An empowerment model for managing menopause.

Menopause eventually happens to all people with typically functioning ovaries, and almost one billion women worldwide are postmenopausal. Although the biology of typical menopause is ubiquitous, the experience varies substantially. Factors contributing to the experience include not only individual factors, such as the nature and severity of symptoms, but also psychological, social, and contextual considerations, many of which are modifiable. In this first paper in the Lancet Series on menopause, we argue for a new approach that goes beyond the treatment of specific symptoms, to encompass a broad model to support women transitioning this life stage, using the model of empowerment. WHO defines empowerment as an active process of gaining knowledge, confidence, and self-determination to self-manage health and make informed decisions about care. Rather than focusing on menopause as an endocrine deficiency, we propose an empowerment model that recognises factors modifying the experience, in which the patient is an expert in their own condition and the health-care worker supports the patient to become an equal and active partner in managing their own care.

Using functional principal component analysis (FPCA) to quantify sitting patterns derived from wearable sensors.

BACKGROUND: Sedentary behavior (SB) is a recognized risk factor for many chronic diseases. ActiGraph and activPAL are two commonly used wearable accelerometers in SB research. The former measures body movement and the latter measures body posture. The goal of the current study is to quantify the pattern and variation of movement (by ActiGraph activity counts) during activPAL-identified sitting events, and examine associations between patterns and health-related outcomes, such as systolic and diastolic blood pressure (SBP and DBP). METHODS: The current study included 314 overweight postmenopausal women, who were instructed to wear an activPAL (at thigh) and ActiGraph (at waist) simultaneously for 24 hours a day for a week under free-living conditions. ActiGraph and activPAL data were processed to obtain minute-level time-series outputs. Multilevel functional principal component analysis (MFPCA) was applied to minute-level ActiGraph activity counts within activPAL-identified sitting bouts to investigate variation in movement while sitting across subjects and days. The multilevel approach accounted for the nesting of days within subjects. RESULTS: At least 90% of the overall variation of activity counts was explained by two subject-level principal components (PC) and six day-level PCs, hence dramatically reducing the dimensions from the original minute-level scale. The first subject-level PC captured patterns of fluctuation in movement during sitting, whereas the second subject-level PC delineated variation in movement during different lengths of sitting bouts: shorter (< 30 minutes), medium (30 -39 minutes) or longer (> 39 minute). The first subject-level PC scores showed positive association with DBP (standardized ß ^ : 2.041, standard error: 0.607, adjusted p = 0.007), which implied that lower activity counts (during sitting) were associated with higher DBP. CONCLUSION: In this work we implemented MFPCA to identify variation in movement patterns during sitting bouts, and showed that these patterns were associated with cardiovascular health. Unlike existing methods, MFPCA does not require pre-specified cut-points to define activity intensity, and thus offers a novel powerful statistical tool to elucidate variation in SB patterns and health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03473145; Registered 22 March 2018; https://clinicaltrials.gov/ct2/show/NCT03473145 ; International Registered Report Identifier (IRRID): DERR1-10.2196/28684.

Racial and Ethnic Inequities in Spatial Access to Pharmacies: A Geographic Information System Analysis.

BACKGROUND: Pharmacy accessibility is crucial for equity in healthcare access because community pharmacists may reach individuals who do not have access to other healthcare providers. OBJECTIVE: To determine whether spatial access to pharmacies differs among racial/ethnic groups across the rural-urban continuum. METHODS: We obtained a 30% random sample of the Research Triangle Institute (RTI) synthetic population, sampled at the census block level. For each individual, we defined optimal pharmacy access as having a driving distance ≤2 miles to the closest pharmacy in urban counties, ≤5 miles in suburban counties, and ≤10 miles in rural counties. We used a logistic regression model to measure the association between race/ethnicity and pharmacy access, while controlling for racial/ethnic composition of the census tract, Area Deprivation Index, income, age, gender, and US region. The model included an interaction between race/ethnicity and urbanicity to evaluate whether racial/ethnic inequities differed across the rural-urban continuum. RESULTS: The sample included 90,749,446 individuals of whom 80.6% had optimal pharmacy access. Racial/ethnic inequities in pharmacy access differed across the rural-urban continuum (p-value for interaction= <0.0001). In rural areas, Black (OR 0.87; 95%CI 0.86-0.87), Hispanic (OR 0.80; 95%CI 0.79-0.80), and Indigenous (OR 0.47; 95%CI 0.47-0.48) individuals had lower odds of optimal pharmacy access, compared to White individuals. Hispanic (OR 0.96; 95%CI 0.96-0.97) and Indigenous individuals (OR 0.75; 95%CI 0.75-0.76) had lower odds of optimal pharmacy access compared to White individuals in suburban areas. In Western states, Asian had lower odds of optimal pharmacy access in suburban (OR 0.88; 95%CI 0.86-0.90) and rural areas (OR 0.91; 95%CI 0.87-0.95) compared to White Individuals. CONCLUSIONS: Racial/ethnic inequities in spatial access to community pharmacies vary between urban and rural communities. Underrepresented racial/ethnic groups have significantly lower pharmacy access in rural and some suburban areas, but not in urban areas.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years. Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up. Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Loneliness, social isolation, and cardiovascular disease among nonveteran and veteran women.

We examined the prospective associations of social isolation and loneliness with incident cardiovascular disease (CVD) among aging nonveteran and veteran women, and effect modification by veteran status. Participants with no history of myocardial infarction (MI), stroke, coronary heart disease (CHD), or coronary heart failure from the Women's Health Initiative Extension Study II self-reported social isolation, loneliness, health behaviors, health status, and veteran status. CVD and CVD subevents were physician adjudicated. Hazard ratios (HR) and 95% confidence intervals (CI) for the Interquartile Range (IQR) in social isolation (IQR = 1) and loneliness (IQR=.33) were calculated using Cox proportional hazard models adjusting for sociodemographic, health behavior, and health status characteristics. Veteran status was tested as an effect modifier. Among 52,442 women (Mean age = 79 ± 6.1; veterans n = 1023; 89.2% non-Hispanic White), 3579 major CVD events occurred over an average 5.8 follow-up years. Compared to nonveterans, veteran women reported higher levels of social isolation (p < .01) and loneliness (p < .01). The CVD HR was 1.07 (95% CI, 1.04-1.10) for the IQR in social isolation and 1.03 (95% CI, 1.10-1.06) for the IQR in loneliness. The HR for the IQR in both social isolation and loneliness was 1.10 (95% CI, 1.05-1.15). Social isolation was associated with CHD (HR = 1.12; 95% CI, 1.03-1.21). The CHD HR for the IQR in social isolation was 1.12 (95% CI, 1.03-1.21). Associations did not differ by veteran status (all p-interactions > 0.08). Findings suggest that the adverse associations of social isolation and loneliness with CVD are similar among veteran and nonveteran women.

Accelerometer-measured physical activity and postmenopausal breast cancer incidence in the Women's Health Accelerometry Collaboration.

BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women's Health Accelerometry Collaboration (WHAC). METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women's Health Study [WHS]; 5714 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI). RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64-0.99), 0.84 (95% CI, 0.69-1.02), 0.89 (95% CI, 0.73-1.08), and 0.81 (95% CI, 0.64-1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than <30 kg/m2 for LPA. CONCLUSION: Greater levels of accelerometer-assessed PA were associated with lower BC risk. Associations varied by age and obesity and were not independent of BMI or physical function.

Low movement, deep-learned sitting patterns, and sedentary behavior in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE).

BACKGROUND/OBJECTIVES: Sedentary behavior (SB) has both movement and postural components, but most SB research has only assessed low movement, especially in children. The purpose of this study was to compare estimates and health associations of SB when derived from a standard accelerometer cut-point, a novel sitting detection technique (CNN Hip Accelerometer Posture for Children; CHAP-Child), and both combined. METHODS: Data were from the International Study of Childhood Obesity, Lifestyle, and the Environment (ISCOLE). Participants were 6103 children (mean ± SD age 10.4 ± 0.56 years) from 12 countries who wore an ActiGraph GT3X+ accelerometer on the right hip for approximately one week. We calculated SB time, mean SB bout duration, and SB breaks using a cut-point (SBmovement), CHAP-Child (SBposture), and both methods combined (SBcombined). Mixed effects regression was used to test associations of SB variables with pediatric obesity variables (waist circumference, body fat percentage, and body mass index z-score). RESULTS: After adjusting for MVPA, SBposture showed several significant obesity associations favoring lower mean SB bout duration (b = 0.251-0.449; all p < 0.001) and higher SB breaks (b = -0.005--0.052; all p < 0.001). Lower total SB was unexpectedly related to greater obesity (b = -0.077--0.649; p from <0.001-0.02). For mean SB bout duration and SB breaks, more associations were observed for SBposture (n = 5) than for SBmovement (n = 3) or SBcombined (n = 1), and tended to have larger magnitude as well. CONCLUSIONS: Using traditional measures of low movement as a surrogate for SB may lead to underestimated or undetected adverse associations between SB and obesity. CHAP-Child allows assessment of sitting posture using hip-worn accelerometers. Ongoing work is needed to understand how low movement and posture are related to one another, as well as their potential health implications.

Accelerometer-measured physical activity and sitting with incident mild cognitive impairment or probable dementia among older women.

INTRODUCTION: Physical activity (PA) is prospectively inversely associated with dementia risk, but few studies examined accelerometer measures of PA and sitting with rigorously-adjudicated mild cognitive impairment (MCI) and dementia risk. METHODS: We examined the associations of accelerometer measures (PA and sitting) with incident MCI/probable dementia in the Women's Health Initiative (n = 1277; mean age = 82 ± 6 years) RESULTS: Over a median follow-up of 4.2 years, 267 MCI/probable dementia cases were identified. Adjusted Cox regression HRs (95% CI) across moderate-to-vigorous PA (MVPA) min/d quartiles were 1.00 (reference), 1.28 (0.90 to 1.81), 0.79 (0.53 to 1.17), and 0.69 (0.45 to 1.06); P-trend = 0.01. Adjusted HRs (95% CI) across steps/d quartiles were 1.00 (reference), 0.73 (0.51 to 1.03), 0.64 (0.43 to 0.94), and 0.38 (0.23 to 0.61); P-trend < 0.001. The HR (95% CI) for each 1-SD increment in MVPA (31 min/d) and steps/d (1865) were 0.79 (0.67 to 0.94) and 0.67 (0.54 to 0.82), respectively. Sitting was not associated with MCI/probable dementia. DISCUSSION: Findings suggest ≥ moderate intensity PA, particularly stepping, associates with lower MCI and dementia risk. HIGHLIGHTS: Few studies have examined accelerometer-measured physical activity, including steps, and sitting with incident ADRD. Moderate-to-vigorous physical activity and steps, but not light physical activity or sitting, were inversely associated with lower ADRD risk. Among older women, at least moderate intensity physical activity may be needed to reduce ADRD risk.

Associations of Accelerometer-Measured Physical Activity and Sedentary Time With All-Cause Mortality by Genetic Predisposition for Longevity.

The goal of this study was to examine associations between accelerometer-measured physical activity (PA) and sedentary time (ST) with mortality by a genetic risk score (GRS) for longevity. Among 5,446 women, (mean [SD]: age, 78.2 [6.6] years), 1,022 deaths were observed during 33,350 person-years of follow-up. Using multivariable Cox proportional hazards models, higher light PA and moderate to vigorous PA were associated with lower mortality across all GRS for longevity categories (low/medium/high; all ptrend < .001). Higher ST was associated with higher mortality (ptrend across all GRS categories < .001). Interaction tests for PA and ST with the GRS were not statistically significant. Findings support the importance of higher PA and lower ST for reducing mortality risk in older women, regardless of genetic predisposition for longevity.

Binge eating age of onset, frequency, and associated emotional distress among women aged 60 years and over.

Emerging research indicates that binge eating is prevalent among older adult women. This study explored the characteristics of older women (aged 60+ years) with objective binge episodes (OBE) in later-life, including age of onset, distress, and frequency of OBE. Data consist of telephone clinical interviews conducted with individuals presenting for participation in a biomedical study of older women with OBE to establish inclusion criteria. Of 71 participants interviewed, 77.5% met DSM-5 criteria for OBE (≥1/week for ≥3 months); 33.3% reported OBE onset before age 40, 17.9% reported midlife onset (ages 40-55), and 48.7% reported late-life onset (56+). Regarding distress, older women with OBE in later-life reported themes of age-related self-blame surrounding eating, loss of control, and cognitive fixation on satiation. Among older women with OBE in later-life, onset in mid- to later-life may be relatively common. Furthermore, distress regarding OBEs was significant, highlighting the need for intervention research among this population.

CHAP-child: an open source method for estimating sit-to-stand transitions and sedentary bout patterns from hip accelerometers among children.

BACKGROUND: Hip-worn accelerometer cut-points have poor validity for assessing children's sedentary time, which may partly explain the equivocal health associations shown in prior research. Improved processing/classification methods for these monitors would enrich the evidence base and inform the development of more effective public health guidelines. The present study aimed to develop and evaluate a novel computational method (CHAP-child) for classifying sedentary time from hip-worn accelerometer data. METHODS: Participants were 278, 8-11-year-olds recruited from nine primary schools in Melbourne, Australia with differing socioeconomic status. Participants concurrently wore a thigh-worn activPAL (ground truth) and hip-worn ActiGraph (test measure) during up to 4 seasonal assessment periods, each lasting up to 8 days. activPAL data were used to train and evaluate the CHAP-child deep learning model to classify each 10-s epoch of raw ActiGraph acceleration data as sitting or non-sitting, creating comparable information from the two monitors. CHAP-child was evaluated alongside the current practice 100 counts per minute (cpm) method for hip-worn ActiGraph monitors. Performance was tested for each 10-s epoch and for participant-season level sedentary time and bout variables (e.g., mean bout duration). RESULTS: Across participant-seasons, CHAP-child correctly classified each epoch as sitting or non-sitting relative to activPAL, with mean balanced accuracy of 87.6% (SD = 5.3%). Sit-to-stand transitions were correctly classified with mean sensitivity of 76.3% (SD = 8.3). For most participant-season level variables, CHAP-child estimates were within ± 11% (mean absolute percent error [MAPE]) of activPAL, and correlations between CHAP-child and activPAL were generally very large (> 0.80). For the current practice 100 cpm method, most MAPEs were greater than ± 30% and most correlations were small or moderate (≤ 0.60) relative to activPAL. CONCLUSIONS: There was strong support for the concurrent validity of the CHAP-child classification method, which allows researchers to derive activPAL-equivalent measures of sedentary time, sit-to-stand transitions, and sedentary bout patterns from hip-worn triaxial ActiGraph data. Applying CHAP-child to existing datasets may provide greater insights into the potential impacts and influences of sedentary time in children.

Markers of kidney function, genetic variation related to cognitive function, and cognitive performance in the UK Biobank.

BACKGROUND: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function. METHODS: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual memory. Adjustment for confounding factors was performed using multivariate regression and propensity-score matching. Interaction between kidney function markers and a polygenic risk score for general cognitive function was also assessed. RESULTS: Albuminuria was associated with worse performance on tasks of verbal-numeric reasoning (ß(points) = -0.09, p < 0.001), reaction time (ß(milliseconds) = 7.06, p < 0.001) and visual memory (ß(log errors) = 0.013, p = 0.01). A polygenic score for cognitive function modified the association between albuminuria and verbal-numeric reasoning with significantly lower scores in those with albuminuria and a lower polygenic score (p = 0.009). Compared to participants with eGFRcre ≥ 60 ml/min, those with eGFRcre < 60 ml/min had lower verbal-numeric reasoning scores and slower mean reaction times (verbal numeric reasoning ß = -0.11, p < 0.001 and reaction time ß = 6.08, p < 0.001 for eGFRcre < 60 vs eGFRcre ≥ 60). Associations were stronger using cystatin C-based eGFR than creatinine-based eGFR (verbal numeric reasoning ß = -0.21, p < 0.001 and reaction time ß = 11.21, p < 0.001 for eGFRcys < 60 vs eGFRcys ≥ 60). CONCLUSIONS: Increased urine albumin is associated with worse cognition, but this may depend on genetic risk. Cystatin C-based eGFR may better predict cognitive performance than creatinine-based estimates.

Community-Dwelling Older Adults and Physical Activity Recommendations: Patterns of Aerobic, Strengthening, and Balance Activities.

Though it is known that most older adults do not meet the recommended physical activity (PA) guidelines, little is known regarding their participation in balance activities or the full guidelines. Therefore, we sought to describe PA patterns among 1,352 community-dwelling older adult participants of the Adult Changes in Thought study, a longitudinal cohort study exploring dementia-related risk factors. We used a modified version of the Community Healthy Activities Model Program for Seniors questionnaire to explore PA performed and classify participants as meeting or not meeting the full guidelines or any component of the guidelines. Logistic regression was used to identify factors associated with meeting PA guidelines. Despite performing 10 hr of weekly PA, only 11% of participants met the full guidelines. Older age, greater body mass index, needing assistance with instrumental daily activities, and heart disease were associated with decreased odds of meeting PA guidelines. These results can guide interventions that address PA among older adults.

Associations Between Perceived Neighborhood Walkability and Device-Based Physical Activity and Sedentary Behavior Patterns in Older Adults.

Neighborhood walkability has been associated with self-reported sedentary behavior (SB) and self-reported and objective physical activity. However, self-reported measures of SB are inaccurate and can lead to biased estimates, and few studies have examined how associations differ by gender and age. The authors examined the relationships between perceived neighborhood walkability measured with the Physical Activity Neighborhood Environment Scale (scored 1.0-4.0) and device-based SB and physical activity in a cohort of community-dwelling older adults (N = 1,077). The authors fit linear regression models adjusting for device wear time, demographics, self-rated health, and accounting for probability of participation. The Higher Physical Activity Neighborhood Environment Scale was associated with higher steps (+676 steps/point on the Physical Activity Neighborhood Environment Scale, p = .001) and sit-to-stand transitions (+2.4 transitions/point, p = .018). Though not statistically significant, stratified analyses suggest an attenuation of effect for those aged 85 years and older and for women. Consistent with previous literature, neighborhood walkability was associated with more steps, though not with physical activity time. The neighborhood environment may also influence SB.

Accelerometer-Measured Daily Steps, Physical Function, and Subsequent Fall Risk in Older Women: The Objective Physical Activity and Cardiovascular Disease in Older Women Study.

Steps per day were measured by accelerometer for 7 days among 5,545 women aged 63-97 years between 2012 and 2014. Incident falls were ascertained from daily fall calendars for 13 months. Median steps per day were 3,216. There were 5,473 falls recorded over 61,564 fall calendar-months. The adjusted incidence rate ratio comparing women in the highest versus lowest step quartiles was 0.71 (95% confidence interval [0.54, 0.95]; ptrend across quartiles = .01). After further adjustment for physical function using the Short Physical Performance Battery, the incidence rate ratio was 0.86 ([0.64, 1.16]; ptrend = .27). Mediation analysis estimated that 63.7% of the association may be mediated by physical function (p = .03). In conclusion, higher steps per day were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults.

Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.

BACKGROUND: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.

Determinants, circumstances and consequences of injurious falls among older women living in the community.

OBJECTIVE: To identify the risk factors of women who fell with injury relative to women who did not fall or fell without injury and to describe the circumstances and consequences of injurious and non-injurious falls. METHODS: We analysed 5074 older women from the Objective Physical Activity and Cardiovascular Health Study who prospectively tracked their falls using a 13-month calendar. Women with a reported fall were phone interviewed about fall-related details, including injuries. Risk factors were identified from surveys and clinical home visits. Logistic regression models were used to calculate adjusted ORs and 95% CIs for injurious falls relative to not falling or falling without injury. Circumstances of injurious and non-injurious falls were compared. RESULTS: At least one fall was experienced by 1481 (29%) participants. Of these, 1043 were phone interviewed, of whom 430 (41%) reported at least one injurious fall. Relative to not falling, the risk factor most strongly associated with experiencing an injurious fall was having fallen ≥2 times (OR 4.0, CI 2.7 to 5.8) in the past year. Being black was protective for fall-related injury (OR 0.6, CI 0.4 to 0.9). No strong associations in risk factors were observed for injurious relative to non-injurious falls. Injurious falls were more likely to occur away from and outside of the home (p<0.05). Over half of those who injured self-managed their injury. CONCLUSION: Falling repeatedly is a powerful risk factor for injurious falls. Those who have fallen more than once should be prioritised for interventions to mitigate the risk of an injurious fall.

Associations between physical function and device-based measures of physical activity and sedentary behavior patterns in older adults: moving beyond moderate-to-vigorous intensity physical activity.

BACKGROUND: Research supports that moderate-to-vigorous intensity physical activity (MVPA) is key to prolonged health and function. Among older adults, substantial changes to MVPA may be infeasible, thus a growing literature suggests a shift in focus to whole-day activity patterns. METHODS: With data from 795 older adults aged 65-100 in the Adult Changes in Thought Activity Monitoring study, we used linear regression to estimate associations between ActiGraph and activPAL measured activity patterns - including light intensity physical activity, steps, standing, and sedentary behaviors - and physical function as measured by a short Performance-based Physical Function (sPPF) score (range 0-12), a composite score based on three standardized physical performance tasks: gait speed, timed chair stands, and grip strength. We examined whether relationships persisted when controlling for MVPA or differed across age, gender, or quartiles of MVPA. RESULTS: In models unadjusted for MVPA, a 1-standard deviation (SD) increment of daily sitting (1.9 h more), mean sitting bout duration (8 min longer average), or time spent in sedentary activity (1.6 h more) was associated with ~ 0.3-0.4 points lower mean sPPF score (all p < 0.05). A 1-SD increment in daily steps (~ 3500 more steps) was associated with ~ 0.5 points higher mean sPPF score (95% CI: 0.22 to 0.73). MVPA adjustment attenuated all relationships. The association between physical function and steps was strongest among adults aged 75+; associations of worse function with greater sedentary behavior were more pronounced in participants with the lowest levels of MVPA. CONCLUSIONS: We found associations between function and activity metrics other than MVPA in key subgroups, findings that support research on broader activity patterns and may offer ideas regarding practical intervention opportunities for improving function in older adults.

Recruitment of a multi-site randomized controlled trial of aerobic exercise for older adults with amnestic mild cognitive impairment: The EXERT trial.

INTRODUCTION: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking. METHODS: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants. RESULTS: Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations. DISCUSSION: Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.

Sedentary behavior and cardiovascular disease in older women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study.

Background: Evidence that higher sedentary time is associated with higher risk for cardiovascular disease (CVD) is based mainly on self-reported measures. Few studies have examined whether patterns of sedentary time are associated with higher risk for CVD. Methods: Women from the Objective Physical Activity and Cardiovascular Health (OPACH) Study (n=5638, aged 63-97, mean age=79±7) with no history of myocardial infarction (MI) or stroke wore accelerometers for 4-to-7 days and were followed for up to 4.9 years for CVD events. Average daily sedentary time and mean sedentary bout duration were the exposures of interest. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for CVD using models adjusted for covariates and subsequently adjusted for potential mediators (body mass index (BMI), diabetes, hypertension, and CVD-risk biomarkers [fasting glucose, high-density lipoprotein, triglycerides, and systolic blood pressure]). Restricted cubic spline regression characterized dose-response relationships. Results: There were 545 CVD events during 19,350 person-years. Adjusting for covariates, women in the highest (≥ ~11 hr/day) vs. the lowest (≤ ~9 hr/day) quartile of sedentary time had higher risk for CVD (HR=1.62; CI=1.21-2.17; p-trend <0.001). Further adjustment for potential mediators attenuated but did not eliminate significance of these associations (p-trend<.05, each). Longer vs. shorter mean bout duration was associated with higher risks for CVD (HR=1.54; CI=1.27-2.02; p-trend=0.003) after adjustment for covariates. Additional adjustment for CVD-risk biomarkers attenuated associations resulting in a quartile 4 vs. quartile 1 HR=1.36; CI=1.01-1.83; p-trend=0.10). Dose-response associations of sedentary time and bout duration with CVD were linear (P-nonlinear >0.05, each). Women jointly classified as having high sedentary time and long bout durations had significantly higher risk for CVD (HR=1.34; CI=1.08-1.65) than women with both low sedentary time and short bout duration. All analyses were repeated for incident coronary heart disease (MI or CVD death) and associations were similar with notably stronger hazard ratios. Conclusions: Both high sedentary time and long mean bout durations were associated in a dose-response manner with increased CVD risk in older women, suggesting that efforts to reduce CVD burden may benefit from addressing either or both component(s) of sedentary behavior.