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Background: The respiratory quotient (RQ), defined as the ratio of carbon dioxide exhaled to oxygen uptake, reflects substrate utilization when energy is expended. Fat and alcohol have RQ values of approximately 0.7, compared with 1.0 for carbohydrate, and approximately 0.8 for protein. Here, the association between RQ and postmenopausal breast cancer risk is studied.Methods: Paired RQ measurements were obtained, separated by approximately 6 months, for women in the reliability subset of a Women's Health Initiative (WHI) Nutrition and Physical Activity Assessment Study. Linear regression of the average of the paired log RQ assessments on a corresponding log food quotient (FQ) average and other study subject characteristics, including age, body mass index, race, and education, yielded calibration equations for predicting RQ.Results: Calibration equations, using any of food frequency, food record, or dietary recall data, explained an appreciable fraction of measured log RQ variation, and these were used to compute calibrated RQ estimates throughout WHI cohorts. Calibrated RQ estimates using 4-day food record (4DFR) data related inversely (P = 0.004) to (invasive) breast cancer risk in the WHI Dietary Modification trial comparison group, and corresponding RQ estimates using food-frequency data related inversely (P = 0.002) to breast cancer incidence in this cohort combined with the larger WHI observational study.Conclusion: Although preliminary, these analyses suggest a substantially higher postmenopausal breast cancer risk among women having relatively low RQ.Impact: RQ elevation could provide a novel target for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev; 22(12); 2374–83. ©2013 AACR.

Background: Multiple primary cancers account for approximately 16% of all incident cancers in the United States. Although genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC).Methods: As part of the National Human Genome Research Institute (NHGRI) Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort (MEC) and Women's Health Initiative (WHI). Incident MPC (IMPC) cases (n = 1,385) were defined as participants diagnosed with more than one incident cancer after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n = 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the associations between 188 cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false-positive report probability (FPRP) to determine statistical significance.Results: A nicotine dependence–associated and lung cancer variant, CHRNA3 rs578776 [OR, 1.16; 95% confidence interval (CI), 1.05–1.26; P = 0.004], and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR, 1.16; 95% CI, 1.04–1.28; P = 0.005 and OR, 1.13; 95% CI, 1.03–1.23; P = 0.006), were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (P < 0.05) after removing subjects who had lung or breast cancers, respectively (P ≤ 0.046). These associations did not show significant heterogeneity by smoking status (Pheterogeneity ≥ 0.53).Conclusions: Our study has identified rs578776 and rs11249433 as risk variants for IMPC.Impact: These findings may help to identify genetic regions associated with IMPC risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2568–78. ©2014 AACR.

Supplementary Table 1. Summary of Study Design and Case/Control Definitions for participating studies. Supplementary Table 2. Distribution of the incident index and second cancer site among incident multiple primary cancer cases, stratified by study and cancer latency. Supplemental Table 3. Detailed distribution of incident index and second cancer site among incident multiple primary cancer cases for WHI study. Supplemental Table 4. Detailed distribution of incident index and second cancer site among incident multiple primary cancer cases for MEC study. Supplemental Table 5. Frequency and cancer site of IMPC cases with 3 or more cancers. Supplementary Table 6. Meta-analysis of the non-significant associations (p{greater than or equal to}0.05) between 178 risk variants for other cancers and incident multiple primary cancer risk. Supplementary Table 7. Ten SNPsa associated with other cancers and multiple primary cancer risk by race/ethnicityb

PDF file - 59K, The description of studies included in this pooled analysis

Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association.Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors.Results: Current smokers [OR, 1.26; 95% confidence interval (CI), 1.11–1.43] and former smokers (OR, 1.18; 95% CI, 1.09–1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, −0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01–0.30; P = 0.04).Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking.Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology. Cancer Epidemiol Biomarkers Prev; 21(11); 1974–85. ©2012 AACR.

PDF file - 66K, Total Energy Calibration Equation Coefficients from Linear Regression of Log DLW Energy on Log Self-Reported Energy and Personal Characteristics, Using Data from 450 NPAAS Women.

PDF file - 68K, Characteristics of Breast Cancer Cases and Controls in Four-day Food Record (4DFR)-Based Case-Control Analyses, and Food Frequency Questionnaire (FFQ)-Based Cohort Analyses from the Women's Health Initiative.

Supplemental Table 3. Environmental Factors and colorectal cancer: associations by study design

PDF file - 68K, The description of smoking variables included in this analysis

Background: Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene–environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279.Methods: Data on 9,160 cases and 9,280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, postmenopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons.Results: None of the permutation-adjusted P values reached statistical significance.Conclusions: The associations between recently identified genetic susceptibility loci and colorectal cancer are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors.Impact: Results suggest no evidence of strong gene–environment interactions involving the recently identified 16 susceptibility loci for colorectal cancer taken one at a time. Cancer Epidemiol Biomarkers Prev; 23(9); 1824–33. ©2014 AACR.

The current coronavirus disease (COVID-19) pandemic has placed unprecedented strain on underfunded public health resources in the Southeastern United States. The Memphis, TN, metropolitan region has lacked infrastructure for health data exchange. This manuscript describes a multidisciplinary initiative to create a community-focused COVID-19 data registry, the Memphis Pandemic Health Informatics System (MEMPHI-SYS). MEMPHI-SYS leverages test result data updated directly from community-based testing sites, as well as a full complement of public health data sets and knowledge-based informatics. It has been guided by relationships with community stakeholders and is managed alongside the largest publicly funded community-based COVID-19 testing response in the Mid-South. MEMPHI-SYS has supported interactive Web-based analytic resources and informs federally funded COVID-19 outreach directed toward neighborhoods most in need of pandemic support. MEMPHI-SYS provides an instructive case study of how to collaboratively establish the technical scaffolding and human relationships necessary for data-driven, health equity-focused pandemic surveillance, and policy interventions.

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

Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear.To examine the association of initiating uric acid-lowering therapy with the incidence of CKD.This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022.Newly started uric acid-lowering therapy.The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease.A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less.These findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.

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.

Introduction: Patients with advanced non-dialysis-dependent CKD (NDD-CKD) have a reduced ability for maintaining plasma potassium ( K) in normal range. Deviation from normal plasma K ranges is associated with increased mortality; however, the average trajectory of plasma K over time in patients with advanced NDD-CKD and the outcomes associated with plasma K trajectory are unknown. Methods: We identified 34,167 US veterans with advanced NDD-CKD transitioning to dialysis between October 2007 and March 2015 with at least 1 K measurement each year over a 3-year period prior to dialysis transition (3-year prelude). The K trajectory defined as the change in K (slope) per year over the entire 3-year prelude was estimated using linear mixed-effects models. The association between unadjusted (crude) K slope (categorized as stable [−0.09 to 0.09 mEq/L/year], decreasing [≤−0.10 mEq/L/year], and increasing [≥0.10 mEq/L/year]) and time to all-cause and cardiovascular mortality during the 6 months following dialysis initiation was assessed using multivariable-adjusted survival models. Results: The crude and multivariable-adjusted K slopes (mean, 95% CI) over the 3-year prelude were 0.008 (0.0059, 0.0110) and −0.15 mEq/L/year (−0.19, −0.11), respectively. Decreasing K slope was associated with higher multivariable-adjusted risk of all-cause mortality (adjusted hazard ratio [95% CI] vs. stable K slope: 1.08 [1.00–1.17]). No association was observed between K slope and cardiovascular mortality. Discussion/Conclusion: The average intraindividual plasma K trajectory is remarkably stable in patients with advanced NDD-CKD. A decreasing K slope is associated with higher all-cause mortality risk.

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: Patients with advanced chronic kidney disease (CKD) are at a high risk for dyskalemias, which may induce arrhythmias requiring immediate emergent or hospital care. The association of dyskalemias with short-term hospital/emergency room (ER) visit in advanced CKD is understudied. OBJECTIVE: The aim of this study is to assess the association of dyskalemias with short-term hospital/ER visit in an advanced CKD population. METHODS: From among 102,477 US Veterans transitioning to dialysis between 2007-2015, we identified 21,366 patients with 2 pre-dialysis outpatient eGFR 5.5 mEq/L] vs. referent [3.5-5.5 mEq/L] with separate hospital and ER visits within 2 calendar days following each oK value over the one-year follow-up period from the index. We used generalized estimating equations with binary distribution and logit link to model the exposure-outcome relationship adjusted for various confounders. We conducted various subgroup and sensitivity analyses to test the robustness of our results. RESULTS: Over the one-year follow-up, 125,266 oK measurements were observed of which 6.8% and 3.7% were classified as hyper- and hypokalemia, respectively. In the multivariable-adjusted model, both hyperkalemia (adjusted odds ratio [aOR]; 95% confidence interval [CI]: 2.04; 1.88-2.21) and hypokalemia (aOR; 95% CI: 1.66; 1.48-1.86) were associated with a significantly higher odds of hospital visits. Similarly, both hyperkalemia (aOR; 95% CI: 1.83; 1.65-2.03) and hypokalemia (aOR; 95% CI: 1.24; 1.07-1.44) were associated with a significantly higher odds of ER visits. Results were robust to subgroups and sensitivity analyses. CONCLUSIONS: In patients with advanced CKD, dyskalemias are associated with higher risk of hospital/ER visits. Interventions targeted at lowering the risk of dyskalemias might help in reducing the healthcare utilization and associated economic burden amongst patient with advanced CKD experiencing dyskalemias.

Background: The current social and legal landscape is likely to foster the medicinal and recreational use of cannabis. Synthetic cannabinoid use is associated with acute kidney injury (AKI) in case reports; however, the association between natural cannabis use and AKI risk in patients with advanced chronic kidney disease (CKD) is unknown. Materials and Methods: From a nationally representative cohort of 102,477 U.S. veterans transitioning to dialysis between 2007 and 2015, we identified 2215 patients with advanced CKD who had undergone urine toxicology (UTOX) tests within a year before dialysis initiation and had inpatient serial serum creatinine levels measured within 7 days after their UTOX test. The exposure of interest was cannabis use compared with no use as ascertained by the UTOX test. We examined the association of this exposure with AKI using logistic regression and inverse probability of treatment weighting with extensive adjustment for potential confounders. Results: The mean age of the overall cohort was 61 years; 97% were males, 51% were African Americans, 97% had hypertension, 76% had hyperlipidemia, and 75% were diabetic. AKI occurred in 56% of the cohort, and in multivariable-adjusted analysis, cannabis use (when compared with no substance use) was not associated with significantly higher odds of AKI (odds ratio 0.85, 95% confidence interval 0.38-1.87; p=0.7). These results were robust to various sensitivity analyses. Conclusions: In this observational study examining patients with advanced CKD, cannabis use was not associated with AKI risk. Additional studies are needed to characterize the impact of cannabis use on risk of kidney disease and injury.

BACKGROUND Incontrovertible predictors of shunt malfunction remain elusive. OBJECTIVE To determine predictors of shunt failure within 30 d of index surgery. METHODS This was a single-center retrospective cohort study from January 2010 through November 2016. Using a ventricular shunt surgery research database, clinical and procedural variables were procured. An "index surgery" was defined as implantation of a new shunt or revision or augmentation of an existing shunt system. The primary outcome was shunt failure of any kind within the first 30 days of index surgery. Bivariate models were created, followed by a final multivariable logistic regression model using a backward-forward selection procedure. RESULTS Our dataset contained 655 unique patients with a total of 1206 operations. The median age for the cohort at the time of first shunt surgery was 4.6 yr (range, 0-28; first and third quartile, .37 and 11.8, respectively). The 30-day failure rates were 12.4% when analyzing the first-index operation only (81/655), and 15.7% when analyzing all-index operations (189/1206). Small or slit ventricles at the time of index surgery and prior ventricular shunt operations were found to be significant covariates in both the "first-index" (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

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.

Introduction: Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. Methods: From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates 2 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K 5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. Results: A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q1–Q3) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. Discussion/Conclusion: In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.

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.

The COVID-19 pandemic is broadly undercutting global health and economies, while disproportionally impacting socially disadvantaged populations. An impactful pandemic surveillance solution must draw from multi-dimensional integration of social determinants of health (SDoH) to contextually inform traditional epidemiological factors. In this article, we describe an Urban Public Health Observatory (UPHO) model which we have put into action in a mid-sized U.S. metropolitan region to provide near real-time analysis and dashboarding of ongoing COVID-19 conditions. Our goal is to illuminate associations between SDoH factors and downstream pandemic health outcomes to inform specific policy decisions and public health planning.

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

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.