Faculty Bibliography

BACKGROUND:KwaZulu-Natal (KZN) has the second highest HIV prevalence of any province in South Africa and high prevalences of Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD), which increase HIV risk behaviors. We identified the impact and cost-effectiveness of screening and treatment for AUD and MDD as strategies to reduce HIV burden in KZN. METHODS:Using a HIV compartmental transmission model, we simulated the impact of AUD and MDD screening and treatment on reducing HIV transmission for the general population and key populations. Screening tools included AUDIT and PHQ-9. Treatment strategies included behavioral and pharmacologic interventions. Key populations included female sex workers (FSW), men who have sex with men (MSM), people in care with unsuppressed viral load, adolescent girls and young women (AGYW), adolescent boys and young men, and men ages 25-34. Outcomes were HIV infections averted through 2030, quality-adjusted life-years (QALYs) gained through 2030, cost (2019 US$) per infection averted, and cost per QALY gained. RESULTS:Among the general population, MDD screening and behavioral treatment was most cost effective ($340/infection averted; $480/QALY gained). Combined AUD and MDD screening and behavioral and pharmacological treatment averted 179,560 infections ($2,100/infection averted) and gained 129,460 QALYs ($2,980/QALY gained). Targeting key populations substantially improved cost-effectiveness. The most cost-effective strategy was MDD screening and behavioral treatment among FSW ($350/infection averted; $490/QALY gained); followed by sequential scale-up to MSM ($690/infection averted; $960/QALY gained). CONCLUSIONS:Targeted AUD and MDD screening and treatment could substantially reduce HIV transmission in KZN with very favorable cost-effectiveness.

BACKGROUND/UNASSIGNED:Differentiated service delivery (DSD) is increasingly available for HIV treatment. DSD has been shown to improve treatment retention, but DSD modalities incur higher costs than the clinic-based standard-of-care (SoC). We conducted a cost-effectiveness (CE) analysis to assess what DSD modalities, in what settings, would constitute an efficient use of limited HIV program resources. METHODS/UNASSIGNED:) to project HIV trends (incidence, prevalence, mortality), disability-adjusted life years (DALYs), and costs (2021 USD) arising from DSD versus SoC over 2022-2062 in four settings: South Africa, Malawi, Zambia, and a collective representation of African low- and middle-income countries (LMICs). We compared three DSD modalities: healthcare worker-managed community adherence groups (CAG), client-managed urban adherence group (UAG), and home ART delivery (HomeART). We calculated incremental cost-effectiveness ratios (ICERs) of DSD versus SoC from the health system perspective using country-specific CE thresholds, and performed one-way sensitivity analyses for key assumptions. RESULTS/UNASSIGNED:Community adherence groups (ICER: $274-$604/DALY averted) and UAG (ICER: $590-$720/DALY averted) were cost-effective for all country/model settings. HomeART was dominated by UAG in all settings. In nearly all settings, CE estimates of CAG were robust to uncertainty in DSD effectiveness (except Zambia), DSD costs, CE threshold (except South Africa), HIV-associated disability weights, and discount rates. Cost-effectiveness of UAG was highly sensitive to uncertainty in DSD effectiveness in all settings. CONCLUSIONS/UNASSIGNED:Community adherence groups and UAG can provide cost-effective alternatives to the clinic-based SoC in multiple African settings.

BACKGROUND:Most branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) are indolent, but distinguishing those harboring high-grade dysplasia or invasive cancer remains difficult. This analysis focuses not on incidental small BD-IPMNs but on the subset whose cyst characteristics bring surgery into the decision-making discussion. Surgery prevents malignant progression but carries morbidity; surveillance avoids overtreatment but risks delayed cancer detection. Current guidelines rely on fixed thresholds that may not reflect individual variation. Our study compared immediate surgery and initial surveillance in patients with BD-IPMNs, using a decision-analytic model that incorporates patient-specific risk factors. METHODS:A Markov decision model compared immediate surgery with initial surveillance, incorporating age, comorbidities, and cyst location. Health states reflected progression from low-grade to high-grade dysplasia and invasive cancer, postoperative complications, recurrence, and quality-of-life decrements. Transition probabilities were derived from published studies and American College of Surgeons (ACS)-National Surgical Quality Improvement Program data. The primary outcome was quality-adjusted life-years (QALYs). RESULTS:For a 60-year-old patient with mild comorbidities and a pancreatic head BD-IPMN, immediate surgery provided 16.8 QALYs versus 16.3 with surveillance (incremental gain, 0.5 QALYs). Lifetime cancer probability was lower with surgery (24.5% vs 33.5%), as was cancer-related mortality (9.3% vs 20.3%), though surgery resulted in more resections for low-grade dysplasia (55.0% vs 15.3%). Age, baseline cancer probability, and perioperative mortality were the strongest determinants of the preferred strategy. CONCLUSIONS:Among patients with BD-IPMNs being considered for surgery, immediate resection offers a modest benefit for younger, healthier individuals, whereas surveillance remains appropriate for older or comorbid patients. These findings support individualized, risk-based management rather than universal application of guideline thresholds.

BACKGROUND:Co-occurring alcohol, substance, and mood-related (CASM) conditions are prevalent, mutually reinforcing, and under-diagnosed contributors to morbidity, mortality, and health disparities. OBJECTIVE:To evaluate screening strategies leveraging the predictive value arising from patterns of CASM co-occurrence in populations with high CASM prevalence. DESIGN/METHODS:Individual-based health risks model validated to predict US life expectancy and causes of death by sex and age decile, including CASM conditions of depression, anxiety, chronic pain, and unhealthy alcohol, tobacco, opioid and stimulant use. The model includes CASM co-occurrence patterns, mutual reinforcement across CASM conditions, and reduced engagement in other preventative care due to CASM. PARTICIPANTS/METHODS:Veterans Aging Cohort Study (VACS), a large longitudinal cohort of in-care US veterans. INTERVENTIONS/METHODS:(1) Screening alcohol, tobacco, and/or depression symptoms; (2) adding further screening of CASM conditions likely to co-occur with those screened positive, with variation in the minimum co-occurrence rate; (3) screening all CASM conditions (hypothetical maximum). MAIN MEASURES/METHODS:Estimated life expectancy (LE) and quality-adjusted life-years (QALYs). KEY RESULTS/RESULTS:The maximum strategy added 0.52 years to estimated LE (95% CI: 0.51 - 0.54) and 0.68 QALYs/person (95% CI: 0.67 - 0.69). Screening individual CASM conditions added a small fraction of this benefit, the largest LE gain from tobacco screening: 0.08 years (95% CI: 0.07 - 0.09). Screening for depression, alcohol, and tobacco provided 34.6% of the maximum strategy's LE gain (0.19 years, 95% CI: 0.17 - 0.20). Additionally screening conditions with moderate (≥ 20%) probability of co-occurring with those already screened positive provided 84.8% of the maximum strategy's LE gain. Screening all CASM conditions if depression, alcohol, and/or tobacco screened positive provided 86.6% of the maximum strategy's LE gain. CONCLUSIONS:Compared to common practice of screening one or few CASM conditions, large health benefits are possible by further assessing CASM conditions most likely to co-occur with those already screening positive, improving health without increasing up-front screening burden in populations with high CASM prevalence.

BACKGROUND:With declining HIV/AIDS funding globally, countries need to identify the optimally efficient mix of HIV interventions to avert new HIV infections. We evaluated optimal HIV/AIDS intervention portfolios to enable Eswatini to meet the 2030 Ending the HIV Epidemic (EHE) goal of a 90% reduction in HIV incidence compared to 2010. METHODS:Using Eswatini national demographic data and expenditure data on clinical, behavioral, and public health HIV interventions, we employed a validated HIV transmission model to simulate the effects of HIV interventions on diagnosis, treatment, and viral load suppression (costs, infections averted, life years gained, and quality-adjusted life years (QALYs) gained) for the Eswatini adult population from 2022 through 2030.We evaluated eleven alternative combinations of scaling-up interventions to goal coverage levels, with and without reallocating resources away from other interventions. RESULTS:With the current resource allocation, Eswatini will be delayed in meeting the EHE goal. However, with additional programmatic funding of US$8 million to additionally scaling up HST and LA-PrEP for the highest risk population and additional funding for defaulter tracing and risk communication, Eswatini will meet its EHE goal by 2030 by averting an additional 3,500 infections. CONCLUSION/CONCLUSIONS:Eswatini could meet its EHE goal with additional funding or resource reallocation from less efficient toward highly efficient interventions. These findings can inform allocation decisions that are more practical and realistic in this resource-limited setting with high HIV disease burden.

The degree to which alcohol use is associated with the risk of all-cause mortality and hepatic decompensation after hepatitis C (HCV) diagnosis, treatment, and cure remains unknown. We sought to address this question among patients achieving sustained virologic response (SVR) after direct-acting antiviral treatment in the largest HCV health system in the United States. We extracted data on alcohol use, HCV treatment, SVR, HIV co-infection, demographics, risk behaviours, hepatic decompensation, and mortality from all patients in the 1945 to 1965 VA Birth Cohort. Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and diagnostic codes for alcohol use disorder (AUD): abstinent without a history of AUD, abstinent with a history of AUD, current lower-risk consumption, current moderate-risk consumption, and current high-risk consumption with or without AUD. Cox proportional hazard models were used to examine associations between alcohol category and the risk of hepatic decompensation and all-cause mortality. Among 50,581 patients in the analytic cohort, compared to current drinkers exhibiting lower risk alcohol consumption (referent), current high-risk consumption with or without AUD was associated with increased risk of all-cause mortality (aHR: 1.40, 95% CI: 1.21-1.63) and hepatic decompensation (HR: 2.15, 95% CI: 1.60-2.89) as was abstinence with a history of AUD diagnosis (mortality aHR: 1.63, 95% CI: 1.41-1.89; hepatic decompensation aHR: 1.85, 95% CI: 1.36-2.51). AUD and high-risk alcohol consumption are associated with the risk of hepatic decompensation and all-cause mortality among Veterans who have achieved SVR, including those categorised as being currently abstinent. Interventions for alcohol consumption and use disorder among individuals treated for HCV infection may reduce morbidity and mortality in this population.

We developed and implemented a PrEP navigation program ("SNAPS") in a NYC safety-net hospital with the objectives to co-locate navigation, clinical PrEP services, and payment assistance. Adherence and retention to PrEP-related care were assessed by mean medication possession ratios (MPRs) and number of appointments over 12 months. Compared to the pre-SNAPS cohort, the post-SNAPS cohort was less likely to be cisgender male (64.8% vs. 84.2%), White (6.5% vs. 23%) and to speak English (33.3% vs. 80.6%) (all p < 0.001). Mean MPR was lower for post-SNAPS (0.68, SD = 0.33) compared to pre-SNAPS (0.89, SD = 0.22) (p = 0.001). Among post-SNAPS patients, cisgender men and MSM were more likely to be retained in PrEP care compared to cisgender women (p < 0.05). Although SNAPS linked diverse patients to PrEP-care, mean MPR was lower post-SNAPS compared to the pre-SNAPS. Continued investments to strengthen later stages of the PrEP cascade model for all populations vulnerable to HIV are needed.

OBJECTIVE:We aimed to better understand patients' treatment preferences and quantify the level of cancer risk at which treatment preferences change (risk threshold) to inform better counseling of patients with intraductal papillary mucinous neoplasms (IPMNs). SUMMARY BACKGROUND DATA/BACKGROUND:The complexity of IPMN management provides an opportunity to align treatment with individual preference. METHODS:We surveyed a sample of healthy volunteers simulating a common scenario: undergoing an imaging study that incidentally identifies an IPMN. In the scenario, the estimated risk of cancer in the IPMN was 5%. Patients were asked their treatment preference (surgery or surveillance), to quantify the level of cancer risk in the IPMN at which their treatment preference would change (i.e. risk threshold), and their level of cancer anxiety as measured on a 5-point Likert scale. We examined associations between participant characteristics, treatment preferences, and risk threshold using multivariable linear regression. RESULTS:The median risk threshold among the 520 participants was 25% (IQR 2.3-50%). The risk threshold had a bimodal distribution: 40% of participants had a risk threshold between 0-10% and 47% had a risk threshold above 30%. When informed that the risk of cancer was 5%, 62% of participants (n=323) preferred surveillance, and the remaining 38% (n=197) preferred surgery. After adjusting for potential confounders, participants who expressed "worry" or "extreme worry" about the malignancy risk of IPMN had significantly lower risk thresholds than participants who were "not at all worried" (Coefficient -12, 95%CI -21 to -2, P=0.015 and Coefficient -18, 95%CI -29 to -8, P<0.001, respectively). CONCLUSIONS:Participants varied in treatment preference and risk threshold of incidentally identified IPMNs. Given the uncertainty in estimating the true malignant potential of IPMNs, a better understanding of a patient's risk threshold, as influenced by patient concern about malignancy, will help inform the shared decision-making process.