Ashley I. Naimi

The parametric g-formula for time-to-event data: intuition and a worked example.

Background: The parametric g-formula can be used to estimate the effect of a policy, intervention, or treatment. Unlike standard regression approaches, the parametric g-formula can be used to adjust for time-varying confounders that are affected by prior exposures. To date, there are few published examples in which the method has been applied. Methods: We provide a simple introduction to the parametric g-formula and illustrate its application in an analysis of a small cohort study of bone marrow transplant patients in which the effect of treatment on mortality is subject to time-varying confounding. Results: Standard regression adjustment yields a biased estimate of the effect of treatment on mortality relative to the estimate obtained by the g-formula. Conclusions: The g-formula allows estimation of a relevant parameter for public health officials: the change in the hazard of mortality under a hypothetical intervention, such as reduction of exposure to a harmful agent or introduction of a beneficial new treatment. We present a simple approach to implement the parametric g-formula that is sufficiently general to allow easy adaptation to many settings of public health relevance.

Causal Inference in Occupational Epidemiology: Accounting for the Healthy Worker Effect by Using Structural Nested Models

In a recent issue of the Journal, Kirkeleit et al. (Am J Epidemiol. 2013;177(11):1218-1224) provided empirical evidence for the potential of the healthy worker effect in a large cohort of Norwegian workers across a range of occupations. In this commentary, we provide some historical context, define the healthy worker effect by using causal diagrams, and use simulated data to illustrate how structural nested models can be used to estimate exposure effects while accounting for the healthy worker survivor effect in 4 simple steps. We provide technical details and annotated SAS software (SAS Institute, Inc., Cary, North Carolina) code corresponding to the example analysis in the Web Appendices, available at http://aje.oxfordjournals.org/.

Human Chorionic Gonadotropin Partially Mediates Phthalate Association With Male and Female Anogenital Distance.

CONTEXTnPrenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placental glycoprotein hormone human chorionic gonadotropin (hCG) is required for male development, and may be a target of phthalate exposure.nnnOBJECTIVEnThis study aimed to test the hypothesis that phthalates disrupt placental hCG differentially in males and females with consequences for sexually dimorphic genital development.nnnDESIGNnThe Infant Development and Environment Study (TIDES) is a prospective birth cohort. Pregnant women were enrolled from 2010-2012 at four university hospitals.nnnPARTICIPANTSnParticipants were TIDES subjects (n = 541) for whom genital and phthalate measurements were available and who underwent prenatal serum screening in the first or second trimester.nnnMAIN OUTCOME MEASURESnOutcomes included hCG levels in maternal serum in the first and second trimesters and anogenital distance (AGD), which is the distance from the anus to the genitals in male and female neonates.nnnRESULTSnHigher first-trimester urinary mono-n-butyl phthalate (MnBP; P = .01), monobenzyl phthalate (MBzP; P = .03), and mono-carboxy-isooctyl phthalate (P < .01) were associated with higher first-trimester hCG in women carrying female fetuses, and lower hCG in women carrying males. First-trimester hCG was positively correlated with the AGD z score in female neonates, and inversely correlated in males (P = 0.01). We measured significant associations of MnBP (P < .01), MBzP (P = .02), and mono-2-ethylhexyl phthalate (MEHP; P < .01) with AGD, after adjusting for sex differences. Approximately 52% (MnBP) and 25% (MEHP) of this association in males, and 78% in females (MBzP), could be attributed to the phthalate association with hCG.nnnCONCLUSIONSnFirst-trimester hCG levels, normalized by fetal sex, may reflect sexually dimorphic action of phthalates on placental function and on genital development.

Secular Trends in Preeclampsia Incidence and Outcomes in a Large Canada Database: A Longitudinal Study Over 24 Years

BACKGROUNDnThe incidence of preeclampsia is increasing, but effects on women and infants are unclear. We measured the incidence of preeclampsia over time in a large Canadian population, and assessed trends in maternal and infant morbidity and mortality.nnnMETHODSnWe carried out a population-based study of 1,901,376 linked hospital discharge abstracts for all deliveries in the province of Quebec, Canada from 1989 through 2012. We computed the annual incidence of preeclampsia, and used log binomial models to determine associations with severe morbidity and mortality for preeclamptic vs nonpreeclamptic pregnancies. Main outcomes included maternal, fetal, and infant mortality, admission to intensive care, intubation, preterm delivery, growth restriction, cesarean delivery, transfusion, and severe medical complications.nnnRESULTSnThe incidence of preeclampsia increased from 26.4 per 1000 deliveries in 1989 to 50.6 in 2012. Maternal, fetal, and infant mortality decreased with time for preeclamptic but not for nonpreeclamptic pregnancies. By 2007-2012, risk for women with preeclampsia had declined for most maternal morbidities, except acute renal failure, which increased relative to no preeclampsia (risk ratio, 21.5; 95% confidence interval, 16.9-27.3). Risk of infant morbidity also decreased, but this coincided with an increase in the excess number of intubations and admissions for intensive care for preeclampsia relative to no preeclampsia.nnnCONCLUSIONSnThe incidence of preeclampsia increased during the study, but with little effect on the risk of maternal and infant morbidity and mortality. For most outcomes, the risk decreased relative to no preeclampsia, with more aggressive medical management over time.

Counterfactual Theory in Social Epidemiology: Reconciling Analysis and Action for the Social Determinants of Health

There is a strong and growing interest in applying formal methods for causal inference with observational data in social epidemiology. A number of challenges in defining, identifying, and estimating counterfactual-based causal effects have been especially problematic in social epidemiology, particularly for commonly used exposures such as race, education, occupation, or socioeconomic position. The purpose of this article is to revisit these challenges in light of the conceptual and analytic advancements in causal inference over the last two decades. We focus on a central assumption for causal inference known as the stable unit treatment value assumption, which can be divided into two component assumptions: counterfactual consistency and the absence of interference. We give simple hypothetical examples to illustrate how and why these assumptions are often violated in research on the social determinants of health (e.g., education, race/ethnicity, socioeconomic position) and provide strategies that can be used to sidestep these assumptions. In particular, we note that a recently proposed mediation analysis strategy can be used to explore questions about health disparities in a more formal causal inference framework. We emphasize that a central obstacle to estimating causal effects variables such as race, education (e.g., high school versus no high school), or occupation is the need to identify an intervention (possibly hypothetical) that will lead to changes in the exposure of interest.

Three alternative methods to resolve paradoxical associations of exposures before term

AbstractnTo propose three methods to estimate associations between pregnancy exposures and outcomes before term, including the association between preeclampsia and preterm fetal-infant mortality, while avoiding the selection bias found in conventional analytic designs. Population-level analysis of 1,099,839 women who delivered live or stillborn infants in Quebec hospitals from 1989 to 2012, covering nearly a quarter of Canadian births. The exposure of interest was preeclampsia at 20–29, 30–33, 34–36, and ≥37xa0weeks of gestation. We compared preeclamptic with non-preeclamptic pregnancies in parametric survival models with a Weibull distribution using three analytic designs: (1) fetuses-at-risk; (2) bias correction factors; and (3) analysis of pregnancies at high risk of preterm delivery. Main outcome measures were occurrence of fetal or postnatal infant death before discharge. In models affected by bias due to selection of preterm births, women with preeclampsia early in gestation had paradoxically lower risks of fetal and infant mortality than women without preeclampsia. All three analytic approaches reversed the associations, showing a harmful effect of preeclampsia before term. At 20–29xa0weeks, for example, preeclampsia was associated with 1.35 times the risk of infant mortality (95xa0% confidence interval 1.14–1.60) and 1.40 times the risk of stillbirth (95xa0% confidence interval 1.18–1.67) with the fetuses-at-risk approach. Paradoxically protective benefits of exposures such as preeclampsia before term are artifacts of inappropriate analytic design. Outcomes before term should be analyzed with care, using methods that address bias due to selection of preterm deliveries.

Delivery at Term: Impact of University Education by Week of Gestation

OBJECTIVEnData on risk factors for early term delivery are scant despite greater complications in infants born at 37 and 38 weeks gestation. We determined the probability of delivery by gestational week at term according to level of maternal education, an established risk factor for preterm birth.nnnMETHODSnWe analyzed 2 319 697 live singleton births at term (≥37 weeks) in Quebec from 1981 to 2010. We estimated hazard ratios with 95% confidence intervals (CI) of delivery according to level of maternal education, adjusting for individual characteristics. The main outcome measure was the probability of delivery at term by week of gestation for women with university education versus high school education.nnnRESULTSnEarly term birth at 37 and 38 weeks of gestation was less common for university-educated women (23.1%) than for high school-educated women (25.8%; P < 0.001). Compared with women with a high school education, university-educated women had a 15% lower probability of delivery at 37 to 38 weeks (95% CI: 0.84 to 0.86), a 4% lower probability of delivery at 39 weeks (95% CI: 0.96 to 0.97) and a 2% lower probability of delivery at 40 weeks (95% CI: 0.97 to 0.98). University-educated women were, however, more likely to deliver at 41 weeks.nnnCONCLUSIONnA higher level of education was associated with longer duration of pregnancy at term. Women who were university-educated had a lower chance of delivery at 37, 38, 39, and even 40 weeks of gestation. Clinicians should be aware that women with lower levels of education are more likely to deliver earlier at term.

The Feasibility of a Randomized Trial Using a Progressive Exercise Program in Patients with Severe Hip Osteoarthritis

Objectives: To examine the feasibility of a home strengthening program in severe hip osteoarthritis [OA] patients. Methods: We randomized patients to progressive resistance exercise or control and measured the Western Ontario and MacMaster Osteoarthritis Index [WOMAC], timed 50-foot walk, and timed stair climb. Results: Several strength tests were too painful in the first few patients and, therefore, were not considered feasible and dropped. Although not statistically significant in the 15 subjects completing the pilot study, there was less deterioration in the strengthening group for WOMAC function subscale and stair climb test. Conclusions: A strength program is feasible in patients with severe hip osteoarthritis, but patients may be unable to perform some common strength exercises. Future studies may show that home resistance exercise programs improve function in these patients and should identify specific effective exercises that sedentary subjects can easily learn.

Prevalence and predictors of burnout among obstetrics and gynecology residents in Canada

The aim of this study is to evaluate the prevalence of burnout syndrome among obstetrics and gynecology residents, as well as the relationship between several demographic and work-related characteristics and the prevalence of burnout. We surveyed 143 residents in obstetrics and gynecology programs across eight provinces in Canada using an electronic survey questionnaire and the Maslach Burnout Inventory Human services survey. The prevalence of high emotional exhaustion was 12.6xa0% higher among younger than older residents and 12.4xa0% higher among female compared to male residents. The prevalence of high depersonalization was13.0xa0% higher among male versus female residents. The prevalence of high emotional exhaustion among residents who reported sufficient supervision during the night shift was significantly lower than among those who reported insufficient supervision (95xa0% CI −49.7, −8.6). Additionally, we found that adequate access to food during the night shift was associated with a lower prevalence of any burnout (95xa0% CI −31.8, −0.2). Similar associations were observed for high emotional exhaustion and high depersonalization. We also found a 22.1xa0% (95xa0% CI −60.0, 15.7) lower prevalence of emotional exhaustion among residents who work 60xa0h/week or less. Our results suggest decreased levels of burnout in resident physicians who reported sufficient staff supervision, adequate access to food during the night shift, and fewer working hours. Future studies should be directed to examine the effectiveness of different strategies to improve the residency training in obstetrics and gynecology.

Correction to: Prevalence and predictors of burnout among obstetrics and gynecology residents in Canada

Following the publication of this article [1], the authors have removed the “Maslach Burnout Inventory, Forms: General Survey, Human Services Survey & Educators Survey” from the supplementary materials of the article [1] due to copyright restrictions.