Characterising HIV acquisition risk, treatment gaps and populations reached through venue-based outreach and clinical services in Blantyre, Malawi: findings from a district-wide CLOVE Study.

BACKGROUND: In 2017, Blantyre district had the highest adult HIV prevalence in Malawi (17.7%) and lowest viral suppression (60%). In response, the Ministry of Health expanded prevention and treatment services. We assessed whether outreach to social venues could identify individuals with increased HIV acquisition risk or with unsuppressed HIV not currently reached by clinic-based services. METHODS: We conducted a cross-sectional bio-behavioral survey in Blantyre, Malawi, from January to March 2022. We visited social venues where people meet new sexual partners and government clinics providing HIV testing or STI screening. Participants aged > 15 years were interviewed, and tested for HIV infection if not on ART. HIV recency tests were performed on those testing positive, and dried blood spots (DBS) was collected to quantify viral load and also to identify acute infection in those with HIV- results. RESULTS: HIV prevalence (18.5% vs 8.3%) and unsuppressed HIV infection (3.9% vs 1.7%) were higher among venue-recruited (n=1802) compared with clinic-recruited participants(n=2313). Among PLHIV at both clinics (n=199) and venues (n=289), 79% were virally suppressed. Few had acute(n=1) or recent infection(n=8). Among women, HIV prevalence was four times higher (38.9% venue vs 8.9% clinic). At clinics, PLHIV reporting visiting venues were less likely to be suppressed (54.6 vs 82.6%). More men at venues than at clinics reported paying for sex (49% vs 30%) or having multiple sex partners in the past 4 weeks (32% vs 16%). CONCLUSIONS: Enhanced venue-based prevention and testing for men and women could reduce treatment lapses, HIV treatment outcomes and reduce onward transmission.

Longitudinal changes in a claims-based frailty proxy measure compared to concurrent changes in the Fried frailty phenotype.

BACKGROUND: Frailty is a dynamic aging-related syndrome, but measuring frailty transitions is challenging. The Faurot frailty index is a validated Medicare claims-based frailty proxy based on demographic and billing information. We evaluated whether three-year changes in the Faurot frailty index were consistent with concurrent changes in the frailty phenotype in a cohort of older adults. METHODS: We used longitudinal data from the National Health and Aging Trends (NHATS) study with Medicare claims linkage (2010-2018). We identified older adults (66+ years) in the 2011 and 2015 NHATS cohorts with at least one year of Medicare fee-for-service continuous enrollment (N=6,951). We described annual changes in mean claims-based frailty for up to three-years, based on concurrent transitions in the frailty phenotype. RESULTS: At baseline, 32% were robust, 48% prefrail, and 19% frail based on the frailty phenotype. Mean claims-based frailty for older adults who were robust at baseline and worsened to frail increased over three-years (0.09-0.25). Similarly, those who worsened from prefrail to frail experienced an increase in mean claims-based frailty (0.14-0.26). Improvements in the frailty phenotype did not correspond to decreases in claims-based frailty. Older adults whose frailty phenotype improved over time had a lower baseline claims-based frailty score than those who experienced stable or worsening frailty. CONCLUSIONS: Older adults who experienced a frailty phenotype worsening over three years experienced concurrent increases in the Faurot frailty index. Our results suggest that claims data may be used to identify clinically meaningful worsening in frailty.

Semiparametric g-computation for survival outcomes with time-fixed exposures: An illustration.

PURPOSE: Generalized (g-) computation is a useful tool for causal inference in epidemiology. However, in settings when the outcome is a survival time subject to right censoring, the standard pooled logistic regression approach to g-computation requires arbitrary discretization of time, parametric modeling of the baseline hazard function, and the need to expand one's dataset. We illustrate a semiparametric Breslow estimator for g-computation with time-fixed treatments and survival outcomes that is not subject to these limitations. METHODS: We compare performance of the Breslow g-computation estimator to the pooled logistic g-computation estimator in simulations and illustrate both approaches to estimate the effect of a 3-drug vs 2-drug antiretroviral therapy regimen among people with HIV. RESULTS: In simulations, both approaches performed well at the end of follow-up. The pooled logistic approach was biased at times between the endpoints of the discrete time intervals used, while the Breslow approach was not. In the example, both approaches estimated a 1-year risk difference of about 6 % in favor of the 3-drug regimen, but the shape of the survival curves differed. CONCLUSIONS: The Breslow g-computation estimator of counterfactual risk functions does not rely on strong parametric assumptions about the time-to-event distribution or onerous dataset expansions.

Evaluating a multifaceted implementation strategy and package of evidence-based interventions based on WHO PEN for people living with HIV and cardiometabolic conditions in Lusaka, Zambia: protocol for the TASKPEN hybrid effectiveness-implementation stepped wedge cluster randomized trial.

BACKGROUND: Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease-HIV-to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as "TASKPEN," that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness. METHODS: The trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor's Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM. DISCUSSION: Findings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).

Intimate Care Products and Incidence of Hormone-Related Cancers: A Quantitative Bias Analysis.

PURPOSE: Intimate care products may contain substances associated with increased risk of hormone-related cancers. The relationship between genital talc use and ovarian cancer, in particular, has been well studied, but concerns about recall bias and exposure misclassification have precluded conclusions. We examined the association between intimate care products and female hormone-related cancers, accounting for potential biases, using data from a US-based cohort study. METHODS: The Sister Study enrolled 50,884 women who had a sister with breast cancer. Data on genital talc use and douching were collected at enrollment (2003-2009) and follow-up (2017-2019). We used Cox proportional hazards models to estimate hazard ratios (HRs) for associations between intimate care product use and breast, ovarian, and uterine cancers. To account for potential exposure misclassification and recall bias, we conducted quantitative bias analyses under various exposure reassignment assumptions. RESULTS: Across considered scenarios, 41%-64% of participants douched and 35%-56% used genital talc. In models adjusted for exposure misclassification, genital talc use was positively associated with ovarian cancer (HR range, 1.17-3.34) Frequent douching and douching during young adulthood were positively associated with ovarian cancer, but neither douching nor talc was associated with breast or uterine cancer. Differential reporting of talc use by cases and noncases likely produces positive biases, but correcting for error still resulted in HRs above 1.0. For example, HR, 1.40 (95% CI, 1.04 to 1.89) when 25% of exposed cases and 10% of unexposed noncases had talc status reassigned. CONCLUSION: Although results show how differential recall would upwardly bias estimates, corrected results support a positive association between use of intimate care products, including genital talc, and ovarian cancer.

Longitudinal trajectories of a claims-based frailty measure during adjuvant chemotherapy in women with stage I-III breast cancer.

BACKGROUND: Frailty is a dynamic syndrome characterized by reduced physiological reserve to maintain homeostasis. Prospective studies have reported frailty worsening in women with breast cancer during chemotherapy, with improvements following treatment. We evaluated whether the Faurot frailty index, a validated claims-based frailty measure, could identify changes in frailty during chemotherapy treatment and identified predictors of trajectory patterns. METHODS: We included women (65+ years) with stage I-III breast cancer undergoing adjuvant chemotherapy in the SEER-Medicare database (2003-2019). We estimated the Faurot frailty index (range: 0-1; higher scores indicate greater frailty) at chemotherapy initiation, 4 months postinitiation, and 10 months postinitiation. Changes in frailty were compared to a matched noncancer comparator cohort. We identified patterns of frailty trajectories during the year following chemotherapy initiation using K-means clustering. RESULTS: Twenty-one thousand five hundred and ninety-nine women initiated adjuvant chemotherapy. Mean claims-based frailty increased from 0.037 at initiation to 0.055 4 months postchemotherapy initiation and fell to 0.049 10 months postinitiation. Noncancer comparators experienced a small increase in claims-based frailty over time (0.055-0.062). We identified 6 trajectory patterns: a robust group (78%), 2 resilient groups (16%), and 3 nonresilient groups (6%). Black women and women with claims for home hospital beds, wheelchairs, and Parkinson's disease were more likely to experience nonresilient trajectories. CONCLUSIONS: We observed changes in a claims-based frailty index during chemotherapy that are consistent with prior studies using clinical measures of frailty and identified predictors of nonresilient frailty trajectories. Our study demonstrates the feasibility of using claims-based frailty indices to assess changes in frailty during cancer treatment.

Emotional and functional well-being in long-term breast cancer survivorship.

PURPOSE: Emotional and functional well-being (EWB and FWB) are important components of mental health and quality of life. This study aims to evaluate long-term EWB and FWB in breast cancer (BC) survivors. METHODS: The Carolina Breast Cancer Study Phase 3 oversampled Black and younger (< 50 years in age) women so that they each represent approximately 50% of the study population and assessed participants' EWB and FWB with the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 5- (baseline), 25-, and 84-months post diagnosis. Multinomial logit models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and clinical characteristics and well-being change relative to baseline. RESULTS: Among 2,781 participants with BC, average EWB and FWB improved with time since diagnosis. Persistent FWB decrements were associated with Black race [OR 1.4 (95% CI 1.2-1.7) and 1.3 (95% CI 1.1-1.6), at 25-months and 84-months respectively], older age [OR 1.4 (95% CI 1.1-1.7) and 1.5 (95% CI 1.2-1.8), respectively], no chemotherapy, and recurrence [OR 2.9 (95% CI 1.8-4.8) and 3.1 (95% CI 2.1-4.6), respectively]. EWB decrements were associated with advanced stage and recurrence. Decrements in combined (FWB+EWB) well-being were associated with recurrence at both follow-up survey timepoints [ORs 4.7 (95% CI 2.7-8.0) and 4.3 (95% CI 2.8-6.6), respectively]. CONCLUSIONS: Long-term well-being varies by demographics and clinical features, with Black women and women with aggressive disease at greatest risk of long-term decrements.

Hepatitis B Virus Prevalence and Transmission in the Households of Pregnant Women in Kinshasa, Democratic Republic of Congo.

Background: The World Health Organization Africa region has high regional hepatitis B virus (HBV) prevalence, and evidence suggests more frequent horizontal HBV transmission than other regions. Context-specific epidemiological studies are needed to inform additional HBV prevention measures. Methods: In the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care in high-volume maternity clinics in Kinshasa, Democratic Republic of Congo. We recruited households of pregnant women ("index mothers") who were HBsAg-positive and HBsAg-negative, defining households as index-positive and index-negative, respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1006 participants from 200 households (100 index-positive, 100 index-negative) across Kinshasa. HBsAg-positivity prevalence was more than twice as high in index-positive households (5.0% [95% confidence interval {CI}, 2.8%-7.1%]) as in index-negative households (1.9% [95% CI, .6%-3.2%]). HBsAg-positivity prevalence was 3.3 (95% CI, .9-11.8) times as high among direct offspring in index-positive versus index-negative households. Factors associated with HBsAg positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among offspring in index-positive households. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

Performance of a Claims-Based Frailty Proxy Using Varying Frailty Ascertainment Lookback Windows.

BACKGROUND: Frailty is an aging-related syndrome of reduced physiological reserve to maintain homeostasis. The Faurot frailty index has been validated as a Medicare claims-based proxy for predicting frailty using billing information from a user-specified ascertainment window. OBJECTIVES: We assessed the validity of the Faurot frailty index as a predictor of the frailty phenotype and 1-year mortality using varying frailty ascertainment windows. RESEARCH DESIGN: We identified older adults (66+ y) in Round 5 (2015) of the National Health and Aging Trends Study with Medicare claims linkage. Gold standard frailty was assessed using the frailty phenotype. We calculated the Faurot frailty index using 3, 6, 8, and 12 months of claims prior to the survey or all-available lookback. Model performance for each window in predicting the frailty phenotype was assessed by quantifying calibration and discrimination. Predictive performance for 1-year mortality was assessed by estimating risk differences across claims-based frailty strata. RESULTS: Among 4253 older adults, the 6 and 8-month windows had the best frailty phenotype calibration (calibration slopes: 0.88 and 0.87). All-available lookback had the best discrimination (C-statistic=0.780), but poor calibration. Mortality associations were strongest using a 3-month window and monotonically decreased with longer windows. Subgroup analyses revealed worse performance in Black and Hispanic individuals than counterparts. CONCLUSIONS: The optimal ascertainment window for the Faurot frailty index may depend on the clinical context, and researchers should consider tradeoffs between discrimination, calibration, and mortality. Sensitivity analyses using different durations can enhance the robustness of inferences. Research is needed to improve prediction across racial and ethnic groups.

Higher-order evidence.

Higher-order evidence is evidence about evidence. Epidemiologic examples of higher-order evidence include the settings where the study data constitute first-order evidence and estimates of misclassification comprise the second-order evidence (e.g., sensitivity, specificity) of a binary exposure or outcome collected in the main study. While sampling variability in higher-order evidence is typically acknowledged, higher-order evidence is often assumed to be free of measurement error (e.g., gold standard measures). Here we provide two examples, each with multiple scenarios where second-order evidence is imperfectly measured, and this measurement error can either amplify or attenuate standard corrections to first-order evidence. We propose a way to account for such imperfections that requires third-order evidence. Further illustrations and exploration of how higher-order evidence impacts results of epidemiologic studies is warranted.

HIV Prevention Among Men Who Have Sex With Men: Tenofovir Alafenamide Combination Preexposure Prophylaxis Versus Placebo.

BACKGROUND: While noninferiority of tenofovir alafenamide and emtricitabine (TAF/FTC) as preexposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) has been shown, interest remains in its efficacy relative to placebo. We estimate the efficacy of TAF/FTC PrEP versus placebo for the prevention of HIV infection. METHODS: We used data from the DISCOVER and iPrEx trials to compare TAF/FTC to placebo. DISCOVER was a noninferiority trial conducted from 2016 to 2017. iPrEx was a placebo-controlled trial conducted from 2007 to 2009. Inverse probability weights were used to standardize the iPrEx participants to the distribution of demographics and risk factors in the DISCOVER trial. To check the comparison, we evaluated whether risk of HIV infection in the shared tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) arms was similar. RESULTS: Notable differences in demographics and risk factors occurred between trials. After standardization, the difference in risk of HIV infection between the TDF/FTC arms was near zero. The risk of HIV with TAF/FTC was 5.8 percentage points lower (95% confidence interval [CI], -2.0% to -9.6%) or 12.5-fold lower (95% CI, .02 to .31) than placebo standardized to the DISCOVER population. CONCLUSIONS: There was a reduction in HIV infection with TAF/FTC versus placebo across 96 weeks of follow-up. CLINICAL TRIALS REGISTRATION: NCT02842086 and NCT00458393.

Leveraging External Validation Data: The Challenges of Transporting Measurement Error Parameters.

Approaches to address measurement error frequently rely on validation data to estimate measurement error parameters (e.g., sensitivity and specificity). Acquisition of validation data can be costly, thus secondary use of existing data for validation is attractive. To use these external validation data, however, we may need to address systematic differences between these data and the main study sample. Here, we derive estimators of the risk and the risk difference that leverage external validation data to account for outcome misclassification. If misclassification is differential with respect to covariates that themselves are differentially distributed in the validation and study samples, the misclassification parameters are not immediately transportable. We introduce two ways to account for such covariates: (1) standardize by these covariates or (2) iteratively model the outcome. If conditioning on a covariate for transporting the misclassification parameters induces bias of the causal effect (e.g., M-bias), the former but not the latter approach is biased. We provide proof of identification, describe estimation using parametric models, and assess performance in simulations. We also illustrate implementation to estimate the risk of preterm birth and the effect of maternal HIV infection on preterm birth. Measurement error should not be ignored and it can be addressed using external validation data via transportability methods.

Risk of Malaria Following Untreated Subpatent Plasmodium falciparum Infections: Results Over 4 Years From a Cohort in a High-Transmission Area in Western Kenya.

BACKGROUND: People with suspected malaria may harbor Plasmodium falciparum undetected by rapid diagnostic test (RDT). The impact of these subpatent infections on the risk of developing clinical malaria is not fully understood. METHODS: We analyzed subpatent P. falciparum infections using a longitudinal cohort in a high-transmission site in Kenya. Weighted Kaplan-Meier models estimated the risk difference (RD) for clinical malaria during the 60 days following a symptomatic subpatent infection. Stratum-specific estimates by age and transmission season assessed modification. RESULTS: Over 54 months, we observed 1128 symptomatic RDT-negative suspected malaria episodes, of which 400 (35.5%) harbored subpatent P. falciparum. Overall, the 60-day risk of developing clinical malaria was low following all episodes (8.6% [95% confidence interval, 6.7%-10.4%]). In the low-transmission season, the risk of clinical malaria was slightly higher in those with subpatent infection, whereas the opposite was true in the high-transmission season (low-transmission season RD, 2.3% [95% confidence interval, .4%-4.2%]; high-transmission season RD, -4.8% [-9.5% to -.05%]). CONCLUSIONS: The risk of developing clinical malaria among people with undetected subpatent infections is low. A slightly elevated risk in the low-transmission season may merit alternate management, but RDTs identify clinically relevant infections in the high-transmission season.

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission.

Loop diuretics are a standard pharmacologic therapy in heart failure (HF) management. Although furosemide is most frequently used, torsemide and bumetanide are increasingly prescribed in clinical practice, possibly because of superior bioavailability. Few real-world comparative effectiveness studies have examined outcomes across all 3 loop diuretics. The study goal was to compare the effects of loop diuretic prescribing at HF hospitalization discharge on mortality and HF readmission. We identified patients in Medicare claims data initiating furosemide, torsemide, or bumetanide after an index HF hospitalization from 2007 to 2017. We estimated 6-month risks of all-cause mortality and a composite outcome (HF readmission or all-cause mortality) using inverse probability of treatment weighting to adjust for relevant confounders. We identified 62,632 furosemide, 1,720 torsemide, and 2,389 bumetanide initiators. The 6-month adjusted all-cause mortality risk was lowest for torsemide (13.2%), followed by furosemide (14.5%) and bumetanide (15.6%). The 6-month composite outcome risk was 21.4% for torsemide, 24.7% for furosemide, and 24.9% for bumetanide. Compared with furosemide, the 6-month all-cause mortality risk was 1.3% (95% confidence interval [CI]: -3.7, 1.0) lower for torsemide and 1.0% (95% CI: -1.2, 3.2) higher for bumetanide, and the 6-month composite outcome risk was 3.3% (95% CI: -6.3, -0.3) lower for torsemide and 0.2% (95% CI: -2.5, 2.9) higher for bumetanide. In conclusion, the findings suggested that the first prescribed loop diuretic following HF hospitalization is associated with clinically important differences in morbidity in older patients receiving torsemide, bumetanide, or furosemide. These differences were consistent for the effect of all-cause mortality alone, but were not statistically significant.

Medications for Opioid Use Disorder and Mortality and Hospitalization Among People With Opioid Use-related Infections.

BACKGROUND: Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections. METHODS: An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay. RESULTS: In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6). CONCLUSION: In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.

Fusing trial data for treatment comparisons: Single vs multi-span bridging.

While randomized controlled trials (RCTs) are critical for establishing the efficacy of new therapies, there are limitations regarding what comparisons can be made directly from trial data. RCTs are limited to a small number of comparator arms and often compare a new therapeutic to a standard of care which has already proven efficacious. It is sometimes of interest to estimate the efficacy of the new therapy relative to a treatment that was not evaluated in the same trial, such as a placebo or an alternative therapy that was evaluated in a different trial. Such dual-study comparisons are challenging because of potential differences between trial populations that can affect the outcome. In this article, two bridging estimators are considered that allow for comparisons of treatments evaluated in different trials, accounting for measured differences in trial populations. A "multi-span" estimator leverages a shared arm between two trials, while a "single-span" estimator does not require a shared arm. A diagnostic statistic that compares the outcome in the standardized shared arms is provided. The two estimators are compared in simulations, where both estimators demonstrate minimal empirical bias and nominal confidence interval coverage when the identification assumptions are met. The estimators are applied to data from the AIDS Clinical Trials Group 320 and 388 to compare the efficacy of two-drug vs four-drug antiretroviral therapy on CD4 cell counts among persons with advanced HIV. The single-span approach requires weaker identification assumptions and was more efficient in simulations and the application.

Transportability Without Positivity: A Synthesis of Statistical and Simulation Modeling.

Studies designed to estimate the effect of an action in a randomized or observational setting often do not represent a random sample of the desired target population. Instead, estimates from that study can be transported to the target population. However, transportability methods generally rely on a positivity assumption, such that all relevant covariate patterns in the target population are also observed in the study sample. Strict eligibility criteria, particularly in the context of randomized trials, may lead to violations of this assumption. Two common approaches to address positivity violations are restricting the target population and restricting the relevant covariate set. As neither of these restrictions is ideal, we instead propose a synthesis of statistical and simulation models to address positivity violations. We propose corresponding g-computation and inverse probability weighting estimators. The restriction and synthesis approaches to addressing positivity violations are contrasted with a simulation experiment and an illustrative example in the context of sexually transmitted infection testing uptake. In both cases, the proposed synthesis approach accurately addressed the original research question when paired with a thoughtfully selected simulation model. Neither of the restriction approaches was able to accurately address the motivating question. As public health decisions must often be made with imperfect target population information, model synthesis is a viable approach given a combination of empirical data and external information based on the best available knowledge.

Mass Probation: Effects of Sentencing Severity on Mental Health for Black and White Individuals.

BACKGROUND: Incarceration is associated with negative impacts on mental health. Probation, a form of community supervision, has been lauded as an alternative. However, the effect of probation versus incarceration on mental health is unclear. Our objective was to estimate the impact on mental health of reducing sentencing severity at individuals' first adult criminal-legal encounter. METHODS: We used the US National Longitudinal Survey on Youth 1997, a nationally representative dataset of youth followed into their mid-thirties. Restricting to those with an adult encounter (arrest, charge alone or no sentence, probation, incarceration), we used parametric g-computation to estimate the difference in mental health at age 30 (Mental Health Inventory-5) if (1) everyone who received incarceration for their first encounter had received probation and (2) everyone who received probation had received no sentence. RESULTS: Among 1835 individuals with adult encounters, 19% were non-Hispanic Black and 65% were non-Hispanic White. Median age at first encounter was 20. Under hypothetical interventions to reduce sentencing, we did not see better mental health overall (Intervention 1, incarceration to probation: RD = -0.01; CI = -0.02, 0.01; Intervention 2, probation to no sentence: RD = 0.00; CI = -0.01, 0.01) or when stratified by race. CONCLUSION: Among those with criminal-legal encounters, hypothetical interventions to reduce sentencing, including incremental sentencing reductions, were not associated with improved mental health. Future work should consider the effects of preventing individuals' first criminal-legal encounter.

Hepatitis B virus prevalence and transmission in the households of pregnant women in Kinshasa, Democratic Republic of Congo.

Background: Despite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC's capital, Kinshasa, to inform additional prevention efforts. Methods: We introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as "exposed" and "unexposed," respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.