E-PROOF: E-intervention for protein intake and resistance training to optimize function: A study protocol.

BACKGROUND: Accounting for more than 60% of cancer survivors, older (≥65 years) cancer survivors have a 2- to 5-fold risk of physical function impairment, compared to cancer-free peers. One strategy to improve physical function is dietary and resistance training interventions, which improve muscle strength and mass by stimulating muscle protein synthesis. The E-PROOF (E-intervention for Protein Intake and Resistance Training to Optimize Function) study will examine the feasibility, acceptability, and preliminary efficacy of a 12-week randomized controlled trial of an online, tailored nutritional and resistance training education and counseling intervention to improve physical function and associated health outcomes (muscle strength, health-related quality of life (HRQoL), self-efficacy, and weight management). METHODS: In this study, 70 older cancer survivors will be randomized to one of two groups: experimental (receiving remote behavioral counseling and evidence-based education and resources), and control (general survivorship education). We will examine the intervention effects on physical function, muscle strength, HRQoL, self-efficacy, weight, and waist circumference during a 12-week period between the experimental and control groups. Three months following the end of the intervention, we will conduct a follow-up assessment to measure physical function, muscle strength, and HRQoL. SIGNIFICANCE AND IMPACT: This study is the first synchronous, online protein-focused diet and resistance training intervention among older cancer survivors. This novel study advances science by promoting independent health behaviors among older cancer survivors to improve health outcomes, and provide foundational knowledge to further address this growing problem on a wider scale through online platforms.

Low physical function Post-Cancer diagnosis is associated with higher mortality risk in postmenopausal women.

BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond that expected through aging alone due to cancer and its treatments. The aim of this study is to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. METHODS: This prospective cohort study included 8,068 postmenopausal women enrolled in the Women's Health Initiative (WHI) who were diagnosed with cancer and had physical function assessed within 1-year of cancer diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the RAND 36-Item Health Survey. Cause of death was determined by medical record review with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. RESULTS: Over a median follow-up of 7.7 years from cancer diagnosis 3,316 (41.1%) women died. Our results showed that for every 10% decline in the physical function score after cancer diagnosis, all-cause mortality and cancer-specific mortality were significantly reduced by 12% (HR, 0.88; 95% CI, 0.87 to 0.89) and (HR, 0.88; 95%CI, 0.86 to 0.91), respectively. Further categorical analyses showed a significant dose-response relationship between post-diagnosis physical function categories and mortality outcomes (trend test P < .001), where the median survival time for women in the lowest physical function quartile was 9.1 (8.6, 10.6) years compared to 18.4 (15.8, 22.0) years for women in the highest physical function quartile. CONCLUSION: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.

Longitudinal Associations Between Optimism and Objective Measures of Physical Functioning in Women.

Importance: Identifying factors contributing to sustained physical functioning is critical for the health and well-being of the aging population, especially as physical functioning may precede and predict subsequent health outcomes. Prior work suggests optimism may protect health, but less is known about the association between optimism and objective physical functioning measures as individuals age. Objective: To evaluate the longitudinal association between optimism and 3 physical functioning measures. Design, Setting, and Participants: This was a prospective cohort study using data from the Women's Health Initiative (WHI) with participants recruited from 1993 to 1998 and followed up over 6 years. Data analysis was conducted from January 2022 to July 2022. Participants included postmenopausal women older than 65 years recruited from 40 clinical centers in the US. Exposure: Optimism was assessed at baseline using the Life Orientation Test-Revised. Main Outcomes and Measures: Physical functioning was measured at 4 time points across 6 years by study staff evaluating performance in grip strength, timed walk, and chair stands. Results: The final analytic sample included 5930 women (mean [SD] age, 70 [4] years). Linear mixed-effects models controlling for demographics, depression, health status, and health behaviors showed that higher optimism was associated with higher grip strength (ß = 0.36; 95% CI, 0.21-0.50) and number of chair stands (ß = 0.05; 95% CI, 0.01-0.10) but not timed walk at baseline. Higher optimism was also associated with slower rates of decline in timed walk (ß = -0.09; 95% CI, -0.13 to -0.04) and number of chair stands (ß = 0.01; 95% CI, 0-0.03) but not grip strength over time. Cox proportional hazards models showed that higher optimism was associated with lower hazards of reaching clinically defined thresholds of impairment for all 3 outcomes over 6 years of follow-up. For example, in fully adjusted models, for a 1-SD increase in optimism, hazard ratios for reaching impairment thresholds were 0.86 (95% CI, 0.80-0.92) for grip strength, 0.94 (95% CI, 0.88-1.01) for timed walk, and 0.91 (95% CI, 0.85-0.98) for chair stands. Conclusion and Relevance: In this cohort study of postmenopausal women, at baseline, higher optimism was associated with higher grip strength and number of chair stands but not with the time it took to walk 6 m. Higher optimism at baseline was also associated with maintaining healthier functioning on 2 of the 3 performance measures over time, including less decline in walking speed and in number of chair stands women could perform over 6 years of follow-up. Given experimental studies suggesting that optimism is modifiable, it may be a promising target for interventions to slow age-related declines in physical functioning. Future work should explore associations of optimism with maintenance of physical functioning in diverse populations.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Factors associated with insomnia symptoms over three years among premenopausal women with breast cancer.

PURPOSE: We examined longitudinal trends and factors associated with insomnia over 3 years in a cohort of young breast cancer patients. METHODS: Women with stage I-III breast cancer at ≤ 45 years were recruited at five institutions from New York, Texas, and North Carolina, within 8 months of diagnosis (n = 836). Participants completed questionnaires every 6 months for 3 years. Linear mixed-effects models were used to examine insomnia over time, using the Women's Health Initiative Insomnia Rating Scale (WHIIRS). We evaluated the relations of insomnia with demographic (age, race, education, income, employment, marital status), clinical (cancer stage, histologic grade, chemotherapy, radiation, hormone therapy, surgery, tumor size, body mass index, hot flashes), and social/behavioral variables (smoking status, social support, physical activity, depressive symptoms). RESULTS: At baseline, 57% of participants met or exceeded the cut-off for clinical insomnia (WHIIRS score ≥ 9). Insomnia symptoms were most prevalent at baseline (p < 0.0001), but decreased significantly throughout follow-up (p < 0.001). However, 42% of participants still experienced insomnia symptoms 3 years after diagnosis. In multivariable models, older age (p = 0.02), hot flashes (p < 0.0001), and depressive symptoms (p < 0.0001) remained significantly associated with insomnia over time. CONCLUSIONS: Insomnia symptoms were most frequent closer to breast cancer diagnosis and treatment, but persisted for some women who were older and those reporting higher hot flashes and depressive symptoms. Survivorship care should include assessing insomnia symptoms, particularly during and immediately after primary treatment. Implementing early interventions for sleep problems may benefit young breast cancer survivors and improve their quality of life.

A descriptive study of policy and system-level interventions to address cancer survivorship issues across six United States health systems.

PURPOSE: To describe policy and system-level interventions with potential to improve cancer care at six sites. METHODS: In 2016, six institutions received foundation support to develop unique multi-component interventions aimed at improving cancer care for underserved populations. These organizations, located across the United States, participated in a cross-site evaluation to assess the overall initiative impact and to identify potentially promising policy and system-level solutions for dissemination and broader implementation. A health system and policy tracking tool was developed to collect data from each site and included a description of their efforts, strategies employed, and changes achieved (e.g., new policies, clinical protocols). Tracking tool data were analyzed using rapid qualitative analyses and a matrix approach. Semi-structured interviews were conducted with site leaders (N = 65) and were analyzed by thematic analysis. RESULTS: Sites reported 20 system and policy efforts, which resulted in improvements to electronic health records and telehealth strategies, changes to hospital/health system policies, and standardized clinical protocols/guidelines, among others. Efforts were aimed at: (1) coordinating care across multiple providers, supported by patient navigators; (2) expanding psychosocial and supportive care; (3) improving patient-provider communication; and (4) addressing barriers to accessing care. Interview analyses provided insights into successful strategies, challenges, and implications of the COVID-19 pandemic on cancer care. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Despite advances in diagnosis and treatment, cancer care remains inequitable. System-level improvements aimed at eliminating common barriers faced by underserved populations offer opportunities to improve the delivery of equitable, effective, and efficient care.

Association of Later-Life Weight Changes With Survival to Ages 90, 95, and 100: The Women's Health Initiative.

BACKGROUND: Associations of weight changes and intentionality of weight loss with longevity are not well described. METHODS: Using longitudinal data from the Women's Health Initiative (N = 54 437; 61-81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured at baseline, year 3, and year 10, and participants were classified as having weight loss (≥5% decrease from baseline), weight gain (≥5% increase from baseline), or stable weight (<5% change from baseline). Participants reported intentionality of weight loss at year 3. RESULTS: A total of 30 647 (56.3%) women survived to ≥90 years. After adjustment for relevant covariates, 3-year weight loss of ≥5% vs stable weight was associated with lower odds of survival to ages 90 (OR, 0.67; 95% CI, 0.64-0.71), 95 (OR, 0.65; 95% CI, 0.60-0.71), and 100 (OR, 0.62; 95% CI, 0.49-0.78). Compared to intentional weight loss, unintentional weight loss was more strongly associated with lower odds of survival to age 90 (OR, 0.83; 95% CI, 0.74-0.94 and OR, 0.49; 95% CI, 0.44-0.55, respectively). Three-year weight gain of ≥5% vs stable weight was not associated with survival to age 90, 95, or 100. The pattern of results was similar among normal weight, overweight, and obese women in body mass index (BMI)-stratified analyses. CONCLUSIONS: Weight loss of ≥5% vs stable weight was associated with lower odds of longevity, more strongly for unintentional weight loss than for intentional weight loss. Potential inaccuracy of self-reported intentionality of weight loss and residual confounding were limitations.

Reaching Populations to Address Disparities in Cancer Care Delivery: Results From a Six-Site Initiative.

BACKGROUND: Large segments of the US population do not receive quality cancer care due to pervasive and systemic inequities, which can increase morbidity and mortality. Multicomponent, multilevel interventions can address inequities and improve care, but only if they reach communities with suboptimal access. Intervention studies often underenroll individuals from historically excluded groups. METHODS: The Alliance to Advance Patient-Centered Cancer Care includes 6 grantees across the United States who implemented unique multicomponent, multilevel intervention programs with common goals of reducing disparities, increasing engagement, and improving the quality of care for targeted populations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework informed the evaluation efforts across sites. Each Alliance site identified their intended populations, which included underrepresented minorities (eg, Black and Latinx persons), individuals who prefer a language other than English, and rural residents. We evaluated the demographic characteristics of participants to determine program reach. RESULTS: Between 2018 and 2020, a total of 2,390 of 5,309 potentially eligible participants were enrolled across the 6 sites. The proportion of enrolled individuals with selected characteristics included 38% (n=908) Black adults, 24% (n=574) Latinx adults, 19% (n=454) preferring a language other than English, and 30% (n=717) rural residents. The proportion of those enrolled who were the intended population was commensurate to the proportion with desired characteristics in those identified as potentially eligible. CONCLUSIONS: The grantees met or exceeded enrollments from their intended populations who have been underserved by quality cancer care into patient-centered intervention programs. Intentional application of recruitment/engagement strategies is needed to reach individuals from historically underserved communities.

Bayesian semiparametric joint modeling of a count outcome and inconveniently timed longitudinal predictors.

The Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study is an excellent resource for studying the quality of life following breast cancer treatment. At study entry, women were asked about new symptoms that appeared following their initial cancer treatment. In this article, we were interested in using regression modeling to estimate associations of clinical and lifestyle factors at cancer diagnosis (independent variables) with the number of new symptoms (dependent variable). Although clinical and lifestyle data were collected longitudinally, few measurements were obtained at diagnosis or at a consistent timepoint prior to diagnosis, which complicates the analysis. Furthermore, parametric count models, such as the Poisson and negative binomial, do not fit the symptom data well. Thus, motivated by the issues encountered in LILAC, we propose two Bayesian joint models for longitudinal data and a count outcome. Our two models differ according to the assumption on the outcome distribution: one uses a negative binomial (NB) distribution and the other a nonparametric rounded mixture of Gaussians (RMG). The mean of each count distribution is dependent on imputed values of continuous, binary, and ordinal variables at a time point of interest (e.g. diagnosis). To facilitate imputation, longitudinal variables are modeled jointly using a linear mixed model for a latent underlying normal random variable, and a Dirichlet process prior is assigned to the random subject-specific effects to relax distribution assumptions. In simulation studies, the RMG joint model exhibited superior power and predictive accuracy over the NB model when the data were not NB. The RMG joint model also outperformed an RMG model containing predictors imputed using the last value carried forward, which generated estimates that were biased toward the null. We used our models to examine the relationship between sleep health at diagnosis and the number of new symptoms following breast cancer treatment in LILAC.

Resiliency Among Women's Health Initiative Women Aged 80 and Older by Race, Ethnicity, and Neighborhood Socioeconomic Status.

OBJECTIVES: A comprehensive examination of resilience by race, ethnicity, and neighborhood socioeconomic status (NSES) among women aged ≥80 is needed, given the aging of the U.S. population, increasing longevity, and growing racial and ethnic diversity. METHODS: Participants were women aged ≥80 enrolled in the Women's Health Initiative. Resilience was assessed with a modified version of the Brief Resilience Scale. Descriptive statistics and multiple linear regression examined the association of demographic, health, and psychosocial variables with resilience by race, ethnicity, and NSES. RESULTS: Participants (n = 29,367, median age = 84.3) were White (91.4%), Black (3.7%), Hispanic (1.9%), and Asian (1.7%) women. There were no significant differences by race and ethnicity on mean resiliency scores (p = .06). Significant differences by NSES were observed regarding mean resiliency scores between those with low NSES (3.94 ± 0.83, out of 5) and high NSES (4.00 ± 0.81). Older age, higher education, higher self-rated health, lower stress, and living alone were significant positive correlates of resilience in the sample. Social support was correlated with resilience among White, Black, and Asian women, but not for Hispanic women. Depression was a significant correlate of lower resilience, except among Asian women. Living alone, smoking, and spirituality were significantly associated with higher resilience among women with moderate NSES. DISCUSSION: Multiple factors were associated with resilience among women aged ≥80 in the Women's Health Initiative. Despite some differing correlates of resilience by race, ethnicity, and NSES, there were many similarities. These results may aid in the design of resilience interventions for the growing, increasingly diverse population of older women.

Feasibility of an embedded palliative care clinic model for patients with an advanced thoracic malignancy.

PURPOSE: Early palliative care (PC) with standard oncology care has demonstrated improved patient outcomes, but multiple care delivery models are utilized. This study prospectively evaluated the feasibility of an embedded PC clinic model and collected patient-reported outcomes (PROs) and caregiver needs. METHODS: In this observational study of embedded outpatient PC for patients with advanced thoracic malignancies treated at The Ohio State University Thoracic Oncology clinic, patients received same-day coordinated oncology and palliative care visits at one clinic location. PC encounters included comprehensive symptom assessment and management, advanced care planning, and goals of care discussion. Multiple study assessments were utilized. We describe the feasibility of evaluating PROs and caregiver needs in an embedded PC model. RESULTS: Forty patients and 28 caregivers were enrolled. PROs were collected at baseline and follow-up visits. Over a 12-month follow-up, 36 patients discontinued study participation due to hospice enrollment, death, study withdrawal, or COVID restrictions. At baseline, 32 patients (80%) rated distress as moderate-severe with clinically significant depression (44%) and anxiety (36%). Survey completion rates significantly decreased over time: 3 months (24 eligible, 66% completed), 6 months (17 eligible; 41% completed), 9 months (9 eligible; 44% completed), and 12 months (4 eligible; 50% completed). CONCLUSION: We found that an embedded PC clinic was feasible, although there were challenges encountered in longitudinal collection of PROs due to high study attrition. Ongoing assessment and expansion of this embedded PC model will continue to identify strengths and challenges to improve patient and caregiver outcomes.

Self-reported symptoms among cancer survivors in the Women's Health Initiative (WHI) Life and Longevity after Cancer (LILAC) cohort.

PURPOSE: Due to cancer survivors living longer and morbidity associated with cancer treatments, it is necessary to understand symptoms experienced by cancer survivors. This study will analyze the symptom burden among a large cohort of survivors across multiple cancer sites. METHODS: Data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study were used to examine the symptom burden of older cancer survivors. Poisson regression with robust standard errors was utilized to determine differences in symptoms by cancer site, treatment, and other covariates. RESULTS: The most frequently reported symptoms among cancer survivors were fatigue (15.8%) and feeling sad or depressed (14.1%). Multivariable analyses indicated that more symptoms were reported among survivors who were younger (p = 0.002), divorced or separated (p = 0.03), and had a combination of public and private insurance (p = 0.01). Survivors who received chemotherapy (p < 0.001), radiation (p = 0.01), or hormone therapy (p = 0.02) reported more symptoms than survivors who did not receive these treatments. Survivors diagnosed with cancer < 5 years ago reported fewer symptoms than longer-term survivors, particularly those diagnosed > 10 years ago (p = 0.02). CONCLUSIONS: Results indicate that common physical and psychological symptoms are reported across cancer types. Cancer survivors diagnosed with cancer 10 or more years ago reported more symptoms than those recently diagnosed. This suggests that symptoms may remain a problem for some survivors decades after their diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Future research should focus on implementing active surveillance of cancer survivors. Healthcare providers and those who care for cancer survivors should understand that the symptom burden associated with cancer may persist even decades following diagnosis.

Social Support, social ties, and cognitive function of women with breast cancer: findings from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study.

PURPOSE: This study examined associations between self-reported cognitive functioning and social support as well as social ties among women with breast cancer. METHODS: The study included 3351 women from the Women's Health Initiative Life and Longevity After Cancer cohort who were diagnosed with breast cancer stages I-III. Social support was assessed using a modified Medical Outcomes Study (MOS) Social Support Survey, and marital status was obtained from the baseline questionnaire. We also assessed social ties (e.g., number of friends, relatives, living children) and cognitive function (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-COG]) on the year-1-follow up questionnaire. Multivariable quantile regression was used to estimate the changes in median cognitive scores. Kruskal-Wallis tests were used to assess the association of cognitive function with social ties. RESULTS: The majority of participants were non-Hispanic White (93.3%), presently married (49%), with at least a 4-year college degree (53.2%), and had been diagnosed with localized breast cancer (79%). A 10-point higher social support score correlated to a 0.32 higher (better) median cognitive score (p < 0.001). Women who were presently married tended to have better cognition than women who were divorced/separated or widowed (p = 0.01). Significant associations were also present for having close relatives (p < 0.001) or friends (p < 0.001), with cognitive scores being higher in those with at least one close relative or friend compared to none. CONCLUSION: Women reporting higher social support and greater numbers of friends or relatives have higher cognitive functioning. Compared to divorced or separated women, married women were likely to have higher cognitive functioning. These findings suggest that social support assessments have the potential to help identify women at higher risk of cognitive decline.

The severity of individual menopausal symptoms, cardiovascular disease, and all-cause mortality in the Women's Health Initiative Observational Cohort.

OBJECTIVE: The aim of this study was to examine the association between common menopausal symptoms (MS) and long-term cardiovascular disease (CVD) and all-cause mortality. METHODS: In an observational cohort of 80,278 postmenopausal women with no known CVD at baseline from the Women's Health Initiative, we assessed individual MS severity (mild vs none; moderate/severe vs none) for night sweats, hot flashes, waking up several times at night, joint pain or stiffness, headaches or migraines, vaginal or genital dryness, heart racing or skipping beats, breast tenderness, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating. Outcomes included total CVD events (primary) and all-cause mortality (secondary). Associations between specific MS, their severity, and outcomes were assessed during a median of 8.2 years of follow-up. All results were multivariable adjusted, and individual associations were Bonferroni corrected to adjust for multiple comparisons. A machine learning approach (least absolute shrinkage and selection operator) was used to select the most parsimonious set of MS most predictive of CVD and all-cause mortality. RESULTS: The severity of night sweats, waking up several times at night, joint pain or stiffness, heart racing or skipping beats, dizziness, feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating were each significantly associated with total CVD. The largest hazard ratio (HR) for total CVD was found for moderate or severe heart racing or skipping beats (HR, 1.55; 95% confidence interval [CI], 1.29-1.86). The individual severities of heart racing or skipping beats, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating were associated with increased all-cause mortality. Moderate or severe dizziness had the largest HR (1.58; 95% CI, 1.24-2.01). Multiple symptom modeling via least absolute shrinkage and selection operator selected dizziness, heart racing, feeling tired, and joint pain as most predictive of CVD, whereas dizziness, tremors, and feeling tired were most predictive of all-cause mortality. CONCLUSION: Among postmenopausal women with no known CVD at baseline, the severity of specific individual MS was significantly associated with incident CVD and mortality. Consideration of severe MS may enhance sex-specific CVD risk predication in future cohorts, but caution should be applied as severe MS could also indicate other health conditions.

Patient-driven research: Initial results from a prospective health-related quality of life study performed at the request of patients living with hairy cell leukemia.

A diagnosis of leukemia can have a profound effect on patients' health-related quality of life (HRQoL), however this has not been measured prospectively in patients with hairy cell leukemia (HCL). At the request of patients living with HCL who had identified this gap in knowledge about the disease, we conducted a longitudinal study of HRQoL among patients enrolled in the HCL Patient Data Registry (PDR). From September 1, 2018 to September 1, 2020, 165 patients were enrolled in the study and completed the baseline survey. The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) was used to measure patients' HRQoL. Results show that newly diagnosed HCL patients reported the lowest HRQoL, followed by patients in relapse and those on "watch and wait." Factors associated with higher (better) FACT-Leu total scores in the multivariable analysis included older age, higher social support, and greater physical activity. These same factors were associated with lower levels of fatigue. In rare diseases where it is difficult to perform large prospective studies, patient/researcher collaborations are critical for the identification of studies that are of importance to patients and their families in order to maximize the benefits of the research and improve the lives of patients living with HCL.

Cumulative Endogenous Estrogen Exposure Is Associated With Postmenopausal Fracture Risk: The Women's Health Initiative Study.

We aimed to evaluate the relationship between cumulative endogenous estrogen exposure and fracture risk in 150,682 postmenopausal women (aged 50 to 79 years at baseline) who participated in the Women's Health Initiative. We hypothesized that characteristics indicating lower cumulative endogenous estrogen exposure would be associated with increased fracture risk. We determined ages at menarche and menopause as well as history of irregular menses from baseline questionnaires and calculated years of endogenous estrogen exposure from ages at menarche and menopause. Incident clinical fractures were self-reported over an average 16.7 years of follow-up. We used multivariable proportional hazards models to assess the associations between the estrogen-related variables and incidence of any clinical fracture. In fully adjusted models, those with the fewest years of endogenous estrogen exposure (<30) had an 11% higher risk of developing central body fractures and a 9% higher risk of lower extremity fractures than women with 36 to 40 years of endogenous estrogen exposure (the reference category). In contrast, women with the most years of endogenous estrogen exposure (more than 45 years) had a 9% lower risk of lower extremity fractures than the reference category. Women with irregular (not monthly) menstrual cycles were 7% to 8% more likely to experience lower extremity fractures than women with regular monthly cycles. Our findings support the hypothesis that characteristics signifying lower cumulative endogenous estrogen exposure are associated with higher fracture risk. © 2022 American Society for Bone and Mineral Research (ASBMR).

Psychotropic medication use and Parkinson's disease risk amongst older women.

OBJECTIVE: To examine associations of antidepressant, anxiolytic and hypnotic use amongst older women (≥65 years) with incident Parkinson's Disease (PD), using data from Women's Health Initiative linked to Medicare claims. METHODS: PD was defined using self-report, first diagnosis, medications and/or death certificates and psychotropic medications were ascertained at baseline and 3-year follow-up. Cox regression models were constructed to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI), controlling for socio-demographic, lifestyle and health characteristics, overall and amongst women diagnosed with depression, anxiety and/or sleep disorders (DASD). RESULTS: A total of 53,996 WHI participants (1,756 PD cases)-including 27,631 women diagnosed with DASD (1,137 PD cases)-were followed up for ~14 years. Use of hypnotics was not significantly associated with PD risk (aHR = 0.98, 95% CI: 0.82, 1.16), whereas PD risk was increased amongst users of antidepressants (aHR = 1.75, 95% CI: 1.56, 1.96) and anxiolytics (aHR = 1.48, 95% CI: 1.25, 1.73). Compared to non-users of psychotropic medications, those who used 1 type had ~50% higher PD risk, whereas those who used ≥2 types had ~150% higher PD risk. Women who experienced transitions in psychotropic medication use ('use to non-use' or 'non-use to use') between baseline and 3-year follow-up had higher PD risk than those who did not. We obtained similar results with propensity scoring and amongst DASD-diagnosed women. INTERPRETATION: The use of antidepressants, anxiolytics or multiple psychotropic medication types and transitions in psychotropic medication use was associated with increased PD risk, whereas the use of hypnotics was not associated with PD risk amongst older women.

Sleep and affective disorders in relation to Parkinson's disease risk among older women from the Women's Health Initiative.

OBJECTIVES: To evaluate sleep and affective (mood/anxiety) disorders as clinical predictors of incident Parkinson's disease (PD) among women ≥65 years of age. METHODS: We performed secondary analyses with available data from the Women's Health Initiative Clinical Trials and Observational Study linked to Medicare claims. Sleep, mood and anxiety disorders at baseline were defined using diagnostic codes. Incident PD was defined using self-reported PD, first PD diagnosis, use of PD medications, and/or deaths attributed to PD. Cox regression was applied to estimate hazard ratios (HR) with 95 % confidence intervals (CI), controlling for socio-demographic/lifestyle/health characteristics. Time-to-event was calculated from baseline (1993-1998) to year of PD event, loss to follow-up, death, or December 31, 2018, whichever came first. RESULTS: A total of 53,996 study-eligible WHI participants yielded 1756 (3.25 %) PD cases over ~14.39 (±6.18) years of follow-up. The relative risk for PD doubled among women with affective disorders (HR = 2.05, 95 % CI: 1.84, 2.27), mood disorders (HR = 2.18, 95 % CI: 1.97, 2.42) and anxiety disorders (HR = 1.97, 95 % CI: 1.75, 2.22). Sleep disorders alone (without affective) were not significantly associated with PD risk (HR = 0.85, 95 % CI: 0.69, 1.04), whereas affective disorders alone (without sleep) (HR = 1.93, 95 % CI: 1.72, 2.17) or in combination with sleep disorders (HR = 2.18, 95 % CI: 1.85, 2.56) were associated with twice the PD risk relative to no sleep/affective disorders. LIMITATIONS: Observational design; Selection bias; Information bias; Generalizability. CONCLUSIONS: Among older women, joint sleep/affective disorders and affective disorders alone are strong clinical predictors of incident PD over 14 years.

Diet and Health-related Quality of Life Among Men on Active Surveillance for Early-stage Prostate Cancer: The Men's Eating and Living Study (Cancer and Leukemia Group 70807 [Alliance]).

BACKGROUND: Health-related quality of life (HRQoL) among patients with localized prostate cancer (PC) on active surveillance (AS) and whether it may be improved through lifestyle-focused interventions remain underdefined. OBJECTIVE: To assess longitudinal changes in HRQoL in patients who received and those who did not receive a behavioral intervention that increased vegetable intake. DESIGN, SETTING, AND PARTICIPANTS: A secondary analysis of participants in the Men's Eating and Living (MEAL) study (Cancer and Leukemia Group 70807 [Alliance]), a randomized trial of vegetable consumption in patients on AS, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient-reported outcomes (PROs) included the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the Expanded Prostate Cancer Index Composite 26 (EPIC-26), and the Functional Assessment of Cancer Therapy Scale-Prostate (FACT-P). Areas under the curves (AUCs) were used to summarize serial HRQoL. RESULTS AND LIMITATIONS: PROs were completed in 87% (n = 387) of the intention-to-collect population. Baseline characteristics of patients completing HRQoL measures did not differ significantly from the entire study population or between groups. Baseline scores were high for all PROs and remained stable over 24 mo, with no significant differences from baseline at any time point. In adjusted analyses, there were no significant differences in summary AUC measures comparing control with intervention for the total MAX-PC score (p = 0.173); EPIC-26 domains of urinary incontinence (p = 0.210), urinary obstruction (p = 0.062), bowel health (p = 0.607), sexual health (p = 0.398), and vitality (p = 0.363); and total FACT-P scores (p = 0.471). CONCLUSIONS: Among men with localized PC on AS enrolled in a randomized trial, HRQoL was high across multiple domains at baseline, remained high during follow-up, and did not change in response to a behavioral intervention that increased vegetable intake. PATIENT SUMMARY: Patients with localized prostate cancer enrolled on active surveillance experience minimal cancer-associated anxiety, suffer low levels of cancer-associated symptoms, and perceive high physical and emotional well-being.