Faculty Bibliography

BACKGROUND:cohort and investigate virologic outcomes among individuals who resumed treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). METHODS:We identified adults with HIV-1 who were active in care and on an oral ART regimen with ≥ 2 antiretrovirals, including ≥ 1 anchor agent, between 30JUN2021 and 31AUG2023. Individuals with ≥ 1 period of ≥ 45 days without any ART, based on supply from last prescription, were considered to have experienced a treatment interruption. Individuals who resumed treatment by 31AUG2023 were defined as having experienced a treatment interruption with resumption. Each interruption observed during the study period was described, allowing for multiple interruptions per person. Treatment interruptions, pre-interruption regimens, and post-interruption regimens were described. Among individuals who resumed treatment with B/F/TAF, virologic outcomes were investigated through 29FEB2024 using Kaplan-Meier methods. All analyses were repeated with treatment interruption definitions of ≥ 60 and ≥ 90 days. RESULTS:Of 76,883 people for whom a treatment interruption could be observed, 8,550 (11%) experienced ≥ 1 period of ≥ 45 days without any ART. By 31AUG2023, 4,163 (49%) individuals resumed treatment (mean: 1.25 per person) and were included in the study population. The median age was 44 years, 81% were male, 52% Black, 41% White, and 18% Hispanic. Median time since HIV diagnosis was 118 months. B/F/TAF was the most common pre- and post-interruption regimen (49% and 51%, respectively). The cumulative probability of achieving virologic suppression on B/F/TAF was 68% (95% CI: 57, 78) when the viral load measurement was ≥ 200 copies/mL at resumption. CONCLUSIONS:Treatment interruptions occurred in 11% of ART users in routine clinical care during the 26-month study period. Despite treatment interruption increasing the risk for viral rebound, most individuals who resumed treatment with B/F/TAF were able to achieve virologic suppression or avoid virologic failure.

BACKGROUND:Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). METHODS:This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long-COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative (N3C), National Patient-Centered Clinical Research Network (PCORnet), and PEDSnet) implemented its own long-COVID definition. We introduced a harmonized definition for adults in a supplementary analysis. RESULTS:Overall, 4% of children and 10-26% of adults developed long-COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5-6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. CONCLUSION/CONCLUSIONS:Our findings indicate that preventing and mitigating long-COVID remains a public health priority. Examining temporal patterns and risk factors of long-COVID incidence informs our understanding of etiology and can improve prevention and management.

BACKGROUND:Opioid addiction is a worldwide public health crisis. In the United States, for example, opioids cause more drug overdose deaths than any other substance. However, opioid addiction treatments have limited efficacy, meaning that additional treatments are needed. METHODS:To help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies of opioid use disorder and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex of people who died of opioid overdose and control individuals. RESULTS:We identified 211 highly interrelated genes identified by genome-wide association studies or dysregulation in the dorsolateral prefrontal cortex of people who died of opioid overdose that implicated the Akt, BDNF (brain-derived neurotrophic factor), and ERK (extracellular signal-regulated kinase) pathways, identifying 414 drugs targeting 48 of these opioid addiction-associated genes. Some of the identified drugs are approved to treat other substance use disorders or depression. CONCLUSIONS:Our synthesis of multiomics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.

The number and complexity of obesity treatments has increased rapidly in recent years. This is driven by the approval of new anti-obesity medications (AOMs) that produce larger degrees of weight loss than previously approved AOMs. Unfortunately, access to these highly effective therapies and to integrated team-based obesity care is limited by intra-/interpersonal patient, institutional/practitioner, community, and policy factors. We contextualized these complexities and the impact of patients' social drivers of health (SDOH) by adapting the social ecological model for obesity. Without multi-level intervention, these barriers to care will deepen the existing inequities in obesity prevalence and treatment outcomes among historically underserved communities. As General Internal Medicine (GIM) physicians, we can help our patients navigate the complexities of evidence-based obesity treatments. As care team leaders, GIM physicians are well-positioned to (1) improve education for trainees and practitioners, (2) address healthcare-associated weight stigma, (3) advocate for equity in treatment accessibility, and (4) coordinate interdisciplinary teams around non-traditional models of care focused on upstream (e.g., policy changes, insurance coverage, health system culture change, medical education requirements) and downstream (e.g., evidence-based weight management didactics for trainees, using non-stigmatizing language with patients, developing interdisciplinary weight management clinics) strategies to promote optimal obesity care for all patients.

BACKGROUND:Minoritized populations face many barriers to accessing evidence-based diabetes intervention. OBJECTIVES/OBJECTIVE:To evaluate the feasibility, acceptability, and potential efficacy of a social media-based intervention to improve glycemic control among Chinese Americans with type 2 diabetes. DESIGN/METHODS:A pilot randomized controlled trial (RCT) with 3-month and 6-month follow-ups. PARTICIPANTS/METHODS:Chinese Americans (n = 60, mean age 54.3 years old) with limited education (70.0% with high school or less) and low income (50.0% with annual household income < $25,000), and 88.3% have limited English proficiency. INTERVENTION/METHODS:Culturally and linguistically tailored diabetes videos (two videos/week for 12 weeks) delivered via social media and support calls from community health workers. MAIN MEASURES/METHODS:Primary outcomes include feasibility (video watch rate, biweekly call completion rate, and retention rates), acceptability (patient satisfaction), and HbA1c. Secondary health-related outcomes include body weight, BMI, physical activity, and dietary intake. Video watch rate and biweekly call completion rate were assessed at baseline and 3 months, while others were measured at baseline, 3 months, and 6 months. RESULTS:We observed high feasibility and acceptability of the intervention, with retention rates over 87%, an 89% video watch rate, 80% biweekly phone call completion, and a satisfaction rating of 9 out of 10. The intervention group showed a significantly greater increase in fruit intake compared to the control group (0.15 cups vs. - 0.44 cups, adj_p = 0.023) at 3 months. While no significant differences in other outcomes were observed between the groups, the intervention group showed significant improvements in key outcomes, including reduced HbA1c levels (- 1.08%, adj_p < 0.001), weight loss (- 5.15 lbs, adj_p = 0.004), lower BMI (- 0.83, adj_p = 0.023), and reduced starchy food intake (- 0.33 cups, adj_p = 0.033) at 6 months. CONCLUSIONS:The observed high feasibility and acceptability suggest the intervention's feasibility. However, due to the limited sample size, a larger-scale RCT is warranted to test the efficacy of the intervention. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/ct2/show/NCT03557697.

[This corrects the article DOI: 10.1016/j.lana.2024.100895.].

CONTEXT AND OBJECTIVE/UNASSIGNED:The lack of efficacy of somatostatin receptor subtype 2 (SST2) preferring somatostatin analogs in patients with Cushing's disease (CD) results from a downregulating effect of hypercortisolism on SST2 expression. Our objective is to evaluate the efficacy of a strategy with sequential treatment of ketoconazole to reduce cortisol levels and potentially restore SST2 expression followed by octreotide as maintenance therapy in patients with CD. PATIENTS AND DESIGN/UNASSIGNED:Fourteen adult patients with CD were prospectively enrolled. Patients started with ketoconazole. Once cortisol levels were normalized, octreotide was initiated. After 2 months of combination therapy, patients were maintained on octreotide monotherapy until the end of the study period (9 months). Treatment success was defined by normalization of urinary free cortisol (UFC) levels. RESULTS/UNASSIGNED:). CONCLUSION/UNASSIGNED:Sequential treatment with ketoconazole to lower cortisol levels followed by octreotide to maintain biochemical remission according to UFC may be effective in a subset of patients with mild CD, suggesting that cortisol-mediated suppression of SST2 expression is a reversible process.

BACKGROUND/UNASSIGNED:infection (CDI) introduced new recommendations for managing initial and recurrent CDI. Since then, new microbiome-based therapies for preventing recurrent CDI have become available. We surveyed infectious diseases (ID) clinicians to understand their experiences, practices, and challenges in CDI management. METHODS/UNASSIGNED:An electronic survey was distributed to members of the IDSA Emerging Infections Network in May 2024, targeting ID physicians and healthcare professionals in the United States who manage adult CDI. The survey assessed treatment preferences, clinical practices, and barriers to accessing and prescribing CDI therapies. RESULTS/UNASSIGNED:Of the 500 respondents who reported treating CDI in the past year, 83% (417/500) indicated that vancomycin was their most frequently prescribed agent for initial, nonfulminant CDI. Additionally, 72% (357/498) reported that their institutional guidelines recommended vancomycin as the first-line agent. The most common barrier to fidaxomicin use was challenges with outpatient insurance coverage (82% [408/496]). Bezlotoxumab was available to 74% (370/500) of respondents, though 33% (165/497) indicated they do not use bezlotoxumab routinely. Most clinicians (87% [437/500]) had previously recommended fecal microbiota transplantation (FMT) for recurrent CDI, though only 48% (239/500) had current access to FMT using donor stool. Fecal microbiota live-jslm was available to 36% (179/500), and fecal microbiota spores live-brpk was available to 30% (150/500). CONCLUSIONS/UNASSIGNED:Significant barriers, including high costs, insurance challenges, and limited availability of CDI therapies, impact clinical decision-making and adherence to guideline recommendations.