The role of causal reasoning in understanding Simpson's paradox, Lord's paradox, and the suppression effect: covariate selection in the analysis of observational studies

Tu et al present an analysis of the equivalence of three paradoxes, namely, Simpson's, Lord's, and the suppression phenomena. They conclude that all three simply reiterate the occurrence of a change in the association of any two variables when a third variable is statistically controlled for. This is not surprising because reversal or change in magnitude is common in conditional analysis. At the heart of the phenomenon of change in magnitude, with or without reversal of effect estimate, is the question of which to use: the unadjusted (combined table) or adjusted (sub-table) estimate. Hence, Simpson's paradox and related phenomena are a problem of covariate selection and adjustment (when to adjust or not) in the causal analysis of non-experimental data. It cannot be overemphasized that although these paradoxes reveal the perils of using statistical criteria to guide causal analysis, they hold neither the explanations of the phenomenon they depict nor the pointers on how to avoid them. The explanations and solutions lie in causal reasoning which relies on background knowledge, not statistical criteria

Reported associations between asthma and acute lymphoblastic leukemia: insights from a hybrid simulation study.

Numerous studies have reported a protective association between asthma and acute lymphoblastic leukemia (ALL), but the causal structure of this association remains unclear. We present a hybrid simulation to examine the compatibility of this association with uncontrolled confounding by infection or another unmeasured factor. We generated a synthetic cohort using inputs on the interrelations of asthma, ALL, infections, and other suggested risk factors from the literature and the Danish National Birth Cohort. We computed odds ratios (ORs) between asthma and ALL in the synthetic cohort with and without adjustment for infections and other (including unmeasured) confounders. Only if infection was an extremely strong risk factor for asthma (OR of 10) and an extremely strong protective factor against ALL (OR of 0.1) was the asthma-ALL association compatible with the literature (OR of 0.78). Similarly, strong uncontrolled confounding by an unmeasured factor could downwardly bias the asthma-ALL association, but not enough to replicate findings in the literature. This investigation illustrates that the reported protective association between asthma and ALL is unlikely to be entirely due to uncontrolled confounding by infections or an unmeasured confounder alone. Simulation can be used to advance our understanding of risk factors for rare outcomes as demonstrated by this study

The impact of human development on individual health: a causal mediation analysis examining pathways through education and body mass index

ABSTRACT Background. The macro environment we live in projects what we can achieve and how we behave, and in turn, shapes our health in complex ways. Policymaking will benefit from insights into the mechanisms underlying how national socioeconomic context affects health. This study examined the impact of human development on individual health and the possible mediating roles of education and body mass index (BMI). Methods. We analyzed World Health Survey data on 109,448 participants aged 25 or older from 42 low-and middle-income countries with augmented human development index (HDI) in 1990. We used principal components method to create a health score based on measures from eight health state domains, used years of schooling as education indicator and calculated BMI from self-reported height and weight. We used causal mediation analysis technique with random intercepts to account for the multilevel structure. 6.62,] for females). We found a small positive effect of HDI on health via education across reference HDI levels (b ranging from 0.24 to 0.29 for males and 0.40 to 0.49 for females) but not via pathways involving BMI only. Conclusion. Human development has a non-linear effect on individual health, but the impact appears to be mainly through pathways other than education and BMI

Measuring professionalism in medicine and nursing : Results of a European survey

Background: Leveraging professionalism has been put forward as a strategy to drive improvement of patient care. We investigate professionalism as a factor influencing the uptake of quality improvement activities by physicians and nurses working in European hospitals. Objective: To (i) investigate the reliability and validity of data yielded by using the self-developed professionalism measurement tool for physicians and nurses, (ii) describe their levels of professionalism displayed, and (iii) quantify the extent to which professional attitudes would predict professional behaviors. Methods and Materials: We designed and deployed survey instruments amongst 5920 physicians and nurses working in European hospitals. This was conducted under the cross-sectional multilevel study "Deepening Our Understanding of Quality Improvement in Europe" (DUQuE). We used psychometric and generalized linear mixed modelling techniques to address the aforementioned objectives. Results: In all, 2067 (response rate 69.8%) physicians and 2805 nurses (94.8%) representing 74 hospitals in 7 European countries participated. The professionalism instrument revealed five subscales of professional attitude and one scale for professional behaviour with moderate to high internal consistency and reliability. Physicians and nurses display equally high professional attitude sum scores (11.8 and 11.9 respectively out of 16) but seem to have different perceptions towards separate professionalism aspects. Lastly, professionals displaying higher levels of professional attitudes were more involved in quality improvement actions (physicians: b = 0.019, P<0.0001; nurses: b = 0.016, P<0.0001) and more inclined to report colleagues' underperformance (physicians - odds ratio (OR) 1.12, 95% CI 1.01-1.24; nurses - OR 1.11, 95% CI 1.01-1.23) or medical errors (physicians - OR 1.14, 95% CI 1.01-1.23; nurses - OR 1.43, 95% CI 1.22-1.67). Involvement in QI actions was found to increase the odds of reporting incompetence or medical errors. Conclusion: A tool that reliably and validly measures European physicians' and nurses' commitment to professionalism is now available. Collectively leveraging professionalism as a quality improvement strategy may be beneficial to patient care quality. © 2014 Lombarts et al

Maternal pre-pregnancy obesity and timing of puberty in sons and daughters: a population-based cohort study.

BackgroundIn many countries, an increased prevalence of obesity in pregnancy has coincided with a declining pubertal age. We aimed to explore the potential effect of maternal pre-pregnancy overweight and obesity on timing of puberty in sons and daughters.MethodsBetween 2012 and 2018, 15 819 of 22 439 invited children from the Danish National Birth Cohort, born 2000-03, provided half-yearly information from the age of 11 years on the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne and axillary hair. We estimated adjusted mean monthly differences (with 95% confidence intervals) in age at attaining the pubertal milestones for children exposed to maternal pre-pregnancy obesity [body mass index (BMI) ≥30.0 kg/m2] or overweight (BMI 25.0 to 29.9 kg/m2) with normal weight (BMI 18.5 to 24.9 kg/m2) as reference. In mediation analysis, we explored whether childhood BMI at age 7 years mediated the associations.ResultsMaternal pre-pregnancy obesity was associated with earlier age at attaining most pubertal milestones in sons, and pre-pregnancy overweight and obesity were associated with earlier age at attaining all pubertal milestones in daughters. When combining all pubertal milestones, pre-pregnancy obesity [sons: -1.5 (-2.5, -0.4) months; daughters: -3.2 (-4.2, -2.1) months] and overweight [daughters only: -2.6 (-3.3, -1.8) months] were associated with earlier timing of puberty. The associations in sons were completely mediated by higher childhood BMI and partly so in daughters.ConclusionsMaternal pre-pregnancy obesity appears to lower timing of puberty through childhood obesity in sons and mainly through other mechanisms in daughters

Risk of selection bias due to non-participation in a cohort study on pubertal timing.

BackgroundNon-participation in aetiologic studies of pubertal timing is frequent. However, little effort has been given to explore the risk and potential impact of selection bias in studies of pubertal timing.ObjectiveWe aimed to explore the risk of selection bias due to non-participation in a newly established puberty cohort.MethodsWe evaluated whether three maternal exposures chosen a priori (pre-pregnancy obesity, smoking, and alcohol drinking during pregnancy) were associated with participation, whether pubertal timing was associated with participation, and whether selection bias influenced the associations between these exposures and pubertal timing. In total, 22 439 children from the Danish National Birth Cohort born 2000-2003 were invited to the Puberty Cohort and 15 819 (70%) participated. Exposures were self-reported during pregnancy. Pubertal timing was measured using a previously validated marker, "the height difference in standard deviations" (HD:SDS), which is the difference between pubertal height and adult height, both in standard deviations. For this study, pubertal height at around 13 years in sons and around 11 years in daughters was obtained from an external database, and adult height was predicted based on parental height reported by mothers.ResultsParticipation was associated with most exposures but not with pubertal timing, measured by HD:SDS. The associations between exposures and HD:SDS were comparable for participants only and all invited for participation.ConclusionIn conclusion, the risk of selection bias in aetiologic studies on pubertal timing in the Puberty Cohort appears minimal