Large-scale characterization of gender differences in diagnosis prevalence and time to diagnosis.

We carry out an analysis of gender differences in patterns of disease diagnosis across four large observational health datasets and find that women are routinely older when first assigned most diagnoses. Among 112 acute and chronic diseases, women experience longer lengths of time between symptom onset and disease diagnosis than men for most diseases regardless of metric used, even when only symptoms common to both genders are considered. These findings are consistent for patients with private as well as government insurance. Our analysis highlights systematic gender differences in patterns of disease diagnosis and suggests that symptoms of disease are measured or weighed differently for women and men. Data and code leverage the open-source common data model and analytic code and results are publicly available.

Global Cross-Sectional Study Evaluating the Attitudes towards a COVID-19 Vaccine in Pregnant and Postpartum Women.

Pregnant and postpartum women have an increased risk of severe complications from COVID-19. Many clinical guidelines recommend vaccination of these populations, and it is therefore critical to understand their attitudes toward COVID-19 vaccines. We conducted a cross-sectional online survey in November 2020 of currently pregnant and ≤1-year postpartum women in Brazil, India, the United Kingdom (UK), and the United States (US) that assessed their openness to COVID-19 vaccines and reasons for vaccine hesitancy. Logistic regression analyses were conducted to evaluate openness to receiving a vaccine. Out of 2010 respondents, 67% were open to receiving a COVID-19 vaccine themselves. Among pregnant and postpartum participants, 72% and 57% were willing to receive a vaccine, respectively. Vaccine openness varied significantly by country: India (87%), Brazil (71%), UK (59%), and US (52%). Across all participants, among the 33% who were unsure/not open to receiving a COVID-19 vaccine, the most common reason cited was safety/side effect concerns (51%). Participants were similarly open to their children/other family members receiving a COVID-19 vaccine. Presence of a comorbidity, a positive COVID-19 test result, and pregnancy were all significantly associated with positive vaccine acceptance. Targeted outreach to address pregnant and postpartum women's concerns about the COVID-19 vaccine is needed.

New Jersey maternal mortality dashboard: an interactive social-determinants-of-health tool.

OBJECTIVES: The United States maternal mortality (MM) rate is the highest amid developed/industrialized nations, and New Jersey's rate is among the highest. Healthcare professionals, public health officials, and policy makers are working to understand drivers of MM. An interactive data visualization tool for MM and health-related information (New Jersey Maternal Mortality Dashboard [NJMMD]) was recently developed. METHODS: NJMMD is an open-source application that uses data from publicly available state/federal government sources to provide a cross-sectional, high-level depiction of potential relationships between MM and demographic, social, and public health factors. RESULTS: MM rates or ratios (maternal deaths/1,000 women aged 15-49 years or 100,000 live births, respectively) are available by year (2005-2017), age (5-year [15-49] periods), and race/ethnicity (non-Hispanic White, Black, or Asian; Hispanic; or other), and by contextual social determinants of health (percent insured; percent covered by Medicaid; difference in nulliparous, term, singleton, vertex Cesarian birth rate from New Jersey goal; number of obstetrician/gynecologists or midwives per capita; and poverty rate). Bar graphs also can be produced with these variables. CONCLUSIONS: NJMMD is the first publicly available, interactive, state-focused MM tool that takes into account the intersection of social and demographic determinants of health, which play important roles in health outcomes. Trends and patterns in variables associated with MM and health can be identified for New Jersey and each of its 11 counties, and inform areas of focus for further analysis. Outputs may enable researchers, policy makers, and others to develop appropriate interventions and be better positioned to set benchmarks, allocate resources, and evaluate outcomes.

Interest in Home Birth During the COVID-19 Pandemic: Analysis of Google Trends Data.

INTRODUCTION: Nearly all (94%-99%) pregnant persons in developed countries search for pregnancy-related information online. The advent of the novel coronavirus disease 2019 (COVID-19) and the associated restrictions in hospital policies may have pushed pregnant persons in the United States to consider giving birth at home to achieve their desired birth experience. METHODS: Google Trends is an open, rich source of real-time, anonymized, relative data on disease patterns and population behavior that provides data in the form of search volume index (SVI): the search volume for a queried term relative to overall search volume for a given time frame and geographic location. The SVI is normalized to a scale of 0 to 100. After the World Health Organization declared COVID-19 a pandemic on March 11, 2020, Google Trends was queried on February 21, 2021, for the search term home birth with location set to the United States and the time frame March 11, 2019 to February 21, 2021. RESULTS: The median SVI for home birth during nominally pre-COVID-19 baseline (weeks of March 17, 2019 to March 8, 2020) was relatively constant at 43 (range, 25-56) and increased sharply to 77 during the week of March 15, to 86 during the week of March 22, and peaked at 100 during the week of March 29, 2020. The SVI declined substantially in the following weeks but remained significantly elevated compared with baseline levels. During the approximate 2-year period of query, the states with the highest SVI values (≥80) were Arkansas, Washington, Montana, and Georgia. DISCUSSION: Interest in home birth spiked in the United States immediately after COVID-19 was declared a pandemic and remained significantly elevated thereafter. These results have implications for caregivers and health systems to ensure safe pregnancies and childbirths through the resolution of the ongoing pandemic.

Algorithm of Transvaginal Ultrasound and/or Hysterosalpingogram for Confirmation Testing at 3 Months after Essure Placement.

STUDY OBJECTIVE: To evaluate the algorithm of transvaginal ultrasound (TVU) and/or modified hysterosalpingogram (HSG) confirmation testing 3 months after Essure placement to determine if women can rely on the device for permanent birth control. DESIGN: Interim analysis of an ongoing 10-year, prospective, multicenter, nonrandomized, single-arm, international trial (Canadian Task Force classification II-2). SETTING: Twenty study centers in the United States (n = 12), Canada (n = 1), The Netherlands (n = 6), and Spain (n = 1). PATIENTS: Women undergoing the Essure procedure for permanent birth control. INTERVENTIONS: Based on the algorithm for confirmation testing, women with an uncomplicated Essure procedure underwent TVU as the confirmation test; modified HSG was used for women ineligible for TVU, when TVU findings were abnormal or inconclusive, or based on the physician's discretion. MEASUREMENTS AND MAIN RESULTS: Co-primary endpoints (intention-to-treat [ITT] population) were the reliance rate and the 1-year pregnancy rate. Safety evaluation was based on adverse events. Bilateral insert placement was attempted in 597 women (ITT population) and achieved in 582 of 597 (97.5%). A total of 547 women were told to rely on Essure for permanent birth control. Both co-primary endpoints met prespecified limits: based on Bayesian statistics, the reliance rate was 91.6% (547/597; 95% credible interval, 89.2%-93.6%) and the 1-year pregnancy rate .67% (95% credible interval, .16%-1.53%). Using the algorithm for confirmation testing, of 547 subjects told to rely on Essure, 470 (86%) underwent TVU alone, 30 (6%) had modified HSG alone, and 47 (9%) had TVU followed by modified HSG. Four women became pregnant after being told to rely on Essure. They all had confirmation testing with TVU alone, and each initially read incorrectly as optimal insert locations. In each case postpregnancy follow-up and root cause analysis revealed unsatisfactory insert locations, 2 of which were perforations. Most adverse events were mild and unrelated to Essure. CONCLUSION: The algorithm of TVU and/or modified HSG confirmation testing 3 months after Essure placement can determine that a woman can rely on the device for permanent birth control. The adverse events observed are consistent with the known safety profile of Essure. (clinicaltrials.gov: NCT01327105.).

Effects of 50 and 100 mg desvenlafaxine versus placebo on sexual function in patients with major depressive disorder: a meta-analysis.

The primary objective of this post-hoc analysis was to evaluate the effect of short-term treatment with desvenlafaxine versus placebo on sexual dysfunction (SD), assessed from Arizona Sexual Experiences Scale scores, in adult outpatients with major depressive disorder. Data from three randomized, double-blind, placebo-controlled trials of 50 or 100 mg/day desvenlafaxine for major depressive disorder were pooled. SD status, determined from Arizona Sexual Experiences Scale scores, was assessed at baseline and week 8, last observation carried forward. Subgroup analyses addressed the effects of sex, baseline SD, and antidepressant response. At week 8, last observation carried forward (n=1562), SD rates were 54, 47, and 49% for 50 mg/day desvenlafaxine, 100 mg/day desvenlafaxine, and placebo, respectively [adjusted odds ratios (95% confidence interval) vs. placebo: 1.205 (0.928, 1.564) and 1.129 (0.795, 1.604), respectively]. The treatment by baseline SD interaction approached statistical significance (P=0.0663), mainly driven by poorer scores for desvenlafaxine versus placebo in the 100 mg group. Treatment by sex interactions were not statistically significant. Small but statistically significant treatment by sex interactions were observed for sex drive (P=0.0011) and ease of erection/lubrication (P=0.0151). Although there was no overall effect of desvenlafaxine on SD, a treatment by baseline SD interaction was suggested for 100 mg desvenlafaxine.

Effects of desvenlafaxine on blood pressure in patients treated for major depressive disorder: a pooled analysis.

OBJECTIVE: To evaluate the effect of the serotonin-norepinephrine re-uptake inhibitor desvenlafaxine on blood pressure and incidence of new onset hypertension in pooled short-term studies and in two longer-term, randomized withdrawal studies. RESEARCH DESIGN AND METHODS: Data from patients randomly assigned to desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8-12 weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive disorder (MDD) were pooled for analysis; two desvenlafaxine randomized withdrawal studies (36 and 46 weeks) were analyzed separately. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov , NCT00072774, NCT00073762, NCT00277823, NCT00300378, NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457, NCT00075257, NCT00887224. MAIN OUTCOME MEASURES: Outcomes included change from baseline in supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis, and incidence of hypertension (defined as three consecutive second SDBP measures ≥90 mm Hg AND increase of ≥10 mm Hg from baseline and/or SSBP ≥140 mm Hg AND increase of ≥10 mm Hg), analyzed using Cochran Mantel Hanzael tests. Potential predictors of change in SSBP and SDBP at LOCF were examined by including predictor variables in a regression model. RESULTS: In the pooled, short-term studies, mean changes from baseline over time in SSBP and SDBP were statistically significant compared with placebo for the desvenlafaxine doses of 10 mg/day or greater for SSBP (p ≤ 0.0004; MMRM) and 25 mg/day or greater for SDBP (p ≤ 0.0449; MMRM). The proportion of patients with new onset hypertension differed significantly from placebo for the 50, 200, and 400 mg/day doses (1.9%, 2.4%, 4.8%, respectively, vs 0.8%; all p ≤ 0.0244). Predictors of change in BP included baseline SDBP, baseline SSBP, dose, body mass index, gender, age, race, and history of hypertension. LIMITATIONS: Data were pooled from studies which differed somewhat in study design and patient demographics. None of the studies were originally designed to examine treatment effects on BP. Study entry criteria limit generalization of these results to medically stable patients with a primary diagnosis of MDD. CONCLUSIONS: Short-term desvenlafaxine treatment was associated with small but statistically significant increases in SSBP and SDBP.

Desvenlafaxine 50 and 100 mg/d versus placebo for the treatment of major depressive disorder: a phase 4, randomized controlled trial.

OBJECTIVE: To assess short-term efficacy and safety of desvenlafaxine 50 and 100 mg/d versus placebo for treating major depressive disorder (MDD). Assessment of sexual function was a secondary objective. METHOD: Outpatients (≥ 18 years) who met criteria for MDD from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and had screening and baseline 17-item Hamilton Depression Rating Scale (HDRS17) total scores ≥ 20 were randomly assigned to placebo or desvenlafaxine 50 or 100 mg/d in an 8-week study conducted from October 2011 to August 2012. The primary efficacy end point was change from baseline in HDRS17 total score at week 8, analyzed using a mixed-effects model for repeated measures. Sexual function was assessed using the Arizona Sexual Experiences Scale (ASEX). RESULTS: The safety population included 909 patients (intent-to-treat population, n = 886). Significantly greater improvement in adjusted mean HDRS17 total score from baseline to week 8 was observed for desvenlafaxine 50 mg (-11.28; P = .006) and desvenlafaxine 100 mg (-11.67; P < .001) compared with placebo (-9.71), with adjustment for multiplicity. In the ASEX total score analysis (n = 422), the treatment by gender interaction was not significant; thus, genders were combined for subsequent analyses. Comparisons for desvenlafaxine versus placebo for change from baseline in ASEX total and all item scores found P > .05, with no adjustment for multiplicity. Rates of sexual dysfunction based on ASEX were comparable among treatment groups. CONCLUSIONS: These results support previous findings demonstrating antidepressant efficacy, safety, and tolerability of desvenlafaxine 50 and 100 mg/d versus placebo. Sexual function was comparable between desvenlafaxine and placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01432457.

Maintenance of the efficacy of desvenlafaxine in menopausal vasomotor symptoms: a 1-year randomized controlled trial.

OBJECTIVE: The purpose of this study was to assess the 1-year maintenance of the efficacy of desvenlafaxine 100 mg/day (administered as desvenlafaxine succinate) established on week 12 in a 1-year, double-blind, randomized, placebo-controlled trial in postmenopausal women seeking treatment of bothersome vasomotor symptoms. METHODS: Primary efficacy endpoints were changes in hot flush (HF) frequency and severity on weeks 12, 26, and 52 in an efficacy substudy population (≥50 moderate and severe HFs per week at baseline). Secondary endpoints were Greene climacteric scale, patient global impression symptom rating, and patient global impression of change scores (weeks 12, 26, and 52) for the main study efficacy population. Safety was assessed throughout the trial. RESULTS: The mean baseline HF frequency (efficacy substudy population, n = 365) was 12 moderate and severe HFs per day; the mean baseline severity score was 2.4. At 1 year, women treated with desvenlafaxine maintained the efficacy established on week 12. Desvenlafaxine reduced HF frequency by 7.47 moderate and severe HFs per day on week 12 (adjusted mean difference from placebo, -2.48; 95% CI, -3.47 to -1.50; P < 0.001) and by 7.70 moderate and severe HFs per day on month 12 (adjusted mean difference from placebo, -2.86; 95% CI, -4.14 to -1.57; P < 0.001). Desvenlafaxine reduced the mean severity score by 0.63 on week 12 (placebo, -0.30; P < 0.001) and by 0.75 on month 12 (placebo, -0.44; P = 0.003). Reductions in Greene Climacteric Scale total score (main study efficacy population, n = 1,950) were significantly greater for desvenlafaxine than for placebo on months 3, 6, and 12 (all P < 0.001). Treatment-emergent adverse event rates were 84% for desvenlafaxine and 79% for placebo (P = 0.006). Full safety results are reported separately. CONCLUSIONS: The treatment efficacy of desvenlafaxine 100 mg/day achieved on week 12 in postmenopausal women with vasomotor symptoms is maintained for 1 year.

Cardiovascular, cerebrovascular, and hepatic safety of desvenlafaxine for 1 year in women with vasomotor symptoms associated with menopause.

OBJECTIVE: A previous trial of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine (administered as desvenlafaxine succinate) raised concerns on potential serious cardiovascular and hepatic events. The current study was designed to estimate these events in desvenlafaxine versus placebo in a larger population followed for 1 year. METHODS: Healthy postmenopausal women seeking treatment of vasomotor symptoms were randomized to placebo or desvenlafaxine 100 mg/day in a 1-year, multicenter, double-blind study. Safety was monitored throughout. Potential ischemic cardiovascular events (coronary heart disease-related death, new-onset myocardial infarction or unstable angina requiring hospitalization, and unscheduled revascularization procedures) and cerebrovascular events (definite stroke or probable stroke) identified by investigator reports and periodic adverse event review based on Standardized medical dictionary for regulatory activities Query were reviewed by blinded adjudication boards. Hepatic events (aspartate aminotransferase or alanine aminotransferase >5 times the upper limit of normal) were evaluated. RESULTS: A total of 2,118 participants (1,066 desvenlafaxine, 1,052 placebo) took one or more doses of study medication (mean, 280 d). There was one cardiovascular event; a placebo-treated participant was adjudicated to have had a myocardial infarction. One desvenlafaxine-treated participant was adjudicated to have had a probable stroke. Two participants in each treatment group had hepatic events. The excess risk (90% CI) of desvenlafaxine over placebo per 1,000 woman-years was -1.07 (-2.86 to 0.72) for cardiovascular events, 1.11 (-0.68 to 2.9) for cerebrovascular events, and 0.08 (-3.51 to 3.67) for hepatic events. CONCLUSIONS: There is no evidence for an increased risk of cardiovascular, cerebrovascular, or hepatic events associated with desvenlafaxine 100 mg/day compared with placebo for the treatment of menopausal vasomotor symptoms.

Desvenlafaxine compared with placebo for treatment of menopausal vasomotor symptoms: a 12-week, multicenter, parallel-group, randomized, double-blind, placebo-controlled efficacy trial.

OBJECTIVE: The aim of this study was to assess the 12-week efficacy of desvenlafaxine in treating moderate to severe vasomotor symptoms and the clinical relevance of improvements in postmenopausal women experiencing 50 or more moderate to severe hot flashes per week. METHODS: Participants were randomized to placebo or desvenlafaxine 100 mg/day in the 12-week efficacy substudy of a year-long, multicenter, parallel-group, double-blind study. Coprimary outcomes were changes from baseline in the daily number and severity of hot flashes on weeks 4 and 12. The percentage of women achieving the minimal clinically important difference (MCID) in the number of hot flashes on week 12 was determined. RESULTS: The efficacy substudy modified intent-to-treat population included 365 women (desvenlafaxine, n = 184; placebo, n = 181). Desvenlafaxine 100 mg/day significantly reduced the number and severity of hot flashes versus placebo on week 4 (P < 0.001) and week 12 (P < 0.001). On week 12, desvenlafaxine reduced the number of moderate and severe hot flashes by 7.3 (62%) per day (placebo, -4.5 [38%] per day) and the severity score by 0.59 (25%) per day (placebo, -0.28 [12%] per day). MCID-a reduction of 5.35 moderate and severe hot flashes per day-was achieved by 64% of desvenlafaxine-treated women (placebo, 41%; P < 0.001). In all, 17.2% (67/390) of participants discontinued, 10.0% (20/200) of participants taking desvenlafaxine and 3.7% (7/190) of participants taking placebo discontinued because of adverse events (P = 0.016), and 2.5% (5/200) of participants taking desvenlafaxine and 8.4% (16/190) of participants taking placebo discontinued because of lack of efficacy (P = 0.012). CONCLUSIONS: Postmenopausal women with moderate to severe hot flashes who are treated with desvenlafaxine achieve rapid symptom reduction that is clinically relevant based on MCID.

The effect of dose titration and dose tapering on the tolerability of desvenlafaxine in women with vasomotor symptoms associated with menopause.

OBJECTIVE: To determine whether titrating up and tapering down of desvenlafaxine (administered as desvenlafaxine succinate) improves its tolerability in postmenopausal women with vasomotor symptoms (VMS). METHODS: In the 1-week titration phase, participants received desvenlafaxine 100 mg/d (no titration), desvenlafaxine 50 mg/d, desvenlafaxine 25 mg/d (4 days) then 50 mg/d (3 days), or desvenlafaxine 25 mg/d. Participants then received open-label desvenlafaxine 100 mg/d for 15 weeks. In the 2-week taper phase, participants received placebo, desvenlafaxine 50 mg/d then placebo (7 days each), desvenlafaxine 50 mg/d then 25 mg/d (7 days each), or desvenlafaxine 50 mg/d every other day. Primary endpoints included nausea incidence during the first 2 weeks of treatment and Discontinuation-Emergent Signs and Symptoms (DESS) Checklist total scores after taper weeks 1 and 2. RESULTS: Nausea incidence was significantly lower for the desvenlafaxine 25 mg/d (19%) and 50 mg/d (22.6%) titration regimens vs. no titration (35.2%; p=0.004 and p=0.035, respectively). At taper week 1, mean DESS scores were significantly lower for desvenlafaxine 50 mg every other day (2.26, p<0.001), 50/25 mg/d (2.28, p<0.001), and 50 mg/d-placebo (1.84, p<0.001) taper regimens vs. no taper (7.07). At week 2, the mean DESS total score was significantly higher for the desvenlafaxine 50 mg/d-placebo regimen vs. no taper (4.46 vs. 2.44, respectively; p=0.009). Desvenlafaxine 50 mg every other day was the least tolerated of the taper regimens. CONCLUSIONS: Titration regimens may improve tolerability of desvenlafaxine 100 mg/d in postmenopausal women with VMS. Taper regimens of desvenlafaxine 50 mg/d-placebo or 50/25-mg/d, were better tolerated than abrupt discontinuation or desvenlafaxine 50 mg given every other day taper regimen.