Age Differences in the Associations Between Incarceration and Subsequent Substance Use, Sexual Risk-Taking, and Incident STI Among Black Sexual Minority Men and Black Transgender Women in the HIV Prevention Trials 061 Cohort.

Incarceration can lead to different risk behaviors often due to increased distress and disruption of social networks. It is not well known, however, how these associations may differ by age. In this study, we measure age differences in longitudinal associations between incarceration and substance use, sex risk, and sexually transmitted infection (STI) among Black sexual minority men and Black transgender women (BSMM/BTW). We recruited BSMM/BTW from 2009 to 2011 that were part of the HIV Prevention Trials Network 061 study. We compared those less than 30 years old (n = 375) to those 30 years old or greater (n = 794) examining substance use, sex risk, and STI infection stratified by age. Logistic regression with inverse probability weighting was used for the statistical analysis. Approximately 59% of the sample reported incarceration history. In adjusted analysis, incarceration was more strongly associated with alcohol use and stimulant use among older individuals as was sexual risk behaviors including buying and selling sex. Concurrent partnerships were associated with the younger age groups. STI incidence was associated with younger individuals while associations with HIV infection were similar for the two age groups. Understanding differences in substance use and STI risk among age cohorts is imperative to the design and implementation of re-entry programs. Younger BSMM/BTW participating in re-entry support programs may benefit in particular from HIV/STI prevention and care efforts, while post-release substance abuse treatment and harm reduction programs should target older individuals with continued substance abuse.

Neighborhood Food Environment and Birth Weight Outcomes in New York City.

Importance: Infants born with unhealthy birth weight are at greater risk for long-term health complications, but little is known about how neighborhood characteristics (eg, walkability, food environment) may affect birth weight outcomes. Objective: To assess whether neighborhood-level characteristics (poverty rate, food environment, and walkability) are associated with risk of unhealthy birth weight outcomes and to evaluate whether gestational weight gain mediated these associations. Design, Setting, and Participants: The population-based cross-sectional study included births in the 2015 vital statistics records from the New York City Department of Health and Mental Hygiene. Only singleton births and observations with complete birth weight and covariate data were included. Analyses were performed from November 2021 to March 2022. Exposures: Residential neighborhood-level characteristics, including poverty, food environment (healthy and unhealthy food retail establishments), and walkability (measured by both walkable destinations and a neighborhood walkability index combining walkability measures like street intersection and transit stop density). Neighborhood-level variables categorized into quartiles. Main Outcomes and Measures: The main outcomes were birth certificate birth weight measures including small for gestational age (SGA), large for gestational age (LGA), and sex-specific birth weight for gestational age z-score. Generalized linear mixed-effects models and hierarchical linear models estimated risk ratios for associations between density of neighborhood-level characteristics within a 1-km buffer of residential census block centroid and birth weight outcomes. Results: The study included 106 194 births in New York City. The mean (SD) age of pregnant individuals in the sample was 29.9 (6.1) years. Prevalence of SGA and LGA were 12.9% and 8.4%, respectively. Residence in the highest density quartile of healthy food retail establishments compared with the lowest quartile was associated with lower adjusted risk of SGA (with adjustment for individual covariates including gestational weight gain z-score: risk ratio [RR], 0.89; 95% CI 0.83-0.97). Higher neighborhood density of unhealthy food retail establishments was associated with higher adjusted risk of delivering an infant classified as SGA (fourth vs first quartile: RR, 1.12; 95% CI, 1.01-1.24). The RR for the association between density of unhealthy food retail establishments and risk of LGA was higher after adjustment for all covariates in each quartile compared with quartile 1 (second: RR, 1.12 [95% CI, 1.04-1.20]; third: RR, 1.18 [95% CI, 1.08-1.29]; fourth: RR, 1.16; [95% CI, 1.04-1.29]). There were no associations between neighborhood walkability and birth weight outcomes (SGA for fourth vs first quartile: RR, 1.01 [95% CI, 0.94-1.08]; LGA for fourth vs first quartile: RR, 1.06 [95% CI, 0.98-1.14]). Conclusions and Relevance: In this population-based cross-sectional study, healthfulness of neighborhood food environments was associated with risk of SGA and LGA. The findings support use of urban design and planning guidelines to improve food environments to support healthy pregnancies and birth weight.

Does the Association Between Stimulant use and High Risk Sexual Behavior Vary by Injection Drug Use, Sexual Minority Status, or HIV Infection Status? A Meta-analysis.

There is strong evidence linking stimulant use, namely methamphetamine use, to sexual risk behavior among sexual minority men (SMM); we do not, however, have a good understanding of this relationship among other at-risk populations. In this study, we systematically reviewed associations between stimulant use (i.e., methamphetamine, crack cocaine, cocaine) and sexual risk behaviors among populations facing elevated risk of HIV transmission and acquisition (i.e., SMM, people who inject drugs (PWID), and people living with HIV/AIDS (PLWH)). Random-effects meta-analyses and sensitivity analyses that included crude and adjusted estimates separately were conducted to evaluate the impact of potential confounding variables. The results showed strong relationships between stimulant use and condomless sex, transactional sex, and multiple sexual partners. Results were broadly consistent when analyses were stratified by type of stimulant (methamphetamine, crack cocaine, and other stimulants) and risk group. Sensitivity analyses with confounding variables did not greatly impact results. The results indicate that stimulant use is associated with numerous sexual risk behaviors regardless of risk group, suggesting prevention efforts focused on reducing methamphetamine-related HIV risk should target a range of at-risk populations.

Emulating Target Trials to Avoid Immortal Time Bias - An Application to Antibiotic Initiation and Preterm Delivery.

BACKGROUND: Randomized trials in pregnancy are extremely challenging, and observational studies are often the only option to evaluate medication safety during pregnancy. However, such studies are often susceptible to immortal time bias if treatment initiation occurs after time zero of follow-up. We describe how emulating a sequence of target trials avoids immortal time bias and apply the approach to estimate the safety of antibiotic initiation between 24 and 37 weeks gestation on preterm delivery. METHODS: The Tsepamo Study captured birth outcomes at hospitals throughout Botswana from 2014 to 2021. We emulated 13 sequential target trials of antibiotic initiation versus no initiation among individuals presenting to care <24 weeks, one for each week from 24 to 37 weeks. For each trial, eligible individuals had not previously initiated antibiotics. We also conducted an analysis susceptible to immortal time bias by defining time zero as 24 weeks and exposure as antibiotic initiation between 24 and 37 weeks. We calculated adjusted risk ratios (RR) and 95% confidence intervals (CI) for preterm delivery. RESULTS: Of 111,403 eligible individuals, 17,009 (15.3%) initiated antibiotics between 24 and 37 weeks. In the sequence of target trials, RRs (95% CIs) ranged from 1.04 (0.90, 1.19) to 1.24 (1.11, 1.39) (pooled RR: 1.11 [1.06, 1.15]). In the analysis susceptible to immortal time bias, the RR was 0.90 (0.86, 0.94). CONCLUSIONS: Defining exposure as antibiotic initiation at any time during follow-up after time zero resulted in substantial immortal time bias, making antibiotics appear protective against preterm delivery. Conducting a sequence of target trials can avoid immortal time bias in pregnancy studies.

Association of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection With Maternal Mortality and Neonatal Birth Outcomes in Botswana by Human Immunodeficiency Virus Status.

OBJECTIVE: To evaluate the combined association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) infection on adverse birth outcomes in an HIV-endemic region. METHODS: The Tsepamo Study abstracts data from antenatal and obstetric records in government maternity wards across Botswana. We assessed maternal mortality and adverse birth outcomes for all singleton pregnancies from September 2020 to mid-November 2021 at 13 Tsepamo sites among individuals with documented SARS-CoV-2 screening tests and known HIV status. RESULTS: Of 20,410 individuals who gave birth, 11,483 (56.3%) were screened for SARS-CoV-2 infection; 4.7% tested positive. People living with HIV were more likely to test positive (144/2,421, 5.9%) than those without HIV (392/9,030, 4.3%) (P=.001). Maternal deaths occurred in 3.7% of those who had a positive SARS-CoV-2 test result compared with 0.1% of those who tested negative (adjusted relative risk [aRR] 31.6, 95% CI 15.4-64.7). Maternal mortality did not differ by HIV status. The offspring of individuals with SARS-CoV-2 infection experienced more overall adverse birth outcomes (34.5% vs 26.6%; aRR 1.2, 95% CI 1.1-1.4), severe adverse birth outcomes (13.6% vs 9.8%; aRR 1.2, 95% CI 1.0-1.5), preterm delivery (21.4% vs 13.4%; aRR 1.4, 95% CI 1.2-1.7), and stillbirth (5.6% vs 2.7%; aRR 1.7 95% CI 1.2-2.5). Neonates exposed to SARS-CoV-2 and HIV infection had the highest prevalence of adverse birth outcomes (43.1% vs 22.6%; aRR 1.7, 95% CI 1.4-2.0). CONCLUSION: Infection with SARS-CoV-2 at the time of delivery was associated with 3.7% maternal mortality and 5.6% stillbirth in Botswana. Most adverse birth outcomes were worse among neonates exposed to both SARS-CoV-2 and HIV infection.

Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study.

BACKGROUND: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. OBJECTIVE: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. DESIGN: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. SETTING: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). PATIENTS: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. MEASUREMENTS: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. RESULTS: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). LIMITATION: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. CONCLUSION: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further. PRIMARY FUNDING SOURCE: National Institutes of Health.

Cessation of self-reported opioid use and impacts on co-occurring health conditions.

BACKGROUND: Among veterans in care reporting opioid use, we investigated the association between ceasing opioid use on subsequent reduction in report of other substance use and improvements in pain, anxiety, and depression. METHODS: Using Veterans Aging Cohort Study survey data collected between 2003 and 2012, we emulated a hypothetical randomized trial (target trial) of ceasing self-reported use of prescription opioids and/or heroin, and outcomes including unhealthy alcohol use, smoking, cannabis use, cocaine use, pain, and anxiety and depressive symptoms. Among those with baseline opioid use, we compared participants who stopped reporting opioid use at the first follow-up (approximately 1 year after baseline) with those who did not. We fit logistic regression models to estimate associations with change in each outcome at the second follow-up (approximately 2 years after baseline) among participants with that condition at baseline. We examined two sets of adjusted models that varied temporality assumptions. RESULTS: Among 2473 participants reporting opioid use, 872 did not report use, 606 reported use, and 995 were missing data on use at the first follow-up. Ceasing opioid use was associated with no longer reporting cannabis (adjusted odds ratio [AOR]=1.82, 95% confidence interval [CI] 1.10, 3.03) and cocaine use (AOR=1.93, 95% CI 1.16, 3.20), and improvements in pain (AOR=1.53, 95% CI 1.05, 2.24) and anxiety (AOR=1.56, 95% CI 1.01, 2.41) symptoms. CONCLUSION: Cessation of opioid misuse may be associated with subsequent cessation of other substances and reduction in pain and anxiety symptoms, which supports efforts to screen and provide evidence-based intervention where appropriate.

Clinical and population-based study design considerations to accelerate the investigation of new antiretrovirals during pregnancy.

INTRODUCTION: Pregnant women are routinely excluded from clinical trials, leading to the absence or delay in even the most basic pharmacokinetic (PK) information needed for dosing in pregnancy. When available, pregnancy PK studies use a small sample size, resulting in limited safety information. We discuss key study design elements that may enhance the timely availability of pregnancy data, including the role and timing of randomized controlled trials (RCTs) to evaluate pregnancy safety; efficacy and safety outcome measures; stand-alone protocols, platform trials, single arm studies, sample size and the effect that follow-up time during gestation has on analysis interpretations; and observational studies. DISCUSSION: Pregnancy PK should be studied during drug development, after dosing in non-pregnant persons is established (unless non-clinical or other data raise pregnancy concerns). RCTs should evaluate the safety during pregnancy of priority new HIV agents that are likely to be used by large numbers of females of childbearing age. Key endpoints for pregnancy safety studies include birth outcomes (prematurity, small for gestational age and stillbirth) and neonatal death, with traditional adverse events and infant growth also measured (congenital anomalies are best studied through surveillance). We recommend that viral efficacy be studied as a secondary endpoint of pregnancy RCTs, once PK studies confirm adequate drug exposure in pregnancy. RCTs typically use a stand-alone protocol for new agents. In contrast, master protocols using a platform design can add agents over time, possibly speeding safety data ascertainment. To speed accrual, stand-alone pregnancy trial protocols can include pre-specified starting rules based upon adequate PK levels in pregnancy; and seamless master protocols or platform trials can include a pregnancy PK and safety component. When RCTs are unethical or cost-prohibitive, observational studies should be conducted, preferably using target trial emulation to avoid bias. CONCLUSIONS: Pregnancy PK needs to be obtained earlier in drug evaluation. Timely RCTs are needed to understand safety in pregnancy for high-priority new HIV agents. RCTs that enrol pregnant women should focus on outcomes unique to pregnancy, and observational studies should focus on questions that RCTs are not equipped to answer.

Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system.

Background: In the EPIC-HR trial, nirmatrelvir plus ritonavir led to an 88% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. Clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. Objective: To assess whether nirmatrelvir plus ritonavir reduces risk of hospitalization among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune evasive SARS-CoV-2 lineages. Design: Population-based cohort study analyzed to emulate a clinical trial utilizing two-stage, inverse-probability weighted models to account for anticipated bias in testing and treatment. Setting: A large healthcare system providing care for 1.5 million patients in Massachusetts and New Hampshire during Omicron wave (January 1 to May 15, 2022) with staged access and capacity to prescribe nirmatrelvir plus ritonavir. Patients: 30,322 non-hospitalized adults (87.2% vaccinated) aged 50 and older with COVID-19 and without contraindications to nirmatrelvir plus ritonavir. Measurement: Primary outcome was hospitalization within 14 days of COVID-19 diagnosis. Results: During the study period, 6036 (19.9%) patients were prescribed nirmatrelvir plus ritonavir and 24,286 (80.1%) patients were not. Patients prescribed nirmatrelvir were more likely to be older, have more comorbidities, and be unvaccinated. Hospitalization occurred in 40 (0.66%) and 232 (0.96%) patients prescribed and not prescribed nirmatrelvir plus ritonavir, respectively. The adjusted risk ratio was 0.55 (95% confidence interval 0.38 to 0.80, p = 0.002). Observed risk reduction was greater among unvaccinated patients and obese patients. Limitations: Potential for residual confounding due to differential access and uptake of COVID-19 vaccines, diagnostics, and treatment. Conclusions: The overall risk of hospitalization was already low (<1%) following an outpatient diagnosis of COVID-19, but this risk was 45% lower among patients prescribed nirmatrelvir plus ritonavir. Funding: National Institutes of Health (P30 AI060354 and R01 CA236546).

Iron, folic acid, and multiple micronutrient supplementation strategies during pregnancy and adverse birth outcomes in Botswana.

BACKGROUND: Antenatal multiple micronutrient supplementation (MMS) with iron, folic acid, and other micronutrients might improve birth outcomes, but it is not currently universally recommended by WHO. METHODS: In this observational cohort study, we surveyed pregnancies for adverse birth outcomes at eight hospitals from July, 2014, to July, 2018, and 18 hospitals from August, 2018, to December, 2020, in Botswana to assess four routine supplementation strategies in women presenting before 24 weeks' gestation: folic acid only, iron only, iron and folic acid supplementation (IFAS), and MMS. Women with singleton pregnancies; a known HIV status, age, and delivery site; haemoglobin measured within 7 days of presenting to antenatal care; and weight measured within 31 days of presenting to care were included in our analysis. Data were abstracted from the maternity obstetric record (a record of antenatal care) at the time of birth from all women giving birth at selected hospitals throughout the country. We estimated risk differences overall and in key subgroups, adjusting for demographic and clinical factors. FINDINGS: Between July 6, 2014, and Dec 8, 2020, 96 341 eligible women (21 659 [22·5%] of whom had HIV) were included in the study. 36 334 (37·7%) women initiated iron only supplementation, 1133 (11·8%) initiated folic acid only supplementation, 23 101 (24·0%) initiated IFAS, and 31 588 (32·8%) women initiated MMS. Women who initiated iron only and folic acid only supplementation had higher risks of stillbirth, preterm birth, very preterm birth, low and very low birthweight, and neonatal death compared with women who received IFAS (adjusted risk differences for iron only supplementation vs IFAS ranged from 0·22% [95% CI 0·04 to 0·40] for neonatal death to 2·39% [1·78 to 3·00] for preterm birth; and adjusted risk differences for folic acid only supplementation vs IFAS ranged from 0·77% [-0·80 to 2·34] for neonatal death to 5·75% [1·38 to 10·13] for preterm birth), with greater difference in women with HIV and those aged 35 years and older. Compared with IFAS, women who initiated MMS had lower risks of preterm and very preterm births, and low and very low birthweight (adjusted risk differences ranged from -0·50% [-0·77 to 0·23] for very preterm birth to -1·06% [-1·69 to -0·42] for preterm birth). INTERPRETATION: Nationwide data from Botswana support improved birth outcomes with MMS compared with IFAS. FUNDING: National Institutes of Health, National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

High risk of adverse birth outcomes among adolescents living with HIV in Botswana compared to adult women living with HIV and adolescents without HIV.

BACKGROUND: Adolescent girls are three times more likely to be living with HIV than boys of the same age. Prior studies have found associations between adolescent pregnancies and increased maternal morbidity and infant mortality, but few studies have assessed the impact of HIV infection on maternal and infant outcomes in adolescents. METHODS: The Tsepamo Study abstracts maternal and infant data from obstetric records in government maternity wards in Botswana. We assessed maternal complications and adverse birth outcomes for all singleton pregnancies from August 2014 to August 2020 at eighteen Tsepamo sites among adolescents (defined as 10-19 years of age) and adults (defined as 20-35 years of age), by HIV status. Univariate and multivariate logistic regression using a complete case analysis method were used to evaluate differences in outcomes. RESULTS: This analysis included 142,258 singleton births, 21,133 (14.9%) to adolescents and 121,125 (85.1%) to adults. The proportion of adults living with HIV (N = 22,114, 22.5%) was higher than adolescents (N = 1593, 7.6%). The proportion of most adverse birth outcomes was higher in adolescents. Among adolescents, those with HIV had increased likelihoods of anemia (aOR = 1.89, 95%CI 1.66, 2.15) and cesarean sections (aOR = 1.49, 95%CI 1.3,1.72), and infants with preterm birth (aOR = 1.15, 95%CI 1.0, 1.32), very preterm birth (aOR = 1.35, 95%CI 1.0,1.8), small for gestational age (aOR = 1.37, 95%CI 1.20,1.58), and very small for gestational age (aOR = 1.46, 95%CI 1.20, 1.79). CONCLUSIONS: Adolescent pregnancy and adolescent HIV infection remain high in Botswana. Adolescents have higher risk of adverse maternal and infant birth outcomes than adults, with the worst outcomes among adolescents living with HIV. Linking HIV prevention and family planning strategies for this age group may help minimize the number of infants with poor birth outcomes among this already vulnerable population.

A case study and proposal for publishing directed acyclic graphs: The effectiveness of the quadrivalent human papillomavirus vaccine in perinatally HIV Infected girls.

BACKGROUND: Developing a causal graph is an important step in etiologic research planning and can be used to highlight data flaws and irreparable bias and confounding. As a case study, we consider recent findings that suggest human papillomavirus (HPV) vaccine is less effective against HPV-associated disease among girls living with HIV compared to girls without HIV. OBJECTIVES: To understand the relationship between HIV status and HPV vaccine effectiveness, it is important to outline the key assumptions of the causal mechanisms before designing a study to investigate the effect of the HPV vaccine in girls living with HIV infection. METHODS: We present a causal graph to describe our assumptions and proposed approach to explore this relationship. We hope to obtain feedback on our assumptions before data analysis and exemplify the process for designing causal graphs to inform an etiologic study. CONCLUSION: The approach we lay out in this paper may be useful for other researchers who have an interest in using causal graphs to describe and assess assumptions in their own research before undergoing data collection and/or analysis.

The associations of incarceration and depression with healthcare experiences and utilization among Black men who have sex with men in HPTN 061.

Associations of incarceration with healthcare access and utilization among Black sexual minority men (BSMM) and differences in association among those with and without pre-incarceration symptoms of depression were measured. Secondary analysis using survey data from the longitudinal cohort HIV Prevention Trials Network 061 study was conducted among 1553 BSMM from six major U.S. cities from 2009 to 2011. We used modified log-binomial regression with robust standard errors to estimate associations of incarceration (reported at 6 month follow-up) on next six-month healthcare utilization and access (reported at the 12 month follow-up). We tested the significance of baseline depressive symptoms by incarceration interaction and reported differences in associations when observed. Participants with a history of incarceration were more likely to have depressive symptoms at baseline compared to those without. Recent incarceration was associated with almost twice the risk of mistrust in healthcare providers and emergency room utilization. Among men reporting depressive symptoms, a history of incarceration was associated with almost tripled risk of reporting providers do not communicate understandably. Among those with depression, one in five reported a missed visit regardless of incarceration status.

Cannabis use, pain interference, and prescription opioid receipt among persons with HIV: a target trial emulation study.

Concomitant with expanded legalization, cannabis is increasingly used to treat chronic pain among persons with HIV (PWH), despite equivocal benefit in research limited by small sample sizes and short duration of follow-up. To address these limitations, among a sample of PWH with pain interference enrolled in the Veterans Aging Cohort Study, we performed a target trial emulation study to compare the impact of four cannabis use strategies on pain interference. Among those receiving long-term opioid therapy (LTOT), we also explored impact of these strategies on ≥ 25% LTOT dose reduction. Among the analytic sample (N = 1284), the majority were men with a mean age of 50. Approximately 31% used cannabis and 12% received LTOT at baseline. Adjusting for demographic and clinical factors, cannabis use in any of 4 longitudinal patterns was not associated with resolved pain interference over 12- to 24-month follow-up. Among 153 participants receiving LTOT at baseline, cannabis use at both baseline and follow-up was negatively associated with LTOT dose reduction compared to no use at both baseline and follow-up. These findings support other observational studies finding no association between cannabis use and improved chronic pain or LTOT reduction among PWH.

Incarceration and Subsequent Pregnancy Loss: Exploration of Sexually Transmitted Infections as Mediating Pathways.

Background: Incarceration is linked to risk of sexually transmitted infection (STI) postrelease among women. There has been little examination of incarceration's association with related sexual and reproductive outcomes such as pelvic inflammatory disease (PID) and pregnancy loss, or the role of STI in this relationship and whether these relationships differ between Black and White women. Methods: Using data from the National Longitudinal Study of Adolescent to Adult Health, we examined cross-sectional associations between incarceration (Wave IV; 2007-2008; ages 24-34) and history of STI and PID (n = 5,968), and longitudinal associations between incarceration and later pregnancy loss in mid-adulthood (Wave V; 2016-2018; ages 34-43) among women who had ever been pregnant (n = 2,353); we estimated racial differences. Using causal mediation, we explored whether STI mediated associations with pregnancy loss. Results: Incarceration was associated with a history of STI (White adjusted prevalence ratio [APR]: 1.54, 95% confidence interval [CI] 1.14-2.06; Black APR: 1.26, 95% CI 1.02-1.56); the association between incarceration and PID was null among White women (APR: 0.99, 95% CI 0.47-2.09) and elevated among Black women (APR: 2.82, 95% CI 1.36-5.83). Prior incarceration did not appear associated with pregnancy loss among White women (APR: 1.01, 95% CI 0.70-1.45), but was associated among Black women (APR: 1.38, 95% CI: 0.97-1.97), with STI appearing to partially mediate. Conclusions: Pregnancy loss may be elevated among Black women who have been incarcerated, and incarceration-related increases in STI may account for some of this association.

Seasonality of adverse birth outcomes in women with and without HIV in a representative birth outcomes surveillance study in Botswana.

INTRODUCTION: Sub-Saharan Africa has the largest number of people with HIV, one of the most severe burdens of adverse birth outcomes globally and particular vulnerability to climate change. We examined associations between seasonality and adverse birth outcomes among women with and without HIV in a large geographically representative birth outcomes surveillance study in Botswana from 2015 to 2018. METHODS: We evaluated stillbirth, preterm delivery, very preterm delivery, small for gestational age (SGA), very SGA, and combined endpoints of any adverse or severe birth outcome. We estimated the risk of each outcome by month and year of delivery, and adjusted risks ratios (ARRs) of outcomes during the early wet (1 November-15 January), late wet (16 January-31 March) and early dry (1 April-15 July) seasons, compared with the late dry (16 July-31 October) season. Analyses were conducted overall and separately by HIV status. RESULTS: Among 73 178 women (24% with HIV), the risk of all adverse birth outcomes peaked in November-January and reached low points in September. Compared with the late dry season, the ARRs for any adverse birth outcome were 1.03 (95% CI 1.00 to 1.06) for the early dry season, 1.08 (95% CI 1.04 to 1.11) for the early wet season and 1.07 (95% CI 1.03 to 1.10) for the late wet season. Comparing the early wet season to the late dry season, we found that ARRs for stillbirth and very preterm delivery were higher in women with HIV (1.23, 95% CI 0.96 to 1.59, and 1.33, 95% CI 1.10 to 1.62, respectively) than in women without HIV (1.07, 95% CI 0.91 to 1.26, and 1.19, 95% CI 1.04 to 1.36, respectively). CONCLUSIONS: We identified a modest association between seasonality and adverse birth outcomes in Botswana, which was greatest among women with HIV. Understanding seasonal patterns of adverse birth outcomes and the role of HIV status may allow for mitigation of their impact in the face of seasonal extremes related to climate change.

Brief original report: Does smoking status provide information relevant to screening for other substance use among US adults?

We assessed whether tobacco screening provides clinically meaningful information about other substance use, including alcohol and other drug use, potentially facilitating targeting of screening for substance use. Using data from the Veterans Aging Cohort Study survey sample (VACS; N = 7510), we calculated test performance characteristics of tobacco use screening results for identification of other substance use including sensitivity, specificity, positive-likelihood-ratio (+LR = [sensitivity/(1-specificity)]: increase in odds of substance use informed by a positive tobacco screen), and negative-likelihood-ratio (-LR: [(1-sensitivity)/specificity]: reduction in odds of substance use informed by a negative tobacco screen). The sample was 95% male, 75% minority, and 43% were current and 33% were former smokers. Never smoking, versus any history, indicated an approximate four-fold decrease in the odds of injection drug use (-LR = 0.26), an approximate 2.5-fold decrease in crack/cocaine (-LR = 0.35) and unhealthy alcohol use (-LR = 0.40), an approximate two-fold decrease in marijuana (-LR = 0.51) and illicit opioid use (-LR = 0.48), and an approximate 30% decrease in non-crack/cocaine stimulant use (-LR = 0.75). Never smoking yielded more information than current non-smoking (never/former smoking). Positive results on tobacco screening were less informative than negative results; current smoking, versus former/never smoking, provided more information than lifetime smoking and was associated with a 40% increase in the odds of non-crack/cocaine stimulant use (+LR = 1.40) and opioid use (+LR = 1.44), 50% increase in marijuana use (+LR = 1.52) and injection drug use (+LR = 1.55), and an 80-90% increase in crack/cocaine use (+LR = 1.93) and unhealthy alcohol use (+LR = 1.75). When comprehensive screening for substance use is not possible, tobacco screening may inform decisions about targeting substance use screening.

Assessing knowledge, attitudes, and practices towards causal directed acyclic graphs: a qualitative research project.

Causal graphs provide a key tool for optimizing the validity of causal effect estimates. Although a large literature exists on the mathematical theory underlying the use of causal graphs, less literature exists to aid applied researchers in understanding how best to develop and use causal graphs in their research projects. We sought to understand why researchers do or do not regularly use DAGs by surveying practicing epidemiologists and medical researchers on their knowledge, level of interest, attitudes, and practices towards the use of causal graphs in applied epidemiology and health research. We used Twitter and the Society for Epidemiologic Research to disseminate the survey. Overall, a majority of participants reported being comfortable with using causal graphs and reported using them 'sometimes', 'often', or 'always' in their research. Having received training appeared to improve comprehension of the assumptions displayed in causal graphs. Many of the respondents who did not use causal graphs reported lack of knowledge as a barrier to using DAGs in their research. Causal graphs are of interest to epidemiologists and medical researchers, but there are several barriers to their uptake. Additional training and clearer guidance are needed. In addition, methodological developments regarding visualization of effect measure modification and interaction on causal graphs is needed.

Estimating optimal dynamic treatment strategies under resource constraints using dynamic marginal structural models.

Methods for estimating optimal treatment strategies typically assume unlimited access to resources. However, when a health system has resource constraints, such as limited funds, access to medication, or monitoring capabilities, medical decisions must account for competition between individuals in resource usage. The problem of incorporating resource constraints into optimal treatment strategies has been solved for point exposures (1), that is, treatment strategies entailing a decision at just one time point. However, attempts to directly generalize the point exposure solution to dynamic time-varying treatment strategies run into complications. We sidestep these complications by targeting the optimal strategy within a clinically defined subclass. Our approach is to employ dynamic marginal structural models to estimate (counterfactual) resource usage under the class of candidate treatment strategies and solve a constrained optimization problem to choose the optimal strategy for which expected resource usage is within acceptable limits. We apply this method to determine the optimal dynamic monitoring strategy for people living with HIV when resource limits on monitoring exist using observational data from the HIV-CAUSAL Collaboration.