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.

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.

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).

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.

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.

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.

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.

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.

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.

Quadriceps Strength and Volitional Activation After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

CONTEXT:: Quadriceps function is a significant contributor to knee joint health that is influenced by central and peripheral factors, especially after anterior cruciate ligament reconstruction (ACLR). OBJECTIVE:: To assess differences of unilateral quadriceps isometric strength and activation between the involved limb and contralateral limb of individuals with ACLR and healthy controls. DATA SOURCES:: Web of Science, SportDISCUS, PubMed, CINAHL, and the Cochrane Database were all used during the search. STUDY SELECTION:: A total of 2024 studies were reviewed. Twenty-eight studies including individuals with a unilateral history of ACLR, isometric knee extension strength normalized to body mass, and quadriceps activation measured by central activation ratios (CARs) through a superimposed burst technique were identified for meta-analysis. The methodological quality of relevant articles was assessed using a modified Downs and Black scale. Results of methodological quality assessment ranged from low to high quality (low, n = 10; moderate, n = 8; high, n = 10). STUDY DESIGN:: Meta-analysis. LEVEL OF EVIDENCE:: Level 2. DATA EXTRACTION:: Means, standard deviations, and sample sizes were extracted from articles, and magnitude of between-limb and between-group differences were evaluated using a random-effects model meta-analysis approach to calculate combined pooled effect sizes (ESs) and 95% CIs. ESs were classified as weak ( d < 0.19), small ( d = 0.20-0.49), moderate ( d = 0.50-0.79), or large ( d > 0.80). RESULTS:: The involved limb of individuals with ACLR displayed lower knee extension strength compared with the contralateral limb (ES, -0.78; lower bound [LB], -0.99; upper bound [UB], -0.58) and healthy controls (ES, -0.76; LB, -0.98; UB, -0.53). The involved limb displayed a lower CAR compared with healthy controls (ES, -0.84; LB, -1.18; UB, -0.50) but not compared with the contralateral limb (ES, -0.15; LB, -0.37; UB, 0.07). The ACLR contralateral limb displayed a lower CAR (ES, -0.73; LB, -1.39; UB, -0.07) compared with healthy control limbs but similar knee extension strength (ES, -0.24; LB, -0.68; UB, -0.19). CONCLUSION:: Individuals with ACLR have bilateral CAR deficits and involved limb strength deficits that persist years after surgery. Deficits in quadriceps function may have meaningful implications for patient-reported and objective outcomes, risk of reinjury, and long-term joint health after ACLR.

Metabolites Associated With the Risk of Incident Venous Thromboembolism: A Metabolomic Analysis.

Background Venous thromboembolism ( VTE ) is a complex thrombotic disorder that constitutes a major source of mortality and morbidity. To improve understanding of the cause of VTE , we conducted a metabolomic analysis in a case-control study including 240 incident VTE cases and 6963 controls nested within 3 large prospective population-based cohorts, the Nurses' Health Study, the Nurses' Health Study II , and the Health Professionals Follow-Up Study. Methods and Results For each individual, we measured 211 metabolites and collected detailed information on lifestyle factors. We performed logistic regression and enrichment analysis to identify metabolites and biological categories associated with incident VTE risk, accounting for key confounders, such as age, sex, smoking, alcohol consumption, body mass index, and comorbid diseases (eg, cancers). We performed analyses of all VTEs and separate analyses of pulmonary embolism. Using the basic model controlling for age, sex, and primary disease, we identified 60 nominally significant VTE - or pulmonary embolism-associated metabolites ( P<0.05). These metabolites were enriched for diacylglycerols ( Ppermutation<0.05). However, after controlling for multiple testing, only 1 metabolite (C5 carnitine; odds ratio, 1.25; 95% confidence interval, 1.10-1.41; Pcorrected=0.03) remained significantly associated with VTE . After further adjustment for body mass index, no metabolites were significantly associated with disease after accounting for multiple testing, and no metabolite classes were enriched for nominally significant associations. Conclusions Although our findings suggest that circulating metabolites may influence the risk of incident VTE , the associations we observed were confounded by body mass index. Larger studies involving additional individuals and with broader metabolomics coverage are needed to confirm our findings.

Adiposity throughout the life course and risk of venous thromboembolism.

OBJECTIVE: Adult body mass index (BMI) is strongly associated with venous thromboembolism (VTE), however whether earlier-life adiposity or other measures of adult adiposity are associated with VTE risk remains largely unknown. MATERIALS AND METHODS: We evaluated associations of childhood somatotype, BMI in early adulthood, adult adiposity, and change in weight since early adulthood with incident VTE risk over ≥20 years of follow-up among 205,935 participants from Nurses' Health Studies (NHS/NHS II) and Health Professionals Follow-Up Study (HPFS), ages 29-76 at baseline. We estimated multivariable-adjusted hazard ratios for VTE using Cox proportional hazards models. RESULTS AND CONCLUSIONS: Somatotype in childhood and young adulthood BMI were not significantly associated with VTE risk, after accounting for adult BMI. Adult BMI was strongly associated with VTE in all three cohorts (e.g., multivariable-adjusted HRs comparing ≥35 kg/m2 vs. <22.5 kg/m2: NHS:3.03[95% CI: 2.58, 3.56], NHS II:3.82[95% CI: 3.24, 4.51], HPFS:2.81 [95% CI: 2.08, 3.80]; all p-trends < 0.01). Adult waist circumference was associated with greater VTE risk, even after adjusting for adult BMI (all p-trends < 0.01). Increasing weight gain from young adulthood was significantly associated with VTE after adjusting for current BMI among women (HR comparing gain ≥20 kg vs. no change: NHS:1.36[95% CI: 1.13, 1.65], NHS II:1.48[95% CI: 1.17, 1.87]) and not men (HPFS:1.20[95% CI: 0.97, 1.50]). These results indicate that BMI and adiposity are likely more important acutely than cumulatively over time in the etiology and prevention of VTE. Clinically, encouraging weight loss in individuals who are overweight or obese could help reduce VTE risk.

Mediterranean diet and risk of frailty syndrome among women with type 2 diabetes.

Background: Previous research indicates that patients with type 2 diabetes are at higher risk of becoming frail. Emerging evidence also indicates that the Mediterranean diet may prevent frailty in the older population. Objective: The aim of this study was to assess whether a Mediterranean-style diet pattern was associated with lower risk of frailty among older women with diabetes. Design: This was a prospective cohort study in 8970 women aged ≥60 y with type 2 diabetes from the Nurses' Health Study. Adherence to the alternate Mediterranean diet (aMED) score was first measured in 1990 and repeated every 4 y until 2010. Frailty occurrence was ascertained up to 2012 and was defined as having ≥3 of the following 5 criteria from the fatigue, resistance, aerobic, illnesses, loss of weight (FRAIL) scale: Fatigue, low Resistance, low Aerobic capacity, having ≥5 Illnesses, and weight Loss of ≥5%. Those with frailty at baseline were excluded. Results: During follow-up, we identified 569 incident cases of frailty. After adjustment for lifestyle factors and medication use, the HR (95% CI) of frailty was 1 for the lowest quartile of the aMED score, 0.88 (0.71, 1.10) for the second quartile, 0.69 (0.53, 0.88) for the third quartile, and 0.54 (0.42, 0.71) for the highest quartile (P-trend < 0.001). A 2-point (∼1 SD) increase in the aMED score was associated with a 28% (95% CI: 19%, 36%) reduced risk of frailty. The largest reduction in the risk was observed for a higher consumption of vegetables and fruit, as well as for alcohol intake. Conclusions: A Mediterranean-style diet pattern was associated with reduced risk of frailty syndrome in older women with type 2 diabetes.

Social integration and healthy aging among U.S. women.

BACKGROUND: Social integration has been related to risk of chronic diseases and mental health conditions. PURPOSE: We investigated the association between social integration in midlife with subsequent health and well-being in aging. METHODS: We included women from the Nurses' Health Study in the United States, who had no major chronic diseases in 1996 when we assessed social integration, using the Berkman-Syme Social Network Index. We defined healthy aging after 16 years of follow-up, when women ranged from 66 to 91 years, on the basis of survival along with 4 health criteria, assessed in 2012: no history of major chronic disease diagnosis, no self-reported impairment in memory, and no major impairments in physical function or mental health. RESULTS: Of the 41,013 surviving participants in 2012 with information on social integration and health criteria, 6206 (15.1%) were healthy agers (i.e., met all four criteria) and the remaining 34,807 (84.9%) were usual agers. After multivariable adjustment, women who were socially integrated at midlife had modestly better odds (odds ratio = 1.38, 95% confidence interval: 1.23, 1.55) of healthy aging compared to women who were socially isolated. CONCLUSIONS: In this study, we found that women who were more socially integrated were more likely to be healthy agers. The results provide evidence for a longitudinal association between social integration and healthy aging.

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.

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.

Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary Embolism.

Pulmonary embolism (PE) is a common and potentially fatal form of venous thromboembolism that can be challenging to diagnose and manage. PE occurs when there is obstruction of the pulmonary vasculature and is a common cause of morbidity and mortality in the United States. A combination of acquired and inherited factors may contribute to the development of this disease and should be considered, since they have implications for both susceptibility to PE and treatment. Patients with suspected PE should be evaluated efficiently to diagnose and administer therapy as soon as possible, but the presentation of PE is variable and nonspecific so diagnosis is challenging. PE can range from small, asymptomatic blood clots to large emboli that can occlude the pulmonary arteries causing sudden cardiovascular collapse and death. Thus, risk stratification is critical to both the prognosis and management of acute PE. In this review, we discuss the epidemiology, risk factors, pathophysiology, and natural history of PE and deep vein thrombosis.

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.

Adult height, dietary patterns, and healthy aging.

Background: Adult height has shown directionally diverse associations with several age-related disorders, including cardiovascular disease, cancer, decline in cognitive function, and mortality.Objective: We investigated the associations of adult height with healthy aging measured by a full spectrum of health outcomes, including incidence of chronic diseases, memory, physical functioning, and mental health, among populations who have survived to older age, and whether lifestyle factors modified such relations.Design: We included 52,135 women (mean age: 44.2 y) from the Nurses' Health Study without chronic diseases in 1980 and whose health status was available in 2012. Healthy aging was defined as being free of 11 major chronic diseases and having no reported impairment of subjective memory, physical impairment, or mental health limitations.Results: Of all eligible study participants, 6877 (13.2%) were classified as healthy agers. After adjustment for demographic and lifestyle factors, we observed an 8% (95% CI: 6%, 11%) decrease in the odds of healthy aging per SD (0.062 m) increase in height. Compared with the lowest category of height (≤1.57 m), the OR of achieving healthy aging in the highest category (≥1.70 m) was 0.80 (95% CI: 0.73, 0.87; P-trend < 0.001). In addition, we found a significant interaction of height with a prudent dietary pattern in relation to healthy aging (P-interaction = 0.005), and among the individual dietary factors characterizing the prudent dietary pattern, fruit and vegetable intake showed the strongest effect modification (P-interaction = 0.01). The association of greater height with reduced odds of healthy aging appeared to be more evident among women with higher adherence to the prudent dietary pattern rich in vegetable and fruit intake.Conclusions: Greater height was associated with a modest decrease in the likelihood of healthy aging. A prudent diet rich in fruit and vegetables might modify the relation.