce to meet with local civic and business leaders to obtain support for this endeavor. Dr Taylor and Dr Andrew Sorensen, past-president of USC, subsequently chaired a planning committee and presented to the USC Board of Trustees a detailed business plan for the new medical school. In June 2010, both the GHS and USC Boards of Trustees approved expansion of the Greenville, SC campus to establish USCSOM Greenville as a health care system-based medical school complementary to the university-based USCSOM Columbia.

Following board approval, an Institutional SelfStudy Task Force was formed to address the Liaison Committee on Medical Education (LCME)

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application process. This committee was chaired

by Dr Taylor and involved invaluable involvement from Dr Youkey, Dr Sorensen, external consultants, and more than 100 faculty and administrators from GHS and USC. For approximately 10 months, this committee labored to create USCSOM Greenville, which was thoroughly described within the 1500-page LCME application.

Although significant challenges and impediments had to be overcome along the way, in October 2011

the LCME granted preliminary accreditation and in August 2012 USCSOM Greenville matriculated its inaugural class.5 During this time, the Patient Protection and Affordable Care Act (ACA) was signed into law and called for significant health care reform, emphasizing increased access to value-based care characterized by efficiency and high quality. In contradistinction to the traditional practice of medicine

Figure 1 Breakdown of residencies matched—for inaugural 2016 class.

Class of 2016 Match Results (N = 49) Urology, 1 General Surgery, 3

Anesthesiology, 3

Psychiatry, 2

Emergency Medicine, 4

Pediatrics, 9

Family Medicine, 8

Pathology, 2

Orthopaedic Surgery, 2 Internal Medicine, 7 OB/GYN, 7 Neurological Surgery, 1

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GHS Proc. May 2016; 1 (1): 9-12

NEW KIND OF MEDICAL SCHOOL involving individual autonomy, doctor-centered illness care, and disregard of cost, the ACA has progressively required health systems to take responsibility for the overall health of their patients and the associated cost. The practice of medicine in the 21st century will be increasingly patient-centered, requiring a team-based, multidisciplinary approach. The “Do No Harm” mantra of the past has officially been replaced with “Do Good.”

Currently, the state of SC ranks 38th among our 50 states in the number of physicians per 100 000 population and 40th in the number of primary care physicians.6 While the University of South Carolina School of Medicine Greenville (USCSOM Greenville) was originally focused on increasing the number of physicians in SC, both partners (GHS and USC) quickly recognized the rare opportunity in front of them: educate and train physicians better prepared to practice and lead in the 21st century.

With the population health focus of value-based care and the growing physician shortage in mind, the leadership and faculty at USCSOM Greenville constructed an integrated curriculum based on a variety of modern, yet proven, medical education approaches used throughout the US and Canada.

For instance, at USCSOM Greenville, each week medical students (M1-M2) are given a clinical “case of the week” that intersects with the scheduled biomedical sciences education topic. Several weeks of the M1 year are spent studying cancer, but 1 complete week is dedicated to breast cancer due to its prevalence. Subsequent to the learning modules on relevant basic science material such as molecular biology, cellular biology, and genetics, the students are asked to take what they learned and apply it to the case of the week—a patient with breast cancer. Students then meet with several breast cancer survivors from the community, during which the survivors openly share how they received their diagnosis, what happened to their self-image when they lost their hair, what happened to their libido, whether or not they got genetic counseling, as well as other social aspects of their disease. The goal and design of this highly integrated, case-based curriculum is to graduate physicians who better understand interdisciplinary, systems-based health care from the perspective of the patient.

Although other medical schools have adopted integrated curricula with a simulation center and a “flipped classroom” approach to learning—a concept in which the actual classroom time is used for discussion, question and answer (Q&A), and GHS Proc. May 2016; 1 (1): 9-12

group learning, while the content/lecture material is delivered prior to class—there are 2 aspects that make USCSOM Greenville unique. The first involves EMT training. While some medical programs send their students on EMT calls and/ or have short-term training sessions, USCSOM Greenville was the first US medical school to implement full EMT certification during the first few weeks of medical school. In addition, USCSOM Greenville students are expected to continue volunteering at least 1 shift (12 hours) each month throughout their M1 and M2 years. The purposes of this EMT training are three-fold: 1) for the students to learn that people get sick and injured where they live, work, and play—that illness and injuries don’t happen right outside the Emergency Department door, but rather within the social context of the patient’s individual living environment; 2) for the students to gain better insight into the diversity and health needs of their overall community; and 3) for the early clinical exposure to help students better understand why they need to learn what they’re being taught. This early patient exposure in real-life settings is enhanced by advanced clinical training in the simulation center, which serves as a “practice field” for clinical education until the students begin their true clinical M3-M4 years in the hospital. Through these efforts, it appears that USCSOM Greenville students are more clinically advanced and better prepared to participate in and learn from their M3-M4 clinical care teams. The second aspect that makes USCSOM Greenville different is its location directly on the GHS tertiary care Greenville Memorial Medical Campus. This results in physician faculty being able to walk back and forth from the hospital to the school, a convenient feature that has facilitated PhD/MD team teaching and resulted in remarkably high educational involvement by clinician faculty.

Acknowledgments The authors wish to thank Kindal Dankovich, USCSOM Greenville class of 2016; Spence M. Taylor, MD, USCSOM Greenville Senior Associate Dean for Academic Affairs and Diversity; Jerry R. Youkey, MD, USCSOM Greenville Founding Dean; and Ben Haskew, President/CEO of the Greenville Chamber of Commerce for their time, stories, and support of this article.

Correspondence Address to: William Bolton, MD Greenville Health System, Medical Oncology 890 W Faris Rd #320 Greenville, SC 29605 (wbolton@ghs.org)

LCME preliminary accreditation of USCSOM Greenville in 2011 officially progressed to full accreditation in February 2016, approximately 3 months prior to the graduation of the inaugural class. Since then, all 49 students have “matched” into a variety of residency programs throughout the US, including Pediatrics (18%), Family Medicine (16%), Internal Medicine (14%), Obstetrics and Gynecology (14%) and Surgery—General, Orthopaedic, or Neurological (12%) (Fig. 1). Overall, 43% will be staying in the state of SC, with 22% remaining in Greenville at GHS. Although demand remains, approximately 100 additional physicians prepared to practice medicine in the 21st century will eventually graduate annually.

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References 1. U.S. Dept. of Health and Human Services Health Resources Administration: Report of the graduate medical education national advisory committee. Vol. 1: summary report. DHHS Publication No. (HRA) 81-651, Washington, D.C. U.S. Government Printing Office, 1980.

2. Association of American Medical Colleges (AAMC) Center for Workforce Studies, June 2010 Analysis.

Physician Shortages to Worsen Without Increases in Residency Training. Accessed on March 4, 2016. https://www.aamc.org/download/150584/data/physician_shortages_factsheet.pdf 3. AAMC Calls for 30 Percent Increase in Medical School Enrollment. Washington, D.C., June 19, 2006.

Accessed on March 1, 2016. https://www.aamc.org/ newsroom/newsreleases/2006/82904/060619.html

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4. 2015 Association of American Medical Colleges. U.S. Medical School Applications and Matriculations by School, State of Legal Residence, and Sex, 2015-2016.

Accessed on March 1, 2016. https://www.aamc.org/ download/321442/data/factstablea1.pdf 5. Taylor SM. Vascular Surgery, self-awareness, and the University of South Carolina School of Medicine Greenville. J Vasc Surg. 2013;58:1106-14.

6. 2013 State Physician Workforce Data Book. South Carolina Physician Workforce Profile. Association of American Medical Colleges (AMMC) Center for Workforce Studies. Accessed on March 1, 2016. https://www.aamc.org/download/152174/data/south_ carolina.pdf

GHS Proc. May 2016; 1 (1): 9-12

Original Research

Contemporary Indications for Vascular Surgery Fail to Achieve Desired Patient-Centered Outcomes When Applied to Critical Limb Ischemia Matthew F. Hudson, PhD; John J. McLeod; Kaitlyn M. Dunphy, BS; William M. Bristow Jr, BS; Gabrielle S. Genal, BS; Yonge R. Jones, MHA; Brent L. Johnson, PhD; Peggy J. Wagner, PhD; David L. Cull, MD; and Spence M. Taylor, MD From the Greenville Health System Clinical University, Greenville, SC (M.F.H., J.J.M., K.M.D., W.M.B., G.S.G., Y.R.J., B.L.J., D.L.C., S.M.T.); and University of South Carolina School of Medicine Greenville, Greenville, SC (M.F.H., P.J.W., D.L.C., S.M.T.)

Abstract Background: The purpose of this analysis is to examine desired patient outcomes after vascular surgery and to measure the achievement of these outcomes when applied to a large cohort of patients undergoing intervention for critical limb ischemia (CLI).

Methods: To understand patient expectations after vascular intervention, 102 consecutive patients undergoing elective operations were prospectively administered a standardized preoperative questionnaire regarding the characteristics of a successful outcome. The following were identified: 1) maintenance of living independence, 2) maintenance of ambulatory status, 3) control/relief of pain, 4) no additional/nonroutine physician visits, and 5) survival for 1 year. These outcomes were then applied retrospectively to a cohort of 954 consecutive patients with CLI (37% rest pain, 37% ischemic ulceration, 26% gangrene) undergoing planned intervention (57% open, 41% endo, 2% both) to analyze patient-centered success.

Results: While 12-month overall success for maintenance of independence was 89% (n = 849), maintenance of ambulation 84% (n = 802), control/relief of pain 48% (n = 461), no additional physician visits 36% (n = 340), and 1-year survival 79% (n = 755), overall patient-entered success (achievement of all 5 patient-centered success outcomes) was accomplished in only 23% (n = 218) of patients. Of 20 variables examined, end-stage renal disease (OR [95%CI] 2.21[1.26-3.88]; P = .006) and impaired ambulatory status preoperatively (OR [95%CI] 1.76 [1.12-2.79]; P = .015) were independent predictors of failure. The probability of experiencing patient-centered failure was 93% in patients with both end-stage renal disease and impaired ambulatory status preoperatively.

Conclusions: If patients alone are allowed to define their outcomes after vascular intervention, success is infrequent. These data suggest that successful overall outcome may best be achieved when physicians and patients mutually target specific attainable goals and strive to achieve them.

W

hen planning intervention for their patients, surgeons are trained to achieve the best outcome possible.

Typically, that outcome is defined by evidence accumulated through medical research from surgical investigators who often focus on postoperGHS Proc. May 2016; 1 (1): 13-21

ative goals they deem as important. In the case of vascular disease, surgeons define treatment success referencing parameters such as survival, intervention patency rate, 30-day complication rate, and freedom from comorbid vascular event.

Though important, these definitions of success 13

Figure 1 The questionnaire utilized when determining patient-centered outcomes for 102 patients undergoing elective vascular surgery.

RESEARCH STAFF: Check the line below if patient refused to participate and save this questionnaire as if patient completed it Patient Refused:_________ RESEARCH STAFF: ASK THE QUESTIONS BELOW AND WRITE THE RESPONSES IN THE SPACES BY OR UNDER THE QUESTIONS: (1)

What is the reason you are having surgery?

(2)

Is there anything that helped you decide surgery was the best choice for you?

(3)

What will surgery allow you to do that you cannot do now?

(4)

What do you consider a successful surgery outcome?

(5)

Is there anything you will need to do to help you get better after surgery?

(6)

How long do you think it will take you to recover after your surgery?

(7a) Do you think the surgery may keep you from doing things you want?

[if “yes” to above question]

(7b) What are the things you think surgery will keep you from doing?

(8)

How many times do you think you will have to come back to the doctor for “follow up”?

(9)

We listed some things that some people hope surgery improves. I’ll put a check by any items you hope your surgery improves. I can check as many or as few as you like.

Pain Relief_________ Daily functioning (washing, shopping)_________ Work attendance_________ Avoiding repeat doctor visits for the same problem_________ Hobbies_________ Mobility_________ Anything not listed, but important to you? [IF YES, RESEARCH STAFF WRITE IN “OTHER”]_________

(10) Thinking about what you checked above. Help me order them by how important they are to you; I’ll number the item you think most important with a “1”, the item you think is second most important with a “2”, the item you think is third most important with a “3”. I’ll continue numbering until rank all items you checked.

Pain Relief_________ Improve daily functioning(washing, shopping)_________ Work attendance_________ Avoiding repeat doctor visits for the same problem_________ Hobbies_________ Mobility_________ “Other” item patient identified above_________ (11) What is your gender Male _________ Female_________ (12) How old were you on your last birthday Age_________ (13) Are you Hispanic, Latino, or Spanish Origin?

No, not Hispanic, Latino or Spanish Origin_________ Yes, Mexican, Mexican American, Chicano_________ Yes, Puerto Rican_________ Yes, Cuban_________ Yes, another Hispanic Latino or Spanish origin_________ (14) What is your Race? Check All that Apply White_________ Black (African American)_________ American Indian or Alaskan Native_________ Asian_________ RESEARCH STAFF: READ THE STATEMENT BELOW TO THE PATIENT: THERE ARE NO MORE QUESTIONS FOR YOU TO ANSWER! THANK YOU FOR SHARING WITH US! For Research Staff Note the surgery patient is scheduled to undergo: Carotid Endarterectomy_________ Endovascular Surgery_________ Aortic Aneurysm Repair_________ Aneurysm: Open_________ Closed_________ Revascularization of Lower Extremities_________ Other_________

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are primarily defined by the medical team. While assumed to be the same parameters valued by the patient, in reality, there is relatively little information on the comparative effectiveness of planned intervention for patients undergoing surgical intervention. This is particularly true of critical limb ischemia (CLI), a chronic, debilitating disease, often occurring in older individuals with multiple medical comorbidities where the objective is more often palliative than curative. The purpose of this study is to investigate outcomes vascular surgery patients deem important and determine the degree of success surgery achieves when measuring these outcomes against a cohort of patients undergoing intervention for CLI.

Methods Our study is comprised of 2 components: 1) a prospective cohort solicitation of patient-perceived outcome priorities, and 2) a retrospective review and assessment of outcome success using the prospectively identified outcome criteria.

Prospective Cohort Participants We solicited 108 consecutive adults (≥18 years of age) being scheduled for elective vascular surgery by a vascular surgeon within Greenville Health System (GHS), whom the research nurses observed to have the physical and emotional capacity for participation.

Instruments Study investigators (M.F.H., S.M.T., and P.J.W.) developed a standardized preoperative questionnaire (Fig. 1) that posed open-ended questions regarding patients’ perceived need for vascular intervention and qualitatively inquired about their perception of a successful outcome. The questionnaire asked patients to rank 6 health improvement targets: pain relief, daily functioning (eg, washing, shopping), work attendance, avoiding repeat doctor visits for the same problem, hobbies, and mobility. The questionnaire also provided an opportunity for patients to identify improvement targets not listed (eg, “Anything not listed, but important to you?”).

Procedure Subsequent to both physician consultation (ie, standard clinical practice) and surgery scheduling, a research nurse solicited patient participation in the research project by first introducing the project and acknowledging, “Surgery is important care for many people, but we think that each person has different hopes and goals for surgery.

GHS Proc. May 2016; 1 (1): 13-21

SURGERY OVERLOOKS PATIENT-CENTERED OUTCOMES We want to ask you questions that help us learn about the care outcomes that are most important to you.” The research nurse facilitated informed consent and mitigated coercion by informing the patient of the right to decline participation without compromising care. Research nurses posed the respondents’ questions orally and immediately noted/marked the responses accordingly on the questionnaire while the patient was present in the outpatient vascular clinic.

Retrospective Data Review The Vascular Surgery Database was established in 1992, registering all cases performed on the vascular surgery teaching service. Since 1998, a subset of patients with lower extremity peripheral arterial disease (PAD) has been closely scrutinized and actively followed under the aegis of the GHS Institutional Review Committee. Each lower extremity vascular procedure is entered on an Excel spreadsheet (Microsoft Corp., Redmond, Wash.). Preoperative demographics are entered into the database at presentation. Functional information, to include ambulatory and independent living status, is also included. Information is updated with each follow-up office visit. Routine follow-up for infrainguinal bypass grafts includes noninvasive duplex scan derived graft flow velocities obtained at 1 month, every 3 months for the first 18 months, and then every 6 months thereafter. Interventions for failing bypass grafts (intrinsic or juxta anastomotic stenoses with a graft flow velocity >300 cm per second and distal velocities <45 cm per second) are performed to restore normal hemodynamics. Patients receiving bypass for aortoiliac occlusive disease are followed with a patient visit and an ankle-brachial index (ABI) study at 1 month and then at 6-month intervals.

Patients receiving an endovascular procedure are assessed with ABIs within 1 month of intervention and followed with repeat ABIs every 6 months.

To complement information obtained at each follow-up visit, the database is scrutinized each summer by independent research workers looking for missing data points or missing patients. Sources used to attain follow-up include the hospital computerized Lifetime Clinical Record, the computerized radiology Picture Archiving Communication System (PACS), and the online obituary services of all statewide newspapers.

For the purposes of the study, we adapted the findings of the patient-derived expected outcomes survey (see right) to define 5 separate 12-month patient-centered outcomes. Next, the team retrospectively applied these 5 outcomes to a cohort of GHS Proc. May 2016; 1 (1): 13-21

954 consecutive patients from our Vascular Surgery Database undergoing intervention for CLI using standard indications from January 1998 through December 2007. To be included, a patient must have had complete follow-up (to death), or at least 9 months of follow-up with a vascular surgeon and known to be alive (some interaction with the health system) for at least 12 months following the index procedure date. For patients with both limbs enrolled in the database, we included only the first limb, per date of index procedure.

The evaluation tool used to retrospectively review the lower extremity database is shown in Table 1.

Based on the overall findings of the questionnaire, the study team defined patient-centered success as achieving each of the following: 1) mainte-

Table 1 Assessment tool used for retrospective analysis of 954 patients undergoing intervention for critical limb ischemia to determine successful patientcentered outcomes.

Daily Activity/Independence 0. Independent 1. Nursing home 2. Independent then nursing home 3. Nursing home then independent Mobility/Ambulation Status 1. Ambulatory 2. Homebound ambulatory 3. Ambulatory transfer 4. Immobile Pain Relief 0. No pain after 3 mos of date of initial procedure (DOIP) 1. Constant pain after DOIP 2. No pain w/in 3 mos of DOIP but then some after 3 mos Nonroutine Doctor Visits 0. Routine surveillance or less often 1. More often than routine surveillance 2. Death during hospital stay of DOIP Death within 1 Year of Procedure 0. Death 1. Survival

15

Table 2 Patient demographics and planned surgeries for 102 patients surveyed for characteristics they consider to be a successful postprocedure outcome.

Male

Female

Total

61

41

102

64 ± 10

66 ± 11

57 (93.4)

34 (82.9)

91

4 (6.6)

7 (17.1)

11

Carotid endarterectomy

14 (23.0)

14 (34.1)

28

Endovascular surgery

23 (37.7)

14 (34.1)

37

Aortic aneurysm—open repair

1 (1.6)

2 (4.9)

3

Aortic aneurysm—EVAR

7 (11.5)

1 (2.4)

8

Lower extremity revascularization

11 (18.0)

9 (22.0)

20

Other

5 (8.2)

1 (2.4)

6

N Age, mean ± SD Race, no. (%) Caucasian African American Procedure, no. (%)

EVAR, endovascular aortic repair

Figure 2 A graphic depiction (in percentages) with 95% confidence intervals of outcomes in 102 surveyed patients believed to be most important when undergoing intervention for critical limb ischemia. In two instances, 2 patients listed 2 outcomes as equally most important.

Patient-Affirmed Expectations of Vascular Surgery (N=102 Respondents)

40 31.4

16.7 8.8

er th O

y ili t ob M

bi ob H

nd an ce Av oi d M Re D p Vi ea si t t s

ng W or

ct Fu n

kA tte

io

ni

li e Re in il y Da

1.0

es

1.0

0

Pa

16

23.5

21.6

20

f

Response Rate (95% Confidence Interval)

60

nance of living independence, 2) maintenance of ambulatory status, 3) control/relief of pain, 4) no additional/nonroutine physician visits, and 5) survival for 1 year. For the purpose of the study, we defined “maintenance of living status” and “maintenance of ambulatory status” as maintenance or improvement in status 1 year following intervention. We defined “failure” as deterioration in status (eg, “independent” to “nursing home” or “ambulatory” to “homebound ambulatory”). For “control/relief of pain,” we defined success as no pain requiring narcotics 3 months following the initial procedure. For “no additional/nonroutine physician visits,” we defined success as needing no more than routine surveillance (routine surveillance was defined as an outpatient physician visit 1 week posthospital discharge, 1 visit 4-6 weeks postdischarge, and every 3 months for the first 18 months). In patients with tissue loss, wound center visits for wound management were scheduled as needed after intervention and were considered routine follow-up for the purpose of the study.

For “survival,” success was defined as survival for 12 months postprocedure. For the purpose of the analysis, we considered an overall patient-centered outcomes success as achievement of success for all 5 outcome parameters listed in Table 1. Using the above criteria, follow-up was completed (within 9 months) on all 954 patients studied.

Next, we employed bivariate analysis to predict patient-centered success/failure after intervention.

Variables analyzed included age, sex, ethnicity, history of cigarette smoking, presence of diabetes, presence of end-stage renal disease, presence of coronary artery disease (moderate to high risk as scored by the Eagle criteria),1 presence of hypertension, presence of hyperlipidemia, obesity (BMI >30), presence of chronic obstructive pulmonary disease, history of cerebrovascular accident, history of associated cerebrovascular disease, history of dementia, history of prior vascular surgery, independent living status, preoperative ambulatory status, level of atherosclerotic disease (aortoiliac versus infrainguinal), presentation (ischemic ulcer versus gangrene), and type of intervention (endovascular or open bypass). Our database characterizes preoperative ambulatory status as ambulatory (independent ambulation out of house), ambulatory/homebound (ambulatory in home only), nonambulatory/transfer (eg, uses legs to transfer from bed to chair or from the chair to the commode), or nonambulatory/bedridden. In each case, ambulatory status is determined by physical conditions thought to be independent of their vascular condition. Thus, “ambulatory status” is defined as GHS Proc. May 2016; 1 (1): 13-21

SURGERY OVERLOOKS PATIENT-CENTERED OUTCOMES the patient’s functional status immediately before the development of vascular symptoms. With this definition, ambulatory impairment is typically a function of other medical comorbidities such as arthritis, sequelae of cerebrovascular and cardiovascular disease, or advanced age. If the impairment was indeed a function of the patient’s vascular disease, it was assumed that the functional status would change (improve) accordingly after revascularization. Further, for the purpose of this study, the study team defined “change in ambulatory status” as a permanent postoperative change in ambulatory classification, despite full recovery from surgery. Our analysis grouped patients classified as ambulatory/homebound or nonambulatory/ transfer only together, and termed them “impaired ambulatory status.” Nonambulatory/bedridden patients are typically not offered intervention in our practice and were not included in the analysis.

Last, we entered comorbidities and variables determined significant in bivariate analysis into a multivariate model using logistic regression analysis predicting success/failure. We calculated odds ratios (OR) and 95% confidence intervals. After determining these independent predictors of success/ failure, we calculated probability of failure (%) for each predictor and for combinations of predictors.

Statistical Analysis Chi-square tests were used for bivariate analyses of success/failure and categorical patient characteristics. We employed Fisher’s exact tests when fewer than 5 observations existed in any subgroup. We employed student’s t-test to compare mean age of successes and failures. We employed logistic regression to model the likelihood of a failed outcome given specific patient characteristics. Odds ratios and 95% confidence intervals were estimated. All variables that were significant in the bivariate analyses were included in the full model. Probability of failure (%) was determined using logistic regression. Last, we employed Kaplan Meier life table analysis to determine limb salvage over time. The data analysis was generated using SAS software, Version 9.1.3 of the SAS System (SAS Inc., Cary, NC).

Results Patient demographics and procedure type of the prospective cohort are depicted in Table 2. When asked, 66% of the patients reported that the reason for surgery was because the surgeon advised it. Of the health improvement targets that patients were asked to rank as important, 82% selected “avoid repeat doctor visits,” 65% chose “mainteGHS Proc. May 2016; 1 (1): 13-21

nance of daily functioning,” 61% selected “maintenance of mobility,” 58% selected “pain relief,” and 54% selected “maintaining current hobbies.”

Patient responses rarely varied according to the vascular condition at presentation (eg, patients needing carotid intervention answered similarly to patients needing lower extremity PAD). When asked to rank these targets as “most important” to “least important,” 4 targets emerged as being most important (Fig. 2): 1) pain relief, 2) maintenance of mobility, 3) avoid repeat doctor visits, and 4) maintenance of daily functioning. Based on these findings, we selected our 5 parameters of patient-centered success (maintenance of living independence, maintenance of ambulatory status, control/relief of pain, no additional/nonroutine physician visits, and survival for 1 year).

Application of outcome measures for patient-centered success was completed for all 954 patients.

We have previously reported, in detail, traditional outcomes of interventional patency, limb salvage, maintenance of ambulatory status, and maintenance of independent living status after intervention for lower extremity PAD for the GHS Vascular Database.2,3 For this study cohort, 243 of the 954 patients (25.5%) eventually underwent limb amputation (187 of these amputations occurred within 12 months of index procedure). Using life-table analysis, limb salvage at 24 months was 75 ± 1% (468 remaining at risk). Thirty-day/in-hospital mortality occurred in 41 patients (4.3%).

Table 3 depicts the proportion of patients achieving successful patient-centered outcomes utilizing the composite definition. While success for the individual patient-centered outcome components ranged from 35.6% (no additional or nonroutine

Table 3 The proportion of patients achieving successful patient-centered outcomes for each individual parameter and overall success (success for all 5 outcomes) in 954 patients undergoing intervention for critical limb ischemia.

Success N (%)

Failure N (%)

Independent living

849 (89.0)

105 (11.0)

Mobility/Ambulation

802 (84.1)

152 (15.9)

Postoperative pain

461 (48.3)

493 (51.7)

No additional (nonroutine) MD visits

340 (35.6)

614 (64.4)

Survival for 1 year

755 (79.1)

199 (20.9)

Overall (success for all 5 outcomes)

218 (22.9)

736 (77.1)

Outcome

17

Characteristic, no. (%)

Failure N = 736

Success N = 218

Type of intervention

.216

Open

407 (55.3)

135 (61.9)

Endovascular

313 (42.5)

80 (36.7)

Both Age, mean ± SD

16 (2.2)

3 (1.4)

67.4 ± 12.0

68.2 ± 10.7

Sex Male

127 (58.3)

Caucasian

536 (72.8)

171 (78.4)

Other

200 (27.2)

47 (21.6)

508 (69.0)

148 (67.9)

434 (59.0)

105 (48.2)

Race

.097

Smoker

.752

Diabetes Yes

.005

End-stage renal disease Yes

<.001 133 (18.1)

16 (7.3)

438 (59.5)

117 (53.7)

610 (82.9)

166 (76.1)

Coronary artery disease Yes

.125

Hypertension Yes

.025

Hyperlipidemia Yes

.908 304 (41.3)

91 (41.7)

118 (16.0)

29 (13.3)

Obese (BMI >30) Yes

.327

Chronic obstructive pulmonary disease (COPD) Yes

.888 162 (22.0)

47 (21.6)

153 (20.8)

33 (15.1)

Cerebral vascular accident Yes

.064

Cerebral vascular disease Yes

.532 191 (26.0)

52 (23.9)

55 (7.5)

10 (4.6)

280 (38.0)

76 (34.9)

Dementia Yes

.138

History of prior vascular surgery Yes

.394

Independent living status Independent

.146 703 (95.5)

213 (97.7)

33 (4.5)

5 (2.3)

Ambulatory

580 (78.8)

192 (88.1)

Impaired ambulation

156 (21.2)

26 (11.9)

Non-Independent Ambulatory

.002

Disease level

.017

Aortoiliac occlusive disease

137 (18.6)

60 (27.5)

Infrainguinal

562 (76.4)

149 (68.4)

37 (5.0)

9 (4.1)

261 (35.5)

92 (42.2)

Ischemic ulceration

269 (36.5)

87 (39.9)

Gangrene

206 (28.0)

39 (17.9)

Both Presentation Rest pain

18

Table 4 Bivariate analysis of 20 variables/factors on success or failure of achieving patient-centered outcomes in 954 patients undergoing intervention for critical limb ischemia.

.373 .809

422 (57.3)

Yes

P Value

physician visits) to 89.0% (independent living), the overall patient-centered outcomes success was 22.9%. Limb loss was a statistically significant predictor of patient-centered failure (P < .001). Of the 187 patients undergoing limb amputation within 12 months of the index procedure, 9 (4.8%) were considered successes according to the patient-centered outcomes criteria; 178 (95.2%) were considered failures.

Table 4 shows the effect of 20 specific patient and procedural variables on the success and failure of patient-centered outcomes using bivariate analysis. Significant predictors included the presence of diabetes, end-stage renal disease, hypertension, preoperative ambulatory status, level of vascular disease, and clinical presentation. However, when entering these significant factors into logistic regression, only the presence of end-stage renal disease and impaired ambulatory status at presentation independently predicted failure from the perspective of patient-centered outcomes derived from our prospective questionnaire (Table 5). Overall, 667 patients had neither endstage renal disease nor impaired ambulation at baseline; 105 had end-stage renal disease, but not impaired ambulation; 138 had impaired ambulation, but no end-stage renal disease; and 44 had both end-stage renal disease and impaired ambulation. Alternatively stated, just over 30% of the cohort possessed at least 1 independent predictor of patient-centered outcomes failure.

Last, Table 6 shows the probability of achieving a patient-centered outcomes failure with and without the presence of independent patient predictors.

While the probability of failure is 93% in patients with both impaired ambulatory status at presentation and end-stage renal disease, failure still occurs in 73% of patients without either predictor.

Discussion .010

Current interest in reforming the nation’s healthcare system compels investigators not only to discover novel therapies, but also better understand the outcomes of existing therapies. Treatment for vascular disease is no exception. In fact, the Institute of Medicine identified cardiovascuGHS Proc. May 2016; 1 (1): 13-21

SURGERY OVERLOOKS PATIENT-CENTERED OUTCOMES lar treatment as one of the national priorities for comparative effectiveness research.4 Comparative effectiveness research—the head-on-head comparison of proven therapies for the same illness, particularly considering value and reproducibility—and patient-centered outcomes research are growing funding priorities for national agencies such as the National Institutes of Health.4 This prioritization suggests an increasing awareness of discord between treatment capability and treatment effectiveness. Providers need practical parameters to help guide effective therapy, which is true for all types of surgery but particularly true for vascular intervention and chronic PAD of the lower extremities. For the past 4 decades, hundreds of studies documenting outcomes after arterial intervention for PAD have been published. Assessment typically focused on such parameters as arterial patency, limb salvage, and mortality. While these parameters are important, their technical nature often can fail to consider the perspective of the patient and do not account for patient comorbidities at presentation that might warrant modification of expectations. Previous analyses inform our perspective.2 Intrigued by an introspective and critical report from the University of Oregon where patients undergoing surgery for CLI experienced less favorable outcomes when endpoints became more patient centric,5 we considered nontraditional factors that might influence outcome in a series of 1000 consecutive interventions performed for CLI. We discovered intrinsic patient comorbidities, such as preoperative functional status, were as important as limb salvage to the functional outcome of patients being treated.2 Since our study, others have reported similar findings.6 Later, we reported quality-of-life data using the SF 36 survey in patients undergoing angioplasty for claudication and discovered that patient satisfaction was not necessarily dependent upon long-term arterial patency of the intervention.7 These findings, also observed by others, questioned whether the maintenance of arterial patency, considered by many to be the primary objective of all intervention, really determined success.6,8,9 Since then, we have learned that success may be variably defined and depends upon what outcomes are valued and from what perspective they are being considered—that of the physician, the patient, or society.

In 2009, we attempted to define successful outcome postintervention for tissue loss from the patient’s perspective, using a set of intuitive (albeit surgeon-derived) outcome measures. We defined success using 4 measures: 1) patency of vascular reconstruction to the point of wound healing, 2) limb GHS Proc. May 2016; 1 (1): 13-21

salvage for 1 year, 3) maintenance of ambulation for 1 year, and 4) survival for 6 months.10 When applied to a cohort of 677 patients with CLI and tissue loss, success (measured as achieving all 4 parameters) was achieved in only 41% of cases. Independent predictors of failure included impaired ambulatory status at presentation, the presence of end-stage renal disease, diabetes, or gangrene, and prior vascular intervention. If all 5 predictors were present, success was achieved in fewer than 10% of cases. While this study helped inform decision making in our practice, there were several shortcomings. Most notably, the study team derived the outcome measures without patient input.

Table 5 Odds ratios (OR) and 95% confidence intervals after logistic regression analysis of 10 factors found to be statistically significant in impacting success or failure during bivariate analysis.

Characteristic

OR (95% CI)

P Value

Diabetes

1.21 (0.86-1.70)

.270

End-stage renal disease

2.21 (1.26-3.88)

.006

Hypertension

1.31 (0.90-1.91)

.164

Impaired ambulation

1.76 (1.12-2.79)

.015

Infrainguinal disease only

1.00 (Referent)

---

Suprainguinal disease only

1.42 (0.98-2.06)

.062

Both infra- and supra-inguinal disease

1.64 (0.74-3.66)

.225

Rest pain

1.00 (Referent)

---

Ischemic ulceration

0.85 (0.59-1.22)

.379

Gangrene

1.25 (0.80-1.98)

.329

Table 6 The probability of failure and odds ratio for factors found to be independent predictors of failure to achieve patient-centered success after intervention for critical limb ischemia.

Probability of failure (%)

Odds ratio of given profile compared to a “healthy” person

(#1) End-stage renal disease

87.7

2.62

(#2) Impaired ambulation at baseline

83.4

1.85

#1 and #2

92.9

4.84

Baseline/“healthy” person

73.1

1.00

Patient characteristic(s) present

19

In this current analysis, we again attempt to measure success from the patient’s perspective, but presently employ success measures derived from the patient. When examining these success measures, we discovered that patients value functional or practical outcomes linked to quality of life. They desire problem resolution and pain-free mobility conducive to activities of daily living. When we quantified this into discernable metrics (pain relief, maintenance of mobility, avoidance of repeat doctor visits, maintenance of daily activities, and 1-year survival) and applied it to a cohort of 954 patients with CLI intervened upon for standard indications, we found that success occurred infrequently (only 23% of cases). The presence of endstage renal disease and impaired ambulatory status at the time of presentation were independent predictors of failure. When both of these factors are present, the probability of failure exceeded 92%.

These results suggest that if success were solely being judged by the patient, our contemporary outcomes leave considerable room for improvement.

This study has several practical and conceptual limitations. First, our study includes 2 distinct cohorts—a prospective cohort providing responses informing a separate/distinct and a retrospective cohort analysis. It is possible the 2 cohorts value different outcomes (or differentially value similar outcomes). Consequently, one may object to using one cohort’s responses to define surgery “success” for another. However, our analyses may provide a baseline for subsequent studies prospectively considering patient outcome values/preferences and actual outcomes within the same cohort. We additionally concede our survey tool lacked any validation. Ideally, our tool would benefit from a substantive pilot test to ensure question concordance between questions posed and constructs they purportedly represent. Indeed, our purported “patient-centered measures” originated from ideas and questions by the study team and not from the patient. While the answers might represent the wishes of the patients, the questions are certainly not without some bias despite all efforts to mitigate. Despite potential bias, ample opportunity was given for open-ended responses. Third-party study investigators administered the survey and patients were reassured that their answers were to be blinded to the treating surgeon. Consequently, while our measures may not be purely patient-centered, we believe the questionnaire has face validity and allows for subsequent psychometric scholarship to scrutinize its validity and utility.

Second, patient expectations, as derived via openended survey, may actually depict “patient hopes” 20

as opposed to pragmatic “patient-centered outcomes.” Patients may hope for a painless intervention requiring no follow-up, but this goal is currently unrealistic, if not unattainable. Third, our study may employ an unduly rigorous definition of success. Achieving all 5 outcome measures, especially when one of the measures (no additional nonroutine physician visit) may include a disproportionate number of failures, may be too austere a measure to evaluate overall success. However, even if our analysis depicts results too pessimistically, the findings underscore several opportunities for improvement. For example, in this series 66% of patients undergoing elective vascular surgery did so solely on the advice of the surgeon, which highlights a potential education opportunity where the patient and surgeon may better discuss details of the patient’s current vascular condition and establish realistic expectations after surgery.

Another limitation includes potential discord between the patient population used to derive our patient-centered outcome criteria and the population in which we chose to apply these outcomes. This study surveyed patients with a variety of vascular problems, many of whom did not have lower extremity PAD. Our study population consisted solely of patients with CLI. It is reasonable to assume that our patient-centered outcome measures might have differed had the population surveyed been confined to patients with CLI. However, this reasoning may fail to solve the discord as well. It can be argued that “patients with CLI” may also be too generic a category. Perhaps it would have been best to sample patients with similar presenting symptoms (rest pain, ischemic ulcer, or gangrene). Same could be said for similar comorbidities or similar functional states.

This last study limitation highlights the general inadequacy of all literature looking at patient-centered outcomes. In reality, patient-centered outcomes is a “moving target” contingent upon the individual patient’s vacillating psycho-social state, environment, and disease progression. Consequently, it may be unsound practice to ever measure “blanket patient-centered outcomes” from one population and apply it to another. Future work addressing “successful patient-centered outcome” might best be achieved when analyzing patients individually—customized upfront and based on unique characteristics and circumstances at presentation. As an example, Lidsky and his colleagues published the outcomes from a series of patients with arteriovenous malformations (AVM) treated in a multidisciplinary fashion.11 While the study highlighted the work of a group of dediGHS Proc. May 2016; 1 (1): 13-21

SURGERY OVERLOOKS PATIENT-CENTERED OUTCOMES cated physicians managing a difficult problem, the studyâ&#x20AC;&#x2122;s most intriguing aspect arguably involved how success was measured. It was acknowledged with each patient up front that AVMs are not usually curable and that palliation is often the treatment goal. Conditioned upon that understanding, the physician and the patient subsequently determined the optimal achievable outcome for each case. If that outcome was achieved, then the patient and provider deemed the overall outcome successful. Realistically, PAD of the lower extremities is a multifaceted, debilitating condition that is probably no more curable than a vascular malformation.

Palliation is almost always the goal. It is conceivable that targeted results involving physician-centered, society-centered, and patient-centered outcomes could be discussed with each patient and determined prior to intervention. Similar to the Lidsky study, if that result is achieved, then the overall treatment should be considered successful. There is evidence in our data to support this.

Counter to what most vascular surgeons might expect, nearly 5% of patients in our study reported achieving patient-centered success despite having a major lower extremity amputation. Had the physician and the patient decided preoperatively that amputation was the best achievable goal, then

perhaps a shared satisfactory outcome could have been targeted, vascular intervention could have been avoided, and a less complex, more cost-effective treatment plan could have been implemented.

Conclusion In summary, this study is intended to introduce the concept of patient-centered outcomes as an important consideration in the management of patients undergoing planned surgery. Our findings suggest that patients undergoing vascular intervention desire pain control, maintenance of daily activity, maintenance of mobility, and the minimization of trips to the doctor. When we applied these desired outcomes to a cohort of patients undergoing treatment for CLI using standard indications, we achieved overall patient-centered success in fewer than 25% of cases. Patients with endstage renal disease and significant physical debility at presentation were at significantly higher risk for poor outcome. These data support the premise that overall outcome success might best be derived by a blend of physician, patient, and society-centered goals tailored to the individual, after fully discussing and understanding treatment limitations, as well as patient-specific factors impacting satisfaction with the surgical outcome.

Abbreviations and Acronyms CLI = critical limb ischemia GHS = Greenville Health System PAD = peripheral arterial disease ABI = ankle-brachial index OR = odds ratio AVM = arteriovenous malformation

Correspondence Address to: Dr Spence M. Taylor Greenville Health System, Memorial Campus Health Sciences Administration Building 701 Grove Rd, Greenville, SC 29605 (staylor@ghs.org)

References 1. Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Report of the American College of Cardiology/American Heart Association Task Force Practice Guidelines (Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol. 1996;27:910-48.

2. Taylor SM, Kalbaugh CA, Blackhurst DW, Cass AL, Trent EA, Langan EM III, Youkey JR. Determinants of functional outcome after revascularization for critical limb ischemia: an analysis of 1000 consecutive vascular interventions. J Vasc Surg. 2006;44:747-56.

3. Taylor SM, Cull DL, Kalbaugh CA, et al. Comparison of interventional outcomes. according to preoperative indication: a single center analysis of 2240 limb revascularizations. J Am Coll Surg. 2009;208:770-80.

4. Institute of Medicine. Committee on Comparative Effectiveness Research (2009). Initial national priorities for comparative effectiveness research. Washington, D.C.: Institute of Medicine of the National Academies Press.

outcomes after infrainguinal bypass surgery. J Vasc Surg. 2010;51:351-8.

7. Kalbaugh CA, Taylor SM, Blackhurst DW, Dellinger MB, Trent EA, Youkey JR. One-year prospective quality-of-life outcomes in patients treated with angioplasty for symptomatic peripheral arterial disease. J Vasc Surg. 2006;44:296-303.

8. Mazari FAK, Carradice D, Abdul Rahman MNA, Khan JA, Mockford K, Mehta T, McCollum PT, and Chetter IC. An analysis of relationship between quality of life indices and clinical improvement following intervention in patients with intermittent claudication due to femoropopliteal disease. J Vasc Surg.

2010;52:77-84.

9. Nordanstig J, Karlsson J, Pettersson M, Wann-Hansson C. Psychometric properties of the disease-specific health-related quality of life instrument VascuQoL in a Swedish setting. Health Qual Life Outcomes.

2012,10:45-52.

5. Nicoloff AD, Taylor LM, McLafferty RB, Moneta GL, Porter JM. Patient recovery after infrainguinal bypass grafting for limb salvage. J Vasc Surg. 1998;27:256-66.

10. Taylor SM, York JW, Cull DL, Kalbaugh CA, Cass AL, Langan EM III. Clinical success using patient-oriented outcome measures after lower extremity bypass and endovascular intervention for ischemic tissue loss. J Vasc Surg. 2009;50:534-41.

6. Crawford RS, Cambria RP, Abularrage CJ, Conrad MF, Lancaster RT, Watkins MT, LaMuraglia GM. Preoperative functional status predicts perioperative

11. Lidsky ME, Markovick JM, Shortell CK. Treatment of congenital vascular malformations using a multidisciplinary approach. J Vasc Surg. 2012;56:1355-62.

GHS Proc. May 2016; 1 (1): 13-21

21

Original Research

Medicare Shared Savings Program Second-Year Results: Predictors of Success Susan E. Sutherland, PhD; Brent M. Egan, MD; Douglas O. Fleming, MPH; George A. Helmrich, MD; Robert A. Davis, MS; Valinda Rutledge, MSN, MBA; and Angelo Sinopoli, MD From the Care Coordination Institute, Greenville Health System, Greenville, SC (S.E.S., B.M.E., D.O.F., R.A.D., V.R., A.S.); University of South Carolina School of Medicine Greenville, Greenville, SC (S.E.S., B.M.E., D.O.F., G.A.H., R.A.D., A.S.), Department of OB/GYN, Greenville Health System, Greenville, SC (G.A.H.); and Department of Medicine, Greenville Health System, Greenville, SC (A.S.)

Abstract Background: The Affordable Care Act (ACA) established the Medicare Shared Savings Program (MSSP) to improve quality of care and reduce unnecessary costs.1 Accountable Care Organizations (ACOs) participating in MSSP are rewarded for meeting healthcare performance measures while controlling costs for their assigned Medicare beneficiaries.

Methods: We examined the characteristics and quality metrics that predicted generated savings. The Centers for Medicare & Medicaid Services recently released the second year of quality metrics for 333 ACOs in the MSSP. Univariate and multivariate methods were used to compare ACOs that generated savings with those that did not. Stepwise linear regression models were used to estimate the variance in savings explained by ACO characteristics and quality measures.

Results: Of 333 ACOs in MSSP, 92 (28%) generated savings. ACOs that generated savings had more years of experience in MSSP and had higher overall quality scores. ACOs that saved money had $915 higher baseline costs per beneficiary. Among ACOs that reduced cost, 8 variables accounted for 59% of variance in savings. Four were positively associated with savings: baseline costs (31.5% of variance), hypertension control in diabetes (7.5%), LDL-cholesterol control in diabetes (1.6%), and mammography screening (1.4%); 4 were negatively associated: patientsâ&#x20AC;&#x2122; rating of doctor (8.6%), number of beneficiaries (4.2%), health/functional status (2.3%), and coronary artery disease composite score (1.8%). ACOs that reduced costs had higher baseline expenditures, which accounted for 31.5% of savings generated.

Conclusions: While quality is critical for ACOs to receive a portion of savings, the relationship of healthcare quality to savings is variable.

T

he Affordable Care Act (ACA) established the Medicare Shared Savings Program (MSSP) to improve healthcare quality and reduce costs.1 Accountable Care Organizations (ACOs) participating in MSSP are financially rewarded for meeting quality performance measures while reducing costs for attributed Medicare beneficiaries. Both quality and financial components are included to prevent the sacrifice of one versus the other.2 ACOs apply to join the MSSP, a voluntary program, and, if accepted, they participate for a minimum of 3 years.

22

For the 2014 program year, MSSP provided 2 tracks for participants: a one-sided model in which savings are shared only during the initial term, and a two-sided model in which there is a sharing of both savings and losses.3 The two-sided model provides greater potential for shared savings.

Each ACO is assigned a target or benchmark expenditure amount derived from the most recent 3 years of Part A and Part B Medicare Fee-for-Services claims data.4 More weight is assigned to the most recent year and adjusted by characteristics GHS Proc. May 2016; 1 (1): 22-27

MSSP SAVINGS AND QUALITY of the assigned beneficiaries, other factors determined by the Secretary, and growth in national per capita expenditures during this performance year. Recent changes by the Centers for Medicare & Medicaid Services (CMS) will change the weight assigned by year. Minimum Savings Rates (MSR) and Minimum Loss Rates (MLR) are assigned by the CMS based on the number of beneficiaries to determine if an ACO is qualified to receive savings or share in losses.

Participating organizations are judged on metrics designed to capture their quality of care.

Thirty-three quality measures are reported annually. These quality measures are organized into 4 domains: 1) patient or caregiver experience, 2) care coordination and patient safety, 3) preventive health, and 4) at-risk populations. The measures are reported through various Web interfaces for reporting quality measures and patient surveys, claims and administrative data, and the Medicare Electronic Health Record (EHR) Incentive program.5 During the first year of participation, ACOs are required to demonstrate reporting capability on 22 quality measures.4 In the second and subsequent years of participation, quality measures are compared to benchmarks as part of the criteria for determining shared savings. Pay for performance criteria are applicable to 25 measures in year 2 and 32 measures in year 3.

CMS recently released results for the second performance year.6,7,8 In a recent blog, we compared the quality measures and characteristics of ACOs that generated savings.9 This paper expands upon those findings and discusses the challenges and opportunities for participants regarding quality measurements and healthcare costs.

Methods Establishment of benchmarks and scoring methodology has been previously described by CMS.3,10 In August 2015, CMS released the second year of quality metrics for 333 MSSP ACOs.6 The results were downloaded from the applicable website and imported into SAS® Enterprise Guide 7.1 for analysis.11 Scores of zero on individual quality metrics were considered as missing and not included in analysis. Comparisons between ACOs with generated savings and without generated savings were made using Chi-square statistics for categorical responses and Fisher’s exact tests where the sample size was less than 5. Comparisons of continuous type data were made using pooled t-tests with Satterthwaite’s adjustment in cases of unequal GHS Proc. May 2016; 1 (1): 22-27

variance. Statistical significance was defined a priori by a type I error rate of 0.05. No adjustments were made for multiple comparisons. Stepwise linear regression models were used to estimate the variance in savings amounts explained by specific

Table 1 Comparison of ACOs with and without savings.

Generated Savings (N = 92)

No Generated Savings (N = 241)

P Value

Beneficiaries assigned, no.

15 087 ± 1558

16 356 ± 971

.494

Benchmark/Member

$10 947 ± 290

$10 032 ± 158

.004

Savings (higher cost)

$732 ± 49

$165 ± 24

Participation year, no. (%)

.012

Year 1

23 (25.0)

96 (39.8)

Year 2

28 (30.4)

75 (31.1)

Year 3

41 (44.6)

70 (29.1)

Track, no. (%)

.186

One-sided model

90 (97.8)

240 (99.6)

Two-sided model

2 (2.2)

1 (0.4)

Beneficiaries, no. (%) <5,000

.617 6 (6.5)

8 (3.3)

5001−10 000

35 (38.0)

98 (40.7)

10 001−20 000

33 (35.9)

78 (32.4)

20 001−30 000

9 (9.8)

23 (9.5)

30 001−40 000

6 (6.5)

17 (7.1)

>40 000

3 (3.3)

17 (7.1)

Quality score, no. (%) P4R

.017 23 (25.0)

96 (39.6)

<75%

8 (8.7)

9 (3.7)

75-79%

9 (9.8)

14 (5.8)

80-84%

9 (9.8)

23 (9.5)

85-89%

21 (22.8)

61 (25.3)

90-94%

20 (21.7)

38 (15.8)

2 (2.2)

0 (0.0)

>95%

Means and standard error of the mean are shown for continuous measures; number and percentage are shown for categorical data. P4R= pay for reporting in participation year 1.

23

Table 2 Comparison of quality measures for ACOs with savings versus no savings.

Generated No Generated Savings Savings (N = 92) (N = 241) P Value Patient/Care giver experience Getting timely care, appointments, information

79.7 ± 0.44

80.3 ± 0.23

.181

How well your doctors communicate

92.3 ± 0.20

92.4 ± 0.11

.547 .468

Patient’s rating of doctor

91.5 ± 0.21

91.6 ± 0.11

Access to specialists

84.2 ± 0.28

83.9 ± 0.16

.377

Health promotion and education

58.9 ± 0.40

58.1 ± 0.23

.060

Shared decision making

74.7 ± 0.29

74.6 ± 0.17

.670

Health status/functional status1

70.6 ± 0.30

71.3 ± 0.14

.023

Risk standardized, all readmissions2

15.2 ± 0.08

15.1 ± 0.05

.474

Admission for COPD or asthma in older adults2

1.2 ± 0.05

1.1 ± 0.02

.046

Heart failure2

1.2 ± 0.03

1.2 ± 0.02

.254

Percent PCP qualified for EHR incentive3

72.8 ± 2.24

78.2 ± 1.10

.032

Medication reconciliation after discharge

84.4 ± 2.31

83.6 ± 1.28

.749

Screening for fall risk

48.7 ± 2.36

44.6 ± 1.54

.154

Influenza immunization

58.8 ± 1.75

57.4 ± 0.94

.465

Pneumococcal vaccination

56.3 ± 2.12

54.8 ± 1.27

.565

Adult weight screening and follow-up

71.5 ± 1.61

65.6 ± 1.02

.003

Tobacco use assessment, intervention

89.0 ± 0.98

86.3 ± 0.98

.058

Depression screening

43.7 ± 2.41

38.2 ± 1.47

.052

Colorectal cancer screening

57.6 ± 1.56

55.6 ± 1.00

.298

Mammography screening

63.1 ± 1.49

61.1 ± 0.93

.252

Adults with BP screen in last 2 years

63.3 ± 2.36

59.8 ± 1.37

.198 .855

Care coordination/Patient safety

Preventive health

At-risk population—diabetes Hemoglobin A1C control (<8%)

69.9 ± 0.85

69.7 ± 0.66

LDL <100 mg/dL

59.0 ± 0.98

56.4 ± 0.66

.037

BP <140/90 mmHg

71.0 ± 0.92

69.6 ± 0.61

.228

Tobacco non use

75.5 ± 1.77

75.2 ± 1.14

.902

Aspirin use

81.9 ± 1.51

80.6 ± 0.95

.470

69.7 ± 0.88

67.9 ± 0.58

.093

At-risk population—hypertension BP control At-risk population—ischemic vascular disease Complete lipid profile & LDL control

60.2 ± 1.08

57.0 ± 0.71

.017

Aspirin or antithrombotic

83.0 ± 1.22

80.4 ± 1.08

.108

86.1 ± 1.67

84.4 ± 0.90

.252

Drug therapy for lowering LDL

77.9 ± 1.27

72.9 ± 1.10

.003

ACE inhibitor or ARB for CAD and diabetes and/or LVSD

77.6 ± 1.04

75.0 ± 0.77

.047

Diabetes composite

26.2 ± 1.13

25.4 ± 0.62

.503

CAD composite

70.8 ± 1.34

65.5 ± 1.08

.002

At-risk population—heart failure Beta blocker for LVSD At-risk population—CAD

Composite measures

Numbers shown are means with standard errors: 1Not Scored; 2Indicates reverse scoring; 3Double-weighted measure.

24

quality measures and ACO characteristics. The significance level for entry and retention in the model was 0.15.

Results A total of 333 ACOs participated in the 2014 MSSP, and 92 (28%) generated savings. Table 1 (previous page) shows characteristics of ACOs by the presence or absence of generated savings. Among 92 ACOs generating savings, 6 did not earn savings due to failing to successfully report quality measures despite meeting financial goals.

While there were no differences in the average number of beneficiaries assigned to ACOs generating savings and those that did not, there was a difference in the per member benchmark. On average, those who received savings had a benchmark of $915 more per member. ACOs with savings had an average $732 per member savings versus an average excess cost of $165 per member for ACOs not generating savings. Almost all ACOs chose the one-sided model. Three-quarters of ACOs with savings were second- and thirdyears participants. Differences were noted in the total quality scores between the 2 groups of ACOs, with 24% of ACOs receiving savings having a total score of 90% or greater versus 16% of ACOs not reducing costs.

Table 2 illustrates differences in quality measures between ACOs with savings and those failing to generate savings. At least 1 measure in each of the 4 quality domains emerged as a significant differentiator. Under the patient and care giver experience domain, ACOs that generated savings had an average lower score (inverse relationship) on health/functional status (P = .023) and a trend towards higher scores on health promotion and education (P = .060). However, the scores on health/functional status did not contribute to the overall quality score as it was a pay-for-reporting requirement only.

Two measures in the care coordination/patient safety domain emerged as statistically different between the 2 groups of ACOs, both with an inverse relationship. Admissions for the Ambulatory Care Sensitive (ACS) condition of chronic obstructive pulmonary disease (COPD) or asthma in older adults was lower in those ACOs that did not generate savings (P = .046). The percentage of primary care physicians (PCPs) who qualified for the EHR incentive payment was higher in those who did not generate savings (P = .032).

GHS Proc. May 2016; 1 (1): 22-27

MSSP SAVINGS AND QUALITY Among the preventive health measures, ACOs with savings had significantly higher scores for adult weight screening and follow-up (P = .003) and marginally higher scores for depression screening (P = .052). There was also a trend toward higher scores for tobacco use assessment and cessation intervention in ACOs with savings (P = .058).

All the measures for at-risk populations were higher for ACOs with generated savings. These included greater LDL-cholesterol control among patients with diabetes (P = .04), blood pressure control among patients with hypertension (P = .09), complete lipid profiles and LDL control among those with ischemic vascular disease (IVD) (P = .02), aspirin or antithrombotic medications for patients with IVD (P = .108), drug therapy for lowering LDL-cholesterol among patients with coronary artery disease (CAD) (P = .003), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy for patients with CAD and diabetes and/ or left ventricular systolic dysfunction (LVSD) (P = .047), and CAD composite score (P = .002). The measures for CAD, however, were designated as pay-for-reporting in participation year 2.

To further understand the relationship between ACO characteristics, quality measures, and savings for the 92 ACOs generating savings, we undertook a multi-variable approach using stepwise linear regression. Variables in the model included all individual and composite measures, number of assigned beneficiaries, years of experience, and the per member benchmark. Table 3 shows the results of the final model. The first variable selected was the per member benchmark, accounting for 31% of the variance in the amount of savings generated.

The remaining variables chosen were as follows: the patientâ&#x20AC;&#x2122;s rating of the doctor (inverse relationship), blood pressure control in diabetes, the total number of assigned beneficiaries (inverse relationship), health status/functional status (inverse relationship), LDL-cholesterol control with diabetes, CAD composite score (inverse relationship), and mammography screening. Together, these 8 factors accounted for almost 60% of the variance in savings per member. Years of experience was not a significant predictor of amount of savings in the multivariable setting.

We also explored the relationship between amount of savings and the various factors in a subset of the ACOs with greater than 5000 beneficiaries and who also successfully reported quality measures in performance years 2 and 3. The results were similar.

GHS Proc. May 2016; 1 (1): 22-27

Table 3 Predictors of savings amount among ACOs with generated savings.

Standardized Estimate Partial R2 Model R2

P Value

Benchmark per member

0.553

0.3149

0.3149

<.001

Patientâ&#x20AC;&#x2122;s rating of doctor

-0.302

0.0861

0.4010

.002

0.188

0.0754

0.4763

.002

Number of beneficiaries

-0.190

0.0417

0.5181

.014

Health status/functional status

-0.264

0.0231

0.5412

.059

0.310

0.0156

0.5568

.116

-0.253

0.0183

0.5751

.085

0.174

0.0141

0.5892

.126

BP control in diabetes

LDL control in diabetes CAD composite Mammography screening

Discussion Despite the large number of logical contributors to financial success of the ACO, there are few drivers that separate the successful and unsuccessful.

The results of the 2014 MSSP second year evaluation show the ability to generate savings is largely influenced by the per-member benchmark, even more than experience.9,12 More specifically, the ACOs with generated savings had baseline benchmark costs per patient that were on average $915 higher than ACOs that did not generate savings.

Logically, it appears the greater room for lowering cost may yield the greatest savings. ACOs with savings lowered their cost by $732 while ACOs without savings increased cost by $165, resulting in a net cost difference of only $18 per beneficiary.

The patient experience domains appear to have little influence on the ability to create savings.

In fact, a negative association is seen between the patientsâ&#x20AC;&#x2122; perceptions of their physician. The dichotomy between patient satisfaction and quality of care has been demonstrated previously.13-15 The number of beneficiaries assigned to the ACO was not significantly different between those with and without generated savings; however, it was negatively associated with the amount of savings, contributing 4% of the variance in the amount.

Perhaps this points to the complex nature of coordinating care in networks.16 Results of quality measures were mixed. CMS reported improvement on 27 of the 33 quality measures among ACOs reporting in both 2013 and 2014.17,18 A previous report on performance in the first year of MSSP showed almost no cor25

Abbreviations and Acronyms ACO = Accountable Care Organization; MSSP = Medicare Shared Savings Program; ACA = Affordable Care Act; CMS = Centers for Medicare & Medicaid Services; MSR = Minimum Savings Rates; MLR = Minimum Loss Rates; EHR = electronic health record; ACS = ambulatory care sensitive; PCP = primary care physicians; IVD = ischemic vascular disease; CAD = coronary artery disease; ACE = angiotensinconverting enzyme; ARB = angiotensin receptor blocker; LVSD = left ventricular systolic dysfunction; APM = Alternative Payment Models; MACRA = Medicare Access & CHIP Authorization; MIPS = Merit-Based Incentive Payment System

Correspondence Address to: Susan E. Sutherland, PhD Care Coordination Institute Greenville, SC 29601 (ssutherland@ ccihealth.org)

relation between overall quality scores and expenditures resulting in savings, although ACOs were only required to successfully report scores during that year.17 Simiarly, we found higher quality scores did not consistently correspond to greater financial success in the second year of MSSP when scores were used to determine eligibility for savings. Several measures were more favorable for ACOs that did not generate savings, including health status/function status, admissions for COPD or asthma, and the percent of PCPs who qualified for the EHR incentive. However, measures for the at-risk populations were consistently higher for ACOs generating savings (Table 2).

Cardiometabolic disease and cancer are chronic diseases that account for a disproportionate share of Medicare expenses.19 In this regard, ACOs that generated savings had higher quality scores on several measures that could impact costs for these common and costly chronic conditions, including 1) adult weight screening and follow-up, 2) tobacco use assessment and intervention, 3) LDL-cholesterol control in patients with diabetes and/or with ischemic vascular disease, 4) drug-therapy for LDL-cholesterol, and 5) renin-angiotensin system blockers in patients with diabetes and/or CAD. It will be interesting to see if these trends persist in subsequent years as more ACOs join the MSSP and gain experience in managing care of their beneficiaries.

Shared Savings Program (SSP) adjustments are required to accurately weigh the quality of care ACOs are providing into the shared savings equation.20-22 CMS published an update to the SSP final rule in June of 2015.23 The update incorporated changes that seek to alleviate issues highlighted

CMS, through the Medicare Access & CHIP Authorization Act of 2015 (MACRA), seeks to create additional programs and refinements through the Merit-Based Incentive Payment System (MIPS) and Alternative Payment Models (APMs). MACRA was signed into law on April 16, 2015.24 While details have yet to be announced, MIPS and APMs will become effective in 2019 and will drastically change how Medicare-enrolled physicians and other providers are compensated

by Medicare. It is important for physician and healthcare system leaders to understand the proposed changes as they navigate a changing health environment to improve patients’ access to, experience with, and engagement to achieve better outcomes while constraining growth in cost.

Conclusion Success in generating savings and the amount of savings are largely due to the baseline per-member benchmark. The influence of quality metrics was mixed with higher scores not necessarily predictive of success in generating savings. The journey toward creating a successful ACO is complex. While keys to success in meeting the 33 quality metrics have been published, they do not appear to be the same drivers of financial success.25 ACOs with cost savings had higher quality scores on several variables linked to cardiometabolic disease and cancer, which are major drivers of Medicare costs.

References 1. Halterman S, Balezentis M. Accountable care organizations: the missing link to engagement in health and health care? Benefits Q. 2015;31:29-39.

cms.gov/medicare/medicare-fee-for-service-payment/sharedsavingsprogram/downloads/mssp-qmbenchmarks.pdf Accessed January 8, 2016.

2. Holzhauer K. Accountable care organizations: the first two years’ performance and directions for the future. AMA J Ethics. 2015;17:630-6.

5. Quality Measures, Reporting and Performance Standards.CMS.gov. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/sharedsavingsprogram/Quality-Measures-Standards.html Updated December 18, 2015. Accessed January 8, 2016.

3. Centers for Medicare & Medicaid Services. Medicare Learning Network. Methodology for determining shared savings and losses under the Medicare shared savings program. https://www.cms.gov/Medicare/ Medicare-Fee-for-Service-Payment/sharedsavingsprogram/Downloads/ACO_Methodology_Factsheet_ICN907405.pdf ICN 907405. Published April 2014. Accessed January 6, 2016.

4. Center for Medicare & Medicaid Services. Medicare shared savings program quality measure benchmarks for the 2014 and 2015 reporting years. https://www.

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in this and other papers. Of note, CMS created a third track for SSP program and refined the methodology for resetting benchmarks. Both program changes are designed to create a stronger and more accurate assessment of MSSP ACOs.23

6. Medicare Shared Savings Program Accountable Care Organizations Performance Year 2014 Results.

Data.CMS.gov. https://data.cms.gov/ACO/Medicare-Shared-Savings-Program-Accountable-Care-O/ ucce-hhpu. Accessed September 1, 2015.

7. Walker T. ACO results released: what health execs should know. Manage Healthc Exec. 2015;25:15-16.

8. Medicare ACOs provide improved care while slowing

GHS Proc. May 2016; 1 (1): 22-27

MSSP SAVINGS AND QUALITY cost growth in 2014. CMS.gov. https://www.cms.gov/ Newsroom/MediaReleaseDatabase/Fact-sheets/2015Fact-sheets-items/2015-08-25.html. Published August 25, 2015. Accessed January 8, 2016.

9. Sutherland S, Egan B. Davis R, Rutledge V, Sinopoli A. Diving into the pool of ACO quality measures: MSSP year 2 performance metrics. Health Affairs Blog. http://healthaffairs.org/blog/2015/12/21/divinginto-the-pool-of-aco-quality-measures-mssp-year-2performance-metrics/. Published December 21, 2015.

Accessed January 8, 2016.

10. Centers for Medicare & Medicaid Services. Medicare Learning Network. Improving quality of care for Medicare patients: accountable care organization. https://www.cms.gov/medicare/medicare-fee-forservice-payment/sharedsavingsprogram/downloads/ aco_quality_factsheet_icn907407.pdf ICN 907407.

Published April 2014. Accessed January 6, 2016.

11. SAS/STAT software, Version 9.4 of SAS Enterprise Guide 7.1. Copyright© 2014 SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute, Cary, NC. 12. Introcaso D, Berger G. MSSP Year Two: Medicare ACOs show muted success. Health Affairs Blog. http://healthaffairs.org/blog/2015/09/24/mssp-yeartwo-medicare-acos-show-muted-success/ Published September 24, 2015. Accessed January 6, 2016.

13. Fenton JJ, Jerant AF, Bertakis KD, Franks P. The cost of satisfaction: a national study of patient satisfaction, health care utilization, expenditures, and mortality.

Arch Intern Med. 2012;172:405-11.

16. Health Care Transformation Task Force. Proactively identifying the high cost population. http://www. hcttf.org/resouces-tools/2015/5/14/whitepaper Published July 1, 2015. Updated August 11, 2015. Accessed January 10, 2015.

17. Muhlestein D. ACO quality results: good but not great. Health Affairs Blog. http://healthaffairs.org/ blog/2014/12/18/aco-quality-results-good-but-notgreat/ Published December 18, 2014. Accessed January 7, 2016.

18. Daly R. Few MSSP ACOs garner shared savings.

Healthc Financ Manage. 2015;69:11.

19. Centers for Medicare & Medicaid Services. Chronic Conditions Chartbook: 2012 Edition. CMS.gov. ht t ps://w w w.cms.gov/Resea rch-Stat ist ics-Data-and-Systems/Statistics-Trends-and-Reports/ Chronic-Conditions/2012ChartBook.html.

Published April 25, 2013. Accessed January 14, 2016.

20. Daly R. CMS modifies ACO rules. Healthc Financ Manage. 2015;69:11.

21. Valuck T, Dugan D, Dubois RW, Westrich K, Penso J, McClellan M. Solutions for filling gaps in accountable care measure sets. Am J Manag Care. 2015;21:723-8.

22. Perez K. New MSSP ACO rule practicing the art of the possible. Healthc Financ Manage. 2015;69:98-9.

23. Centers for Medicare & Medicaid Services. Medicare Program; Medicare shared savings program: accountable care organizations. Fed Register. 2015;80: 32692847. Codified at 42 CFR §425.

14. Chang JT, Hays RD, Shekelle PG, et. al. Patients’ global ratings of their health care are not associated with the technical quality of their care. Ann Intern Med. 2006;144:665-72.

24. Centers for Medicare & Medicaid Services. The Medicare access & CHIP reauthorization act of 2015: path to value. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/ Value-Based-Programs/MACRA-MIPS-and-APMs/ MACRA-LAN-PPT.pdf Accessed January 8, 2015.

15. Manary MP, Boulding W, Staelin R, Glickman SW. The patient experience and health outcomes. N Eng J Med. 2013;368:201-3.

25. Damore JF. Building the foundation for a successful Medicare shared savings program. J Healthc Manag.

2015;60:390-4.

GHS Proc. May 2016; 1 (1): 22-27

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Original Research

A Retrospective Data Analysis of Levetiracetam as Initial Monotherapy in Pediatric Epilepsy Patients Addie S. Hunnicutt, MD; Augusto Morales, MD; Randall R. Blouin, MD; Emily T. Foster, MD; Anna L. Cass, PhD; and Mansi Patel, MD From the Department of Pediatrics, Division of Pediatric Neurology, Greenville Health System, Greenville, SC (A.S.H, A.M., R.R.B., E.T.F.); University of South Carolina School of Medicine Greenville, Greenville, SC (A.S.H., A.M., R.R.B., E.T.F., A.L.C.); and St. Elizabethâ&#x20AC;&#x2122;s Medical Center, Boston, Mass (M.P.)

Abstract Background: Levetiracetam has high oral bioavailability, rapid absorption, and minimal drug interactions. It is frequently prescribed as an initial antiepileptic medication, although it is approved as adjunctive therapy.

Methods: We performed a retrospective chart review of new-onset seizure patients from September 1, 2008 to September 1, 2010 (N = 301). Patients were followed until May 31, 2012 in a pediatric neurology practice in a community based academic hospital.

Results: Seventy percent of all patients had focal seizures; 28% were primarily generalized. Eighty-two percent of all patients were initially placed on either levetiracetam (66%) or oxcarbazepine (16%).

From the 198 patients on levetiracetam, 65% had â&#x2030;Ľ50% reduction in seizures and 32% became seizure free. Both of these treatment groups (levetiracetam and oxcarbazepine) had a similar responder rate (P = .26) and seizure freedom rate (P = .66). Patients with multiple seizures per day were less likely to become seizure free on levetiracetam (15% vs. 41% without, P < .01); however, there was no difference in responder rate of 50% reduction in seizures (67% vs. 65%, P = .84). Fifty-nine percent of patients on levetiracetam as initial monotherapy continued it alone throughout the study with mean retention of 21.6 months (range: 1-39 months). Twenty-four percent discontinued levetiracetam, with 21% switching to another medication and 1.5% electing no medication. Two-thirds (64%) of patients discontinued levetiracetam due to side effects and one-third (36%) discontinued for ineffectiveness. Seventeen percent continued levetiracetam but also added another medication. From the patients not started on levetiracetam as initial monotherapy, 30% switched to levetiracetam.

Side effects occurred in 32% of all patients on levetiracetam, the majority of which were related to behavioral problems (95%).

Conclusions: Overall, levetiracetam appears safe and effective as initial monotherapy in pediatric patients with new-onset seizures.

L

evetiracetam is a novel antiepileptic medication with efficacy against a broad range of seizure types. One of the mechanisms is that it selectively inhibits high-voltage-activated calcium channels and binds to synaptic vesicle protein 2A, which provides broad-spectrum antiepileptic activity, although the exact mechanism is unknown. It has been approved by the United

28

States Food and Drug Administration as adjunctive therapy in partial onset seizures and in generalized tonic clonic seizures in children greater than 4 years of age. It has linear pharmacokinetics, with little protein binding and ability for rapid titration.1,2 Typical dosing is 40-120 mg/kg/day in 2 or 3 equally divided doses. Side effects include behavioral disturbances, irritability, drowsiness,

GHS Proc. May 2016; 1 (1): 28-31

LEVETIRACETAM INITIAL MONOTHERAPY nervousness, loss of appetite, and sleep disturbances; however, no life-threatening or persistent serious side effects have been reported.1 Levetiracetam has been shown to be effective in decreasing seizure frequency in partial seizures and in generalized seizures when used as an adjunctive therapy. The median responder rate is 40%-60%.2 Small trials have shown a favorable responder rate (≥50% reduction in seizure frequency) in patients given levetiracetam as monotherapy, including either conversion to monotherapy or as initial monotherapy. In a total of 18 patients, 16 were transitioned from prior antiepileptic medications.3 In another nonrandomized retrospective review of patients ≥12 years of age, there was a 54.4% seizure freedom rate on levetiracetam monotherapy.4 Levetiracetam is frequently used as initial monotherapy in clinical settings because of its broad spectrum and favorable side effect profile. A randomized, controlled trial comparing levetiracetam to lamotrigine in patients with new-onset epilepsy in children and adults over the age of 12 years showed no significant difference between levetiracetam and lamotrigine in efficacy or tolerability. Subgroup analysis did show increased recurrence of seizure in the patients under the age of 18 years. The investigators also noted that lack of tolerability was more likely the cause of discontinuation, rather than recurrence of seizures.

Tiredness and aggression were more frequent in patients receiving levetiracetam.5 There have been no randomized controlled trials for initial monotherapy in pediatric patients. Recent evidence reviewed by the International League Against Epilepsy (ILAE) showed no clear evidence on any medication used as initial monotherapy in children with either partial-onset or generalized-onset seizures.6 We report our experience using levetiracetam as initial monotherapy and its comparison to other medications.

Methods Any child (1 month-18 years of age) seen at Greenville Health System’s (GHS) Division of Pediatric Neurology between September 1, 2008 and September 1, 2010 with a diagnosis of seizure, epilepsy, or abnormal electroencephalogram (EEG) was identified utilizing International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes in hospital administrative data. There were a total of 10 137 patient encounters attributed to 1 of the included diagnosis codes: seizure (780.39), epilepsy (345), or abnormal EEG (794.02). The source population was narrowed to pediatric patients with new-onset seizures and initial monotherapy. We excluded patients as not receiving initial monotherapy if they received treatment with a medication other than an emergent benzodiazepine prior to initiation of the monotherapy antiepileptic medication.

Figure 1 Descriptive analysis of patients treated with levetiracetam as initial monotherapy.

Levetiracetam as initial monotherapy N = 196

Continued on levetiracetam as monotherapy throughout study period N = 116

Added additional therapy N = 34

Discontinued medication due to side effects N=3

Switched to a different medication N = 41

Experienced ≥50% reduction in seizure frequency N = 98 (84%)

Experienced ≥50% reduction in seizure frequency N = 10 (29%)

Experienced ≥50% reduction in seizure frequency N = 0 (0%)

Experienced ≥50% reduction in seizure frequency N = 19 (46%)

Seizure free N = 52 (45%)

Seizure free N = 0 (0%)

Seizure free N = 0 (0%)

Seizure free N = 9 (22%)

GHS Proc. May 2016; 1 (1): 28-31

Lost to follow-up N=2

29

Table 1 Patient characteristics.

Patient Characteristics

Patient Group

Total population, N

301

Age (range)

1 mo.-18 yrs.

Sex, no. (%) Female

147 (48.8)

Focal seizures, no. (%)

211 (70.1)

Generalized seizures, no. (%)

88 (29.2)

We also excluded neonates under the age of 30 days and patients with acute symptomatic seizures, defined as events occurring in close temporal relationship with an acute central nervous system insult, which may be metabolic, toxic, structural, infectious, or due to inflammation.7

Initial monotherapy, no. (%)

Chart review was conducted to obtain Levetiracetam 198 (65.8) information on initial Oxcarbazepine 48 (15.9) medication as well as patient age, sex, medEthosuximide 13 (4.3) ical history, type of seizures (focal, genPhenobarbital 10 (3.3) eralized, or undeterOther* 32 (10.6) mined), epilepsy syndrome (if available), *Valproic Acid, Fosphenytoin, Lamotrigine, EEG, magnetic resoTopiramate, Adrenocorticotropin Hormone, or Phenytoin nance imaging (MRI) results, side effects, reduction in seizure frequency, and continuation on the initial monotherapy or switch to a second medication. Seizure type was defined by the revised terminology of the ILAE.8 The study was approved by GHS’ Institutional Review Board.

A descriptive analysis was performed to provide a safety and effectiveness profile of levetiracetam as initial monotherapy in our study population. We evaluated based on intention to treat in our analysis. Comparisons of outcomes across seizure types and treatment groups were made using Chi-square tests, and where appropriate due to small numbers, Fisher’s exact test. An alpha-level of .05 was used to determine statistical significance.

Results Patient Population The study population included 301 pediatric patients with new-onset seizures. Patient characteristics are described in Table 1. Approximately 70% of patients had focal seizures and 29.2% had generalized seizures (1% were undetermined).

Over a quarter of patients were experiencing multiple seizures per day. Most patients (65.8%) were initially treated with levetiracetam monotherapy, followed by oxcarbazepine (15.9%) and ethosuz-

30

imide (4.3%). Four patients were lost to follow-up during the study period and were not included in the outcomes analysis.

Levetiracetam Levetiracetam was administered with a mean maximum dose of 38 mg/kg/day divided 2 or 3 times daily (range: 4-100 mg/kg/day). Of the 196 patients in the outcomes analysis population who were initially treated with levetiracetam, 64.7% demonstrated at least a 50% reduction in seizure frequency; 32.1% were seizure free on this therapy (Fig. 1, Page 29). Fifty-nine percent (116/196) of patients initially treated continued on levetiracetam as a monotherapy throughout the study period; mean retention time was 21.6 months (range: 1-39 months). Among these 116 patients, a significant majority (84.4%) received ≥50% reduction in seizures and almost half (44.8%) were seizure free.

Forty-four of the patients initially treated discontinued levetiracetam during the study follow-up period; all but 3 (93%) of these patients switched to a different medication. Oxcarbazepine was the most common medication to replace levetiracetam as monotherapy (45.5%), followed by topiramate (20.5%). Of the patients who discontinued use of levetiracetam, 28 patients (63.6%) did so due to side effects, the majority of which were related to behavioral problems (96.4%); the remaining 16 patients (36.4%) discontinued because of the drug’s ineffectiveness. Prior to discontinuation, the drug showed effectiveness for some of the patients unable to tolerate it due to side effects, as half of the patients (14/28) experienced ≥50% reduction in seizure frequency, and 32.1% were seizure free.

Of those not started on levetiracetam as initial monotherapy, 30% switched to levetiracetam as second treatment. Thus, 76.1% of our study population was on levetiracetam as monotherapy at some point during the study period.

Comparative Analysis In patients with focal-onset seizures, responder rate was similar between levetiracetam and oxcarbazepine (63.3% vs. 53.4%, P = .26). Seizure freedom rate was also similar between these patient groups (34.5% vs. 30.4%, P = .66). In patients with generalized seizures, two thirds were placed on levetiracetam as initial monotherapy. The response rate in this group was 69.6%; 25.0% were seizure free on levetiracetam. A majority (61.1%) of levetiracetam initial monotherapy patients with generalized seizures continued on levetiracetam as initial monotherapy.

GHS Proc. May 2016; 1 (1): 28-31

LEVETIRACETAM INITIAL MONOTHERAPY Patients with multiple seizures per day were less likely to become seizure free on levetiracetam monotherapy than those without (15% vs. 41%; P < .01), but there was no difference in responder rate of those who experienced ≥50% reduction in seizure frequency (67% vs. 65%, P = .84).

Discussion There is a striking lack of data on initial monotherapy choices in pediatric epileptic populations. This deficit leads to medication choices typically based only on side effects and ease of administration.

The benefits of ease of administration (including liquid preparation), no mandated laboratory evaluations, and lack of medication interactions make levetiracetam a frequent initial monotherapy in our practice. Clinical decisions were made to treat with an initial antiepileptic medication based on diagnosis of 2 seizures or more, or 1 first seizure with a high risk for recurrence, such as a lesion on cerebral imaging, a focal neurological deficit, based on ictal symptomatology, or a pathological EEG (either for interictal epileptiform discharges or focal slowing). As a primary referral center, we were able to accumulate a large number of patients with new-onset seizures. We are thus well positioned to evaluate initial monotherapy medication trials in comparison to larger centers that treat more complex patients.

We evaluated the efficacy of levetiracetam as defined by responder rate (≥50% reduction in seizure frequency), seizure freedom rate, and retention on levetiracetam. There was an excellent responder rate at 84% with ≥50% reduction

in seizures and 45% seizure freedom rate. The majority of patients (59%) started on levetiracetam as initial monotherapy remained on that medication throughout the study period of up to 39 months, with a mean retention time of 21.6 months. We also evaluated the reason for discontinuation of levetiracetam as initial monotherapy, with specific attention to failure of efficacy or side effects. Two-thirds (64%) of patients who discontinued levetiracetam stopped because of side effects and one-third (36%) because of ineffectiveness. In patients with focal-onset seizures, there was no significant difference in 50% reduction in seizures between levetiracetam (63%) compared to oxcarbazepine (54%), which is frequently prescribed as first-line therapy for focal-onset seizures.

Overall, our study had a better responder rate than had been reported in other trials (84%), but also a higher incidence of side effects at 32%.

Levetiracetam was successful as initial monotherapy in the majority of the patients based on retention time, responder rate, and side effects. The present study was observational in nature. While our study demonstrates safety and effectiveness of levetiracetam in pediatric epilepsy patients, future research should include randomized trials of initial monotherapy options including levetiracetam.

Abbreviations and Acronyms ILAE = International League Against Epilepsy GHS = Greenville Health System EEG = electroencephalogram MRI = magnetic resonance imaging

Correspondence Address to: Addie S. Hunnicutt, MD Greenville Health System, Pediatric Neurology 200 Patewood Dr Suite A350 Greenville, SC 29615 (ahunnicutt@ghs.org)

Conclusion Overall, levetiracetam appears safe and effective as initial monotherapy in pediatric patients with new-onset seizures.

References 1. Verrotti A, D’Adamo E, Parisi P, Chiarelli F, Curatolo P. Levetiracetam in childhood epilepsy. Pediatr Drugs.

2010;12:177-86.

2. Wheless JW. Levetiracetam in the treatment of childhood epilepsy. Neuropsychiatr Dis Treat. 2007; 3:409-21.

3. Khurana DS, Kothare SV, Valencia I, Melvin JJ, Legido A. Levetiracetam monotherapy in children with epilepsy. Pediat Neurol. 2007;36:227-30.

4. Stephen LJ, Kelly K, Parker P, Brodie MJ. Levetiracetam monotherapy—outcomes from an epilepsy clinic.

Seizure. 2011;20:554-7.

5. Rosenow F, Schade-Brittinger C, Burchardi N, et al.

The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalized epilepsy—an open-label, pro-

GHS Proc. May 2016; 1 (1): 28-31

spective, randomized controlled multicenter study. J Neurol Neurosurg Psychiatry. 2012;83:1093-8.

6. Glauser T, Ben-Menachem E, Bourgeois B, et al.

Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia.

2013;54:551-63.

7. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia. 2010;51:671-5.

8. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia.

2010;51:676-85.

31

Original Research

Discharge mEdication reconciliation by Pharmacists to improve Transitions following Hospitalization (DEPTH) Rebecca T. Sawyer, PharmD, BCPS; Jessica M. Odom, PharmD, BCPC, BC-ADM; Jasmine Jennings, PharmD, BCPS; Julianne Orr, PharmD; and Anna L. Cass, PhD From the Department of Pharmacy, Greenville Health System, Greenville, SC (R.T.S., J.M.O, J.J., J.O.), and University of South Carolina School of Medicine Greenville, Greenville, SC (A.L.C.)

Abstract Background: Study objectives were to evaluate readmission rates and cost avoidance associated with pharmacist-led discharge medication reconciliation.

Methods: This prospective, cohort pilot study was conducted from September through October 2012.

Patients eligible were adults with more than 1 discharge medication. During this pilot phase, only patients seen by hospitalist physicians on the pulmonary unit and discharged between 8:00 am and 4:00 pm on Monday through Friday received pharmacist-led medication reconciliation. The primary outcomes included the number and type of pharmacist intervention and the potential cost avoidance associated with the intervention. Secondary outcomes included change in 30-day readmission rates and change in HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey scores.

Results: Fifty-eight patients were included for receiving pharmacy-led discharge medication reconciliation. Sixty patients discharged from the same unit during the study period did not meet inclusion criteria and served as the comparison group. There were 116 recommendations across the 58 patients in the intervention population. Seventy-four of 116 recommendations (63.7%) were accepted by the physician. The total cost avoidance of all the recommendations was estimated to be $66 192. Seventeen percent of patients receiving pharmacy-led discharge medication reconciliation were readmitted to our institution within 30 days of hospital discharge, which was not statistically different from the comparison group. No significant difference was seen between HCAHPS scores in the 2 groups.

Conclusions: Pharmacists have a valuable role in the discharge medication reconciliation process.

Pharmacistsâ&#x20AC;&#x2122; interventions at discharge can contribute to more interdisciplinary collaboration and prevent unnecessary medication costs.

S

everal studies have linked poor medication reconciliation to increased adverse drug events (ADEs) and a rise in hospital and emergency department (ED) readmissions.

Unplanned hospital readmissions continue to be an outcome measure used to evaluate the quality of hospital care. One in 5 hospitalized Medicare beneficiaries is readmitted within 30 days of discharge, leading to increased healthcare costs, averaging $17.4 billion in 2004.1 Both the Joint Commission and Centers for Medicare & Medicaid Services (CMS) have focused on reducing readmission rates and have included medication

32

reconciliation as an important component in achieving that goal. The Joint Commission has outlined the following 5 steps as essential elements to completing medication reconciliation: 1) obtain a home medication list, 2) obtain a list of medications to be prescribed during the hospitalization, 3) compare the 2 lists, 4) identify and resolve discrepancies, and 5) communicate any changes to the patient or caregivers.2 The importance of admission medication reconciliation is well documented in the literature.

Previous studies have indicated that more than GHS Proc. May 2016; 1 (1): 32-37

DEPTH STUDY 50% of patients have more than 1 unintended medication discrepancy on admission.3 It is also estimated that incomplete medication histories at the time of admission contribute to as many as 27% of all hospital prescribing errors.4 While admission errors are quite common, some studies suggest that medication errors at the time of discharge may lead to even more ADEs.5-6 A review of literature has shown that pharmacists’ involvement at the time of admission and discharge has resulted in decreased medication errors and ADEs, decreased readmissions, decreased ED visits, and improvement in patient understanding and compliance with medications.7-14 While the medication reconciliation process is often limited to nurses and physicians, pharmacists are ideal candidates to identify drug-related problems, dosage errors, disease-state interactions, and drug interactions. We evaluated the impact of incorporating pharmacists in the medication reconciliation process, evaluating the number and type of pharmacist interventions, potential cost savings, readmission rates, and patient satisfaction scores.

Methods Study Setting This prospective, cohort pilot study was conducted from September through October 2012 at a 750-bed academic medical center with an estimated 100 admissions and discharges daily. At the time the study was conducted, the pharmacy department consisted of 70 pharmacists, including 15 clinical pharmacy specialists. The staffing model included a 24-hour centralized pharmacy for distribution and several satellite pharmacies throughout the hospital. Clinical pharmacy specialists currently service 12 medical groups in the inpatient and outpatient settings. Staff and clinical pharmacists participate in daily multidisciplinary discharge rounds in order to help identify obstacles to patient discharge.

This institution has historically utilized nurses as the primary healthcare providers to conduct medication histories and perform discharge counseling.

In January of 2012, pharmacists began performing medication histories on 6 of 12 nonintensive care units. At the time of this study, pharmacists were only involved in discharge counseling for anticoagulants. Physicians were responsible for admission and discharge medication reconciliation.

Study Design and Outcomes This study evaluated the implementation of a pharmacist-led medication reconciliation process.

Patients eligible for this process were adults (>18 GHS Proc. May 2016; 1 (1): 32-37

years of age) with more than 1 discharge medication. During this pilot phase, only patients seen

by Hospitalist physicians on the pulmonary unit and discharged between 8:00 am and 4:00 pm on Monday through Friday received pharmacist-led medication reconciliation. Patients admitted to Hospitalist Services during the study period and discharged after hours or during the weekends received standard physician-led medication reconciliation and served as a comparison group. The

Table 1 Baseline patient characteristics.

Patient Characteristics

Intervention Group (N = 58)

Comparison Group (N = 60)

Sex, no. (%) Male

.47 30 (51.7)

35 (58.3)

Race, no. (%) African American

P Value

.32 15 (25.9)

11 (18.3)

1 (1.7)

0 (0.0)

42 (72.4)

49 (81.7)

Public

32 (55.2)

41 (68.3)

.14

Private

12 (20.7)

19 (31.7)

.18

None

14 (24.1)

10 (16.7)

.31

4 (8.3)

5 (6.9)

1.00

42 (72.4)

48 (80.0)

.33

3 (5.2)

5 (8.3)

.72

Endocrine/Electrolytes/Fluid

22 (37.9)

30 (50.0)

.19

Gastrointestinal

16 (27.6)

19 (31.7)

.63

Oncology

19 (32.8)

22 (36.7)

.66

Neurology/Psychology

35 (60.3)

26 (43.3)

.06

Pulmonary

17 (29.3)

28 (46.7)

.05

Renal/Urology

30 (22.4)

16 (26.7)

.59

Age, mean ± SD, years

61 ± 15.4

65 ± 14.3

.16

LOS, median, days, (25th & 75th percentiles)

7 (5, 11)

6 (4, 10)

.33

0.5 (0, 2)

1 (0, 3)

.15

Hispanic Caucasian Insurance type, no. (%)

Hospital sponsored Previous medical history, no. (%) Cardiovascular disease Dermatology

Prior hospitalizations in 12 months prev, median (25th & 75th percentiles)

33

study was approved by the Institutional Review Board and met the criteria for a waiver of the requirement for written consent.

A group of pharmacists and pharmacy representatives performed data collection, including patient demographics (age, sex, past medical history), total number of discharge medications, length of hospital stay (LOS), and date/reason for readmission (if applicable) for patients admitted during the study period. The team focused on obtaining accurate patient medication histories when patients were admitted. For patients admitted during the study period, discharge medication reconciliation was conducted either by the physician or by the physician and pharmacist prior to discharge.

Discharge medication reconciliation as performed by the pharmacist consisted of comparing the discharge medication list to the admission medication list as well as reviewing the discharge list for drug-related problems, dosage errors, disease-state interactions, drug interactions, and drug allergies.

All identified discrepancies were reviewed with the discharging physician prior to discharge.

The number, type, and acceptance rates of pharmacist interventions were recorded. Interventions made by pharmacists to discharge medications were categorized as follows: drug interactions, prevention or management of a drug allergy, adjustment of a dose or frequency, addressing an untreated diagnosis, prevention or management of an adverse drug event, lack of drug indication, and/or duplication of therapy. The amount of time spent on each patient by the pharmacist or phar-

Table 2 Cost avoidance associated with pharmacist interventions.

Type of Recommendation Drug interaction

Average Cost Number of Avoided per Recommendations Recommendation (% of total) ($)

Total Cost Avoided ($)

1 (1.5)

1647

1647

23 (33.8)

1106

25 438

Duplicate therapy

7 (10.3)

165

1155

Drug allergy

0 (0.0)

1375

0

Prevent ADE

10 (14.7)

1098

10 980

Adjust dose/frequency

16 (23.5)

1188

19 008

Drug not indicated

11 (16.2)

724

7964

Untreated diagnosis

Total cost savings

34

66 192

macy representative was documented. The primary outcomes of this study included the number and type of pharmacist intervention and the potential cost avoidance associated with the intervention. Secondary outcomes included change in 30-day readmission rates and change in HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey scores.

Statistical Analysis Chi-square tests or Fisherâ&#x20AC;&#x2122;s exact tests were used for categorical variables where percentages are reported. For continuous variables with normal distribution, a t-test was used for comparisons.

Wilcoxon rank-sum test was used for comparisons when continuous variables were not normally distributed. Potential cost avoidance associated with the interventions was calculated based on the findings of a Veterans Affairs (VA) model.15 The VA study calculated average cost savings per each intervention category. The categories and average cost savings outlined in the VA study were used to calculate the cost avoidance for this study.

Results Study Cohort During the study period, 58 patients met the inclusion criteria for receiving pharmacy-led discharge medication reconciliation. Patients in the comparison group (N = 60) were discharged from the same unit during the study period but did not meet inclusion criteria. Both groups were comparable with regard to baseline characteristics of age, sex, race, insurance type, previous medical history, and number of hospitalizations in the previous year (Table 1, Page 33). The pharmacy intervention and comparison groups also experienced comparable hospital LOS (P = .33).

Pharmacy Intervention Pharmacists obtained an updated record of home medications for all patients upon admission, including those who did not receive pharmacy-led discharge medication reconciliation. This process took an average of 17 minutes per patient [median 16; interquartile range (IQR) 9.5, 23], the longest of any of the other components of the medication reconciliation process. Other elements of medication reconciliation occurred shortly before discharge and were conducted for intervention patients only. For these patients, pharmacists spent an average of 8 minutes reconciling medications (median 7.5; IQR 5, 10), 5 minutes per patient answering patient questions (median 5; IQR 2, 10), 6 minutes contacting another provider

GHS Proc. May 2016; 1 (1): 32-37

DEPTH STUDY (median 5; IQR 5, 5), and 11 minutes counseling patients (median 10; IQR 10, 15). These individual components added up to an average of 21 minutes per patient (median 15; IQR 10, 31.5).

Using the average of 21 minutes of pharmacist time spent per patient, we calculated that 20.3 hours of pharmacist time was utilized on 58 patients in this study. Based on the national average salary for a pharmacist ($54.51/hour) in 2012, the total pharmacy cost associated with this project was $1106.55, or $19.08 per patient.16 The process resulted in a median of 1 recommendation per patient, with a maximum of 12 recommendations per patient. There were a total of 116 recommendations across the 58 patients in the intervention population. Seventy-four of 116 (63.7%) recommendations were accepted by the physician. Thirty-eight patients (66%) had at least 1 recommendation from the pharmacist. The discharging physician accepted all pharmacy recommendations for 55% (21/38) of these patients and at least 1 of the pharmacy recommendations for 76% (29/38) of patients.

Patients receiving pharmacy-led discharge medication reconciliation were discharged with a median of 12.5 medications (IQR 7, 17). This was similar to patients in the comparison arm (median 11; IQR 5, 15).

Seventeen percent of patients receiving pharmacy-led discharge medication reconciliation were readmitted to our institution within 30 days of hospital discharge. This was similar to the readmission rates among the patients on the same unit during the study period who did not receive pharmacy-led discharge medication reconciliation (18%). Seventeen percent of the patients in the intervention group returned to the ED within 30 days, while 7% of patients in the comparison group had an ED visit in the same period.

Cost Avoidance Potential cost avoidance was estimated based on a VA model.15 Table 2 provides data on the 7 types of interventions made by the pharmacist during the study period and the cost avoidance associated with each intervention. Twenty-three recommendations were made to address an untreated diagnosis; thus, yielding the highest estimated cost avoidance ($25 438). The total cost avoidance of all the recommendations was estimated to be $66 192. Therefore, the average cost avoidance per intervention patient was $1141.24.

GHS Proc. May 2016; 1 (1): 32-37

HCAHPS Scores HCAHPS scores are determined based on patients’ answers to questions from a survey after discharge. The 2 questions that pertain to medications are “Did the staff tell you what the new medication was for?” and “Did the staff describe medication side effects?” The patient can answer “never, sometimes, usually, or always.” Scores indicate the percentage of time the patient responded “always.”

Because the nature of the data did not allow for a comparison of HCAHPS scores between patients who did and did not receive medication reconciliation from a pharmacist during the study period, we used HCAHPS scores from the same months in the previous year for comparison. Table 3 compares HCAHPS scores for the pulmonary medicine unit from October and November of 2011 and 2012. Our data did not suggest any difference between HCAHPS scores from 2011 and 2012 when this study was conducted.

Discussion This study demonstrated the value of pharmacists in medication reconciliation at discharge through the number of recommendations from pharmacists accepted by physicians and the respective cost avoidance. Due to the difficulty in quantifying the value of these interventions, a VA model was

Table 3 Comparison of HCAHPS survey scores for the pulmonary unit.

HCAHPS Question Were you given a medication that you haven’t taken before?

Did the staff tell you what the new medication was for?

Did the staff describe medication side effects?

Patient Response

September 2011 N (%)

October 2011 N (%)

September 2012 N (%)

October 2012 N (%)

Yes

12 (92)

25 (74)

6 (67)

13 (81)

No

1 (8)

9 (26)

3 (33)

3 (19)

Never

1 (7)

1 (4)

0 (0)

0 (0)

Sometime

0 (0)

5 (20)

0 (0)

1 (7)

Usually

1 (7)

5 (20)

0 (0)

3 (20)

Always

13 (87)

14 (56)

7 (100)

11 (73)

Never

4 (27)

7 (29)

0 (0)

3 (21)

Sometimes

1 (7)

5 (21)

0 (0)

0 (0)

Usually

4 (27)

6 (25)

3 (50)

4 (29)

Always

6 (40)

6 (25)

3 (50)

7 (50)

35

Abbreviations and Acronyms HCAHPS = Hospital Consumer Assessment of Healthcare Providers and Systems ADE = adverse drug events ED = emergency department VA = veterans affairs

Correspondence Address to: Rebecca Sawyer, PharmD, BCPS, Medication Safety Officer Greenville Health System, Department of Pharmacy 701 Grove Rd, Greenville, SC 29605 (rsawyer@ghs.org)

chosen to assess cost savings. That study demonstrated considerable cost avoidance through the pharmacists’ interventions and recommendations. Estimations of cost avoidance may differ for private or public institutions outside the VA model. However, the authors believe applying this model to the study population still demonstrates the value of pharmacy services. Although we did not calculate the cost associated with reducing the amount of time spent by physicians or nurses at the time of discharge, we did look at 2 important elements related to cost of implementation. While the cost avoidance associated with pharmacists’ recommendations was substantial, the cost associated with the time spent by pharmacists was relatively minimal. The cost avoidance seen in our study was similar to the cost avoidance seen in the study by Wilkinson et al.10 Another point of interest in the current study is that there were more discharge medications in the intervention group than the comparison group (723 vs. 661). Although this study was not randomized, comparable baseline characteristics suggested the non-intervention group was an appropriate comparison group. An increase in discharge medications could suggest that pharmacists were able to successfully intervene on an untreated or inadequately treated diagnosis during the medication reconciliation process and possibly prevent future ADEs. Additionally, the high rate of acceptance of pharmacists’ recommendations shows the physicians at this institution are willing to accept pharmacists’ involvement in the medication reconciliation process.

Limitations Although medication reconciliation has been widely embraced as an important function to improve patient safety, studies have been mixed in proving that this aspect alone reduces 30-day readmissions. Our results agreed with the findings of a meta-analysis by Kwan et al, in which the authors concluded that discharge medication reconciliation alone did not reduce 30-day readmissions.17 The authors hypothesized that many errors, such as omissions of home medications, may not result in an immediate rehospitalization but rather may have longer term effects. They suggested that looking beyond 30 days may be more appropriate to assess readmissions.

While HCAHPS scores are increasingly used as quality measures, this data source has significant limitations in evaluating the impact of improvement efforts. A secondary endpoint for this study was the effect pharmacists’ involvement at 36

discharge would have on the HCAHPS medication-related scores on the pulmonary medicine unit. However, due to the fact that HCAHPS surveys are anonymous, the scores for the intervention group and the comparison group are mixed.

Also, HCAHPS scores encompass all patients discharged from the nursing unit, and this study only focused on patients in Hospitalist Services.

Finally, this study did not focus on the education component of discharge medication reconciliation and only a small proportion of the intervention group received education from a pharmacist.

At our institution, most medication education is completed by nurses during medication administration and at discharge. Without direct pharmacist involvement, it may be difficult to impact HCAHPS scores.

Although the limited scope of the current study may have prevented us from observing a clinically relevant impact, valuable insights were gained on implementing a new pharmacy process. Poor communication and lack of access to discharge medication lists before discharge paperwork was completed proved to be major barriers to pharmacists’ involvement at the time of discharge.

The pharmacist recommendation rejection rate of 36.3% can largely be attributed to the timing of the pharmacist intervention to the completion of discharge paperwork. Recommendations were more likely to be accepted by physicians if made earlier in the discharge process. To have direct involvement in the discharge process, pharmacists need to be available on each nursing unit to make interventions before discharge paperwork is finalized.

In the current departmental model, 1 pharmacy satellite cares for numerous nursing units within close proximity, but pharmacists are not physically present on each unit. Pharmacists must be available at the time of discharge to reconcile medications, provide recommendations, and potentially provide education without delaying patient discharge. To be successful in the discharge process, the pharmacy department would need to make significant changes to the current practice model.

Conclusion Pharmacists have a valuable role in the discharge medication reconciliation process. Pharmacists’ interventions at discharge can contribute to more interdisciplinary collaboration, as well as prevent unnecessary medication costs. In the era of Accountable Care Organizations and emphasis on providing high-quality, evidence-based, and affordable health care, pharmacists can lead the way in providing effective transitional care.

GHS Proc. May 2016; 1 (1): 32-37

DEPTH STUDY

References 1. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med. 2009;360:1418-28.

2. The Joint Commission. National patient safety goals. http://www.jointcommission.org/assets/1/18/NPSG_ Chapter_Jan2012_HAP.pdf Accessed on June 20, 2012.

3. Vira T, Colquhoun M, Etchells E. Reconcilable differences: correcting medication errors at hospital admission and discharge. Qual Saf Health Care.

2006;15:122-6.

4. Dobrzanski S, Hammond I, Khan G, Holdsworth H. The nature of hospital prescribing errors. Br J Clin Govern. 2002;7:187-93.

5. Varkey P, Cunningham J, O’Meara J, Bonacci R, Desai N, Sheeler R. Multidisciplinary approach to inpatient medication reconciliation in an academic setting. Am J Health-Syst Pharm. 2007;64:850-4.

6. Unroe KT, Pfeiffenberger T, Riegelhaupt S, Jastrzembski J, Lokhnygina Y, Colón-Emeric C. Inpatient medication reconciliation at admission and discharge: a retrospective cohort study of age and other risk factors for medication discrepancies. Am J Geriatr Pharmacother. 2010;8:115-26.

7. Murphy EM, Oxencis CJ, Klauck JA, Meyer DA, Zimmerman JM. Medication reconciliation at an academic medical center: implementation of a comprehensive program from admission to discharge. Am J Health-Syst Pharm. 2009;66:2126-31.

8. Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program.

Arch Intern Med. 2009;169:2003-10.

9. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166:565-71.

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10. Wilkinson ST, Pal A, Couldry RJ. Impacting readmission rates and patient satisfaction: results of a discharge pharmacist pilot program. Hosp Pharm.

2011;46:876-83.

11. Calabrese AT, Cholka K, Lenhart SE, et al. Pharmacist involvement in a multidisciplinary inpatient medication education program. Am J Health-Syst Pharm.

2003;60:1012-8.

12. Cornish PL, Knowles SR, Marchesano R, Tam V, Shadowitz S, Jurrlink DN, Etchells EE. Unintended medication discrepancies at the time of hospital admission. Arch Intern Med. 2005;165:424-9.

13. Koehler BE, Richter KM, Youngblood L, Cohen BA, Prengler ID, Cheng D, Masica Al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4:211-8.

14. Lu Y, Clifford P, Bjorneby A, Thompson B, VanNorman S, Won K, Larsen K. Quality improvement through implementation of discharge order reconciliation. Am J Health-Syst Pharm. 2013;70:815-20.

15. Lee AJ, Boro MS, Knapp KK, Meier JL, Korman NE. Clinical and economic outcomes of pharmacist recommendations in a Veterans Affairs medical center.

Am J Health-Syst Pharm. 2002;59:2070-7.

16. US News and World Reports. Best healthcare jobs.

Pharmacist: salary. http://money.usnews.com/ careers/best-jobs/pharmacist/salary Accessed on Sept 2, 2013.

17. Kwan JL, Lo L, Sampson M. Medication reconciliation during transitions as a patient safety strategy.

Ann Intern Med. 2013;158:397-403.

37

Review Article

Modern Management of Abdominal Wall Hernias Jeremy A. Warren, MD; William S. Cobb IV, MD; and Alfredo M. Carbonell II, DO From the Department of Surgery and Division of Minimally Invasive Surgery, (J.A.W., W.S.C., A.M.C.); The Hernia Center, Greenville, SC (J.A.W., W.S.C., A.M.C.); and University of South Carolina School of Medicine Greenville, Greenville, SC (J.A.W., W.S.C., A.M.C.)

A

lthough one of the most commonly performed operations in the United States (US), much debate exists regarding the optimal approach for ventral hernia repair (VHR).

Over 4 million laparotomies are performed annually, with a resulting incisional hernia rate of 20% or higher.1,2 Nearly 350 000 hernia repairs were performed in 2006, excluding the federal Veterans Affairs system, with a significant annual increase in inpatient cases over the previous 5 years.2 Mesh herniorrhaphy is clearly superior to suture repair alone, the latter resulting in a 63% recurrence rate.

Recurrence after mesh repair, however, remains as high as 32% in long-term follow-up,1 in spite of the many advances made in mesh materials, surgical technique, and perioperative care.

Meaningful interpretation of the hernia literature is difficult due to the innumerable combinations of surgical approach, operative technique, mesh selection, mesh fixation method, mesh position, and perioperative management. Heterogeneity of study populations, lack of long-term follow-up, and non-standard language used in reporting techniques and outcomes add to the difficulty. The majority of studies report outcomes over 1-2 years, with relatively few reporting results 5 or 10 years after repair. Wound complications are frequently cited outcomes for VHR, but can encompass a wide range of events, depending on the study. The Centers for Disease Control and Prevention (CDC) has specific definitions for surgical site infections (SSI), including classification into superficial, deep, and organ space infections. Surgical site occurrence (SSO) is a broader term that encompasses all SSIs, as well as other wound events that incur morbidity, but do not meet the criteria for infection, such as seroma, hematoma, skin dehiscence, skin necrosis, cellulitis, and suture granuloma/abscess. Mesh position in the abdominal wall has a significant impact on postoperative complications, including recurrence, but is often inadequately reported in the literature.

38

This article presents an overview of the current state of abdominal wall hernia repair techniques and prevention, including recent advances and quality initiatives that hold promise to standardize and improve outcomes of this common surgical procedure.

Indication for Surgery Apart from asymptomatic, small umbilical defects measuring less than 2 cm and containing only fat, most abdominal wall hernias warrant surgical repair, as long as the patient is medically able to tolerate the operation. Watchful waiting is generally safe, and the risk of requiring emergency hernia surgery is approximately 4% over 5 years, though crossover from watchful waiting to elective repair approaches 20%.3 However, the risk for progressively worsening symptoms, acute incarceration, strangulation, and obstruction should be considered since emergent hernia repair confers a significantly higher risk for bowel resection, need for reoperation, hospital readmission, and 30-day mortality.4 Hernias will enlarge over time, becoming increasingly complex and more challenging to repair, which increases the risk for perioperative complications. Surgical repair can be managed in an open fashion, or by a minimally invasive approach with laparoscopy or robotic surgery, depending on patient risk factors, hernia morphology, and surgeon expertise.

Open Surgery Open surgery remains the most common approach, accounting for approximately 75% of cases.5 This approach involves an incision directly over the hernia defect, reduction of herniated contents into the visceral cavity, and closure of the fascial defect with or without mesh reinforcement. This approach is particularly useful for very small, primary hernia defects, such as umbilical and epigastric hernias, as well as for very large hernias that are not amenable to a minimally invasive approach. However, GHS Proc. May 2016; 1 (1): 38-46

MODERN MANAGEMENT OF ABDOMINAL WALL HERNIAS there is great heterogeneity in the specific technical aspects of open VHR (OVHR). Suture repair is appropriate for small primary hernias with acceptable recurrence rates of less than 10%.6,7 For defects larger than 2-3 cm, and most incisional hernias, mesh reinforcement is necessary. Mesh selection among surgeons varies widely, as does its position against the abdominal wall and technique of mesh fixation, which are discussed further below.

Compared to minimally invasive approaches, open hernia repair generally has a higher rate of postoperative SSI and SSO, though this varies according to technique and mesh position.8,9 Various adjuncts to OVHR have also been described to aid in the closure of abdominal wall defects. Often collectively called “component separation,” these include various techniques that separate the musculofascial layers of the abdominal wall to allow sliding of the muscular components back to the midline and decrease tension on the closure. First described by Oscar Ramirez, “component separation” begins with elevation of the skin and subcutaneous tissues off of the anterior abdominal wall fascia, followed stepwise by release of the posterior rectus sheath, then the external oblique aponeurosis to allow reconstruction of the midline fascia. This technique allows for closure of defects up to 20 cm by allowing approximately 8-10 cm medialization of the rectus sheath bilaterally.10 Though effective for defect closure, the technique carries significant morbidity, with nearly half of patients experiencing wound complications.11 Several modifications of the originally described technique, such as minimally invasive component separation12 and endoscopic component separation,13 have been introduced with improvement in wound morbidity. Release of the rectus sheath was actually described by Jean Rives,14 though not previously termed “component separation.” This technique involves separation of the posterior rectus sheath from the rectus muscle, continuing laterally up to the linea semilunaris, and extended superiorly and inferiorly to allow mesh overlap of the hernia defect. The posterior sheath is then closed, thus excluding the viscera; mesh is placed behind the muscle (“sublay”), and the anterior midline fascia is closed over the mesh. If additional mobilization is required, a transversus abdominis release (TAR) may be performed, which involves division of the transversus abdominis muscle and fascia with dissection of the plane between the muscle and peritoneum laterally.15 This minimizes subcutaneous dissection, allows myofascial release to decrease midline tension, and permits wide mesh coverage in a well vascularized compartment separated from the visceral cavity. Many hold this as the gold stanGHS Proc. May 2016; 1 (1): 38-46

dard for OVHR, and is the authors’ preferred technique. However, its adoption is relatively low, at an estimated 13%.16 Table 1 summarizes selected studies of OVHR using the Rives-Stoppa technique.

Laparoscopic Surgery Laparoscopic VHR (LVHR) was first described in 1993 by LeBlanc and Booth,17 and was adopted fairly widely, peaking at its current rate of approximately 20%-25% of hernia repairs. LVHR is performed through multiple small incisions peripheral to the hernia defect, with mesh placed against the underside of the abdominal wall, in an intraperitoneal position. Intraperitoneal mesh placement mandates some form of mesh fixation, most commonly with transfascial sutures or tacks, and a barrier coating on the mesh to minimize visceral adhesions. This approach significantly reduces the incidence of SSO and SSI related to hernia repair.9,18-20 Hernia recurrence, however, is essentially unchanged from that of OVHR in several more recent studies with longer follow-up.21-23 Unlike most minimally invasive procedures, LVHR is not necessarily less painful than OVHR.20,22,24 Patient satisfaction and quality of life can be negatively impacted by bridging larger defects with intraperitoneal mesh, resulting in eventration of the mesh through the previous defect (“pseudorecurrence”).24,25 This has been somewhat mitigated by the current trend of transcutaneous closure of the central hernia defect, which also appears to lower the risk of seroma and, possibly, recurrence.26-28 Additionally, there is the potential of long-term morbidity with intraperitoneal mesh,

Table 1 Open Rives-Stoppa ventral hernia repair: selected studies.

Author

Year

Study Type

N

Follow-up (months)

Rives

1992

R

258

McLanahan 1997

R

106

24

Petersen

2004

R

175

20

Israelsson

2006

R

228

12-24

Iqbal

2007

R

254

70

4.0%

7.0%

5.0%

Poghoysan

2012

R

262

58

6.0%

0.8%

3.0%

Mehrabi

2010

R

176

96

1.7%

2.8%

1.1%

Novitsky

2015

P

306

11.8%

15.7%

--

Cobb

2015

R

255

37.7%

19.6%

16.9%

17

SSO

SSI

Recurrence

7.7%

6.2% 3.5%

7.4%

6.3%

9.0% 7.3%

R, Retrospective; P, Prospective

39

including delayed or secondary mesh infection, enteroprosthetic fistula, and complicated adhesiolysis at the time of future operations. As many as 25% of patients will require a subsequent abdominal operation after hernia repair,29 and bowel injury or resection at the time of reoperation in the presence of intraperitoneal mesh occurs in up to 20% of cases.30,31 Postoperative SSI rate after the subsequent operation is also significantly higher and can result in secondary mesh infection.30 Tables 2 and 3 summarize selected literature on LVHR and laparoscopic versus open trials, respectively.

Robotic Surgery More recently, robotic surgery has emerged as an alternative to laparoscopy for minimally invasive hernia repair. The robotic platform affords several benefits, including enhanced 3D visualization, tremor elimination, and articulating instruments.

Published experience with robotic VHR to date essentially reproduces LVHR, with intraperitoneal mesh placement. Robotic technology, however, makes hernia defect closure technically easier to perform intracorporeally, and eliminates the need for multiple additional stab incisions necessary for transcutaneous closure.32 Intraperitoneal mesh securement can also be easily performed with

Table 2 Laparoscopic ventral hernia repair: selected studies.

Author

Year

Study Type

N

Follow-up (months)

SSO

SSI

Recurrence

Bageacu

2002

R

159

49

25.6%

2.9%

15.7%

Berger

2002

R

150

15

92.7%

1.3%

2.7%

LeBlanc

2003

R

200

36

10.0%

0%

6.5%

Carbajo

2003

R

270

44

14.0%

0%

4.4%

Rosen

2003

R

100

30

5.0%

6.0%

17.0%

Heniford

2003

R

850

20.2

3.5%

0.7%

4.7%

Franklin

2004

R

384

47.1

4.2%

0.8%

2.9%

Bower

2004

R

100

6.5

4.0%

0%

2.0%

Cobb

2006

R

277

21

2.1%

0.7%

4.7%

Banerjee

2012

R

193

10.5

NR

2.1%

4.1%

Sasse

2012

R

225

42

17.3%

0.9%

0.9%

Chelala

2014

R

1326

78

6.6%

0.9%

4.7%

Carter

2014

R

201

39

19.9%

13.8%

12.4%

R, Retrospective

40

circumferential suturing of the mesh rather than transabdominal wall sutures or tacks, anecdotally decreasing both early and late pain associated with standard laparoscopic repair. Potential future complications associated with intraperitoneal mesh, however, remain a risk with this approach.

The authors have utilized robotic technology to develop a technique that replicates the open retromuscular (RM) repair, including transversus abdominis release, thus facilitating a true abdominal wall reconstruction and placement of mesh in an extraperitoneal position. The initial experience with this approach was compared to a matched cohort of similar open RM hernia repairs. Twenty-one patients in each arm were compared, with a similar incidence of SSI (9.8% vs. 0%; P = .48), equivalent recurrence rate, and similar direct hospital cost. The hospital length of stay (LOS), however, was significantly shorter following robotic RM repair (2.3 vs. 4.2 days; P = .046). The authors have currently performed over 100 robotic RM hernia repairs, with continued benefit in LOS and SSI.

Prevention In no area of medicine is the adage that â&#x20AC;&#x153;an ounce of prevention is worth a pound of cureâ&#x20AC;? more applicable than in hernia surgery. For the most common complication following a laparotomy, more effort could be placed on reducing the likelihood that an incisional hernia may result. There are known patient factors that contribute to the formation of incisional hernia. Morbid obesity and chronic cough produce significant mechanical stress on the abdominal wall. Collagen synthesis may be impaired by tobacco abuse, poorly controlled diabetes, chronic steroid therapy, and previous wound infection. These factors can often be mitigated when anticipating elective hernia surgery.

Efforts to encourage weight loss and tobacco cessation prior to surgery have been implemented to improve postoperative outcomes. Better control of glucose as measured by the hemoglobin A1C level and treatment of methicillin-resistant Staphylococcus aureus (MRSA) colonization have also been employed to minimize infectious complications.

Unfortunately, it is often very difficult to control these potential patient factors prior to the index surgery that results in hernia formation. Many times, abdominal surgeries cannot be delayed because they are emergent in presentation or the indication for surgery carries some urgency, such as in the case of malignancy. By identifying certain high-risk patients, maneuvers can be utilized at the time of surgery in an effort to minimize the GHS Proc. May 2016; 1 (1): 38-46

MODERN MANAGEMENT OF ABDOMINAL WALL HERNIAS risk of hernia. Patient populations that are at high risk for hernia formation have been identified.

Those patients undergoing open repair of abdominal aortic aneurysms carry an incisional hernia rate greater than 30%. This is most likely due to a genetic defect in collagen, which is present both in the wall of the aorta that becomes aneurysmal and the abdominal wall. Patients undergoing either creation of an ostomy or reversal of an ostomy pose a difficult challenge to the hernia surgeon. The incidence of parastomal hernia formation (development hernia at the ostomy site) varies widely in the literature from 30% to 60%. The incidence rises in studies where incidence is defined by appearance on computed tomography. Some authors argue that by definition an ostomy is a hernia, given that a segment of intestine is being brought through a fascial defect to reach the skin. The concern for hernia is not over for the patient once the ostomy is reversed, as the rates of hernia formation at the prior ostomy site are as high as 35%.33 Two specific closure techniques have been prospectively shown to reduce the incidence of hernia following laparotomy. First, closure of the midline fascia using a small bite technique and a small gauge (2-0) suture with at least a 4:1 sutureto-wound length ratio has now been evaluated in 2 randomized control trials, reducing the hernia rate from 18.0% to 5.6% in one study,34 and 21% to 13% in the second.35 Second, the placement of prophylactic mesh at the time of laparotomy closure in high-risk patients has been shown to reduce incisional hernia formation.

Following open gastric bypass, the use of a biologic mesh to reinforce the laparotomy closure was shown to reduce the incidence of incisional hernia to 2.7% compared to 17.7% in the traditional closure

group without mesh in one study.36 Synthetic mesh has also proven effective in hernia prevention without increased mesh-related complications. A prospective randomized control trial of 107 patients undergoing elective or colorectal surgery demonstrated a reduction in the incidence of hernia from 31.5% to 11.3%, with no difference in SSI.37 Several other studies have also demonstrated the benefits of mesh reinforcement of the midline closure in high-risk patients, with a variety of mesh types and surgical techniques employed.38-40 Further investigation is needed to determine which patients will ultimately benefit from this intervention, as it has the potential for additional cost and morbidity.

Mesh Materials Hernia surgeons are faced with a veritable cornucopia of mesh options, including absorbable synthetic mesh, permanent synthetic mesh, and biologic mesh (Fig. 1, Page 42). Synthetic mesh can be absorbable, or permanent, with or without an adhesive barrier coating. Absorbable mesh is designed for temporary reinforcement of the abdominal wall, often in the setting of wound contamination, and allows native tissue ingrowth with no remaining permanent material in the operative field. The recently published COBRA study, in which the authors were a participating center, is the only published trial of synthetic absorbable mesh in contaminated and clean-contaminated VHR. Incidence of SSO was 28%, with 18% SSIs, and recurrence at 2 years of just 17%.41 This compares very favorably against the similarly designed RICH trial, in which porcine biologic mesh was used for VHR, which reported a 66% SSO rate, and recurrence rate at 2 years of 28%.42 Permanent mesh is composed of polypropylene (PP), polyester (PE), polytetrafluoroethylene

Table 3 Laparoscopic versus open ventral hernia repair: selected trials.

Author

Year

Study Type

N (open)

N (lap)

Open Follow-up SSO Technique (months) (open)

Olmi

2007

P

85

85

RM

24

Itani

2010

RCT

73

73

Onlay

Kurmann

2011

P

56

69

Retrorectus

Colavita

2012

Registry

402

308

PP, IPOM, RM, Onlay, Inlay

Eker

2013

RCT

100

94

Retrorectus

SSO (lap)

SSI (open)

SSI (lap)

2.4%

7.1%

7.1%

1.1%

1.0%

2.0%

24

31.5%

13.7%

23.3%

5.6%

8.2%

12.5%

32.5

5.8%

14.3%

26.8%

5.8%

17.9%

15.9%

10.2%

10.0%

3.2%

0.3%

6.0%

5.2%

19.0%

18.0%

5.0%

4.0%

14.0%

18.0%

35

Recurrence Recurrence (open) (lap)

P, Prospective; RCT, Randomized Control Trial

GHS Proc. May 2016; 1 (1): 38-46

41

(PTFE), or some combination of PP and PTFE. Additionally, PP and PE mesh may have an added barrier coating, designed to decrease visceral adhesion to the mesh and allow intraperitoneal placement for LVHR. Mesh density, weight, and pore size are also important characteristics when choosing mesh for hernia repair. Use of permanent mesh clearly reduces the risk of hernia recurrence,1 and is widely used for clean surgical cases. However, traditional surgical teaching warns against its use in the setting of contamination for fear of mesh infection, reoperations, and mesh removal.

Due to these fears, biologic meshes were developed. Derived from human or animal tissue, biologic mesh theoretically provides an acellular scaffold, which promotes native tissue ingrowth, collagen deposition, and remodeling to strengthen a hernia repair, thus preventing recurrence. They are frequently used in the setting of contamination with the expectation that biologically derived tissue should be more resistant to infection, although this is not an approved indication for use by the US Food and Drug Administration (FDA). Biologic mesh has not proven to be a panacea as it was touted, and current evidence supporting its use is poor. Several studies have shown that SSI and mesh infection occur with similar frequency with both biologic and synthetic mesh.42-46 Equally disappointing is the long-term data that indicate

Figure 1 Mesh options.

Biologic

Porcine Bovine Human

Synthetic

Absorbable

Polyglactin Polyglactin acid + Trimethylene carbonate Poly-4-hydroxyubterate

Permanent

Polypropylene Polyester Polytetrafluoroethylene

With or without barrier coating Oxy regenerated cellulose Polyethylene glycol Omega-3 fatty acid Silicone Hyaluronate-carboxymethylcellulose Monocryl Polydiaxanone Polytetrafluoroethylene Collagen

42

a higher recurrence rate with the use of biologic mesh,42,47 with one study reporting a recurrence rate as high as suture repair (66%).43 These results are particularly discouraging, given the substantially higher cost of biologic compared to synthetic mesh, a difference of almost 200-fold.44 Contrary to traditional surgical dictum, a growing body of evidence suggests that synthetic mesh is actually safe and efficacious in contaminated hernia repair.48-50 The authors have significant experience with synthetic mesh in contaminated hernia repair. In 100 clean-contaminated and contaminated hernia repairs using a RM technique with large-pore PP mesh, the rate of SSI was 7.1% and 19.0%, respectively. Mesh explantation was required in 4 cases, none of which were a direct complication of the mesh or mesh infection.51 Another large retrospective study corroborates these results, even in the setting of intraabdominal sepsis, with an SSI rate of 17.9% without mesh and 26.3% with mesh reinforcement (non-significant difference), and decreasing hernia occurrence from 33.3% to 5.9% with onlay PP mesh reinforcement.40 A recent American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) study evaluated patients undergoing colorectal surgery with concurrent VHR with or without mesh.52 Superficial SSI occurred in 7.3% of patients with mesh repair and 10.5% of meshfree patients, deep SSI in 3.8% and 2.7%, and organ space SSI in 6.5% and 4.2%, respectively (all non-significant differences). Two recent prospective randomized control trials utilizing PP mesh reinforcement after colorectal surgery demonstrated a significant benefit of mesh prophylaxis in hernia prevention, reducing hernia occurrence from 31.5% to 11.3% in one study37 and 35.9% to 1.5% in the second.39 The rate of SSI between mesh and non-mesh groups in both studies was similar (18.9% vs. 33.3% and 6.3% vs. 7.5%, respectively).

Mesh Position The position of mesh placement relative to the abdominal wall is an important factor in both wound morbidity and recurrence. Mesh can be positioned as an onlay, in which a subcutaneous space is created and mesh placed over the closed anterior fascia; as an inlay, in which the mesh is simply sewn to the edge of the fascia around the hernia defect; or as a sublay, in which the mesh is below the rectus muscle. Sublay can be further divided into retromuscular, with mesh positioned directly dorsal to the rectus muscle, but ventral to the posterior rectus sheath, preperitoneal, with mesh positioned between the posterior rectus sheath, and peritoneum, or intraperitoneal (Fig. 2).

GHS Proc. May 2016; 1 (1): 38-46

MODERN MANAGEMENT OF ABDOMINAL WALL HERNIAS Mesh onlay is a straight-forward technique and does not necessitate full entry into the abdominal cavity, making it an appealing option for patients with a potentially hostile abdomen. The approach, however, disrupts the blood supply of the abdominal wall and leaves only adipose tissue and skin above the mesh, resulting in higher wound morbidity compared with sublay, as well as a higher hernia recurrence rate.53-55 Intraperitoneal positioning is the most commonly performed technique.56 While recurrence rates and wound complications are lower than onlay, a tissue-separating (barrier coated) mesh is recommended to decrease visceral adhesions to the mesh. Mesh placed within the abdominal cavity has the potential to complicate future operations and result in delayed or secondary mesh complications, as noted above.

In particular, should a prosthetic infection occur, it is rarely salvageable when placed within the abdominal cavity.57 Inlay of mesh, also referred to as interposition or bridging mesh, results in the highest rates of recurrence and wound complications and should not be performed.

Preperitoneal mesh placement has the benefit of hiding mesh between the layers of the abdominal wall, thus decreasing the chance of visceral adhesions. However, there is no relief of the tension required to close the midline unless some further myofascial release is performed, and the preperitoneal plane can be difficult to dissect, particularly in multiple reoperative cases. Results are favorable, with recurrence rates less than 10% and SSO/SSI rates between 9% and 12%.58,59 Retromuscular repair, as described by Jean Rives, is the authors preferred technique. Not only is the mesh placed in a contained, well-vascularized compartment separated from the viscera, but it also affords myofascial release of the posterior rectus sheath from the rectus muscle and decreases the tension of the midline closure. Most studies report

recurrence rate of less than 10%, with wound events complicating 6% to 20% of cases.19,60

Abbreviations and Acronyms

Quality Improvement in Ventral Hernia Repair

US = United States; VHR = ventral hernia repair; CDC = Centers for Disease Control and Prevention; SSI = surgical site infection; SSO = surgical site occurrence; TAR = transversus abdominis release; OVHR = open ventral hernia repair; LVHR = laparoscopic ventral hernia repair; RM = retromuscular; PP = polypropylene; PE = polyester, PTFE = polytetrafluoroethylene; GHS = Greenville Health System; ACSNSQIP = American College of Surgeons National Surgical Quality Improvement Program; AHSQC = Americas Hernia Society Quality Collaborative

Much attention has been given to improving outcomes in ventral hernia surgery. Focusing efforts to improve surgical outcomes also makes solid financial sense. The estimated total cost for hernia repair in the US is $3.2 billion. A reduction of the recurrence rate after surgical repair of just 1% would translate into $32 million in savings.2 Particular areas of focus for the improvement of hernia outcomes include efforts to optimize patient comorbidities prior to surgery, development of comprehensive centers of excellence, and creation of a national prospective database.

Known modifiable, patient risk factors exist in the literature. Morbid obesity, tobacco use, and glucose control can all have significant effects on postoperative wound outcomes and the longterm durability of the repair. Morbid obesity independently predicts SSI following open incisional hernia repair.61 In a series of patients undergoing LVHR, the recurrence rate is statistically higher in morbidly obese patients (8.4% vs. 2.9%).62 Nicotine significantly reduces the cutaneous and subcutaneous blood flow. The effects on wound healing at the cellular level take 4 weeks to resolve, once the patient stops smoking.63 In a series of patients undergoing complex open hernia repair with mesh, smoking was the only predictor of wound and mesh related complications. Since all the mesh infections occurred in tobacco users, the authors advocate smoking cessation prior to any elective incisional hernia repair.58 Glycemic control is another important modifiable risk factor in hernia surgery. Postoperative hyperglycemia has been shown to be an independent risk factor of SSI following elective general and vascular surgical pro-

Figure 2 Mesh position.

R EO IO TA

Rectus muscle External oblique muscle Interanal oblique muscle Transversus abdominis muscle P Peritoneum a Onlay b Retromuscular c Preperitoneal d Intraperitoneal (IPOM) GHS Proc. May 2016; 1 (1): 38-46

43

Correspondence Address to: Jeremy A. Warren, MD Greenville Health System The Hernia Center 2104 Woodruff Rd Greenville, SC 20607 (jwarren1@ghs.org)

Potential Conflicting Interests Dr Warren and Dr Carbonell have served as consultants for Ethicon Inc. Dr Warren, Dr Cobb, and Dr Carbonell have served as consultants for MAQUET and W. L. Gore & Associates.

cedures. The risk of postoperative wound infection is increased by 30% with every 40-point increase over normoglycema (<110 mg/dL).64,65 Modifying patient factors to maximize outcomes is a crucial component of incisional hernia care.

Some authors have proposed the concept of centers of excellence for hernia care. Improved outcomes have been demonstrated by isolating care to a handful of centers for complex procedures, such as pancreaticoduodenectomy and esophagectomy.66,67 Due to the large volume of incisional hernias repaired every year, an attempt to centralize all care of incisional hernias is not feasible. However, the establishment of comprehensive centers of hernia care has resulted in focusing more complex cases to large volume centers. In one series at a high-volume hernia center, patients traveling greater than 100 miles had larger hernia defects and more active mesh infections.68 In an analysis of the National Inpatient Sample, Colavita and colleagues demonstrated a significant increase in percentage of ventral hernia cases being performed at high-volume centers in 2008-2009, compared to 10 years prior. Although regionalization seems to be occurring with ventral hernia surgery, complications and mortality rates have not significantly improved thus far, and patient comorbidities seem to influence outcome more than volume.69 Similarly, a comprehensive Hernia Center was created at our institution, the first of its kind in South Carolina. Since its inception, there has been a steady increase in the number and complexity of hernia repairs performed annually, with an increasingly wide referral area. The specialization of our practice allows for focused research in the area of hernia repair and abdominal wall reconstruction, along with development of novel techniques, the application of new technology, and standardization of practice for quality improvement. The impact of this approach on patient outcomes, however, remains unknown.

As stated above, the heterogeneity in technique and outcome reporting has contributed to the

difficulty in reaching a consensus on the optimal VHR technique. The numerous possible combinations of technique and material essentially preclude this issue from being settled in any prospective randomized controlled trial. Large database analysis holds much greater promise for truly elucidating proper technique for a given patient in a given situation. However, all of the current national databases, such as the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, University Health System Consortium, Premier Healthcare database, and ACS-NSQIP, are based on administrative data obtained from chart abstraction. This data inherently misses any technical information regarding repair technique, such as mesh selection, mesh position, fixation, fascia closure technique, or component separation technique. The Americas Hernia Society Quality Collaborative (AHSQC) project was formed in 2013 by the Americas Hernia Society, in conjunction with hernia surgeons in both private practice and academic settings. As the most comprehensive and robust hernia database in existence, the AHSQC utilizes concepts of continuous quality improvement to improve patient outcomes and optimize costs. This is accomplished through surgeon and patient-centered data collection, ongoing performance feedback to clinicians, and improvement based on analysis of collected data and collaborative learning. This unique method of collecting data and continuously analyzing outcomes will allow us to answer the question of how best to repair ventral hernias.

Summary Although VHR is among the most commonly performed operations in the US, many questions remain unanswered, and there is little consensus on best practice. Traditional clinical trials are unlikely to answer many of these questions due to the number of variables and possible combinations. Surgeons must carefully and critically review the surgical literature in order to discern the validity of the stated outcomes for their practice.

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GHS Proc. May 2016; 1 (1): 38-46

MODERN MANAGEMENT OF ABDOMINAL WALL HERNIAS thetic mesh vs suture repair of elective primary ventral herniorrhaphy: a systematic review and meta-analysis.

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8. Itani K, Hur K, Kim LT, Anthony T, et al; Veterans Affairs Ventral Incisional Hernia Investigators. Comparison of laparoscopic and open repair with mesh for the treatment of ventral incisional hernia: a randomized trial. Arch Surg. 2010;145:322-8.

24. Liang MK, Clapp M, Li LT, Berger RL, Hicks SC, Awad S. Patient Satisfaction, chronic pain, and functional status following laparoscopic ventral hernia repair.

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9. Hwang CS, Wichterman KA, Alfrey EJ. Laparoscopic ventral hernia repair is safer than open repair: analysis of the NSQIP data. J Surg Res. 2009;156:213-6.

10. Ramirez OM, Ruas E, Dellon AL. “Components separation” method for closure of abdominal-wall defects: an anatomic and clinical study. Plast Reconstr Surg.

1990;86:519-26.

11. Pauli EM, Rosen MJ. Open ventral hernia repair with component separation. Surg Clin North Am. 2013;93:1111-33.

12. Butler CE, Campbell KT. Minimally invasive component separation with inlay bioprosthetic mesh (MICSIB) for complex abdominal wall reconstruction. Plast Reconstr Surg. 2011;128:698-709.

13. Rosen MJ, Williams C, Jin J, McGee MF, Schomisch S, Marks J, Ponsky J. Laparoscopic versus open-component separation: a comparative analysis in a porcine model. Am J Surg. 2007;194:385-9.

14. Rives J, Pire JC, Flament JB, Convers G. Treatment of large eventrations (apropos of 133 cases). Minerva Chir. 1977;32:749-56.

15. Novitsky YW, Elliott HL, Orenstein SB, Rosen MJ. Transversus abdominis muscle release: a novel approach to posterior component separation during complex abdominal wall reconstruction. Am J Surg.

2012;204:709-16.

16. Albino FP, Patel KM, Nahabedian MY, Sosin M, Attinger CE, Bhanot P. Does mesh location matter in abdominal wall reconstruction? A systematic review of the literature and a summary of recommendations.

Plast Reconstr Surg. 2013;132:1295-1304.

17. LeBlanc KA, Booth WV. Laparoscopic repair of incisional abdominal hernias using expanded polytetrafluoroethylene: preliminary findings. Surg Laparosc Endosc. 1993;3:39-41.

18. Itani KMF, Hur K, Kim LT, et al; Veterans Affairs Ventral Incisional Hernia Investigators. Comparison of laparoscopic and open repair with mesh for the treatment of ventral incisional hernia: a randomized trial.

Arch Surg. 2010;145:322-8.

19. Jin J, Rosen MJ. Laparoscopic versus open ventral hernia repair. Surg Clin North Am. 2008;88:1083-100.

20. Pierce RA, Spitler JA, Frisella MM, Matthews BD, Brunt LM. Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of patient data accrual. Surg Endosc. 2007;21:378-86.

21. Colavita PD, Tsirline VB, Belyansky I, Walters AL, Lincourt AE, Sing RF, Heniford BT. Prospective, long-term comparison of quality of life in laparoscopic versus open ventral hernia repair. Ann Surg.

2012;256:714-22;discussion 722-3.

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25. Carter SA, Hicks SC, Brahmbhatt R, Liang MK. Recurrence and pseudorecurrence after laparoscopic ventral hernia repair: predictors and patient-focused outcomes. Am Surg. 2014;80:138-48.

26. Clapp ML, Hicks SC, Awad SS, Liang MK. Trans-cutaneous Closure of Central Defects (TCCD) in laparoscopic ventral hernia repairs (LVHR).World J Surg.

2013;37:42-51.

27. Banerjee A, Beck C, Narula VK, et al. Laparoscopic ventral hernia repair: does primary repair in addition to placement of mesh decrease recurrence? Surg Endosc. 2012;26:1264-8.

28. Chelala E, Baraké H, Estievenart J, Dessily M, Charara F, Allé JL. Long-term outcomes of 1326 laparoscopic incisional and ventral hernia repair with the routine suturing concept: a single institution experience. Hernia. 2015;20:101-10.

29. Snyder CW, Graham LA, Gray SH, Vick CC, Hawn MT. Effect of mesh type and position on subsequent abdominal operations after incisional hernia repair. J Am Coll Surg. 2011;212:496-502.

30. Halm JA, De Wall LL, Steyerberg EW, Jeekel J, Lange JF. Intraperitoneal polypropylene mesh hernia repair complicates subsequent abdominal surgery. World J Surg. 2007;31:423-9.

31. Gray SH, Vick CC, Graham LA, Finan KR, Neumayer LA, Hawn MT. Risk of complications from enterotomy or unplanned bowel resection during elective hernia repair. Arch Surg. 2008;143:582-6.

32. Gonzalez AM, Romero RJ, Seetharamaiah R, Gallas M, Lamoureux J, Rabaza JR. Laparoscopic ventral hernia repair with primary closure versus no primary closure of the defect: potential benefits of the robotic technology. Int J Med Robot. 2015;11:120-5.

33. Bhangu A, Fletcher L, Kingdon S, Smith E, Nepogodiev D, Janjua U. A clinical and radiological assessment of incisional hernias following closure of temporary stomas. Surgeon. 2012;10:321-5.

34. Millbourn D, Cengiz Y, Israelsson LA. Effect of stitch length on wound complications after closure of midline incisions: a randomized controlled trial. Arch Surg. 2009;144:1056-9.

35. Deerenberg EB, Harlaar JJ, Steyerberg EW, et al. Small bites versus large bites for closure of abdominal midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial. Lancet. 2015;386:1254-60.

36. Sarr MG, Hutcher NE, Snyder S, Hodde J, Carmody B. A prospective, randomized, multicenter trial of Surgisis Gold, a biologic prosthetic, as a sublay reinforcement of the fascial closure after open bariatric surgery.

Surgery. 2014;156:902-8.

37. García-Ureña MÁ, López-Monclús J, Hernando LAB, et al. Randomized controlled trial of the use of a large-

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pore polypropylene mesh to prevent incisional hernia in colorectal surgery. Ann Surg. 2015;261:876-81.

38. Hidalgo MP, Ferrero EH, Ortiz MA, Castillo JM, Hidalgo AG. Incisional hernia in patients at risk: can it be prevented? Hernia. 2011;15:371-5.

39. Caro-Tarrago A, Olona Casas C, Jimenez Salido A, et al. Prevention of incisional hernia in midline laparotomy with an onlay mesh: a randomized clinical trial.

World J Surg. 2014;38:2223-30.

40. Argudo N, Pereira JA, Sancho JJ, Membrilla E, Pons MJ, Grande L. Prophylactic synthetic mesh can be safely used to close emergency laparotomies, even in peritonitis. Surgery. 2014;156:1238-44.

41. Rosen MJ, Bauer JJ, Harmaty M, et al. Multicenter, prospective, longitudinal study of the recurrence, surgical site infection, and quality of life after contaminated ventral hernia repair using biosynthetic absorbable mesh.

The COBRA Study. Ann Surg 2016, Epub ahead of print.

42. Itani KMF, Rosen M, Vargo D, et al; RICH Study Group. Prospective study of single-stage repair of contaminated hernias using a biologic porcine tissue matrix: the RICH Study. Surgery. 2012;152:498-505.

43. Abdelfatah MM, Rostambeigi N, Podgaetz E, Sarr MG. Long-term outcomes (>5-year follow-up) with porcine acellular dermal matrix (Permacolâ&#x201E;˘) in incisional hernias at risk for infection. Hernia. 2015;19:135-40.

44. Fischer JP, Basta MN, Mirzabeigi MN, Kovach SJ 3rd. A comparison of outcomes and cost in VHWG grade II hernias between Rives-Stoppa synthetic mesh hernia repair versus underlay biologic mesh repair. Hernia.

2014;18:781-9.

45. Primus FE, Harris HW. A critical review of biologic mesh use in ventral hernia repairs under contaminated conditions. Hernia. 2013;17:21-30.

46. Cross W, Kumar A Chandru Kowdley G. Biological mesh in contaminated fields-overuse without data: a systematic review of their use in abdominal wall reconstruction. Am Surg. 2014;80:3-8.

47. Rosen MJ, Krpata DM, Ermlich B, Blatnik JA. A 5-Year clinical experience with single-staged repairs of infected and contaminated abdominal wall defects utilizing biologic mesh. Ann Surg. 2013;257:991-6.

48. Bessa SS, Abdel-Razek AH. Results of prosthetic mesh repair in the emergency management of the acutely incarcerated and/or strangulated ventral hernias: a seven years study. Hernia. 2013;17:59-65.

49. Birolini C, Utiyama EM, Rodrigues AJ, Birolini D. Elective colonic operation and prosthetic repair of incisional hernia: does contamination contraindicate abdominal wall prosthesis use? J Am Coll Surg.

2000;191:366-72.

50. Kelly ME, Behrman SW. The safety and efficacy of prosthetic hernia repair in clean-contaminated and contaminated wounds. Am Surg. 2002;68:524-8;discussion 528-9.

51. Carbonell AM, Criss CN, Cobb WS, Novitsky YW, Rosen MJ. Outcomes of synthetic mesh in contaminated ventral hernia repairs. J Am Coll Surg. 2013;217:991-8.

52. Benlice C, Gorgun E, Aytac E, Ozuner G, Remzi FH. Mesh herniorrhaphy with simultaneous colorectal surgery: a case-matched study from the American College of Surgeons National Surgical Quality Improvement Program. Am J Surg. 2015;210:766-71.

46

53. Timmermans L, de Goede B, van Dijk SM, et al.

Meta-analysis of sublay versus onlay mesh repair in incisional hernia surgery. Am J Surg. 2014;207:980-8.

54. Holihan JL, Nguyen DH, Nguyen MT, Mo J, Kao LS, Liang MK. Mesh location in open ventral hernia repair: a systematic review and network meta-analysis.

World J Surg. 2016;40:89-99.

55. Venclauskas L, Maleckas A, Kiudelis M. Oneyear follow-up after incisional hernia treatment: results of a prospective randomized study. Hernia.

2010;14:575-82.

56. Albino FP, Patel KM, Nahabedian MY, Sosin M, Attinger CE, Bhanot P. Does mesh location matter in abdominal wall reconstruction? A systematic review of the literature and a summary of recommendations.

Plast Reconstr Surg. 2013;132:1295-304.

57. Cobb WS, Carbonell AM, Kalbaugh CL, Jones Y, Lokey JS. Infection risk of open placement of intraperitoneal composite mesh. Am Surg. 2009;75:762-7.

58. Novitsky YW, Porter JR, Rucho ZC, et al. Open preperitoneal retrofascial mesh repair for multiply recurrent ventral incisional hernias. J Am Coll Surg.

2006;203:283-9.

59. Le H, Bender JS. Retrofascial mesh repair of ventral incisional hernias. Am J Surg. 2005;189:373-5.

60. Cobb WS, Warren JA, Ewing JA, Burnikel A, Merchant M, Carbonell AM. Open retromuscular mesh repair of complex incisional hernia: predictors of wound events and recurrence. J Am Coll Surg. 2015;220:606-13.

61. Liang MK, Goodenough CJ, Martindale RG, Roth JS, Kao LS. External validation of the ventral hernia risk score for prediction of surgical site infections. Surg Infect (Larchmt). 2015;16:36-40.

62. Tsereteli Z, Pryor BA, Heniford BT, Park A, Voeller G, Ramshaw BJ. Laparoscopic ventral hernia repair (LVHR) in morbidly obese patients. Hernia.

2008;12:233-8.

63. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255:1069-79.

64. Ata A, Lee J, Bestle SL, Desemone J, Stain SC. Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg. 2010;145:858-64.

65. Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248:585-91.

66. McPhee JT, Hill JS, Whalen GF, et al. Perioperative mortality for pancreatectomy: a national perspective.

Ann Surg. 2007;246:246-53.

67. Brusselaers N, Mattsson F, Lagergren J. Hospital and surgeon volume in relation to long-term survival after oesophagectomy: systematic review and meta-analysis. Gut. 2014;63:1393-400.

68. Raigani S, De Silva GS, Criss CN, Novitsky YW, Rosen MJ. The impact of developing a comprehensive hernia center on the referral patterns and complexity of hernia care. Hernia. 2014;18:625-30.

69. Colavita PD, Walters AL, Tsirline VB, et al. The regionalization of ventral hernia repair: occurrence and outcomes over a decade. Am Surg. 2013;79:693-701.

GHS Proc. May 2016; 1 (1): 38-46

Case Studies

Yolk Sac Diameter in Multiple Gestations Chelsea Fox, MD; Karenne Fru, MD, PhD; and Bruce A. Lessey, MD, PhD From the Department of OB/GYN, Greenville Health System, Greenville, SC (C.F., B.A.L.), University of South Carolina School of Medicine Greenville, Greenville, SC (B.A.L.), and Department of Obstetrics and Gynecology, New Hanover Regional Medical Center, Wilmington, NC (K.F.)

Abstract Enlargement of the yolk sacs is an ominous sign even in multi-gestational pregnancies.

T

he yolk sac functions as the primary route of exchange between the embryo and mother prior to the establishment of the placental circulation. It is well established that an abnormally large yolk sac serves as a prognostic indicator for early pregnancy failure in singleton gestation. However, no studies have been performed to describe normal versus abnormal yolk sac diameters (YSD) in multiple gestations. In this case, we describe a patient with triplet pregnancy consisting of monochorionic-monoamniotic twins both with enlarged yolk sacs in addition to singleton pregnancy in a separate sac with a normal yolk sac. The monochorionic-monoamniotic twins were later diagnosed with a fetal demise suggesting large YSD may serve as a poor prognostic indicator in multiple gestations as well.

Case Description A 34-year-old woman opting for in vitro fertilization (IVF) as treatment for primary infertil-

ity conceived after placement of 2 embryos on post-retrieval day 3. Quantitative hCG levels were higher than expected and transvaginal ultrasound at 6 weeksâ&#x20AC;&#x2122; gestation demonstrated a triplet pregnancy with a singleton sac and a separate monochorionic-monoamniotic versus conjoined twin pregnancy with symmetrically enlarged yolk sacs, each with cardiac activity present (Figs. 1A and B).

The yolk sacs associated with the twin pregnancy were 6.15 mm and 7.37 mm, respectively, while the singleton had a normal yolk sac. A repeat ultrasound 10 days later confirmed absence of fetal cardiac activity in the monochorionic-monoamniotic sac, with increased crown rump length of the singleton pregnancy, which maintained persistent cardiac activity. This embryo went on to normal development and delivery. A second example of a twin pregnancy with normal yolk sacs is shown in Figure 1C. In this example, these twins went on to sustain normal development and were delivered successfully.

Figure 1 (A and B) Yolk sac size in a multi-gestational pregnancy predicted an adverse outcome of the affected monomono twins of a triplet pregnancy. (C) Another twin pregnancy with dichorionic-diamniotic embryos with reassuring normal appearing yolk sacs continued and developed normally.

GHS Proc. May 2016; 1 (1): 47-48

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Correspondence Address to: Chelsea Fox, MD Greenville Health System, Dept of OB/GYN 890 W Faris Rd Greenville, SC 29605 (cfox@ghs.org)

Discussion The routine use of ultrasound is a key feature in the modern management of early pregnancy. In particular, the yolk sac has been studied as a prognostic indicator for pregnancies. The secondary yolk sac is the primary source of exchange between the embryo and the mother during organogenesis.1 It is first visualized at 5 weeksâ&#x20AC;&#x2122; gestation, or when the gestational sac reaches 10 mm2, and regresses by the 12th week of gestation in normal pregnancies.2,3 A normal range of yolk sac diameters has been described, particularly in singleton pregnancies with abnormal outcome in all cases where YSD was greater than 5.6 mm.1 Lindsay et al followed 486 first-trimester pregnancies and found a YSD >2SDs (standard deviations) above the mean was associated with abnormal outcomes with a sensitivity of 15.6%, specificity of 97.4%, and a positive predictive value of 60.0%.1 There is a paucity of data for normal versus abnormal YSD in multiple gestations. However, there is no reason to suspect that similar guidelines regarding enlarged yolk sacs and poor prognosis would not apply.

While it is widely accepted that monoamniotic twins share a yolk sac, recent evidence shows monoamniotic twins with 2 yolk sacs.4,5 This case also challenges the previously held idea that the number of yolk sacs is equal to amnionicity in both monochorionic-monoamniotic and monochorionic-diamniotic twin pregnancies.4 While the question of amnionicity may require further study, this case bears out the fact that abnormally large yolk sacs are predictive of abnormal pregnancy even in multiple gestations. Moreover, only the affected sacs with enlarged yolk sacs suffered the expected adverse sequelae. The singleton pregnancy was carried to term with no further evidence of the twin pregnancy following embryonic demise. This is, to the best of our knowledge, the first case report demonstrating that enlarged yolk sacs in twins may be associated with adverse outcomes similar to singleton pregnancies; the case also adds to the growing body of literature suggesting yolk sac number does not always correlate with amnionicity in first-trimester monochorionic multiple gestations.6-10

References 1. Lindsay DJ, Lovett IS, Lyons EA, Levi CS, Zheng XH, Holt SC, Dashefsky SM. Yolk sac diameter and shape at endovaginal US: predictors of pregnancy outcome in the first trimester. Radiology. 1992;183:115-8.

H, Torii Y. Monochorionic monoamniotic twin pregnancies with two yolk sacs may not be a rare finding: a report of two cases. Ultrasound Obstet Gynecol.

2010;36:384-6.

2. Jauniaux E, Jurkovic D, Henriet Y, Rodesch F, Hustin J. Development of the secondary human yolk sac: correlation of sonographic and anatomic features. Hum Reprod. 1991;6:1160-6.

7. Malinowski W. Yolk sacs in twin pregnancy. Acta Genet Med Gemellol (Roma). 1998;47:177-81.

3. Berdahl DM, Blaine J, Van Voorhis B, Dokras A. Detection of an enlarged yolk sac on early ultrasound if associated with adverse pregnancy outcomes. Fertil Steril. 2010;94:1535-7.

4. Levi CS, Lyons EA, Dashefsky SM, Lindsay DJ, Holt SC. Yolk sac number, size and morphologic features in monochorionic monoamniotic twin pregnancy. Can Assoc Radiol J. 1996;47:98-100.

5. Bishop DK. Yolk-sac number in monoamniotic twins.

Obstet Gynecol. 2010;116:504-7.

6. Murakoshi T, Ishii K, Matsushita M, Shinno T, Naruse

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8. Shen O, Samueloff A, Beller U, Rabinowitz R. Number of yolk sacs does not predict amnionicity in early first-trimester monochorionic multiple gestations.

Ultrasound Obstet Gynecol. 2006;27:53-5.

9. Corbett S, Shmorgun D. Yolk sac number does not predict reliably amnionicity in monochorionic twin pregnancies: a case of monochorionic monoamniotic twin pregnancy with two distinct yolk sacs on early first-trimester ultrasound. Ultrasound Obstet Gynecol. 2012;39:607-8.

10. Meller C, Wojakowski A, Izbisky G, Aiello H, OtaĂąo L. Number of yolk sacs in the diagnosis of monoamnionicity. J Ultrasound Med. 2014;33:1091-7.

GHS Proc. May 2016; 1 (1): 47-48

Case Studies

Complex Perirectal Abscess Extending to the Preperitoneum and Space of Retzius Caleb J. Mentzer, DO; James R. Yon, MD; Ray King, MD; and Jeremy A. Warren, MD From the Department of Surgery, Minimally Invasive and Digestive Surgery Section, Augusta University, Augusta, Ga (C.J.M., J.R.Y., R.K., J.A.W.)

Abstract Space of Retzius infections are rare and can be insidious until presenting as a large abscess cavity spreading to other extraperitoneal compartments. Knowledge of anatomy and of possible management pitfalls is key to successful treatment. We describe a case of space of Retzius abscess due to ascending infection from a perirectal abscess that was managed successfully and offer a review of the anatomy, pathophysiology, and management of this infection pattern. The case reported required multiple drainage procedures of the perirectal abscess and extraperitoneal spaces and treatment with antibiotics. After appropriate drainage, the patient progressed well to eventual discharge. This case highlights the complex anatomic compartments and potential spaces that exist which allowed a common, typically benign perirectal abscess to extend and cause severe systemic illness.

I

nfections presenting in the space of Retzius are historically attributed to bladder infections, urachal infections, osteomyelitis of the pubic symphysis, or granulomatous disease. Increasingly, surgeons are entering this space for procedures such as prostatectomies, orthopaedic manipulation of the pelvis, and laparoscopic inguinal hernia repairs.

As with other extraperitoneal infections, patients typically present with vague and nonspecific complaints. These patients often lack physical exam findings, creating a diagnostic dilemma and potentially delaying definitive treatment. Additionally, the complex extraperitoneal anatomic planes allow extension of disease from distant sites. We present a previously unreported space of Retzius infection arising from a perirectal abscess, along with anatomic review and summary of the literature.

the patient was transferred to our academic tertiary referral center for further workup, approximately 36 hours after initial presentation. The patient appeared uncomfortable with tachypnea and fever, but was otherwise hemodynamically stable. His

Figure 1 Axial CT scan demonstrating air and fluid collection deep to anterior abdominal wall fascia. Area of interest outlined, displaying typical “molar tooth” shape.

Case Description A 49-year-old man with no past medical history presented to an outside hospital complaining of perirectal and abdominal pain. The patient’s white count was 19 000 with a bandemia of 58%. A computer tomography (CT) scan revealed proctitis and a perirectal fluid collection. He was placed on broad-spectrum antibiotics, and the perirectal abscess was incised and drained, and a Penrose drain was placed. Secondary to worsening sepsis, GHS Proc. May 2016; 1 (1): 49-51

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exam was nonspecific with vague, diffuse, abdominal tenderness. He had normal bowel sounds, normal urinalysis, and no masses palpated on rectal exam. Bowel function was reportedly normal. The Penrose drain placed by the referring hospital was intact, and the incision and drainage appeared open. After review of the patient’s original CT scan, the decision was made to re-examine the patient in the operating room with a proctoscope to evaluate for any undrained collections, with the concern being there was an area of multi-loculated Figure 2 abscess that was not fully Sagittal CT scan showing extent of abscess drained. The abscess cavity from perirectal area to umbilicus. Area of appeared to be adequately interest outlined. drained and no other pathology was noted.

Figure 3 Diagram of abscess. A = Abscess, B = Bladder, C = Rectum.

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In the setting of continued sepsis with an unidentified source, a repeat CT scan was performed (Figs. 1 and 2). This revealed bilateral pneumonia and an extraperitoneal fluid collection that extended from retroperitoneum anteriorly to the space of Retzius, and superiorly to the umbilicus without intraperitoneal involvement. Air within the fluid collection, as well as the patient’s clinical condition, was indicative of an undrained abscess.

Figure 3 is a diagram showing the extent of the abscess and can be compared with Figure 2. The patient was taken to the operating room where a lower midline incision was used to gain access into the preperitoneal compartment. A large abscess was evacuated that extended from the pelvic prevesicular space into the retroperitoneum abutting the spine, creating a free-floating peritoneum. The peritoneum remained intact and no intraperitoneal structures were involved.

Separate incisions placed in laterally dependent

areas in the patient’s flanks allowed for adequate drainage and wound care using negative pressure wound therapy (NPWT). Wound cultures revealed Escheridia coli, Bacteroides thetaiotamicron, and Clostridium species. With serial washouts of this space, NPWT, and broad-spectrum antibiotic therapy, the patient went on to recover completely over the next several months with no long-term complications.

Discussion This rare extension of distant infection to the space of Retzius highlights the complex anatomic planes that make up the retroperitoneal and extraperitoneal compartments. Anders Retzius initially defined the prevesical space in 1856 at a report presented to the Academy of Stockholm with subsequent description of the first described infection in the area by Wenzel Gruber in 1862.1 Familiarity with this anatomy and the potential interconnecting spaces is critical for early recognition and treatment of such complex infections as presented here.

The anterior extraperitoneal space is created by 1 central and 2 paired folds of peritoneum extending from the umbilicus known as the median, medial, and lateral umbilical ligaments. The lateral umbilical ligaments are formed by the inferior epigastric vessels.2 The medial umbilical ligaments are formed by the remnants of the obliterated umbilical arteries. The centrally located median umbilical ligament is a peritoneum-covered ridge formed by the obliterated urachus, connecting the umbilicus to the anterior dome of the bladder.2 Surrounding the median umbilical ligament (urachus) and extending laterally to the medial umbilical ligaments is the umbilicovesical fascia. It is the combination of these folds and ligaments that forms the pathognomonic “molar tooth” outline of abscesses seen on CT. Inferiorly, the umbilicovesical fascia is contiguous with the visceral fascia of the bladder.

Anteriorly, the umbilicovesical fascia is the umbilical-prevesical fascia, and it extends from the umbilicus to the inferolateral surface of the bladder. The space between the umbilicovesical fascia and the umbilical-prevesical fascia at the level of the pubis is known as the retropubic space of Retzius.3 This space normally contains fat, loose fibrous tissue, and a perivesical venous plexus.2 Laterally, this extends to the space of Bogros, which lies below the inguinal ligament and contains the iliofemoral vessels medially and the iliopsoas muscle more laterally. Continuing posterolaterally, this is directly contiguous with the infrarenal retroperitoneal compartments, and caudally extends to the supralevator extraperitoneal space, potentially allowing direct spread of infection between these spaces.3 In GHS Proc. May 2016; 1 (1): 49-51

COMPLEX SPACE OF RETZIUS ABSCESS our patientâ&#x20AC;&#x2122;s case, the original perirectal abscess most likely extended cephalad through the supralevator space, continued into the iliac space, and then progressed in a lateral-to-medial direction into the prevesical space. Chen et al4 and Auh et al5 have demonstrated that there is a direct communication from pararectal space to the vesicle extraperitoneal space without a separating fascial layer due to the umbilicovesical fascia ending at the reflection of the vesical peritoneum. From the prevesical space, the infection was able to spread through the entire space of Retzius anteriorly, as well as into other pelvic compartments, and the retroperitoneum posteriorly, through direct spread.

Space of Retzius infection, as with other extraperitoneal infections, is insidious and difficult to diagnose secondary to the absence of physical signs. Patients can have vague and nonspecific complaints, with urinary frequency and urgency being the most specific to infections of the prevesical space.6 Bowel function is usually reported as normal, as reported in our case. While CT can reveal and delineate many abscesses, infections in the space of Retzius are often harder to identify due to the difficulty of ascertaining whether a fluid collection is intra- or extraperitoneal.7 Because of the occult nature and indolent presentation of extraperitoneal abscesses, there is often a delay in diagnosis, and a high index of suspicion is needed.

On average, this delay has been reported as 12.7 days for all extraperitoneal abscesses.8 In that study, postdrainage fever was a major prognostic indicator. Patients who defervesced postoperatively in less than 3 days had an 89% survival rate compared to those who remained febrile.6 Patients

who remained febrile had a reported 71% mortality rate.8 Overall, mortality rate of extraperitoneal abscesses ranges from 22% to 46%.8 As our case corroborates, most extraperitoneal infections are due to Escheridia coli and Bacteroides species.8 Management of complex extraperitoneal abscesses has been extensively discussed in the literature, with percutaneous approaches being the favored method as opposed to open surgical approaches.9-12 With increasing surgical manipulation of these planes, the general surgeon must be familiar with their potential interconnections when considering both source and intervention. Transperitoneal drainage should be avoided, as this leads to high rates of recurrence and increases mortality.8

Correspondence Address to: James Yon, MD Cook County Department of Trauma and Burn 1900 W Polk St Suite 1300 Chicago, IL 60612 (jyon@ cookcountyhhs.org)

Conclusion Though a rare presentation, this case highlights the complex anatomic compartments and potential spaces that exist in the extraperitoneum that allowed a common, typically benign perirectal abscess to extend to the supralevator space, and eventually to the space of Retzius. In the absence of rapid clinical improvement after initial drainage, the clinician must have a high index of suspicion for more complex disease and seek additional workup and treatment. Computed tomography scanning is probably the best tool for evaluation, as the clinical presentation of extraperitoneal abscesses is more insidious and can have little to no physical exam signs with non-specific laboratory studies. Early consideration and identification of extraperitoneal abscesses is crucial for timely intervention in a patientâ&#x20AC;&#x2122;s care, as delays in diagnosis and treatment carry significantly higher morbidity and mortality.

References 1. Rising EH. Prevesical abscess. Ann Surg. 1908:48: 224-36.

7. Kobayashi S. Hematoma in the space of Retzius. J Trauma. 2006;61:1556.

2. Marilas P, Skandalakis JE. Surgical anatomy of the retroperitoneal spaces part II: the architecture of the retroperitoneal space. Am Surg. 2010;76:33-42.

8. Crepps JT, Welch JP, Orlando R. Management and outcome of retroperitoneal abscesses. Ann Surg.

1987;205:276-81.

3. Korobkin M, Silverman PM, Quint LE, Francis IR. CT of the extraperitoneal space: normal anatomy and fluid collections. Am J Roentgenol. 1992;159:933-41.

4. Auh YH, Rubenstein WA, Schneider M, Reckler JM, Whalen JP, Kazam E. Extraperitoneal paravesical spaces: CT delineation with US correlation. Radiology.

1986;159:319-28.

5. Chen N, Min PQ, Liu ZY, Wu B, Yang KQ, Lu CY. Radiologic and anatomic study of the extraperitoneal space associated with the rectum. Am J Roentgenol.

2010;194:642-52.

6. Bellina PV, Lang EK, Hanemann M. Anterior abdominal wall and space of Retzius abscess. J La State Med Soc. 1980;132:160-2.

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9. Benoist S, Panis Y, Pannegeon V, Soyer P, Watrin T, Boudiaf M, Valleur P. Can failure of percutaneous drainage of postoperative abdominal abscesses be predicted? Am J Surg. 2002;184:148-53.

10. Brolin RE, Nosher JL, Leiman S, Lee WS, Greco RS. Percutaneous catheter versus open surgical drainage in the treatment of abdominal abscesses. Am Surg.

1984;50:102-8.

11. Cantasdemir M, Kara B, Cebi D, Selcuk ND, Numan F. Computed tomography-guided percutaneous catheter drainage of primary and secondary iliopsoas abscesses. Clin Radiol. 2003;58:811-5.

12. Gerzof SG, Johnson WC, Robbins AH, Nabseth DC. Expanded criteria for percutaneous abscess drainage.

Arch Surg. 1985;120:227-32.

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Case Studies

A Revertant of the Pathogenic Germline Mutation in BRCA1 as a Possible Cause of Breast Cancer Chemoresistance Phillip Callihan, PhD; Anatole Ghazalpour, PhD; and W. Jeffery Edenfield, MD From the University of South Carolina School of Medicine Greenville, Greenville, SC (P.C.); Department of Molecular Genetics, Caris Life Sciences, Phoenix, Ariz (A.G.); and Institute for Translational Oncology Research (ITOR), Cancer Institute of Greenville Health System, Greenville, SC (W.J.E.)

Abstract Inherited mutations in BRCA genes increase the risk of developing both breast and ovarian cancers.

Wild-type BRCA proteins are involved in DNA repair mechanisms, and DNA damaging chemotherapeutics take advantage of these repair deficiencies in BRCA mutated cancers. However, chemoresistance often develops and currently represents one of the most significant barriers to effective breast and ovarian cancer therapy. Secondary somatic BRCA mutations that restore functional BRCA proteins could contribute to the development of chemoresistance, but clinical case reports demonstrating these mutations are lacking. The following case report outlines a BRCA1 somatic mutation that could rescue the function of BRCA1 proteins and provides clinical evidence of the role BRCA1 plays in the development of chemoresistance.

T

he clinical relevance of BRCA1 and BRCA2 are well established in the biology of breast and ovarian cancers. Working through related mechanisms, these proteins are involved in DNA repair and the maintenance of chromosomal stability.1,2 Mutation of the wild-type BRCA1 or 2 allele results in the accumulation of DNA damage in healthy cells facilitating cellular transformation and ultimately tumor formation.

BRCA1, the focus of the following report, participates in the repair of double-strand DNA breaks by mediating homologous recombination through multiple distinct mechanisms.2 While a lack of BRCA activity plays an integral role in tumor formation, this characteristic also leaves tumor cells vulnerable to DNA-damaging chemotherapeutic agents. Indeed, DNA-damaging agents have been a mainstay in therapy for BRCA-deficient breast and ovarian cancers.

Additionally, poly (ADP-ribose) polymerase-1 (PARP) inhibitors are being added to this treatment arsenal. This novel class of chemotherapeutics works through inhibition of a pathway that repairs single-strand DNA breaks and indirectly exploits the deficiency of the cancer cell to repair DNA damage.3 Unfortunately, cancer cells often

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become refractory to these therapies. The mechanisms through which tumors develop this chemoresistance are an area of great interest, and the role of BRCA genes in this process is under investigation.

Secondary mutations in BRCA genes have been implicated in the development of chemoresistance in cancer cell lines and clinical specimens.4,5 A recent review suggests a model in which platinum-sensitive tumors treated with platinum-based chemotherapeutics are placed under a selective pressure that favors the survival of cells harboring secondary BRCA mutations.6 These secondary mutations potentially rescue BRCA protein function, producing tumor cells that can now escape cell death caused by DNA cross-linking agents and/or PARP inhibitors.

The development of this model is largely based on in vitro studies utilizing cancer cell lines, as well as clinical samples of ovarian cancer. The current literature distinctly lacks clinical case reports detailing specific secondary mutations in BRCA genes associated with the development of chemoresistance in patients. Such reports are needed to validate models of BRCA-related chemoresistance, GHS Proc. May 2016; 1 (1): 52-54

CASE OF BRCA1 MUTANTS AND CHEMORESISTANCE and to present examples of specific secondary mutations with clinical relevance. The following report will begin to address this need through the presentation of a potentially novel BRCA1 rescue mutation in a patient with breast cancer.

Case Description A 27-year-old Colombian woman without family history of breast or ovarian malignancy presented for evaluation of a palpable left breast mass. She denied any skin or nipple changes but her perception was an enlargement of the left breast compared to the right. Initial breast imaging revealed no conclusive findings and short-term follow-up was recommended. Over the next several weeks, the breast mass enlarged and she returned for interval assessment. At that time, the mass expanded to over 5 cm and now had suspicious imaging characteristics prompting urgent biopsy.

The mass proved to be an invasive ductal cancer, grade II, which was negative for estrogen receptor (ER = 0%), progesterone receptor (PR = 1%, intensity 1+), and was HER2 negative by immunohistochemistry (IHC). Given the locally advanced nature of the lesion, she was counseled for neoadjuvant chemotherapy for 6 cycles. Following 2 cycles, clinical examination and a repeat breast MRI demonstrated a marked interval diminution in tumor burden from pre-treatment (7.1 cm x 6.8 cm x 5.5 cm to 2.1 cm x 2.4 cm x 2.7 cm). While additional cycles were administered, her clinical examination was not further changed. During her neoadjuvant chemotherapy, genetic counseling and germline testing revealed a single-base substitution resulting in a pathogenic BRCA1 nonsense mutation (p.W1508X, c.4523G>A); on this basis, bilateral mastectomy was planned as her definitive surgical procedure. Prior to surgery, a repeat MRI was performed which suggested that the tumor had grown, now reflecting multiple foci of tumor, although the overall burden of disease was decreased. At surgery, she was found to have a 4.5 cm residual tumor, now grade III (undifferentiated), with multiple foci of lymphovascular invasion, and 1 of 10 axillary lymph nodes involved with metastatic disease.

Out of concern for the emergence of resistance, repeat molecular analysis of the tumor was performed demonstrating the persistence of the native BRCA1 mutation in 87% of sequencing reads analyzed and a new, presumably somatic substitution mutation, W1508Q (Trp1508Gln), in 25% of the reads. Further investigation revealed that the secondary substitution is in “cis” configuration (on the same allele) with the germline variGHS Proc. May 2016; 1 (1): 52-54

ant (p.W1508Q, c.4522_4523TG>CA). This observation is consistent with 2 separate mutations affecting the wild type allele in which the wild type sequence initially mutated from tryptophan to a stop codon (TGG → TAG) and the secondary mutation reverted the stop codon to glutamine (TAG → CAG) (Fig. 1). This secondary mutation is predicted to reverse the loss of function seen with the germline mutation. It should be noted that the 87% allele frequency found for W1508X was obtained in the background of 70% tumor.

According to the loss of heterozygosity model, if a variant is germline, we would expect 85% frequency when testing a sample that contains 70% tumor. Thus the allele frequency obtained during tumor testing corroborates and supports that W1508X was in fact a germline variant.

Discussion The BRCA1 gene product is composed of 1863 amino acids, contains an N-terminal RING domain, 2 C-terminal BRCT domains, and nuclear localization signals.2 Mutations affecting both the RING domain and BRCT domains are known to compromise the tumor suppressive activities of BRCA1.7 The W1508X nonsense mutation

Figure 1 A) General structure of BRCA1 protein is shown with a focus on the wildtype (WT) DNA and amino acid sequences. B) Pathogenic BRCA1 germline mutation detected during neoadjuvant chemotherapy demonstrating the nonsense mutation leading to a premature stop codon. C) Revertant mutation resulting in glutamine in place of the stop codon potentially restoring the DNA repair function of the BRCA1 protein.

A. BRCA1 Protein

WT DNA Sequence

WT Protein Sequence

B. Germline DNA Sequence

Germline Protein Sequence

C. Revertant DNA Sequence

Revertant Protein Sequence

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Correspondence Address to: Jeff Edenfield, MD Greenville Health System, ITOR 900 W Faris Rd Greenville, SC 29605 (jedenfield@ghs.org)

Potential Conflicting Interests Dr Anatole Ghazalpour is an employee of Caris Life Sciences and has stock options.

sequenced from this patient’s initial biopsy would result in a truncated protein product lacking structurally sound C-terminal BRCT domains. Consistent with the germline testing results, W1508X mutations have also been documented as a class 5 germline variant in 23 cases in the Breast cancer Information Core (BIC) database.

As described above, repeat molecular analysis revealed a subpopulation of cells harboring a rare W1508Q mutation. The conversion of tryptophan to glutamine requires a double substitution in DNA, which in our case possibly resulted from 2 distinct mutational events. The first event, which was inherited and was detected during neoadjuvant chemotherapy, converted tryptophan to a stop codon. The second event converted the stop codon to glutamine, which was the secondary mutant discovered on subsequent analysis. The effects of W1508Q have not been fully characterized and have not been published in the literature or reported in mutation databases such as BIC, Biobase, LOVD, ClinVar, and Catalogue of Somatic Mutations in Cancer (COSMIC).

We utilized 3 algorithms to predict the effect of Glutamine substitution for Tryptophan at residue 1508. In our in silico analysis, 2 of the 3 algorithms predicted neutrality: SIFT algorithm predicted that the substitution is “damaging” (SIFT score of 0.01) and Polyphen2 and Align GVGD predicted neutrality, suggesting that this variant is more likely to not affect the BRCA1 function.8 In addition, the presence of W1508Q results in removal of the premature stop codon and a full-length protein product containing both C-terminal BRCT domains. The structural restoration of BRCA1 in the cells containing the W1508Q mutation would then allow these cells to survive the DNA-damaging chemotherapeutics intended to take advantage of deficient DNA repair mechanisms. We believe this rescue mutation allowed a subpopulation of

cells to evade chemotherapy-induced cell death in this patient, which potentially accounts for the observed tumor growth during neoadjuvant chemotherapy. Future in vitro experiments, such as those used to investigate the role of secondary BRCA2 mutations in ovarian cancer,4 will assist in determining the true effect of W1508Q variant on BRCA1 function and resolve the inconsistent in silico prediction results.

The clinical course and molecular analysis described in this case present an example of BRCA1-mediated chemoresistance in a breast cancer patient. These observations were made possible by the repeat molecular analysis performed following tumor growth suggesting that serial molecular profiling of tumors before, during, and after treatment may lead to novel genetic and epigenetic findings. Additionally, serial molecular profiling could improve outcomes by allowing clinicians to adapt treatment regimens to both respond to and avoid potential chemoresistance.

The main limitation to this suggestion is the availability of chemotherapeutics with diverse mechanisms of action that could target signal transduction pathways still relevant to the survival of tumor cells. Countless studies currently underway are designed to investigate these survival pathways and to design novel therapeutics targeting specific signal mediators. The introduction of PARP inhibitors into the treatment arsenal is a prime example of the success of such efforts.

Case reports such as this are crucial to inform the design of translational studies investigating the development of chemoresistance. This report details a secondary somatic mutation that potentially rescues the function of BRCA1. Analysis of the functional relevance of this mutation is warranted and has the potential to further our understanding of in vivo mechanisms of chemoresistance.

References 1. Jasin M. Homologous repair of DNA damage and tumorigenesis: the BRCA connection. Oncogene.

2002;21:8981-93.

2. Venkitaraman A. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002;108:171-82.

3. O’Sullivan Coyne G, Chen A, Kummar S. Delivering on the promise: poly ADP ribose polymerase inhibition as targeted anticancer therapy. Curr Opin Oncol.

2015;27:475-81.

4. Sakai W, Swisher EM, Karlan BY, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008;451:1116-20.

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5. Swisher EM, Sakai W, Karlan BY, Wurz K, Urban N, Taniguchi T. Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance. Cancer Res. 2008;68:2581-6.

6. Dhillon KK, Swisher EM, Taniguchi T. Secondary mutations of BRCA1/2 and drug resistance. Cancer Sci. 2011;102:663-9.

7. Boulton SJ. Cellular functions of the BRCA tumour-suppressor proteins. Biochm Soc Trans.

2006;34:633-45.

8. Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248-9.

GHS Proc. May 2016; 1 (1): 52-54

Department of Medicine: Making Lives Healthier The GHS Department of Medicine leads the Upstate in groundbreaking, life-saving treatment: • Cardiology: GHS’ Congestive Heart Failure Program is first in the Upstate to use the CardioMEMS Heart Failure System to prevent readmission, with excellent results to date. (Carolina Cardiology Consultants, 1-877-611-9965) • Dermatology: GHS offers Mohs micrographic surgery, the most advanced and effective treatment procedure for basal cell and squamous cell carcinomas with cure rates 98% or higher. (Carolina Dermatology of Greenville, 233-6338) • Neurology: Recently awarded the 2016 Certificate of Distinction for Primary Stroke Centers, the GHS Stroke Center is the only upstate facility offering endovascular treatment of ischemic stroke and subarachnoid hemorrhage.

(Neuroscience Associates, 454-4500) • Gastroenterology: GHS internal medicine physicians, in partnership with the USC School of Public Health, are conducting a study about perceptions of screening for colorectal cancer, the third leading cancer in the U.S. (GHS Gastroenterology & Liver Center, 455-2888; Gastroenterology Consultants of Internal Medicine Associates of Greenville, 255-5609)

ghs.org/medicine

16-0331

Case Studies

Fatal Clostridium difficile Enteritis as a Delayed Complication of Loop Ileostomy for Fulminant C difficile Colitis Summer N. Rochester, DO; Robert Farrar, MD; R. Jared Sanders, MD; Megan K. Straughan, MD; and Meghann L. Kaiser, MD From the Department of Surgery, Greenville Health System, Greenville, SC (S.N.R., R.J.S., M.K.S, M.L.K.), and Department of Pathology, Greenville Health System, Greenville, SC (R.F.)

Abstract The recent introduction of loop ileostomy with colonic lavage represents a powerful surgical intervention for fulminant Clostridium difficile colitis, but is not without potential hazards. We present a case of fatal recurrent C difficile small bowel enteritis, a heretofore unreported potential complication of ileostomy reversal. A review of the literature suggests potential mechanisms and means to prevent this devastating outcome.

C

lostridium difficile is an opportunistic pathogen that multiplies when more benign intestinal flora is lacking and produces a damaging, intensely inflammatory toxin capable of transmural permeation.1 C difficile colitis (CDC) has rapidly increased in incidence over recent decades and is now the most common cause of nosocomial diarrhea.2 It complicates the hospital stays of an increasingly frail geriatric population, frequently resulting in septic shock, organ dysfunction, and even death, despite maximal medical management. Thus surgical therapy remains the mainstay of salvage intervention.

However, after failing various pharmaceuticals, many patients have deteriorated into multi-system organ dysfunction, rendering them less than ideal candidates for the conventional operation: an extensive, highly morbid total abdominal colectomy with permanent end-ileostomy. In 2011, Neal and colleagues at the University of Pittsburgh presented a less drastic alternative: minimally invasive creation of a loop ileostomy to allow for antegrade large-volume polyethylene glycol (PEG) and vancomycin enemas, accompanied by systemic intravenous metronidazole.3 Patients in that study undergoing this gentler option exhibited less than half the mortality of those receiving colectomy in short-term follow-up. As a result, for many general surgeons, temporary laparoscopic loop ileostomy with colonic lavage has become the preferred first option in a staged salvage approach

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to refractory CDC, reserving colectomy only for those that fail. We ourselves have found success creating many such loop ileostomies for fulminant CDC; however, we have since encountered a devastating potential complication of reversing these stomas: recurrent C difficile invading the small bowel, otherwise known as Clostridium difficile enteritis (CDE), an infection associated with overwhelming sepsis and a mortality of 30%.4

Case Description GC was an 81-year-old Caucasian man with a history of coronary artery disease, dyslipidemia, and gastroesophageal reflux, for which he took multiple medications, including proton pump inhibitors. He was in otherwise good health and highly functioning, living at home with his spouse. He presented to his primary care physician complaining of unilateral facial tenderness and swelling, was given a diagnosis of parotiditis, and completed an empiric course of clindamycin. His symptoms, however, did not resolve, and further work-up ultimately revealed a malignant parotid tumor, likely metastatic melanoma.

In the interim, the patient developed diarrhea that persisted despite a 3-week course of oral ciprofloxacin and metronidazole at home, necessitating hospital admission for dehydration with acute kidney injury. Highly sensitive polymerase chain reaction (PCR) testing (Xpert C difficile/ GHS Proc. May 2016; 1 (1): 56-59

RECURRANT FATAL C DIFFICLE AFTER ILEOSTOMY TAKEDOWN Epi, Cepheid Inc, Sunnyvale, Calif.) revealed a particularly virulent B1/NAP/027 strain of C difficile. He was initially treated with systemic intravenous metronidazole as well as vancomycin per oral and rectum. Nonetheless, his condition continued to deteriorate, and surgical consultation was sought. The computed tomography (CT) scan obtained was suggestive of severe CDC (Fig. 1). After lengthy discussion, taking into account the patientâ&#x20AC;&#x2122;s advanced age, comorbidities, and worsening clinical status, the patient elected to proceed with emergent loop ileostomy on hospital day 3. The colon was closely inspected laparoscopically and found to be boggy and congested but otherwise viable. We accordingly proceeded with laparoscopic creation of loop ileostomy within a few centimeters of the ileocecal valve, allowing for easy cannulation, through which large-volume PEG and a 10-day course of vancomycin colonic flushes were administered, along with systemic intravenous metronidazole. Despite a complicated 30-day hospital course, the patient did exhibit complete clinical resolution of CDC and was discharged to a skilled nursing facility. Infectious disease consultants advised he be maintained on a regimen of enteric cholestyramine, to bind and inactivate C difficile toxin, and Saccharomyces boulardii probiotic supplements, to maintain healthy colonic flora. Repeat PCR testing of rectal output revealed no further evidence of C difficile.

After undergoing radical parotidectomy, complicated by a superficial wound infection, the patient was treated with a course of cephalexin and experienced no return of diarrhea or other gastrointestinal complaints. Multiple discussions were had with both patient and family throughout this period. The patient acknowledged that ileostomy reversal was not medically necessary; nevertheless, he felt the stoma adversely affected his quality of life and ardently desired reversal. Five months after initial ileostomy creation, and 1 month following his parotidectomy, the patient underwent elective ileostomy reversal. One gram of prophylactic cefoxitin was administered preoperatively, and a stapled anastomosis was created without incident. The patient was extubated immediately thereafter and transferred to a monitored floor bed. By postoperative day (POD) 2 the patient was tolerating an oral diet and ambulating without complaints. On POD3, however, he acutely decompensated into respiratory distress with frank peritonitis. Broad-spectrum antibiotics, including intravenous metronidazole, were initiated. CT (Fig. 2) was concerning for possible small and large bowel ischemia, and the patient returned GHS Proc. May 2016; 1 (1): 56-59

to the operating room for emergent exploratory laparotomy. Once again, the colon was noted to be boggy and friable, as was the ileum. The anastomosis was intact without biliary staining, and the mesenteric vessels surveyed via Doppler transmitted strong signals throughout. With no other obvious explanation for the patientâ&#x20AC;&#x2122;s clinical findings, we elected to proceed with resection of the involved bowel, which entailed a total abdominal colectomy and partial distal small bowel entrectomy. The specimens grossly exhibited mucosal pseudomembranes with cobblestoning not only throughout the colon but also extending a significant distance proximally past our anastomoses and into the resected ileal portion (Fig. 3, Page 58).

Formalin fixation prevented definitive testing for the C difficile toxin. However, vessels were noted to be patent, making primary ischemia an unlikely explanation. Multiple pathologists judged CDE the most likely pathology (Fig. 4, Page 58).

Intraoperatively the patient continued to deteriorate, and we elected to leave him in discontinuity with an open abdomen to expedite aggressive fluid resuscitation in the intensive care unit. Overnight, despite heroic efforts, including vancomycin per rectum and nasogastric tube, severe shock unre-

Figure 1 Initial CT scan showing edematous, fluid-filled colon (white arrow) and juxtaposed normalappearing small bowel (black arrow), consistent with diagnosis of C difficile colitis.

Figure 2 CT scan showing edematous fluid-filled loops of both small and large bowel.

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sponsive to fluids, pressors, and inotropes ensued.

The family elected to withdraw support in accordance with the patientâ&#x20AC;&#x2122;s previously expressed wishes, and he expired shortly thereafter on POD4.

both pathogen and toxin. While a more neutral pH encouraged proliferation of the C difficile microorganism,6 the B1/NAP/027 genotype simultaneously enabled far greater toxin production.7

Discussion

A recent study found that ileostomy effluent collected from 16% of asymptomatic patients carried the C difficile toxin.8 A survey of jejunal specimens harvested at autopsy from patients without known gastrointestinal pathology likewise revealed a 3% rate of C difficile colonization.9 These findings suggest that, far from being the innocent bystander once thought, the small bowel may in fact represent a silent reservoir for recurrent C difficile infections. Ileostomy reversal and right hemicolectomy are especially linked to CDC,10 suggesting that breach of the ileocecal barrier may release the pathogen. Our case study supports this hypothesis. Following loop ileostomy and vancomycin enemas, our patient was asymptomatic and rectal specimen tested negative for persistent C difficile toxin, but an ileal sample was not obtained. Moreover, the patient received a maintenance regimen of toxin-binders and probiotics, which may have rendered small bowel colonization subclinical.

Later, however, stapled anastomosis of a very distal ileostomy using a long, 75 mm cartridge likely extended across and thereby compromised his ileocecal valve. This insult, coupled with additional antibiotic exposure and the immunosuppression of malignancy with recent surgery allowed the pathogen to re-enter and flourish in the colon. Thus circumstances set the stage for a fulminant and ultimately fatal infection encompassing both large and small bowel. In the future, potential precautionary steps we are considering include 1) sampling ileostomy effluent to identify asymptomatic carriers, 2) performing hand-sewn end-to-end ileal anastomoses to preserve the integrity of the ileocecal valve, and 3) administering newer pharmaceuticals such as fidaxomicin that are associated with significantly lower recurrence rates than vancomycin.11

CDE was once felt to be a rare entity with dismal prognosis, affecting primarily postcolectomy patients suffering from inflammatory bowel disease (IBD). Between 1980 and 2000, only 9 cases were reported in the literature.2 Subsequently, a relative multitude have erupted, many associated with neither IBD nor colectomy.4 This exponential rise is likely the product of heightened clinical suspicion, coupled with the prevalence of several factors now recognized to increase susceptibility, including advanced age, immunosuppression, recent antibiotic exposure, hospitalization, white race, gastric acid suppression, and the B1/NAP/027 strain of C difficile.5 Our patient exhibited many of these risk factors, but the last 2 may be particularly damaging. Clinically significant infection of the small bowel likely requires a greater burden of

Figure 3 Lumen of the excised terminal ileum, revealing cobblestoning and pseudomembranes, consistent with a diagnosis of C difficile enteritis.

Conclusion

Figure 4 Histology of excised terminal ileum, revealing a dense inflammatory infiltrate and sloughing pseudomembranes (bracket) with transmural necrosis.

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The recent introduction of loop ileostomy with colonic lavage has improved short-term survival rates among patients with fulminant CDC. Nevertheless, increasingly virulent strains affecting an elderly, complicated patient population compel surgeons to suspect the small bowel as a potential source of ongoing colonization and CDE as a potentially fatal ultimate outcome. Research efforts are certainly warranted to determine what steps should be taken prior to and during ileostomy reversal to ensure our patientsâ&#x20AC;&#x2122; continued wellbeing.

GHS Proc. May 2016; 1 (1):56-59

RECURRANT FATAL C DIFFICLE AFTER ILEOSTOMY TAKEDOWN

References 1. Killeen S, Martin ST, Hyland J, O’ Connell PR, Winter DC. Clostridium difficile enteritis: a new role for an old foe. Surgeon. 2014;12:256-62.

2. Dineen SP, Bailey SH, Pham TH, Huerta S. Clostridium difficile enteritis: A report of two cases and systematic literature review. World J Gastrointest Surg.

2013;5:37-42.

3. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg. 2011;254:423-7; discussion 427-9.

4. Beal EW, Bass R, Harzman AE. Two patients with fulminant Clostridium difficile enteritis who had not undergone total colectomy: a case series and review of the literature. Case Rep Surg. 2015;2015:957257.

5. Kim JH, Muder RR. Clostridium difficile enteritis: a review and pooled analysis of the cases. Anaerobe.

2011;17:52e5.

6. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of communi-

GHS Proc. May 2016; 1 (1): 56-59

Correspondence ty-acquired Clostridium difficile-associated disease.

JAMA. 2005;294:2989-95.

7. Lavalle´e C, Laufer B, Pe´pin J, Mitchell A, Dube´ S, Labbe´ AC. Fatal Clostridium difficile enteritis caused by the BI/NAP1/027strain: a case series of ileal C. difficile infections. Clin Microbiol Infect. 2009;15:1093e9.

8. Tsiouris A, Neale JA, Reickert CA, Times M. Clostridium difficile of the ileum following total abdominal colectomy,with or without proctectomy: who is at risk? Dis Colon Rectum. 2012;55:424e8.

Address to: Meghann L. Kaiser, MD Greenville Health System, Dept of Surgery 3rd Floor Support Tower 701 Grove Rd Greenville, SC 29605 (mkaiser@ghs.org)

9. Testore GP, Nardi F, Babudieri S, Giuliano M, Di Rosa R, Panichi G. Isolation of Clostridium difficile from human jejunum: identification of a reservoir for disease? J Clin Pathol. 1986;39:861e2.

10. Randall JK, Young BC, Patel G, Fitzgerald A, George BD. Is Clostridium difficile infection a particular problem after reversal of ileostomy? Colorectal Dis. 201;13:308-11.

11. Louie TJ, Miller MA, Mullane KM, et al; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422e31.

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Case Studies

Outcomes of Treatment with Radiation Therapy for Residual Soft Tissue Sarcoma of the Hand Following “Unplanned” Initial Resection Drew Ratner, MD; S. John Millon, MD; and Scott E. Porter, MD, MBA, FACS From the Department of Orthopaedics and Neurosurgery, Division of Orthopaedic Oncology, Greenville Health System, Greenville, SC (D.R., S.J.M., S.E.P.)

Abstract Extremity soft tissue sarcomas (ESTSs) of the hand are at high risk for unplanned surgical resection.

The consequence of subsequent surgical treatment is potentially profound given the detrimental effects of wide re-resection or amputation on hand function. We present a series of patients with ESTS who did not undergo re-excision or amputation but who underwent successful external beam radiation therapy (XRT) alone.

S

even thousand new cases of soft tissue sarcoma (STS) are diagnosed each year in the United States (US) with an overall annual incidence of 1.5 to 2 cases per 100 000 people.

Extremity STSs (ESTSs) account for approximately 50% of all STSs.1 Patients with STSs in the distal extremity have historically undergone amputation to minimize the risk of recurrence.2 It has been shown that radiotherapy after wide resection of STSs improves local control when a satisfactory local excision with negative or minimal microscopically positive resection margins is achieved;3 alternative treatment by local excision followed by external beam radiation therapy (XRT) first began in the early 1980s.4 More recently, the primary treatment regimen for ESTS has been refined to include planned wide resection of the malignancy to obtain negative margins followed by the judicious use of XRT to reduce the risk of local recurrence and optimize extremity function.5 There is, however, very little written about the management of significant residual disease after primary surgical resection.1,4,6 It has been suggested that patients with grossly positive margins after surgical resection have a high risk of recurrence, and thus amputation should be the preferred treatment in these instances.7-9 We present a series of patients who were referred for treatment to the orthopaedic oncology service

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at our institution after an unplanned primary surgical resection of ESTS of the hand that resulted in positive surgical margins. None of these patients underwent re-excision of the tumor to achieve negative margins. Instead, all underwent treatment with XRT alone to allow for preservation of hand function. We review their courses of treatment, incidence of local recurrence, incidence of metastatic disease, and quantify their function at last follow-up, determining the Musculoskeletal Tumor Society Scale (MSTS) for upper extremity function and the Michigan Hand Outcomes Questionnaire (MHQ) score for hand function.

Case Descriptions Patient 1 RH is an 86-year-old man with Alzheimer’s dementia who presented to a hand surgeon with a left distal forearm/wrist mass in proximity to the median nerve. The patient felt the mass had been increasing in size, and he began to have paresthesias in the distribution of the median nerve. The patient could not undergo an MRI because of a peripheral stent, so an ultrasound was performed for further assessment. The ultrasound showed a 3.7 x 2.1 x 3.2 cm mass described by the musculoskeletal radiologist as having “heterogeneity to the echogenicity with some anechoic regions with increased through transmission suggesting cystic GHS Proc. May 2016; 1 (1): 60-63

HAND FUNCTION AFTER STS EXCISION AND RADIATION fluid” consistent with a hematoma. The patient was experiencing subtle decreased sensation in the distribution of the median nerve but the ultrasound showed that the mass did not appear to involve the median nerve. Due to the increasing size and median nerve symptoms, the surgeon recommended surgical excision of the mass.

Intraoperatively, the mass was distinct from the median nerve, and it was excised in a single piece without apparent violation of its borders. Intraoperative pathology showed the mass to be a synovial sarcoma. The margins of resection could not be interpreted because the mass was incised after resection on the back table; the operative surgeon, however, believed that the margins were “relatively” negative since the mass was easily removed with no soft tissue attachments.

After referral to our orthopaedic oncology service, further treatment with either amputation, re-excision with wide margins, or radiation therapy were discussed with the patient and his family.

Both he and the family were adamantly opposed to either amputation or repeat wide resection due to concerns for loss of function that would be unacceptable to the patient. Therefore, he was treated definitively with radiation therapy with a cumulative dose of 60 Gray (Gy).

He is now 4 years after radiation therapy without evidence of local recurrence or metastatic disease. He lives in an assisted living facility due to his Alzheimer’s dementia, and his left upper extremity is without pain and has subjectively normal function. Objectively his function is well preserved and equal bilaterally. Grip strength is 41 lbs. Wrist flexion is 30°. Wrist extension is 60°.

MCP and PIP flexion/extension is equal and full in all fingers. 2pt discrimination is 5-7 mm in all fingers. The Revised Musculoskeletal Tumor Society Rating Scale is 30 (out of 30). The Michigan Hand Outcomes Questionnaire (MHQ) scores are shown in Figure 1.

Patient 2 BS is currently a 31-year-old, right-hand dominant woman who originally presented to an orthopaedic surgeon for an enlarging mass on the dorsal and ulnar part of her right hand in the area of her 4th and 5th metacarpals. The mass was excised and pathology examination determined it to be a lowgrade giant cell tumor. It recurred, and the mass was re-resected 10 months later by a hand surgeon who noted, “The tumor itself was somewhat adherent to a significant portion of the overlying skin. This had some adherence to the dorsal fascia GHS Proc. May 2016; 1 (1): 60-63

Figure 1 Michigan Hand Outcomes Questionnaire (MHQ) scores (range, 0-100) for each patient following external beam radiation therapy.

Patient 1

Patient 2

Patient 3

Patient 4

Hand

Right Left

Right Left

Right Left

Right Left

Overall Hand Function

100

100

95

100

100

100

100

100

Activities of Daily Living

50

50

100

100

100

100

100

100

Work

N/A N/A

90

90

100

100

100

100

Pain

100

100

100

100

100

100

100

100

Aesthetics

100

100

100

100

100

100

100

100

Satisfaction

100

100

100

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100

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100

100

over her hypothenar musculature, primarily her abductor. The tumor itself was densely adherent to several large branches of her dorsal sensory branch of the ulnar nerve, which clearly had to be taken with the specimen to get even a marginal margin.” The tumor itself was 4.5 x 2.0 x 1.5 cm.

Following this resection, pathology confirmed that this was an intermediate-grade giant cell tumor with microscopically positive margins.

After referral to our service, further treatment options were discussed. In order to obtain negative margins, revision surgical resection including all of the dorsal extensor tendons of her hand or a trans-forearm amputation of the dominant extremity would have been required. Neither of these options was acceptable to the patient and her family, and radiation therapy alone was elected by the patient. The patient was therefore treated definitively with radiation therapy with a cumulative dose of 63 Gy. BS has now gone 4 years without local recurrence or metastatic disease and is working as a guidance counselor for high school students. She has no pain with her hand and no complaints except for subtle paresthesias in her ulnar digits. Her grip strength is 70 lbs in her right hand (affected hand) and 44 lbs in her left hand. Wrist flexion is 50° bilaterally. Wrist extension is 60° on the right and 50° on the left. MCP and PIP joint flexion and extension are identical in all digits bilaterally. 2pt discrimination was less than 5 mm in all of the 61

digits on both hands. The MSTS is 29. The MHQ is shown in Figure 1 (Page 61).

Patient 3 TH is a 62-year-old man who was employed as a painter and is an avid guitarist. He initially presented to an orthopedic surgeon with the complaint of an enlarging mass of the volar aspect of the distal left forearm, his nondominant extremity. The mass was excised but not sent to pathology for examination. The mass recurred and underwent re-excision by the same surgeon. This specimen was sent to pathology and determined to be dedifferentiated pleiomorphic sarcoma with microscopically positive margins.

Examination after referral to our service showed him to have postoperative ecchymosis that suggested the need for an elbow disarticulation or a trans-humeral amputation. After explanation of the risks, benefits, and alternatives of the surgical plans versus radiation therapy, the patient decided to pursue radiation therapy instead of further surgery. The patient was therefore treated definitively with radiation therapy with a cumulative dose of 60 Gy. He is now 5 years postradiation therapy without local recurrence or evidence of metastatic disease.

He works as a painter, continues to play guitar, and has no complaints with his affected extremity.

His grip strength is 82 lbs on the right and 85 lbs on the left. Wrist flexion and extension is 75° on the right and 70° on the left. Flexion and extension at the MCP joints and PIP joints are symmetrical bilaterally. The MSTS is 30. The MHQ is shown in Figure 1.

Patient 4 PL is a 55-year-old, right-hand dominant woman who first noticed a mass on the palmar aspect of the base of her right index finger. There was continued slow growth of the mass over the next 2 years, and she presented to a local hand surgeon.

An excisional biopsy was performed, and the results of the pathology showed a 4 cm acral myxoinflammatory fibroblastic sarcoma with microscopically positive margins.

She was referred to our institution and underwent MRI imaging for further assessment. It was determined that in order to obtain negative surgical margins, ray amputations of the 2nd through the 4th rays of her dominant extremity would be required. Following explanation of the risks, benefits, and alternatives of further surgery versus radiation therapy, and after several second opin62

ions, the patient decided to pursue treatment with definitive radiation therapy with a cumulative dose of 60 Gy. She has now gone 4 years without either local recurrence or evidence of metastatic disease. She is employed as an education consultant. Subjectively, she notes that her manual dexterity in the right hand is slightly worse than her left hand.

Objective functional measurements show grip strength is 30 lbs on the right and 35 lbs on the left. Wrist flexion and extension are equal bilaterally at 50o for both flexion and extension. She has normal range of motion in her MCP and PIP joints bilaterally. MSTS is 28. Her MHQ is shown in Figure 1.

Discussion Residual disease rates after unplanned primary surgical resections have been reported to be as high as 39% to 59%,10 and it is well established that the perioperative metrics for sarcoma excisions are significantly improved when STSs undergo planned surgical resection at specialized centers of care by musculoskeletal oncologists.11 ESTSs of the hand and distal upper extremity, however, present unique challenges to this optimal treatment paradigm. ESTS is rare, with benign soft tissue extremity tumors outnumbering malignant ones by over 100:1.12 ESTSs, benign tumors, or processes such as hematoma or ganglion cysts are also often similar in presentation and appearance.

A resulting “low index of suspicion” for malignancy can lead to suboptimal surgical treatment of an unrecognized ESTS by a surgeon, other than an orthopaedic oncologist, if resection does not achieve negative surgical margins.

If surgical excision of ESTSs in the hand results in residual disease, subsequent treatment to eradicate the malignancy surgically may have significant detrimental functional consequences if subsequent wide resection or amputation is required.

Adjuvant radiation therapy to the distal extremity is also not without significant consequences or complications. Studies show that high-dose XRT adversely affects posttreatment extremity function through chronic pain, chronic lymphedema, decreased strength, and limited range of motion.13 Unfortunately there is very little written about the management of residual ESTSs in the revision surgery setting to guide our management of these patients.14 Two relatively recent studies indicate improved outcomes with resection with wide margins or amputations in patients with distal ESTSs. Lin et al examined 115 patients with STS of the GHS Proc. May 2016; 1 (1): 60-63

HAND FUNCTION AFTER STS EXCISION AND RADIATION hand or foot. Their patient cohort had a 10-year recurrence-free survival that was significantly greater in patients that received wide re-resection (88%) versus no re-resection (58%). They recommended wide re-resection to include amputation of digits if necessary to achieve negative margins when presented with a patient with residual ESTS of the hand who had been previously undergone surgery at an outside facility.9 Similarly, Pradhan et al reported on 63 patients with ESTS of the hand. They showed a local recurrence of 6% when treated by amputation compared with 42% in those who underwent attempted limb salvage.

The high recurrence rate seemed to be driven by inadequate margins, with a 12 times greater risk of local recurrence in those with positive margins when compared with those in whom a wide margin of resection had been achieved. Furthermore, they were unable to demonstrate any role for radiotherapy in decreasing the risk of local recurrence when there was an inadequate margin of resection.8 In contrast to the recommendations of these studies of larger groups of patients, our limited cohort of 4 patients underwent definitive radiation therapy for treatment of residual disease after previous

resection of ESTS that resulted in positive surgical margins. Each of these patients adamantly refused our initial recommendation for amputation as the recommended course of treatment and instead opted for radiation therapy. With at least 4-year follow-up, all 4 patients have no evidence of local recurrence or metastatic disease. Instead of significant functional compromise that would have resulted from amputation, all 4 patients have normal or near normal function in the affected extremity. High-dose radiation therapy has not adversely affected their function.

Correspondence Address to: Scott E. Porter, MD, MBA, FACS Greenville Health System, 2nd Floor Support Tower 701 Grove Rd, Greenville, SC 29605 (sporter@ghs.org)

Conclusion ESTSs of the hand are at high risk for unplanned surgical resection by surgeons who do not have specialized training in orthopaedic oncology. The consequence of subsequent surgical treatment is potentially profound given the detrimental effects of wide re-resection or amputation on hand function. XRT may be a feasible treatment alternative in select patients to effectively eradicate residual malignancy and preserve normal or near normal hand function. Further study will be needed to determine if this is a reasonable treatment option in a significant proportion of these patients.

References 1. Brennan M, Alektiar KM, Maki RG: Soft tissue sarcoma, in DeVita VT, Hellmann S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology. Philadelphia, PA, Lippincott Williams & Wilkins, 2001, pp 1841-1891.

2. Owens JC, Shiu MH, Smith R, Haidu SI. Soft tissue sarcomas of the hand and foot. Cancer. 1985;55:2010-8.

3. Yang JC, Chang AE, Baker AR, et al: Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol. 1998;16:197-203.

4. Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. 1982;196:305-15.

5. Wolfe SW, Hotchkiss RN, Pederson WC, Kozin SH. Greenâ&#x20AC;&#x2122;s Operative Hand Surgery, 6th ed. Elsevier/Churchill Livingstone, Philadelphia, PA; 2011:680-704.

6. Keus RB, Rutgers EJ, Ho GH, Gortzak E, Albus-Lutter CE, Hart AA. Limb-sparing therapy of extremity soft tissue sarcomas: treatment outcome and long-term functional results. Eur J Cancer. 1994;30A:1459-63.

7. Puhaindran ME, Rohde RS, Chou J, Morris CD, Athanasian EA. Clinical outcomes for patients with soft tissue sarcoma of the hand. Cancer. 2011;117:175-9.

GHS Proc. May 2016; 1 (1): 60-63

8. Pradhan A, Cheung YC, Grimer RJ, et al. Soft-tissue sarcomas of the hand: oncological outcome and prognostic factors. J Bone Joint Surg Br. 2008;90:209-14.

9. Lin PP, Guzel VB, Pisters PW, et al. Surgical management of soft tissue sarcomas of the hand and foot.

Cancer. 2002;95:852-61.

10. Lewis JJ, Leung D, Espat J, Woodruff JM, Brennan MF. Effect of reresection in extremity soft tissue sarcoma. Ann Surg. 2000;231:655-63.

11. Van Geel AN, Eggermont AMM, Hanssens PEJ, Schmitz PIM. Factors influencing prognosis after Initial Inadequate Excision (IIE) for soft tissue sarcoma.

Sarcoma. 2003;7:159-65.

12. Rydholm A, Berg NO, Gullberg B, Thorngren KG, Persson BM. Epidemiology of soft-tissue sarcoma in the locomotor system. A retrospective population-based study of the inter-relationships between clinical and morphologic variables. Acta Pathol Microbiol Immunol Scand A. P.1984;92:363-74.

13. Rohde RS, Puhaindran ME, Morris CD., et al. Complications of radiation therapy to the hand after soft tissue sarcoma surgery. J Hand Surg Am. 2010;35:1858-63.

14. Stinson SF, DeLaney TF, Greenberg J, et al: Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma. Int J Radiat Oncol Biol Phys. 1991;21:1494-9.

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Case Studies

Diagnostic Management of Urinary Retention: Why Multiple Sclerosis Should Be Included as a Differential Diagnosis Amanda Raines, MD; Samantha C. Ward, BS; and W. Patrick Springhart, MD From the University of South Carolina School of Medicine, Columbia, SC (A.R.); University of South Carolina School of Medicine Greenville, Greenville, SC (S.C.W., W.P.S.); and Department of Surgery, Division of Urology, Greenville Health System, Greenville, South Carolina (W.P.S.)

Abstract Patients with multiple sclerosis (MS) typically present with neurological symptoms. Although urinary incontinence and overactive bladder have also been reported, urinary retention is considered uncommon. This case describes a rare initial presentation of urinary retention secondary to MS lesions of the pontine micturition center.

M

ultiple sclerosis (MS) is a chronic and progressive neurological disease with relapsing and remitting features known to manifest in a variety of signs and symptoms.

Although the majority of MS patients initially present with neurological symptoms, approximately 3%-10% have accompanying urinary complaints. The majority of these patients, however, develop urinary incontinence or detrusor sphincter dyssynergia, a dysfunction that primarily stems from a neurological disorder or a spinal injury. Very few reports in the literature describe urinary retention as a presenting symptom of MS. In this case report, we describe the diagnostic management of a young man who presented with urinary retention with no obvious etiology.

Case Description A 33-year-old Caucasian man presented to Greenville Memorial Medical Centerâ&#x20AC;&#x2122;s Emergency Department (GMMC-ED) with acute onset paresthesia on the left side of his face and left upper extremity weakness. Because of suspicion for transient ischemic attack (TIA), he was admitted, evaluated, and discharged home.

One week later, he presented to a different hospital with diplopia and vertigo. The patient then returned to GMMC-ED 2 weeks later with urinary retention and right-sided paresthesia to

64

his face. The patient reported several weeks of progressive difficulty urinating, with symptoms including incomplete emptying, urinary intermittency, hesitancy, and straining. He described a normal sensation of bladder fullness, which progressed over several hours to an inability to voluntarily urinate. He denied urgency, frequency, dysuria, hematuria, or incontinence. On physical exam, multiple neurologic findings were noted, including ataxic dysarthria, vertical nystagmus, cerebellar ataxia, and gait ataxia. Upon further questioning, he described difficulty with depth perception and an inability to visually focus on objects. However, when he closed his left eye, his sight improved, and he was able to read and focus without trouble.

Management of Care During the patientâ&#x20AC;&#x2122;s initial ED visit, a carotid duplex and echocardiogram were performed, as well as magnetic resonance imaging (MRI), magnetic resonance angiogram (MRA) without contrast, computed tomography (CT) scans, and a CT angiography (CTA) of his head and neck. The carotid duplex and echocardiogram revealed no abnormalities. The MRI showed T2 hyperintense signal abnormalities of the central anterior pons slightly left of midline (11.6 x 9.4 mm) and right lateral corpus splenium (5 mm) (Fig. 1). A minute lesion was also noted in the left middle cerebel-

GHS Proc. May 2016; 1 (1): 64-67

URINARY RETENTION SECONDARY TO MS LESIONS lar peduncle on T2 imaging (8.5 mm). Etiology of the lesions was unclear, but vascular versus demyelination was suggested. The CT scan was normal, and the only abnormality on MRA was an absent anterior cerebral artery, an incidental developmental anomaly. CTA of the head and neck showed a 1.7 mm aneurysm of the left middle cerebral artery with no other abnormalities.

The patientâ&#x20AC;&#x2122;s lab work was within normal limits.

Three weeks later, when the patient returned with urinary retention and paresthesia, a Foley urinary catheter was placed and a follow-up MRI showed an enlargement of the lesions in the left pons (14 x 15 mm) (Fig. 2). The lesion of his middle cerebellar peduncle was visible on T2 and measured 17 x 17.5 mm. Urinalysis showed 3 to 5 red blood cells but was otherwise normal. Urine culture showed no growth. Cerebrospinal fluid analysis after lumbar puncture revealed oligoclonal bands.

These laboratory and radiologic findings, along with his evolving symptoms, bolstered multiple sclerosis (MS) as the most likely etiology.

The patient was subsequently started on IV steroids, and his vision began to improve. He was

discharged on a 16-day prednisone taper and instructed to follow-up with urology in 2 weeks.

At follow-up, the Foley catheter was removed and a renal ultrasound (US) performed to rule out upper tract abnormalities. US showed normal echogenicity of the kidneys and postvoid residual of 37 mL. The patient was educated on clean intermittent catheterization and started on tamsulosin. Neurology also saw the patient after 2 weeks and started him on glatiramer for the management of MS. At his 6-week follow-up with urology, the patient was voiding well with minimal urinary symptoms. His other MS symptoms were also improving.

Follow-up MRI 4 months later showed stable lesions in both the left anterior pons and the left middle cerebellar peduncle. However, both lesions had decreased signal abnormalities and were mildly smaller in size, with the anterior pontine lesion measuring 11.3 x 10 mm and the middle cerebellar peduncle lesion measuring 10 x 7 mm (Fig. 3, Page 66). At this time, the patient has no urinary symptoms and is continuing to take glatiramer for long-term management of his MS.

Figure 1

Figure 2

Head MRI without contrast performed on initial presentation showing lesion in the left anterior pons (white arrow). Axial T2 weighted.

Head MRI without contrast performed on presentation of urinary retention showing lesions in left anterior pons (white arrow) and left middle cerebellar peduncle (gray arrow). Axial T2 weighted.

GHS Proc. May 2016; 1 (1): 64-67

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Correspondence Address to: Patrick Springhart, MD, Greenville Health System, Regional Urology 11 Park Creek Dr Greenville, SC 29605 (pspringhart@ghs.org)

Discussion Multiple sclerosis (MS) is a disease process in which the immune system directs an abnormal response toward the central nervous system (CNS). This immune-mediated attack on the CNS manifests as various signs and symptoms.

As a chronic and progressive disease, MS demonstrates remissions and relapses that characteristically disrupt motor and sensory function, as demonstrated in this patient. MS is most commonly diagnosed between the ages of 20 and 50 years and is more prevalent in women.1 The majority of MS patients present with neurological symptoms; only 3%-10% of these patients present with urinary symptoms as their initial complaint.2 While most patients with urinary symptoms from MS develop incontinence or detrusor sphincter dyssynergia (DSD), the patient described in this case developed urinary retention without other lower urinary tract symptoms.

While micturition in adults is an autonomic reflex, it is under voluntary control. At certain filling pressures, an important neural signal triggers a change from bladder storage to elimination, after

Figure 3 Head MRI without contrast performed at 4-month follow-up showing lesions of the left anterior pons (white arrow) and left middle cerebellar peduncle (gray arrow). Axial T2 weighted.

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which micturition is able to proceed in a reflexlike manner. This switch is purported to be activated by the pontine micturition center (PMC).3 Since the PMC is responsible for a key step in micturition, lesions in this region can result in urinary retention.4 Lesions between the PMC and sacral micturition center typically produce problems with urine storage, bladder emptying, and DSD.2,5 There has been very little reported on patients with MS lesions within the pons.

To treat the urinary dysfunction of MS, the underlying cause of the dysfunction must be addressed. Numerous drugs treat the pathophysiologic process behind the disease, as well as the symptoms. This patient was started on steroids at the hospital to treat the acute flare of MS. At his outpatient follow-up with neurology, he was started on glatiramer to manage the disease.

Approaching patient treatment as a multidisciplinary team is important for successful MS therapy as the disease course can change with every relapse.

Because MS can affect any portion of the CNS, the presentation will differ based on the location of the lesion. As a result, treatment is dependent on the foci of involvement. Anticholinergics and pelvic floor training are the main therapies for patients with urinary symptoms related to MS. These treatments, however, are only helpful when the symptoms involve detrusor over activity, urgency, and incontinence and are inappropriate when the patient is experiencing urinary retention.1 For patients experiencing incomplete emptying or symptoms of retention, Îą-adrenergic antagonists may be used and can reduce postvoid residual. However, studies on the use of these drugs, specifically in MS patients, are limited.5 Patients with components of retention may also benefit from clean intermittent catheterization.

The patient in this study had an indwelling catheter placed for his urinary retention. The catheter remained until his 2-week follow-up visit. At that point, it was removed, and the patient and his wife were educated on how to perform clean intermittent catheterization. At his 6-week follow-up, the patient reported no difficulty with micturition and had not been self-catheterizing.

The patient had a follow-up visit and MRI at 4 months. As seen in Figure 3, the lesions were still visible, even though his symptoms had improved. This is consistent with the literature, as MS lesions usually decrease in size and intensity on T2-weighted imaging but continue to be seen on MRI and do not dissipate completely.6 GHS Proc. May 2016; 1 (1): 64-67

URINARY RETENTION SECONDARY TO MS LESIONS

Conclusion In conclusion, we present a rare case of multiple sclerosis with a lesion of the pontine micturition center resulting in urinary retention. Although urinary symptoms of MS are typically related to

urinary incontinence and overactive bladder, in patients presenting with retention with no obvious etiology, MS should be considered a differential diagnosis.

References 1. Corcos J. A urological challenge: voiding dysfunction in multiple sclerosis. Can Urol Assoc J. 2013;7:S181-2.

4. McDougal WS, Wein AJ, Kavoussi LR, et al. Campbell-Walsh Urology Tenth Edition Review. Elsevier Saunders 2012.

2. Sand PK, Sand RI. The diagnosis and management of lower urinary tract symptoms in multiple sclerosis patients. Dis Mon. 2013;59:261-8.

5. Andersson KE. Current and future drugs for treatment of MS-associated bladder dysfunction. Ann Phys Rehabil Med. 2014;57:321-8.

3. Michels L, Blok BF, Gregorini F, et al. Supraspinal control of urine storage and micturition in men-an fMRI study. Cereb Cortex. 2015;25:3369-80.

6. Bakshi R, Minagar A, Jaisani Z, Wolinsky JS. Imaging of multiple sclerosis: role in neurotherapeutics.

NeuroRx. 2005;2:277-303.

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Value Vignette

Choosing High-Value Medications Misty L. McDowell, MD, and Lauren D. Demosthenes, MD From the Department of OB/GYN, Greenville Health System, Greenville, SC (M.L.M., L.D.D.)

Clinical Scenario A 20-year-old gravida 1 (G1) patient presented to labor and delivery for induction of labor at 41 weeks. Her pregnancy had been uncomplicated to this point. She denied rupture of membranes and reported good fetal movement.

A physician evaluated the patient and noted the following vital signs: Temp 98.7o, HR 85, BP 110/70, RR 12, O2 Sat 100% RA. Her cervix was 25% effaced, 1 cm dilated, and high with a Bishop score of 1. The nonstress test was reactive.

Treatment Options Option A: We counsel the patient on induction of labor and place a dinoprostone vaginal insert for cervical ripening.

Figure 1 Annual cost of dinoprostone vaginal insert.

Option B: We counsel the patient on induction of labor and give misoprostol orally for cervical ripening.

$134,400

Discussion Questions Which cervical ripening agent is more effective, dinoprostone vaginal insert or oral misoprostol?

$67,900

$61,669

What is the cost difference between the dinoprostone vaginal insert and oral misoprostol?

Costs* Option A: Dinoprostone vaginal insert: $333.00 Pre-Intervention (May 2012-April 2013)

Pre-Intervention Post-Intervention (May 2013-April 2014) (May 2014-April 2015)

Option B: Oral misoprostol: $1.00/dose *Costs were obtained from healthcarebluebook.com.

These costs are estimates and represent the amount typically paid by an insurance company for this medication.

Figure 2 Annual utilization of dinoprostone vaginal insert (units).

Teaching Moment 384

194

Pre-Intervention (May 2012-April 2013) 68

174

Pre-Intervention Post-Intervention (May 2013-April 2014) (May 2014-April 2015)

The patient in this case was a low-risk patient at 41.0 weeks presenting for induction of labor. Current ACOG (American Congress of Obstetricians and Gynecologists) practice guidelines regarding management of late-term pregnancies recommend induction of labor between 41.0 and 42.0 weeks due to perinatal morbidity and mortality increasing beyond 42.0 weeks.1 This patient discussed the risks and benefits of induction of labor with her physician and desired to proceed with induction.

More than 22% of all gravid women undergo induction of labor in the United States. The goal GHS Proc. May 2016; 1 (1): 68-69

CHOOSING HIGH-VALUE MEDICATIONS of induction of labor is to achieve vaginal delivery by stimulating uterine contractions before the spontaneous onset of labor.2 The Bishop score is used to evaluate how favorable a cervix is for labor. A score of â&#x2030;¤6 indicates an unfavorable cervix, and cervical ripening is recommended prior to labor induction. The goal of cervical ripening is to facilitate the process of cervical softening, thinning, and dilating necessary for labor.2-4 Multiple methods are available to an obstetric provider for cervical ripening, including mechanical cervical dilators and synthetic prostaglandins (PGE-1-misoprostol and PGE-2-dinoprostone).3,5 The choice of which agent to use for cervical ripening is largely dependent on the preference of the provider.

Mechanical cervical dilators have been shown to be equally efficacious as synthetic prostaglandins.6 Additionally, labor induction with oral misoprostol compared to vaginal dinoprostone has demonstrated a shorter time to vaginal deliv-

ery as well as fewer cesarean deliveries, without compromising safety.7 Given the safety, efficacy, and cost difference between misoprostol ($1.00/dose) and dinoprostone ($333.00) (Fig.â&#x20AC;Ż1), choosing misoprostol over the dinoprostone vaginal insert is a simple and significant intervention, generalizable to all institutions and capable of providing high-value, cost-conscious care.

Correspondence Address to: Misty McDowell, MD Greenville Health System, Department of OB/GYN 890 W Faris Rd Suite 470 Greenville, SC 29605 (mmcdowell2@ghs.org)

Intervention and Result In 2013, the obstetrics and gynecology residents and faculty at Greenville Health System were educated about the efficacy, safety and cost of the dinoprostone vaginal insert versus oral or vaginal misoprostol. Utilization of the dinoprostone vaginal insert was monitored for the following 2 years and a significant drop after this intervention was noted (Fig. 2). This information was subsequently reported to our maternal-fetal medicine committee who supported removal of this product from the hospital formulary.

References 1. American College of Obstetricians and Gynecologists. Practice bulletin no. 146: Management of late-term and postterm pregnancies. Obstet Gynecol.

2014;124:390-6.

2. ACOG Committee on Practice Bulletinsâ&#x2C6;&#x2019;Obstetrics.

ACOG Practice bulletin no. 107: Induction of Labor.

Obstet Gynecol. 2009;114:386-97.

3. Swamy GK. Current methods of labor induction.

Semin Perinatol. 2012;36:348-52.

4. Demosthenes L, Eichelberger K. Outpatient cervical ripening: has its time come? Contemporary OB/GYN. 2015:1-4.

GHS Proc. May 2016; 1 (1): 68-69

5. Gelber S, Sciscione A. Mechanical methods of cervical ripening and labor induction. Clin Obstet Gynecol.

2006;49:642-57.

6. Vaknin Z, Kurzweil Y, Sherman D. Foley catheter balloon vs locally applied prostaglandins for cervical ripening and labor inductions: a systematic review and meta-analysis. Am J Obstet Gynecol. 2010;203:418-29.

7. Faucett AM, Daniels K, Lee HC, El-Sayed YY, Blumenfeld YJ. Oral misoprostol versus vaginal dinoprostone for labor induction in nulliparous women at term. J Perinatol. 2014;34:95-9.

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Editorial

Mercy Robert A. Saul, MD From the Center for Pediatric Medicine, Greenville Health System, Greenville, SC Correspondence Address to: Robert A. Saul, MD Greenville Health System, Center for Pediatric Medicine 20 Medical Ridge Dr Greenville, SC 29605 (rsaul@ghs.org)

References 1. ONESouthCarolina Conference (The DLI Graduate Weekend), Hilton Head Island, SC, March 2013.

2. Stevenson B: Just Mercy: A Story of Justice and Redemption.

Spiegel and Grau, 2014, New York.

3. Daaleman TP. The quality of mercy: will you be my doctor?

JAMA. 2014;312: 1863-4.

4. Keenan JF. The Works of Mercy. Lanham, MD: Rowman & Littlefield; 2007.

5. Saul RA. Columbine High School−April 20, 1999. What can I do to help my own community?

J S C Med Assoc.

2005;101:35-7.

6. Saul RA. My Children’s Children: Raising Young Citizens in the Age of Columbine.

CreateSpace, 2013, Charleston, SC.

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I

am always amazed at how seemingly disjointed events can fortuitously be linked. One can argue that it is divine providence or just pure coincidence. I don’t have the answer to that argument but choose to relish in the glory that such revelations can provide and “listen” to the message going forward. Let me discuss three such recent events.

First, in 2013, I had the thrilling pleasure to hear Bryan Stevenson at an event sponsored by the Riley Institute of Furman University.1 Mr. Stevenson is the executive director of the Equal Justice Initiative in Montgomery, Alabama. I was moved to hear the passionate description of his work on behalf of people wrongly accused of crimes yet incarcerated for inhumane periods of times under equally inhumane conditions. He further goes on to detail the unequal justice system in our country, especially for our citizens of color. The mass incarceration of our less fortunate countrymen raises serious questions about our ability to fairly apply the standards of justice in our country. His work had left a haunting impression and struck a real chord. I remember his statement—the opposite of poverty is not wealth; the opposite of poverty is justice—as a call to action. I just did not know the action.

Next, in October 2014, I saw that Bryan Stevenson just published his book (Just Mercy) about the experiences above.2 Mr. Stevenson poignantly chronicles his work and engages the reader in a way unanticipated. He reminds us that the measure of our society (and us as citizens) is how we treat the poor, the disfavored, the incarcerated, and the condemned.

Last, I picked up the November 12, 2014, issue of the Journal of the American Medical Association and found an article—“The quality of mercy: will you be my doctor?”3 This article addresses the calling of medicine and the difficulties with providing care to certain “difficult” patients. The author notes a previously attributed quote that “mercy is a willingness to enter into the chaos of

another.”4 He further states that mercy is a “developed human capacity that involves hard, uncertain, and hidden work.” Works of mercy cannot be measured or specifically quantified yet they define the essential elements of our ability to provide meaningful care.

I now see that mercy, and the discomfort that it invites, is a vital part of my mission going forward. The work of Bryan Stevenson reminds me of my responsibility to my fellow citizens. Neither Mr. Stevenson nor I is an advocate of no punishment for unjust deeds. Rather, it is critical that punishment in our country be fair and just—and equal. We must work constantly to reverse the social issues that lead to the situations that allow inequities to exist. Poverty and the lack of equal opportunity in education, employment, and health unfortunately are the breeding ground for so many of the problems that we face and have to be addressed as a communal responsibility.

As we engage in the work of our community, it is critical that mercy be at the forefront of our actions.

It involves hard work, and if we are willing to engage in the “chaos” of others, great things can be accomplished. Five Steps to Community Improvement that may provide a template for action in our community involvement include the following, learn to be the best parent you can be, get involved, stay involved, love others, and forgive.5,6 The chaos of others can be quite discomforting.

It is difficult to accept our roles at times to treat the less fortunate as we would our own family. Yet that is the measure of our ability to exhibit mercy and provide the nurturing care that is necessary to improve our lives, the lives of our fellow citizens, and the life of our community. As Dr. Daaleman states, “If the arc of medicine is to ultimately bend toward healing, mercy will be its fulcrum.”3 Whether engaged in medical service as a physician or community service as a citizen, we need to let mercy be our guide and let compassion and forbearance lead us forward.

GHS Proc. May 2016; 1 (1): 70

Graduates of 2016

USCSOM Greenville Class of 2016 Ahmer Ansari Kara Barlow Ryan Batson Robert Bonanno Chanel Bonds Natalie Bott C. Phillip Callihan Alexis Cannon Michelle Caskey Thomas Cochran Jensyn Cone Amanda Craig Brittany Crum

Kindal Dankovich Jennifer Davis Matthew Eisenstat Eric Fulmer Trevor Gravely Kristie Griffin Myah Griffin Christina Gutta R. Maglin Halsey Mollie Hamilton Justin Harold Alysa James J. Evans James

B. Keith Johnson Alec Kitch Stewart Lee Georgia Lesser Julie Lortz Madison Merritt Christopher Parsons Kathryn Peterson Shea Ray Shane Reighard Jennifer Reinovsky Kyle Ryberg Elyse Sadow

Andrew See Chelsea Smith Steven Swinehart R. Kyle Townsend Charlotte Van Hale Jeffrey VanderWood Benjamin Velky Samantha Ward Paige Woodham Darrell Wright

2016 GHS Residents and Fellows Family Medicine Daniel Musser, MD India Robinson, MD Karl Szafranski, MD Primary Care Sports Medicine Stephanie Bailey, MD Asad Sidiqqi, DO Internal Medicine Virginia Adkins, MD William Beam, MD Stephen Carey, DO Julie Daniel, DO Carter Edwards, MD Mary Hotz, MD Torey Killom, DO Tim Maddux, MD Ryan Porter, MD Maximilien Rappaport, DO Darion Showell, DO Travis Sizemore, DO Internal Medicine/Pediatrics Andrew Burgess, MD Shannon Burgess, MD Elizabeth Dewald, MD Teresa Williams, MD

GHS Proc. May 2016; 1 (1): 71

Pediatrics Meagan Aiken, MD Matthew Bradshaw, MD Lee Glenn, MD S. Chad Hayes, MD Nicholas Kelley, MD Mark Krom, DO Sara McNemar, MD Garrison Moore, MD Mary Norton, MD Easter Pennington, MD Emily Wolroth, MD Developmental-Behavioral Pediatrics Caroline Buchanan, MD Obstetrics & Gynecology Lesley Bundon, MD Kimberly Fryer, MD Sheena Gamble, DO Dianna Gurich, MD Andrew Lane, MD William Perez, MD Orthopaedic Surgery Stephen Finley, MD Garland Gudger, MD Justin Langan, MD Julia Lee, MD

Orthopaedic Sports Medicine Jeffrey Abildgaard, MD Jared Bentley, MD Colten Luedke, DO Troy Roberson, MD Psychiatry Arun Handa, MD Brian LeDuc, MD Sidra Kahlon, MD Louis Viamonte, MD Surgery Amanda Eckenrode, MD Matthew Epps, MD April Grant, MD Ivaylo Mitsiev, MD John Richey, MD R. Jared Sanders, MD Vascular Surgery Joseph-Vincent Blas, MD Sagar Gandhi, MD Minimally Invasive Surgery Roozbeh Mansour, MD Puraj Patel, DO

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2015 Publications of Greenville Health System Medical and Scientific Staff Cancer Institute 1.

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Brana I, Berger R, Golan T, Haluska P, Edenfield J, Fiorica J, Stephenson J, Martin LP, Westin S, Hanjani P, Jones MB, Almhanna K, Wenham RM, Sullivan DM, Dalton WS, Gunchenko A, Cheng JD, Siu LL, Gray JE. A parallel-arm phase I trial of the humanised anti-IGF-1R antibody dalotuzumab in combination with the AKT inhibitor MK-2206, the mTOR inhibitor ridaforolimus, or the NOTCH inhibitor MK-0752, in patients with advanced solid tumours. Br J Cancer.

2014;11:1932-44.

Chen WY. The many faces of prolactin in breast cancer. Adv Exp Med Biol. 2015;846:61-81.

Rappaport MJ, Showell DL, Edenfield WJ. Metastatic ghost cell odontogenic carcinoma: description of a case and search for actionable targets. Rare Tumors. 2015;7:5813.

McCoy G, Edenfield WJ. A case of newly diagnosed chronic myelomonocytic leukemia with rheumatoid arthritis presentation. J Clin Case Rep. 2014; 4:414.

Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006-17.

Rapp SR, Case LD, Peiffer A, Naughton MM, Chan MD, Stieber VW, Moore DF Jr, Falchuk SC, Piephoff JV, Edenfield WJ, Giguere JK, Loghin ME, Shaw EG. Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial. J Clin Oncol.

2015;33:1653-9.

Rogers A. Louder than words. Clin J Oncol Nurs.

2014;18:602.

Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, Oâ&#x20AC;&#x2122;Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol. 2014 ;32:3483-9.

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Sterba KR, Armeson K, Franco R, Harper J, Patten R, Kindall S, Bearden J, Zapka J. A pilot randomized controlled trial testing a minimal intervention to prepare breast cancer survivors for recovery. Cancer Nurs. 2015;38:E48-56.

Care Coordination Institute 10. Boan AD, Egan BM, Bachman DL, Adams RJ, Feng WW, Jauch EC, Ovbiagele B, Lackland DT. Antihypertensive medication persistence 1-year post-stroke hospitalization. J Clin Hypertens.

2014;16:869-74.

11. Egan BM, Li J, Hutchison FN, Ferdinand KC. Hypertension in the United States 1999-2012: progress toward healthy people 2020 goals. Circulation. 2014. [Epub ahead of print].

12. Egan BM, Li J, Small J, Nietert PJ, Sinopoli A. The growing gap in hypertension control between insured and uninsured adults: national health and nutrition examination survey 1988 to 2010.

Hypertension. 2014;64:997-1004.

13. Egan BM, Stevens-Fabry S. Prehypertension-prevalence, health risks, and management strategies. Nat Rev Cardiol. 2015;12:289-300.

14. Egan BM. Opportunities for multidisciplinary ASH clinical hypertension specialists in an era of population health and accountable care: ASH leadership message. J Am Soc Hypertens.

2014;8:451-6.

15. Egan BM, Stevens-Fabry S. The importance of masked hypertension in adults with prehypertension. Nat Rev Cardiol. 2015;12:497.

16. Egan BM. Elijah Saunders in Memoriam. J Clin Hypertens. 2015;17:415-7.

17. Egan BM, Bland VJ, Brown AL, Ferdinand KC, Hernandez GT, Jamerson KA, Johnson WR, Kountz DS, Li J, Osei K, Reed JW, Saunders E. Hypertension in african americans aged 60 to 79 years: statement from the international society of hypertension in blacks. J Clin Hypertens.

2015;17:252-9.

18. Egan BM. Effectiveness of a tailored behavioral intervention to improve hypertension control.

Hypertension. 2015;65:273-5.

19. Jones JB, Shatat IF, Egan BM, Paulo RC. Decreased heart rate variability is associated with in-

GHS Proc. May 2016; 1 (1): 72-82

2015 PUBLICATIONS

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creased transcranial Doppler velocities in children with sickle cell disease. Ethn Dis. 2014;24:451-5.

Lopes HF, Klein RL, Garvey WT, Goodfriend T, Egan BM. Influence of acute hyperlipidemia to adipocyte-derived hormones in lean normotensive and subjects with metabolic syndrome.

Diabetol Metab Syndr. 2014;6:132.

Moran WP, Zhang J, Gebregziabher M, Brownfield EL, Davis KS, Schreiner AD, Egan BM, Greenberg RS, Kyle TR 3rd, Marsden JE, Ball SJ, Mauldin PD. Chaos to complexity: leveling the playing field for measuring value in primary care. J Eval Clin Pract. 2015 Feb 4.[Epub ahead of print].

Nietert PJ, Shaftman SR, Silver RM, Wolf BJ, Egan BM, et al. Raynaud phenomenon and mortality: 20+ years of follow-up of the Charleston Heart Study cohort. Clin Epidemiol. 2015;7:161-8.

Page BR, Shaw EG, Lu L, Bryant D, Grisell D, et al. Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue. Neuro Oncol.

2015;17:1393-40.

Sperling LS, Mechanick JI, Neeland IJ, Herrick CJ, DesprĂŠs JP, Ndumele CE, Vijayaraghavan K, Handelsman Y, Puckrein GA, Araneta MR, Blum QK, Collins KK, Cook S, Dhurandhar NV, Dixon DL, Egan BM, Ferdinand DP, Herman LM, Hessen SE, Jacobson TA, Pate RR, Ratner RE, Brinton EA, Forker AD, Ritzenthaler LL, Grundy SM. The CardioMetabolic Health Alliance: working toward a new care model for the metabolic syndrome. J Am Coll Cardiol. 2015;66:1050-67.

Emergency Medicine 25. Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low-risk venous thromboembolism diagnosed in two US emergency departments: A one-year preplanned analysis. Acad Emerg Med. 2015;22:788-95.

26. Ellis J, Courson R, Daniels B. Spinal trauma. Curr Rev Musculoskelet Med. 2014;7:381-6.

27. Faul M, Dailey MW, Sugerman DE, Sasser SM, Levy B, Paulozzi LJ. Disparity in naloxone administration by emergency medical service providers and the burden of drug overdose in US rural communities. Am J Public Health. 2015;105:e26-32.

28. Faul M, Sasser SM, Lairet J, Mould-Millman NK, Sugerman D. Trauma center staffing, infrastructure, and patient characteristics that influence trauma center need. West J Emerg Med. 2015;16:98-106.

GHS Proc. May 2016; 1 (1): 72-82

29. Kahler ZP, Beam DM, Kline JA. Cost of treating venous thromboembolism with heparin and warfarin versus home treatment with rivaroxaban.

Acad Emerg Med. 2015;22:796-802.

30. Kopec KT, Yen M, Bitner M, Evans CS, Gerardo CJ. Marked hypofibrinogenemia and gastrointestinal bleeding after copperhead (Agkistrodon contortrix) envenomation. Wilderness Environ Med. 2015;26:488-90.

31. Lerner EB, McKee CH, Cady CE, Cone DC, Colella MR, Cooper A, Coule PL, Lairet JR, Liu JM, Pirrallo RG, Sasser SM, Schwartz R, Shepherd G, Swienton RE. A consensus-based gold standard for the evaluation of mass casualty triage systems. Prehosp Emerg Care. 2015;19:267-71.

32. Sundararaj K, Pleasant DL, Moschella PC, Panneerselvam K, Balasubramanian S, Kuppuswamy D. mTOR complexes repress hypertrophic gonist-stimulated expression of connective tissue growth factor in adult cardiac muscle cells. J Cardiovasc Pharmacol. 2016;67:110-20.

Family Medicine 33. Asif IM, Prutkin JM. Modern standards of ECG interpretation in young athletes: yield and effectiveness. J Electrocardiol. 2015;48:292-7.

34. Asif IM, Price D, Fisher LA, Zakrajsek RA, Larsen LK, et al. Stages of psychological impact after diagnosis with serious or potentially lethal cardiac disease in young competitive athletes: A new model. J Electrocardiol. 2015;48:298-310.

35. Asif IM, Yim ES, Hoffman JM, Froelicher V. Update: causes and symptoms of sudden cardiac death in young athletes. Phys Sportsmed.

2015;43:44-53.

36. Asif IM, Price D, Harmon KG, Salerno JC, Rao AL, et al. The psychological impact of cardiovascular screening in young athletes: perspectives across age, race, and gender. Clin J Sport Med. 2015;25:464-71.

37. Asif IM, MD, Roberts WO, Frederickson M, Froelicher V. The Cardiovascular Preparticipation Evaluation (PPE) for the primary care and sports medicine physician, part I. Curr Sports Med Rep. 2015;14:246.

38. Asif IM, MD, Roberts WO, Frederickson M and Froelicher V. The Cardiovascular Preparticipation Evaluation (PPE) for the primary care and sports medicine physician, part II. Curr Sports Med Rep. 2015;14:333.

39. Gardner JK, Zhang S, Liu H, Klipple G, Stewart C, Milner CE, Asif IM. Effects of toe-in angles on knee biomechanics in cycling of patients

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with medial knee osteoarthritis. Clin Biomech.

2015;30:276-82.

40. Harmon KG, Asif IM, Maleszewski JJ, Owens DS, Prutkin JM, Salerno JC, Zigman ML, Ellenbogen R, Rao AL, Ackerman MJ, Drezner JA. Incidence, cause, and comparative frequency of sudden cardiac death in national collegiate athletic association athletes: a decade in review. Circulation.

2015;132:10-9.

41. Rao AL, Asif IM, Drezner JA, Toresdahl BG, Harmon KG. Suicide in national collegiate athletic association (NCAA) athletes: a 9-year analysis of the NCAA resolutions database. Sports Health.

2015;7:452-7.

42. Writing Committee Members, Lawless CE, Asplund C, Asif IM, Courson R, Emery MS, Fuisz A, Kovacs RJ, Lawrence SM, Levine BD, Link MS, Martinez MW, Matherne GP, Olshansky B, Roberts WO, Salberg L, Vetter VL, Vogel RA, Whitehead J. Protecting the heart of the American athlete: proceedings of the American College of Cardiology Sports and Exercise Cardiology Think Tank October 18, 2012, Washington, DC. J Am Coll Cardiol. 2014;64:2146-71.

Internal Medicine 43. Avasarala JR, Zachariah P. Vitamin D deficiency in multiple sclerosis: should testing and treatment be based on racial background? J Neurol Sci. 2015;15:417-8.

44. Avasarala JR. Clinically isolated syndrome— rethinking the diagnosis. J Neurol Sci. 2015;353:79-80.

45. Avasarala JR. Newer multiple sclerosis drugs and disability scores-are key data analyses missing? J Clin Pharmacol. 2015;55:1218-20.

46. Avasarala JR. Stem cell therapies in multiple sclerosis—united we stand, divided we fail. Clin Case Rep Rev. 2015;1:199-200.

47. Avasarala, JR. Letter to the Editor re: Multiple sclerosis in US minority populations: clinical practice insights. Neurol Clin Pract. 2015;5:13242.

48. Avasarala, JR. Time to rethink CIS criteria. Multiple Sclerosis Discovery Forum. 12 May 2015.

49. Escaned J, Echavarria-Pinto M, Garcia-Garcia HM, van de Hoef TP, de Vries T, Baucum J, et al.

Prospective assessment of the diagnostic accuracy of instantaneous wave-free ratio to assess coronary stenosis relevance. JACC Cardiovasc Interv. 2015;8:824-33.

50. Emery MS, Quandt EF. Legal and ethical issues in the cardiovascular care of elite athletes. Clin Sports Med. 2015;34:507-16.

51. Grim SA, Layden JE, Roth P, Gallitano S, Adams W, Clark NM. Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes. Transpl Infect Dis. 2015;17:768-77.

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52. Jerome SD, Tilkemeier PL, Farrell MB, Shaw LJ. Nationwide laboratory adherence to myocardial perfusion imaging radiation dose reduction practices: a report from the intersocietal accreditation commission data repository. JACC Cardiovasc Imaging. 2015;8:1170-6.

53. Jindal M. Herpes Zoster. Consultant360. 2015 May; 55:390.

54. Jones JA, Shuler MJ, Zlotoff BJ. Levonorgestrel-releasing intrauterine system causes a lichenoid drug eruption. Cutis. 2015;96:E13-5.

55. Kelly JW, Blackhurst D, Steed C, Diller T. A response to the article, “Comparison of hand hygiene monitoring using the my 5 moments for hand hygiene method versus a wash in-wash out method”. Am J Infect Control. 2015;43:901-2.

56. Kelly VE, Johnson CO, McGough EL, Shumway-Cook A, Horak FB, Chung KA, Espay AJ, Revilla FJ, Devoto J, Wood-Siverio C, Factor SA, Cholerton B, Edwards KL, Peterson AL, Quinn JF, Montine TJ, Zabetian CP, Leverenz JB. Association of cognitive domains with postural instability/gait disturbance in Parkinson’s disease.

Parkinsonism Relat Disord. 2015;21:692-7.

57. Korpacz D, Tilkemeier P, Blissmer B, Lamont LS. Effects of social support on individual’s results of 12-weeks of cardiac rehabilitation. J Cardiopulm Rehabil. 2015;35:288.

58. Laub HN, Dwivedi AK, Revilla FJ, Duker AP, Pecina-Jacob C, Espay AJ. Diagnostic performance of the “Huffing and Puffing” sign in psychogenic (functional) movement disorders.

Mov Disord Clin Pract. 2015;2:29-32.

59. Marcus BH, Dunsiger SI, Pekmezi D, Larsen BA, Marquez B, Bock BC, Gans KM, Morrow KM, Tilkemeier P. Twelve-month physical activity outcomes in Latinas in the Seamos Saludables trial. Am J Prev Med. 2015;48:179-82.

60. Mata IF, Jang Y, Kim CH, Hanna DS, Dorschner MO, Samii A, Agarwal P, Roberts JW, Klepitskaya O, Shprecher DR, Chung KA, Factor SA, Espay AJ, Revilla FJ, Higgins DS, Litvan I, Leverenz JB, Yearout D, Inca-Martinez M, Martinez E, Thompson TR, Cholerton BA, Hu SC, Edwards KL, Kim KS, Zabetian CP. The RAB39B p.G192R mutation causes X-linked dominant Parkinson’s disease. Mol Neurodegener. 2015;10:50.

61. Mata IF, Leverenz JB, Weintraub D, Trojanowski JQ, Hurtig HI, Van Deerlin VM, Ritz B, Rausch R, Rhodes SL, Factor SA, Wood-Siverio C, Quinn JF, Chung KA, Peterson AL, Espay AJ, Revilla FJ, Devoto J, Hu SC, Cholerton BA, Wan JY, Montine TJ, Edwards KL, Zabetian CP. APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurol. 2014;71:1405-12.

62. Mata IF, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, Van Deerlin VM, Ritz B, Rausch R, Factor SA, Wood-Siverio C, Quinn JF, Chung KA, Peterson-Hiller AL, Goldman GHS Proc. May 2016; 1 (1): 72-82

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JG, Stebbins GT, Bernard B, Espay AJ, Revilla FJ, Devoto J, Rosenthal LS, Dawson TM, Albert MS, Tsuang D, Huston H, Yearout D, Hu SC, Cholerton BA, Montine TJ, Edwards KL, Zabetian CP. GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson’s disease.

Mov Disord. 2016;31:95-102.

Nagueh SF, Farrell MB, Bremer ML, Dunsiger SI, Gorman BL, Tilkemeier PL. Predictors of delayed accreditation of Echocardiography Laboratories: an analysis of the Intersocietal Accreditation Commission database. J Am Soc Echocardiogr.

2015;28:1062-9.

O’Toole JK, Friedland AR, Gonzaga AR, Hartig JR, Holliday S, Kolarik R. The practice patterns of recently graduated internal medicine-pediatric hospitalists. Hospital Pediatrics. 2015;5:309-14.

Rao SV, Hess CN, Barham B, Aberle LH, Anstrom KJ, Patel TB, Jorgensen JP, Mazzaferri EL Jr, Jolly SS, Jacobs A, Newby LK, Gibson CM, Kong DF, Mehran R, Waksman R, Gilchrist IC, McCourt BJ, Messenger JC, Peterson ED, Harrington RA, Krucoff MW. A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial. JACC Cardiovasc Interv. 2014;7:857-67.

Shukla A, Mani A, Bhattacharya A,Revilla FJ. Understanding postural response of Parkinson’s subjects using nonlinear dynamics and support vector machines. Austin J Biomed Eng. 2014;1:1005.

Revilla, FJ. Cognitive profile of LRRK2-related Parkinson’s disease. Mov Disord. 2015;30:728-33.

Serber E, Ciccolo J, Palmer K, Cobb V, Tilkemeier P, Bock B. The feasibility of exercise videogames for cardiovascular risk reduction among adults: A pilot for “Wii Heart Fitness.” J Sports Med Phys Fitness. 2015 [Epub ahead of print].

Tilkemeier PL, Mahmarian JJ, Wolinsky DG, Denton EA. ImageGuide™ Update. J Nucl Cardiol.

2015;22:994-7.

Urrea-Mendoza E, Kanter D, Revilla FJ, Dornoff E, Espay AJ. Stiff-arm syndrome. Neurology.

2015;85:1088-9.

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OB/GYN 71. Ahn SH, Edwards AK, Singh SS, Young SL, Lessey BA, Tayade C. IL-17A Contributes to the pathogenesis of endometriosis by triggering proinflammatory cytokines and angiogenic growth factors. J Immunol. 2015;195:2591-600.

72. Brazell HD, O’Sullivan DM, Forrest A, Greene JF. Effect of a decision aid on decision making for the treatment of pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 2015;21:231-5.

73. Buery-Joyner SD, Dalrymple JL, Abbott JF, Craig LB, Forstein DA, Graziano SC, Hampton BS, GHS Proc. May 2016; 1 (1): 72-82

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Hopkins L, Page-Ramsey SM, Pradhan A, Wolf A. and McKenzie ML. Overcoming electronic medical record challenges on the obstetrics and gynecology clerkship. © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/15. Vol. 126, No. 3, September 2015, Pages 553-8.

Chapela PJ, Broaddus RR, Hawkins SM, Lessey BA, Carson DD. Cytokine stimulation of MUC4 expression in human female reproductive tissue carcinoma cell lines and endometrial cancer. J Cell Biochem. 2015;116:2649-57.

Demosthenes LD, Eichelberger KY. Outpatient cervical ripening: has its time come? Contemporary OB/GYN. July 17, 2015.

Eichelberger KY, Morse JE, Connolly AM, Autry M. Opportunities and barriers in global women’s health training during obstetrics and gynecology residencies in the USA. Int J Gynecol Obstetr.

2015;128:148-51.

Eichelberger KY. A prolonged second stage should prompt increased vigilance for postpartum maternal complications. BJOG. 2016;123:617.

Eichelberger KY, Bengtson AM, Tolleson-Rinehart S, Menard MK. Training needs in operative obstetrics for maternal-fetal medicine fellows. J Matern Fetal Neonatal Med. 2015;28:1467-70.

Franasiak JM, Burns KA, Slayden O, Yuan L, Fritz MA, Korach KS, Lessey BA, Young SL. Endometrial CXCL13 expression is cycle regulated in humans and aberrantly expressed in humans and Rhesus macaques with endometriosis. Reprod Sci. 2015;22:442-51.

Gill SE, Forstein DA, Helmrich GA, Mabie B. Spontaneous splenic Rupture Mimicking Placental Abruption in the second trimester: a case report and review of the literature. J SC Med Assoc. 2015; 111:41-76.

Gray SL, Lackey BR, Boone WR. Impact of kudzu and puerarin on sperm function. Reprod Toxicol.

2015 Mar 28;53:54-62.

Hampton BS, Craig LB, Abbott JF, Buery-Joyner SD, Dalrympie JL, Forstein DA, Hopkins L, McKenzie ML, Page-Ramsey SM, Pradhan A, Wolf A, Graziano SC. To the point: teaching the obstetrics and gynecology medical student in the operating room. Am J Obstet Gynecol. 2015;213:464-8.

Heberlein E, Picklesimer A, Billings D, Covington-Kolb S, Farber N, Frongillo EA. The comparative effects of group prenatal care on psychosocial outcomes. Arch Womens Ment Health. 2015 Aug 11 [Epub ahead of print].

Hood BL, Liu B, Alkhas A, Shoji Y, Challa R, Wang G, Ferguson S, Oliver J, Mitchell D, Bateman NW, Zahn CM, Hamilton CA, Payson M, Lessey B, Fazleabas AT, Maxwell GL, Conrads TP, Risinger JI. Proteomics of the human 75

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endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle. Biol Reprod. 2015;92:106.

Illston JD, Wheeler TL, Parker CR, Conner MG, Burgio KL, Goode PS, Richter HE. Low-dose 17-β-estradiol cream for vaginal atrophy in a cohort without prolapse: Serum levels and vaginal response including tissue biomarkers associated with tissue remodeling. Maturitas.

2015;81:475-9.

Joshi NR, Su RW, Chandramouli GV, Khoo SK, Jeong JW, Young SL, Lessey BA, Fazleabas AT. Altered expression of microRNA-451 in eutopic endometrium of baboons (Papio Anubis) with endometriosis. Hum Reprod. 2015;30:2881-91.

Kim BG, Yoo JY, Kim TH, Shin JH, Langenheim JF, Ferguson SD, Fazleabas AT, Young SL, Lessey BA, Jeong JW. Aberrant activation of signal transducer and activator of transcription-3 (STAT3) signaling in endometriosis. Hum Reprod. 2015;30:1069-78.

Kim TH, Yoo JY, Wang Z, Lydon JP, Khatri S, Hawkins SM, Leach RE, Fazleabas AT, Young SL, Lessey BA, Ku BJ, Jeong JW. ARID1A is essential for endometrial function during early pregnancy.

PLoS Genet. 2015;11:e1005537.

Lane A, Tyson A, Thurston E. Providing re-Essure-ance to the nickel-allergic patient considering hysteroscopic sterilization. J Minim Invasive Gynecol. 2016;23:126-9.

Lane AS, Stallworth JL, Eichelberger KY, Trofatter KF. Vitamin K deficiency embryopathy from hyperemesis gravidarum. Case Rep Obstet Gynecol. 2015;2015:324173.

Lee C. Abdominal pregnancy in a low-resource setting. Obstet Gynecol. 2015;125:1039-41.

Lessey BA, Savaris RF, Ali S, Brophy S, Tomazic-Allen S, Chwalisz K. Diagnostic accuracy of urinary cytokeratin 19 fragment for endometriosis. Reprod Sci. 2015;22:551-5.

Miller PB, Savaris RF, Forstein DA, Likes CE, Nichols C, Cooper LJ, Lessey BA. Laparoscopic surgery improves pregnancy outcomes in women with suspected endometriosis with or without pathological confirmation. Clin Exp Obstet Gynecol. 2016;27:31-6.

Picklesimer A, Heberlein E, Covington-Kolb S. Group prenatal care: has its time come? Clin Obstet Gynecol. 2015;58:380-91.

Su RW, Strug MR, Joshi NR, Jeong JW, Miele L, Lessey BA, et al. Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization. J Clin Endocrinol Metab. 2015;100:E433-42.

Szwarc MM, Kommagani R, Lessey BA, Lydon JP. The p160/steroid receptor coactivator family: potent arbiters of uterine physiology and dysfunction. Biol Reprod. 2014;91:122.

Wheeler TL, Illston JD, Markland AD, Goode

PS, Richter HE. Life Space Assessment in older women undergoing non-surgical treatment for urinary incontinence. Open J Obstet Gynecol.

2014;4:809-16.

Orthopaedics 98. Adams JD Jr, Tanner SL, Jeray KJ. Far cortical locking screws in distal femur fractures. Orthopedics. 2015;38:e153-6.

99. Aneja A, Yang E, Briscoe M, Graves ML, Porter SE, Bergin P, Russell GV. Intramedullary nailing of femur fractures in the obese: a retrospective comparison of patients with normal weight versus the obese. Austin J Trauma Treat. 2014;1:5.

100. Bailey LB, Beattie PF, Shanley E, Seitz AL, Thigpen CA. Current rehabilitation applications for shoulder ultrasound imaging. J Orthop Sports Phys Ther. 2015;45:394-405.

101. Bergin PF, Kneip C, Pierce C, Hendrix ST, Porter SE, Graves ML, Russell GV. Modifier 22 for acetabular fractures in morbidly obese patients: does it affect reimbursement? Clin Orthop Relat Res. 2014;472:3370-4.

102. Broome CB, Burnikel B. Novel strategies to improve early outcomes following total knee arthroplasty: a case control study of intra articular injection versus femoral nerve block. Int Orthop.

2014;38:2087-9.

103. Burgers PT, Poolman RW, Van Bakel TM, Tuinebreijer WE, Zielinski SM, Bhandari M, Patka P, Van Lieshout EM; HEALTH and FAITH Trial Investigators (Jeray KJ, Goetz DR, Pace TB, Schaller TM, Porter SE, Tanner SL, Snider RG, Nastoff LA, Bielby SA). Reliability, validity, and responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index for elderly patients with a femoral neck fracture. J Bone Joint Surg Am. 2015;97:751-7.

104. Cook JB, Tokish JM. Surgical management of acromioclavicular dislocations. Clin Sports Med. 2014;33:721-37.

105. Dickens JF, Owens BD, Cameron KL, Kilcoyne K, Allred CD, Svoboda SJ, Sullivan R, Tokish JM, Peck KY, Rue JP. Return to play and recurrent instability after in-season anterior shoulder instability: a prospective multicenter study. Am J Sports Med. 2014;42:2842-50.

106. Ernat JJ, Song DJ, Brugman SC, Shaha SH, Tokish JM, Lee GY. Mental health medication use correlates with poor outcome after femoroacetabular impingement surgery in a military population. J Bone Joint Surg Am. 2015;97:1272-7.

107. Gottschalk MB, Premkumar A, Sweeney K, Boden SD, Heller J, Yoon ST, Rhee JM, Leckie SK, Braly B, Simpson AK, Lenehan E. Posterolateral lumbar arthrodesis with and without interbody arthrodesis for L4-L5 degenerative spondylolisthesis: a comparative value analysis.

Spine (Phila Pa 1976). 2015;40:917-25.

GHS Proc. May 2016; 1 (1): 72-82

2015 PUBLICATIONS 108. Hagen JE, Miller AN, Ott SM, Gardner M, Morshed S, Jeray K, Alton TB, Ren D, Abblitt WP, Krieg JC. Association of atypical femoral fractures with bisphosphonate use by patients with varus hip geometry. J Bone Joint Surg Am. 2014;96:1905-9.

109. Jeray KJ, Frick SL. A survey of resident perspectives on surgical case minimums and the impact on milestones, graduation, credentialing, and preparation for practice: AOA Critical Issues. J Bone Joint Surg Am. 2014;96:e195.

110. Mellema JJ, Doornberg JN, Guitton TG, Ring D; Science of Variation Group (Jeray KJ, Palmer MJ). Biomechanical studies: science (f)or common sense? Injury. 2014;45:2035-9.

111. Noonan TJ, Shanley E, Bailey LB, Wyland DJ, Kissenberth MJ, Hawkins RJ, Thigpen CA. Professional Pitchers With Glenohumeral Internal Rotation Deficit (GIRD) display greater humeral retrotorsion than pitchers without GIRD. Am J Sports Med. 2015;43:1448-54.

112. Owens BD, Tokish JM, Provencher MT. Dedication. Clin Sports Med. 2014;33:xvii-xviii.

113. Pace T, Finley S, Snider R, Looper J, Tanner S. Short-term results of novel constrained total hip arthroplasty. Orthop Rev (Pavia). 2015;7:5779.

114. Pappas ND. Commentary on “biomechanical comparison of bicortical locking versus unicortical far-cortex-abutting locking screw-plate fixation for comminuted radial shaft fractures”. J Hand Surg Am. 2014;39:1914.

115. Shaha JS, Cook JB, Song DJ, Rowles DJ, Bottoni CR, Shaha SH, Tokish JM. Redefining “critical” bone loss in shoulder instability: functional outcomes worsen with “subcritical” bone loss. Am J Sports Med. 2015;43:1719-25.

116. Shanley E, Kissenberth MJ, Thigpen CA, Bailey LB, Hawkins RJ, Michener LA, Tokish JM, Rauh MJ. Preseason shoulder range of motion screening as a predictor of injury among youth and adolescent baseball pitchers. J Shoulder Elbow Surg. 2015;24:1005-13.

117. Tabbaa SM, Horton CO, Jeray KJ, Burg KJ. Role of vascularity for successful bone formation and repair. Crit Rev Biomed Eng. 2014;42:319-48.

118. Thigpen CA, Noonan TJ, Shanley E, Bailey LB, Wyland DJ, Kissenberth M, Hawkins RJ. Humeral retrotorsion in pitchers with GIRD: Response.

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119. Thigpen CA, Shaffer MA, Kissenberth MJ. Knowing the speed limit: weighing the benefits and risks of rehabilitation progression after arthroscopic rotator cuff repair. Clin Sports Med. 2015;34:233-46.

120. Watson ST, Wyland DJ. Return to play after nonoperative management for a severe type III acromioclavicular separation in the throwing shoulder of a collegiate pitcher. Phys Sportsmed.

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Pediatrics 121. Anderson AW, Smith PB, Corey KM, Hill KD, Zimmerman KO, Clark RH, Hornik CP. Clinical outcomes in very low birth weight infants with major congenital heart defects. Early Hum Dev. 2014;90:791-5.

122. Arnold CJ, Ericson J, Cho N, Tian J, Wilson S, Chu VH, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. Cefepime and ceftazidime safety in hospitalized infants. Pediatr Infect Dis J. 2015;34:964-8.

123. Arnold CJ, Ericson J, Kohman J, Corey KL, Oh M, Onabanjo J, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB, Chu VH; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. Rifampin use and safety in hospitalized infants. Am J Perinatol.

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124. Autmizguine J, Hornik CP, Benjamin DK Jr, Laughon MM, Clark RH, Cotten CM, Cohen-Wolkowiez M, Benjamin DK, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee.

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125. Becker KC, Hornik CP, Cotten CM, Clark RH, Hill KD, Smith PB, Lenfestey RW. Necrotizing enterocolitis in infants with ductal-dependent congenital heart disease. Am J Perinatol.

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126. Bergin SP, Thaden JT, Ericson JE, Cross H, Messina J, Clark RH, Fowler VG Jr, Benjamin DK Jr, Hornik CP, Smith PB; Antibacterial Resistance Leadership Group. Neonatal Escherichia coli bloodstream infections: clinical outcomes and impact of initial antibiotic therapy. Pediatr Infect Dis J. 2015;34:933-6.

127. Bupp CP, Demmer LA, Saul RA. Surveying the current landscape of clinical genetics residency training. Genet Med. 2015;17:386-90.

128. Chandler J. Incidental findings of nonparentage should be disclosed. Pediatrics. 2015;135:e284.

129. Chu PY, Hill KD, Clark RH, Smith PB, Hornik CP. Treatment of supraventricular tachycardia in infants: Analysis of a large multicenter database.

Early Hum Dev. 2015;91:345-50.

130. Clark RH, Latypov RF, De Imus C, Carter J, Wilson Z, Manchulenko K, Brown ME, Ketchem RR. Remediating agitation-induced antibody aggregation by eradicating exposed hydrophobic motifs. MAbs. 2014;6:1540-50.

131. Dancel LD, Perrin E, Yin SH, Sanders L, Delamater A, Perreira KM, Bronaugh AB, Eden S, Shintani A, Rothman RL. The relationship between acculturation and infant feeding styles in a Latino population. Obesity (Silver Spring). 2015;23:840-6.

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132. Ellsworth MA, Harris MN, Carey WA, Spitzer AR, Clark RH. Off-label use of inhaled nitric oxide after release of NIH consensus statement.

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133. Ericson JE, Arnold C, Cheeseman J, Cho J, Kaneko S, Wilson E, Clark RH, Benjamin DK Jr, Chu V, Smith PB, Hornik CP; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. Use and safety of erythromycin and metoclopramide in hospitalized infants. J Pediatr Gastroenterol Nutr.

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134. Ericson JE, Thaden J, Cross HR, Clark RH, Fowler VG Jr, Benjamin DK Jr, Cohen-Wolkowiez M, Hornik CP, Smith PB; Antibacterial Resistance Leadership Group. No survival benefit with empirical vancomycin therapy for coagulase-negative staphylococcal bloodstream infections in infants. Pediatr Infect Dis J. 2015;34:371-5.

135. Gardner SE, Gonzaga AM, Kolarik RC. New program requirements present challenges and inspire innovations in med-peds programs. Acad Pediatr.

2014;14:556-8.

136. Gulack BC, Laughon MM, Clark RH, Sankar MN, Hornik CP, Brian Smith P. Comparative effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus. Early Hum Dev. 2015;91:725-9.

137. Hock R, Kinsman A, Ortaglia A. Examining treatment adherence among parents of children with autism spectrum disorder. Disabil Health J. 2014;8:407-13.

138. Hornik CP, Chu PY, Li JS, Clark RH, Smith PB, Hill KD. Comparative effectiveness of digoxin and propranolol for supraventricular tachycardia in infants. Pediatr Crit Care Med. 2014;15:839-45.

139. Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network.

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140. Jacob J, Kamitsuka M, Clark RH, Kelleher AS, Spitzer AR. Etiologies of NICU deaths. Pediatrics.

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141. Laughon MM, Chantala K, Aliaga S, Herring AH, Hornik CP, Hughes R, Clark RH, Smith PB. Diuretic exposure in premature infants from 1997 to 2011. Am J Perinatol. 2015;32:49-56.

142. Malowitz JR, Hornik CP, Laughon MM, Testoni D, Cotten CM, Clark RH, Smith PB. Management practice and mortality for infants with congenital diaphragmatic hernia. Am J Perinatol.

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143. Olsen IE, Lawson ML, Ferguson AN, Cantrell R, Grabich SC, Zemel BS, Clark RH. BMI curves for preterm infants. Pediatrics. 2015;135:e572-81.

144. Samiee-Zafarghandy S, Raman SR, van den Anker JN, McHutchison K, Hornik CP, Clark RH, Smith PB; Best Pharmaceuticals for Children 78

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145. Saul RA. Molecular diagnostic testing. Genet Med. 2015;17:761.

146. Sokhadze EM, Tasman A, Sokhadze GE, El-Baz AS, Casanova MF. Behavioral, cognitive, and motor preparation deficits in a visual cued spatial attention task in autism spectrum disorder. Appl Psychophysiol Biofeedback. 2016;41:81-92.

147. Spitzer AR, Ellsbury D, Clark RH. Erratum to: The Pediatrix BabySteps® data warehouse—a unique national resource for improving outcomes for neonates. Indian J Pediatr. 2015;82:669.

148. Spitzer AR, Ellsbury D, Clark RH. The Pediatrix BabySteps® Data Warehouse—a unique national resource for improving outcomes for neonates.

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149. Testoni D, Hornik CP, Neely ML, Yang Q, McMahon AW, Clark RH, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee. Safety of octreotide in hospitalized infants. Early Hum Dev. 2015;91:387-92.

150. Tolia VN, Murthy K, McKinley PS, Bennett MM, Clark RH. The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants. JAMA Pediatr.

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151. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, Clark RH, Spitzer AR. Increasing incidence of the neonatal abstinence syndrome in US neonatal ICUs. N Engl J Med. 2015;372:2118-26.

152. Wang Y, Hensley MK, Tasman A, Sears L, Casanova MF, Sokhadze EM. Heart rate variability and skin conductance during repetitive TMS course in children with autism. Appl Psychophysiol Biofeedback. 2016;41:47-60.

153. Zeidán-Chuliá F, de Oliveira BN, Casanova MF, Casanova EL, Noda M, Salmina AB, Verkhratsky A. Up-regulation of oligodendrocyte lineage markers in the cerebellum of autistic patients: evidence from network analysis of gene expression.

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154. Zimmerman KO, Hornik CP, Ku L, Watt K, Laughon MM, Bidegain M, Clark RH, Smith PB. Sedatives and analgesics given to infants in neonatal intensive care units at the end of life. J Pediatr. 2015;167:299-304.e3.

Surgery 155. Alexander NS, Liu JZ, Bhushan B, Holinger LD, Schroeder JW Jr. Postoperative observation of children after endoscopic type 1 posterior laryngeal cleft repair. Otolaryngol Head Neck Surg 2015;152:153-8.

156. Betala JV, Langan EM 3rd, LaBerge M. Drug-coatGHS Proc. May 2016; 1 (1): 72-82

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157. Bhatia G, Davis BR, Wright CC. Analysis of patients undergoing coronary artery bypass grafting who have already had prior percutaneous coronary intervention. Am Surg. 2015;81:284-6.

158. Bolton WD, Richey J, Ben-Or S, Hale AL, Ewing JA, Stephenson JE. Electromagnetic navigational bronchoscopy: a safe and effective method for fiducial marker placement in lung cancer patients.

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159. Bour ES. Evidence supporting the need for bariatric surgery to address the obesity epidemic in the United States. Curr Sports Med Rep. 2015;14:100-3.

160. Bowling MR, Kohan MW, Walker P, Efird J, Ben-Or S. The effect of general anesthesia versus intravenous sedation on diagnostic yield and success in electromagnetic navigation bronchoscopy.

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161. Brzezienski MA, Jarrell JA 4th. Autologous fat grafting to the breast using REVOLVE system to reduce clinical costs. Ann Plast Surg. 2015 Jul 23.

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162. Claudeanos KT, Hudgins J, Keahey G, Cull DL, Carsten CG 3rd. Fistulas in octogenarians: are they beneficial? Ann Vasc Surg. 2015;29:98-102.

163. Cobb WS, Warren JA, Ewing JA, Burnikel A, Merchant M, et al. Open retromuscular mesh repair of complex incisional hernia: predictors of wound events and recurrence. J Am Coll Surg.

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164. Creager MA, Gornik HL, Gray BH, Hamburg NM, Iobst WF, Mohler ER 3rd, White CJ. COCATS 4 Task Force 9: Training in vascular medicine. J Am Coll Cardiol. 2015;65:1832-43.

165. Creager MA, Gornik HL, Gray BH, Hamburg NM, Iobst WF, Mohler ER 3rd, White CJ. COCATS 4 Task Force 9: Training in vascular medicine: endorsed by the society for vascular medicine. Vasc Med. 2015;20:384-94.

166. Cull DL, Manos G, Hartley MC, Taylor SM, Langan EM, Eidt JF, Johnson BL. An early validation of the Society for Vascular Surgery Lower Extremity Threatened Limb Classification System. J Vasc Surg. 2014;60:1535-42.

167. Davis JR, Trocha SD, Hale AL, Bartz MJ. Videoscopic inguinal lymphadenectomy in malignant melanoma: safe in pregnancy? J Surg Case Rep. 2014;11.

168. Davis JR, Ewing JA, Hale AL, Lokey JS. Indeterminate thyroid nodule: knowing what we do not know. Am Surg. 2015;81:294-6.

169. Davis JR, Hale AL, Smith DE. Jet ski hydrostatic perineal injuries from a level I trauma experience.

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170. Eckenrode AH, Ewing JA, Kotrady J, Hale AL, Smith DE. HIDA Scan with ejection fraction is over utilized in the management of biliary dyskinesia. Am Surg. 2015;81:669-73.

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171. Fercana G, Bowser D, Portilla MM, Langan EM, Carsten CG, Cull DL, Sierad LN, Simionescu DT. Platform technologies for decellularization, tunic-specific cell seeding and in vitro conditioning of extended length, small diameter vascular grafts.

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172. Fitzgerald R, McArthur D. A 5-year follow up to the essential skills for targeted limb salvage: Being DRRAFTed. Wound Care Hyperbar Med. 2014;5:46-51.

173. Glickman MH, Burgess J, Cull D, Roy-Chaudhury P, Schanzer H. Prospective multicenter study with a 1-year analysis of a new vascular graft used for early cannulation in patients undergoing hemodialysis. J Vasc Surg. 2015;62:434-41.

174. Goldman MP, Huber TS, Eidt JF, Hansen KJ, Naslund TC, Taylor SM, Endean ED, Edwards MS. A regional experience with vascular surgery mock oral examinations. J Surg Educ.

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175. Gray BH. From the Masters: Seven lessons from a master clinicianâ&#x20AC;&#x201D;Dr Jess Youngâ&#x20AC;&#x2122;s clinical method.

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176. Gray BH, Diaz-Sandoval LJ, Dieter RS, Jaff MR, White CJ. SCAI expert consensus statement for infrapopliteal arterial intervention appropriate use. Catheter Cardiovasc Interv. 2014;84:539-45.

177. Gray BH, Jaff MR, Slovut DP, Bacharach JM, Carman T, Creager M, Halperin J, von Mering G, Kinlay S. The first 10 years of the American Board of Vascular Medicine. Vasc Med. 2015 Feb;20:69-73.

178. Gray BH, Jaff MR, White CJ. Introduction to expert consensus statements for peripheral interventions from the society for cardiovascular angiography and interventions. Catheter Cardiovasc Interv. 2014;84:519.

179. Gray WA, Feiring A, Cioppi M, Hibbard R, Gray B, Khatib Y, Jessup D, Bachinsky W, Rivera E, Tauth J, Patarca R, Massaro J, Stoll HP, Jaff MR. S.M.A.R.T. self-expanding nitinol stent for the treatment of atherosclerotic lesions in the superficial femoral artery (STROLL): 1-year outcomes.

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180. Jones WB, Jordan P, Pudi M. Pain management of pancreatic head adenocarcinomas that are unresectable: celiac plexus neurolysis and splanchnicectomy. J Gastrointest Oncol. 2015;6:445-51.

181. Koleilat I, Eidt J. A rare combination of atypical cerebral vascular anatomy. Vascular. 2015;23:53941.

182. Koleilat I, Moore E, Hanover T, Eidt J. An unusual cause of spinal cord ischemia after thoracic endovascular repair. Vascular. 2015 Jan 6. [Epub ahead of print].

183. Koleilat I, Hanover T. Carotid endarterectomy in the face of a persistent hypoglossal artery. Ann Vasc Surg. 2015;29:1660.e1-4.

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184. Matsumura JS, Stroupe KT, Lederle FA, Kyriakides TC, Ge L, Freischlag JA (Eidt J): for the Open Versus Endovascular Repair (OVER) Veterans Affairs Cooperative Study Group; for the Open Versus Endovascular Repair OVER Veterans Affairs Cooperative Study Group. Costs of repair of abdominal aortic aneurysm with different devices in a multicenter randomized trial. J Vasc Surg. 2015;61:59-65.

185. McKinley B, Lehtinen S, Davis S, Collins J, Blackhurst D, Schammel CM, Schammel DP, Trocha SD. Management of periampullary adenocarcinoma by pancreaticoduodenectomy at a regional teaching hospital. J Gastrointest Oncol.

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186. Mitchell EL, Eidt JF, Rhodes RS, Valentine RJ; Vascular Surgery Milestone Working Group. The vascular surgical milestones project. J Vasc Surg.

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187. Parikh SA, Shishehbor MH, Gray BH, White CJ, Jaff MR. Appropriate use criteria for renal artery stenting: an expert consensus statement from SCAI. Catheter Cardiovasc Interv. 2014;84:116371.

188. Ponce J, Woodman G, Swain J, Wilson E, English W, Bour E et al. The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity. Surg Obes Relat Dis. 2015;11:874-81.

189. Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, Brodmann M, Pilger E, Zeller T, Krishnan P, Gammon R, Müller-Hülsbeck S, Nehler MR, Benenati JF, Scheinert D; LEVANT 2 Investigators (Gray B, Androes M, Carsten C, Cull DL, Hanover T, Langan E, Snyder B, Taylor S). Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373:145-53.

190. Shishehbor MH, Gray BH. Commentary: endovascular hemodynamic pressure wire assessment in lower extremities: has the time come? J Endovasc Ther. 2014;21:633-4.

191. Singapogu RB, Long LO, Smith DE, Burg TC, Pagano CC, Prabhu VV, Burg KJ. Simulator-based assessment of haptic surgical skill: a comparative study. Surg Innov. 2015;22:183-8.

192. Slovut DP, Saiar A, Gray BH. Endovascular medicine certification 2005-2014 report from the American Board of Vascular Medicine. Vasc Med. 2015;20:245-50.

193. Todd KL 3rd, Wright DI, VANISH-2 Investigators (Stanbro M). The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 05% and 10% compared with placebo for the treatment of saphenofemoral junction incompetence. Phlebology. 2014;29:608-18.

194. Trocha SD. Pancreas cancer: why bother? J Gas-

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195. Warren JA, Ewing JA, Hale AL, Blackhurst DW, Bour ES, Scott JD. Cost-effectiveness of bariatric surgery: increasing the economic viability of the most effective treatment for type II diabetes mellitus. Am Surg. 2015;81:807-11.

196. Warren JA, Epps M, Debrux C, Fowler JL 3rd, Ewing JA, Cobb WS 4th, Carbonell AM. Surgical site occurrences of simultaneous panniculectomy and incisional hernia repair. Am Surg.

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197. Wei JT, Feng Z, Partin AW, Brown E, Thompson I, et al (Busby JE). Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol. 2014;32:4066-72.

198. Weinberg I, Gu X, Giri J, Kim SE, Bacharach MJ, Gray BH, Katzen BT, Matsumoto AH, Chi YW, Rogers KR, Froehlich J, Olin JW, Gornik HL, Jaff MR. Anti-platelet and anti-hypertension medication use in patients with fibromuscular dysplasia: results from the United States Registry for Fibromuscular Dysplasia. Vasc Med. 2015;20:447-53.

199. Wells J, Miller M, Perry B, Ewing JA, Hale AL, Scott JD. Preservation of Fat-free Mass after Bariatric Surgery: A Comparison of Malabsorptive and Restrictive Procedures. Am Surg.

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200. Weyhe D, Cobb W, Lecuivre J, Alves A, Ladet S, Lomanto D, Bayon Y. Large pore size and controlled mesh elongation are relevant predictors for mesh integration quality and low shrinkage— systematic analysis of key parameters of meshes in a novel minipig hernia model. Int J Surg.

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202. Russ-Sellers R. The cost-effectiveness of pay-for-performance: a multidimensional approach to analysis. Med Care. 2015;53:104-5.

Nursing 203. Johnson B, Conner B. What works: Physician and nurse rounding improves patient satisfaction. American Nurse Today. 2014 Dec; 9(12).

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205. Macaluso JD, Weissenbach M. Staying Ahead of the Curve: Monitoring Epidemiology and Geographic Distribution by ZIP Code of Enterovirus D68. Am J of Infect Control. 2015;43:S71.

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2015 PUBLICATIONS Pharmacy 206. Foushee JA, Fox LM, Gormley LR, Lineberger MS. Physical compatibility of cisatracurium with selected drugs during simulated Y-site administration. Am J Health Syst Pharm. 2015;72:483-6.

Rehabilitation 207. Healy S, Manganelli J, Rosopa PJ, Brooks JO. An exploration of the nightstand and over-thebed table in an inpatient rehabilitation hospital.

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USCSOM Greenville: Biomedical Sciences Faculty, Staff, & Students 208. Adegbola AJ, Soyinka JO, Adeagbo BA, Igbinoba SI, Nathaniel TI. Alteration of the disposition of quinine in healthy volunteers after concurrent ciprofloxacin administration. Am J Ther.

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209. Chambers BS, Li Y, Hodinka RL, Hensley SE: Recent H3N2 influenza virus clinical isolates rapidly acquire hemagglutinin or neuraminidase mutations when propagated for antigenic analyses. J Virol. 2014;88:10986-9.

210. Cook KD, Kline HC, Whitmire JK. NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection. J Leukoc Biol. 2015; 98:153-62.

211. Hamdy RF, Stein RE, Larru B, Bellah RD, Grossman AB, Hodinka RL, Feemster KA. Gallbladder wall thickening in an adolescent with acute mononucleosis: A case report and brief review of the literature. J Pediatr Infect Dis Soc. 2015;4:26771.

212. Horani T, Best RG, Edwards E, DiPette DJ. Genetics of Hypertension: What is Next? Current Cardiovascular Risk Reports. 2015;9:1-12.

213. Igbinoba SI, Akanmu MA, Onyeji CO, Soyinka JO, Owolabi AR, Nathaniel TI, Pullela SV, Cook JM. Influence of a Nigerian honey on CYP3A4 biotransformation of quinine in healthy volunteers. J Clin Pharm Ther. 2015 Jul 14. [Epub ahead of print].

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215. Johnson TR, Khalil MK, Peppler RD, Davey DD, Kibble JD. Use of the NBME comprehensive basic science examination as a progress test in the preclerkship curriculum of a new medical school.

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216. Kajon AE, Lamson D, Shudt M, Oikonomopoulou Z, Fisher B, Klieger S, St. George K, Hodinka RL. Identification of a novel intertypic recombi-

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217. Kennedy AB, Trilk JL. A standardized, evidence-based massage therapy program for decentralized elite paracyclists: creating the model. Int J Ther Massage Bodywork. 2015;8:3-9.

218. Lawson TR, Brown IE, Westerkam DL, Blackhurst DW, Sternberg S, Leacock R, Nathaniel TI. Tissue plasminogen activator (rt-PA) in acute ischemic stroke: outcomes associated with ambulation. Restor Neurol Neurosci. 2015;33:301-8.

219. Linderman SL, Chambers BS, Zost SJ, Parkhouse K, Li Y, Hermann C, Ellebedy AH, Carter DM, Andrews SF, Zheng NY, Huang M, Huang Y, Strauss D, Shaz BH, Hodinka RL, Reyes-Teran G, Ross TM, Wilson, PC, Ahmed R, Bloom JD, Hensley SE. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season.

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220. Lopez CB, Sun Y, Jain D, Genoyer E, Gilbert M, Tapia K, Koziol-White C, Panettieri RA, Hodinka RL. Immunostimulatory defective viral genomes from respiratory syncytial virus promote a strong innate antiviral response during infection in mice and humans. PLOS Pathog. 2015;11:e1005122.

221. Nathaniel TI, Soyinka JO, Adedeji A, Imeh-Nathaniel A. Molecular and physiological factors of neuroprotection in hypoxia-tolerant models: pharmacological clues for the treatment of stroke.

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222. Nathaniel TI, Williams-Hernandez A, Hunter LA, Liddy C, Peffley DM, Umesiri FE, Imeh-Nathaniel A. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models. Brain Res Bull. 2015;114:1-12.

223. Phillips E, Pojednic R, Polak R, Bush J, Trilk J. Including lifestyle medicine in undergraduate medical curricula. Med Educ Online. 2015;20:26150.

224. Sansone RA, Wiederman MW. Religiosity/spirituality: relationships with non-suicidal self-harm behaviors and attempted suicide. Int J Soc Psychiatry. 2015;61:762-7.

225. Sansone RA, Bohinc RJ, Wiederman MW. Childhood bullying and healthcare adherence in adulthood. Int J Soc Psychiatry. 2015;61:725-8.

226. Sansone RA, Bohinc RJ, Wiederman MW. Adherence with general healthcare among internal medicine outpatients with mental health treatment histories. Innov Clin Neurosci. 2015;12:11-3.

227. Sansone RA, Elliott K, Wiederman MW. A survey of self-directed physical aggression among perpetrators of partner violence. Prim Care Companion CNS Disord. 2015;17.

228. Sansone RA, Wiederman MW. The self-harm inventory: A meta-analysis of its relationship to the personality diagnostic questionnaire-4 as a

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229. Sansone RA, Wiederman MW, Sawyer RJ. Effective research strategies for trainees in internal medicine residency programs. Prim Care Companion CNS Disord. 2015;17.

230. Sansone RA, Elliott K, Wiederman MW. Suicide attempts among men and women with partner violence according to borderline personality status. Innov Clin Neurosci. 2015;12:10-1.

231. Sansone RA, Bohinc RJ, Wiederman MW. Body mass index and self-reported compliance with general health care. South Med J. 2015;108:79-81.

232. Sansone RA, Bohinc RJ, Wiederman MW. Borderline personality symptomatology and compliance with general health care among internal medicine outpatients. Int J Psychiatry Clin Pract.

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233. Sansone RA, Elliott K, Wiederman MW. Distancing oneself from God among perpetrators of partner violence. Int J Soc Psychiatry.

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234. Simoes EAF, DeVincenzo JP, Boeckh M, Bont L, Crowe Jr JE, Griffiths P, Hayden FG, Hodinka RL, Smyth RL, Spencer K, Thirstrup S, Walsh EE, Whitley RJ. Challenges and opportunities in developing respiratory syncytial virus therapeutics. J Infect Dis. 2015;211:S1-S20.

235. Trilk JL, Kennedy AB. Using lifestyle medicine in us Health care to treat obesity: too many bariatric surgeries? Curr Sports Med Rep. 2015;14:96-9.

236. Umesiri FE, Lick A, Fricke C, Funk J, Nathaniel TI. Anti-tubercular activity of EDTA and household chemicals against mycobacterium smegmatis, a surrogate for multi-drug resistant tuberculosis. Europ Scientif J. 2015;11:133-49.

237. Zash RM, Shapiro RL, Leidner J, Wester C, McAdam A, Hodinka RL, Thior I, Moffat C, Makhema J, McIntosh K, Essex M, Lockman S. The aetiology of diarrhea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding. Paediatr Int Child Health. 2015 [Epub ahead of print].

GHS Proc. May 2016; 1 (1): 72-82

Presenting GHS Surgery Surgeons from the finest training programs in the nation have come together to make Greenville Health System a leader in surgical care. With more than 75 percent having fellowship-level training in their specialty, GHS surgeons are setting the standard with advanced skills, evidence-based medicine, leading-edge research and groundbreaking procedures.

Alma Maters of GHS Surgeons • Baylor College of Medicine • Carolinas Medical Center • The Cleveland Clinic Foundation • Duke University Medical Center • Emory University School of Medicine • Geisinger Medical Group • Georgetown University School of Medicine • George Washington University Hospital • Harvard Combined (Massachusetts General Hospital and Brigham and Women’s Hospital) • John Wayne Cancer Institute • Johns Hopkins University School of Medicine • Mayo School of Graduate Medical Education

• • • • • • • • • • • • • •

MD Anderson Cancer Center Medical College of Georgia Medical University of South Carolina Memorial Sloan-Kettering Cancer Center University of Chicago Pritzker School of Medicine University of Michigan Medical School University of North Carolina School of Medicine University of Pennsylvania School of Medicine University of South Carolina School of Medicine University of Texas Southwestern Medical Center University of Virginia School of Medicine Walter Reed Army Medical Center Yale School of Medicine And other foremost medical programs

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May 2016 | Volume 1 | Issue 1

From the Editor

Case Studies

7

47 Yolk Sac Diameter in Multiple Gestations

by C Fox et al

Changing the Culture by WD Bolton

Special Article 9

Launching a New Kind of Medical School— The University of South Carolina School of Medicine Greenville by AL Hale and WD Bolton

Original Research 13 Contemporary Indications for Vascular Surgery Fail to Achieve Desired Patient-Centered Outcomes When Applied to Critical Limb Ischemia by MF Hudson et al 22 Medicare Shared Savings Program Second-Year Results: Predictors of Success

by SE Sutherland et al 28 A Retrospective Data Analysis of Levetiracetam as Initial Monotherapy in Pediatric Epilepsy Patients by AS Hunnicutt et al 32 Discharge mEdication reconciliation by Pharmacists to improve Transitions following Hospitalization (DEPTH)

by RT Sawyer et al

Review Article 38 Modern Management of Abdominal Wall Hernias by JA Warren et al

49 Complex Perirectal Abscess Extending to the Preperitoneum and Space of Retzius

by CJ Mentzer et al 52 A Revertant of the Pathogenic Germline Mutation in BRCA1 as a Possible Cause of Breast Cancer Chemoresistance by P Callihan et al 56 Fatal Clostridium difficile Enteritis as a Delayed Complication of Loop Ileostomy for Fulminant C difficile Colitis by SN Rochester et al 60 Outcomes of Treatment with Radiation Therapy for Residual Soft Tissue Sarcoma of the Hand Following “Unplanned” Initial Resection

by D Ratner et al 64 Diagnostic Management of Urinary Retention: Why Multiple Sclerosis Should Be Included as a Differential Diagnosis by A Raines et al

Value Vignette and Editorial 68 Choosing High-Value Medications

by ML McDowell and LD Demosthenes 70 Mercy by RA Saul

Miscellany 71 2016 Graduates of Greenville Health System and University of South Carolina School of Medicine Greenville 72 2015 Publications of Greenville Health System’s Medical and Scientific Staff

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