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Concept: Confounding


BACKGROUND:Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. METHODS:We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis. RESULTS:We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute in crease in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin- angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithro mycin was not associated with acute kidney injury. INTERPRETATION:We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin- angiotensin-system blockers.

Concepts: Acute kidney injury, Case, Gh, Confounding, Quinolone, Statistical terminology, Logistic regression, Trigraph


The present paper provides an overview of research concerning both acute and chronic effects of exposure to noise on children’s cognitive performance. Experimental studies addressing the impact of acute exposure showed negative effects on speech perception and listening comprehension. These effects are more pronounced in children as compared to adults. Children with language or attention disorders and second-language learners are still more impaired than age-matched controls. Noise-induced disruption was also found for non-auditory tasks, i.e., serial recall of visually presented lists and reading. The impact of chronic exposure to noise was examined in quasi-experimental studies. Indoor noise and reverberation in classroom settings were found to be associated with poorer performance of the children in verbal tasks. Regarding chronic exposure to aircraft noise, studies consistently found that high exposure is associated with lower reading performance. Even though the reported effects are usually small in magnitude, and confounding variables were not always sufficiently controlled, policy makers responsible for noise abatement should be aware of the potential impact of environmental noise on children’s development.

Concepts: Present, Confounding, Toxicology, Psychology, Perception, Understanding, Cognition, Noise pollution


Research has consistently found lower cognitive ability to be related to increased risk for violent and other antisocial behaviour. Since this association has remained when adjusting for childhood socioeconomic position, ethnicity, and parental characteristics, it is often assumed to be causal, potentially mediated through school adjustment problems and conduct disorder. Socioeconomic differences are notoriously difficult to quantify, however, and it is possible that the association between intelligence and delinquency suffer substantial residual confounding.

Concepts: Confounding, Psychology


There is some evidence from studies in adults and limited evidence from studies in children that eating later in the day may increase the risk of overweight and obesity. In this cross-sectional study, we investigated associations between evening meal timing in children and their weight status and energy intake. Dietary data obtained from the UK’s National Diet and Nutrition Survey Rolling Programme (2008-2012) for 768 children aged 4-10 years and 852 children aged 11-18 years were analysed. We tested for an association between evening meal timing (consuming the evening meal before or after 20.00 hours) and risk of overweight and/or obesity, adjusting for relevant confounding variables. We also explored whether evening meal timing was associated with overall nutrient intake. We found no association between evening meal timing and risk of obesity or risk of overweight and obesity combined in either the 4-10 years age group (obesity: OR 1·43; 95 % CI 0·49, 4·13; obesity and overweight combined: OR 1·33; 95 % CI 0·53, 3·33) or the 11-18 years age group (obesity: OR 0·50; 95 % CI 0·24, 1·02; obesity and overweight combined: OR 0·83; 95 % CI 0·50, 1·38), split by sex or as combined. No significant associations were found between evening meal timing and energy intake, and no clear patterns in variation of nutrient intakes with evening meal times were identified. In conclusion, we found no evidence that, for children aged 4-18 years in the UK, eating the evening meal after 20.00 hours was associated with excess weight or increased energy intake.

Concepts: Confounding, Death, Cancer, Overweight, United Kingdom, Obesity, Dieting, Nutrition


Tiotropium, a long-acting anticholinergic, is delivered via HandiHaler(®) or via Respimat(®). RCTs suggest that use of Tiotropium Respimat(®) increases the risk of dying. We compared the risk of mortality between tiotropium Respimat(®) vs. HandiHaler(®).Within the Integrated Primary Care Information database, we defined a source population of patients, ≥40 years, with at least 1 year of follow-up. Based on prescription data, we defined episodes of tiotropium use (Respimat(®) or Handihaler(®)). The risk of mortality, within these episodes, was calculated using a Cox proportional hazard regression analysis.From the source population, 11287 patients provided 24522 episodes of tiotropium use. 496 patients died while being exposed to Handihaler(®) or Respimat(®). Use of Respimat(®) was associated with almost 30% increased risk of dying (HRadj 1.27, 95% CI 1.03-1.57) with the highest risk for cardiovascular/cerebrovascular death (HRadj 1.56, 95% CI 1.08-2.25). The risk was higher in patients with co-existing cardiovascular disease (HRadj 1.36, 95% CI 1.07-1.73) than in patients without (HRadj 1.02, 95% CI 0.61-1.71).Use of tiotropium Respimat(®) was associated with an almost 30% increase of mortality compared to Handihaler(®) and the association was the strongest for cardiovascular/cerebrovascular death. It is unclear whether this association is causal or due to residual confounding by COPD severity.

Concepts: The Strongest, Cardiovascular disease, Source, Confounding, Tiotropium, Disease, Demography, Death


The Wong-Baker FACES Pain Rating Scale (WBS) is preferred by parents and patients for reporting pain severity. However, it is speculated that the “no hurt” and “hurts worst” anchors confound pain measurement with nonnociceptive states. The objective of our study was to determine if fear confounds reporting of pain severity on the WBS. We hypothesized that the WBS would correlate with a psychometrically different pain severity scale (the visual analog scale [VAS]) and not correlate with a fear measure, the Child Medical Fear Scale (CMFS).

Concepts: Theory, Visual analogue scale, Confounding, Measurement, Psychometrics, Pain scale


BACKGROUND: Chromo-zoom endoscopy has been demonstrated to be valuable in assessing the degree of intestinal villous atrophy in patients with suspected celiac disease. OBJECTIVE: To evaluate the diagnostic accuracy of chromo-zoom endoscopy in patients with difficult diagnosis because of nonconcordant test results and/or the confounding of a gluten-free diet initiated before an appropriate diagnosis of celiac disease and to compare the findings to a recent reference standard, the in vitro gliadin challenge test. DESIGN: Prospective, case-control study. SETTING: Tertiary-care referral hospital. PATIENTS: Patients without celiac disease (negative control group, n = 9), patients with celiac disease (positive control group, n = 41), and patients with difficult diagnosis (n = 27). INTERVENTION: Chromo-endoscopy with indigo carmine and endoscopic zoom-magnification were performed. Duodenal fragments were collected for the in vitro gliadin challenge test. The area under the receiver operating characteristic curve (ROC) was used for statistical analyses on accuracy. MAIN OUTCOME MEASUREMENTS: Diagnostic accuracy of chromo-zoom endoscopy for detection of mucosal abnormalities in patients with difficult diagnosis. RESULTS: Chromo-zoom endoscopy had a high accuracy for celiac disease diagnosis in analyses on negative controls and positive controls (area under roc = 0.99). In the difficult diagnosis group, the accuracy of chromo-zoom endoscopy was lower (area under roc = 0.83), but it increased after exclusion of patients with celiac disease on gluten-free diet (area under roc = 0.88). LIMITATIONS: There was a 4% failure rate in the ability to cultivate biopsies. Also, the study was done at an academic medical center. CONCLUSION: Chromo-zoom endoscopy has high accuracy for cases of difficult diagnosis of celiac disease but only in untreated patients with celiac disease.

Concepts: Gluten-free diet, Confounding, Case-control study, Wheat, Gluten, Scientific control, Receiver operating characteristic, Coeliac disease


Many case-control tests of rare variation are implemented in statistical frameworks that make correction for confounders like population stratification difficult. Simple permutation of disease status is unacceptable for resolving this issue because the replicate data sets do not have the same confounding as the original data set. These limitations make it difficult to apply rare-variant tests to samples in which confounding most likely exists, e.g., samples collected from admixed populations. To enable the use of such rare-variant methods in structured samples, as well as to facilitate permutation tests for any situation in which case-control tests require adjustment for confounding covariates, we propose to establish the significance of a rare-variant test via a modified permutation procedure. Our procedure uses Fisher’s noncentral hypergeometric distribution to generate permuted data sets with the same structure present in the actual data set such that inference is valid in the presence of confounding factors. We use simulated sequence data based on coalescent models to show that our permutation strategy corrects for confounding due to population stratification that, if ignored, would otherwise inflate the size of a rare-variant test. We further illustrate the approach by using sequence data from the Dallas Heart Study of energy metabolism traits. Researchers can implement our permutation approach by using the R package BiasedUrn.

Concepts: Covariate, Permutation, Data set, Experimental design, Hypergeometric distribution, Case-control study, Confounding, Statistics


Recent research suggests that diet quality influences depression risk; however, a lack of experimental evidence leaves open the possibility that residual confounding explains the observed relationships. The aim of this study was to document the cross-sectional and longitudinal associations between dietary patterns and symptoms of depression and to undertake a detailed examination of potential explanatory factors, particularly socioeconomic circumstances, in the diet-depression relationship.

Concepts: Confounding, Philosophical terminology, Critical thinking, Nutrition, Theory, Experimental design, Explanation, Scientific method


Douching was recently reported to be associated with elevated levels of urinary metabolites of endocrine disrupting phthalates, but there is no literature on douching in relation to ovarian cancer. Numerous case-control studies of genital talc use have reported an increased risk of ovarian cancer, but prospective cohort studies have not uniformly confirmed this association. Behavioral correlation between talc use and douching could produce confounding.

Concepts: Talc, BRCA2, Ovarian cancer, Confounding, Case-control study, Study design, Epidemiology, Experimental design