VOL. LIX • NO. 10 • 2019

VOLUME LX • NO. 10 • 2019

A fabulous holiday gift for anyone in medicine!

Pickup in Ridgeland for $49.95 or $57.95 includes shipping.

Order three or more to receive a discount at: http://tinyurl.com/yb7ab974 “ Images In Mississippi Medicine by Dr. Luke Lampton and Karen Evers is a handsome and impressive book,

filled with stories and scenes ranging from primitive operating rooms and rows of hospitalized tornado victims a century ago to the new teaching complex at the University of Mississippi Medical Center with its modern breakthroughs. The volume is a piece of our history that every Mississippian can appreciate.”

– Curtis Wilkie, journalist, author, and professor at Ole Miss

Images in Mississippi Medicine: A Photographic History of Medicine in Mississippi; MSMA; Jackson, MS: 2018.

VOL. LX • NO. 10 • OCTOBER 2019

SCIENCE OF MEDICINE

EDITOR Lucius M. Lampton, MD ASSOCIATE EDITORS D. Stanley Hartness, MD Philip T. Merideth, MD, JD

THE ASSOCIATION President J. Clay Hays, Jr., MD President-Elect W. Mark Horne, MD

MANAGING EDITOR Karen A. Evers

Secretary-Treasurer Joe Austin, MD

PUBLICATIONS COMMITTEE Sheila Bouldin, MD, Chair Dwalia S. South, MD, Chair Emeritus Thomas C. Dobbs, MD Wesley Youngblood, M4 and the Editors

Speaker Geri Lee Weiland, MD Vice Speaker Jeffrey A. Morris, MD Executive Director Claude D. Brunson, MD

JOURNAL OF THE MISSISSIPPI STATE MEDICAL ASSOCIATION (ISSN 0026-6396) is owned and published monthly by the Mississippi State Medical Association, founded 1856, located at 408 West Parkway Place, Ridgeland, Mississippi 39157. (ISSN# 0026-6396 as mandated by section E211.10, Domestic Mail Manual).

Periodicals postage paid at Jackson, MS and at additional mailing offices.

CORRESPONDENCE: Journal MSMA, Managing Editor, Karen A. Evers, P.O. Box 2548, Ridgeland, MS 39158-2548, Ph.: 601-853-6733, Fax: 601-853-6746, www.MSMAonline.com.

SUBSCRIPTION RATE: $83.00 per annum; $96.00 per annum for foreign subscriptions; $7.00 per copy, $10.00 per foreign copy, as available.

ADVERTISING RATES: furnished on request. Karen A. Evers, Journal MSMA, Managing Editor. Ph. 601-853-6733, ext. 323, Email: KEvers@MSMAonline.com POSTMASTER: send address changes to Journal of the Mississippi State Medical Association, P.O. Box 2548, Ridgeland, MS 39158-2548.

The views expressed in this publication reflect the opinions of the authors and do not necessarily state the opinions or policies of the Mississippi State Medical Association.

Copyright © 2019 Mississippi State Medical Association.

Official Publication

MSMA • Since 1959

Physicians Helping Physicians: A Template for Success Scott Hambleton, MD

324

Mumps Infection in a Previously Vaccinated Child with a Positive Rapid Strep Test: A Case Report 328

Jordan Sexe, OMSIV; Ned Miller, DO

Drug Testing in the Chronic Pain Management Population: Recommendations from the University of Mississippi Medical Center Opioid Task Force 331 Patrick B. Kyle, PhD; William E. Gusa Jr., MD; Ann M. Kemp, RPh, MD; Jefferson D. Parker, PhD; Rob Rockhold, PhD; Penny Rogers, DHA, MOT

Top 10 Facts You Should Know about Liver Disease Elizabeth R. Paine, MD

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DEPARTMENTS From the Editor – Curing Deafness Before Church Lucius M. Lampton, MD

322

Editorial – Touch Where It Hurts D. Stanley Hartness, MD

341

President’s Page – Transplant Medicine J. Clay Hayes, Jr., MD

344

Images in Medicine – Archie Jackson Stacy, Sr., MD Lucius M. Lampton, MD

345

Poetry and Medicine – Blood Transfusion Merrill Moore, MD

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New Members

348

RELATED ORGANIZATIONS Mississippi State Department of Health Reportable Disease Statistics

342

ABOUT THE COVER American Chameleon – Dermatologist Philip R. Loria, Jr., MD, took

this fall photograph of a young Anole lizard (Anolis carolinensis) on dried black-eyed Susan (Rudbeckia hirta) flowers in his front garden. Taken with a Nikon D40 with a Sigma 150 macro lens at 1/160 F7.1 ISO 400, this photo shows a line that runs along the dorsal surface, from the neck down the back, ending before the tail begins indicating this is likely a female. Males have a pink or red throat fan or dewlap. Anoles are often called chameleons because they can change color from bright green to brownish-green or dark brown in seconds, which can be triggered by temperature, background color or mood. A hormone called intermedin secreted by the pituitary gland is responsible for these changes. Darker brown and black colors, produced by melanophores, typically signal cold or stressed conditions. Green anoles tend to remain green when temperatures are more than 70°F., whereas they tend to remain brown during cool weather conditions. Color variation results from layers of pigmented cells called chromatophores. Three types of pigment cells are present: xanthophores, cyanophores, and melanophores, each responsible for distinct color variations. Many factors affect color change and variation; most often, it is dependent upon the climate and excitation, such as increased territorial activity or competition.

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Curing Deafness Before Church

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patient contacted me before church recently. She awoke stricken with panic. All of a sudden, she couldn’t hear out of her left ear. She was convinced that she had suffered a stroke or some other terrible malady and was filled with anxiety. In talking with her, I knew this was a problem, however minor medically, which could not wait. My patient needed me, and in my rural town with no ER, I got my otoscope and paid her a house Lucius M. Lampton, MD call. On examination, I discovered her Editor acute deafness was the result of a severe case of cerumen impaction. I used appropriate ear drops and performed an ear lavage and cured her deafness before church that Sunday morning.

Long ago, my senior partner encouraged me to surrender to being available to my patients, even if after hours. As his younger peers attempted to hide away whenever they could, he continued to list his telephone number in the phone book. Being available was elemental to his being a physician. Coming to mind after removing wax from my patient’s ear were the words of Jesus in the Bible, who asked the

Pharisees, after they looked sideways at him for healing on the Sabbath, “Which of you whose son or ox falls into a well, will not immediately pull him out on the Sabbath day?” (Luke 14:5) As Jesus relates, some medical urgencies must be dealt with immediately, even if that means an inconvenient time. Sometimes on the Sabbath, a physician must indeed pull the proverbial ox out of a well or even wash wax out of an ear!

A wise old physician once told me that the most important thing a doctor must be is available. No matter how brilliant, a physician is of little value to patients if that physician is absent. The patient-physician relationship requires the physician to be present and available. Physicians often fight this and evaporate when off duty, allowing their answering service or the ER to care for their patients at bothersome times. As you tend to the needs of your flock, remember that being available to them when they need you, even if on Sunday mornings before church, is one of the most important things you can do as a physician. n

Contact me at lukelampton@cableone.net.

— Lucius M. Lampton, MD, Editor

JOURNAL EDITORIAL ADVISORY BOARD ADDICTION MEDICINE Scott L. Hambleton, MD

EMERGENCY MEDICINE Philip Levin, MD

INTERNAL MEDICINE/EPIDEMIOLOGY Thomas E. Dobbs, MD

ALLERGY/IMMUNOLOGY Stephen B. LeBlanc, MD Patricia H. Stewart, MD

FAMILY MEDICINE Tim J. Alford, MD Diane K. Beebe, MD Jennifer J. Bryan, MD J. Edward Hill, MD Ben Earl Kitchens, MD

MEDICAL STUDENT John F. G. Bobo, M3

GASTROENTEROLOGY James Q. Sones, MD

OBSTETRICS & GYNECOLOGY Sidney W. Bondurant, MD Sheila Bouldin, MD Darden H. North, MD

ANESTHESIOLOGY Douglas R. Bacon, MD John W. Bethea, Jr., MD CARDIOVASCULAR DISEASE Thad F. Waites, MD CHILD & ADOLESCENT PSYCHIATRY John Elgin Wilkaitis, MD CLINICAL NEUROPHYSIOLOGY Alan R. Moore, MD DERMATOLOGY Robert T. Brodell, MD Adam C. Byrd, MD

GENERAL SURGERY Andrew C. Mallette, MD HEMATOLOGY Carter Milner, MD INFECTIOUS DISEASE Rathel "Skip" Nolen, III, MD INTERNAL MEDICINE Daniel P. Edney, MD Daniel W. Jones, MD Brett C. Lampton, MD

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NEPHROLOGY Harvey A. Gersh, MD Sohail Abdul Salim, MD

ORTHOPEDIC SURGERY Chris E. Wiggins, MD OTOLARYNGOLOGY Bradford J. Dye, III, MD PEDIATRIC OTOLARYNGOLOGY Jeffrey D. Carron, MD PEDIATRICS Michael Artigues, MD Owen B. Evans, MD

PLASTIC SURGERY William C. Lineaweaver, MD Chair, Journal Editorial Advisory Board PSYCHIATRY Beverly J. Bryant, MD June A. Powell, MD PUBLIC HEALTH Mary Margaret Currier, MD, MPH PULMONARY DISEASE Sharon P. Douglas, MD John R. Spurzem, MD RADIOLOGY P. H. (Hal) Moore, Jr., MD RESIDENT / FELLOW Cesar Cardenas, MD UROLOGY W. Lamar Weems, MD VASCULAR SURGERY Taimur Saleem, MD

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The MACM Claims Department spares no expense defending quality medicine and the reputation of our insureds. After all, that is the reason you purchase professional liability insurance.

Let us handle the X’s, so you can focus on the O’s.

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Physicians Helping Physicians: A Template for Success SCOTT HAMBLETON, MD Physician Health Programs and Safety Physician Health Programs (PHPs) have a well-documented history of tremendous success in rehabilitating physicians.1,2 Outcome data reported in one longitudinal study involving 16 PHPs indicated that 78% of the 904 physicians monitored for addictive disorders were sober after 5 years, without a single relapse. In Mississippi, 89.8% of the physicians monitored by the Mississippi Physician Health Program (MPHP) for addictive illnesses involving substances were sober, without a single relapse, in the 5-year period ending December 31, 2018. (Hambleton S. Annual Report to MPHP Board of Directors.

Update on MPHP participants. May 2019). With few exceptions, these documented long-term rates of recovery are unparalleled in the general population of individuals with addictive illnesses.

Additionally, physicians monitored by PHPs are safe physicians. In the previously mentioned study of 904 physicians, there was only one case of documented patient harm during the period of monitoring and that case involved improper prescribing. Another study demonstrated that PHP monitoring is associated with a lowered risk of malpractice claims and that physicians constituted a 20% lower risk than the matched cohort, after monitoring.3 Considering the epidemic of fatal drug overdoses in the United States, solutions to the underlying problem of addiction are desperately needed. The PHP approach to managing physicians with addictive disorders is unequivocally effective and hopefully will one day be utilized to help all individuals suffering from addictive illnesses.

Addiction, Impairment and Shame Like no other condition, addiction is an insidious and remarkably effective disease process that ravages sufferers and all those who know and love the sufferer. Many people who have recovered from addiction report a sense of unimaginable hopelessness during active addiction, in some cases believing that death is the only legitimate way out. Addiction adroitly protects itself as a disease process and without treatment will progress, ensuring that the sufferer afflicted with it will lose everything: spiritual connectedness, relationships with family and friends, health, self-respect, the ability to practice medicine and ultimately life itself.

Becoming a physician is an incredibly arduous process, and successfully enduring the rigors of medical education and training requires remarkable perseverance. Not surprisingly, physicians with addiction will attempt to exert control over their substance use so that it does not impact their ability to practice medicine safely. However, even in

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physicians, control over substance use diminishes as the addiction progresses and may result in overt impairment.

An important point is that untreated addiction in physicians does not always manifest with overt impairment, and illness often predates impairment by a period of years.1,2,4-7 Considering that addictive disorders are classified as mild, moderate or severe, it makes sense that earlier intervention is more efficacious than intervention in later stages of disease. Impairment is a functional classification, and an impaired physician is unable to fulfill patient care responsibilities safely and effectively. The risk of impairment is a primary reason to support early referral to a PHP to identify and treat addiction prior to its progression to functional impairment.

Shame is another prominent feature of addiction that contributes to the cycle of continuous substance use. Behavior that occurs during addiction is often harmful to others, and appropriate feelings of guilt, combined with the inability to stop using substances effectively, contribute powerfully to the addicted individual’s sense of shame.

Unfortunately, the stigma of addiction promotes secrecy and increases resistance to seeking or accepting treatment. Shame is especially prominent in physicians who are trained to function independently and are reluctant to ask for help. Unfortunately, during the process of training, many physicians incorporate the idea that asking for help is a sign of weakness, which fosters the need for even more secrecy and results in persistent, untreated addiction.

Why are PHPs so successful?

Physician Health Programs (PHPs) have been in existence since the 1970s and have continued to evolve, with increasing effectiveness.1,2,4-7 The Federation of State Physician Health Programs (FSPHP) is

the national membership organization for PHPs and an invaluable resource for the Mississippi Physician Health Program (MPHP), providing tremendous leadership and guidance to all PHPs for the last thirty years. Additionally, the Mississippi State Board of Medical Licensure (MSBML) consists of physician members and an Executive Director with extensive knowledge about physician impairment and recovery. The MSBML strongly supports MPHP and the rehabilitative approach.

PHPs utilize contingency management, a type of behavioral therapy rooted in the basis of operant conditioning which modifies behavior by reinforcement or punishment.8 Medical Boards are authorized to discipline a licensee and prohibit or restrict that licensee’s ability to practice medicine, which represents a highly effective stimulus to encourage compliance with PHP monitoring requirements. Ultimately, the promise of practicing medicine is a powerful reward or reinforcer that motivates physicians to comply with the monitoring process and is a major factor that contributes to PHP success. Quality treatment for addiction and long-term abstinence from addictive substances with intensive longitudinal monitoring utilizing prompt and meaningful consequences for non-compliance are the core elements that enable physician participants to recover from addictive illness successfully.

Drug Courts also have well documented success in reducing re-arrest rates for individuals with diagnosed substance use disorders who have been convicted of criminal offenses.9 Like PHPs, they utilize contingency management styled long-term monitoring of participants.

Cessation of substance use is documented with toxicology testing with positive tests resulting in prompt consequences, including incarceration.

Since the mid-1990s, Mississippi Physician Health Program (MPHP) has utilized a confidential, alternative-to-discipline monitoring process for physicians with potentially impairing substance use or mental health disorders. Before this, all referrals to MPHP were known and/ or disciplined by the Mississippi State Board of Medical Licensure (MSBML). By 1998, two years after MPHP began implementing a confidential monitoring process, the number of participants monitored by MPHP increased over 400%. Without the incentive of confidentiality, these physicians would not have participated in MPHP monitoring, continuing to practice medicine with untreated addiction, and increasing the likelihood that their addiction would progress to overt impairment and subsequent patient harm.

However, there are limits to confidentiality, and when a monitored physician participant in MPHP is unable or unwilling to comply with the monitoring process, MPHP is required to immediately notify the Mississippi State Board of Medical Licensure (MSBML) which may result in formal discipline, including licensure suspension or revocation.

When Medical Boards and PHPs work closely utilizing a confidential, rehabilitative approach, the incentive to participate in PHP monitoring increases dramatically, resulting in increased referrals to PHPs and earlier detection and treatment of addiction. Considering that over 95% of MPHP participants with addictive disorders are able to return to safe and productive medical practices and that other states with robust PHPs have similar rates of recovery it is apparent that PHPs functionally represent a “new paradigm” for addiction management,

effectively setting a new standard which demonstrates that recovery (rather than relapse) can be the expected outcome of treatment for addiction.

Mississippi Physician Health Committee Mississippi State Medical Association established the Mississippi Physician Health Committee (MPHC) to provide oversight and support to MPHP. MPHC consists of physicians who volunteer their time for free, providing the foundation of incredible experience and wisdom which supports all MPHP activities. Undoubtedly, MPHC is a major reason that the Mississippi Physician Health Program (MPHP) is so successful. MPHP primarily focuses on physicians with substance use disorders or other treatable psychiatric illnesses, as well as age related cognitive issues. MPHP also provides assistance and education related to professional burnout which now impacts the majority of practicing physicians.10 As a result of the charitable service of these MSMA members, MPHP has helped hundreds of doctors and their families to recover and, in some cases, from seemingly hopeless situations. None of these miracles would have been possible without the compassionate vision of our founders and the selfless service of the physician volunteers of the Mississippi Physician Health Committee.

National Epidemic of Drug Overdose Deaths: Physician Leadership Needed We are amid an epidemic of fatal drug overdoses unparalleled in our nation’s history. According to a report by the Council of Economic Advisors, the actual cost of the opioid crisis has been significantly underreported and likely exceeded $500 billion in 2015, representing 2.8% of GDP that year.11 Based on preliminary data, more than 68,000 Americans died from drug overdoses in 2018, which represents an actual decline from the estimated 70,000 drug overdose deaths in 2017.12 However, according to the Surgeon General’s Report on Alcohol, Drugs, and Health, which is the first report ever issued by the Surgeon General on the topic, one in seven Americans suffer from substance use disorders, and the vast majority will not receive treatment.13 As leaders of the healthcare team, physician direction is desperately needed. Considering the tens of millions of Americans suffering from addiction and that less than 13% receive treatment,14 a reasonable question is: How is this possible, in the United States? How is it possible that only 13% of the millions of Americans suffering from a treatable, potentially fatal illness receive treatment?

The Surgeon General explained that substance misuse has traditionally been seen as a social or criminal problem, and responsibility for treatment and prevention services was shifted away from health care systems to other entities, such as the criminal justice system.13 As a result, people needing care for substance use disorders have had access to a very limited range of treatment options that were generally not covered by insurance. The report recommends the integration of prevention, treatment, and recovery services across health care systems. It makes sense that physicians, as leaders of the healthcare team, will need to step up to the challenge to ensure significant and lasting change throughout the healthcare system.

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A Call for Action and Utilization of the PHP Model of Addiction Management Monumental change is necessary to effectively address the crisis of untreated addiction in the United States. The decrease in overdose fatalities in 2018 indicates that we are on the right track. However, increased education about addiction is needed at every level of healthcare and especially with physicians. Lack of understanding about addiction as a brain disease has negatively impacted the actual practice of medicine and is clearly an underlying cause of the inappropriate use of opioid pain medication which has fueled the crisis of opioid related fatalities in the United States.15 Ultimately, physicians are unequipped to manage addiction because of a lack of education.15,16 Physicians receive excellent education and training related to treating the medical problems caused by addiction, but very little education and training related to preventing, identifying or treating addiction itself. Education of medical students and residents about addiction is not commensurate with education about other chronic illnesses, such as diabetes or heart disease. A report by the National Center on Addiction and Substance Abuse at Columbia University (CASA Columbia) harshly criticized the medical profession at every level, stating that, “most medical professionals who should be providing addiction treatment are not sufficiently trained to diagnose or treat it.”

Fortunately, change is happening. In July 2016, the Comprehensive Addiction and Recovery Act (CARA) was signed into law, expanding access to patients for addiction treatment in the United States.17 The American College of Graduate Medical Education (ACGME) has begun to address the addiction related education gap in the United States with the development of program requirements for graduate medical education in addiction medicine.18 Additionally, the American Association of Medical Colleges is partnering with several universities, including Harvard Medical School and Boston University School of Medicine to utilize a new set of 10 core competencies to shape opioidrelated education and training. Many regulatory agencies require prescriber education related to prescribing controlled substances, including the Mississippi State Board of Medical Licensure.

Hopefully, as physician education evolves, the PHP model of addiction management will be utilized in the development of addiction related educational material, especially related to the concept of addiction as a brain disease and the possibility of lasting recovery. While it is true that addiction is characterized as a chronic, relapsing illness, the experience of PHPs suggests that lasting recovery from addiction is a very reasonable expectation.19 The Physician Health Program model of managing individuals with addictive disorders is unequivocally successful, and while presently this approach may not be feasible for all patients with addiction, optimistically it may one day become the template for managing addiction in all patients. n Acknowledgment: The author has no conflict of interest to disclose.

References 1. DuPont RL. Creating a new standard for addiction treatment outcomes: A report from the institute for behavior and health, inc. Institute for Behavior and Health, Inc. Rockville, MD. https://www.ibhinc.org/s/IBH_Report_Creating_a_ New_Standard_for_Addiction_Treatment_Outcomes.pdf Published Aug 2014.

Accessed June 21, 2019.

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2. McLellan AT, Skipper GE, Campbell MG, DuPont RL. Five-year outcomes in a cohort study of physicians treated for substance use disorders in the United States.

Brit Med J. 2008; 337:a2038. doi: 10.1136/bmj.a2038 3. Brooks E, Gendel MH, Gundersen DC, et al. Physician health programmes and malpractice claims: reducing risk through monitoring. Occup Med (Lond). 2013; 63(4):274-80. doi: 10.1093/occmed/kqt036. Epub 2013 Apr 19.

4. Candilis PJ, Kim DT, Sulmasy LS, for the ACP Ethics, Professionalism and Human Rights Committee. Physician impairment and rehabilitation: Reintegration into medical practice while ensuring patient safety: A position paper from the American College of Physicians. Annals Intern Med. 2019; 170:871–879. doi:10.7326/M183605 5. Carr GD, Hall PB, Finlayson R, DuPont RL. Physician health programs: The US model. In: Brower KJ, Riba MB, eds. Physician Mental Health and WellBeing: Research and Practice. Springer, Cham. https://link.springer.com/ chapter/10.1007%2F978-3-319-55583-6_12. Published July 5, 2017. Accessed August 1, 2019.

6. Merlo LJ, Teitelbaum SA, Thompson K. Substance use disorders in physicians: Assessment and treatment. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2018.

7. DuPont R. L., McLellan A. T., White W. L., Merlo L., and Gold M. S. Setting the standard for recovery: Physicians Health Programs evaluation review. J Subst Abuse Treat. 2009; 36(2), 159-171. http://citeseerx.ist.psu.edu/viewdoc/ download?doi=10.1.1.423.1766&rep=rep1&type=pdf. Accessed July 16, 2019.

8. Prendergast, M, Podus D, Finney J, Greenwell L, Roll J. Contingency management for treatment of substance use disorders: A meta-analysis. Addiction 2006; 101(11):1546–1560. doi: 10.1111/j.1360-0443.2006.01581.

9.

National Association of Drug Court Professionals. Adult drug court best practice standards: Volume I. Alexandria, VA: National Association of Drug Court Professionals. https://www.nadcp.org/wp-content/uploads/2018/12/ Adult-Drug-Court-Best-Practice-Standards-Volume-I-Text-RevisionDecember-2018-1.pdf. Revised Dec 2018. Accessed August 19, 2019.

10. Shanafelt T, Hasan O, Dyrbe LN, et al. Changes in burnout and satisfaction with work-life balance in physicians and the general US working population between 2011 and 2014. Mayo Clinic Proceedings. 2015; 90(12): 1600 – 1613. doi: 10.1016/j.mayocp.2015.08.023 11. The Whitehouse Council of Economic Advisors. Council of economic advisers report: The underestimated cost of the opioid crisis. https://www.whitehouse. gov/briefings-statements/cea-report-underestimated-cost-opioid-crisis/. Issued Nov 20, 2017. Accessed July 24, 2019.

12. Centers for Disease Control and Prevention. National Vital Statistics System. Vital statistics rapid release: Provisional drug overdose death counts. https://www.cdc. gov/nchs/nvss/vsrr/drug-overdose-data.htm. Accessed July 24, 2019.

13. U.S. Department of Health and Human Services (HHS), Office of the Surgeon General. Health care systems and substance use disorders. In: Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health [Internet].

Washington (DC): US Department of Health and Human Services. https:// addiction.surgeongeneral.gov/sites/default/files/surgeon-generals-report.pdf.

Published Nov 2016. Accessed June 21, 2019.

14. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2017 National Survey on Drug Use and Health. Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration; 2018. HHS Publication No. SMA 18-5068, NSDUH Series H-53. https://www.samhsa.gov/data/report/2017-nsduh-annual-national-report.

Published Sept 2018. Accessed June 21, 2019.

15. Wood E, Samet JH, Volkow ND. Physician education in addiction medicine.

JAMA. 2013; 310(16):1673–1674. doi:10.1001/jama.2013.280377.

16. National Centre on Addiction and Substance Abuse at Columbia University.

Addiction medicine: closing the gap between science and practice. 2012. http:// www.casacolumbia.org/upload/2012/20120626addictionmed.pdf. Published June 2012. Accessed July 27, 2019.

17. U.S. Congress. S. 524 (114th): Comprehensive Addiction and Recovery Act of 2016. 2016. https://www.govtrack.us/congress/bills/114/s524. Updated July 14, 2016. Accessed July 16, 2019.

18. Accreditation Council for Graduate Medical Education (ACGME). ACGME program requirements for graduate medical education in addiction medicine. https://www.acgme.org/Portals/0/PFAssets/ProgramRequirements/404_ AddictionMedicine_2019_TCC.pdf ?ver=2019-05-03-102431-393. Editorial revision effective July 1, 2019. Accessed August 27, 2019.

19.

American Society of Addiction Medicine. Public policy statement: Short definition of addiction. Chevy Chase, MD. American Society of Addiction Medicine; 2011. http://www.asam.org/docs/default-source/public-policystatements/1definition_of_addiction_short_4-11.pdf ?sfvrsn=0.

Published August 15, 2011. Accessed August 22, 2016.

Corresponding Author: Scott L. Hambleton, MD, DFASAM, Medical Director, Mississippi Physician Health Program, 408 West Parkway Place, Ridgeland, MS 39158-2548 Ph: (601)420-0240 (SHambleton@ MSPHP.com).

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xpress your opinion in the JMSMA through a letter to the editor or guest editorial. The Journal MSMA welcomes letters to the editor. Letters for publication should be less than 300 words. Guest editorials or comments may be longer, with an average of 600 words. All letters are subject to editing for length and clarity. If you are writing in response to a particular article, please mention the headline and issue date in your letter. Also include your contact information. While we do not publish street addresses, e-mail addresses, or telephone numbers, we do verify authorship, as well as clarify ambiguities, to protect our letterwriters. You can submit your letter via email to: KEvers@MSMAonline.com or mail it to the Journal office at MSMA headquarters: P.O. Box 2548, Ridgeland, MS 39158-2548.

Calling All Mississippi Physician-Photographers Enter the 2020 Journal Cover Photo Contest

Film or Digital Shoot anything you can capture as a high-resolution image. Subjects given the highest consideration are those indicative of Mississippi.

Photos of original artwork are also acceptable.

The MSMA Committee on Publications will judge the entries on the merits of quality, composition, originality, and appropriateness to the JMSMA. Specifications: Vertical composition.

Color slides, digital files & photos (at least 300 DPI/PPI). A hard copy print is required for judging.

Please include a brief description of the photo and information about the physician/photographer.

Submit your narrative of the image to appear as “About the cover” in the magazine.

Size: Vertical format 5 x 7” or 8 x 10” Deadline: January 1, 2020

For more info contact:

Karen Evers, Managing Editor 601-853-6733, ext. 323 or KEvers@MSMAonline.com

Mail to:

P.O. Box 2548 Ridgeland, MS 39158-2548 or deliver to MSMA headquarters 408 W. Parkway Place, Ridgeland, MS 39157

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Mumps Infection in a Previously Vaccinated Child with a Positive Rapid Strep Test: A Case Report JORDAN SEXE, OMSIV; NED MILLER, DO ABSTRACT Mumps is a viral infection largely prevented and controlled through vaccination in industrialized countries.1 However, there has been an increase in the number of mumps cases recently, which is hypothesized relative to factors such as lower than expected vaccine efficacy, vaccine strains not sufficiently covering wild strains, waning neutralizing antibodies, or an underestimate of the threshold for herd immunity.2 Of note, the rural community of West Point reported 5 new cases during November and December of 2018. This report details a pediatric case of mumps in a previously-vaccinated patient presenting with non-classic symptoms and a positive rapid strep test (RST). This case serves to reinforce the importance of avoiding “anchor bias” and to facilitate further discussion regarding the increasing incidence of mumps infections and the potential presentation of such cases.

Keywords: Mumps, pharyngitis, rapid strep test INTRODUCTION Mumps is a well-controlled and largely preventable viral illness through the work of routine childhood vaccines in industrialized countries.1 However, mumps infections have seen an increased incidence in recent years. This is especially true in groups that have close contact with many people, such as educational institutions.2 This is hypothesized to be related to factors such as lower than expected vaccine efficacy, vaccine strains not sufficiently covering wild strains, waning neutralizing antibodies, or an underestimate of the threshold for herd immunity.2 In this report, we describe a case of mumps that presented with nonclassic symptoms and a concomitantly positive rapid strep test (RST), which may have easily led to a misdiagnosis and an increased potential for serious complications such as aseptic meningitis, pancreatitis, or oophoritis.3 This case was further complicated by the mumps result requiring several days for a result in contrast to the relative immediacy of the RST. C CASE REPORT An 8-year-old female presented to our family medicine clinic on December 11, 2018, with a 5-day history of worsening fever, vomiting, nausea, abdominal pain, and diarrhea. The family reported temperatures of over 102 F and use of Ibuprofen. No immediate family members reported being sick. There had been 4 reported new cases of mumps within the local community; all documented cases had been ages 6 to 37 years, including several cases in the local school system.

The patient had a past medical history of acute pharyngitis, influenza A, and eczema. There was no past surgical history. The patient received 328 VOL. 60 • NO. 10 • 2019

all recommended childhood vaccines at appropriate times, including the MMR vaccine on Dec 9, 2011, and the MMRV vaccine on April 8, 2016. Vital signs were within normal limits, including an oral temperature of 99.3 F. The patient was alert, well nourished, and playful with good eye contact. The salivary glands were non-tender and noninflamed. The tonsillar pillars were Grade 1-2 with moderate erythema.

The posterior pharynx was moderately erythematous. The rest of the physical exam was normal.

LABS: A CBC was drawn and was unremarkable. A rapid strep test (RST) from a throat swab was positive. Peripheral blood testing for EBV VCA IgG, EBV VCA IgM, and EBNA antibodies was negative. A CRP level was elevated at 2.0 mg/ dL (reference < 1.0 mg/ dL). PCR testing for Adenovirus from a nasal swab was negative. A throat swab for Influenza A and B antigen was negative. Peripheral blood testing also showed a positive enzyme immunoassay for IgM antibodies to mumps virus with an index of 0.96 (reference 0.00 to 0.79). The mumps antibody IgG was also positive with an index of 2.2 (reference for vaccinated > 1.1), consistent with prior immunization. The mumps IgM and IgG results were not available to us until 2 days after collection as they required analysis by the Mayo Clinic Jacksonville Clinical Lab in Jacksonville, FL. TREATMENT: On the day of presentation, the patient was treated with intramuscular injections of 4 mg Dexamethasone and 600,000 Units of Penicillin G benzathine for streptococcal pharyngitis. The patient was also prescribed a 5-day course of 5 mg oral Prednisolone once daily and a 10-day course of 480 mg oral Amoxicillin twice daily.

On December 13, 2018, two days after presentation to the clinic, the positive mumps IgM result was made available to us. The patient’s father was contacted via phone and informed of the result. We counseled the father on preventative precautions, continuing the currently prescribed regimen, and indications to seek additional medical attention. Since the patient was given both an injection of steroids before leaving the clinic and prescribed a 5-day oral course, and since no specific therapy for mumps infection is currently recommended,3 no further medications were prescribed. The result was reported to the Mississippi State Department of Health in Jackson, MS by phone. The patient recovered uneventfully and is currently doing well.

DISCUSSION This case represents a complex clinical picture, as a positive RST in the presence of a positive mumps IgM result could represent several situations.

One explanation for these findings could be a false positive mumps IgM result. It has been reported that other viruses such as EpsteinBarr virus (EBV), parainfluenza 1, 2, and 3, adenovirus, and HHV-6 can cause a positive mumps IgM result.4 Our patient tested negative for both EBV and adenovirus on the day of initial presentation. The absence of respiratory symptoms, lower prevalence of parainfluenza infection during winter months, and the patient’s age being over 5 years effectively rule out a parainfluenza 1-3 infection.5 HHV-6 infection is unlikely due to the absence of a rash, no reported high-grade fever, and age over 3 years.6 Also, the specificity of a positive mumps IgM in previously vaccinated individuals has been reported to be 95.6 to 99.7%.7 Furthermore, the IgM response to mumps in vaccinated individuals has been reported to be lower and even absent due to viral shedding occurring at very low levels in these patients.8 Therefore, the index of suspicion for mumps infection with even marginally positive IgM levels in vaccinated individuals should be considered highly indicative of active or very recent mumps infection.

These findings could also be explained by a co-infection by both mumps virus and Group A Strep. A co-infection is possible due to the overlap of symptoms between each infection as well as both organisms having a peak incidence in the winter months. This explanation is also supported by the patient’s physical exam showing an erythematous pharynx, which suggests pharyngeal inflammation. Furthermore, this patient’s non-specific symptoms could have also been explained by being in the prodromal stage of mumps, which may present with nonspecific constitutional symptoms.3 It should be noted that up to 50% of the population will display only non-specific symptoms when infected with mumps, and that an additional 20% may be asymptomatic.3 A third potential explanation could be that the patient is a chronic carrier of GAS. This patient had been diagnosed previously with acute pharyngitis, and it is possible that the patient did not receive adequate antibiotic therapy, which could result in incomplete resolution of GAS colonization despite symptom resolution.9 To investigate this possibility further, at the patient’s follow-up visit approximately 2 weeks after initial presentation to our clinic, we performed another RST. The result of this test was negative. Our clinic uses the BD Veritor brand of RST, which has a reported sensitivity of 76.2%.10 A negative RST in the absence of pharyngitis symptoms and physical exam findings suggests that this patient is not currently a chronic strep carrier. However, it should be noted that the patient received an IM dose of Penicillin in addition to 10 days of oral Amoxicillin after she was initially diagnosed with streptococcal pharyngitis, which may have eradicated potential GAS colonization.

Another explanation for these findings could be a false positive RST. Our clinic uses the BD Veritor brand of RST, which has a reported specificity of 93.6%.10 This would make a false positive RST statistically unlikely. In addition, this patient had moderately erythematous Grade 1-2 tonsils, further suggesting active pharyngitis.

This patient’s clinical picture and laboratory findings combined with the increased number of mumps cases within the local community imply a mumps virus infection. The ease and convenience of the inoffice RST may provoke an “anchor bias” when evaluating patients with nonspecific exam findings and contribute to a misdiagnosis of a potentially serious condition.

It should be noted that the administration of steroids for mumps and pharyngitis is outside of the standard therapy.11,12 Steroid administration has been reported to reduce inflammatory symptoms,13 so it was decided to treat this patient’s worsening symptoms with an intramuscular dose of Dexamethasone in addition to a 5-day oral course of Prednisone. However, the use of steroids for streptococcal pharyngitis is not recommended as the side effect profile does not outweigh the potential benefits. This patient also received dual antibiotic therapy (intramuscular Penicillin G benzathine and oral Amoxicillin) to prevent progression of the patient’s symptoms and promote eradication of streptococcal colonization. This is outside of the standard therapy of 10 days of oral Penicillin, and we do not recommend dual antibiotic therapy for streptococcal pharyngitis.12 CONCLUSIONS In this case, we stressed the importance of the increasing incidence of mumps infections and how these infections may potentially present in previously-vaccinated patients. This case also serves to encourage knowledge of local epidemiologic patterns and thorough clinical decision making in the midst of easier explanations. n Acknowledgment: The authors have no conflicts of interest to disclose.

REFERENCES 1. Rubin S, Eckhaus M, Rennick LJ, et al. Molecular biology, pathogenesis and pathology of mumps virus. J Pathol. 2015;235(2):242-52. doi: 10.1002/path.4445.

2. Quinlisk MP. Mumps control today. J Infect Dis. 2010;202(5):655–656. doi: 10.1086/655395.

3. White SJ, Boldt KL, Holditch SJ, Poland GA, Jacobson RM. Measles, mumps, and rubella. Clin obstet gyn. 2012;55(2):550. doi: 10.1097/GRF.0b013e31824df256.

4. Mumps — laboratory confirmation by IgM serology and questions and answers.

Centers for Disease Control and Prevention website. https://www.cdc.gov/ mumps/lab/overview-serology.html#positive-igm. Published November 2017.

Accessed January 7, 2019.

5. Centers for Disease Control and Prevention. Human parainfluenza viruses clinical overview. Centers for Disease Control and Prevention. https://www.cdc. gov/parainfluenza/hcp/clinical.html. Published October 2017. Accessed January 7, 2019.

6. Hall CB, Long CE, Schnabel KC, et al. Human herpesvirus-6 infection in children: a prospective study of complications and reactivation. N Engl J Med. 1994;331:432438. doi: 10.1056/NEJM199408183310703.

7. Hatchette T, Davidson R, Clay S, et al. Laboratory diagnosis of mumps in a partially immunized population: the nova scotia experience. Can J Infect Dis Med Microbiol.

2009;20(4):157-62.

8. Trotz-Williams LA, Mercer NJ, Paphitis K, et al. Challenges in interpretation of diagnostic test results in a mumps outbreak in a highly vaccinated population. Clin Vaccine Immunol. 2017;24(2):e00542-16. Published 2017 Feb 6. doi:10.1128/ CVI.00542-16.

9. X DeMuri GP, Wald ER. The group A streptococcal carrier state reviewed: still an enigma. J Pediatric Infect Dis Soc. 2014;3(4):336-342. doi: 10.1093/jpids/piu030.

10. Berry GJ, Miller CR, Prats MM, et al. Comparison of the alere i strep A test and the bd veritor system in the detection of group a streptococcus and the hypothetical impact of results on antibiotic utilization. J Clin Microbiol. 2018;56(3):e01310-17.

Published 2018 Feb 22. doi: 10.1128/JCM.01310-17.

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11. Albrecht MA. Mumps. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/mumps? search=mumps%20treatment& sectionRank=1&usage_type=default&anchor=H30&source=machine Learning&selectedTitle=1~150&display_rank=1#H30. Published May 17, 2019.

Accessed Nov 6, 2019.

12. Pichichero ME. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https:// www.uptodate.com/contents/treatment-and-prevention-of-streptococcalpharyngitis?search=pharyngitis%20steroid&topicRef=2875&source=see_ link#H4122245295. Published Oct 10, 2019. Accessed Nov 6, 2019.

13. Drutz JE. Sore throat in children and adolescents: symptomatic treatment. UpToDate.

Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/sore-throatin-children-and-adolescents-symptomatic-treatment?search=pharyngitis%20 steroid&source=search_result&selectedTitle=2~150&usage_type=default& display_rank=2#H595059845. Published May 23, 2018. Accessed November 6, 2019.

Author Information Author Information: Fourth-year medical student, William Carey University College of Osteopathic Medicine, Hattiesburg (Sexe).

Family medicine physician, West Point Medical Clinic-North Mississippi Medical Center. Adjunct Clinical Professor, William Carey University College of Osteopathic Medicine (Miller).

Corresponding Author: Jordan Sexe, Columbus, MS 39705.

Ph: (515)890-8532 (Jsexe356167@student.wmcarey.edu).

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Drug Testing in the Chronic Pain Management Population: Recommendations from the University of Mississippi Medical Center Opioid Task Force PATRICK B. KYLE, PHD; WILLIAM E. GUSA JR., MD; ANN M. KEMP, RPH, MD; JEFFERSON D. PARKER, PHD; ROB ROCKHOLD, PHD, FAPE; PENNY ROGERS, DHA, MAT, OTR/L Abstract New Mississippi State Board of Medical Licensure prescribing regulations require drug screening when opioids are prescribed for chronic pain management. Urine drug testing (UDT) is commonly used to assess patient adherence with prescription therapies and detect possible substance misuse.

Recognizing the complexities of accurate specimen collection, testing modalities, interpretation of laboratory results, and the potential for urine adulteration, this article presents evidence-based UDT recommendations to assist providers. While immunoassay tests can be a relatively inexpensive and rapid means of assessing opioid use and ruling out misuse of other substances, there are limitations of which practitioners must be aware. Mass spectrometry is generally more expensive and lengthy but offers greater sensitivity and accuracy for the confirmation of immunoassay results. Providers should recognize the limitations of both forms of testing and are encouraged to seek guidance from laboratory testing professionals whenever needed.

Keywords: Pain management, urine drug testing, test interpretation Introduction Changes in the application of opioid pharmacotherapy to manage acute and chronic pain are occurring nationwide, being driven, at least in part, by highly publicized increases in morbidity and mortality that have been associated with opioid prescribing practices over the past two decades.1 The Mississippi State Board of Medical Licensure (MSBML) recently implemented changes to prescribing regulations in the Mississippi Code, Regulation Title 30:2640 Prescribing, Administering, and Dispensing, Rule 1.1-1.16.2 The new rules parallel much of the CDC guidelines for Prescribing Opioids for Chronic Pain3 and were implemented in an effort to decrease the morbidity and mortality associated with opioid use disorder and misuse.4 In 2018, the University of Mississippi Medical Center assembled an Opioid Task Force (OTF) composed of specialists in addiction medicine, anesthesiology, clinical toxicology, family medicine, laboratory analytical practice, medical education, pain management, and other specialties. The objective of this group is to educate our healthcare professionals and learners on best practices for prescribing, pain management treatment, substance use disorders, laboratory testing, and Mississippi prescribing regulations. The Opioid Task Force also seeks to establish recommendations that provide guidance to educators and practitioners seeking to respond to the changing health care environment. The purpose of the present recommendation is to provide an evidence-based approach to the availability, selection, and specificity of laboratory (drug) testing commonly encountered during opioid use, and to guide practitioners in establishing procedures to obtain the most accurate specimens for laboratory assessment.

The primary changes in the prescribing regulations for opioids in Mississippi are summarized in Table 1. Please note that points in the table are listed as a

tool to assist providers in summarizing some of the regulations. All providers should visit the MSBML website (http://www.msbml.ms.gov/Regulation_ Filings) to view the actual regulation changes themselves. As noted above, regular drug testing is now required for individuals receiving chronic opioid therapy for chronic noncancerous / nonterminal pain, and there are multiple reasons for this. Although many patients prescribed controlled substances use them responsibly and as directed by their providers, some do not. Some patients are known to mix potentially harmful illicit drugs with prescribed opioids. Testing this patient population assists providers in identifying patients that are using/abusing prescription, illicit or other mood altering drugs. It is not only illicit drugs that can be potentially dangerous when mixed with opioids. The FDA has issued a black box warning for the concomitant prescription of opioids and benzodiazepines due to exponentially increased risk of misuse, abuse, addiction, overdose and death.5 Another reason to test this patient population involves diversion and the lucrative practice of selling prescription opioids. Some patients participate in “doctor shopping” in order to acquire several prescriptions that they may sell.

As one example, the current street price of a single 5-10 mg hydrocodone/ oxycodone tablet is $5-$10 USD, whereas an extended-release tablet may bring $40-$80 USD each.6,7 An individual could easily sell the contents of a 30-day prescription for over $1,500. Sometimes patients feign injuries in order to obtain prescription medications, and addicted individuals may injure themselves in order to receive opioid therapy. Both of these populations contribute to the problem of opioid use disorder. Therefore, drug testing should be employed in order to: a) ascertain prescription compliance as well as b) evaluate the use of other controlled substances and illicit drugs.

Types of Urine Drug Testing Two primary methodologies are currently used for drug testing: immunoassay screening and chromatography with mass spectrometry. Explanations of these follow.

Immunoassay Screening Immunoassay urine screens are the most common tests employed for screening purposes because they are available on automated chemistry analyzers, offer rapid results, and can be inexpensive. More recently, immunoassay screens have been adapted to lateral flow devices that function in the same manner as common home pregnancy tests. Some lateral flow devices have even been incorporated into urine specimen containers that may also be used for specimen collection. At a minimum, the MSBML requires regular immunoassay screening as these tests allow clinicians to determine if opiates/ benzodiazepines are present quickly and commonly abused drugs are absent.

However, the sensitivity of immunoassay tests varies from manufacturer to manufacturer. Clinicians should be aware that immunoassay screening techniques exhibit significant shortcomings and are often inadequate for monitoring patients treated for chronic pain.8 OCTOBER • JOURNAL MSMA

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2 Table 1. Summary Recent Changes in Opioid Prescribing Regulations in Mississippi.2 Table 1. Summary of RecentofChanges in Opioid Prescribing Regulations in Mississippi.

1.

Use caution when prescribing controlled substances.

2.

Review the Mississippi Prescription Monitoring Program database (MPMP) prior to each outpatient opioid or benzodiazepine prescription; document review of the MPMP in the patient chart. Practitioners should note that the MPMP does not include controlled substances administered in a clinic, inpatient, or emergency department setting.

3.

Document MPMP review of all other controlled substance prescriptions and at least every 3 months thereafter (exceptions include: amphetamines for patients <16 y/o, Lomotil, Lyrica, pseudoephedrine, and testosterone).

4.

Order point of service drug testing 3 times per year if prescribing Schedule II opioids for chronic noncancerous/nonterminal pain, or benzodiazepines for chronic psychiatric or medical conditions.

5.

Limit each individual prescription for acute pain opioid treatment to 3-10 days.

6.

Prescribe the lowest effective dose.

7.

Strive to keep opioid total below 50 Morphine Milligram Equivalent (MME)/day and avoid 90 MME/day or greater for chronic noncancerous/nonterminal pain.

8.

Refer the patient for a consultation with a pain specialist if 100 MME/day or greater is indicated for chronic noncancerous/nonterminal pain in order to verify or optimize the current treatment plan.

9.

Avoid prescribing benzodiazepines, opioids and/or carisoprodol together unless documentation supports medical necessity.

10. Follow prescribing requirements for chronic noncancerous/nonterminal pain.

All providers are encouraged to visit the Mississippi State Board of Medical Licensure (MSBML) website (http://www.msbml.ms.gov/Regulation_Filings) to view the actual regulation changes.

Immunoassay deficiencies include: a) False-positive results. Immunoassay screens are formulated to detect multiple compounds in a class of drugs. As a result, positive results may be caused by structurally similar but unrelated compounds. b) False-negative results. Immunoassay screens may exhibit negative results with low drug concentrations and with newer synthetic or semisynthetic compounds that do not cross-react with the immunoassay. Examples include oxycodone, fentanyl, and tramadol not being detected by an opiate immunoassay.

Mass Spectrometry Testing Tests involving chromatography coupled with mass spectrometry offer improved sensitivity and specificity compared to immunoassay screens. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatographymass spectrometry (LC-MS) are gold standard techniques for drug identification in forensic analyses.9,10 These mass spectrometry analyses also have high clinical utility for monitoring drug therapy in pain management patients. Mass spectrometry analyses are typically used for a) drug confirmation and/or b) comprehensive testing.

Drug Confirmation The confirmation of a positive drug class is typically performed using mass spectrometry after a positive immunoassay result. Mass spectrometry confirmation is a targeted analysis that identifies individual compounds and is recommended for monitoring chronic noncancerous / nonterminal pain management patients.11,12 Parent drugs and one or more metabolites (i.e., oxycodone, noroxycodone) are often identified by mass spectrometry. The presence of metabolites assures that metabolism, instead of drug spiking such

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as pill scraping (illustrated below), has occurred. A targeted drug confirmation may also be requested when false-negative results are suspected or for drug classes in which there are no immunoassay tests available as in the synthetic opioids and synthetic cannabinoids.

Comprehensive Testing Comprehensive mass spectrometry testing offers positive drug identification in a comprehensive but untargeted analysis. Current mass spectrometry libraries contain 2,000-4,000 compounds that include illicit street drugs, synthetic designer drugs, prescription medications, over-the-counter medications, pesticides, and chemicals. Analytes such as caffeine, ibuprofen, nicotine, carisoprodol, and meprobamate are commonly detected in pain management patients using untargeted mass spectrometry testing. The identification of common OTC or prescribed compounds can increase the confidence of specimen validity when subversion is suspected.13 Due to its high sensitivity and specificity, mass spectrometry analysis has been recommended by several guidelines.11 It should be recognized that an untargeted screen can miss compounds that may be highly lipophilic or thermally unstable. For this reason, immunoassay screens still confer valuable information to the clinical personnel.

Test Cost The cost for drug testing ranges widely and is determined by the tests performed which vary from laboratory to laboratory. Inexpensive point-ofcare immunoassay cups or cards typically range from $10 to $50, whereas laboratory-performed immunoassay panels generally range from $30-$300.

These prices are highly dependent on the number of drug classes, specimen validity tests, temperature strips, and other options that may be included.

Mass spectrometry testing, although more complex, can range from $35-$100 for confirmation of a single drug class. Comprehensive mass spectrometry testing is the most complex and generally ranges from $200-$300, costs

6.

Prescribed the lowest effective dose.

7.

Strive to keep opioid total below 50 Morphine Milligram Equivalent (MME)/day greater for chronic noncancerous/nonterminal pain. that are not significantly different from immunoassay panels obtained in the an addiction medicine specialist? More information is needed. for a consultation a pain specialist if 100 inpatient setting. In general, inpatient hospital charges will be higher8.thanRefer patientIt is known that codeinewith is metabolized to morphine, but MME/day morphine or greater in order to verify optimize current treatm outpatient or reference lab charges due to the increased overhead required fornoncancerous/nonterminal is not metabolizedpain to codeine (Figure 1). or However, lowthe levels nursing staff, administration, building maintenance, and other factors. of contaminants are allowed in pharmaceutical manufacturing 9. Avoid prescribing benzodiazepines, opioids and/or carisoprodol together. processes. The USP allows up to 0.5% codeine as a contaminant 14-16 Interpretation of Results in the production of morphine indicated in Table 2. The 10. Follow prescribing requirements for chronicasnoncancerous/nonterminal pain.

Some scenarios may require thoughtful interpretation and/or additional concentrations of morphine and codeine are needed in order to providers are determine encouraged visit the website (http://www.msbml.ms.gov testing. The following vignette recently occurred in an outpatient clinicAlland if thetocodeine wasMSBML a contaminant or was taken as a nonview the actual regulation changes. Consultation with the laboratory revealed illustrates many key differences in immunoassay versus mass spectrometry prescribed medication. testing. Several thought-provoking questions are also included for the reader’s that the morphine concentration was 300,000 ng/ml, and codeine consideration. was 53 ng/ml making this likely a result of impurity allowed in the manufacturing process.

A cancer patient was prescribed extended-release morphine sulfate 200 mg BID and oxycodone/acetaminophen 10/325 mg QID prn for breakthrough pain. During the last two visits, the patient related that he had run out of his Table 2. Impurities Allowed in USP Pharmaceutical Preparations.14-16 14-16 oxycodone as his pain has increased which required extra Table 2. Impurities allowed in USP pharmaceutical preparations. pills. Despite being out of breakthrough medication for 5 days, the patient appears relatively comfortable in the exam Process Allowable Typically room. You decide to obtain a urine drug screen, and the Formulation Impurities Limit (%) Observed (%) immunoassay results are positive for opiates but negative for an oxycodone-specific screen.

Codeine Morphine 0.15 0.01 - 0.1

What is your interpretation of the patient’s clinical presentation and lab results?

These immunoassay results are expected given the patient’s morphine use and no oxycodone for 5 days. You then decide to request confirmation of the immunoassay results to identify definitive medications. The patient’s opioid confirmation by mass spectrometry is positive for morphine, hydromorphone, dihydrocodeine, noroxycodone and hydrocodone. A review of the patient’s MPMP information indicates only morphine and oxycodone/acetaminophen prescriptions for the last 12 months.

Hydrocodone

Codeine

0.15

0 - 0.1

Hydromorphone

Morphine

0.15

0 - 0.025

Hydrocodone

0.10

0 - 0.025

Codeine

0.50

0.01 - 0.05

Oxycodone

Hydrocodone

1.00

0.02 - 0.12

Oxymorphone

Hydromorphone

0.15

0.03 - 0.1

Oxycodone

0.50

0.05 - 0.4

Morphine

What do these lab results indicate?

The morphine was prescribed. The hydromorphone was not prescribed but was a metabolite of morphine. The hydrocodone was not prescribed and produced the metabolites hydromorphone and dihydrocodeine. Noroxycodone was a metabolite of the oxycodone that was prescribed. These results are consistent with the patient taking his morphine, not having oxycodone for a few days, and taking hydrocodone from an unknown source. The patient was confronted with the results and admitted to having an older prescription at home which he consumed because he was out of oxycodone. You discussed with the patient that all old medications must be appropriately destroyed and that future noncompliant drug test results may lead to the discontinuation of opioids. The patient is seen one month later, and his urine immunoassay screen is positive for opiates and oxycodone which is appropriate for his prescribed medications. The subsequent opioid confirmation is positive for morphine, oxymorphone, codeine, noroxycodone and oxycodone.

What do these lab results indicate?

The morphine was prescribed. The oxycodone was prescribed and produced the metabolites oxymorphone and noroxycodone. The codeine was not prescribed.

Is the patient noncompliant with his prescribed medications again?

Should you start weaning him off of his medications, or refer him to

The following scenarios may also occur.

False-negative Immunoassay Results Case 1: A patient using PRN medications or one that has a dilute urine specimen may have false-negative results. In these instances, the prescribed drug may be present but below the cutoff concentration required for a positive result. It may be helpful to consider the date of the patient’s last dose in relation to typical detection windows in urine (Table 3). Confirmation testing with mass spectrometry which is more sensitive to lower concentrations may be clinically indicated in this scenario.

Case 2: A patient prescribed synthetic or semisynthetic opioids may have a false-negative immunoassay result due to the structural differences of these compounds compared to the opiates.

Oftentimes opioids such as oxycodone, buprenorphine, fentanyl, meperidine, and tramadol do not react with opiate immunoassays, but this is manufacturer dependent. Similarly, benzodiazepine immunoassays are typically engineered to detect diazepam, nordiazepam, and oxazepam but may not be sufficiently sensitive to clonazepam, lorazepam, or other benzodiazepines. If a compound of interest is not detected by an immunoassay screen, then confirmation by mass spectrometry may be clinically indicated.

Case 3: A patient who consumes frequently abused substances that are not typically detected by immunoassay panels would have a false-negative immunoassay result. Commonly abused substances such as dextromethorphan, gabapentin, mitragynine,

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Table 3. Estimated detection windows for common drugs of abuse in urine.17-19

Table 3. Estimated Detection Windows for Common Drugs of Abuse in Urine.17-19 False-Positive Immunoassay Results

Compound Alcohol Ethanol Ethyl Glucuronide Ethyl Sulfate Amphetamines Amphetamine Methamphetamine MDMA Barbiturates Short-acting (pentobarbital) Intermediate (butalbital) Long-Acting (phenobarbital) Benzodiazepines Short-acting (lorazepam) Long-acting (diazepam) Cocaine Cocaine Cocaine metabolites Marijuana Occasional use (1x-2x/week) Daily use Chronic heavy use Opioids Buprenorphine Fentanyl Hydrocodone Hydromorphone Methadone Oxycodone Phencyclidine (PCP)

Detection Time 7-12 hours 1-3 days 1-3 days 2-3 days 2-3 days 2 days 3 days 7 days 15 days 3-5 days 10 days <1 day 2-4 days 3 days 10-15 days 30 days 7 days 3 days 2-4 days 2-4 days 3 days 2-4 days 8 days

promethazine are not typically detected on immunoassays. If detection of such use is needed clinically, comprehensive mass spectrometry would be needed.

Case 4: A patient using illicit drugs or another person’s prescription medications may adulterate his voided urine with water, hand soap, or other products. This can render some analytes undetectable by interfering with the test system. The use of specimen validity tests (pH, specific gravity, creatinine) can resolve acceptable specimens from those deemed dilute or as per published federal guidelines.20 Case 5: A patient using illicit drugs or another person’s prescription medications may submit another person’s urine or synthetic urine for a drug test. Negative immunoassay and negative mass spectrometry results would occur. This scenario is best prevented by observed collection and/or use of temperature strips on the collection containers.

334 VOL. 60 • NO. 10 • 2019

Case 6: False-positive immunoassay results may occur from the presence of structurally similar but unrelated compounds. In one manufacturer’s amphetamine immunoassay, false-positive results can occur from pseudoephedrine, phentermine, and phenylpropanolamine, whereas false-positive benzodiazepine results can occur from the NSAID oxaprozin. Mass spectrometry confirmation would yield a “negative” result because no amphetamines or benzodiazepines were present. Similarly, comprehensive mass spectrometry analysis would yield negative results for amphetamines/benzodiazepines, and the cross-reacting substances would likely be identified.

Case 7: A patient who is selling (diverting) his prescription medications may scrape or dip a prescription tablet into his voided urine, which will produce a positive immunoassay result even though the patient is not taking his medication. Mass spectrometry confirmation would identify the compound from the tablet, but no metabolites.

Unexpected Results Case 8: A patient who takes his opiate prescription as indicated tests positive by immunoassay and multiple opiates are detected upon mass spectrometry confirmation. This may result from the normal metabolism of the parent compound. The metabolic pathways of common opiates and their metabolites are indicated in Figure 1.

Case 9: A patient taking a high dose of one medication (example: oxycodone) may also test positive for a similar but different Figure 1. Metabolic Pathways of Common Opiates.

compound (example: hydrocodone).

The United States Pharmacopeia manufacturing practices allow small amounts of impurities in pharmaceutical preparations14-16, as indicated in Table 2. High doses (>100 mg/day morphine) are typically required for the pharmaceutical impurity to be detected. Although infrequently encountered, this scenario can cloud the interpretation of results.

It is important to remember that no test is perfect and that practitioners must rely on their clinical judgment. Most guidelines recommend the use of drug testing as only one tool in the practice of pain management. If an unexpected test result is obtained, the provider may wish to contact a laboratory expert for assistance with interpretation or to request additional testing. We recommend that confirmatory testing be performed before changing a patient’s treatment plan.

Specimen Collection The requirement for point of service drug testing brings into sharp focus the preparation of clinics and offices for accurate collection of biological specimens. Some patients may be motivated to use deception to obtain normal/expected drug screen results. Deceptive practices may include specimen adulteration, specimen dilution, or specimen substitution. It is for these reasons that a discussion of best practices may be needed for the treating clinician. The U.S. Department of Transportation maintains a rigorous drug testing program and published a manual that details the specimen collection methods most likely to yield unadulterated and unsubstituted urine samples.21 Since the collection and analysis of spontaneously voided urine are commonly used to assess patient compliance, the following recommendations are offered by the University of Mississippi Medical Center’s Opioid Task Force (OTF).

Recommendations for the Collection of Urine 1) Remove all cleaning supplies (ammonia, bleach, etc.) from the collection room prior to use. Some cleaning agents can be used as oxidants to alter drugs within the urine which can skew drug screen results.

2) Observed specimen collection is recommended, whenever feasible, in order to ensure the accuracy of results. Inexpensive, available synthetic urine products are commercially available via the internet as well as at local convenience stores. Many of these products are formulated to mimic physiologic pH, specific gravity, creatinine, and are synthesized to yield negative drug screen results when tested.

Most are supplied with instructions for substitution, including directions for heating and concealment. Some manufacturers offer concealable pouches with male or female prosthetic devices used to dispense synthetic urine. The observed collection is the only means to reduce the rate of urine substitution with synthetic products reliably. However, the OTF readily recognizes that observed specimen collection may not be practical for a busy clinical practice.

3) Add dye to the toilet water and inactivate lavatory faucets if an observed collection is not feasible (Figure 2). These measures will prevent patients from diluting a specimen with water, which is often performed to prevent the detection of illicit substances.22 Tip: Turn off the hot/cold water supply valves for the lavatory and, if possible, remove the valve handles. Each valve handle is typically secured with a single screw. Most handles are keyed/slotted and can simply be pressed on to open/close the valve. This allows staff to operate the valves without having to reattach them with a tool. Collection sites may also be outfitted with water valves outside the collection room.

4) Use a specimen collection cup or container that incorporates a thermometer strip. The temperature indicated on the strip should be recorded in order to verify the physiologic temperature of the specimen. Urine specimens should not be accepted with temperatures less than 90 degrees Fahrenheit.

5) Seal and label the specimen as soon as possible to prevent contamination and the potential for mislabeling.

6) Submit the specimen to the laboratory immediately. Samples that cannot be sent immediately should be refrigerated until analysis.

Figure 2. Specimen Collection Adjustments to Toilet Water and Lavatory.

LEFT Colored dye added to the toilet can help prevent and identify specimen dilution from toilet water. RIGHT Lavatory water can be inactivated by the control valves and handles easily removed via a single screw as indicated by the arrow.

Orders for Laboratory Testing Minimum testing should include immunoassay screens and the confirmation of positive results. Confirmation is necessary to identify the exact parent drugs and/or verify the presence of metabolites.

1) Ideally, immunoassay screening, confirmation of positive results, and comprehensive mass spectrometry testing should be ordered.

This combination offers sensitive and comprehensive results.23 Clinicians should confer with the laboratory to verify the drugs that will be detected. Relating the patient’s current prescription information to the laboratory during the test order process may be helpful.

2) Specimen validity tests should be ordered if available. Specimen validity tests typically include pH, specific gravity and creatinine, and help ensure that the specimen has not been diluted.

Testing Frequency Several groups and agencies recommend urine drug testing upon initiation of therapy and once per year thereafter for low-risk patients.23-25 More frequent testing is recommended for moderate- and high-risk patients or if any red flags are noted. Indicators may include suspicious drug screen results, changes in behavior, or requests for early prescription refills. It should be noted that the current requirement in Mississippi is to test three times yearly for chronic non-cancer pain patients on opioids and patients being prescribed benzodiazepines.2 Testing Schedule Should drug testing for the pain management population be scheduled or random? There are two important reasons that random UDT may have more value in detecting abuse as patients. The first is that, when testing is scheduled or linked to an appointment, patients fearing a positive test result may load up on fluids, use a commercial “detox” product, temporarily suspend their drug abuse,26 or simply cancel or not appear for their appointment.27 The second reason is that random UDT has been shown to cause a “reactive effect” or “treatment effect” in which the patient truly decreases his illicit drug use. The strength of this effect is related to the frequency of random testing and the contingent value of prescriber-provided pain management.28,29

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Summary This Best Practice article has been written to offer providers, educators and learners a guide for appropriate and effective drug testing. Changes in prescribing regulations for managing chronic pain have made the necessity of drug testing a reality. Each Mississippi provider has a responsibility to review the changes on the MSBML site. Urine drug screening is a tool for monitoring the chronic pain management patient with benefits and limitations as described above. The provider should be aware of those and make the decision based on the objective data as well as clinical judgment. If a drug screen result is not congruent with the clinical expectation, a provider should rely on clinical judgement and if necessary seek assistance with appropriate toxicology or laboratory personnel. n Acknowledgments The authors would like to gratefully acknowledge Dr. Claude Brunson, Past President of the Mississippi State Board of Medical Licensure, for assisting in the review of this manuscript. The authors report no conflicts of interest.

References

15. West R, Crews B, Mikel C, et al. Anomalous observations of codeine in patients on morphine. Ther Drug Monit. 2009;31:776-8.

16. West R, West C, Crews B, et al. Anomalous observations of hydrocodone in patients on oxycodone. Clin Chim Acta. 2011;412:29-32.

17. Nelson ZJ, Stellpflug SJ, Engebretsen KM. What can a urine drug screening immunoassay really tell us? J Pharm Practice. 2016;29:516-526.

18. Moeller KE, Lee KC, Kissack JC. Urine drug screening: Practical guide for clinicians. Mayo Clin Proc. 2008;83:66-76.

19. Helander A, Böttcher M, Fehr C, Dahmen N, and Beck O. Detection Times for Urinary Ethyl Glucuronide and Ethyl Sulfate in Heavy Drinkers during Alcohol Detoxification. Alcohol Alcohol. 2009;44:55-61.

20. Mandatory guidelines for federal workplace drug testing programs. Department of Health and Human Services. Substance Abuse and Mental Health Services Administration (SAMHSA). Document 82 FR 792082. Fed Regist. 2017;7920-7970.

1.

Guy GP Jr, Zhang K, Bohm MK, et al. Vital Signs: Changes in opioid prescribing in the United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66:697-704.

Published 2017 Jul 7. doi:10.15585/mmwr.mm6626a4 .

21. DOT Urine Specimen Collection Guidelines for the U.S. Department of Transportation Workplace Drug Testing Programs (49 CFR Part 40). Office of Drug and Alcohol Policy and Compliance, United States Department of Transportation. 2018.

2.

Rules pertaining to prescribing, administering and dispensing medication. Mississippi Code 1972 as amended. Part 2640, Chapter 1. https://www.msbml.ms.gov/sites/default/files/Rules_Laws_Policies/ Part2640_Pertaining_to_Prescribing_Administering_and_Dispensing_of_ Medication.pdf Accessed February 28, 2019.

22. Blatt A, Chen Z, McClure L, et al. Prescription drug misuse in America: diagnostic insights in the continuing drug epidemic battle. Quest Diag Health Trend Prescription Drug Monit Rep. 2015;1-16.

3.

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm Rep. 2016;65(No. RR-1):1–49.

4.

Wolfe A. Mississippi overhauls opioid prescription rules amid epidemic. Clarion-Ledger. 2017:Oct 3. https://www.clarionledger.com/story/news/politics/2017/10/03/mississippi-overhauls-opioid-prescription-rules-amid-epidemic/722938001/ Accessed February 28, 2019.

5.

FDA Warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requiring its strongest warning. FDA Drug Safety Communication. 9-20-2017. Accessed February 28, 2019. https://www.fda. gov/Drugs/DrugSafety/ucm518473.htm .

6.

Dasgupta N, Freifeld C, Brownstein JS, et al. Crowdsourcing black market prices for prescription opioids. J Med Int Research. 2013;15:e178.

7.

Lebin JA, Murphy DL, Severtson SG, et al. Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone. Pharmacoepidemiol Drug Saf. 2019;28:25-30.

8.

Snyder ML, Fantz CR, Melanson S. Immunoassay-based drug tests are inadequately sensitive for medication compliance monitoring in patients treated for chronic pain. Pain Physician. 2017;20(2S):SE1–SE9.

9.

Molina DK. Methodology. Handbook of Forensic Toxicology for Medical Examiners.

CRC Press, Boca Raton FL; Taylor & Francis Group LLC; 2009:7-10.

10. Imran M. Screening for unknown compounds in forensic toxicology. ARC J Forensic Sci. 2016;1:10-12.

11. Jannetto PJ, Bratanow N, Clark WA, et al. Executive Summary: American Association of Clinical Chemistry Laboratory Medicine Practice Guideline-Using clinical laboratory tests to monitor drug therapy in pain management patients. J Applied Lab Med. 2018;2:489-526.

12. Sobolesky PM, Smith BE, Pesce AJ, et al. Interpretation of pain management testing results using case examples. J Applied Lab Med. 2018;2:610-621.

13. Goggin MM, Tann C-M, Miller A, et al. Catching fakes: New markers of urine sample validity and invalidity. J Anal Toxicol. 2017;41:121-126.

14. Pesce A, West C, City KE, et al. Interpretation of urine drug testing in pain patients.

Pain Med. 2012;13:868-885.

336 VOL. 60 • NO. 10 • 2019

23. Argoff CE, Allford DP, Fudin J, et al. Rational urine drug monitoring in patients receiving opioids for chronic pain: Consensus Recommendations. Pain Med. 2018;19:97-117.

24. Washington State Agency Medical Directors’ Group. Interagency guidelines on prescribing opioids for pain. 2015. Accessed February 28, 2019. http://www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline. pdf.

25. Mahajan G. Role of urine drug testing in the current opioid epidemic. Anesth Analg.

2017;125:2094-2104.

26. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic, noncancer pain. J Pain 2009;10:113-130.

27. Krishnamurthy P, Ranganathan G, Williams C, et al. Impact of urine drug screening on no shows and dropouts among chronic pain patients: A propensity-matched cohort study. Pain Physician. 2016;19:89-100.

28. Pesce A, West C, Rosenthal M, et al. Illicit drug use in the pain patient population decreases with continued drug testing. Pain Physician. 2011;14:189-193.

29. Manchikanti L, Manchukonda R, Pampati V et al. Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids? Pain Physician 2006;9:123-129.

Author Information Author Information: All authors are from the University of Mississippi Medical Center, Jackson, MS. Director of Clinical Chemistry and Toxicology Laboratories, Professor of Pathology (Kyle). Vice Chair, Pain Medicine, Department of Anesthesiology (Gusa). Clinical Associate Professor of Pharmacy Practice, Professor of Family Medicine (Kemp). Professor of Psychiatry and Human Behavior, Co-Director, UMMC Neuro Institute Addictions (Parker). Professor of Pharmacology and Toxicology, Deputy Chief Academic Officer (Rockhold). Capstone Coordinator, Occupational Therapy Doctoral Program Associate Professor, School of Health Related Professions (Rogers).

Corresponding Author: Patrick Kyle PhD, DABCC, FAACC; Director of Clinical Chemistry and Toxicology, Professor of Pathology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216 Ph: (601) 984-2352 (pkyle@umc.edu).

Small Town Mississippi Greenwood Leflore Hospital, a 208 bed, Level IV trauma center has proudly served the heart of the Mississippi Delta since 1906. We serve as a regional referral center for a range of medical specialties including Anesthesiology, Cardiology, Diabetes Education, Emergency, Family Practice, Gastroenterology, General Surgery, HIV, Internal Medicine, Interventional Radiology, Medical Oncology, Neurology, Neurosurgery, Obstetrics/Gynecology, Orthopedic Surgery, Otolaryngology, Pain Management, Pathology, Pediatrics, Podiatry, Psychiatry, Pulmonology, Radiation Oncology, Radiology, Rehabilitation, Sleep Disorders, Vascular Surgery, Urology, and Wound Care.

Greenwood Leflore Hospital is expanding services and is seeking physicians in the following specialties. We are interested in physicians who are immediately available or those who are near completion of training in: • • • • •

Emergency Medicine Family Medicine General Surgery Hospitalist Internal Medicine

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OB/GYN Orthopedic Surgery Otolaryngology Pediatrics Urology

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For information regarding career opportunities, please contact physician recruiter, Lea Denton at 662-459-7113 or ldenton@glh.org.

S C I E N C E

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M E D I C I N E

Top 10 Facts You Should Know about Liver Disease ELIZABETH R. PAINE, MD Introduction Liver disease encompasses a wide variety of pathologies that can result in multiple complications. Chronic liver disease results in almost two million deaths each year and is most commonly due to viral hepatitis or alcoholic liver disease.1 Keywords: chronic liver disease, hepatitis, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, esophageal varices, hepatocellular carcinoma Non-Alcoholic Fatty Liver Disease (NAFLD) is an underrecognized cause of liver disease, particularly among patients with metabolic syndrome.

The prevalence of NAFLD in North America has been reported as approximately 24%, with worldwide prevalence approximately the same.2 Associations between NAFLD and obesity, dyslipidemia, and diabetes have commonly been reported, and modification of risk factors for these conditions like obesity is a proven treatment of NALFD.3 Alcoholic liver disease can cause varying degrees of hepatic fibrosis, and alcohol cessation is the cornerstone of treatment.

Frequent alcohol use damages the liver, but not every patient develops cirrhosis. It has been reported that cirrhosis develops in up to 41% of a patient population, including women drinking more than 20 grams of alcohol per day and men drinking more than 60-80 grams of alcohol per day for at least 10 years.4 In those who drink and develop hepatic scarring/fibrosis, this fibrosis can improve with alcohol abstinence.5 A period of alcohol abstinence is a requirement of most transplant centers in considering candidacy for liver transplant.

Drug-induced liver injury should be considered in patients with abnormal liver function tests or acute liver failure without a clear cause.

Presentations of drug-induced liver injury can range from mildly abnormal liver enzymes to hepatic failure (Table). This condition is typically a diagnosis of exclusion after other causes of abnormal liver tests have been ruled out.

Pregnancy-related liver diseases, including intrahepatic cholestasis of pregnancy, HELLP syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets), and acute fatty liver of pregnancy are uncommon but can be serious.

Patients with intrahepatic cholestasis of pregnancy typically are in their third trimester and present with itching, abnormal liver tests, and increased bile acids and can have deleterious obstetric complications including preterm birth and stillbirth.7 HELLP syndrome presents with indicators of hemolysis, abnormal liver tests (typically ALT and AST), and thrombocytopenia and can result in hepatic hemorrhage, infarction, or rupture.8 Acute fatty liver of pregnancy presents with liver failure and can cause complications including disseminated intravascular coagulation, hypoglycemia, encephalopathy, stillbirth, and renal insufficiency.9

338 VOL. 60 â&#x20AC;˘ NO. 10 â&#x20AC;˘ 2019

Table. Common Medication Etiologies of Drug-Induced Liver Injury and the Table. Common Medication Etiologies of Drug-Induced Liver Injury and their Usual Presentations Presentations Medication

Drug-Induced Liver Injury

Amoxicillin/clavulanate

Cholestasis, can be after drug course

Trimethoprim/sulfamethoxazole

Cholestasis, can have rash or eosinophilia

Nitrofurantoin, Minocycline

Mimic autoimmune hepatitis

Amiodarone

Macrovesicular steatosis

Acetaminophen

Acute hepatitis with ALT/AST in thousands

Valproate

Encephalopathy

Non-steroidal anti-inflammatories

Elevated ALT and AST

Methotrexate

Hepatic steatosis and fibrosis

Allopurinol

Increased ALT/AST, granulomas on biopsy

Although the numbers of patients diagnosed with Hepatitis C have risen overall in the last 5 years, new treatments are curing more patients than ever before.

The numbers of cases of past and present diagnoses of Hepatitis C have increased between 2012 and 2015 per CDC statistics (Figure).10 Increases in diagnosis are due at least in part to the CDC guidelines issued in 2012, recommending that patients born between 1945 and 1965 have HCV screening once.11 Treatment regimens vary based on the Hepatitis C genotype, prior Hepatitis C treatments received, and degree of hepatic fibrosis, and nearly all patients can be successfully treated with current regimens.12 Ascites due to cirrhosis can often be controlled with a low sodium diet, alcohol cessation, paracenteses, and diuretics.

Large volume ascites causes patients to become uncomfortably distended and short of breath and often results in a need for further symptomatic management. Education of patients regarding adherence to a diet with less than two grams of sodium per day is paramount, as is alcohol cessation. Patients should also undergo a paracentesis with the initial onset of ascites with lab tests evaluating for the etiology of the ascites and for the presence of spontaneous bacterial peritonitis (SBP). Patients can undergo serial paracenteses as needed for symptom control if diuretics and diet do not control the fluid accumulation. Spironolactone and furosemide are the diuretics most frequently used in controlling ascites.13 Spontaneous bacterial peritonitis frequently recurs after the initial diagnosis, and it is imperative that patients with prior episodes be on long-term prophylactic antibiotics.

Spontaneous bacterial peritonitis is diagnosed by finding more than 250 absolute polymorphonuclear leukocytes in ascitic fluid in the absence of other identified infections within the abdomen.13 After

Figure. Cases of Confirmed Hepatitis C Past Present Infections 2012-2015 Figure.

Cases of confirmed Hepatitis C or past or present infections 2012-2015 Conclusion

Number of Cases

Number of Hepatitis C Cases Past and Present 200000 180000 160000 140000 120000 100000 80000 60000 40000 20000 0

Number of Hepatitis C Cases Past and Present 2012

2013 2014 Year

2015

Adapted from CDC statistics on Viral Hepatitis C 10

initial diagnosis, one study found that SBP recurred in 1 year in 69% of patients.14 Prophylactic antibiotics used for prevention of subsequent episodes of SBP in those who have previously had an episode of SBP include trimethoprim-sulfamethoxazole or norfloxacin.13 Of note, since norfloxacin is not available in the United States, ciprofloxacin is frequently substituted.

Hepatic encephalopathy does not always cause asterixis, and increased ammonia levels are not needed for diagnostic purposes.

Hepatic encephalopathy describes a spectrum of symptoms in patients with liver disease, ranging from subtle sleep-wake cycle disturbances to decorticate positioning. Asterixis is often not seen until overt hepatic encephalopathy symptoms are occurring. In hepatic encephalopathy, ammonia levels do not augment the staging or prognosis of this condition, do not correlate with the severity of symptoms at higher levels, and can also be technically challenging to obtain accurately.15 Bleeding from esophageal varices is often of large volume, requires endoscopy with ligation after resuscitation, and mandates a course of antibiotics.

Esophageal variceal bleeding is a medical emergency initially requiring hemodynamic stabilization and volume resuscitation.

Therapeutic endoscopy should subsequently be performed within 12 hours of presentation. Due to the association between variceal bleeding and SBP and other infections in cirrhotic patients, antibiotics for a maximum of 7 days is recommended.16 Hepatocellular carcinoma (HCC) screening should be performed every 6 months with ultrasound.

After diagnosis, HCC is typically treated in a multidisciplinary fashion, with treatment decisions determined after consultation with a specialized tumor board.

Physicians with specialties in Hepatology, Radiology, Hepatobiliary Surgery, Interventional Radiology, and Oncology are usually involved in the care of HCC patients. Treatment modalities include curative options such as surgical resection and liver transplant and palliative options like locoregional therapies and chemotherapy. The stage of the hepatocellular carcinoma, the patient performance status, and the Child-Pugh and MELD scores are all utilized in determining what treatments should be offered to patients.17

Liver diseases are common health conditions in the US population. The sequelae of chronic liver disease which include ascites, spontaneous bacterial peritonitis, esophageal varices, and hepatocellular carcinoma can result in the early death of these patients. The early recognition, diagnosis, and management of these conditions prolong the quality and length of life of these individuals. n References 1. Udompap P, Kim D, Kim WR. Current and future burden of chronic nonmalignant liver disease. Clin Gastroenterol Hepatol. 2015;13:2013-2041.

2. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease- Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84.

3. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guidelines by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005-23.

4. O’Shea RS, Dasarathy S, McCullough AJ, Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease.

Hepatology. 2010;51:307-328.

5. Bardou-Jacquet E, Legros L, Soro D, et al. Effect of alcohol consumption on liver stiffness measured by transient elastography. World J Gastroenterol. 2013;19:516522.

6. Lo Re V, Haynes K, Forde K, et al. Risk of acute liver failure in patients with druginduced liver injury: evaluation of Hy’s law and a new prognostic model. Clin Gastroenterol Hepatol. 2015;15:2360-2368.

7. Vural Yilmaz Z, Geoncosmanoglu TG, Daglar K, et al. Elevated red blood cell distribution width is associated with intrahepatic cholestasis of pregnancy. Ginekol Pol 2017;88:75-80.

8. You JS, Chung YE, Chung HS, et al. Spontaneous hepatic rupture caused by hemolysis, elevated liver enzymes, and low platelet count syndrome. Am J Emerg Med. 2017;32:686.e3-4.

9. Castro MA, Fassett MJ, Reynolds TB, et al. Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases. Am J Obstet Gynecol 1999;181:389-395.

10. Centers for Disease Control and Prevention. Viral Hepatitis Statistics and Surveillance. https://www.cdc.gov/hepatitis/statistics/Accessed October 10, 2017.

11.

Centers for Disease Control and Prevention. Recommendations for the identification of chronic Hepatitis C virus infection among persons born during 1945-1965. MMWR. 2012;61(RR04);1-18.

12. American Association for the Study of Liver Diseases /Infectious Disease Society of America HCV Guidance Panel. Hepatitis C guidance: AASLDIDSA recommendations for testing, managing, and treating adults infected with Hepatitis C virus. Hepatology. 2015;62:932-954.

13. Runyon B, American Association for the Study of Liver Diseases. Introduction to the revised American Association for the Study of Liver Diseases practice guidelines management of adult patients with ascites due to cirrhosis 2012.

Hepatology. 2013;57-1651-1653.

14. Tito L, Rimola A, Gines P, et al. Recurrence of spontaneous bacteria peritonitis in cirrhosis: frequency and predictive factors. Hepatology 1988;8:27-31.

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15. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guidelines by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.

Hepatology. 2014;60:715-735.

16. Garcia-Tsao G, Abraldes JG, Berzigotti, et al. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases.

Hepatology. 2017;65:310-335.

17.

Bruix J, Sherman M, Practice Guidelines Committee of the American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-1022.

Author Information

Helping you build a more secure future.

We invest our own money alongside yours, so we are invested in your success.

Corresponding Author: Elizabeth R. Paine, MD, FACG, G.V. (Sonny) Montgomery VA Medical Center; Associate Professor of Medicine and Associate Program Director for Digestive Diseases.

Fellowship at the University of Mississippi Medical Center, Department of Internal Medicine, Division of Digestive Diseases, 2500 N. State St., Jackson, MS 39216. Ph: 601-984-4540 (epaine@ umc.edu).

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We work with each patient to develop a plan of care that is unique to their specific situation. Physical therapy, IV therapies, radiation and other comforting treatments approved by the physician may be included in the patient’s plan of care.

Our Heart of Hospice team works 24/7 to help eligible patients and families who need our care.

For more information please call 1.844.464.0411 or visit heartofhospice.net 340 VOL. 60 • NO. 10 • 2019

E D I T O R I A L

Touch Where It Hurts Editorial

It Touch was an eyebrow-raising proposition, and to reach forth to the lips of their patients as Homer portrayed Where It Hurts to say the least. In the August 27 issue Achilles touching Priam’s lips in respect and pity, or Priam’s of JAMA, an essay entitled “How to Fix touching Achilles in ritual supplication. More to the point, either It wasCurriculum—Another an eyebrow-raising proposition, thesignaling least. mutuality as well as a the Premedical is possible while bothtoaresay correct, In the AugustM. 27Ratzan, issue of JAMA, an essay entitled “How to Fix Try”

by Richard MD, moment of connection and compassion. board emergency medicine the certified Premedical Curriculum—Another Try” by Richard M.

I don’t know if any med school admissions committee physician of Hartford, CT, revisited Ratzan, MD, board certified emergency medicine physician of what then was certainly a radical members will be reading this, but as an inadvertent voice of Hartford, CT, revisited what then wasI certainly radical experience, firmly believeathat a two-year smorgasbord of liberal proposal espoused by physicianarts study before ordering from an asome la carte menu of premed D. Stanley Hartness, MD proposal espoused physician-essayist Lewis Thomas essayist Lewis Thomas some by forty-one Associate Editor courses stood me in good stead in my role as a family physician— years ago. forty-one years ago. and for life in general. We all know that if we listen to our patients

Thomas heretically suggested that medical school long enough, we’ll be led to their diagnosis. And I’ve always been heretically thatofmedical applicants who were traditionalThomas premed science majors suggested be an advocate the simpleschool but profound advice offered by one considered last—if at all—for admission.premed Rather, preference of our med instructors, “Touch where applicants who were traditional science majors beschool considered last—if at the patient says it should be given to students who concentrated on “some central, hurts.” It’s magical! n all—for admission. Rather, preference should be given to students who1 6/28/18 10:25 AM Johns A2Z Ad 4.25x5.5.pdf core discipline, universal within the curricula of all the colleges, concentrated on for “some central, which could be used evaluating the freecore rangediscipline, of a student’s universal within the curricula of mind, tenacity and resolve, for the all thehis(sic) colleges, which couldhis beinnate usedcapacity for evaluating the free range of a student’s understanding of tenacity human beings andresolve, his affection the human mind, his(sic) and hisforinnate capacity for the understanding of condition.”

human beings and his affection for the human condition.”

His fairly astounding conclusion was that classical Greek (in original language) be conclusion restored as thewas centerpiece Histhefairly astounding that classical Greek (in the original of undergraduate education. He specifically cited the dramatic language) beofrestored the centerpiece of undergraduate education. He scene at the end Homer’s Theas Iliad which he felt represented the specifically cited the dramatic scene at the end various contingencies of human life– honor, compassion, grief,of Homer’s The Iliad which he felt loss at the handsthe of apparently forces beyond our life– honor, compassion, grief, represented various meaningless contingencies of human control, tragedy, and our human capacity and willingness to shape loss at the hands of apparently meaningless forces beyond our control, tragedy, all of these even with those who have hurt us, preparing medical and ourtohuman capacity willingness to shape students incorporate these in and their clinical relationships with all of these even with those who have hurt us, preparing medical students to incorporate these in their clinical patients.

relationships with patients.

Since Thomas’ proposal obviously fell for the most

“If you can think it, we can print it.”

part on deaf ears, Ratzen suggested a more modest proposal in which all med school applicants major in obviously the humanitiesfell withfor an the most part on deaf ears, Since Thomas’ proposal optional minor in biology and science topics; the science training Ratzen suggested a more modest proposal in which all med school applicants would follow after their acceptance. This would hopefully afford major the humanities withlearned an optional patientsin care by physicians “who have as much asminor anyone in biology and science topics; the science would after their This would hopefully afford can learntraining in our colleges andfollow universities about howacceptance. human beings havecare alwaysby lived out their lives. ” patients physicians “who have learned as much as anyone can learn in our

John Mathews

601-540-2864 jonm9564@gmail.com

colleges and universities about have always their 2125 TV lived Roadout • Jackson, MS 39204

Ratzen views journeying intohow and human through beings the lives.” humanities, studying them, and discussing them to be the fruits of www.a2zprinting.net the education Thomas wanted physicians to enjoy for themselves

Ratzen views journeying into and through the humanities, studying them, and discussing them to be the fruits of the education Thomas wanted physicians

OCTOBER • JOURNAL MSMA

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M I S S I S S I P P I

S T A T E

D E P A R T M E N T

O F

H E A L T H

Mississippi Mississippi ProvisionalReportable ReportableDisease DiseaseStatistics* Statistics* Provisional September 2019

September 2019

*Monthly statistics are provisional. Disease totals may change depending on additional reporting from healthcare providers and public health investigation. These numbers do not *Monthly statistics are provisional. totals may change depending on additional reflect the finalDisease case counts. reporting from healthcare providers and public health investigation. These numbers do not reflect the final case counts.

Public Health District

Sexually Transmitted Diseases

Primary & Secondary Syphilis Early Latent Syphilis Gonorrhea Chlamydia HIV Disease Mycobacterial Diseases

Pulmonary Tuberculosis (TB) Extrapulmonary TB Mycobacteria Other Than TB Diphtheria Pertussis

Vaccine Preventable Diseases

Tetanus Poliomyelitis Measles Mumps Hepatitis B (acute) Invasive H. influenzae disease Invasive Meningococcal disease Hepatitis A (acute) Enteric Diseases

Salmonellosis Shigellosis Campylobacteriosis

Zoonotic Diseases

E. coli O157:H7/STEC/HUS Animal Rabies (bats) Lyme disease Rocky Mountain spotted fever

State Totals*

I

II

III

IV

V

VI

VII

VIII

IX

5

6

5

4

9

7

2

9

9

6

12

9

3

3

4

0

4

0

133 100 116

3

28

81

243

0

3

254 199 216 185 519 0 0 0 0 0 0 0 0 0 3 0 2

0 1 0 1 0 0 0 0 0 0 0 2

10

53

0

1

0 7 0 0 2

1 9 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0

2 0 1 0 0 0 0 0 0 0 0 0 0

13 0 2 0 2 0 0 0 0 1 0 0 1

8

3 0 1 0 0 0 0 0 0 0 0

11

26

11

0

1

1

3

2 0 0 0

3 2 1 0 0

2

12 0 0 2

4 2 0 0 1

1 0 0 0 0 0 0 0 0 0 1

456

330

12

27

0

0

0

0

0

0

0

0

0

41

4

0

0

56

29

0

0

YTD 2018

3

138

1

YTD 2019

81

59

202 128

Sept 2018

5

6

97

2 0

4

Sept 2019

234 0 1 0 2 0 0 0 0 1 0 0

170 1,137 1 0

4 2

0

0

0

0

1

2

8

14

0

6

0

0

1

5

22

14

158

0

0

1

7

0

7

0 0 0 1

0 1 0 0 1

1

11

0

1

13

48

1

1

0 0 0 0 0 0 0 0 0 0 West Nile virus *Totals include reports from Department of Corrections and those not reported from a specific District.

342 VOL. 60 â&#x20AC;˘ NO. 10 â&#x20AC;˘ 2019

763

852

693

8,918 7,284

276 2,213 1,683 19,187 16,630

9 0

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recently had the pleasure of taking care of a patient who had been blown up here from New Orleans

by Katrina several years ago. She was an elderly widow who had come to Jackson to be closer to her son. She could not believe how friendly her neighbors were. She said that she had always heard about Mississippi being the hospitality state but had never really thought about it. She also spoke about her new church and what a great family they had become to her.

being able to share a moment with someone who is so grateful for your care is a feeling that is not easily forgotten.

Physician burnout is a hot topic in medicine these days. We often get tripped up by the daily hassles of electronic records, preauthorization forms, overbooked schedules and other things that always seem to take away one of our most precious commodities– time. However In the midst of these challenges it’s nice to be able to stop and slow down when something grabs your heart. That truly is the joy of medicine. n

I got involved with her case while making rounds over a holiday at the hospital. She had been seen by one of my partners when she developed unstable angina. She received a drug-coated stent and initially did well. She had a history of chronic DVT and had been J. Clay Hayes, Jr., MD on apixaban prior to admission — obviously, this complicated President, Mississippi State Medical Association things in that she needed to be on both an antiplatelet agent and full anticoagulation. The decision was made to put her on ticagrelor and apixaban, and she was sent home.

Several weeks later, she developed bloody stools and hematuria.

Her neighbors brought her to the hospital, and she was subsequently found to be severely anemic. She received two units of blood and felt better. Ultrasound of her lower extremities showed no evidence of clot and apixaban was stopped.

During her stay, she was seen by multiple physicians, including cardiologists, hospitalists, and hematologists as well as nurses, physical therapy, dietary, and other staff members. She said that she could not believe how friendly everyone was and how much she appreciated being cared for. In addition, her neighbors and church members came to see her every day. She confided to me that she never felt so loved. It had been 11 years since her husband had passed away, and she was very tearful when she told me about their life together. Her son had been out of town a lot for work, and she did not want to burden him with her problems. To be able to experience this emotional conversation with her was very humbling and gratifying.

This is one of the reasons why I went into medicine. It’s not just the practice of medicine with all the wonderful technology and treatments that we have to offer; it’s the moments of intimacy with our patients that really matter. Seeing someone pour out their heart to you without any hesitation is a very emotional thing.

Much like the high of seeing your child do something wonderful,

344 VOL. 60 • NO. 10 • 2019

I M A G E S

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M I S S I S S I P P I

M E D I C I N E

ARCHIE JACKSON STACY, SR., MD (1888-1956), TUPELO, PIONEER MISSISSIPPI RADIOLOGIST – This photographic image, from an Ole Miss yearbook of 1908, is of one of the radiology pioneers of Mississippi: Archie Jackson Stacy, Sr., MD, of Tupelo. The ninth of fifteen children of Isaiah D. and Mollie Stacy, born in Reid, Mississippi, on February 26, 1888, Stacy graduated from the 2-year medical school at Ole Miss and then completed his medical studies at Tulane by 1918, after which he received his medical license. His was a long journey to his medical degree, a common thing for a poor Mississippi boy. He worked and studied his way through Ole Miss, then worked for several years teaching school to accumulate monies to further his medical education, and then even swept the floors at Tulane to pay for his tuition. His license, issued in June 1918, noted that he was 30 years of age, resided in Calhoun County with the post office address of the old Chickasaw County settlement of Houlka, which was his father’s longtime homeplace. After Tulane, Archie interned in St. Louis at the Frisco Railroad Hospital. He would remain a “Frisco doctor” until his death and loved to tell his family about the joy of riding up front with the engineer! On September 15, 1919, he married Roberta Valliant (1895-1987), with whom he would rear a family of one son and two daughters. After his marriage, the couple moved to Burdette, Arkansas, where he was the doctor for a large plantation before locating in Tupelo in 1923. There he would remain the rest of his professional life. When the Great Depression arrived, many of his patients paid him in quilts and vegetables. In April 1936, Tupelo was devastated by one of the deadliest tornadoes in national history. Over 700 people were injured, and more than 200 died. The night storm leveled 48 city blocks, even blowing the roof off the city hospital. Stacy sheltered and sutured patients on his front porch (no anesthesia – his daughter still remembers the screaming) and his wife fed them meals cooked on her wood stove as the whole city had lost electricity and gas. He early developed an interest in radiology, then a developing specialty, training at the Cook County Hospital in Chicago. Taking on significant debt to open his new radiology clinic, he brought the first radiology equipment to northeast Mississippi. There was great resistance from the general public to the specialty of radiology, many fearing it was dangerous, and he continued to perform anesthesia and other medical procedures to support his family.

When his son, Jack, Jr., returned from serving in World War II, they opened a new clinic on Main Street in Tupelo. After the North Mississippi Medical Center was built, he was honored by having his portrait painted and hung in the radiology department in the opening ceremonies. He served as secretary-treasurer of the Northeast Mississippi Medical Society and in 1939 served as a member of the American Board of Radiology.

He also was one of the founders of Calvary Baptist Church and served on the Board of Trustees for Blue Mountain College. He died on September 29, 1956, and was buried at Tupelo’s Memorial Park Cemetery. My thanks and appreciation are extended to his granddaughter Beth Taylor of Jackson, who provided this image of Dr. Stacy and biographical information for this essay. If you have an old or even somewhat recent photograph which would be of interest to Mississippi physicians, please send it to me at lukelampton@cableone.net or by snail mail to the Journal. n — Lucius M. “Luke” Lampton, MD JMSMA Editor OCTOBER • JOURNAL MSMA

345

P O E T R Y

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M E D I C I N E

Edited by Lucius Lampton, MD; JMSMA Editor

[This month, I continue a multi-issue focus on the poetry of the late physician-poet Merrill Moore, MD (19031957), a noted American psychiatrist and neurologist who also achieved fame as a poet and sonneteer. I plan to bring you more of his best poems that possess medical content. This poem’s subject, a blood transfusion, is a common practice in medicine since Moore’s day, becoming even safer to utilize over the intervening years. The miraculous improvement of an exsanguinated patient after a transfusion still impresses physician witnesses, who see it often dramatically restore vigor and color with one or two units of PRBCs. Dr. Moore paints this common scene as a religious rite of a holy cult, clad in white, whose masked priest lifts up a cup of sacrificial blood to the heavens, seeking a blessing to change the course of nature. Moore follows the transfused blood along vascular “avenues,” watching it dispel the bluish hues of “face and finger,” imagining the blood entering the heart’s first chamber (he calls a “trembling room”) in marriage to this other body as a joyous bridegroom. This poem is from “M: One Thousand Autobiographical Sonnets” published in 1938 (see page 923). Any physician is invited to submit poems for publication in the Journal either by email at lukelampton@cableone.net or regular mail to the Journal, attention: Dr. Lampton.] — Ed.

Blood Transfusion The scene is set now: Here is a silent room And a woman exsanguinated on a bed.

Enter the cult in mask and white cloth clad, Bearing borrowed blood in a red cup The first tall foremost priest holds and lifts up.

The arm is cleansed – a needle in the vein, Then rosy color soon returns again…

Averted the proximity of doom.

And joyous the new blood enters avenues Of old veins and dispels the bluish hues Of face and finger – joyous as a bridegroom The new blood enters in the trembling room That is the heart’s first chamber, whence it flows And does the miracles men know it does.

— Merrill Moore, MD (1903-1957)

346 VOL. 60 • NO. 10 • 2019

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