Daniel Westreich

• PhD
• Professor (Full) at University of North Carolina at Chapel Hill

Positive attitudes towards aging (ATA) are associated with better mental and physical health in the general population and with lower depressive symptoms among men living with HIV. Little is known about ATA among women of reproductive age living with HIV (WWH), who often experience premature aging, depression, and chronic pain. This study examined...

Background Women with human immunodeficiency virus (HIV; WWH) and with substance use (SU) have poorer HIV-related outcomes. We characterized SU and treatment across reproductive life stages among Study of Treatment And Reproductive Outcomes (STAR) participants. Methods The STAR is a prospective cohort of WWH and women without HIV (WWoH) across 6 S...

Objective We compared the contraceptive effectiveness of typical-use LNG implant and depot medroxyprogesterone acetate (DMPA) injectable during efavirenz use. Design We conducted a prospective cohort study of women living with HIV (WLHIV) on efavirenz-containing antiretroviral treatment in Lilongwe, Malawi. Eligible participants were 18–40 years o...

Introduction Sexually transmitted infections (STI) are highly prevalent among women of reproductive age (WRA) and increase the risk of HIV acquisition and transmission. However, the burden of extragenital STIs is understudied among WRA in the US. Estimates of disease are urgently needed among women living with (WWH) and without HIV (WWOH), to infor...

Background Epidemiologists frequently employ right censoring to handle missing outcome, covariate, or exposure data incurred when participants have large gaps between study visits or stop attending study visits entirely. But, if participants who are censored are more or less likely to experience outcomes of interest than those not censored, such ce...

Objectives To explore the prevalence of depressive symptoms and associated factors among reproductive-aged women participating in the Study of Treatment and Reproductive outcomes (STAR) cohort. Design Cross-sectional analysis. Methods We analyzed baseline data from women with HIV (WWH) and women without HIV (WwoH) but at risk for HIV enrolled in...

Purpose Concomitant use of antiretroviral therapy (ART), hormonal contraception, and isonicotinic acid hydrazide (isoniazid) for tuberculosis prevention is common among women of reproductive age who are living with HIV in sub‐Saharan Africa. We estimated the effect of isoniazid on 6‐month pregnancy risk among Malawian women living with HIV in the F...

Background Few studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes. Methods In a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democrat...

Selection bias has long been central in methodological discussions across epidemiology and other fields. In epidemiology, the concept of selection bias has been continually evolving over time. In this issue of the Journal, Mathur and Shpitser (Am J Epidemiol. XXXX;XXX(XX):XXXX–XXXX) present simple graphical rules for using a Single World Interventi...

In sub-Saharan Africa, adolescent girls and young women aged 15-24 (AGYW) experience high risk of early and unintended pregnancy. We assessed the impact of youth-friendly health services (YFHS) on pregnancy risk among AGYW who participated in the Girl Power study. In 2016, Girl Power randomly assigned four government-run health centers in Lilongwe,...

Among 103 reproductive-aged women with HIV in the U.S. South surveyed post-approval of long-acting injectable (LAI) cabotegravir/rilpivirine, nearly two-thirds reported willingness to try LAI antiretroviral therapy (ART). Most expressed preference for LAI over daily oral ART and had minimal concerns over potential LAI-ART use impacting reproductive...

Background Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero.

Selection bias has long been central in methodological discussions across epidemiology and other fields. In epidemiology, the concept of selection bias has been continually evolving over time. In this issue of the Journal, Mathur and Shpitser (Am J Epidemiol. XXXX;XXX(XX):XXXX–XXXX) present simple graphical rules for using a Single World Interventi...

Background Trachomatous trichiasis (TT) is a painful, potentially blinding eye condition that can be managed through epilation or surgery. Women are affected by TT approximately twice as often as men and are believed to face gendered barriers to receiving surgical care to prevent vision loss. Methods We used data from 817 cross-sectional surveys c...

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 dif...

In epidemiology, collider stratification bias, the bias resulting from conditioning on a common effect of two causes, is oftentimes considered a type of selection bias, regardless of the conditioning methods employed. In this commentary, we distinguish between two types of collider stratification bias: collider restriction bias due to restricting t...

OBJECTIVE We estimated the effect of early initiation of dual therapy vs monotherapy on drug administration and related outcomes in mechanically ventilated, critically ill children. METHODS We used the electronic medical record at a single tertiary medical center to conduct an active comparator, new user cohort study. We included children <18 year...

Studies assessing patient-centred outcomes of novel rifampicin resistant tuberculosis (RR-TB) diagnostics are rare and mostly apply conventional methods which may not adequately address biases. Even though the Xpert MTB/RIF molecular assay was endorsed a decade ago for simultaneous diagnosis of tuberculosis and RR-TB, the impact of the assay on mor...

Inverse probability weighting can be used to correct for missing data. New estimators for the weights in the nonmonotone setting were introduced in 2018. These estimators are the unconstrained maximum likelihood estimator (UMLE) and the constrained Bayesian estimator (CBE), an alternative if UMLE fails to converge. In this work we describe and illu...

Background Trachoma is the leading infectious cause of blindness. To reduce transmission, water, sanitation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce tr...

Background In the presence of effect measure modification, estimates of treatment effects from randomized controlled trials may not be valid in clinical practice settings. The development and application of quantitative approaches for extending treatment effects from trials to clinical practice settings is an active area of research. Methods In th...

Objective: Hypertension is a critical cause of cardiovascular disease, and women with HIV have a higher prevalence of hypertension compared to women without HIV. The relationship between hypertension and mortality has not been well characterized in women with treated HIV. Here, we estimate the effect of hypertension on one-year risk of all-cause m...

Importance: Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received. Objective: To compare oxaliplatin delivery between MOSAIC trial partici...

Pooled testing has been successfully used to expand SARS-CoV-2 testing, especially in settings requiring high volumes of screening of lower-risk individuals, but efficiency of pooling declines as prevalence rises. We propose a differentiated pooling strategy that independently optimizes pool sizes for distinct groups with different probabilities of...

Objective To illustrate the difference between exposure effects and population attributable effects. Methods We examined the effect of mid‐pregnancy short cervical length (<25 mm) on preterm birth using data from a prospective cohort of pregnant women in Lusaka, Zambia. Preterm birth was live birth or stillbirth before 37 weeks of pregnancy. For e...

Purpose: We aim to assess the reporting of key patient-level demographic and clinical characteristics among COVID-19 related randomized controlled trials (RCTs). Methods: We queried English-language articles from PubMed, Web of Science, clinicaltrials.gov, and the CDC library of gray literature databases using keywords of 'coronavirus', 'covid',...

Positivity, the assumption that every unique combination of confounding variables that occurs in a population has a non-zero probability of an action, can be further delineated as deterministic positivity and stochastic positivity. Here, we revisit this distinction, examine its relation to nonparametric identifiability and estimability, and discuss...

Selection bias remains a subject of controversy. Existing definitions of selection bias are ambiguous. To improve communication and the conduct of epidemiologic research focused on estimating causal effects, we propose to unify the various existing definitions of selection bias in the literature by considering any bias away from the true causal eff...

The union of distinct covariate sets, or the superset, is often used in proofs for identification or the statistical consistency of an estimator when multiple sources of bias are present. However, use of a superset can obscure important nuances. Here, we provide two illustrative examples: one in the context of missing data on outcomes, and one in w...

Background: It is not definitively known if people with HIV (PWH) are more likely to be SARS-CoV-2 tested or test positive than people without HIV (PWoH). We describe SARS-CoV-2 testing and positivity in 6 large geographically and demographically diverse cohorts of PWH and PWoH in the United States. Setting: The Corona-Infectious-Virus Epidemiol...

Background: Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV)....

A randomized controlled trial and a regression discontinuity design, out for a causal stroll together, duck into the Potential Outcomes Tavern and step up to the factual counter. The bartender says, “All right, folks, I need to see your identifiability.” The trial says, “Look, I didn’t bring it with me, but it’s by design.” “Fair enough,” says the...

Objectives We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct‐acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. Design Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995–2017, excluding those w...

Poverty alleviation programs can reduce HIV incidence but may have greater impacts when combined with other psychosocial interventions. We modeled the change in HIV incidence among South African adolescent girls and young women (AGYW) associated with combining a cash transfer (the South African Child Support Grant (CSG)) with other structural and b...

A correction to this paper has been published: https://doi.org/10.1007/s10461-021-03261-5

In this brief communication, we discuss the confusion of mortality with fatality in the interpretation of evidence in the COVID-19 pandemic, and how this confusion affects the translation of science into policy and practice. We discuss how this confusion has influenced COVID-19 policy in France, Sweden, and the United Kingdom, and discuss the impli...

Objectives: To define a smoking cessation "cascade" among US women with and without HIV and examine differences by sociodemographic characteristics. Design: Observational cohort study using data from smokers participating in the Women's Interagency HIV Study between 2014 and 2019. Methods: We followed 1165 women smokers with and without HIV fr...

Inverse probability weights are increasingly used in epidemiological analysis, and estimation and application of weights to address a single bias are well discussed in the literature. Weights to address multiple biases simultaneously (i.e. a combination of weights) have almost exclusively been discussed related to marginal structural models in long...

Objective To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB. Methods We analysed singleton live‐born pregnancies among women from 1995 to 2019 in the Women's Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status...

Background: Prior studies suggest neighborhood poverty and deprivation are associated with adverse health outcomes including death, but evidence is limited among persons with HIV, particularly women. We estimated changes in mortality risk from improvement in three measures of area-level socioeconomic context among participants of the Women's Inter...

Background Improved sanitation has been associated with improved child growth in observational studies, but multiple randomized trials that delivered improved sanitation found no effect on child growth. We assessed to what extent differences in the effect estimated in the two study designs (the effect of treatment in observational studies and the e...

Alternatives to nasopharyngeal sampling are needed to increase capacity for SARS-CoV-2 testing. Among 275 participants, we piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including polyester flocked swabs as well as 3D-printed plastic lattice swabs, placed into viral transport media or an RNA stabilization agent. Flock...

e18706 Background: Real-world patients often differ from trial participants in prognostic factors such as age, sex, and cancer substage. New methods combine covariate data from real-world patients (the “target population”) with outcome and covariate data from a trial to estimate treatment effects in the target population that take these differences...

1521 Background: Patterns of chemotherapy delivery are likely to differ between trial and real-world populations. Typical measures used to compare these patterns are calculated at treatment completion, potentially missing key differences in the timing and trajectory of delays and dose reductions. We used a new measure, longitudinal cumulative dose...

BACKGROUND Nearly one quarter of the 1.1 million individuals living with HIV in the United States (US) are women, and racial/ethnic minority women in the Southern US are disproportionately impacted by the epidemic. Reproductive age women with HIV (WWH) are prone to poor HIV outcomes but remain underrepresented in HIV research. We will answer contem...

Background: Nearly a quarter of the 1.1 million individuals with HIV in the United States are women. Racial and ethnic minority women in the Southern United States are disproportionately impacted. Reproductive-age women with HIV are prone to poor HIV outcomes but remain underrepresented in HIV research. We will answer contemporary questions relate...

Efavirenz was associated with increased suicidal thoughts/behaviors in an analysis of randomized trials. However, analyses of observational data have found no evidence of increased hazard. To assess whether population differences explain this divergence we transported the effect of efavirenz from these trials to a specific target population. Using...

Objective: People with HIV (PWH) experience increased prevalence of obstructive lung disease (OLD), regardless of greater observed smoking behaviors. We investigated whether the effect of incident OLD on mortality differed by HIV and HIV viral suppression among persons who inject drugs (PWID) and report smoking history. Design: ALIVE is a longit...

Adjuvant chemotherapy regimens take months to complete. Despite this, studies evaluate chemotherapy adherence via measures assessed at the end of treatment (eg, number of patients missing any dose, relative dose intensity [RDI]). This approach ignores information like the timing of treatment delays. We propose longitudinal cumulative dose (LCD) to...

Machine learning is gaining prominence in the health sciences, where much of its use has focused on data-driven prediction. However, machine learning can also be embedded within causal analyses, potentially reducing biases arising from model misspecification. Using a question-and-answer format, we provide an introduction and orientation for epidemi...

Background: Standard nasopharyngeal swab testing for SARS-CoV-2 detection by PCR is not always feasible due to limitations in trained personnel, personal protective equipment, swabs, PCR reagents, and access to cold chain and biosafety hoods. Methods: We piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including both st...

Subgroup analyses of randomized controlled trials guide resource allocation and implementation of new interventions by identifying groups of individuals who are likely to benefit most from the intervention. Unfortunately, trial populations are rarely representative of the target populations of public health or clinical interest; unless the relevant...

Background Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. Methods We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learni...

Background The global COVID-19 pandemic has the potential to indirectly impact the transmission dynamics and prevention of HIV and other sexually transmitted infections (STI). It is unknown what combined impact reductions in sexual activity and interruptions in HIV/STI services will have on HIV/STI epidemic trajectories. Methods We adapted a model...

Objective To estimate the effect of clinical chorioamnionitis on the risk of patent ductus arteriosus (PDA). Study design A secondary analysis of all deliveries >23 gestational weeks from the U.S. Consortium on Safe Labor (CSL) study. The primary exposure was a clinical diagnosis of chorioamnionitis, and the outcome was a diagnosis of PDA. General...

Background Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors as...

Background: Parametric g-computation is an analytic technique that can be used to estimate the effects of exposures, treatments and interventions; it relies on a different set of assumptions than more commonly used inverse probability weighted estimators. Whereas prior work has demonstrated implementations for binary exposures and continuous outco...

Background: The global COVID-19 pandemic has the potential to indirectly impact the transmission dynamics and prevention of HIV and other sexually transmitted infections (STI). Studies have already documented reductions in sexual activity ("sexual distancing") and interruptions in HIV/STI services, but it is unknown what combined impact these two...

In trials with noncompliance to assigned treatment, researchers might be interested in estimating a per-protocol effect-a comparison of two counterfactual outcomes defined by treatment assignment and (often time-varying) compliance with a well-defined treatment protocol. Here, we provide a general counterfactual definition of a per-protocol effect...

Background: Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus. But evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes...

: As policies built on "Undetectable = Untransmittable" become more popular, use of durable viral suppression (DVS) as an outcome in analyses is increasing. We identified a case series of recent HIV-related publications that study the DVS outcome. The majority did not distinguish between a definition of DVS and the operationalization of that defini...

Illustrations of the g-computation algorithm to evaluate population average treatment and intervention effects have been predominantly implemented in settings with complete exposure information. Thus, worked examples of approaches to handle missing data in this causal framework are needed to facilitate wider use of these estimators. We illustrate t...

When estimating causal effects, careful handling of missing data is needed to avoid bias. Complete case analysis is commonly used in epidemiologic analyses. Previous work has shown that covariate-stratified effect estimates from complete case analysis are unbiased when missingness is independent of the outcome conditional on the exposure and covari...

High-throughput molecular testing for SARS-CoV-2 may be enabled by group testing in which pools of specimens are screened, and individual specimens tested only after a pool tests positive. Several labs have recently published examples of pooling strategies applied to SARS-CoV-2 specimens, but overall guidance on efficient pooling strategies is lack...

Objective Subgroup analyses of clinical trial data can be an important tool for understanding when treatment effects differ across populations. That said, even effect estimates from pre-specified subgroups in well-conducted trials may not apply to corresponding subgroups in the source population. While this divergence may simply reflect statistical...

7067 Background: Treatment effects may differ between trials and community settings, in part due to underrepresentation of certain patient subgroups in trials. We used a hybrid approach combining clinical trial and real-world data to compare the effectiveness of adjuvant FOLFOX vs 5FU for stage II-III colon cancer in community oncology practice. Me...

3522 Background: Adjuvant chemotherapy regimens take months to complete. Despite this, trials and observational studies evaluate chemotherapy adherence via measures assessed at the end of treatment (e.g. number of patients missing any dose, relative dose intensity [RDI]). This approach misses information that impacts outcomes, like treatment delays...

Background HIV testing rates in many hyper-endemic areas are lower than needed to curtail the HIV epidemic. New HIV testing strategies are needed to overcome barriers to traditional clinic based testing; HIV self-testing is one modality that offers promise in reaching individuals who experience barriers to clinic-based testing. Methods We conducte...

Objectives To determine adverse maternal and neonatal outcomes among women with preeclampsia with severe features who delivered <34 weeks comparing those with versus without a comorbid condition. Study design A retrospective analysis from the U.S. Consortium on Safe Labor Study of deliveries <34 weeks with preeclampsia with severe features. We exa...

Transportability provides a principled framework to address the problem of applying study results to new populations. Here, we consider the problem of selecting variables to include in transport estimators. We provide a brief overview of the transportability framework and illustrate that while selection diagrams are a vital first step in variable s...

This chapter discusses the measures of contrast between two groups within the study population. Whereas in Chapter 1 the researcher might describe the total number of cases of a disease in a large population as a whole, in this chapter the researcher is interested in (for example) contrasting risk among those exposed to a drug and those unexposed t...

In Chapter 8, the author discusses several other key study designs, including some of the more “traditional” epidemiologic designs, among them case reports and series, case-crossover studies, and cross-sectional studies, as well as several “hybrid” designs that combine aspects of randomized trials with aspects of observational studies—including sys...

In Chapter 5, the author describes randomized trials. The chapter gives a broad overview of types of trials and the steps in conducting a trial and also describes how trials meet (and fail to meet) core causal identification conditions. The author provides a brief introduction to the analysis of randomized trial data. As well, the chapter introduce...

Chapter 3 discusses basic concepts in causal inference, beginning with an introduction to potential outcomes and definitions of causal contrasts (or causal estimates of effect), concepts, terms, and notation. Many concepts introduced here will be developed further in subsequent chapters. The author discusses sufficient conditions for estimation of...

In contrast to a randomized trial, an observational cohort study is one in which the investigator observes a group of participants with varying levels of an exposure and then follows-up those participants for a period of time to examine the incidence of one or more specified outcomes. This chapter addresses observational cohort studies in much the...

In Chapter 9, the author discusses the causal impact framework, an approach to epidemiologic methods that can be used to move from internally valid estimates to externally valid estimates to valid estimates of the effects of population interventions. Such work is essential if epidemiologists want the results of their experimental or observational s...

Surveillance, diagnostic testing, and screening are central (and related) concepts in epidemiology, and are all addressed together in this chapter. Both description and prediction are also important goals of epidemiology, and these differ in important ways from causal epidemiology. In Chapter 4, the author discusses concepts in diagnostic testing,...

As the cornerstone science of public health, evidence-based medicine, and comparative effectiveness research, a clear understanding of study designs is central to the study of epidemiology. Causal inference is increasingly being understood as the theoretical foundation underlying epidemiologic study designs and the science as a whole. This textbook...

In contrast to an observational cohort study in which participants are identified, exposures are measured, and then outcomes status is measured after follow-up, a case-control study is an observational study in which researchers sample participants based on their outcome status, often only after all outcomes have already occurred. This chapter echo...

The first task of epidemiology is to understand in some depth the concepts of prevalence and incidence, how to quantify them, and key types of error that can affect the measurements of each. In Chapter 1, the author describes prevalence and incidence in single samples (a single population), as well as how to quantify these measures. The chapter wil...

The number needed to treat (NNT) is a widely used measure of the potential impact of a treatment or intervention, but it is often calculated and discussed in ways which oversimplify critical issues. Specifically, the NNT itself depends on the population under study and the specific form that "treatment" would take in that population. We discuss how...

Background: The cost of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) prompted many payers to restrict treatment to patients who met non-evidence-based criteria. These restrictions have implications for survival of people with HCV, especially for people with human immunodeficiency virus (HIV)/HCV coinfection who are at high risk for...

Concerns have been raised about progestin-containing contraceptives and risk of HIV acquisition. Based on health insurance data from 622,565 women in the U.S. with intrauterine device (IUD) insertions during 2011-2018, there was no increased risk of incident HIV diagnosis among women using levonorgestrel-releasing IUDs compared with those using cop...

Background: Several health agencies define microcephaly for surveillance purposes using a single criterion, a percentile or Z-score cut-off for newborn head circumference. This definition, however, conflicts with the reported prevalence of microcephaly even in populations with endemic Zika virus. Objective: We explored possible reasons for this...

Nonparametric bounds for the risk difference are straightforward to calculate and make no untestable assumptions about unmeasured confounding or selection bias due to missing data (e.g., dropout). These bounds are often wide and communicate uncertainty due to possible systemic errors. An illustrative example is provided.

Background Respiratory exposure to silica is associated with the risk of death due to malignant and non-malignant disease. 2.3 million U.S. workers are exposed to silica. Occupational exposure limits for silica are derived from a number of lines of evidence, including observational studies. Observational studies may be subject to healthy worker sur...

In the absence of strong assumptions (e.g., exchangeability), only bounds for causal effects can be identified. We describe bounds for the risk difference of a binary exposure on a binary outcome under four common study settings: observational and randomized studies, each with and without simple random selection from the target population. Through...