A Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) Investigation of Self-Reported Menopausal Palpitation Distress.

Background: Study to describe the degree of menopausal palpitation distress and its demographic, clinical, symptom, and quality-of-life (QOL) correlates. Analysis of existing, baseline, data from peri- and postmenopausal women, 42 to 62 years of age, who participated in the Menopause Strategies-Finding Lasting Answers for Symptoms and Health (MsFLASH) clinical trials testing interventions for vasomotor symptoms (n = 759). Up to 46.8% of menopausal women report having palpitations, yet the symptom is relatively understudied. Little is known about palpitation distress or its correlates. Materials and Methods: Degree of distress from "heart racing or pounding" was self-reported over the past two weeks as "not at all," "a little bit," "moderately," "quite a bit," or "extremely." Other measures included self-report forms, clinic-verified body mass index (BMI), vasomotor symptom diaries, and validated symptom and QOL tools. Results: The percentage who reported palpitation distress was 19.6%, 25.2%, and 33.5% in the three trials or 25.0% overall. In multivariate analysis, the odds of reporting palpitation distress was lower in past smokers (odds ratio [OR] = 0.59 [95% confidence interval (CI) 0.38-0.90]) and current smokers (OR = 0.48 [0.27-0.87]) relative to never-smokers and lower with every 5 kg/m2 higher BMI (OR = 0.82 [0.69-0.98]).The odds of reporting palpitation distress was higher with every five point more severe insomnia (OR = 1.28 [1.05-1.54]), five point worse depressive symptoms (OR = 1.47 [1.11-1.95]), five point worse perceived stress (OR = 1.19 [1.01-1.39]), and one point worse menopausal QOL (OR = 1.29 [1.06-1.57]). Conclusions: Menopausal palpitation distress is common and associated with demographic, clinical, symptom, and QOL factors. Findings can be used for screening in clinical practice and to justify additional research on this understudied symptom.

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

OBJECTIVE: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects on menopause-related QOL relative to control in women with VMS. METHODS: We pooled individual-level data from 1,005 peri- and postmenopausal women with 14 or more VMS/week across the four RCTs. Interventions included escitalopram 10 to 20 mg/d; yoga/aerobic exercise; 1.8 g/d omega-3-fatty acids; oral 17-beta-estradiol 0.5 mg/d; venlafaxine XR 75 mg/d; and cognitive behavioral therapy for insomnia (CBT-I). Outcomes measures were the Menopause-specific Quality of Life scale and its subscales. RESULTS: Significant improvements in total Menopause-specific Quality of Life from baseline were observed with estradiol, escitalopram, CBT-I, and yoga, with mean decreases of 0.3 to 0.5 points relative to control. The largest improvement in the vasomotor subscale was observed with estradiol (-1.2 points), with more modest but significant effects seen with escitalopram, yoga, and CBT-I. Significant improvements in the psychosocial subscale were observed for escitalopram, venlafaxine, and CBT-I. For the physical subscale, the greatest improvement was observed for CBT-I and exercise, whereas for the sexual subscale, the greatest improvement was observed for CBT-I, with yoga and estradiol demonstrating smaller effects. CONCLUSIONS: These results suggest that for menopause-related QOL, women have a variety of treatment strategies to choose from and can select an approach based on most bothersome symptoms and individual preferences.

Small changes in glucose variability induced by low and high glycemic index diets are not associated with changes in ß-cell function in adults with pre-diabetes.

Oscillating glucose levels can increase oxidative stress and may contribute to ß-cell dysfunction. We tested the hypothesis that increased glycemic variability contributes to ß-cell dysfunction by experimentally altering glucose variability with controlled diets varying in glycemic index (GI). Fifty-two adults with prediabetes received a 2-week moderate GI (GI = 55-58) control diet followed by randomization to a four-week low GI (LGI: GI < 35) or high GI (HGI HI > 70) diet. Those on the HGI diet were randomized to placebo or the antioxidant N-acetylcysteine (NAC). Participants underwent blinded CGMS, fasting oxidative stress markers and an intravenous glucose tolerance test to estimate ß-cell function (disposition index: DI). On the control diet, DI was inversely correlated with SD glucose (r = -0.314, p = 0.03), but neither DI nor glucose variability were associated with oxidative stress markers. The LGI diet decreased SD glucose (Control 0.96 ±â€¯0.08 vs. LGI 0.79 ±â€¯0.06, p = 0.02) while the HGI diet increased it (Control 0.88 ±â€¯0.06 vs. HGI 1.06 ±â€¯0.07, p = 0.03). Neither DI nor oxidative stress markers changed after the LGI or HGI diets. NAC had no effect on DI, glucose variability or oxidative stress markers. We conclude small changes in glucose variability induced by dietary GI in adults with pre-diabetes are unlikely to contribute to ß-cell dysfunction.

Patient-centered change in the day-to-day impact of postmenopausal vaginal symptoms: results from a multicenter randomized trial.

BACKGROUND: Vulvovaginal symptoms, which include dryness, irritation, and pain with intercourse, are common among postmenopausal women and are associated with impaired sexual functioning and quality of life. Previous assessment of treatment strategies for these symptoms has been limited by a lack of sensitive patient-centered outcome measures that assess symptom impact on functional and quality-of-life domains. OBJECTIVE: We aimed to (1) examine change in the impact of postmenopausal vulvovaginal symptoms on multiple aspects of well-being and functioning in relation to vaginal estradiol and moisturizer treatment and (2) guide meaningful interpretation of scores on a structured-item questionnaire measure of condition-specific impact. STUDY DESIGN: Data were drawn from postmenopausal women who were enrolled in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health Vaginal Health Trial (a 12-week, double-blind, placebo-controlled randomized trial of treatment for vulvovaginal symptoms) who were assigned to vaginal 10-µg estradiol tablet plus placebo gel (n=98), vaginal moisturizer plus placebo tablet (n=97), or dual placebo (n=94). At baseline and 12-week follow up, participants completed the Day-to-Day Impact of Vaginal Aging questionnaire to assess the impact of vaginal symptoms on 4 domains (activities of daily living, emotional well-being, sexual functioning, and body image), each on a 0-4 point scale. Day-to-Day Impact of Vaginal Aging sensitivity to change was assessed by the examination of the associations between change in Day-to-Day Impact of Vaginal Aging domain scores and vulvovaginal symptom severity from baseline to 12 weeks with analysis of covariance. Within-woman and between-group minimal clinically important improvement was assessed with the use of an anchor-based approach that relates change in Day-to-Day Impact of Vaginal Aging domain scores with self-reported benefit from treatment. RESULTS: Participants in all treatment arms (n=289) demonstrated reduced impact of vulvovaginal symptoms on all domains of well-being and functioning as assessed by Day-to-Day Impact of Vaginal Aging at 12-week follow up, with no significant differences in improvement between women who were assigned to either estradiol tablet or vaginal moisturizer compared with placebo. For all Day-to-Day Impact of Vaginal Aging domains, mean impact scores were reduced when participants reported symptom improvement (-0.3 to -0.8 point change in Day-to-Day Impact of Vaginal Aging scores for <2-point symptom severity change vs -0.4 to -1.6 point change in Day-to-Day Impact of Vaginal Aging scores for 2+ point symptom severity change; all P<.001). Minimal clinically important change in Day-to-Day Impact of Vaginal Aging domain scale scores, which are anchored to self-reported meaningful benefit from treatment at 12 weeks, ranged from -0.4 to -1.3 (within-woman) and -0.2 to -0.7 (between-group). Observed change and minimal clinically important difference were largest for the sexual functioning domain. CONCLUSION: The impact of vulvovaginal symptoms on day-to-day activities, sexual function, emotional well-being, and body image may be improved with low-dose vaginal estradiol, moisturizer, or topical placebo. The Day-to-Day Impact of Vaginal Aging questionnaire demonstrates sensitivity to change with treatment of vulvovaginal symptoms, particularly Day-to-Day Impact of Vaginal Aging scales that focus on symptom impact on sexual functioning and body image. Minimal clinically important improvement in the impact of vulvovaginal symptoms as measured by the Day-to-Day Impact of Vaginal Aging can be defined with the use of these measures.

Lights on MsFLASH: a review of contributions.

OBJECTIVE: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health clinical trials network was funded by the National Institutes of Health to find new ways to alleviate the most common, bothersome menopausal symptoms by designing and conducting multiple concurrent clinical intervention studies, accommodating a wide scope of populations and intervention strategies. METHODS: Trials were conducted in Boston, Indianapolis, Minneapolis, Oakland, Philadelphia, and Seattle, with the Data Coordinating Center in Seattle, and were designed with standardized eligibility criteria and endpoints. Primary outcomes focused on vasomotor symptoms, sleep quality and insomnia symptoms, and vaginal symptoms. Secondary outcomes included quality of life, sexual function, and mood. RESULTS: We completed five randomized clinical trials and three ancillary studies, testing nine interventions in over 1,300 women and collecting nearly 16,000 bio-specimens. Escitalopram, venlafaxine hydrochloride extended release, and low-dose estradiol diminished hot flashes by approximately 50% as compared with a 30% decrease by placebo. No benefits on vasomotor symptoms were observed with yoga or exercise compared with usual activity, nor with omega-3 supplementation compared with placebo. Cognitive behavioral therapy for insomnia reduced self-reported insomnia symptoms and improved overall sleep quality compared with menopause education control. We did not find significant benefit from a vaginal estradiol tablet or a vaginal moisturizer compared with placebo tablet and gel in diminishing the severity of vaginal symptoms. CONCLUSIONS: The MsFLASH trials contributed substantially to our understanding of bothersome menopausal symptom treatment. It is important that clinicians counseling women about available treatment options consider all therapies-both nonhormonal and hormonal.

Trends in Medicare Payment Rates for Noninvasive Cardiac Tests and Association With Testing Location.

Importance: To control spending, the Centers for Medicare & Medicaid Services reduced Medicare fee-for-service (FFS) payments for noninvasive cardiac tests (NCTs) performed in provider-based office settings (ambulatory offices not administratively affiliated with hospitals) starting in 2005. Contemporaneously, payments for hospital-based outpatient testing increased. The association between differential payments by site and test location is unknown. Objectives: To quantify trends in differential Medicare FFS payments for NCTs performed in hospital-based and provider-based settings, determine the association between the hospital-based outpatient testing to provider-based office testing payment ratio and the proportion of hospital-based NCTs, and to examine trends in test location between Medicare FFS and 3 Medicare Advantage health maintenance organizations for which Centers for Medicare & Medicaid Services payments do not depend on testing location. Design, Setting, and Participants: This observational claims-based study used Medicare FFS claims from 1999 to 2015 (5% random sample) and Medicare Advantage claims from 3 large health maintenance organizations (2005-2015) among Medicare FFS beneficiaries aged 65 years or older and a health maintenance organization control group. Statistical analysis was performed from May 1, 2017, to July 15, 2019. Exposures: The weighted mean payment ratio of Medicare FFS hospital-based outpatient testing to provider-based office testing for outpatient NCTs. Main Outcomes and Measures: Proportion of outpatient NCTs performed in the hospital-based setting and Medicare FFS costs. Results: The data included a mean of 1.72 million patient-years annually in Medicare FFS (mean age, 75.2 years; 57.3% female in 2015) and a mean of 142 230 patient-years annually in the managed care control group (mean age, 74.8 years; 56.2% female in 2015). The Medicare payment ratio of FFS hospital-based outpatient testing to provider-based office testing increased from 1.05 in 2005 to 2.32 in 2015. The FFS hospital-based outpatient testing proportion increased from 21.1% in 2008 to 43.2% in 2015 and was correlated with the payment ratio (correlation coefficient with a 1-year lag, 0.767; P < .001). In contrast, the hospital-based outpatient testing proportion for the control group declined from 16.6% in 2008 to 15.2% in 2015 (correlation coefficient, -0.024, P = .95). The estimated extra costs owing to tests shifting to the hospital-based outpatient setting in the Medicare FFS group was $661 million in 2015, including $161 million in patient out-of-pocket costs. Conclusions and Relevance: In settings in which reimbursement depends on test location, increasing hospital-based payments correlated with greater proportions of outpatient NCTs performed in the hospital-based outpatient setting. Site-neutral payments may offer an incentive for testing to be performed in the more efficient location.

Facebook advertising for recruitment of midlife women with bothersome vaginal symptoms: A pilot study.

BACKGROUND: The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network recruited into five randomized clinical trials (n = 100-350) through mass mailings. The fifth trial tested two interventions for postmenopausal vulvovaginal symptoms (itching, pain, irritation, dryness, or pain with sex) and thus required a high level of sensitivity to privacy concerns. For this trial, in addition to mass mailings we pilot tested a social media recruitment approach. We aimed to evaluate the feasibility of recruiting healthy midlife women with bothersome vulvovaginal symptoms to participate in the Vaginal Health Trial through Facebook advertising. METHODS: As part of a larger advertising campaign that enrolled 302 postmenopausal women for the 12-week randomized, double-blind, placebo-controlled Vaginal Health Trial from April 2016 to February 2017, Facebook advertising was used to recruit 25 participants. The target population for recruitment by mailings and by Facebook ads included women aged 50-70 years and living within 20 miles of study sites in Minneapolis, MN and Seattle, WA. Design of recruitment letters and Facebook advertisements was informed by focus group feedback. Facebook ads were displayed in the "newsfeed" of targeted users and included a link to the study website. Response rates and costs are described for both online ads and mailing. RESULTS: Facebook ads ran in Minneapolis for 28 days and in Seattle for 15 days, with ads posted and removed from the site as needed based on clinic flow and a set budget limit. Our estimated Facebook advertising reach was over 200,000 women; 461 women responded and 25 were enrolled at a cost of US$14,813. The response rate per estimated reach was 0.22%; costs were US$32 per response and US$593 per randomized participant. The social media recruitment results varied by site, showing greater effectiveness in Seattle than in Minneapolis. We mailed 277,000 recruitment letters; 2166 women responded and 277 were randomized at a cost of US$98,682. The response rate per letter sent was 0.78%; costs were US$46 per response and US$356 per randomized participant. Results varied little across sites. CONCLUSION: Recruitment to a clinical trial testing interventions for postmenopausal vaginal symptoms is feasible through social media advertising. Variability in observed effectiveness and costs may reflect the small sample sizes and limited budget of the pilot recruitment study.

Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study.

OBJECTIVE: Women with prediabetes are identified from screening for overt diabetes in early pregnancy, but the clinical significance of prediabetes in pregnancy is unclear. We examined whether prediabetes in early pregnancy was associated with risks of adverse outcomes. STUDY DESIGN: We conducted a retrospective cohort study of pregnant women enrolled in Kaiser Permanente Washington from 2011 to 2014. Early pregnancy hemoglobin A1C (A1C) values, covariates, and outcomes were ascertained from electronic medical records and state birth certificates. Women with prediabetes (A1C of 5.7-6.4%) were compared with those with normal A1C levels (<5.7%) for risk of gestational diabetes mellitus (GDM) and other outcomes including preeclampsia, primary cesarean delivery, induction of labor, large/small for gestational age, preterm birth, and macrosomia. We used modified Poisson's regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 7,020 women, 239 (3.4%) had prediabetes. GDM developed in 48% of prediabetic women compared with 11% of women with normal A1C levels (adjusted RR: 2.8, 95% CI: 2.4-3.3). Prediabetes was not associated with all other adverse maternal and neonatal outcomes. CONCLUSION: Prediabetes in early pregnancy is a risk factor for GDM. Future research is needed to elucidate whether early intervention may reduce this risk.

One-Step Approach to Identifying Gestational Diabetes Mellitus: Association With Perinatal Outcomes.

OBJECTIVE: To compare perinatal outcomes before and after a clinical guideline change from a two-step to a one-step approach to screening for gestational diabetes mellitus (GDM). METHODS: We conducted a before-after cohort study of women with singleton live birth deliveries within Kaiser Permanente Washington, a mixed-model health plan in Washington state. We used Kaiser Permanente Washington electronic health data and linked birth certificates. We compared outcomes before (January 2009-March 2011) and after (April 2012-December 2014) the guideline change among women who received prenatal care from health care providers internal to Kaiser Permanente Washington (n=4,977 before, n=6,337 after). We made the same comparison among women who received prenatal care from external health care providers (not exposed to the guideline change; n=3,386 before, n=4,454 after) to control for time trends unrelated to the guideline change. Adjusted relative risks and 95% CIs were estimated using Poisson generalized estimating equations. RESULTS: After the guideline change, receipt of the one-step approach became widespread among women cared for by Kaiser Permanente Washington internal providers (87%), and use of insulin increased 3.7-fold from 1.2% to 4.4%. Among women cared for by Kaiser Permanente Washington internal providers, GDM increased from 6.9% to 11.4%, induction of labor from 25.2% to 28.6%, neonatal hypoglycemia from 1.3% to 2.0%, and outpatient nonstress testing from 134.6 to 157.0 test days per 100 women. After accounting for background trends in outcomes (based on the women cared for by external providers), the guideline change was associated with increased incidence of GDM (relative risk [RR] 1.41, 95% CI 1.17-1.69), labor induction (RR 1.20, 95% CI 1.09-1.32), neonatal hypoglycemia (RR 1.77, 95% CI 1.14-2.75), and nonstress testing (RR 1.12, 95% CI 1.02-1.24% per 100 women). There was no association with other outcomes including cesarean delivery or macrosomia. CONCLUSION: Adopting the one-step approach was associated with a 41% increase in the diagnosis of GDM without improved maternal or neonatal outcomes.

Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial.

Importance: Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments. Objective: To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms. Design, Setting, and Participants: This 12-week multicenter randomized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration. Interventions: Vaginal 10-µg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week) (n = 102) vs placebo tablet plus vaginal moisturizer (n = 100) vs dual placebo (n = 100). Main Outcomes and Measures: The main outcome was decrease in severity (0-3) of most bothersome symptom (MBS) between enrollment and 12 weeks. Additional measures included a composite vaginal symptom score, Female Sexual Function Index (FSFI) score (2-36), modified Female Sexual Distress Score-Revised item 1, treatment satisfaction and meaningful benefit, Vaginal Maturation Index, and vaginal pH. Results: The 302 women had a mean (SD) age of 61 (4) years and were primarily white (267 [88%]), college educated (200 [66%]), and sexually active (245 [81%]). Most women (294 [97%]) provided data for the primary analysis. The most commonly reported MBS was pain with vaginal penetration (182 [60%]), followed by vulvovaginal dryness (63 [21%]). Mean baseline MBS severity was similar between treatment groups: estradiol, 2.4 (95% CI, 2.3 to 2.6); moisturizer, 2.5 (95% CI, 2.3 to 2.6); placebo, 2.5 (95% CI, 2.4 to 2.6). All treatment groups had similar mean reductions in MBS severity over 12 weeks: estradiol, -1.4 (95% CI, -1.6 to -1.2); moisturizer, -1.2 (95% CI, -1.4 to -1.0); and placebo, -1.3 (95% CI, -1.5 to -1.1). No significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo. Mean total FSFI improvement was similar between estradiol (5.4; 95% CI, 4.0 to 6.9) and placebo (4.5; 95% CI, 2.8 to 6.1) (P = .64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo (P = .17). Conclusions and Relevance: Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms. Trial Registration: clinicaltrials.gov Identifier: NCT02516202.

Effects of Pharmacologic and Nonpharmacologic Interventions on Insomnia Symptoms and Self-reported Sleep Quality in Women With Hot Flashes: A Pooled Analysis of Individual Participant Data From Four MsFLASH Trials.

Study Objectives: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects relative to control in women with comparably severe insomnia symptoms and VMS. Methods: We analyzed pooled individual-level data from 546 peri- and postmenopausal women with Insomnia Severity Index (ISI) ≥ 12, and ≥14 bothersome VMS/week across the four RCTs. Interventions included the following: escitalopram 10-20 mg/day; yoga; aerobic exercise; 1.8 g/day omega-3 fatty acids; oral 17-beta-estradiol 0.5-mg/day; venlafaxine XR 75-mg/day; and cognitive behavioral therapy for insomnia (CBT-I). Outcome measures were ISI and Pittsburgh Sleep Quality Index (PSQI) over 8-12 weeks of treatment. Results: CBT-I produced the greatest reduction in ISI from baseline relative to control at -5.2 points (95% CI -7.0 to -3.4). Effects on ISI were similar for exercise at -2.1 and venlafaxine at -2.3 points. Comparably small decreases in ISI were observed with escitalopram, yoga, and estradiol. The largest reduction in PSQI from baseline was with CBT-I at -2.7 points (-3.9 to -1.5), although PSQI decreases of 1.2 to 1.6 points were significantly better than control with escitalopram, exercise, yoga, estradiol, and venlafaxine. Omega-3 supplements did not improve insomnia symptoms. Conclusions: This study's findings support current recommendations for CBT-I as a first line treatment in healthy midlife women with insomnia symptoms and moderately bothersome VMS.

Being overweight or obese is associated with harboring a gut microbial community not capable of metabolizing the soy isoflavone daidzein to O-desmethylangolensin in peri- and post-menopausal women.

OBJECTIVE: Obesity can be a considerable health concern for peri- and post-menopausal women. Evidence suggests an association between the gut microbiome and obesity. The study objective was to evaluate the association between being overweight or obese and phenotypic markers of having an overall gut microbial environment not capable of metabolizing the isoflavone daidzein to equol or O-desmethylangolensin (ODMA). STUDY DESIGN: Cross-sectional study of 137 peri- and 218 post-menopausal women, aged 44-55 years, who consumed at least three servings per week of soy (source of daidzein). Equol and ODMA producers and non-producers were identified based on urinary concentrations of daidzein, equol and ODMA in a 24-h urine sample. MAIN OUTCOME MEASURES: Mean body mass index (BMI) and odds of obesity. RESULTS: Fifty-one women were ODMA non-producers and 226 were equol non-producers. The ODMA non-producer phenotype was positively associated with obesity (OR: 3.33, 95% CI: 1.53, 7.23), and mean BMI was significantly higher in non-producers (28.9kg/m2) than in producers (26.7kg/m2), after adjusting for age, ethnicity, and menopausal status. Positive associations with being obese were observed in both peri-menopausal (OR=3.92, 95% CI: 0.90, 17.0) and post-menopausal (OR=3.00, 95% CI: 1.22, 7.70) women. The equol non-producer phenotype was not associated with obesity (OR=1.13, 95% CI: 0.64, 1.98), and mean BMI was not significantly different between equol producers (27.3kg/m2) and non-producers (26.5kg/m2). CONCLUSIONS: These results suggest that the ODMA non-producer phenotype is associated with obesity in peri- and post-menopausal women. Further work is needed to confirm these observations in additional populations and to evaluate possible mechanisms.

High rates of severe hypoglycemia among African American patients with diabetes: the surveillance, prevention, and Management of Diabetes Mellitus (SUPREME-DM) network.

AIMS: Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. METHODS: SH events were identified via any primary or principal diagnosis from emergency department or inpatient encounters among African American, Asian, Latino and White adult diabetes patients treated with insulin or secretagogues (Sulfonylureas or Meglitinides), receiving care from integrated healthcare delivery systems across the United States. We calculated age- and sex-standardized annual SH rates and average annual percent change (AAPC) in SH rates. RESULTS: Annual SH rates ranged from 1.8% to 2.1% during this 7-year observation period (2,200,471 person-years). African Americans had consistently higher SH rates compared with Whites, while Latinos and Asians had consistently lower rates compared with Whites in each of the 7 years (all p < 0.01). The trend increased significantly only among African Americans (AAPC = +4.3%; 95% CI: +2.1, +6.5%); in the other groups, the AAPC was not significantly different from zero. CONCLUSIONS: Surveillance efforts should monitor the racial/ethnic-specific rates. The factors underlying substantially higher rates of hypoglycemia in African Americans should be evaluated. Clinically and culturally-appropriate strategies to reduce the risk of SH need to be developed and tested.

Trends in Incidence of Hospitalized Acute Myocardial Infarction in the Cardiovascular Research Network (CVRN).

BACKGROUND: Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations. METHODS: We examined trends in hospitalized acute myocardial infarction incidence among adults aged ≥25 years in 13 US health plans in the Cardiovascular Research Network. The first hospitalization per member for acute myocardial infarction overall and for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge codes in each calendar year from 2000 through 2008. Age- and sex-adjusted incidence was calculated per 100,000 person-years using direct adjustment with 2000 US census data. RESULTS: Between 2000 and 2008, we identified 125,435 acute myocardial infarction hospitalizations. Age- and sex-adjusted incidence rates (per 100,000 person-years) of acute myocardial infarction decreased an average 3.8%/y from 230.5 in 2000 to 168.6 in 2008. Incidence of ST-segment elevation myocardial infarction decreased 8.7%/y from 104.3 in 2000 to 51.7 in 2008, whereas incidence of non-ST-segment elevation myocardial infarction increased from 126.1 to 129.4 between 2000 and 2004 and then decreased thereafter to 116.8 in 2008. Age- and sex-specific incidence rates generally reflected similar patterns, with relatively larger decreases in ST-segment elevation myocardial infarction rates in women compared with men. As compared with 2000, the age-adjusted incidence of ST-segment elevation myocardial infarction in 2008 was 48% lower among men and 61% lower among women. CONCLUSIONS AND RELEVANCE: Among a large, diverse, multicenter community-based insured population, there were significant decreases in incidence of hospitalized acute myocardial infarction and the more serious ST-segment elevation myocardial infarctions between 2000 and 2008. Decreases in ST-segment elevation myocardial infarctions were most pronounced among women. While ecologic in nature, these secular decreases likely reflect, at least in part, results of improvement in primary prevention efforts.

Effects of Yoga and Aerobic Exercise on Actigraphic Sleep Parameters in Menopausal Women with Hot Flashes.

STUDY OBJECTIVES: To determine effects of yoga and aerobic exercise compared with usual activity on objective assessments of sleep in midlife women. METHODS: Secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) network conducted among 186 late transition and postmenopausal women aged 40-62 y with hot flashes. Women were randomized to 12 w of yoga, supervised aerobic exercise, or usual activity. The mean and coefficient of variation (CV) of change in actigraph sleep measures from each intervention group were compared to the usual activity group using linear regression models. RESULTS: Baseline values of the primary sleep measures for the entire sample were mean total sleep time (TST) = 407.5 ± 56.7 min; mean wake after sleep onset (WASO) = 54.6 ± 21.8 min; mean CV for WASO = 37.7 ± 18.7 and mean CV for number of long awakenings > 5 min = 81.5 ± 46.9. Changes in the actigraphic sleep outcomes from baseline to weeks 11-12 were small, and none differed between groups. In an exploratory analysis, women with baseline Pittsburgh Sleep Quality Index higher than 8 had significantly reduced TST-CV following yoga compared with usual activity. CONCLUSIONS: This study adds to the currently scant literature on objective sleep outcomes from yoga and aerobic exercise interventions for this population. Although small effects on self-reported sleep quality were previously reported, the interventions had no statistically significant effects on actigraph measures, except for potentially improved sleep stability with yoga in women with poor self-reported sleep quality.

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis.

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and postmenopausal women. We used baseline data from 898 peri- and postmenopausal women recruited from multiple communities, ages 42-62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and postmenopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and postmenopausal women.

A yoga & exercise randomized controlled trial for vasomotor symptoms: Effects on heart rate variability.

OBJECTIVES: Heart rate variability (HRV) reflects the integration of the parasympathetic nervous system with the rest of the body. Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV. We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a randomized clinical trial of treatments for vasomotor symptoms in peri/post-menopausal women. DESIGN: Randomized clinical trial of behavioral interventions in women with vasomotor symptoms (n=335), 40-62 years old from three clinical study sites. INTERVENTIONS: 12-weeks of a yoga program, designed specifically for mid-life women, or a supervised aerobic exercise-training program with specific intensity and energy expenditure goals, compared to a usual activity group. MAIN OUTCOME MEASURES: Time and frequency domain HRV measured at baseline and at 12 weeks for 15min using Holter monitors. RESULTS: Women had a median of 7.6 vasomotor symptoms per 24h. Time and frequency domain HRV measures did not change significantly in either of the intervention groups compared to the change in the usual activity group. HRV results did not differ when the analyses were restricted to post-menopausal women. CONCLUSIONS: Although yoga and exercise have been shown to increase parasympathetic-mediated HRV in other populations, neither intervention increased HRV in middle-aged women with vasomotor symptoms. Mixed results in previous research may be due to sample differences. Yoga and exercise likely improve short-term health in middle-aged women through mechanisms other than HRV.

Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms: A MsFLASH Randomized Clinical Trial.

IMPORTANCE: Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings. OBJECTIVE: To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). DESIGN, SETTING, AND PARTICIPANTS: A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. INTERVENTIONS: Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health. MAIN OUTCOMES AND MEASURES: Primary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. RESULTS: At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, -3.9 to -1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (-15.7; 95% CI, -20.4 to -11.0) compared with the MEC group (-7.1; 95% CI, -14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (-22.8; 95% CI, -28.6 to -16.9) and MEC group (-11.6; 95% CI, -19.4 to -3.8) (P = .003). CONCLUSIONS AND RELEVANCE: Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01936441.