The natural history of urinary incontinence subtypes in the Nurses' Health Studies.

BACKGROUND: Urinary incontinence subtypes often differ by symptom severity and treatment profiles; in particular, mixed urinary incontinence is generally associated with worse symptoms and less successful treatment. Yet, limited information exists on the natural history of different urinary incontinence subtypes, which could help to better identify and treat patients prior to development of more intractable disease. OBJECTIVE: To evaluate the onset of urinary incontinence subtypes, and transitions between subtypes over 8 years, using 2 large cohorts of middle-aged and older women with incident urinary incontinence. MATERIALS AND METHODS: We identified 10,349 women with incident urinary incontinence (stress, urgency, and mixed subtypes) from the Nurses' Health Study and the Nurses' Health Study II who were 41-83 years of age, using repeated mailed questionnaires. We defined stress urinary incontinence as leakage with coughing, sneezing, or activity; urgency urinary incontinence as urine loss with a sudden feeling of bladder fullness or when a toilet was inaccessible; and mixed urinary incontinence when women reported that stress and urgency symptoms occurred equally. In subsequent questionnaires 4 and 8 years later, we continued to track symptom severity and subtypes. In addition, to obtain predicted probabilities of urinary incontinence subtypes 4 years and 8 years after urinary incontinence onset, we used multivariable-adjusted generalized estimating equations with a multinomial outcome. RESULTS: At urinary incontinence onset in 2004-2005, 56% of women reported stress urinary incontinence symptoms, 23% reported urgency urinary incontinence symptoms, and 21% reported mixed urinary incontinence symptoms. Women with stress urinary incontinence or urgency urinary incontinence at onset were likely to report the same urinary incontinence type 4 and 8 years later (stress urinary incontinence at onset: 70% and 60% reported stress urinary incontinence at years 4 and 8, respectively; urgency urinary incontinence at onset: 68% and 64% reported urgency urinary incontinence at years 4 and 8, respectively). Nonetheless, for both stress and urgency urinary incontinence, women with more severe symptoms at onset were more likely to progress to mixed urinary incontinence. Women with mixed urinary incontinence at onset had more variation over time, although the largest subset continued to report mixed urinary incontinence (45% reported mixed urinary incontinence at year 4; 43% reported mixed urinary incontinence at year 8). Few women across all urinary incontinence subtypes reported resolution of symptoms over 4-8 years of follow-up (4-12%). When considering the likelihood of remaining with or progressing to mixed urinary incontinence over follow-up, according to age, body mass index, and urinary incontinence severity, we found that older and younger women had similar predicted probability of remaining with or progressing to mixed urinary incontinence (eg, women <60 years of age at onset with severe mixed urinary incontinence had a 54% (95% confidence interval, 53-55) probability of mixed urinary incontinence 8 years later, vs 57% (95% confidence interval, 56-58) of women ≥70 years of age with severe mixed urinary incontinence at onset). Obese women were somewhat more likely to progress to mixed urinary incontinence regardless of urinary incontinence type at onset (eg, women with body mass index <25 kg/m2 at onset with severe stress urinary incontinence had a 30% predicted probability of mixed urinary incontinence 8 years after onset, vs 36% of women with body mass index of 30+ kg/m2 at onset with severe stress urinary incontinence). CONCLUSION: Most women with incident stress and urgency urinary incontinence continued to experience similar subtype symptoms over 8 years. However, obese women and those with more severe symptoms were more likely to remain with or progress to mixed urinary incontinence.

The Relationship Between Vertical Ground Reaction Force, Loading Rate, and Sound Characteristics During a Single-Leg Landing.

CONTEXT: Landing kinetic outcomes are associated with injury risk and may be persistently altered after anterior cruciate ligament injury or reconstruction. However, it is challenging to assess kinetics clinically. The relationship between sound characteristics and kinetics during a limited number of functional tasks has been supported as a potential clinical alternative. OBJECTIVE: To assess the relationship between kinetics and sound characteristics during a single-leg landing task. DESIGN: Observational Setting: Laboratory. PARTICIPANTS: There was total of 26 healthy participants (15 males/11 females, age = 24.8 [3.6] y, height = 176.0 [9.1] cm, mass = 74.9 [14.4] kg, Tegner Activity Scale = 6.1 [1.1]). INTERVENTION: Participants completed single-leg landings onto a force plate while audio characteristics were recorded. MAIN OUTCOME MEASURES: Peak vertical ground reaction force, linear loading rate, instantaneous loading rate, peak sound magnitude, sound frequency were measured. Means and SDs were calculated for each participant's individual limbs. Spearman rho correlations were used to assess the relationships between audio characteristics and kinetic outcomes. RESULTS: Peak sound magnitude was positively correlated with normalized peak vertical ground reaction force (ρ = .486, P = .001); linear loading rate (ρ = .491, P = .001); and instantaneous loading rate (ρ = .298, P = .03). Sound frequency was negatively correlated with instantaneous loading rate (ρ = -.444, P = .001). CONCLUSIONS: Peak sound magnitude may be more helpful in providing feedback about an individual's normalized vertical ground reaction force and linear loading rate, and sound frequency may be more helpful in providing feedback about instantaneous loading rate. Further refinement in sound measurement techniques may be required before these findings can be applied in a clinical population.

Interaction of a genetic risk score with physical activity, physical inactivity, and body mass index in relation to venous thromboembolism risk.

INTRODUCTION: Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. METHODS: Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. RESULTS: We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. CONCLUSION: We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk.

Outpatient Evaluation and Management Visits for Urinary Incontinence in Older Women.

PURPOSE: The aims of this investigation were to examine how often outpatient visits addressing urinary incontinence in women with self-reported incontinence symptoms occur and to explore characteristics associated with an outpatient visit for incontinence. MATERIALS AND METHODS: We studied the records of 18,576 women from the Nurses' Health Study who were 65 years old or older, reported prevalent incontinence symptoms in 2012 on a mailed questionnaire and were linked with Medicare utilization data. We compared demographic, personal and clinical characteristics in women with and without claims for outpatient visits for urinary incontinence. In logistic regression models we controlled for potential confounding factors, including age, race, parity, body mass index, medical comorbidities, smoking status, health seeking behavior, disability, physical function and geographic region. RESULTS: In this linkage between symptom report and insurance claims data we found that only 16% of older women with current incontinence symptoms also had an outpatient visit addressing incontinence in the prior 2 years. In multivariable adjusted models severe vs slight incontinence (OR 3.75, 95% CI 3.10-4.53) and urgency vs stress incontinence (OR 1.80, 95% CI 1.56-2.08) were the strongest predictors of undergoing outpatient evaluation. CONCLUSIONS: Overall only a small percent of women who report urinary incontinence symptoms also have medical outpatient visits for incontinence, which is a marker of care seeking. Our study highlights the discordance between the high prevalence of incontinence in older women and the lack of clinical assessment despite symptoms even among nurses with high health care literacy.

Association Between Proton Pump Inhibitor Use and Cognitive Function in Women.

BACKGROUND & AIMS: Studies have reported associations between proton pump inhibitor (PPI) use and dementia. However, data are lacking on long-term PPI use and cognitive function. We therefore examined associations between PPI use and performance in tests of cognitive function. Because of shared clinical indications, we examined associations for H2 receptor antagonists (H2RAs) as a secondary aim. METHODS: We used prospectively collected data on medication use and other potential risk factors from 13,864 participants in the Nurses' Health Study II who had completed a self-administered computerized neuropsychological test battery. Multivariable linear regression models were used to examine associations between medication use and composite scores of psychomotor speed and attention, learning and working memory, and overall cognition. RESULTS: We observed a modest association between duration of PPI use and scores for psychomotor speed and attention (mean score difference for PPI use of 9-14 years vs never users, -0.06; 95% confidence interval, -0.11 to 0.00; Ptrend = .03). After controlling for H2RA use, the magnitude of this score difference was attenuated. Among individuals who did not use PPIs regularly, duration of H2RA use was associated with poorer cognitive scores, with the strongest association apparent for learning and working memory (mean score difference for H2RA users of 9-14 years vs never users, -0.20; 95% confidence interval, -0.32 to -0.08; Ptrend < .001). CONCLUSIONS: In an analysis of data from the Nurses' Health Study II, we did not observe a convincing association between PPI use and cognitive function. Our data do not support the suggestion that PPI use increases dementia risk. Because our primary hypothesis related to PPI use, our findings for H2RAs should be interpreted with caution.

A prospective study of the natural history of urinary incontinence in women.

BACKGROUND: Symptoms of urinary incontinence are commonly perceived to vary over time; yet, there is limited quantitative evidence regarding the natural history of urinary incontinence, especially over the long term. OBJECTIVE: We sought to delineate the course of urinary incontinence symptoms over time, using 2 large cohorts of middle-aged and older women, with data collected over 10 years. STUDY DESIGN: We studied 9376 women from the Nurses' Health Study, age 56-81 years at baseline, and 7491 women from the Nurses' Health Study II, age 39-56 years, with incident urinary incontinence in 2002 through 2003. Urinary incontinence severity was measured by the Sandvik severity index. We tracked persistence, progression, remission, and improvement of symptoms over 10 years. We also examined risk factors for urinary incontinence progression using logistic regression models. RESULTS: Among women age 39-56 years, 39% had slight, 45% had moderate, and 17% had severe urinary incontinence at onset. Among women age 56-81 years, 34% had slight, 45% had moderate, and 21% had severe urinary incontinence at onset. Across ages, most women reported persistence or progression of symptoms over follow-up; few (3-11%) reported remission. However, younger women and women with less severe urinary incontinence at onset were more likely to report remission or improvement of symptoms. We found that increasing age was associated with higher odds of progression only among older women (age 75-81 vs 56-60 years; odds ratio, 1.84; 95% confidence interval, 1.51-2.25). Among all women, higher body mass index was strongly associated with progression (younger women: odds ratio, 2.37; 95% confidence interval, 2.00-2.81; body mass index ≥30 vs <25 kg/m2; older women: odds ratio, 1.93; 95% confidence interval, 1.62-2.22). Additionally, greater physical activity was associated with lower odds of progression to severe urinary incontinence (younger women: odds ratio, 0.86; 95% confidence interval, 0.71-1.03; highest vs lowest quartile of activity; older women: odds ratio, 0.68; 95% confidence interval, 0.59-0.80). CONCLUSION: Most women with incident urinary incontinence continued to experience symptoms over 10 years; few had complete remission. Identification of risk factors for urinary incontinence progression, such as body mass index and physical activity, could be important for reducing symptoms over time.

Optimism and Cause-Specific Mortality: A Prospective Cohort Study.

Growing evidence has linked positive psychological attributes like optimism to a lower risk of poor health outcomes, especially cardiovascular disease. It has been demonstrated in randomized trials that optimism can be learned. If associations between optimism and broader health outcomes are established, it may lead to novel interventions that improve public health and longevity. In the present study, we evaluated the association between optimism and cause-specific mortality in women after considering the role of potential confounding (sociodemographic characteristics, depression) and intermediary (health behaviors, health conditions) variables. We used prospective data from the Nurses' Health Study (n = 70,021). Dispositional optimism was measured in 2004; all-cause and cause-specific mortality rates were assessed from 2006 to 2012. Using Cox proportional hazard models, we found that a higher degree of optimism was associated with a lower mortality risk. After adjustment for sociodemographic confounders, compared with women in the lowest quartile of optimism, women in the highest quartile had a hazard ratio of 0.71 (95% confidence interval: 0.66, 0.76) for all-cause mortality. Adding health behaviors, health conditions, and depression attenuated but did not eliminate the associations (hazard ratio = 0.91, 95% confidence interval: 0.85, 0.97). Associations were maintained for various causes of death, including cancer, heart disease, stroke, respiratory disease, and infection. Given that optimism was associated with numerous causes of mortality, it may provide a valuable target for new research on strategies to improve health.

Posttraumatic stress disorder symptoms and cognitive function in a large cohort of middle-aged women.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been linked to cognitive decline, but research in women is generally lacking. We examined whether trauma and elevated PTSD symptoms were associated with worse cognitive function in middle-aged civilian women. A secondary objective was to investigate the possible role of depression in the relation of PTSD symptoms to cognitive function. METHODS: The sample comprised 14,029 middle-aged women in the Nurses' Health Study II. Lifetime trauma exposure, lifetime PTSD symptoms, and past-week depressive symptoms were measured in 2008. Cognitive function was measured in 2014-2016 using the Cogstate Brief Battery, a self-administered online cognitive battery that assesses psychomotor speed, attention, learning, and working memory. We used linear regression models to estimate mean differences in cognition across PTSD symptom levels. RESULTS: Compared to no trauma, elevated PTSD symptoms consistent with probable PTSD (i.e., 4+ symptoms on a screening questionnaire) were associated with worse performance on psychomotor speed/attention (b = -0.08 standard units, p = .001) and learning/working memory (b = -0.09, p < .001) composites, after adjusting for sociodemographics. Although attenuated, associations remained significant when adjusted for depressive symptoms and other cognitive risk factors. We found the strongest associations among women with comorbid probable PTSD and depression. CONCLUSIONS: PTSD symptoms were negatively related to measures of psychomotor speed/attention and learning/working memory in middle-aged women. Our study adds to a growing literature that suggests that mental disorders are associated with worse cognitive function over the life course.

Greater Adherence to the Alternative Healthy Eating Index Is Associated with Lower Incidence of Physical Function Impairment in the Nurses' Health Study.

BACKGROUND: Physical function is integral to healthy aging, in particular as a core component of mobility and independent living in older adults, and is a strong predictor of mortality. Limited research has examined the role of diet, which may be an important strategy to prevent or delay a decline in physical function with aging. OBJECTIVE: We prospectively examined the association between the Alternative Healthy Eating Index-2010 (AHEI-2010), a measure of diet quality, with incident impairment in physical function among 54,762 women from the Nurses' Health Study. METHODS: Physical function was measured by the Medical Outcomes Short Form-36 (SF-36) physical function scale and was administered every 4 y from 1992 to 2008. Cumulative average diet was assessed using food frequency questionnaires, administered approximately every 4 y. We used multivariable Cox proportional hazards models to estimate the HRs of incident impairment of physical function. RESULTS: Participants in higher quintiles of the AHEI-2010, indicating a healthier diet, were less likely to have incident physical impairment than were participants in lower quintiles (P-trend < 0.001). The multivariable-adjusted HR of physical impairment for those in the top compared with those in the bottom quintile of the AHEI-2010 was 0.87 (95% CI: 0.84, 0.90). For individual AHEI-2010 components, higher intake of vegetables (P-trend = 0.003) and fruits (P-trend = 0.02); lower intake of sugar-sweetened beverages (P-trend < 0.001), trans fats (P-trend = 0.03), and sodium (P-trend < 0.001); and moderate alcohol intake (P-trend < 0.001) were each significantly associated with reduced rates of incident physical impairment. Among top contributors to the food components of the AHEI-2010, the strongest relations were found for increased intake of oranges, orange juice, apples and pears, romaine or leaf lettuce, and walnuts. However, associations with each component and with specific foods were generally weaker than the overall score, indicating that overall diet pattern is more important than individual parts. CONCLUSIONS: In this large cohort of older women, a healthier diet was associated with a lower risk of developing impairments in physical function.

Epidemiology of Major Neurodegenerative Diseases in Women: Contribution of the Nurses' Health Study.

OBJECTIVES: To review the contribution of the Nurses' Health Study (NHS) to identifying the role of lifestyle, diet, and genetic or biological factors in several neurodegenerative diseases, including cognitive decline, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. METHODS: We completed a narrative review of the publications of the NHS and NHS II between 1976 and 2016. RESULTS: In primary findings for cognitive function, higher intake of nuts, moderate alcohol consumption, and higher physical activity levels were associated with better cognitive function. Flavonoids, physical activity, and postmenopausal hormone therapy were related to cognitive decline over 2 to 6 years. The NHS also has been integral in establishing Epstein-Barr virus infection, inadequate vitamin D nutrition, cigarette smoking, and obesity as risk factors for multiple sclerosis and inverse associations between cigarette smoking and caffeine and risk of Parkinson's disease. Increased risk of amyotrophic lateral sclerosis has been associated with cigarette smoking and decreased risk associated with obesity. CONCLUSIONS: The NHS has provided invaluable resources on neurodegenerative diseases and contributed to their etiological understanding. We anticipate that the NHS cohorts will continue to make important contributions to the field of neurodegenerative diseases.

Evaluation of a Self-Administered Computerized Cognitive Battery in an Older Population.

OBJECTIVE: The aim of this study is to assess the utility of the Cogstate self-administered computerized neuropsychological battery in a large population of older men. METHODS: We invited 7,167 men (mean age of 75 years) from the Health Professionals Follow-up Study, a prospective cohort of male health professionals. We considered individual Cogstate scores and composite scores measuring psychomotor speed and attention, learning and working memory and overall cognition. Multivariate linear regression was used to assess the association between risk factors measured 4 and 28 years prior to cognitive testing and each outcome. RESULTS: The 1,866 men who agreed to complete Cogstate testing were similar to the 5,301 non-responders. Many expected risk factors were associated with Cogstate scores in multivariate adjusted models. Increasing age was significantly associated with worse performance on all outcomes (p < 0.001). For risk factors measured 4 years prior to testing and overall cognition, a history of hypertension was significantly associated with worse performance (mean difference of -0.08 standard units (95% CI -0.16, 0.00)) and higher consumption of nuts was significantly associated with better performance (>2 servings/week vs. <1 serving/month: 0.15 (0.03, 0.27)). CONCLUSIONS: The self-administered Cogstate battery showed significant associations with several risk factors known to be associated with cognitive function. Future studies of cognitive aging may benefit from the numerous advantages of self-administered computerized testing.

Phobic Anxiety and Plasma Levels of Global Oxidative Stress in Women.

BACKGROUND AND OBJECTIVES: Psychological distress has been hypothesized to be associated with adverse biologic states such as higher oxidative stress and inflammation. Yet, little is known about associations between a common form of distress - phobic anxiety - and global oxidative stress. Thus, we related phobic anxiety to plasma fluorescent oxidation products (FlOPs), a global oxidative stress marker. METHODS: We conducted a cross-sectional analysis among 1,325 women (aged 43-70 years) from the Nurses' Health Study. Phobic anxiety was measured using the Crown-Crisp Index (CCI). Adjusted least-squares mean log-transformed FlOPs were calculated across phobic categories. Logistic regression models were used to calculate odds ratios (OR) comparing the highest CCI category (≥6 points) vs. lower scores, across FlOPs quartiles. RESULTS: No association was found between phobic anxiety categories and mean FlOP levels in multivariable adjusted linear models. Similarly, in multivariable logistic regression models there were no associations between FlOPs quartiles and likelihood of being in the highest phobic category. Comparing women in the highest vs. lowest FlOPs quartiles: FlOP_360: OR=0.68 (95% CI: 0.40-1.15); FlOP_320: OR=0.99 (95% CI: 0.61-1.61); FlOP_400: OR=0.92 (95% CI: 0.52, 1.63). CONCLUSIONS: No cross-sectional association was found between phobic anxiety and a plasma measure of global oxidative stress in this sample of middle-aged and older women.

Severe Hypoglycemia and Impaired Awareness of Hypoglycemia Persist in People With Type 1 Diabetes Despite Use of Diabetes Technology: Results From a Cross-sectional Survey.

OBJECTIVE: To determine how diabetes technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems, impact glycemic metrics, prevalence of severe hypoglycemic events (SHEs), and impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes in a real-world setting within the U.S. RESEARCH DESIGN AND METHODS: In this retrospective, observational study with cross-sectional elements, participants aged ≥18 years were enrolled from the T1D Exchange Registry/online community. Participants completed a one-time online survey describing glycemic metrics, SHEs, and IAH. The primary objective was to determine the proportions of participants who reported achieving glycemic targets (assessed according to self-reported hemoglobin A1c) and had SHEs and/or IAH. We performed additional subgroup analyses focusing on the impact of CGM and insulin delivery modality. RESULTS: A total of 2,074 individuals with type 1 diabetes were enrolled (mean ± SD age 43.0 ± 15.6 years and duration of type 1 diabetes 26.3 ± 15.3 years). The majority of participants (91.7%) were using CGM, with one-half (50.8%) incorporating AID. Despite high use of diabetes technologies, only 57.7% reported achieving glycemic targets (hemoglobin A1c <7%). SHEs and IAH still occurred, with ∼20% of respondents experiencing at least one SHE within the prior 12 months and 30.7% (95% CI 28.7, 32.7) reporting IAH, regardless of CGM or AID use. CONCLUSIONS: Despite use of advanced diabetes technologies, a high proportion of people with type 1 diabetes do not achieve glycemic targets and continue to experience SHEs and IAH, suggesting an ongoing need for improved treatment strategies.

Impact of Risankizumab on PASI90 and DLQI0/1 Duration in Moderate-to-Severe Psoriasis: A Post Hoc Analysis of Four Phase 3 Clinical Trials.

INTRODUCTION: Novel therapies have allowed psoriasis patients to achieve high levels of skin clearance and meaningful improvements in health-related quality of life measures; however, duration of these outcomes has not been evaluated. This study aimed to estimate the duration of Psoriasis Area and Severity Index (PASI) 90 and Dermatology Life Quality Index (DLQI) 0/1 among patients with moderate-to-severe psoriasis receiving risankizumab and other treatments. METHODS: Pooled data from four phase 3 randomized clinical trials of risankizumab were used to estimate the number and proportion of days with PASI90 and DLQI0/1 during the 1-year post-baseline period with an area-under-the-curve approach. Patients were classified into five cohorts on the basis of their treatment experience during the follow-up period: risankizumab (RISA) only, RISA followed by re-randomization to RISA or placebo (RISA and RISA/PBO), adalimumab (ADA) followed by re-randomization to ADA or RISA (ADA and ADA/RISA), ustekinumab (UST) only, and placebo followed by risankizumab (PBO/RISA). RESULTS: A total of 2101 patients were included in this analysis. Mean age was 47.5 years, 70% were males, and mean duration since psoriasis diagnosis was 18.6 years. Patients treated with RISA only throughout the study period experienced the longest PASI90 [245.7 days (67% over 1 year)] and DLQI0/1 [213.7 (59%)] duration. Patients treated with PBO/RISA [156.8 (43%)] and UST only [154.2 (42%)] experienced the shortest PASI90 duration. Similarly, patients treated with PBO/RISA experienced the shortest DLQI0/1 duration during the 52-week study period [90.5 (25%)]. CONCLUSION: Patients with moderate-to-severe psoriasis treated with risankizumab exhibited longer durations of PASI90 and DLQI0/1 than patients treated with other therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: UltIMMa-1 (NCT02684370), NCT02684357 (UltIMMa-2), IMMvent (NCT02694523), IMMhance (NCT02672852).

Oral postmenopausal hormone therapy and genetic risk on venous thromboembolism: gene-hormone interaction results from a large prospective cohort study.

OBJECTIVE: Oral postmenopausal hormone therapy (HT) has been shown to be associated with venous thromboembolism (VTE), but whether this association is modified by VTE-associated genetic susceptibility is unknown. We examined interactions between oral HT use and a genetic risk score (GRS) of VTE. METHOD: Eligible women were postmenopausal women who had data on oral HT use, VTE incidence between 1990 and 2012, and genetic data in the Nurses' Health Study. We built a GRS aggregating 16 VTE-related genetic variants. We used Cox regression to estimate associations of HT use with incident VTE and assessed interactions between HT use and VTE GRS. We also estimated incidence of VTE between age 50 and 79 years for groups of women defined by HT use and VTE GRS. RESULTS: We identified 432 incident VTE cases. Current HT users were at higher risk of VTE than never users (HR: 1.9, 95% CI: 1.5-2.6), with slightly higher risk for estrogen plus progestin HT than estrogen only (HR: 2.4 vs 1.9). The GRS was associated with VTE risk (HR comparing 4th quartile to 1st: 2.0, 95% CI: 1.2-3.4). We did not observe significant multiplicative interactions between HT use and GRS. The estimated VTE risk difference (per 10,000 person-years) comparing 50-year-old current HT users to never users was 22.5 for women in the highest GRS quartile and 9.8 for women in the lowest GRS quartile. CONCLUSION: The VTE GRS might inform clinical guidance regarding the balance of risks and benefits of HT use, especially among younger women.

Patient-Provider Discussions About Urinary Incontinence Among Older Women.

BACKGROUND: Urinary incontinence (UI) is prevalent in women and has been associated with decreased quality of life and institutionalization. Despite this, and the fact that several treatment options exist, few women discuss UI with clinicians. The aim of this study was to examine the proportion of middle aged and older women with urinary incontinence who have discussed UI with clinicians, focusing on female health professionals as a way to examine this question outside of issues of health care access. METHODS: Data are from the Nurses Health Studies (NHS), two ongoing observational, prospective, cohort studies. The surveys collected detailed information about UI, including frequency, amount and type. Women were also asked if they had discussed UI with a clinician. We used multivariable-adjusted logistic regression to estimate odds ratios (OR) of participants reporting discussion about UI. RESULTS: 94,692 women with UI aged 49-91 years old were included in this study. Of these, 34% reported that they had discussed their incontinence with a clinician. Women with daily UI had 4.4 times greater odds of discussing it with clinicians when compared to those with monthly UI (OR = 4.36, 95% confidence interval [CI] 4.06-4.69). When controlling for severity of symptoms, the oldest women, greater than eighty years, were 20% less likely to have discussed UI with their clinician, compared to the youngest women (OR = 0.81, 95% CI 0.73-0.89). CONCLUSIONS: A minority of women with UI, even among health professionals, discuss their symptoms with clinicians. Oldest women were the least likely to discuss their UI with a provider.

Confirmed disability progression provides limited predictive information regarding future disease progression in multiple sclerosis.

BACKGROUND: Although confirmed disability progression (CDP) is a common outcome in multiple sclerosis (MS) clinical trials, its predictive value for long-term outcomes is uncertain. OBJECTIVE: To investigate whether CDP at month 24 predicts subsequent disability accumulation in MS. METHODS: The Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital includes participants with relapsing-remitting MS or clinically isolated syndrome with Expanded Disability Status Scale (EDSS) scores ≤5 (N = 1214). CDP was assessed as a predictor of time to EDSS score 6 (EDSS 6) and to secondary progressive MS (SPMS) using a Cox proportional hazards model; adjusted models included additional clinical/participant characteristics. Models were compared using Akaike's An Information Criterion. RESULTS: CDP was directionally associated with faster time to EDSS 6 in univariate analysis (HR = 1.61 [95% CI: 0.83, 3.13]). After adjusting for month 24 EDSS, CDP was directionally associated with slower time to EDSS 6 (adjusted HR = 0.65 [0.32, 1.28]). Models including CDP had worse fit statistics than those using EDSS scores without CDP. When models included clinical and magnetic resonance imaging measures, T2 lesion volume improved fit statistics. Results were similar for time to SPMS. CONCLUSIONS: CDP was less predictive of time to subsequent events than other MS clinical features.

Health care resource utilization and cost burden of hemophilia B in the United States.

Hemophilia B is a rare congenital blood disorder characterized by factor IX deficiency. Clinical profiles of hemophilia B range from mild to severe forms of the disease. The objective of this study was to characterize the economic burden associated with differing clinical profiles of hemophilia B from a US health system perspective. Using the IBM MarketScan database (June 2011-February 2019), a claims-based algorithm was developed to identify 4 distinct profiles (mild, moderate, moderate-severe, and severe) in adult males with hemophilia B based on the frequency of hemorrhage events and factor IX replacement claims. Mean annual health care resource use (HRU) and costs were statistically compared between patients with hemophilia B (N = 454) and 1:1 demographic-matched controls (N = 454), both overall and with stratification by clinical profile. Compared with matched controls, patients with hemophilia B had a significantly higher comorbidity burden (Charlson Comorbidity Index, mean ± standard deviation [SD]: 0.9 ± 1.7 vs 0.3 ± 0.9, P < .001). Across all clinical profiles, patients with hemophilia B had significantly higher HRU vs matched controls (mean ± SD: 0.3 ± 0.6 vs 0.1 ± 0.3 inpatient admissions; 0.6 ± 1.2 vs 0.2 ± 0.6 emergency department visits; 17.7 ± 22.9 vs 8.0 ± 11.0 outpatient visits; all P < .001). Annual total health care costs per patient among patients with hemophilia B were more than 25-fold higher vs matched controls (mean ± SD: $201 635 ± $411 530 vs $7879 ± $29 040, respectively, P < .001). Annual total health care costs per patient increased with increasing severity (mean ± SD: mild, $80 811 ± $284 313; moderate, $137 455 ± $222 021; moderate-severe, $251 619 ± $576 886; severe, $632 088 ± $501 270). The findings of this study highlight the substantial burden of illness associated with hemophilia B.

Diet quality and risk of frailty among older women in the Nurses' Health Study.

BACKGROUND: The frailty syndrome is associated with higher risk of disability and death after accounting for multimorbidity. Therefore, the determinants of frailty need to be identified to ensure older adults live not only longer but also healthier lives. However, the effect of diet quality on frailty is mostly unknown. OBJECTIVES: We aimed to evaluate the alternate Mediterranean diet (AMED), the Dietary Approaches to Stop Hypertension (DASH) diet, and the alternate Healthy Eating Index-2010 (AHEI-2010) in association with frailty risk among older women. METHODS: We analyzed data from 71,941 women aged ≥60 y participating in the Nurses' Health Study. The AMED, DASH, and AHEI-2010 were computed from validated FFQs in 1990 and repeated every 4 y until 2010. Frailty was defined as having ≥3 of the following 5 criteria from the FRAIL scale: fatigue, reduced resistance, reduced aerobic capacity, having ≥5 illnesses, and weight loss ≥5%. The occurrence of frailty was assessed every 4 y. RESULTS: During follow-up we identified 11,564 incident cases of frailty. After adjusting for potential confounders, the RRs (95% CIs) of frailty per 1-SD increase in the AMED, DASH, and AHEI-2010 scores were 0.87 (0.85, 0.90), 0.93 (0.91, 0.95), and 0.90 (0.88, 0.92), respectively. All diet quality scores were associated with lower risk of the individual frailty criteria fatigue, reduced resistance, reduced aerobic capacity, and weight loss. Lower consumption of red and processed meat, a lower sodium intake, a higher ratio of monounsaturated to saturated fat, vegetables, and moderate alcohol intake were components of the diet quality scores independently associated with lower risk of frailty. CONCLUSIONS: Adherence to a healthy diet, as defined by the AMED, DASH, and AHEI-2010 scores, was associated with reduced risk of frailty in older women.

Water-soluble calix[4]resorcinarenes as chiral NMR solvating agents for bicyclic aromatic compounds.

Water-soluble calix[4]resorcinarenes with proline, 3-hydroxyproline, and 4-hydroxyproline substituent groups are evaluated as chiral NMR solvating agents on a series of bicyclic aromatic compounds with naphthyl, indole, dihydroindole, and indane rings. The substrates interact with the calixresorcinarene through insertion of the aromatic ring into the cavity. Most of the substrates are analyzed as cationic species, although one anionic species is analyzed. All of the substrates exhibit enantiomeric discrimination in the 1H-NMR spectrum with one or more of the calixresorcinarenes. In most cases, the hydroxyproline derivatives are more effective at causing enantiodifferentiation than the corresponding proline derivative. Presumably, the hydroxyl group on the proline moieties is involved in interactions with the substituent groups of the substrate that are important in creating chiral recognition. The enantiomeric discrimination in the 1H-NMR spectrum is large enough for many resonances to permit the analysis of enantiomeric purity.