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


It is common to present multiple adjusted effect estimates from a single model in a single table. For example, a table might show odds ratios for one or more exposures and also for several confounders from a single logistic regression. This can lead to mistaken interpretations of these estimates. We use causal diagrams to display the sources of the problems. Presentation of exposure and confounder effect estimates from a single model may lead to several interpretative difficulties, inviting confusion of direct-effect estimates with total-effect estimates for covariates in the model. These effect estimates may also be confounded even though the effect estimate for the main exposure is not confounded. Interpretation of these effect estimates is further complicated by heterogeneity (variation, modification) of the exposure effect measure across covariate levels. We offer suggestions to limit potential misunderstandings when multiple effect estimates are presented, including precise distinction between total and direct effect measures from a single model, and use of multiple models tailored to yield total-effect estimates for covariates.

Concepts: Logit, Odds ratio, Confounding, Real number, Covariate, Statistical terminology, Interpretation, Language interpretation


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, Psychology, Understanding, Cognition, Toxicology, Perception, Confounding, 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: Psychology, Confounding


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


Variation in burial location and treatment is often observed in the prehistoric archaeological record, but its interpretation is usually highly ambiguous. Biomolecular approaches provide the means of addressing this variability in a way not previously possible, linking the lives of individuals to their funerary treatment. Here, we undertake stable carbon and nitrogen isotope analyses on a substantial sample of 166 individuals from a series of broadly contemporary Late Neolithic/ Early Chalcolithic (3500 to 2900 cal BC) mortuary monuments (El Sotillo, Alto de la Huesera, Chabola de la Hechicera and Longar) and caves (Las Yurdinas II, Los Husos I and Peña Larga) within a very spatially restricted area of north-central Spain, with sites separated by no more than 10 km on average. This spatial and temporal proximity allows us to focus on the question at the appropriate scale of analysis, avoiding confounding variables such as environmental change, diachronic trends in the subsistence economy, etc. The results demonstrate a statistically significant difference in human δ13C values between those interred in caves and those placed in monuments. The difference appears to be correlated with fine-grained environmental factors (elevation/ temperature/ precipitation), suggesting that use of the landscape was being divided at a very local scale. The reasons for this partitioning may involve differential social status (e.g. those interred in caves may be of lower standing with more restricted access to the valley’s arable resources) or economic specialization (e.g. upland herding vs. valley farming) within the same community or, alternatively, different populations performing different funerary practices and following distinct subsistence economies in some respect. Our results contribute to a better understanding of the development of social differentiation and community specialisation on the scale of the immediate lived landscape.

Concepts: Agriculture, Statistical significance, Sociology, Economics, Confounding, Burial, Economy, Funeral


Some studies have shown a direct relationship between nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting, defined as a percentage of the ideal body weight for age, has been shown to be an independent predictor of mortality in CF. With respect to height only two studies were performed and these studies suggested that stunting is an important determinant of survival but both did not adjust statistical analysis for confounding variables. We aimed at determining the association between stunting and risk of mortality in CF patients.

Concepts: Statistics, Obesity, Actuarial science, Mass, Cystic fibrosis, Confounding, Analysis of variance, Core issues in ethics


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


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: Measurement, Psychometrics, Confounding, Visual analogue scale, Theory, 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: Scientific control, Wheat, Confounding, Case-control study, Receiver operating characteristic, Coeliac disease, Gluten, Gluten-free diet