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BACKGROUND: Depressive symptoms are associated with age-related cognitive impairment, but the relative risk of specific subtypes of mild cognitive impairment (MCI) conferred by depressive symptoms is unclear. The purpose of this exploratory study was to determine the longitudinal association between baseline depressive symptoms and incident cases of MCI subtypes (amnestic vs. non-amnestic) and probable dementia (PD) (Alzheimers disease, vascular, mixed) among postmenopausal women. METHODS: Depressive symptoms were assessed at study baseline using an 8-item Burnam algorithm in 7043 postmenopausal women who participated in the Womens Health Initiative Memory Study (WHIMS) and the WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) extension study. During the median 9.4-year follow-up interval, the presence of MCI and PD was classified by a central adjudication committee. Classification of participants by MCI subtype (amnestic single and multi-domain, non-amnestic single and multi-domain) was done algorithmically based on established criteria using data from annual cognitive testing. RESULTS: At baseline, 557 women (7.9%) had clinically significant depressive symptoms based on Burnam algorithm cut-point of 0.06. Depressive symptoms at baseline were associated with an increased risk of incident amnestic MCI (hazard ratio [HR] = 1.91, 95% confidence interval [CI] 1.32-2.78, p

Ovarian carcinoma histotypes are distinct diseases with variable clinical outcomes and response to treatment. There is a need for new subtype-specific treatment modalities, especially for women with widespread and chemo-resistant disease. Stimulator of interferon genes (STING) is a part of the cGAS-STING pathway that mediates innate immune defence against infectious DNA-containing pathogens and also detects tumour-derived DNA and generates intrinsic antitumour immunity. The STING signalling pathway is suppressed by several mechanisms in a variety of malignant diseases and, in some cancers that may be a requirement for cellular transformation. The aim of this study was to use immunohistochemistry to evaluate STING protein expression across normal tissue, paratubal and ovarian cysts, and ovarian tumour histotypes including ovarian carcinomas. Herein, we show that the fallopian tube ciliated cells express STING protein, whereas the secretory cells are negative. STING expression differs among ovarian cancer histotypes; low-grade serous ovarian carcinomas and serous borderline tumours have uniform high STING expression, while high-grade serous and endometrioid carcinomas have heterogeneous expression, and clear cell and mucinous carcinomas show low expression. As low-grade serous carcinomas are known to be genomically stable and typically lack a prominent host immune response, the consistently high STING expression is unexpected. High STING expression may reflect pathway activation or histogenesis and the mechanisms may be different in different ovarian carcinoma histotypes. Further studies are needed to determine whether the STING signalling pathway is active and whether these tumours would be candidates for therapeutic interventions that trigger innate immunity activation.

PurposeMany rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes.Experimental designWe compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed in vitro using cell lines and patient-derived xenograft mouse models representing SCCOHT.ResultsGlobal proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype in vitro. Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth in vivo.ConclusionsPreclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.

Tubo-ovarian transitional cell carcinoma (TCC) is grouped with high-grade serous carcinoma (HGSC) in the current World Health Organization classification. TCC is associated with BRCA mutations and a better prognosis compared with HGSC. Previous papers examining the immunohistochemical features of TCC have studied limited numbers of samples. No marker reflecting the biological difference between TCC and HGSC is known. We collected a large cohort of TCC to determine whether TCC and HGSC could be distinguished by immunohistochemistry. A tissue microarray was built from 89 TCC and a control cohort of 232 conventional HGSC. Immunohistochemistry was performed, scored, and statistically analyzed for routine markers of HGSC and urothelial tumors: PAX8, WT1, p53, p16, ER, p63, and GATA3. Using scoring cutoffs commonly employed in clinical practice, the immunohistochemical profile of TCC was indistinguishable from HGSC for all markers. However, more detailed scoring criteria revealed statistically significant differences between the 2 groups of tumors with respect to ER, PAX8, and WT1. HGSC showed more diffuse and intense staining for PAX8 (P=0.004 and 0.001, respectively) and WT1 (P=0.002 and 0.002, respectively); conversely, TCC showed more intense staining for ER (P=0.007). TCC and HGSC therefore show subtle differences in their immunohistochemical profiles which might reflect underlying (epi)genetic differences. Further studies using proteomic analysis will focus on the identification of differentially expressed proteins that might serve as markers of TCC-like differentiation, which could help explain biologic differences between TCC and HGSC and might identify other cases of HGSC with a better prognosis.

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses versus lenalidomide/dexamethasone. Trial Registration: clinicaltrials.gov identifier: 02076009.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

BackgroundWe compared the simplified Women's Health Initiative (sWHI) and the standard Cardiovascular Health Study (CHS) frailty phenotypes in predicting falls, hip fracture, and death in older women.MethodsParticipants are from the WHI Clinical Trial. CHS frailty criteria included weight loss, exhaustion, weakness, slowness, and low physical activity. The sWHI frailty score used two items from the RAND-36 physical function and vitality subscales, one item from the WHI physical activity scale plus the CHS weight loss criteria. Specifically, level of physical function was the capacity to walk one block and scored as severe (2-points), moderate (1-point), or no limitation (0). Vitality was based on feeling tired most or all of the time (1-point) versus less often (0). Low physical activity was walking outside less than twice a week (1-point) versus more often (0). A total score of 3 resulted in a frailty classification, a score of 1 or 2 defined pre-frailty, and 0 indicated nonfrailty. Outcomes were modeled using Cox regression and Harrell C-statistics were used for comparisons.ResultsApproximately 5% of the participants were frail based on the CHS or sWHI phenotype. The sWHI frailty phenotype was associated with higher rates of mortality (hazard ratio [HR] = 2.36, p ≤ .001) and falls (HR = 1.45, p = .005). Comparable HRs in CHS-phenotype were 1.97 (p < .001) and 1.36 (p = .03), respectively. Neither phenotype predicted hip fracture. Harrell C-statistics revealed nonsignificant differences in HRs between the CHS and sWHI frailty phenotypes.ConclusionThe sWHI phenotype, which is self-reported and brief, might be practical in settings with limited resources.

ObjectivesTo compare the ability of the commonly used Women's Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older.DesignLongitudinal cohort study.SettingWHI Clinical Trial.ParticipantsParticipants with data for WHI and CHS frailty phenotypes (N = 3,558).MeasurementsFrailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness (RAND-36 physical function scale score 78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments.ResultsApproximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio (HR) = 1.48, P = .003), hip fracture (HR = 1.87, P = .04), and death (HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 (P = .04), 1.08 (P = .83), and 1.91 (P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models (P > .50 for all).ConclusionThe WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs.

Many animal species communicate using chemical signals. In Drosophila, cuticular hydrocarbons (CHCs) are involved in species and sexual identification, and have long been thought to act as stimulatory pheromones as well. However, a previous study reported that D. melanogaster males were more attracted to females that were lacking CHCs. This surprising result is consistent with several evolutionary hypotheses but is at odds with other work demonstrating that female CHCs are attractive to males. Here, we investigated natural variation in male preferences for female pheromones using transgenic flies that cannot produce CHCs. By perfuming females with CHCs and performing mate choice tests, we found that some male genotypes prefer females with pheromones, some have no apparent preference, and at least one male genotype prefers females without pheromones. This variation provides an excellent opportunity to further investigate the mechanistic causes and evolutionary implications of divergent pheromone preferences in D. melanogaster males.

ObjectivesTo identify potentially modifiable factors associated with overall and poor-quality-of-life (QoL) survival in physically frail older women.DesignProspective study with 7 years of follow-up to examine mortality and, in survivors with a QoL measurement within the next 3 years, to examine poor- versus good-QoL patterns of survival.SettingWomen's Health Initiative Observational Study (WHI OS).ParticipantsFrail older women (N = 11,070; average age 72.6, range 65-82).MeasurementsFrailty was defined using the modified Fried criteria. Study outcomes were overall survival and global QoL. Risk factors were measured at the first follow-up clinic visit for WHI OS participants between 1997 and 2001.ResultsOf 11,070 frail women, 1,487 (13%) died. After 2,677 survivors with poor or unknown QoL were excluded at study baseline, 3,153 (46%) reported good QoL, and 1,263 (18%) reported poor QoL at the end of study follow-up; QoL measures for 2,490 (38%) were unavailable. Older age, history of cardiovascular disease, diabetes mellitus, poor self-rated health, body mass index less than 25.0 kg/m(2) , waist circumference greater than 88 cm, systolic blood pressure greater than 140 mmHg, high number and severity of somatic symptoms, smoking, and low education were associated with greater likelihood of poor-QoL survival. Cumulative baseline risk scores demonstrated an approximately linear increase in probability of poor-QoL survival with an increase in risk factors. The probability of poor-QoL survival was 0.19 (95% confidence interval (CI) = 0.15-0.22) in those with zero to two risk factors and 0.40 (95% CI = 0.35-0.44) in those with six or more risk factors.ConclusionSeveral potentially important risk factors for aging well that can be monitored in clinical and research settings, some of which are modifiable, were identified in a large group of frail old women.

BackgroundAs the proportion of the population aged 80 and over accelerates, so does the value of understanding the processes of aging well. The purposes of this article are to: (a) review contemporary theoretical and conceptual perspectives on aging well, (b) describe indicators of aging well that reflect key concepts and perspectives as assessed in the Women's Health Initiative (WHI) and (c) characterize the status of aging among women aged 80 and older using data obtained from WHI participants at the WHI Extension 2 follow-up.MethodsData from the Lifestyle Questionnaire, which was administered from 2011 to 2012 during the WHI Follow-up Study (Extension 2), were analyzed to provide a profile of the WHI cohort with respect to aging well.ResultsData revealed substantial diversity in the cohort with respect to the various measures of aging well. Although many reported physical functioning levels consistent with disability, most rated their health as good or better. Most reported moderately high levels of resilience, self-control, and self-mastery but lower levels of environmental mastery. Finally, the cohort reported high levels of optimal aging as reflected by their high levels of emotional well-being and moderately high levels of life satisfaction and social support, but more modest levels of personal growth and purpose in life.ConclusionsThe wide range of some dimensions of aging well suggest that further examination of predictors of positive coping and resilience in the face of aging-related disability could identify opportunities to support and facilitate aging well among U.S. women.

BackgroundMost research has focused on definitions and predictors of successful aging. However, racial/ethnic minorities are often under represented in this research. Given that the U.S. population is aging and becoming more racially diverse, we examined correlates of "successful aging," as defined by physical functioning and overall quality of life (QOL), among racial/ethnic minority women aged 80 years and older in the Women's Health Initiative.MethodsParticipants included 1,924 racial/ethnic minority women (African Americans, Asian/Pacific Islanders, Hispanic/Latinos, and American Indian/Alaskan Natives) 80 years of age and older who are enrolled in the Women's Health Initiative and have physical functioning data after turning 80 years of age. Analysis of covariance was used to examine between and within group differences in physical functioning and selfrated overall QOL for African Americans, Asian/Pacific Islanders, and Hispanic/Latinos.ResultsWe found no significant differences in physical functioning between racial/ethnic minority groups in adjusted analyses. However, overall QOL was significantly different between racial/ethnic minority groups. Age, recreational physical activity, and overall selfrated health were independent correlates of physical functioning across racial/ethnic minority groups, whereas overall selfrated health was the only consistent correlate of overall QOL across the minority groups for the within minority group comparisons.ConclusionsBetween racial/ethnic minority group differences in physical functioning are largely explained by demographic, psychosocial, behavioral, and health-related variables. We found statistically significant differences in selfrated overall QOL between racial/ethnic minority groups.

ObjectivesTo evaluate the association between currently recommended guidelines and commonly used clinical criteria for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) and all-cause mortality in frail older women.DesignLongitudinal prospective cohort study.SettingWomen's Health Initiative (WHI)-Observational Study.ParticipantsA sample of women aged 65-84 with complete data to characterize frailty in the third year of WHI follow-up (N = 11,070).MeasurementsFrailty phenotype was determined using the modified Fried criteria. Information on anthropometric measures (BMI, WC, WHR) was collected in clinical examinations. Cox proportional hazards models were used to estimate the effect of BMI, WC, and WHR on mortality adjusted for demographic characteristics and health behaviors.ResultsOver a mean follow-up of 11.5 years, there were 2,911 (26%) deaths in the sample. Women with a BMI from 25.0 to 29.9 kg/m(2) (hazard rate ratio (HR) = 0.80, 95% confidence interval (CI) = 0.73-0.88) and those with a BMI from 30.0 to 34.9 kg/m(2) (HR = 0.79, 95% CI = 0.71-0.88) had lower mortality than those with a BMI from 18.5 to 24.9 kg/m(2) . Women with a WHR greater than 0.8 had higher mortality (HR = 1.16, 95% CI = 1.07-1.26) than those with a WHR of 0.8 or less. No difference in mortality was observed according to WC. Stratifying according to chronic morbidity or smoking status or excluding women with early death and unintentional weight loss did not substantially change these findings.ConclusionIn frail, older women, having a BMI between 25.0 and 34.9 kg/m(2) or a WHR of 0.8 or less was associated with lower mortality. Currently recommended healthy BMI guidelines should be reevaluated for frail older women.

Purpose of the studyTrajectories of physical activity (PA) and sedentary time (ST) after military separation are likely important determinants of women's health outcomes later in life, because low PA and high ST are known contributors to premature mortality risk. Our objective was to compare longitudinal trajectories of recreational PA and ST between Veteran and non-Veteran postmenopausal women from the Women's Health Initiative (WHI).Design and methodsWomen Veteran (n = 3,719) and non-Veteran (n = 141,800) WHI participants were included. Self-reported participation in recreational PA, converted to metabolic equivalent (MET)-hours/week, was prospectively assessed over 8 years. Self-reported ST, defined as hours/day sitting or lying down, was collected at baseline and at Years 3 and 6. Generalized estimating equations were used to compare trajectories of PA and ST between Veterans and non-Veterans, adjusted for demographics and lifestyle behaviors.ResultsVeterans had higher baseline PA than non-Veterans (13.2 vs 12.5 MET-hours/week, p = .03). PA declined for both groups, with a steeper decline among Veterans (change/visit year -0.19 vs -0.02 MET-hours/week; interaction p < .001). At baseline, Veterans and non-Veterans had similar levels of ST (107.2 vs 105.9 hours/week, p = 0.42). Over time, ST remained stable among Veterans but declined slightly among non-Veterans (change/visit year -0.19 vs -0.49 hours/week; interaction p = .01).ImplicationsThe less favorable longitudinal trajectories of PA and ST we observed for women Veterans may contribute to worse health among these individuals later in life. Understanding barriers to enhancing PA and reducing ST in women Veterans could lead to more effective approaches to intervening on these health behaviors.

Purpose of the studyA comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI).Design and methodsWe studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods.ResultsCompared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke).ImplicationsVeteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve.

Although re-sequencing of gene panels and mRNA expression profiling are now firmly established in clinical laboratories, in-depth proteome analysis has remained a niche technology, better suited for studying model systems rather than challenging materials such as clinical trial samples. To address this limitation, we have developed a novel and optimized platform called SP3-Clinical Tissue Proteomics (SP3-CTP) for in-depth proteome profiling of practical quantities of tumour tissues, including formalin fixed and paraffin embedded (FFPE). Using single 10 μm scrolls of clinical tumour blocks, we performed in-depth quantitative analyses of individual sections from ovarian tumours covering the high-grade serous, clear cell, and endometrioid histotypes. This examination enabled the generation of a novel high-resolution proteome map of ovarian cancer histotypes from clinical tissues. Comparison of the obtained proteome data with large-scale genome and transcriptome analyses validated the observed proteome biology for previously validated hallmarks of this disease, and also identified novel protein features. A tissue microarray analysis validated cystathionine gamma-lyase (CTH) as a novel clear cell carcinoma feature with potential clinical relevance. In addition to providing a milestone in the understanding of ovarian cancer biology, these results show that in-depth proteomic analysis of clinically annotated FFPE materials can be effectively used as a biomarker discovery tool and perhaps ultimately as a diagnostic approach.

We examined whether dispositional optimism relates to change in global quality of life (QOL) as a function of either chronological age or years to impending death. We used a sample of 2,096 deceased postmenopausal women from the Women's Health Initiative clinical trials who were enrolled in the 2005-2010 Extension Study and for whom at least 1 global QOL and optimism measure were analyzed. Growth curve models were examined. Competing models were contrasted using model fit criteria. On average, levels of global QOL decreased with both higher age and closer proximity to death (e.g., M(score) = 7.7 eight years prior to death vs. M(score) = 6.1 one year prior to death). A decline in global QOL was better modeled as a function of distance to death (DtD) than as a function of chronological age (Bayesian information criterion [BIC](DtD) = 22,964.8 vs. BIC(age) = 23,322.6). Optimism was a significant correlate of both linear (estimate(DtD) = -0.01, SE(DtD) = 0.005; ρ = 0.004) and quadratic (estimate(DtD) = -0.006, SE(DtD) = 0.002; ρ = 0.004) terminal decline in global QOL so that death-related decline in global QOL was steeper among those with a high level of optimism than those with a low level of optimism. We found that dispositional optimism helps to maintain positive psychological perspective in the face of age-related decline. Optimists maintain higher QOL compared with pessimists when death-related trajectories were considered; however, the gap between those with high optimism and those with low optimism progressively attenuated with closer proximity to death, to the point that is became nonsignificant at the time of death.

Backgroundthe factors that moderate decline in physical functioning as death approaches are understudied. This study aimed to assess death-related decline in global quality of life (QoL) and physical functioning and to test whether baseline QoL moderates terminal decline in physical functioning.Methodsfour thousand six hundred and fifty-one decedents from the Women's Health Initiative Study (WHI) rated QoL and physical functioning each year throughout 5 years of follow-up.Resultsboth QoL and physical functioning showed a steeper decline as a function of years to death than as a function of chronological age. Moreover, decedents with higher QoL at baseline showed a less steep decline in physical functioning as death approached than those with lower QoL at baseline.Conclusionalthough QoL strongly decreases across the terminal years, its beneficial influence on physical functioning is evident till the very end of life.

BackgroundAspects of eudaimonic well-being, such as personal growth (PG) and purpose in life (PL), have been highlighted as important to older adults' health. We investigated the relationship of PG and PL with patterns of survival to the age of 85 years and older.MethodsThe sample included 8,880 women from the Women's Health Initiative cohort who reached 85 years of age by December 1, 2013, and for whom data on the PG and PL constructs were available. Women were classified into mutually exclusive outcomes: Healthy, Prevalent, Incident, Disabled, and Deceased. PG and PL were each assessed using a modified seven-item measure derived from the Psychological Well-Being scale.ResultsWomen were most commonly classified as Healthy (38.2%, n = 3,395), followed by Incident (24.4%, n = 2,163), Disabled (19.0%, n = 1,685), Prevalent (14.3%, 1,273), and Deceased (4.1%, n = 364). Women with low PL and PG levels were more likely to have prevalent mobility disability and disease or incident death before the age of 85 years. Specifically, those who reported low levels of PG and PL had a 2.1- and 3.6-fold higher risk, respectively, of death.ConclusionsThese findings indicate that even among the oldest old, experience of purposeful life engagement and continuing PG may contribute to better health outcomes.

Advancements in sport technology have made quantifying match-play external load (e.g., total distance, sprint distance, number of sprints) a popular option for athletics personnel. These variables of volume and intensity are useful for both objectively monitoring training in field-based sports and for designing training programs. As physical abilities differ across playing levels, match-play demands likely also differ. This narrative review compiles and compares the match-play external load data for women’s soccer at the professional and collegiate levels. Databases were searched through July 2022, yielding 13 primary articles that assessed the match-play demands of women’s soccer (3 professional, 8 Division I, 1 Division II, and 1 Division III). The results indicate that the average total distance covered were similar between the professional, Division I and Division III levels, but the variability was greater among Division III compared to professional and Division I players. Data for Division II are scarce, but the total distance covered appears to be less than for professional, Division I and Division III. There was also large variability for sprint distance and number of sprints across data at all playing levels. Considering the lack of studies of Division II and Division III players, more research is necessary to determine how playing level may affect external load profiles, as isolated studies likely only reflect data from isolated teams.

BackgroundThe purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics.MethodsWomen age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories.ResultsA five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories.ConclusionAging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.

Despite the variety of available analytic methods, longitudinal research in nursing has been dominated by use of a variable-centered analytic approach. The purpose of this article is to present the utility of person-centered methodology using a large cohort of American women 65 and older enrolled in the Women's Health Initiative Clinical Trial (N = 19,891). Four distinct trajectories of energy/fatigue scores were identified. Levels of fatigue were closely linked to age, socio-demographic factors, comorbidities, health behaviors, and poor sleep quality. These findings were consistent regardless of the methodological framework. Finally, we demonstrated that energy/fatigue levels predicted future hospitalization in non-disabled elderly. Person-centered methods provide unique opportunities to explore and statistically model the effects of longitudinal heterogeneity within a population.

ObjectivesTo examine associations between angiotensin-converting enzyme (ACE) inhibitor and statin medications and baseline and mean annual change in physical performance measures and muscle strength in older women.DesignProspective cohort study.ParticipantsParticipants from the Women's Health Initiative Clinical Trials aged 65 to 79 at baseline who had physical performance measures, self-report of health insurance, and no prior history of stroke or congestive heart failure were included (N = 5,777). Women were recruited between 1993 and 1998.MeasurementsMedication use was ascertained through a baseline inventory. Physical performance measures (timed 6-m walk, repeated chair stands in 15 seconds) and grip strength were assessed at baseline and follow-up Years 1, 3, and 6. Multivariable-adjusted linear repeated-measures models were adjusted for demographic and health characteristics.ResultsACE inhibitor use was associated with lower mean grip strength at baseline (22.40 kg, 95% confidence interval (CI) = 21.89-22.91 vs 23.18 kg, 95% CI 23.02-23.34; P = .005) and greater mean annual change in number of chair stands (-0.182, 95% CI -0.217 to -0.147 vs -0.145, 95% CI -0.156 to -0.133; P = .05) than nonuse. Statin use was not significantly associated with baseline measures or mean annual change for any outcome. A subgroup analysis suggested that statin use was associated with less mean annual change in chair stands (P = .006) in the oldest women.ConclusionThese results do not support an association between statin or ACE inhibitor use and slower decline in physical performance or muscle strength and thus do not support the use of these medications for preserving functional status in older adults.

BackgroundAtrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.Methods and resultsThe Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.ConclusionsIncident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.Clinical trial registration informationClinicalTrials.gov; Identifier: NCT00000611.

BackgroundTo develop a positive aging phenotype, we undertook analyses to describe multiple dimensions of positive aging and their relationships to one another in women 65 years of age and older and evaluate the performance of individual indicators and composite factors of this phenotype as predictors of time to death, years of healthy living, and years of independent living.MethodsData from Women's Health Initiative clinical trial and observational study participants ages 65 years and older at baseline, including follow-up observations up to 8 years later, were analyzed using descriptive statistics and principal components analysis to identify the factor structure of a positive aging phenotype. The factors were used to predict time to death, years of healthy living (without hospitalization or diagnosis of a serious health condition), and years of independent living (without nursing home admission or use of special services).ResultsWe identified a multidimensional phenotype of positive aging that included two factors: Physical-Social Functioning and Emotional Functioning. Both factors were predictive of each of the outcomes, but Physical-Social Functioning was the strongest predictor. Each standard deviation of increase in Physical-Social Functioning was accompanied by a 23.7% reduction in mortality risk, a 19.4% reduction in risk of major health conditions or hospitalizations, and a 26.3% reduction in risk of dependent living.ConclusionsPhysical-Social Functioning and Emotional Functioning constitute important components of a positive aging phenotype. Physical-Social Functioning was the strongest predictor of outcomes related to positive aging, including years of healthy living, years of independent living, and time to mortality.

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.

ObjectivesTo investigate whether midlife and older women who reported prior-year physical abuse, verbal abuse, or both abuse types had higher mortality risk than peers who did not report prior-year abuse.DesignRetrospective analysis.SettingCommunity.ParticipantsOne hundred sixty-thousand six hundred seventy-six community-dwelling women ages 50 to 79 at baseline enrolled in one of two major Women's Health Initiative (WHI) study components who responded to baseline abuse questions. Observational study enrollment was N=93,676 (1994-1998; 90 months average follow-up). Clinical trial enrollment was N=68,132 (1993-1998; 96 months average follow-up).MeasurementsTotal mortality was measured from 1993 to 2005 using all available data sources. Blinded physician adjudicators measured cause-specific mortality. Ninety-six percent of death records were adjudicated.ResultsPrior-year self-reported abuse prevalence was 11.3%. Women who reported physical abuse had the highest age-adjusted mortality rate, followed by women who reported both abuse types. Abuse independently predicted mortality risk after controlling for age, education, ethnicity, and WHI component. High mortality risk remained for physically abused women (hazard ratio (HR)=1.54, 95% confidence interval (CI)=1.09-2.18) after adjusting for demographic and health-related factors. Further adjustment for psychosocial variables diminished this association (HR=1.40, 95% CI=0.93-2.11), but high risk remained.ConclusionCommunity-dwelling middle-aged and older women who reported prior-year physical, verbal, or both types of abuse had significantly higher adjusted mortality risk than women who did not report abuse. These findings highlight the need for longitudinal research into prevention of abuse in later life and accompanying excess mortality and emphasize the importance of abuse prevention in later life.

BackgroundThe immune and blood coagulation systems have been implicated in the pathophysiology of the geriatric syndrome of frailty, but limited prospective data examining the relationship of clotting/inflammation biomarkers to risk of incident frailty exist.MethodsThis prospective analysis was derived from a nested case-control study within the Women's Health Initiative. Among women 65 to 79 years free of frailty at enrollment, we randomly selected 900 incident cases from those developing frailty within 3 years; 900 non-frail controls were individually matched on age, ethnicity, and blood collection date. Biomarkers assessed for risk of incident frailty included fibrinogen, factor VIII, D-dimer, C-reactive protein, interleukin-6, and tissue plasminogen activator (t-PA).ResultsWhen examined by quartiles in multivariable adjusted models, higher D-dimer and t-PA levels were each associated with increased risk of frailty (P trend = .04). Relative to the lowest quartile, the odds ratios for frailty compared with the upper quartile were 1.52 (95% confidence interval, 1.05-2.22) for t-PA and 1.57 (95% confidence interval, 1.11-2.22) for D-dimer. For women having high t-PA and high D-dimer compared with women having lower levels of both biomarkers, the odds of frailty was 2.20 (1.29-3.75). There was little evidence for association between coagulation factor VIII, fibrinogen, C-reactive protein, or interleukin-6 levels and incident frailty.ConclusionThis prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.

ObjectivesTo examine the associations between current use, duration, and potency of angiotensin-converting enzyme (ACE) inhibitors and incident frailty in women aged 65 and older who were not frail at baseline.DesignData were from the Women's Health Initiative Observational Study (WHI-OS), a prospective study conducted at 40 U.S. clinical centers.ParticipantsWomen aged 65 to 79 at baseline who were not frail (N=27,378).MeasurementsCurrent ACE inhibitor use was ascertained through direct inspection of medicine containers at baseline. Components of frailty were self-reported low physical function or impaired walking, exhaustion, low physical activity, and unintended weight. Frailty was ascertained through self-reported and physical measurements data at baseline and 3-year clinic contacts.ResultsBy the 3-year follow-up, 3,950 (14.4%) women had developed frailty. Current ACE inhibitor use had no association with incident frailty (multivariate adjusted odds ratio=0.96, 95% confidence interval=0.82-1.13). Duration and potency of ACE inhibitor use were also not significantly associated with incident frailty. A similar pattern of results was observed when incident cardiovascular disease events were studied as a separate outcome or when the sample was restricted to subjects with hypertension.ConclusionOverall, incidence of frailty was similar in current ACE inhibitor users and nonusers.

BackgroundInflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older.MethodsThe authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline (n = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty.ResultsAmong the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend =.02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events.ConclusionsOverall, incidence of frailty was similar in current statin users and nonusers.

ObjectivesTo define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability.DesignProspective study, the Women's Health Initiative Observational Study.SettingForty U.S. clinical centers.ParticipantsForty thousand six hundred fifty-seven women aged 65 to 79 at baseline.MeasurementsComponents of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up.ResultsBaseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions.ConclusionThese results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.

Abstract: This study investigated how dissatisfaction with various aspects of the body is associated with overall body dissatisfaction among female adolescents in Western and Asian cultures. Data used in the study were obtained from 58 Malaysian Malays, 95 Malaysian Chinese, 242 Chinese from China, and 81 non-Asian Australians aged 12–19 years (M =15.72, SD =1.72) who were recruited from high schools. Participants completed a questionnaire assessing dissatisfaction with their body overall, and dissatisfaction with varying aspects of their body. Malaysian Chinese were the most dissatisfied with their bodies. After controlling for body mass index (BMI), age and dissatisfaction with weight/shape, upper, middle and lower body, and muscles, dissatisfaction with the face was positively correlated with overall body dissatisfaction among Malaysian Malays and Australians. These findings demonstrate the importance of using assessment measures that address all possible areas of body focus as well as being tailored to the relevant culture. [Copyright &y& Elsevier]