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Background: Studies on the safety of prenatal medication use require valid estimation of the pregnancy duration. However, gestational age is often incompletely recorded in administrative and clinical databases. Our objective was to compare different approaches to estimating the pregnancy duration.Methods: Using data from the Clinical Practice Research Datalink and Hospital Episode Statistics, we examined the following four approaches to estimating missing gestational age: (1) generalized estimating equations for longitudinal data; (2) multiple imputation; (3) estimation based on fetal birth weight and sex; and (4) conventional approaches that assigned a fixed value (39 weeks for all or 39 weeks for full term and 35 weeks for preterm). The gestational age recorded in Hospital Episode Statistics was considered the gold standard. We conducted a simulation study comparing the described approaches in terms of estimated bias and mean square error.Results: A total of 25,929 infants from 22,774 mothers were included in our "gold standard" cohort. The smallest average absolute bias was observed for the generalized estimating equation that included birth weight, while the largest absolute bias occurred when assigning 39-week gestation to all those with missing values. The smallest mean square errors were detected with generalized estimating equations while multiple imputation had the highest mean square errors.Conclusions: The use of generalized estimating equations resulted in the most accurate estimation of missing gestational age when birth weight information was available. In the absence of birth weight, assignment of fixed gestational age based on term/preterm status may be the optimal approach. [ABSTRACT FROM AUTHOR]

Background: The appropriate use criteria considers cardiac stress testing within 2 years after percutaneous coronary intervention (PCI) to be rarely appropriate, unless prompted by symptoms or change in clinical status. Little is known about the patterns of cardiac stress testing after PCI in the single-payer Canadian healthcare system, where mechanisms for reimbursement are different from the United States.Methods and Results: Frequency and timing of cardiac stress testing within 2 years of PCI performed between April 2004 and March 2013 in Ontario, Canada, was determined from linked provincial databases. Subsequent rates of coronary angiography and revascularization after stress testing were ascertained. Of the 112 691 patients with PCI, 67 442 (59.8%) underwent at least 1 stress test, with 38 267 (34.0%) undergoing repeat stress testing (ie, >1 stress test) within 2 years. Patients who underwent stress testing were younger, had less medical comorbidities, were more likely to reside in urban areas, and had higher incomes. Spikes in incidence of repeat stress testing were observed at 3 to 4 months, 6 to 7 months, and 12 to 13 months after the prior stress test. Of those tested, only 5.9% underwent subsequent coronary angiography, and only 3.1% underwent repeat revascularization within 60 days of stress testing.Conclusions: More than half of all patients undergo cardiac stress testing within 2 years of PCI, with one third undergoing repeat stress tests. Only 1 of 30 tested patients underwent repeat revascularization. These findings reinforce the appropriate use criteria recommendations against routine stress testing after PCI. Further work is needed to aid with the selection of patients most likely to benefit from stress testing after PCI. [ABSTRACT FROM AUTHOR]

Background: Although the efficacy and safety of smoking cessation interventions are well established, their efficacy and safety in patients with cardiovascular disease (CVD) remain unclear. The objective of this study was to evaluate the efficacy and safety of pharmacological and behavioral smoking cessation interventions in CVD patients via a meta-analysis of randomized controlled trials.Methods and Results: EMBASE, PsycINFO, MEDLINE, PubMed, and the Cochrane Tobacco Addiction Specialized Register were searched for randomized controlled trials evaluating the efficacy of smoking cessation pharmacotherapies and behavioral therapies in CVD patients. Outcomes of interest were smoking abstinence at 6 and 12 months, defined using the most rigorous criteria reported. Data were pooled across studies for direct comparisons using random-effects models. Network meta-analysis using a graph-theoretical approach was used to generate the indirect comparisons. Seven pharmacotherapy randomized controlled trials (n=2809) and 17 behavioral intervention randomized controlled trials (n=4666) met our inclusion criteria. Our network meta-analysis revealed that varenicline (relative risk [RR]: 2.64; 95% confidence interval [CI], 1.34-5.21) and bupropion (RR: 1.42; 95% CI, 1.01-2.01) were associated with greater abstinence than placebo. The evidence about nicotine replacement therapies was inconclusive (RR: 1.22; 95% CI, 0.72-2.06). Telephone therapy (RR: 1.47; 95% CI: 1.15-1.88) and individual counseling (RR: 1.64, 95% CI: 1.17-2.28) were both more efficacious than usual care, whereas in-hospital behavioral interventions were not (RR: 1.05; 95% CI, 0.78-1.43).Conclusions: Our meta-analysis suggests varenicline and bupropion, as well as individual and telephone counseling, are efficacious for smoking cessation in CVD patients. [ABSTRACT FROM AUTHOR]

Background: Targeted maximum likelihood estimation has been proposed for estimating marginal causal effects, and is robust to misspecification of either the treatment or outcome model. However, due perhaps to its novelty, targeted maximum likelihood estimation has not been widely used in pharmacoepidemiology. The objective of this study was to demonstrate targeted maximum likelihood estimation in a pharmacoepidemiological study with a high-dimensional covariate space, to incorporate the use of high-dimensional propensity scores into this method, and to compare the results to those of inverse probability weighting.Methods: We implemented the targeted maximum likelihood estimation procedure in a single-point exposure study of the use of statins and the 1-year risk of all-cause mortality postmyocardial infarction using data from the UK Clinical Practice Research Datalink. A range of known potential confounders were considered, and empirical covariates were selected using the high-dimensional propensity scores algorithm. We estimated odds ratios using targeted maximum likelihood estimation and inverse probability weighting with a variety of covariate selection strategies.Results: Through a real example, we demonstrated the double robustness of targeted maximum likelihood estimation. We showed that results with this method and inverse probability weighting differed when a large number of covariates were included in the treatment model.Conclusions: Targeted maximum likelihood can be used in high-dimensional covariate settings. In high-dimensional covariate settings, differences in results between targeted maximum likelihood and inverse probability weighted estimation are likely due to sensitivity to (near) positivity violations. Further investigations are needed to gain better understanding of the advantages and limitations of this method in pharmacoepidemiological studies. [ABSTRACT FROM AUTHOR]

Background--Stenting is an endovascular alternative to endarterectomy for the management of carotid stenosis, but its long-term safety and efficacy relative to endarterectomy remain unclear. Our objective was to compare the safety and efficacy of stenting with those of endarterectomy, with a particular focus on long-term outcomes, via meta-analysis of randomized controlled trials (RCTs). Methods and Results--We systematically searched PubMed, EMBASE, MEDLINE, and the Cochrane Library for RCTs with ≥50 patients that compared stenting with endarterectomy in patients with carotid stenosis. Periprocedural and longterm outcomes were assessed, with data pooled across RCTs using random-effects models. Eight RCTs were included in our meta-analysis (n=7091), with follow-up ranging from 2.0 to 10.0 years. When compared with endarterectomy, stenting was associated with an increased risk of periprocedural stroke (relative risk, 1.49, 95% confidence interval [CI], 1.11 to 2.01; risk difference, 1.7%; 95% CI, 0.3 to 3.0) but a decreased risk of periprocedural myocardial infarction (relative risk, 0.47; 95% CI, 0.29 to 0.78; risk difference, -0.4%; 95% CI, -0.8% to 0.1%). During long-term follow-up, stenting was associated with an increased risk of stroke (relative risk, 1.36; 95% CI, 1.16 to 1.61) and a composite end point of ipsilateral stroke, periprocedural stroke, or periprocedural death (relative risk, 1.45; 95% CI, 1.20 to 1.75). Conclusions--Although stenting has more favorable periprocedural outcomes with respect to myocardial infarction, the observed increased risk of stroke and death throughout follow-up with stenting suggests that endarterectomy remains the treatment of choice for carotid stenosis. [ABSTRACT FROM AUTHOR]

Background: Chest pain is one of the most common reasons for emergency department (ED) visits in developed countries. Whether higher volume EDs have better outcomes, specifically for patients with chest pain, is unknown and pertinent.Methods and Results: We conducted a study using population-based data on 498 291 patients ≥40 years old, presenting to ED in Ontario, Canada from 2008 to 2014, with chest pain and were discharged after assessment. We evaluated processes of care after discharge from ED. The primary outcome was a composite of all-cause death or hospitalization for acute coronary syndrome. Hierarchical logistic regression models adjusting for potential confounding variables were used to evaluate the association of annual ED chest pain volume and outcome. We also determined if there was a volume threshold above which an increased ED volume was not associated with a lower adverse outcome. The mean age of our patients was 59 years, 46.7% were men, and 20% had diabetes mellitus. Patients discharged from higher volume EDs had higher rates of cardiologist consultations, cardiac medication use, and cardiac testing within 30 days of ED assessment. Higher ED volume was associated with significantly lower adjusted odds ratio for mortality or acute coronary syndrome (odds ratio, 0.87; 95% CI, 0.82-0.92 per each unit increase in the log of volume) at 30 days and at 1 year (odds ratio, 0.92; 95% CI, 0.88-0.92). Once the annual ED chest pain volume reached 1400 cases (95% CI, 910-1900), an increase of annual chest pain volume of 100 was associated with relative decrease in the odds of the composite outcome at 30 days of <1%.Conclusions: Evaluations of chest pain in EDs with higher chest pain volume had lower rates of death or hospitalizations for acute coronary syndrome. There was a volume threshold above which an increase in volume was no longer associated with reduced outcomes. [ABSTRACT FROM AUTHOR]

Background: Targeted maximum likelihood estimation has been proposed for estimating marginal causal effects, and is robust to misspecification of either the treatment or outcome model. However, due perhaps to its novelty, targeted maximum likelihood estimation has not been widely used in pharmacoepidemiology. The objective of this study was to demonstrate targeted maximum likelihood estimation in a pharmacoepidemiological study with a high-dimensional covariate space, to incorporate the use of high-dimensional propensity scores into this method, and to compare the results to those of inverse probability weighting., Methods: We implemented the targeted maximum likelihood estimation procedure in a single-point exposure study of the use of statins and the 1-year risk of all-cause mortality postmyocardial infarction using data from the UK Clinical Practice Research Datalink. A range of known potential confounders were considered, and empirical covariates were selected using the high-dimensional propensity scores algorithm. We estimated odds ratios using targeted maximum likelihood estimation and inverse probability weighting with a variety of covariate selection strategies., Results: Through a real example, we demonstrated the double robustness of targeted maximum likelihood estimation. We showed that results with this method and inverse probability weighting differed when a large number of covariates were included in the treatment model., Conclusions: Targeted maximum likelihood can be used in high-dimensional covariate settings. In high-dimensional covariate settings, differences in results between targeted maximum likelihood and inverse probability weighted estimation are likely due to sensitivity to (near) positivity violations. Further investigations are needed to gain better understanding of the advantages and limitations of this method in pharmacoepidemiological studies.