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OBJECTIVE: Constipation is highly prevalent in advanced chronic kidney disease (CKD), due in part to dietary (e.g., fiber) restrictions, and is often managed by laxatives; however, the effect of laxative use on kidney function in advanced CKD remains unclear. We aimed to examine the association of laxative use with longitudinal change in estimated glomerular filtration rate (eGFR) in patients with advanced CKD. DESIGN AND METHODS: In a retrospective cohort of 43,622 US veterans transitioning to end-stage renal disease (ESRD) from 2007–2015, we estimated changes in eGFR (slope) by linear mixed-effects models using ≥2 available outpatient eGFR measurements during the 2-year period before transition to ESRD. The association of laxative use with change in eGFR was examined by testing the interaction of time-varying laxative use with time for eGFR slope in the mixed-effects models with adjustment for fixed and time-varying confounders. RESULTS: Laxatives were prescribed in 49.8% of patients during the last 2-year pre-ESRD period. In the crude model, time-varying laxative use was modestly associated with more progressive eGFR decline compared with non-use of laxatives (median [IQI], −7.1 [−11.9, −4.3] vs. −6.8 [−11.6, −4.0] mL/min/1.73 m(2)/year, P

BACKGROUND: Patients with advanced CKD experience increased intestinal potassium excretion. This compensatory mechanism may be enhanced by laxative use; however, little is known about the association of laxative use with risk of dyskalemia in advanced CKD. METHODS: Our study population encompassed 36,116 United States veterans transitioning to ESKD from 2007 to 2015 with greater than or equal to one plasma potassium measurement during the last 1-year period before ESKD transition. Using generalized estimating equations with adjustment for potential confounders, we examined the association of time-varying laxative use with risk of dyskalemia (i.e., hypokalemia [potassium 5.5 mEq/L]) versus normokalemia (3.5–5.5 mEq/L) over the 1-year pre-ESKD period. To avoid potential overestimation of dyskalemia risk, potassium measurements within 7 days following a dyskalemia event were disregarded in the analyses. RESULTS: Over the last 1-year pre-ESKD period, there were 319,219 repeated potassium measurements in the cohort. Of these, 12,787 (4.0%) represented hypokalemia, and 15,842 (5.0%) represented hyperkalemia; the time-averaged potassium measurement was 4.5 mEq/L. After multivariable adjustment, time-varying laxative use (compared with nonuse) was significantly associated with lower risk of hyperkalemia (adjusted odds ratio [aOR], 0.79; 95% confidence interval [95% CI], 0.76 to 0.84) but was not associated with risk of hypokalemia (aOR, 1.01; 95% CI, 0.95 to 1.07). The results were robust to several sensitivity analyses. CONCLUSIONS: Laxative use was independently associated with lower risk of hyperkalemia during the last 1-year pre-ESKD period. Our findings support a putative role of constipation in potassium disarrays and also support (with a careful consideration for the risk-benefit profiles) the therapeutic potential of laxatives in hyperkalemia management in advanced CKD.

Evidence has established obesity as a risk factor for total knee replacement (TKR) due to osteoarthritis. Obesity is a risk factor for TKR. Randomized trials such as Look AHEAD (Action for Health in Diabetes) have shown long-term successful weight loss with an intensive lifestyle intervention (ILI). It is unknown, however, if intentional weight loss can reduce the risk of TKR.Look AHEAD randomized persons aged 45-76 with type 2 diabetes who had overweight or obesity to either an ILI to achieve/maintain 7% weight loss or to standard diabetes support and education (DSE). Reported knee pain was assessed using the Visual Analog Scale and Western Ontario McMaster University Osteoarthritis Index questionnaire in 5125 participants without previous TKR. Cox proportional hazard regression was used to model differences in risk of TKR in relation to randomization group assignment (ILI vs DSE) along with baseline body mass index category and baseline knee pain as potential confounders from baseline through Look AHEAD-Extension.Baseline mean ± SD Western Ontario McMaster University Osteoarthritis Index knee pain scores did not differ by treatment assignment (ILI: 3.6 ± 2.9, DSE: 3.9 ± 3.0, P = .08); as expected due to randomization. During follow up, the 631 (12%) participants who reported having a TKR were more likely to have been heavier (P.001) and older (P.001) at enrollment, but risk of TKR did not differ by treatment group assignment (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.91-1.25, P = .43). Heterogeneity of treatment effect was observed according to baseline knee pain (interaction P = .02). In persons without knee pain at baseline, there was a 29% reduced risk of TKR in ILI compared to DSE (HR 0.71, 95% CI 0.52-0.96). However, in persons with knee pain at baseline, there was no statistically significant association of treatment assignment with respect to subsequent TKR incidence (HR 1.11, 95% CI 0.92-1.33).Findings suggest that intensive lifestyle change including physical activity, dietary restriction and behavioral changes to achieve weight loss for prevention of TKR may be most effective in preventing TKR prior to the development of knee pain.

BACKGROUND: Triple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors. METHODS: A total of 128,623 Black and White women aged 50–79 years from the Women’s Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework. RESULTS: Black women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52–2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors. CONCLUSION: Our study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction.

Since its global emergence in 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused multiple epidemics in the United States. When medical treatments for the virus were still emerging and a vaccine was not yet available, state and local governments sought to limit its spread by enacting various social-distancing interventions, such as school closures and lockdowns; however, the effectiveness of these interventions was unknown. We applied an established, semimechanistic Bayesian hierarchical model of these interventions to the spread of SARS-CoV-2 from Europe to the United States, using case fatalities from February 29, 2020, up to April 25, 2020, when some states began reversing their interventions. We estimated the effects of interventions across all states, contrasted the estimated reproduction numbers before and after lockdown for each state, and contrasted the predicted number of future fatalities with the actual number of fatalities as a check of the model’s validity. Overall, school closures and lockdowns were the only interventions modeled that had a reliable impact on the time-varying reproduction number, and lockdown appears to have played a key role in reducing that number to below 1.0. We conclude that reversal of lockdown without implementation of additional, equally effective interventions will enable continued, sustained transmission of SARS-CoV-2 in the United States.

The relationship between vitamin D and glaucoma is controversial. The objective of this study was to examine women from the Women's Health Initiative (WHI) to determine if there is an association between vitamin D and incident glaucoma in postmenopausal women. We examined the association between dietary vitamin D intake, vitamin D supplements and serum 25 hydroxyvitamin D (25(OH)D) levels and the risk of developing glaucoma. 143,389 postmenopausal women from the WHI including a subset with serum 25(OH) D measurements were examined to determine the association of dietary, supplemental and serum levels of vitamin D to the development of glaucoma. Dietary intakes of vitamin D, use of vitamin D supplements and serum levels of 25(OH) D were predictors examined for the main outcome of incident glaucoma. In multivariable models adjusted for demographic, clinical variables and medication use, dietary vitamin D, vitamin D supplements, total vitamin D intake (diet plus supplements) and serum 25 (OH) D measurements were not significantly associated with incident glaucoma. In the CaD placebo-controlled intervention clinical trial, there was also no association in the active intervention arm with glaucoma. We conclude that dietary vitamin D intake, supplements and serum levels are not significantly related to the risk of developing glaucoma in postmenopausal women.

OBJECTIVE: The clinical benefit of warfarin therapy for thromboprophylaxis after incident atrial fibrillation (AF) diagnosis in late-stage chronic kidney disease (CKD) patients transitioning to dialysis is unknown. The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of AF in late-stage CKD patients transitioning to dialysis. METHODS: In this retrospective cohort analysis, the study population was a national cohort of 22,771 US veterans with incident end stage renal disease (ESRD) who developed incident AF prior to initiating renal replacement therapy. We examined the association of warfarin therapy following the diagnosis of incident AF with ischemic-cerebrovascular accidents (CVA) (ischemic stroke or transient ischemic attack), ischemic-CVA related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event related hospitalizations and post-dialysis all-cause mortality in multivariable adjusted Cox regression analyses adjusting for demographic characteristics and comorbidities. RESULTS: The mean (SD) age of the cohort was 73.5±8.8 years, 13% were African American and the mean CHA2DS2-VASc score was 5.7±2.1. Among overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow up period. The hazard ratios (95% confidence intervals) for ischemic-CVA, bleeding events and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97) compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic-CVA and bleeding event related hospitalizations also. CONCLUSIONS: In late-stage CKD patients transitioning to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events, but lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in advanced CKD patients with incident AF.

Introduction Patients with advanced non–dialysis-dependent chronic kidney disease (NDD-CKD) are prone to potassium (K) imbalances due to reduced kidney function. Both hypo- and hyperkalemia are associated with increased mortality; however, it is unclear if K variability before dialysis initiation is associated with outcomes after dialysis initiation. Methods We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 1, 2007, through March 31, 2015, who had at least 1 K measurement each year over a 3-year period before transition (3-year prelude). For each patient, a linear mixed-effects model was used to regress K over time (in years) over the 3-year prelude to derive K variability (square root of the average squared distance between the observed and estimated K). The main outcomes of interest were 6-month all-cause and cardiovascular mortality after dialysis initiation. Multivariable Cox and Fine-Gray competing risk regression adjusted for 3-year prelude K intercept, K slope (per year), demographics, smoking status, comorbidities, length of hospitalizations, body mass index, vascular access type, medications, average estimated glomerular filtration rate, and number of K measurements over the 3-year prelude were used to assess the association of K variability (expressed as quartiles) with all-cause and cardiovascular mortality, respectively. Results Higher prelude K variability was associated with higher multivariable-adjusted risk of all-cause mortality but not cardiovascular mortality (adjusted hazard/subhazard ratios [95% confidence interval] for highest quartile [vs. lowest] of K variability, 1.14 [1.03–1.25] and 0.99 [0.85–1.16] for all-cause and cardiovascular mortality, respectively). Conclusion Higher K variability is associated with higher all-cause mortality after dialysis initiation., Graphical abstract

BACKGROUND: Angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) improve predialysis outcomes; however, ACEi/ARB are underutilized in patients transitioning to dialysis. We examined the association of different patterns of predialysis ACEi/ARB use with postdialysis survival, and whether potentially modifiable adverse events are associated with lower predialysis ACEi/ARB utilization. METHODS: This was a historic cohort study of 34,676 US veterans with, and 10,690 without ACEi/ARB exposure in the 3-year predialysis period who subsequently transitioned to dialysis between 2007–2014. Associations of different patterns of predialysis ACEi/ARB utilization with postdialysis all-cause mortality and with predialysis acute kidney injury and hyperkalemia events were examined using multivariable adjusted regression analyses. RESULTS: The mean age of the cohort was 70 years, 98% were males and 27% were African Americans. Compared to ACEi/ARB nonuse, continuous ACEi/ARB use was associated with lower postdialysis all-cause mortality (adjusted hazard ratio (aHR); 95% confidence interval [95% CI] 0.87; 0.83–0.92). In analyses modeling the duration of predialysis ACEi/ARB utilization, ACEi/ARB use of 50–74 and ≥75% were associated with lower mortality compared to nonuse (aHR, 95% CI 0.96, 0.92–0.99 and 0.91; 0.88–0.94, respectively), while no increase in postdialysis survival was observed with shorter predialysis ACEi/ARB use. Predialysis acute kidney injury was associated with shorter duration (

BACKGROUND: Adherence to prescribed medications is connected with, but is not a guarantee of, improved disease management and health outcomes. It remains unclear whether underlying health disparities exist among patients adherent to therapy and whether differences in outcomes vary by race and residential areas of the country. OBJECTIVE: To determine the extent of racial and regional variation in outcomes within 5 years of oral antidiabetic drug initiation among veterans adherent to therapy. DESIGN: Retrospective cohort study of 83,265 US Veterans Health Administration data, 2002–2014 PATIENTS: US veterans with uncomplicated diabetes and taking oral antidiabetic agents MAIN MEASURES: Veterans initially adherent to oral antidiabetic therapy were followed for up to 5 years, and comparisons focused on differences between non-Hispanic White and non-Hispanic Black veterans across geographic region and residential type (urban or rural). Outcomes included composite cardiovascular events, composite cerebrovascular events, or all-cause mortality using Poisson and adjusted Cox proportional hazards models. KEY RESULTS: Cardiovascular event and all-cause mortality rates differed by race and region, while urban/rural differences were evident for cerebrovascular events and all-cause mortality. For non-Hispanic Blacks, the mortality rate was half that compared to non-Hispanic Whites (6.5 [95% CI 5.8–7.2] versus 13.3 [95% CI 12.9–13.8], p

Background Diabetes remains a growing public health threat but evidence supports the role that pharmacists can play in improving diabetes medication use and outcomes. To improve the quality of care, the Veterans Health Administration has widely adopted care models that integrate clinical pharmacists, but more data are needed to interpret the impact of these services. Our objective was to assess clinical pharmacy services’ impact on outcomes and oral antidiabetic medication (OAD) use among veterans with uncontrolled diabetes in the first year of therapy. Methods This was a retrospective cohort analysis using the Veterans Affairs (VA) Corporate Data Warehouse to identify the first diagnosis of and initiation of OAD therapy for uncomplicated, uncontrolled diabetes (A1C > 7.0%) during 2002–2014. Receipt of clinical pharmacy services was identified using codes within VA electronic health records, and clinical values were obtained at or near the initial fill date and 365 days later. Use of OADs was assessed by proportion of days covered (PDC) for one year following the first filled prescription. Veterans having received clinical pharmacy services were matched 1:1 to those having not seen a clinical pharmacist in the first year of therapy, and generalized linear models assessed changes and differences in outcomes. Results The analysis included 5749 patients in each cohort. On average, patients saw a clinical pharmacist 2.5 times throughout the first year of OAD therapy. Adherence to OAD medications was higher in veterans having seen a pharmacist (84.3% vs. 82.4%, p

Medication nonadherence is a prevalent public health issue, particularly among patients with diabetes mellitus (DM), and negatively affects health outcomes. Because of the prevalence of DM among U.S. veterans, it is crucial to understand how well these patients adhere to oral antidiabetic (OAD) medication and whether certain subgroups are more likely to be nonadherent.To assess initial OAD medication use among veterans with uncomplicated DM and determine factors associated with adherence in the first 2 years of treatment.This was a retrospective cohort study using data from the Veterans Affairs (VA) Corporate Data Warehouse from 2002 through 2014. The first diagnosis for uncomplicated DM was determined, and then medication use was assessed following OAD initiation. OAD use was assessed by proportion of days covered (PDC) for the first 2 years of therapy using outpatient VA pharmacy records. Adherence was determined both continuously and categorically, with a PDC of ≥ 80% used to indicate adherence. Logistic regression was used to determine if certain patient characteristics were associated with being adherent to OADs.A total of 148,544 veterans with uncomplicated DM were assessed, most of whom were white, aged ≥ 55 years, and initiated OAD therapy on metformin. A large portion resided in the southern part of the United States. In the first year, PDC averaged 79.2% (SD = 25.9), and 63.2% were adherent to OAD therapy; however, these numbers declined in the second year, when the average PDC was 71.3% (SD = 35.8), and only 59.1% were adherent. Over the course of both years, PDC averaged 75.3% (SD = 28.4), and 50.9% were adherent. The odds of being adherent were higher among older adults and significantly lower among veterans self-identifying as either African American (OR = 0.61; 95% CI = 0.59-0.63), Native American (OR = 0.67; 95% CI = 0.61-0.75), or Hawaiian/Pacific Islander (OR = 0.84; 95% CI = 0.76-0.92) when compared with whites. Veterans who were either divorced/separated (OR = 0.86; 95% CI = 0.83-0.88) or never married (OR = 0.89; 95% CI = 0.86-0.93) also had lower odds of being initially adherent to OAD therapy compared with those who reported being married. Being nonadherent in year 1 was highly predictive of remaining nonadherent in year 2 (OR = 12.8; 95% CI = 12.23-12.94), with only 22.2% nonadherent in the first year (8.2% overall) becoming adherent in the second year of therapy. Across both years, all minorities were less likely to be adherent (compared with whites), and average adherence differed among all geographic regions of the country.Within the first year of OAD therapy, medication adherence was suboptimal among veterans with DM, and second-year results indicate that adherence is likely to decline over time. Future studies should consider deeper regional and subgroup analysis to determine what contributes to variation in medication use in communities across the country.This study was supported by a KL2 Career Development Grant from the University of Tennessee Health Science Center's Institute for Research, Innovation, Synergy and Health Equity and by resources from the U.S. Department of Veterans Affairs. Hung and Kovesdy are employees of the Department of Veterans Affairs. Opinions expressed are those of the study authors and do not necessarily reflect the views of the Department of Veterans Affairs. None of the authors declared significant relevant financial conflicts of interest. Results of this study were presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference on October 3-6, 2016, in National Harbor, Maryland.

Introduction: Abrupt declines in kidney function often occur in patients with advanced chronic kidney disease and may exacerbate the need to initiate dialysis treatment. It is unclear how frequently such events occur in patients transitioning to chronic dialysis therapy, and what outcomes they are associated with. Methods: We examined a national cohort of 23,349 US veterans with incident end-stage renal disease (ESRD) and with available pre-ESRD estimated glomerular filtration rate (eGFR) to identify abrupt declines in kidney function, defined as an unexpected >50% decrease in eGFR at the time of chronic dialysis transition. Associations with all-cause mortality and with renal recovery were examined in Cox proportional hazard and competing risk regression models. Results: A total of 4804 (21%) patients experienced an abrupt decline in kidney function at dialysis transition. Renal recovery occurred in 586 (12.2%) and 297 (1.6%) patients with and without an abrupt decline, respectively (adjusted subhazard ratio: 4.42; 95% confidence interval [CI]: 3.72–5.27; P < 0.001). In the first 6 months after dialysis transition 1178 patients (24.5%) with abrupt decline died (annualized mortality rate 574/1000 patient-years), compared with 2354 deaths (12.7%) in patients without abrupt decline (274 deaths/1000 patient-years). An abrupt decline was associated with 45% higher mortality after multivariable adjustments (hazard ratio: 1.45; 95% CI: 1.33–1.57). Conclusion: Abrupt declines in kidney function are common in patients transitioning to chronic dialysis, and are associated with higher mortality. Patients with abrupt declines also experience a higher rate of renal recovery; hence, careful attention to residual kidney function is warranted in these patients. Keywords: acute kidney injury, chronic kidney disease, dialysis, end-stage renal disease, kidney function recovery, mortality

Objective To evaluate whether a behavioral weight management program combined with a smoking cessation program delivered via interactive technology could prevent postcessation weight gain. Methods Three hundred and thirty young adult smokers, age 18 to 35 years, were randomized to a smoking cessation program alone (comparison group), which included behavioral counseling and nicotine replacement, or to a behavioral weight management program adapted from the Look AHEAD trial plus the same smoking cessation program (intervention group). Results The Treating Adult Smokers at Risk for Weight Gain with Interactive Technology study randomized 164 participants to the comparison group and 166 participants to the intervention group. On average, the participants gained 0.91 kg after 24 months in the trial (comparison group + 1.45 kg and intervention group + 0.32; P = 0.157). The only variable systematically affecting weight change over time was smoking abstinence, in which those who were abstinent, on average, gained 0.14 kg more per month compared with those who continued to smoke (P

Albuminuria is a robust predictor of CKD progression. However, little is known about the associations of changes in albuminuria with the risk of kidney events outside the settings of clinical trials.In a nationwide cohort of 56,946 United States veterans with an eGFR≥60 ml/min per 1.73 mThe mean age was 64 (SD, 10) years old; 97% were men, and 91% were diabetic. There was a nearly linear association between 1-year fold changes in albuminuria and incident CKD. The multivariable-adjusted hazard ratios (95% confidence intervals) of incident CKD associated with more than twofold decrease, 1.25- to twofold decrease, 1.25- to twofold increase, and more than twofold increase (versus1.25-fold decrease to1.25-fold increase) in albuminuria were 0.82 (95% confidence interval, 0.77 to 0.89), 0.93 (95% confidence interval, 0.86 to 1.00), 1.12 (95% confidence interval, 1.05 to 1.20), and 1.29 (95% confidence interval, 1.21 to 1.38), respectively. Qualitatively similar associations were present for rapid eGFR decline (adjusted odds ratios; 95% confidence intervals for corresponding albuminuria changes: adjusted odds ratio, 0.86; 95% confidence interval, 0.78 to 0.94; adjusted odds ratio, 0.98; 95% confidence interval, 0.89 to 1.07; adjusted odds ratio, 1.18; 95% confidence interval, 1.08 to 1.29; and adjusted odds ratio, 1.67; 95% confidence interval, 1.54 and 1.81, respectively).Relative changes in albuminuria over a 1-year interval were linearly associated with subsequent risk of kidney outcomes. Additional studies are warranted to elucidate the underlying mechanisms of the observed associations and test whether active interventions to lower elevated albuminuria can improve kidney outcomes.

Higher SBP visit-to-visit variability (SBPV) has been associated with increased risk of adverse events in patients with chronic kidney disease, but the association of SBPV in advanced nondialysis-dependent chronic kidney disease with mortality after the transition to end-stage renal disease (ESRD) remains unknown. Among 17 729 US veterans transitioning to dialysis between October 2007 and September 2011, we assessed SBPV calculated from the SD of at least three intraindividual outpatient SBP values during the last year prior to dialysis transition (prelude period). Outcomes included factors associated with higher prelude SBPV and post-transition all-cause, cardiovascular, and infection-related mortality, assessed using multivariable linear regression and Cox and competing risk regressions, respectively, adjusted for demographics, comorbidities, medications, cardiovascular medication adherence, SBP, BMI, estimated glomerular filtration rate, and type of vascular access. Modifiable clinical factors associated with higher prelude SBPV included higher SBP, use of antihypertensive medications and erythropoiesis-stimulating agents, inadequate cardiovascular medication adherence, and catheter use. After multivariable adjustment, higher prelude SBPV was significantly associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality [hazard/subhazard ratios (95% confidence interval) for the highest (vs. lowest) quartile of SBPV, 1.08 (1.01–1.16), 1.02 (0.89–1.15), and 1.41 (1.10–1.80) for all-cause, cardiovascular, and infection-related mortality, respectively]. High pre-ESRD SBPV is potentially modifiable and associated with higher all-cause and infection-related mortality following dialysis initiation. Further studies are needed to test whether modification of pre-ESRD SBPV can improve clinical outcomes in incident ESRD patients. http://links.lww.com/HJH/A772

Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown.Observational study.17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years.Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (120 to ≥160mmHg in 10-mmHg increments) and 5 (60 to ≥90mmHg in 10-mmHg increments) categories, respectively, and as continuous measures.Postdialysis all-cause mortality, assessed over different follow-up periods (ie, 3, 3-6, 6-12, and ≥12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access.Mean predialysis SBP and DBP were 141.2±16.1 (SD) and 73.7±10.6mmHg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP140mmHg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP 120, 120 to 130, 130 to 140, 150 to 160, and ≥160 (vs 140-150) mmHg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality.Results cannot be inferred to show causality and may not be generalizable to women or the general US population.Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.

Intussusception is uncommon in children older than 3 years, and use of enema reduction in older children is controversial. We sought to determine whether older children are at greater risk of requiring operative intervention and/or having pathology causing lead points, such that enema reduction should not be attempted.The Pediatric Health Information System database was reviewed from January 1, 2009-June 30, 2014. Patients were followed for 6 months from initial presentation or until bowel resection occurred. Successful enema reduction was defined as having radiologic reduction without additional procedures.A total of 7,412 patients were identified: 6,681 were3 years old, 731 patients were3 years old. In those3 years old, 450 (62%) were treated successfully with enema reduction; the rate of patients with a tumor diagnosis was similar in patients3 years old and patients3 years old (5% vs 6%, P = .07). The rate of a Meckel's diagnosis was greater in patients3 years old (2% vs 14%, P .0001). In patients3 years old, duration of stay between patients who underwent primary operative therapy versus those who underwent operative therapy after enema reduction was similar (4 days vs 4 days, P = .06). Older age was not associated with increased risk of recurrent admission for intussusception (P = .45).Pediatric Health Information System data suggest that enema reduction may be safe and effective for a majority of children even if older than 3 years.

We compared the effectiveness of a ‘stepped care’ approach with increasing treatment intensity (‘Step Care’) to one with repeated treatments (‘Recycle’) among cigarette smokers interested in quitting smoking. Step 1 of the Step Care intervention consisted of a single counseling session, nicotine patch for six weeks and telephonic contact. For smokers not achieving tobacco abstinence 6 months after randomization with Step 1, the intensity of the intervention increased to four counseling sessions, bupropion sustained-release, nine telephone calls and three mailings (Step 2). For those not achieving tobacco abstinence 12 months after randomization, smokers received six behavioral counseling sessions, nicotine patch and nicotine gum, nine telephone calls and three mailings (Step 3). The Recycle participants received one session of health behavior counseling, six weeks of the nicotine patch and a telephone call at each step. 270 cigarette smokers were randomized. At 24 months after randomization using an intention to treat analysis, no statistically significant difference was observed in prolonged smoking abstinence between the Step Care and Recycle condition (16.9% versus 9.4%; adjusted OR = 1.88; 95% CI 0.88–4.01; P =0.10). Additional research is needed to explore whether a stepped care intervention increases long-term smoking abstinence rates compared with repeating the same intervention.

Respiration is controlled by central pattern generating circuits in the brain stem, whose activity can be modulated by inputs from other brain areas to adapt respiration to autonomic and behavioral demands. The cerebellum is known to be part of the neuronal circuitry activated during respiratory challenges, such as hunger for air, but has not been found to be involved in the control of spontaneous, unobstructed breathing (eupnea). Here we applied a measure of intrinsic rhythmicity, the CV2, which evaluates the similarity of subsequent intervals and is thus sensitive to changes in rhythmicity at the temporal resolution of individual respiratory intervals. The variability of intrinsic respiratory rhythmicity was reduced in a mouse model of cerebellar ataxia compared to their healthy littermates. Irrespective of that difference, the average respiratory rate and the average coefficient of variation (CV) were comparable between healthy and ataxic mice. We argue that these findings are consistent with a proposed role of the cerebellum in modulating the duration of individual respiratory intervals, which could serve the purpose of coordinating respiration with other rhythmic orofacial movements, such as fluid licking and swallowing., Summary: The cerebellum was believed to have no role in controlling eupneic respiration. Our findings suggest a cerebellar involvement in the coordination of breathing with other orofacial movements, such as swallowing.

INTRODUCTION: Every year, more than 500,000 US Emergency Department visits are associated with cocaine use. People who use cocaine tend to have a lower incidence of true ST-elevation myocardial infarction (STEMI). OBJECTIVE: To identify the factors associated with true STEMI in patients with cocaine-positive (CPos) findings. METHODS: We retrospectively analyzed 1144 consecutive patients with STEMI between 2008 and 2013. True STEMI was defined as having a culprit lesion on coronary angiogram. Multivariate and univariate analyses were used to identify risk factors and create a predictive model. RESULTS: A total of 64 patients with suspected STEMI were CPos (mean age 53.1 ± 11.2 years; male = 80%). True STEMI was diagnosed in 34 patients. Patients with CPos true STEMI were more likely to be uninsured than those with false STEMI (61.8% vs 34.5%, p = 0.03) and have higher peak troponin levels (21.1 ng/mL vs 2.12 ng/mL, p = < 0.01) with no difference in mean age between the 2 groups (p = 0.24). In multivariate analyses, independent predictors of true STEMI in patients with CPos findings included age older than 65 years (odds ratio [OR] = 19.3, 95% confidence iterval [CI] = 1.2–318.3), lack of health insurance (OR = 4.9, 95% CI = 1.2–19.6), and troponin level higher than 0.05 (OR = 24.0, 95% CI = 2.6–216.8) (all p < 0.05). A multivariate risk score created with a C-statistic of 82% (95% CI = 71–93) significantly improved the identification of patients with true STEMI. CONCLUSION: Among those with suspected STEMI, patients with CPos findings had a higher incidence of false STEMI. Older age, lack of health insurance, and troponin levels outside of defined limits were associated with true STEMI in this group.

Background and aims Constipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, little is known about its association with incident cardiovascular events. Methods In a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke. Results Among 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio [HR], 1.12; 95% CI, 1.11–1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08–1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15–1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs [95% CI], 1.15 [1.13–1.16] and 1.14 [1.12–1.15], respectively), incident CHD (HRs [95% CI], 1.11 [1.07–1.15] and 1.10 [1.05–1.15], respectively) and incident ischemic stroke (HRs [95% CI], 1.19 [1.14–1.23] and 1.21 [1.16–1.26], respectively). Conclusions Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke.

Constipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m2, we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope

Multiple recruitment strategies are often needed to recruit an adequate number of participants, especially hard to reach groups. Technology-based recruitment methods hold promise as a more robust form of reaching and enrolling historically hard to reach young adults. The TARGIT study is a randomized two-arm clinical trial in young adults using interactive technology testing an efficacious proactive telephone Quitline versus the Quitline plus a behavioral weight management intervention focusing on smoking cessation and weight change. All randomized participants in the TARGIT study were required to be a young adult smoker (18–35 years), who reported smoking at least 10 cigarettes per day, had a BMI

Background: To determine the association of vancomycin with acute kidney injury (AKI) in relation to its serum concentration value and to examine the risk of AKI in patients treated with vancomycin when compared with a matched cohort of patients receiving non-glycopeptide antibiotics (linezolid/daptomycin). Methods: From a cohort of > 3 million US veterans with baseline estimated glomerular filtration rate ≥60 mL/min/1.73 m2, we identified 33,527 patients who received either intravenous vancomycin (n = 22,057) or non-glycopeptide antibiotics (linezolid/daptomycin, n = 11,470). We examined the association of the serum trough vancomycin level recorded within the first 48 h of administration with subsequent AKI in all patients treated with vancomycin and association of vancomycin vs. non-glycopeptide antibiotics use with the risk of incident AKI. Results: The overall multivariable adjusted ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptides were 1.1 (1.1–1.2), 1.2 (1–1.4), and 1.4 (1.1–1.7), respectively. When examined in strata divided by vancomycin trough level, the odds of AKI were similar or lower in patients receiving vancomycin compared to non-glycopeptide antibiotics as long as serum vancomycin levels were ≤20 mg/L. However, in patients with serum vancomycin levels > 20 mg/L, the ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptide antibiotics were 1.5 (1.4–1.7), 1.9 (1.5–2.3), and 2.7 (2–3.5), respectively. Conclusions: Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L.

A history of posttraumatic stress disorder (PTSD), if uncontrolled, represents a contraindication for kidney transplantation. However, no previous large study has assessed the association between pretransplant history of PTSD and posttransplantation outcomes. We examined 4479 US veterans who had undergone transplantation. The diagnosis of history of PTSD was based on a validated algorithm. Measured covariates were used to create a matched cohort (n = 560). Associations between pretransplant PTSD and death with functioning graft, all-cause death, and graft loss were examined in survival models. Posttransplant medication nonadherence was assessed using proportion of days covered (PDC). From among 4479 veterans, 282 (6.3%) had a history of PTSD. The mean age ± standard deviation (SD) of the cohort at baseline was 61 ± 11 years, 91% were male, and 66% and 28% of patients were white and African American, respectively. Compared to patients without a history of PTSD, patients with a history of PTSD had a similar risk of death with a functioning graft (subhazard ratio [SHR] 0.97, 95% confidence interval [CI] 0.61-1.54), all-cause death (1.05, 0.69-1.58), and graft loss (1.09, 0.53-2.26). Moreover, there was no difference in immunosuppressive drug PDC in patients with and without a history of PTSD (PDC: 98 ± 4% vs 99 ± 3%, P = .733 for tacrolimus; PDC: 99 ± 4% vs 98 ± 7%, P = .369 for mycophenolic acid). A history of PTSD in US veterans with end-stage renal disease should not on its own preclude a veteran from being considered for transplantation.

PURPOSE: Although ~25% of colorectal cancer or polyps (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. METHODS: We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk associated variant and 2440 controls. We repeated this analysis using an additional 73 CRC/P cases. We also compared the frequency of PDVs in select genes among CRC/P cases with two publicly available data sets. RESULTS: We found a significant enrichment of PDVs in cases versus controls: 20% of cases vs. 11.5% of controls with ≥ 1 PDV (OR=1.9, p=0.01) in the original set of cases. Among the second cohort of CRC/P cases, 18% had a PDV, significantly different from 11.5% (p=0.02). Logistic regression, adjusting for ancestry and multiple testing, indicated association between CRC/P and PDVs in NTHL1 (p=0.0001), BRCA2 (p=0.01) and BRIP1 (p=0.04). However, there was no significant difference in the frequency of PDVs at each of these genes between all 157 CRC/P cases and two publicly available data sets. CONCLUSION: These results suggest an increased presence of PDVs in CRC/P cases and support further investigation of the association of NTHL1, BRCA2 and BRIP1 variation with CRC/P.

Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritiswith an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m(2) or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m(2)) and change in eGFR (

Objective To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. Methods We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. Results Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. Conclusion By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium.

Introduction: Abnormal phosphorus homeostasis develops early in chronic kidney disease (CKD). It is unclear if its correction results in improved clinical outcomes in non–dialysis dependent CKD. Methods: We conducted a randomized controlled, parallel design clinical trial in 120 patients with estimated glomerular filtration rate 15 to 59 ml/min per 1.73 m2 and abnormal phosphorus homeostasis (serum phosphorus >4.6 mg/dl, parathyroid hormone [PTH] >70 pg/ml or tubular reabsorption of phosphorus [TRP]

Purpose Earlier Women’s Health Initiative Dietary Modification trial findings suggested that a low-fat eating pattern may reduce breast cancers with greater mortality. Therefore, as a primary outcome-related analysis from a randomized prevention trial, we examined the long-term influence of this intervention on deaths as a result of and after breast cancer during 8.5 years (median) of dietary intervention and cumulatively for all breast cancers diagnosed during 16.1 years (median) of follow-up. Patients and Methods The trial randomly assigned 48,835 postmenopausal women with normal mammograms and without prior breast cancer from 1993 to 1998 at 40 US clinical centers to a dietary intervention with goals of a reduction of fat intake to 20% of energy and an increased intake of fruits, vegetables, and grains (40%; n = 19,541) or to a usual diet comparison (60%; n = 29,294). Results In the dietary group, fat intake and body weight decreased (all P < .001). During the 8.5-year dietary intervention, with 1,764 incident breast cancers, fewer deaths occurred as a result of breast cancer in the dietary group, which was not statistically significant (27 deaths [0.016% per year] v 61 deaths [0.024% per year]; hazard ratio [HR], 0.67; 95% CI, 0.43 to 1.06; P = .08). During the same period, deaths after breast cancer (n = 134) were significantly reduced (40 deaths [0.025% per year] v 94 deaths [0.038% per year]; HR, 0.65; 95% CI, 0.45 to 0.94; P = .02) by the dietary intervention. During the 16.1-year follow-up, with 3,030 incident breast cancers, deaths after breast cancer also were significantly reduced (234 deaths [0.085% per year] v 443 deaths [0.11% per year]; HR, 0.82; 95% CI, 0.70 to 0.96; P = .01) in the dietary group. Conclusion Compared with a usual diet comparison group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer.

Author(s): Sumida, Keiichi; Diskin, Charles Dyer; Molnar, Miklos Z; Potukuchi, Praveen K; Thomas, Fridtjof; Lu, Jun Ling; Rhee, Connie M; Streja, Elani; Yamagata, Kunihiro; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P | Abstract: BackgroundHemoglobin variability (Hb-var) has been associated with increased mortality both in non-dialysis dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD) patients. However, the impact of Hb-var in advanced NDD-CKD on outcomes after dialysis initiation remains unknown.MethodsAmong 11,872 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 through September 2011, we assessed Hb-var calculated from the residual SD of at least 3 Hb values during the last 6 months before dialysis initiation (prelude period) using within-subject linear regression models, and stratified into quartiles. Outcomes included post-transition all-cause, cardiovascular, and infection-related mortality, assessed in Cox proportional hazards models and adjusted for demographics, comorbidities, length of hospitalization, medications, estimated glomerular filtration rate (eGFR), type of vascular access, Hb parameters (baseline Hb [i.e., intercept] and change in Hb [i.e., slope]), and number of Hb measurements.ResultsHigher prelude Hb-var was associated with use of iron and antiplatelet agents, tunneled dialysis catheter use, higher levels of baseline Hb, change in Hb, eGFR, and serum ferritin. After multivariable adjustment, higher prelude Hb-var was associated with higher post-ESRD all-cause and infection-related mortality, but not cardiovascular mortality (adjusted hazard ratios [95% CI] for the highest [vs. lowest] quartile of Hb-var, 1.10 [1.02-1.19], 1.28 [0.93-1.75], and 0.93 [0.79-1.10], respectively).ConclusionsHigh pre-ESRD Hb-var is associated with higher mortality, particularly from infectious causes rather than cardiovascular causes. Further research is required to clarify the underlying mechanisms and true causal nature of the observed association.

Background Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Methods and Results Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min −1 1.73 m −2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than −5 mL min −1 1.73 m −2 y −1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min −1 1.73 m −2 and in patients without HF were 59±14 years and 84±16 mL min −1 1.73 m −2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. Conclusions HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications.

Background and objectives Depression in patients with nondialysis-dependent CKD is often undiagnosed, empirically overlooked, and associated with higher risk of death, progression to ESRD, and hospitalization. However, there is a paucity of evidence on the association between the presence of depression in patients with advanced nondialysis-dependent CKD and post-ESRD mortality, particularly among those in the transition period from late-stage nondialysis-dependent CKD to maintenance dialysis. Design, setting, participants, & measurements From a nation-wide cohort of 45,076 United States veterans who transitioned to ESRD over 4 contemporary years (November of 2007 to September of 2011), we identified 10,454 (23%) patients with a depression diagnosis during the predialysis period. We examined the association of pre-ESRD depression with all-cause mortality after transition to dialysis using Cox proportional hazards models adjusted for sociodemographics, comorbidities, and medications. Results Patients were 72±11 years old (mean±SD) and included 95% men, 66% patients with diabetes, and 23% blacks. The crude mortality rate was similar in patients with depression (289/1000 patient-years; 95% confidence interval, 282 to 297) versus patients without depression (286/1000 patient-years; 95% confidence interval, 282 to 290). Compared with patients without depression, patients with depression had a 6% higher all-cause mortality risk in the adjusted model (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.09). Similar results were found across all selected subgroups as well as in sensitivity analyses using alternate definitions of depression. Conclusion Pre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis.

Background In ST-elevation myocardial infarction (STEMI), acute kidney injury (AKI) may increase subsequent morbidity and mortality. Still, it remains difficult to predict AKI risk in these patients. We sought to 1) determine the frequency and clinical outcomes of AKI and, 2) develop, validate and compare a web-based tool for predicting AKI. Methods & findings In a racially diverse series of 1144 consecutive STEMI patients, Stage 1 or greater AKI occurred in 12.9% and was severe (Stage 2-3) in 2.9%. AKI was associated with increased mortality (5.7-fold, unadjusted) and hospital stay (2.5-fold). AKI was associated with systolic dysfunction, increased left ventricular end-diastolic pressures, hypotension and intra-aortic balloon counterpulsation. A computational algorithm (UT-AKI) was derived and internally validated. It showed higher sensitivity and improved overall prediction for AKI (area under the curve 0.76) vs. other published indices. Higher UT-AKI scores were associated with more severe AKI, longer hospital stay and greater hospital mortality. Conclusions In a large, racially diverse cohort of STEMI patients, Stage 1 or greater AKI was relatively common and was associated with significant morbidity and mortality. A web-accessible, internally validated tool was developed with improved overall value for predicting AKI. By identifying patients at increased risk, this tool may help physicians tailor post-procedural diagnostic and therapeutic strategies after STEMI to reduce AKI and its associated morbidity and mortality.

Background/Aims: All hemodialysis (HD) patients are generally recommended to create a fistula first; but to create a mature arteriovenous fistula (AVF) can be challenging in elderly individuals. It is unclear if elderly incident HD patients derive a survival benefit from an AVF over an arteriovenous graft (AVG) or a tunneled central venous catheter (TDC). Methods: We examined the association of vascular access type (AVF, AVG, and TDC with and without a maturing AVF/AVG at dialysis transition) at HD initiation with all-cause, cardiovascular (CV), and infection-related mortality in 46,786 US veterans using Cox models with adjustment for confounders. Effect modification by age was examined by examining associations in pre-specified age subgroups (Results: Patients numbering 8,940 (19%) started HD with an AVF, 1,090 (3%) with an AVG, 8,262 (18%) with a TDC and a maturing AVF/AVG and 28,494 (61%) with a TDC without a maturing AVF/AVG. A total of 13,303 all-cause, 4,392 CV, and 1,058 infection-related deaths were observed in the first year after HD transition. Compared to patients with AVF, those with AVG and TDC with and without maturing AVF/AVG had incrementally higher overall risk of all-cause mortality and CV mortality. Only TDC use was associated with higher infection-associated mortality. These associations were not modified by age. Conclusion: Although most of our patients consisted of male veterans and the results may not be generalized to the general population, the use of TDCs is associated with poor outcomes even in the most elderly incident HD patients.

Background: Mortality in the immediate post-hemodialysis transition period is extremely high. Many end-stage renal disease (ESRD) patients in the US start dialysis in an inpatient setting, but the characteristics of patients starting dialysis as inpatients, and the association of inpatient hemodialysis transition with mortality remain unclear. Methods: We examined 48,261 US veterans who transitioned to hemodialysis between October 2007 and September 2011. Associations of inpatient hemodialysis starting with all-cause mortality were examined in Cox proportional hazard models, with adjustments for demographics, comorbidities, vascular access type, pre-dialysis nephrology care and medication use, and last pre-ESRD estimated glomerular filtration rate and hemoglobin. Results: A total of 22,338 (46.3%) patients received the first hemodialysis treatment in an inpatient setting. Inpatient hemodialysis transition was associated with older age, presence of a tunneled catheter, higher comorbidity burden, and lack of pre-dialysis nephrology care. A total of 8,674 patients died (mortality rate 405/1,000 patient-years, 95% CI 397-413) during the first 6 months after transition to hemodialysis. The starting of inpatient vs. outpatient hemodialysis was associated with significantly higher crude all-cause mortality, but this association was attenuated after multivariable adjustments. Conclusions: Transition to hemodialysis in an inpatient setting is more common in older and sicker individuals, and in patients without pre-dialysis nephrology care and those who used a catheter for vascular access. Future studies are needed to determine if a higher proportion of patients could start hemodialysis treatment in outpatient clinics, through interventions targeting modifiable risk factors such as timely vascular access placement or earlier nephrology referrals.

Author(s): Sumida, Keiichi; Molnar, Miklos Z; Potukuchi, Praveen K; Thomas, Fridtjof; Lu, Jun Ling; Ravel, Vanessa A; Soohoo, Melissa; Rhee, Connie M; Streja, Elani; Yamagata, Kunihiro; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P | Abstract: BackgroundPrior studies have suggested that arteriovenous fistula (AVF) or graft (AVG) creation may be associated with slowing of estimated glomerular filtration rate (eGFR) decline. It is unclear if this is attributable to the physiological benefits of a mature access on systemic circulation versus confounding factors.MethodsWe examined a nationwide cohort of 3026 US veterans with advanced chronic kidney disease (CKD) transitioning to dialysis between 2007 and 2011 who had a pre-dialysis AVF/AVG and had at least three outpatient eGFR measurements both before and after AVF/AVG creation. Slopes of eGFR were estimated using mixed-effects models adjusted for fixed and time-dependent confounders, and compared separately for the pre- and post-AVF/AVG period overall and in patients stratified by AVF/AVG maturation. In all, 3514 patients without AVF/AVG who started dialysis with a catheter served as comparators, using an arbitrary 6-month index date before dialysis initiation to assess change in eGFR slopes.ResultsOf the 3026 patients with AVF/AVG (mean age 67 years, 98% male, 75% diabetic), 71% had a mature AVF/AVG at dialysis initiation. eGFR decline accelerated in the last 6 months prior to dialysis in patients with a catheter (median, from -6.0 to -16.3 mL/min/1.73 m2/year, P l 0.001), while a significant deceleration of eGFR decline was seen after vascular access creation in those with AVF/AVG (median, from -5.6 to -4.1 mL/min/1.73 m2/year, P l 0.001). Findings were independent of AVF/AVG maturation status and were robust in adjusted models.ConclusionsThe creation of pre-dialysis AVF/AVG appears to be associated with eGFR slope deceleration and, consequently, may delay the onset of dialysis initiation in advanced CKD patients.

Importance Previous studies have suggested an association between cataract surgery and decreased risk for all-cause mortality potentially through a mechanism of improved health status and functional independence, but the association between cataract surgery and cause-specific mortality has not been previously studied and is not well understood. Objective To examine the association between cataract surgery and total and cause-specific mortality in older women with cataract. Design, Setting, and Participants This prospective cohort study included nationwide data collected from the Women’s Health Initiative (WHI) clinical trial and observational study linked with the Medicare claims database. Participants in the present study were 65 years or older with a diagnosis of cataract in the linked Medicare claims database. The WHI data were collected from January 1, 1993, through December 31, 2015. Data were analyzed for the present study from July 1, 2014, through September 1, 2017. Exposures Cataract surgery as determined by Medicare claims codes. Main Outcomes and Measures The outcomes of interest included all-cause mortality and mortality attributed to vascular, cancer, accidental, neurologic, pulmonary, and infectious causes. Mortality rates were compared by cataract surgery status using the log-rank test and Cox regression models with time-varying covariate cataract surgery status adjusting for demographics, systemic and ocular comorbidities, smoking, alcohol use, body mass index, and physical activity. Results A total of 74 044 women with cataract in the WHI included 41 735 who underwent cataract surgery. Mean (SD) age was 70.5 (4.6) years; the most common ethnicity was white (64 430 [87.0%]), followed by black (5293 [7.1%]) and Hispanic (1723 [2.3%]). The mortality rate was 2.56 per 100 person-years in the cataract surgery group and 1.45 per 100 person-years in the cataract diagnosis group. In covariate-adjusted Cox models, cataract surgery was associated with higher all-cause mortality (adjusted hazards ratio [AHR], 1.07; 95% CI, 1.02-1.11) as well as higher mortality specific to vascular (AHR, 1.36; 95% CI, 1.26-1.46), cancer (AHR, 1.27; 95% CI, 1.18-1.38), accidental (AHR, 1.36; 95% CI, 1.05-1.76), pulmonary (AHR, 1.96; 95% CI, 1.62-2.37), and infectious (AHR, 1.37; 95% CI, 1.14-1.65) diseases. Neurologic death causes were not associated with cataract surgery (AHR, 0.98; 95% CI, 0.83-1.17) Conclusions and Relevance In older women with cataract in the WHI, cataract surgery was associated with higher risk for total and cause-specific mortality (except for neurologic causes). Further study of the interplay of cataract surgery, systemic disease, disease-related mortality, and the best timing of when to undergo cataract surgery would be informative for improved patient care.

Objective To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation. Patients and Methods In this retrospective cohort study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre–end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders. Results Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than −10, −10 to less than −5, −5 to 2 per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17). Conclusion Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis cases.

Introduction: Among 48,835 postmenopausal women randomized in the Women's Health Initiative Dietary Modification (WHI DM) primary prevention trial, 1,767 women were diagnosed with breast cancer during the 8.3 years of dietary intervention. While differences were not statistically significant, there were fewer breast cancers diagnosed in the low fat dietary group women (HR 0.92 95% CI 0.84-1.01, P=0.09) with somewhat lower breast cancer mortality (HR 0.77 95% CI 0.48-1.22) than seen in control group women (JAMA 2006; 295:629). These findings were recently updated, and after 10.9 years (mean) post-diagnosis follow-up, breast cancer overall survival among these 1,767 women measured from diagnosis was greater in the dietary group (10 year survival, 82% vs 78%, 168 (2.24%) versus 319 (2.71%) deaths; HR 0.80 95% CI 0.66-0.97, P=0.02) (AACR Annual Meeting 2016, abstract CT0433, Clinical Trials Plenary Session). We now report low-fat dietary pattern influence on breast cancer overall survival in subgroups defined by breast cancer characteristics. Methods: The WHI DM trial, conducted at 40 US clinical centers, from1993-1998 enrolled 48,835 postmenopausal women, aged 50-79, without prior breast cancer, with normal mammogram and dietary fat intake >32% of total energy. Participants were randomly assigned to a dietary intervention group (40%, n=19,541) with goals of fat intake reduction to 20% of energy and increased fruits, vegetables and grain intake, or a usual diet control group (60%, n=29,294). As previously reported, the dietary modification program reduced fat intake, increased fruit, vegetable and grain intake and was associated with modest weight loss (all P< 0.001). The current secondary analysis outcome is breast cancer overall survival in subgroups defined by breast cancer characteristics for cases diagnosed during the dietary intervention period. Because of possible selection prior to breast cancer diagnosis, these analyses do not compare randomized outcomes. Therefore, careful attention is paid to control of risk factors for breast cancer in the analysis. Results: The examined subgroups included histology (ductal, lobular, other), estrogen receptor (ER) status (positive vs. negative by local laboratory), progesterone receptor (PR) status, HER2 status, triple negative (yes/no), stage (local, regional or distant), grade (well, moderately, poorly differentiated), tumor size (=2 cm), and nodal involvement (none, 1-3, 4+). None of the tests of interaction in subgroups were statistically significant. All subgroup hazard ratios (HR) were less than one except for ER negative cancers, triple negative cancers and those with 4+ positive lymph nodes. The results are suggestive of no influence of the low-fat dietary pattern on triple negative cancers (HR 1.64 95% CI 0.73-3.70 for triple negative vs. HR 0.73 95% CI 0.56-0.95 for other breast cancers, interaction P=0.06). Conclusion: Compared to a usual diet control group, women randomized to a dietary intervention group providing a low-fat dietary pattern had a significantly increased overall survival following a breast cancer diagnosis with the possible exception of those developing triple negative cancers. Citation Format: Chlebowski RT, Aragaki AK, Thomson CA, Anderson G, Manson JE, Simon MS, Rohan TE, Snetselar LG, Lane D, Barrington WE, Vitolins M, Womack C, Qi L, Hou L, Thomas F, Prentice RL. Low-fat dietary pattern and breast cancer overall survival in the women's health initiative dietary modification randomized controlled trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S5-04.

Author(s): Sumida, Keiichi; Molnar, Miklos Z; Potukuchi, Praveen K; Thomas, Fridtjof; Lu, Jun Ling; Obi, Yoshitsugu; Rhee, Connie M; Streja, Elani; Yamagata, Kunihiro; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P | Abstract: BackgroundHigher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation.MethodsAmong 17n732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation.ResultsDuring a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (l66.0 U/L), those in the highest quartile (≥111.1 U/L) had multivariable-adjusted hazard/subhazard ratios (95% confidence interval) of 1.42 (1.34-1.51), 1.43 (1.09-1.88) and 1.39 (1.09-1.78) for all-cause, cardiovascular and infection-related mortality, respectively. The associations remained consistent in various subgroups and after further adjustment for liver enzymes, serum phosphorus and intact parathyroid hormone levels.ConclusionsHigher pre-ESRD serum ALP levels are independently associated with higher post-ESRD mortality risk. Further studies are warranted to determine if interventions that lower pre-ESRD ALP levels reduce mortality in incident dialysis patients.

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or

When data are sparse and/or predictors multicollinear, current implementation of sparse partial least squares (SPLS) does not give estimates for non-selected predictors nor provide a measure of inference. In response, an approach termed “all-possible” SPLS is proposed, which fits a SPLS model for all tuning parameter values across a set grid. Noted is the percentage of time a given predictor is chosen, as well as the average non-zero parameter estimate. Using a “large” number of multicollinear predictors, simulation confirmed variables not associated with the outcome were least likely to be chosen as sparsity increased across the grid of tuning parameters, while the opposite was true for those strongly associated. Lastly, variables with a weak association were chosen more often than those with no association, but less often than those with a strong relationship to the outcome. Similarly, predictors most strongly related to the outcome had the largest average parameter estimate magnitude, followed by those with a weak relationship, followed by those with no relationship. Across two independent studies regarding the relationship between volumetric MRI measures and a cognitive test score, this method confirmed a priori hypotheses about which brain regions would be selected most often and have the largest average parameter estimates. In conclusion, the percentage of time a predictor is chosen is a useful measure for ordering the strength of the relationship between the independent and dependent variables, serving as a form of inference. The average parameter estimates give further insight regarding the direction and strength of association. As a result, all-possible SPLS gives more information than the dichotomous output of traditional SPLS, making it useful when undertaking data exploration and hypothesis generation for a large number of potential predictors.

Background The aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with weight change in kidney transplant recipients and to gain insights into the underlying mechanisms of weight gain. Methodology/Principal Findings A secondary data analysis was done on a subgroup (n = 26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients. Measurements taken included adipose tissue gene expression profiles at time of transplant, baseline and six-month weight, and demographic data. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p

Background There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Conclusions Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules.

Context: The Women's Health Initiative Dietary Modification trial randomized 48,835 postmenopausal women at 40 US clinical centers from 1993 to 1998. With 1,767 incident breast cancers, during 8.3 years (mean) dietary intervention, there were fewer breast cancers in the dietary group (HR 0.92 95% CI 0.84-1.01, P = 0.09) with somewhat fewer deaths from breast cancer (HR 0.77 95% CI 0.48-1.22), but no apparent post-intervention influence (JAMA 2006; 295:629; Cancer Epi Bio Prev 2014; 23:2924). These findings suggested dietary intervention may reduce breast cancers associated with greater mortality. New information on breast cancer mortality is analyzed here. Objective: To examine low-fat dietary pattern influence on breast cancer mortality for cases diagnosed during the dietary intervention period. Design and Setting: Secondary analyses from a randomized controlled dietary modification trial. Participants: 48,835 postmenopausal women, 50 to 79 years old, with no previous breast or colorectal cancer, with dietary fat intake greater than 32% of total energy and with a mammogram not suspicious for cancer at entry. Interventions: Dietary group (40%, n = 19,541) which included nutritionist led group sessions throughout the 8.3 year (mean) dietary intervention. Usual diet control group participants received diet-related education materials (60%, n = 29,294). Main Outcome Measures: Deaths from breast cancer (breast cancer followed by deaths directly attributed to the cancer) and deaths after breast cancer (breast cancer followed by death from any cause) during 8.3 years (mean) dietary intervention including all 48,835 study participants measured from randomization. Secondarily, breast cancer overall survival (survival from diagnosis with death from any cause) for the 1767 breast cancer cases identified during the dietary intervention period and followed through August, 2014. Results: Baseline demographic characteristics and breast cancer risk factors were closely comparable in the two randomization groups as was screening mammography frequency throughout. In the dietary group, fat intake decreased, vegetable, fruit and grain consumption increased and body weight was modestly reduced (all P cases; HR 0.65 95% CI 0.45-0.94, P = 0.02). Breast cancer overall survival, among the 1,767 breast cancer cases, after 10.9 years (mean) post-diagnosis follow-up, was greater in the dietary group (10 year survival, 82% vs 78%, HR 0.80 95% CI 0.66-0.97, P = 0.02). Temporal trends for dietary modification influence on breast cancer overall survival identified more favorable effect during dietary intervention then post-intervention (interaction P = 0.02). Causes of death (available for 400 of 487 breast cancer cases) included breast cancer (41%, 165 deaths), other cancer (17%, 67 deaths), and cardiovascular disease (16%, 64 deaths, HR 0.45 95% CI 0.25-0.81 for dietary influence). Conclusion: Compared to a usual diet control group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer. This reduction is due, in part, to better survival following breast cancer diagnosis. Citation Format: Rowan T. Chlebowski, Aaron K. Aragaki, Garnet L. Anderson, Cynthia A. Thomson, Joanne E. Manson, Michael S. Simon, Barbara V. Howard, Thomas E. Rohan, Linda Snetselaar, Dorothy Lane, Wendy E. Barrington, Mara Z. Vitolilns, Catherine Womack, LiHong Qi, Lifang Hou, Fridtjof Thomas, Ross L. Prentice. Low-fat dietary pattern and breast cancer mortality in the Women's Health Initiative (WHI) randomized trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT043.

Importance Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. Objective To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. Design, Setting, and Participants Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women’s Health Initiative (WHI) observational study. Participants in the prospective cohort included 93 676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. Main Outcomes and Measures Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. Results Of the 93 676 participants, 90 014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28 718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. Conclusions and Relevance Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women.