Northeast Florida Medicine - Autumn 2016 - Pain Management

AUTUMN

CME:

Responsible

Opioid

Pre s cr i b i n g

Northea st Florida

MedicinE

Published by the DCMS Foundation Marking 163 Years of Local Organized Medicine

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In partnership with the Medical Societies of Duval, Clay and Nassau Counties

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ALSO IN THIS ISSUE: – Biologic Therapies for IBD – Case Study on Chronic Sinusitis – Sun Safety & Children in Northeast FL

Pain Management

VOLUME 67, NUMBER 3 Pain Management Autumn 2016

Autumn 2016 Contents

EDITOR IN CHIEF Ruple Galani, MD MANAGING EDITOR Kristy Wolski ASSOCIATE EDITORS James Altomare, MD Megan Deacon-Casey, MD Mark Fleisher, MD Sunil Joshi, MD

Autumn CME Responsible Opioid Prescribing

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Ali Kasraeian, MD John Long, MD Amy Pollak, MD James St. George, MD John Stauffer, MD

CHIEF EXECUTIVE OFFICER Bryan Campbell DCMS FOUNDATION BOARD OF DIRECTORS President: Todd Sack, MD President Elect: Ashley Norse, MD Secretary/Treasurer: Ruple Galani, MD Douglas Baer Richard Brock Solomon G. Brotman, DDS Alan Harmon, MD Kelli Wells, MD

By Timothy Sternberg, DMD, MD

Prescription drug abuse has become an epidemic in recent years, often facilitated in Florida by licensed physicians. Disastrous outcomes resulting from this abuse have led to a reformulation of local, statewide and national medical practice guidelines and legal statutory regulations in order to decrease morbidity and mortality. Responsible prescribing requires an understanding of opioid pharmacology, knowledge of the medical standard of care, familiarity with the applicable Florida Statutes, and diligence in preventing abuse and diversion.

2016 FOUNDATION DONORS Raed Assar, MD Richard and Janice Brock, MD William Parker Clarke, MD Jerry A. Dorsch, MD Robert E. Duncan, MD George H. Fink, MD Allan A. Girouard, MD Robert G. Harmon, MD Walter Alan Harmon, MD Kenneth A. Horn, MD Stephen Mandia, MD Russell D. Metz, MD Thomas Peters, MD Guy T. Selander, MD Joseph B. Stokes, Jr., MD N.H. Tucker III, MD Jacksonville Jaguars Foundation

Departments 8

7

6

From the Editor’s Desk

From the President’s Desk

From the Chief Executive Officer’s Desk

11 Residents’ Corner 13 Guest Editorial 66 Creative Corner

Features Forks and Feet: Pain and the 16 Power of Food and Movement

By Stephan Esser, MD, USPTA

Psychological Implications of Chronic Pain Management

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By Deanna Hughes, Psy.D.

Interventional Pain Management for Cancer Pain

24

By Bernard R. Canlas, MD

Advances in Technology for Managing Chronic Pain

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By Frank R. Collier, Jr., MD

Also in this Issue A Case of Chronic Sinusitis and Recurrent Pneumonia in a Middle-Aged Man

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By Sunil Joshi, MD

Biologic Therapy for Patients 49 with Inflammatory Bowel Diseases: Scratching the Surface

By Mark Fleisher, MD

Sun Safety Knowledge, Attitudes and 61 Behaviors Among Children in Northeast Florida

By Allison S. Bechtel, DO, Julie Williams Merten, PhD and Eric Sandler, MD

Please note: Editorial and contents of this magazine reflect the records of the Duval County Medical Society (DCMS). The DCMS has done their best to provide useful and accurate information, but please take into account that some information does change. E&M Consulting, Inc., publishers and the DCMS take no responsibility for the accuracy of the information printed, inadvertent omissions, printing errors, nor do they endorse products and services. We take no responsibility regarding representations or warranties concerning the content of advertisements of products/services for a particular use, including all information, graphics, copyrighted materials, and assertions included in the advertisements. The reader is advised to independently check all information before basing decisions on such information.

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Northeast Florida Medicine Vol. 67, No. 3 2016 5

From the Editor’s Desk

A Pandora’s Box: The New Physician – Patient Encounter About two weeks ago I had the opportunity to see a young woman in her early 40’s for chest pain. Prior to entering the room, I reviewed her medical summary sheet (ironically, printed out from our EMR). I noticed she was last seen in 2014 in our practice by another partner. She had a history of mitral valve prolapse, recurrent chest pain, and tobacco abuse. Interestingly, she had a left heart catheterization in 2012. This invasive test revealed, not to my surprise, normal coronary arteries. In 2014, she had an echocardiogram that DID NOT show mitral valve prolapse, and showed NO mitral regurgitation, and normal left ventricular function.

After I entered the room, I politely introduced myself and asked her to describe Ruple Galani, MD Editor-in-Chief her symptoms. She immediNortheast Florida Medicine ately told me that she had a long-standing history of mitral valve prolapse since her early 20’s.

She has been told then, and still felt, the mitral valve prolapse (again, NOT seen on a 2014 echo) was causing her to have palpitations. She very strongly felt that her mitral valve prolapse was causing a sharp pain under her left breast and into her ribs. She’d had her “mitral valve prolapse chest pain” for about two weeks.

When I asked further, the pain was always at rest, lasted less than 15 seconds, and was not at all associated with exertional activity.

On my exam, her vitals were normal. When I auscultated her heart, I did not hear any murmurs, clicks, or evidence of mitral valve prolapse or mitral regurgitation. Her ECG was normal.

Based on her history, normal exam, and normal ECG, I told her that her symptoms were not cardiac and that she did not need further cardiac evaluation.

Upon hearing my opinion, which I felt was sound and correct with my years of medical training, she began to question my logic. She essentially demanded I order an echocardiogram to “check her mitral valve prolapse” and even consider doing another heart catheterization to make sure she “did not get a new blocked artery.” I calmly told her that there was no indication by history and exam to do an echocardiogram or subject her to an invasive procedure that is not risk free. Because of my age, a

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mere 3-4 years younger than her, she doubted my opinion and grudgingly left the room to “go see a more experienced doctor.”

This encounter brings up many dynamic aspects of the patient – physician encounter. First, with the era of the internet, patients often have more information, questions, and opinions about their symptoms, diagnosis, and treatment. Many times this information is misleading and can actually cause more harm than good. As physicians, we are now obligated, in our 15 minute time slot, to correct or dispel Dr. Google, MD. With the cost of health care rising, patients, such as the one I encountered, find it a waste of time and money if a physician decides to “do nothing.” We live in a society in which the great medical adage of watchful waiting is deemed somehow substandard or incomplete care. As a physician, we need to remind patients, families, and fellow physicians that “doing nothing” is actually the right medical decision for the patient.

I have found, however, it takes more time and effort to explain to patients why I chose not to order a test/procedure than it takes to click on that EMR box and move on to the next visit.

Finally, we are always faced with the over diagnosis of clinically insignificant problems. For my patient, she was told for years she had mitral valve prolapse. Even the most famed cardiologists would agree the clinical diagnosis of this disorder is very hard on exam.

Despite high grade ultrasound technology that proved her mitral valve prolapse did not exist, she clung to that diagnosis as the cause of her symptoms and as the sole reason why she sought out cardiology care. With advanced imaging technology, we now have clinically insignificant findings (mild valve disease, incidental small nodules on CT scans, etc.) that get added to patient records and diagnoses. We are often told by our billers and coders to include “every” possible diagnosis to increase reimbursement without pause on how little this would change our care. Physicians find it easier to order a test (often in the name of defensive medicine) than to spend the time explaining why a test/procedure is not needed. These seemingly insignificant practices often lead to further testing and office visits for a diagnosis/problem that is unlikely to be an issue in the future. For patients, this is added cost, hours searching on Dr. Google, MD, anxiety, and possible tense interactions with their physician.

The physician-patient encounter is truly the biggest Pandora’s Box in medicine today. v

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From the President’s Desk

A Delegation of Leaders During the last weekend in July, physicians from all over the state came together for the annual Florida Medical Association (FMA) meeting in Central Florida. This has always been a wonderful time for us to meet and mingle with our colleagues from the Panhandle to the Keys and from the I-4 corridor to Fernandina.

Though physicians from all over Florida participate in the meeting, it is always truly remarkable to see the overwhelming support from Northeast Florida and, in particular, Duval County. At Sunil Joshi, MD 2016 DCMS President this year’s meeting there were more than 30 physicians from the DCMS present as either members of our Medical Society Delegation or representing their own State Specialty Societies. They were there to discuss many important issues related to the practice of medicine.

One of the responsibilities of the FMA House of Delegates is to elect leaders to represent physicians at the state and national level. The DCMS is very proud that one of our Past Presidents, Dr. John Montgomery, was reelected as a Delegate to the American Medical Association (AMA) House of Delegates. We are equally excited that the DCMS President-Elect, Dr. Tra’Chella Johnson-Foy, and Past-President, Dr. Tom Peters, were both elected as Alternate Delegates to the AMA House of Delegates.

Dr. Mobeen Rathore, DCMS Past-President, was elected to serve as the District B representative to the FMA Board of Governors. This district contains Duval, Clay, Nassau, St. Johns and Putnam counties. We are pleased that he will represent the physicians in this region for the next three years.

During the meeting of the FMA House of Delegates, physicians discussed many important issues related to the practice of medicine. The most popular of these was a topic that many

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physicians strongly oppose: the time consuming and costly maintenance of certification (MOC) and secured examinations.

Through the leadership of the FMA, the AMA has now made a strong statement against the burdensome MOC and recertification examinations. Hopefully, the American Board of Internal Medicine and the American Board of Medical Specialties will take heed and amend the recertification process while removing the high stakes secured examinations.

On the final day of the FMA meeting, DCMS Past-President Dr. Ashley Booth-Norse officially announced her candidacy for Vice-Speaker of the FMA House of Delegates. The election will be held at next summer’s annual meeting and we are all extremely excited about the possibility of having a DCMS member as the next Vice-Speaker and, eventually, as the Speaker of the FMA House of Delegates. This is just another reason to look forward to the 2017 FMA annual meeting.

The DCMS Foundation continues to move forward with its exciting advocacy effort titled Mission First. The most popular of the Mission First initiatives is the 904 Mission One Million program. This is a challenge from Mayor Lenny Curry and myself to the residents of Northeast Florida to lose one million pounds. This effort is moving forward and we already have a total of over 16,300 pounds pledged to be lost. In a few short months, we have raised over $255,000 from DCMS members so that we can appropriately promote this unique initiative. This alone speaks volumes about the passion and commitment of our members in supporting the health of our community. We are looking forward to the day when we reach our goal and, in the process help make Duval County the healthiest in Florida.

Once again, please feel free to contact me directly if you are interested in any of our initiatives and/or have suggestions on ways we can do things differently. I look forward to seeing you at one of our upcoming CME membership meetings and hope to see you at our DCMS Annual Meeting and Inaugural Ball on December 2nd, as we celebrate another year of “helping physicians care for the health of our community.” v

Northeast Florida Medicine Vol. 67, No. 3 2016 7

From the CEO’s Desk

Leading from the Front I probably was in over my head.

Back in 2009, I was asked to serve on the Clay County Charter Review Commision. This is a group that is made up of citizens every four years to review the Charter (ie: Constitution) of the county. The group has the authority to place Charter Amendments directly onto the ballot for citizens to vote on. This is a big responsibility, and one that I did not take lightly.

“You should step up and be the Chair.”

The voice - my friend and the County Commissioner who nominated me to serve.

Bryan Campbell DCMS Chief Executive Officer

“I don’t think I should. I’m new to this process.”

My reluctance to step into that leadership role was well-founded. I’d never served on a government committee. I was only vaguely familiar with the Charter at the time. Clearly, this was a job for someone else to handle. I’d be content sitting on the sidelines and watching.

My reluctance to step into that leadership role was also misguided. As the nine-month process of reviewing and recommending modifications to the Charter began, it was clear that there was a lack of leadership on the Commission. Members fought with other members, called them names, and made the front page of the County newspaper on multiple occasions. The Commission became the butt of many jokes and hurt the reputation of the process so severely that people began calling for the process to be repeated only once every ten years, instead of every four.

In 2013, I was once again asked to serve, and this time I agreed and volunteered to be the Commission Chair. Utilizing experience from working with many different Boards of Directors, we were able to navigate some tough topics including adding term-limits to some elected officials and debating the issue of elected or appointed Superintendent of Schools. These issues were not without controversy, but with a dispassionate approach and a fair leadership style, we were able to conduct and conclude our business without being on the front page of the paper even once.

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It taught me a valuable lesson. Leadership is a skill independent of rank or title. It’s the ability and willingness to step forward and do what’s right, because it’s right.

In my position as the CEO of the Duval County Medical Society, I am honored to say that I see this type of leadership displayed every day by your friends and colleagues. The volunteers that give of their time to give back to the community do it because they know how important it is to the profession and to the community.

On page 7, DCMS President Dr. Sunil Joshi discusses the volunteer representation at the Florida Medical Association House of Delegates. More than 30 physicians from Duval County gave countless hours of their time to participate in the meeting. It’s not just time that they give, either. Time away from the office has a real financial impact, as well as the simple cost of travel. However, these volunteers understand the importance of leading from the front. They know that issues like MACRA and Maintenance of Certification matter to you, but that not everyone has the ability to take that leadership role.

To the dozens of physicians who volunteer to serve on the DCMS Board, committees, FMA delegation… on behalf of the entire DCMS membership, myself, and the staff, I say THANK YOU! Now, the DCMS actually has a program to help those who may be considering getting involved in leadership, either in the Medical Society, your office or hospital, or in the community.

The DCMS Leadership Academy is now taking applications for our Class of 2017. The sessions will take place on February 3, March 3 and April 7. Topics will include time management, emotional intelligence, strategic thinking, creating high performance teams, influencing organizational culture and so much more! If you are interested in signing up, call the DCMS office at (904) 355-6561. For a limited time, DCMS members can attend for just $399. Space is limited, so get your application in early.

We are always looking for new leaders to get involved with the DCMS. If you are interested in serving, attending the Leadership Academy, or just want to learn more about the opportunities available to you, please reach out to me at bcampbell@dcmsonline.org and I’d love to talk with you. v

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Residents’ Corner: Mayo Clinic School of Graduate Medical Education

Internal Medicine Residents 2014-2015

An Inside Look at Mayo Clinic Graduate Medical Education

By Christopher Lamb, MD Overview of Training Program Mayo Clinic School of Graduate Medical Education was one of the first medical specialty teaching programs in the world, with more than 24,000 graduates of residencies and fellowship programs across all medical and surgical specialties. Mayo Clinic Florida hospital now operates at an expanded capacity of over 304 beds, 22 operating rooms, 20 medical and 15 surgical specialties and an Emergency Department. There are presently more than 200 residents and fellows in training in over 45 programs.

Mayo Clinic Florida welcomed its 22nd class of residents this year in July since the initial class of residents in internal medicine in 1994. Residents and fellows are allotted further clinic opportunities at nearby institutions including: Mission House of Jacksonville, Nemours Children’s Clinic, Wolfson Children’s Hospital, University of North Florida, UF Health Jacksonville, and the Jacksonville Naval Hospital. Mayo Clinic also provides opportunities to rotate in Arizona and Minnesota, as well as the very unique opportunity to venture internationally as part of the Mayo International Health Scholars Program.

medical decision-making through repetition; residents are trained by the leading minds in medicine in a manner which balances advancement of their clinical acumen with academic interests that further the progress of medicine. Teachers encourage residents, fellows, and trainees to expand their contributions to the field of medicine and embrace them in the atmosphere of collegiality summarized by Mayo Clinic’s three shields: patient care, education, and research.

Patient Care, Medical Practice, and Community Outreach

A Great Place to Work and Train

As excellent examples of residents’ dedication to patient care here and abroad, Drs. Monia Werlang and Martin Gibbs left Jacksonville and travelled to Nepal and Haiti, respectively, as part of the Mayo International Health Scholarship program. Dr. Gibbs spent time in three different settings in Haiti, including an urban hospital in Port-Au-Prince and two rural clinics, healing many ill patients with very few clinical resources. The Mayo International Health Scholarship program provides scholarships for Mayo residents to travel abroad to over 50 sites worldwide in underserved populations.

Fortune 500 again ranked Mayo Clinic among the “100 Best Companies to Work For” in 2016, and Mayo Clinic’s training programs are no exception. What makes a residency at Mayo Clinic so great? Residents’ training includes more than honing

Through the Mayo Fellows Association, Mayo Clinic residents and fellows also remain very active in the local community, providing their time and clinical expertise to those in need. Here are several examples of their activities:

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Northeast Florida Medicine Vol. 67, No. 3 2016 11

Residents’ Corner: Mayo Clinic School of Graduate Medical Education

Dr. Martin Gibbs visited Haiti as part of the Mayo International Health Scholarship program to provide care for the underserved populations.

The Mayo Clinic Jacksonville Residents’ Soccer team won the Beaches Adult Corporate Soccer League championship match against the PGA Tour team.

Dr. Jordon C. Ray was awarded the Mayo Brothers Distinguished Fellowship Award in April 2016.

• Yearly holiday clothing drives and a weekly free clinic for Mission House of Jacksonville.

• Annual canned food drive for the Second Harvest Food Bank.

•A nnual blood and bone marrow drive for The Blood Alliance.

Education in the Arts and Humanities The Fellows and Residents’ Health and Wellness Initiative (FERHAWI), created by the Mayo Fellows Association (MFA), is a grant-funded program combating burnout and fatigue among residents with the use of focused educational sessions revolving around arts and humanities. This initiative has received national attention and was highlighted at the annual meeting of the American Medical Association in 2015. The program continues with monthly sessions; past sessions have featured blind drawing, wood flute music, meditation training, and the Cummer Museum’s artist in residency.

Resident Research Staff physicians and teachers continue to support and encourage residents’ academic pursuits, large and small. Residents at Mayo Clinic have been awarded winning posters at contests on the local, county, state, national, and international levels. All residents participate in at least one research project, and most participate in even more.

Below are just a few of many examples of Residents’ outstanding research: • Dr. Jordon C. Ray was awarded the Mayo Brothers Distinguished Fellowship Award, the highest award presented to only six trainees among all three Mayo locations based on outstanding clinical performance, humanitarian

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features, and outstanding scholarly activity. Dr. Ray has produced more than 10 peer-reviewed research articles during his three year residency as well as numerous poster and oral presentations.

• Dr. Lauren Cornell continues her research in breast cancer with a recently published review of HER2 therapy in Breast Cancer: Targets and Therapy. Another of her projects, presented at the American Society of Clinical Oncology, focuses on management of breast cancer brain metastases, and is currently submitted for publication.

• Dr. Sebastian Lopez-Chiriboga recently published a review of metabotropic glutamate type 1 receptor autoimmune disease featuring eleven patients with this rare disease in Neurology.

Excellence and Teamwork outside the Hospital The Mayo Clinic Jacksonville Residents’ Soccer team won the Beaches Adult Corporate Soccer League championship match against the PGA Tour team, earning the 1st place trophy. The residents’ soccer team took first place for the regular season last year as well, and will continue on as three new interns will be joining the team with hope to retain the title.

Conclusion Residents at Mayo Clinic are fortunate to be trained by superb educators and leading minds in medicine in a manner which instills and kindles intellectual curiosities and compassionate practice. In the words of Dr. Charles H. Mayo (the younger of the Mayo brothers),“What a privilege it is to be able to teach, and how comparatively few of the many who possess the knowledge to teach are able to impart it to the student in a manner to make a permanent rather than a fleeting impression on his mind…” v

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Guest Editorial

Marijuana: Needed Medical Therapy or Trojan Horse?

According to ancient Greek mythology, there once was a vanity spat between the major goddesses Athena, Hera, and Aphrodite when Eris, the goddess of strife and discord, gave them a golden apple (“Apple of Discord”) which would go to the most beautiful, the “most fairest.”1 To settle this conflict, Zeus sent the goddesses to Troy where Paris, the Trojan leader, judged Aphrodite as “the fairest” who should receive the apple. A thankful Aphrodite then made Helen, the most beautiful of all (mortal) women, fall in Timothy Sternberg, DMD, MD love with Paris, who took her to Guest Editor Troy. Helen’s husband Menelaus, majorly ticked, joined with his brother Agamemnon, king of Mycenae, to lead an expedition of Achaean (Greek) troops to besiege Troy and correct this insult. Though there would be many military campaigns throughout history that would turn futile, this Trojan War initiated by the Greeks was disastrous.

After a seemingly interminable war that accomplished nothing, the Greeks decided they needed a different tactic to achieve their objectives. A false pretext. They would trick their opponent by constructing a giant wooden horse, surreptitiously fill it with Achaean warriors, and leave it in front of the gates of Troy. The Trojans, thinking they had received a gift from their opponents, brought the armored troop carrier into the city walls. The Greek warriors then deployed from the vehicle and laid waste to Troy.

And the rest is history. Or mythology.

Approximately three and a half millennia later, while I was a college freshman, and the scent of cannabis was seemingly in the hallway of every undergraduate dormitory, there formed a group called the National Organization for the Reform of Marijuana Laws (NORML). The group’s mission was, and is, to decriminalize cannabis for recreational use.2 As marijuana seemed no more harmful than alcohol or cigarettes, and appeared to produce a pleasant enough high, I, as a budding libertarian, thought why not? As long as a responsible adult does not harm or endanger a fellow citizen, he or she should be able to do just about whatever they want to do to themselves, be it harmful or not.

Fast forward to modern times. Though there are some states and localities where personal use, including smoking, of marijuana has become legal, NORML’s desired objective basically has not

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been accomplished. Those who wanted to smoke marijuana needed a different strategy. A different pretext. There comes “medical marijuana.”

As of May 2016, 23 states have legalized marijuana for medical use (“medical marijuana”). Here in Florida, in 2014 Governor Scott signed a bill, the Compassionate Medical Cannabis Act (FL statute 381.986), legalizing low-THC cannabis for specific indications. In the elections of November 2014, a more liberal state referendum legalizing (including smoking) “medical marijuana,” Florida Right to Medical Marijuana Initiative, almost passed, and will undoubtedly find its way on the ballot again.

This ambiguously worded amendment would have legalized the use of marijuana (smoking or otherwise) “by a qualifying patient or personal caregiver.”3 The licensed physician who would have authorized a person’s use of marijuana would not have been required to be DEA registered. The physician would only have had to diagnose a “debilitating medical condition.” The measure defined a “debilitating medical condition” to include “other conditions for which a physician believes that the medical use of marijuana would likely outweigh the potential health risks for a patient.” The indication therefore would have been just about anything the physician would pronounce it to be.

As the would-be tools for any possible “medical marijuana” prescriptions in this state, Florida physicians must be knowledgeable of the available evidence about the potential medical benefits, and known harmful effects, of marijuana.

Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat diseases or to alleviate symptoms.4 Components of cannabis (cannabinoids) exert their biological effect on the endocannabinoid system (ECS) via cannabinoid receptors in the central and peripheral nervous system. There are several cannabinoids, such as cannabidiol (CBD), that generally do not produce euphoria but do affect the ECS. Delta-9 tetrahydrocannabinol (THC) is the euphoric producing cannabinoid.

There are currently several legal low-THC cannabinoids available.

Dronabinol (Marinol®) and nabilone (Cesamet®) are used to treat chemo-related nausea/vomiting and AIDS-associated anorexia/ weight loss. Nabiximols (Sativex®), a combination of CBD and THC, has been used in the U.K. to treat spasticity due to multiple sclerosis (though it failed to be effective in a recent study of cancer pain). Florida’s Compassionate Medical Cannabis Act (FL statute 381.986), has legalized low-THC (< 0.8%) high CBD (> 10%) cannabis for specific patients “who suffer from Northeast Florida Medicine Vol. 67, No. 3 2016 13

Guest Editorial

cancer or a physical medical condition that chronically produces symptoms of seizures or severe and persistent muscle spasms….. if no other satisfactory alternative treatment options exist.”5 This would include “Charlotte’s Web,” a cannabis sativa strain of non-euphoric marijuana high in CBD, but low (< 0.3%) in THC, to treat patients with childhood epilepsy.

Is there data for marijuana’s potential benefit? In a recent systematic review and meta-analysis in JAMA, “Cannabinoids for Medical Use,”4 79 articles were reviewed, only four of which were judged at low risk of bias. Though most investigations showed improvement of the symptom studied, many did not reach statistical significance.

There was evidence in some trials that cannabinoids may be beneficial for chronic neuropathic and cancer pain and MS related spasticity.

The evidence was “low quality” that cannabinoids were helpful in chemo-related nausea/vomiting, weight gain in HIV, and sleep disorders. The evidence was “very low quality” for improvement in anxiety or depression. Adverse drug effects (ADE’s) were common and included asthenia, balance problems, disorientation, fatigue, nausea, and hallucinations.

In contrast, there is abundant hard data of the harmful effects of smoking marijuana. There is evidence showing structural abnormalities in the brain with regular marijuana use.6 There is increased risk of serious cardiovascular disorders.7 There is the real association between regular smoking cannabis and psychosis.8 In Colorado, the first state to legalize “medical marijuana,” there has been more widespread smoking of marijuana in adolescents since the law went into effect.6 In Colorado, teenagers comprise 36 percent of that state’s population requiring treatment for marijuana use disorders.9 Since legalizing marijuana in Colorado, the percentage of motor vehicle fatalities testing positive for cannabis essentially doubled.10 THC en-utero exposure produces negative effects on the fetal brain.11 Most troubling is the persistent neuropsychological detriment in intelligence and motivation in adolescent marijuana smokers.12 Finally, inhaling the smoke of an ignited or burnt substance, whether that be tobacco, marijuana, or smog, produces known deleterious effects on the lungs.

Can we get any expert advice in guiding Floridian patients and voters to make the proper decision? The American and Florida Medical Association, American Psychiatric Association, American Society of Addictions Medicine, National Institute of Drug Abuse, Office of the National Drug Control Policy, and the Florida Sheriffs Association are against legalizing smoking marijuana.

Most medical associations call for objective scientific studies, just as with any other medication, before marijuana is legalized for medical purposes. The consensus: we need data, not hyperbole.

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Of all the diagnoses, the supporters state, that are undertreated and need marijuana, the most common diagnosis is “pain.”13 Does Florida really need another remedy for pain? With Florida having had the highest per capita oxycodone use in the country, and the United States having the highest per capita opioid use in the world, could anyone really believe marijuana is going to alleviate pain rather than adding to the dismaying public health problem of prescription drug abuse?

I recently made the mistake of attempting an informed conversation with a misguided proponent, asking for my signature to put a “medical marijuana” amendment again on the ballot. After he tried to convince me of all the symptoms and diseases smoking pot would surely cure, I tried, unsuccessfully, to add science to the conversation. After failing to convince him of the lack of medical evidence, I asked “why his group did not devote their energies into simply decriminalizing the smoking of marijuana.” As a now more seasoned libertarian, I propose: stand up, be counted, and work for what you believe. But please, do not hide this under a false medical decoy. His reply: “But this is the first step.”

The Trojans deeply regretted their mistake of accepting a seemingly gift horse under a false pretext, and their society never recovered. Let us not make the same mistake. Smoking marijuana simply isn’t medical. It’s mythology.

I am honored to have trusted and knowledgeable colleagues who will step up to the plate, without outward reward, to help their fellow medical colleagues. The coauthors in this edition of Northeast Florida Medicine are such people. The doctors who have helped put this journal together are my consultants, those who I would trust my family and patients to for specialized expertise.

Dr. Stephen Esser, a most versatile and intelligent physical medicine and rehabilitation physician, submits a lifestyle approach to decreasing pain via healthy living. Dr. Deanna Hughes, PhD clinical psychologist, is my go-to mental health practitioner for my patients who may benefit from cognitive behavioral therapy.

Dr. Frank Collier, a fellow interventional pain management subspecialist, brings us up-to-date on technological advances in pain management. Finally, Dr. Bernard Canlas, another pain management co-specialist, educates us on specific interventions that can be useful when our patients with cancer-related pain are not effectively served by the WHO analgesic ladder. I, and the entire Duval County Medical Society, thank you. v

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Guest Editorial

References 1. Homer. The Iliad. Athens. 5-6th Century B.C. 2. NORML. Washington, DC. Available from: http://norml.org/.

3. Florida Right to Medical Marijuana Initiative, Amendment 2 (2014) [Internet]. Available from: http://ballotpedia.org/Florida_Right_to_Medical_Marijuana_Initiative,_Amendment_2_ (2014).

4. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use, A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73.

5. 2014 Bill Summaries, The Florida Senate. Available from: https://www.flsenate.gov/Committees/BillSummaries/2014/ html/819.

6. Gilman JM, Kuster JK, Lee S, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdyla abnormalities in young adult and recreational users. J Neurosci. 2014 Apr 16;34(16):5529-38.

7. Jouanjus E, Lapeyre-Mestre M, Micallef J, et al. Cannabis use: Signal of increasing risk of cardiovascular disorders. J Am Heart Assoc. 2014 Feb 2;3(2):e000638.

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8. Radhakrishnan R, Wilkinson ST, Dâ&#x20AC;&#x2122;Souza DC. Gone to pot- A review of the association between cannabis and psychosis. Front Psychiatry. 2014 May 22;5:54.

9. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2003-2013 National Admissions to Substance Abuse Treatment Services. Rockville (MD): Substance Abuse and Mental Health Services Administration; 2015.

Report No.: BHSIS Series S-75, HHS Publication No. (SMA) 15-4934.

10. Salomonsen-Sautel S, Min SJ, et al. Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado. Drug Alcohol Depend. 2014 Jul 1;140:137-44.

11. Jaques SC, Kingsbury A, Henschcke P, et al. Cannabis, the pregnant woman and her child: Weeding out the myths. J Perinatol.

2014 Jun;34(6):417-24.

12. Meir MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife.

Proc Natl Acad Sci USA. 2012 Oct 2;109(40): E2657-64.

13. Finn K. Sequelae of Cannabis as Medicine. Pain Medicine. 2015 Jul;16(7):1447-9.

Northeast Florida Medicine Vol. 67, No. 3 2016 15

Pain Management

Forks and Feet: Pain and the Power of Food and Movement

By Stephan Esser, MD, USPTA Abstract: Exercise and nutrition are personal choices and can be powerful interventions that can enhance health and function and manage pain.

Clinicians and healthcare systems should continue to assist patients in developing low risk, high yield interventions to prevent and manage pain.

Based on the science to date, use of appropriately guided exercise and nutritional interventions should be a foundational intervention for every patient experiencing pain.

Introduction: Whether a stubbed toe, fibromyalgia or metastatic bone cancer, pain is part of the human experience. It is estimated that more then 100 million Americans suffer with chronic pain1 and daily acute pain is a ubiquitous experience. As society and science evolve, our notions, perceptions and acceptance of pain have varied widely.

A common thread through human history has been a desire to eliminate or reduce pain when and as much as possible. Our battle with pain in the 21st century has largely focused on advances in procedural innovations, surgical techniques and pharmacologic preparations, yet a growing body of scientific evidence suggests that movement and food are powerful pain altering interventions.

State of the Nation: Despite the awareness that physical activity and nutrition play a pivotal role in health, the United States leads the way in obesity and related cardiometabolic disease. 2 of 3 American adults are overweight or obese, 1 in 3 has high blood pressure, 1 in 6 has high cholesterol, 1 in 9 has diabetes and nearly 20 percent of all Americans continue to abuse nicotine.2 These trends reflect a global transition. According to the World Health Organization (WHO), by 2020 two-thirds of the global burden of disease will be attributable to “non-communicable” disease associated with a transition towards refined foods, foods of animal origin, sedentary behaviors and tobacco use.3 These trends in cardiometabolic risk also increase the risk of pain and commonly treated injury.4,5,6,7,8,9 In view of this association, exercise and nutrition should be encouraged as foundational methods to address both areas of concern.

Address correspondence to: Stephan Esser MD, USPTA 232 Ponte Vedra Park Drive Ponte Vedra Beach, FL 32082

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Movement is Medicine: Exercise truly is “medicine.”10 As Hippocrates wrote, “If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health.” No single intervention has such far ranging and multisystem effects as exercise. In view of the copious amount of evidence of benefit, the federal government presently recommends that all adults achieve 150 minutes per week of cardiovascular exercise and get two to three days per week of resistance training and balance/flexibility work.11 Despite this, fewer then 21 percent of adults achieve these weekly goals.

The effects of exercise on cardiometabolic risk, endocrine health, cognition, psychiatric health, risk of neoplasm and maintenance of function are well cataloged.11 The benefits of exercise for pain management have also been demonstrated, yet exercise is frequently not recommended by physicians.12 Exercise affects pain through mechanical, biochemical and neurologic mechanisms. As with most therapeutic interventions, overuse or misapplication of the treatment can result in symptom progression, injury or inadequate response. Similar to the use of medications, it is important that practitioners understand fully the indications and contraindications for exercise’s use and potential side effects. Physicians should identify an individual’s need, determine risk to the individual of beginning an exercise program, write an exercise prescription, apply the program and re-evaluate intermittently (Figure 1).

Motion is Lotion: Regarding the mechanical influence of exercise on pain, knee osteoarthritis (OA) and chronic low back pain are prototypical examples. According to projections, the prevalence of self-reported, doctor-diagnosed arthritis in the United States is expected to increase from 47.8 million individuals in 2005 to nearly 67 million by 2030 (25 percent of the adult population).13 The personal and societal implications of this exponential increase are concerning.

Exercise is a low cost intervention to both prevent and treat this condition.14 One of the accepted risk factors for progressive knee OA is muscular imbalance across the joint.15,16 By improving quadriceps and hamstring strength and balance, pain and progressive pathology can be reduced.14 Similar outcomes are seen in rotator

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cuff pathology, pelvic floor syndromes, chronic ankle instability and many other musculoskeletal pain syndromes. If biomechanical forces across a joint are evenly distributed in a manner which optimizes mechanical efficiency and mediates torque forces, then pain and progressive disease can be mitigated. Furthermore, in the knee OA model, regular moderate loading of cartilage cells improves diffusion of nutrients to the cartilage and enhances glycosaminoglycan content14 further slowing joint degeneration.

In patients with chronic low back pain, mechanical forces are also objectively altered. Whether reactive to chronic pain or itself a cause of progressive pain, individuals with chronic low back pain develop a decline in the cross sectional surface area of the intrinsic muscles of the spine.17 In addition, a combination of genetics and environment may lead to scoliotic curvatures, progressive facet degeneration and degenerative spondylolisthesis. These factors influence the biomechanical forces through the low back and any efforts to reduce pain should also maximize mechanical input. Voluntary muscle firing, which occurs during therapeutic exercise, can alter forces through the low back and provide therapeutic benefit.

For example, in chronic low back pain due to facet arthropathy, patients frequently present with relatively deconditioned hip extensor musculature, in particular the gluteus maximus. This results in increased lumbar lordosis which leads to further facet loading.

Prolonged sitting may also selectively shorten the iliopsoas further exacerbating this condition. Exercise focused on gluteal strengthening and iliopsoas stretching can alter the mechanical loads through the lumbar facets in a more favorable manner thereby reducing pain. Studies of chronic low back pain and exercise demonstrate improvements in global pain scales, depression indices and a reduced burden of disability.18 In view of this, all patients with axial low back pain without “red-flag” symptoms should be encouraged to engage in age and condition-appropriate exercise on a daily basis.

At the Cellular Level: Beyond the readily apparent mechanical, postural and hypertrophic improvements that exercise may lead to, it also has the potential to alter pain experience at a biomechanical level.

Oxygen and nutrient delivery is essential for tissue health. Impaired blood flow may lead to hypoxia, altered pH, and potential tissue necrosis. On the extreme, patients with severe peripheral arterial disease may lose a limb due to impaired blood flow. In a less dramatic fashion, patients with fibromyalgia demonstrate altered tissue perfusion with exercise.19 This leads to poor tissue perfusion, inadequate oxygen and nutrient delivery, impaired cellular waste removal and a more acidic tissue pH. This relatively

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hypoxic environment alters C fiber depolarization thresholds and results in increased pain. Exercise has powerful normalizing effects on this cascade. It improves cardiac output and efficiency and promotes angiogenesis and arterial vasodilatation to skeletal muscle. As a result tissue perfusion is enhanced and both nutrient/oxygen delivery and metabolic waste removal are promoted.

Exercise also alters neuro-hormonal function. It releases a cocktail of endorphins which reduce pain and improve depressive symptoms on par with commonly used anti-depressants.20 In addition, exercise participants also reduce their risk of common diseases and improve self-efficacy scores and physical function.

At the genetic level, exercise even alters genetic expression.21 This epigenetic influence may be the foundational mechanism by which exercise produces such widespread, multisystem effects.

Master Organ: The Brain: The central nervous system (CNS) maintains a remarkable balance of inhibition and activation. This balance fosters variable periods of rest and activity in all cells. The CNS can facilitate an enhanced sensitivity to both nociceptive (pain producing) and non-nociceptive inputs. Intentionally and repetitively stimulating a region of stimulus of the CNS can lower the threshold of neural depolarization and increase the sensitivity to the structure or region. For example, an individual wishing to learn to play the piano pays careful attention to the position, movement and pressure of each finger on the keyboard. With intentional repetition, the tips of the fingers gain increased sensitivity to touch and allow the individual to create nuanced tones. Similarly, the pitching athlete gives “value” to each phase of the throw. In time and with intentional, centrally guided repetition, the pitcher is able to perform a choreographed activity with great precision and efficiency. These changes are neurologic in nature though the layperson often refers to “muscle memory.” These changes in depolarization are mediated mostly in the CNS and are termed “central sensitization.” As it relates to pain, repetitive nociceptive input matched with reduced non-nociceptive input results in an increased sensitivity (reduced depolarization threshold) of pain fibers. These changes are engaged in the experience of chronic pain. However, if non-nociceptive fibers (muscle stretch receptors, pressure, vibration, thermal sensors) are fired more and in exclusion of nociceptive fibers (C fibers, pain fibers), then chronic pain is diminished. This is part of the mechanism by which it is believed massage, electrical stimulation, cryotherapy and exercise act to reduce pain. Clinicians can harness this by using exercise as a method to gently, progressively desensitize the central nervous

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system. Begin with mild, non-pain producing activities which predominantly stimulate areas distal from the focus of pain and then gradually increase exercise stimulus intensity, volume and frequency while localizing toward the area of greatest pain.

Exercise truly is medicine in the management of painful conditions and the side effects from its use include multisystem benefits. All clinicians should increase their awareness of its implementation in patient care and in their own personal lives.

The Food We Eat: The second pillar of human health is nutrition. As the Chinese proverb is quoted, “He that takes medicine and neglects diet wastes the time of his doctor.” The food and fluids we consume have powerful effects on mood, growth, energy, function and even pain. The potential is impressive when one considers that individuals make more then 200 decisions about food per day.22 If various combinations of food can influence pain, then specific nutritional recommendations could be powerful therapeutic assets. It is theorized that food can influence pain via mechanical influence (caloric effects), vascular influence, biochemical inflammation and neural stabilizing effects among others.

Calories are often spoken of but rarely understood by the average person. From a medical perspective, a calorie is the amount of energy needed to increase the temperature of one gram of water by one degree Celsius. In the last 30 years, Americans have increased average caloric consumption by nearly 550 kcal per person per day and as a result 2 in 3 Americans are overweight or obese.2 This increase in weight significantly increases loading forces through the spine and lower extremities. With increased weight comes increased risk of osteoarthritis and pain. Fortunately, weight reduction can powerfully reduce pain and improve function. For example, as related to knee OA, for each percentage point reduction in body fat, Western Ontario and McMaster University Osteoarthritis (WOMAC) scores increase by 10 percent23 and for each pound of weight loss there is a fourfold reduction in the load exerted on the knee per step during daily activities.24 Although exercise is a powerful adjunct for weight loss, modified nutrition is even more effective and is essential for long term success. By making meaningful and sustainable nutritional changes, weight loss can be achieved.

On a vascular level, food influences blood flow. Alteration in blood flow affects the delivery of nutrition and oxygen and the removal of cellular wastes. Some foods promote vasoconstriction while others promote vasodilatation. A single high fat meal can reduce vasodilatation by up to 50 percent for four hours.25 An

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individual eating the “Standard American Diet” replete with high fat foods may expect to experience impaired blood flow most of the day. In comparison, foods rich in plant-based polyphenols and nitrates have a positive effect on blood vessel health including the mediation of vasodilatation.26,27 Altering the diet to increase consumption of these substances may also reduce pain and joint stiffness in both fibromyalgic patients and those struggling with inflammatory joint syndromes.28 High fat foods often accompany cholesterol. Risks of multiple pain conditions have been associated with elevated levels of serum cholesterol.6,29 It is hypothesized that elevated cholesterol and its concomitant oxidation may result in atherosclerotic disease within the microvasculature thus impairing blood flow to at risk tissues.25 Impaired blood flow, results in dysfunction at the cellular level, alters cell function and increases the risk of degenerative changes.

Science related to nutrition and systemic inflammation is rapidly evolving. Work in the area of “phyto-nutrition” shows particular promise. Animal foods are significant sources of arachidonic acid, the precursor to prostaglandins. For this reason, diets high in animal based foods promote prostaglandin production and may promote cellular pain signaling.30 Similarly, animal based foods and alcoholic beverages are primary sources of uric acid in the western diet. Uric acid is well known in relation to gout, but its relationship to chronic musculoskeletal pain is less commonly discussed.31 Much of the “anti-inflammatory” food literature focuses on the positive effects of plant based foods or phytonutrients.

Spices, berries, deep green vegetables and sources of omega 3 fats appear to have robust pain modulating affects. As individual substances, many rival conventional pharmacologic treatments.

For example, curcumin appears as effective as naproxen in managing active rheumatoid arthritis pain with fewer side effects.32 Ginger shows promise in the treatment of pain from primary dysmenorrhea.33 Many other spices show potential including boswellia and cinnamon. Although more research is needed, increasing consumption of these spices is of plausible benefit and low risk to the patient. If choosing to incorporate these spices in a “prescribed” medicinal fashion, clinicians should review safety and packaging data for each brand used. Other nutritional interventions to be considered include the use of omega 3 fats.

Studies to date demonstrate pain reduction for some diagnoses equal to nonsteroidal anti-inflammatory drugs (NSAIDs).34 The clinician should also consider adjuvant B-Vitamins, as used for low back pain in multiple “DOLOR” studies.35 Supplementation is only the edge of nutritional modifications.

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to patients should promote a whole-food, plant-based program.

Not only does such an approach help reduce cardiometabolic disease risk, but multiple studies show that such nutritional recommendations have powerful pain modulating effects.36,28,37,38

Challenges Ahead: Knowledge of the therapeutic benefits of lifestyle interventions is simple, but application in clinical practice is complex.

Prior to recommending behavior change, clinicians must evaluate the patient’s “readiness for change” using Prochaska’s Transtheoretical Model of Health Behavior Change (Figure 2).39 Motivational interviewing techniques should be used to facilitate change in a positive direction and close follow-up should be maintained. Patients should be asked to identify their own GROW (Goals, Reality today, Obstacles and Will to change) and assisted in developing SMART Goals (Specific, Measurable, Attainable, Realistic, Time Bound).

At the heart of using exercise and nutrition in the management of pain is the belief that personal choices are powerful interventions that can enhance health and function. Individual clinicians and healthcare systems at large should continue to assist patients in developing low risk, high yield interventions to prevent and manage pain. Based on the science to date, use of appropriately guided exercise and nutritional interventions should be a foundational intervention for every patient experiencing pain. v

Figure 1: Exercise Prescription Identify individual need/goals è Determine Risk of participation è Provide Exercise Prescription è Apply Intervention è Re-evaluate outcomes

Figure 2: Stages of Change Pre-Contemplation Contemplation Preparation Action Maintenance Adapted from Prochaska’s Transtheoretical Model of Health Behavior Change39

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References 1. Institute of Medicine: Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research.

Washington, DC: The National Academies Press, 2011.

2. Centers for Disease Control and Prevention. Obesity and Overweight [Internet]. Atlanta (GA): U.S. Department of Health & Human Services; [updated 2015 Sep 30; cited 2016 Jan 5]. Available from: http://www.cdc.gov/nchs/fastats/obesity-overweight.htm.

3. Chopra M, Galbraith S, Darnton-Hill I. A global response to a global problem: the epidemic of overnutrition. Bull World Health Organ. 2002;80(12):952-8.

4. Heim N, Snijder MB, Deeg DJ, et al. Obesity in Older Adults Is Associated With an Increased Prevalence and Incidence of Pain. Obesity (Silver Spring). 2008 Nov;16(11):2510-7.

5. Wright LJ, Schur E, Noonan C, et al. Chronic Pain, overweight, and obesity: findings from a community-based twin registry. J Pain. 2010 Jul;11(7):628-35.

6. Kauppila, L. Atherosclerosis and disc degeneration/low-back pain – a systematic review. Eur J Vasc Endovasc Surg. 2009 Jun;37(6):661-70.

7. Hangai M, Kaneoka K, Kuno S, et al. Factors associated with lumbar intervertebral disc degeneration in the elderly. Spine J. 2008 Sep-Oct;8(5):732-40.

8. Longo UG, Franceschi F, Ruzzini L, et al. Higher fasting plasma glucose levels within the normoglycaemic range and rotator cuff tears. Br J Sports Med. 2009;43:284-287.

9. Mork P, Vasseljen O, Nilsen TI. Association between physical exercise, body mass index, and risk of fibromyalgia: Longitudinal data from the Norwegian Nord-Trøndelag Health Study.

Arthritis Care Res (Hoboken). 2010 May;62(5):611-7.

10. Sallis RE. Exercise is medicine and physicians need to prescribe it! Br J Sports Med. 2009;43:3-4.

11. Centers for Disease Control and Prevention. Physical Activity and Health [Internet]. Atlanta (GA): U.S. Department of Health & Human Services; [updated 2015 Jun 4; cited 2016 Jan 15.] Available from: http://www.cdc.gov/physicalactivity/ basics/pa-health/.

12. Schutzer KA, Graves BS. Barriers and motivations to exercise in older adults. Prev Med. 2004 Nov;39(5):1056-61.

13. Hootman J, Helmick C. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum.

2006 Jan;54(1):226-9.

14. Esser S, Bailey A. Effects of exercise and physical activity on knee osteoarthritis. Curr Pain Headache Rep. 2011 Dec;15(6):423-30.

15. Slemenda C, Brandt KD, Heilman DK, et al. Quadriceps weakness and osteoarthritis of the knee. Ann Intern Med. 1997 Jul 15;127(2):97–104.

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16. Hurley MV, Scott DL. Improvements in quadriceps sensorimotor function and disability of patients with knee osteoarthritis following a clinically practicable exercise regime. Br J Rheumatol. 1998 Nov;37(11):1181–7.

17. Danneels LA, Vanderstraeten GG, Cambier DC, et al. CT imaging of trunk muscles in chronic low back pain patients and healthy control subjects. Eur Spine J. 2000 Aug; 9(4):266-72.

18. Rainville J, Hartigan C, Martinez E, et al. Exercise as a treatment for chronic low back pain. Spine J. 2004 JanFeb;4(1):106-115.

19. Elvin A, Siösteen AK, Nilsson A, et al. Decreased muscle blood flow in fibromyalgia patients during standardised muscle exercise: a contrast media enhanced colour Doppler study. Eur J Pain. 2006 Feb;10(2):137-44.

30. Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int. 2003 Jan;23(1):27-36.

31. Aarflot T, Bruusgaard D. Chronic Musculoskeletal Complaints and Subgroups with Special Reference to Uric Acid. Scand J Rheumatol. 1994;23(1):25-9.

32. Chandran B, Goel A. A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother Res. 2012 Nov;26(11):1719-25.

33. Rahnama P, Montazeri A, Huseini HF, et al. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med. 2012 Jul 10;12:92.

20. Rethorst CD, Wipfli BM, Landers DM. The antidepressive effects of exercise: a meta-analysis of randomized trials. Sports Med. 2009;39(6):491-511.

34. Maroon JC, Bost JW. Omega 3 Fatty Acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006 Apr;65(4):326-31.

21. Melov S, Tarnopolsky MA, Beckman K, et al. Resistance Exercise Reverses Aging in Human Skeletal Muscle. PLoS ONE. 2007;2(5):e465.

35. Mibielli MA, Geller M, Cohen JC, et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009 Nov;25(11):2589-99.

22. Lang S. ‘Mindless autopilot’ drives people to dramatically underestimate how many daily food decisions they make, Cornell study finds [Internet]. 2006 Dec [cited 2015 Nov 21].

Available from: http://www.news.cornell.edu/stories/2006/12/ mindless-autopilot-drives-people-underestimate-food-decisions.

36. Kaartinen K, Lammi K, Hypen M, et al. Vegan diet alleviates fibromyalgia symptoms. Scand J Rheumatol. 2000;29(5):308313.

23. Christensen R, Astrup A, Bliddal H. Weight loss: the treatment of choice for knee osteoarthritis? A randomized trial.

Osteoarthritis cartilage. 2005 Jan;13(1):20-7.

24. Messier SP, Gutekunst DJ, Davis C, et al. Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum 2005 Jul;52(7):2026-32.

37. Ellis FR, Sanders TA. Angina and vegan diet. Am Heart J. 1977 Jun;93(6):803-5.

38. Crane M, Sample C. Regression of Diabetic Neuropathy with Total Vegetarian (Vegan) Diet. J Nutr Med. 1994;4(4):431-9.

39. Prochaska JO. Velicer WF. The transtheoretical model of health behavior change. Am J Health Promot. 1997 SepOct;12(1):38-48.

25. Vogel RA, Corretti MC, Plotnick GD. Effect of a Single HighFat Meal on Endothelial Function in Healthy Subjects. Am J of Cardiol. 1997 Feb 1:79(3):350-4.

26. Lara J, Ashor AW, Oggioni C, et al. Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis. Eur J Nutr. 2015 Mar 13.

27. Ghosh D, Scheepens A. Vascular action of polyphenols. Mol Nutr Food Res. 2009 Mar;53(3):322-31.

28. Hanninen, Kaartinen K, Rauma AL, et al. Antioxidants in vegan diet and rheumatic disorders. Toxicology. 2000 Nov 30;155(1-3):45-53.

29. Abbound JA, Kim JS. The effect of hypercholesterolemia on rotator cuff disease. Clin Orthop Relat Res. 2010 Jun;468(6):1493-7.

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Psychological Implications of Chronic Pain Management

By Deanna Hughes, Psy.D. Abstract: Chronic pain is a ubiquitous problem that hampers societal functioning and is associated with rising medical costs and disability claims. The psychological impact of chronic pain can be devastating on the individual and family systems. Consequently, chronic pain conditions are understood from a biopsychosocial spiritual paradigm.

There are various pain models, coping strategies, co-morbid psychiatric conditions, and treatment approaches that should be considered.

Introduction: Chronic pain is a pervasive societal concern estimated to impact 47 percent of adults and 25 percent of children and adolescents.1 Pain is the primary reason patients visit the emergency room, pursue outpatient medical care, and seek medication. It is conservatively estimated that healthcare and loss of productivity in the United States costs 560-635 billion dollars per year, which is higher than the combined costs of treating cancer, diabetes, and heart disease.1 The International Association for the Study of Pain defines pain as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”2 Despite the subjective experience of the patient emphasized in this definition, the psychological aspects of pain are often overlooked. Understanding the meaning of the patient’s pain rather than actual tissue damage is the largest predictor of pain related disability and narcotic requests. A patient who has an uncertain diagnosis has increased worry and belief in illness.3 It is important to consider the psychological factors of pain in clinical practice (Table 1).4

Pain Models: The emergence of psychology’s role in pain modulation began with the Gate Control Theory proposed by Melzach and Wall.5 In the dorsal horn of the spinal cord or the gate, there are excitatory and inhibitory factors that open or close the

Address correspondence to: Deanna Hughes, Psy.D. Licensed Psychologist 4114 Herschel Street, Suite #110 Jacksonville, FL 32210 904-504-5412 deannahug@gmail.com DCMS online . org

gate, thereby controlling the pain intensity and quality. Factors such as attention, mood, expectations, and beliefs determine the extent to which the gate is opened or closed. Based on this theory, a patient who is actively engaged in life and diverts his attention away from pain is likely to have less pain intensity.5 In the operant model for pain developed from psychological learning theory, the healthcare provider’s motive is to change the environment to improve the patient’s overall functioning.6 This model suggests that all behavior is governed by environmental effects. Pain behaviors are learned by observation and reinforcing events. Behaviors such as exercise, work, and resumption of daily activities are positively reinforced by providers and family thereby increasing the likelihood of their reoccurrence.

Based on the complex and multifaceted nature of chronic pain, the biopsychosocial spiritual perspective weaves together a patient’s biological, cultural, personality, and spiritual backgrounds.7 A dualistic separation of the mind and body is harmful because it reinforces a pain patient’s perceptions that

Table 1: Using psychological factors in clinical practice (Adapted from C. Eccleston)12 Pain vigilance:

Patients are distracted due to pain. Communication should be clear and brief with repetition of key points.

Patients are not hypochondriacs if pain is excessively discussed since pain is in their immediate attention.

Avoidance:

Patients naturally avoid pain and painful procedures.

Habitual pattern of avoidance may lead to chronic pain.

It is imperative for patients to understand that pain does not always reflect tissue damage.

Anger:

Increased irritation is a normal reaction to pain which has nothing to do with the medical provider so do not take their reaction personally. Intense emotionality makes it difficult for the patient to understand treatment information. Providing written information is helpful.

Involve the Patient:

Assess a patient’s coping behaviors when confronted with predictable pain such as a dental visit. Ask yourself does the patient prefer to be distracted or know specifics of procedures? Tailor treatment needs to the patient’s style of coping. Providing detailed information about a procedure could maximize patient’s control or cause greater anxiety depending on the preferred coping style.

Expectations:

Creating positive expectations for patients is associated with decreased activity in pain areas of brain and release of endogenous opioids. The healthcare provider might say, “I am excited to see how the spinal cord trial will help you.”

Adapted with permission from: Eccleston C. Role of psychology in pain management. Br J Anaesth. 2001;87:144-52.

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he is viewed as “crazy” rather than acknowledging suffering of the mind, body, and spirit.

Psychological factors play a salient role as the pain transitions from acute to chronic. Unlike acute pain that is typically the result of a sudden injury or trauma that lasts for a designated time period, chronic pain lasts longer than six months and is often associated with loss of employment, relationships, hobbies, and self-worth.2 Chronic pain conditions such as arthritis, neuropathy, fibromyalgia, and low back pain are considered illnesses rather than diseases because the physician’s aim is managing rather than curing. Similarly, the mental health provider’s goal is to promote change through empowering and enhancing control rather than eliminating the pain.

Co-Morbidity: Depression, anxiety, and sleep disorders are the most frequently cited co-morbid psychological conditions associated with chronic pain patients. Inadequate sleep increases mood disturbance and pain intensity. The reciprocal relationships between mood, chronic pain, and sleep are attributed to the same neurochemical pathways involving serotonin and noradrenaline.8 Notably, 50 percent of chronic pain patients struggle with depression and have two to three times the suicide rate relative to the normal population.9 Research indicates that depressed patients exhibit greater treatment non-compliance, pain intensity, disability, and passive coping.8 Catastrophizing is a common distorted thought process among depressed and anxious pain patients. Patients with a catastrophic outlook expect the worst and view pain as endless and unfixable. This causes perceptions of helplessness. Catastrophizing is associated with chronicity, immediate post-surgical pain, and higher levels of disability two years post-surgery.10 Prior trauma exposure has been linked to chronic pain through central sensitization of the nervous system. Trauma causes the secretion of cortisol and adrenaline which impairs memory by blocking hippocampal functioning and increasing encoding of implicit memory, which uses past experiences to recall things without thinking of them. Traumatic events are stored as bodily sensations and/or flashbacks through muscle memory. Ninety percent of women diagnosed with fibromyalgia and 76 percent of patients with low back pain have a history of trauma.11 It is also hypothesized that trauma creates a heightened arousal state in the nervous system through inflammation of the glial cells that predisposes patients to chronic pain.11

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Cognitive Behavioral Treatment: Cognitive behavioral therapy is an effective tool for treating chronic pain.12 This approach utilizes self-regulatory and cognitive techniques to help patients manage their pain. Examples of behavioral strategies include pacing of activities, exercising, and sleeping hygiene.

Self-regulatory techniques such as guided imagery, diaphragmatic breathing, hypnosis, biofeedback, progressive/passive muscle relaxation, mindfulness meditation, and autogenic training are effective because they enhance a patient’s sense of control.12 These techniques also modulate the emotional responses to pain, reduce muscle tension, and divert attention.

Further examination of the self-regulatory technique of hypnosis indicates that patients and medical professionals often have misconceptions that prevent the use of this powerful pain management strategy. The state of hypnosis allows the patient to narrow his attentional field to focus, physically relax, and remain open to suggestion. While the patient remains in full control, the provider makes suggestions for altering pain intensity, separating self from pain, and neutralizing pain. The patient is also encouraged to dissociate to a pleasant place, view stabbing pain as vibration or numbness, and/or move his pain to a different body part. Hypnosis is associated with an increase in alpha brain waves and a decrease in beta brain waves.13 Biofeedback, another self-regulatory technique, provides a patient with information about his physiological functioning.

Electromyographic biofeedback, a technique that is best suited for tension headaches and soft tissues disorders, directs a patient’s awareness to the pain site’s electrical activity through auditory and visual feedback. The patient learns positions and relaxation techniques to decrease tension. Thermal biofeedback is effective for pain conditions related to vasodilation such as migraine headaches, reflex sympathetic dystrophy, and Raynaud’s disease.12 A temperature sensor is placed on the patient’s index finger and allows the patient to learn how to adjust his body temperature.

Within the cognitive domain of cognitive behavioral treatment, patients are taught to recognize cognitive distortions, challenge them, and develop coping statements. Fortune telling, catastrophizing, overgeneralization, and all or nonethinking are examples of distorted thinking. For example, a patient who believes that his lumbar pain has ruined his life due to non-changing pain levels learns a more adaptive and rational outlook. He is taught to use Socratic questioning to

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determine the evidence for his thoughts. As a result, he might tell himself, “My body is always changing so pain intensity has to change. My life is not ruined because I have a loving family and wonderful career. I have been through flare-ups before and the pain intensity will pass. I know that a hot shower reduces pain.” A positive thought process changes the chemicals in the brain and reduces pain and improves mood; however, as previously indicated, studies indicate that catastrophic thinking is associated with poor sleep, increased disability, depression, negative views of overall health, and conflictual social relations.10

Conclusion: Pain is a biopsychosocial experience, not a unidimensional transmission between isolated nerves. Encompassing psychology is imperative to the effective management of chronic pain. Patient success is most likely to occur when health care providers tailor treatment to the individual’s pain condition and adopt a biopsychosocial spiritual lens. Healthcare professionals are at risk of providing substandard care without the implementation of behavioral health as a core part of chronic pain service.14 v

9. Fisher BJ, Haythornthwaite JA, Heinberg LJ, et al. Suicidal intent in patients with chronic pain. Pain. 2001 Jan;89(23):199-206.

10. Theurissen, M., Peters, M.C., Bruce, J., Smith, M.T. Preoperative anxiety and catastrophizing: a systemic review and meta-analysis of the association with chronic post-surgical pain. Clinical Journal of Pain. 2012 Nov-Dec;28(9):819-41.

11. Otis JD, Keane TM, Kerns RD. An examination of the relationship between chronic pain and post-traumatic stress disorder. J Rehabil Res Dev. 2003 Sep-Oct;40(5):397-405.

12. Turk DC. Psychosocial aspects of chronic pain. In: Benzon HT. Practical Management of Pain. 5th ed. Philadelphia, PA: Elsevier Mosby; 2014:chap 12.

13. Kaplan, G. Solving the mystery of chronic pain and depression: total recovery. New York: Rodale; 2014.

14. Foreman, J. A nation in pain: healing our biggest health problem. New York: Oxford University Press; 2014.

References 1. Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving pain in America: A blueprint for transforming prevention, care, education, and research. Washington (DC): National Academies Press; 2011.

2. International Association for the Study of Pain, European Federation of IASP Chapters. Unrelieved pain is a major global healthcare problem. 2012 Aug 29. Report 4A. Available from: http://www.efic.org/userfiles/Pain%20 Global%20Healthcare%20Problem.pdf.

3. Beecher HK. Relationship of significance of wounded to pain experienced. J Am Med Assoc. 1956 Aug 25;161(17):1609-13.

4. Eccleston C. Role of psychology in pain management. Br J Anesth. 2001 Jul;87(1):144-52.

5. Melzack R, Wall PD. Pain mechanisms: a new theory.

Science. 1965 Nov 19;150(3699):971-9.

6. Fordyce,W.E. Behavioural methods for chronic pain and illness. St. Louis (MO): CV Mosby; 1976.

7. Koenig, H. Religion, spirituality, and medicine: research findings and implications for clinical practice. South Med J. 2004 Dec;97(12):1194-200.

8. Finan, PH, Smith, MT. The comorbidity of insomnia, chronic pain, and depression: dopamine as a putative mechanism. Sleep Med Rev. 2013 Jun;17(3):173-83.

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Pain Management

Interventional Pain Management for Cancer Pain

By Bernard R. Canlas, MD

Introduction Cancer is the second leading cause of death, according to the latest CDC statistics, with an estimated 591,699 deaths per year.1 Estimates by the American Cancer Society for new cancer cases show that in men, the top four malignancies are in the prostate, lung, colon/rectum and urinary bladder. In women, the top four sites are breast, lung, colon/rectum and uterine corpus. Malignancy of the lung and bronchus is the leading cause of death in both sexes, followed by prostate, colon and rectum in men, and breast, colon and rectum in women. The lifetime probability of developing cancer is 42 percent for an American male and 38 percent for an American female. Despite this risk, the trend in five-year survival has increased to 69 percent according to the latest statistics from 2005-2011.2

A study by Deandrea et al showed that most patients will accept mild pain, whereas moderate to severe pain requires attention.5 The study used the Pain Management Index (PMI) to evaluate the congruence between the patient’s reported level of pain and the intensity/strength of analgesic therapy.

Results showed that 43 percent of patients had negative PMI and nearly 1 of 2 is undertreated. In 2011, a national survey of U.S. medical oncologists’ attitudes and practice in cancer pain management noted that referrals to pain management and palliative care specialists were reported by only 14-16 percent of respondents.6 Researchers concluded that a “focus on cancer pain has not adequately addressed the perception of treatment barriers or limitations in pain-related knowledge and practice with the oncology community.”

Figure 1:

The medical community has made great strides in cancer screening, earlier detection and treatment. According to the latest cancer epidemiology study by de Moor et al, the number of cancer survivors increased from over 3 million in 1977 to 13.7 million as of January 1, 2012. The projected prevalence is expected to approach 18 million cancer survivors by 2022.3 Sixty four percent have survived cancer five years or more from the time of diagnosis. Forty percent have survived over 10 years and 15 percent have survived over 20 years. Regarding cancer pain, a recent comprehensive systematic review found the prevalence to be very high.4 Sixty four percent of patients with advanced, metastatic or terminal disease experienced pain. Fifty nine percent of patients had pain while on anticancer treatment and 33 percent still had pain once cured. More than one third of cancer patients rated their pain as moderate (Visual Analog Scale- VAS > 4 or more, based on an 11-point scale).

Address Correspondence to: Bernard R. Canlas, MD S-112 Pain Clinic Department of Veterans Affairs Puget Sound Health Care System 1660 South Columbian Way Seattle, WA 98108 bernard.canlas@va.gov

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Cancer pain can be classified as acute, chronic, persistent, basal or breakthrough. Pain can also be classified according to its nature: nociceptive, neuropathic, inflammatory or mixed. The etiology of cancer pain could be related to the cancer itself, as a result of its treatment, or unrelated to the disease. The World Health Organization (WHO) Pain Relief Ladder (Figure 1) for cancer pain relief has been around for more than 20 years. A 10-year validation study suggested that 76 percent of patients could achieve good pain relief using the principles of the ladder.7 The WHO Pain Relief Ladder DCMS online . org

Pain Management

is based on the prompt administration of drugs in the following order. Step 1 in the ladder involves the use of non-opioids such as NSAIDs and/or acetaminophen with or without adjuvant medications (e.g. anti-depressants, anti-convulsants). If pain persists, the patient is advanced to step 2 of the ladder, which involves administration of a mild opioid such as codeine, with or without adjuvant medications. If the patient is experiencing severe pain, then the use of strong opioids like morphine or oxycodone is recommended until the patient is free of pain.

A 2011 editorial by Forbes estimated that 12 percent of patients have inadequate pain management despite our best efforts.8 This is an opportunity for interventional techniques to be considered. There has been clamor for inclusion of interventional pain techniques as the fourth step of the WHO ladder.

Miguel, in 2000, advocated for interventional treatments for patients experiencing inadequate pain relief despite the use of oral or transdermal opioids or those who have undesirable/intolerable side effects.9 Another article published in the Journal of Supportive Oncology in 2004 stated, “The practicing oncologist should understand that pain management procedures are most often used in concert with standard analgesic regimens to reduce opioid side effects or gain better analgesic efficacy.”10 Interventional techniques are part of a multimodal approach in managing cancer pain; they are not stand-alone treatments.

A prerequisite is a complete patient history, pain evaluation, physical and neurologic examination. The coagulation status has to be considered if spinal or transvascular procedures are performed. An informed consent is necessary as serious risks like permanent sensory and motor deficits may occur, especially with neurolytic procedures.

Trigger Point Injections Myofascial pain occurs in peripheral muscular and connective tissue. The application of pressure on “trigger points” in the muscles causes pain. In the cancer population, a prospective study of breast cancer surgery patients noted that myofascial pain syndrome was present in 44.8 percent of the patients 12 months after surgery.11 Injection with local anesthetic followed immediately by stretching as part of a multimodal approach can offer good outcome.12

Paravertebral Nerve Blocks Painful sensations are transmitted from peripheral nerve fibers and relayed in the dorsal horn of the spinal cord, to the spinothalamic tract and eventually processed in the brain.

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Infiltration of local anesthetic with or without steroids at a peripheral nerve and sometimes local anesthetic infusion could provide immediate relief. It could minimize the side effects of medications used for neuropathic pain such as anti-depressants and anti-convulsive medications. Intercostal nerve injury is a common long lasting effect of a thoracotomy incision used for exposure and removal of thoracic malignancies. It is caused by intraoperative rib retraction.13 Thoracic paravertebral block was first pioneered to provide abdominal analgesia.14 Interest was rekindled by Eason and Wyatt15 using a catheter technique.

A randomized, prospective comparison between continuous epidural and paravertebral blocks showed that paravertebral analgesia was superior in terms of analgesia, neuroendocrine response, pulmonary function and side effects.16 Several studies show the advantage of thoracic paravertebral blocks in managing neuralgia.15,17, 18 With multimodal analgesia, brachial plexus blocks decrease the incidence of acute and chronic pain after breast cancer surgery,19 with the incidence of chronic pain six months after surgery 30 percent in the treatment group as compared to 57 percent in the control group.

Intercostal Nerve Block Intercostal nerves arise as the ventral rami of thoracic nerves from T1 to T11, with the twelfth ventral ramus below the twelfth rib called the subcostal nerve.20 As noted by Rogers et al, intercostal nerve injury after rib retraction can cause persistent pain and suffering.13 Wong and his colleagues performed intercostal nerve blocks in cancer patients with rib metastasis from 1995-2005.21 If pain relief was satisfactory with a local anesthetic diagnostic block, a neurolytic blockade with 10 percent phenol followed. Eighty percent of the 25 patients had optimal pain control and 56 percent experienced reduction in analgesic use after the block. Thirty two percent did not have recurrence of the pain until the end of their lives.

Sympathetic Stellate Ganglion Block Preganglionic neurons with cell bodies located in the anterior lateral horn of the first and second thoracic spinal cord segment yield the sympathetic nerve supply to the head. In 80 percent of the population, the stellate ganglion is formed by the fusion of the inferior cervical ganglia and the first thoracic ganglia22 (Figure 2). The sympathetic nerves that supply the head and neck and most of the supply of the upper extremity traverse through the stellate ganglion.22 Blockade of the stellate ganglion has been used as a diagnostic, prognostic and therapeutic

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Figure 2: Fluoroscopic view of right stellate ganglion block

Figure 3: Fluoroscopic view of celiac plexus block. Note outline of aorta, renal arteries, and celiac trunk

Figure 4: Fluoroscopic view of celiac plexus block, lateral view

Used with permission from Timothy Sternberg, DMD, MD

technique for various conditions. It has been used extensively in complex regional pain syndromes of the upper extremities.23,24,25 Blockade has also been used for lymphedema of the upper extremity following mastectomy,23,26 breast pain following mastectomy26,27 and neuropathic pain syndromes in cancer.26,28 Stellate ganglion blocks can decrease the number of hot flushes and night awakenings in breast cancer survivors who can have frequent prolonged severe and distressing hot flushes.29,30

Sympathetic Celiac Plexus Block Perhaps no other interventional procedure for cancer pain has been more studied than the celiac plexus block (CPB).

The celiac plexus is the largest visceral plexus, located deep in the retroperitoneum, over the anterolateral surface of the aorta and around the origin of the celiac trunk (Figures 3, 4). It is a relay center for nociceptive impulses arising from the upper abdominal viscera, from the stomach to the proximal transverse colon.30 Malignancies in the abdomen may produce life quality altering pain.31 Pancreatic cancer is the fourth leading cause of cancer mortality in the United States with an estimated 41,780 deaths due to this in 2016.31 Pancreatic cancer causes severe pain in 50 to 70 percent of patients.32 Diagnostic CPB’s with local anesthetics provide temporary relief of the patient’s pain. Neurolytic CPB’s can provide more long-term relief.33,34 Neurolytic agents commonly used are absolute alcohol or phenol.33,34 In a series of sixty patients with abdominal or pelvic cancer pain who underwent neurolytic CPB, superior hypogastric plexus block or lumbar sympathetic block, most had a significant reduction of pain, opioid consumption and better quality of

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life compared to those who received pharmacotherapy only.35 The author advocated these interventions for the management of cancer pain early in the disease.35 A clinical review on the use of neurolytic CPB for pain control in unresectable pancreatic cancer concluded that neurolytic CPB was associated with improved pain control, reduced narcotic usage and constipation compared with standard treatment.36 Alcohol neurolytic CPB causes fewer adverse effects than opioids. CPB with alcohol reduces pain scores and opioid consumption.37,38 The authors concluded that “although statistical evidence is minimal for the superiority of pain relief over analgesic therapy, the fact that celiac plexus block causes fewer adverse effects than opioids is important for patients.”37,38 Nagels et al published a follow-up systematic review in 2013.39 The conclusion was that neurolytic CPB “is a valuable treatment to reduce visceral pain in patients with upper abdominal cancer pain. This review indicates that percutaneous CPB is a safe procedure, associated with a significant decrease in pain, opioid use, and therefore opioid-induced side effects.”

Superior Hypogastric Nerve and Ganglion Impar Block The superior hypogastric plexus carries visceral afferents from the lower abdomen and pelvis. It lies anterior to the L5-S1 disc and vertebrae. Performing neurolytic blockade of this plexus may be used to reduce pain from malignancy.40 In a study of 227 patients41 with advanced pelvic cancer of gynecological, colorectal and genito- urinary origin who received either one or two neurolytic blocks, 72 percent had good pain control and 28 DCMS online . org

Pain Management

percent had moderate pain control. The benefit was maintained at three months. The positive responders had significantly reduced opioid intake.

The ganglion impar or ganglion of Walther is the unpaired midline termination of the sympathetic chains. It is located in the post-rectal space and lies anterior to the sacrococcygeal junction. It receives afferents from the rectum and lower bowel.41 Plancarte and his colleagues first reported performing neurolytic blockade of this ganglion for malignant pain arising from the rectum.42 A review article in 200843 cited two prospective studies reporting good efficacy using six percent phenol. Another study using radiofrequency ablation produced a 50 percent decrease in the pain scores.

Implantable Drug Delivery System (IDDS) The dorsal horn of the spinal cord is richly innervated with opioid mu-receptors. In 1979, Wang and his colleagues injected intrathecal morphine in eight patients with cancer that had spread to the lumbosacral plexus.44 Six patients had complete pain relief lasting 12 to 24 hours. When maximum systemic analgesic fails to provide adequate pain relief, or produces intolerable side effects, it may be advantageous to target the dorsal horn mechanisms.45 The subarachnoid (intrathecal) space provides direct communication with the spinal cord and as such the dose required for the subarachnoid administration is one-tenth the dose required for epidural dosing, and a fraction of the dose required for oral dosing.

Smith and his group published two studies comparing IDDS versus comprehensive medical management. They concluded, “IDDS improved clinical success, reduced pain scores, relieved most toxicity of pain control drugs and was associated with increased survival for the duration of the six-month trial.”46,47 Although survival was not the primary end point, they observed that patients who had IDDS therapy had improved survival, with 52-54 percent alive at six months compared with 32 percent of the non-IDDS group. The increased survival may be associated with increased mobility and alertness, reduced anorexia, and possibly the effects of systemic morphine on the immune system.46 A Cochrane review supports intrathecal opioid therapy for pain inadequately controlled by systemic therapy.48

Spinal Cord Stimulation (SCS) Electrical spinal cord stimulation (SCS) uses pulsed electrical energy near the spinal cord or adjacent structures to control DCMS online . org

pain.49 This involves placement of the leads in the epidural space to transmit pulsed energy across the spinal cord or near the desired nerve areas.50 This modality is thought to be based on the “gate control” theory of pain,51 which postulates that stimulation of large diameter cutaneous afferent or A-Beta fibers inhibits transmission of pain signals from small diameter fibers to spinal neurons that project to the brain.

Cata and his group reported two patients with chemotherapy-induced neuropathy (CIPN) who underwent permanent SCS implantation and reported that both patients had improved pain scores, reduction of medication and improved gait and leg flexibility.50 They also noted improvement in touch and sharpness detection thresholds.50 Yakovlev reported the use of SCS in the management of cancer related chest wall pain and for intractable neuropathic cancer pain.52,53 A Cochrane review54 on the use of SCS for cancer pain concluded that current evidence is insufficient to establish the role of SCS in treating cancer-related pain. However, evidence from non-randomized controlled trials is generally positive and is consistent with stronger evidence in non-cancer pain.

Conclusion The WHO Pain Relief Ladder has been around for many years, and has served as a practical guide for managing cancer pain for most patients in most clinical situations. However, it has its deficiencies and limitations. Many patients have adverse drug effects and at least 10 percent of cancer patients suffer significant pain despite adherence to the analgesic ladder. Interventional techniques should be considered earlier in WHO algorithm as part of the multimodal approach to affect the maximum pain relief.

References 1. Centers for Disease Control and Prevention. Leading Causes of Death [Internet]. 2015 Oct 7 [updated 2016 Apr 27; cited 2016 Jun 3].

Available from: http://www.cdc.gov/nchs/fastats/leading-causes-ofdeath.htm#.

2. American Cancer Society. Cancer Facts & Figures 2016 [Internet].

Atlanta: American Cancer Society Cancer Statistics Center. [Cited 2016 Jun 3]. Available from: https://cancerstatisticscenter.cancer. org/?_ga=1.178492452.1273981606.1464968229#/.

3. De Moor JS, Mariotto AB, Parry C, et al. Cancer Survivors in the United States: Prevalence across the Survivorship Trajectory and Implications for Care. Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):561-70.

4. Ven den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, et al.

Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007 Sep;18(9):1437-49.

Northeast Florida Medicine Vol. 67, No. 3 2016 27

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5. Deandrea S, Montanari M, Moja L, et al. Prevalence of undertreatment in cancer pain. A review of published literature. Ann Oncol.

2008 Dec;19(12):1985-91.

25. Hogan QH, Abram SE. Neural blockade for diagnosis and prognosis.

A review. Anesthesiology. 1997 Jan;86(1):216-41.

6. Breuer B, Fleishman SB, Cruciani RA, Portenoy RK. Medical oncologistsâ&#x20AC;&#x2122; attitudes and practice in cancer pain management: a national survey. J Clin Oncol. 2011 Dec 20;29(36):4769-75.

26. Bonica JJ. Sympathetic Nerve Blocks for Pain Diagnosis and Therapy: Technical Considerations, Volume 2. Block of stellate ganglion and cervicothoracic and thoracic chains. Winthrop-Breon Laboratories; 1984. p 61-77.

7. Zech DF, Grond S, Lynch J, et al. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study.

Pain. 1995 Oct;63(1):65-76.

27. Wassef MR. Phantom pain with probable reflex sympathetic dystrophy: efficacy of fentanyl infiltration of the stellate ganglion. Reg Anesth. 1997 May-Jun;22(3):297-90.

8. Forbes K. Pain in patients with cancer: the World Health Organization analgesic ladder and beyond. Clin Oncol (R Coll Radiol). 2011 Aug;23(6):379-80.

28. Lofstrom B, Cousins M. Sympathetic neural blockade of the upper and lower extremity. In: Neural Blockade in Clinical Anesthesia and Management of Pain, ed.2. Cousins M, Bridenbaugh PO, editors.

London: J.P. Lippincott; 1988.

9. Miguel R. Interventional treatment of cancer pain: the fourth step in the World Health Organization analgesic ladder? Cancer Control.

2000 Mar-Apr;7(2):149-56.

10. Sloan PA. The evolving role of interventional pain management in oncology. J Support Oncol. 2004 Nov-Dec;2(6):491-500, 503.

11. Torres Lacomba M, Mayoral del Moral O, Coperias Zazo JL, et al.

Incidence of myofascial pain syndrome in breast cancer surgery: a prospective study. Clin J Pain. 2010 May;26(4):320-5.

12. Esenyel M, Caglar N, Aldemir T. Treatment of myofascial pain. Am J Phys Med Rehabil. 2000 Jan-Feb;79(1):48-52.

13. Rogers ML, Henderson L, Mahajan RP, et al. Preliminary findings in the neurophysiological assessment of intercostal nerve injury during thoracotomy. Eur J Cardiothorac Surg. 2002 Feb;21(2):298-301.

14. Shaw WM. Medial approach for paraverterbral somatic nerve block. J Am Med Assoc. 1952 Mar 1;148(9):742-4.

29. Lipov EG, Joshi JR, Sanders S, et al. Effects of stellate-ganglion block on hot flushes and night awakenings in survivors of breast cancer: a pilot study. Lancet Oncol. 2008 Jun;9(6):523-32.

30. Carpenter JS, Andrykowski MA, Cordova M, et al. Hot flushes in postmenopausal women treated for breast carcinoma. Cancer. 1998 May;82(9):1682-91.

31. American Cancer Society. Key statistics for pancreatic cancer [Internet]. 2016 Mar 14 [updated 2016 April 5; cited 2016 Jun 3].

Available from: http://www.cancer.org/cancer/pancreaticcancer/detailedguide/pancreatic-cancer-key-statistics.

32. Arcidiacono PG, Calori G, Carrara S, et al. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007519.

15. Eason MJ and Wyatt R. Paravertebral thoracic block-a reappraisal.

Anaesthesia. 1979 Jul-Aug;34(7):638-42.

33. Kamabadakone A, Thabet A, Gervais DA, et al. CT-guided celiac plexus neurolysis: a review of anatomy, indications, techniques and tips for successful treatment. Radiographics. 2011 Oct;31(6):1599621.

16. Richardson J, Sabanathan S, Jones J, et al. A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoractomy pain, pulmonary function and stress responses. Br J Anaesth. 1999 Sep;83(3):387-92.

34. Wong GY, Schroeder DR, Carns PE, et al. Effect of neurolytic celiac plexus block on pain relief, quality of life and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. JAMA. 2004 Mar 3;291(9):1092-9.

17. Karmakar MK. Thoracic paravertebral block. Anesthesiology. 2001 Sep;95(3):771-80.

35. de Oliveira R, dos Reis MP, Prado WA. The effects of early or late neurolytic sympathetic plexus block on the management of abdominal or pelvic cancer pain. Pain. 2004 Jul;110(1-2):400-8.

18. Antila H, Kirvelä O. Neurolytic thoracic paravertebral block in cancer pain: A clinical report. Acta Anaesthesiol Scand. 1998 May;42(5):5815.

36. Penman ID. Coeliac plexus neurolysis. Best Pract Res Clin Gastroenterol. 2009;23(5):761-6.

19. Fassoulaki A, Triga A, Melemeni A, et al. Multimodal analgesia with gabapentin and local anesthetics prevents acute and chronic pain after breast cancer. Anesth Analg. 2005 Nov;101(5):1427-32.

37. Noble M, Gress FG. Techniques and results of neurolysis for chronic pancreatitis and pancreatic cancer pain. Curr Gastroenterol Rep. 2006 Apr;8(2):99-103.

20. Omoigui S, Do Y, Adewumi P. Omoigui Diffusion Technique of Intercostal Nerve Block. J Anesthe Clin Res. 2013 Aug;4:344.

38. Yan BM, Myers RP. Neurolytic celiac plexus block for pain control in unresectable cancer. Am J Gastroeneterol. 2007 Feb;102(2):430-8.

21. Wong FC, Lee TW, Yuen KK, et al. Intercostal nerve blockade for cancer pain: effectiveness and selection of patients. Hong Kong Med J. 2007 Aug;13(4):266-70.

39. Nagels W, Pease N, Bekkering G, et al. Celiac plexus neurolysis for abdominal cancer pain: a systematic review. Pain Med. 2013 Aug;14(8):1140-63.

22. Elias M. Cervical sympathetic and stellate ganglion blocks. Pain Physician. 2000 Jul;3(3):294-304.

40. de Courcy JG. Interventional techniques for cancer pain management. J Clin Oncol. 2011;23(6):407-7.

23. Buckley FP, Morricca G, Murphy T. Neurolytic blockade and hypohysectomy. In: Bonica JJ (ed). The Management of Pain, ed 2, vol 2.

Philadelphia: Lea and Febiger, 1990. p. 2012-2014.

41. Plancarte R, de Leon-Casasola OA, El-Helaly M, et al. Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Reg Anesth. 1997 Nov-Dec;22(6):562-8.

24. Elias M. The anterior approach for thoracic sympathetic ganglion block using a curved needle. Pain Clinic. 2000 Mar 1;12(1):17-24.

42. Plancarte R, Amescua C, Patt RB, et al. Presacral blockade of the ganglion of Walther (ganglion impar). Anesthesiology. 1990;73.

28 Vol. 67, No. 3 2016 Northeast Florida Medicine

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43. Christo PJ, Mazloomdoost D. Cancer pain and analgesia. Ann N Y Acad Sci. 2008 Sep;1138:278-298.

44. Wang JK, Nauss L, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979 Feb;50(2):149-51.

45. Dickenson AH. Spinal cord pharmacology of pain. Br J Anaesth. 1995 Aug;75(2):193-200.

46. Smith TJ, Coyne PJ, Staats PS, et al. An implantable drug delivery system (IDDS) for refractory cancer provides sustained pain control, less drug-related toxicity and possibly better survival compared with comprehensive medical management (CMM). Ann Oncol. 2005 May;16(5):825-33.

47. Smith TK, Staats PS, Deer T, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity and survival. J Clin Oncol. 2002 Oct 1;20(19):4040-9.

50. Cata JP, Cordella JV, Burton AW, et al. Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case report. J Pain Symptom Manage. 2004 Jan;27(1):72-8.

51. Melzack R, Wall PD. Pain mechanisms: a new theory. Survey of Anesthesiology. 1967;11(2):89-90.

52. Yakovlev AE, Resch BE, Karasev SA. Treatment of cancer-related chest wall pain using spinal cord stimulation. Am J Hosp Palliat Care. 2010 Dec;27(8):552-6.

53. Yakovlev AE, Elias Y. Spinal cord stimulation as a treatment option for intractable neuropathic cancer pain. Clin Med Res. 2008 Dec;6(34):103-6.

54. Lihua P, Su M, Zhou Z, et al. Spinal cord stimulation for cancer-related pain in adults. The Cochrane Library. 2013.

48. Ballantyne JC, Carwood CM. Comparative efficacy of epidural, subarachnoid and intracerebroventricular opioids in patients with pain due to cancer. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD005178.

49. Kumar K, Toth C, Nath R, et al. Epidural spinal cord stimulation for treatment of chronic pain-some predictors of success. A 15-year experience. Surg Neurol. 1998 Aug;50(2);110-20.

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CME

Responsible Opioid Prescribing Background: The Duval County Medical Society (DCMS) is proud to provide its members with free continuing medical education (CME) opportunities in subject areas mandated and suggested by the State of Florida Board of Medicine to obtain and retain medical licensure. The DCMS would like to thank the St. Vincent’s Healthcare Committee on CME for reviewing and accrediting this activity in compliance with the Accreditation Council on Continuing Medical Education (ACCME).

This issue of Northeast Florida Medicine includes an article, “Responsible Opioid Prescribing” authored by Timothy Sternberg, DMD, MD, which has been approved for 2 AMA PRA Category 1 credits.TM For a full description of CME requirements for Florida physicians, please visit www.dcmsonline.org.

Faculty/Credentials: Timothy Sternberg, DMD, MD, Spine Care & Pain Management, Ancora Pain Recovery.

Objectives: 1.

Understand the epidemiology of opioid prescription abuse.

2.

Have a general knowledge of the risks, benefits, and limitations of chronic opioid therapy.

3.

Be acquainted with the applicable Florida Statutes regarding prescribing chronic opioids.

4.

Be informed enough of the standard of care for chronic opioid prescribing to come to a

personal decision whether you would want this to be a part of your professional practice.

Date of release: Sept. 1, 2016

Date Credit Expires: Sept. 1, 2018

Estimated Completion Time: 2 hours

How to Earn this CME Credit: 1. Read the “Responsible Opioid Prescribing” article.

2. Complete the posttest. Scan and email your test to Kristy Wolski at kristy@dcmsonline.org or mail

it to 1301 Riverplace Boulevard, Suite #1638, Jacksonville, FL 32207.

3. You can also go to www.dcmsonline.org to read the article and take the CME test online.

4. All non-members must submit payment for their CME before their test can be graded.

CME Credit Eligibility: A minimum passing grade of 70% must be achieved. Only one re-take opportunity will be granted. A certificate of credit/completion will be emailed within four to six weeks of submission. If you have any questions, please contact Kristy Wolski at 904.355.6561 or kristy@dcmsonline.org.

Faculty Disclosure: Timothy Sternberg, DMD, MD reports no significant relations to disclose, financial or otherwise with any commercial supporter or product manufacturer associated with this activity.

Disclosure of Conflicts of Interest: St. Vincent’s Healthcare (SVHC) requires speakers, faculty, CME Committee and other individuals who are in a position to control the content of this educations activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity.

All identified conflicts of interest are thoroughly evaluated by SVHC for fair balance, scientific objectivity of studies mentioned in the presentation and educational materials used as basis for content, and appropriateness of patient care recommendations.

Joint Sponsorship Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of St. Vincent’s Healthcare and the Duval County Medical Society.

St. Vincent’s Healthcare designates this educational activity for a maximum of 2 AMA PRA Category 1 credits.TM Physicians should only claim credit commensurate with the extent of their participation in the activity.

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Responsible Opioid Prescribing

By Timothy Sternberg, DMD, MD Abstract: Prescription drug abuse has become an epidemic in recent

years, often facilitated in Florida by licensed physicians. Disastrous outcomes resulting from this abuse have led to a reformulation of local, statewide and national medical practice guidelines and legal statutory regulations in order to decrease morbidity and mortality. Responsible prescribing requires an understanding of opioid pharmacology, knowledge of the medical standard of care, familiarity with the applicable Florida Statutes, and diligence in preventing abuse and diversion.

Introduction: In the 1990s, appropriate management of pain became an accepted clinical goal by physicians and a medical-moral imperative by public demand. The prevailing thought among experts in the field was that opioid analgesics were being inappropriately withheld from patients suffering from chronic pain. Long accepted as appropriate medical therapy for the treatment of acute, post-operative and cancer pain, opioids then were touted as medically indicated for chronic pain regardless of etiology. Early clinical dosing guidelines implied that the opioid dose should be titrated up until an appropriate clinical response (acceptable pain control per patients’ self-report) or a dose limiting adverse drug effect (ADE) was achieved, since there was felt to be no true organ toxicity with chronic exposure.

Consequently, opioid prescribing climbed sharply, simultaneously increasing supply and demand.1 This greater access led to patients with legitimate clinical needs and individuals seeking opioid-induced euphoria being increasingly exposed to easily available narcotics. In 2010, enough opioids were sold in the United States to medicate every American adult with 5 mg of hydrocodone every four hours for one month.1 There arose in Florida a particular group of physicians, misguided at best, who started cash only self-described “pain clinics” (more commonly referred to as “pill mills”), and prescribed and dispensed inordinate amounts of opioids (mostly oxycodone) and benzodiazepines (mostly alprazolam). At one time, there was more oxycodone (both mg amount and numbers of prescriptions) dispensed in Florida than in the entire United States and

Address correspondence to: Timothy Sternberg, DMD, MD Spine Care & Pain Management/Ancora Pain Recovery 3 Shircliff Way, Suite #521 Dillon Professional Building, SVMC Jacksonville, FL 32204 (904) 479-0707 32 Vol. 67, No. 3 2016 Northeast Florida Medicine

80 percent of this was from Broward County.1 Opioid sales in Florida in 2008-2009 were the highest in the nation at 12.6 kg per 10,000 citizens.1 Pill mills rapidly spread throughout Florida which became a pipeline for oxycodone into Kentucky, Ohio and many areas of the United States.2 From 1999-2008, opioid overdose death rates, sales, and substance abuse treatment admissions increased in parallel.1 The incidence of death secondary to overdose of narcotics increased yearly from 2000-2010. In 2007, nearly 100 persons died per day of drug overdoses in the United States.1 The overdose death rate in 2007 was roughly three times the rate in 1991, mostly from prescription opioids.3 In 2010, 4.8 percent of the U.S. population above the age of 12 used opioids non-medically.4 In Florida, the overall opioid overdose death rate per 100,000 was 16.5, significantly above the national rate of 11.9.1 Florida’s death rate for prescription drugs increased 84.2 percent from 2003 to 2009, with the greatest increase observed for oxycodone (264.6 percent), followed by alprazolam (233.8 percent).5 Though touted, and heavily marketed, as effective therapy for chronic pain, evidence for the benefit of chronic opioid therapy for non-malignant pain is limited. A Cochrane Review concluded evidence that long-term opioid therapy produced significant pain relief was weak, and evidence for improvement of quality of life or functioning was inconclusive.6 Additionally, evidence that high dose opioids or controlled release opioids are any more beneficial than low dose short acting opioids is lacking.7 In response to the plethora of “pill mill” physicians unnecessarily prescribing and dispensing large amounts of narcotics, the Florida Legislature acted. In 2010, laws were enacted that required “pain clinics” to register with the state and have a physician owner. The laws also established prescribing and dispensing requirements. In 2011, despite initial opposition from Governor Rick Scott, the state’s Prescription Drug Monitoring Program (PDMP) became operational.

To responsibly prescribe opioids, physicians must understand the aforementioned problems associated with opioids, their benefit versus risk, the current standard of care, and the applicable Florida Statutes.

Opioid Analgesics: Opioids are the most potent analgesics for acute pain. They work as agonists on opioid receptors (mostly mu, but also kappa, sigma, and delta) in the central nervous system. Besides analgesia, other potential benefits may include sedation, cough

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CME

suppression, and relief of dyspnea. The most commonly prescribed opioids are oxycodone and hydrocodone.

Predictable adverse drug effects (ADE’s) of opioids, when used on a short term basis, are respiratory depression, orthostatic hypotension, nausea, vomiting, constipation, urinary retention, pruritus, and meiosis. Opioid overdose deaths are usually due to hypoxemia from respiratory arrest. When used on an intermediate term and chronic basis, predictable ADE’s are constipation, tolerance (requiring increased dosing for same clinical benefit), and physical dependence (characterized by abstinence syndrome with abrupt discontinuation). Other common ADE’s are xerostomia, sweating, somnolence, disrupted sleep cycle, and hypogonadotropic hypogonadism with sexual dysfunction.8 A potential ADE, especially when used for non-medical purposes and even a small risk when used properly, is addiction (biopsychosocial disorder characterized by compulsive use despite harm).

Medical Standard of Care: There are several practice guidelines on opioid therapy from pain management and other medical associations.9,10 Most guidelines for responsible opioid prescribing reflect common sense medical care, and include: patient history and physical examination, abuse risk assessment, determination of clinical goals, a treatment plan, informed consent, medication selection, outcome measurement, monitoring side effects, consideration of alternative strategies, and proper documentation. This practice is consistent with the “Universal Precautions” as applied to opioid prescribing (Table 1).11 In 2016, the Centers for Diseases Control and Prevention also issued an opioid prescribing guideline, providing recommendations for primary care clinicians prescribing opioids for chronic non-malignant pain.12 History: The patient’s history is particularly important when evaluating for opioid therapy. The nature of the pain must be investigated. Does this patient have a pain that is amenable to

opioid analgesia? Generally, acute moderate to severe pain due to trauma or surgery is effectively controlled with opioids. Nociceptive somatic pain (due to real or impending tissue damage) is more effectively treated with opioids than neuropathic pain (due to neural damage or dysfunction). For chronic nociceptive pain due to musculoskeletal disorders (the most common indication for long term opioid therapy), opioid benefit can be real though modest. An important aspect of the patient’s history is the use of benzodiazepines, which increases risk of overdose with concurrent use of opioids.12 Risk is also increased in elderly patients and those with sleep-disordered breathing, renal impairment, or hepatic insufficiency.12 Physical examination: Is the patient irritable? Are the pupils overly constricted or dilated relative to ambient light?

Does the patient perseverate in asking about pain medications?

Are there smoke stains on teeth or fingers? Are there tract marks in skin overlying veins? Is there tremor unexplained by known neurological disease?

Risk Assessment: The patient must be evaluated for risk of opioid abuse and/or diversion. Elements that increase risk of abuse are a history of mental illness, incarceration, alcohol abuse, drug of abuse (DOA), smoking, long term unemployment, and noncompliance with previous narcotic therapy. Older adolescents and young adults have a higher risk than those older than 45 years. There are several validated instruments of variable length available to evaluate risk. A practical one is the Opioid Risk Tool (Table 2), a five item questionnaire exploring the patient’s personal and/or family history of substance abuse, age, history of preadolescent sexual abuse, and psychological disease.13 Treatment goals: Goals of therapy should be established prior to initiating treatment. For opioids to be considered effective, analgesia must be accompanied by improved functioning. Expected analgesia from opioids for chronic pain must be explained explicitly: modest. When effective, opioids may reduce the

Table 1: Universal precautions as applied to opioid prescribing11 1. Make a diagnosis with an appropriate differential.

2. Conduct a patient assessment, including risk for substance use disorders.

4. Have a written treatment agreement that sets forth the expectations and obligations of both the patient and the treating physician.

5. Initiate an appropriate trial of opioid therapy, with or without adjunctive medications.

6. Perform regular assessments of pain and function.

7. Reassess the patient’s pain score and level of function.

8. Regularly evaluate the patient in terms of the “5 A’s”: Analgesia, Activity, Adverse effects, Aberrant behaviors, and Affect.

9. Periodically review the pain diagnosis and any comorbid conditions, including substance use disorders, and adjust the treatment regimen accordingly.

10. Keep careful and complete records of the initial evaluation and each follow-up visit.

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Used with permission of D. Gourlay

3. Discuss the proposed treatment plan with the patient and obtain informed consent.

CME

Mark each box that applies

Table 2: Opioid Risk Tool13 1. Family History of Substance Abuse

2. Personal History of Substance Abuse

Item Score if Male

Alcohol

[

]

1

3

Illegal Drugs

[

]

2

3

Prescription Drugs

[

]

4

4

Alcohol

[

]

3

3

Illegal Drugs

[

]

4

4

Prescription Drugs

[

]

5

5

[

]

1

1

[

]

3

0

[

]

2

2

[

]

1

1

[

] Moderate Risk 4 – 7

High Risk > 8

3. Age (Mark box if 16 – 45) 4. History of Preadolescent Sexual Abuse 5. Psychological Disease

Item Score if Female

Attention Deficit Disorder Obsessive Compulsive Disorder Bipolar Schizophrenia Depression

TOTAL Total Score Risk Category

Low Risk 0 – 3

Used with permission: Webster LR, Webster R. Predicting aberrant behaviors in Opioid-treated patients: preliminary validation of the Opioid risk tool. Pain Med. 2005;6(6):432.

patient’s self-assessed pain score 2-3 points on a 10-point scale.

The patient must understand that eliminating the pain entirely is unobtainable, even contraindicated. Seldom do opioids, by themselves, adequately control pain. Analgesics should be one part of a comprehensive pain management strategy, which usually includes a physical therapy or home exercise program, a cognitive readjustment, and consideration of interventional therapies.

Informed Consent: Besides a physician-patient discussion, there should also be a written, signed, and maintained opioid agreement, consent, or “contract.” Though there are many available, including templates in some EHR’s, the basic elements are similar.

The patient agrees to: the risks and benefits of opioid therapy; obtaining all prescription analgesics from one source, no DOA, no diversion (selling, trading, and giving away), non-replacement of lost, stolen, and misplaced drugs, compliance testing, and an understanding when opioids would be tapered and discontinued.

Medication Selection: The most commonly used outpatient opioids, in approximate order of potency, are: tramadol < codeine < tapentadol < hydrocodone/morphine < oxycodone < oxymorphone < methadone < hydromorphone < fentanyl. Tramadol (Ultram) can be an effective analgesic when non-opioid analgesics fail to provide adequate relief and, since it is a Schedule IV drug, multiple refills can be written. Codeine, combined with acetaminophen, is a weak analgesic; though chronic use is limited by excess constipation relative to analgesia. Tapentadol (Nucynta) is somewhat stronger than tramadol; however DEA classification as a Schedule II drug prohibits refills. Hydrocodone (Norco, 34 Vol. 67, No. 3 2016 Northeast Florida Medicine

Zohydro) was changed by the DEA to a Schedule II drug in 2013; though it remains the most commonly prescribed opioid.

Oxycodone (Percocet, Oxycontin) is the second most commonly prescribed. Generics are available for both. Oxymorphone (Opana) and hydromorphone (Dilaudid) are stronger and also available as extended release formulations, Opana ER and Exalgo, respectively.

Methadone is an effective and inexpensive long acting opioid but requires a slow titration, can be associated with prolonged QT induced arrhythmias, and is best left to those experienced with its dosing. Fentanyl is very potent and available as transdermal patch (Duragesic) and transmucosal (Actiq, Fentora).

Besides the relative potency, the choice of an immediate versus a controlled release preparation should be considered for optimal pain management treatment. Timed or controlled release preparations (MS Contin, Kadian, Avinza, Oxycontin, Exalgo, Opana ER, Zohydro) are released over a 12-24 hour period and theoretically provide steady prolonged analgesia.

They are generally considered in opioid tolerant patients when analgesia cannot be maintained with a reasonable number of daily short acting doses (4-6). Neither short or timed release opioids have been shown to be more effective or safer than the other.7 As with most drugs, a physician should start with a low dose and titrate up until the clinical objective (reasonable analgesia) is obtained or dose limiting ADE’s occur. An example of an escalating opioid treatment algorithm often used by the author, when acetaminophen and NSAID’s are either ineffective or contraindicated, begins with a trial of tramadol 50 mg TID. If benefit is appreciated DCMS online . org

CME

but pain control still suboptimal after one month, the medication is increased over a period of months to a maximum of 100 mg QID. If tramadol is ineffective or contraindicated, hydrocodone would be the next step, using a dose of 5-10 mg with 325 mg acetaminophen preparation up to QID. If hydrocodone is insufficient after a several month trial, oxycodone at the same dose would be a logical step up. If a regimen of 10 mg hydrocodone or oxycodone QID trialed over a period of 2-3 months is sub therapeutic, then a timed release preparation would be considered.

sleep cycle, and sexual dysfunction. The latter is a common though underappreciated adverse effect of chronic opioids.

Treatment Outcome: Analgesia and patient functioning are monitored and used as measures of treatment success. The patient’s self-report of pain using the numerical rating scale (NRS), 0-10 on a 10 point scale, is a clinically simple measure to use despite its deficiencies. It is also important to measure the patient’s functional improvement with treatment. The patient’s activities of daily living (ADL’s), work, or family interactions that are facilitated by the current treatment are closely followed by the caregiver and there are several proprietary forms that can also be used.

Compliance: Compliance with dosing and aberrant drug taking behavior should be continuously monitored. Some red flags are: reports of missing or stolen drugs, requests for early refills, obtaining opioids from another physician, and an overriding concern about obtaining the medications instead of the analgesia the drug may provide. Several tools to assure compliance include pill counting, urinary drug testing (UDT), and the Florida Prescription Drug Monitoring (FLPDM) Report. However, no single measure is specifically required by law and there is no absolute standard of care on the frequency of such testing. The FLPDM, which any Florida licensed physician can access, is a particularly effective method to monitor duplicate prescribing from multiple sources for a single patient. DOA’s, non-prescribed narcotics, and not taking the prescribed opioid can be detected by UDT. Urinary testing every patient, every month, regardless of risk stratification, should not be considered standard of care.12

Side effects: Constipation is the most common and almost universal ADE with increasing opioid doses. Other side effects that should be explored are lethargy, mental clouding, disrupted

A simple strategy to use at follow up evaluation is the “5 A’s:” Analgesia, Adverse side effects, Activities of daily living, Affect, and Aberrant drug taking behavior.14

Table 3: Adapted from the Federation of States Medical Boards Model Policy on the Use of Opioid Analgesics in the Treatment of Chronic Pain15 Innappropriate management of pain, and considered a departure from accepted best clinical practices, are: • Inadequate attention to initial assessment to determine if opioids are clinically indicated • Inadequate determination of risks • Inadequate monitoring during the use of potentially abusable medications • Unjustified dose escalation without adequate attention to risks or alternative treatments • Excessive reliance on opioids, particularly high dose opioids for chronic pain management • Not making use of available tools for risk mitigations (i.e., state prescription drug monitoring program) Criteria to be used in evaluating a physician when prescribing opioids for chronic pain: • Understanding Pain (physician must understand relevant pharmacology and clinical issues) • Patient Evaluation and Risk Stratification (prior to deciding to prescribe opioid therapy) • Development of a Treatment Plan and Goals (reasonable analgesia and improvement, improvement of function, and avoiding excess medications) • Informed Consent and Treatment Agreement • Initiating an Opioid Trial (defined period of time with specific endpoints) • Ongoing Monitoring and Adapting the Treatment Plan • Periodic Drug Testing (e.g., UDT’s, pill counting, or PDMP report) • Consultation and Referral (pain, addiction, mental health, or other specialist as needed) • Discontinuing Opioid Therapy (when risks outweigh benefits, clinical goals not obtained, ADE’s, misuse/diversion) • Medical Records • Compliance with Controlled Substance Laws and Regulations (DEA registration, state license)

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Medicolegal Concerns: Most states, including Florida, use the Federation of States Medical Boards Model Policy on the Use of Opioid Analgesics in the Treatment of Chronic Pain (MPUOA) as the basis of their statutes.15 MPUOA has also been adopted by the American Academy of Pain Medicine, the Drug Enforcement Administration, the American Pain Society, and the National Association of State Controlled Substances Authorities.

MPUOA views pain management as an important area of patient care integral to the practice of medicine, that opioid analgesics may be necessary for the relief of certain pain conditions, and that physicians should not be sanctioned solely for prescribing opioid analgesics. However, prescribers must only prescribe opioids for legitimate medical purposes and will be held to a safe and best clinical practice. MPUOA makes clear what state medical boards will consider as inappropriate management of pain, and has adopted criteria for use in evaluating a physician’s management of a patient with pain (Table 3).

Florida Statutes: Florida physicians prescribing opioids should be aware of several Florida Statutes.16 Probably the most important for non-pain management specialists is Statute 456.44, Controlled substance prescribing. Statute 456.44 mandates that a physician who prescribes controlled substances for the treatment of chronic nonmalignant pain must designate himself or herself as a controlled substance prescribing practitioner on the physician’s practitioner profile. In the Standard of Practice section of Statute 456.44, physician requirements are defined.

A complete medical history and a physical examination must be conducted before beginning treatment. The medical record must document the nature and intensity of the pain, current and past treatments, coexisting diseases, the effect of the pain on physical and psychological function, a review of previous medical records, previous diagnostic studies, and history of alcohol and substance abuse. The record shall document the presence of a recognized medical indication for the use of a controlled substance. There must be a written plan for assessing each patient’s risk of aberrant drug-related behavior, which may include drug testing. Physicians must assess each patient’s risk for aberrant drug-related behavior and monitor that risk on an ongoing basis. The physician must develop a written treatment plan that states objectives to be used in determining treatment success, such as pain relief and psychosocial function. The physician shall use and maintain a written controlled substance agreement. The physician shall adjust drug therapy to the individual medical needs of each patient. Other treatment modalities, including a rehabilitation program, should be considered. Risks, including that of abuse and addiction, must be discussed. The 36 Vol. 67, No. 3 2016 Northeast Florida Medicine

patient shall be seen by the physician at regular intervals, not to exceed three months, to assess treatment efficacy, ensure the controlled substance remains indicated, evaluate progress toward treatment objectives, consider adverse drug effects, and review the etiology of the pain. The physician shall refer the patient as necessary for additional evaluation and treatment in order to achieve treatment objectives. Accurate, current, and complete records must be maintained. Patients with signs or symptoms of substance abuse shall be immediately referred to a board-certified pain management physician, an addiction medicine specialist, or a mental health addiction facility.

Statute 456.44 specifically exempts from this subsection any board-eligible or board-certified anesthesiologist, physiatrist, rheumatologist, or neurologist, or a board-certified physician who has surgical privileges at a hospital or ambulatory surgery center and primarily provides surgical services. This subsection does not apply to board-eligible or board-certified medical specialists who have completed an approved fellowship in pain medicine and perform interventional pain procedures of the type routinely billed using surgical codes.

Chapter 893, Drug Abuse Prevention and Control16 contains Statute 893.055, Prescription drug monitoring program, which mandates that each time a controlled substance is dispensed to an individual, the controlled substance shall be reported to the department, and then to the electronic data base. Statute 893.11, Suspension, revocation, and reinstatement of business and professional licenses, considers that any physician convicted of the sale or trafficking in a controlled substance constitutes an immediate serious danger to the public health and safety, and is grounds for disciplinary action including immediate emergency suspension of an individual professional license.

Chapter 58, Medical Practices, contains Statute 458.326, Intractable pain; authorized treatment, which defines “intractable pain” as pain for which the cause cannot be removed and otherwise treated, and authorizes that a physician may prescribe or administer any controlled substance to a person for the treatment of intractable pain, provided the physician does so in accordance with that level of care, skill, and treatment recognized by a reasonably prudent physician under similar conditions and circumstances.

Statute 458.3265, Pain-management clinics, defines a pain management clinic as any publically or privately owned facility that advertises any type of pain-management services; or where a majority of patients are prescribed opioids, benzodiazepines, barbiturates, or carisoprodol for the treatment of chronic nonmalignant pain. Each pain-management clinic must register with the department. Specific exemptions to the registration requirement for physicians are the same as those of Statute 456.44.

The department shall deny registration to any clinic that is not fully owned by a physician, or to a physician whose application DCMS online . org

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for a license to prescribe or administer a controlled substance has been denied or revoked, or who has been convicted of the receipt of illicit and diverted drugs. A physician, or physician extender, must perform a physical examination of a patient on the same day that a controlled substance is prescribed. If the physician prescribes more than a 72-hour dose of controlled substances for the treatment of chronic nonmalignant pain, the physician must document the reason in the patient’s record.

Conclusion: Opioids are an integral component of acute and chronic pain management, and can be used, with modest benefit, for chronic non-malignant pain. Excessive and inappropriate opioid prescribing led to a major epidemic in prescription drug abuse and preventable mortality, necessitating the state to make appropriate statutory changes. Opioids can be used if the practice is consistent with current medical standard of care and FL Statues. Knowledge of both is required in order to practice due diligence in preventing abuse and diversion. v

References

pain: Tailoring therapy to meet patient needs. Mayo Clin Proc. 2009 Jul;84(7):602-12.

8. Sehgal N, Colson J, Smith HS. Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy. Expert Rev Neurother. 2013 Nov;13(11): 1201-20.

9. Furlan AD, Reardon R, Weppler C, National Opioid Use Guideline Group. Opioids for chronic noncancer pain: A new Canadian Practice Guideline. CMAJ. 2010 Jun 15;182(9):923-30.

10. Chou R. 2009 Clinical Guidelines from the American Pain Society and the American Academy of Pain Medicine on the use of chronic opioid therapy in chronic noncancer pain: What are the key messages for clinical practice? Pol Arch Med Wewn. 2009 Jul-Aug;119(7-8):469-77.

11. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in paid medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005 Mar-Apr;6(2):107-12.

12. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016.

MMWR. 2016 Mar 18;65(1):1-49.

13. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005 Nov-Dec;6(6):432-42.

1. Centers for Disease Control and Prevention (CDC). Vital Signs: Overdoses of prescription opioid pain relievers-United States, 1999-2008. MMWR Morb Mortal Wkly Rep. 2011 Nov 4;60(43):1487-92.

14. Pain Management Network. 5 A’s- Opioid therapy monitoring tool [Internet]. [Cited 2016 March 15]. Available from: http://www.aci.health.nsw.gov.au/__data/assets/ pdf_file/0019/212761/5_As_of_Analgesia.pdf.

2. Estep B, Hjalmarson, Abdullah H. OxyContin abuse spreads from Appalachia across U.S. [Internet]. Washington: McClatchy Newspapers; 2011 Mar 13 [cited 2016 March 15]. Available from: http://www.mcclatchydc.com/ news/crime/article24616228.html.

15. Federation of State Medical Boards. Model policy on the use of opioid analgesics in the treatment of chronic pain [Internet]. 2013 Jul [cited 2016 March 15]. Available from: http://www.fsmb.org/Media/Default/PDF/FSMB/Advocacy/pain_policy_july2013.pdf.

3. Warner M, Chen L, Makuc D. Increase in fatal poisonings involving opioid analgesics in the United States, 1999-2006. NCHS Data Brief, No. 22. Hyattsville (MD): National Center for Health Statistics; Sep 2009.

16. 2016 Florida Statutes, Florida Legislature. Available from: http://www.leg.state.fl.us/statutes/index.cfm?App_ mode=Display_Statute&URL=0800-0899/0893/0893. html.

4. US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration.

Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of national findings. Rockville (MD): Office of Applied Studies, NSDUH; 2010 Sept.

Report No.: Series H-38A, HHS Publication No. SMA 10-4586Findings.

5. Goldberger B, Thogmartin J, Johnson H, et al. Drug Overdose Deaths --- Florida, 2003—2009. MMWR. 2011 Jul 8;60(26):869-72.

6. Noble, M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD006605.

7. Argoff CE, Silvershein DI. A comparison of long- and short-acting opioids for the treatment of chronic noncancer

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CME



Responsible Opioid Prescribing, Continuing Medical Education CME Questions & Answers (circle one answer)/Free to DCMS Members/$55.00 charge non-members* (Return by March 1, 2018 by mail: 1301 Riverplace Blvd. Suite 1638, Jacksonville, FL 32207 or online: www.dcmsonline.org.)

1. Which of the following is not true regarding opioids from 2000-2010? a. Opioid overdose death rates, sales, and substance abuse treatment admissions increased in parallel. b. The incidence of death secondary to overdose of opioids increased yearly. c. The increased incidence of drug overdose death rate was mostly due to non-prescription drugs of abuse. d. In Florida, the overall opioid overdose death rate was significantly above the national rate.

2. Regarding opioids: a. Therapeutic benefit is mediated primarily via mu opioid receptors. b. Cochrane Review concluded that there is strong evidence that long-term opioid therapy for non-malignant pain can provide significant pain relief. c. Cochrane Review concluded that there is moderate evidence that long-term opioid therapy for non-malignant pain improves quality of life and functioning. d. Generally, opioids provide better relief of chronic than acute pain.

3. Adverse drug effects of opioids typically include: a. Hypertension and tachypnea b. Generalized hyperarousal state c. Constipation d. Polyuria e. Improved sexual performance 4. Medical standards of care in opioid prescribing: a. Differ significantly from standards of care of other medical treatment. b. Differ from other medical standards in not requiring a physical examination. c. Require either urinary drug testing or pill counting every visit. d. Require a history, risk assessment, regular follow-up and monitoring.

5. In assessing risk for opioid abuse and/or diversion, which of the following is not a risk factor? a. Psychiatric illness b. History of childhood sexual abuse c. Age 46-55 d. Personal history of alcohol or prescription drug abuse e. Family history of alcohol or prescription drug abuse 6. In assessing treatment outcomes when using chronic opioid therapy, a. Level of pain control by patient’s self-report is the only concern. b. Forms must be filled out by patient stating level of pain on 10 point scale. c. A practical strategy which can be used clinically is asking the patient about the 5 “b’s.” d. Level of functioning is as important as pain control.

7. I n attempting to assure compliance with chronic opioid therapy, Florida physicians are required to: a. Follow up with the patient monthly. b. Perform a urinary drug test at least every three months. c. See the patient at regular intervals to assess treatment efficacy and ensure controlled substance treatment remains indicated. d. Discharge the patient within 30 days of breaking the opioid agreement.

8. Which of the following is not mandated by Statute 456.44, Controlled substance prescribing? a. A physician who prescribes controlled substances for the treatment of chronic nonmalignant pain must designate himself as a controlled substance prescribing practitioner. b. Physician must perform monthly urinary drug testing. c. A complete medical history and a physical examination must be conducted before beginning treatment. d. The physician shall use and maintain a written controlled substance agreement.

1. What will you do differently as a result of this information? ___________________________________________________________________________________ __________________________________________________________________________________________________________________________________ __________________________________________________________________________________________________________________________________ 2. How will you apply what you learned to your practice? _______________________________________________________________________________________ __________________________________________________________________________________________________________________________________ __________________________________________________________________________________________________________________________________

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Evaluation questions & CME Credit Information (Please evaluate this article. Circle one number using this scale: 1= Strongly Agree to 5= Strongly Disagree) The articles met the stated objectives: 1 2 3 4 5 The articles were appropriate to my practice: 1 2 3 4 5 The topics were current and well presented: 1 2 3 4 5 Comments:

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Pain Management

Advances in Technology for Managing Chronic Pain

By Frank R. Collier, Jr., MD Abstract: Despite increasing resources being spent treating chronic back pain, outcomes have not improved, with both costs and decreased outcomes being related to opiate use. Treatment that has been shown to be beneficial is early physical therapy, especially functional restorative programs, and spinal cord stimulators (SCS). Advances in design and programming have significantly improved SCS utility. Regenerative medicine utilizing platelet rich plasma may offer a unique benefit for painful musculoskeletal conditions.

Introduction: Chronic pain can stem from multiple causes, the most common of which is lower back pain (LBP). Chronic musculoskeletal pain has become a major public health problem resulting in significant impact and economic burden on individuals and society.

Healthcare costs for LBP continue to grow at a pace greater than those for other pain conditions.1,2 Despite increased resources being spent on chronic LBP symptoms, outcomes of care have been declining and the rates of progression of lower back pain continue to increase.1,2 Studies continue to demonstrate that one of the most determinant factors resulting in increased cost and utilization of services is opiate use.3,4,5,6 Early utilization of opiates for lower back pain consistently results in less favorable outcomes and higher long term costs.7,8 The clinical use of prescription opioids for treating chronic pain nearly doubled from 2000-2010.9 Along with this trend, addiction, injury and mortality rates have risen as well.9 Novel strategies and advances in technologies are continuing to evolve to better address and hopefully reverse these trends by lowering long-term healthcare costs and improving outcomes.

Practice guidelines have been developed and generally advocate an initial strategy of self-care, which includes limited bed rest, and the initiation of non-steroidal anti-inflammatory agents.10 Poor adherence to these guidelines has been shown to actually decrease function with increased risk of developing a chronic pain condition.10

The Effects of Physical Therapy on Lower Back Pain Recovery: Recent studies have suggested that the earlier physical therapy is initiated, the more likely it will impact the recovery

Address Correspondence to: Frank R. Collier Jr., MD Collier Spine Institute 6859 Belfort Oaks Place Jacksonville, FL 32216 FCollier@collierspine.com 40 Vol. 67, No. 3 2016 Northeast Florida Medicine

from lower back pain.1 Studies from the U.S. Navy suggest functional restorative programs (FRPP) reduce chronic musculoskeletal pain.10 It has been reported that chronic pain has become a big issue in the military because of associated escalating healthcare, disability costs, and loss of productivity according to researchers from the Naval Medical Center in San Diego, California and the University of Washington, Seattle. The FRPP focuses on increasing patientsâ&#x20AC;&#x2122; physical and mental coping strategies and encouraging patients to become independent of medical treatment resources through the promotion of â&#x20AC;&#x153;self-efficacy and enhanced resilience.â&#x20AC;? FRPP is a five-day per week, eight-week program that combines optimization of medical management. This program consists of providing physical therapy and exercise rehabilitation, case management, psychological coping strategies, provision for complimentary alternative medicine, modalities and sleep care.

The pilot study found that 73 percent of participating active members were later cleared for full duty after completing the program.11 It was clear, after extensive review of studies, that a multidisciplinary approach which stresses early intervention and management of musculoskeletal pain conditions would be best suited to improve long term outcomes.

Spinal Cord Stimulation: Despite best efforts, conditions resulting in chronic intractable pain will continue and need to be addressed. Advances in technology offer new hope in addressing chronic pain issues by decreasing discomfort, increasing function and thereby increasing independence. For example, dorsal column stimulators, better known as spinal cord stimulators (SCS), were initially approved by the U.S. Food and Drug Administration in 1989. Patient outcomes have demonstrated substantial improvement of clinical symptoms with the use of this device.12 With the proper placement of electrodes along the dorsal columns of the spinal cord in the lower thoracic region, chronic neuropathic pain was significantly reduced and sometimes even eliminated completely.13 Although early long term outcomes were limited due to barriers in technology, over recent years many of these barriers have been overcome. This has provided patients with extraordinary improvement of clinical symptoms and has enabled severely debilitated patients to return to a more fulfilling life with improved function, mobility, and substantially decreased pain.14 A unique feature of SCS is placing the power to control pain into the hands of those who are experiencing it.

The ideal candidates for neurostimulation are those with any neuropathic condition resulting from injury or irritation to nerves, which causes pain or dysesthesia. The most commonly treated conditions include post laminectomy pain syndrome, DCMS online . org

Pain Management Figure 2: Lateral fluoroscopic view

of dual octrode SCS lead placement

of dual octrode SCS lead placement

Used with permission from Timothy Sternberg, DMD, MD

Figure 1: Posterior-anterior fluoroscopic view

radiculopathy, polyneuropathy, arachnoiditis, complex regional pain syndrome and peripheral nerve injuries. Stimulators may also be used in patients with peripheral vascular disease with vascular claudication, refractory angina, chronic pancreatitis and occipital neuralgia. Advances in the technology of the electrode arrays, which is the portion of the stimulator that gets implanted into the spinal canal, have offered better coverage of somatic type pain in the back and neck.15

This change in delivery modifies the patient’s biological response to the stimulus, thus more effectively reducing painful sensations and essentially eliminating the paresthesia commonly associated with traditional stimulators. This is an important advancement given that one of the most common reasons for failure of treatment is poor tolerance to the paresthesia experienced by patients with traditional devices that provide “tonic” or fixed frequency stimulation.

The simplest explanation for how traditional neurostimulators work is replacement of the sensation of pain with a comfortable low-level paresthesia. SCS have been found to work very well to alleviate pain without affecting motor function or discrete sensory function.16

In the Journal of Neuromodulation, researchers concluded “burst” stimulation is more effective than “tonic” spinal cord stimulation in the attenuation of visceral nociception.1 Burst stimulation has a greater inhibitory effect on neuronal response to noxious somatic stimuli. This includes LBP and associated symptoms of extremity discomfort. As mentioned, it also substantially reduced the paresthesia associated with tonic stimulation, which is the most common reason for failure of treatment.

Breakthrough advances in the programming and design of dorsal column stimulators will one day include burst stimulation and dorsal root ganglion (DRG) stimulation. Both show significant promise in managing intractable pain conditions.

DRG technology allows for better placement of the electrodes to improve upon the localization and specificity of the stimulation. The most notable clinical trial of DRG stimulation to date is a one-year follow up study involving human subjects with back, neck and foot pain in which electrodes were placed over a specific dorsal root ganglion within the exiting neural foramen of the spinal canal.2 It was concluded that DRG stimulation is comparable to traditional spinal cord stimulation in terms of pain relief but has improved benefits in its ability to achieve precise pinpoint pain relief in the regions that are typically difficult to target with standard spinal cord stimulator leads.

In addition to DRG, “burst” stimulation shows great promise as well. Burst stimulation is a new development in the programming of the stimulator, which modifies the frequency of electrical impulses emitted by the device into small “bursts.”

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Neurostimulation or SCS are highly favored modalities because they are patient centered. It is one of the few instances where a patient can undergo a trial period of utilization before permanent placement. This allows the patient to experience the benefits of this procedure before undergoing surgical implantation. The trial implantation, which involves the temporary insertion of leads for three to four days, can be performed in an outpatient surgical center or properly equipped clinical office setting.

The procedure is performed under fluoroscopy to confirm lead placement (Figures 1 and 2). Test stimulations are performed in order to properly center the leads so as to most effectively alleviate the patient’s symptomatology. IV antibiotics are usually provided prior to this treatment. After the temporary lead is placed, a period of programming is performed to optimize coverage. Patient training is also provided for a remote control Northeast Florida Medicine Vol. 67, No. 3 2016 41

Pain Management

unit that contains five preset programs allowing the patient to operate the system by varying the intensity and/or patterns of the signal. These programs allow for coverage variations depending on the location and the type of pain a patient experiences throughout their day. For example, as a patientâ&#x20AC;&#x2122;s pain changes due to changes in position and activity, they can utilize the remote control to address the changes they are experiencing.

After completion of a three to four day trial period, the leads are removed. Discussions with the patient determine the efficacy of the system and whether they will move forward with permanent placement. Permanent implantation is usually performed in an outpatient surgical setting or outpatient hospital basis.

Paddle leads are commonly utilized because they offer a broad array of electrodes. This allows for greater programming options resulting in potentially improved pain control and outcomes. Technological advances in batteries are now FDA approved for greater than 10 years of operation. These devices can be recharged through the skin on a weekly basis.

Most recent battery advances provide seven years of operation without recharging. The varying response to long term implantation is anywhere from 60-90 percent improvement of symptomatology.17 Many patients are able to wean off of, or significantly reduce, their utilization of opiates and adjuvant medications, with markedly improved function and mobility.17 Studies performed at John Hopkins University looked at the efficacy of SCS versus repeated lumbosacral spine surgery for chronic pain.2 SCS was shown to be more effective than repeated operation as a treatment for persistent radicular pain after initial lumbosacral surgery.17 Furthermore, in a great majority of patients it was determined to obviate the need for reoperation.

A 20 year review of literature on the safety and efficacy of spinal cord stimulation found in the Journal of Neurosurgery determined that SCS can also provide significant positive symptomatic long term improvement of pain for patients with refractory angina, severe ischemic limb pain due to peripheral vascular disease, peripheral neuropathy, chronic neuropathic pain, complex regional pain syndrome and failed back surgery syndrome.3 Since 2004, substantial improvements in technological advances in both the hardware and software programs of SCS have created a â&#x20AC;&#x153;breakthroughâ&#x20AC;? tool for use in the management of chronic long-term pain and disability.

Regenerative Medicine: Besides SCS, another promising advancement made in the management of chronic pain is regenerative medicine (RM). RM typically utilizes platelet rich plasma (PRP) or concentrations of stem cells to regenerate and heal tissues.

RM is a relatively new field in the area of biologics, which offers a novel approach to treat and potentially reverse cellular degenerative processes. These benefits span across many fields of medicine, but in particular they provide a unique benefit for musculoskeletal conditions. RM offers hope for improving 42 Vol. 67, No. 3 2016 Northeast Florida Medicine

those conditions leading to chronic pain such as degenerative joint disease and discogenic lower back pain.

According to the results of a 100 patient Phase II international clinical trial conducted at the Emory University Orthopedic Spine Center, a single injection of stem cells into symptomatic degenerative discs reduced lower back pain for at least 12 months.4 The trial used injections of bone marrow derived stem cells, or mesenchymal progenitor cells, (MPCs) to reduce pain. On average, the researchers found a pain reduction of greater than 50 percent at 12 months. Additionally, there was less need for pain medication, improvement in function and less need for surgical and nonsurgical spine interventions.

These results were found in patients with moderate to severe discogenic low back pain. This Phase II clinical trial, built on a previously reported preclinical study, showed highly purified MPCs were able to repair and restore in vitro disc structures.

All findings from the trial were statistically better from those receiving stem cells versus those in control groups. Currently, there is no adequate treatment for discogenic low back pain.

Researchers are finding that both conservative and surgical treatments fall short. These positive results have paved the way for a Phase III study that should start in 2016.

A recent study performed at the Hospital for Special Surgery in New York City assessed patients with chronic lumbar discogenic pain, treated with one intradiscal PRP injection.5 These patients had pathology that may have otherwise undergone fusion. 109 patients were assessed. Selection process was performed using discography and symptomatic discogenic pain with the criteria of Grade IV or less annular tear and discogenic internal disruption. The cohort compromised 25 males and 15 females with the average age of 41 years old, ranging from 22 to 61 years old. No treatment group experienced any complications of progressive disc herniation, neurologic injury or disc space infection. This study was designed to evaluate the clinical effects of a biological intradiscal treatment for a subset of patients with chronic lumbar discogenic pain. This is one of the first human studies to investigate both the safety and efficacy of intradiscal injections of autologous PRP. There was a statistically significant improvement in patients measured at both one and four years post procedure.

There was also evidence of reduction in size of high intensity zone on follow up MRI. Ultimately, this study demonstrated that the patients that received PRP had statistical improvement in pain, function and satisfaction when compared to those who received contrast agent alone. This improvement in pain and function were sustained up to one-year post injection. Studies looking at stem cell, intradiscal therapies and PRP intradiscal studies are in their early stages. This new field of study may demonstrate even more positive outcomes, while avoiding the iatrogenic complications and high costs of surgeries and spinal fusions.

Other Neurostimulatory Advances: Technological advances obtained from non-pharmaceutical cognitive approaches to pain continue to be identified. Well DCMS online . org

Pain Management

known treatments include: 1) Transcutaneous electrical nerve stimulation (TENS)- When properly used TENS is highly effective in at least 75 percent of acute pain problems and is of significant benefit in at least 60 percent of chronic pain problems for periods of breakthrough pain.18 This helps limit medication utilization and improve function. 2) Pulse electromagnetic field therapy- This therapy has also demonstrated significant benefits in managing chronic and acute pain conditions from musculoskeletal injury and neuropathic pain.18 3) Cranial electrical stimulation- This is one of the best alternatives to medications for treating anxiety and depression.18

Cognitive Behavioral Advances: Advances in hypnosis, guided imagery and mindful meditation, when utilized in an appropriate fashion, demonstrate marked improvement in tolerance of chronic pain conditions, markedly reducing stress and anxiety of greater than or equal to 50 percent on average in the population.19 It has also been noted when utilizing these modalities, pre and post operatively, there is marked improvement of surgical recovery with demonstrated decreased cortisol levels, stress and anxiety.20

Conclusion: Management of acute and chronic musculoskeletal conditions requires informed and thoughtful approaches, not a one-size-fits-all model. There should be a cohesive attempt to search for safer and more effective therapies. Guidelines to include provisions for complimentary alternative medicines, sleep care, physical therapy and exercise rehabilitation should be considered in addition to a multidisciplinary approach.

Early interventions in the management of musculoskeletal pain would be best suited to improve long term outcomes, and reduce healthcare costs and the economic burden on individuals and society. v

References 1. Freburger JK, Holmes GM, Agans RP, et al. The Rising Prevalence of Chronic Low Back Pain. Arch Intern Med. 2009; 169:251/8.

2. Martin BI, Deyo RA, Mirza SK, et all. Expenditures and Health Status Among Adults with Back and Neck Problems. JAMA. 2008;299:6562/64.

3. Ritzwoller DP, Crounse L, Shetterly S, Rublee D. The association of comorbidities, utilization and costs for patients identified with low back pain. BMC Musculoskel Dis. 2006;7:72.

4. Franklin GM, Stover BD, Turner JA, Fulton-Kehoe D, Wickizer TM. Early opioid prescription and subsequent disability among workers with back injuries: the Disability Risk Identification Study Cohort. Spine. 2008;33:199-204.

5. Vogt MT, Kwoh CK, Cope DK, Osial TA, Culyba M, Starz TW. Analgesic usage for low back pain: impact on health care costs and service use. Spine. 2005;30:1075-81.

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6. Webster BS, Verma SK, Gatchel RJ. Relationship between early opioid prescribing for acute occupational low back pain and disability duration, medical costs, subsequent surgery and late opioid use. Spine. 2007;32:2127-32.

7. Chou R, Huffman LH. Medications for Acute and Chronic Low Back Pain: a review of the Evidence for an American Pain Society/American College of Physicians Clinical Practice Guideline.

Ann Intern Med. 2007;147:505/14.

8. Martell BA, O’Connor PG, Kerns RD, et all. Systematic review: opioid treatment for chronic low back pain: prevalence, efficacy and association with addiction. Ann Intern Med. 2007;146:116/27.

9. Baumblatt JA, Wiedeman C, Dunn J, et al. High-risk use by patients prescribed opioids for pain and its role in overdose deaths.

JAMA Intermed. 2014 May;174(5):796-801.

10. Medina-Torne S, Hanling S, Lesnik I. US Navy’s first functional restoration pain program: Improving readiness, restoring function, and relieving pain. American Academy of Pain Medicine Annual Meeting; 2015; National Harbor, Maryland.

11. Leung, Martin. “Navy Study Suggests Functional Restoration Program Reduces Chronic Musculoskeletal Pain.” PainMedicine News 13, no. 4 (May 2015).

12. Van Buyten JP. Neurostimulation for chronic neuropathic back pain in failed back surgery syndrome. J Pain Symptom Manage.

April 2006;31(4S):S25-29.

13. Stojanovic MP. Stimulation methods for neuropathic pain control. Curr Pain Headache Rep. 2001;5:130/137.

14. Taylor RS. Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic back and leg pain/failed back surgery syndrome: results of a systematic review and meta-analysis. J Pain Symptom Manage. 2006;31(4S):S13-S19.

15. Barrolat G, Oakley JC, Law JD, North RB, Ketcik B, Sharan A. Epidural spinal cord stimulation with a multiple electrode paddle lead is effective in treating intractable low back pain. Neuromodulation. 2001;4:59-66.

16. North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56:98106; discussion 106-107.

17. North RB, Ewend MG, Lawton MT, et al. Failed back surgery syndrome: 5-Year follow-up after spinal cord stimulator implantation. Neurosurgery. 1991 May;28(5):692-9.

18. Advances in Neurology; John J Bonica (ed) NY NY. Raven Press 1974:775-782.

19. Shealy N. Guided Imagery, Mindful Meditation, and Hypnosis for Pain Management; [Internet]. Practical Pain Management; 2015 Oct 1 [updated 2015 Oct 21]. Available from: http:// www.practicalpainmanagement.com/treatments/complementary/ biobehavioral/guided-imagery-mindful-meditation-hypnosis-pain-management.

20. Zautra AJ, Davis MC, Reich JW, et al. Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression. J Consult Clin Psychol. 2008 Jun;76(3):408-21.

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A/I Corner

A Case of Chronic Sinusitis and Recurrent Pneumonia in a Middle-Aged Man

By Sunil Joshi, MD

Case: Mr. EG, a very pleasant 56-year-old, comes in for a referral secondary to chronic/recurrent respiratory tract infections.

Over the last 15-20 years, Mr. EG has been suffering with symptoms of chronic rhinitis including nasal congestion, thick postnasal drainage, throat clearing, discolored nasal mucous and headaches. He has been diagnosed with sinusitis at least six times a year for the last five years. Antibiotics are somewhat helpful at diminishing his symptoms for brief periods of time.

Mr. EG’s sinus symptoms have been complicated by lower respiratory tract infections as well. When his sinus symptoms flare, he typically also suffers with chest coughing, congestion and production of yellowish green sputum. He is usually diagnosed with bronchitis at the same time he suffers with sinusitis. Long courses (over three to four weeks) of oral steroids along with antibiotics are helpful at diminishing his chest symptoms for a few weeks at a time. He has also been diagnosed with pneumonia (confirmed by chest x-ray) three times in the last 15 years with one requiring hospitalization.

In 2013, Mr. EG was diagnosed with chronic sinusitis and had a septoplasty and endoscopic sinus surgery with balloon dilation of the osteomeatal units bilaterally. This helped his sinus symptoms for “about six months.”

Recently, a CT sinus revealed chronic maxillary sinusitis bilaterally with partial obstruction of the osteomeatal units. The rest of the sinuses and upper airway anatomy appeared unremarkable.

A recent chest x-ray was non-revealing, but a chest CT revealed mild peripheral bronchiectasis.

His past medical history includes hypertension and hypercholesterolemia and social history is noteworthy for him being married with no children.

Mr. EG’s family history is unknown, since he was adopted. His current medications include amlodipine 5 mg once a day and pravastatin 20 mg once a day. He has no known drug allergies.

The physical exam is unremarkable with exception of erythematous nasal mucosa with thick white/yellow anterior nasal mucous.

Percutaneous skin testing to indoor and outdoor environmental allergens is non-revealing.

A spirometry shows an FEV1 of 3.08 which is 92 percent of predicted and his FEV1/FVC ratio is 0.85.

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Laboratory evaluation shows a normal CBC with differential; unremarkable chemistry (20) panel and thyroid stimulating hormone level.

His immune globulins were as follows: IgG 223mg/dl (normal range 650-1600 mg/dl); IgA 15 mg/dl (normal range 80-350 mg/dl); IgM 48 g/dl (normal range 45-250 mg/dl).

Streptococcal pneumonia titers revealed protection to one of 23 serotypes evaluated.

The functionality of Mr. EG’s humoral immune system was further investigated as he was provided with the unconjugated pneumococcal vaccine. Six weeks later the streptococcal pneumonia titers were repeated. He did not have a significant improvement to his titers. Mr. EG was then given the conjugated pneumococcal vaccine and again did not have an appropriate response to his titers when evaluated six weeks later. He was then diagnosed with common variable immune deficiency.

Discussion: Common variable immune deficiency (CVID) is a primary immune deficiency disorder. Its clinical manifestations include recurrent sinusitis, otitis media, pulmonary infections, chronic lung diseases, autoimmune disorders, gastrointestinal diseases and an increased risk of malignancies, in particular lymphoma.1 It affects approximately one in every 25,000 people and, in the United States, the majority of patients are diagnosed between the ages of 20 and 45 years.2 Typically, the patient has been evaluated by several medical specialists and may go years prior to being diagnosed, with an average of seven years between symptom onset and diagnoses.3 Among a registry of over 900 patients in the European Society of Immune Deficiency database, the most commonly reported disorders were sino-pulmonary infections (94 percent), hematologic/organ-specific autoimmunity (29 percent), chronic lung disease (29 percent), bronchiectasis (11 percent), granulomatous diseases (18 percent) and lymphoma (8 percent).4 The most common pathogens involved in sinus infections, otitis media and pneumonia include Streptococcus pneumoniae, Haemophilus influenza, and atypical mycoplasma.5 Gastrointestinal infections can be due to Giardia causing refractory diarrhea, malabsorption and/or weight loss. Other GI pathogens can commonly include norovirus, Campylobacter Jejuni, and Salmonella.6 Northeast Florida Medicine Vol. 67, No. 3 2016 47

A/I Corner

Patients with common variable immunodeficiency have an increased risk of developing malignancies but most commonly an increased risk for non-Hodgkin lymphoma (NHL) at eight percent. The NHLs associated with CVID are typically B-cell in nature and well-differentiated.3 Evaluation of suspected individuals should include blood work to assess for serum immunoglobulins with the hallmark of CVID being low total IgG but also low IgA, IgM or both. However, this alone is not enough to make the diagnosis. Evaluation of responses to both protein and polysaccharide-based vaccines should be assessed with pre and post vaccination titers. If the patient does not have an appropriate immunologic response to the vaccines (typically evaluated six weeks after vaccination), then a diagnosis of a humoral immune deficiency, such as CVID, can be made.7 The gold standard of treatment for CVID is immunoglobulin replacement therapy.7 Immunoglobulin can be administered intravenously or subcutaneously. The initial dose calculation is approximately 300-600 mg/kg every four weeks for the intravenous formulation. The subcutaneous dosing is usually once per week but can be in varying intervals, including once per month depending on the formulation and dosing required for individual patients. A serum trough IgG level is usually measured every six months so that dose adjustments may be considered. Higher doses of immunoglobulin replacement may be necessary for patients with severe chronic sinus infections and/or those with bronchiectasis.8 Immunoglobulin replacement therapy significantly improves the clinical course by decreasing infections, the need for antibiotics, hospitalizations and its associated complications.8 The incidence of pneumonia and antibiotic use decreases by 56 percent and the rate of hospitalizations by 50 percent during just the first year of treatment.8 Thus, immunoglobulin replacement therapy can be very helpful and it is imperative that the individual be diagnosed in a timely manner in order to prevent complications and improve overall quality of life.

After six weeks of treatment, his total IgG level was 1150 mg/dl.

He had one further episode of bacterial bronchitis approximately two months after starting on subcutaneous immunoglobulin but has since gone 26 months without a bacterial infection requiring antibiotics. v

References 1. Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000 May;120(2):225-231.

2. Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications.

Q J Med. 1993 Jan;86(1):31-42.

3. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999 Jul;92(1):34-48.

4. Resnick ES, Moshier EL, Godbold JH, et al. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012 Feb 16;119(7):1650-7.

5. Urschel S, Kayikci L, Wintergerst U, et al. Common variable immunodeficiency disorders in children: delayed diagnosis despite typical clinical presentation. J Pediatr. 2009 Jun;154(6):888-94.

6. Quinti I, Soresina A, Spadaro G, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007 May; 27(3):308-16.

7. Cunningham-Rundles Cw. How I treat common variable immune deficiency. Blood. 2010 Jul 8;116(1):7-15.

8. Quartier P, Debre M, De Blic J, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. 1999 May;134(5):589-96.

Case Conclusion: Mr. EG was started on a loading dose of IVIG at 600 mg/ kg IV x1. One week later he was switched to subcutaneous immunoglobulin once a week. After appropriate instructions, the patient was able to infuse independently at home and has been maintained on subcutaneous immunoglobulin, 14 g every week.

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GI Corner

Biologic Therapy for Patients with Inflammatory Bowel Diseases: Scratching the Surface

By Mark Fleisher, MD

Introduction If there is one thing we know in life, it’s that what we don’t know far outweighs what we do know. The field of Inflammatory Bowel Disease (IBD) certainly is an appropriate example of this axiom. The cause and cure of this spectrum of illnesses remains elusive. However, we seem to be closer to the finish line than ever before.

Here are things we do know • Steroids, although commonly used, have never been FDA approved for usage in IBD.1,2 • 5asa products, such as mesalamine, although commonly used, have never been approved by the FDA for use in Crohn’s Disease (CD).3,4 • Immunotherapy agents such as methotrexate (MTX), azathioprine (AZA) and 6-mercaptopurine (6MP), although commonly used, have never been approved by the FDA for use in IBD. • Antibiotics, such as xifaxan, ciprofloxacin and metronidazole, although commonly used, have never been approved for use in IBD.5 It is in this setting that I have always found trepidation regarding biologic agents in the treatment of our patients to be quite bizarre. This is the largest and at times the only class of drugs that IS approved for use in IBD. Physicians would use ineffective medications that were never FDA approved to treat their patients with IBD, as opposed to effective FDA approved drugs. It turns out that the earlier application of appropriate therapy, the less likely the patient would have irreversible consequences from IBD. Finally, after almost two decades of experience, a great majority of gastroenterologists are using biologic therapy for IBD.

Another class of drugs inhibits lymphocyte trafficking selectively to the GI tract (vedolizumab). This has been FDA approved for use in both CD and UC. Adding to the armamentarium of biologics, will be ustekinumab for CD and etrolizumab in UC. The former targets IL 12/23p40 and the latter interrupts linkage with the beta7 dimer of alpha 4 beta7 and alpha epsilon beta 7, thereby blocking both lymphocyte trafficking and adherence to epithelial surfaces. Finally, the treatment of clostridium difficile may soon employ treatment with bezlotoxumab, a biologic being tested to decrease recurrence rates of this nefarious infection that seems to be omnipresent.6-18

Choosing a Biologic Agent Let’s assume that a patient with IBD has already failed a course of conventional and non-FDA approved therapy. The patient has received 5asa treatment and steroids and now it’s time to apply a biologic therapy. Which biologic agent should a physician choose and how should they choose? A good starting point is the evaluation of the absolute reduction of risk, also known as the therapeutic gain. This is also the inverse of the number needed to treat. However, when only one trial is evaluated, it must be taken in the context of validity and reliability: Valid in the hope that the data is true and accurate. Reliable in that outcome has been found to be similar in other studies. Next, proceed to meta-analyses. These reviews pool the data from multiple similar trials in order to get an overall gestalt of trends throughout the literature. The problem with meta-analyses is that it may compound computation errors and compilation may be heterogeneous. It would be nice if there were head to head trials between the biologics. Knowing that head to head to head trials within one class of biologics will likely never occur because of funding, choosing between biologics for patients and physicians is a daunting and imprecise task.

Biologic Agents

Trials

There are now numerous biologic agents on the market.

There are even a few classes of biologic agents. There is one class that binds and blocks the activity of tumor necrosis factor (anti-TNF-alpha). Some have been approved for just CD (ie Certolizumab Pegol), some for just ulcerative colitis (UC) (Golimumab), and some for both (Infliximab and adalimumab).

Perhaps we should just take a look at a few of the initial landmark trials for each agent. For example, the first was infliximab. It has approved for use in fistulizing and non-fistulizing CD, as well as UC. Prior to biologics, the approach to a fistulae was to divert the fecal stream with a diverting colostomy. Although this approach could allow for healing, studies showed that the benefit would not endure once the patient was reanastamosed. Then in 1999, a short term trial demonstrated that infliximab closed fistulae in CD after three doses with a median response of 12 weeks. A long term trail revealed that responders after three doses were shown to often maintain this response long term. Here are some numbers for the long term trail of infliximab for CD patients

Address correspondence to: Mark R. Fleisher, MD Borland-Groover Clinic Jacksonville, FL mfleisher@bgclinic.com DCMS online . org

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GI Corner

with fistulae: The therapeutic gain after a year is 17 percent with complete closure of any and all draining fistulae.6,7,8,12,13 Please refer to Table 1 and Table 2 for a summarization of the initial trials of infliximab for CD. Infliximab has also been studied in ulcerative colitis. The efficacy of the drug for induction and maintenance in UC revealed a therapeutic gain at week 8 and week 54 of 24 percent.6,7,8,12,13 Infliximab studies revealed that those who do not respond to 5 mg/kg infusion or lose responsiveness to these infusions may benefit from increasing the dose to 10 mg/kg.6,7,8,12,13 Please refer to Tables 3 and 4 for summarization of the infliximab studies in ulcerative colitis.

Further studies were done to evaluate if biologic therapy in combination with immunotherapy was more effective than either therapy alone. Although combination therapy has been found to be more effective, the potential deleterious side effects are also compounded. Thus, a risk-benefit ratio quagmire exists.

Tables 5 and 6 summarize these studies in CD and UC. Adalimumab in CD is delivered not by an infusion like infliximab, but by subcutaneous injection. The remission rates at week 4 and week 54 had a therapeutic gain of 24 percent.

For those patients who do not respond to injections every other week there is no proof that increasing the injections to a weekly schedule will be of benefit.15,17 Tables 7 through 18 help unravel the efficacy of adalimumab in patients who are naĂŻve to biologic therapy or who have been intolerant or failed previous biologic therapy. Moreover, these tables help to evaluate the efficacy of adalimumab for induction and maintenance of remission in patients with CD and UC. While infliximab and adalimumab have similar therapeutic gains, not all anti-tnf agents can make this claim.

Certolizumab pegol is an injectable anti tnf agent that is approved to treat CD. It had a therapeutic gain at week 26 of 19 percent.10,11 Tables 19 through 24 review the efficacy of certolizumab pegol for induction and maintenance in patients with CD who are either naĂŻve or failed previous biologic therapy.

Golimumab is an injectable anti tnf agent that is approved to treat UC. It has a 54 week therapeutic gain of 11 percent for remission.14,18 Finally, vedolizumab has been found to have therapeutic gains at the end of the year of 32 percent in UC and 25 percent in CD. However, the patients in these trials were often those who failed other biologic agents. Thus, this agent has higher therapeutic gains in the initial trial while studying patients who had more intractable disease.

Tables 25 and 26 display the efficacy of vedolizumab in CD and UC for induction and maintenance of remission. Moreover, the tables display the strength of this drug in those who have already failed anti-tnf agents.

However, these are merely the landmark trials for each of

50 Vol. 67, No. 3 2016 Northeast Florida Medicine

these agents. Numerous other studies have been performed whereby the results were both valid and reliable. Moreover, the application, manipulation and monitoring of these drugs is an evolving art. If the drug seems to wane in efficacy it could be that antibodies to these agents have been formed. If the drug does not seem to work at all, it could be that the patient has issues not with tnf-alpha, but with one of a myriad of other cytokines.

Discussions regarding these numbers with patients can become quite complicated but they are compelling and compulsory. Patients will need to decide if they prefer an infusion, such as vedolizumab and infliximab, to an injection, such as adalimumab, certolizumab pegol or golimimab. If they prefer infusion, they need to know that infliximab is two hours and vedolizumab is 30 minutes.

Lastly, just a cursory perusal of these numbers seem to create a three tiered pyramid of biologics when it comes to long term maintenance of response and remission. The anti-integrin vedolizumab seems to eek out the gold medal, with infliximab and adalimumab taking the silver and the bronze going to golimumab and certolizumab pegol. However, one should keep in mind that there are numerous erudite meta analyses that swap the gold and silver medalists.

Conclusion In review, the biologic agents for UC and CD are certainly more effective than previous, non FDA approved medications.

Moreover, the efficacy of the drugs are, for the most part, quite close. The monitoring of not merely potential side effects but factors that could attenuate efficacy, such as antibody formation, need to be vigilantly monitored.19 In fact, the monitoring of drug levels combined with antibody to drug levels, along with measurement of cytokine levels, has taken the treatment of IBD patients to a whole new level. v

Table 1: ACCENT 1 Trial: Maintenance study for infliximab responders in non fistulizing CD (54 week trial)20 Dose of Infliximab Given to CD patient

Remission at week 30

Placebo

21

5 mg/kg

39 (18)

10 mg/kg

45 (23)

573 patients received infliximab 58% responded at week 2 to a single infusion These subjects then received placebo, 5 mg/kg or 10 mg/kg at weeks 2/6 and every 8 weeks thereafter Loss of responsiveness: 19 weeks for those that received only a single remicade More than 54 weeks for those on maintenance treatment The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy â&#x20AC;&#x201C; Placebo Efficacy)

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GI Corner

Table 2: ACCENT 2 Trials: Maintenance treatment with

Table 6: SUCCESS Trial (UC): 16 week trial: Infliximab,

infliximab in patients with fistulizing CD (54 week trial)21

azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis24

Dose of Infliximab Given to CD patient

Remission at week 30

All patients receive 5 mg/kg at weeks 0, 2 and 6 44.8% closed at week 14 72.2% were not draining at week 14 Responders then receive placebo or 5 mg/kg every 8 weeks thereafter The placebo group had average closure duration of 33 weeks while the maintenance group had an average closure duration of 46 weeks.

Table 3: Efficacy of Infliximab Induction therapy for ulcerative colitis: the ACT-1 and -2 extension studies22 Dose of Infliximab Given to UC patient

Responded at week 8 – ACT 1

Responded at week 8 – ACT 2

Placebo

69

29

5 mg/kg

61 (32)

64 (35)

10 mg/kg

37 (24)

69 (40)

Regimen Given to CD patient

Remission

Response

Mucosal Healing

AZA + Infliximab

40

77

63

Infliximab alone

22

69

55

AZA alone

24

50

37

Table 7: CLASSIC 1 Trial: Evaluate efficacy of in adalimumab induction therapy in CD25 Dose of adalimumab given to CD patient

Remission at week 4

Response at week 4

Placebo

12

25

40/20

18 (6)

34 (9)

80/40

24 (12)

40 (15)

160/80

36 (24)

50 (25)

Infliximab for induction and maintenance therapy in UC

299 patients at weeks 0/2 received 40 mg/20 mg, 80 mg/40 mg, 160 mg/80 mg or placebo

ACT 1: 54 week trial (last infusion at week 46)

11% of patients had fistulae

ACT 2: 30 week trial (last infusion at week 22)

No difference in fistula healing

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Table 4: Further Analysis of Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies

Table 8: CLASSIC 2 Trial: Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial26 Dose of adalimumab given to CD patient

Percentage of Original 55 responders who maintained remission at week 56

20

Placebo

44

5 mg/kg

45 (25)

40 q o week

79 (35)

10 mg/kg

44 (24)

40 q week

83 (39)

Dose of Infliximab Given to UC patient

Responded at week 54 – ACT 1

Placebo

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Evaluate efficacy of adalimumab maintenance therapy in CD 276 patients from CLASSIC 1 enrolled in CLASSIC 2 and received 40 mg at week 0 (week 4 of CLASSIC 1)

Table 5: SONIC Trial (CD): 50 week trial: Comparing the efficacies of azathioprine, infliximab and combination therapy in CD23 Regimen Given to CD patient

Steroid free remission at weeks 26 and 50

Mucosal healing at week 26

AZA + Infliximab

56.8

43.9

Infliximab alone

44.4

30.1

AZA alone

30

16.5

DCMS online . org

55 patients were in remission These patients were randomized to receive 40 q o week, 40 q week or placebo for 56 weeks The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Northeast Florida Medicine Vol. 67, No. 3 2016 51

GI Corner

Table 9: Further Evaluation of CLASSIC 2 Trial: Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial26 Dose of adalimumab given to CD patient

Clinical remission at week 56

Clinical responder at week 56

46% (No ARR)

64% (No ARR)

NO PLACEBO ARM 40 mg q o week

204 patients not in remission were given open label 40 mg every other week. No placebo arm for these people.

NOTE: 50% had to dose escalate from q o week to q week

Table 10: Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial27

Table 12: Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial28 Dose of adalimumab After Induction given to CD patient

Mucosal healing at week 12

Mucosal Healing at week 52

Remission at week 12

Remission at week 52

Placebo

13

0

28

9

40 mg q o week

27 (14)

24 (24)

47 (19)

33 (24)

Evaluate induction and maintenance of mucosal healing in CD 52 week trial Induction with 160/80 at weeks 0 and 2 then maintenance with 40 mg or placebo q o week The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Dose of adalimumab given to CD patient

Remission at week 26

Remission at week 56

Table 13: Gain Trial: Evaluate CD patients who were either

Placebo

17

12

intolerant of or lost responsiveness to infliximab29

40 q o week

40 (23)

36 (24)

40 q week

47 (30)

41 (29)

Evaluate the efficacy of adalimumab in the maintenance of response and remission in CD Patients received open label induction with 80 mg at week 0 then 40 mg at week 2 then randomized to 40 q week and 40 q o week 56 week trial 8.9% drop out rate 27% required dose escalation and 76% were then able to capture responsiveness The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Table 11: CHARM OLE (Open Label extension) Trial: Evaluation of the Duration of response in responders to adalimumab27 108 weeks 40 patients who were responders at end of CHARM and continued 40 mg q o week through week 108 36/40 (90%) were in remission at end of trial

Dose of adalimumab given to CD patient who didn’t do well with infliximab

Remission at week 4

Placebo

44

160/80 induction

21 (14)

4 week trial The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Table 14: Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 330 Regimen of adalimumab given to UC patient

Remission at week 8

Placebo

9.2

80/40/40/40

10 (0.8)

160/80/40/40

18.5 (9.3)

Evaluate two induction doses of adalimumab in patients with UC (ULTRA 1 Trial) All patients were TNF naive Regimens were administered q o week as follows: 160/80/40/40 vs. 80/40/40/40 vs placebo The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

52 Vol. 67, No. 3 2016 Northeast Florida Medicine

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GI Corner

Table 15: Evaluate adalimumab for induction therapy in UC30 Regimen of Overall adalimumab given Remission at to UC patient week 8

Overall Response at week 8

Overall Mucosal Healing at week 8

Placebo

9

32

32

160/80/40 then 40 mg q o week thereafter

17 (8)

50 (18)

41 (9)

40% had already received anti TNF therapy (ULTRA 2)

Dose of certolizumab pegol given to patient with CD

Response at week 6

Response at week 26

Placebo

27

16

400 mg at weeks 0/2/4

35 (8)

23 (7)

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

pegol maintenance therapy in CD32

Table 16: Evaluate adalimumab for maintenance therapy in UC30 Overall Response at week 52

Overall Mucosal healing at week 52

Placebo

9

18

15

160/80/40 then 40 mg q o week thereafter

17 (8)

30 (12)

25 (10)

Regimen given to patient with CD

Response at week 26

Remission at week 26

400 mg at weeks 0/2/4 then placebo every 4 weeks

36

29

400 mg at weeks 0/2/4 then 400 mg every 4 weeks

63 (27)

48 (19)

All patients received open label induction of 400 mg of certolizumab pegol followed by placebo or 400mg every four week 64% had a response at week 6 43% had remission at week 6 Responders then continued on in the trial

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Table 17: TNF naïve and previous TNF therapy for patients with UC treated with adalimumab

30

Regimen of adalimumab given to TNF naïve patient who has UC

Remission at week 8

Remission at week 52

Placebo

11

12.4

160/80/40 then 40 mg q o week thereafter

21.3 (10.3)

22 (9.6)

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Table 18: TNF naïve and previous TNF therapy for patients with UC treated with adalimumab30 Regimen of adalimumab given to TNF veteran who has UC

Remission at week 8

Remission at week 52

Placebo

6.9

3

160/80/40 then 40 mg q o week thereafter

9.2(2.3)

10.2 (7.2)

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy) DCMS online . org

induction therapy in CD31

Table 20: PRECISE 2 Trial: Evaluate certolizumab

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Regimen of Overall adalimumab given Remission at to UC patient week 52

Table 19: PRECISE 1 Trial: Evaluate certolizumab pegol

Table 21: PRECISE 3 Trial: Ongoing evaluation of CD patients from PRECISE 2 who have received certolizumab pegol either continuously or episodically33 Dosing and frequency of certolizumab pegol in patient with CD

Response rate at week 26

Remission Response rate at rate at week 80 week 80 Remission for those for those in responding remission rate at week 26 at week 26 at week 26

400 mg every 4 weeks continuously

56

48

66

62

400 mg every four weeks but in an interrupted fashion

38

32

63

63

Table 22: Overview of Precise 4 Trial34 This is a study regarding recapturing responsiveness by re-induction therapy with certolizumab pegol in patients who lost responsiveness to certolizumab pegol This is re-induction without dose escalation.

Week 4: 64% respond Week 52: 55% respond Northeast Florida Medicine Vol. 67, No. 3 2016 53

GI Corner

Table 23: WELCOME TRIAL: Evaluation of certolizumab pegol in patients who either failed or were intolerant of infliximab35 Regimen of certolizumab pegol Given to CD patient who did not fare well with infliximab but responded to certolizumab pegol induction

Response at week 26

Table 26: GEMINI 2 (52 weeks): Vedolizumab as induction and maintenance therapy for Crohn’s disease38 Dose of Vedolizumab Given to CD patient

Prior anti TNF

Remission

Anti TNF Naive

Remission at week 26

Placebo

12.8

21.6

26.8

300 q 4

28 (15.2)

39 (17.4)

51.5 (24.7)

300 q 8

27.3 (14.5)

36.4 (14.8)

46.5 (19.7)

400 mg every two weeks

37

30

400 mg every 4 weeks

40

29

Open label induction of 400 mg given at weeks 0/2 and 4 then every 2 or 4 weeks thereafter

The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

26 week trial Only responders at week 6 would continue in the study

References

Respond at week 6: 62%

1. Summers RW, Switz DN, Sessions JT, et al. National Cooperative Crohn’s Disease Study. Gastroenterology. 1979; 77: 847-69.

Remission at week 6: 39%

Table 24: Pursuit Trial: 54 week trial evaluating Maintenance of Efficacy and Continuing Safety of Golimumab for Active Ulcerative Colitis36 Dose of Golimumab Given to UC patient

Response at week 54

Remission at week 54

Mucosal Healing at week 54

Placebo

31.2

15.6

26.6

47 (15.8)

23.2 (7.6)

41.7 (15.1)

49.7 (18.5) 27.8 (12.2)

42.4 (15.8)

50 100

an IgG1 anti-TNF approved to treat UC Sub Q Weeks 0 at 200 mg then week 2 at 100 mg and every 4 weeks thereafter at 100 mg The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy)

Table 25: GEMINI 1 (52 weeks): Vedolizumab as induction and maintenance therapy for ulcerative colitis37 Dose of Vedolizumab Given to UC patient

Response

Remission

Mucosal healing

Placebo

23.8

15.9

19.8

300 q 4 300 q 8

56.6 (32.8) 41.8 (25.9) 51.6 (31.8) 52 (28.2)

44.8 (28.9)

56 (36.2)

IgG1 monoclonal antibody to alpha 4Beta7 integrins for use in CD and UC Prevents binding to MADCAM1 on intestinal endothelial cells Selective binging prevents lymphocyte trafficking to gut without impacting alpha-4 brain receptor The therapeutic gains are in parentheses.

The Therapeutic Gain = Absolute Reduction of Risk = (Drug Efficacy – Placebo Efficacy) 54 Vol. 67, No. 3 2016 Northeast Florida Medicine

2. Munkholm P, Langholz E, Davidsen M, et al. Frequency of Glucocorticoid Resistance and Dependancy in Crohn’s Disease. Gut. 1994 Mar;35(3):360-2.

3. Camma C, Giunta M, Roselli M, et al. Mesalamine in the Maintenance Treatment of Crohn’s Disease: A Meta-analysis Adjusted for Confounding Variables. Gastroenterology. 1997 Nov;113(5):1465-73.

4. Modigliani R, Colombel JF, Dupas JL, et al. Mesalamine in Crohn’s Disease with Steroid-Induced Remission: Effect on Steroid Withdrawl and Remission Maintenance. Gastroenterology. 1996 Mar;110(3):688-93.

5. Greenbloom SL, Steinhart AH, Greenberg GR. Combination Ciprofloxacin and Metronidazole for Active Crohn’s Disease. Can J Gastroenterol. 1998 Jan-Feb;12(1):53-6.

6. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the Treatment of Fistulas in Patients With Crohn’s Disease. N Engl J Med. 1999 May 6;340:1398-1405.

7. Targan SR, Hanauer SB, van Deventer SJ, et al. A Short Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor Alpha For Crohn’s Disease. N Engl J Med. 1997 Oct 9;337(15):1029-35.

8. Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and Safety of Retreatment With Anti-tumor Necrosis Factor Antibody (Infliximab) to Maintain Remission in Crohn’s Disease.

Gastroenterology. 1999 Oct;117(4):761-9.

9. MODIFY 1 and 2 Trials, presented at DDW conference 2016.

10. Schrreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance Therapy with Certolizumab Pegol for Crohn’s Disease. N Engl J Med. 2007 Jul 19;357:239-50.

11. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumbab Pegol for the Treatment of Crohn’s Disease. N Engl J Med. 2007 Jul 19;357:228-38.

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GI Corner

12. Rutgeerts P, Sandborn WJ, Feagan BG, et al Infliximab for induction and Maintenance Therapy for Ulcerative Colitis.

N Engl J Med. 2005 Dec 8;353(23):2462–76.

26. Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007 Sep;56(9):1232-9.

13. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance Infliximab for Crohn’s Disease: the Accent 1 randomized trial. Lancet. 2002 May 4;359(9317):1541-9.

27. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007 Jan;132(1):52-65.

14. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous Golimumab Maintains Clinical response in Patients With Moderate to Severe Ulcerative Colitis. Gastroenterology. 2014 Jan;146(1):96-109.

15. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for Maintenance of Clinical response and Remission in patients with Carton’s Disease: the CHARM trial. Gastroenterology. 2007 Jan;132(1):52–65.

16. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance Infliximab for Crohn’s Disease: the Accent 1 randomized trial. Lancet. 2002 May 4;359(9317):1541-9.

17. Hanauer S. Human Anti-Tumor Necrosis Factor Monoclonal Antibody (Adalimumab) in Crohn’s Disease: The CLASSIC -1 Trial. Gastroenterology. 2006;130: 323 – 333.

18. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous Golimumab Induces Clinical Response and remission in patients with Moderate to Severe Ulcerative colitis. Gastroenterology. 2014 Jan;146(1):85–95.

19. Baert F, Noman M, Vermeire S, et al. Influence of Immunogenicity on the long term efficacy of infliximab in Crohn’s disease. N Engl J Med. 2003 Feb 13;348(7):601-8.

20. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance Infliximab for Crohn’s Disease: the Accent 1 randomized trial. Lancet. 2002 May 4;359(9317):1541-9.

21. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004 Feb 26;350(9):876-85.

22. Reinisch W, Sandborn WJ, Rutgeerts P, et al. Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies. Inflamm Bowel Dis. 2012 Feb;18(2):201-11.

23. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010 Apr 15;362(15):1383-95.

24. Panaccione R, Ghosh S, Middleton S, et al. Infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis: The UC SUCCESS trial.

Presentation at: European Crohn’s and Colitis Organization; 2011; Dublin, Ireland.

25. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC I trial. Gastroenterology.

2006 Feb;130(2):323-33.

DCMS online . org

28. Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102-1111.

29. Hinojosa J, Gomollon F, Garcia S, et al. Efficacy and safety of short-term adalimumab in Patients with Acrice Crohn’s Disease who lost response or showed intolerance to Infliximav: a prospective, open-label multicenter trial. Aliment Pharmacol Ther. 2007 Feb 15;25(4):409–18.

30. Colombel JF, Sandborn WJ, Ghosh S, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 3. Am J Gastroenterol. 2014 Nov;109(11):1771-80.

31. Sanborn WJ, Feagan BG, Stoinov S, et al. Certolizumab Pegol for the Treatment of Crohn’s Disease. N Engl J Med. 2007 Jul 19;357:228-38.

32. Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007 Jul 19;357:239–50.

33. Sandborn WJ, Melmed GY, McGovern DP, et al. Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn’s disease: analyses from the 7-year PRECiSE 3 study. Aliment Pharmacol Ther. 2015 Aug;42(3):330-42.

34. Lee SD, Rubin DT, Sandborn WJ, et al. Reinduction with Certolizumab Pegol in Patients with Crohn’s Disease Experiencing Disease Exacerbation: 7-Year Data from the PRECiSE 4 Study. Inflamm Bowel Dis. 2016 Aug;22(8):1870-80.

35. Sandborn WJ, Schreiber S, Hanauer SB, et al. Reinduction with certolizumab pegol in patients with relapsed Crohn’s disease: results from the PRECiSE 4 Study. Clin Gastroenterol Hepatol. 2010 Aug;8(8):696-702.

36. Gibson PR, Feagan BG, Sandborn WJ, et al. Maintenance of Efficacy and Continuing Safety of Golimumab for Active Ulcerative Colitis: PURSUIT-SC Maintenance Study Extension Through 1 Year. Clin Transl Gastroenterol. 2016 Apr 28;7:e168.

37. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710.

38. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013 Aug 22;369(8):711-21.

Northeast Florida Medicine Vol. 67, No. 3 2016 55

Special Submission

Sun Safety Knowledge, Attitudes and Behaviors Among Children in Northeast Florida

By Allison S. Bechtel, DO1, Julie Williams Merten, PhD2 and Eric Sandler, MD3 1

University of Florida/Nemours, 807 Children’s Way, Jacksonville, FL 32207 2

University of North Florida, 1 UNF Drive, Jacksonville, FL 32224 3

Nemours, 807 Children’s Way, Jacksonville, FL 32207

Abstract: Background: Skin cancer is a common and increasingly prevalent cancer. The development of skin cancer is directly linked to sun exposure accumulated throughout life. Florida has the second highest number of skin cancer cases in the U.S. Methods: Children (n=65) between the ages of seven and twelve attending summer camps in Northeast Florida were surveyed about their sun protection and sun exposure attitudes, behaviors and knowledge.

Results: The majority of the children were able to identify sun protection methods and felt sun protection was important, yet sun protection practices were inadequate. The majority of children reported more than three sunburns in the past year and high rates of sun exposure.

Discussion: There is a disconnect between sun protection knowledge and sun protection behavior, with the majority of children engaging in high-risk behavior. This study underscores the need for multilevel sun safety intervention including infrastructure change, policy advocacy and parental education.

Background Skin cancer is the most common cancer in the United States (U.S.), with more than 3.5 million cases of basal and squamous cell skin cancer diagnosed in the U.S. ever year. Melanoma, the deadliest type of skin cancer, and 6th most common cancer, accounted for more than 76,000 cases of skin cancer in 2014.

The risk factors associated with skin cancer include sun sensitivity, a history of excessive sun exposure, sunburns, use of indoor tanning, diseases that suppress the immune system and a past history of basal cell or squamous cell skin cancers.1 Of these risk factors, it should be noted that the vast majority are preventable behaviors.

Address Correspondence to: Allison S. Bechtel, DO University of Florida/Nemours 807 Children’s Way Jacksonville, FL 32207 (573) 355-2093

DCMS online . org

Less than a third of U.S. children practice what would be considered effective sun protection by avoiding the sun during peak hours and properly wearing sunscreen and sun protective clothing.3 Even in families with a parent who had a diagnosis of melanoma, half of the children reported a sunburn in the last year with some evidence suggesting these burns may be due to overreliance on sunscreen, and not using other protection methods.1,2 Poor sun protection practices were further supported by State of Florida data from 2006 that showed that 15 percent of Floridians do not use any skin protection products and over 50 percent of Floridians “purposely tan.”

When specifically surveying adolescents, it was found that 51.4 percent of young adults never or rarely wear sunscreen with SPF 15 or greater.3 Despite the compelling evidence linking sun exposure to skin cancer and research indicating the effectiveness of sun safety education and the increased risk for sunburn during childhood, only three percent of public schools in the nation include mandatory sun safety education.

Purpose The purpose of this study is to examine the attitudes, behaviors and knowledge of sun safety practices among a sample of children in coastal Northeast Florida (Duval and St. Johns counties).

Methods This Institutional Review Board (IRB) approved study was conducted in two summer camps in coastal Northeast Florida within Duval and St. Johns counties. Sixty-five children between the ages of seven and twelve were surveyed over a five-day period.

Parental consent was obtained in cooperation with the summer camp organizers and administrators. No incentives were used and the survey was delivered during indoor rest periods between outdoor activities.

The widely-used and validated Sun Safety Survey (Figure 1) was used to assess participant knowledge of proper sun protection, attitudes toward the importance of sun protection and current sun safety behaviors. Demographic information from the participants was also collected. The questionnaire was written at the reading level of an eight year old (third grade) child and pilot tested with individuals of this level for Northeast Florida Medicine Vol. 67, No. 3 2016 61

Special Submission Figure 1: Sun Safety Survey

Table 1: Demographic characteristics of the study sample (n=65) n

%

Male

33

51.0

Female

32

49.0

White

42

61.5

African American

10

16.1

Hispanic

8

12.9

Other races

5

8.0

Characteristic Sex

Race/ethnicity

Age 7 to 9

52.1

10 to 12

47.0

62 Vol. 67, No. 3 2016 Northeast Florida Medicine

comprehension prior to use. De-identified data was entered by the researchers and analysis was conducted using SPSS 19.1, a software program for statistical analysis in the social sciences.

Results Children (n=65) were between the ages of seven and twelve with a mean age of 9.12, SD=1.269. Of the participants, the majority (65 percent) were white, non-Hispanic with 16 percent African American, 13 percent Hispanic and 6.5 percent of other races. Gender was relatively evenly distributed with 51 percent boys and 49 percent girls. See Table 1 for complete demographic information.

Only 28.4 percent of children reported they had a school lesson on sun protection, with girls more likely to report sun safety education (p=0.034). The majority of the children (56.8 percent) didnâ&#x20AC;&#x2122;t think their skin would burn when exposed to the sun. However, 42 percent reported more than three sunburns in their life and over half reported at least one red and painful sunburn.

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Special Submission

Table 2: Sun protection and sun exposure of the study sample (n=65) Sun protection*

n

%

33

51.2

0 – 1 days

6

9.5

48.8

2 – 3 days

8

11.9

4 – 5 days

22

34.5

More than 6 days

29

44

Sunscreen use Always or often

n

Sun exposure

%

Days spent per week outside during previous summer during peak hours

Sometimes, rarely, or never Sun Protection Factor (SPF) used SPF less than 15

1

2.4

SPF 15 – 29

3

3.7

SPF greater than 30

28

42.7

Unsure

33

51.2

Friend

26

40.7

Sibling

33

51.7

Parent

22

33.7

Reminded someone to use sunscreen

Wide-brimmed hat Always or often

19

28.6

Sometimes, rarely, or never

46

71.4

Wear a shirt that covers the shoulders Always or often

5

8.0

Sometimes, rarely, or never

60

92.0

Sunglasses

Hours spent per day outside in previous summer uring peak hours Less than an hour

8

12.9

1 – 2 hours

20

30.6

3 – 4 hours

18

27.1

More than 5 hours

19

29.4

Sunburn in the past year None

22

34.1

1–2

16

23.9

3–4

27

42

More than five Painful sunburn in the past year None

20

30.6

1–2

17

25.9

Always or often

21

32.2

3–4

16

24.7

Sometimes, rarely, or never

44

67.8

I have not had a sunburn

12

18.8

Notes: *The question asks when the participant is outside on a warm, sunny day and answers are on a 5 point Likkert scale ranging from Never to Always. Always or Often is considered adequate use; Sometimes, Rarely, Never is considered inadequate use

Approximately half (53 percent) of the children correctly identified sunscreen as a protection mechanism from the sun and 62 percent reported they felt sun protection was important. Nonetheless, these perspectives did not transfer over to behavior as the majority of children reported insufficient sun protection behaviors (Table 2). Nearly 60 percent of the children reported that keeping their skin safe from the sun “is easy to do.” However, 48 percent reported rarely or never wearing sunscreen when outside, 71.4 percent did not wear a hat, 67.8 percent did not wear sunglasses and 92 percent did not cover their arms and shoulders. Consistent with other studies of sun protection in other age groups, there were gender differences in behaviors with girls more likely to report sunscreen use (p=0.006) and boys more likely to wear a hat – likely a baseball hat which does not count as a “widebrimmed hat” (p=0.004).

The children reported spending several days per week outside with 44 percent spending six to seven days per week outside and nearly 40 percent spending over four hours outside each day. There were no statistically significant differences in outdoor behaviors among children age seven to nine compared to 10 to 12 year olds except for sunscreen usage with older children

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more likely to use sunscreen (p=0.047). Interestingly, children that reported burning easily were more likely to use sunscreen and spent less time outside during the day.

Discussion Consistent with national data, children in Northeast Florida are not using adequate sun protection which is significantly increasing their risk of future skin cancer. Despite the perceived “common” knowledge of the risks of unprotected sun exposure, the study demonstrates that knowledge does not extend to behavioral change among children in Northeast Florida.

Both the Centers for Disease Control (CDC) and the Florida Department of Health have released guidelines and goals addressing sun exposure and skin cancer prevention.

The CDC framework includes policies within the schools to prevent sun exposure: providing an environment that supports skin safety, providing health education within the schools, involving family members, educating the professional staff within the schools, complementing prevention with health services and periodically evaluating the schools and their ability to implement these practices.3 The Florida State Cancer Plan through the Florida Department of Health also specifically Northeast Florida Medicine Vol. 67, No. 3 2016 63

Special Submission

promotes sun safety measures, provides appropriate cancer education materials for the targeted age group and develops cancer-specific public awareness campaigns for education.

This study reinforces the call for elementary schools to include formal sun safety education aimed at behavioral change in the curriculum. There is mounting evidence that repeated, evidence-based education has the ability to change behaviors and knowledge about sun exposure, particularly when done in elementary schools. In Australia, the timing of public-education campaigns correlates with a decreasing trend in childhood melanoma incidence.4 In Germany, a nationwide environmental education program, called SunPass, promoted a significant improvement in hat wear and improved shade practices with kindergarten children. However, it did not change sunscreen use.5 In other elementary schools, promotion of hat use did result in increased wear in the intervention schools.6 In French primary schools, a program specifically addressing practical skills related to sun prevention showed a significant difference in knowledge base of those who received the education.7 Some programs focused more on the adult population who were surrounding the children, e.g. teachers and parents.

Educating the caregivers and instructors showed a significant increase in knowledge (assessed through pre and post-testing), as well as a desire and recognition of the need for a consistent program and policy change within the schools.8 In the U.S., the SunWise curriculum, created by the U.S. Environmental Protection Agency, has demonstrated successful behavioral change. In a broad study of 85 schools in 35 states there was a significant increase of all three outlined knowledge variables (appropriate sunscreen use for outdoor play, and use of hats and shirts outside) and minor behavioral improvements at post intervention follow up.9,10 Further study of this program by the same group of researchers, noted that this program was most beneficial when also focusing on policy, as well as providing technical assistance.11 Through 2015, the SunWise program is expected to prevent greater than 50 premature deaths, almost 11,000 skin cancer cases and 960 quality-adjusted life-years among those who participate. The investigators estimated that for every dollar spent in SunWise, two to four dollars in medical care costs and productivity losses are saved.12

References 1. American Cancer Society. Cancer Facts and Figures 2012.

Atlanta (GA): American Cancer Society; 2012. 68 p.

2. Glenn, BA, Bastani R, Chang LC, et al. Sun protection practices among children with a family history of melanoma: a pilot study. J Cancer Educ. 2012 Dec;27(4):731-7.

3. Rouhani P, Parmet Y, Bessell AG, et al. Knowledge, attitudes, and behaviors of elementary school students regarding sun exposure and skin cancer. Pediatr Dermatol. 2009 SepOct;26(5):529-35.

4. Baade PD, Green AC, Smithers BM, et al. Trends in melanoma incidence among children: possible influence of sun-protection programs. Expert Rev Anticancer Ther. 2011 May;11(5):661-4.

5. StÖver LA, Hinrichs B, Petzold U, et al. Getting in early: primary skin cancer prevention at 55 German kindergartens.

Br J Dermatol. 2012 Aug;167(2): 63-9.

6. Hunter S, Lover-Jackson K, Abdulla R et al. Sun protection at elementary schools: a cluster randomized trial. J Natl Cancer Inst. 2010 Apr 7;102(7):484-92.

7. Sancho-Garnier H, Pereira B, Césarini P. A Cluster Randomized Trial to Evaluate a Health Education Programme “Living with Sun at School.” Int J Environ Res Public Health. 2012 Jul;9(7):2345-61.

8. Walker DK. Skin Protection for (SPF) Kids Program. J Pediatr Nurs. 2012 Jun;27(3):233-42.

9. Geller AC, Cantor M, Miller DR, et al. The Environmental Protection Agency’s National SunWise School Program: sun protection education in US schools (1999-2000). J Am Acad Dermatol. 2002 May;46(5):683-9.

10. Geller A, Rutsch L, Kenausis K, et al. Evaluation of the SunWise School Program. J Sch Nurs. 2003 Apr;19(2):93-9.

11. Emmons KM, Gellar AC, Viswanath V, et al. The SunWise Policy Intervention for School-Based Sun Protection: a pilot study. J Sch Nurs. 2008 Aug;24(4):215-21.

12. Kyle JW, Hammitt JK, Lim HW, et al. Economic evaluation of the US Environmental Protection Agency’s SunWise program: sun protection education for young children. Pediatrics.

2008 May;121(5):e1074-84.

Conclusion Consistent education integrated into the school system is crucial to the future health of children of the United States, particularly in the state of Florida. This has the potential to change some dangerous attitudes and behaviors in the short term and to prevent premature deaths and save many health care dollars in the long term.

64 Vol. 67, No. 3 2016 Northeast Florida Medicine

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Creative Corner

Dragonflies

By Mark R. Fleisher, MD We rode Bus “T” bound for Brooklyn Day Camp, which was over the bridge and somewhere in Queens, naturally. Supposedly, the original camp had become too popular for its own good. With no room to grow in compact Brooklyn, it merely shifted over one borough and kept the name.

Its misnomer was part of its charm.

The bus that shuttled my siblings and me was the only blue one in the camp. Driven and owned by Bernie, The Bluebird picked us up first and dropped us off last. After a hard day at camp, this seemed truly unfair even though my parents probably paid an exorbitant sum for such choice placement. As we neared the camp, Mark Fleisher, MD the bus always passed the same elderly woman. She would just be hanging laundry or sitting in a chair. We’d wave to her and she’d wave back. It seems so simple now. Just a hello. Just people.

Six days a week, Monday through Saturday, every day was the same at Brooklyn Day Camp. Leading off was baseball, my passion. Every morning I’d check the skies. I can recall many a day after a deluge, playing in the swamps of deep right field. Half the time I’d pay more attention to the dive-bombing dragonflies than to the game. Who can deny that three swings are worth the threat of malaria? We’d sully the national pastime for a few hours until someone noticed the time. Yikes! What kind of budding neurotic wears a watch to day camp anyway?

Swimming was next, so no one would complain. No one except me; I hated swimming. I still do. Let me correct that; I can’t swim. Let me be blunt—I’m afraid of the water. I fell in the deep end of a pool once and that was enough for me. I’d hide anywhere to avoid swimming. Inside bathroom stalls, under the boxing ring or up the weeping willow was where you could find me. Finally, I’d hear the squishing of soggy suits and sodden thongs and, presto, I would reappear in time for lunch. Who could resist hamburgers, franks and fried chicken? I have to admit that Uncle Freddie put out a sumptuous spread. Lest I forget, Fred Nislow owned the camp.

As per the whims of autocracy, he preferred the title of Uncle Fred. For some reason Uncle Fred wore his Bermuda shorts only in a downpour. Yet in heat that could stroke the maddest of Englishmen, he always wore long pants. Along with Uncle Fred was his wife, Mrs. Nislow or more casually: Uncle Fred’s wife. There was his sister, Dolly, who ran the concession stand. Icy Cokes in real glass bottles sold for twenty cents. Aiding and abetting in this larceny was their mother, appropriately deemed Granny.

Early afternoons were sort of ad lib. I liked basketball but I was terrible. I detested tennis and I was terrible (notice the pattern to my athleticism). If one was truly cursed, you were scheduled for boating. We’d paddle endlessly around a tiny urban inlet. What could be better than to top off lunch with nausea?

Soon spirits would perk up as the counselor would shout “Get dressed for swimming!” Once again a furtive search for cover would lead me to the camp’s nether regions. On a good day, Jeff and I would go off and play

baseball. “Come on, I’ll let you hit,” I’d offer. Helplessly, he’d fall prey to the sirens of the diamonds. I can still remember thinking that we’d always be friends. Best friends. We always kept in touch, even during the school year. It was always great to get a phone call when I was little. Now, when one comes in, I wave like the grounds crew at a SAC base to avoid the call.

“Wow, the phone is for me!” It was always Jeff checking to see if I’d be back.

“Of course! Are you?”

“Yep!” “Great! I’ll see you in July.”

We’d always request to be together. Same group, same baseball team that always lost, and usually because of its pathetic right fielder avoiding dragonflies. I remember camp picture day. Every year, each team took a picture along with their counselor and, of course, the almighty group leader. He was the commander of all groups within one age range. What qualified these men to be entrusted with such power? That’s right: they were all relatives of Uncle Fred. There was Jerry for Chiefs (the oldest boys) and Mike for Junior Chiefs. If you did something wrong, he’d make you sit all day in the sun under the vent from the kitchen. I knew nothing about the girls groups. If you did, obviously you spent one summer too many at Brooklyn Day Camp. Anyway, one year Jeff and I decided to take the picture while holding up cards of our favorite ballplayers. It would be our secret. He held Willie Mays. I had The Mick. I still have that photo. We’d sit on the swings underneath the tallest trees I’d ever seen. We laughed as we kicked higher and higher. I was so relieved that he wanted to be a doctor, too. We were going to open a practice together. We even knew how the office was going to look.

You could smell the leather chairs and mahogany desks. We’d be partners.

Soon swimming was over and we could resurface. We’d return to our assigned lunch tables to get ice cream. Saturday brought the end of the camp week and with it came Awards Day. Each camper would get a button that read “swimming award” or “baseball award” or “clean table award” if the counselor happened to remember who dropped the lazy fly ball in deep right field.

At day’s end, everyone would line up for Flag Lowering. Standing at attention with baseball caps over our hearts, Old Glory would be lowered to a scratchy recording of “God Bless America.” Or was it “The Star Spangled Banner”? As soon as the last note was sung, Jeff and I would run to our bus to get a good seat. We always sat together. Yep, Jeff would be my best friend forever.

We were college freshmen when Jeff died. I guess sometimes that’s all forever lasts. Rare is the day without a reminder: a leather chair, a mahogany desk, a partnership offer. Each day I wonder: am I the physician we wanted to be?

Bernie’s Bluebird would cruise past Uncle Freddie and his kin. We’d wave and they’d wave back. We’d pass that elderly woman on our way out of Queens. We’d wave and she’d wave back. Just people. With Brooklyn Day Camp fading behind us, everything in life was simple—except how to play deep right field. v Creative Corner articles do not necessarily reflect the views of the Duval County Medical Society or DCMS Foundation.

Want to contribute to the Creative Corner? Email your submission to kristy@dcmsonline.org 66 Vol. 67, No. 3 2016 Northeast Florida Medicine

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