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Using 1998-2022 Women's Health Initiative (WHI) data, our study provides contemporary fracture data by race and ethnicity, specifically focusing on Hispanic and Asian women. Fractures of interest included any clinical, hip, and major osteoporotic fractures (MOFs). We utilized the updated race and ethnicity information collected in 2003, which included seven Asian and five Hispanic origin groups. We computed crude and age-standardized fracture incidence rates per 10 000 woman-years across race and ethnic categories and by Asian and Hispanic origin. We used Cox proportional hazards model, adjusting for age and WHI clinical trial arm, to evaluate the risk of fracture (1) by race compared to White women, (2) Asian origin compared to White women, (3) Hispanic compared to non-Hispanic women, and (4) Asian and Hispanic origins compared the most prevalent origin group. Over a median (interquartile range) follow-up of 19.4 (9.2-24.2) years, 44.2% of the 160 824 women experienced any clinical fracture, including 36 278 MOFs and 8962 hip fractures. Compared to White women, Black, Pacific Islander, Asian, and multiracial women had significantly lower risk of any clinical and MOFs, while only Black and Asian women had significantly lower hip fracture risk. Within Asian women, Filipina women had 24% lower risk of any clinical fracture compared to Japanese women. Hispanic women had significantly lower risk of any clinical, hip, and MOF fractures compared to non-Hispanic women, with no differences in fracture risk observed within Hispanic origin groups. In this diverse sample of postmenopausal women, we confirmed racial and ethnic differences in fracture rates and risk, with novel findings among within Asian and Hispanic subgroups. These data can aid in future longitudinal studies evaluate contributors to racial and ethnic differences in fractures.
We provided contemporary fracture rates by race and ethnicity, specifically focusing on multiple Hispanic and Asian subgroups, using 1998-2022 data from the Women's Health Initiative. Over a median follow-up of 19.4 years, 43.4% of the 154 948 women experienced any clinical fracture, including 8679 hip and 34 546 major osteoporotic fractures. Compared to White women, Black, Pacific Islander, Asian, and multiracial women had significantly lower risk of any clinical and major osteoporotic fractures (MOFs); while only Black and Asian women had significantly lower hip fracture risk when compared to White women. Within Asian women, Filipina women had 24% lower risk of any clinical fracture compared to Japanese women. Hispanic women had significantly lower risk of any clinical, hip, and MOF fractures compared to non-Hispanic women, with no differences in fracture risk observed within Hispanic women. In this diverse sample of postmenopausal women, we confirmed racial and ethnic differences in fracture rates and risk, with novel findings among Pacific Islander women and within Asian and Hispanic subgroups.
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Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research.
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BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.
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Doenças Cardiovasculares , Doenças Inflamatórias Intestinais , Pós-Menopausa , Humanos , Feminino , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Idoso , Modelos de Riscos Proporcionais , AVC Isquêmico/epidemiologia , AVC Isquêmico/etiologia , Fatores de Risco , Estados Unidos/epidemiologia , Fatores de Risco de Doenças Cardíacas , Doença das Coronárias/epidemiologiaRESUMO
Long-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older. INTRODUCTION: Physical functioning trajectory following lower arm or wrist fracture is not well understood. PURPOSE: This study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age. METHODS: We performed a nested case-control study of prospective data from the Women's Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining. RESULTS: Mean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19-1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29-1.88); age 70-79 years aOR 1.29 (95% CI 1.09-1.52); age < 70 years aOR 1.15 (95% CI 0.86-1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level. CONCLUSIONS: Women with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experience declines in physical functioning than women without such fractures, independent of baseline physical functioning level.
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Fraturas por Osteoporose , Traumatismos do Punho , Humanos , Feminino , Idoso , Traumatismos do Punho/fisiopatologia , Traumatismos do Punho/epidemiologia , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/reabilitação , Pessoa de Meia-Idade , Estudos Prospectivos , Pós-Menopausa/fisiologia , Fatores Etários , Fraturas do Rádio/fisiopatologia , Fraturas do Rádio/epidemiologia , Estados Unidos/epidemiologia , Osteoporose Pós-Menopausa/fisiopatologia , Osteoporose Pós-Menopausa/complicaçõesRESUMO
BACKGROUND: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring. OBJECTIVE: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring. METHODS: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models. RESULTS: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring. CONCLUSION: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making.
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Fibrilação Atrial , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Saúde da Mulher , Humanos , Feminino , Complexos Ventriculares Prematuros/epidemiologia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Prevalência , Idoso , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Estados Unidos/epidemiologia , Eletrocardiografia Ambulatorial/métodos , Pessoa de Meia-Idade , Eletrocardiografia , Fatores de Risco , Programas de Rastreamento/métodosRESUMO
OBJECTIVE: This study aimed to advance understanding of vasomotor symptom (VMS) outcomes measurement using pooled data from three Menopause Strategies Finding Lasting Answers to Symptoms and Health (MsFLASH) trials. METHODS: Participants self-reported VMS frequency, severity, and bother using daily diaries; completed standardized measures of VMS interference, insomnia severity, and sleep quality/disturbance; and completed four treatment satisfaction items. Analyses included descriptive statistics, Pearson correlations (baseline pooled sample, posttreatment pooled sample, posttreatment placebo only), t tests, and analysis of variance. RESULTS: Participants were mostly postmenopausal (82.9%) and a mean of 54.5 years old. VMS frequency was fairly correlated with severity, bother, and interference for pooled baseline and placebo posttreatment samples ( r values = 0.21-0.39, P values < 0.001) and moderately correlated with severity, bother, and interference for pooled posttreatment ( r values = 0.40-0.44, P values < 0.001). VMS severity, bother, and interference were moderately correlated ( r values = 0.37-0.48, P values < 0.001), with one exception. VMS severity and bother were strongly correlated ( r values = 0.90-0.92, P values < 0.001). VMS interference was moderately correlated with insomnia ( r values = 0.45-0.54, P values < 0.001) and fairly to moderately correlated with sleep quality/disturbance ( r values = 0.31-0.44, P values < 0.001). Other VMS outcomes were weakly to fairly correlated with insomnia ( r values = 0.07-0.33, P values < 0.001 to < 0.05) and sleep quality/disturbance ( r values = 0.06-0.26, P values < 0.001 to > 0.05). Greater improvement in VMS and sleep over time was associated with higher treatment satisfaction ( P values < 0.001). CONCLUSIONS: This pooled analysis advances understanding of VMS outcomes measurement and has implications for selecting measures and creating future research.
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Fogachos , Distúrbios do Início e da Manutenção do Sono , Feminino , Humanos , Pessoa de Meia-Idade , Fogachos/tratamento farmacológico , Menopausa , Avaliação de Resultados em Cuidados de Saúde , Sono , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: For patients with resected stage III colon cancer, 6 months of adjuvant fluoropyrimidine-based chemotherapy has been the standard of care. The IDEA collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy was noninferior to 6 months. Despite failing to meet its primary endpoint, the subgroup analyses demonstrated noninferiority based on regimen and treatment duration when a risk-stratified approach was used. PATIENTS AND METHODS: To evaluate the impact of the results of the IDEA collaboration, we evaluated adjuvant chemotherapy prescribing practice patterns, including planned adjuvant treatment regimen and duration from January 1, 2016, to January 31, 2021. The time period was selected to evaluate chemotherapy prescribing patterns prior to the abstract presentation of the IDEA collaboration in June 2017 and after full manuscript publication in March 2018. RESULTS: A total of 399 patients with stage III colon cancer who received adjuvant chemotherapy were included in the analysis. A significant increasing trend for use of 3 months of adjuvant chemotherapy was observed after presentation of the IDEA abstract (P<.001). A significant change in CAPOX (capecitabine/oxaliplatin) prescribing was also observed, increasing from 14% of patients prior to presentation of the IDEA abstract to 48% after presentation (P<.001). Comparing 3 months of CAPOX with 6 months of FOLFOX (fluorouracil/leucovorin/oxaliplatin), 3 months of CAPOX use also steadily increased over time (adjusted odds ratio [aOR], 1.28; 95% CI, 1.20-1.37; P<.001). Among subgroups of interest, no differences in adoption of CAPOX were observed. The adoption of 3 months of CAPOX was similar in patients with low-risk cancer (aOR, 1.27; 95% CI, 1.17-1.37) and those with high-risk cancer (aOR, 1.31; 95% CI, 1.16-1.47). CONCLUSIONS: Despite the IDEA collaboration failing to demonstrate noninferiority of 3 months' duration of adjuvant therapy compared with 6 months, the findings have influenced practice prescribing patterns, favoring CAPOX and a shorter duration of planned adjuvant treatment.
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Neoplasias do Colo , Fluoruracila , Humanos , Fluoruracila/uso terapêutico , Oxaliplatina/uso terapêutico , Intervalo Livre de Doença , Estadiamento de Neoplasias , Neoplasias do Colo/terapia , Capecitabina/uso terapêutico , Quimioterapia Adjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucovorina/uso terapêuticoRESUMO
Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks (P for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. Conclusions Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.
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Fibrilação Atrial , Distúrbios do Início e da Manutenção do Sono , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Pós-Menopausa , Estudos Retrospectivos , Saúde da MulherRESUMO
OBJECTIVE: The aim of the study is to describe the location, severity, and frequency of genitourinary symptoms in postmenopausal women enrolled in a randomized trial of treatment for vulvovaginal discomfort. METHODS: This is a post hoc analysis of enrollment responses for participants in the MsFLASH Vaginal Health Trial. Participants were asked about the severity (0-3), frequency (in days per week) and location (vulvar or vaginal) of itch, dryness, pain/soreness, irritation, as well as severity and frequency of pain with penetration, vaginal discharge, urinary incontinence, and urinary urgency. RESULTS: A total of 302 participants were enrolled, with a mean age of 60.9 ± 4.1 years. The mean number of moderate-severe vulvovaginal symptoms experienced by trial participants in the month before enrollment was 3.4 ± 1.5, with a range from 1 to 7. The most commonly reported symptom across all severity categories was vaginal dryness (285/302, 94%), but the one most frequently rated as severe was pain with vaginal penetration (121/302, 40%). Vaginal dryness was the symptom with highest frequency; 53% of participants with that symptom reported experiencing it ≥4 d/wk. For vaginal symptoms, 80% of participants (241/302) reported that at least one of these symptoms occurred during or after sex while only 43% (158/302) reported that at least one vulvar symptom occurred during or after sex. Urinary incontinence (202/302, 67%) and urinary frequency (128/302, 43%) were the two most commonly reported urinary issues. CONCLUSIONS: Our data highlight the complexity of genitourinary syndrome of menopause symptoms in quantity, severity, and frequency, suggesting that measuring distress, bother, or interference may be the most comprehensive measure.
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Incontinência Urinária , Doenças Vaginais , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Menopausa , Doenças Vaginais/patologia , Vagina/patologia , Vulva/patologia , Incontinência Urinária/patologia , Atrofia/patologiaRESUMO
Importance: The best approach to identify younger postmenopausal women for osteoporosis screening is uncertain. The Fracture Risk Assessment Tool (FRAX), which includes self-identified racial and ethnic information, and the Osteoporosis Self-assessment Tool (OST), which does not, are risk assessment tools recommended by US Preventive Services Task Force guidelines to identify candidates for bone mineral density (BMD) testing in this age group. Objective: To compare the ability of FRAX vs OST to discriminate between younger postmenopausal women who do and do not experience incident fracture during a 10-year follow-up in the 4 racial and ethnic groups specified by FRAX. Design, Setting, and Participants: This cohort study of Women's Health Initiative participants included 67â¯169 women (baseline age range, 50-64 years) with 10 years of follow-up for major osteoporotic fracture (MOF; including hip, clinical spine, forearm, and shoulder fracture) at 40 US clinical centers. Data were collected from October 1993 to December 2008 and analyzed between May 11, 2022, and February 23, 2023. Main Outcomes and Measures: Incident MOF and BMD (in a subset of 4607 women) were assessed. The area under the receiver operating characteristic curve (AUC) for FRAX (without BMD information) and OST was calculated within each racial and ethnic category. Results: Among the 67â¯169 participants, mean (SD) age at baseline was 57.8 (4.1) years. A total of 1486 (2.2%) self-identified as Asian, 5927 (8.8%) as Black, 2545 (3.8%) as Hispanic, and 57â¯211 (85.2%) as White. During follow-up, 5594 women experienced MOF. For discrimination of MOF, AUC values for FRAX were 0.65 (95% CI, 0.58-0.71) for Asian, 0.55 (95% CI, 0.52-0.59) for Black, 0.61 (95% CI, 0.56-0.65) for Hispanic, and 0.59 (95% CI, 0.58-0.59) for White women. The AUC values for OST were 0.62 (95% CI, 0.56-0.69) for Asian, 0.53 (95% CI, 0.50-0.57) for Black, 0.58 (95% CI, 0.54-0.62) for Hispanic, and 0.55 (95% CI, 0.54-0.56) for White women. For discrimination of femoral neck osteoporosis, AUC values were excellent for OST (range, 0.79 [95% CI, 0.65-0.93] to 0.85 [95% CI, 0.74-0.96]), higher for OST than FRAX (range, 0.72 [95% CI, 0.68-0.75] to 0.74 [95% CI, 0.60-0.88]), and similar in each of the 4 racial and ethnic groups. Conclusions and Relevance: These findings suggest that within each racial and ethnic category, the US FRAX and OST have suboptimal performance in discrimination of MOF in younger postmenopausal women. In contrast, for identifying osteoporosis, OST was excellent. The US version of FRAX should not be routinely used to make screening decisions in younger postmenopausal women. Future investigations should improve existing tools or create new approaches to osteoporosis risk assessment for this age group.
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Osteoporose , Fraturas por Osteoporose , Feminino , Humanos , Pessoa de Meia-Idade , Etnicidade , Estudos de Coortes , Pós-Menopausa , Osteoporose/diagnóstico , Saúde da Mulher , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/diagnóstico , Densidade Óssea , Medição de Risco , Fatores de Risco , Absorciometria de FótonRESUMO
Bacterial replisomes often dissociate from replication forks before chromosomal replication is complete. To avoid the lethal consequences of such situations, bacteria have evolved replication restart pathways that reload replisomes onto prematurely terminated replication forks. To understand how the primary replication restart pathway in E. coli (PriA-PriB) selectively acts on replication forks, we determined the cryogenic-electron microscopy structure of a PriA/PriB/replication fork complex. Replication fork specificity arises from extensive PriA interactions with each arm of the branched DNA. These interactions reshape the PriA protein to create a pore encircling single-stranded lagging-strand DNA while also exposing a surface of PriA onto which PriB docks. Together with supporting biochemical and genetic studies, the structure reveals a switch-like mechanism for replication restart initiation in which restructuring of PriA directly couples replication fork recognition to PriA/PriB complex formation to ensure robust and high-fidelity replication re-initiation.
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Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA Helicases/metabolismo , Replicação do DNA , DNA/metabolismo , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , DNA Bacteriano/metabolismoAssuntos
Cálcio , Neoplasias , Feminino , Humanos , Seguimentos , Causas de Morte , Incidência , Vitamina D , Cálcio da Dieta , Saúde da Mulher , Neoplasias/epidemiologia , Suplementos NutricionaisRESUMO
BACKGROUND: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1ß, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. METHODS: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease. RESULTS: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1ß log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log [pg/mL] increase, P= .24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-α. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF. CONCLUSIONS: In this large cohort of postmenopausal women, there was no significant association between IL-1ß and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF.
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Fibrilação Atrial , Interleucina-1beta , Pós-Menopausa , Feminino , Humanos , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Incidência , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Interleucina-6 , Pós-Menopausa/metabolismo , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.
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Doenças Cardiovasculares , Neoplasias , Feminino , Humanos , Cálcio , Causas de Morte , Incidência , Seguimentos , Suplementos Nutricionais , Vitamina D , Cálcio da Dieta , Saúde da Mulher , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: The association of pelvic radiation with pelvic fracture risk has not been examined in prospective cohort settings with comprehensive fracture risk assessment, cancer-free comparison populations, and long-term follow-up. Our objective is to better characterize pelvic fracture and overall mortality risks in postmenopausal women participating in the Women's Health Initiative. METHODS: A total of 135â743 Women's Health Initiative participants aged 50 to 79 years enrolled from 40 US clinical centers from 1993 to 1998 who had entry Fracture Risk Assessment Tool scores were eligible. Outcomes included pelvic cancer diagnosis, pelvic fracture occurrence, and mortality. Cox proportional hazards regression models were used to examine associations of pelvic cancer and pelvic radiation with pelvic fracture and mortality risk. RESULTS: After 17.7 years (median) follow-up, 4451 pelvic cancers, 10â139 pelvic fractures, and 33â040 deaths occurred. In multivariable analyses, women with incident pelvic cancer, compared with women who remained pelvic cancer free, had higher pelvic fracture risk (hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.43) and higher overall mortality risk (HR = 2.91, 95% CI = 2.77 to 3.05). Women with pelvic cancer treated with pelvic radiation, compared with women with pelvic cancer not treated with pelvic radiation, had higher pelvic fracture risk (HR = 1.98, 95% CI = 1.41 to 2.78) and higher overall mortality after pelvic cancer (HR = 1.32, 95% CI = 1.15 to 1.52). CONCLUSIONS: Postmenopausal women with pelvic cancer, especially those receiving pelvic radiation, are at higher pelvic fracture risk and higher overall mortality risk. As therapeutic advances have reduced cancer mortality, attention to and interventions for pelvic fracture prevention may be important in pelvic cancer survivors.
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Fraturas Ósseas , Neoplasias , Feminino , Humanos , Estudos Prospectivos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Saúde da Mulher , Sobreviventes , Atenção à Saúde , Fatores de Risco , Neoplasias/epidemiologiaRESUMO
BACKGROUND: Asymptomatic atrial fibrillation (AF) is associated with an increased risk of stroke. The yield of serial electrocardiographic (ECG) screening for AF is unknown. OBJECTIVES: The aim of this study was to determine the frequency of AF detected by serial, 7-day ECG patch screenings in older women identified as having an elevated risk of AF according to the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology)-AF clinical prediction score. METHODS: Postmenopausal women with a 5-year predicted risk of new-onset AF ≥5% according to CHARGE-AF were recruited from the ongoing WHISH (Women's Health Initiative Strong and Healthy) randomized trial of a physical activity intervention. Participants with AF at baseline by self-report or medical records review were excluded. Screening with 7-day ECG patch monitors was performed at baseline, 6 months, and 12 months from study enrollment. RESULTS: On baseline monitoring, 2.5% of the cohort had AF detected, increasing to 3.7% by 6 months and 4.9% cumulatively by 12 months. Yield of patch screening was higher among participants with a higher (≥10%) CHARGE-AF score: 4.2% had AF detected at baseline, 5.9% at 6 months, and 7.2% at 12 months. Most participants with patch-identified AF never had a clinical diagnosis of AF (36 of 46 [78%]). CONCLUSIONS: Older women with an elevated CHARGE-AF score had a high prevalence of AF on 7-day ECG patch screening. Serial screening over 12 months substantially increased the detection of AF. These data can be useful in helping identify high-risk participants for enrollment in future studies of the management of asymptomatic AF.(Women's Health Initiative Silent Atrial Fibrillation Recording Study [WHISH STAR]; NCT05366803.).
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/complicações , Eletrocardiografia , Coração , Programas de RastreamentoRESUMO
Importance: Half of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention. Objective: To compare serum estrogen concentrations with the use of vaginal estrogen, 10 µg, tablet vs placebo in women who are postmenopausal. Design, Setting, and Participants: This is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022. Interventions: Participants were randomly assigned to vaginal estradiol tablet (10 µg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks. Main Outcomes and Measures: In this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics. Results: A total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain. Trial Registration: ClinicalTrials.gov Identifier: NCT02516202.
Assuntos
Estradiol , Estrona , Humanos , Feminino , Pessoa de Meia-Idade , Pós-Menopausa , Cremes, Espumas e Géis Vaginais , Estrogênios , ComprimidosRESUMO
OBJECTIVES: The aim of this study was to quantify changes in serum total estradiol (E2) and estrone (E1) concentrations with initiation of low-dose oral estradiol treatment and evaluate whether changes in concentrations mediate the effect of treatment in reducing vasomotor symptom (VMS) frequency. METHODS: We analyzed baseline and week 8 (W8) data from 171 perimenopausal and postmenopausal women with VMS enrolled in low-dose 17ß estradiol ( n = 72) and placebo ( n = 99) groups of a randomized clinical trial. RESULTS: From baseline to W8, women in the low-dose estradiol group had a fourfold increase in E2, resulting in a W8 E2 of 23 pg/mL, and a fivefold increase in E1, resulting in a W8 E1 of 110.7 pg/mL. In contrast, E2 and E1 among women in the placebo group were unchanged from baseline to W8. Changes in E2 and E1 from baseline to W8 met criteria for mediating the effect of low-dose estradiol treatment on VMS frequency. With change in estrogen concentration added to treatment assignment in a regression model predicting W8 VMS frequency, the effect of treatment with low-dose estradiol versus placebo was attenuated, with change in E2 representing a 44.1% reduction ( P = 0.03) and change in E1 representing a 69.5% reduction ( P = 0.02) in total intervention effect. CONCLUSION: Among perimenopausal and postmenopausal women with VMS, treatment with low-dose oral estradiol versus placebo results in four- to fivefold increases in serum E2 and E1. The increases in serum E2 and E1 with low-dose oral estradiol treatment seem to mediate in part the effect of treatment in reducing VMS frequency.
Assuntos
Estradiol , Terapia de Reposição de Estrogênios , Terapia de Reposição de Estrogênios/métodos , Estrogênios/farmacologia , Estrona , Feminino , Humanos , Pós-MenopausaRESUMO
BACKGROUND & AIMS: The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. METHODS: This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. RESULTS: A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. CONCLUSION: In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. LAY SUMMARY: For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Feminino , Humanos , Masculino , Albuminas , Bilirrubina , Ensaios Clínicos como Assunto , Cirrose Hepática/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Estudos Retrospectivos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Aging is generally accompanied by decreasing physical activity (PA), which is associated with a decline in many health parameters, leading to recommendations for older adults to increase or at least maintain PA. METHODS: We determined relationships between social connectedness and decreasing or increasing PA levels during the coronavirus disease 2019 pandemic among 41 443 participants of the Women's Health Initiative Extension Study. Outcomes of logistic regression models were decreasing PA activity (reference: maintaining or increasing) and increasing PA activity (reference: maintaining or decreasing). The main predictor was social connectedness as a combined variable: not living alone (reference: living alone) and communicating with others outside the home more than once/week (reference: once/week or less). We adjusted for age, race, ethnicity, body mass index, physical function level, and education. RESULTS: Compared with participants who were not socially connected, socially connected participants had lower odds of decreasing PA (adjusted odds ratio 0.91, 95% confidence interval 0.87-0.95). Odds of increasing PA (vs decreasing or maintaining PA) were not significantly different among socially connected and not socially connected participants. Associations between social connectedness and decreasing PA did not significantly differ by age (<85 vs ≥85 years), race/ethnicity (non-Hispanic White vs other races/ethnicity), education (college vs