VOL. LX • NO. 2 • 2019 by Journal MSMA

VOL. LX • NO. 2 • 2019

ADDICTION SPECIAL EDITION

Regularly priced at $80, the book is on sale now! Images in Mississippi Medicine: A Photographic History of Medicine in Mississippi

MD and Karen A. Evers Lucius "Luke" M· Lampron,

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.

OF THE MISSISSIPPI STATE MEDICAL ASSOCIATION VOL. LX • NO. 2 • FEBRUARY 2019

SPECIAL ARTICLES

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

THE ASSOCIATION President Michael Mansour, MD

Juul Awareness, Trial, and Continued Use among Undergraduate 44 Students in Mississippi - Emily McClelland, MS; Nell Valentine, MS; Julie Gorzkowski, MSW; Amy Winter, MS; Robert McMillen, PhD

A Comprehensive Evaluation of Mississippi Opioid Prescribing Practices 51 by Strength and Days of Supply, 2012-2017: A Summary of Updated Mississippi Board of Medical Licensure Opioid Prescribing Rules Manuela Staneva, MPH; Meg Pearson, PharmD; Thomas Dobbs, MD, MPH; Paul Byers, MD

Backstories on the US Opioid Epidemic. Good Intentions Gone Bad, 56 an Industry Gone Rogue, and Watchdogs Gone to Sleep Richard D deShazo, MD; McKenzie Johnson, BS; Ike Eriator, MD; Kathryn Rodenmeyer, BA

Vice Speaker Jeffrey A. Morris, MD

Marijuana’s Effects on Brain Structure and Function: What Do We Know 64 and What Should We Do? A Brief Review and Commentary Richard D deShazo, MD; Sara B. Parker, BA; Daniel Williams, PhD; John B. Ingram, MD; Mahmoud Elsohly, PhD; Kathryn Rodenmeyer, BA; Kyle McCullouch, BBA

Executive Director Claude D. Brunson, MD

The PROMISE Initiative: Who Should Give Patients 68 Information on Opioids? - Mary Nelson Robertson, MA; Daniel Williams, PhD; Holli Seitz, PhD; Laura Downey, DrPH; Alisha Hardman, PhD; David Buys, PhD

President-Elect J. Clay Hays, Jr., MD

MANAGING EDITOR Karen A. Evers

Secretary-Treasurer W. Mark Horne, MD

PUBLICATIONS COMMITTEE Dwalia S. South, MD Chair Richard D. deShazo, MD Sheila Bouldin, MD Wesley Youngblood, M3 and the Editors

Speaker Geri Lee Weiland, 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 39158-2548. (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. Jill Gordon, MSMA Director of Marketing. Ph. 601-853-6733, ext. 324, Email: JGordon@MSMAonline.com

Current Approaches in Perioperative Management of the Opioid Tolerant Patient - Rene Hulet, MD; Lakshmi N. Kurnutala, MD

DEPARTMENTS From the Editor – Vaping in the Age of Addiction Lucius M. Lampton, MD

Editorial – The Phenomenon of Practice Drift: Liars, Pimps and 80 Snake Oil Salesmen Heddy-Dale Matthias, MD Commentary – Understanding Levels of Care in Substance Use 84 Disorder Treatment R. Stephen Pannel, DO

A Conversation with Thomas Payne, PhD on Limiting E-Cigarette Sales to Teens to Prevent Nicotine Addiction

MSMA – Brunson Named New Executive Director

POSTMASTER: send address changes to Journal of the Mississippi State Medical Association, P.O. Box 2548, Ridgeland, MS 39158-2548.

President’s Page – Professionalism and Population Health Management Michael Mansour, MD

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.

Images in Medicine – Junkie: Pulp Fiction Confessions of an Unredeemed 101 Drug Addict, 1953 Lucius M. Lampton, MD

Poetry and Medicine – He Was a Different Fellow After a Few Drinks Merrill Moore, MD

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Vaping in the Age of Addiction

I ,

Lucius M. Lampton, MD Editor

n this age of addiction, physicians on the front-line daily see a variety of patients abusing multiple substances and lament the numerous preventable diseases caused or worsened by such self-destructive behavior. While our serious attention to the opioid epidemic remains critical, there are numerous other substance addictions which demand our attention: alcohol, tobacco, methamphetamines, marijuana, cocaine, and a long list of others. Perhaps the most pressing addiction “epidemic” to be placed on the American physician’s radar is the recent surge of e-cigarette use, also called vaping.

Vaping is inhaling and exhaling an aerosol, often called vapor (mistaken for water vapor), produced by an e-cigarette or similar device. The aerosols contain various toxic chemicals, which have been linked to cancer as well as cardiac and respiratory disease. The most popular vaping product is the JUUL, a stylish device resembling a computer USB flash drive. Containing high doses of nicotine, each product comes in several enticing flavors like fruit medley, cool mint, crème brûlée, and mango.

The United States Surgeon General Vice Admiral Jerome Adams in midDecember issued an urgent advisory on what he termed the “epidemic of youth e-cigarette use,” stressing the importance of “protecting children from a lifetime of nicotine addiction and associated health risks.” (https://ecigarettes.surgeongeneral.gov/.) Adams reports that since their introduction in 2007, e-cigarette use among U.S. middle and high school students has exploded, increasing 900% during 2011-2015, with current use increasing by 78% among high school students during the past year, from 11.7% in 2017 to 20.8% in 2018. Last year, statistics reveal that more than 3.6 million American youth, including 1 in 5 high school students and 1 in 20 middle school students, currently use e-cigarettes. HHS Secretary Alex Azar adds, “In the data sets we use, we have never seen use of any substance by America’s young people rise as rapidly as e-cigarette use is rising.” Despite possible benefits in smoking cessation, a growing body of evidence underscores the dangers of vaping. We physicians must caution our patients that vaping’s extraordinary risks, especially to our youth, may outweigh any benefits. 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

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

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

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

42 VOL. 60 • NO. 2 • 2019

GENERAL SURGERY Andrew C. Mallette, MD

INTERNAL MEDICINE/ EPIDEMIOLOGY Thomas E. Dobbs, MD

PEDIATRICS Michael Artigues, MD Owen B. Evans, MD

MEDICAL STUDENT John F. G. Bobo, M3

PLASTIC SURGERY William C. Lineaweaver, MD, Chair

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

PSYCHIATRY Beverly J. Bryant, MD June A. Powell, MD

HEMATOLOGY Carter Milner, MD

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

INFECTIOUS DISEASE Rathel "Skip" Nolen, III, MD

ORTHOPEDIC SURGERY Chris E. Wiggins, MD

INTERNAL MEDICINE Daniel P. Edney, MD Daniel W. Jones, MD Brett C. Lampton, MD Kelly J. Wilkinson, MD

OTOLARYNGOLOGY Bradford J. Dye, III, MD PEDIATRIC OTOLARYNGOLOGY Jeffrey D. Carron, 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

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Juul Awareness, Trial, and Continued Use among Undergraduate Students in Mississippi EMILY MCCLELLAND, MS; NELL VALENTINE, MS; JULIE GORZKOWSKI, MSW; AMY WINTER, MS; ROBERT MCMILLEN, PHD Abstract Objective: This study assessed awareness, prevalence of trial, and frequency of Juul use among undergraduate students at 3 Mississippi universities. Methods: A random sample of students responded to web-based surveys assessing Juul awareness, trial, and use. Results: Most students were aware of Juul (69.5%) and recognized that a Juul pod provides as much nicotine as a pack of cigarettes (59.4%). A third of students had tried Juuls (37.1%), and three-quarters of trial users reported past 30-day use (76.1%). Among trial users, smokers and students in the Greek system were more likely to report past 30day use than others, p<.05.

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Conclusion: Awareness and trial of Juul are high. Moreover, most trial users report daily or past week use, in contrast to many previous studies finding that most trial use is discontinued. Universities and policy makers need to be aware of Juul use among undergraduates, particularly those who are non-smokers. Keywords: Electronic cigarettes; Juul; young adults Introduction E-cigarettes are a rapidly evolving class of battery-powered devices that heat nicotine, flavor additives, and chemicals to the point of areolation. The e-cigarettes introduced to the U.S. market in 2007 did not efficiently deliver nicotine to the brain and were poor substitutes for cigarettes.1 However, producers have advanced the capability of e-cigarettes to

rapidly deliver nicotine to the brain. Many of the currently available open systems (i.e., devices that are refillable with nicotine solutions) are capable of proficient delivery of nicotine to the brain but can be bulky, require maintenance, and produce large amounts of visible aerosol.2 Juul Labs developed a novel approach to these products in 2015 producing an e-cigarette that could approximate the ability of a cigarette to rapidly deliver nicotine to the brain3,4 in a device that is easy to maintain and use. The Juul is a pod-based, closed system that uses a non-refillable pod of nicotine solution. Each Juul pod contains 59 milligrams of nicotine, or 5% nicotine as displayed on the package. The level of nicotine in each pod is equivalent to a pack of cigarettes,3,5 significantly higher than the nicotine delivered by other e-cigarettes currently on the market. These features may be appealing to adult cigarette smokers looking for a product to replace cigarettes, but the tech sleekness, ease of discreet use and availability in eight flavors* (Mango, Cool Mint, Virginia Tobacco, Cool Cucumber, Classic Menthol, Fruit Medley, Crème Brulee, and Classic Tobacco) may also attract non-smoking youth and young adults. Juuls are small and produce less noticeable aerosol plumes due to higher level of propylene glycol compared to other e-cigarettes.6 The potent delivery of nicotine raises concerns that nicotine-naïve trial users are at risk for nicotine addiction. A recent survey of U.S. adult Juul users found that 12.7% of users were never smokers when they first used a Juul.7 Moreover, longitudinal studies have suggested that e-cigarette use among never smokers is associated with future cigarette smoking. Youth who use e-cigarettes at baseline but who do not fit the psychological profile of someone at risk for initiating cigarette smoking are more likely than peers to have initiated cigarette smoking a year later.8-13 Both a recent meta-analysis and consensus study review found that e-cigarette use at baseline is consistently associated with a higher risk of future cigarette smoking, even while controlling for multiple potential confounding factors.14,15 Arising from concerns that non-smokers are attracted to Juuls, there are currently three lawsuits against Juul Labs and an investigation by the Food and Drug Administration (FDA) into the reported high rates of use among youth.16 The complaints filed against Juul target the use of nicotine salts in the Juul pods and branding and marketing that appeals to youth.17 The concern is that nicotine salts can deliver nicotine into the bloodstream at a higher rate than other e-cigarettes and that Juul Lab’s marketing practices have led to the addiction of a new group of consumers who were not previously using tobacco products or at risk for using these products. In September, the FDA also recently issued more than 1,300 warning letters and civil money penalty fines to retailers who illegally sold Juul and other e-cigarette products to minors during the summer of 2018 and alerted Juul Labs that they had 60 days to prove that they have a viable strategy to prevent minors from obtaining their products.18 Otherwise, the FDA may take the flavored products off the market.19 In response to government and public pressure, Juul Labs announced intentions to suspend sales of most of * These were the available flavors when the surveys were administered.

its flavored pods in retail stores.20 Despite public health concerns and legal challenges, Juul e-cigarettes are becoming a widespread phenomenon.21 Juul is currently the best and fastest selling e-cigarette on the market and represented 72.2% market share in the four-week period ending August 11, 2018, according to Nielsen data.22 Juul has changed the e-cigarette landscape in a short span of time, yet little is known about Juul use among young adults. In what is likely the first survey of Juul awareness and use among youth and young adults, conducted in November 2017, researchers found that a quarter of respondents were aware of Juul, ten percent had tried a Juul, and that most trial users continued use.23 Earlier this year, surveys administered to a national probability-based sample found that 6.0% of respondents ages 15-34 reported ever using Juul and 3.3% reported past 30-day Juul use.24 The current study investigates awareness and use of Juul among undergraduate students at three Mississippi universities. Specifically, the current study assessed awareness and nicotine perceptions of Juul and the prevalence of trial and continued past 30-day use, as well as frequency of use among trial users. We also examined misclassification issues in survey assessment of e-cigarette and Juul use. There is no standard terminology for this diverse class of products,25 and we were interested in examining surveillance challenges to estimating prevalence of e-cigarette use. Methods Design and sample This study is a cross-sectional, web-based survey of undergraduate students at three Mississippi universities and part of a larger surveillance and evaluation project for the Office of Tobacco Control, Mississippi State Department of Health. In the spring semester of 2018, we administered a web-based survey via Qualtrics survey software to students at three Mississippi universities. Procedures The study population included undergraduate students 18 years of age or older at these universities during April 2018. The three universities provided 15,303, 16,741 and 10,596 undergraduate student e-mail addresses, and 50% of the email addresses provided were randomly sampled to take part in the survey. University policies for student surveys prevented sampling more than half of the student body. Completed surveys were obtained from 593, 614, and 252 students, respectively. Students at each university received an initial e-mail asking for their participation in the survey. Students who chose to participate clicked on an embedded URL address that linked students to the survey website. Within the e-mail, an additional embedded URL address existed that gave students in the sample the option to not participate in the survey and receive no further communication. Respondents who did not finish the survey or who did not start the survey after the initial e-mail were sent two additional emails requesting their participation.

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Respondents who started the survey but did not finish it were able to start the survey where they left off. No more than three e-mails were sent to any student in the sample. Precautions were taken to protect the privacy of respondents. The information collected by each respondent was kept separate from personal identifiers (e-mail addresses). Vice Presidents for Research at each university granted permission for the survey to be conducted, and Information Technology Services (ITS) at each university provided student e-mail addresses. Prior to data collection, the Mississippi State University Institutional Review Board declared the study exempt from review. Measures E-cigarettes Respondents were provided the following information concerning e-cigarettes: “The next questions are about electronic cigarettes, also known as e-cigarettes, vaping devices, or hookah pens. E-cigarettes look like regular cigarettes but are battery-powered and produce vapor instead of smoke.” Then respondents were asked, “Have you ever used an e-cigarette, even one or two puffs?” Students who selected “Yes” were classified as trial e-cigarette users. Trial e-cigarette users were asked, “When did you last use an e-cigarette, even one or two times?” Trial users were asked about frequency of use rather than past 30-day use in order to avoid equating any level of past 30-day use with current use.26 Those who selected “Earlier today” or “Not today but sometime during the past 7 days” were classified as daily or weekly users; students who replied “Not during the past 7 days but sometime during the past 30 days” were classified as past 30-day users; and those who reported that last use of an e-cigarette was more than 30 days ago were classified as having not used an e-cigarette in the past 30 days. Any trial user who reported use within the past 30 days was considered to have continued use and to be a past 30-day user. Juul Students may not consider Juul devices to be e-cigarettes but rather view Juul as a new class of product. To address this possibility, questions about Juul were asked independently of previous responses to e-cigarette questions. That is, all respondents were asked about Juul Table 1. Population and Sampleand Characteristics Table 1. Population Sample

trial, not just the students who had previously reported e-cigarette trial. The survey allowed the possibility for a student to not report e-cigarette use but to report Juul use later in the survey. Following questions about e-cigarettes, all respondents were provided an image of the Juul and this statement, “The Juul nicotine-delivery device looks like a USB flash drive,” and asked, “Have you ever seen or heard of the Juul before this study?” Those who replied “Yes” were asked, “Are you aware that the amount of nicotine in one Juul pod (e-liquid flavor cartridge) is equivalent to a pack of cigarettes?” to assess nicotine perceptions of Juul. To assess Juul use, respondents who had seen or heard of the Juul were asked, “Have you ever used a Juul, even one or two puffs?” Those who selected “Yes” were classified as trial Juul users. Past 30-day Juul use among trial users was assessed using the same protocol as past 30-day e-cigarette use. Demographic variables and smoking status Self-reported gender, race, year in school, cigarette smoking status, and membership in a Greek organization were included as covariates in analyses. Respondents were asked, “Have you ever tried cigarette smoking, even one or two puffs?” Those who reported “No” were classified as non-smokers. Those who reported “Yes” were asked, “How old were you when you smoked a whole cigarette for the first time?” Those who reported, “I have never smoked a whole cigarette” were classified as non-smokers. Those who reported “Yes” were asked, “On how many of the last 30 days did you smoke cigarettes?” Students who reported, “I did not smoke cigarettes at all in the past 30 days” were classified as non-smokers. Those who reported smoking on at least one day but not all 30 days were classified as nondaily smokers, whereas those who reported, “I smoked cigarettes every day in the past 30 days” were classified as daily smokers. Data analysis Sample demographics from each university are presented alongside population distributions (provided by the Institutional Research website for each university) in order to assess the representativeness of each sample. Descriptive analyses for Juul awareness, trial, and use provide prevalence estimates, while Chi-squared tests compare these

Characteristics Universities

Freshman Freshman Sophomore Sophomore Junior Junior Senior ≥ Senior~ Female Female Male Male Black Black White White Other Other

Population Population

Sample Sample

Population Population

Sample Sample

Population Population

Sample Sample

23.9% 21.0% 22.4% 32.7% 49.2% 50.8% 20.2% 72.1% 7.8%

24.6% 20.7% 29.3% 25.4% 47.6% 52.4% 6.1% 85.8% 8.1%

26.0% 22.3% 23.2% 28.5% 54.8% 45.2% 12.5% 78.0% 9.6%

28.3% 19.7% 23.6% 28.3% 55.5% 44.5% 5.6% 85.6% 8.8%

20.8% 16.5% 25.0% 37.6% 62.8% 37.2% 28.6% 60.9% 10.5%

12.9% 17.9% 27.5% 41.8% 65.4% 33.8% 13.8% 76.4% 9.8%

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Table 2. JUUL Awareness Table 2. JUUL Awareness

Overall Gender Male Female Race White African American Other Year First Year Sophomore Junior Senior Cigarette Smoking Nonsmoker Smokes on Some Days Daily Smoker Member/Greek Organization Yes No

Had heard or seen of the JUUL (n=1,371)

Aware that one JUUL pod has an equivalent amount of nicotine to a pack of cigarettes (n=951)

69.5% p<.001 74.5% 64.7% p<.001 75.4% 21.2% 60.2% p<.001 80.4% 80.0% 65.0% 57.3% p<.001 64.6% 89.9% 61.0% p<.001 95.9% 56.7%

59.4% p<.001 68.9% 50.9% n/a 60.9% n/a 52.7% p=.004 64.2% 66.0% 55.4% 51.8% p<.001 52.9% 75.9% 66.7% p<.001 71.7% 49.5%

outcome variables across demographic variables and by cigarette smoking status. Chi-squared tests also compared the percentage of trial users who continued as past 30-day users among those who had tried e-cigarettes (but not Juuls) and those who had tried Juuls. To examine misclassification issues in survey assessment of e-cigarette and Juul use, frequency analysis provided the percent of students who reported Juul use but not e-cigarette use, while Chi-squared tests compared these outcome variables across demographic variables and by cigarette smoking status. Results Participants Sample and population demographic characteristics of each university (provided on the website for Institutional Research) are presented in Table 1. The demographic distributions within each university’s undergraduate student population and the survey sample were similar; however, African American students were underrepresented in survey results for each of the three universities. Juul Awareness and Nicotine Perceptions Most students had seen or heard of Juul, and more than half of those who had heard of Juul were aware that one Juul pod has an equivalent amount of nicotine to a pack of cigarettes (Table 2). Awareness tended to be higher among males, white students, younger students, non-daily smokers, and members of Greek organizations, p<.05. More than half of students (59.4%) who were aware of Juul had accurate perceptions of the amount of nicotine in a Juul pod.

Juul Use More than a third of students (37.1%) reported having tried Juuls, and trial was higher among males, students who were not African American, first-year/sophomore students, smokers, and students in the Greek system. Most trial users also reported current past 30-day use. More than half of trial users reported either daily or past week Juul use, 20.5% reported past 30-day use (but not in the past week), and the remaining quarter had not used a Juul in the past 30 days (Table 3). Males, smokers, and students in the Greek system were more likely to report daily or past week Juul use than others, p<.05. Continued use following Juul trial was more likely than continued use following trial of other forms of e-cigarettes. Past 30-day use among trial users was more than three times higher among students who had tried a Juul (74.4%) than those who had tried e-cigarettes but not a Juul (19.5%), p<.001. Conversely, more students who had tried e-cigarettes but not Juul discontinued use more than six months ago (63.6%) versus those who had discontinued Juul use (8.7%), p<.001. Assessment of Juul and e-Cigarette Use All respondents were asked about e-cigarette trial prior to being presented with questions specific to Juul. These e-cigarette questions did not mention Juul. To address the possibility that some students did not consider Juuls to be e-cigarettes, we examined responses to the earlier question about e-cigarette trial among students who later reported trial of the Juul. Indeed, 9.9% of students who reported Juul trial did not report e-cigarette trial. Females, non-smokers, and students in the Greek system were more likely to report Juul but not e-cigarette trial (Table 4).

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Table 3. JUUL Trial and Current Use

Trial use (n=1459)

Daily or Weekly user

Overall Gender Male Female Race White African American Other Year First Year Sophomore Junior Senior Cigarette Smoking Non-smoker Smokes on Some Days Daily Smoker Member/ Greek Organization

Yes No

37.1% p<.001 48.0% 27.2% p<.001 40.4% 4.4% 33.3% p<.001 47.1% 46.2% 32.3% 26.7% p<.001 27.4% 71.5% 44.1% p<.001 68.3% 21.6%

Conclusions Awareness of Juul is high. Most young adults in our sample of Mississippi undergraduate students were aware of Juul, and more than half of those students recognized that one Juul pod is equivalent to a pack of cigarettes. Awareness and accurate nicotine perceptions were higher among males, white students, students at a lower year in school, and students in Greek organizations. More than a third of students report Juul trial. Moreover, most trial users report past 30-day or more frequent use, in striking contrast to many previous studies finding that most trial e-cigarette use is discontinued and only a small percentage of trial users are current users.23,27-29 Furthermore, continued use of Juul among trial users in this sample was three times higher than in previous annual surveys of e-cigarette use among this population. In 2017, approximately a quarter of trial e-cigarette users continued as past 30-day users, whereas more than three-quarters of Juul trial users did so in 2018.30-32 This finding suggests that many Juul users may not be experimenting with the device but using it regularly.23 Overall, past-30 day use among trial Juul users was high, and this study also highlighted some potentially important variations in continued use. Continued use was highest among nondaily smokers and members of Greek organizations. It is not clear from this cross-sectional study why continued use among nondaily smokers would be higher than among daily smokers. Although trial and continued use were lower

48 VOL. 60 • NO. 2 • 2019

Current JUUL use among trial users (n=507)

55.6% 60.4% 48.8% 55.4% n/a 56.1% 60.9% 54.9% 55.5% 49.0% 43.5% 72.7% 57.7% 61.5% 45.4%

Past 30‐day user, but not in the past week

20.5% p=.004 15.7% 27.4% ns 20.5% n/a 19.5% ns 17.4% 20.5% 21.8% 24.0% 24.7% 15.2% 15.4% p<.001 22.1% 18.9%

Has not used in past 30 days

23.9% 23.9% 23.9% 24.1% n/a 24.4% 21.7% 24.6% 22.7% 26.9% p<.001 31.8% 12.1% 26.9% 16.4% 35.7%

among nonsmokers, more than a quarter of nonsmokers had tried Juuls and two-thirds had continued use. Higher use among students in Greek organizations likely relates to students’ financial situations23 and possibly social influences. Juul use began to attract scholarly and media attention in the fall of 2017.21,23 As noted previously, a survey of youth and young adults in November of 2017 found that a quarter of respondents were aware of Juul, ten percent had tried a Juul, and that most trial users continued use.23 Four months later, twice as many students in the current study were aware of Juul and had accurate nicotine perceptions. Moreover, more students had tried Juul, and most of these students also continued use as past 30-day users. These findings, along with sales data indicating an increasing market share,22,33 illustrate the rapid pace with which Juul is becoming ingrained into the social climate of youth and young adults. Although the FDA has recently begun to address the rising popularity of these products among youth,18,34 public health efforts to curb use among nonsmokers will likely face substantial challenges as use becomes more prevalent. This study also highlights the challenges in survey surveillance of e-cigarette trends in a rapidly evolving product landscape. To illustrate, surveys conducted before Juul began to gain market share consistently found that adolescents and adults tended to prefer open system, refillable devices over closed, cartridge-based systems.35-39 However, preferences appear to have changed from open-systems toward pod-

Reports

4. Reports of e-Cigarette Trial among JUUL Trial Users Users ofTable e-Cigarette Trial among JUUL Trial

Overall Gender Male Female Race White African American Other Year First Year Sophomore Junior Senior Cigarette Smoking Nonsmoker Smokes on Some Days Daily Smoker Member/ Greek Organization Yes No

Did not report e‐cigarette trial (n=507) 9.9% p<.001 4.1% 18.9% ns 10.0% n/a 9.8% ns 9.9% 5.7% 13.4% 10.6% p<.001 15.5% 3.0% 0.0% p=.049 12.0% 6.6%

based systems since these surveys were administered, as illustrated by Juul Lab’s dominant market share22 and the prevalence of Juul use found in this study. Surveys of representative samples may be the gold standard for assessing prevalence of use, but social media analyses40 and sales data22 may be more suitable for early detection of emerging trends. Another challenge facing survey surveillance concerns terminology.26 Researchers use many different terms for e-cigarettes, such as electronic cigarettes, e-cigarettes, electronic nicotine delivery systems (ENDS), alternative nicotine delivery systems (ANDS), and aerosol nicotine delivery systems (ANDS); and survey respondents are unlikely to be familiar with most of these terms. Youth and young adults are more likely to use terms, such as vapes, or even Juul.21,23 As previously stated, one in ten students who reported Juul use did not report e-cigarette use earlier in the survey, suggesting that these respondents did not consider Juul use to be e-cigarette use. Researchers need to carefully consider terminology when designing surveys about these products. Limitations There are several potential limitations to this study. First, the response rates for each university were low. However, the demographic distribution of each sample closely matched that of the undergraduate students as a whole, with one exception. The under-representation of African American students, who are less likely to use e-cigarettes,

may have inflated estimates of Juul use. Second, the survey could not differentiate between students who used Juul e-cigarettes exclusively and those who used Juul and other types of e-cigarettes. Students who reported Juul trial but not e-cigarette trial likely only had tried podbased systems. However, students who reported both e-cigarette and Juul trial may have tried both Juul and other forms of e-cigarettes or may have tried the Juul e-cigarette exclusively but recognized this product as an e-cigarette when responding to the e-cigarette trial question. Third, several other pod-based systems entered the market from the time we designed the survey to the time when we concluded data collection. Our survey asked about Juul by brand name and did not address other brands of pod-based systems. Estimates may not accurately describe trial and use for pod-based systems in general. Finally, these findings are from undergraduate students in Mississippi and may not be representative of students outside of the state. Conclusion Awareness and trial use of Juul are high. Moreover, most trial users report daily or past week use in contrast to many previous studies finding that most trial use is discontinued. Universities and policy makers need to be aware of Juul use among undergraduates, particularly those who are non-smokers. n References 1. Goniewicz M. Nicotine Levels in Electronic Cigarettes. Nicotine Tob Res. 2013;15(1):158-166. 2. Pax JUUL Review. Vape Ranks Website. https://vaperanks.com/reviews/paxjuul-review/. Published 2016. Accessed September 14, 2018. 3. Kee C. Everything You Need To Know About The Juul, Including The Health Effects. Buzzfeed News website. https://www.buzzfeednews.com/article/ carolinekee/juul-ecigarette-vape-health-effects. Published February 5, 2018. Accessed September 13, 2018. 4. Lawler R. Vaporization Startup Pax Labs Introduces Juul, Its Next-Gen E-Cigarette. TechCrunch website. https://techcrunch.com/2015/04/21/paxjuul/. Published 2015. Accessed September 26, 2018. 5. JUUL pod Basics. Juul website. https://support.juul.com/home/learn/faqs/ juulpod-basics. Published 2018. Accessed September 13, 2018. 6. Stealth Vaping: How to Become a Vaping Ninja. Vaping360 website. November 2016. https://vaping360.com/stealth-vaping/. 7. Russell, C., McKeganey, N and Haseen, F. Transitions in cigarette smoking associated with use of the JUUL vaping device among 18,799 adults in the United States. Centre for Substance Use Research: Glasgow, UK. 2018;July:1-58. 8. Miech R, Patrick ME, O’Malley PM, Johnston LD. E-cigarette use as a predictor of cigarette smoking: results from a 1-year follow-up of a national sample of 12th grade students. Tobacco Control. 2017;26(e2):e106-e111. doi:10.1136/ tobaccocontrol-2016-053291. 9. Spindle TR, Hiler MM, Cooke ME, Eissenberg T, Kendler KS, Dick DM. Electronic cigarette use and uptake of cigarette smoking: A longitudinal examination of U.S. college students. Addict Behav. 2017;67(C):66-72. doi:10.1016/j. addbeh.2016.12.009. 10. Barrington-Trimis JL, Urman R, Berhane K, et al. E-Cigarettes and Future Cigarette Use. PEDIATRICS. 2016;138(1):e20160379-e20160379. doi:10.1542/ peds.2016-0379. 11. Primack BA, Soneji S, Stoolmiller M, Fine MJ, Sargent JD. Progression to Traditional Cigarette Smoking After Electronic Cigarette Use Among US Adolescents and Young Adults. JAMA Pediatr. 2015;169(11):1018–6. doi:10.1001/jamapediatrics.2015.1742.

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12. Leventhal AM, Strong DR, Kirkpatrick MG, et al. Association of Electronic Cigarette Use With Initiation of Combustible Tobacco Product Smoking in Early Adolescence. JAMA. 2015;314(7):700-708. doi:10.1001/jama.2015.8950.

29. Amato MS, Boyle RG, Levy D. How to define e-cigarette prevalence? Finding clues in the use frequency distribution. Tobacco Control. 2016;25(e1):e24-e29. doi:10.1136/tobaccocontrol-2015-052236.

13. Conner M, Grogan S, Simms-Ellis R, et al. Do electronic cigarettes increase cigarette smoking in UK adolescents? Evidence from a 12-month prospective study. Tobacco Control. 2017;27(4):365-372. doi:10.1136/tobaccocontrol-2016-053539.

30. Mississippi Tobacco Data. The University Survey of Tobacco Control: Mississippi State University. 2017. https://mstobaccodata.org/wp-content/ uploads/2018/01/2017-university-report-msu.pdf. Accessed January 19, 2019.

14. Soneji S, Barrington-Trimis JL, Wills TA, et al. Association Between Initial Use of e-Cigarettes and Subsequent Cigarette Smoking Among Adolescents and Young Adults. JAMA Pediatr. 2017;171(8):788–10. doi:10.1001/ jamapediatrics.2017.1488.

31. Mississippi Tobacco Data. The University Survey of Tobacco Control: University of Mississippi. 2017. https://mstobaccodata.org/wp-content/ uploads/2018/01/2017-university-report-um.pdf. Accessed January 19, 2019.

15. National Academies of Sciences, Engineering, Medicine. Public Health Consequences of E-Cigarettes. (Stratton K, Kwan LY, Eaton DL, eds.). Washington, D.C.: The National Academies Press; 2018. doi:10.17226/24952. 16. U.S. Food & Drug Administration. Press Announcements - Statement from FDA Commissioner Scott Gottlieb, M.D., on new enforcement actions and a Youth Tobacco Prevention Plan to stop youth use of, and access to, JUUL and other e-cigarettes. FDA website. https://www.fda.gov/newsevents/newsroom/ pressannouncements/ucm605432.htm. Published April 24, 2018. Accessed September 13, 2018. 17. Becker R. Juul users sue over the addictive e-cigarette. The Verge website. https:// www.theverge.com/2018/7/23/17605290/juul-nicotine-addiction-lawsuitsvaping-electronic-cigarettes. Published July 23, 2018. Accessed September 13, 2018. 18. U.S. Food & Drug Administration. Warning Letters and Civil Money Penalties Issued to Retailers for Selling JUUL and Other E-Cigarettes to Minors. FDA website. https://www.fda.gov/TobaccoProducts/NewsEvents/ucm605278.htm. Accessed September 13, 2018. 19. ODonnell J. FDA proposes ban on menthol cigarettes, restricts sales of sweet e-cigarettes. November 2018. USA Today website. https://www.usatoday.com/ story/news/health/2018/11/15/fda-ban-vaping-flavors-electronic-cigarettesmenthol-cigars-scott-gottlieb/2003219002/. 20. Kaplan S, Hoffman J. Juul Suspends Selling Most E-Cigarette Flavors in Stores. November 2018. The New York Times website. https://www.nytimes. com/2018/11/13/health/juul-ecigarettes-vaping-teenagers.html. 21. Teitell B. “Juuling”: The most widespread phenomenon you’ve never heard of. November 2017. Boston Globe website. https://www.bostonglobe.com/ metro/2017/11/15/where-teenagers-are-high-school-bathrooms-vaping/ IJ6xYWWlOTKqsUGTTlw4UO/story.html. 22. LaVito A. Popular e-cigarette Juul’s sales have surged almost 800 percent over the past year. CNBC website. https://www.cnbc.com/2018/07/02/juul-e-cigarettesales-have-surged-over-the-past-year.html. Published July 2, 2018. Accessed September 13, 2018. 23. Willett JG, Bennett M, Hair EC, et al. Recognition, use and perceptions of JUUL among youth and young adults. Tobacco Control. 2019;28:115-116. doi:10.1136/ tobaccocontrol-2018-054273. 24. Vallone DM, Bennett M, Xiao H, Pitzer L, Hair EC. Prevalence and correlates of JUUL use among a national sample of youth and young adults. Tobacco Control. Published online first: October 29, 2018. doi:10.1136/ tobaccocontrol-2018-054693. 25. Pearson JL, Reed DM, Villanti AC. Vapes, E-cigs, and Mods: What Do Young Adults Call E-cigarettes? Nicotine Tob Res. 2018;23(3):iii3-iii5. doi:10.1093/ntr/ nty223. 26. Pearson JL, Hitchman SC, Brose LS, et al. Recommended core items to assess e-cigarette use in population-based surveys. Tobacco Control. 2018;27(3):341-346. doi:10.1136/tobaccocontrol-2016-053541. 27. Johnston LD, O’Malley PM, Miech RA, Bachman JG, Schulenberg JE. Monitoring the Future national survey results on drug use, 1975–2016: Volume II, College students and adults ages 19–55. Ann Arbor: Institute for Social Research, The University of Michigan. 2015:1-120. 28. Delnevo CD, Giovenco DP, Steinberg MB, et al. Patterns of electronic cigarette use among adults in the United States. Nicotine Tob Res. 2016;18(5):715-719. doi:10.1093/ntr/ntv237.

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32. Mississippi Tobacco Data. The University Survey of Tobacco Control: University of Southern Mississippi 2017. https://mstobaccodata.org/wp-content/uploads/ 2018/01/2017-university-report-usm.pdf. Accessed January 19, 2019. 33. Huang J, Duan Z, Kwok J, et al. Vaping versus JUULing: how the extraordinary growth and marketing of JUUL transformed the US retail e-cigarette market. Tobacco Control. Published online first: May 31, 2018. doi:10.1136/ tobaccocontrol-2018-054382. 34. F.D.A. Targets Vaping, Alarmed by Teenage Use. September 2018. The New York Times website. https://www.nytimes.com/2018/09/12/health/juul-fda-vapingecigarettes.html. 35. Hitchman SC, Brose LS, Brown J, Robson D, McNeill A. Associations between e-cigarette type, frequency of use, and quitting smoking: findings from a longitudinal online panel survey in Great Britain. Nicotine Tob Res. 2015;17(10):1187-1194. doi:10.1093/ntr/ntv078. 36. Wagener T, Shaikh R, Meier E, et al. Examining the smoking and vaping behaviors and preferences of vape shop customers. Tob Prev Cessation. 2016;2(September):1-7. doi:10.18332/tpc/65150. 37. Dawkins L, Turner J, Roberts A, Soar K. “Vaping” profiles and preferences: an online survey of electronic cigarette users. Addiction. 2013;108(6):1115-1125. doi:10.1111/add.12150. 38. Giovenco DP, Lewis MJ, Delnevo CD. Factors Associated with E-cigarette Use. Am J Prev Med. 2014;47(4):476-480. doi:10.1016/j.amepre.2014.04.009. 39. McMillen R, Tanski S, Wilson K, Klein JD, Winickoff JP. Adolescent use of different e-cigarette products. PEDIATRICS. September 2018:e20180260–10. doi:10.1542/peds.2018-0260. 40. Kavuluru R, Han S, Hahn EJ. On the popularity of the USB flash drive-shaped electronic cigarette Juul. Tobacco Control. 2019;28:110-112. doi:10.1136/ tobaccocontrol-2018-054259.

Author Information Data Management Coordinator at Mississippi State University; provides surveillance for the MSDH Office of Tobacco Control (McClelland). Project Coordinator at Mississippi State University; provides surveillance for the MSDH Office of Tobacco Control (Valentine). Director of the Division of Tobacco Control, the American Academy of Pediatrics (Gorzkowski). Director of the MSDH Office of Tobacco Control (Winter). Professor at Mississippi State University; serves as Principal Investigator on a grant to provide surveillance and evaluation to the MSDH Office of Tobacco Control (McMillen). Conflicts of interest: None. Corresponding Author: Robert McMillen, Professor, Social Science Research Center, Mississippi State University, One Research Boulevard, Suite 103, Starkville, MS, 39759 (robert.mcmillen@ssrc.msstate.edu).

Funding This publication was made possible by the Office of Tobacco control, Mississippi State Department of Health and the Flight Attendant Medical Research Institute (FAMRI) under Award Number #052302_CoE to the American Academy Pediatrics (AAP). The information, views, and opinions contained herein are those of the authors and do not necessarily reflect the views and opinions of these organizations.

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A Comprehensive Evaluation of Mississippi Opioid Prescribing Practices by Strength and Days of Supply, 2012-2017:

Summary of Updated Mississippi Board of Medical Licensure Opioid Prescribing Rules MANUELA STANEVA, MPH; MEG PEARSON, PHARMD, MS; THOMAS DOBBS, MD, MPH; PAUL BYERS, MD

Key Points • While the total number of opioid analgesic prescriptions decreased slightly between 2012 and 2017, there was a disturbing increase in both the strength of opioids (measured in MME) and the days’ supply prescribed. • Combined, the overall 6-year increase in total MMEs and total days of supply was driven by a spike in prescriptions for one opioid: oxycodone. • During this same timeframe, the number of opioid overdose deaths continued to climb, from 107 in 2012 to 172 in 2016. • Providers should follow the 2018 Mississippi State Board of Medical Licensure’s Opioid Prescribing Regulations for acute or chronic pain, “Start low, and go slow.”

Background: Though slight decreases in the state’s prescribing rates for opioid analgesics have been observed, during 2017 Mississippi had the fourth highest opioid prescription rate in the nation, exceeded only by Tennessee, Arkansas, and Alabama.1 Even though there were slight decreases, a disturbing trend has emerged in the opioid prescribing practices in Mississippi, with increases in both morphine milligram equivalents (MME) prescribed and in the duration of prescription measured in days’ supply.

for high-dose opioid prescriptions, MME totals, MME per prescription, total days’ supply, and prescriptions by days of supply (≥30 days and <30 days) (available at https://www.cdc. gov/drugoverdose/pdf/pubs/2018-cdc-drug-surveillancereport.pdf).2 Only opioids used as analgesics were included in the analysis (opioids indicated for addiction treatment and cough suppression were excluded). What follows is a brief overview of those prescribing trends in Mississippi between 2012 and 2017 (Table 1).

A comprehensive assessment of opioid prescribing requires an evaluation of both the dose and duration of opioid prescriptions in addition to looking at prescription rates. Using metrics suggested by the Centers for Disease Control and Prevention, we analyzed the Mississippi Prescription Monitoring Program (MPMP) from 2012 through 2017

Prescriptions for Opioid Analgesics in Mississippi, 2012-2017 Opioid Prescribing Numbers and Rates: High-dose prescriptions, defined as opioid prescriptions ≥ 90 MME per day, accounted for 7.2% of the total 3,107,616 prescriptions

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(MPMP)

every 3 months thereafter for all controlled medications other than opioids ◦

Must document MPMP review (must include time from last check)

◦

PMP check not required for inpatients but must be checked if discharged on opioids Table 1. Prescriptions for Opioid Analgesics in Mississippi, 2012-2017 ◦ Point of Service Drug Testing must be done at least 3 times per calendar Drug Screening year when Schedule for the treatment PRESCRIPTION 2012 2013 II medications 2014 are written 2015 2016 of chronic 2017 Change non-cancerous/non-terminal pain OPIOIDS 2012‐ ◦

Applies also for Benzodiazepines for chronic medical and/or psychiatric

Prescriptions 3,373,334 3,353,854 3,350,348 3,269,040 3,233,684 3,107,616 conditions which are non-cancerous/non-terminal Dosage (MME) Total MME 2,222,314,71 2,251,444,10 2,340,706,70 2,312,774,96 2,203,336,88 ◦ Inpatient treatment/hospice patients2,351,026,63 exempt Mean MME/ Rx 658.8 671.3 698.6 719.2 715.2 709.0 Days’ supply ◦ Terminal/Cancer treatment Exemptions Total days’ 54,647,583 55,406,994 56,809,275 57,298,147 57,986,245 56,427,649 ◦ Hospice patients Days per Rx < 30 days 2,211,714 2,081,417 1,946,563 1,882,523 1,782,736 ◦ Inpatients2,155,103 (nursing home, rehab, hospitals, etc.) ≥ 30 days 1,161,620 1,198,751 1,268,931 1,322,477 1,351,161 1,324,880 ◦ Prescriptions for Pseudoephedrine, Lomotil, Lyrica, Testosterone, and/ or Major opioids Hydrocodone 2,165,252 2,130,928 2,020,591 1,745,745 Amphetamines prescribed for patients 1,805,216 under the age of 16 for the 1,629,054 Oxycodone 370,217 392,107 449,145 518,754 560,660 treatment of Attention Deficit Hyperactivity Disorder 541,298 Tramadol 485,907 483,350 517,318 553,072 556,248 543,550 *MME = Morphine Milligram Equivalent *MME = Morphine Milligram Equivalent

for opioid analgesics in 2017. While the annual prescribing rate for opioid analgesics decreased by 7.9% between 2012 and 2017 (113.0 to 104.1 prescriptions per 100 persons), the annual prescribing rate for high-dose opioid prescriptions remained relatively consistent during the same timeframe (8.0 in 2012 compared to 7.5 in 2017). Prescribing Dosages: During 2017, the total amount of MME prescribed in Mississippi was 2,203,336,886 and the average amount of MME per prescription was 709.0. The total amount of MME prescribed increased cumulatively by 4.1% between 2012 and 2016, but this uptrend started to reverse in 2016. For the six-year period, the average MME per prescription increased significantly by 7.6%, from 658.8 MME/prescription in 2012 to 709.0 MME/prescription in 2017, but this metric also demonstrated a small decrease since 2016.

2017 -7.9%

Change 2016‐ 2017 -3.9%

-0.9% +7.6%

-4.7% -0.9%

+3.3%

-2.7%

-19.4% +14.1%

-5.3% -1.9%

-24.8% +51.4% +11.9%

-6.7% +3.6% -2.3%

each year. Prescriptions for oxycodone, an opioid 1.5 times stronger than hydrocodone, jumped by 51.4% between 2012 and 2017, fueling the overall increases seen in MME. Although several opioids contributed to the increase in the days of supply, oxycodone was the driving force behind this uptrend. Between 2012 and 2017, the total days’ supply for oxycodone doubled from 6,508,235 days in 2012 to 11,128,216 days in 2017, an increase of 71.0%.

Prescribed Supply in Days: The total days’ supply reached 56,427,649 days in 2017, an increase of 3.3% compared to 2012, albeit with a small dip of 2.7% between 2016 and 2017. The overall increase in days’ supply for the six-year period was due to two opposing trends: a downtrend in the number of prescriptions for < 30 days and an uptrend in the number of long-term prescriptions for ≥30 days. The analysis of prescription duration revealed that 42.6% of all prescriptions had duration of 30 days in 2017 as compared to 34.4% in 2012.

Discussion: Between 2012 and 2017, the overall rate of opioid prescriptions went down due to a 24.8% decrease in the number of hydrocodone prescriptions. This is a promising change, although the state’s opioid prescribing rate has remained among the highest in the country. The decline in the opioid prescription was offset by the increase in the total MME and total opioid days’ supply. Such a spike in the dose and duration of opioid prescriptions occurred in parallel with an escalating number of opioid-related overdose deaths.3 Our analyses suggested that these diverging trends may be driven, in part, by a shift in prescribing practices toward prescribing more potent opioid formulations for longer periods of time. The decrease in total prescription rates, therefore, masked the fact that potent opioids, such as oxycodone, were being prescribed in higher numbers and length than previously, intensifying the strength and duration of the opioids remaining in circulation and leading to a spike in adverse outcomes.

Prescribed Opioids: The top three prescribed opioids between 2012 and 2017 were hydrocodone, oxycodone, and tramadol, accounting for around 90.0% of the total opioid prescriptions

What Can Mississippi Providers Do? Evidence suggests that the duration of opioid use is the strongest predictor of future addiction, reinforcing the need to use the shortest course of

52 VOL. 60 • NO. 2 • 2019

Table 2. Mississippi State Board of Medical Licensure Prescribing Rules Summary

Acute Pain Acute Pain

◦◦

Recommended < 3 days Recommended < 3 days

◦◦

Max 10 days, may give 1 additional (max 10 day) prescription Max 10 days, may give 1 additional (max 10 day) prescription

Chronic Pain Chronic Pain

Benzodiazepines Benzodiazepines

Mississippi Mississippi Prescription Prescription Monitoring Monitoring Program Program (MPMP) (MPMP)

Drug Screening Drug Screening

Exemptions Exemptions

◦◦

Use Uselowest lowesteffective effectivedose dose

◦◦

Recommend Recommend≤≤50 50MME MMEdaily daily

◦◦

Should Shouldnot notexceed exceed90 90MME MMEdaily daily

◦◦

IfIf>>100 100MME MMEmust mustbe beininpain painclinic clinic

◦◦

Methadone Methadonefor forchronic chronicpain painonly onlythrough throughpain painclinics clinics(by (byphysician) physician)

◦◦

Max Max90 90days daysper perprescription prescription

◦◦

Should Shouldnot notco-administer co-administerwith withopioids opioids ◦◦

Short Shortterm termacceptable acceptable

◦◦

Patients Patientson onchronic chronicbenzodiazepines benzodiazepinesand andopioids opioidsshould shouldbe be gradually graduallyweaned weanedoff offone oneor orboth both

◦◦

Chronic Chronicco-administration co-administrationininrare, rare,extreme extremecircumstances circumstances

◦◦

All Alllicensees licenseesmust mustregister registerwith withMPMP MPMP

◦◦

Must Mustcheck checkon onall allopioid opioidprescriptions prescriptionsfor foracute acuteand/or and/orchronic chronicnonnoncancerous/non-terminal cancerous/non-terminalpain painupon uponissuance issuance

◦◦

Must Mustutilize utilizethe theMPMP MPMPupon uponinitial initialcontact contactwith withnew newpatients patientsand andat atleast least every every33months monthsthereafter thereafterfor forall allcontrolled controlledmedications medicationsother otherthan thanopioids opioids

◦◦

Must Mustdocument documentMPMP MPMPreview review(must (mustinclude includetime timefrom fromlast lastcheck) check)

◦◦

PMP PMPcheck checknot notrequired requiredfor forinpatients inpatientsbut butmust mustbe bechecked checkedififdischarged discharged on onopioids opioids

◦◦

Point Pointof ofService ServiceDrug DrugTesting Testingmust mustbe bedone doneat atleast least33times timesper percalendar calendar year yearwhen whenSchedule ScheduleIIIImedications medicationsare arewritten writtenfor forthe thetreatment treatmentof ofchronic chronic non-cancerous/non-terminal non-cancerous/non-terminalpain pain

◦◦

Applies Appliesalso alsofor forBenzodiazepines Benzodiazepinesfor forchronic chronicmedical medicaland/or and/orpsychiatric psychiatric conditions conditionswhich whichare arenon-cancerous/non-terminal non-cancerous/non-terminal

◦◦

Inpatient Inpatienttreatment/hospice treatment/hospicepatients patientsexempt exempt

◦◦

Terminal/Cancer Terminal/Cancertreatment treatment

◦◦

Hospice Hospicepatients patients

◦◦

Inpatients Inpatients(nursing (nursinghome, home,rehab, rehab,hospitals, hospitals,etc.) etc.)

◦◦

Prescriptions Prescriptionsfor forPseudoephedrine, Pseudoephedrine,Lomotil, Lomotil,Lyrica, Lyrica,Testosterone, Testosterone,and/ and/or or Amphetamines Amphetaminesprescribed prescribedfor forpatients patientsunder underthe theage ageof of16 16for forthe the treatment treatmentof ofAttention AttentionDeficit DeficitHyperactivity HyperactivityDisorder Disorder

*MME = Morphine Milligram Equivalent *MME = Morphine Milligram Equivalent

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opioids possible.4 In addition; research has demonstrated that a daily dosage of ≥ 50 MME increases the risk of overdoses.5 To mitigate such risks, prescribers should comply with the Mississippi State Board of Medical Licensure’s opioid prescribing rules (summary of Prescribing Rules provided in Table 2), which became effective October 29, 2018 and are highlighted below: 1. Use the lowest effective dose for acute or chronic noncancerous/non-terminal pain and should not exceed 90 MME daily. 2. Do not prescribe opioids for acute pain for more than three days. 3. Utilize the Mississippi Prescription Monitoring Program upon initial contact with new patients in need of opioid treatment. 4. Perform drug screening tests for chronic opioid treatments. For a complete list of rules, please visit: http://www.msbml.ms.gov/ Regulation_Filings. A summary version is provided (Table 2). n Author Information Epidemiologist, Mississippi State Department of Health (Staneva). Director, State Public Health Pharmacy (Pearson). State Health Officer, Mississippi State Department of Health (Dobbs). State Epidemiologist, Mississippi State Department of Health (Byers). Corresponding Author: Paul Byer, MSDH Department of Epidemiology, 570 East Woodrow Wilson Ave., Jackson, MS 39216. ph: (601) 576-7725 (paul.byers@msdh.ms.gov).

ABOUT THE COVER Addiction Edition – This cover image of an e-cigarette calls attention to the lead article “Juul Awareness, Trial, and Continued Use among Undergraduate Students in Mississippi.” On December 18, 2018, Surgeon General Jerome Adams issued a rare advisory – the fourth in 10 years from his office. “I am officially declaring e-cigarette use [vaping] among youth an epidemic in the United States,” Dr. Adams said. The FDA and the Centers for Disease Control and Prevention have looked at data from the 2018 National Youth Tobacco Survey (NYTS). This nationally representative survey, conducted of middle and high school students, shows astonishing increases in kids’ use of e-cigarettes and other electronic nicotine delivery systems (ENDS), reversing years of favorable trends in the fight to prevent youth addiction to tobacco products. From 2017 to 2018, there was a 78 % increase in current e-cigarette use among high school students and a 48 % increase among middle school students. The total number of middle and high school students currently using e-cigarettes rose to 3.6 million – that’s 1.5 million more students using these products than the previous year. Additionally, more than a quarter (27.7 percent) of high school current e-cigarette users are using the product regularly (on 20 or more days in the past month). More than twothirds (67.8 percent) are using flavored e-cigarettes. Both these numbers have risen astonishingly. Vaping, predominantly with nicotine but also marijuana, appeared VOL. LX • NO. 2 • 2019

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References 1. Centers for Disease Control and Prevention. 2018 Annual Surveillance Report of Drug-Related Risks and Outcomes — United States. Surveillance Special Report. Centers for Disease Control and Prevention. U.S. Department of Health and Human Services. August 31, 2018. 2. Centers for Disease Control and Prevention. U.S. Opioid Prescribing Rate Maps.

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3. Drug Overdose Deaths Involving Opioids in Mississippi, 2011-2016. Mississippi State Department of Health. February 2, 2018. Jackson. Mississippi.

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4. Brat GA, Agniel D, Beam A, Yorkgitis B, Bicket M, Homer M, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: Retrospective cohort study. BMJ 2018;360:j5790. 5. Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, et al. Opioid prescriptions for chronic pain and overdose: A cohort study. Ann Intern Med. 2010;152:85-92. doi: 10.7326/0003-4819152-2-201001190-00006: http://annals.org/aim/article-abstract/ 745518/opioid-prescriptions-chronic-pain-overdose-cohort-study.

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throughout the report as a surging problem. Most e-cigarettes contain nicotine, and the most popular brand among teenagers, Juul, has particularly high levels of it. One Juul cartridge or pod has as much nicotine as a pack of cigarettes. Nicotine is highly addictive. Peer/social pressure and well-targeted ads lead teens to vape. Adolescents need to be protected from a lifetime of cancer-causing addiction and associated health risks. Parents, who often don’t know the dangers and facts, need to know vaping is not a “risk-free” version of smoking. Teens report not being able to get through class without a vape because of nicotine withdrawal. And, kids using e-cigarettes are more

likely to try combustible cigarettes later. This is a large pool at future risk to become hooked. The data make unmistakably clear, if we’re to break the cycle of addiction to nicotine then preventing youth initiation to nicotine is a paramount imperative. As a physician, you have unique opportunities to reach youth and their parents with credible, correct information about e-cigarettes and ENDS. Your JMSMA encourages doctors to ask about e-cigarette usage during annual check-ups, educate teens and parents on the risks of e-cigarettes for young people, even secondhand aerosol. n

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Brunini, Grantham, Grower & Hewes, PLLC is pleased to announce that William B. Grete has joined the firm as a Partner in its Jackson office. As the former Vice President and General Counsel of Mississippi Baptist Health Systems Inc., Mr. Grete brings over 20 years of healthcare experience to the firm as an accomplished legal healthcare executive and trusted advisor.

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S C I E N C E

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A D D I C T I O N

Backstories on the US Opioid Epidemic:

Good Intentions Gone Bad, an Industry Gone Rogue, and Watchdogs Gone to Sleep RICHARD D. DESHAZO, MD; MCKENZIE JOHNSON, BS; IKE ERIATOR, MD; KATHRYN RODENMEYER, BA

Abstract Epidemics of opioid use are old news in the United States, but an epidemic that kills over 200,000 Americans is not. A multiplicity of intertwined factors has brought us to this place. From 30,000 feet, it is the story of good intentions gone bad, a drug industry gone rogue, and government watchdog agencies gone to sleep. At ground level, it is the story of physicians unfamiliar with addictive drugs and drug addiction, new long-acting opioids deceptively marketed, cheap black tar heroin, encouragement to use opioids for chronic noncancer pain by professional organizations with conflicts of interest and without science, a culture intolerant to pain and tolerant to drug use, and the greedy response of the pharmaceutical industry and drug cartels to an expanding market opportunity. These factors are among those that have joined to form a tsunami of addiction and deaths that keeps on coming. A better understanding of them could speed the end of the present cycle of opioid abuse, perhaps prevent others, and inform future decisions about pain management. Keywords: Addiction; drug industry; opioid-related deaths; opioids; pain

Figure 1. Responses to the Question, “Who Is Most Responsible for the Nation’s Opioid Crisis?” from a Random Survey of 3,645 Individuals by Fortune Magazine

I I

DRUG USERS

PHYSICIANS

OTHER/ DON •T KNOW

15%

DRUG COMPANIES

11%

DRUG DEALERS

DRUG DISTRIBUTORS

Adapted from Reference 3

Table 1. Some Factors Promoting an Escalation of Opioid Use in the United States Around 1996 Table 1. Some Factors Promoting Escalation of Opioid Use in the United States Around 1996 1.

A well‐intentioned effort among some physician groups to better manage chronic pain

2. 3. 4. 5. 6. 7. 8. 9. 10.

False marketing claims about addiction to new, longer‐acting opioids Lack of physician education on the use of drugs with high abuse potentials Direct‐to‐physician marketing Provider‐run pill mills Culture of drug use and abuse Multitude of cheap, widely available drugs of abuse including black tar heroin Over‐prescription of narcotics Expansion of Mexican drug cartels Corporate greed

Adapted from Reference 3 Adapted from Reference 3

56 VOL. 60 • NO. 2 • 2019

Table 2. Representative Over-the-Counter Patented Medicines and Kits for Dispensing Opioids Table 2. Representative Over‐the‐Counter Patented Medicines and Kits for Dispensing Opioids Product

Content

Indication

Mrs. Winslow’s Soothing Syrup Bangor, Maine (1894)

Morphine Sulfate 65 mg/oz

Sleep aid and analgesic for children

Stickney and Poor’s Pure Paregoric Use (1905)

Opium 1

Asthma for patients 5 days old and up

Bayer & Company’s‐Heroin (1890)

Heroin 1/24 grain per pill and in elixirs

Antitussive

Vapor‐Oil Treatment No. 6 National Vaporizers Co. Kalamazoo, Mich. (Late 1800’s)

Opium 35 mg/oz in alcohol

Asthma and “spasmodic affections”

Parke‐Davis & Company’s “Emergency Kit” (1894)

Cocaine, morphine, atropine, strychnine, and a hypodermic syringe

“Emergencies”

8/16

gr/oz in 46% alcohol

Introduction The current American epidemic of opioid-related deaths began in the 1990s and has resulted in over 200,000 deaths.1 The average American does not know who to blame (Figure 1).2 The only systematic review on causation suggests that the factors are multiple, intertwined, and frequently changing (Table 1).3 That review determined that physician behavior is clearly one of them. This paper reviews backstories on some factors that may help inform our response as physicians. America’s Long Tarantella with Opioids Extracts of the poppy plant have been used for medicinal purposes since the Sumerians named it the “joy plant” 5000 years ago. By the time of the American Revolution, an alcohol-based tincture of 10% powdered opium called “laudanum” was widely prescribed in the United States and many became addicted. Morphine was isolated from opium about 50 years before it caused “Soldier’s Disease,” an epidemic of addiction during the Civil War.4 Bayer Pharmaceuticals marketed heroin in 1874 as an analgesic and claimed it was less addictive than other opioids, claims made about the new opioids to follow. During this period, opium, heroin, and cocaine were used in over-the-counter patent medicines and sold over the counter in “emergency kits” equipped with hypodermic syringes and needles (Table 2). By 1925, there were an estimated 200,000 heroin addicts in the United States. The problem of opioid addiction led to passage of federal legislation to control it in 1906, 1909, 1914, and 1924 (Table 3). Tolerance for illicit drug use increased after young people smoked marijuana in public and Jimi Hendrix followed his psychedelic version of the national anthem with his song “Purple Haze” at the 1969 Woodstock Music and Art Fair. By 1971, 15% of soldiers in Vietnam had become heroin addicts. In response, President Nixon declared drug addiction “public enemy number one” in 1972 and established federally supported methadone clinics, only to have methadone quickly become a drug of abuse.5 Around 1996, the confluence of a new pain movement and the pharmaceutical industry was associated with a substantial escalation of prescription opioid use, abuse, and opioid-related deaths in the United States.

The Confluence of the Pain Movement and Pharma In 1980, a one-paragraph “Letter to the Editor” in the New England Journal of Medicine reported that of 11,882 hospitalized patients treated with narcotics, <1% of them became addicted.6 The letter was subsequently “uncritically cited” in 439 articles published in scientific journals.7 Meanwhile, a shared interest in better management of cancer pain led Raymond Houde, MD, Katherine Foley, MD, and Russell Portenoy, MD at Cornell University-Weill Medical College to become leaders in the American Pain Society (APS). Two of them concluded that opioid maintenance therapy for chronic noncancer pain was safe and humane.8 The APS became an advocacy group for opioid treatment of pain and eventually received most of its support from Purdue Pharma (Stamford, Conn), maker of the opioids MS Contin® and OxyContin®.9 In 1995, the APS proposed that pain be measured as the “5th Vital Sign” and trademarked the term. They published a consensus statement with the American Academy of Pain Medicine in 1997 and declared that there was insufficient evidence to show that addiction occurs when opioids are appropriately prescribed for the treatment of pain.10 In 2010, the International Association for the Study of Pain added a patient’s rights component to the pain movement when it declared that all patients were entitled access to pain management and treatment, including opioids.10 Another advocacy group, the American Pain Foundation organized e-mail campaigns to media outlets they determined to be biased against opioids for pain treatment at a time when it received 90% of its funding from the drug and device industry. Many “thought leaders” from pain societies gave Pharma-supported lectures to provider groups to encourage treatment of pain with opioids.10 The APS was joined by the Veterans Affairs Medical System (VA), the Joint Commission for Accreditation of Health Organizations (now The Joint Commission [TJC]), the American Medical Association, the American Academy of Family Physicians, and patient advocacy groups in support of Pain as the 5th Vital Sign.11 Opioid manufacturers and pain management advocates then convinced the US Congress to declare “A Decade of Pain Control and Research” in 2000.10 By 2001, new TJC Pain Management Standards, used as a component

FEBRUARY • JOURNAL MSMA

of hospital accreditation and reimbursement, were implemented and required pain to be assessed and addressed in all hospitalized patients.12 The commission also implemented its own pain initiative and developed educational materials for it with support from Purdue Pharma and the National Pharmaceutical Council, Inc. These included the monograph Improving the Quality of Pain Management through Measurement and Action, which advocated opioid use for pain and was co-branded with the logos of TJC and the National Pharmaceutical Council.13 A nurse developed and copyrighted the Wong Baker Facial Scale that allowed patients to grade their pain from 1-10 by choosing faces that smiled or frowned, a subjective measure that soon came to be used as an objective one. The VA mandated the measurement of Pain as the 5th Vital Sign and that it be addressed in every clinical encounter in 1999. In 2016, as opioid deaths exploded, Physicians for Responsible Opioid Prescribing petitioned TJC to stop their support of opioid use and claimed their pain standards “foster dangerous pain control practices” which “often lead to the inappropriate prescribing of opioids” and “disastrous consequences.”13 A 2015 opinion piece noted the physiological futility of using pain intensity to guide pain treatment and the need to return to the basics of pain management, which were already outlined in a 2010 National Institute of Health Pain Initiative.14 All of this eventually led to the 2011 Institute of Medicine report, Relieving Pain in America.15 About the same time, both the American Medical Association and the American Academy of Family Physicians voted to rescind their previous support of pain as the 5th Vital Sign.14

The actions of 3 New York City psychiatrists, the Sackler brothers, played a major role in this story.16 Dr. Arthur Sackler (d.1987) became a wealthy pharmaceutical marketing executive, publisher of medical trade publications, and father of direct-to-physician marketing. He and his brothers Mortimer (d. 2010) and Raymond (d. 2017) purchased Purdue Frederick, a New York drug manufacturer that produced an ear wax remover, a laxative, Betadine®, and a tonic that was 11% alcohol under the name Purdue Pharma. Their first new product was the long-acting morphine MS Contin® released in 1984, followed by OxyContin®, a long-acting oxycodone.17 After Food and Drug Administration (FDA) approval in 1995, OxyContin® was marketed as a “less addictive opioid.” OxyContin® was launched only after the Sackler brothers deployed a carefully considered marketing plan using a 600-person sales force and a list of over 90,000 physicians judged likely to prescribe OxyContin®. Physicians received free trips to exotic locations to hear paid members of the Purdue “Speakers Bureau” give talks supporting opioid use for chronic pain, and patients received coupons for an up-to-30-day supply of OxyContin® for free. Both the unsubstantiated “Theory of Pseudo-Addiction” suggesting that drugseeking by pain patients treated with opioids reflected undertreatment of pain, and the report of a 1% addiction rate of opioids were included in OxyContin® marketing. These same erroneous claims were included in a publication of opioid use for pain management by the Federation of State Medical Bonds (FSMB) sponsored by Purdue Pharma.18 In 2007, Purdue paid $630 million dollars to settle FDA claims for false

Table 3. Representative Federal Legislation to Control Opioid Use in the United States Table 3. Representative Federal Legislation to Control Opioid Use in the United States Date

Title

Action

1909

Smoking Opium Exclusion Act

Criminalizes the importation, possession, or smoking or opium

1914

Harrison Narcotic Tax Act

Creates registry of all who produce, import, manufacture, dispense, or give away any product of the poppy or coca leaf. Singles out addiction as a moral not a medical issue. Limits prescriptions for small amounts of narcotics to doctors

1924

Heroin Act

Makes production and possession of heroin illegal

1919‐1933

21st Amendment to the US Constitution

Period of Prohibition via Comprehensive Drug Abuse Prevention Act (Title II)

1970

Controlled Substances Act

Regulates manufacture and distribution of narcotics. Establishes 5 narcotics schedules. Marijuana becomes a controlled substance

1973

US Reorganization Plan No. 2 of 1973

Reorganizes federal drug law enforcement and establishes the Drug Enforcement Agency (DEA) in the Department of Justice

1974

Narcotic Addict Treatment Act

Allows physicians to register to provide narcotics to addicts for “maintenance treatment” and establishes the National Institute of Drug Addiction (NIDA)

2016

Comprehensive Addiction and Recovery Act of 2016 (CARA)

Authorizes $181 million dollars for prevention and treatment of the opioid epidemic

1906

Pure Food and Drug Act

58 VOL. 60 • NO. 2 • 2019

Requires patent medicines with opiates to be labeled as “dangerous or addictive”

marketing of OxyContin®, and several company officials paid an additional $34 million in fines (Table 4). More FDA investigation continued and opioid makers and distributors looked for relief. The Pain Policy Study Group composed of social science faculty at the University of Wisconsin, Madison received $2.5 million dollars in grants from the pharmaceutical industry, including $1.6 million dollars from Purdue Pharma in the process of its work on opioids-prescribing policies.20 In 2002, the Pain Policy Study Group reported a 10-year collaboration with the FSMB to “update and clarify state medical board policies on the use of opioid analgesics to treat pain.” Their report was used to develop Model Guidelines for the FSMB to address “prescribing of opioid analgesics for pain and physicians fears of regulatory scrutiny”21 (Table 5). In 2003, Purdue provided $100,000 for the printing of 300,000 widely distributed copies of the FSMB Model Guidelines, which were highly supportive of opioid use for chronic pain and used to develop opioid-prescribing policies by most state boards.22 The Guidelines were developed in the absence of high quality scientific studies and reflected the opinions of the pain management community who collaborated on their formation.19 The Failures in Oversight of Opioid Manufacture, Distribution, Prescribing, Diversion, and Importation The Controlled Substance Act of 1970 relaxed the antiopioid portions of the Harrison Narcotics Act of 1914 and recognized that opioids had legitimate medical purposes (Table 3).23 It established the US Drug Enforcement Agency (DEA) to set production quotas and to monitor and control diversion and excessive production of narcotics.24 In response to the pain movement, the DEA joined with 21 health care organizations in 2001 to call for improved approaches to ensure that prescription opioids were available for medical use and prevented from diversion.25 Surprisingly, for a drug enforcement agency, they noted that pain was undertreated and that opioids were the most effective treatment for many patients. Between 1996 and 2007, the DEA approved increases in US production of the opioids hydrocodone fourfold, fentanyl 10-fold, and hydromorphone four and a half-fold, Table 4. Pharmaceutical Companies and Distributors Settlements with the U.S. Department of Justice as of 2017 for Complicity in the Opioid Epidemic Table 4. Pharmaceutical Companies and Distributors Settlements With the US Department of Justice as of 2017 for Complicity in the Opioid Epidemic Purdue Pharma

$630 M

2007

AmeriSource Bergen

$13.2 M

2008

Cardinal Health

$44 M

2017

McKesson

$150 M

2017

Adapted from Reference 19

Table 5. Purpose of the Federation of State Medical Boards (FSMB) Model Guidelines for Use of

Table 5. Purpose of the Federation of State Medical Boards (FSMB) Model Guidelines for Controlled Substances for the Treatment of Pain (1998) Use of Controlled Substances for the Treatment of Pain (1998)* 1. Promote safe and effective pain relief, including the use of opioid analgesics 2. Ensure that physicians will not be sanctioned for prescribing such medication for legitimate medical purposes 3. Stress the need to safeguard against medication diversion and abuse *From Reference 22

Adapted from Reference 22

but sanctioned <0.1% of physicians for narcoticprescribing violations from 1999 to 2003.26,27 In 2016, The Washington Post reported that the Ensuring Patient Access and Effective Drug Enforcement Act (H.R. 4709) was “the crowning achievement of a multi-faceted campaign of the drug industry to weaken DEA enforcement activities against drug distribution companies that were supplying corrupt physicians and pharmacists who peddled narcotics on the black market.”27 The industry had contributed $1.5 million dollars to the campaigns of 23 lawmakers who sponsored H.R. 4709, including $100,000 to Representative Tom Marino. Marino withdrew from President Trump’s nomination as DEA director in 2017 after his conflict of interest was exposed.28 The DEA also closed its Special Operations Unit that covertly collected internal phone records used to monitor drug traffic after congressional criticism.29 In the fall of 2017, the acting head of the DEA resigned. The FDA, charged with ensuring drug safety, efficacy, marketing, and labeling, was also affected by pain treatment advocacy. In the 1990s, the FDA implemented an “Enriched Enrollment Protocol” to speed approval process for pain medication. The Initiative on Method, Measurement and Pain Assessment in Clinical Trials, a group funded by the pharmaceutical industry, helped develop the protocol.30 This protocol resulted in decreased drug failure rates in clinical trials for narcotics and was criticized for increasing the risks of undetected side effects in new drugs.31 The FDA is also responsible for ensuring that the information supplied in drug advertising and promotion is accurate, balanced, and truthful, but is understaffed in that effort.31 The FDA review of the original FDA New Drug Application for OxyContin® missed the implications of a disclosure that crushing tablets immediately released 68% of the oxycodone and thus promoted it to become a drug of abuse; it also missed the disingenuous original manufacturer’s label stating that addiction to it was “very rare.”31 The 2004 label revision of OxyContin® cautioned patients not to chew or bite the tablet, which further clued abusers to crush it for illicit use. When OxyContin® was reformulated to make it more difficult to abuse in 2010, many OxyContin® addicts switched to black tar heroin.31 By then, the Sackler brothers’ corporate worth was $14 billion dollars. Between 2009 and 2010, 50%

FEBRUARY • JOURNAL MSMA

of patients admitted to hospitals for medical conditions received narcotics, and huge volumes of oxycodone and other opioids were produced, distributed, used, diverted, and abused.32 Opioid addiction and deaths, especially from heroin, continued to skyrocket.

Figure 2. Historical production and geographic sources of heroin Figure 2. Historical Production and Geographic Sources of Heroin

Mexico is the largest source of the heroin used in the United States (Figure 2). The increasing demand for heroin that developed in the early 1970s resulted in the emergence of a new breed of Mexican drug cartels (Figure 3). They grew poppies where they lived, produced high-quality, less expensive black tar heroin, and packaged and smuggled it in small quantities to trusted family members serving as distributors throughout the United States. Heroin was delivered in balloons held in the mouths of distributors or their clients so evidence of the sale could be swallowed if police or thieves appeared.32

POPPIES

l l l

POPPY POD SAP

OPIUM

WHITE POWDER (ASIA)

Fentanyl, an opioid 80 times more potent than heroin, was brought to market in the United States as Duragesic® by

BLACK TAR (MEXICO)

HEROIN

BROWN POWDER (COLUMBIA, PAKISTAN and AFGHANISTAN)

Figure 3. Present Locations of Drug Cartels Operating in the United States.

Figure 3. Present locations of drug cartels operating in the United States

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WN1 PMT18eactl OO

M,..,.. Foo,

(U) Cartel"'°"'""" it mea,wre<l bl' ae11ve COnsolidated Pnority Otganizolion Tatget cases;,, FY16 and te-.ets of influence ate wejghted band on tho number of cans agamst popul.at»on dctf'la1ty.

so..r..: Drug Enlo<.. menl Adminlou.lion (01:A) and Orgon,zed Omo 0,ug Enlo«emonl Talk FO<C4 (OCOETF) current

of FebNOt')' 2016

l ',.

-==-. -~ .... ''\._

.. """"'

Source : DEA

Adapted from Reference 23. Adapted from Reference 23

60 VOL. 60 • NO. 2 • 2019

Janssen Pharmaceuticals, now owned by Johnson & Johnson, Inc. (New Brunswick, NJ).33 In the early 1990s, drug dealers began mixing fentanyl with heroin to produce a greater high. After 350 related deaths occurred between 2005 and 2007 in Cook County, Illinois, the combination came to be noted as “Drop Dead.”31 By 2016, half of overdose deaths in Illinois were fentanyl-related.34 When overproduction of fentanyl by the US companies was finally curtailed, chemists in China produced fentanyl in large quantities and developed countless derivatives made available to heroin producers in Mexico and drug users in the United States by mail and otherwise. By 2016, carfentanil, initially used to tranquillize elephants and 100 times more potent than fentanyl, was a frequent cause of drug overdoses in Ohio, New York, Pennsylvania, Florida, and neighboring states.35 The Plaintiffs Bar to the Rescue The failure to control the scourge of America’s present opioid epidemic has many similarities to America’s long fight to limit tobacco use, another drug protected by the money and power of an industry. It was not until the 1964 report of Surgeon General Luther L. Terry, MD that science broke through the dissonance of the tobacco industry’s attempts to hide the facts about its deleterious effects on health. Efforts of federal health agencies and the US Congress to stem the tide of tobacco related disease were blocked. The best the US Congress could do was to pass 2 acts that required health warnings on cigarettes and banned tobacco advertising in broadcasting. The 42-year-old Democratic Attorney General of Mississippi, Mike Moore, filed the first successful law suit against “Big Tobacco” in 1994 to recover state Medicaid costs for the treatment of tobacco-related disease.36 The success of that suit and similar ones by other states led to the capitulation of the 4 major tobacco manufactures and the largest corporate legal settlement in US history in 1997. Among other accomplishments, the Tobacco Master Settlement of 1998 generated an award worth over $200 billion dollars that continues to fund smoking cessation and prevention programs for all 50 states.38 Subsequent to the settlements paid by opioid manufacturers and distributers to federal regulatory agencies to settle charges by federal agencies (Table 4), additional suits were filed between 2008 and 2017 on behalf of individuals addicted while taking opioids “as directed” on the manufacturer’s label. But like Big Tobacco, Big Pharma considered product litigation the cost of doing business. By 2012, enough opioids were dispensed in Ohio to provide 68 pills each for every resident.36 The Ohio and Mississippi attorneys general selected Mike Moore to lead their litigation to recover state expenditures for opioid addiction. Moore filed suit in May of 2017 against Purdue Pharma, Endo Pharma, Johnson & Johnson’s Janssen Pharmaceuticals, Teva Pharmaceutical Industries, and Allergan Pharma. A gathering army of state and local jurisdictions has followed. Just as tobacco manufacturers had done, the drug companies have responded with a public campaign to deny culpability.37 Lessons Learned The lessons learned from this opioid epidemic are many. For organized

medicine, the principal one seems old. That is, making medical treatment recommendations, policies, and decisions without solid scientific data is dangerous for all concerned. Those who are most comfortable doing so are likely to have conflicts of interest, ethical issues, and greed. The opioid epidemic has now been declared a “national emergency,” when many of the questions about the biology of pain, the treatment of acute and chronic pain, and the treatment of opioid addiction remain unanswered.38 The course of the epidemic to date reflects our ignorance of the neurobiology of the brain’s reward system and the need for investment in basic and clinical research to understand why drugs of abuse are so attractive to so many. The National Academies have proposed a way forward.39 We should follow their suggestions. n Acknowledgement The authors appreciate the assistance of Leigh Skipworth and Kyle McCullouch in the preparation of this manuscript. Author Information Department of Medicine, University of Mississippi Medical Center, Jackson (deShazo; Johnson). Department of Pediatrics, University of Mississippi Medical Center, Jackson (deShazo). Mississippi Public Broadcasting, Jackson (deShazo; Rodenmeyer). Department of Anesthesiology, University of Mississippi Medical Center, Jackson (Eriator). Corresponding Author: Richard D. deShazo, MD, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216. Ph. 601-506-1397 (rdeshazo@ umc.edu). Funding Source: The Selby and Richard McRae Foundation. Conflicts of Interest: None. _____________________________________________________ RAdapted from Am J Med. 2018;131(6):595-601. doi: https://doi.org/10.1016/j. amjmed.2017.12.045.

References 1. Meldrum ML. The ongoing opioid prescription epidemic: historical context. Am J

Public Health. 2016;106:1365-1366.

2. Fry E. Here’s who Americans blame most for the opioid epidemic. Fortune website. June 21, 2017. Available at: http://fortune.com/2017/06/21/ opioid-epidemic-blame-doctors/. Accessed February 23, 2018. 3. King NB, Fraser V, Boikos C, Richardson R, Harper S. Determinants of increased opioid related mortality in the United States and Canada, 19902013: A systematic review. Am J Public Health. 2014;104:e32-e42. 4. Hyams KC, Wignall FS, Roswell R. War syndromes and their evaluation: from the U.S. Civil War to the Persian Gulf War. Ann Intern Med. 1996;125:398-405. 5. U.S. Food and Drug Administration. Consumer Updates [11/2006]. FDA Public Health Advisory: Methadone use for pain control may result in death and life-threatening changes in breathing and heartbeat. Available at: http://www.methadone.org/downloads/documents/fda_comsumer_ updates_2006_methadone_pain_control_death_changes_breathing_ heart_beat_nov_.pdf. Accessed November 11, 2017. 6. Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. 1980;302:123. 7. Leung PTM, Macdonald EM, Stanbrook MB, Dhalla IA, Juurlink DN. A 1980 letter on the risk of opioid addiction. N Engl J Med. 2017;376:e2194-e2195.

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8. Portenoy RK, Foley KM. Chronic use of opioid analgesics in nonmalignant pain: Report of 38 cases. Pain. 1986;25:171-186.

Administration. Available at: https://www.usa.gov/federal-agencies/drugenforcement-administration. Accessed December 1, 2017.

9. Ballantyne J, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349:1943-1953.

25. US Drug Enforcement Administration. 2001. DEA to join pain advocates in issuing statement on prescription pain medicine. Available at: https://www. dea.gov/pubs/pressrel/pr102301.html. Accessed December 1, 2017.

10. Brennan F. The US congressional “Decade on pain control and research” 2001-2011; a review. J Pain Palliat Care Pharmacother. 2015;29:212-227. 11. Geriatrics and Extended Care Strategic Healthcare Group National Pain Management Coordinating Committee. Department of Veterans Affairs. Pain as the 5th vital sign toolkit. Available at: https://www.va.gov/ PAINMANAGEMENT/docs/Pain_As_the_5th_Vital_Sign_Toolkit.pdf. Accessed December 12, 2017. 12. Joint Commission for Accreditation of Health Organizations (JCAHO). Improving the Quality of Pain Management through Measurement and Action. Oakbrook Terrace, IL: Joint Commission Resources, Inc.; 2003. 13. Accreditation Insider. Petitions ask Joint Commission and CMS to change pain management policies. HCPro; 2016. Available at: http://www.hcpro. com/content.cfm?dp=ACC&content_id=326464&publication=4634&. Accessed December 1, 2017. 14. Ballantyne JC, Sullivan MD. Intensity of chronic pain—the wrong metric? N Engl J Med. 2015;373(22):2098-2099. 15. Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: The National Academies Press; 2011. 16. Ryan H, Girion L, Glover S. OxyContin goes global – “we’re only just getting started”. Los Angeles Times Web site. December 18, 2016. Available at: http:// www.latimes.com/projects/la-me-oxycontin-part3/. Accessed November 11, 2017. 17. Glueck G. Arthur Sackler Dies at 73; Philanthropist and Arts Patron. The New York Times Web site. May 27, 1987. Available at: http://www.nytimes. com/1987/05/27/obituaries/dr-arthur-sackler-dies-at-73-philanthropistand-art-patron.html?mcubz=1. Accessed November 11, 2017. 18. Joranson DE, Gibson A, Dahl JL, et al. Pain management, controlled substances, and state medical board policy: A decade of change. J Pain Symptom Manage. 2002;23(2):138-147. 19. Fauber, J. Follow the money: pain, policy and profit. Medpage Today Web site. February 19, 2012. Available at: https://www.medpagetoday.com/ neurology/painmanagement/31256. Accessed February 23, 2018. 20. Fauber J. UW a force in pain drug growth. Milwaukee Journal Sentinel Web site. April 12, 2011. Available at: http://archive.jsonline.com/watchdog/ watchdogreports/119130114.html/. Accessed December 1, 2017. 21. Federation of State Medical Boards. Position of the Federation of State Medical Boards in support of adoption of pain management guidelines; 1998. Available at: https://www.fsmb.org/Media/Default/PDF/FSMB/Advocacy/1998_ grpol_Pain_Management_Guidelines.pdf. Accessed December 1, 2017. 22. Federation of State Medical Boards. Model policy on the use of opioid analgesics in the treatment of chronic pain; 2013. Available at: https://www.fsmb.org/ Media/Default/PDF/FSMB/Advocacy/pain_policy_july2013.pdf. Accessed February 8, 2017. 23. US Drug Enforcement Administration. 2016. Controlled Substance Act. Available at: https://www.dea.gov/druginfo/csa.shtml. Accessed December 1, 2017. 24. US Drug Enforcement Administration. 2017. Drug Enforcement

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26. Temple J. American Pain: How a Young Felon and His Ring of Doctors Unleashed America’s Deadliest Drug Epidemic. Gilford, Conn: First Lyons Press; 2016:3756, [Chapter 2]. 27. Higham S, Bernstein L. The drug industry’s triumph over the DEA. The Washington Post Web site. October 15, 2017. Available at: https://www. washingtonpost.com/graphics/2017/investigations/dea-drug-industrycongress/?utm_term=.7754e7332099. Accessed December 1, 2017. 28. Higham S, Bernstein L. Rep. Tom Marino: drug czar nominee and the opioid industry’s advocate in congress. The Washington Post Web Site. October 15, 2017. Available at: https://www.washingtonpost.com/investigations/reptom-marino-drug-czar-nominee-and-the-opioid-industrys-advocate-incongress/2017/10/15/555211a0-b03a-11e7-9e58-e6288544af98_story. html?utm_term=.fcf11133e054. Accessed December 1, 2017. 29. McVeigh K. US drug agency surveillance unit to be investigated by Department of Justice. The Guardian Web site. August 6, 2013. Available at: https://www.theguardian.com/world/2013/aug/06/justice-departmentsurveillance-dea Accessed December 1, 2017. 30. Dworkin RH, Turk DC, Farrar JT. Topical review and recommendations, core outcome measures for chronic pain clinical trials: IMMPACT recommendation. Pain. 2005;113:9-19. 31. Denton S, Donoghue E, McReynolds J, Kalelkar M. An epidemic of illicit fentanyl deaths in Cook County, Illinois: September 2005 through April 2007. J Forensic Sci. 2008;53:452-454. 32. Quinones S. Dreamland: The True Tale of America’s Opiate Epidemic. New York, NY: Bloomsberry Press; 2015;92-99. 33. Mandal A. Fentanyl history. News Medical Web Site. 2014. Available at: https://www.news-medical.net/health/Fentanyl-History.aspx. Accessed December 1, 2017. 34. Tribune news services. More than 50,000 overdose deaths: A grim tally soars to all-time U.S. high. Chicago Tribune Web site. December 8, 2016. Available at: http://www.chicagotribune.com/news/nationworld/ct-us-overdosedeaths-20161208-story.html. Accessed December 1, 2017. 35. Drug Enforcement Administration (DEA). DEA issues carfentanil warning to the police and public. Springfield, VA: United States Drug Enforcement Administration; 2016. 36. Deprez EE, Barrett P. The lawyer who beat big tobacco takes on the opioid industry. Bloomberg Businessweek Web site. October 15, 2017. Available at: https://www.bloomberg.com/news/features/2017-10-05/the-lawyer-whobeat-big-tobacco-takes-on-the-opioid-industry. Accessed December 1, 2017. 37. Tobacco Control Legal Consortium. The master settlement agreement: an overview. Tobacco Control Legal Consortium, St. Paul, Minnesota. Available at: http://www.publichealthlawcenter.org/sites/default/files/resources/ tclc-fs-msa-overview-2015.pdf. Accessed December 1, 2017. 38. Gostin LO, Hodge JG, Noe SA. Reframing the opioid epidemic as a national emergency. JAMA. 2017;318(16):1539-1540. 39. Bonnie RJ, Kesselheim AS, Clark DS. Both urgency and balance needed in addressing the opioid epidemic. A report in the National Academies of Sciences, Engineering and Medicine. JAMA. 2017;318(5):423-424.

17TH ANNUAL

CME IN THE SAND May 24 – 28, 2019 Sandestin Golf and Beach Resort Sandestin, Florida

SCHEDULE OF EVENTS: FRIDAY, MAY 24 6:00 pm Welcome Reception SATURDAY, MAY 25 7:00 am Breakfast with Exhibitors 8:00 am CME (4 hours) 2:00 pm MACM Golf Tournament SUNDAY, MAY 26 7:00 am Breakfast with Exhibitors 7:00 am Prescribing CME (5 hours) 6:30 pm Family Dinner MONDAY, MAY 27 7:00 am Breakfast with Exhibitors 8:00 am CME (4 hours) TUESDAY, MAY 29 7:30 am CME (4 hours) Register today! Visit www.MSMAonline.com/YPS For reservations at Sandestin Golf & Beach Resort, call 850.320.8115 or BOOK ONLINE AT www.Sandestin.com and enter group code 23H2N8

TOPICS Include:

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A Brief Review and Commentary

Marijuana’s Effects on Brain Structure and Function: What Do We Know and What Should We Do? RICHARD D. DESHAZO, MD; SARA B. PARKER, BA; DANIEL WILLIAMS, PHD; JOHN B. INGRAM, MD; MAHMOUD ELSOHLY, PHD; KATHRYN RODENMEYER, BA; KYLE MCCULLOUCH, BBA Abstract The recent US Food and Drug Administration approval of the marijuana constituent cannabidiol (CBD) as safe and effective for treatment of two rare forms of epilepsy has raised hopes that others of the 500 chemicals in marijuana will be found to be therapeutic. However, the long term consequences of street marijuana use are unclear, and recent studies raise red flags about its effects. Changes in brain maturation and intellectual function including decreases in intelligence quotient have been noted in chronic users and appear permanent in early users in most but not all studies. These studies suggest that at a minimum, regular marijuana use should be discouraged in individuals under the age of 21.

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Key Words: Marijuana; brain development; adolescents; teenager Introduction The present epidemic of opioid addiction and the enthusiasm about marijuana use by advocates of its legalization may have diverted attention from its reported adverse health effects. These include clinical studies that demonstrate chronic marijuana use is associated with long term deleterious effects on cognition.1 Neuroscientists have been carefully pairing neurodiagnostic tools with newer neuroimaging technologies to understand the relationships between the human brain endocannabinoid system and the effects on the system by exogenous cannabinoids,

including the major psychoactive cannabinoid from marijuana, tetrahydrocannabinol (THC). Meta-analyses support observations that when compared to non-users, regular users of marijuana have diminished executive function, attention, learning, memory, and motor skills that persist for varying times after abstinence occurs.2,3 Combined structural and functional imaging show that morphological brain alterations in the medial temporal and frontal cortex and cerebellum are likely related to the degree of cannabis use. Even more troubling data suggest that when marijuana use begins before brain maturation is complete, changes in brain structure and function may persist. If substantiated, these findings have major medical and social implications. Marijuana Use and Effects on Brain Maturation, Structure, and Function Marijuana use starts early in Americans and is the most commonly used illicit drug in Americans 12-years-old and older.4,5 Seven percent of 8th graders, 15% of 10th graders, and 21% of 12th graders report the use of marijuana in the last month.6 Of adolescent users, 2.7% meet criteria for addiction (Cannabis Use Disorder) as compared with 4.9% of young adult users. Lifetime marijuana use reported in 2016 averaged 15% ages 12-17, 52% ages 18-25, 46% ages 26-65 and 22% ages 65 and older.7 Few Americans believe that regular cannabis use is harmful to health, and legalization of marijuana in 29 states and District of Columbia has increased the public’s interest in its possible benefits.8,9 Regular use of marijuana is associated with a range of behavioral abnormalities.1,10 Adolescents who use marijuana are twice as likely to smoke more marijuana and become addicted than those who begin smoking cannabis at a later age. The regular use of cannabis is associated with a decline in short term memory and cognitive function, poor school or work performance, mood disorders and psychosis.10,11 Marijuana impairs the operation of airplanes, automobiles, motorcycles, and trains and its’ effects appear to be dose-dependent.12,13 For instance, automobile accidents occur 2-7 times more frequently while using marijuana.14 Now there is evidence of permanent neurological changes associated with marijuana use that begins before the age of 21.15-18 Investigators in New Zealand evaluated the association between regular cannabis use, the results of longitudinal neuropsychological testing and whether or not functional neurologic decline was disproportionately greater those who began cannabis use as adolescents than those who begin use as adults.19 Individuals (1,037) in a prospective birth cohort were followed from birth to 38-years-old. The presence of cannabis use was determined from interviews of the participants at ages 18, 21, 26, 32, and 38, and neuropsychological testing was conducted at age 13, before cannabis use, and again at age 38 after patterns of cannabis use had been established. Statistical methods corrected for possible confounders. Regular use was associated with decline across all neuropsychological domains as demonstrated by comprehensive neuropsychological testing. Adverse effects on executive function, memory and verbal deficits were consistent among users across the cohort, but worse in those who began use of cannabis as adolescents when compared to adults, and greater functional decline was associated with more persistent use. Unfortunately, cessation of cannabis use did not fully restore the diminished neuropsychological functioning present in those who began use before age 21. Those findings persisted thereafter with an average 6 point decline in intelligence quotient (IQ) from childhood to adulthood as compared to non-users.

The authors concluded that there is a “neurotoxic effect of cannabis on the adolescent brain” that demonstrates “the importance of prevention and policy efforts targeting adolescent use of marijuana.”19 A probable explanation for these neuropsychological findings exists in the biology of brain development. Neuroimaging and neurodiagnostic testing performed in tandem show that brain maturation persists throughout the adolescent and young adult years.20 Grey matter normally decreases in volume during brain maturation due to neuronal pruning, and white matter increases with myelination. Less frequently used neurons are pruned in the preteen years to build complex networks for the decision making of adulthood. The limbic system below and posterior to the cortex matures before the grey matter of the prefrontal cortex that is responsible for logical thought and impulse regulation. This appears to explain problems with control of emotion-linked decision making, risk-taking, and experimentation associated with immaturity.21,22 Increased myelination in the brain may be visualized and quantitated on brain imaging as an increased volume of “white matter.”23 Myelin-coated nerve fibers distributed within the inner components of the brain facilitate rapid conduction of neuronal electrical potentials and thus communication among regions of the cerebral cortex and between the brain and structures below it, including the midbrain and spinal cord. These cortico-cortical and cortico-subcortical pathways facilitate cognitive and motor functions. Structural differences are present in the brains of adolescents who are chronic marijuana users when compared to non-users.24 White matter, grey matter, the limbic system and the cerebellum all showed abnormalities with cannabis use. These findings were summarized as, “Cannabis users show thicker cortices in the left entorhinal cortex and thinner temporal lobes and frontal cortex-volume changes in the cortex, prefrontal cortex, parietal cortex, amygdala, and hippocampus.” These same cannabis users performed less well “in tasks requiring attention, memory, processing speed, visuospatial functioning, and executive function.”24 Thus, the abnormalities noted in neuropsychological testing in adolescents who regularly smoke marijuana appear to correlate with abnormalities in functional brain imaging in areas of the brain normally facilitating them. These findings are also present in animal models of chronic cannabis exposure where changes in both brain structure and function are present and correlate with age and duration of exposure.25 Increasing Potency of Street and Synthetic Marijuana Over 120 of the 500 chemicals in marijuana are psychoactive compounds termed cannabinoids.26,27 The National Center for Natural Products at the University of Mississippi campus in Oxford, Mississippi, provides standardized plant marijuana for research and assays for THC content of street marijuana to the US government. Studies there show that marijuana growers have produced marijuana with increasing concentrations of cannabinoids that are rapidly absorbed.28 Street marijuana now exceeds 10% THC on average, but illicit extracts of cannabis like hash oil have much higher THC content and cannabis concentrated extracts may contain up to 80% THC. Hashish, a paste made from cannabis flowers contains about 4 times the content of THC in street marijuana. With combustion, the chemicals in cannabis undergo pyrolysis, and hundreds of new chemicals are generated.26 The vaping of marijuana oil or waxes using e-cigarettes and other devices results in inhalation of even higher concentrations of cannabinoids than produced

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by smoking. Urine assays for the THC become positive and mild impairments on tests of motor function occur in nonsmokers confined to areas of marijuana smoking, a daunting problem in pregnant females and families with children.29 Tetrahydrocannabinol binds to and is a partial agonist of both CB1 and CB2 cannabinoid receptors. The CB1 cannabinoid receptors are localized in the cortex, motor system, limbic system and hippocampus, are active in the “brain reward system,” also known as the “dopaminergic mesolimbic brain circuit” and enhance the release of presynaptic dopamine. This circuit appears to mediate the pleasant effects of drugs of abuse. Chronic use of marijuana down-regulates CB1 receptors, requiring higher doses for effect, and abstinence from chronic use leads to CB1 receptor up-regulation and withdrawal symptoms.30 Marijuana users experience “mild euphoria, relaxation, and perceptual alterations, including time distortion, and intensification of ordinary experiences such as hunger, eating, and listening to music.”31 Some also experience dysphoria, anxiety or paranoia, especially with synthetic cannabinoids like herbal incense and spice and synthetic cathinones like bath salts. They are direct agonists with a high affinity for the CB1 receptor, probably explaining their extreme toxicity. The human brain produces endogenous brain endocannabinoids that modulate pain through interaction with its cannabinoid receptors at sites receiving impulses from peripheral sensory nerve endings. They have analgesic effects as well as effects on appetite, nausea, behavior, and memory. Most available information about mammalian endocannabinoids comes from animal studies.25,32 Is There Special Need for Marijuana Avoidance Efforts? Meier and colleagues have concluded, “Increasing efforts should be directed toward delaying the onset of cannabis use by young people, particularly given the recent trend of younger ages of cannabis-use initiation in the United States.”19 Although there are potential pitfalls in any complex research, their findings are supported by other clinical33-36 and basic studies.37,38 Two twin studies of marijuana use were unable to confirm adverse effects of marijuana use on intelligence.39,40 Marijuana use in adolescents has not only been associated with cognitive effects but with an increased incidence of psychosis that persists into adulthood and an increased risk of clinical depression after the age of seventeen.41,11 What Next? With this information in mind, what should be done? The National Institutes of Health (NIH) has funded the Adolescent Brain Cognitive Development (ABCD) Study and awarded 13 grants to perform a prospective 10- year longitudinal evaluation of 10,000 9-10- year-olds in the US. Data to be collected include psychometric and psychosocial assessments, brain imaging and academic performance, genetic testing and substance use data. 42,43 When completed, data will become available on the effects of marijuana and other substance use in a cohort of users and nonusers large enough to address possible pitfalls in smaller studies. This is important as contrary to findings in youth, two systematic reviews on the effects of marijuana on cognition in adult users suggest that at least some recovery of cognitive defects after cessation of chronic marijuana use.44,45 Delayed effects of marijuana, to include dementia syndromes in adults, have not been reported.

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Until more data on the adverse effects of chronic marijuana use are available, the information here supports advocacy by physicians against regular marijuana use in individuals younger than 21. How to go about such advocacy is a conundrum. There is a developing consensus among physician groups that screening individuals as an index to detect marijuana use and some form of intervention is optimal. Since many young people regularly see physicians, physician-initiated screenings could provide the opportunity for information sharing about marijuana use and referral to mental health professionals for therapy of cannabis use disorder. Rate limiting steps in accomplishing these recommendations include parental consent for younger patients, confidentiality and ethical considerations, the availability of in-clinic resources to perform screenings and substance abuse education, reimbursement for services, and the limited availability of referral sources for mental health consultation and treatment. Moreover, there are inadequate data to define who should be referred or the effectiveness of referral and treatment in young people. A structured, evidence-based patient screening for substance use is available as the “Screening Brief Intervention and Referral to Treatment” (SBIRT).46 A SBIRT adaptation for adolescents has been endorsed by the American Academy of Pediatrics, the National Institute on Drug Abuse, and the American Medical Association, among many others. The screening includes questions on alcohol and drug use and the option for a brief intervention based on Motivational Interviewing. Adaptations incorporate non-physician caregivers into the assessment process and software embedded into ambulatory clinic registration. What about drug testing? Many school athletic programs now require parental permission for drug screening as a prerequisite for participation in sports, as do many employers in adult work environments. Drug testing could be considered a voluntary component of routine preventive health evaluations for students from middle school forward or as part of the state driver’s licensure process. What to do for those who test positive is unclear. A rate-limiting factor in basic and clinical research with cannabis is the ability to obtain approval for the use of standardized marijuana under protocol for research. Some solution to the problem of access to marijuana for scientific research is overdue.47 n References 1. Volkow ND, Baker RD, Compton WM, et al. Adverse health effects of marijuana use. N Eng J Med. 2014; 370:219-2227. 2. Grant I, Gonzalez R, Carey CL, Natarajan L, Wolfson T. Non acute (residual) neurocognitive effects of cannabis use: A meta-analytic study. J Int Neuropsychol Soc. 2003;9:679-89. 3. Shreiner AM, Dunn, ME. Residual effects of cannabis use on neurocognitive performance after prolonged abstinence: A meta-analysis. Exp Clin Psychopharmacol. 2012;20:420-429. 4. United Nations’ Office on Drugs and Crime, World Drug Report, Vienna 2016. https://www.unodc.org/doc/wdr2016/WORLD_DRUG_REPORT_2016_ web.pdf. Accessed May 31, 2017. 5. Center for Behavioral Health Statistics and Quality (2015). Behavioral Health Trends in the United States: Results of the 2014 National Survey on Drug Use and Health. https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/ NSDUH-FRR1-2014.pdf. Accessed May 31, 2017. 6. National Institute on Drug Abuse: Advancing Addiction Science. Monitoring the

Future survey: High school and youth trends. www.drugabuse.gov/publications/ drugfacts/high-school-youth-trends. Accessed May 31, 2017.

31. Hall W, Degenhardt L. Adverse effects of non-medical cannabis use. Lancet. 2009; 372:1383-1391.

7. Substance Abuse and Mental Health Administration. Center for Behavioral Health Statics and Quality, National Survey on Drug Use and Health, 2015 and 2016. Available at https://www.samhsa.gov/data/sites/default/files/NSDUHFFR1-2016/NSDUH-FFR1-2016.htm.

32. Manzaneres J, Julian MD, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4:239–257.

8. Weir K. Marijuana and the developing brain. Am Psychol. 2015:46:48. http://www. apa.org/monitor/2015/11/marijuana-brain.aspx. Accessed May 31, 2017. 9. Harrison G, Pope HG, Jr, Yurgelun-Todd D. The residual cognitive effects of heavy marijuana use in college students. JAMA. 1996;275:521-527. doi:10.1001/ jama.1996.03530310027028. 10. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013. https:// dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596. dsm16#x29473.2601838. Accessed January 17, 2019. 11. Jensen FE, Nutt AE. The Teenage Brain: A Neuroscientist’s Survival Guide to Raising Adolescents and Young Adults. New York, NY. Harper Collins Publishers; 2015.141158. 12. Leirer VO, Yesavage JA, Morrow DG. Marijuana carry-over effects on air craft pilot performance. Aviat Space Environ Med. 1991;62:221-227. 13. Leggett T, United Nations Office on Drugs and Crime. A review of the world cannabis situation. Bull Narc. 2006;58:1-155. 14. Rogeberg O, Elvik R. The effects of cannabis intoxication on motor vehicle collision revisited and revised. Addiction. 2016;111:1348-1359. 15. Murray RM, Morrison PD, Henquet C, Di Forti M. Cannabis, the mind and society: The harsh realities. Nat Rev Neurosci. 2007;8:885-895. 16. Pope HG, Jr, Gruber AJ, Hudson JI, et al. Early-onset cannabis use and cognitive defects: What is the nature of the association? Drug Alcohol Depend. 2003;69:303310. 17. Gruber SA, Sagar KA, Dahlgren MK, et. al. Age of Onset of Marijuana Use and Executive Function. Psychol Addict Behav. 2012;26:496-506. 18. Winters KC, Arria AM. Adolescent brain development and drugs. Prev Res. 2011;18:21-24. 19. Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Pro Natl Acad Sci. USA. 2012;109:E2657-E2664. 20. Giedd JN. Structural Magnetic Resonance Imaging of the Adolescent Brain. Ann N Y Acad Sci. 2004;1021:77-85. 21. Gogtay N, Giedd JN, Lusk L, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Nat Acad Sci. 2004;101:8174-8179. 22. Squeglia LM, Jacobus J, Tapert SF. The influence of substance use on adolescent brain development. Clin EEG Neurosci. 2009;40:31-38. 23. Ladouceur CD, Peper JS, Crone EA, Dahl RE. White matter development in adolescence: the influence of puberty and implications for affective disorders. Dev Cogn Neurosci. 2012;2:36-54.

33. Schweinsburg AD, Brown SA, Tapert SF. The influence of marijuana use on neurocognitive functioning in adolescents. Curr Drug Abuse Rev. 2008;1:99-111. 34. Pope Jr HG, Yurgelun-Todd D. The residual cognitive effects of heavy marijuana use in college students. JAMA. 1996; 275: 521-527. 35. Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R, et al. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA. 2002;287:1123-1131. 36. Camchong J, Lim KO, Kumra S. Adverse effects of cannabis on adolescent brain development: A longitudinal study. Cerebral Cortex. 2017; 27:1922-1930. 37. Mizrahi R, Watts JJ, Tseng KY. Mechanisms contributing to cognitive deficits in cannabis users. Neuropharmacology. 2017:124:84-88. 38. Lawston J, Borella A, Robinson JK, Whitaker-Azmitia PM. Changes in hippocampal morphology following chronic treatment with the synthetic cannabinoid WIN 55,212-2. 2000. Brain Res. 877(2): 407-410. 39. Lyons MJ, Bar JL, Panizzon MS, Toomey R, Eisen S, Xian, H, and Tsuang MT. Neuropsychological consequences of regular marijuana use: A twin study. Psychol Med. 2004;34(7):1239-1250. 40. Jackson NJ, Isen JD, Khoddam R, et al. Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies. PNAS Early Addition. 2016. http://www.pnas.org/content/113/5/E500. 41. Kuepper R, van Os J, Lieb Roselind, et al. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. British Med J. 342:d738. 42. Collaborative Research on Addiction at NIH. Adolescent Brain Cognitive Development Study. https://addictionresearch.nih.gov/abcd-study. Accessed May 31, 2017. 43. Adolescent Brain Cognitive Development. Teen Brains. Today’s Science. Brighter Future. http://www.ABCDStudy.org. Accessed May 31, 2017. 44. Broyd SJ, Van Hell HH, Beale C, et al. Acute and chronic effects of cannabinoids on human cognition – A systematic review. Biol Psychiatry. 2016;79:557-567. 45. Nader DA, Sanchez ZM. Effects of regular cannabis use on neurocognition, brain structure and function: A systematic review of findings in adults. Am J Drug Alcohol Abuse. 2018;44(1):4-18. doi: 10.1080/00952990.2017.1306746. 46. Substance Abuse and Mental Health Services Administration. Screening, Brief Intervention, and Referral to Treatment (SBIRT). https://www.samhsa.gov/sbirt. Accessed May 31, 2017. 47. Bostwick JM. Blurred Boundaries: The therapeutics and politics of medical marijuana. Mayo Clinic Proc. 2012;87:172-186. _____________________________________________________

24. Meruelo AD, Castro N, Cota CI, et al. Cannabis and alcohol use, and the developing brain. Behav Brain Res. 2017;325:44-50.

Adapted from Am J Med. 2018 Sep 18. doi: 10.1016/j.amjmed.2018.09.006, reprinted with permission.

25. Jager G, Ramsey NF. Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research. Curr Drug Abuse Rev. 2008;1:114-123.

Author Information

26. ElSohly HN and ElSohly MA. Marijuana Smoke Condensate: Chemistry and Pharmacology, In ElSohly MA (Ed.) Marijuana and Cannabinoids. New York, NY: Humana Press; 2007:67-97. 27. Atakan Z. Cannabis, a complex plant: different compounds and different effect on individuals. Ther Adv Psychopharmacol. 2012;2:241-254. 28. Elsohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995-2014): Analysis of current data in the United States. Biol Psychiatry. 2016;79:613-19. 29. NIDA. Marijuana. National Institute on Drug Abuse. https://www.drugabuse.gov/ publications/research-reports/marijuana. June 25, 2018. Accessed January 26, 2018. 30. Herkenham M, Lynn AB, Little MD et al. Cannabinoid receptor location in the brain. Proc Natl Acad Sci USA 1990; 87:1932-1936.

Departments of Medicine and Pediatrics, University of Mississippi Medical Center, Mississippi Public Broadcasting, Jackson (deShazo). Department of Medicine, University of Mississippi Medical Center, Jackson (Parker). Department of Psychiatry, University of Mississippi Medical Center, Jackson (Williams). Departments of Pediatrics and Neurology, University of Mississippi Medical Center, Jackson (Ingram). National Center for Natural Products Research, University of Mississippi, Oxford (Elsohly). Mississippi Public Broadcasting, Jackson (Rodenmeyer). Department of Medicine, University of Mississippi Medical Center, Jackson (McCullouch). Funding Source: The Selby and Richard McRae Foundation. Conflicts of interest: None. Corresponding author: Richard D. deShazo, MD; 2500 North State Street, Jackson, MS 39216. Ph: (601) 506-1397 (rdeshazo@umc.edu).

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The PROMISE Initiative: Who Should Give Patients Information on Opioids? MARY NELSON ROBERTSON, MA; DANIEL WILLIAMS, PHD; HOLLI SEITZ, PHD; LAURA DOWNEY, DRPH; ALISHA HARDMAN, PHD; DAVID BUYS, PHD

Abstract Mississippi has been disproportionately affected by the opioid epidemic, ranking 5th in the nation for per capita annual opioid prescriptions and 173 overdose deaths involving opioids. To assess the prescription opioid information seeking and scanning behaviors of Mississippians, we developed a questionnaire and collected data from a quota-driven sample of 335 Mississippians, 30-59 years of age based on sex and race. Participants were recruited by Qualtrics to participate in the 164-item web-based survey. Nearly 87% of respondents cited healthcare providers as the source from which they prefer to seek information about prescription opioids. Forty-six percent of respondents heard about prescription opioids from their healthcare provider in the past 12 months when they were not actively seeking information. By comparison, 60% of respondents received information about opioids from television, and 54.9% received opioid information from the internet. The results suggest that Mississippians trust healthcare providers for information about prescription opioids but are currently more likely to receive information from media sources including television and the internet than from physicians or other interpersonal sources. Our findings suggest an opportunity to enhance communication about opioid use by encouraging physicians to ask patients if they need information on opioids during routine patient care encounters. Keywords: Opioids; physician-patient relations; seeking and scanning behaviors Introduction While illicit drugs such as heroin have been a public health and safety concern for many years, misuse and abuse of opioid-based prescription drugs have reached epidemic rates and are disproportionately affecting rural populations. These drugs include medications such as oxycodone, hydrocodone, morphine, and others. Recent data suggest they are probably no more effective for pain than NSAIDs and that their use led to 22,598 deaths from overdoses in 2015. This represents a 461% increase since 1999.1 The annual societal cost for this epidemic is around $78 billion and it has put a strain on healthcare, the workforce, and the criminal justice system.2

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In the latest America’s Health Rankings® Annual Report, Mississippi ranked 50th.3 Furthermore, Mississippi ranked 8th for “deaths of despair” which includes deaths by suicide, alcohol, and drug overdose. Mississippi also ranked 45th for its number of mental health providers per capita, indicating a disparity between need and service providers for addiction and other mental health problems. During 2017, over 3.3 million opioid prescriptions were dispensed in Mississippi, which is higher than the number of Mississippi’s residents, and 256 Mississippians died from drug overdose.4 Of those reported, 173 (67.6%) were opioid-related and 83 (32.4%) were prescription opioid-related.4 A distinguishing characteristic of prescription opioids relative to other addictive drugs is that they are primarily obtained through prescriptions from a physician or other health care provider. Research shows that prescriptions for opioids as short as 5 days can predict ongoing opioid prescriptions one year later, an important finding given that the majority of treatment-seeking heroin users initiated to opioid misuse through use of prescribed opioids.5,6 Thus, health care providers have a unique opportunity to curb the crisis affecting Mississippi and the nation. To develop effective interventions, it is important to understand how individuals access health information and the sources of information they prefer. Information seeking is defined as ‘‘active efforts to obtain specific information outside of the normal patterns of exposure to mediated and interpersonal sources.”7 Mediated sources include print, digital, and social media. It is also important to understand where people encounter health information when they are not actively seeking it. This type of health information exposure is often referred to as information scanning.8 Health information seeking and scanning behaviors have changed as available media forms have changed. Although national data exist on general health information seeking trends, there are few data on information seeking and scanning behaviors related to opioids. 9-11 Additionally, there is a lack of information about whether there may be differences in opioid information seeking and scanning behaviors that are linked to demographic characteristics. In this report, we sought to determine where Mississippians prefer

Table 1. Descriptive statistics of participants in the PROMISE Cohort

Table 1. Descriptive Statistics of Participants in the PROMISE Cohort

Variable Variable

N (%/SD) N (%/SD)

Participants Rurality Rural Nonrural Sex Male Female Race/Ethnicity White Black or African American Other Hispanic Hispanic Non‐Hispanic Education Level Less than high school High school graduate or higher Bachelor’s degree or higher

335

Annual Household Income**

Number in Household Age (years)

MS Census MSCensus Data(%)* Data (%)*

Methods

192 (57.30) 143 (42.70)

50.65 49.35

171 (51.00) 164 (49.00)

48.5 51.5

199 (59.40) 123 (36.70) 13 (3.90)

59.2 37.8 3

36 (10.70) 299 (89.30)

3.2 96.8

23 (6.90) 212 (63.30) 100 (29.90)

83 21

Mean Mean

Mean M ean $21,650

3 (1.50) 43 (8.40)

*2010 **Annual income of Mississippians at the time of this study was $40,000 to $49,999.

Table 2. Health information-seeking and opioid-related factors among Mississippians in the PROMISE Cohort

Table 2. Health Information‐Seeking and Opioid‐related Factors Among Mississippians in the PROMISE Cohort Information‐seeking Behavior History Information-seeking Behavior History

Yes*

No*

Have you ever looked for information about health or medical topics from any source? Have you ever looked for information about prescription opioids from any source?

275 (82.10)

32 (09.60)

163 (48.70)

139 (41.50)

Perceptions of Prescription Opioid‐related Issues Perceptions of Prescription Opioid-related Issues . Good Bad The use of prescription opioids is 200 (59.60) 135 (40.30) . The misuse of prescription opioids is 27 (08.10) 308 (91.90) Agree 240 (71.60) 252 (75.30)

*Difference in sum of shown percentage and 100 is respondents who "Don't recall"

Data In 2016, the authors (Buys and Downey) received funding from the United States Department of Agriculture to develop the PReventing Opioid Misuse In the SouthEast Initiative (PROMISE Initiative). As part of that larger project, we explored opportunities to prevent opioid misuse in Mississippi. We developed a 164-item web-based survey to assess Mississippians current approaches to obtaining health information and their perceptions and preferences for gathering information on the opioid crisis.12 Mississippians 30–59 years of age were recruited to participate in the web-based survey by a proprietary company, Qualtrics (Provo, UT), from various sources including website intercept recruitment, member referrals, targeted email lists, gaming sites, customer loyalty web portals, permissionbased networks, and social media.13 Quota sampling was used to gather a representative sample of the state of Mississippi, based on the 2010 U.S. Census Bureau data of Mississippians’ sex and race.14

Disagree Prescription opioids are a reliable way to 95 (28.30) manage pain. Opioid misuse is a problem in my community. 83 (24.80)

to obtain information about opioid-related issues and where they are currently receiving it. We also assessed the preferences of Mississippians for ascertaining information broadly about healthrelated topics and their perceptions of opioid use and misuse.

A variety of data points was obtained using the survey we developed. We initially sought demographic information from participants, including rurality, sex, race, ethnicity, education level, annual household income, number of residents in each household, and age (Table 1). Second, we asked participants about their history of having sought health-related or opioid-specific information (Tables 2 and 3). We defined an opioid for participants with the following language: “An opioid is a substance that is a prescription medication (pill or patch), prescribed for pain relief.14 The illegal drug heroin is also an opioid. However, for the purpose of this survey, opioid refers to prescription opioids.18 Examples of prescribed opioid pain relievers contain the active ingredients Oxycodone (OxyContin®, Percocet®), Hydrocodone (Vicodin®), Morphine (Kadian®, Avinza®), Codeine, and Fentanyl to name a few.”15 Opioid misuse is defined as taking a medication in a manner or dose other than prescribed; taking someone else’s prescription, even if for a legitimate medical complaint such as pain; or taking a medication to feel euphoria (i.e., to get high).16 The specific questions asked of participants may be found in Tables 1, 2, and 3. We sought to explore Mississippians’ health and opioid information seeking and scanning behaviors using adapted versions of validated

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Table 3. Information sources for Mississippians in the PROMISE Cohort in search of health and opioid-related messages Table 3. Information Sources for Mississippians in the PROMISE Cohort in Search of Health and Opioid‐related Messages

Source Source

Think about the most recent time you looked for information about health or medical topics. Think of the top 3 places that you looked for information about health and medical topics at that time.*

258 (77.0) 200 (59.7) 182 (54.3) 75 (22.4) 74 (22.1) 62 (18.5) 30 (9.0) 23 (6.9) 15 (4.5) 15 (4.5) 11 (3.3) 5 (1.5)

Healthcare Provider Internet Family/ Friends Books Pamphlet Magazine Television Social Media Pastor/ Religious Leader MSU Extension Service Newspaper Radio

*n/%

information seeking and scanning measures.8 General health information seeking was measured by asking the questions in Table 2. Analysis. Using SPSS version 25,17 we conducted univariate descriptive statistics (frequencies, percentages, means, and standard deviations). We also conducted bivariate analyses to assess what differences may exist between demographic factors and the outcomes of interest. Significant findings from these analyses are presented in the text. Human Subjects Protections. This project was reviewed and approved by the office of the Institutional Review Board at Mississippi State University. Results A total of 495 participants were asked to participate in the 164item web-based survey. Of these, 335 participants provided all the demographic data requested and answered all of the questions asked and composed the study cohort. Study participants (n=335) were slightly more rural than urban, nearly equally stratified by sex, primarily white, non-Hispanic, and with at least a high school degree (Table 1). Respondents had a mean of 3 persons in their household

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Imagine you have a strong need to get information about prescription opioids. Select the top 3 places that you would look for information about prescription opioids.*

How many times did you hear or come across information about prescription opioids from each of the following sources when you were not actively looking for it?*

290 (86.6) 198 (59.1) 165 (49.3) 90 (26.9) 78 (23.3) 46 (13.7) 18 (5.4) 14 (4.2) 20 (6.0) 27 (8.1) 4 (1.2) 6 (1.8)

155 (46.2) 184 (54.9) 159 (47.5) 73 (21.8) 105 (31.3) 95 (28.4) 201 (60.0) 134 (40.0) 60 (17.9) 50 (14.9) 106 (31.6) 95 (28.4)

and were, on average, 43 years old (SD=8.4). Most respondents reported an income in the $40,000-49,999 range, which was the only characteristic substantially different from the state characteristics. This may be because recruitment for this survey occurred via the internet and those with internet access are more likely to have higher incomes.18 Participants reported having previously sought health information (82.1%) and having looked for information specifically about opioids (48.7%;)(Table 2). They also indicated that they thought opioid use is bad (59.6%), even having been given information on what opioids are and how misuse is defined. An even greater proportion of the population thought that misuse was bad (91.9%). However, 71.6% thought that opioids are a reliable way to manage pain. When asked if they thought that opioid misuse was a problem in their community, a large majority reported that it is (75.3%). Blacks were more likely than whites to report believing that opioid use is bad (70.7% vs. 51.8%; p<.001). There were no differences between age and race groups and rural and urban dwellers on beliefs about opioid misuse or the value of opioids for pain management. However, whites were more likely than blacks to report believing the problem is impacting their community (79.4% vs. 67.5%, p<.05); and people in urban areas were more likely than those in rural areas to report believing the problem is affecting

their community (81.8% vs. 70.3%, p<.05). There were no differences between age groups on the belief that opioids are affecting their community. The majority of participants indicated that when looking for general health information, they sought information from their healthcare provider (77%), the internet (59.7%), family/friends (54.3%), books (22.4%), and pamphlets (22.1%) (Table 3). When asked what sources they would pursue for opioid-specific information, the order of the sources was the same, but the percentage of those indicating they would seek information from a health care provider increased to 86.6%. Other categories include the internet (59.1%), family/friends (49.3%), books (26.9%), and pamphlets (23.3%). Furthermore, fewer participants reported coming across information about prescription opioids when not actively looking for it than those who said they had not (115/ 34.30% vs. 139/ 41.5%). In the final question, designed to assess where individuals are currently receiving information about opioids when they are not actively looking for it, they reported hearing from healthcare providers at a much lower rate and behind other sources: television (60%), internet (54.9%), family/friends (47.5%), healthcare provider (46.2%), and social media (40%). Discussion These results indicate that individuals in Mississippi are interested in obtaining information about opioids from their healthcare providers and fit with a emerging body of research on the importance of physicians and other health care professionals integrating substanceabuse prevention and detection skills into their encounters with patients. Recent Centers for Disease Control and Prevention (CDC) guidelines on prescribing opioids recommend that providers discuss the risk and benefits of opioid therapy as well as clinician responsibilities, including the dangers to other household members beyond the patient.19 The CDC also suggests that physicians have conversations with their patients about alternative treatment options to prescription opioids to treat chronic pain. Based on the results of this study, there appears to be opportunities for Mississippi healthcare providers to provide increased opioid-related education to patients who welcome such information. This is particularly important given data on opioid misuse in Mississippi showing that for ages 12 and over, 4.3% of Mississippians misuse opioids and 7.30% of Mississippians age 18-25 met criteria for opioid misuse. 20 These rates are comparable to the percentages in the overall United States and slightly higher than those in the Northeast and the South overall. Prior research has examined differences in health information seeking by gender, socioeconomic status, ethnicity, and other factors. Women are more likely than men to look for health information in general and more likely to use the internet for information seeking;21 people with lower levels of education are generally less likely to seek health information than those with higher education levels; and there are some differences in information seeking associated with ethnicity.22,23

We hope to examine whether this same difference exists in the context of opioid information seeking and scanning in future studies. The CDC guidelines also recommend initial and ongoing evaluation for substance abuse and potential for misuse. More recently, the US Preventive Services Task Force released a recommendation statement endorsing both screening and brief behavioral counseling interventions for unhealthy alcohol use in primary care settings in adults.24 One example of this approach is Screening, Brief Intervention, and Referral to Treatment for substance use (SBIRT), an evidencebased approach to conducting screenings for substance misuse providing brief interventions designed for physicians to integrate into their clinical practice. It can include screening for opioids in addition to other drugs of abuse and alcohol.25 While SBIRT is a part of the University of Mississippi Medical School , research suggests that SBIRT takes too much time for physicians; therefore, training nurses, office personnel, and volunteers to provide this information under the supervision of physician could be effective.26 Providers have 1530 minutes with each patient; therefore, it might be challenging for providers to discuss opioids with every patient. Thus, providers could deliver opioid-related information through a short video in the waiting room, written materials, or trained staff, all of which are approaches supported by SBIRT. Limitations While this study provides valuable insights into how information on opioids can be shared with Mississippians, there are limitations to our study. First, our cohort may not be precisely representative of the state since it was not constructed using random sampling. Second, we do not know how many participants saw a healthcare provider in the past 12 months. In future research, we will include a variable asking that question, and we recommend that other investigators do the same. Third, we do not have a measure of opioid information seeking from all sources, only a general measure. Nonetheless, we are confident that these findings support the need for more and better communication between patients and healthcare providers on matters related to opioid misuse prevention. Conclusion The results from this study are congruent with recent recommendations made in Mississippi opioid prescribing guidelines. They identify the need for Mississippi physicians and other health care providers to discuss benefits and risks and provide evidence-based information on opioids to Mississippians interested in receiving it.27,28 n References 1. Hedegaard H, Warner M, Minino AM. Drug overdose deaths in the United States, 1999â&#x20AC;&#x201C;2016. National Center for Health Statistics Data Brief, No. 273, February 2017. 2017;(273):8. https://www.cdc.gov/drugoverdose/index. html. Accessed December 1, 2018. 2. Florence CS, Zhou C, Luo F, Xu L. The economic burden of prescription opi-

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oid overdose, abuse, and dependence in the United States, 2013. Med Care. 2016;54(10):901-906. doi:10.1097/MLR.0000000000000625. Accessed December 1, 2018. 3. United Health Foundation. America’s Health Rankings® Annual Report, December 2017. https://assets.americashealthrankings.org/app/uploads/2017annualreport.pdf. Accessed March 1, 2018. 4. Staneva M. The Mississippi opioid and heroin data collaborative. 2018:11. 5. Shah A. Characteristics of initial prescription episodes and likelihood of longterm opioid use — United States, 2006–2015. MMWR Morb Mortal Wkly Rep. 2017;66. doi:10.15585/mmwr.mm6610a1. 6. Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry. 2014;71(7):821-826. doi:10.1001/jamapsychiatry.2014.366. 7. Niederdeppe J, Hornik RC, Kelly BJ, et al. Examining the dimensions of cancer-related information seeking and scanning behavior. Health Commun. 2007;22(2):153-167. doi:10.1080/10410230701454189. 8. Kelly BJ, Niederdeppe J, Hornik RC. Validating measures of scanned information exposure in the context of cancer prevention and screening behaviors. J Health Commun. 2009;14(8):721-740. doi:10.1080/10810730903295559. 9. Hesse BW, Nelson DE, Kreps GL, et al. Trust and sources of health information: the impact of the internet and its implications for health care providers: findings from the first health information national trends survey. Arch Intern Med. 2005;165(22):2618. doi:10.1001/archinte.165.22.2618. 10. National Cancer Institute. Health information national trends survey (HINTS 5 Cycle 1), 2017. https://hints.cancer.gov/. Accessed December 1, 2018. 11. National Cancer Institute. Health information national trends survey (HINTS 5 Cycle 2), 2018. https://hints.cancer.gov/. Accessed December 1, 2018.

Care Poor Underserved. 2012;23(4):1477-1493. doi:10.1353/hpu.2012.0181. 22. Rooks RN, Wiltshire JC, Elder K, BeLue R, Gary LC. Health information seeking and use outside of the medical encounter: Is it associated with race and ethnicity? Soc Sci Med. 2012;74(2):176-184. doi:10.1016/j.socscimed.2011.09.040. 23. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2016 national survey on drug use and health (HHS Publication No. SMA 17-5044, NSDUH Series H-52), 2017. Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/. Accessed December 1, 2018. 24. O’Connor EA, Perdue LA, Senger CA, et al. Screening and behavioral counseling interventions in primary care to reduce unhealthy alcohol use in adolescents and adults: Updated systematic review for the US preventive services task force: Evidence synthesis No. 171. Rockville, MD: Agency for healthcare research and quality; 2018. AHRQ publication 18-05242-EF-1. 25. Bray JW, Del Boca FK, McRee BG, Hayashi SW, Babor TF. Screening, brief intervention and referral to treatment (SBIRT): rationale, program overview and cross‐site evaluation. Addiction, 2017;112:3–11. doi: 10.1111/add.13676. 26. deShazo, RD, Johnson, M, Eriator, I, Rodenmeyer, K. Backstories on the US opioid epidemic. Good intentions gone bad, an industry gone rogue, and watch dogs gone to sleep. Am J Med. 2018;131:595-601. 27. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. 2018 annual surveillance report of drug-related risks and outcomes — United States. Surveillance Special Report 2, August 21, 2018. https://www.cdc.gov/drugoverdose/pdf/pubs/2018-cdc-drug-surveillancereport.pdf. Accessed December 20, 2018.

12. Qualtrics, 2018, Provo, UT, USA.

28. Mississippi State Board of Medical Licensure. Mississippi state board of medical licensure prescribing rules summary, November 13, 2018. Accessed on December 20, 2018.

13. Qualtrics, Provo, UT, USA. Everything you need to know when working with your IRB. 2018.

Acknowledgments

14. United States Census Bureau. Quick facts: Mississippi 2010. https://www.census.gov/quickfacts/ms. Accessed December 1, 2018. 15. National Institutes of Health. Prescription opioids. https://www.drugabuse. gov/publications/drugfacts/prescription-opioids. Published June 7, 2018. Accessed December 10, 2018. 16. Substance Abuse Center for Behavioral Health Statistics and Quality. Results from the 2016 national survey on drug use and health: Detailed tables, SAMHSA, CBHSQ. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.htm. Accessed December 10, 2018. Summary of misuse of prescription drugs. https://www.drugabuse.gov/ publications/research-reports/misuse-prescription-drugs/summary. Published September 7, 2017. Accessed March 7, 2018. 17. IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. 18. PEW Research Center. Internet/Broadband fact sheet. http://www.pewinternet.org/fact-sheet/internet-broadband/. Accessed December 1, 2018. 19. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain – United States, 2016. MMWR Recomm Rep 2016;65 (No. RR1):1-49. DOI:http://dx.doi.org/10.15585/mmwr.rr6501e1. 20. Manierre MJ. Gaps in knowledge: Tracking and explaining gender differences in health information seeking. Soc Sci Med. 2015;128:151-158. doi:10.1016/j. socscimed.2015.01.028. 21. Richardson A, Allen JA, Xiao H, Vallone D. Effects of race/ethnicity and socioeconomic status on health information-seeking, confidence, and trust. J Health

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This project was supported by the FY17 USDA NIFA Rural Health and Safety Education Competitive Grants Program of the National Institute of Food and Agriculture, USDA, Grant # 2017-46100-27225.

Author Information Extension Associate III, Department of Food Science, Nutrition and Health Promotion, Mississippi State University (Robertson). Associate Professor, Department of Psychiatry, University of Mississippi Medical Center; Supervisory Psychologist, Addictive Disorders Treatment Program, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS (Williams). Assistant Professor, Department of Communication; Director, The Message Laboratory, Social Science Research Center, Mississippi State University (Seitz). Associate Extension Professor, School of Human Sciences, Mississippi State University; Evaluation Specialist, Mississippi State University Extension Service (Downey). Assistant Professor, Department of Human Development and Family Science, Mississippi State University; Family Life Specialist; Evaluation Specialist, Mississippi State University Extension Service (Hardman). State Health Specialist, Mississippi State University Extension Service; Assistant Professor, Department of Food Science, Nutrition and Health Promotion; Adjunct Professor of Medicine, UAB, Birmingham, AL; Associate Director, Myrlie Evers-Williams Institute for the Elimination of Health Disparities, University of Mississippi Medical Center and Mississippi State University; President, Mississippi Public Health Association, Jackson, MS (Buys). Corresponding Author: David Buys, PhD, Mississippi State University Extension Service, 945 Stone Boulevard, 107 Herzer, Mississippi State, MS, 39762 (david. buys@msstate.edu).

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Current Approaches in Perioperative Management of the Opioid-Tolerant Patient RENE HULET, MD; LAKSHMI N. KURNUTALA, MD

Abstract Chronic pain is one of the major growing issues in the USA. As patients with chronic pain increase, the prescription of opioid medications, increases. It is a challenge for the anesthesiologist to control perioperative pain of patients who chronically use opioids, because of interactions between opioids and other medications, tolerance to opioids, their action on different receptors and systemic effects of opioids. As a perioperative physician, we have to understand the optimal treatment of these patients. In this current article, we discuss the perioperative management of opioid-tolerant patients, and patients on opioid addiction treatment. Introduction Chronic pain is a growing issue in the United States. It can be from a malignant cause or non-malignant cause, with opioids being the mainstay of treatment for moderate to severe pain. Before the year 2000, most long term opioid use was in individuals with malignant cancer pain, but as opioid use became more widely accepted, physicians had more comfort prescribing them. There has been an increase in opioid prescriptions for non-cancer chronic pain including lower back pain, neuropathic pain, obesity, end-stage renal disease (ESRD), osteoarthritis, etc.1,2,3 There has also been an increase in the use of Methadone, as well as Buprenorphine and Suboxone® (combination of Buprenorphine with Naloxone) in chronic pain and opioid addiction respectively. There are a million prescribers registered with the Drug Enforcement Agency (DEA), 4 million registered patients receiving long-acting or extended-release opioids in the United States, and about 235 million opioid prescriptions with the numbers growing every year.4 Management of the opioid-tolerant patient is a challenging issue for anesthesiologists during the perioperative period. As a perioperative physician, we have to understand that optimal treatment of these patients has to focus on adequate pain relief. These patients with chronic opioid consumption are likely to have tolerance and/or withdrawal symptoms to opioid doses that would normally be used in the opioid naïve patient. Special attention needs to be paid to the patient’s mental state, as they have physiological and psychological dependence upon opioids, with fear that their pain is not going to be adequately treated. The anesthesiologist also needs to be aware that

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chronic opioid consumption causes opioid-induced hyperalgesia (OIH).1,5,6 Tolerance is defined as the need to increase the dose of a drug in order to attain the same analgesic effect.1,5,7 de Leon-Casasola exhibited that in opioid-tolerant patients undergoing surgery, up to three times the normal dose of opioid was used, and up to three times the duration of treatment for an opioid naïve patient was used, opioid-tolerant patients would have adequate pain control, with no withdrawal symptoms.8 This is important to note since a recent study has shown that opioidtolerant patients have an increased length of stay, and a higher 30-day re-admission rate, with an increase in hospital cost.9 Dependence can be defined as apparent withdrawal symptoms when a drug dose is reduced too quickly, antagonists are given, or when drug use is suddenly stopped or interrupted.1,5,7 Hyperalgesia is a withdrawal symptom as well as restlessness, fear, emesis, hyperventilation, yawning, and insomnia which make the physician’s job difficult to distinguish whether the patient is in withdrawal, or having acute pain.1,5 Hyperalgesia is defined as increased perception of pain to something that was not initially very painful. Opioid-induced hyperalgesia is a noted phenomenon that occurs when patients have been on high doses of opioids or have been exposed to opioids for long periods of Table 1. Chronic Noncancerous Pain Table 1. Chronic Noncancerous Pain

Nociceptive pain – Acute and Chronic Somatic pain – Joint pain (osteoarthritis, degenerative disc disease); diffuse muscle pain (fibromyalgia) Visceral pain – Abdominal pain (irritable bowel syndrome, pancreatitis, peptic ulcer disease)

Neuropathic pain Peripheral related- Diabetic neuropathy, nutrition related peripheral neuropathy, complex regional pain syndrome I & II, post herpetic neuralgia, failed back syndrome, trigeminal neuralgia, post amputation phantom pain. Central related- Multiple sclerosis, Dejerine–Roussy syndrome (post stroke pain), spinal cord injury related

Table 2. Perioperative Assessment and Management of the Chronic Pain Patient

Table 2. Perioperative Assessment and Management of the Chronic Pain Patient 

In preoperative anesthesia clinic- Identification of chronic pain patient, and team approach of the patient



Discuss the management with the surgeon, primary care physician or pain physician providing the pain treatment for the patient, and psychiatrist if needed.



During assessment in anesthesia preoperative clinic – Documenting the chronic pain condition and current pain location and intensity



Current opioids (type, dose, frequency, route of administration, continuous, PRN use, side effect profile)



Adequacy of current pain control



Discussion with the surgeon regarding the type and extent of surgery



Patient expectations and fear about the surgery and postoperative pain control



Discussion about increased chances of pain during perioperative period



History of previous surgeries and what modalities of pain control used in the past to control patient pain



Thorough discussion of perioperative pain control, risks, benefits, and alternatives of different approaches of pain control modalities (IV PCA, Nonopioid pain control, Regional anesthesia, local anesthesia)



Providing information and education material to patient about surgical procedure and pain management



Providing adequate anxiolysis preoperatively and intraoperative analgesia (preemptive analgesia)



Plan for multimodal analgesia for postoperative pain control.



Frequent postoperative visits by anesthesiologist to assess the pain control and side effects



Plan for discharge pain medications and follow up with a primary care physician or pain physician to titrate opioids once the postoperative pain is better controlled.

time.1,5,7 Hyperalgesia results from activation of the NMDA system with increased release of excitatory neurotransmitters which activate descending efferents, leading to a more intensive spinal synaptic transmission. This phenomenon makes acute pain management of these patients quite difficult, as it causes severe intraoperative and postoperative pain. Pseudo hyperalgesia is related to inadequate pain control.

well as their expected role in continuing their pain management care after the patient leaves the PACU. This should all be discussed with the patient, before continuing to the operating room. (Table 2)

There is limited evidence available to guide therapy on opioidtolerant patients in the perioperative period. Patients can show up on a multitude of opioids including morphine, hydromorphone, OxyContin, fentanyl patches, methadone, buprenorphine and Suboxone, and may have been on any of these medications for weeks to years. Most of these patients also have psychiatric comorbidities, which can influence their pain.10

Preoperative assessment and dialogue with the patient are important. Discussion of patient expectations and education from the anesthesia provider of what is to be accepted should be discussed, at length. Asking about what medication regimen worked for them in the past for prior surgeries will guide the physician with the appropriate perioperative pain management for that specific patient. Communicating with the primary care physician or pain physician who is providing their pain management care is also always useful to determine the proper perioperative care plan to control the pain adequately. Be cognizant that the patient may not directly tell the team how much medication they are taking or they may hide the illegal drug use.

Preoperative considerations Perioperative pain management control begins in the preoperative anesthesia clinic, with proper identification of the opioid-tolerant patient, and thorough documentation of their condition, including, current location and intensity of their pain, as well as adequacy of current pain control. (Table 1) Discussion between the surgeon and anesthesiologist regarding the type, length and extent of surgery, as

Determining what pain medications the patient is on and how often they are actually being used is also important, as well as administration of daily maintenance opioids before induction of any sort of anesthesia.7 If the patient has missed their morning dose of opioids they should be treated with an equivalent loading dose of morphine or hydromorphone in the preoperative holding area, or it should be given intravenously at the induction of anesthesia. (Table 3) Patients

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that are on methadone or Suboxone therapy will be addressed later in this paper. It is also recommended for patients taking a COX-2 inhibitor to continue the medication the morning of surgery based on the type of surgery, especially those patients using it for pain, but patients on general NSAIDs should discontinue use two to three days before major surgery.7,10 Patients using antiepileptics (Gabapentin, Lyrica), tricyclic anti-depressants, as well as SSRI/SNRI should continue throughout the perioperative period.11 Patients who are on a fentanyl patch, and the surgery limited to short duration, not requiring warming, should continue their fentanyl patch, and if the patient removed their fentanyl patch, an IV fentanyl infusion may be used to maintain plasma fentanyl levels.7 If the surgery is going to require warming, remove the patch, and start a continuous IV infusion of fentanyl or other IV opioid agonist medication as warming the patch may lead to overdose.12 Because the contextsensitive half-time of fentanyl is longer and if the surgery is going to be long duration, use a longer acting IV mu-opioid. During immediate postoperative period if the patient is allowed oral medications, start on long and short-acting oral opioids and titrate to patient pain control. Patients presenting with an epidural or intrathecal opioid infusion via implanted devices should be maintained throughout the perioperative period. The only time to consider turning off an infusion would be if the patient is receiving Baclofen, but the possibility of severe withdrawal syndrome may occur including hypotension, high fever, severe spasticity, rhabdomyolysis, seizures, organ failure and death. It may be sensible to decrease the rate as this drug can enhance neuromuscular blockade, and may cause sedation or hypotension.7 There is an increasing number of patients presenting on Suboxone (Buprenorphine and naloxone) or Subutex (Buprenorphine) due to increased prescriptions for opioid abuse therapy, as it can be prescribed in a primary care clinic, and does not come with the same stigma as methadone.13 Buprenorphine is a partial mu-receptor agonist, and full antagonist at the kappa and delta opioid receptors. It has a slow dissociation from the receptors, and it occupies the mu receptor maximally.14,15,16 This makes it a challenge for the anesthesiologists who deal with intraoperative and postoperative pain in these patients. Acute pain management for patients on chronic Suboxone or Subutex has few clear guidelines. One recommendation is to convert the patient to a full opioid agonist preoperatively, while another recommendation is to continue Buprenorphine throughout the perioperative period and use a full agonist for pain control with respiration monitoring. It has been shown that morphine can be given at 20% of the basal regimen, on patients using transdermal buprenorphine with no withdrawal symptoms occurring.17 One more recommendation has been made to discontinue the Buprenorphine 3-5 days before surgery and convert to a full agonist to eliminate the existence of any partial blockade.14 Special consideration for the patients who are using Buprenorphine for opioid addiction therapy should be discussed with the patient and the surgeon, as these patients have a fear of re-initiating their opioid abuse after the surgery. Discuss the use of regional anesthetic techniques, local anesthetic infiltration

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at the incisional site, and postoperative intravenous ketorolac use for substitution of opioids for pain control.18,19 Current recommendations for perioperative management of patients on Suboxone/Subutex Elective procedure: Patient for minimally invasive surgery with mild or no pain If they are still on Suboxone/Subutex • Continue in the perioperative period, and do not change their dose. • Routine prescription/dosing of other opioids is not always necessary. • Consider using local anesthetic infiltration, regional anesthesia, Tylenol, NSAIDS. • An additional dose of buprenorphine may cover postoperative pain. • If they discontinued Suboxone/Subutex prior to surgery • Surgical team should contact buprenorphine provider and confirm they are aware of patient’s surgery. Plan should be confirmed between surgeon and buprenorphine provider to re-initiate therapy. • Discuss possible increased length of stay with surgeon. • Discuss time since last dose. -- If the following dose/time intervals are met, treat with traditional opioids using opioid-tolerant dosing: 0-4 mg per day – stop x 24 hours prior to surgery >4-8 mg per day – stop x 48 hours prior to surgery >8-12 mg per day – stop x 72 hours prior to surgery >12 mg – requires preoperative management plan with buprenorphine provider. Patient undergoing intermediate and major surgery with moderate to severe pain Patient still taking Buprenorphine • Consider canceling/postponing surgery and re-scheduling so patient can return to buprenorphine provider to be placed on shortacting opioid, or be completely weaned off prior to surgery. Use time recommendations already given. • Patient discontinued use with appropriate time frames discussed • Patient will have opioid requirements similar to opioid-tolerant patient. • Consider NSAIDs, acetaminophen, local anesthetic agents, and regional anesthesia to help with Post-op pain control. • Follow up with buprenorphine provider needs to be made upon discharge from hospital and confirmed by surgical team. Emergency surgery and known Suboxone/Subutex user Patients that have mild to no pain can be treated the same in each category as if it was an elective surgery If they are having moderate to severe pain and are still taking Buprenorphine • Discontinue buprenorphine and start a PCA. This may require a

Table 3. Equianalgesic Dosage Table 3. Equianalgesic Dosage

Drug

Equianalgesic dosage (IV/IM/SC)

Equianalgesic dosage (Oral)

Half-life (hours)

Duration (hours)

Morphine

10 mg

30 mg

2- 4

3-6

Codeine

100-120 mg

200 mg

3-4

4-6

Hydrocodone

20 mg

3.3-4.5

4-8

Oxycodone

20 mg

2-6

4-6

3-7

1-2

2-4

4-5

Fentanyl Hydromorphone

100 mcg 1.5 mg

7.5 mg

Methadone

1-10 mg *

6-150

15-30

Meperidine

75 mg

2-20 mg 300 mg

3-4

2-4

Levorphanol

2 mg

4 mg

6- 8

12-16 3-6 4-6

Oxymorphone

1 mg

10 mg

NA¥

Prophoxyphene

130 –200 mg

6-12

* Short term 5-10 mg, chronic use 1-4 mg # Short term 20 mg, chronic use 2-4 mg. Many equianalgesic tables underestimate methadone potency – more studies are needed. The conversion of methadone in acute and chronic opioid use with lower and higher doses highly variable. Because of longer half-life, the dose adjustment of methadone done in 3-4 days if needed. ¥ For single dose half-life 7-13 hrs, for multiple doses half-life not applicable

continuous opioid infusion, and at much higher opioid doses. • Consider having the patient in the ICU in the immediate postoperative period for continuous monitoring as the half-life of buprenorphine can be from 24-60 hours, and the patients will need to decrease the doses of their opioids as it clears, and increased monitoring for respiratory depression due to high doses. Dexmedetomidine may also be considered in the ICU to decrease opioid consumption and irritability. • Consider continuous peripheral catheter and regional anesthesia for intra- and postoperative pain management. • Add Acetaminophen around the clock, and consider pregabalin or gabapentin for adjunctive therapy. • Continue opioid therapy for postoperative pain after discharge and make sure patient follows up with their buprenorphine provider after discharge for weaning of their opioids and reinstitution of their buprenorphine. Methadone is another chronic pain drug that is being used with increased frequency for opioid agonist therapy. Methadone works at both the opioid receptor and the NMDA receptor, as well as inhibits the reuptake of norepinephrine and serotonin.20 The anesthesiologist must understand that patients using methadone for opioid addiction do not receive analgesia from its use, as the duration for analgesia is only 4-8 hours with the suppression of opioid withdrawal being up to 50 hours.5 The difficulty in treating these patients for acute pain is that they must receive a baseline opioid requirement for their actual

addiction treatment and also adequate analgesia. Continuing their baseline methadone dose, with opioid analgesia and all other adjuncts is the current recommendation. The patient methadone maintenance provider should also be contacted for verification of the dose, hospital admission, and should be told about discharge plans and dates, so they are aware of opioid use as well as follow-up.5 For patients not receiving oral intake, the methadone dose can be given parenterally (IV or subcutaneously), with the IM and subcutaneous doses being given as half the maintenance dose, divided into 2 to 4 equal doses, but IM route is not recommended because of the variability of absorption and the onset of action and duration. It is also important to remember in patients using methadone that mixed agonist-antagonist opioids may precipitate acute opioid withdrawal.5 The anesthesiologist must also be aware that the methadone can prolong the QTc and to consider this when using other medications that may also prolong the QTc, that are consistently used during the perioperative period.22,23 The anesthesiologist needs to be aware that there is very little evidence-based guidance in methadone use and preoperative recommendations, as well as conversions between other opioids to methadone, or IV to PO methadone conversions24 (Table 3). Other considerations during the perioperative period are to administer Pregabalin or Gabapentin preoperatively, as several studies have shown that Pregabalin or Gabapentin will decrease post-operative pain scores, as well as postoperative opioid consumption in the first 24 hours after surgery.25 Gabapentin has also been shown to possibly help with opioid withdrawal (but only in doses of 1600 mg/day).26 One major side effect of Gabapentin is that it does increase sedation.

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In children, it has been shown that use of either Paracetamol or NSAIDs will decrease perioperative opioid use, and NSAIDs alone show a 30-40% reduction in opioid requirements.2,27 However, this effect only results due to the low analgesic effect of paracetamol which is improved by an additional NSAID. Because of the low therapeutic margin of paracetamol, we should rather prefer the NSAIDs directly.

during the intraoperative period, as each patient will have their own tolerance and dependence. Consideration should be placed on chronic baseline needs, incision size, type of surgery (open vs. laparoscopic) and pain. Titration of opioids to a respiratory rate between 14-16 breaths a minute should be attempted in the spontaneously ventilating patient.1

Regional anesthesia should be a consideration in patients with surgeries that are suitable. Thoracic epidural analgesia with a combination of local anesthetic and lipid soluble opioid has been demonstrated to show advantages in comparison with just IV opioid analgesia. In opioid-tolerant patients, even with a peripheral regional block or epidural anesthesia they still need an initial dose of 40-50% of opioid to prevent acute withdrawal symptoms. Consideration must be made for local anesthetic epidural solution only if extremely high doses of parenteral opioids are being used or an increased need for monitoring needs to be considered.2 In patients where epidural fentanyl or morphine is not sufficient, Sufentanil was used successfully for complete pain control despite lower equivalent analgesic doses used with a starting dose 2 micrograms/mL at a rate of 7 mL/hr.28

Postoperative considerations

Intraoperative considerations Subanesthetic doses of intraoperative and postoperative Ketamine have been shown to be of benefit for reduction of opioid consumption in opioid naïve patients.29 Ketamine in subanesthetic doses also helps block the processing of nociceptive input in opioid-tolerant patients, and has been shown to reduce postoperative pain scores for the first postoperative day at rest and with physical therapy in opioid-tolerant patients, as well as patients reporting a reduction in pain intensity at 6 weeks post-surgery.30,31 Dexmedetomidine is α-2 agonist agent, used intraoperatively to provide sedation but it also provides analgesia and anxiolysis. In a double-blind study done by Dr. Cheung et al., Dexmedetomidine has shown significant reduction in postoperative pain scores for 48 hrs.32 Preoperative oral dose of Clonidine (α-2 agonist) 150 mcg, 90 minutes prior to surgery reduce postoperative pain scores in patients undergoing dental procedures along with adequate anxiolysis.33 In a double-blinded, randomized, placebo-controlled clinical trial done by Kim et al., intraoperative infusion of lidocaine ((a 1.5-mg/kg bolus followed by a 2-mg/kg/h infusion until the end of the surgical procedure) has shown reduction in postoperative pain scores and consumption of postoperative opioids after lumbar spine surgery.34 Remifentanil would not be a good choice in these patients as remifentanil has been shown to cause hyperalgesia after discontinuation, which would not help in opioid-tolerant patients that may already have hyperalgesia.35 In comparison with inhalational versus total intravenous anesthesia (TIVA), intraoperative hemodynamics, postoperative recovery, and perioperative pain scores were better with TIVA, but the total cost was significantly higher.36 There is no current evidence to support or suggest any specific opioid

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Continuation of multi-modal analgesia is imperative in the PACU. It depends on preoperative patient condition, type of surgery, and intraoperative management. Consider opioid PCA use, a Dexmedetomidine infusion as its analgesic effect is increased with opioid use, while decreasing the overall dose of opioids used,37 Ketamine, NSAIDS, and regional anesthesia if appropriate in PACU, as well as on the floors. Postoperative use of ketamine infusion also reduces the incidence of hyperalgesia and reduction of opioid use. If the patient has not received any regional pain procedure intraoperatively, plan for appropriate regional technique to reduce the postoperative pain and decrease postoperative opioid consumption. Verify with the primary team that the patient will be placed on all appropriate therapy once leaving the PACU. Another discussion with the surgical team about all postoperative multi-modal options should be had, as well as a discussion with the patient about pain score goals, and participation in physical therapy. The anesthesiologist can recommend followup by the Acute Pain Service for opioid-tolerant patients, as well as opioid naïve patients if they are having difficulty with their pain. The perioperative period is a good time to talk with the patient if the patient needs any behavioral therapy or psychological care to address psychological issues related to chronic pain or drug abuse. In 2016, CDC (Centers for Disease Control and Prevention) developed guidelines intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death.38 Conclusion Care of the opioid-tolerant patient is a challenging issue today for anesthesiologists. The pain management plan varies from patient to patient and should be planned after discussion with the patient, the surgical team, and the pain management service team as a multidisciplinary approach. n Author Information Department of Anesthesiology, University of Mississippi Medical Center (UMMC) (Hulet; Kurnutala). Corresponding author: Lakshmi N. Kurnutala, MD, Department of Anesthesiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216 (lkurnutala@umc.edu). Conflicts of Interest: None

References 1. Richebé P, Beaulieu P. Perioperative pain management in the patient treated with opioids: Continuing professional development. Can J Anaesth. 2009;56(12):969981. 2. Swenson JD, Davis JJ, Johnson KB. Postoperative care of the chronic opioidconsuming patient. Anesthesiol Clin North America. 2005;23(1):37-48. 3. Dahan A, Overdyk F, Smith T, Aarts L, Niesters M. Pharmacovigilance: A review of opioid-induced respiratory depression in chronic pain patients. Pain Physician. 2013;16(2):E85-94. 4. Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med. 2010;363(21):19811985. 5. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med. 2006;144(2):127-134. 6. Stromer W, Michaeli K, Sandner-Kiesling A. Perioperative pain therapy in opioid abuse. Eur J Anaesthesiol. 2013;30(2):55-64. 7. Mitra S, Sinatra RS. Perioperative management of acute pain in the opioiddependent patient. Anesthesiology. 2004;101(1):212-227. 8. de Leon-Casasola OA, Myers DP, Donaparthi S, Bacon DR, Peppriell J, Rempel J, Lema MJ. A comparison of postoperative epidural analgesia between patients with chronic cancer taking high doses of oral opioids versus opioid-naive patients. Anesth Analg. 1993 Feb;76(2):302-307 9. Gulur P, Williams L, Chaudhary S, Koury K, Jaff M. Opioid tolerance: A predictor of increased length of stay and higher readmission rates. Pain Physician. 2014;17(4):E503-507. 10. Leese PT, Hubbard RC, Karim A, Isakson PC, Yu SS, Geis GS. Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized, controlled trial. J Clin Pharmacol. 2000;40(2):124-132. 11. Gooby-Toedt D, Jackson JL. Kroenke K. Chronic medications in the perioperative period. South Med J. 1998;91(4):358-364. 12. Frölich MA, Giannotti A, Modell JH. Opioid overdose in a patient using a fentanyl patch during treatment with a warming blanket. Anesth Analg. 200;93(3):647648. 13. Liebschutz JM, Crooks D, Herman D, et al. Buprenorphine treatment for hospitalized, opioid-dependent patients: a randomized clinical trial. JAMA Intern Med. 2014;174(8):1369-1376. 14. Vadivelu N, Anwar M. Buprenorphine in postoperative pain management. Anesthesiol Clin. 2010;28(4):601-609. 15. Chen KY, Chen L, Mao J. Buprenorphine-naloxone therapy in pain management. Anesthesiology. 2014;120(5):1262-1274. 16. Oifa S, Sydoruk T, White I, Ekstein MP, et al. Effects of intravenous patientcontrolled analgesia with buprenorphine and morphine alone and in combination during the first 12 postoperative hours: a randomized, double-blind, four-arm trial in adults undergoing abdominal surgery. Clin Ther. 2009;31(3):527-541. 17. Gevirtz C, Frost EA, Bryson EO. Perioperative implications of buprenorphine maintenance treatment for opioid addiction. Int Anesthesiol Clin. 2011;49(1):147155. 18. Mercadante S, Villari P, Ferrera P, et al. Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine. J Pain Symptom Manage. 2006;32(2):175-179. 19. Chern SY, Isserman R, Chen L, Ashburn M, Liu R. Perioperative pain management for patients on chronic buprenorphine: a case report. J Anesth Clin Res. 2013;30;3(250):1000250. 20. Manfredi PL, Houde RW. Prescribing methadone, a unique analgesic. J Support Oncol. 2003;1(3):216-220.

21. Callahan RJ, Au JD, Paul M, Liu C, Yost CS. Functional inhibition by methadone of N-methyl-D-aspartate receptors expressed in Xenopus oocytes: stereospecific and subunit effects. Anesth Analg. 2004;98(3):653-659. 22. Chou R, Cruciani RA, Fiellin DA, Compton P, et al. Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. J Pain. 2014;15(4):321-337. 23. Chou R, Weimer MB, Dana T. Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. J Pain. 2014;15(4):338-365. 24. Weimer MB, Chou R. Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. J Pain. 2014;15(4):366-376. 25. Rivkin A, Rivkin MA. Perioperative nonopioid agents for pain control in spinal surgery. Am J Health Syst Pharm. 2014;71(21):1845-1857. 26. Salehi M, Kheirabadi GR, Maracy MR, Ranjkesh M. Importance of gabapentin dose in treatment of opioid withdrawal. J Clin Psychopharmacol. 2011;31(5):593596. 27. Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013;23(6):475-495. 28. de Leon-Casasola OA, Lema MJ. Epidural bupivacaine/sufentanil therapy for postoperative pain control in patients tolerant to opioid and unresponsive to epidural bupivacaine/morphine. Anesthesiology. 1994;80(2):303-309. 29. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006;(1):CD004603. 30. Urban MK, Ya Deau JT, Wukovits B, Lipnitsky JY. Ketamine as an adjunct to postoperative pain management in opioid tolerant patients after spinal fusions: a prospective randomized trial. HSS J. 2008;4(1):62-65. 31. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113(3):639-646. 32. Cheung CW, Qiu Q, Ying AC, Choi SW, Law WL, Irwin MG. The effects of intraoperative dexmedetomidine on postoperative pain, side-effects and recovery in colorectal surgery. Anaesthesia. 2014;69(11):1214-1221. 33. Fanini D, Poglio M, Marci MC, Iovinelli G, Antenucci F. [Oral premedication with clonidine as an alternative in dental practice. The effects on the pain threshold, blood pressure and salivary flow] [article in Italian]. Minerva Stomatol. 1998;47(9):453-464. 34. Kim KT, Cho DC, Sung JK, et al. Intraoperative systemic infusion of lidocaine reduces postoperative pain after lumbar surgery: a double-blinded, randomized, placebo-controlled clinical trial. Spine J. 2014;14(8):1559-1566. 35. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000;93(2):409-417. 36. Ozkose Z, Ercan B, Unal Y, et al. Inhalation versus total intravenous anesthesia for lumbar disc herniation: comparison of hemodynamic effects, recovery characteristics, and cost. J Neurosurg Anesthesiol. 2001;13(4):296-302. 37. Honey BL, Benefield RJ, Miller JL, Johnson PN. Alpha2-receptor agonists for treatment and prevention of iatrogenic opioid abstinence syndrome in critically ill patients. Ann Pharmacother. 2009;43(9):1506-1511. 38. 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):149.

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C O M M E N T A R Y

The Phenomenon of Practice Drift: Liars, Pimps and Snake Oil Salesmen

Should Physicians and Nurse Practitioners Practice Outside their Training and Expertise? HEDDY-DALE MATTHIAS, MD

t the end of the year, and at the nearing of the end of my career, I’ve been inundated with examples of my colleagues practicing “outside” their training, board-certification, and “scope-of-practice.” I am concerned about this “practice drift” towards lucrative, cash-based procedures performed in physician offices. “Practice drift” may occur in three ways: 1. “Upward drift” is the practice of medicine “above” the physician’s level of training such as a family practice physician performing vascular surgery or dermatology. 2. “Downward drift” is the practice of medicine “below” the physician’s training, such as a thoracic surgeon practicing family practice or hormone replacement therapy. 3. “Daffy drift” is performing procedures or administering services without any scientific or medical basis of efficacy. In most states, a license to practice medicine allows the unrestricted practice of medicine and surgery. (Look at your physician license.) Boards of Medical Licensure do not, and apparently, cannot, dictate what a physician may do in his or her office. (Although the Mississippi Board of Medical Licensure regulations state that physicians practicing outside their training must petition the Board for approval, this happens infrequently, if at all.)1 The Board can only regulate false advertising. 2 The only regulatory “agency” that matches training/expertise/board qualifications with the practice of medicine and surgery is a surgery center and a hospital credentialing committee. Most reputable institutions spend a great deal of time ensuring that a physician is actually trained and qualified for privileges (medical and surgical) performed at their organizations, for legal protection, and, hopefully, for ethical reasons. Surgeons, especially, must submit, via board-certification and training/procedure documentation, evidence of proficiency. If a surgical procedure is new, a physician must demonstrate training and

80 VOL. 60 • NO. 2 • 2019

usually be monitored by a qualified physician. This is well and good to protect both patients and facilities alike. However, to generate billing/cash-flow and to avoid the mindnumbing morass of federal, state and insurance regulations, many physicians have allowed their practices to ‘drift” outside their areas of training and expertise to quick and easy cash-based office practices. This “drift” includes not only physicians but has also gathered great speed in dental and nursing practices. To wit, last week I stumbled across the following medical services by nurse practitioners (physicians also offer some of these services): 1. $2500 worth of laboratory tests so obscure I had to look them up. They were ordered for an overweight and depressed woman. This clinic also offers intravenous cocktails of saline and watersoluble vitamins for “pick-me-ups.” 3 2. A number of clinics offer the “O-Shot” for enhanced sexual pleasure. This involves taking blood, spinning it for platelet-rich plasma, and injecting the PRP into the woman’s clitoris. (Currently, there are no FDA-approved treatments of female orgasmic disorder [FOD].) There are trials underway, and previous trials have been small and not blind or controlled. 3. “FemiWave” is described on a few local websites as delivering a “diffused energy of pulse waves to restore blood vessels and improve circulation in the vaginal region.” (The FDA issued a stern warning to several manufacturers in August 2018 about using these devices for vaginal atrophy, urinary incontinence, or reduced sexual function.) The American College of Gynecology (ACOG) has never endorsed these types of procedures. There are no randomized, controlled clinical trials to date. There are some in progress. 4. “Whole Body Cryotherapy,” performed by either physicians, nurse practitioners, or providers with absolutely no medical training whatsoever, is advertised on local billboards for weight loss, sports injuries, general and skin “rejuvenation” and other anti-aging aspects.

“Core Cryotherapy,” a national chain, uses gasiform nitrogen to rapidly lower the skin surface temperature to 30 to 32 degrees F in a cryosauna temperature ranging between minus 238 to minus 272 for two to three minutes of treatment. The website recommends 7-10 treatments for various ailments, and weekly “maintenance” therapy after that. Cost estimates are from $40 to 70 per treatment. It is not covered by health insurance. Many small studies which included elite male athletes are using whole-body cryotherapy, and most studies claim there is little longterm efficacy over conventional cold therapies such as ice and ice baths. A 2015 Cochrane Review determined “there is insufficient evidence to support the claims of its benefits or safety.” The FDA has not cleared or approved any whole-body cryotherapy devices. There are no controlled clinical trials regarding skin rejuvenation, or weight loss. I have yet to understand how this therapy is lawful by anyone at this time, especially those with no medical training whatsoever. But, “buyer beware!” Like the majority of other states in the US, the Mississippi Board of Dental Examiners has allowed the injection of Botox and intradermal fillers for a few years.4 How this is justified under the Mississippi Dental Practice Act is unclear. The removal of wrinkles and creases for cosmetic reasons is not the practice of dentistry. (There are some disorders treated by oral surgeons that can justify the use of Botox.) At least dentists are very familiar with nerve anatomy of the face, unlike the majority of providers who administer Botox. In Mississippi, Botox and fillers are administered by family practitioners, nurse practitioners, radiologists, neonatologists, pediatricians, pathologists, anesthesiologists, internists, and probably the old lady who lives up the street. Those most qualified, plastic surgeons and dermatologists, probably administer less than half the Botox in Mississippi, although this is merely a guess. Last week I found a Mississippi osteopath’s website extolling the wonders of hyperbaric oxygen for “rejuvenation.” This is nonsense. This website also advertises the “Vampire Facelift” which includes Botox, fillers, and platelet-rich plasma injection (PRP) of the face. An article from the Journal of Dermatological Treatment in 2016 concluded that while the “literature may be consistent with a modest benefit for specific indications, there is not sufficient evidence supporting the efficacy of PRP to justify a role in routine dermatological practice at present. However, since PRP is generally well tolerated with few reported complications, further study may be justified in the context of organized trials.”5 However, the most egregious cases of drift are of physicians and nurses practicing completely outside their residency training and “updrifting.” We have physicians trained in relieving surgical pain now

performing surgeries such as phlebectomies and CO2 facial lasers. Many of my colleagues will attack my criticism. So be it. A weekend or six-week “Holiday Inn course” will never replace a full residency training program, despite those practitioners arriving home with certificates of “board-certification” in a nonsensical, non-existent specialty such as “aging medicine” or “rejuvenation medicine.” I believe that if you want to be a surgeon, do a surgical residency. If you wish to be a plastic surgeon or dermatologist, do a residency program. However, I’m most concerned that many of these physicians have not obtained approval from the Mississippi Board of Medicine to perform services outside their training as required by regulations. I suspect that the Mississippi Board of Nursing is unaware of most of these practices. I am not without sympathy regarding the financial difficulties of traditional medical practice in the present day. I do understand. However, I believe that physicians are called to abide by higher ethical standards than entertaining every lucrative, consumer-driven service coming down the pike encouraged by an enthusiastic salesperson and visions of “green” dancing in our eyes. Physicians should not administer services they know have no proven efficacy simply because their patients demand it. This is “daffy drift.” It includes intravenous fluids, intravenous water-soluble vitamins, B12 injections without B12 deficiency, testosterone preparations without documentation of “age-specific” testosterone levels, other homeopathic “vitamins” and other compounds, “organic” hormone replacement therapies, etc. This is clearly prohibited by the Mississippi State Board of Medical Licensure.3 We owe it to ourselves, to our profession, and, above all, to our patients to practice with the highest levels of training and expertise available. I hope that most physicians agree with this standard and will begin to speak out about the possible harm that “practice drift” is causing and will continue to cause in the future to the detriment of our profession.6 It’s pathetic that medicine has come to this. I became a physician because of its previously high ethical standards as I believe most of my colleagues did as well. We were proud of our years of training and our expertise. We should all be sad, unhappy, and, yes, disgusted with “practice drift.” As Linda Hunt said at the close of The Year of Living Dangerously, “What then must we do?” n References 1. Mississippi State Board of Medical Licensure Rules and Regulations. Mississippi State Board of Medical Licensure Administrative Code. October 2018. Rule 2.5 Level II Office Surgery, D. Training Required 57. “To perform office-based surgery, the physician must be able to document satisfactory completion of surgical

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training such as board certification or board eligibility by a board approved by the American Board of Medical Specialties or American Board of Osteopathic Specialties. The certification should include training in the procedures performed in the office setting. Alternative credentialing for procedures outside the physician’s core curriculum must be applied for through the Mississippi State Board of Medical Licensure and reviewed by a multi-specialty board appointed by the Director.” 2. Mississippi State Board of Medical Licensure Rules and Regulations. Mississippi State Board of Medical Licensure Administrative Code. October 2018. Rule 12.3 Requirements E.5:73. “No physician shall advertise or otherwise hold himself or herself out to the public as being “Board Certified” without, (i) a complete disclosure in the advertisement of the specialty board by which the physician was certified, and (ii) can submit proof of current certification by a specialty board recognized by the American Board of Medical Specialties or the American Osteopathic Association. The term “Board Certified” frequently appears in conjunction with a list of services that the physician or clinic provides. The general public could easily be misled into thinking that the physician is certified in all of those services.”. 3. Mississippi State Board of Medical Licensure Policies. Rev. July 2018. 3.03 Complementary and Alternative Medicine “The Board feels that physicians and providers should never accede to invalidated treatment.” 4. Mississippi Board of Dental Examiners. Frequently Asked Questions. Scope of Practice for Dentists website: https://www.dentalboard.ms.gov/msbde/ msbde.nsf/webpages/FAQ_scope?OpenDocument. Accessed February 1,

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2019. May Botox be utilized by licensed Mississippi dentists in the treatment of TMD? Yes. At its 02/24/2017 meeting, the Board considered a request to revisit its prior determinations and reaffirmations regarding injectable pharmacologics and extraoral cosmetic procedures. Please see the Board’s 02/24/2017 determination regarding injectable pharmacologics for additional information and the specific language of the Board’s 02/24/2017 determination. As a result of the 02/24/2017 determination, the Board RESCINDED its 05/08/2009 determination regarding Dentox and Botox. Additionally, the 02/24/2017 determination nullifies a 10/16/2015 reaffirmation of the Board’s original 10/19/2007 determination. Refer to Miss. Code Ann. §73-9-3 and Board Regulation 7. 5. Lynch MD, Bashir S. Applications of platelet-rich plasma in dermatology: a critical appraisal of the literature, J Dermatolog Treat. 2016;27(3):285-289. doi: 10.3109/09546634.2015.1094178. 6. Federation of State Medical Boards. Position Statement on Practice Drift. April 2016. Available at: https://www.fsmb.org/siteassets/advocacy/policies/ position-statement-on-practice-drift.pdf Accessed January 18, 2018.

Author Information Dr. Matthias is board-certified in Anesthesiology, Internal Medicine, and Critical Care Medicine. (hdmatthias@comcast.net)

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Understanding Levels of Care in Substance Use Disorder Treatment R. STEPHEN PANNEL, DO, ABPN, ABAM

rimary-care physicians have a front-line role in recognizing when a patient may have a problem with drugs or alcohol. With some patients, a substance use disorder is easily identified. For example, those who regularly seek out pain-medication prescriptions will trigger an obvious red flag. In other patients, however, the problem may be well-concealed. People with addictions work hard to hide them. Sometimes, it is only when treatment for other medical conditions fails to have the results; it should start when a physician starts to dig deeper to discern what is going on with the patient. Physicians should be aware that, statistically speaking, one out of every 10 to 12 patients they see needs treatment for problems related to drugs or alcohol. Physicians may also observe a correlation between potential substance abuse and medical problems. Substance abuse and chemical use can harm a wide range of primaryhealth conditions. For example, people living with substance use disorders have: • 9 times greater risk of congestive heart failure

Modern treatment approaches are guided by a Continuum of Care described by the American Society of Addiction Medicine (ASAM). When patients receive an assessment for substance use disorder, the purpose is to identify not only whether or not they have a problem, but also where on the spectrum their problem falls. For some patients, the severity of their addiction and/or co-occurring mental health disorders will call for an intervention at the most intensive level of care. For others, however, a less-intensive level of care will be the appropriate entry point based on their assessment. The Continuum of Care is not designed as a start-to-finish path to recovery. Rather, patients enter the continuum at the level that best fits their needs. Based on their progress in treatment, they can step up to a more intense level of care or down to a less intense level. This model takes into account the realities that each patient’s pattern of progress is unique, that relapse is common, and that successful recovery is a longterm prospect.

• 12 times greater risk of liver cirrhosis

Here is an overview of how today’s standard levels of care in addiction treatment relate to the ASAM Continuum of Care.

• 12 times greater risk of developing pneumonia

Level 4: Medically Managed Intensive Inpatient Services

Meanwhile, abuse of alcohol and illicit drugs can be damaging to cardiovascular health, leading to high blood pressure and heart failure. Even when a substance use problem becomes apparent in the scope of treating primary-care issues, many physicians are hesitant to refer a patient for treatment because of their expectations about what it will mean for the patient. Physicians may anticipate that if they refer a patient for treatment, it will mean the patient must go away for one, two or even three months, separated from their home, work and family. Those high stakes often cause physicians to hold off on intervening until it seems a patient has hit “rock bottom” and knows that he or she needs help. While this approach may have made sense in the past, our understanding of the disease model of addiction today has shifted the treatment model away from an all-or-nothing concept. As with other diseases, addiction can be prevented and treated early. Different levels of treatment are appropriate for different levels of dysfunction. 84 VOL. 60 • NO. 2 • 2019

For patients with a daily substance abuse problem who experience difficult or dangerous withdrawals, this is where treatment begins. At this most intensive level of care, patients receive 24-hour nursing care and daily physician care. Inpatient medical detox programs fall into this category. Fortunately for patients, however, this level of care is no longer limited to only those withdrawals which may be life-threatening. In the past, medical detox was only available to patients for alcohol, opioids and benzodiazepines. Today, due to increased awareness and parity in substance-abuse treatment coverage, the medical community recognizes that withdrawals from other substances can also be so severe and painful that they warrant medical care and support. While not life-threatening, withdrawals from substances including cocaine, crack, methamphetamines and even marijuana can be so painful that patients have virtually no chance of being able to stop using for more than 24 or 48 hours on their own. This recognition has led to broader access to withdrawal management care for patients, regardless of their substance of abuse.

In this level of care, patients are removed from their home environment, removing access to substances. They receive medical support for withdrawal symptoms which can include nausea, vomiting, anxiety and insomnia. While medical detox still manages the dangers of withdrawals for those abusing alcohol, benzos and opioids, providing access to withdrawal management care for those abusing stimulants has led to a significant increase in people with those addictions doing well in treatment. Previously, it was more common to see people abusing those substances continue to use and spiral out of control until some kind of medical or legal consequence forced them to get help. Now we have a chance to bring them in sooner and provide support in an appropriate environment. Level 3: Residential/Inpatient Services For most physicians, this is the level of care in addiction treatment that is most familiar and expected. Patients are removed from their home environment, where they would have access to substances and be very vulnerable to relapse. They stay in a supportive environment 24 hours a day for several weeks, receiving six to nine hours a day of treatment services. Those services include individual and group therapy, as well as education about the nature of addiction as a brain disorder. While the basic structure of residential treatment remains unchanged, recent years have seen an evolution toward a more patient-centered approach to treatment. In the past, residential programs were standardized and manualized, relying primarily on 12-step models. Patients were educated in a program of recovery and told that if they followed it, they would be successful. In the past five to seven years, however, the patient-centered approach has emphasized a focus on the patients’ buy-in. Patients are engaged in discovering their own needs, while treatment revolves around the patients’ needs as well as education. Most residential programs also include a strong family component as well, where patient families come to the treatment center for tailored programming geared toward educating them about the nature of addiction. Level 2: Intensive Outpatient/Partial Hospitalization Services In this level of care, patients can continue living at home or in a soberliving environment while receiving outpatient treatment. Intensive Outpatient and Partial Hospitalization are distinct programs, each with its own programming and interventions. Patients in Partial Hospitalization programs receive 20 or more hours a week of services, while those in Intensive Outpatient programs receive nine or more hours a week. These programs extend the patientcentered approach in education and therapy, including a focus on relapse prevention.

Patients can access this level of care in multiple ways. For some, IOP/ PHP programs are their entry-point to the Continuum of Care, if their assessment shows their needs are appropriate for a moderate level of intensity in treatment. For those with greater needs, they may enter an IOP/PHP program after completing withdrawal management and residential treatment. Still, others may begin at a lower level of care and move up on the continuum into IOP/PHP if they need greater support to avoid relapse. One important aspect of IOP/PHP programs is standard drug screenings. Administered as part of the treatment program, screenings are a low-cost way to provide a high level of accountability and to boost the confidence of those who are progressing well in treatment. Those in outpatient treatment may be required to undergo drug screenings as often as three times a week. In primary-care practices, drug screenings tend to have a bad connotation, due to the turmoil that can ensue for both the physician and the patient when a drug screen comes back positive. In substanceabuse treatment practices, however, drug screenings are as ordinary as blood-pressure tests. They are a standard measure of how well a patient is responding to treatment. When a patient passes them consistently over many weeks, the screenings actually become an encouragement to the patient as positive, objective proof of success. At the IOP/PHP level of care, an additional advantage for patients can be living in a supportive housing environment while they are receiving treatment. Generally speaking, the concept of a community-enforced sober living environment has a poor reputation. But when managed correctly, sober homes are effective for people as they work to regain independence and establish new skills for successful long-term sobriety. While there are relatively few sober-living operations to choose from in Mississippi, aspects to look for include a requirement for frequent drug screenings, a commitment to providing a very safe environment, and continued outpatient care for residents. Level 1: Outpatient Services In this level of care, patients receive less than nine hours a week of treatment services. Typically, they live on their own or at home. This level of treatment allows people to continue working or going to school alongside their treatment schedule. Level 0.5: Early Intervention The ASAM Criteria includes a level of care for those who are at risk of developing substance-related problems. As with any other medical problem, substance-abuse disorders can be prevented from becoming full-blown crises through prevention and early intervention. Physicians need not wait until a patient reaches “rock bottom” to express concern over his or her substance abuse — any more than you would wait for a heart attack to recommend a patient change poor eating habits for the sake of cardiovascular health. FEBRUARY • JOURNAL MSMA

When a patient shows signs of substance-abuse problems, physicians can recommend he or she get an assessment to determine whether there is a problem and, if so, how severe. Physicians and their staffs have more options than they may realize when it comes to referring for an assessment. Any center where people can go for treatment will also perform assessments, as will community mental health centers. One of the simplest things a physician’s office can do is to call the patient’s insurance provider and ask for a recommendation on where to send the patient for an assessment. A physician who has identified a potential substance abuse disorder can then bring up his or her concern with the patient, be prepared to make the referral immediately if the patient is willing to consider treatment. While the assessment could point to a need for residential care, it could also indicate that only outpatient care is needed and the interruption to the patient’s life could be minimal. Both physicians and patients need to know that their expectations about what treatment means may be out-of-date. They may expect that treatment always translates into a residential level of care, when it may mean only a few hours of treatment per week. If physicians and patients overestimate the intensity of treatment required, they probably also underestimate the typical duration of a treatment course — especially for those patients who do need to begin treatment at a higher level of care. Successfully working through the treatment levels can take as long as 12 to 24 months, even if more than half of that time is spent only in outpatient treatment.

Both within and without the medical community, the attention on substance abuse has never been higher. The nature of diagnosis and treatment continues to mature and advance and to become better integrated into the broader healthcare system. These are welcome changes for the estimated more than 20 million Americans who suffer from substance-abuse disorders, and for all of us involved in their care. n Dr. Pannel is Medical Director of Oxford Treatment Center. He specializes in treating dual diagnosis issues. He is certified by the American Board of Psychiatry and Neurology and the American Board of Addiction Medicine.

References 1. Substance Abuse: Clinical Issues in Intensive Outpatient Treatment. (2006) Treatment Improvement Protocol (TIP) Series, No. 47. Center for Substance Abuse Treatment. Rockville (MD): Substance Abuse and Mental Health Services Administration (US) Retrieved from http://www.samhsa.gov/. 2. SAMHSA-HRSA Center for Integrated Health Solutions. Integrating Addiction and Primary Services. Becky Vaughn, MSEd, CEO, State Associations of Addiction Services (SAAS), and Aaron Williams, MA, Director of Training and Technical Assistance for Substance Abuse, CIHS. Retrieved from https://www.integration. samhsa.gov/. 3. Kozor, R., Grieve, S. M., Buchholz, S., Kaye, S., Darke, S., Bhindi, R., Figtree, GA. (2014). Regular cocaine use is associated with increased systolic blood pressure, aortic stiffness and left ventricular mass in young otherwise healthy individuals. PloS one, 9(4), e89710. doi:10.1371/journal.pone.0089710. 4. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15-4927, NSDUH Series H-50). Retrieved from http://www.samhsa.gov/ data/.

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86 VOL. 60 • NO. 2 • 2019

Committee Seeks Candidates for Vacancies in MSMA Offices

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Delegates attending the 151st MSMA Annual Session August 16-17, 2019, in Jackson will cast ballots to fill new terms of office for a number of association posts. The Nominating Committee is seeking input from the membership as the committee prepares a slate of candidates. The slate developed by the Nominating Committee will be published to the entire membership in June. All nominees must be active members of the association. No physicians may be put forth on the ballot unless that physician has expressed a willingness to serve if elected. The chart below lists the vacancies that will be filled by election in 2019. The names of incumbents and the incumbent’s eligibility to be re-elected are indicated. Terms of office follow. The Nominating Committee is composed of the nine most recent Past Presidents of the association residing in Mississippi. The Immediate Past President is the chair. Only names in black are eligible for reelection.

OFFICERS & TRUSTEES President-elect at large Secretary /Treasurer Trustee District 2 Trustee District 4 Trustee District 5 Trustee Resident/Fellow Trustee/Student

INCUMBENT J. Clay Hays, Jr. W. Mark Horne Brett Lampton Jennifer Bryan J. Lee Valentine Chelsea Rick Avani K. Patel

COUNCILS Accreditation at large Accreditation at large Budget & Finance at large Budget & Finance at large Constitution & Bylaws Constitution & Bylaws Constitution & Bylaws Constitution & Bylaws Ethical & Judicial Affairs Legislation District 1 Legislation District 2 Legislation District 3 Legislation Resident Legislation Student Medical Education District 2 Medical Education District 4 Medical Education District 5 Medical Service District 4 Medical Service District 5 Medical Service Resident Medical Service Student Public Information District 1 Public Information District 2 Public Information District 3 JOURNAL MSMA Associate Editor

INCUMBENT Lori Marshall Crystal Tate Susan Chiarito Chip Holbrook Crystal Tate J. Martin Tucker Samuel Crosby Angela Wingfield John J. Cook Katherine Patterson Son Lam Kenneth Thomas Brock Banks William Buck June Powell Jonathan Jones Matthew Cassell J. Anthony Cloy Michael Shrock David Green Kandice Bailey Nathaniel Brown Troy Cappleman Charlotte Magnussen INCUMBENT Philip Merideth

Terms of Office: President-elect: 1 year 2019-2020; Officers, Trustees & Councils (physicians): 3 years 2019 – 2022; Trustees & Councils (students & residents): 1 year 2019-2020. Journal Associate Editor: 2 years 2019 – 2021. Incumbents NOT eligible for re-election are noted in gray type. Email Nominations to VJackson@MSMAonline.com or any member of the Nominating Committee: William M. Grantham, MD; Lee Voulters, MD; Daniel P. Edney, MD; Claude D. Brunson, MD; James A. Rish, MD; Steve Demetropoulos, MD; Thomas E. Joiner, MD; Timothy J. Alford, MD; Randy Easterling, MD.

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s winter fades, we know that spring will soon bring forth new beginnings. It is a time of new life and vigor, the promise of things that are to come and in that same spirit, the MSMA Board of Trustees is pleased to welcome our new Executive Director, Dr. Claude Brunson. Walt Disney once said, “Every leader is telling a story…about what he or she values.” It’s easy to see what Dr. Brunson values if you spend just an afternoon shadowing him or watching him “work.” He attaches great importance to better the practice of medicine at both the state and national levels. For those who have worked closely with him, they will tell you that medicine is his passion. He is a natural communicator, consensus builder, a gifted anesthesiologist and a highly effective leader having educated many of Mississippi’s physicians. In addition to these roles as a physician, he is also a business executive having overseen and managed extensive budgets and personnel throughout his tenure at UMMC. One of Dr. Brunson’s greatest strengths as a physician leader is that he is committed to and supportive of the mentoring process. He has a reputation for assisting young physicians growing in leadership, and the only thing he asks in return is for them to “help someone else when you’re given a chance.” Countless accomplished physicians across our organization and others credit Dr. Brunson’s mentorship with helping them to grow in organized medicine leadership and beyond. All of these traits point to a leader who excels in the categories needed to conduct the business of our association. Dr. Brunson is no stranger to leadership within MSMA having served in almost every capacity including Chairman of the Board of Trustees as well as President. He possesses extensive experience in organized medicine having most recently led the external affairs division at UMMC since 2010 as a senior advisor to the Vice Chancellor. An anesthesiologist and former chair of the Department of Anesthesiology at UMMC as well as previous Director of Government Affairs, he achieved the rank of Professor and is now retiring from his celebrated career there with over 30 years of experience. In 2013, Dr. Brunson was elected president of MSMA, the first African American to hold that position in our history. He makes history again today as our first African American executive director.

90 VOL. 60 • NO. 2 • 2019

Among his many accomplishments, he is a graduate of the Levinson Institute leadership course for physician executives offered by Harvard University. He has been a member of the board of directors of the American Society of Anesthesiologists since 2002 and has served on expert panels of the Food and Drug Administration. He has been appointed by the Governor to the Emergency Medical Services Committee, Mississippi State Board of Medical Licensure (recently serving as its President) and the Governor’s Task Force on Heroin and Opioid Abuse. He is graciously stepping down from his post on the State Board of Medical Licensure to concentrate on his new position at MSMA. A native of Auburn, Alabama, Dr. Brunson earned his B.S. degree from the University of Alabama after a four-year tour with the U.S. Navy as a hospital corpsman and field medicine technician with the Fleet Marine Force. He graduated medical school at the University of Alabama at Birmingham and completed his residency in anesthesiology at UMMC. After graduating, Brunson joined the faculty of the School of Medicine and later served as chief of the medical staff. Dr. Brunson is bright and politically savvy. He understands the issues that are most important to our members. As a former head of government affairs at UMMC, he is well known by lawmakers and is widely respected at the legislature. There was vast interest in the position of MSMA executive director. However, throughout our deliberations, we returned again and again to the candidate who certainly was the most qualified of the applicant pool and also the one who had the deepest love and admiration for our association. Your Board of Trustees is confident Dr. Claude Brunson is the right person for the job and will serve our organization well as we transition into the next era. We are pleased to have a Mississippi physician leader at the helm who understands our physicians’ struggles and also has the key relationships in place at various regulatory and policy-making institutions to assist us in achieving our goals. We welcome Dr. Brunson “home” to MSMA and look forward to the years ahead under his steady leadership. n — Jennifer J. Bryan, MD Chair, MSMA Board of Trustees

Claude D. Brunson, MD, MSMA's new executive director

FEBRUARY â&#x20AC;¢ JOURNAL MSMA

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The Opioid Crisis: Ongoing Epidemic and Evolving Solutions

rug overdose deaths, including those involving opioids, continue to be a major concern for the general public, medical community, and law enforcement agencies. This tragedy afflicts men and women, all races, and adults of nearly all ages. Overdose deaths from opioids, including prescription opioids, heroin and synthetic opioids (like fentanyl), have increased almost 6 times since 1999. Overdoses involving opioids killed more than 47,000 people in 2017, and 36% of those deaths involved prescription opioids.1,2,3 Prescription opioids continue to be involved in a significant proportion of drug overdose deaths. Three distinct but interconnected waves are driving the overdose epidemic: an increase in deaths from prescription opioid overdoses since the 1990s; an increase in heroin deaths starting in 2010; and a more recent surge in deaths from illicitly manufactured fentanyl (IMF), including fentanyl analogs that have been detected in decedents. 2,4 The Centers for Disease Control and Prevention is committed to supporting states and communities in efforts to combat the opioid overdose epidemic. The CDC’s Overdose Prevention in States (OPIS) effort includes three programs that equip states with resources such as the Prevention for States (PfS), Data Driven Prevention Initiative (DDPI), and Enhanced State Opioid Overdose Surveillance (ESOOS). The resources and information from the OPIS programs help combat prescription and elicit opioid abuse and overdose and are the heart of the CDC’s work on this epidemic. Medicare, Medicaid, and private insurers can be involved in efforts to combat the opioid epidemic. Utilization management strategies are common for opioids. Insurers have the opportunity to re-design coverage policies to improve pain management and reduce opioid related injuries and deaths. States have broad authority to influence and regulate the prescribing and dispensing of prescription drugs and do so in a variety of ways. The CDC provides data and resources to equip and inform states about putting into practice strategies that help prevent high-risk prescribing and improve treatment for opioid use disorder. States can advance promising strategies such as the prescription drug monitoring program and Medication Assisted Treatment (MAT) to increase access to substance abuse treatment services. They can identify opportunities to expand first responder access to naloxone; and the CDC’s “Evidence-Based Strategies for Preventing Opioid Overdose: What’s Working in the United States”. The CDC-developed “CDC Guideline for Prescribing Opioids for Chronic Pain” can ensure patients have access to safer, more effective chronic pain treatment. 94 VOL. 60 • NO. 2 • 2019

The Mississippi State Department of Health (MSDH) has authorized the dispensing and administration of naloxone without a prescription. Pharmacies are able to provide naloxone to a family member, friends, or other person in a position to assist someone at risk of opioid overdose. The MSDH has had an active educational campaign Michael Mansour, MD among the Mississippi medical community since 2017. In 2017 the Mississippi Opioid and Heroin Data Collaborative was established. This is a joint effort of the MSDH, Mississippi Department of Mental Health, Mississippi Bureau of Narcotics, and the Mississippi Board of Pharmacy. The partnership’s goals are to share data and conduct comprehensive statewide opioid surveillance. The Mississippi State Medical Association continues to provide and promote educational programs to its members regarding the opioid crisis. Collaboration is essential for success in preventing opioid overdose deaths. Medical personnel, Public Safety officials, mental health and substance abuse treatment providers, and community-based organizations all bring awareness and expertise to address this complex epidemic. The medical community must remain fully engaged and committed not only to addressing the 36% of overdose deaths involving prescription drugs but also to participating in the continued education and support of our colleagues, our patients, and all organizations involved in efforts to overcome this epidemic. n

Michael Mansour, MD President, Mississippi State Medical Association References 1. Hedegaard H, Minino AM, Warner M. Drug overdose deaths in the United States. 1999-2017. NCHS Data Brief, no 329. Hyattsville, MD: National Center for Health Statistics. 2018. 2. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: National Center for Health Statistics; 2018. 3. Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and Opioid-Involved Overdose Deaths – United States.2013-2017. Morb Mortal Wkly Rep. ePub: 21 December 2018. 4. Gladden RM, Martinez P, Seth P. Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths – 27 States. 2013-2014. MMWR Morb Mortal Wkly Rep. 2016;65(33):837-843.

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C O M M E N T A R Y

A Conversation with Thomas Payne, PhD on Limiting E-Cigarette Sales to Teens to Prevent Nicotine Addiction

igarette smoking among the junior and senior high crowd plummeted by about 50% between 2011 and 2017 – good news, seeing that statistics show nearly 90% of adult smokers started before age 18. But it’s the rampant use of electronic nicotine delivery systems, or ENDS, that is undermining gains made in keeping children away from addictive tobacco. Vaping has increased by nearly 80% among high schoolers and 50% among middle schoolers since last year. Overall, it increased among high school students by 900% from 2011 to 2015, according to the U.S. Food and Drug Administration.. The news is so alarming that the FDA is proposing new limits on the sale and accessibility of flavored nicotine products that critics say purposefully target younger smokers. The FDA also says it will start the process of banning menthol in cigarettes and cigars, a flavor favorite of all ages. “These data shock my conscience,” FDA Commissioner Dr. Scott Gottlieb said in issuing a November 15 statement. “We’re committed to utilizing the full range of our regulatory authorities to directly target the places kids are getting these products and address the role flavors and marketing are playing,” he said. The FDA’s pronouncement is a step in the right direction – but only a step, a University of Mississippi Medical Center tobacco cessation expert says. “It’s not quite going far enough,” said Dr. Thomas Payne, professor of otolaryngology and communicative sciences and executive director of UMMC’s ACT Center for Tobacco Treatment, Education and Research. “If you restrict flavors in e-cigarettes, what will likely happen is that people will look for other areas where they can get flavored tobacco, like little cigars. The restriction should be across the board for all tobacco products,” Payne said. “That could tremendously reduce the use of tobacco products in general.” The Centers for Disease Control and Prevention estimates about 3.6 million high school and middle school students vape. That’s the term for using e-cigarettes, battery-operated devices that emit high doses of vaporized nicotine that the user inhales. They’re marketed to adults as a way to stop or cut down on tobacco smoking, an argument that’s

98 VOL. 60 • NO. 2 • 2019

Dr. Thomas Payne explains the use of a Juul e-cigarette in the shape of a flash drive.

often panned by health experts. About 10.3% of Mississippi high school students use e-cigarettes – the national average is 20.8% – and about 9.4% of Mississippi high schoolers smoke tobacco, according to the Campaign for TobaccoFree Kids. The national high school smoking rate is 7.6%. Although they’re not supposed to be sold to those under age 21, e-cigarette products in fruity flavors, chocolate, vanilla, coffee and other aromas or tastes are often easily accessible at convenience stores, gas stations and online. The leading e-cigarette maker, Juul, produces a version that’s shaped like a USB flash drive. “You can have kids in the back of the classroom using these products,” Payne said. “Teachers often don’t know it’s a vaping device. It’s hard to detect. Kids play with things in their mouths all the time.” Gottlieb wants their sale limited to age-restricted, in-person locations,

or, if sold online, with age verification. Juul vowed earlier this month to halt most retail sales of flavor products while restricting flavor sales to adults 21 and older on its secure website. Don’t get too excited about the e-cigarette industry doing the right thing, Payne warns. “This is a page right out of the tobacco industry playbook,” he said. “They come across as helpful when they are finally nailed, and they want to self-regulate. This will require federal intervention for an industry that’s out there to make money, and their cash crop is kids. “The devil is in the details. Online sites (such as that touted by Juul) are secure because you’re entering a credit card number. It doesn’t verify who the purchaser is or their age.” It’s important to remember that no research backs up claims that smoking e-cigarettes are less dangerous than smoking traditional tobacco, Payne said. A significant research study released this year also showed that in a test group of smokers who used e-cigarettes to try to kick the habit, only about 5% were successful. That’s the same rate as you find in people who try to quit cold turkey, Payne said.

smoking cigarettes with lower levels of tar or nicotine doesn’t reduce the risk for CVD or cancer. Dr. Michael Hall, associate professor of cardiology, and Payne are part of a five-year, multi-center research project funded through the National Institutes of Health and the FDA that examines the long-term effects of smoking e-cigarettes. There are several compounds such as acrolein, a colorless liquid, that are present in the aerosol produced in vaping, Hall said. “These compounds cause injury to blood vessels,” he said. “With e-cigarettes, we don’t have data to show what the long-term effects are,” he said. “But downstream, they may cause bad things in the heart to occur. E-cigarettes use nicotine, which can increase blood pressure and heart rate.” The FDA’s regulatory powers “give them much wider control over the development of e-cigarettes and advertising,” Payne said. “We knew from the beginning that it would take years to implement this. It looks like the FDA is taking the next steps. This can decrease the number of kids who move on to cigarettes as their tobacco product choice.” “I ask my patients about smoking, but we don’t do a good enough job of asking patients about newer products such as e-cigarettes,” Hall said. “Some of my patients say that they quit smoking, and now they vape instead. “There is nothing good that comes out of any of those products. The message should be not to use any of them.” — UMMC Public Affairs n

Gottlieb is not proposing immediate limits on mint and menthol flavors that are attractive to adults who believe e-cigarettes will help wean them from tobacco products. “I don’t want to create a situation where the combustible products have features that make them more attractive than the non-combustible products,” he said in the statement. “But at the same time … I believe these mentholflavored products represent one of the most common and pernicious routes by which kids initiate on combustible cigarettes.” Most 16-year-olds don’t like the taste of an unflavored e-cigarette, Payne said. “And the FDA move to eliminate menthol is absolutely wonderful. We’ve been waiting for that for a very long time.” The CDC says smoking kills more than 480,000 people annually. Smoking is a major cause of cancer, as well as cardiovascular disease, or CVD, and causes about one out of every four deaths from CVD. Even people who smoke fewer than five cigarettes a day are at huge risk to develop CVD – and experts say

E-cigarettes come in many styles, ranging from the size of a pen to the shape of a flash drive.

FEBRUARY • JOURNAL MSMA

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 Mississippi Provisional ReportableDisease Disease Statistics* Provisional Reportable Statistics Provisional Reportable Disease Statistics* February 2018 December 2018

December 2018

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

*Monthly statistics are provisional. Disease totals may change depending on additional reporting from healthcare providers and public health investigation. These final case Public numbers do not reflect theState Health District Totals* counts. IV

VII

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Feb 2018

3Public0 2 Health District 1 1 1 2

III

Pulmonary Tuberculosis (TB)

Gonorrhea

Extrapulmonary TB

Mycobacteria Other Than TB

Chlamydia

346

124

108

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1 0

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Rocky Mountain spotted fever

West Nile virus

0 0

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Animal Rabies (bats)

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E. coli O157:H7/STEC/HUS

0 0

0 7

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848 9

9420

0 9,731

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496

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320

0 323

441

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451

555

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445 95

43 21

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0 1 0 0 0

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Invasive H. influenzae disease

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0 35

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Salmonellosis

750

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Hepatitis A (acute)

0174 0

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0 64

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186

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612

487

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147

172

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Zoonotic Diseases

Shigellosis

100 VOL. 60 â&#x20AC;˘ NO. 2 â&#x20AC;˘ 2019

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JUNKIE: PULP FICTION CONFESSIONS OF AN UNREDEEMED DRUG ADDICT, 1953 – This graphic image is the cover of a pulp fiction book from the early 1950s. In that era, many “pulp” paperbacks, featuring sensual covers with stories usually of crime, horror or scifi, were printed for the masses in large quantities on low-quality paper manufactured from wood pulp, thus termed “pulp fiction.” This book, entitled “Junkie: Confessions of an Unredeemed Drug Addict,” was written by William Lee, a pseudonym for William S. Burroughs (February 5, 1914 – August 2, 1997), a major figure of the Beat Generation and a postmodernist author. Burroughs wrote eighteen novels and novellas, six collections of short stories and four collections of essays. Born in St. Louis, he later connected with Allen Ginsberg and Jack Kerouac, and their friendship would prove a defining influence for 1960s counterculture. Much of Burroughs’s work is semi-autobiographical, principally drawn from his experiences as a heroin addict. “Junkie” was his confessional first novel, and the lurid cover features in pulp fiction style a beautiful blond struggling in tight fitting clothes reaching for her syringe and another hit, with other tools of the drug trade spilling on the ground. Burroughs is perhaps best known for his third novel “The Naked Lunch” (1959), a highly controversial work. This book reveals plainly that opioid addiction is nothing new (although its current manifestation is particularly devastating) and has been a plague on mankind for centuries. In the nineteenth century, the addiction was termed “opium eating” and was appreciated as a frequent phenomenon. The twentieth century saw opiate addiction evolve with increased utilization of intravenous administration. We as physicians may be able to control the tragic surge in addiction today better, but the lessons learned will need to be applied and reapplied with our patients in future years to battle coming waves of an ancient disease. If you have an old or even somewhat recent photograph or image 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 FEBRUARY • JOURNAL MSMA

101

P O E T R Y

A N D

M E D I C I N E

Edited by Lucius Lampton, MD; JMSMA Editor

He Was a Different Fellow After a Few Drinks [This month, I begin a multi-issue focus on the poetry of the late physician-poet Merrill Moore (1903-1957), a noted American psychiatrist and neurologist who also achieved fame as a poet and sonneteer. Born and educated in Tennessee, he became a member of the Fugitives, a group of poets, literary scholars, and novelists who came together at Vanderbilt University in the 1920s and included such notables as John Crowe Ransom, Allen Tate, Donald Davidson, and Robert Penn Warren. Inspired by the sonnets of American poet Edwin Arlington Robinson (who wrote such classic poems as “Richard Cory” and “Miniver Cheevy”), Moore began writing 14-line sonnets in 1920, which he would term “fourteeners” over his prolific literary career (although not all his poems, like the one below, are held to 14 lines). He received his MD from Vanderbilt School of Medicine in 1928 and interned at the St. Thomas Hospital in Nashville for a year. He moved to Boston and taught neurology at the Harvard Medical School, conducting not only a large psychiatric practice but also publishing research on alcoholism, addiction, suicide, and the psychoneurosis of war in the “New England Journal of Medicine” and other respected medical journals. His sonnets were always intelligent and well-crafted, usually witty, and often revealing his physician skill of clinical observation. The poem below from his 1949 collection entitled “Clinical Sonnets” explores the psychological influences often behind alcoholism and drug addiction, the so-called “release” given to an underlying personal demon. Expect more Moore sonnets in coming months. 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.

He was usually tense and frozen, cold and still Until he got a few drinks in him, then He turned into an utterly different person--Friendly, affable, kindly, genuine, And altered as though the warmth of summer itself Were flowing through his arteries and veins. Nothing was too good for his delight, Nothing would ever turn his day to night, For he was beaming, radiant and fresh As though he did not live closed in the mesh Of something that was timid and self-conscious. Something that possessed him but would not be named, Something that upset his inner peace, Something that was deeply a part of him From which, for a moment alcohol gave release. — Merrill Moore, MD (1903-1957) Native of Columbia, TN Long a resident of Boston, MA

102 VOL. 60 • NO. 2 • 2019

M S M A

Welcoming Our Newest Members

ANDERSON, LEAH, Waynesboro, Family Medicine

MARION, LAURA, Amory, Obstetrics & Gynecology

BLOMBERG, CHRISTOPHER, Lucedale, Family Medicine

MCDONNELL, PRESTON, Crystal Springs, Family Medicine

DINNING, JENNIFER, Tupelo, General Surgery

PHAM, HUONG, Clarksdale, Obstetrics & Gynecology

HALL, JOHN, Pascagoula, General Surgery

QUECK, SARAH, Laurel, Ophthalmology

HARRISON, HUNTER, Meridian, Family Medicine

RAJ, MARC, Pascagoula, Physical Medicine & Rehabilitation

HERRINGTON, ELIZABETH, Vicksburg, Hematology (Int Med)

SANDIFER, PHILLIP, Oxford, Orthopaedic Surgery

JOHNSON, ASHLEY, Jackson, Obstetrics & Gynecology

THAGGARD, DOUGLAS, Olive Branch, Internal Medicine

LIVINGSTON, DONALD, Amory, Internal Medicine

WASHINGTON, TECHKSELL, Pascagoula, Medical Oncology

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November 24-26, 2019 Express 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 letter writers. 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.

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