Project description:The authors developed a sensitivity analysis method to address the issue of uncontrolled confounding in observational studies. In this method, the authors use a 1-dimensional function of the propensity score, which they refer to as the sensitivity function (SF), to quantify the hidden bias due to unmeasured confounders. The propensity score is defined as the conditional probability of being treated given the measured covariates. Then the authors construct SF-corrected inverse-probability-weighted estimators to draw inference on the causal treatment effect. This approach allows analysts to conduct a comprehensive sensitivity analysis in a straightforward manner by varying sensitivity assumptions on both the functional form and the coefficients in the 1-dimensional SF. Furthermore, 1-dimensional continuous functions can be well approximated by low-order polynomial structures (e.g., linear, quadratic). Therefore, even if the imposed SF is practically certain to be incorrect, one can still hope to obtain valuable information on treatment effects by conducting a comprehensive sensitivity analysis using polynomial SFs with varying orders and coefficients. The authors demonstrate the new method by implementing it in an asthma study which evaluates the effect of clinician prescription patterns regarding inhaled corticosteroids for children with persistent asthma on selected clinical outcomes.
Project description:While prior prospective iso-caloric substitution studies show a robust association between higher intake of animal protein and risk of mortality, associations observed for mortality risk in relation to major food sources of animal protein have been generally more diverse. We used the EPIC-Heidelberg cohort to examine if confounding, notably, by smoking, adiposity, or alcohol intake, could cause inconsistencies in estimated mortality hazard ratios (HR) related to intake levels of different types of meat and dairy products. Higher intakes of red or processed meats, and lower intakes of milk or cheese, were observed among current heavy smokers, participants with obesity, or heavy alcohol drinkers. Adjusting for age, sex, and total energy intake, risk models showed increased all-cause, cardiovascular, and cancer-related mortality with higher red or processed meat intakes (HR ranging from 1.25 [95% confidence interval = 1.15-1.36] to 1.76 [1.46-2.12] comparing highest to lowest tertiles), but reduced risks for poultry, milk, or cheese (HR ranging from 0.55 [0.43-0.72] to 0.88 [0.81-0.95]). Adjusting further for smoking history, adiposity indices, alcohol consumption, and physical activity levels, the statistical significance of all these observed was erased, except for the association of processed meat intake with cardiovascular mortality (HR = 1.36 [CI = 1.13-1.64]) and cheese intake with cancer mortality (HR = 0.86 [0.76-0.98]), which, however, were substantially attenuated. These findings suggest heavy confounding and provide little support for the hypothesis that animal protein, as a nutrient, is a major determinant of mortality risk.
Project description:Observational analyses of the association between body mass index (BMI) and all-cause mortality often suggest that overweight is neutral or beneficial, but such analyses are potentially confounded by smoking or by reverse causation. The use of BMI measured in early adulthood offers one means of reducing the latter problem. We used a cohort who were first measured while 16-24 year old students at Glasgow University in 1948-1968 and subsequently re-measured in 2000-2003, offering a rare opportunity to compare BMI measured at different ages as a predictor of mortality. Analysis of the later BMI measurements suggested that overweight was beneficial to survival, while analysis of BMI measured in early adulthood suggested that overweight was harmful and that the optimum BMI lay towards the lower end of the recommended range of 18.5-25?kg m-2. We interpret the association with later BMI as being probably distorted by reverse causality, although it remains possible instead that the optimum BMI increases with age. Differences when analyses were restricted to healthy non-smokers also suggested some residual confounding by smoking. These results suggest that analyses of BMI recorded in middle or old age probably over-estimate the optimum BMI for survival and should be treated with caution.
Project description:People are having children later in life. The consequences for offspring adult survival have been little studied due to the need for long follow-up linked to parental data and most research has considered offspring survival only in early life. We used Swedish registry data to examine all-cause and cause-specific adult mortality (293,470 deaths among 5,204,433 people, followed up to a maximum of 80 years old) in relation to parental age. For most common causes of death adult survival was improved in the offspring of older parents (HR for all-cause survival was 0.96 (95% CI: 0.96, 0.97) and 0.98 (0.97, 0.98) per five years of maternal and paternal age, respectively). The childhood environment provided by older parents may more than compensate for any physiological disadvantages. Within-family analyses suggested stronger benefits of advanced parental age. This emphasises the importance of secular trends; a parent's later children were born into a wealthier, healthier world. Sibling-comparison analyses can best assess individual family planning choices, but our results suggested a vulnerability to selection bias when there is extensive censoring. We consider the numerous causal and non-causal mechanisms which can link parental age and offspring survival, and the difficulty of separating them with currently available data.
Project description:Clinical trials had provided evidence for the benefit effect of antihypertensive treatments in preventing future cardiovascular disease (CVD) events; however, the association between hypertension, whether treated/untreated or controlled/uncontrolled and risk of mortality in US population has been poorly understood. A total of 13,947 US adults aged ≥18 years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used to conduct this study. Mortality outcome events included all-cause, CVD-specific, heart disease-specific and cerebrovascular disease-specific deaths, which were obtained from linked 2011 National Death Index (NDI) files. During a median follow-up of 19.1 years, there were 3,550 all-cause deaths, including 1,027 CVD deaths. Compared with normotensives, treated but uncontrolled hypertensive patients were at higher risk of all-cause (HR = 1.62, 95%CI = 1.35-1.95), CVD-specific (HR = 2.23, 95%CI = 1.66-2.99), heart disease-specific (HR = 2.19, 95%CI = 1.57-3.05) and cerebrovascular disease-specific (HR = 3.01, 95%CI = 1.91-4.73) mortality. Additionally, untreated hypertensive patients had increased risk of all-cause (HR = 1.40, 95%CI = 1.21-1.62), CVD-specific (HR = 1.77, 95%CI = 1.34-2.35), heart disease-specific (HR = 1.69, 95%CI = 1.23-2.32) and cerebrovascular disease-specific death (HR = 2.53, 95%CI = 1.52-4.23). No significant differences were identified between normotensives, and treated and controlled hypertensives (all p > 0.05). Our study findings emphasize the benefit of secondary prevention in hypertensive patients and primary prevention in general population to prevent risk of mortality later in life.
Project description:Adolescents who share meals with their parents score better on a range of well-being indicators. Using three waves of the National Longitudinal Survey of Adolescent Health (N = 17,977), we assessed the causal nature of these associations and the extent to which they persist into adulthood. We examined links between family dinners and adolescent mental health, substance use, and delinquency at wave 1, accounting for detailed measures of the family environment to test whether family meals simply proxy for other family processes. As a more stringent test of causality, we estimated fixed effects models from waves 1 and 2, and we used wave 3 to explore persistence in the influence of family dinners. Associations between family dinners and adolescent well-being remained significant, net of controls, and some held up to stricter tests of causality. Beyond indirect benefits via earlier well-being, however, family dinners associations did not persist into adulthood.
Project description:BackgroundAdjusting for multiple biases usually involves adjusting for one bias at a time, with careful attention to the order in which these biases are adjusted. A novel, alternative approach to multiple-bias adjustment involves the simultaneous adjustment of all biases via imputation and/or regression weighting. The imputed value or weight corresponds to the probability of the missing data and serves to 'reconstruct' the unbiased data that would be observed based on the provided assumptions of the degree of bias.MethodsWe motivate and describe the steps necessary to implement this method. We also demonstrate the validity of this method through a simulation study with an exposure-outcome relationship that is biased by uncontrolled confounding, exposure misclassification, and selection bias.ResultsThe study revealed that a non-biased effect estimate can be obtained when correct bias parameters are applied. It also found that incorrect specification of every bias parameter by +/-25% still produced an effect estimate with less bias than the observed, biased effect.ConclusionsSimultaneous multi-bias analysis is a useful way of investigating and understanding how multiple sources of bias may affect naive effect estimates. This new method can be used to enhance the validity and transparency of real-world evidence obtained from observational, longitudinal studies.
Project description:ObjectiveThe study objective was to examine the associations among visceral fat (VF), all-cause mortality, and obesity-related mortality.Research design and methodsA total of 733 Japanese Americans were followed for 16.9 years. Hazard ratios (HRs) per interquartile range increase in VF were calculated using time-dependent Cox proportional hazard models censored at age 82 years, with age as the time axis adjusted for sex and smoking.ResultsHigher VF was associated with all-cause mortality (HR 1.39 [95% CI 1.11-1.75] 107 deaths) and obesity-related mortality (1.39 [1.04-1.85], 68 deaths from cardiovascular disease, diabetes, or obesity-related cancer). After further adjustment for waist circumference, VF remained significantly associated with all-cause mortality (1.41 [1.04-1.92]) but not with obesity-related mortality. The associations between mortality and VF were not independent of BMI.ConclusionsVF was associated with all-cause mortality and obesity-related mortality in Japanese Americans. VF did not significantly improve mortality risk assessment beyond that of BMI.
Project description:In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0-29.9 kg/m2 [HR25-29.9 vs 21-24.9 kg/m2: 0.85; 95% CI, 0.73-1.00] while the highest risk was in those who were underweight [HRBMI <21 kg/m2 vs BMI 21-24.9 kg/m2: 1.82; 95% CI 1.30-2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI <21 kg/m2 vs BMI 21-24.9 kg/m2: 1.64; 95% CI 1.26-2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.