Background We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an internet-based preconception cohort study in the U.S. and Canada. Methods We recruited female participants age 21–45 and their male partners through internet advertisements, word of mouth, and flyers. Female participants were randomized with 50% probability to receive a subscription to FertilityFriend.com (FF), a web-based program that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart (Snart-Gravid), and validated retrospectively-reported date of last menstrual period (LMP) against FF data. Results After 99 weeks of recruitment (2013–2015), 2,421 women enrolled; 1,384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomization groups. Cohort retention was similar among those randomized vs. not randomized to FF (84% vs. 81%). At study enrollment, 56%, 22%, and 22% couples had been trying to conceive for <3, 3–5, and ≥6 months, respectively. The cost per subject enrolled was $146 (2013 $US), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, >97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. Conclusions Use of the internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective.

Disinfectant use has been associated with adverse respiratory effects among healthcare workers. However, the specific harmful agents have not been elucidated. We examined the association between occupational exposure to disinfectants and asthma control in the Nurses’ Health Study II, a large cohort of female nurses. Nurses with asthma were invited in 2014 to complete two questionnaires on their current occupation and asthma (response rate: 80%). Asthma control was defined by the Asthma Control Test (ACT). Exposure to major disinfectants was evaluated by a Job-Task-Exposure Matrix (JTEM). Analyses included 4,102 nurses with asthma (mean age: 58 years). Asthma control was poor (ACT=16–19) in 12% of nurses and very poor (≤15) in 6%. Use of disinfectants to clean medical instruments (19% exposed) was associated with poorly (odds ratio 1.37; 95%CI: [1.05–1.79]) and very poorly (1.88 [1.38–2.56]) controlled asthma (P-trend 0.004, after adjustment for potential confounders). Using JTEM estimates, exposure to formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide and enzymatic cleaners was associated with poor asthma control (all P-trend<0.05); exposure to quaternary ammonium compounds and alcohol was not. Use of several disinfectants was associated with poor asthma control. Our findings suggest targets for future efforts to prevent worsening of asthma control in healthcare workers.

Rationale: Sarcoidosis is a systemic granulomatous and inflammatory disorder that most often involves the lungs but also affects many other organs. Data on sarcoidosis from large epidemiological studies remain scarce.Objectives: To evaluate the baseline prevalence and 22-year incidence of sarcoidosis and their associations with demographic and geographic characteristics in a large cohort of U.S. women. Methods:The Nurses' Health Study II is a prospective cohort study of U.S. female nurses enrolled in 1989 (aged 25-44 yr, n = 116,430). Data on major illnesses were collected through biennial questionnaires . Cases were identified by the nurses' self-report of physician-diagnosed sarcoidosis. Associations of demographic and geographic characteristics with sarcoidosis were evaluated by logistic regression and Cox models. Measurements and Main Results:A total of 377 sarcoidosis cases were identified. The baseline prevalence was 100/100,000 women. The average annual incidence rate was 11/100,000 during 2,275,028 person-years of follow up. Incidence rate increased with age (P = 0.003), from 9 to 15/100,000 in women aged less than 35 to 55 or more years, respectively. Black women had a higher prevalence (odds ratio, 5.24; 95% confidence interval, 2.87-9.55) and incidence (hazard ratio, 3.80; 95% confidence interval, 2.31-6.24) than white women. Across U.S. regions, more than twofold differences were observed in sarcoidosis prevalence and incidence, with consistently higher rates in the Northeast. Conclusions:We provide recent national data on the epidemiology of sarcoidosis among U.S. women. Important differences in prevalence and incidence were observed across U.S. regions. Large epidemiological studies are needed to better understand the causes of the observed demographic and geographic differences in sarcoidosis.

Objectives Occupational exposure to disinfectants is associated with work-related asthma, especially in healthcare workers. However, little is known about the specific products involved. To evaluate disinfectant exposures, we designed job-exposure (JEM) and job-task-exposure (JTEM) matrices, which are thought to be less prone to differential misclassification bias than self-reported exposure. We then compared the three assessment methods: self-reported exposure, JEM, and JTEM. Methods Disinfectant use was assessed by an occupational questionnaire in 9,073 U.S. female registered nurses without asthma, aged 49–68 years, drawn from the Nurses’ Health Study II. A JEM was created based on self-reported frequency of use (1–3, 4–7 days/week) of 7 disinfectants and sprays in 8 nursing jobs. We then created a JTEM combining jobs and disinfection tasks to further reduce misclassification. Exposure was evaluated in 3 classes (low, medium, high) using product-specific cut-offs (e.g., <30%, 30–49.9%, ≥50%, respectively, for alcohol); the cut-offs were defined from the distribution of self-reported exposure per job/task. Results The most frequently reported disinfectants were alcohol (weekly use: 39%), bleach (22%) and sprays (20%). More nurses were classified as highly exposed by JTEM (alcohol 41%, sprays 41%, bleach 34%) than by JEM (21%, 30%, 26%, respectively). Agreement between JEM and JTEM was fair-to-moderate (kappa: 0.3–0.5) for most disinfectants. JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration. Conclusion The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Use of the JTEM is likely to reduce exposure misclassification.

Context Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated. Objective To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. Design and Intervention Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. Setting Academic medical center. Patients Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3). Main Outcome Measure Depressive symptoms (MADRS score). Results During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (β = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; β = −2.62 [95% CI, −4.52 to −0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events. Conclusions Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.

Objectives Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. Methods The Nurses' Health Study II is a prospective study of U.S. female nurses enrolled in 1989 (ages 24-44 years). Job status and asthma were assessed in biennial (1989-2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5, 311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. Results The analytic cohort included 98,048 nurses. Compared to nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio: 0.73[95%CI, 0.63-0.86]) and ER/inpatient units (0.89[0.82-0.97]). During 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (hazard ratio: 1.13[1.07-1.18]), especially among those with more severe asthma (hazard ratio for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared to intermittent asthma, P trend: 0.004). Conclusion Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses.

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