Four targets: an enhanced framework for guiding causal inference from observational data.

Observational studies play an increasingly important role in estimating causal effects of a treatment or an exposure, especially with the growing availability of routinely collected real-world data. To facilitate drawing causal inference from observational data, we introduce a conceptual framework centered around "four targets"-target estimand, target population, target trial, and target validity. We illustrate the utility of our proposed "four targets" framework with the example of buprenorphine dosing for treating opioid use disorder, explaining the rationale and process for employing the framework to guide causal thinking from observational data.

The Effect of Intensive Treatment of Hypertension on Cardiovascular Events, Generalized to Middle-Aged to Older Americans Living with Hypertension.

The Systolic Blood Pressure Intervention Trial (SPRINT) estimated the effect of intensive SBP treatment (target <120 mmHg) compared to standard (<140 mmHg) on the risk of cardiovascular events in adults aged 50+ years. Clinical trial participants may differ from an intervention's target population. We generalized the SPRINT results to U.

Clinical effects of dexamethasone among patients with sickle cell disease hospitalized with COVID-19: Outcomes from a single academic health system.

Background: Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD.

Methods And Findings: We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022.

Weighing risks and benefits in the presence of competing risks.

Purpose Of Review: When competing events occur, there are two main options for handling them analytically that invoke different assumptions: 1) censor person-time after a competing event (which is akin to assuming they could be prevented) to calculate a conditional risk; or 2) do not censor them (allow them to occur) to calculate an unconditional risk. The choice of estimand has implications when weighing the relative frequency of a beneficial outcome and an adverse outcome in a risk-benefit analysis.

Recent Findings: We review the assumptions and interpretations underlying the two main approaches to analyzing competing risks.

Cohort profile update: the Johns Hopkins HIV clinical cohort, 1989-2023.

The Johns Hopkins HIV Clinical Cohort, established in 1989, links comprehensive, longitudinal clinical data for adults with HIV receiving care in the Johns Hopkins John G. Bartlett Specialty Practice in Baltimore, Maryland, USA, to aid in understanding HIV care and treatment outcomes. Data include demographics, laboratory results, inpatient and outpatient visit information and clinical diagnoses, and prescribed and dispensed medications abstracted from medical records.

An evolved interpretation of Austin Bradford Hill's causal viewpoints and their influence on epidemiologic methods.

In 1965, Sir Austin Bradford Hill articulated nine viewpoints for evaluating whether a body of evidence about the relationship between an exposure and outcome should be interpreted causally. In this commentary, we highlight a selection of the ways in which these viewpoints have had an impact on the field of epidemiology in terms of methods development, study design, and interpretation of results. Additionally, we opine on how the viewpoints relate to our understanding of basic epidemiologic concepts - for example, our choice of absolute or relative measures of effect, our evolving understanding of the role of context in the generalizability of study results, and modern epistemologies for causal inference (i.

The anxiety care continuum and its association with viral suppression among persons with HIV.

Objective: It is unclear how often anxiety is diagnosed and treated and whether anxiety treatment is associated with improved viral suppression in persons with HIV. In this study, we characterized the anxiety care continuum and its association with viral suppression in a large urban HIV clinic in the United States.

Design: Observational cohort study.

Spatio-temporal patterns of excess mortality from non-COVID causes of death in the United States, march-December 2020.

Objectives To estimate the burden of excess mortality from 17 underlying causes of death between March-December 2020 in the United States, and to compare trends in excess deaths from non-COVID causes vs. from COVID-19. Methods Using time series models, we estimated monthly counts of all-cause and cause-specific excess deaths.

Association between switching to integrase strand transfer inhibitors and incident diabetes in people with HIV.

Objective: Integrase strand transfer inhibitors (INSTI) are associated with weight gain in people with HIV (PWH), but their impact on diabetes is unclear. We evaluated the association between switching from nonnucleoside reverse-transcriptase inhibitors (NNRTI) or protease inhibitors (PI) to INSTI and incident diabetes.

Design: Longitudinal cohort study.

Incidence of non-AIDS defining comorbidities among young adults with perinatally acquired HIV in North America.

Objective: The aim of this study is to describe the incidence of diabetes mellitus type 2 (T2DM), hypercholesterolemia, hypertriglyceridemia, hypertension, and chronic kidney disease (CKD) from 2000 to 2019 among North American adults with perinatally acquired HIV (PHIV) aged 18-30 years.

Design: Description of outcomes based on electronic health records for a cohort of 375 young adults with PHIV enrolled in routine HIV care at clinics contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

Methods: We estimated overall, sex, and race-stratified cumulative incidences using Turnbull estimation, and incidence rates using quasi-Poisson regression.

Association of Alcohol Use with COVID-19 Infection and Hospitalization Among People Living with HIV in the United States, 2020.

Alcohol use was associated with elevated COVID-19 risk in the general population. People with HIV (PWH) have high prevalences of alcohol use. To evaluate the effect of alcohol use on COVID-19 risks among PWH, we estimated the risk of COVID-19 diagnosis and COVID-19-related hospitalization among PWH in routine care at 8 HIV primary care centers that contributed data to the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort according to their alcohol use just prior to the COVID-19 pandemic.

The association of changes in depression severity after the onset of the COVID-19 pandemic and viral nonsuppression among people with HIV.

Objective: This study sought to characterize changes in depressive symptom severity during the COVID-19 pandemic and the association of these changes with HIV viral nonsuppression among people with HIV (PWH).

Design: A clinical cohort study.

Methods: We included PWH in the Johns Hopkins HIV Clinical Cohort who completed the Patient Health Questionnaire 8 (PHQ-8) prepandemic (1 March 2018 to 28 February 2020) and during the COVID-era (1 September 2020 to 28 February 2022).

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

"Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency.

Effects of Race and Gender Classifications on Atherosclerotic Cardiovascular Disease Risk Estimates for Clinical Decision-Making in a Cohort of Black Transgender Women.

Introduction: Despite their dynamic, socially constructed, and imprecise nature, both race and gender are included in common risk calculators used for clinical decision-making about statin therapy for atherosclerotic cardiovascular disease (ASCVD) prevention.

Methods And Materials: We assessed the effect of manipulating six different race-gender categories on ASCVD risk scores among 90 Black transgender women.

Results: Risk scores varied by operationalization of race and gender and affected the proportion for whom statins were recommended.

Effect of implementation strategies on pre-exposure prophylaxis persistence among female sex workers in South Africa: an interrupted time series study.

Background: A disproportionate number of new HIV infections in South Africa are among female sex workers; pre-exposure prophylaxis (PrEP) for HIV prevention is freely available to female sex workers in the country, but unique barriers challenge PrEP persistence. TB HIV Care, a large South African non-profit organisation that provides daily oral PrEP (tenofovir disoproxil fumarate and emtricitabine), has implemented multiple strategies to improve PrEP persistence. We aimed to evaluate the effect of different implementation strategies on PrEP persistence in a large-scale real-world setting.

Cardiovascular Disease Risk Estimation for Transgender and Gender-Diverse Patients: Cross-Sectional Analysis of Baseline Data From the LITE Plus Cohort Study.

Introduction: Approximately 2% of the U.S. population identifies as transgender, and transgender people experience disproportionate rates of cardiovascular disease mortality.

Implementing a peer-supported, integrated strategy for substance use disorder care in an outpatient infectious disease clinic is associated with improved patient outcomes.

Background: Substance use disorder (SUD) and infectious disease (ID) care integration may lead to improvements in SUD and ID outcomes. We assessed implementation of integrating peer-supported SUD care in an outpatient ID setting.

Methods: In this implementation study, we describe REcovery in Specialty care Through medication and OutREach (RESTORE), a low-threshold SUD program implemented in a Baltimore outpatient ID clinic.

Investigating the impact of suboptimal prescription of preoperative antiplatelets and statins on race and ethnicity-related disparities in major limb amputation.

Background: Non-Hispanic Black and Hispanic patients with symptomatic PAD may receive different treatments than White patients with symptomatic PAD. The delivery of guideline-directed medical treatment may be a modifiable upstream driver of race and ethnicity-related disparities in outcomes such as limb amputation. The purpose of our study was to investigate the prescription of preoperative antiplatelets and statins in producing disparities in the risk of amputation following revascularization for symptomatic peripheral artery disease (PAD).

Measuring time in buprenorphine treatment stages among people with HIV and opioid use disorder by retention definition and its association with cocaine and hazardous alcohol use.

Background: We use a novel, longitudinal approach to describe average time spent in opioid use disorder (OUD) cascade of care stages for people with HIV (PWH) and with OUD, incorporating four definitions of treatment retention. Using this approach, we describe the impact of cocaine or hazardous alcohol use on time spent retained on buprenorphine.

Methods: We followed PWH with OUD enrolled in the Johns Hopkins HIV Clinical Cohort from their first buprenorphine treatment episode between 2013 and 2020.

Joint effects of substance use disorders and recent substance use on HIV viral non-suppression among people engaged in HIV care in an urban clinic, 2014-2019.

Aims: To estimate the joint effects of substance use disorder (SUD) and recent substance use on human immunodeficiency virus (HIV) non-suppression.

Design: Retrospective clinical cohort study with repeated observations within individuals.

Setting: Baltimore, Maryland, United States.