Faculty Bibliography

An observational cohort study was conducted with data from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort to investigate weight gain among virologically suppressed people with HIV (PWH) switching to regimens containing tenofovir alafenamide/emtricitabine/ (TAF/FTC). Virologically suppressed, ART-experienced PWH switching to TAF/FTC with either darunavir/cobicistat (DRV/c), elvitegravir (EVG)/c, dolutegravir (DTG) or bictegravir (BIC) were selected. Cox proportional hazards models were used to assess the risk of excessive weight gain (i.e. ≥5% gain within 28 weeks or ≥10% within 54 weeks), by regimen. A linear mixed effects model with random intercept and restricted cubic splines on time was used to assess continuous changes in weight. Confounding was controlled for with both inverse probability of treatment weighting and traditional covariate adjustment. Among 5,536 PWH, 18% gained ≥5% of their weight within 28 weeks, and 9% gained ≥10% within 54 weeks. There were no differences in the risk of excessive weight gain by regimen, although there was a non-statistically significant 20% increase in the risk of gaining ≥10% within 54 weeks with all regimens compared to DRV/c. Throughout follow-up, the mean predicted weight remained fairly constant, with no notable differentiation between regimens. Expected weight gains ranged from +0.2 kg to +0.3 kg at 6 months and from +0.5 kg to +0.6 kg at 24 months. In conclusion, in this study of virologically suppressed, ART-experienced PWH switching to regimens containing TAF/FTC and either DRV/c, EVG/c, DTG or BIC, up to 18% experienced excessive levels of weight gain. However, no statistically significant difference was observed across regimens.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is causing an emerging global epidemic. The global burden of disease (GBD) study estimates the burden of NAFLD in 203 countries and geographic areas across the world, providing a unique opportunity to understand the landscape of this disease.
Method(s): Prevalence, mortality, and disability-adjusted life years (DALYs) of NAFLD from 1990 to 2019 by region and country in all sex and age groups were collected from the Global Health Data Exchange (GHDx) results tool (Available from http://ghdx.healthdata.org/gbd-results-tool). DALYs are the sum of years lost due to premature death and years lived with disability. The socio-demographic index (SDI) categorizes countries and geographic areas by development (low, low-middle, middle, high-middle, and high).
Result(s): Between 1990 to 2019, the global prevalence of NAFLD increased from 10.9% to 16.6% (increased by 52.6%; linear regression beta-coefficient 0.2, P < .001). In 2019, an estimated 1.3 billion people were affected by NAFLD worldwide. Mortality attributed to NAFLD increased from 93,000 to 169,000. DALYs of NAFLD increased from 2.7 million years to 4.4 million years. Significant uptrends were observed in all SDI regions, more prominent in the middle SDI regions (Table). Changes in the prevalence of NAFLD by countries are depicted in Figure. All but three countries demonstrated an increase in the prevalence of NAFLD. More notable increases (>=10%) were mostly observed in North African and Middle Eastern countries.
Conclusion(s): NAFLD's prevalence increased by more than 50% globally from 1990 to 2019. The mortality and DALYs also increased. The increase in NAFLD prevalence is more prominent in countries with middle SDI and countries in North African and Middle Eastern regions, possibly due to changes in lifestyle in these areas over the past 30 years. (Figure Presented)

SOURCE CITATION:JAMA. 2022;327:2326-33. 35727271.

BACKGROUND:Pediatric MetS prevalence varies due to lack of consensus on evaluative criteria and associated thresholds, with most not recommending a diagnosis <10 years. However, MetS risk components are becoming evident earlier in life and affect races and ethnicities disproportionately. OBJECTIVES:To compare the prevalence of MetS based on existing definitions and elucidate racial- and ethnic-specific characteristics associated with MetS prevalence. METHODS:The baseline and follow-up samples included 900 and 557 children 7-10 years, respectively. Waist circumference, BMI percentile, blood pressure, fasting plasma glucose (FPG), insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured. Agreement between MetS definitions was quantified via kappa statistics. MetS and risk factor prevalence and the predictability of metabolic parameters on MetS eight months later was evaluated via logistic regression. McFadden pseudo-R2 was reported as a measure of predictive ability, and the Akaike information criterion evaluated fit of each model. RESULTS:The baseline sample was 55.0% male and 71.6% Hispanic, followed by non-Hispanic White (NHW) (17.3%) and non-Hispanic Black (NHB) (11.1%), with an average age of 9.2 years. MetS prevalence ranged from 7.6% to 21.4%, highest in Hispanic (9.0%-24.0%) and lowest in NHB children (4.0%-14.0%). Highest agreement was between Ford et al. and Cook et al. definitions (K = 0.88) and lowest agreements were consistently with the International Diabetes Federation criteria (K ≤ 0.57). Compared to NHW children, Hispanic children had higher odds for MetS (OR: 1.7; p = 0.03) and waist circumference, HDL-C, and FPG risk factors (p < 0.05), while NHB children had higher odds for the FPG risk factor (p ≤ 0.007) and lower odds for the plasma triglycerides risk factor (p = 0.002), across multiple MetS definitions. In longitudinal analyses, HDL-C was the strongest independent predictor of MetS in Hispanic and NHW children (p < 0.001 and p < 0.01, respectively), while plasma triglycerides was the strongest independent predictor of MetS in NHB children (p < 0.05). CONCLUSIONS:MetS prevalence was high in children ≤10 years, and proposed criteria are susceptible to racial and ethnic bias, diagnosing some populations more than other populations with high cardiovascular risk. Earlier preventative measures should be imposed in clinical settings, accounting for racial and ethnic differences, to mitigate disease onset.

Introduction: Biloma is an extrahepatic bile collection secondary to iatrogenic or traumatic biliary tree disruption. It is a rare complication of laparoscopy cholecystectomy with an incidence rate of approximately 2.5%. Without proper management, biloma can become infected and cause life-threatening complications such as peritonitis, biliary fistula, bilhemia and hemobilia. Here we described a case of complicated biloma after laparoscopic cholecystectomy. Case Description/Methods: The patient was a 24-year-old female with a past medical history of hypertension, obesity, and recent laparoscopic cholecystectomy complicated by hepatic subcapsular biloma. It was managed by biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous drainage during the previous hospitalization. However, 6 days later, she presented with fever, chills, nausea, and right upper quadrant pain. Vital signs were fever 102.3 F and tachycardia 110 to 120 per min. The CT abdomen revealed decreased size in perihepatic fluid collection with air bubbles (14 x 11 x 18 cm; Figure). It also showed a common bile duct stent in place and a percutaneous drainage catheter tip in the inferior aspect of the collection. Lab results showed leukocytosis to 10.3, normal AST/ALT, total/direct bilirubin 2.1/12 mg/dL, and GGT 152 U/L. Broad-spectrum antibiotics were given in ED. The surgery team performed a laparoscopic lavage and discovered that the drain was not connected with the biloma. Two new drains were placed during the operation. She was discharged with PO antibiotics, and an outpatient follow-up was scheduled for drain removal.
Discussion(s): The management of biloma depends on the severity of the disease. Endoscopic therapy, such as a transpapillary biliary stent placement, can decrease the transpapillary pressure gradient, thus allowing preferential transpapillary bile flow rather than accumulation at the leaking site. However, given that stent placement does not reabsorb formed collection, patients failing ERCP should undergo percutaneous drainage or bile duct repair.Iatrogenic biloma can be detected by post-operational physical exams and image studies. Laparoscopic lavage with drainage should be considered in unresolved or infected biloma due to the high risk of peritonitis

Introduction/UNASSIGNED:Platelet dysfunction and cardiovascular risk are well-recognized features of chronic kidney disease (CKD). Platelets drive the development and progression of cardiovascular disease (CVD). The relationships between kidney function, platelet activity, and cardiovascular risk are poorly defined. Methods/UNASSIGNED:) using data from the Platelet Activity and Cardiovascular Events study, a prospective cohort study that enrolled adults with peripheral artery disease (PAD) undergoing lower extremity revascularization. Platelet activity was measured using light transmission aggregometry (LTA) in response to submaximal dose agonist stimulation, and the subjects were followed for incident adverse cardiovascular events for a median of 18 months. Results/UNASSIGNED: < 0.05 for each). Following multivariable adjustment, subjects with CKD had elevated risk for myocardial infarction (MI) (adjusted hazard ratio 2.2, 95% confidence interval [1.02-4.9]) and major adverse cardiovascular events (MACE) (1.9 [1.2-3.3]) compared to those without CKD. Platelet aggregation in response to submaximal dose agonist stimulation mediated 7% to 26% of the excess risk for cardiovascular events associated with CKD. Conclusion/UNASSIGNED:Among subjects with PAD undergoing lower extremity revascularization, CKD is associated with increased platelet activity that mediates, in part, elevated cardiovascular risk.

 /UNASSIGNED:Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), resting pain, movement-evoked pain (MEP), and other somatic symptoms that interfere with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for spontaneous (or resting) pain and MEP in a preclinical model of CWP. For preclinical measures, the acidic saline model of FM was used to induce widespread muscle pain in adult female mice. Two intramuscular injections of acidic or neutral pH saline were administered following baseline measures, five days apart. An array of adapted evoked and spontaneous pain measures and functional assays were assessed for three weeks. A novel paradigm for MEP assessment showed increased spontaneous pain following activity. For clinical measures, resting and movement-evoked pain and function were assessed in adult women with FM. Moreover, we assessed correlations between the preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between pain assays that comprise resting and MEP existed in both settings. For both preclinical and clinical outcomes, MEP was significantly associated with mechanical pain sensitivity. Preclinically, it is imperative to expand how the field assesses spontaneous pain and MEP when studying multi-symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models. SUMMARY/CONCLUSIONS:Preclinical assessments of chronic musculoskeletal pain recapitulate several outcome measures for clinical assessment of patients with FM, particularly prolonged spontaneous (resting) pain, and MEP.

BACKGROUND:During the first wave of the COVID-19 pandemic physicians worked on the front lines, immersed in uncertainty. Research into perspectives of frontline physicians has lagged behind clinical innovation throughout the pandemic. OBJECTIVE:To inform ongoing and future efforts in the COVID-19 pandemic, we conducted a qualitative exploration of physician perspectives of the effects of policies and procedures as well as lessons learned while caring for patients during the height of the first wave in the spring of 2020. DESIGN/METHODS:A confidential survey was emailed to a convenience sample. Survey questions included demographic data, participant role in the pandemic, and geographic location. Eleven open-ended questions explored their perspectives and advice they would give going forward. Broad areas covered included COVID-19-specific education, discharge planning, unintended consequences for patient care, mental health conditions to anticipate, and personal/institutional factors influencing workforce well-being amid the crisis. PARTICIPANTS/METHODS:We received fifty-five surveys from May through July 2020. Demographic data demonstrated sampling of frontline physicians working in various epicenters in the USA, and diversity in gender, race/ethnicity, and clinical specialty. APPROACH/METHODS:Inductive thematic analysis. KEY RESULTS/RESULTS:Four themes emerged through data analysis: (1) Leadership can make or break morale; (2) Leadership should engage frontline workers throughout decision-making processes; (3) Novelty of COVID-19 led to unintended consequences in care delivery; and (4) Mental health sequelae will be profound and pervasive. CONCLUSIONS:Our participants demonstrated the benefit of engaging frontline physicians as important stakeholders in policy generation, evaluation, and revision; they highlighted challenges, successes, unintended consequences, and lessons learned from various epicenters in the first wave of the COVID-19 pandemic. There is much to be learned from the early COVID-19 pandemic crisis; our participants' insights elucidate opportunities to examine institutional performance, effect policy change, and improve crisis management in order to better prepare for this and future pandemics.