SIMULATION IN PRACTICE: THE BALANCING INTERCEPT

Simulation is an important tool within epidemiology for both learning and developing new methodology (1–5). Unfortunately, few epidemiology training programs teach basic simulation methods. Briefly, when conducting a simulation experiment, we generally follow the same basic steps. We first decide which variables to include, as well as their distributions and associations—often aided by a causal diagram. We then generate those variables by sampling from their specified distributions and estimate whatever target parameter is of interest (e.g., sample average or causal effect). We finally repeat the processmultiple times, building a distribution for the target parameter from the estimates obtained in each replicate

Past-month cannabis use among U.S. individuals from 2002–2015: An age-period-cohort analysis

Background: Cannabis is the most commonly used illicit drug among U.S. adolescents and adults, but little is known about factors that drive trends in cannabis use prevalence. To better understand drivers of these trends, we aimed to estimate age, period, and cohort effects on past-month cannabis use among U.S. individuals age 12 and older from 2002 to 2015. Methods: We conducted an age-period-cohort analysis on past-month cannabis use among participants ages 12 and older using the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional nationally-representative survey of drug use. Additionally, we examined how age, period, and cohort effects differed across gender. Participants (n = 779,799) self-reported cannabis patterns using a computer-assisted telephone interview (CATI). Results: Past-month cannabis use in this population increased from 6.0% in 2002 to 8.1% in 2015. Distinct age, period, and cohort effects were observed. Compared to participants ages 12–13, participants ages 18–21 (PR: 16.8, 95% CI: 15.6, 18.1) and 22–25 (PR: 13.2, 95% CI: 12.2, 14.4) had dramatically higher prevalence of past-month cannabis use. Compared to participants in 2002, participants in 2014 (PR: 1.2, 95% CI: 1.1, 1.4) and 2014 (PR: 1.2, 95% CI: 1.1, 1.4) had slightly higher prevalence of past-month cannabis use. Compared to the 1940s birth cohort, the 1950s birth cohort (PR: 1.8, 95% CI: 1.5, 2.2) had a higher prevalence of past-month cannabis use. Conclusions: Past-month cannabis use is prevalent and increasing among U.S. adults. Distinct age, period, and cohort effects are at play, though age effects are strongest

Association of household opioid availability and prescription opioid initiation among household members

Importance Increases in prescription opioid use in the United States have been attributed to changing prescribing guidelines and attitudes toward pain relief; however, the spread of opioid use within households through drug diversion may also be a contributing factor. Objective To investigate whether individuals living in a household with a prescription opioid user are more likely to initiate prescription opioids themselves, compared with individuals in households with a prescription nonsteroidal anti-inflammatory drug (NSAID) user. Design, Setting, and Participants This was a retrospective cohort study using administrative health care claims data from 2000 to 2014 of commercial insurance beneficiaries sharing a health plan with continuous prescription drug coverage, without opioid or NSAID use in the prior year. Enrollees were followed from the date of the first prescription filled by a household member for an eligible opioid or NSAID until initiation of prescription opioids, disenrollment, or administrative censoring after 1 year or the end of follow-up on December 31, 2014. Risk of opioid initiation was derived from inverse probability-weighted (IPW) Kaplan-Meier estimators that adjusted for potential confounders, prognostic factors, and predictors of censoring. Exposure Outpatient pharmacy dispensing of a prescription opioid or prescription NSAID. Main Outcomes and Measures Incident outpatient pharmacy fill for a prescription opioid by a household member. Results From 2000 to 2014, 12 695 280 individuals were exposed to prescription opioids and 6 359 639 to prescription NSAIDS through an index prescription to a household member. The IPW estimated risk of opioid initiation in the subsequent year was 11.83% (95% CI, 11.81%-11.85%) among individuals exposed to prescription opioids in the household, compared with 11.11% (95% CI, 11.09%-11.14%) among individuals exposed to prescription NSAIDs, resulting in a risk difference of 0.71% (95% CI, 0.68%-0.74%). An unmeasured confounder that is modestly associated with the exposure (eg, prevalence difference = 0.9%) and the outcome (eg, risk difference = 0.9) after adjustment for all measured variables could explain our observed estimate of the overall risk difference (0.71%). Conclusions and Relevance Living in a household with a prescription opioid user may increase risk of prescription opioid use, which may reflect both increased access to these products as well as shared risk factors, such as prescriber preference and prescription drug monitoring

Associations between HIV, antiretroviral therapy and preterm birth in the US Women’s Interagency HIV Study, 1995–2018: a prospective cohort

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 and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB < 34 weeks, and, secondarily, < 28 and < 37 weeks. We analysed self-reported birth data, and separately modelled the associations between HIV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count. Results: We analysed 488 singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB < 34 weeks was similar among women with and without HIV, but the risk of PTB < 37 weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07–1.91] among women with HIV. The risk of PTB < 34 weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08–0.44). The associations between HAART and PTB < 28 and < 37 weeks were similar. Conclusions: Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring

Association Between HIV and Prevalence and Manifestations of Asthma: Analysis of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study

Background:The association between HIV and asthma prevalence and manifestations remains unclear, with few studies including women.Setting:A retrospective observational cohort study from the Multicenter AIDS Cohort Study and Women's Interagency HIV Study.Methods:Asthma was defined in 2 ways: (1) self-report and (2) robust criteria requiring all the following: lack of fixed airflow obstruction, presence of wheeze on the St. George's Respiratory Questionnaire (SGRQ), and report of asthma therapies. Estimates of asthma prevalence and asthma-related manifestations were compared by HIV serostatus.Results:A total of 1815 men and 2122 women were included. Asthma prevalence did not differ between people with HIV (PWH) and people without HIV regardless of definition: self-report (men, 12.0% vs. 11.2%; women, 24.3% vs. 27.5%) and robust criteria (men, 5.0% vs. 3.4%; women, 12.8% vs. 13.2%). Among men with asthma, worse respiratory symptom burden was reported among those with HIV, regardless of asthma definition. Among women with self-reported asthma, those with HIV had less respiratory symptom burden. Regardless of serostatus, women with robust-defined asthma had similar respiratory symptoms across SGRQ domains and similar frequencies of phlegm, shortness of breath, and wheezing.Conclusions:Among PWH and people without HIV, asthma prevalence was 2-fold to 3-fold higher using self-reported definition rather than robust definition. In men and women, HIV was not associated with increased asthma prevalence. In men, HIV was associated with more respiratory symptoms when asthma was self-reported; the relationship was attenuated with the robust criteria. Further studies are needed to explore asthma phenotypes among PWH

Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geocoding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8–91.9%; adjusted estimate: 82.5%, 95% CI 65.6–91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES

Intermittent preventive therapy in pregnancy and incidence of low birth weight in malaria-endemic countries

Objectives. To estimate the impact of hypothetical antimalarial and nutritional interventions (which reduce the prevalence of low midupper arm circumference [MUAC]) on the incidence of low birth weight (LBW). Methods. We analyzed data from 14 633 pregnancies from 13 studies conducted across Africa and the Western Pacific from 1996 to 2015. We calculated population intervention effects for increasing intermittent preventive therapy in pregnancy (IPTp), full coverage with bed nets, reduction in malaria infection at delivery, and reductions in the prevalence of low MUAC. Results. We estimated that, compared with observed IPTp use, administering 3 or more doses of IPTp to all women would decrease the incidence of LBW from 9.9% to 6.9% (risk difference = 3.0%; 95% confidence interval = 1.7%, 4.0%). The intervention effects for eliminating malaria at delivery, increasing bed net ownership, and decreasing low MUAC prevalence were all modest. Conclusions. Increasing IPTp uptake to at least 3 doses could decrease the incidence of LBW in malaria-endemic countries. The impact of IPTp on LBW was greater than the effect of prevention of malaria, consistent with a nonmalarial effect of IPTp, measurement error, or selection bias

Body mass index, calcium supplementation and risk of colorectal adenomas

Calcium supplementation (1,200 mg/day) did not significantly reduce colorectal adenomas in our recent randomized, controlled trial (Vitamin D/Calcium Polyp Prevention Study, VCPPS, 2004–2013) in contrast to our previous trial (Calcium Polyp Prevention Study, CPPS, 1988–1996). To reconcile these findings, we identified participant characteristics that differed between the study populations and modified the effect of calcium supplementation on adenomas or high-risk findings (advanced or multiple adenomas). Compared to the CPPS, more participants in the VCPPS were obese (body mass index (BMI) ≥30 kg/m 2 ; 37.5% vs. 24.4%) and fewer had normal BMI (BMI &lt;25 kg/m 2 ; 18.5% vs. 31%). BMI appeared to modify the effect of calcium supplementation on adenomas and especially on high risk-findings: in the VCPPS, there was a 44% reduction in high-risk findings among individuals whose BMI was normal (RR = 0.56, 95% CI = 0.26–1.23), but not among overweight (RR = 1.09, 95% CI = 0.62–1.91) or obese (RR = 1.54, 95% CI = 0.92–2.57) individuals (p interaction = 0.03). Similarly, in the CPPS, there was a 56% reduction in high-risk findings among individuals whose BMI was normal (RR = 0.44, 95% CI = 0.26–0.74), but not among overweight (RR = 0.87, 95% CI = 0.55–1.39) or obese (RR = 1.02, 95% CI = 0.57–1.82) individuals (p interaction = 0.02). Standardization of each trial's findings to the BMI distribution in the other attenuated calcium's protective effect on adenomas in the CPPS but enhanced it in the VCPPS. In conclusion, 1,200 mg/day calcium supplementation may reduce risk of colorectal adenomas among those with normal BMI but not in overweight or obese individuals; and differences in BMI distribution partially account for the apparent difference in calcium efficacy between the two trials