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How likely is unmeasured confounding to explain meta-analysis-derived associations between alcohol, other substances, and mood-related conditions with HIV risk behaviors?

Manandhar-Sasaki, Prima; Ban, Kaoon Francois; Richard, Emma; Braithwaite, R Scott; Caniglia, Ellen C
BACKGROUND:HIV transmission and disease progression may be driven by associations HIV risk behaviors have with a constellation of alcohol, other substance, and mood-related conditions (CASM). However, observational study-based measures of these associations are often prone to unmeasured confounding. While meta-analysis offers a systematic approach to summarize effect sizes across studies, the validity of these estimates can be compromised if similar biases exist across studies. Our analysis assesses the likelihood that unmeasured confounding explains meta-analysis-derived measures of association between CASM and HIV risk behaviors, and provides bias-adjusted estimates. METHODS:We first conducted systematic reviews and meta-analyses to assess associations between CASM conditions and four HIV risk behaviors (medication non-adherence, unprotected sex, transactional sex, and multiple sexual partners). We then adjusted for potential unmeasured confounders using two methods designed for meta-analyses - Point Estimate and Proportion of Meaningfully Strong Effects methods. We selected "risk propensity" as an illustrative and potentially important unmeasured confounder based on the extant literature and mechanistic plausibility. RESULTS:In analyses unadjusted for unmeasured confounding, 89% (24/27) of odds ratios (ORs) show strong evidence of a positive association, with alcohol use and stimulant use emerging as dominant risk factors for HIV risk behaviors. After adjusting for unmeasured confounding by risk propensity, 81% (22/27) of ORs still showed strong evidence of a positive association. Associations between mood-related conditions and HIV risk behaviors were more robust to unmeasured confounding than associations between alcohol use and other substance use and HIV risk behaviors. CONCLUSION/CONCLUSIONS:Despite residual confounding present in constituent studies, there remains strong evidence of associations between CASM and HIV risk behaviors as well as the clustered nature of CASM conditions. Our analysis provides an example of how to assess unmeasured confounding in meta-analysis-derived measures of association.
PMCID:11887180
PMID: 40055588
ISSN: 1471-2288
CID: 5808002

"Men Take Care of Each Other": Evaluation of a Community-Based Model for Pre-exposure Prophylaxis Services Among Male Bar Patrons in Rural South Africa

Chen, Phoebe; Nkosi, Sebenzile; Moll, Anthony P; Braithwaite, R Scott; Ngubane, Siya Goodman; Shenoi, Sheela V
Low engagement with HIV services persists among young men with harmful alcohol use in South Africa. We previously piloted a rural community-based HIV service delivery model to engage this key population. In the initial study, male nurses visited alcohol-serving venues to provide HIV testing and pre-exposure prophylaxis (PrEP) services. From November 1 to December 30, 2021, we conducted interviews with 17 of 34 male pilot participants to evaluate program barriers, facilitators, and suggestions. All interviewees were satisfied with HIV testing and PrEP services. Participants overcame testing avoidance through peer influence and enhanced privacy. Barriers for PrEP initiation were stigma (PrEP mistaken for HIV treatment) and complacency toward HIV, while facilitators included desire to mitigate alcohol-associated risks, social support, and comfort with male community nurses. Most participants self-reported good adherence due to daily routines, nurse follow-ups, and social support, with lapses due to travel and alcohol use. Post-pilot, only three participants transferred to clinics to continue PrEP due to inconvenient access, unwelcoming environment, and stigma of clinic attendance. All participants wanted to restart community-based PrEP due to convenience, preference for male nurses, and avoidance of stigma. A few participants reported privacy concerns regarding peer-pressure to disclose test results and pills or home visits being mistaken for HIV treatment. Future suggestions included school/church visits, unmarked vehicles, nurse assistance with facilitated PrEP disclosure, patient ambassadors, and injectable PrEP. Community-based PrEP services using male nurses at alcohol-serving venues can reach men who otherwise would not engage in HIV services.
PMID: 39761130
ISSN: 1557-7449
CID: 5778292

Identifying an optimal cancer risk threshold for resection of pancreatic intraductal papillary mucinous neoplasms

Sacks, Greg D; Wojtalik, Luke; Kaslow, Sarah R; Penfield, Christina A; Kang, Stella K; Hewitt, D B; Javed, Ammar A; Wolfgang, Christopher L; Braithwaite, R S
BACKGROUND:IPMN consensus guidelines make implicit judgments on what cancer risk level should prompt surgery. We used decision modeling to estimate this cancer risk threshold (CRT) for BD-IPMN patients. METHODS:We created a decision model to compare quality-adjusted life years (QALYs) following surgery or surveillance for BD-IPMNs. We simulated treatment decisions for hypothetical patients, varying age, comorbidities and lesion location (pancreatic head/tail). The base case was a 60-year-old patient with mild comorbidities and pancreatic head IPMN. Probabilities, life expectancies, and utilities were incorporated from literature/public datasets. CRT was defined as the level of cancer risk at which the expected value of QALYs for surgery first exceeded that of surveillance. RESULTS:In the base case, surgery was preferred over surveillance, yielding 21.90 vs. 21.88 QALYs. The optimal CRT for a BD-IPMN patient depended on age, comorbidities, and location. CRT in the base case was 20 % and 3 % for an IPMN in the head and tail of the pancreas, respectively. Other drivers of preferred treatment were age and likelihood of postoperative mortality. CONCLUSION/CONCLUSIONS:For BD-IPMNs, the optimal CRT varies depending on patient age and risk of surgical complications. Personalized risk threshold values could guide treatment decisions and inform future treatment consensus guidelines.
PMID: 39505679
ISSN: 1477-2574
CID: 5803672

Implications of Diminishing Lifespan Marginal Utility for Valuing Equity in Cost-Effectiveness Analysis

Braithwaite, R Scott
UNLABELLED: HIGHLIGHTS/UNASSIGNED:Diminishing marginal lifespan utility (DMLU) means that the value of extending lifespan may differ based on the duration of life already lived.DMLU is not typically considered in cost-effectiveness analyses.Not considering DMLU may bias cost-effectiveness analyses against equity.Not considering DMLU may reduce the accuracy of distributive cost-effectiveness analyses and other approaches to consider equity along with efficiency.
PMCID:11748391
PMID: 39839684
ISSN: 2381-4683
CID: 5802242

A Parsimonious Approach to Remediate Concerns about QALY-Based Discrimination

Braithwaite, Ronald Scott
Important barriers to the use of QALYs in the United States include concerns about disability and age discrimination.Modifications to the utility function underlying QALYs have been proposed to mitigate these concerns, but some find them challenging to consider and/or to apply.Unrelated to these concerns, QALYs have been adapted within the framework of distributional cost-effectiveness analysis to allow consideration of inequality as well as efficiency.I outline how this framework can also remediate concerns about disability and age discrimination.
PMID: 39707829
ISSN: 1552-681x
CID: 5765042

Decisional Control Preferences in Managing Intraductal Papillary Mucinous Neoplasms of the Pancreas

England, Bryce; Habib, Joseph R; Sharma, Acacia R; Hewitt, D Brock; Bridges, John F P; Javed, Ammar A; Wolfgang, Christopher L; Braithwaite, R Scott; Sacks, Greg D
OBJECTIVES/OBJECTIVE:To evaluate patient preferences for decision-making role in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to identify individual characteristics associated with those preferences. BACKGROUND:Management of IPMNs is rooted in uncertainty with current guidelines failing to incorporate patients' preferences and values. METHODS:A representative sample of participants aged 40-70 were recruited to evaluate a clinical vignette where they were given the option to undergo surveillance or surgical resection of their IPMN. Their preferred role in the decision-making process for the vignette was evaluated using the Control Preference Scale. The relationship between control preference and variables including cancer anxiety, health literacy, and education level was analyzed. RESULTS:Of the 520 participants in the study, most preferred an active role (65%), followed by shared (29%), and passive roles (6%) in the decision-making process. Lower health literacy was significantly associated with a more passive control preference (p = 0.003). Non-active preference was significantly associated with Latino race compared to White race (odds ratio = 0.52, p = 0.009) in multivariate analysis. We found no significant association between control preference and education level or cancer anxiety. CONCLUSIONS:Most patients preferred an active role in IPMN treatment decisions. Lower health literacy and Latino race were associated with a preference for non-active decision roles. Clinicians should strive to align patient involvement in IPMN treatment decisions with their patient's preferred role.
PMID: 39626203
ISSN: 1536-4828
CID: 5804402

Progression of hypertensive disorders of pregnancy during induction of labor in term nulliparous patients [Letter]

Perelman, Allison D; Braithwaite, R Scott; Caughey, Aaron B; Marty, Lindsay N; Hirschberg, Carly I; Pass, Alexandra R; Penfield, Christina A
PMID: 38992814
ISSN: 1097-6868
CID: 5695822

Cost-effectiveness of screening and treating alcohol use and depression among people living with HIV in Zimbabwe: a mathematical modeling study

Su, Jasmine I-Shin; Yeo, Yao-Rui; Jeetoo, Mellesia; Morojele, Neo K; Francis, Joel M; Shenoi, Sheela; Braithwaite, R Scott
BACKGROUND:Alcohol use disorder (AUD) and major depressive disorder (MDD) drive HIV transmission in many sub-Saharan African settings. The impact of screening and treating AUD and MDD on HIV outcomes is unknown. We aimed to identify the cost-effectiveness of AUD and MDD interventions in Zimbabwe, and their potential contribution to reaching Zimbabwe's Ending the HIV Epidemic 2030 goal. METHODS:Using a validated HIV compartmental transmission model in Zimbabwe, we compared four policy scenarios: prevention as usual (baseline); implement AUD screening (using AUDIT) and treatment (motivational interviewing and cognitive-behavioral therapy); implement MDD screening (using PHQ-9) and treatment (cognitive-behavioral therapy); and implement screening and treatment for both. Outcomes were HIV incidence projections, infections averted through 2030, quality-adjusted life-years gained, cost per infection averted, and cost per QALY gained. Analyses considered "spillover," when treatment for AUD also results in an improvement in MDD and the converse. Sensitivity analyses identified cost reductions necessary for AUD and MDD interventions to be as cost-effective as other HIV interventions, particularly the scale-up of long-acting PrEP. RESULTS:AUD and MDD combined will be responsible for 21.1% of new HIV infections in Zimbabwe by 2030. Without considering spillover, compared to the baseline, MDD intervention can reduce new infections by 5.4% at $2039/infection averted and $3186/QALY. AUD intervention can reduce new infections by 5.8%, but at $2,968/infection averted and $4753/QALY, compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.1% at $2810/infection averted and $4229/QALY, compared to baseline. Considering spillover, compared to the baseline, MDD intervention can reduce new infections by 6.4% at $1714/infection averted and $2630/QALY. AUD intervention can reduce new infections by 7.4%, but at $2299/infection averted and $3560/QALY compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.9% at $2247/infection averted and $3382/QALY compared to baseline. For MDD intervention to match the cost-effectiveness of scaling long-acting PrEP, the cost of MDD intervention would need to be reduced from $16.64 to $12.88 per person. CONCLUSIONS:Implementing AUD and MDD interventions can play an important role in HIV reduction in Zimbabwe, particularly if intervention cost can be decreased while preserving effectiveness.
PMCID:11492560
PMID: 39428460
ISSN: 1741-7015
CID: 5739452

Performance analysis of mathematical methods used to forecast the 2022 New York City Mpox outbreak

Kaftan, David; Kim, Hae-Young; Ko, Charles; Howard, James S; Dalal, Prachi; Yamamoto, Nao; Braithwaite, R Scott; Bershteyn, Anna
In mid-2022, New York City (NYC) became the epicenter of the US mpox outbreak. We provided real-time mpox case forecasts to the NYC Department of Health and Mental Hygiene to aid in outbreak response. Forecasting methodologies evolved as the epidemic progressed. Initially, lacking knowledge of at-risk population size, we used exponential growth models to forecast cases. Once exponential growth slowed, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) model. Retrospectively, we explored if forecasts could have been improved using an SEIR model in place of our early exponential growth model, with or without knowing the case detection rate. Early forecasts from exponential growth models performed poorly, as 2-week mean absolute error (MAE) grew from 53 cases/week (July 1-14) to 457 cases/week (July 15-28). However, when exponential growth slowed, providing insight into susceptible population size, an SEIR model was able to accurately predict the remainder of the outbreak (7-week MAE: 13.4 cases/week). Retrospectively, we found there was not enough known about the epidemiological characteristics of the outbreak to parameterize an SEIR model early on. However, if the at-risk population and case detection rate were known, an SEIR model could have improved accuracy over exponential growth models early in the outbreak.
PMID: 39092792
ISSN: 1096-9071
CID: 5696632

Empirical Development of a Behavioral Intervention for African American/Black and Latino Persons with Unsuppressed HIV Viral Load Levels: An Application of the Multiphase Optimization Strategy (MOST) Using Cost-Effectiveness as an Optimization Objective

Feelemyer, Jonathan; Braithwaite, R Scott; Zhou, Qinlian; Cleland, Charles M; Manandhar-Sasaki, Prima; Wilton, Leo; Ritchie, Amanda; Collins, Linda M; Gwadz, Marya V
We used results from an optimization randomized controlled trial which tested five behavioral intervention components to support HIV antiretroviral adherence/HIV viral suppression, grounded in the multiphase optimization strategy and using a fractional factorial design to identify intervention components with cost-effectiveness sufficiently favorable for scalability. Results were incorporated into a validated HIV computer simulation to simulate longer-term effects of combinations of components on health and costs. We simulated the 32 corresponding long-term trajectories for viral load suppression, health related quality of life (HRQoL), and costs. The components were designed to be culturally and structurally salient. They were: motivational interviewing counseling sessions (MI), pre-adherence skill building (SB), peer mentorship (PM), focused support groups (SG), and patient navigation (short version [NS], long version [NL]. All participants also received health education on HIV treatment. We examined four scenarios: one-time intervention with and without discounting and continuous interventions with and without discounting. In all four scenarios, interventions that comprise or include SB and NL (and including health education) were cost effective (< $100,000/quality-adjusted life year). Further, with consideration of HRQoL impact, maximal intervention became cost-effective enough to be scalable. Thus, a fractional factorial experiment coupled with cost-effectiveness analysis is a promising approach to optimize multi-component interventions for scalability. The present study can guide service planning efforts for HIV care settings and health departments.
PMCID:11415978
PMID: 38662280
ISSN: 1573-3254
CID: 5732902