Propensity score methodology for confounding control in health care utilization databases

Propensity score (PS) methodology is a common approach to control for confounding in nonexperimental studies of treatment effects using health care utilization databases. This methodology offers researchers many advantages compared with conventional multivariate models: it directly focuses on the determinants of treatment choice, facilitating the understanding of the clinical decision-making process by the researcher; it allows for graphical comparisons of the distribution of propensity scores and truncation of subjects without overlapping PS indicating a lack of equipoise; it allows transparent assessment of the confounder balance achieved by the PS at baseline; and it offers a straightforward approach to reduce the dimensionality of sometimes large arrays of potential confounders in utilization databases, directly addressing the “curse of dimensionality” in the context of rare events. This article provides an overview of the use of propensity score methodology for pharmacoepidemiologic research with large health care utilization databases, covering recent discussions on covariate selection, the role of automated techniques for addressing unmeasurable confounding via proxies, strategies to maximize clinical equipoise at baseline, and the potential of machine-learning algorithms for optimized propensity score estimation. The appendix discusses the available software packages for PS methodology. Propensity scores are a frequently used and versatile tool for transparent and comprehensive adjustment of confounding in pharmacoepidemiology with large health care databases

Association of Phosphodiesterase-5 Inhibitors Versus Alprostadil With Survival in Men With Coronary Artery Disease

Abstract Background Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI). Objectives This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease. Methods All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil. Results This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1. Conclusions In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design

The Intergenerational Transmission of Early Childbearing: Examining Direct and Indirect Associations in a Swedish Birth Cohort

Background. Research shows that early childbearing is associated negatively with educational attainment and socioeconomic status (SES). Children born to young versus older mothers often do less well in school, and many have early first births. Some studies suggest that mothers’ early childbearing operates through SES to influence the daughters’ early childbearing, and some argue that the association is strong net of SES. The current study tests these direct and indirect associations. Methods. We estimate the pathways through which mothers’ early childbearing influences daughters’ early childbearing in several steps. First, we examine bivariate associations between mothers’ early childbearing and SES, followed by bivariate associations between mothers’ SES outcomes and their daughters’ early childbearing. We then estimate the average marginal effects (AMEs) of mothers’ early children on daughters’, and a KHB decomposition to examine direct and indirect associations. Results. Findings suggest both direct and indirect associations. Nested models show that, net of a range of SES characteristics, mothers’ early childbearing increases the probability of daughters’ by approximately 8%; and KHB results suggest 37% mediation, with daughters’ school performance (12%) and household educational attainment (10%) contributing the highest shares. Conclusion. Mothers’ early childbearing and subsequent SES collectively influence the long-term wellbeing of children. Thus, early childbearing has consequences both within and across generations

Parental death in childhood and pathways to increased mortality across the life course in Stockholm, Sweden: A cohort study.

BackgroundPrevious studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63.Methods and findingsA cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality. Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study.ConclusionsOur findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality

Bidirectional associations between workplace bullying and sickness absence due to common mental disorders – a propensity-score matched cohort study

Abstract Background The link between workplace bullying and poor mental health is well-known. However, little is known about the prospective and potentially reciprocal association between workplace bullying and mental health-related sickness absence. This 2-year prospective study examined bidirectional associations between exposure to workplace bullying and sickness absence due to common mental disorders (SA-CMD) while controlling for confounding factors from both work and private life. Methods The study was based on propensity score-matched samples (N = 3216 and N = 552) from the Swedish Longitudinal Occupational Survey of Health, using surveys from years 2012, 2014 and 2016. Self-reported exposure to workplace bullying was linked to registry-based information regarding medically certified SA-CMD (≥ 14 consecutive days). The associations were examined by means of Cox proportional hazards regression and via conditional logistic regression analysis. Hazard ratios and odds ratios with 95% confidence intervals were estimated. Results Exposure to workplace bullying was associated with an increased risk of incident SA-CMD (HR: 1.3, 95% CI: 1.0–1.8), after accounting for the influence of job demands, decision authority, previous SA-CMD, as well as other sociodemographic covariates. However, we found no statistically significant association between SA-CMD and subsequent workplace bullying (OR 1.2, 95% CI 0.7–1.9). Conclusions The results support an association between self-reported workplace bullying and SA-CMD, independent of other sociodemographic factors and workplace stressors. Preventing workplace bullying could alleviate a share of the individual and societal burden caused by SA globally

Dietary non enzymatic antioxidant capacity and the risk of myocardial infarction in the Swedish womenâs lifestyle and health cohort

Foods rich in antioxidants have been associated with a reduced risk of myocardial infarction. However, findings from randomized clinical trials on the role of antioxidant supplementation remain controversial. It has been suggested that antioxidants interact with each other to promote cardiovascular health. We therefore investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC), measuring the total antioxidant potential of the whole diet, and the risk of myocardial infarction. We followed 45,882 women aged 30â49 years and free from cardiovascular diseases through record linkages from 1991 until 2012. Dietary NEAC was assessed by a validated food frequency questionnaire collected at baseline. Total dietary NEAC was categorized into quintiles and multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HR) with 95% confidence intervals (CI). During a mean follow-up time of 20.3 years we detected 657 incident cases of myocardial infarction. After adjusting for potential confounders, we found a significant 28% lower risk of myocardial infarction among women in the fourth (HR: 0.72; 95% CI 0.55â0.95) and a 40% lower risk among women in the fifth quintile (HR: 0.60, 95% CI 0.45â0.81) of dietary NEAC compared to women in the first quintile, with a significant trend (p-value < 0.001). Higher dietary NEAC is associated with a lower risk of myocardial infarction in young to middle-aged women. These findings support the hypothesis that dietary antioxidants protect from myocardial infarction and that this effect might be exerted through interactions between antioxidants

Dietary non-enzymatic antioxidant capacity and the risk of myocardial infarction: The Swedish national March cohort

Background: Results from randomized trials of antioxidant supplementation have cast doubt on observational data linking diets high in antioxidants to a reduced risk of cardiovascular diseases. We hypothesized that supplementation of one or a few antioxidants might not simulate the complex actions of all antioxidants in the human diet. We therefore investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC), reflecting the antioxidant potential of the whole diet, and the risk of myocardial infarction (MI). Methods: In the Swedish National March Cohort, 34 543 men and women free from cardiovascular diseases and cancer were followed through record linkages from 1997 until 2010. NEAC was assessed with a validated food-frequency questionnaire at baseline. The distribution of NEAC was categorized into sex-specific quartiles. We fitted multivariable Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: During a mean follow-up time of 12.7 years, we identified 1142 incident cases of MI. Successively higher quartiles (Qs) of dietary NEAC were accompanied by a monotonic trend of decreasing MI incidence, both for overall MI (HR Q4 vs Q1: 0.77; 95% CI: 0.61–0.96; p for trend ¼ 0.008) and non-fatal MI (HR Q4 vs Q1: 0.72; 95% CI: 0.56–0.92; p for trend ¼ 0.004). No such association was found for fatal MI. Conclusions: A diet rich in antioxidants might protect from MI

Substance use disorder and suicide-related behaviour around dates of parental death and its anniversaries: a register-based cohort study.

BACKGROUND: Parental death and its anniversaries, including anticipation of these dates, might cause distress and increase the risk of substance use disorder and suicide-related behaviour in bereaved adolescents and young adults. We examined whether the risk of substance use disorder and suicide-related behaviour increases around the date of parental death and subsequent anniversaries. METHODS: Using Swedish national registers, we conducted a cohort study of individuals aged 12-24 years. We included individuals aged 12-24 years between Jan 1, 2001, and Dec 31, 2014, whose parents were alive at entry (n=1 858 327) and followed up with them until the end of age 24 years. We excluded individuals with a half-sibling, a history of emigration, a previous record of the outcome events, a parental death before study entry, two parental deaths on the same day during the follow-up, or missing data for relevant variables. Follow-up ended on the day of an outcome event or on Dec 31, 2014; at age 25 years, emigration, or death; or a year before the second parental death. We studied substance use disorder and suicide-related behaviour outcomes separately and included non-fatal and fatal events in both outcomes. We used Cox regression to estimate hazard ratios (HRs), controlling for baseline psychiatric, demographic, and socioeconomic characteristics. Parental death was modelled as a time-varying exposure over 72 monthly periods, starting from 1 year before the parental death to the fifth year and later after the death. Unmeasured confounding was also addressed in within-individual comparisons using a case-crossover design. FINDINGS: During follow-up, there were 42 854 substance use disorder events, with a crude rate of 3·1 per 1000 person-years. For suicide-related behaviour, there were 19 827 events, with a crude rate of 1·4 per 1000 person-years. Most of the events studied were non-fatal. In the month of parental death, the HR for substance use disorder risk was 1·89 among male participants, and, for suicide-related behaviour, was 3·76 among male participants and 2·90 among female participants. In male participants, there was an increased risk around the first anniversary (substance use disorder: HR 2·64 [95% CI 1·56-4·46] during the anniversary month; 2·21 [1·25-3·89] for the subsequent month; and for suicide-related behaviour: 3·18 [1·32-7·66] for the subsequent month). Among female participants, an increased risk of substance use disorder recurred around every year consistently in the month before the anniversary of the death and there was an increased risk for suicide-related behaviour in the months of the first and second anniversaries. INTERPRETATION: Although effect sizes were large in this cohort study, the number of individuals who had the outcomes was small. Nevertheless, adolescents and young adults, especially women and girls, who had the death of a parent showed increased risk of substance use disorder and suicide-related behaviour around the first few death anniversaries. Adolescents and young adults, especially women and girls, who had the death of a parent could benefit from preventive measures to reduce distress around the first few years of death anniversaries