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Supplemental Digital Content is available in the text.Instrumental variables are routinely used to recover a consistent estimator of an exposure causal effect in the presence of unmeasured confounding. Instrumental variable approaches to account for nonignorable missing data also exist but are less familiar to epidemiologists. Like instrumental variables for exposure causal effects, instrumental variables for missing data rely on exclusion restriction and instrumental variable relevance assumptions. Yet these two conditions alone are insufficient for point identification. For estimation, researchers have invoked a third assumption, typically involving fairly restrictive parametric constraints. Inferences can be sensitive to these parametric assumptions, which are typically not empirically testable. The purpose of our article is to discuss another approach for leveraging a valid instrumental variable. Although the approach is insufficient for nonparametric identification, it can nonetheless provide informative inferences about the presence, direction, and magnitude of selection bias, without invoking a third untestable parametric assumption. An important contribution of this article is an Excel spreadsheet tool that can be used to obtain empirical evidence of selection bias and calculate bounds and corresponding Bayesian 95% credible intervals for a nonidentifiable population proportion. For illustrative purposes, we used the spreadsheet tool to analyze HIV prevalence data collected by the 2007 Zambia Demographic and Health Survey (DHS).

ABSTRACTRoutine monitoring of HIV-1 RNA or viral load (VL) in patients on antiretroviral therapy (ART) is important, but there are multiple impediments to VL testing in resource-constrained settings. An accurate point-of-care (POC) HIV-1 VL test could alleviate many of these challenges. We compared the performance of the Cepheid Xpert HIV-1 VL assay against the laboratory-based Abbott m2000sp/m2000rt assay (Abbott assay). ART-naive individuals participating in the Botswana Combination Prevention Project in 20 communities provided EDTA-blood specimens during household surveys. Both the POC Xpert HIV-1 VL and Abbott assays were performed on specimens sampled from 277 individuals. We found a high correlation between the Xpert HIV-1 VL and Abbott assay results (r2= 0.92; P< 0.001). The overall mean difference in the HIV-1 RNA values obtained by Xpert HIV-1 VL assay and Abbott assay was 0.34 log10copies/ml (95% confidence interval [CI], 0.26 to 0.40 log10copies/ml) (P< 0.001). Using a clinically relevant level of 1,000 copies/ml as a threshold, agreement was 90.6% (95% CI, 87.9 to 93.1%), with a sensitivity of 98.6% (95% CI, 97.2 to 100%). The two methods agreed on their detectability of HIV-1 RNA (>40 copies/ml) at 97.1% (95% CI, 95.5 to 98.7%), with a sensitivity of 99.6% (95% CI, 97.2 to 100%). The POC Cepheid Xpert HIV-1 VL assay showed high agreement and accuracy with a laboratory-based method of HIV-1 RNA testing. The POC Xpert HIV-1 VL assay tended to overestimate HIV-1 VL, although the difference was below a clinically relevant threshold of 0.5 log10copies/ml. The POC Cepheid Xpert HIV-1 VL assay is a promising tool for monitoring patients on ART in southern Africa.

HIV programmes face challenges achieving high rates of HIV testing and treatment needed to optimise health and to reduce transmission. We used data from the Botswana Combination Prevention Project study survey to assess Botswana's progress toward achieving UNAIDS targets for 2020: 90% of all people living with HIV knowing their status, 90% of these receiving sustained antiretroviral therapy (ART), and 90% of those having virological suppression (90-90-90).

Obtaining representative information from hidden and hard-to-reach populations is fundamental to describe the epidemiology of many sexually transmitted diseases, including HIV. Unfortunately, simple random sampling is impractical in these settings, as no registry of names exists from which to sample the population at random. However, complex sampling designs can be used, as members of these populations tend to congregate at known locations, which can be enumerated and sampled at random. For example, female sex workers may be found at brothels and street corners, whereas injection drug users often come together at shooting galleries. Despite the logistical appeal, complex sampling schemes lead to unequal probabilities of selection, and failure to account for this differential selection can result in biased estimates of population averages and relative risks. However, standard techniques to account for selection can lead to substantial losses in efficiency. Consequently, researchers implement a variety of strategies in an effort to balance validity and efficiency. Some researchers fully or partially account for the survey design, whereas others do nothing and treat the sample as a realization of the population of interest. We use directed acyclic graphs to show how certain survey sampling designs, combined with subject-matter considerations unique to individual exposure-outcome associations, can induce selection bias. Finally, we present a novel yet simple maximum likelihood approach for analyzing complex survey data; this approach optimizes statistical efficiency at no cost to validity. We use simulated data to illustrate this method and compare it with other analytic techniques.

Risk factors for central line–associated bloodstream infections (CLABSI) among children with cancer in the outpatient setting remain poorly defined, and the microbiology may differ from hospital-onset CLABSI.

The Demographic and Health Survey program routinely collects nationally representative information on HIV-related risk behaviors in many countries, using face-to-face interviews and a complex sampling scheme. If respondents skip questions about behaviors perceived as socially undesirable, such interviews may introduce bias. We sought to implement a doubly robust estimator to correct for dependent missing data in this context.

OBJECTIVE To estimate the societal economic burden and the governmental budgetary impact of the following visual disorders among US adults aged 40 years and older: visual impairment, blindness, refractive error, age-related macular degeneration, cataracts, diabetic retinopathy, and primary open-angle glaucoma. DESIGN We estimated 3 components of economic burden: direct medical costs, other direct costs, and productivity losses. We used private insurance and Medicare claims data to estimate direct medical costs; epidemiologic evidence from multiple published sources to estimate other direct costs, such as nursing home costs; and data from the Survey of Income and Program Participation to estimate productivity losses. We used budgetary documents and our direct medical and other direct cost estimates to approximate the governmental budgetary impact. RESULTS We estimated that the annual total financial burden of major adult visual disorders is $35.4 billion ($16.2 billion in direct medical costs, $11.1 billion in other direct costs, and $8 billion in productivity losses) and that the annual governmental budgetary impact is $13.7 billion. CONCLUSIONS Major visual disorders among Americans older than 40 years result in substantial economic costs for the US economy. Well-designed public health programs may have the ability to reduce this burden in the future.Arch Ophtalmol.2006;124:1754-1760 --

We conducted a matched case-control study of 566 HIV-infected children in Botswana during a 2009–2010 measles outbreak to identify the risk factors for measles. Children in the oldest age quartile (≥13.1 years) were 4-fold more likely to acquire measles than those in the youngest quartile (<7.1 years). HIV-infected older children and adolescents may benefit from additional measles vaccination.

We describe rotavirus testing and clinical characteristics for children admitted with acute gastroenteritis during Botswana's 2011 rotavirus season. The rotavirus season extended from June to October with rotavirus-specific case fatality being 2.8. Using molecular testing as reference, the immunochromatographic test had a sensitivity of 76.5 and specificity of 68.0. Rotavirus vaccine may significantly reduce childhood morbidity and mortality in Botswana.

Background Human immunodeficiency virus (HIV)–exposed, uninfected (HIV-EU) children are at increased risk of infectious illnesses and mortality compared with children of HIV-negative mothers (HIV-unexposed). However, treatment outcomes for lower respiratory tract infections among HIV-EU children remain poorly defined. Methods We conducted a hospital-based, prospective cohort study of N = 238 children aged 1–23 months with pneumonia, defined by the World Health Organization. Children were recruited within 6 hours of presentation to a tertiary hospital in Botswana. The primary outcome—treatment failure at 48 hours—was assessed by an investigator blinded to HIV exposure status. Results Median age was 6.0 months; 55% were male. One hundred fifty-three (64%) children were HIV-unexposed, 64 (27%) were HIV-EU, and 20 (8%) were HIV-infected; the HIV exposure status of 1 child could not be established. Treatment failure at 48 hours occurred in 79 (33%) children, including in 36 (24%) HIV-unexposed, 30 (47%) HIV-EU, and 12 (60%) HIV-infected children. In multivariable analyses, HIV-EU children were more likely to fail treatment at 48 hours (risk ratio [RR]: 1.83, 95% confidence interval [CI]: 1.27–2.64, P = .001) and had higher in-hospital mortality (RR: 4.31, 95% CI: 1.44–12.87, P = .01) than HIV-unexposed children. Differences in outcomes by HIV exposure status were observed only among children under 6 months of age. HIV-EU children more frequently received treatment with a third-generation cephalosporin, but this did not reduce the risk of treatment failure in this group. Conclusions HIV-EU children with pneumonia have higher rates of treatment failure and in-hospital mortality than HIV-unexposed children during the first 6 months of life. Treatment with a third-generation cephalosporins did not improve outcomes among HIV-EU children.