Journal MSMA Volume LXI | No. 8 | August 2020

W. Mark Horne, MD · 2020-21 MSMA President

SCIENCE ARTICLES

EDITOR

Lucius M. Lampton, MD

ASSOCIATE EDITORS

D. Stanley Hartness, MD

Philip T. Merideth, MD, JD

MANAGING EDITOR

Ashley Grant

PUBLICATIONS COMMITTEE

Sheila Bouldin, MD, Chair

Dwalia S. South, MD, Chair

Emeritus

Thomas C. Dobbs, MD

Wesley Youngblood, MD and the Editors

THE ASSOCIATION President

J. Clay Hays, Jr., MD

President-Elect

W. Mark Horne, MD

Secretary-Treasurer

Joe Austin, MD

Speaker

Geri Lee Weiland, MD

Vice Speaker

Jeffrey A. Morris, MD

Executive Director

Claude D. Brunson, MD

JOURNAL OF THE MISSISSIPPI STATE MEDICAL ASSOCIATION (ISSN 0026-6396) is owned and published monthly by the Mississippi State Medical Association, founded 1856, located at 408 West Parkway Place, Ridgeland, Mississippi 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, Ashley Grant, P.O. Box 2548, Ridgeland, MS 39158-2548, Ph.: 601-853-6733, Fax: 601-853-6746, www.MSMAonline.com.

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Copyright © 2020 Mississippi State Medical Association.

Official Publication MSMA • Since 1959

184 Review of the Medical Literature

Navigating COVID-19 Experimental Treatments: A Comprehensive

Mary Joyce B. Wingler , PharmD; David A. Cretella , PharmD; and Jason J. Parham, MD, MPH

Newborn screening for Severe Combined Immunodeficiency with TREC assay

192 in Mississippi 2012–2018

Jessica B. Perkins, MD, and Anne B. Yates, MD

Establishment of the Mississippi Pediatric Clinical Trials Center (MPCTC):

196 Opportunities to Improve Children’s Health

Whitney Herring, MD, MPH; Mobolaji Famuyide, MD; Joseph Mark Majure, MD; Connie Baird-Thomas, PhD; Kristen Callahan, BS; Dana Lindsay, BBA, RN; Chad Blackshear, MS; Lacy Malloch, BS; Frederick Barr, MD, MSCI; and Robert

, PhD

SPECIAL

DEPARTMENTS

ABOUT THE COVER

W. Mark Horne, MD, Laurel, became the 153rd President of the Mississippi State Medical Association on August 15, 2020 during the 152nd Annual Session of the MSMA House of Delegates. Dr. Horne is board certified in internal medicine and hospice and palliative care medicine. Dr. Horne graduated with distinction from Mississippi College with an undergraduate degree in biology. He earned his medical degree from the University of Mississippi School of Medicine. While in medical school, he joined the Mississippi National Guard, serving in the 134th Combat Support Hospital. A residency in Internal Medicine followed at Erlanger Medical Center in Chattanooga, TN. While in Chattanooga, he served with the Tennessee Army National Guard, and in 1991-92, was deployed as Battalion Surgeon with the 1-181 Field Artillery Brigade to Southwest Asia in support of Operation Desert Storm. After return, he completed his residency and moved home to Laurel to begin practice at South Central Regional Medical Center (SCRMC) in January 1992. In 2018, he was named Chief Medical Officer of SCRMC where he continues to see patients and serve his administrative duties. Mark and his wife, Danita, have 3 children.

Dr. J. Clay Hays, Jackson, is immediate past president of the association. Geri Lee Weiland, MD, Vicksburg will succeed Dr. Horne as president in August 2021. n

Toothpaste Out of the Tube: COVID-19’s Ongoing Telemedicine Revolution

in the Renaissance, the polymath Nicolaus Copernicus (1473-1543) precipitated a scientific revolution by placing the sun at the universe’s center rather than the earth. Copernicus’s heliocentric “new normal” changed the ground rules of science by emphasizing physical laws and mathematical principles. His perceptive hypothesis displaced Aristotle’s ancient geocentric status quo, resulting in a radical paradigm shift. There was no going back to the old normal. The COVID-19 pandemic appears to be remodeling our own health system in a similarly revolutionary manner. The traditional clinical experience is dramatically changing with curbside consults, the redesign of waiting rooms, and the full embrace of virtual technology, from pre-paperwork to follow-up visits.

Backof the screen, most patients and physicians endorse telehealth as a valuable tool that is long overdue in the patient/physician relationship. Many physicians now perceive telehealth not only as an improvement in quality patient care, but also as an indispensable medical service worthy of appropriate payment. Patients perceive telemedicine as a pragmatic alternate way to access their established physician, often eliminating a long wait or difficult journey.

Lucius M. Lampton, MD Editor

Before COVID-19 arrived, most American physicians rarely utilized telemedicine in their clinical practices. The pandemic and its necessity for physical distancing forced the hands of Centers for Medicare & Medicaid Services (CMS), other insurers, and many practicing physicians to accomplish telehealth capability posthaste. Despite the initial awkwardness on both sides

Paying for and waiving longstanding restrictions on telehealth services have been declared a temporary COVID-19 emergency action. However, there seems little possibility that the old normal can or even should be recovered. Telemedicine is toothpaste out of the tube with little chance of anyone getting it back in. That ship has sailed, that cat is out of the bag, that genie can’t be placed back in the bottle. Telemedicine is now an essential component of medical practice and is a fait accompli. CMS and other insurers should continue to reimburse for telehealth with established patients as they have done during the pandemic, including audio-flexibility for patients and physicians in rural and underserved areas who may not have visual capabilities. Telehealth technology and virtual care should have a permanent place in our health system, especially within an established patient/physician relationship. n

Contact

JOURNAL EDITORIAL ADVISORY BOARD

ADDICTION MEDICINE

Scott L. Hambleton, MD

ALLERGY/IMMUNOLOGY

Richard D. deShazo, MD

Stephen B. LeBlanc, MD

Patricia H. Stewart, MD

ANESTHESIOLOGY

Douglas R. Bacon, MD

John W. Bethea, Jr., MD

CARDIOVASCULAR DISEASE

Thad F. Waites, MD

CHILD & ADOLESCENT PSYCHIATRY

John Elgin Wilkaitis, MD

CLINICAL NEUROPHYSIOLOGY

Alan R. Moore, MD

DERMATOLOGY

Robert T. Brodell, MD

Adam C. Byrd, MD

EMERGENCY MEDICINE

Philip Levin, MD

FAMILY MEDICINE

Tim J. Alford, MD

Diane K. Beebe, MD

Jennifer Bryan, MD

J. Edward Hill, MD

GASTROENTEROLOGY

James Q. Sones, MD

GENERAL SURGERY

Andrew C. Mallette, MD

HEMATOLOGY/ONCOLOGY

Carter Milner, MD

Kelly Wilkinson, MD

INFECTIOUS DISEASE

Rathel "Skip" Nolen, III, MD

INTERNAL MEDICINE

Richard D. deShazo, MD

Daniel P. Edney, MD

Daniel W. Jones, MD

Brett C. Lampton, MD

Kelly J. Wilkinson, MD

INTERNAL MEDICINE/EPIDEMIOLOGY

Thomas E. Dobbs, MD

MEDICAL STUDENT

John F. G. Bobo, M4

NEPHROLOGY

Harvey A. Gersh, MD

Sohail Abdul Salim, MD

NEUROLOGY

Mary Alissa Willis, MD

OBSTETRICS & GYNECOLOGY

Sidney W. Bondurant, MD

Sheila Bouldin, MD

Elizabeth A. Lutz, MD

Darden H. North, MD

ORTHOPEDIC SURGERY

Chris E. Wiggins, MD

OTOLARYNGOLOGY

Bradford J. Dye, III, MD

PEDIATRIC OTOLARYNGOLOGY

Jeffrey D. Carron, MD

PEDIATRICS

Michael Artigues, MD

— Lucius M. Lampton, MD, Editor

PLASTIC SURGERY

William C. Lineaweaver, MD, Chair

PSYCHIATRY

Beverly J. Bryant, MD

June A. Powell, MD

PUBLIC HEALTH

Mary Margaret Currier, MD, MPH

PULMONARY DISEASE

Sharon P. Douglas, MD

John R. Spurzem, MD

RADIOLOGY

Justin Lohmeier, MD

P. H. (Hal) Moore, Jr., MD

RESIDENT/FELLOW

Cesar Cardenas, MD

UROLOGY

Charles R. Pound, MD

VASCULAR SURGERY

Taimur Saleem, MD

Navigating COVID-19 Experimental Treatments: A Comprehensive Review of the Medical Literature

MARY JOYCE B. WINGLER, PHARMD; DAVID A. CRETELLA, PHARMD; AND JASON J. PARHAM, MD, MPH

INTRODUCTION

On March 11, 2020, the Mississippi State Department of Health (MSDH) reported the state’s first case of the novel coronavirus disease 2019 (COVID-19).1 Case and mortality numbers have steadily climbed; as of May 28, 2020, Mississippi has 14,372 confirmed cases and 693 deaths due to COVID-19.1 While there is much that remains unknown about COVID-19, providers caring for infected patients must navigate the available evolving evidence to make difficult management decisions. Early in the pandemic, the University of Mississippi Medical Center staff partnered with the Mississippi Critical Care Organization (MiCCO) to provide evidence-based recommendations for prescribers across the state. In this document, we outline the rationale for these recommendations along with our assessment of the evidence supporting pharmacologic therapies for COVID-19 treatment as of May 28, 2020 (Table 1). Our most up-to-date recommendations can be found at umc.edu/coronavirus/home.

Hydroxychloroquine and Chloroquine

Chloroquine and hydroxychloroquine are members of the 4-aminoquinoline class of antimalarial agents.2,3 In addition to being used for the prevention and treatment of malaria, they have both been used for the treatment of chronic autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus (SLE), due to their anti-inflammatory and immunomodulatory effects. This class of drugs has demonstrated in vitro activity against many viruses, including influenza, Epstein-Barr virus, Zika virus, Ebola virus, other outbreak-associated coronaviruses (severe acute respiratory syndrome coronavirus 1 [SARS-CoV-1] and Middle East respiratory syndrome coronavirus [MERS-CoV]), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).2,4,5 Following the confirmation that the 4-aminoquinline class had in vitro activity, many clinical trials were launched worldwide. Notably, neither chloroquine nor hydroxychloroquine have shown benefit in clinical trials for other viruses, including SARS-CoV-1 or MERS-CoV.2 In midFebruary, reports from a news briefing from China discussed the use of chloroquine phosphate in 100 patients, stating it had “demonstrated marked efficacy and acceptable safety in treating COVID-19

associated pneumonia in multicenter clinical trials in China.”6 To this day, no further data from this trial has been published confirming these claims. Since February, a number of randomized controlled trials and observational studies have been published either in peer-reviewed journals or on preprint servers.

The two hydroxychloroquine studies that have received the most attention are from Gautret and colleagues in France.7,8 The first of their studies compared a single-arm protocol (hydroxychloroquine ± azithromycin) with controls (untreated patients from another hospital and patients refusing to enter the protocol).7 The primary outcome was presence of virus at day six postinclusion. Thirty-six total patients were included (16 in the control arm and 20 patients in the hydroxychloroquine arm, with six receiving concomitant azithromycin). Microbiological eradication was higher in patients who received hydroxychloroquine (14/20, 70%) than the control group (2/16, 12.5%). In the six hydroxychloroquine + azithromycin patients, all had a negative viral load at day six; however, there were no clinical outcomes evaluated in this trial.7 The second study by this group was published a few weeks later.8 This single-arm cohort study evaluated hydroxychloroquine + azithromycin in 80 patients, including the six patients who received hydroxychloroquine + azithromycin from the initial trial. Of the 80 patients, 12 required oxygen therapy, six were transferred to the ICU, and one patient died. The viral cultures for most patients (97.5%) were negative by day five and only two patients were considered contagious. Length of stay in the infectious diseases ward was a mean of 4.6 days.8 Both studies have significant limitations, including small patient populations, inclusion of primarily low-risk patients, and no control group in the larger study.7,8 Notably, on April 3, 2020, the International Society of Antimicrobial Chemotherapy (ISAC) released an official statement about the initial Gautret article in response to critiques from multiple members of the medical community. The statement read: “The ISAC Board believes the article does not meet the Society’s expected standard…;”9 to date, the paper has not been formally retracted.

Two randomized controlled trials from China are currently published.10,11 Both were performed in small patient populations and had results that are difficult to interpret and apply to clinical practice.10,11 Multiple observational trials have been published as well, including

Table 1. Summary of Recommendations for Treatment of COVID-19

Drug or Drug Class Recommendations

Antiviral agents

HCQ/CQ with or without azithromycin

• Recommend use of hydroxychloroquine/chloroquine only in the context of clinical trials.

• If used outside of clinical trials, close monitoring for cardiac toxicities must be performed to ensure no adverse effects occur.

• Strongly recommend against the use of hydroxychloroquine plus azithromycin except in the context of clinical trials.

• Recommend against the use of hydroxychloroquine/chloroquine for prophylaxis except in the context of clinical trials.

• Recommend against the use of LPV/r and other HIV protease inhibitors except in the context of a clinical trial. Remdesivir

HIV protease inhibitors

• Recommend treatment of COVID-19 patients following the Emergency Use Authorization criteria

• Priority should be given to patients within 10 days of symptom onset and risk factors for progression to severe disease due to limited supply and efficacy data

Supportive agents

IL-6/IL-1 inhibitors (tocilizumab, sarilumab, siltuximab, anakinra)

COVID-19 convalescent plasma

Corticosteroids

• Recommend against the use of IL-6/IL-1 inhibitors except in the context of a clinical trial.

• Recommend against the use of COVID-19 convalescent plasma except in the context of a clinical trial.

• Consider a short course of corticosteroids in patients with ARDS.

• Insufficient evidence to recommend for or against corticosteroid treatment for COVID-19 in patients without ARDS.

COVID-19 = coronavirus disease 2019, CQ = chloroquine, HCQ = hydroxychloroquine, IL-6 = interleukin-6, IL-1 = interleukin-1.

several from the United States.12–16 Of the three large retrospective studies from the United States, two performed in New York found no difference in mortality among patients who received hydroxychloroquine or hydroxychloroquine + azithromycin, and one performed in Veterans Administration (VA) patients found the risk of death was significantly higher in patients receiving hydroxychloroquine, even when controlling for increased baseline risk.13–15 It is unclear if hydroxychloroquine contributed to higher mortality rates in the VA study, though there was clearly no signal of treatment benefits.13 On May 22, a retrospective analysis of a large, multinational registry compromised of patients from 671 hospitals on six continents was used to evaluate the treatment effects of hydroxychloroquine, chloroquine, or either agent combined with azithromycin.16 This registry included over 96,000 patients hospitalized with COVID-19 infection. After controlling for confounders, treatment with any of these agents was associated with an increased rate of new ventricular arrhythmia and increased in-hospital mortality.16 There are limitations to the ability to control for confounding in a retrospective analysis, but the data paints a troubling picture about the risks of these agents. Based on the evidence from the Lancet article, the World Health Organization (WHO) temporarily suspended the hydroxychloroquine arm of the SOLIDARITY study to review the safety data.17 Controversy regarding the methods and validity of this study’s data have emerged, prompting both the Lancet and the New England Journal of Medicine to publish “Expression of Concerns.” An independent audit is being

conducted on the data from this trial. The results of this investigation along with ongoing randomized controlled trials will help identify both the risks and benefits of hydroxychloroquine.

The primary safety concerns for chloroquine and hydroxychloroquine are cardiac toxicities, including increased risk of ventricular tachycardia and torsades de pointes. These concerns were highlighted in three recent studies.18–20 The CloroCovid-19 study, based in Brazil, comparing high-dose and low-dose chloroquine had to be halted early due to higher rates of death in the high-dose group.18 More patients in the high-dose group had a QTc interval >500 milliseconds during the trial and two patients in the high-dose group experienced ventricular tachycardia before death. It should be noted that all patients were receiving azithromycin and oseltamivir, both of which can contribute to increasing the QTc interval.18 Two retrospective cohort studies have reported safety data for hydroxychloroquine.19,20 Both observed an increased risk of QTc prolongation with hydroxychloroquine monotherapy (4%–19%) and combination therapy with hydroxychloroquine and azithromycin (21%–36%).19,20 In both trials, multiple patients (11%–43%) discontinued hydroxychloroquine early due to QTc prolongation, and one patient with a QTc of 499 milliseconds developed torsades de pointes. Many patients were receiving other agents that could cause QTc prolongation (50%–53%) which may have contributed to these findings.19,20

Based on the limited data released from China and France from February to early March, many international, national, and local guidelines included chloroquine or hydroxychloroquine as first-line treatment options for hospitalized COVID-19 patients. However, as new data has emerged regarding the safety risks and questioning the early signals of efficacy, there has been a shift in perspective of how to approach the use of these agents in COVID-19. Over 200 clinical trials evaluating chloroquine and hydroxychloroquine for the treatment of COVID-19 have launched worldwide. With the current available data, national guidelines state there is insufficient evidence to support hydroxychloroquine/chloroquine or recommend only using these medications in the context of a clinical trial.21–23 The Infectious Diseases Society of America (IDSA) and the National Institutes of Health (NIH) guidelines recommend against the use of the combination of hydroxychloroquine plus azithromycin outside of clinical trials due to the risk of toxicities and the uncertainty of benefit.21,22

Lopinavir/Ritonavir and Other HIV Protease Inhibitors

HIV protease inhibitors, including lopinavir/ritonavir (LPV/r; Kaletra), act on the enzyme HIV protease and block maturation of the HIV virus. LPV/r has previously demonstrated in vitro activity against SARS-CoV-1 and MERS-CoV and has recently been proven to have in vitro activity against SARS-CoV-2.24,25 Clinical data is limited for previous coronavirus outbreaks and the current COVID-19 pandemic.

Cao and colleagues conducted a randomized, controlled, open-label trial comparing LPV/r to standard of care at a hospital in Wuhan, China.26 The primary endpoint was time to clinical improvement. One hundred and ninety-nine patients were included, and no difference was found in time to clinical improvement, mortality at 28 days, or viral clearance between groups. Other small studies evaluating LPV/r for COVID-19 have also failed to show benefit.27,28

There are several concerns with using HIV protease inhibitors for COVID-19, including serious adverse effects and drug-drug interactions. Focusing on LPV/r, the most common adverse effect is gastrointestinal upset, which occurs in up to 50% of patients; more concerning for COVID-19 patients is the risk of hepatitis.29 Hepatitis occurs in 2%–10% of patients taking LPV/r, and early clinical data for COVID-19 has described a high rate of patients presenting with elevated transaminases (20%–30%).30 Many patients in the clinical trial by Cao and colleagues experienced adverse effects in the LPV/r arm (48%), leading 13 patients (13.8%) to stop the therapy early.26 HIV protease inhibitors such as LPV/r interfere with CYP3A4 mediated drug metabolism, leading to many significant drug interactions.29 Finally, the use of these agents in patients with an unknown HIV status is of concern, as initiation in a patient with untreated HIV infection may promote resistance development.

Currently data does not support the use of these agents for COVID-19. IDSA and NIH only recommend LPV/r in the context of a clinical trial, and the Surviving Sepsis Campaign (SSC) guidelines recommend against the use of LPV/r in critically ill patients.21–23

Remdesivir

Originally designed for the treatment of Ebola virus, remdesivir demonstrates in vitro activity against a wide array of viruses including SARS-CoV-2.4,25 Remdesivir is a directly acting antiviral agent that interferes with viral RNA-dependent RNA polymerase causing termination of transcription.31 The parent drug has a half-life near one hour, but its active metabolite half-life is 20.4 to 25.3 hours, allowing for once daily dosing. Warnings currently associated with remdesivir include its risk for causing transaminase elevations and additional toxicity in patients with renal insufficiency due to accumulation of the formulation excipient sulfobutylether-β-cyclodextrin.31

Clinical data regarding the use of remdesivir for COVID-19 remains limited. To date only one comparative clinical trial has been fully published.32 This randomized, double-blinded, placebo-controlled trial performed at 10 hospitals in Wuhan province, China, included 236 patients, 158 of whom received 10 days of remdesivir treatment. The median age was 65 (interquartile range [IQR] 56–71), 38 (15%) were receiving high-flow nasal cannula or mechanical ventilation at initiation, and 167 (70.7%) had medical comorbidities. There was no difference in 28-day mortality (14% vs 13%) or time to clinical improvement (21 days vs 23 days). In patients enrolled within 10 days of onset, remdesivir showed a nonsignificant trend toward a faster time to clinical improvement [18 vs 23 days (hazard ratio, 1.52; 95% CI, 0.95–2.43)].

Other published data includes the case series of 53 patients who received remdesivir through Gilead’s compassionate use program.33 The median age of participants was 64 (IQR 48–71), 34 (64%) patients were mechanically ventilated at initiation, and 36 (68%) had medical comorbidities. Overall, 36/53 (67.9%) patients experienced either improvement or discharge, and 8/53 (15.1%) worsened. Seven patients died (median age 74.5), and 32 (60%) patients experienced an adverse event, most commonly transaminitis (12, 23%) or renal impairment (7, 14%). Notably, the median time from symptom onset to remdesivir initiation was 12 days.

Preliminary data for two major remdesivir studies were released before full publication.34,35 In the first release from the National Institute of Allergy and Infectious Diseases (NIAID) adaptive trial comparing remdesivir to placebo, remdesivir treatment led to significantly reduced time to clinical recovery (11 days vs 15 days) and numerically lower morality (7.1% vs 11.9%).34 The second early release from the SIMPLE trial showed that in patients without mechanical ventilation at treatment initiation, there was no difference between five and 10 days of remdesivir treatment.35 Full results of both trials were published in late May, confirming the top line numbers, but offering interesting, deeper findings.36,37 Both trials were amended to evaluate patients on a seven-point ordinal scale, stratifying patients based on respiratory support and hospitalization. Full results from the NIAID confirmed remdesivir’s positive effect, but the efficacy of treatment differed dramatically depending on the level of baseline hypoxia.36 Hospitalized patients on no oxygen support or nasal cannula derived the greatest treatment benefit (ratio of recovery 1.38 and 1.47,

respectively), while patients on mechanical ventilation at randomization saw no benefit (ratio of recovery 0.95). There was no difference observed between patients enrolled less than or more than 10 days from symptom onset, though the interquartile range for time to symptom onset was seven to 12 days.36 The initial publication of data from the SIMPLE trial again confirmed the headline supporting five-day treatment courses.37 Clinical improvement was noted in 65% of patients in the five-day arm and 54% in the 10-day arm, which was not significantly different after adjustment for baseline clinical status. Among all patients, the rate of hospital discharge was higher in patients that enrolled within 10 days of symptom onset (62% vs 49%). Among patients receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at day five, 14-day mortality was higher in the five-day treatment group compared to the 10-day group (40% vs 17%), though the number of patients meeting this criteria was small (25 and 41, respectively). No similar signal was observed for patients on any other level of oxygen support.37 This trial has been extended with plans to enroll 5600 patients, including those on mechanical ventilation, to perform a more robust evaluation of optimal treatment duration.

Based upon these data, the Food and Drug Administration (FDA) granted emergency use authorization for remdesivir to treat COVID-19 on May 1.38 During the following week, Health and Human Services (HHS) began distribution of a donated supply to affected health systems and then to state departments of health. As of this publication, the only way to obtain remdesivir is through these federal emergency use distributions or directly from Gilead through its expanded access program or compassionate use requests. Use as part of the expanded access program required that the patient be mechanically ventilated at therapy initiation, while remdesivir obtained through the emergency use authorization can be given to most patients with documented hypoxia. Gilead has announced that the expanded access program is ending on May 29, transitioning all supply to emergency use. At this time, it is unclear when and if remdesivir will be obtainable outside of emergency use distributions. Use of Remdesivir is contraindicated in patients with elevated transaminases.

Taken in total, remdesivir is one of the most promising agents being evaluated for treatment of COVID-19. It is poised to become the preferred treatment option with the potential to reduce healthcare resource utilization through decreases in length of stay. Complete publication of trial data will help put these early results into perspective and identify patients that will benefit most from treatment. Further data and monitoring are also needed to identify less common adverse events and safety in special populations. With two separate signals of benefit linked to treatment within 10 days of symptom onset, every effort should be made to prioritize remdesivir treatment for patients early in their disease course.36,37 The optimal treatment duration is also unclear, but it appears that most patients can be treated with five days of therapy, and with 10-day courses considered for patients on mechanical ventilation or ECMO. Unfortunately, at this time it appears the current supply of remdesivir is inadequate to treat all patients hospitalized with COVID-19 infection. Health systems and state departments of health must work together to devise equitable and transparent allocation decisions and administration guidance.

IL-6 Inhibitors and Cytokine Release Syndrome

Early reports of COVID-19–related mortality highlighted a subset of patients that experienced exaggerated immune response in the setting of critical illness.39–42 Various names have been given to this syndrome, including hyperinflammatory syndrome (HIS), cytokine release syndrome (CRS), and secondary hemophagocytic lymphohistiocytosis (sHLH). They all describe a similar phenotype in which patients exhibit rapidly progressing respiratory failure accompanied by hypercoagulability and elevated inflammatory markers. Identified abnormal laboratory values include ferritin, transaminases, triglycerides, lactate dehydrogenase (LDH), D-dimer, interleukin-6 (IL-6), and fibrinogen.39,40,42–44 Based upon these observations, inhibition of upstream inflammatory mediators, like IL-6 or IL-1, has been theorized to prevent or attenuate severe COVID-19–related inflammation. Consequently, there is concern that this inhibition may lead to increased susceptibility to secondary infections.

Tocilizumab is a monoclonal antibody that inhibits IL-6 and thus far has received the most attention and research in the treatment of COVID-19 CRS because of its efficacy for treating chimeric antigen receptor (CAR) T-Cell induced CRS.40,41 It has been evaluated as either a single dose of 400 mg or an 8 mg/kg dose capped at 800 mg. Published studies are uniformly single-center, nonblinded, nonrandomized, retrospective evaluations, severely limiting interpretation.

There are three studies currently published outlining tocilizumab and evaluating 21, 20, and 15 patients, respectively, that received tocilizumab.45–47 All studies documented improvements in inflammatory markers (most often CRP), as well as a positive rate of clinical improvement, and concluding treatment benefit. The lack of control group comparison as well as heterogeneous groups and severity definitions make it impossible to evaluate the net effect of treatment. It is unclear if there is any clinical benefit associated with the documented reductions in inflammatory markers.

Three articles now submitted for peer review create a more complicated picture. The first by Ramaswamy and colleagues is a case-control study in which 21 patients that received tocilizumab were compared to 65 patients that did not.48 Patients that received tocilizumab had a 75% reduction in risk of inpatient death. A treatment effects model confirmed survival benefit, estimating it to be nearly 50%. Alternatively, an evaluation of 11 patients published by Rimland et al. found no pattern of clinical improvement after treatment with tocilizumab despite significant reductions in IL-6.49 Kimmig et al. reported evidence from a retrospective review of 60 COVID-19 inpatients, of which 28 received tocilizumab.50 Patients that received tocilizumab had a higher rate of secondary bacterial and fungal infection (64.3% vs 31% and 7.1% vs 0%, respectively).

Other agents targeting the inflammatory cascade associated with severe COVID-19 infection include sarilumab, siltuximab (IL-6), and anakinra (IL-1). A number of well-designed clinical trials of tocilizumab and other anti-inflammatory therapies are ongoing, including both severe patients with evidence of CRS and broader patients with critical COVID-19 illness. At present, their lack of clear benefit and risk of

side effects should discourage their mainstream use, which aligns with current guideline recommendations (NIH, IDSA, SSC).21–23

Convalescent Plasma

Like many other experimental COVID-19 treatments, interest in convalescent plasma (CP) stems from prior use in other viral illnesses, including the 1918 pandemic flu, SARS-CoV 1, MERS-CoV, and Ebola.51 Plasma obtained from patients soon after recovery from infection has been found to contain a high concentration of neutralizing antibodies.51,52 In theory, administration of these antibodies to an acutely infected patient would boost immune response.51,52

The practice of collecting and administering CP has been around for more than a century, but its efficacy remains unproven. No randomized controlled trials (RCTs) have been published for the previous pandemic outbreaks, and convalescent plasma is often used in situations where no other treatment has been successful.51 One RCT is available for patients with severe seasonal influenza, showing no benefit over nonimmune plasma.53 A meta-analysis of CP for patients with SARS and severe influenza showed a significant reduction in mortality compared with placebo or no treatment; however, authors noted the studies included were not high quality studies and had a moderate or high risk of bias and additional studies were needed.54

Currently, there are a few small published studies reporting the use of CP for COVID-19.55–60 The total number of patients with reported outcomes following receipt of CP is less than 30. None of these studies had a control group, and all had multiple confounders, including the concomitant use of antiviral agents and other experimental therapies. Most patients also received CP relatively late in their clinical course, which may reduce efficacy.56–60 These studies do provide some limited safety data for the use of CP. No patients reported serious adverse events across the available studies, which must still be interpreted with caution due to the small number of patients. Other theoretical risks of CP exist, including transfusion-related acute lung injury (TRALI), allergic reactions, or thrombotic complications, and patients should be carefully monitored following CP infusion.22,61

In addition to lacking robust data for the safety and efficacy of CP, there are also the issues of obtaining CP. The FDA has provided guidance on the ways to access CP for the treatment of COVID-19: 1) clinical trials, 2) expanded access, or 3) a single patient emergency investigational new drug application (eIND).52 Each of these pathways are described in detail in the FDA’s document “Investigational COVID-19 Convalescent Plasma: Guidance for Industry,” and each institution would need to determine which pathway may work best for them based on availability and resources. Donor and recipient eligibility criteria for the eINDs are also available in the FDA document. As of May 28, 2020, the National Expanded Access Treatment Protocol has enrolled over 17,000 patients to receive CP (https://www.uscovidplasma.org/), and multiple clinical trials are currently active in the United States and other countries.

In the absence of clinical trial data, recommendations from national guidelines are similar to many of the other COVID-19 treatment

options stating there is either insufficient evidence or that CP should only be utilized in the context of a clinical trial (IDSA, NIH).21,22 The SSC guidelines recommend against the routine use of CP in critically ill patients at this time.23 Information regarding access to CP, both nationally and locally, will likely change rapidly and prescribers are encouraged to visit the FDA’s site for the most up-to-date information about CP (https://www.fda.gov/vaccines-blood-biologics/investi gational-new-drug-ind-or-device-exemption-ide-process-cber/ recommendations-investigational-covid-19-convalescent-plasma).

Corticosteroids

Corticosteroids have been evaluated as adjunctive agents for multiple viral pneumonias, including SARS-CoV-1, MERS, and influenza, as well as many other infections.62 For other viral illnesses, corticosteroids have not been proven to improve clinical outcomes, and some studies have shown harm, including increased risk of mortality and secondary bacterial infection, delayed viral clearance, and increased incidence of serious adverse events.62,63 On the other hand, COVID-19 infection appears to be associated with a high risk of developing acute respiratory distress syndrome (ARDS) and cytokine storm, where corticosteroids may provide unique benefit.39

Two studies evaluating the use of corticosteroids for COVID-19 have been published.30,64 Wu and colleagues evaluated risk factors associated with ARDS and observed a decreased risk of death (46% vs 62%) in COVID-19 patients with ARDS treated with methylprednisolone at any point in their hospital stay (hazard radio, 0.38; 95% CI, 0.20–0.72; P = .003).30 Fadel and colleagues performed a pretest/posttest quasi-experiment in Detroit, Michigan, evaluating early intravenous methylprednisolone administration (0.5-1 mg/kg/day in two divided doses for three days).64 The results showed a significantly lower rate in the primary composite endpoint (death, respiratory failure requiring mechanical ventilation, and escalation to ICU care) in patients receiving early corticosteroids (54.3% vs 34.9%; P = .005). Steroids use was over 50% in both groups [56.8% in the standard of care (SOC) group and 68.2% in the early corticosteroid group], but was given closer to the time of admission in the intervention group (median of two days vs five days for SOC). Several clinical trials are ongoing in patients with COVID-19 pneumonia and/or ARDS. Until these studies are published, the benefits and risks must be weighed in each patient.

Guidelines do not provide strong recommendations regarding the use of corticosteroids, but most do recommend against their use in noncritically ill patients (IDSA, NIH).21,22 For patients who are mechanically ventilated with ARDS, the SSC guidelines suggest using steroids (weak recommendation).23 Based on current evidence, it is reasonable to consider a short course of corticosteroids in patients with COVID who develop ARDS, and earlier administration may be more beneficial.

Miscellaneous Medications

There are multiple additional therapies under investigation for the treatment of COVID-19 outside of those discussed above. Some

therapies are not available in the United States and will not be reviewed in this article, including favipiravir (Avigan, Favilavir) and umifenovir (Arbidol). Other agents, including both over-the-counter (OTC) and prescription medications, are listed in Table 2 below with guidance for their use in COVID-19. While some of these therapies do not have a high incidence of adverse effects, there is also no proven benefit, and several are either on shortage or allocation.65,66 Overall, we recommend against the use of each of these options for the treatment of COVID-19 outside of clinical trials until further supportive clinical data is available. There is currently no evidence to support discontinuation in patients diagnosed with COVID-19 who are on these medications for chronic diseases or who have other indications for acute use.

DISCUSSION AND CONCLUSION

The COVID-19 pandemic has created a crisis of confidence for clinicians. They are left with the arduous task of trying to practice

evidence-based medicine when much of the available evidence has been of questionable quality, and treatment recommendations are changing at a rapid pace. Multiple articles about COVID-19 are published daily, and local and national guideline recommendations change each week. History with previous viral outbreaks, including SARS-CoV-1 and MERS-CoV, has taught us to be wary of early trends and anecdotal data as many medications with in vitro activity failed to provide benefit in clinical trials. While many experimental COVID-19 treatments have no evidence of efficacy, the evidence for their toxicity is clear. Side effects, such as QTc prolongation with hydroxychloroquine or increased risk of secondary infections with any of the immune modulators, must be considered in each treatment decision.

We sympathize with COVID-19 infected patients who struggle through the course of their disease without effective treatment available, other than supportive care. We also understand that providers are anxious to offer treatments that may be beneficial, particularly in

• Recommend against the use of IVIG except in the context of a clinical trial. Yes

Janus kinase inhibitors (JAK, baricitinib, ruxolitinib)

ACEi/ARBs

HMG-CoA reductase inhibitors (statins)

Histamine receptor antagonists (famotidine, cimetidine)

Ascorbic acid (vitamin C)

Zinc

Nonsteroidal antiinflammatory drugs (NSAIDs)

• Recommend against the use of JAK inhibitors except in the context of a clinical trial. No

• NIH guidelines note concerns for broad immunosuppressive effects with JAK inhibitors.

• Recommend against using ACEi/ARB for the treatment of COVID-19. No

• Continue ACEi/ARB for patients with cardiovascular disease.

• Recommend against the use of statins except in the context of a clinical trial. No

• Continue therapy in patients receiving statins for the treatment or prevention of cardiovascular disease.

• Recommend against the use of famotidine except in the context of a clinical trial. Yes, IV and oral

• Continue therapy in patients receiving famotidine for appropriate indications, such as GERD or acid reflux.

• Do not use cimetidine due to adverse events and drug interactions (CYP enzyme inhibitor).

• Recommend against the use of ascorbic acid except in the context of a clinical trial. Not posted on FDA or ASHP; check with local suppliers; some products reportedly on shortage or allocation

• Recommend against the use of zinc except in the context of a clinical trial. Not posted on FDA or ASHP; check with local suppliers; some products reportedly on shortage or allocation

• Continue NSAIDS in patients taking for co-morbid conditions. No

• No clinical data to suggest increased risk of COVID-19 in patients on NSAIDs.

• Concern raised by the media due to mechanism of action, but FDA currently advises patients can continue using NSAIDs as directed.

COVID-19 = coronavirus disease 2019, IVIG = intravenous immune globulin, ACEi = angiontensive converting enzyme inhibitor, ARB = angiotensin receptor blocker.

Table 2. Summary of Other Potential Medications

the setting of severe disease. However, this is a crucial time to recall our commitment to “do no harm” and cautiously weigh the potential risks and benefits of unproven treatments.

Our mandate to “do no harm” not only applies to the patients that we are treating for COVID-19, but also to the patients chronically on these medications for other indications. COVID-19 comes amid the normal daily struggles of practicing medicine, as exemplified by ongoing drug shortages. As was seen with hydroxychloroquine, limited in vitro data and an anecdotal news briefing from China led to the drug making it into clinical guidelines across the globe in early March. In mid-March, a study including only 26 patients supporting the efficacy of hydroxychloroquine and azithromycin was published, and within weeks, hydroxychloroquine was on shortage across the nation. Uninfected patients on these medications chronically, where the risk and benefits of therapy have already been evaluated, have been left with uncertainty while countless patients were prescribed these medications without even confirmation of infection. This cycle has repeated with famotidine, now on critical shortage after the initiation of a clinical trial in New York and a shortage of another drug in its class.

There is hope on the horizon. Hundreds of clinical trials are being conducted right now, including in sites here in Mississippi. Larger, more robust trials of hydroxychloroquine, including ORCHID, are on the verge of completion. The early data for remdesivir was generated in well-designed studies and appears to be promising, but the magnitude of its effect was modest, further underscoring that we need to learn more about COVID-19 treatment. We may be entering a new phase in this pandemic with treatment options that offer clear benefit, but we are not there yet. To date, little is known about what we can do for critically ill patients beyond supportive care.

Physicians are the anchor of our healthcare system. In our best moments, we demonstrate an allegiance to evidence-based practice and dogged determination that centers not only on the patient in front of us but also on the community at large. Each provider decision can have an impact beyond the individual circumstance and patient, and can echo throughout our community. We encourage the Mississippi medical community to avoid the allure of recommending unproven and untested therapies, outside of extreme circumstances or within clinical trials, and to share in our goal to do no harm.

Acknowledgments

Conflict of Interest Disclosures: The authors have nothing to disclose.

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Author Information

Department of Antimicrobial Stewardship (Wingler, Cretella, Parham); Department of Medicine-Infectious Diseases (Cretella, Parham), University of Mississippi Medical Center, Jackson.

Corresponding Author: Jason J. Parham, MD, University of Mississippi Medical Center, Department of Pharmacy Practice, 2500 North State Street, Jackson, Mississippi 39216. Ph: (601) 984-5560. Fax: (601) 984-5565. ( Jparham@umc.edu).

Newborn screening for Severe Combined Immunodeficiency with TREC assay in Mississippi 2012–2018

JESSICA B. PERKINS, MD, AND ANNE B. YATES, MD

Abstract

The incidence of Severe Combined Immunodeficiency (SCID) is reported at 1 in 58,000 live births in the US.1 With the advent of newborn screening (NBS), the incidence of SCID is known to be more common than previously reported. In Mississippi, the incidence of SCID is increased compared to the national average at about 1:37,000. This epidemiologic survey will discuss the abnormal screening results for the state of Mississippi during the years 2012–2018, as well as give a brief overview of the pathophysiology of SCID and its treatment. Newborn screening is an essential tool for the early detection of SCID.

Introduction

Severe Combined Immunodeficiency (SCID) is a life-threatening disorder caused by genetic defects in T and B cell function. The most common defects are mutations in IL2RG (common cytokine receptor gamma chain gene), JAK3 (Janus kinase 3 gene), IL7RA (interleukin-7 receptor alpha gene), RAG1 and RAG2 (recombination-activating genes 1 and 2), DCLRE1C (DNA cross-link repair protein 1C gene or Artemis), and ADA (adenosine deaminase gene).2 The classic symptoms of SCID are recurrent severe viral, fungal, and bacterial infections, chronic diarrhea and failure to thrive, and absence of palpable lymph nodes. The only cure for SCID is hematopoietic stem cell transplantation, which is most successful if implemented prior to 3.5 months of age.3 Thus, early detection is critical.

Methods

The state of Mississippi began newborn screening in January 2012. Dried blood from the heel stick of an infant is placed on a Guthrie card, and T-cell receptor excision circles (TRECs) are measured by real-time polymerase chain reaction (PCR). This PCR testing is run by Perkin Elmer Lab in Waltham, MA. TRECs are formed from excised DNA during the cutting and splicing of T cell antigen receptor genes in the thymus2 (see Figure 1). One can infer that if the TREC count is low, T cell numbers are low as well. There is a 100% sensitivity and 99.9% specificity for a TREC count of <30 copies per microliter.4 If an infant’s

TREC count is discovered to be <25 copies per microliter, the patient’s SCID screen will result as a presumptive positive result. SCID, other primary immunodeficiencies resulting in severe lymphopenia, and prematurity can cause a presumptive positive SCID screen, so further testing is needed for confirmation of diagnosis. Generally speaking, SCID is diagnosed when an absent or very low number of T cells (<300 microL) are present, no or very low T cell function (<10% of lower limit of normal) is discovered, or maternal T cell engraftment is present.5 6

Results

These are the results of the abnormal newborn screen for SCID from 2012–2018 (see Table 1). Those infants who were diagnosed with SCID were done so based on the diagnostic criteria for SCID (see Table 2). Those infants who had a presumptive positive result, however, were found not to have SCID and did not meet the diagnostic criteria. They may have shown severe T cell deficiency due to their underlying

Figure 1. TREC Formation in the Thymus

Table 1. Abnormal Screening Results for the State of Mississippi During the Years 2012–2018

at autopsy (no lymph nodes or thymus). Had inconclusive SCID screen at 5-days-old.

1 - 22q11 deletion

1 - Congenital neutropenia with lymphopenia

2 - Non-SCID T cell lymphopenia (with congenital heart disease) Caucasian, urban.

X-linked SCID. Caucasian, urban.

condition, however, they did not show the severe lymphopenia and very low T cell function required for SCID diagnosis.

In 2012, 37,658 patients were screened, and four infants had presumptive positive screens. Two infants were diagnosed with non-SCID T-cell lymphopenia, one had congenital neutropenia with lymphopenia, and one had DiGeorge Syndrome. There was one SCID variant that had an inconclusive SCID screen at five days old, with hypoplastic lung, respiratory failure, and cardiac and renal failure; SCID was diagnosed at autopsy.

In 2013, 37,525 infants were screened, and seven infants had presumptive positives screens. One infant had false positive due to extracorporeal membrane oxygenation (ECMO), one infant was premature with transient severe lymphopenia, one infant had Heterotaxy syndrome, one infant had Goldenhar syndrome, two infants had DiGeorge syndrome, and one infant had X-linked SCID.

1 - Goldenhar syndrome

1 - Heterotaxy syndrome

1 - Transient

1 - False

In 2014, 37,829 infants were screened, and seven infants had presumptive screens. One infant had FOXN1 mutation with severe lymphopenia and normal mitogens, four infants had DiGeorge Syndrome, and two infants had SCID with unknown genotype (female fraternal twins).

In 2015, 37,426 infants were screened with three presumptive positive SCID screens. One infant had transient severe T cell lymphopenia and neutropenia. One infant had persistent T cell lymphopenia with a congenital heart defect. Another had birth asphyxia with a hypoxicischemic brain injury and transiently low CD8 and CD19 cells. No infant had SCID.

In 2016, 36,993 infants were screened with six presumptive positive SCID screens. One infant was diagnosed with leaky SCID, who was a sibling to the twins with SCID born in 2014. One had birth asphyxia with hypoxic-ischemic brain injury and died before the SCID screen

Table 2. SCID Definitions5

A. Typical SCID

SCID definitions

1. Absence or very low number of T cells (< 300 microL), and no or very low T cell function (< 10% of lower limit of normal) or

2. Maternal T cell engraftment

B. SCID variant - leaky SCID

1. Reduced number of CD3 T cells for age: 0 to 2 yr, < 1000/mL for > 2 up to 4 yr, < 800/mL for > 4 yr, < 600/mL

2. Absence of maternal engraftment

3. < 30% of lower limit of normal T-cell function (as measured by response to PHA)

C. Omenn syndrome

1. Generalized skin rash

2. Absence of maternal engraftment

3. Detectable CD3 T cells, > 300/mL

4. Absent or low (< 30% of normal) T-cell proliferation to antigens to which the patient has been exposed

5. If the proliferation to antigen was not performed but at least 4 of the following 10 supportive criteria, at least 1 of which must be among those marked with an asterisk (*) below, were present, the patient was eligible:

Hepatomegaly

Splenomegaly

Lymphadenopathy

Increased IgE level

Increased absolute eosinophil count

*Oligoclonal T cells measured by CDR3 length or flow cytometry

* > 80% of CD31 or CD41 T cells are CD45RO1

*Proliferation to PHA is reduced < 30% of lower limit of normal

*Proliferative response in mixed leukocyte reaction is reduced < 30% of lower limit of normal

*Mutation in SCID-causing gene

D. Reticular dysgenesis

1. Absence or very low number of T cells (CD3 T cells < 300/mL)

2. No or very low (< 10% of lower limit of normal) T-cell function (as measured by response to PHA)

3. Severe neutropenia (absolute neutrophil count < 200/mL)

4. Sensorineural deafness and/or absence of granulopoiesis at bone marrow examination and/or a deleterious AK2 mutation

could be repeated. One had Heterotaxy syndrome. One had severe lymphopenia with a congenital heart defect. One had 22q11 deletion.

In 2017, 36,433 infants were screened with six presumptive positive SCID screens. Two infants were diagnosed with SCID, one with leaky SCID (two heterogenous RAG1 mutations), and one with typical SCID from JAK3 defect. One infant had DiGeorge syndrome, two infants had T cell lymphopenia, and one infant had Turner syndrome with lymphopenia.

In 2018, 35,841 infants were screened, with three presumptive positive SCID screens. No infants were diagnosed with SCID during this year. One had DiGeorge syndrome. Two infants had normal immune evaluations.

Discussion

We have observed the incidence of SCID to be higher in the state of Mississippi in comparison to the national average in the US (1:58,000 live births).1 Consanguinity is a risk factor for several genetic disorders, including SCID. There have been reports of increased SCID incidence in areas where consanguinity is more common.7,8 Although the literature supports higher SCID incidences when consanguinity is present; we note that consanguinity was not discovered in any of the positive SCID cases we reported. Observing the demographic data from the seven infants with SCID from 2012 to 2018, we noted three infants were born in rural areas, and four infants were born in urban areas of Mississippi. Additionally, six infants were Caucasian, one infant was Vietnamese, and no infants were African American. We are unable to correlate race and birth location to incidence increase; however, it is interesting to note these characteristics in our SCID infants. It is also noted that three positive SCID infants came from one family, which increased our incidence as well.

Conclusion

Newborn screening is an essential tool in the early diagnosis of SCID. The two-year survival rate of SCID patients receiving stem cell transplantation before three months old is 90%.9 Without intervention, SCID is fatal, usually in the first one-two years of life. Also, as demonstrated in some of our data, newborn screening is also helpful in diagnosing other primary immunodeficiencies that result in severe lymphopenia besides SCID. This information can help counsel families and help prevent infections by delaying daycare enrollment, avoidance of sick contacts, and starting prophylactic antibiotics if indicated.

With early detection through newborn screening, we are finding that SCID is more common than once thought. Early detection is critical in the diagnosis and treatment of such a time-sensitive and potentially fatal disease.

Acknowledgments

Conflict of Interest Disclosures: The authors have nothing to disclose.

References

1. Kwan A , Abraham RS, Currier R , et al Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States JAMA. 2014; 312:729

2. Puck JM Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: The winner is T-cell receptor excision circles J Allergy Clin Immunol 2012;129(3):607-616.

3. Buckley RH Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes Immunol Res. 2011;49:25-43.

4. Kelly BT, Tam JS, Verbsky JW. Screening for severe combined immunodeficiency in neonates Clin Epidemiol. 2013;5:363-369.

5. Shearer WT, Dunn E, Notarangelo LD, et al Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the primary immune deficiency treatment consortium experience J Allergy Clin Immunol 2014;133:1092-1098

6. Picard C, Al-Herz W, Bousfiha A , et al Primary immunodeficiency diseases: An update on the classification from the International Union of Immunological

Societies Expert Committee for Primary Immunodeficiency 2015 J Clin Immunol 2015;35:696-726.

7. Suliaman F, Al-Ghonaium A , Harfi H High incidence of severe combined immune deficiency in the Eastern Province of Saudi Arabia Pediatr Asthma Allergy Immunol. 2006;19:14-18.

8. Al-Herz W, Al-Mousa H. Combined immunodeficiency: The Middle East experience J Allergy Clin Immunol. 2013;131:658-660.

9. Heimall J, Logan BR , Cowan MJ, et al Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: A PIDTC natural history study Blood. 2017;130(25):2718-2727.

Author Information

Department of Pediatrics, University of Mississippi Medical Center (Perkins, Yates).

Corresponding Author: Jessica Perkins, MD, 2500 North State Street, Jackson, MS, 39216. Ph: (601) 984-5249. Fax: (601) 984-2608. ( jperkins@umc.edu).

Establishment of the Mississippi Pediatric Clinical Trials Center (MPCTC): Opportunities to Improve Children’s Health

WHITNEY HERRING, MD, MPH; MOBOLAJI FAMUYIDE, MD; JOSEPH MARK MAJURE, MD; CONNIE BAIRD-THOMAS, PHD; KRISTEN CALLAHAN, BS; DANA LINDSAY, BBA, RN; CHAD BLACKSHEAR, MS; LACY MALLOCH, BS; FREDERICK BARR, MD, MSCI; AND ROBERT ANNETT, PHD

Abstract

The Mississippi Pediatric Clinical Trials Center (M-PCTC) was funded as part of the NIH’s Environmental Influences on Child Health Outcomes (ECHO) program to increase institutional capacity to conduct pediatric clinical trials that improve health outcomes of children with high priority health conditions. The M-PCTC will engage in pediatric clinical trials, develop pediatric clinical researchers, and improve institutional infrastructure for clinical research. Background for this NIH initiative, pediatric health conditions of interest, child health problems in Mississippi, and plans for statewide collaborations are all described. Mississippi has an opportunity to improve the understanding of the impact and modifiers of pediatric health conditions, particularly those impacting rural and medically underserved communities. The leadership provided by the University of Mississippi Medical Center (UMMC) will increase research capabilities and provide information to Mississippi’s healthcare providers and communities that can improve the health of children and families.

Keywords: Child health, clinical trials, public health, National Institutes of Health

Introduction

The Environmental Influences on Child Health Outcomes (ECHO) program was developed by the National Institutes of Health (NIH) to understand environmental exposures and their effects on the health and development of children. This program is structured to utilize existing research cohort populations that focus on 5 pediatric outcomes with high public health impacts. These domains include pre-, peri-, and postnatal outcomes; upper and lower airway; obesity, neurodevelopmental outcomes, and factors that promote child health. Co-existing with ECHO, the IDeA States Pediatric Clinical Trials Network (ISPCTN) was created to facilitate access and participation of rural and underserved children in clinical trials by utilizing infrastructure at existing IDeA state centers1 and build pediatric research capacity

nationally (Figure 1). The University of Mississippi Medical Center was selected as one of 17 awardees for participation in the ISPCTN.

The Mississippi Pediatric Clinical Trials Center (M-PCTC) is the local ISPCTN site. It aims to establish a university-based clinical research team that implements pediatric clinical trials and provides access to pediatric trials for medically underserved and rural populations, with the expectation of improving health and health outcomes of the children and families of Mississippi. Additionally, the M-PCTC will develop pediatric researchers involving each of the ECHO domains while developing UMMC infrastructure for engagement in ISPCTN studies (Table 1).

Mississippi’s Child Health Needs

Mississippi is largely rural, with a significant portion of children who lack access to clinical trials. Specifically, 68 out of 82 counties contain fewer than 50,000 people, according to the 2016 U.S. Census estimates.2 Mississippi boasts over 1.6 million rural residents and nearly 1.4 million urban residents, according to the USDA Economic Research Service,3 with the majority clustered near Jackson, Hattiesburg, Gulfport/Biloxi and Memphis. Mississippi ranks 50th overall in measures including health status disparity, violent crime, vaccine-preventable disease, access to care, and insurance coverage among others.4 There is a tremendous need for effective ways to ensure that the children of Mississippi have the opportunity to participate in clinical trials that enhance the understanding of major child health conditions and provide newly developed methods of pediatric clinical care to participants.

The Mission of IDeA States Clinical Trials Network

Children and families in Mississippi have had limited access to clinical trials providing state-of-the-science medical care. The M-PCTC will change that through UMMC’s statewide reach. Through its campuses, UMMC’s pediatric healthcare providers provide general pediatric and subspecialty care across the state. This network provides opportunities

1. Build a university-based pediatric clinical research team.

2 Promote engagement in clinical research within largely rural and underserved communities in Mississippi.

3. Improve health and health outcomes among Mississippi children and families through clinical research participation.

4. Develop capacity-building infrastructure for engagement in IDeA States Pediatric Clinical Trials Network (ISPCTN) studies and future state, regional, and national pediatric clinical and population health research efforts.

for integration of clinical care and pediatric trials. The overall goals of the ISPCTN are to 1) provide access to state-of-the-science clinical trials; 2) build institutional research capacity, and 3) apply findings from pediatric cohort studies to children in IDeA states.

IDeA States Clinical Trials Network Focus Areas

Consistent with the key pediatric outcomes, the ISPCTN will focus its selection of clinical trials on the 5 main child health domains of 1) upper and lower airways; 2) obesity; 3) pre-, peri- and postnatal; 4) neurodevelopmental outcomes, and 5) positive child health. The first 4 domains broadly represent child health conditions that have been increasing in frequency. However, relatively little is known of the determinants among children residing in rural and medically underserved communities, let alone clinical interventions that can improve management or diminish adverse long-term health consequences. Moreover, protective factors promoting positive child health among rural children warrants the attention of pediatric researchers.

For example, nationally, there has been an increasing prevalence of pediatric asthma, and new treatments continue to be developed. Yet, asthma is a complex pediatric illness with both biomedical and behavioral components that impact treatment. Treatment is further

Table 1. Goals of the Mississippi Pediatric Clinical Trials Center (M-PCTC)

complicated when a child is overweight or obese. Clinical trials that test clinical practices for children with asthma and obesity residing with rural communities have seldom been conducted. Within the ISPCTN, a large scale trial that can address this gap has been initiated.

Opportunities for Collaboration

Local healthcare providers are the link between a family and a pediatric clinical trial. Families frequently look to their child’s healthcare provider with questions about research participation.5 Therefore, the M-PCTC seeks to inform child healthcare providers about the overarching framework of the ISPCTN so that they can help families in their decision-making process.

With the information provided herein, child healthcare providers can guide families in their participation decision-making and continue to provide primary care. There are many reasons to encourage families to enroll in a pediatric clinical trial. As children can respond differently to clinical treatments, there is a need to conduct trials tailored to children.6 Additionally, pediatric participants that represent the diversity of the U.S. population are necessary to optimize the generalizability of findings to all children. Involving parents, caregivers, and children in the decision-making process is complex.7 Practically speaking, all must be provided with an opportunity for questions and discussion when considering enrollment in a clinical trial. Data suggests that clinical trial participants might have better outcomes compared to those with a similar disease.8 An added benefit is the altruistic contribution to care for future children with the same health problem. A child’s primary care physician is trusted by the child’s parents regarding research participation. Thus, an extension of the M-PCTC into Mississippi’s communities will serve to not only benefit the provider with opportunities for collaboration to improve care, but will also serve the children of Mississippi.

Collaborations will unfold within the UMMC setting as well, with resources that provide opportunities for institutional capacity building and career development. Opportunities for original, investigator-lead protocol production and grant application to the ISPCTN is expected.

All types of clinical trials will be considered if they are focused on the ECHO topics above and ultimately approved by the ISPCTN leadership committee. These will include pharmacokinetic and therapeutic clinical trials, among other types that are proposed and approved through appropriate network channels. A network-enriched sample size increases the impact and generalizability of clinical findings, and, most importantly, a larger number of children can be offered the opportunity to participate in clinical trials, receiving a high level of monitoring and disease-related education that accompanies trial participation. Examples of approved network protocols in Mississippi can be found in Table 2 Funding began for M-PCTC in September of 2016.

Information for the M-PCTC will be accessible through the ISPCTN website, the M-PCTC website, and Facebook, as well as Twitter feeds that are under development. Providers and patients have access to current projects, provider and staff research training opportunities, and contact information needed for answering questions or how to participate. The overarching goal of these communication systems is to make pediatric trial information open and easily accessible.

Conclusions

The M-PCTC is a new network site for the ISPCTN initiative from NIH. Families from rural and medically underserved areas now can have access to pediatric clinical trials that provide an opportunity to participate in the state of science care. Child health research carries with it a significant responsibility for careful monitoring and oversight of children’s health status during a trial. These procedures ensure child safety during trial participation. Moreover, detailed monitoring provides frequent opportunities for families to discuss their child’s health needs with trial staff and physicians. As with all pediatric trials, the overall care of the child continues to reside with the primary care provider, with results from the trial informing subsequent care. The M-PCTC looks forward to ongoing collaborations with Mississippi children, families, and child healthcare providers throughout the state. Together we can better inform the child health care for future generations of Mississippi children.

Table 2. ECHO ISPCTN Clinical Trial Activities in Mississippi

Acknowledgments

This work was supported by the National Institutes of Health (NIH) Grant UG1HD090848-01. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Conflict of Interest Disclosures: Authors Callahan, Lindsay, Majure, Thomas, and Annette report no conflicts of interest. Authors Barr, Herring, Famuyide, Malloch, and Blackshear disclose grant funding from the National Institutes of Health during the conduct of the study. Author Famuyide discloses grant funding from WK Kellogg Foundation and Clinical Trial Agreements from IBT, Inc and ONY, Inc.

References

1. National Institutes of Health. Environmental Health Outcomes on Child Health Outcomes (ECHO) Program. Accessed July 26, 2017. https://www.nih.gov/echo

2. United States Census Bureau, American Fact Finder Annual Estimates of the Resident Population: April 1, 2010 to July 1, 2016: Mississippi. Accessed July 26, 2017. https://factfinder.census.gov/faces/tableservices/jsf/pages/productview. xhtml?src=bkmk

3. United States Department of Agriculture Economic Research Service Population, Income, Food Insecurity, Education, and Employment. State Fact Sheets: Mississippi. June 2017. Accessed July 26, 2017. https://data.ers.usda.gov/reports. aspx?StateFIPS=28&StateName=Mississippi&ID=17854

4. United Health Foundation State Summary: Mississippi. America’s Health Rankings. 2016 Annual Report. Accessed July 26, 2017. http://www. americashealthrankings.org/learn/reports/2016-annual-report/state-summa ries-mississippi

5. Dalen J, Annett RD, Brody JL, Perryman ML Influences upon pediatricians’ willingness to refer patients to clinical research Open Access J Clin Trials. 2010;2:23-28.

6. NIH Clinical research trials and you: For parents and children. Accessed July 26, 2017 www.nih.gov/health-information/nih-clinical-research-trials-you/parentschildren

7. Brody JL, Turner CW, Annett RD, Scherer DG, Dalen J Predicting adolescent asthma research participation decisions from a structural equations model of protocol factors J Adolesc Health. 2012;51(3):252-258.

8. The importance of children in clinical trials NIH Medline Plus. 2012;6:6-7. Accessed July 26, 2017. https://medlineplus.gov/magazine/issues/winter12/ articles/winter12pg6-7.html

Author Information

Director of Pediatric Obesity Medicine and Nutrition at Mississippi Center for Advanced Medicine. Assistant Professor of Pediatrics and Medical Director of Pediatric Weight and Wellness Program, University of Mississippi Medical Center, at the time of manuscript submission; Co-investigator, Mississippi Pediatric Clinical Trials Center (MPCTC) at the time of manuscript submission (Herring) Associate Professor, Division of Newborn Medicine, University of Mississippi Medical Center; Medical Director, NICU and Newborn Services, Children’s of Mississippi Batson Children’s Hospital; Co-investigator of the MPCTC (Famuyide). Professor, Susan T. Miller Chair in Pediatric Pulmonology, University of Mississippi Medical Center; Co-Principal Investigator of the MPCTC (Majure) Associate Director, Social Sciences Research Center of Policy Studies; Director of Mississippi Health Policy Research

Center, Mississippi State University; Consultant for the MPCTC (Thomas). Research Specialist, Department of Pediatrics, University of Mississippi Medical Center; Grant and Regulatory Specialist for the MPCTC (Callahan). Registered Nurse, Clinical Research Support Program, Office of Research, University of Mississippi Medical Center at the time of manuscript submission; Nurse Coordinator for the MPCTC at the time of manuscript submission. Currently, Lead Clinical Transition Specialist AL/ MS Option Care Health (Lindsay). Biostatistician, Department of Data Science within the John D. Bower School of Population Health, University of Mississippi Medical Center; Co-investigator, providing statistical support for the MPCTC (Blackshear). Project Manager, Mississippi Pediatric Clinical Trials Center (MPCTC), Pediatric Research, University of Mississippi Medical Center (Malloch). Former Chairman and Professor of Pediatrics, University of Mississippi Medical Center. Chairman and Professor of Pediatrics and Associate Dean for Child Health, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital (Barr). Professor and Vice Chairman of Research, Department of Pediatrics, University of Mississippi Medical Center; Co-Principal Investigator of the MPCTC, one of the sites in the NIH funded IDeA States Pediatric Clinical Trials Network (Annett).

Corresponding Author: Whitney Herring, MD, MPH, Mississippi Center for Advanced Medicine. Ph: 601-499-0935. (wherring@msadvancedmedicine).

Top 10 Facts About Penicillin Allergy

PRIYA PATEL, MD; STEPHEN LEBLANC, MD; PATRICIA STEWART, MD; AND RICHARD DESHAZO, MD

Penicillin belongs to a family of drugs called beta-lactam antibiotics.

Beta-lactam antibiotics, including penicillin, cephalosporin, and carbapenems, all contain the beta-lactam ring. Penicillins are often the first-line agents for several infections, including dental, skin, and bloodstream. Historically, early preparations had more impurities resulting in a higher frequency of acute reactions.1 Sensitization is most commonly seen in topical forms, followed by parental forms, and finally, oral forms.1 The beta-lactam ring metabolizes into major (penicilloyl-polylysine, also available commercially as Pre-Pen) and minor (benzylpenicillin, penicilloic acid, penilloic acid) antigenic determinates.2,3

About 10% of patients, and as high as 20% in hospitalized patients, report having a penicillin allergy; however, after testing and oral challenge, more than 90% of these cases did not have a true IgE mediated sensitivity as they were incorrectly labeled as allergic or had resolution of the allergy.2 The incidence of anaphylaxis to penicillin is 0.02%–0.04%.2

Clinical presentations Mechanism

Type I immediate: anaphylaxis, urticaria IgE

Type II cytotoxic: hemolytic anemia IgM or IgG

Type III immune complex: serum sickness, nephritis IgG

Type IV delayed: DRESS, SJS/TEN T cell

Most patients with a penicillin allergy generally “lose” the allergy with time.

Patients who have previously tested positive for penicillin allergy have a 10% decrease per year for a subsequent positive reaction.4 Therefore, avoidance of penicillin for 10 years will result in 80%–100% of patients retesting negative for the allergy. A complete history should include the route of administration, time to reaction, symptoms during a reaction, management of the reaction, years since the reaction, indication for the penicillin use, and use of other forms of penicillin since the initial reaction.5

There are multiple risks associated with not evaluating individuals with a listed penicillin allergy.

Penicillin allergy is the most common drug allergy reported by patients, and the most frequent reactions to penicillin are Type 1 and Type IV hypersensitivity reactions.

A “true” penicillin allergy is defined by a Type I IgE mediated crosslinking that causes mast cell degranulation and release of vasoactive substances such as histamine.4 5 This results in signs/symptoms of urticaria, flushing, dyspnea, bronchospasm, wheezing, angioedema, hemodynamic instability, GI upset, or mental status within minutes to an hour.4,5

Lack of penicillin use in methicillin-susceptible Staphylococcus aureus bacteremia due to a listed allergy has resulted in deaths and inferior outcomes.6 These patients have higher rates of Clostridium difficile and vancomycin-resistant enterococci infections.7 Additionally, it is still the drug of choice for many childhood illnesses, skin infections, and surgical site infection prophylaxis. There is also a substantial economic cost associated with avoidance of penicillin usage as patients labeled with an allergy have longer hospital stays and use of more expensive antibiotics. The cost savings associated with delabeling a patient as penicillin-allergic was $1,368.13.8 Therefore, a patient with a listed penicillin allergy should be referred to an allergist-immunologist for further workup.

Patients at low risk may be able to undergo a direct oral challenge.

Patients with a history of benign rash, benign somatic symptoms (pain, fatigue), or unknown history with last penicillin exposure more

than 12 months prior may be evaluated with direct oral challenge.9 Oral challenges are performed only in offices that are prepared to treat anaphylaxis in the event an adverse reaction does occur. An evaluation of 6 large studies showed that out of 3,299 individuals, 42 (1.3%) had immediate onset reactions with subjective reactions being more common than objective ones.8 Amoxicillin is the drug of choice for the challenge as it has an antigenic side chain and will prove tolerance to a wider penicillin family than benzylpenicillin or phenoxymethylpenicillin.10

Patients at high risk require penicillin skin prick testing. Those who do not meet the criteria listed above are considered high risk and should undergo skin testing first to reduce the risk of serious reactions with an oral challenge.8

Currently, in the United States, testing can be done for the major determinant penicilloyl-polylysine, as well as the minor determinants benzylpenicillin and penicilloate.11 Skin testing is done via skin prick and via intradermal testing. The non-irritating concentrations of these agents have been identified. A referral center must be familiar with the storing of the reagents, the dilutions/concentrations for each step, and the proper interpretation of the testing, in order to perform and interpret skin test results. An in vitro test for penicillin specific IgE is not valuable as results do not correlate with oral challenge reactions.8

A negative penicillin skin test should be followed by a graded dose challenge.

The negative predictive value of skin prick testing is 97%, and therefore, a negative result should be confirmed by a graded dose challenge.12 If the skin test is positive, then another antibiotic must be used, or patient must be referred for desensitization.8 Skin testing, graded dose challenge, and desensitization are only useful when concerned for an IgE mediated reaction; if the initial reaction was a severe non-IgE mediated such as Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis or Drug Reaction with Eosinophilia and Systemic Symptoms, then these steps are contraindicated.8

Desensitization is necessary for patients with penicillin allergy who have an infection for which penicillin is the drug of choice.

Desensitization is also referred to as a temporary induction of tolerance.13 Desensitization involves stimulation of the immune system with an allergen in order to prevent the allergic response. In cases where penicillin is the drug of choice, patients with a positive skin test must undergo a multi-step desensitization procedure.14 A patient that has a reaction to an oral challenge has essentially been desensitized. The temporary tolerance to penicillin lasts about 24–48 hours, therefore, continued regular dosing of the drug or repeat desensitization is necessary if the patient requires repeat dosing.

Clinically significant cephalosporin and carbapenem cross-reactivity is rare.

About 40–50 years ago, the reported penicillin and cephalosporin cross-reactivity was 10%; however, more recent data

show the cross-reactivity rate to be of 2%.15 This difference was likely due to contamination of early, first-generation cephalosporins with penicillin. The cross-reactivity between penicillin and carbapenem is even rarer, at less than 1%.15 When necessary, it would be appropriate to refer a patient to an Allergist-Immunologist to help sort out the workup for possible penicillin allergy and their risk of reaction with cephalosporin/carbapenem.

There is also the novel data supporting the use of scoring systems that help identify low-risk individuals who can undergo direct oral challenge through their primary care physicians; however, this topic remains controversial.

Newly published studies in 2020 have developed a scoring system that identified low-risk individuals and among this subgroup, only a small number of individuals were found to have positive skin tests or oral challenges. These studies indicate that direct penicillin oral challenges could be safely utilized for certain low-risk individuals and could be performed under close observation at their primary care physician’s office, during their inpatient hospital stay or through programs led by anti-microbial stewardship. However, the definition of low risk was defined differently in these studies, ranging from a scoring system that included criteria such as a reaction occurring five years or fewer, anaphylaxis/angioedema or a reaction necessitating treatment to including any subjects with a penicillin associated rash that occurred more than over year ago.16–18

Acknowledgments

Conflict of Interest Disclosures: The authors have nothing to disclose.

References

1. Bhattacharya S The facts about penicillin allergy: A review J Adv Pharm Technol Res. 2010;1(1):11-17.

2. Patterson RA , Stankewicz HA Penicillin allergy StatPearls. 2019.

3. National Center for Biotechnology Information PubChem Accessed March 11, 2020. https://pubchem.ncbi.nlm.nih.gov/compound

4. Stone CA , Trubiano J, Coleman DT, Rukasin, CRF, Phillips, EJ. The challenge of de-labeling penicillin allergy Allergy. 2020;75:273-288.

5. Legendre DP, Muzny CA , Marshall GD, Swiatlo E Antibiotic hypersensitivity reactions and approaches to desensitization Clin Infect Dis. 2014;58(8):11401148.

6. Turner NA , Moehring R , Sarubbi C, et al Influence of reported penicillin allergy on mortality in MSSA bacteremia Open Forum Inf Dis. 2018;5(3).

7. Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK Risk of methicillin resistant staphylococcus aureus and clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study BMJ. 2018;361:k2400

8. Macy E, Vyles D. Who needs penicillin allergy testing? Ann Allergy, Asthma Immunol 2018;121(5):523-529.

9. Kuruvilla M, Shih J, Patel K , Scanlon N. Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy Allergy Asthma Proc. 2019;40(1):57-61.

10. Lteif L, Eiland LS The basics of penicillin allergy: What a clinician should know Pharmacy. 2019;7(3):94

11. Adkinson NF, Jr, Mendelson LM, Ressler C, Keogh JC Penicillin minor determinants: History and relevance for current diagnosis Ann Allergy, Asthma Immunol 2018;121(5):537-544.

12. Fox S, Park MA Penicillin skin testing in the evaluation and management of penicillin allergy Ann Allergy, Asthma Immunol. 2011;106(1):1-7.

13. Gonzalez-Estrada A , Radojicic C. Penicillin allergy: A practical guide for clinicians CCJM. 2015;82(5):295-300.

14. Pham MN, Ho H-E, Desai M Penicillin desensitization: Treatment of syphilis in pregnancy in penicillin-allergic patients Ann Allergy, Asthma Immunol 2017;118(5):537-541.

15. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and management of penicillin allergy JAMA. 2019;321(2):188

16. Trubiano JA , Vogrin S, Chua KYL, et al Development and validation of a penicillin allergy clinical decision rule JAMA Intern Med. 2020;180(5):745-752.

17. Stevenson B, Trevenen M, Klinken E, et al Multicenter Australian study to determine criteria for low- and high-risk penicillin testing in outpatients J Allergy Clin Immunol Pract. 2020;8(2):681-689.e3.

18. Stone CA , Jr, Stollings JL, Lindsell CJ, et al Risk-stratified management to remove low-risk penicillin allergy labels in the intensive care unit Am J Respir Crit Care Med. 2020.

Author Information

Department of Internal Medicine (Patel); Department of Allergy and Immunology (LeBlanc, Stewart); Department of Allergy and Immunology (DeShazo).

Corresponding Author: Priya Patel, MD, 2500 N. State St, Jackson, Mississippi 39206. Ph: 601-984-1000. (ppatel3@umc.edu).

COVID-19 Personal Protective Equipment (PPE) for Healthcare Personnel

Facemask

N95 or higher respirators are preferred but facemasks are an acceptable alternative.

Family

An Interview with 2020-21 MSMA President W. Mark Horne, MD

KAREN A. EVERS

[Each year the Journal goes behind the scenes to bring you a special inside look at your incoming MSMA president. For brevity and to accommodate more pictures, the questions have been omitted. —Ed.]

I was born in Laurel, Mississippi, on March 16, 1962, to Willus and Fay Horne. I have three sisters, one older and two younger. My mom is a retired registered nurse, and my late father owned and operated a garden center/nursery and landscape business. We also grew and sold catfish fingerlings and fish bait (minnows, worms, and crickets). I was raised in the family business until I enrolled at Mississippi College as a junior transfer student. These early experiences (I started waiting on customers and running a cash register at age 6) made it easy for me to meet and greet others and made learning to take a history much more comfortable.

My own family began with the excellent decision to say “I do” to Danita Culbertson. We have been married for 27 years. Though it has not always been perfect, when you not only love your spouse but know they are your best friend, and you genuinely respect and trust them, it is easy to stay together. We have been blessed with three wonderful children. Sabine and Kiser are our 21-year-old twins. They just completed their junior

year at Ole Miss; both are in the Honors College. Sabine is also in Lott Leadership and is a public policy leadership major. Kiser is a biology premed major. Fletcher is our “surprise” 15-year-old son, who will be a high school sophomore this fall. He attends Laurel Christian School.

Dr. W. Mark Horne and his family: son Fletcher (15), wife Danita, twins Sabine and Kiser (21).

Lobby of Windsor Court before our annual August meal at Commander’s Palace. Once kids are in K5, they get to go, too.

Going to the Disco, family Halloween costumes.

I received an associate of arts degree in biology from Jones County Junior College (JCJC) in 1982. While at JCJC, I worked as an orderly, then as an EMT on the ambulance service at South Central Regional Medical Center, gaining much-needed experience and exposure to the practice of medicine. I then transferred to Mississippi College, where I graduated in 1984 with a B.S. in Biology. Then it was on to the University of Mississippi Medical Center (UMMC) where I graduated with my M.D. in 1988.

While at UMMC, I joined the Mississippi Army National Guard and served in a combat support hospital that was based in Jackson at that time. This allowed me to gain an appreciation for military medicine and perform clinical clerkships at Brook Army Medical Center and Walter Reed Army Medical Center. From there, I completed an internship and residency in internal medicine at the University of Tennessee, Chattanooga Unit and Erlanger Medical Center.

While there, I transferred to the Tennessee Army National Guard, where I was the Battalion Surgeon for 1-181 FABN, a heavy artillery battalion based in Chattanooga. This association led to the adventure of being called up for active duty during Desert Shield and subsequently Desert Storm, with deployment to Southwest Asia with my unit to provide artillery support for the invasion of Iraq. The 6-month deployment delayed my residency completion until December 1991, after which I moved to Laurel to begin my practice.

Milestones

The most important milestone would be realizing that I was not good enough or strong enough to succeed on my own. At an early age, this discovery led to my salvation through Christ, who has led and guarded me throughout my life.

Next would be meeting and marrying my wife. Her discipline and determination are truly an inspiration. She has been the most precious of answered prayers. She is the most disciplined and tenacious person I know and has a caring heart to match that tenacity.

Learning early in life never to be afraid of hard work has carried me through many a challenge. I first knew I wanted to be a physician in the 4th grade. My great uncle (Chester Farmer, MD) was a dermatologist, and my mom was a nurse. I just could never get enough of medicine or science.

My greatest heroes have been my parents and grandparents. They demonstrated, not only with words but with deeds, that with a life grounded and instructed by true faith in God and backed by hard, consistent work, all things were possible. They were all humble but steadfast, disciplined yet fun, firm, but caring.

My proudest accomplishments are to have a lasting, loving marriage and to have been blessed to raise three children who are not just fine caring humans but who demonstrate faith in how they conduct themselves.

My best medical school memory is of Dr. Peter Blake. When flummoxed by a difficult clinical or ethical situation, his M2 and M3 students would often ask, “What should we do?” His answer was unfailingly, “Young doctor, do the right thing.” It took many years for me to realize the deep wisdom of his advice. It is incumbent on each of us seeking the title of physician to develop not only a deep body of scientific knowledge but also a moral compass to guide us when facts and answers are sparse, yet decisions must be made.

Career

The greatest challenge when I began practice was to teach myself to be a good clinic doctor. My residency was excellent at preparing me to care for the acutely ill in a hospital setting, but as most programs of that era, training in outpatient settings was scant.

More recently, the increasing intrusion of third parties into the physician–patient relationship has become an intense challenge for those of us dedicated to the special trust this bond represents.

I have been affiliated with South Central Regional Medical Center (SCRMC) since 1980, first as an orderly, then as an EMT on the

Dr. and Mrs. (Danita) W. Mark Horne.

ambulance service. Since January 1992, I have been a member of the medical staff of SCRMC. Over the years, I have served on most committees and as president of the medical staff.

Currently, I’m the chief medical officer of SCRMC and continue to practice, though now with a focus on diabetes and associated issues.

Organized Medicine

My first introduction to MSMA was by Drs. James (Jimmy) Waites and Eric Lindstrom. Those of you fortunate enough to have known these men know that resistance was futile.

My MSMA service began with multiple councils, medical education, scientific assembly, finance, etc. Then I was elected to the Board of Trustees. I was a member of the first MSMA Leadership Academy, an amazing experience! Once on the Board, I was elected vice-chairman, then appointed to the vacated post of secretary-treasurer, and now elected as president of MSMA.

During my tenure, we have dealt with many critical events, some of which presented great challenges and threats to MSMA. With the excellent leadership provided by our full-time staff and an amazing group of leaders on the Board of Trustees we were able to overcome these challenges, and MSMA is now stronger and better able to represent its members.

I love the camaraderie of MSMA and the focus on being the primary source of leadership and care for the health care needs of Mississippians.

Delivering meals to healthcare workers for Fletcher’s Eagle Scout project, Feed the Frontline.

Mission Trips to Haiti.

Community Service

I am a member of First Baptist Church of Laurel, where I have served multiple terms as a deacon and as chairman of the deacon body. I serve as the house physician and medical advisor for Mission at the Cross, a faith-based ministry to addicted men. I’m also a long-term member of the Laurel Rotary Club.

Focus

Improving access to medical care is an urgent need for Mississippi. Accomplishing this goal will require advances in insurance coverage and improved access to quality physician-led medical teams. We must increase the number of physicians practicing in Mississippi to accomplish these goals. Expanding access to current telehealth services will also serve a critical need.

Balance and Joys of Living

Enjoy most: I love blending the science of medicine with the art of the practice of medicine.

Like least: The intrusion of bureaucracy and repetitive documentation that takes so much time away from what we do best, care for the sick and injured.

FOR THE FUN OF IT… FILL-IN-THE-BLANK

You’re most likely to see me around: Home, preferably in my kitchen.

On the weekends I love to: Hang out with family and friends, at home or church.

The high school, college or pro sports teams I root for are: Laurel Golden Tornados, University of Tennessee, University of Mississippi, and the New Orleans Saints.

If I’m watching a movie or listening to music, it’s probably: A drama/thriller or war movie. Classic rock or jazz are my favorite styles of music, though I often just enjoy listening to nature or even silence.

Latest splurge: A large outdoor covered porch and kitchen. I am passionate about: The art of medicine and human interactions—also, food and the science and practice of cooking. Something about me not everyone knows: I have completed three marathons, including Big Sur International and Boston. Don’t be too impressed, my times were terrible, but I did finish each marathon.

Do you like to go out or stay in? Mostly stay in.

The perfect meal: Multicourse tasting menu at the Kitchen Table at Commanders Palace.

Perfect day: Wake up without an alarm, and do whatever comes to mind.

Favorite color: Blue.

Cologne: None.

Text, email, or cell phone: Text for quicker turnaround, email for detailed answers.

Pets: Definitely a dog person. We have a mini golden doodle, Gracie.

How do you make time for your personal life? When I am at work, I work. When I am home, I strive mightily to leave work at the office. It is easier said than done, but I compartmentalize fairly well.

What do I do when I’m not working? Mostly, hang out at home with my family. Work in the yard some, cook, read, travel as much as possible (not much of that recently).

What would I like members to know about me?: I want to thank them for the honor of allowing me to serve MSMA over the years and especially now as your President. n

Dr. and Mrs. Horne ran the Boston marathon together in 2014.

Favorite family spot: Modica Market in Seaside, Florida.

MSMA Member since: 1992.

#relationshipsmatter

Over the past year it has been an honor and a pleasure to serve as the President of the Mississippi State Medical Association (MSMA). I’ve had the opportunity of meeting many wonderful people as I have traveled throughout the state representing our organization and what really stood out to me was the importance of relationships. These should never be underestimated.

Many people will remember the contentious Governor’s race of 2019. Because of the longstanding good relationship that MSMA had with then Lt. Governor Tate Reeves, the MSMA political action committee endorsed Tate Reeves for Governor. This was not without hard feelings and controversy among many physicians who supported other candidates. However, in the end, the Lt. Governor became Governor and that relationship has continued to blossom.

Fast forward to the COVID-19 pandemic and who did the governor call upon to lead the efforts against this virus? MSMA. Furthermore, our strong relationship with the Mississippi State Department of Health has been invaluable. State Health Officer Dr. Thomas Dobbs should be hailed as a hero in this battle. He has met with the leadership of MSMA every single week since March. Because our association is the leading voice of medicine, I was asked to put together and lead the Governor’s Medical Advisory group against COVID-19. I was advised to include physicians, hospital leaders, nursing leaders, dental leaders, medical and nursing licensure board members, insurance leaders, and attorneys from all around the state. Because many of us knew each other, we quickly formed a team to respond to this common enemy. There was no bickering or infighting. We only had cooperation with one purpose in mind: protect the health of Mississippians. Our ability to quickly develop a pandemic system of care was simply amazing. No one asked for individual recognition and great ideas happened spontaneously. This is what a team is all about!

A lot of credit should be given to Dr. Steven Stogner and Dr. Harper Stone for rapidly pulling together the Mississippi Healthcare Alliance to

develop a pandemic system of care protocol for all the hospitals in our state. Jim Craig from the State Department of Health was instrumental in helping the alliance with the public data and necessary information. MSMA past president, Dr. Dan Edney did a wonderful job of putting together a corps of physician volunteers to serve in hospitals in need. Dr. Ken Cleveland helped expedite physician licensure, and Rob Jones and Stephanie Edgar with Medical Assurance Company of Mississippi (MACM) provided expert medical malpractice insurance advice. Dr. Alan Jones, Dr. Richard Summers, and Dr. Peter Arnold gave updates to the committee on how the University of Mississippi Medical Center was handling the pandemic while Dr. Mark Phillippi made suggestions on how to best handle the special needs of dialysis patients. The proper care of nursing home patients was discussed by Dr. George Patton while Dr. Larry Field gave the committee perspective on how ambulatory surgery centers were affected. Dr. Hursie Davis-Sullivan with the Medical and Surgical Association highlighted the effect of COVID-19 on the African American population. Finally, Dr. Claude Brunson and the MSMA team provided support through regular email communications and social media.

To see all of these great physicians working together to lead the charge was truly inspiring. We owe them a debt of gratitude as they spent countless hours meeting while away from their practices and families. It has been said that we are often measured by the company that we keep. I am proud to call these fine physicians “Friends and Colleagues” because relationships do matter. n

Job well done!

Clay Hays, Jr, MD President, Mississippi State Medical Association

J. Clay Hays, Jr, MD

MSMA President 2019–2020

Reintroducing The State’s School of Medicine –A Letter to My Colleagues

LORETTA JACKSON-WILLIAMS VICE DEAN FOR MEDICAL EDUCATION, UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE

Ayear ago I wrote a letter to my local newspaper editor in Indianola in response to an article in the paper about a young man who had aspirations of becoming a physician. In that article, I mentioned that 3 characteristics help students become physicians. Those 3 things are commitment, focus, and preparation. I also noted that some students have an interest in pursuing medicine as a career but have some uncertainly about the process. With that uncertainty, students rely on people around them, including their local physicians, to provide insight. With this editorial, I hope to open a dialogue with Mississippi physicians about the state’s medical school so that everyone has updated information about the process of pursuing a medical education and the current state of medical education. Mississippi physicians are the ones who touch the lives of these aspiring medical students and their families and serve as role models. Thank you!

Within the state of Mississippi, there are 2 distinct pathways toward a degree in medicine: the state’s allopathic school and William Carey’s osteopathic school. I will focus only on the allopathic pathway. Our school is accredited by the Liaison Committee on Medical Education (LCME), which provides a set of standards that all allopathic schools must meet. Accreditation establishes the school’s eligibility for selected federal grants and programs. In addition, accreditation is required for our medical students to take licensing examinations by the United States Medical Licensing Examination (USMLE) as a condition for admission to residency programs and as a condition for licensure of our medical school graduates by most state boards of medical licensure. The school’s most recent survey accreditation visit was February 2020 and resulted in continued full accreditation.

The School of Medicine (SOM) began as a 2-year certificate program in 1903 on the Oxford campus of the University of Mississippi. It expanded to a 4-year educational program in 1955 in Jackson, Mississippi. Currently, only Mississippi residents are accepted for the program to encourage the continued growth in the number of physicians practicing within the state. This has been possible with a robust interest in the educational program, as evidenced by the number of applicants over the past 10 years (Figure 1). The school currently accepts a class up to 165.

The educational program is designed to prepare each student for the 13 EPAs (Entrustable Professional Activities) for entering residency1 within 4 years. The first year consists of biochemistry, anatomy, human development, physiology, and histology and cell biology, along with integrated medical neuroscience and behavior I (MN&B I), and an introduction to the medical profession I (IMP I). The second year includes microbiology, pathology, and pharmacology, along with MN&B II and IMP II. In the third year of the medical education program, students are required to complete 7 clerkships, including surgery, family medicine, pediatrics, internal medicine, psychiatry, obstetrics and gynecology, and clinical neuroscience. Also, the third year requires 2 electives allowing students to explore different specialties and the ambulatory setting. Fourth-year requirements include a critical care selective, a procedural selective, an ambulatory selective, a subinternship, and a boot camp that focuses on the transition from medical school to residency. Medical students are also required to take 14 weeks of electives. During this period, as depicted in Figure 2, the students are also working on the licensure process for medicine, which requires taking the United States Licensure Examinations Step 1 and both parts of Step 2.

Figure 1. SOM Applicants and Matriculants

Educational preparation is not the only important focus of the educational program. There is also a deliberate emphasis on professional identity formation, which is an important part of preparing these students who will provide patient care with indirect supervision in residency training. To be effective physicians, some personal characteristics and skills have to be further developed for students to be able to influence the behavior of patients, genuinely care for all people, communicate well with patients and colleagues, navigate complex systems, and meet people where they are. We give these characteristics names such as altruism, compassion, empathy, and leadership. We look for these characteristics in applicants to medical school and continue to support the development and expression of these features through curricular and co-curricular activities.

During medical school, students continue to mature academically, emotionally, physically, and psychologically. This is the reason that it is critical to have support programs in place for students as they progress through this grueling journey. The school provides a proactive academic support program for students managed by the assistant dean for academic affairs. This program includes early identification of students with potential academic risk through the Academic Achievement Program (AAP), tutoring and academic counseling through institutional resources, and personal counseling through the Student Counseling and Wellness Center. Other support programs are noted in Figure 3

The school focuses on the creation of community for students. This concept of community was extended with the creation of the House

Figure 3. Academic Advising/Counseling Services by Curriculum Year

Program. This program was established in 2014 as a medical school community designed to ensure that medical students are connected to campus resources and receive adequate social and academic support with guidance from physician educators.

While in medical school, students must make critical decisions regarding their future career. Many students come to medical school with a desire to be a physician, but with limited information about the many career opportunities available with a medical degree. To help students with this process of career selection, the school has many activities and programs, which are outlined in Figure 4

As a faculty member with teaching and administrative responsibilities, I fully recognize, as stated by Adina Kalet and Calvin Chou, that “Medical Education is a high-stakes endeavor. All our graduates are expected to use powerful cognitive, procedural, technological and pharmacologic tools under complex and uncertain circumstances, with life and limb in the balance. Furthermore, they are expected to do so nearly perfectly for a lifetime. Mistakes can be very consequential. This is not for the faint of heart. We are training physicians.” I strive every day to ensure that we are putting forward the best educational program for our students, faculty, and, most of all, our patients.

Over the next few months, we will continue to reintroduce you to the state’s SOM as we outline some of the successes and challenges in our processes in areas such as admissions, clinical training, curriculum, faculty development, residency training, and support services. n

Acknowledgments

Many thanks to all of the administrators, faculty, staff, residents, and volunteers who work tirelessly every day to care for patients and provide a great environment for learning.

Reference

1. Association of American Medical Colleges. Core entrustable professional activities for entering residency – abridged toolkit. Accessed February 27, 2020. https://www.aamc.org/system/files/c/2/484778-epa13toolkit.pdf

Hospitalists and Home Dialysis: The Great Unknown

VENKATARAMAN PALABINDALA, MD, MBA

Hospitalists are frontline providers involved in newly diagnosed incidents of patients with end-stage renal disease (ESRD) all the time. We help initiate dialysis in hospitals and facilitate the transition of the care to outpatient dialysis units. We take extreme pride in making sure this transition is smooth, safe, and in the best interest of our patients. As principle providers in this process and co-pilots on this critical journey of our patient’s most important life decisions, we are sometimes able to offer newly available alternative options for dialysis that have been shown not only to have better outcomes but also to yield better quality of life. In this article, I am going to discuss home dialysis and lessons learned in Mississippi to share with my hospitalist colleagues across the nation.

Traditionally, when a patient begins dialysis in the hospital, the discharging physician’s mindset is to initiate discharge after confirming a dialysis chair is available in an outpatient unit. Whether this conventional practice serves the long-term interest of the patient is questionable at this time when there is sufficient data to show that home dialysis patients have fewer hospitalizations. How many home dialysis patients have we seen in hospitals with readmissions? In the current scenario where there is an imminent risk of COVID-19 spread in health care facilities like outpatient dialysis units, should we on the frontlines make a difference in hospitalizations and longevity in these relatively immune-compromised patients or remain benighted?

We live in historical times when many of the old rules and ways of doing things are being challenged. One problem we can no longer ignore is how common chronic kidney disease (CKD) is, especially as we reach middle age and beyond. Current estimates are that 37 million people (15% of adults) in the United States have chronic kidney disease, and 90%of those people are unaware that they have a problem. The number of prevalent ESRD cases rises by about 20,000 every year. The United States renal data system shows that more than 31% of patients with acute kidney injury progress to CKD within 1 year, and emergency visits with ESRD are on the rise.1 Unplanned dialysis initiation in hospitals is common these days, especially when close to 33% of patients nationwide are not receiving adequate nephrology care. Total Medicare spending on both CKD and ESRD was over $120 billion in 2017 as reported by united states renal data service, representing 33.8% of total Medicare feefor-service spending, which is a considerable burden on taxpayers.

When the kidneys fail, there is an accumulation of uremic toxins, waste products, and water in the body along with inappropriate natriuresis. Chronic kidney disease is asymptomatic unless the glomerular filtration rate falls below 15%–20%, which can cause leg swelling, shortness of breath, low red blood cell count, and reduced blood pressure control. There is also a higher risk of early death, heart disease, and stroke. More importantly, along with the rise in the number of people with chronic kidney disease, there is an increase in the number of people who lose their kidneys entirely and become dialysis-dependent, or to use the more threatening medical term, endstage renal disease patients.

Mississippi has one of the highest rates of obesity and kidney disease in the nation. In the state of Mississippi alone, 1,721 new patients started on dialysis in 2017, mostly in the 60- to 64-year age group.1 Diabetes and hypertension are the leading causes of weak kidney function leading to dialysis in Mississippi. Race and genetic background are also major contributors: African Americans have the highest risk of kidney disease—three times the risk of whites—and made up 71% of dialysis patients in 2016, leading to many older individuals adapting dialysis as a new way of life. However, that is not where the story stops.

Nephrologists are exploring new avenues to prevent this decline in kidney function. Beyond what we have long known to be important, good blood pressure and diabetes control, along with minimizing protein spillage, there is exciting new data about the importance of bicarbonate supplementation or medical control of elevated uric acid. SGLT-2 inhibitors have proven efficacy in slowing the progression of CKD as well as increasing natriuresis. Of note, from the University of Mississippi, researchers at the Jackson Heart Study say that elevated uric acid is one of the potential drivers of kidney function decline, something easily correctable with medication.2 Avoiding dehydration, smoking, and excesses of weight are also important.

Dr. Lajos Zsom and Dr. Tibor Fülöp, who worked on this study for more than a decade, were among the first to call attention to the importance of treatment time for dialysis patients.3 Put simply, the longer we dialyze our patients, the healthier they will be. However, this approach is extremely difficult to perform with typical, in-center dialysis. Dr. Sohail Abdul Salim and many of his colleagues are making

a concerted effort to foster and promote the development of the home dialysis modality in Mississippi while patients await kidney transplants.

Patients that utilize home dialysis, most commonly overnight, use what is actually a glorified scale with a pump, called a “cycler,” which moves the fluid in and out of the peritoneal cavity to clear uremic toxins. When people learn to do blood dialysis at home, it enables them to spend a long time on the machine, which makes them feel better and indeed keeps them healthier. They are the heroes that should not go unnoticed compared to what their family members can achieve. Many of these patients hold a job and are the primary breadwinners for their families. We also have a proud tradition here to carry on. Dr. John Bower, one of the “founding fathers” of dialysis in Mississippi, was an ardent proponent of home dialysis. Dr. Salim reported a case of a woman who lived for 46 years, a lifetime when it comes to home dialysis, which she started when she was 16.4

In the last decade, more research shows that home dialysis leads to better patient outcomes, including improved mortality, improved quality of life, better control of hypertension and fluid control, decreased left ventricular mass, less pill burden, fewer hospitalizations due to heart disease, and lower rates of depression.5 Pulling fluid faster with in-center dialysis increases the risk of hypotension and risk of death. In-center dialysis patients are many times more fatigued and tired since they have more fluid (3–6 L or kg) taken out of their bodies in a relatively short time. This is referred to as postdialysis fatigue, and it takes around 6 to 8 h to recuperate from it. The recuperation time is reduced to less than 60–90 min with home dialysis therapies. Home dialysis patients (87%) report improved quality of life. Home dialysis patients have more freedom to travel. Dr. Salim documented in his published paper titled, “Successful peritoneal dialysis in large-weight subjects: Clinical features and comparisons with normal-weight subjects,” that neither obesity nor excess of weight is a contraindication for home dialysis modalities.6

Despite all the benefits of home dialysis, the fact is that it is very much underutilized, and less than 2% of patients are on home dialysis in Mississippi. Dr. Salim, in his published paper titled, “Benefits, challenges and opportunities using home dialysis with a focus on Mississippi, a rural southern state,” documents that there was a slight increase in the trend toward home hemodialysis between 2012 and 2015, and then a decline in 2016.7

Dr. Salim’s paper also highlights patients’ barriers to home dialysis: fear of self-cannulation, lack of social support, and burdening of caregivers. Patients likely are not well educated regarding the benefits of home hemodialysis, and physicians might even overlook the potential advantages of home dialysis in regard to improved mortality. Since late 2017, several strategies have been implemented to change physicians’ approach to home therapies, including helping patients better understand their informed choices, recurrent counseling sessions, and more flexibility to those already in the hospitals to start home dialysis. The strategy is to anticipate barriers rather than wait for problems to occur. Since a vast number of patients start dialysis in the hospital, the

arrival of transitional care units (TCU) in Mississippi has lately been helping patients ease the transition from hospital to home dialysis. TCUs help patients, psychologically and medically, adapt to a new home environment and also educate patients and family members on home dialysis modalities, benefits, and cost-effectiveness.

Life is a gift, and how we live is vital. Helping patients reengage the life that they have always loved, increasing time spent with the family, keeping their jobs, and contributing more to society is a dream that can be translated into reality with home dialysis. It is all about empowering patients to create a life plan. Holding their hand through every step of self-care is achievable with a team approach, which not only reduces patients’ fear of dying but also makes living joyful and dignified again. n

References

1. United States Renal Data System. 2018. USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD.

2. Mwasongwe SE, Fülöp T, Katz R, et al. Relation of uric acid level to rapid kidney function decline and development of kidney disease: The Jackson Heart Study. J Clin Hypertens. 2018;20(4):775-783.

3. Zsom L, Zsom M, Fulop T, Flessner MF. Treatment time, chronic inflammation, and hemodynamic stability: the overlooked parameters in hemodialysis quantification. Seminars in Dialysis. 2008;21:395-400.

4. Abdul Salim S, Cheungpasitporn W, Echols V, et al. Forty-five years on home hemodialysis, a case of exceptional longevity. Hemodialysis International. 2019;23(4):E120-E124.

5. Culleton BF, Walsh M, Klarenbach SW, et al. Effect of frequent nocturnal hemodialysis vs. conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial. JAMA. 2007;298(11):1291-1299.

6. Salim SA, Akula Y, Kandhuri Set al. Successful peritoneal dialysis in large-weight subjects: clinical features and comparisons with normal-weight subjects. Adv Perit Dial. 2016;32:61-67.

7. Salim SA, Zsom L, Cheungpasitporn W, Fülöp T. Benefits, challenges, and opportunities using home hemodialysis with a focus on Mississippi, a rural southern state. Semin Dial. 2019;32:80-84.

Venkataraman Palabindala is Medical Director of Utilization Management and Physician Advisory Services and Associate Professor at the School of Medicine, University of Mississippi Medical Center, Jackson.

Invisible Monsters

MYRNA ALEXANDER NICKENS, MD; JACKSON

As I headed toward the door of University Heart at my usual 6 p.m. to get to my car, a rather stout guy working with two other men on the facility’s ceiling fixtures called my name. “Dr. Alexander, how are you? Do you remember me? You put a stent in my heart in 2006.”

Of course, I didn’t recognize him, particularly with eyeglasses and a COVID protective mask hiding much of his wide smile. I was wearing a mask, too, of course. The man used the opportunity to remind his friends that he would never forget the person who inserted a stent into his coronary arteries. I worked in a small cardiology group private practice at the time of the procedure. The guy’s friends were a bit surprised by our friendly conversation.

“How are you doing?” I asked. Although it was clear to see, the man told me that he still struggled with weight issues, patting his protruding belly as he talked. He was quick to add that he was doing well, nevertheless. As we stood there in COVID-19 protective gear, the three white men and I were oblivious to the rest of the world. We were simply people enjoying a conversation.

As I went on to my car, I remembered the excitement and gratification of having performed a successful percutaneous coronary angioplasty that would improve the patient’s symptoms and life. When I performed the procedure, it did not matter that his cardiologist was a black female. He was just happy that the procedure went well. I felt good that 14 years later we could both smile about the outcome. It struck me as very odd, yet gratifying, that while we all wore masks in the hallway of the University of Mississippi Medical Center (UMMC), my former patient recognized me.

For about five months now, an invisible monster called COVID-19 has been killing so many of the world’s inhabitants. Yet, racism— another invisible monster—has carried out a ruthless campaign of fear, destruction, and violence for centuries.

Before my encounter with the former heart patient, my mind was preoccupied with thoughts about my first cousin having a severe case of COVID-19 viral pneumonia and my boss’s daughter protesting for racial injustice.

As a diversity and inclusion officer at UMMC, I am well aware of the need for more inclusion and access to resources in our country— not just for the few, but for all. Racial tension in our world has been

heightened by the death of George Floyd, a black man killed by a white police officer.

Would the presence of a more culturally and gender diverse group of officers while George Floyd was being suffocated have made a difference? If so, would one among them have been bold enough to push the officer off George Floyd’s neck, since it was a slow death? Unfortunately, Mr. Floyd was not the first unarmed black man to be killed by a white police officer during my lifetime. My memories race back to great and ordinary citizens who stood up to racism and were suppressed. These were people like John F. Kennedy, Rev. Martin Luther King Jr., Rosa Parks, Fannie Lou Hamer, and many others who stood up for civil rights for the human race. Most changes throughout the years have come through the efforts of our young teens and adults. Rev. King was in his twenties when he started peaceful protests. Many of our young people now protesting racism and police brutality are no different from those in the 1970s who opposed the Vietnam War, or those in the 1960s who fought for civil rights. I am among those who have benefitted from those protests.

I am a product of segregation, busing for integration, training in a largely impoverished city, and working under a glass ceiling. These experiences have brought growth and reward beyond my imagination. When I was a student at Tougaloo College in the 1970s, I never imagined being at the University of Mississippi Medical Center as a cardiologist. The labor of others during the 1960s and 1970s created a physician, cardiologist, wife, mother, friend, and church member. I was encouraged by UMMC Vice Chancellor Dr. Lou Ann Woodward and new intern Kandice Bailey to put my thoughts in writing. Kandice, a young African American woman, is watching mentors like me.

Dr. Woodward spoke of racism—the unspeakable, the elephant in the room—during her weekly address. Kandice asked for guidance. Should she stay quiet throughout the day or be upset with the country? My response was for her to speak kindly and proudly about the advances that have been made. Being positive and hopeful through the “storm” brought on by the two monsters attacking us is essential. Actions still speak louder than words. As physicians, it is important to treat all patients with dignity and compassion, regardless of their habits, race, sexual orientation, or religious belief.

The world is watching, and more importantly, our children (of every hue) are, too. As I reflect on my childhood, the Kent State University

protest resulting in the death of innocent unarmed students is brought back into my memory bank. I didn’t understand their protest at the time. Protests throughout the years have been organized to bring clear focus and attention to many causes. Fifty years ago, several white Kent State University students were gunned down by military troops in protest of the Vietnam War. These protests of war and civil liberties have included a diverse group of people who saw a critical issue that was unresolved and brought it to the public stage.

Just 100 years ago, women protested for the right to vote (1920). The 19th amendment was passed and included a provision to give women that right. Of course, all African Americans were prohibited from voting until 1965 with the passage of the Voting Rights Act. Nevertheless, Harriet Beecher Stowe, the white female author of Uncle Tom’s Cabin, brought slavery to the consciousness of our America. Her readers were mostly women. She took a bold and risky stand in pointing out how grossly inhumane slavery was. As a result, the wives of slave owners were able to convince some to change. These few persons have impacted large groups.

If we don’t know our history, we will surely repeat it. These words have been noted time and again. Protests are not nice. I would not be one of those brave students standing up to the police, armed with guns and firepower. However, those brave young adults who are a picture of diversity—black, white, Asian, Latino, Native American, and othersunited in their stand that changes in America are necessary.

Many of us employed at UMMC are the beneficiaries of brave men, women, and young people willing to risk everything for the possibility

of a better life for those coming behind them. If you are training at UMMC and don’t know Mississippi and American history, don’t be fooled by the impoverished patients we care for daily. Many impoverished persons fought for your seat at the University.

A national focus of selfishness was interrupted by the COVID-19 virus, making all of us realize what truly is necessary for survival. Shopping, sporting activities, daily restaurant eating, classroom gathering, manicures, pedicures, salon visits, and group worship/ church were taken away. This interruption allowed us time to think and be grateful for a connection to God, and what it really means to be one nation under God.

The fight with two monsters still rages. We confront two deadly enemies—a virus (COVID-19) and racism (the refusal to believe we are indeed one nation under God). Just imagine, if we were going about our usual pre-COVID activities, there would not be tens of thousands of people standing against racial inequities and police brutality. We must use every opportunity to make changes that move us in sync with one another, rather than drive us further apart.

I am grateful for the privilege of taking care of our patients, even though I may not recognize all of them 16 years from now. At the same time, I am more than a little concerned about my 19-year-old African American son. I pray that he will survive to be a mentor to others and be able to stand strong as a good, law-abiding, Godfearing American. n

Help and Hope

At Heart of Hospice our mission is to serve all hospice eligible patients the way they desire to be served.

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

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

For more information please call 1.844.464.0411 or visit heartofhospice.net

The Power of Physician Leadership

THOMAS E. DOBBS, MD, MPH STATE HEALTH OFFICER, MISSISSIPPI STATE DEPARTMENT OF HEALTH

It is impossible to overstate the value of physician leadership in Mississippi’s COVID-19 response. When it comes to trust, for patients or local communities, no voice speaks louder or clearer than that of our physician leaders. We are living through a remarkable time of rapidly changing scientific challenges, evolving therapies, difficult decisions, and misinformation. Through our embrace of medical science, coupled with compassion for those in our charge, we carefully guide our patients and lead our communities in the safest paths forward.

In April 2020, the Mississippi State Department of Health commissioned Jackson State University to conduct a survey of Mississippi residents to better understand their perspectives on COVID-19 and the challenges they faced. One of the most striking findings identified which sources are most trusted for medical information. Personal physicians, followed by CDC, lead the way as the most valued, far outpacing news and social media. This trusted position must be used to not only guide personal medical decisions but to help our communities make the best collective choices when we are forced to consider needed disruptions in our daily lives.

On numerous occasions we have witnessed trusted physician leaders help state and local leaders make the best decisions in support of our overall health. Whether guiding statewide policy or advising local leaders such as mayors and boards of supervisors, the physician’s voice is the necessary element that helps our political leaders make the tough decisions that must be made. I have witnessed many times our local leadership embrace difficult choices only when supported by the local physicians they believe in.

Added to the value of the individual physician’s voice is the collective voice, as best demonstrated by your Mississippi State Medical Association. MSMA has supported the COVID-19 response in ways that could be replicated by no other organization. As a guide for the Governor, the legislature, the Department of Health, and other state decision makers, this coordinated body is able to achieve what no individual ever could. We physicians must remember the power of our voices, both individually and collectively. Long after COVID-19 has become one of the numerous diseases medical science has conquered, we must be sure to raise our voices for those persistent problems that plague our state in addition to new ones that are sure to arise.

Table

MSMA in Orlando

before proceeding with the planned procedure is imperative. Careful anesthetic management, especially airway management and avoiding a pulmonary hypertensive crisis, is critical. Avoiding multiple procedures and anesthetics may be helpful. n

1. Pre-anesthetic evaluation

Ø Complete examinationincluding cardiac evaluation, airway assessment

Ø Multidisciplinary meeting involving surgeon, anesthesiologist, & intensivist to discuss perioperative plan

Acknowledgment

PHILIP L. LEVIN, MD; GULFPORT

Ø Open and honest discussion with family about the risks, expectations, and treatmentplan

Ø Complete anesthesia readiness,including immediate availability of difficult airway equipmentand emergency vasoactive drugs

We would like to thank Khalid Altirkawi, MD, FAAP for giving us permission to use his pictures for the figure.

References

T2. Logistics Readiness

Ø Pediatric anesthesiologist with experience in difficult airway management andcardiac anesthesia

1. Baum VC, O’Flaherty JE. Anesthesia for Genetic, Metabolic, and Dysmorphic Syndromes of Childhood. Third edition. Philadelphia: Wolters Kluwer; 2015.

2. Cereda A, Carey JC. The trisomy 18 syndrome. Orphanet J Rare Dis. 2012;7:81.

3. Intraoperativeanesthesia management

4. Immediatepost-operative management

5. General risk reduction strategy

Ø “Tight” physiological control during anesthetic, including meticulous attention to ventilation and prevention of the pulmonary hypertensive crisis

Ø Post-operative monitoring in intensive care unit and possible ventilatory support.

he year 2020 marks my 42nd year as a physician. My how medicine has changed! When I received my medical degree in 1978, Benadryl was only available as a prescription, the first prescription H1 blocker (Tagamet) had just been released, Dilantin was the only seizure medicine, and Thorazine the only antipsychotic. My teaching hospital in the Houston Medical Center had the only CAT scan in the state, family doctors put on casts and delivered babies, and nurses wore stiff white caps and stood to attention when doctors came onto the ward.

Ø Employ “one-stop shopping” strategy: performing more than one procedure under one anesthetic to reduce multiple anesthesia procedures

3. Meyer RE, Liu G, Gilboa SM, et al. Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study. Am J Med Genet A. 2016 Apr;170A(4):825-37.

4. Banka S, Metcalfe K, Clayton-Smith J. Trisomy 18 mosaicism: report of two cases. World J Pediatr. 2013;9(2):179-181.

5. Kosho T, Nakamura T, Kawame H, Baba A, Tamura M, Fukushima Y. Neonatal management of trisomy 18: clinical details of 24 patients receiving intensive treatment. Am J Med Genet A. 2006;140(9):937-944.

6. Batees H, Altirkawi KA. Trisomy 18 syndrome: Towards a balanced approach. Sudan J Paediatr. 2014;14(2):76-84.

7. Boss RD, Holmes KW, Althaus J, Rushton CH, McNee H, McNee T. Trisomy 18 and complex congenital heart disease: seeking the threshold benefit. Pediatrics. 2013;132(1):161-165.

exacerbating pulmonary hypertension.

Medicine constantly evolves. Every day it seems we are introduced to new medicines, new diseases, new techniques, and new attitudes. How do we, as physicians, keep up with these changes? I used to love the “drug dinners,” fine meals at fancy restaurants with lectures about new medicines. I used to listen to CME on my cassette player in my car. I used to receive CME packets in the mail that I would fill out. Now I mostly utilize Internet study options.

The Mississippi State Medical Association provides attractive alternatives. In May, physicians gather in Destin for “CME in the Sand.” August finds us gathering in Jackson for the annual state medical association meeting, which includes lectures as well as political events.

Muscle rigidity after use of succinylcholine has been reported in these patients.12 However, there is no known risk for malignant hyperthermia in children with Trisomy 18. Brief surgical procedures such as myringotomies can be managed by laryngeal mask airway (LMA).9 Regional nerve block techniques such as an epidural catheter or single shot caudal can be considered for lower abdominal or extremity procedures in combination with general anesthesia. Pain assessment in older patients in the post-operative period can be challenging due to severe mental retardation.

8. Courreges P, Nieuviarts R, Lecoutre D. Anaesthetic management for Edward’s syndrome. Paediatr Anaesth. 2003;13(3):267-269.

9. Bailey C, Chung R. Use of the laryngeal mask airway in a patient with Edward’s syndrome. Anaesthesia. 1992;47(8):713.

as well, such as the lectures on hypnotherapy and one about population studies.

10. Miller C, Mayhew JF. Edward’s syndrome (trisomy 18). Paediatr Anaesth. 1998;8(5):441-442.

11. Friesen RH, Twite MD, Nichols CS, et al. Hemodynamic response to ketamine in children with pulmonary hypertension. Paediatr Anaesth. 2016;26(1):102-108.

12. Matsuda H, Kaseno S, Gotoh Y, Furukawa K, Imanaka K. Muscle rigidity caused by succinylcholine in Edwards’ syndrome. Masui. 1983;32(1):125-128.

Author Information

My favorite was the November Florida event at Disneyworld in 2019 (and to be held at Universal Studios in 2020). The 2019 event featured 9 hours of CME lectures, beginning with an update on Medicaid billing. Disease updates included “Hypertension Emergencies,” “Pediatric Anemia,” and “Lower Extremity Ulcers.” I enjoyed the esoteric subjects

Conclusion

We propose several strategies for safe perioperative management of these patients. These patients should undergo a thorough preanesthetic evaluation and be managed by a pediatric anesthesiologist with experience in managing the difficult airway and cardiac anesthesia. Detailed discussion with the family about treatment options and risks

Orlando is a special place, at 52 million visitors a year, the most popular visitor destination in the world. For the 2019 event, I brought three generations of my family; for two of the children, it was their first-ever Disney adventure. MSMA offered special bonuses, such as a meet and greet including photos with Disney characters. With 2–3 hours of lectures a day, there’s plenty of time to enjoy the parks and get a taxdeductible trip full of education.

Hey, there are many innovations in medicine. What better way to keep current than with a family trip to Orlando? n

Assistant professor, Department of Anesthesiology, Texas Tech University Health Sciences Center, Lubbock, TX (Fishkin). Associate professor, Department of Anesthesiology, Levine Children's Hospital, Charlotte, NC (Sathyamoorthy). CRNA, Department of Anesthesiology, University of Mississippi Medical Center, Jackson, MS (Wardlaw). Professor, Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, MS (Reed). The authors report no financial disclosures or conflict of interest.

Corresponding Author: Semyon Fishkin, MD; Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 8182, Lubbock, TX 79430. Ph: (806) 743-2981 (semyonfishkin@gmail.com).

Table 2. Five Star Approach to the Anesthetic Management of Trisomy 18

2. Five Star Approach to the Anesthetic Management of Trisomy 18

Come Back on the Journey You Didn’t Know You Stopped – and Enjoy the Freedom You Didn’t Know You Could Have

FRANK HAN, MD, FAAP

As a cardiologist, I must rely on medical science and science literacy to best treat my patients. In the current era of an explosion of information, it can be difficult to tell fact from fiction. The best thing about science literacy is that it is available for everyone to share. All you need is a commitment to curiosity and evidence. Come with me on a journey to see how I deploy science literacy.

A 5-year-old boy comes into my clinic whose pediatrician heard an abnormal heart sound when examining him. As a committed scientist, I start on the path of observation, hypothesis, experiment, and conclusion. First, I listen to what the family tells me and luckily, this young boy has no particularly concerning symptoms. My checkup reveals two heart sounds that are not normal. As I have experience with this problem, I can identify several possible causes of abnormal sounds–just like a mechanic can identify noises in a car. I can check whether or not I’m correct by running an ultrasound. The test tells the truth—there is a hole in the heart. At this point, the answer is no longer subject to my opinion or belief system. I can then recommend a plan to fix the hole so this boy never has to worry about heart failure. The scientific method, the revolutionary way humans have developed to understand the world around them, is working.

In the same way, the scientific method can help in understanding the novel coronavirus. Let’s focus on the usage of facemasks. Our goal is simple—to determine whether or not facemasks are essential. Let’s go on the journey again of observation, hypothesis, experiment, and conclusions. The critical consideration is that coronavirus is invisible to the eye, yet potentially deadly. A cheap way of protecting against this virus is needed. The hypothesis is that putting plain cloth masks on everyone decreases the transmission of the virus. This experiment would reveal that wearing masks protects other people first, then the wearer of the mask second.

Let’s also dissect the claim that vaccines are harmful. Some infections are so intense that the body can sustain considerable damage before the disease is under control. As a pediatrician, it is my duty to prevent children from experiencing that damage. If I were encountering vaccines for the first time, I would again go down the path of observation, hypothesis, experiment, and conclusion. The starting point is that vaccines are designed to give the body a “practice” infection. It contains ingredients to provide shelf-life in the same way that you need to pickle a cucumber if you want it to last. It contains bits of cells because viruses require cells for copying. They don’t copy themselves without help. Then, to approach

the hypothesis and experiment, I reach for the vaccine clinical trials, which are all publicly available. These would reveal that the benefit of the vaccine involves not having to deal with the full infection, while the most common side effects include fevers and temporary sore arms.

Before we conclude, imagine for a second that the pertussis bacteria are purple, and a 2-year old has it. Imagine also for a second that your child was born with parts of her immune system missing, and you both had to go to the pediatrician’s office. You would see pertussis as a cloud of purple smoke surrounding the 2-year-old child. Every speck of purple dust has the potential of getting your child into deep trouble with pneumonia. Any parent would shield their child, especially if they had a previous condition, from that cloud of smoke. Every pediatrician thinks this when they advocate for vaccines. Vaccines, therefore, have a substantial benefit and a minimal risk. You may not necessarily personally get the disease a vaccine is made to protect you from. However, the neighbor, or your children, may suffer if these diseases are left unopposed. Again this is science literacy in action. Pediatricians have used a solid evidence base to provide recommendations. Once something is so well tested, it is no longer subject to anyone’s opinion or belief system. The best part is that anyone can do the same thing, as long as they are committed to following the evidence. Science literacy demands only curiosity and a commitment to the evidence.

It may not be obvious, but we are all born scientists. As small children, we explore the world around us as we play and experiment. As adults there are much higher stakes when science literacy is thrown away. Pandemics are harder to control than they should be. Patients get ill and die from trusting miracle cures on TV. Children continue to die from failure to receive vaccines. As a concerned cardiologist, I encourage everyone to rediscover the joy of science literacy. Bring back the skill you didn’t know you stopped using. Be amazed at how easy it is to bring science literacy into your life. You don’t need to have a substantial income and you don’t need to be a professional scientist. You just need to be curious. Don’t be deceived by anyone who cannot prove what they say using sound science. Let’s bring back science literacy, in the name of better health for all. n

Frank Han, MD, FAAP Adult Congenital Cardiologist Pediatric Cardiologist Jackson, Mississippi

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Dr. Robert Emmett “Bob” Brierty Jr.,  of Lake Charles, died on Jan. 31, 2019, in Jennings, Louisiana. Bob was born in Chicago, Illinois on December 27, 1930, the adopted son of Robert Sr. and Lorene M. “Babe” (Hager) Brierty. He was married to Patricia Anne Kelly in 1953; they have 7 children, 22 grandchildren, and 13 greatgrandchildren. In 1984 he married Joan Marie “Jody” Cangelosi in Lake Charles. As an officer, he served as a tissue pathologist in a MASH unit during the Vietnam War. As a civilian, he continued work in pathology from Texas to Georgia. He enjoyed watching all types of sports, particularly golf, and attending Catholic Mass daily after quickly completing the daily crossword puzzle.

Robert is survived by his wife, two sons, Robert (Nelly) Brierty III, Houston, Texas, Timothy (Ashley) Brierty, San Antonio, Texas; five daughters, Kathleen (Don) Dodson, Fort Worth, Texas, Colleen (Robert) Beasley, Snowmass, Colorado, Maureen (Peter) Boyce, Amarillo, Texas, Patricia Corsi, Plano, Texas, Margarett (Jason) Maxwell, Spring Branch, Texas; four stepsons, Paul (Maxine) Williams Jr., Indianapolis, Indiana, Thane Williams, Ocean Springs, Mississippi, Troy (Deborah) Williams, Jemez Springs, New Mexico, Avery (Racquel) Williams, Moss Bluff, Louisiana.; two stepdaughters, Deni Helms, Ocean Springs, Mississippi, Gabrielle (Jody) Treadwell, Jacksonville, Florida.; several grandchildren and great-grandchildren. He was preceded in death by one son-in-law, Ernest J. Helms Jr.

III (Kim), Currie Webster (Mark); sisters Anne Rainer (Jamie) and Kathryn Gates, grandchildren Heather, Austin, Davis, Faith, Jenna, great-grandchild Emma, nieces Gates, Mary, Becky, Amy, nephews Jay, Jimmy, Martin, Chris, great-nieces Emilie, Mary Kate, Maggie, Elizabeth, Molly, great-nephews Jamie, Matt, Trip, Charlie, and James William, and godchildren Rex, Grant, and Gracie.

Dr. Gates was an honor student, artist, and athlete. He played the piano, guitar, and alto saxophone. He enjoyed hunting, fishing, and archery. He took great pride in attaining the rank of Eagle Scout and the God and Country Award, as well as being a scoutmaster and mentoring scouts. He served as president and in other capacities of the Pushmataha Area Council Boy Scouts of America. Dr. Gates was awarded the Silver Beaver Award, the highest award presented to a civilian.

Dr. William “Bill” C. Gates, Jr.,  born in 1937, passed away on April 15, 2020, after an extended illness. He was able to remain with the comforts of his home for the majority of his illness, but he spent the last month and a half of his life in the good care of Dugan Memorial Home in West Point, Mississippi. The family is eternally grateful to the extended family, friends, and health care providers that have provided much love and support. Funeral arrangements have been entrusted to Memorial Gunter Peel Funeral Home & Crematory, 2nd Avenue North. A graveside service for immediate family was held at Friendship Cemetery on April 18, 2020.

Dr. Gates, son of W.C. and Mary Vickery Gates, was born and raised in Greenville, Alabama, and is survived by Linda Simmons Gates, his loving wife of 33 years, his children Jennie Paulding (Ben), Bill Gates

Since his youth, he wanted to become a doctor, and in high school, he was mentored by a local urologist. After graduation, he was awarded a Walter O. Parmer Scholarship and attended Vanderbilt University where he earned a B.A. degree and was a member of the Kappa Alpha Order. As Dr. Gates would say, “I went off to make a doctor.”

Throughout Dr. Gates’ busy professional life, he was known for his patient and family care, medical skills, bedside manner, political advocacy for patients, leadership, wit, creativity, athleticism, culinary arts skills, and love of outdoors. He was a friend, mentor, and teacher to many. He was referred to by some who knew him well as a humble “Renaissance man.”

Dr. Gates attended the Medical College of Alabama, where he served as editor of the class annual, and graduated with the first class required to pass national certification. After interning at Carraway Methodist Hospital, Birmingham, he completed his residencies in surgery and urology there and at Brooks Air Force Base, San Antonio, Texas. Dr. Gates served as a

William C. Gates, Jr, MD (November 02, 1937–April 15, 2020)

flight surgeon in the Alabama National Guard, earned the rank of major, and was a member of the Aerospace Medical Association.

Dr. Gates founded the Columbus Urology Group in 1968 and cofounded Starkville Urology Group in 1993. He served on the medical staff at hospitals in Lowndes, Oktibbeha, and Clay Counties. Due to health issues, he retired in 2005 after 36 years in private practice.

Dr. Gates served in numerous leadership roles of national, state, and regional professional organizations. He was president of the American Association of Clinical Urologists, the Mississippi State Medical Association, Mississippi Urology Society, Lowndes County Medical Society, and Prairie Medical Society. He was elected as a delegate to the American Medical Association, ending his tenure as vice chairman of the Mississippi delegation. He was also a member of the Urological, Southeastern Urological, Southern and American Physician Art Medical Associations. As an artist, he donated paintings for auction for medical student scholarships. He served in numerous other elected and volunteer positions in the medical community, including hospital

chief of staff and the physician representative to the Golden Triangle Foundation which funded indigent care.

Dr. Gates was a Fellow of the American College of Surgeons and the College of Emergency Physicians and a diplomat of the American Board of Urology. He published medical articles in the Mississippi, Alabama, and Urology journals of medicine, and his practice was selected to participate in several clinical research studies.

Dr. Gates was a committed civic leader. He was selected for the prestigious Mississippi State Medical Association Community Service Award, which recognizes an individual physician for outstanding contributions to the betterment of life in their community. He was elected President of Columbus Lowndes Chamber of Commerce and served on the Columbus Lowndes Economic Development Authority and Columbus Tourism boards. Dr. Gates supported Columbus Air Force Base, Lowndes County United Way, Mississippi University for Women, East Mississippi Community College, the Leukemia Society, and numerous other organizations and causes.

Dr. Kelly Eugene Hutchins,  of Laurel passed away on October 6, 2019, at the age of 85.

Kelly was born and raised in Calhoun County. He was an Eagle Scout and enjoyed hunting and fishing. After high school, he went to North West Community College, Samford University, and the University of Alabama (UAB) at Birmingham, where he received a degree in cytotechnology. After a successful career as a cytotechnologist, Kelly went on to receive a medical degree from the UAB. He was head of pathology at South Central Regional Medical Center for many years.

He was a member of the Krewe of Mid-City in New Orleans. He loved the Mardi Gras experience. He loved boating and fishing on his boat in the Gulf of Mexico for many years. He loved having a good time and had a wonderfully quirky sense of humor. He loved to read and especially enjoyed many Mississippi authors.

After retirement, he enjoyed country living, tinkering with his tractor, and spending time with family, including his many fur babies. He was a longtime member at Immaculate Conception Church.

He is survived by his wife Sheila Kyzar Hutchins; daughters Kathy Barber (Mark), Lisa Hartman (Gary), Laura Collins and Ashley Meyers (Tyler); grandchildren Joshua Thomason (Cricket), Sean Collins, Michael Collins, Lillian Collins, and Brennan Collins; and great-grandchild Willow Thomason. He was preceded in death by father Eugene Hutchins; mother Muriel Hutchins; and stepmother Meryl Hutchins.

Kelly Eugene Hutchins, MD (July 21, 1934–October 6, 2019)

Dr. Martin “Mart” McMullan, one of Mississippi’s most prominent cardiovascular surgeons, died on February 23, 2020 at Mississippi Baptist Medical Center from complications arising from dementia. He was 79 years old.

A memorial service was held on Thursday, February 27, at Northminster Baptist Church, and inurnment in the church’s columbarium followed immediately thereafter. Wright & Ferguson assisted with arrangements.

Bearcat, Choctaw, physician, brother, husband, father, grandfather, and friend, Mart lived his life to the fullest. Mart was born on November 26, 1940 to Patrick Hillard McMullan and Mary Elizabeth McMullan. He was joined nine years later by his beloved brother William Russell “Rusty.” Mart made lots of memories growing up in Forest, Mississippi in the 1940s and 1950s, including playing center in football for the Forest High Bearcats, hanging out with his friends at Kat’s Kave, and singing in his quartet with Jimmy Underwood, Rhett Mitchell, and Bob Shuttleworth. (Mart often joked that he got kicked out of the quartet when his friends went off to Millsaps and upgraded their melodist.)

Upon graduating from Forest High School in 1958, Mart enrolled at Mississippi College (MC) in Clinton, Mississippi where he enlarged his circle of friendships. Among other relationships that Mart cherished, he met Ray “Razor” McPhail who would remain his partner in crime for the rest of his life. Mart also relished his days playing center on the Choctaw football team where the influence of team trainer, Van “Doc” Quick, helped lead Mart toward his career in medicine.

After graduating from MC in 1962 he enrolled as a medical student at the University of Mississippi Medical Center (UMMC) in Jackson. He also married his high school sweetheart Lyllian Lee on August 11, 1963. Their 56 years of marriage produced three wonderful children–M’lee, born in 1966, Misti, born in 1969, and Mart, born in 1972, and nine grandchildren, who, as the proverb say, have been “the crown of the aged.” Mart was proud of his children and absolutely loved being a

grandfather. If any of his grandchildren had an event, Mart was going to attend and was going to be enthusiastic and vocal in his support (a trait he passed down to his son….). The times he spent with his grandchildren at hunting camp, on the ski slopes, and at sporting events were sources of tremendous joy for him and them.

At UMMC Mart’s circle of friendships widened even further. During his first year as a medical student he met Joseph Edwin “Joe Ed” Varner, Jr., and James Edward “Jimmy” Keaton, among others, with whom he would share the ups and downs of life for the next 50+ years. Thus began the enduring passion of Mart’s professional career, the practice of medicine, pursuit of lifelong learning, and saving of lives.

Mart remained at UMMC after graduation in 1966 and completed a surgery internship and residency under the legendary Dr. James D. Hardy from 1966–1971. Dr. Hardy’s influence on Mart cannot be overstated, and Mart considered himself fortunate to be one of the “Hardy boys.”

Mart continued his postgraduate education at the Mayo Clinic in Rochester, Minnesota, completing a thoracic and cardiovascular surgery residency in 1973. He and Lyllian then moved their young family back to Jackson where Mart joined the Cardiovascular Surgical Clinic (CSC). He would practice with CSC for 32 amazing years.

On his retirement from the O.R. at age 65, Mart wanted to give back to the place that had shaped his life and took a position as professor emeritus of surgery at UMMC. For the next ten years, Mart served there in various capacities, including Senior Advisor to the Dean of the School of Medicine and Vice-Chancellor for Health Affairs. Mart was thrilled with the opportunity to mentor young doctors and recruit accomplished physicians to come to Mississippi. He widened his circle of friends yet again, establishing a beautiful friendship with, among others, Celeste Eason, who “kept Dr. McMullan in line” and continued to serve him after he retired from the Medical Center.

His professional accomplishments are too numerous to list. Among others, he was a fellow of the American College of Surgeons and the American College of Cardiology; authored multiple papers, served as Chief of the Baptist Hospital Medical Staff, and was the first physician to serve as Chairman of the Board of Trustees for Mississippi Baptist Health Systems.

But his zest for life and the friendships he developed along the way are what Mart will be remembered for most. He especially cherished his times with his Float Road hunting buddies and all his cousins, aunts, and uncles at McMullan Family Farms.

Mart is survived by his wife Lyllian Lee McMullan, daughters M’lee McMullan Williams (Kelley) and Misti McMullan Crisler (Bob), son Martin Brian McMullan (Holly), and ten grandchildren: James Kelley Williams, III (Jake), Martin Zachary Williams (Zach), Anna Katheryn Williams, Patrick Luke Williams, Robert Blanton Crisler, IV, John Martin Crisler (Jack), Lyllian Caroline Crisler, Connor Mart McMullan, Samuel Lee McMullan, and William Robert Seymour.

Martin “Mart” McMullan, MD November 26, 1940–February 23, 2020

Dr. Bernadette Elaine Sherman-Love,  was born on October 13, 1947, at Alcorn State University in Lorman, Mississippi, the daughter of Charles and Lura Wheaton Sherman. Her early education began in Chicago where she graduated with honors from Hyde Park High School in 1965. Dr. Sherman continued her education at YMCA Community College in 1967, Roosevelt University

(1967–69), and Fisk University (1969–71) where she received her bachelor’s degree in psychology. She then aspired to attend medical school at Meharry Medical College in Nashville, and there she received a medical degree in Obstetrics and Gynecology. Dr. Sherman then attended Providence Hospital where she did her residency as well as internship. She received her MBA in Health Care Management from the University of Phoenix.

Dr. Sherman had her private practice in Natchez from 1980–2001. After her private practice, she served at Todd Medical Center, Jefferson Comprehensive Health Center, and Alcorn School of Nursing. Dr. Bernadette Sherman became the first African American Chief of Staff at Natchez Regional Hospital in 1991. Other special awards and honors include Chairman of the Tissue & Transfusion Committee, Chairman of Outpatient Surgical Committee, and Chairman of Prenatal Committee. She was a member of Christian Hope Baptist Church where she served in the choir. She held memberships with the Mississippi Medical Association, Delta Sigma Theta Sorority, Inc., the Links, Inc. She enjoyed singing, playing the piano and organ, swimming, and skating.

She was preceded in death by her parents and her brother, Charles Evans Hughes Sherman. She is survived by her husband, Clarence Love; son, Stephen Love, Sr. and wife Tiesha; grandson, Stephen Love, Jr. and a host of cousins and many friends throughout the nation.

Robertson and Roberta Darville Robertson, and was the eldest of four children. His siblings include Clyde Darville Robertson (predeceased), Kathryn Robertson Stoltz of Pearl River, Louisiana, and Jon Hobson Robertson, M.D. of Memphis, Tennessee. He graduated as cosalutatorian of Messick High School, Memphis, Tennessee, and attended two years at Southwestern University (now Rhodes College), Memphis, Tennessee. He completed medical school at the University of Tennessee College of Medicine in Memphis, Tennessee in 1954, followed by a residency in Neurosurgery at Semmes Murphy Clinic, Memphis, Tennessee.

Dr. James Thomas Robertson,  of Asheville, North Carolina, died on June 30, 2019, in Memphis, Tennessee, at the age of 88. He was born April 5, 1931, in McComb, Mississippi to his parents, Clyde Aubrey

Dr. Robertson was a retired neurosurgeon and Professor Emeritus of the Department of Neurosurgery at the University of Tennessee College of Medicine in Memphis, Tennessee. He was Professor and Chairman of the Department of Neurosurgery for 25 years and trained over 50 neurosurgeons. He was very active in organized neurosurgery, serving as President and Founder of the Society of University Neurosurgeons and President of the Congress of Neurosurgeons, the Academy of Neurosurgeons, and The American Association of Neurosurgery. He was a member and subsequent Chairman of the Residency Review Committee of Neurosurgery, Vice Chairman of The Society of Neurosurgeons, and the American Board of Neurosurgery. He was active in clinical research and held grants in stroke research from the Neurological Institute of the National Institutes of Health, serving on the Advisory Council from 1984–1988. He published over 300 scientific papers on various neurosurgical topics, was a member of several scientific journals’ editorial boards, and participated in

Bernadette Elaine Sherman-Love, MD (October 13, 1947–October 8, 2019)

James Thomas Robertson, MD (April 5, 1931–June 30, 2019)

clinical research protocols on strokes and brain tumors at the National Institutes of Health. He was an active member of the state chapter and the national American Medical Association and the American College of Surgeons. In Memphis, he was Chief of Neurosurgery at Baptist Memorial Hospital and Elvis Presley Trauma Center.

Dr. Robertson served in the United States Air Force from 1956–1964 as Chief of Neurosurgery at Travis Air Force Base, California and Assistant Chief at Lackland Air Force Base in San Antonio, Texas, where he was discharged as Major. In 1989 he joined the Navy Medical Reserve and retired as Captain in 2003. He was on active duty briefly in the First Gulf War.

He was a member of The University Club, Memphis Wine & Food Society, and Commanderie de Bordeaux.

The Robertson Family were members of Evergreen Presbyterian Church for 50 years. Later in his life, Dr. Robertson became a member of St. Giles’ Chapel at Deerfield Episcopal Retirement Community in Asheville, North Carolina.

He is survived by his wife of 66 years Valeria Brower Robertson of Asheville, North Carolina; and their five children: James Thomas Robertson, Jr, of Asheville, North Carolina (Anna), Elizabeth Robertson Morris of Olive Branch, Mississippi (David), Clay Darville Robertson of Hendersonville, North Carolina, Roberta Robertson Beach of Nashville, Tennessee (Clay), and Daniel Payne Robertson, M.D. of Ocala, Florida. He was predeceased by his daughter Catherine Robertson Newman of Olive Branch, Mississippi. He is also survived by 12 grandchildren: Anne M. Fairey (Chris) of Memphis, Tennessee; Elizabeth M. Bass (Jesse) of Olive Branch, Mississippi; James T. Newman of Jacksonville, Florida; The Rev. Robert T. Newman of Fayetteville, North Carolina; Kathryn E. Beach of Chicago, Illinois; Leigh T. Robertson of Columbus, South Carolina; T. Carl Robertson of Asheville, North Carolina; Henry T. Beach of Nashville, Tennessee; Lauren F. Robertson of Miami, Florida; Payne D. Robertson of Columbus, South Carolina; Alison W. Robertson. of Ocala, Florida; and Emily C. Beach of Nashville, Tennessee; and six great-grandchildren: Alice C. Fairey; Emma R. Fairey, Elizabeth (Betsy) B. Bass, Eleanor A. Bass, George T. Fairey, and Clara L. Bass.

20, 1937–June 20, 2020)

Dr. William Briggs Hopson, Jr., wasborninDelhi,Louisiana in 1937. He departed this life on June 20, 2020, when he joined his parents,thelateMaryJaneandW BriggsHopson,Sr.,inheaven.

A graduate of the University of Mississippi, he received his medical degree from the University of Tennessee in Memphis, where he served as chief resident and associate professor of surgery.

He began his medical career in Vicksburg, Mississippi at the Street Clinic in 1967. He continued his medical work in Vicksburg until his retirement in 2018. During that time, he served as chief of staff, president (and chairman of the board) of the local hospital and clinic, respectively. He was elected as a fellow to the American College of Surgeons and a diplomat to the American Board of Surgery. He received numerous accolades throughout his career.

His passion for trauma medicine resulted in him being named State Trauma Director. In this capacity, he was a representative to the American College of Surgeons for over 25 years. He worked with the committee to create national guidelines for Advanced Trauma Life Support. He taught the first ATLS course in the state of Mississippi and taught ATLS courses around the county. He also served 27 years as the State Medical Director of Emergency Medical Services.

Governor Kirk Fordice tapped Dr. Hopson to chair the State’s Committee on Health Care. During this time, he was instrumental in passing Mississippi’s ATLS law, creating levels of trauma centers throughout the state. Governor Ronnie Musgrove appointed him to serve on the Mississippi State Board of Health. He served as president of the Mississippi State Medical Association from 1999–2000 and was a delegate to the American Medical Association for 8 years. Dr. Hopson was a former associate professor at the University of Mississippi Medical Center and was named to the 2016 Medical Center Hall of Fame. He served his country for 18 years, ten of those being command surgeon of the 412th Army Engineering Command. Dr. Hopson devoted a large portion of his time to his alma mater, the University of Mississippi. He was elected president of the Alumni Association from 2001–2003. He was later selected to the Alumni Hall of Fame.

He served as Chairman of the Board of the Miss Mississippi Organization for over 25 years. He and his wife, Pat were instrumental in preparing representatives for the Miss America Pageant and providing millions of dollars of scholarship for the education of young women throughout the state. In 2017 he received the Miss Mississippi Organization Lifetime Achievement Award.

William Briggs Hopson, Jr, MD (September

Dr. Hopson was active and supportive of many charities in Vicksburg. He was a loyal and active member of Crawford Street United Methodist Church as chairman of the administrative board and Sunday school teacher for over 50 years. He served on numerous local boards including the Red Carpet Bowl Committee (Chairman), Hinds Community College, Merchants Bank, and RiverHills Bank. He proudly served as team doctor for Warren Central High School for many years. Dr. Hopson gave generously of his time and resources to help countless people throughout the community, state, and nation.

He is survived by his wife of sixty-two years, Pat Hopson; his brother Jimmy Hopson (Sue) of Delhi, Louisiana; children Karen Hopson Hall (Reggie) of Dallas Texas; Kathy Hopson Ricks (Kerry) of Vicksburg, Mississippi; Senator W. Briggs Hopson III (Ali) of Vicksburg, Mississippi; and Jay Hopson (Michelle) of Hattiesburg, Mississippi; and grandchildren Anna Kate Moen Modisett (Brian), Tanner Hall, Neal Ricks, Travis Hall, Liam Hopson, Walt Hopson, Wesley Ricks, Hyde Hopson, Hannah Hopson, and Jane Hopson.

Dr. William Joseph Burnett, died on May 13, 2020, at home surrounded by family in Oxford, Mississippi, at the age of 80. He was the husband of Martha Grant Burnett, his beloved wife of 59 years.

While Joe was involved in his profession and community in many ways, his top priority was always his family. He is survived by his wife, his children Elizabeth Burnett (Ed Pyle), Margaret Burnett (JasonWolfkill), William Joseph Burnett, Jr. (Joanna), and Kathryn Elliott (Allen Elliott); his grandchildren Grant, Thomas, and Annalise Burnett, William, Miller, and Lock Elliott, and Megan, Brandon,

and Kate Wolfkill; numerous nieces and nephews; his sister Mary Burnett Sims; and many dear friends whom he counted as family. He was predeceased by his parents, Jesse and Florence Burnett, and his brothers, Jesse L. Burnett and John B. Burnett.

Born in Charleston, Mississippi, Joe earned his undergraduate degree from the University of Mississippi and his medical degree from the University of Mississippi School of Medicine.

After completing his internship in Memphis, Tennessee, Dr. Burnett practiced general medicine in Grenada, Mississippi. Following a residency at the University of Tennessee Medical Center and in collaboration with the late Dr. Bo Murry, Dr. Burnett began his otolaryngology practice in Oxford, Mississippi. He created the Ear, Nose, and Throat Clinic of Oxford from which he retired in 1988. After his retirement from the practice of medicine, Dr. Burnett became the Director of the Board of Medical Licensure for the state of Mississippi. Dr. Burnett was a Fellow of the American College of Surgeons, the American College of Otolaryngology, and the College of Facial Plastic Surgery.

Always committed to serving and stepping into leadership, Joe served as the Commander of Sigma Nu Fraternity at the University of Mississippi, a captain in the Mississippi National Guard, and a leader in chartering Oxford Medical Ministries. Dr. Burnett also served as Board Chair and President of the Mississippi State Medical Association and was an alternate delegate to the American Medical Association. Joe was a lifelong Presbyterian who attended the first session at Camp Hopewell. As a member of the First Presbyterian Church in Oxford, Mississippi, he served as an elder and was a faithful member of the men’s Sunday school class. Dr. Burnett chaired the committee that planned and built the First Presbyterian Church Fellowship Hall. Through First PresbyterianOxford, he and Martha were able to serve in Haiti with the church’s Medical Missions team.

William “Joe” Joseph Burnett, Sr., MD (March 27, 1940–May 13, 2020)

Dr. Wesley Leroy McFarland, Sr.,  of Bay St. Louis, Mississippi passed away Tuesday, June 25, 2019, in Biloxi, Mississippi, at the age of 94. Dr. Wesley McFarland served in the United States Navy at 19 years of age. He was granted an Undergraduate Degree in Biology from Ole Miss University in Oxford, Mississippi and a Doctorate Degree in General Medicine from Tulane University in New Orleans, Louisiana. He was a wonderful and loving father, grandfather, great-

grandfather, and uncle who will be sadly missed by his family and friends. He was preceded in death by his wife, Rosemary McFarland; son, Wesley McFarland, Jr.; daughter, Rosemary Heard, and brother, Earl McFarland. He is survived by his two daughters, Margo Keel of Bay St. Louis, Mississippi and Sarah Leopold of Diamondhead, Mississippi; five grandchildren, Celeste, Regan, Ryan, Wesley, and Brett and fourteen great-grandchildren.

Dr. Keith W. McLarnan, passed away on Friday, June 19, 2020 at The Claiborne, Hattiesburg, at the age of 85. Services were held on Friday, June 26, 2020, at Westminster Presbyterian Church and inurnment at the Columbarium at Westminster Presbyterian Church.

Keith is survived by his wife of 32 years, Carolyn McLarnan; his stepmother, Ruth McLarnan; his sister, Janice Kaye Byers; cousins, nieces and nephews, and great-nieces and nephews.

Keith was a retired pediatric neurologist who was well-loved by his patients and colleagues. His love of music and history was well known by friends and he will be greatly missed by those who knew him.

The Great Influenza: The Epic Story of the Deadliest Plague in History

MICHAEL C. TROTTER, MD, JMSMA BOOK EDITOR

Given the current COVID-19 pandemic crisis that we are all experiencing and navigating, it is especially timely to consider John M. Barry’s award-winning and best-selling 2004 book, The Great Influenza: The Epic Story of the Deadliest Plague in History. Barry, as you may recall, wrote another award-winning and best-selling book in 1997, Rising Tide: The Great Mississippi Flood of 1927 and How It Changed America. The Great Influenza is the comprehensive story of the 1918 Spanish flu pandemic set against the backdrop of World War I.

Barry provides the appropriate background for the story by examining the rise of science and medicine and its evolution in America to a world leadership position. He illustrates this through the founding of Johns Hopkins and the rationale behind it, as well as tracing contributions of such familiar names as William Welch, John Shaw Billing, and Simon Flexner. Barry then presents his case for Haskell County, Kansas as the birthplace for the pandemic that would eventually kill 50–100 million people worldwide. The disease infiltrated military training camps and then onto France and Europe with the troops. Surgeon General of the Army William C. Gorgas had prepared as best he could under the circumstances, but the unknown was simply too great. Parallel to the pandemic’s journey is the story of the scientific race to identify a cause and produce a vaccine. Prominent scientists, Paul Lewis, Oswald Avery, and others, have their stories woven through the main fabric of the book and illustrate the transformation of such entities as the Rockefeller Foundation and the Carnegie Foundation.

The disease itself was a formidable adversary: highly contagious, occurring in waves, increasing its virulency, and indiscriminately killing young and old—especially the young and healthy. It tested not only science and medicine but their intersection with politics and history. Prominent examples in the book are the September 1918 Liberty Loan parade in Philadelphia with the subsequent devastating impact on the city’s population and the suppression of public information about the disease in an effort to keep the country solely focused on the war effort. These are told with gripping realism. After the third wave, the pandemic dissipated. By the early 1930s, a viral etiology was determined. The book concludes with lessons learned and warnings for the future. Those warnings are eerily familiar and incredibly poignant as we read Barry’s words of 2004 from the context of our position in 2020. We are living these warnings and lessons today. As has been said before, those who fail to learn from history are doomed to repeat it.

Fortunately, and not surprisingly, Barry has re-emerged in the media today with expert status. In an interview on April 29, 2020, he noted that further research after the book’s publication revealed China to be the most likely source of the 1918 pandemic, although Kansas remains a realistic possibility. The exact location of origin will likely never be known. Today’s COVID-19 pathology is very similar to that of 1918’s Spanish flu. Hand washing, social distancing, wearing masks, and supportive care are basic pandemic tenets today as they were then.

Many of you may have previously read this masterful work. If so, it is worthwhile to consider re-reading it. The book is thorough, meticulously researched, and reads very well. I highly recommend it. n

LIBERTY GROVE TO ASYLUM HILL TO ASYLUM HEIGHTS TO ASYLUM TO FONDREN: A STORY OF THE STATE INSANE ASYLUM AND ITS SURROUNDING COMMUNITY IN CENSUS RECORDS, MAPS, PHOTOGRAPHS, AND POSTMARKS The historic Jackson neighborhood now known as Fondren was the original site of the Mississippi State Lunatic Asylum. After its creation by the state legislature in 1848, the asylum’s commissioners purchased a tract of 140 acres of land two miles north of Jackson off Canton Road (which is now the present location of the University of Mississippi Medical Center). With intent, the institution was located well outside of the then Jackson city limits for both the isolation of its patient population and the benefit of the institution’s agricultural efforts. Despite this distance, being situated at the fork of State Street (then Tougaloo Road) and Canton Road, it remained close enough to the capital city for its many jobs to be filled by Jacksonians. Eventually, the Jackson hospital would reach a census of over 2,000 patients with its grounds spilling over more than 1,300 acres (which were farmed by the patients), and its varied workforce totaling hundreds, many of whom lived on the asylum grounds or nearby. See various images of the asylum in its bucolic setting in the 1890s and early 1900s.

After the Civil War, the local plantations on Jackson’s northern edge around the asylum, including the 5,000-acre Garland estate, began to be broken up and the land parceled into smaller lots and developed for residences, businesses, and farms. An ex-slave, a native to Tennessee named Isham Cade (b.1834), is known to have purchased land in the Fondren area. The 1870 census records him living on the asylum grounds with his wife and children, with him serving as a baker and his wife Mariah as a laundress, listed among the other workers (watchmen, physicians, storekeepers, dairymen, cooks, firemen, attendants, nurses, gardeners, etc.) alongside its respected Superintendent Dr. William Compton and his family, who also lived on the grounds. Cade’s race is recorded as “mulatto.” Old plats reveal an “Isham Cade Survey” (subdivision) in the

current Fondren area, dating to the late 1870s, which supports an oral tradition that in this area Cade purchased, a small African American neighborhood developed which included houses, a school, and a church and came to be called “Asylum Hill” (which was the high ridge above the asylum on North State Street). That area of current North State Street from the Old Canton fork to the Pix/Capri Theatre area was once called “Cade’s Alley,” after this once asylum baker. Cade’s enduring legacy remains Cade’s Chapel Missionary Baptist Church, a church for former slaves, which he helped establish at the end of Cade’s Alley in 1880 on Asylum Hill and which operated at 3005 North State Street (which was near the present-day intersection with Duling Avenue) from 1903-1929. Cade’s Chapel then moved to another site and continues to operate as a vital church in the Jackson area. The 1880 census does not record the name “Asylum Hill” for the area, but rather places the asylum and the evolving village around it in what was called the “Liberty Grove Precinct.” Thus, it appears this large undeveloped area outside Jackson’s limits was first called “Liberty Grove,” a name perhaps with connotations for the liberation of slaves and their new post-Civil War lives. The census of that year paints the community of Liberty Grove as the asylum and a surrounding biracial hub of working-class laborers, operating their own small farms or having jobs in the nearby asylum or businesses helping sustain it. (A 1905 map of Jackson does reveal a “Liberty Grove Church” located two miles northwest of the Asylum, which may have bestowed the name to the precinct.)

Around 1893, two Fondren brothers, Edward Douglas and David Fulton, purchased a large tract near the asylum and began to develop the high ground northwest of the asylum with several different enterprises, including the wood-frame D. F. Fondren & Co. General Merchandise & Fancy Grocery. Their arrival signaled the evolution of the area away from a biracial working-class community into a more upper- and middle-class white community, although Cade’s Chapel would endure for decades as evidence of the community’s biracial roots. This bustling area (which included not only the current Fondren area but also the insane asylum itself) soon came to be called “Asylum Heights” in city directories (corrupted in local speech as ‘Sylum Heights), with an Asylum Heights Road north of the asylum grounds and even an Asylum Heights Episcopal Church established. This village catered specifically to the hospital and the dependent community which had grown up around it, as well as the many travelers going north and south, to and from Jackson, on these two major travel arteries (North State Street and Old Canton Road). In the manner of most small communities, Asylum Heights soon created its own post office as part of its distinct identity and for functionality. National postal records reveal that a post office by the abbreviated name of “Asylum” was established on May 23, 1898, with David Fulton Fondren (1870-1944) as the first postmaster (see the Asylum postmark). Although the post office was Asylum, the community would continue to be called Asylum Heights for years. The post office itself operated in the Fondren general store and grocery at 2715 North

State Street, which was on the high ground of North State Street north of the spur and south of Taylor Street above the fork. There exists an early photograph of the store, dating to 1915-1920, which has a “post office” sign on its front. Asylum Heights appears to have continued as the name of the community until November 7, 1916, when the post office changed its name from “Asylum” to “Fondren.” For a brief two decades, this post office mutation also affected the address of the insane hospital, as can be seen by this official piece of stationery (Superintendent Dr. C. D. Mitchell’s) which records its location officially as not Jackson, but rather Fondren, with a similar Fondren postmark. Fondren’s post office was maintained in the Fondren Grocery from November 8, 1916 to October 31, 1931, when it was discontinued as an office, absorbed by Jackson. (The grocery would close in 1953.)

Nineteenth and early twentieth century maps show the insane asylum situated well outside the city limits on the north-directed Canton Road (which became State Street), which paralleled the Illinois Central rail line. After the Civil War, the railroad built a spur to serve the asylum property, providing a route for incoming supplies and outgoing timber and agricultural products. That rail spur, called the Asylum Switch, ran from the main line at Mill Street across the current stadium grounds crossing North State Street just south of the fork with Old Canton Road and heading back into the asylum grounds. This can be seen on this 1925 map. The physical address of the asylum was considered the intersection of State Street with Asylum Road, which began at State Street heading west to the Illinois Central Railroad along Millsaps’s northern boundary. Old Asylum Road would become Woodrow Wilson Avenue in the 1920s, eventually extending east from State Street toward the Pearl River. The Jackson streetcar system also extended its line north on State Street to the hospital ending at Fondren.

Significant change was occurring in the Fondren area in the 1920s. The vast Asylum lands and Millsaps College had long buffered the city’s development north, resulting in and insulating the Fondren suburb. However, as the twentieth century evolved, Jackson’s population boomed and residential developments such as Woodland Hills pointed Jackson’s growth north and would not be stopped. The City of Jackson would annex the asylum and the land immediately north of it in two bites in 1917 and 1928, although the Fondren address would persist at least until the early 1930s. In 1926, the legislature voted to move the hospital from Fondren, appropriating $2.5 million for a new hospital to be built on 3,333 acres of state-owned land “near Howell” in Rankin County. The 1926 legislation also dropped “Insane” from the hospital’s title, and it became simply “Mississippi State Hospital,” which is reflected on this 1931 envelope. However, because of a significant drop in state income during the Depression and ongoing political squabbles, the hospital’s move from the old site did not occur until 4 March 1935. The University of Mississippi Medical Center would come to occupy the site in the 1950s, resulting in a rebirth of the area. Although Fondren’s own post office would be shuttered in 1931, a community post office would be reestablished less than a block away from the original location on November 16, 1946 as Fondren Station, a part of the Jackson postal system. If you have an old or even somewhat recent photograph which would be of interest to Mississippi physicians, please send it to me at lukelampton@cableone.net or by snail mail to the Journal.

— Lucius M. “Luke” Lampton, MD; JMSMA Editor

Edited by Lucius Lampton, MD; JMSMA Editor

[This month, we print another inspiring poem of appreciation by John D. McEachin, MD, FAAP, a Meridian pediatrician and the Journal’s unofficial poet laureate. He recently penned this fine tribute to one of UMMC’s stellar Pediatric Staff Division Chiefs—Paul H. Parker, MD, currently UMMC professor emeritus of pediatric gastroenterology. A son of a physician and a Meridian native, Parker served as long-time chief of UMMC’s division of pediatric gastroenterology and for many years was the only pediatric gastroenterologist in the state. Graduating from the University of Mississippi School of Medicine, he completed an internship, residency, and chief residency in pediatrics at UMMC. He then completed a fellowship in pediatric gastroenterology at Vanderbilt University, after which he came to UMMC and started its pediatric gastroenterology program in 1981. He was on call for more than 17 years by himself and served on UMMC’s pediatric faculty for more than three decades, caring for the children of the state and training two generations of physicians. His students and residents affectionately called him “Poo Poo Parker” due to his emphasis on the importance of a stool sample in making a diagnosis. Upon his retirement in 2012, UMMC created an endowed chair in his honor: The Paul H. Parker Chair of Pediatric Gastroenterology. For more of Dr. McEachin’s wonderful poetry, see past JMSMAs. To contact the poet, email him at mceachinmd@bellsouth.net. 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.

Paul H. Parker, MD

All in a Day’s Work

(A Liver Transplant)

Walter Wayne had just turned twelve, When he came to the office For a check on that liver–Failing! Long his nemesis.

On this day he was jaundiced— Extremely, to say the least. We knew the day was coming, But now, face to face, the beast!

Decision time was with us; Liver transplant, his dire need. Paul Parker was called, post haste!

He knew this boy, and agreed!

The events that then ensued Were all conducted with speed! Doctor Parker was waiting—

In Jackson, prepared? Indeed!!

He had reached Doctor Starzl— Pittsburgh! “Liver! We need one!” Starzl, the transplant king, blinked!

“We just happen to have one!”

Paul Parker at UMC

Had arranged the urgent flight. Mom and Walter Wayne joined Doc— Family on board at first sight! Meridian, Nine A.M. Left Jackson about Noon! Zoom!

P.M. transplant in Pittsburgh!

The next day, “post op” playroom!!

John D. McEachin, MD, Meridian

*This episode speaks for itself! Dr. Paul Parker, a longtime Chief of Pediatric Gastroenterology at UMC, was a trusted and skilled consultant. This case represented the only pediatric patient seen by our group that ever required a liver transplant. What a fascinating, whirlwind episode, and such a distinct privilege to have been associated with this special physician and friend!