Depression and Oral FTC/TDF Pre-exposure Prophylaxis (PrEP) Among Men and Transgender Women Who Have Sex With Men (MSM/TGW).

We conducted a longitudinal and cross-sectional analysis of depressive symptomology in iPrEx, a randomized, placebo-controlled trial of daily, oral FTC/TDF HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. Depression-related adverse events (AEs) were the most frequently reported severe or life-threatening AEs and were not associated with being randomized to the FTC/TDF arm (152 vs. 144 respectively OR 0.66 95 % CI 0.35-1.25). Center for Epidemiologic Studies Depression scale (CES-D) and a four questions suicidal ideation scale scores did not differ by arm. Participants reporting forced sex at anal sexual debut had higher CES-D scores (coeff: 3.23; 95 % CI 1.24-5.23) and were more likely to have suicidal ideation (OR 2.2; 95 % CI 1.09-4.26). CES-D scores were higher among people reporting non-condom receptive anal intercourse (ncRAI) (OR 1.46; 95 % CI 1.09-1.94). We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services

Evaluating the impact of policies recommending PrEP to subpopulations of men and transgender women who have sex with men based on demographic and behavioral risk factors.

IntroductionDeveloping guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings.MethodsWe use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies.ResultsA policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%).ConclusionsThese findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings

Crude incidence in two-phase designs in the presence of competing risks.

BackgroundIn many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome.MethodsWe develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard.ResultsThe proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care.ConclusionsA valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived

Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events

Active-control trials, where an experimental treatment is compared with an established treatment, are performed when the inclusion of a placebo control group is deemed to be unethical. For time-to-event outcomes, the primary estimand is usually the rate ratio, or the closely-related hazard ratio, comparing the experimental group with the control group. In this article we describe major problems in the interpretation of this estimand, using examples from COVID-19 vaccine and HIV pre-exposure prophylaxis trials. In particular, when the control treatment is highly effective, the rate ratio may indicate that the experimental treatment is clearly statistically inferior even when it is worthwhile from a public health perspective. We argue that it is crucially important to consider averted events as well as observed events in the interpretation of active-control trials. An alternative metric that incorporates this information, the averted events ratio, is proposed and exemplified. Its interpretation is simple and conceptually appealing, namely the proportion of events that would be averted by using the experimental treatment rather than the control treatment. The averted events ratio cannot be directly estimated from the active-control trial, and requires an additional assumption about either: (a) the incidence that would have been observed in a hypothetical placebo arm (the counterfactual incidence) or (b) the efficacy of the control treatment (relative to no treatment) that pertained in the active-control trial. Although estimation of these parameters is not straightforward, this must be attempted in order to draw rational inferences. To date, this method has been applied only within HIV prevention research, but has wider applicability to treatment trials and other disease areas

Skating on thin ice: stimulant use and sub‐optimal adherence to HIV pre‐exposure prophylaxis

IntroductionStimulant and heavy alcohol use are prevalent and associated with elevated risk for HIV seroconversion among men who have sex with men (MSM) and transgender women. In addition, each can pose difficulties for antiretroviral adherence among people living with HIV. Scant research has examined the associations of stimulant and heavy alcohol use with adherence to daily oral pre‐exposure prophylaxis (PrEP) among MSM and transgender women. To address this gap in the literature, we evaluated the hypothesis that stimulant use and binge drinking are prospectively associated with sub‐optimal PrEP adherence.MethodsWe analysed data from participants in a nested case‐cohort in the iPrEx open label extension. Stimulant use (i.e. powder cocaine, crack‐cocaine, cocaine paste, methamphetamine, cathinone) and binge drinking (i.e. ≥5 drinks in a single day) in the last 30 days were assessed. Baseline urine was tested for stimulants using immunoassays to reduce misclassification. Sub‐optimal adherence was defined as tenofovir drug concentrations in dried blood spots less than 700 fmol per punch, indicative of less than four doses per week. We tested the prospective association of stimulant use and binge drinking with sub‐optimal adherence at the 4‐week follow‐up visit.Results and DiscussionData from 330 participants were analysed. The majority of the participants were MSM (89%) with a median age at baseline of 29 years (interquartile range 24 to 39). Approximately 16% (52/330) used stimulants and 22% (72/330) reported binge drinking in the last 30 days. Stimulant users had fivefold greater odds of sub‐optimal PrEP adherence compared to non‐users in adjusted analysis (adjusted odds ratio [aOR] 5.04; [95% CI 1.35 to 18.78]). Self‐reported binge drinking was not significantly associated with sub‐optimal adherence after adjusting for stimulant use and baseline confounders (aOR 1.16 [0.49 to 2.73]). Depressive symptoms, being transgender, and number of sex partners were also not significantly associated with sub‐optimal PrEP adherence (p > 0.05).ConclusionsStimulant use is a risk factor for sub‐optimal PrEP adherence in the month following PrEP initiation. Comprehensive prevention approaches that reduce stimulant use may optimize PrEP adherence. Creating adherence plans that specifically address PrEP dosing in the context of ongoing stimulant use should also be considered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142946/1/jia225103.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142946/2/jia225103_am.pd

Public preferences for social distancing policy measures to mitigate the spread of COVID-19 in Missouri

Importance: Policies to promote social distancing can minimize COVID-19 transmission but come with substantial social and economic costs. Quantifying relative preferences among the public for such practices can inform locally relevant policy prioritization and optimize uptake. Objective: To evaluate relative utilities (ie, preferences) for COVID-19 pandemic social distancing strategies against the hypothetical risk of acquiring COVID-19 and anticipated income loss. Design, Setting, and Participants: This survey study recruited individuals living in the Missouri area from May to June 2020 via randomly distributed unincentivized social media advertisements and local recruitment platforms for members of minority racial and ethnic groups. Participants answered 6 questions that asked them to choose between 2 hypothetical counties where business closures, social distancing policy duration, COVID-19 infection risk, and income loss varied. Main Outcomes and Measures: Reweighted population-level relative preferences (utilities) for social distancing policies, subgroups, and latent classes. Results: The survey had a 3% response rate (3045 of 90 320). Of the 2428 respondents who completed the survey, 1669 (75%) were 35 years and older, 1536 (69%) were women, and 1973 (89%) were White. After reweighting to match Missouri population demographic characteristics, the strongest preference was for the prohibition of large gatherings (mean preference, -1.43; 95% CI, -1.67 to -1.18), with relative indifference to the closure of social and lifestyle venues (mean preference, 0.05; 95% CI, -0.08 to 0.17). There were weak preferences to keep outdoor venues (mean preference, 0.50; 95% CI, 0.39 to 0.61) and schools (mean preference, 0.18; 95% CI, 0.05 to 0.30) open. Latent class analysis revealed 4 distinct preference phenotypes in the population: risk averse (48.9%), conflicted (22.5%), prosocial (14.9%), and back to normal (13.7%), with men twice as likely as women to belong to the back to normal group than the risk averse group (relative risk ratio, 2.19; 95% CI, 1.54 to 3.12). Conclusions And relevance: In this survey study using a discrete choice experiment, public health policies that prohibited large gatherings, as well as those that closed social and lifestyle venues, appeared to be acceptable to the public. During policy implementation, these activities should be prioritized for first-phase closures. These findings suggest that policy messages that address preference heterogeneity (eg, focusing on specific preference subgroups or targeting men) could improve adherence to social distancing measures for COVID-19 and future pandemics

Racial Discrimination is Associated with Binge-Eating Disorder in Early Adolescents: A Cross-Sectional Analysis

Background Racial and ethnic discrimination are known stressors and are associated with negative psychological and physical health outcomes. Previous studies have found relationships between racial/ethnic discrimination and binge-eating disorder (BED), though they have mainly focused on adult populations. The aim of this study was to determine associations between racial/ethnic discrimination and BED in a large, national cohort study of early adolescents. We further sought to explore associations between the racial/ethnic discrimination perpetrator (students, teachers, or other adults) and BED. Methods We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (ABCD) (N = 11,075, 2018-2020). Logistic regression analyses examined associations between self-reported racial or ethnic discrimination and binge-eating behaviors and diagnosis. Racial/ethnic discrimination measures were assessed based on the Perceived Discrimination Scale, which measures experiences of discrimination based on race/ethnicity and frequency of ethnic discrimination by teachers, adults outside of school, and students. Binge-eating behaviors and diagnosis were based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSAD-5), adjusting for age, sex, race/ethnicity, household income, parental education, and site. Results In this racially diverse sample of adolescents (N = 11,075, mean age: 11 years), 4.7% of adolescents reported racial or ethnic discrimination and 1.1% met the criteria for BED at the one-year follow-up. In the adjusted models, racial/ethnic discrimination was associated with 3 times higher odds of having BED (OR 3.31, CI 1.66-7.74); when investigating associations between the racial/ethnic discrimination perpetrator (students, teachers, or other adults) and BED, experiencing ethnic discrimination by students and adults outside school were associated with significantly increased odds of BED diagnosis (OR 1.36, CI 1.10-1.68 & OR 1.42 CI 1.06-1.90, respectively); further, increased odds of binge eating behaviors was only significantly associated with ethnic discrimination perpetuated by students (OR 1.12, CI 1.02-1.23). Conclusions Children and adolescents who have experienced racial/ethnic discrimination, particularly when discrimination was perpetuated by other students, have higher odds of having binge-eating behaviors and diagnoses. Clinicians may consider screening for racial discrimination and providing anti-racist, trauma-informed care when evaluating and treating patients for BED

Differentiation of etiologic agents of bacterial keratitis from presentation characteristics

Presenting characteristics of bacterial corneal ulcers may suggest particular causative organisms, helping to guide treatment decisions before cultures become available. In this study, we analyze the association between presentation demographic and clinical characteristics, using data collected as part of a randomized, controlled clinical trial. Data for this study were collected as part of the Steroids for Corneal Ulcers Trial, a randomized, placebo-controlled, double-masked trial. All patients had a culture-proven bacterial corneal ulcer. Patient history, clinical examination, and photography were performed in a standardized fashion at enrollment. Analysis of variance or Fisher's exact test was used to compare characteristics by organism. Univariate logistic regression was used to analyze predictors of the most common organisms. Five hundred patients were enrolled in the trial, of whom 488 were included in this analysis. The most common organism was Streptococcus pneumoniae (N = 248, 51 %) followed by Pseudomonas aeruginosa (N = 110, 23 %). Compared to other organisms, P. aeruginosa was significantly associated with a larger baseline infiltrate/scar size [odds ratio (OR) 1.6, 95 % confidence interval (CI) 1.4-1.8] and deeper infiltrate (OR 2.4, 95 % CI 1.5-3.8). S. pneumoniae was significantly associated with a smaller baseline infiltrate/scar size (OR 0.8, 95 % CI 0.7-0.9) and dacryocystitis (OR 7.3, 95 % CI 4.1-13.3). Nocardia spp. were significantly associated with longer duration of symptoms prior to presentation (OR 1.4, 95 % CI 1.2-1.6), more shallow infiltrate (OR 0.3, 95 % CI 0.2-0.5), and better baseline visual acuity (OR 0.4, 95 % CI 0.2-0.65). Staphylococcus spp. were less likely to be central in location (OR 0.16, 95 % CI 0.08-0.3). Baseline characteristics of bacterial ulcers may suggest the likely etiology and guide early management