Selection Bias Due to Loss to Follow Up in Cohort Studies

Selection bias due to loss to follow up represents a threat to the internal validity of estimates derived from cohort studies. Over the last fifteen years, stratification-based techniques as well as methods such as inverse probability-of-censoring weighted estimation have been more prominently discussed and offered as a means to correct for selection bias. However, unlike correcting for confounding bias using inverse weighting, uptake of inverse probability-of-censoring weighted estimation as well as competing methods has been limited in the applied epidemiologic literature. To motivate greater use of inverse probability-of-censoring weighted estimation and competing methods, we use causal diagrams to describe the sources of selection bias in cohort studies employing a time-to-event framework when the quantity of interest is an absolute measure (e.g. absolute risk, survival function) or relative effect measure (e.g., risk difference, risk ratio). We highlight that whether a given estimate obtained from standard methods is potentially subject to selection bias depends on the causal diagram and the measure. We first broadly describe inverse probability-of-censoring weighted estimation and then give a simple example to demonstrate in detail how inverse probability-of-censoring weighted estimation mitigates selection bias and describe challenges to estimation. We then modify complex, real-world data from the University of North Carolina Center for AIDS Research HIV clinical cohort study and estimate the absolute and relative change in the occurrence of death with and without inverse probability-of-censoring weighted correction using the modified University of North Carolina data. We provide SAS code to aid with implementation of inverse probability-of-censoring weighted techniques

Estimating the Effects of Multiple Time-varying Exposures Using Joint Marginal Structural Models: Alcohol Consumption, Injection Drug Use, and HIV Acquisition

The joint effects of multiple exposures on an outcome are frequently of interest in epidemiologic research. In 2001, Hernán, Brumback, and Robins (JASA 2001; 96: 440–448) presented methods for estimating the joint effects of multiple time-varying exposures subject to time-varying confounding affected by prior exposure using joint marginal structural models. Nonetheless, the use of these joint models is rare in the applied literature. Minimal uptake of these joint models, in contrast to the now widely used standard marginal structural model, is due in part to a lack of examples demonstrating the method. In this paper, we review the assumptions necessary for unbiased estimation of joint effects as well as the distinction between interaction and effect measure modification. We demonstrate the use of marginal structural models for estimating the joint effects of alcohol consumption and injection drug use on HIV acquisition, using data from 1,525 injection drug users in the AIDS Link to Intravenous Experience cohort study. In the joint model, the hazard ratio (HR) for heavy drinking in the absence of any drug injections was 1.58 (95% confidence interval= 0.67–3.73). The HR for any drug injections in the absence of heavy drinking was 1.78 (1.10–2.89). The HR for heavy drinking and any drug injections was 2.45 (1.45–4.12). The P values for multiplicative and additive interaction were 0.7620 and 0.9200, respectively, indicating a lack of departure from effects that multiply or add. However, we could not rule out interaction on either scale due to imprecision

A prospective study of alcohol consumption and HIV acquisition among injection drug users

Estimate the effect of alcohol consumption on HIV acquisition while appropriately accounting for confounding by time-varying risk factors

Geographic Variation in Influenza Vaccination Disparities Between Hispanic and Non-Hispanic White US Nursing Home Residents

BACKGROUND: Disparities in influenza vaccination exist between Hispanic and non-Hispanic White US nursing home (NH) residents, but the geographic areas with the largest disparities remain unknown. We examined how these racial/ethnic disparities differ across states and hospital referral regions (HRRs). METHODS: This retrospective cohort study included >14 million short-stay and long-stay US NH resident-seasons over 7 influenza seasons from October 1, 2011, to March 31, 2018, where residents could contribute to 1 or more seasons. Residents were aged ≥65 years and enrolled in Medicare fee-for-service. We used the Medicare Beneficiary Summary File to ascertain race/ethnicity and Minimum Data Set assessments for influenza vaccination. We calculated age- and sex-standardized percentage point (pp) differences in the proportions vaccinated between non-Hispanic White and Hispanic (any race) resident-seasons. Positive pp differences were considered disparities, where the proportion of non-Hispanic White residents vaccinated was greater than the proportion of Hispanic residents vaccinated. States and HRRs with ≥100 resident-seasons per age–sex stratum per racial/ethnic group were included in analyses. RESULTS: Among 7 442 241 short-stay resident-seasons (94.1% non-Hispanic White, 5.9% Hispanic), the median standardized disparities in influenza vaccination were 4.3 pp (minimum, maximum: 0.3, 19.2; n = 22 states) and 2.8 pp (minimum, maximum: −3.6, 10.3; n = 49 HRRs). Among 6 758 616 long-stay resident-seasons (93.7% non-Hispanic White, 6.5% Hispanic), the median standardized differences were −0.1 pp (minimum, maximum: −4.1, 11.4; n = 18 states) and −1.8 pp (minimum, maximum: −6.5, 7.6; n = 34 HRRs). CONCLUSIONS: Wide geographic variation in influenza vaccination disparities existed across US states and HRRs. Localized interventions targeted toward areas with high disparities may be a more effective strategy to promote health equity than one-size-fits-all national interventions

The relationship between adverse neighborhood socioeconomic context and HIV continuum of care outcomes in a diverse HIV clinic cohort in the Southern United States

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/μL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding

Association of sex, hygiene and drug equipment sharing with hepatitis C virus infection among non-injecting drug users in New York City

Background: Hepatitis C virus (HCV) rates are higher in non-injecting drug users (NIDUs) than general population estimates. Whether this elevated HCV rate is due to drug use or other putative risk behaviors remains unclear. Methods: Recent non-injection drug users of heroin, crack and/or cocaine were street-recruited from 2000 to 2003 and underwent an interview and venipuncture for HCV antibody assays. Multiple logistic regression analyses were used to assess correlates for HCV infection. Results: Of 740 enrollees, 3.9% were HCV positive. The median age (intraquartile range) was 30 (35–24) years, 70% were male and 90% were Black or Hispanic. After adjustment, HCV seropositives were significantly more likely than seronegatives to be older than 30 [adjusted odds ratio (AOR) = 5.71], tattooed by a friend/relative/acquaintance [AOR= 3.61] and know someone with HCV [AOR= 4.29], but were less likely to have shared nail or hair clippers, razors or a toothbrush [AOR= 0.32]. Conclusions: Non-commercial tattooing may be a mode of HCV transmission among NIDUs and education on the potential risk in using non-sterile tattooing equipment should be targeted toward this population. While no evidence was found for HCV transmission through NIDU equipment sharing or sexual risk behavior, further research is still warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40317/2/Howe_Association of Sex, Hygiene and Drug Equipment_2005.pd

The Role of At-Risk Alcohol/Drug Use and Treatment in Appointment Attendance and Virologic Suppression Among HIV + African Americans

The causes of poor clinic attendance and incomplete virologic suppression among HIV+ African Americans (AAs) are not well understood. We estimated the effect of at-risk alcohol/drug use and associated treatment on attending scheduled appointments and virologic suppression among 576 HIV+ AA patients in the University of Alabama at Birmingham (UAB) 1917 Clinic Cohort who contributed 591 interviews to the analysis. At interview, 78% of patients were new to HIV care at UAB, 38% engaged in at-risk alcohol/drug use or received associated treatment in the prior year, while the median (quartiles) age and CD4 count were 36 (28; 46) years and 321 (142; 530) cells/μl, respectively. In the 2 years after an interview, half of the patients had attended at least 82% of appointments while half had achieved virologic suppression for at least 71% of RNA assessments. Compared to patients who did not use or receive treatment, the adjusted risk ratio (aRR) for attending appointments for patients who did use but did not receive treatment was 0.97 (95% confidence limits: 0.92, 1.03). The corresponding aRR for virologic suppression was 0.94 (0.86, 1.03). Compared to patients who did not receive treatment but did use, the aRR for attending appointments for patients who did receive treatment and did use was 0.86 (0.78, 0.95). The corresponding aRR for virologic suppression was 1.07 (0.92, 1.24). Use was negatively associated with attendance and virologic suppression among patients not in treatment. Among users, treatment was negatively associated with attendance yet positively associated with virologic suppression. However, aRR estimates were imprecise

Urine cadmium and acute myocardial infarction among never smokers in the Danish Diet, Cancer and Health cohort

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993–1997, 19,394 never-smoking participants (ages 50–64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25(th), 75(th) = 0.13, 0.32 μg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the upper versus lowest quartile (aHR = 1.16; 95% CI: 0.86 – 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 – 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked

African American Race and HIV Virological Suppression: Beyond Disparities in Clinic Attendance

Racial disparities in clinic attendance may contribute to racial disparities in plasma human immunodeficiency virus type 1 (HIV-1) RNA levels among HIV-positive patients in care. Data from 946 African American and 535 Caucasian patients receiving HIV care at the University of North Carolina Center for AIDS Research HIV clinic between January 1, 1999, and August 1, 2012, were used to estimate the association between African American race and HIV virological suppression (i.e., undetectable HIV-1 RNA) when racial disparities in clinic attendance were lessened. Clinic attendance was measured as the proportion of scheduled clinic appointments attended (i.e., visit adherence) or the proportion of six 4-month intervals with at least 1 attended scheduled clinic appointment (i.e., visit constancy). In analyses accounting for patient characteristics, the risk ratio for achieving suppression when comparing African Americans with Caucasians was 0.91 (95% confidence interval: 0.85, 0.98). Lessening disparities in adherence or constancy lowered disparities in virological suppression by up to 44.4% and 11.1%, respectively. Interventions that lessen disparities in adherence may be more effective in eliminating disparities in suppression than interventions that lessen disparities in constancy. Given that gaps in care were limited to be no more than 2 years for both attendance measures, the impact of lessening disparities in adherence may be overstated