Confounding-by-indication Research Articles

Association of infant antibiotic exposure and risk of childhood asthma: A meta-analysis

BackgroundInfant antibiotic exposure may be associated with childhood asthma development. ObjectiveTo examine and detail this association considering potential confounders. Study designPubMed, EMBASE, Web of Science, and the Cochrane Library were searched for publications from January 2011 to March 2021. Eligible studies were independently reviewed to extract data and assess quality. Random effect model was used to pool odds ratio (OR) and corresponding 95% confidence intervals (CIs). ResultsA total of 52 studies were included. The association of infant antibiotic exposure and childhood asthma was statistically significant for overall analysis (OR, 1.37; 95% CI, 1.29–1.45) and for studies that addressed reverse causation (RC) and confounding by indication (CbI) (1.19; 95% CI, 1.11–1.28). Significance remained after stratification by adjustment for maternal antibiotic exposure, medical consultation, sex, smoke exposure, parental allergy, birth weight, and delivery mode. In detailed analyses, macrolides (OR, 1.56; 95% CI, 1.31–1.86), antibiotic course≥5 (OR, 1.79; 95% CI, 1.36–2.36), exposure within 1 week of birth (OR, 1.82; 95% CI, 1.34–2.47), asthma developed among 1–3 years (OR, 1.84; 95% CI, 1.63–2.08), short time lag between exposure and asthma onset (OR, 2.05; 95% CI, 1.91–2.20), persistent asthma (OR, 2.61; 95% CI, 1.49–4.59), and atopic asthma (OR, 2.14; 95% CI, 1.58–2.90) showed higher pooled estimates. ConclusionInfant antibiotic exposure is associated with increased risk of childhood asthma considering confounding, and the association varied with different settings of exposure and outcomes. This highlights the need for prevention of asthma after early antibiotic exposure. Heterogeneity among studies called for caution when interpretation.

Evaluation of Confounding and Selection Bias in Epidemiological Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation.

Low-dose, penetrating photon radiation exposure is ubiquitous, yet our understanding of cancer risk at low doses and dose rates derives mainly from high-dose studies. Although a large number of low-dose cancer studies have been recently published, concern exists about the potential for confounding to distort findings. The aim of this study was to describe and assess the likely impact of confounding and selection bias within the context of a systematic review. We summarized confounding control methods for 26 studies published from 2006 to 2017 by exposure setting (environmental, medical, or occupational) and identified confounders of potential concern. We used information from these and related studies to assess evidence for confounding and selection bias. For factors in which direct or indirect evidence of confounding was lacking for certain studies, we used a theoretical adjustment to determine whether uncontrolled confounding was likely to have affected the results. For medical studies of childhood cancers, confounding by indication (CBI) was the main concern. Lifestyle-related factors were of primary concern for environmental and medical studies of adult cancers and for occupational studies. For occupational studies, other workplace exposures and healthy worker survivor bias were additionally of interest. For most of these factors, however, review of the direct and indirect evidence suggested that confounding was minimal. One study showed evidence of selection bias, and three occupational studies did not adjust for lifestyle or healthy worker survivor bias correlates. Theoretical adjustment for three factors (smoking and asbestos in occupational studies and CBI in childhood cancer studies) demonstrated that these were unlikely to explain positive study findings due to the rarity of exposure (eg, CBI) or the relatively weak association with the outcome (eg, smoking or asbestos and all cancers). Confounding and selection bias are unlikely to explain the findings from most low-dose radiation epidemiology studies.

Antibiotic use in early life and childhood asthma: causation or confounding?

The prevalence of childhood asthma has been increased yearly.Based on the hygiene hypothesis, the antibiotic use may increase the risk of the allergic disease by reducing microbial exposure.In the last decade, a number of epidemiological studies have been conducted on the association between early exposure of antibiotic and childhood asthma, and the results are not consistent.The majority retrospective studies have found a positive association but the prospective studies have showed a null or weak association.Reverse causation and confounding-by-indication may partly explain the relation.But it is difficult to deny a causal link between antibiotic use and asthma. Key words: Antibiotics; Asthma; Early life

Pneumothorax as an Adverse Drug Event: An Exploratory Aggregate Analysis of the US FDA AERS Database Including A Confounding By Indication Analysis Inspired by Cornfield's Condition

Introduction: Pneumothorax is either primary or secondary. Secondary pneumothorax is usually due to trauma, including various non-pharmacologic iatrogenic triggers. Although not normally thought of as an adverse drug event (ADE) secondary pneumothorax is associated with numerous drugs, though it is often difficult to determine whether this association is causal in nature, or reflects an epiphenomenon of efficacy or inefficacy, or confounding by indication (CBI). Herein we explore this association in a large health authority drug safety surveillance database.Methods: A quantitative pharmacovigilance (PhV) methodology known as disproportionality analysis was applied to the United States Food and Drug Administration (US FDA) Adverse Event Reporting System (AERS) database to explore the quantitative reporting dependencies between drugs and the adverse event pneumothorax as well the corresponding reporting dependencies between drugs and reported indications that may be risk factors for pneumothorax themselves in order to explore the potential contribution of CBI.Results: We found 1. Multiple drugs are associated with pneumothorax; 2. Surfactants and oncology drugs account for most statistically distinctive associations with pneumothorax; 3. Pulmonary surfactants, pentamidine and nitric oxide have the largest statistical reporting associations 4. CBI may play a prominent role in reports of drug-associated pneumothorax.Conclusions: Disproportionality analysis (DA) can provide insights into the spontaneous reporting dependencies between drugs and pneumothorax. CBI assessment based on DA and Cornfield's inequality presents an additional novel option for the initial exploration of potential safety signals in PhV.

Relationship between Epoetin Alfa Dose and Mortality

Observational studies relating epoetin alfa (EPO) dose and mortality frequently use analytic methods that do not control time-dependent confounding by indication (CBI). The relationship between EPO dose and 1-year mortality, adjusting for the effects of time-dependent CBI, was examined using a marginal structural model. This retrospective cohort study included 27,791 hemodialysis patients between July 2000 and June 2002. Patients were grouped at successive 2-wk intervals into a zero-dose category or four nonzero-dose categories. Ordinal regression was used to calculate inverse probability of treatment weights of patients receiving their own dose level given their covariate and treatment history. Three treatment models with an increasing number of treatment predictors were evaluated to assess the effect of model specification. A small number of excessively large patient weights were truncated. Relative hazards for higher-dose groups compared with the lowest nonzero-dose group varied by treatment model specification and by level of weight truncation. Results differed appreciably between the simplest treatment model, which incorporated only hemoglobin and EPO dosing history with 2% weight truncation (hazard ratio: 1.51; 95% confidence interval: 1.09, 1.89 for highest-dose patients), and the most comprehensive treatment model with 1% weight truncation (hazard ratio: 0.98; 95% confidence interval: 0.76, 1.74). There is appreciable CBI at higher EPO doses, and EPO dose was not associated with increased mortality in marginal structural model analyses that more completely addressed this confounding.