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Older adults aged 70 and older who drive have higher crash death rates per mile driven compared to middle aged (35-54 years) adults who drive in the US. Prior studies have found that depression and or antidepressant medication use in older adults are associated with an increase in the vehicular crash rate. Using data from the prospective multi-site AAA Longitudinal Research on Aging Drivers Study, this analysis examined the independent and interdependent associations of self-reported depression and antidepressant use with driving behaviors that can increase motor vehicle crash risk such as hard braking, speeding, and night-time driving in adults over age 65. Of the 2951 participants, 6.4% reported having depression and 21.9% were on an antidepressant medication. Correcting for age, race, gender, and education level, participants on an antidepressant had increased hard braking events (1.22 [1.10-1.34]) but self-reported depression alone was not associated with changes in driving behaviors.

BACKGROUND: Dietary supplement (DS) use is common and increasing among older adults, though much data available on use frequencies are from surveys and performed cross-sectionally. This paper sought to assess the frequency and pattern of dietary supplement use among older adults over time. METHODS: A secondary analysis of data from the AAA LongROAD study, a longitudinal prospective cohort study of older adult drivers, using data from baseline and the first two years of follow up included a total of 2990 drivers aged 65-79 years recruited at five study sites across the US from July 2015 to March 2017. Participants underwent baseline and annual evaluations, which included a brown bag medication review. DS were identified and categorized according to type and key components. Prevalence and pattern of DS use over time and relationship to demographics were measured with frequency and Chi squared analyses. RESULTS: 84% of participants took at least one dietary supplement during the 2-year study period, and 55% of participants continually reported use. DS accounted for approximately 30% of the total pharmacologic-pill burden in all years. Participants who were White non-Hispanic, female, 75-79 years of age at baseline, and on more non-supplement medications took significantly more dietary supplements (P

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

INTRODUCTION: Frailty and low physical performance are modifiable factors and, therefore, targets for interventions aimed at delaying driving cessation (DC). The objective was to determine the impact of frailty and physical performance on DC. METHODS: Multisite prospective cohort of older drivers. The key inclusion criteria are as follows: active driver age 65-79 years, possessing a valid drivers license, without significant cognitive impairment, and driving a 1996 car or a newer model car. Of the 2,990 enrolled participants, 2,986 (99.9%) had at least one frailty or Short Physical Performance Battery (SPPB) measure and were included in this study. In total, 42% of participants were aged 65-69 years, 86% were non-Hispanic white, 53% were female, 63% were married, and 41% had a high degree of education. The Fried Frailty Phenotype and the Expanded Short Physical Performance Battery (SPPB) from the National Health and Aging Trends Study were utilized. At each annual visit, DC was assessed by the participant notifying the study team or self-reporting after no driving activity for at least 30 days, verified via GPS. Cox proportional hazard models, including time-varying covariates, were used to examine the impact of the SPPB and frailty scores on time to DC. This assessment included examining interactions by sex. RESULTS: Seventy-three participants (2.4%) stopped driving by the end of year 5. Among women with a fair SPPB score, the adjusted hazard ratio (HR) of DC was 0.26 (95% confidence interval (CI) 0.10-0.65) compared to those with a poor SPPB score. For those with a good SPPB score, the adjusted HR of DC had a p-value of

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.

OBJECTIVE: Falls in older adults are associated with increased motor vehicle crash risk, possibly mediated by driving behavior. We examined the relationship of falls and fear of falling (FOF) with subsequent objectively measured driving habits. METHODS: This multi-site, prospective cohort study enrolled 2990 active drivers aged 65-79 (53% female). At enrollment, we assessed falls in the past year and FOF (Short Falls Efficacy Scale-International). Driving outcomes included exposure, avoidance of difficult conditions, and unsafe driving during one-year follow-up, using in-vehicle Global Positioning System devices. RESULTS: Past-year falls were associated with more hard braking events (HBE). High FOF was associated with driving fewer days, miles, and trips, driving nearer home and more HBE. Differences were attenuated and not significant after accounting for health, function, medications and sociodemographics. DISCUSSION: Differences in objectively measured driving habits according to past-year fall history and FOF were largely accounted for by differences in health and medications. Rather than directly affecting driving, falls and FOF may serve as markers for crash risk and reduced community mobility due to age-related changes and poor health.

BACKGROUND: Patients with advanced chronic kidney disease (CKD) are at high risk for dyskalemias, which may induce arrhythmias that require immediate emergent or hospital care. The association of dyskalemias with short-term hospital/emergency room (ER) visits in advanced CKD is understudied. OBJECTIVE: To assess the association of dyskalemias with short-term hospital/ER visits in an advanced CKD population. METHODS: From among 102,477 US veterans transitioning to dialysis from 2007 to 2015, we identified 21,366 patients with 2 predialysis outpatient eGFR < 30 ml/min/1.73m2 90-365 days apart (with the second eGFR serving as the index date) and at least 1 potassium (K) in the baseline period (1 year before index) and 1 outpatient K (oK) in the follow-up (1 year after the index but before dialysis initiation). We examined the association of time-varying hypokalemia (K < 3.5 mEq/L) and hyperkalemia (K > 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 1-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 1-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, hyperkalemia (adjusted odds ratio [aOR] = 2.04; 95% CI = 1.88-2.21) and hypokalemia (aOR = 1.66; 95% CI = 1.48-1.86) were associated with significantly higher odds of hospital visits. Similarly, hyperkalemia (aOR = 1.83; 95% CI = 1.65-2.03) and hypokalemia (aOR = 1.24; 95% CI = 1.07-1.44) were associated with 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 health care utilization and associated economic burden among patients with advanced CKD experiencing dyskalemias. DISCLOSURES: This study was supported by grant 5U01DK102163 from the National Institute of Health (NIH) to Kamyar Kalantar-Zadeh and Csaba P. Kovesdy and by resources from the US Department of Veterans Affairs. The data reported here have been supplied in part by the United States Renal Data System (USRDS). Support for VA/CMS data were provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center (project numbers SDR 02-237 and 98-004). Opinions expressed in this article are those of the authors and do not necessarily represent the opinion of the Department of Veterans Affairs or the funding institution. Kovesdy has received honoraria from Akebia, Ardelyx, Astra Zeneca, Bayer, Boehringer-Ingelheim, Cara Therapeutics, Reata, and Tricida unrelated to this study. Kalantar-Zadeh has received honoraria and/or support from Abbott, Abbvie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, American Society of Nephrology, Astra-Zeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hofstra Medical School, International Federation of Kidney Foundations, International Society of Hemodialysis, International Society of Renal Nutrition & Metabolism, Japanese Society of Dialysis Therapy, Hospira, Kabi, Keryx, Kissei, Novartis, OPKO, National Institutes of Health, National Kidney Foundations, Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, Veterans Affairs, Vifor, UpToDate, and ZS-Pharma, unrelated to this study. Gatwood has received research support from AstraZeneca, Merck & Co., and GlaxoSmithKline unrelated to this study. Obi has received research support from Relypsa/Vifor Pharma Inc. The remaining authors declare that they have no relevant financial interests.

IntroductionPatients 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.MethodsWe 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.ResultsThe 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/conclusionThe 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.

IntroductionHypo- 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.MethodsFrom among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates 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.ResultsA 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/conclusionIn 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.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) improve predialysis outcomes; however, ACEi/ARB are underused 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 use. 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 and 2014. Associations of different patterns of predialysis ACEi/ARB use 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 use, ACEi/ARB use of 50%-74% and ≥75% were associated with lower mortality compared to nonuse (adjusted hazard ratio, 95% confidence interval 0.96, 0.92-0.99 and 0.91; 0.88-0.94, respectively), whereas no increase in postdialysis survival was observed with shorter predialysis ACEi/ARB use. Predialysis acute kidney injury was associated with shorter duration (

BACKGROUND AND OBJECTIVES: Balancing both driver mobility and safety is important for the well-being of older adults. However, research on the association of physical function with these 2 driving outcomes has yielded inconsistent findings. This study examined whether physical functioning of older drivers, as measured by the Short Physical Performance Battery (SPPB), is associated with either driving space or crash involvement. METHODS: Using cross-sectional data of active drivers aged 65-79 years from the AAA Longitudinal Research on Aging Drivers (LongROAD) study (n = 2,990), we used multivariate log-binomial and logistic regressions to estimate the associations of the SPPB with either self-reported restricted driving space in the prior 3 months or any crashes in the past year. Interaction with gender was assessed using likelihood ratio tests. RESULTS: After adjustment, older drivers with higher SPPB scores (higher physical functioning) had lower prevalence of restricted driving space (8-10 vs. 0-7, prevalence ratio [PR] = 0.88, 95% confidence interval [CI]: 0.78-0.99; 11-12 vs. 0-7, PR = 0.78, 95% CI: 0.61-0.99). Fair (8-10), but not good (11-12), scores were significantly associated with reduced crash involvement (8-10 vs. 0-7, odds ratio [OR] = 0.71, 95% CI: 0.60-0.84). Gender was not a significant effect modifier. DISCUSSION AND IMPLICATIONS: This study provides evidence that higher physical functioning is associated with better driving mobility and safety and that the SPPB may be useful for identifying at-risk drivers. Further research is needed to understand physical functionings longitudinal effects and the SPPBs role in older driver intervention programs.

BACKGROUND: Opioid medications are important therapeutic options to mitigate the harmful effects of pain but can also impair driving ability. We sought to explore opioid use, pain levels, and driving experiences among older drivers. METHODS: Cognitively intact drivers ages 65 to 79 years were recruited for the multisite AAA Longitudinal Research on Aging Drivers (LongROAD) study (n = 2990). This cross-sectional analysis used data from the baseline questionnaire and brown-bag medication review. RESULTS: Among LongROAD participants (47% male, 88% white, 41% aged 65 to 69 years), 169 (5.7%) reported currently taking an opioid, with a median daily dose of 20 morphine milligram equivalents. Participants did not differ significantly in opioid use by age, gender, race, or ethnicity (P > .05). After adjustment for age, gender, race and ethnicity, participants who were taking opioids (vs not) were significantly more likely to report self-regulated driving reduction and reduced driving ability. However, these effects became nonsignificant when hospitalization, impaired physical function and other factors associated with opioid use were controlled. CONCLUSIONS: In this study from a large, geographically diverse sample of older adults, there was an association between opioid use and several self-reported measures of driving behavior and ability. However, future work should clarify the effects on driving of opioid use from the effects of the painful medical conditions for which the opioids are being taken. Clinicians should continue to discuss the risks and benefits of opioid medications with patients, including risks related to driving safety.

INTRODUCTION: Little is known about the effect of posttransplant opioid use on adherence to immunosuppressant therapy (IST) among adult renal transplant recipients (RTRs). OBJECTIVE: The aim of this study was to examine the relationship between opioid use and IST adherence among adult RTRs during the first year posttransplant. METHODS: Longitudinal data were analyzed from a retrospective cohort study examining US veterans undergoing renal transplant from October 1, 2007, through March 31, 2015. Data were collected from the US Renal Data System, Centers for Medicare and Medicaid Services Data (Medicare Part D), and Veterans Affairs pharmacy records. Dose of opioid prescriptions was collected and divided based on annual morphine milligram equivalent within a year of transplant. Proportion of days covered of greater than or equal to 80% indicated adherence to tacrolimus. Unadjusted and multivariable-adjusted logistic regression analyses were performed. RESULTS: A study population of 1,229 RTRs included 258 with no opioid use, while 971 opioid users were identified within the first year after transplantation. Compared to RTRs without opioid usage, RTRs with opioid usage had a lower probability of being adherent to tacrolimus in unadjusted logistic regression (odds ratio [OR] (95% confidence interval [CI]): 0.22 [0.07-0.72]) and adjusted logistic regression (OR [95% CI]: 0.11 [0.03-0.44]). These patterns generally remained consistent in unadjusted and adjusted main and sensitivity analyses. CONCLUSIONS: Findings indicate RTRs who use prescription opioids during the first year posttransplant, regardless of the dosage/amount, are less likely to be adherent to tacrolimus. Future studies are needed to better understand underlying causes of the association between opioid use and tacrolimus nonadherence.

IntroductionLittle is known about the effect of posttransplant opioid use on adherence to immunosuppressant therapy (IST) among adult renal transplant recipients (RTRs).ObjectiveThe aim of this study was to examine the relationship between opioid use and IST adherence among adult RTRs during the first year posttransplant.MethodsLongitudinal data were analyzed from a retrospective cohort study examining US veterans undergoing renal transplant from October 1, 2007, through March 31, 2015. Data were collected from the US Renal Data System, Centers for Medicare and Medicaid Services Data (Medicare Part D), and Veterans Affairs pharmacy records. Dose of opioid prescriptions was collected and divided based on annual morphine milligram equivalent within a year of transplant. Proportion of days covered of greater than or equal to 80% indicated adherence to tacrolimus. Unadjusted and multivariable-adjusted logistic regression analyses were performed.ResultsA study population of 1,229 RTRs included 258 with no opioid use, while 971 opioid users were identified within the first year after transplantation. Compared to RTRs without opioid usage, RTRs with opioid usage had a lower probability of being adherent to tacrolimus in unadjusted logistic regression (odds ratio [OR] (95% confidence interval [CI]): 0.22 [0.07-0.72]) and adjusted logistic regression (OR [95% CI]: 0.11 [0.03-0.44]). These patterns generally remained consistent in unadjusted and adjusted main and sensitivity analyses.ConclusionsFindings indicate RTRs who use prescription opioids during the first year posttransplant, regardless of the dosage/amount, are less likely to be adherent to tacrolimus. Future studies are needed to better understand underlying causes of the association between opioid use and tacrolimus nonadherence.

BackgroundRed blood cell distribution width (RDW) is found to be associated with different types of anemia and has recently been studied as a prognostic marker of mortality in hemodialysis patients. However, the relationship of RDW with mortality and hospitalization rate in peritoneal dialysis (PD) patients is less known.MethodsAmong 14 323 incident PD patients between 2007 and 2011 in the USA, we examined the relationship of baseline and time-varying RDW with the risk of mortality and time to first hospitalization using adjusted Cox models. In addition, we examined the relationship of baseline RDW and hospitalization rate using an adjusted negative-binomial regression model. Sensitivity analyses included competing risk models and subgroup analyses.ResultsThe study population comprised patients 56 ± 16 years of age, including 43% females, 23% African Americans and 62% diabetics, with a mean RDW of 15.3 ± 1.6%. In models adjusted for clinical characteristics and laboratory parameters, RDW exhibited an incremental relationship with the mortality risk, where RDW ≥16.5% had a 40% and 69% higher risk of death in baseline and time-varying analyses, respectively, compared with an RDW of 14.5-15.5%. Moreover, higher baseline RDW ≥16.5% was also associated with a higher risk of time to first hospitalization {hazard ratio 1.22 [95% confidence interval (CI) 1.14-1.29]} and a higher rate of hospitalizations [incidence rate ratio 1.16 (95% CI 1.09-1.23)]. These results were consistent across numerous sensitivity analyses.ConclusionsHigher RDW is associated with a higher risk of mortality and hospitalizations among incident PD patients. Further studies are needed to examine the mechanism behind RDW and adverse outcomes.

BackgroundPrevious studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD.MethodsWe examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses.ResultsA total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P

BACKGROUND: Potentially Inappropriate Medication (PIM) use has been studied in a variety of older adult populations across the world. We sought to examine the prevalence and correlates of PIM use in older drivers. METHODS: We applied the American Geriatrics Society 2015 Beers Criteria to baseline data collected from the brown-bag review of medications for participants of the Longitudinal Research on Aging Drivers (LongROAD) study to examine the prevalence and correlates of PIM use in a geographically diverse, community-dwelling sample of older drivers (n = 2949). Proportions of participants who used one or more PIMs according to the American Geriatrics Society 2015 Beers Criteria, and estimated odds ratios (ORs) and 95% confidence intervals (CIs) of PIM use associated with participant characteristics were calculated. RESULTS: Overall, 18.5% of the older drivers studied used one or more PIM. The most commonly used therapeutic category of PIM was benzodiazepines (accounting for 16.6% of the total PIMs identified), followed by nonbenzodiazepine hypnotics (15.2%), antidepressants (15.2%), and first-generation antihistamines (10.5%). Compared to older drivers on four or fewer medications, the adjusted ORs of PIM use were 2.43 (95% CI 1.68-3.51) for those on 5-7 medications, 4.19 (95% CI 2.95-5.93) for those on 8-11 medications, and 8.01 (95% CI 5.71-11.23) for those on ≥12 medications. Older drivers who were female, white, or living in urban areas were at significantly heightened risk of PIM use. CONCLUSION: About one in five older drivers uses PIMs. Commonly used PIMs are medications known to impair driving ability and increase crash risk. Implementation of evidence-based interventions to reduce PIM use in older drivers may confer both health and safety benefits. TRIAL REGISTRATION: Not applicable.

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.

Background Although studies have shown that statin therapy in patients with non-dialysis-dependent chronic kidney disease was associated with a lower risk of death, this was not observed in dialysis patients newly initiated on statins. It is unclear if statin therapy benefits administered during the predialysis period persist after transitioning to end-stage renal disease. Methods and Results In 47 720 veterans who transitioned to end-stage renal disease during 2007 to 2014, we examined the association of statin therapy use 1 year before transition with posttransition all-cause and cardiovascular mortality and hospitalization incidence rates over the first 12 months of follow-up. Associations were examined using multivariable adjusted Cox proportional hazard models and negative binomial regressions. Sensitivity analyses included propensity score and subgroup analyses. The cohort's mean± SD age was 71±11 years, and the cohort included 4% women, 23% blacks, and 66% diabetics. Over 12 months of follow-up, there were 13 411 deaths, with an incidence rate of 35.3 (95% CI , 34.7-35.8) deaths per 100 person-years. In adjusted models, statin therapy compared with no statin therapy was associated with lower risks of 12-month all-cause (hazard ratio [95% CI], 0.79 [0.76-0.82]) and cardiovascular (hazard ratio [95% CI ], 0.83 [0.78-0.88]) mortality, as well as with a lower rate of hospitalizations (incidence rate ratio [95% CI ], 0.89 [0.87-0.92]) after initiating dialysis. These lower outcome risks persisted across strata of clinical characteristics, and in propensity score analyses. Conclusions Among veterans with non-dialysis-dependent chronic kidney disease, treatment with statin therapy within the 1 year before transitioning to end-stage renal disease is associated with favorable early end-stage renal disease outcomes.

ObjectivesCoronary artery bypass grafting (CABG) is associated with better survival than percutaneous coronary intervention (PCI) in patients with mild-to-moderate chronic kidney disease (CKD) and End-Stage Renal Disease (ESRD). However, the optimal strategy for coronary artery revascularization in advanced CKD patients who transition to ESRD is unclear.MethodsWe examined a contemporary national cohort of 971 US veterans with incident ESRD, who underwent first CABG or PCI up to 5 years prior to dialysis initiation. We examined the association of a history of CABG versus PCI with all-cause mortality following transition to dialysis, using Cox proportional hazards models adjusted for time between procedure and dialysis initiation, socio-demographics, comorbidities and medications.Results582 patients underwent CABG and 389 patients underwent PCI. The mean age was 66±8 years, 99% of patients were male, 79% were white, 19% were African Americans, and 84% were diabetics. The all-cause post-dialysis mortality rates after CABG and PCI were 229/1000 patient-years (PY) [95% CI: 205-256] and 311/1000PY [95% CI: 272-356], respectively. Compared to PCI, patients who underwent CABG had 34% lower risk of death [multivariable adjusted Hazard Ratio (95% CI) 0.66 (0.51-0.86), p=0.002] after initiation of dialysis. Results were similar in all subgroups of patients stratified by age, race, type of intervention, presence/absence of myocardial infarction, congestive heart failure and diabetes.ConclusionCABG in advanced CKD patients was associated lower risk of death after initiation of dialysis compared to PCI.

ObjectiveThe impact of glycemic control in diabetic patients with chronic kidney disease (CKD) who may or may not transition to dialysis remains uncertain, given recent interest in the conservative management of advanced CKD without dialysis therapy, which may benefit from alternative glycemic control strategies.Design and methodsAmong a national cohort of US Veterans, we examined the association of glycemic status, defined by averaged random blood glucose and hemoglobin A1c (HbA1c), with mortality after transitioning to dialysis over 2007-2011 (Transition Cohort) compared with patients in a one-to-one matched cohort of CKD patients with diabetes who did not transition to dialysis (Nontransition Cohort).ResultsAmong 17,121 patients in the Transition Cohort, averaged random glucose ≥200 mg/dL was associated with higher mortality in expanded case-mix analyses (reference: 100-

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.

Background/aimsAnemia is common in patients with advanced chronic kidney disease (CKD). A proportion of patients present with macrocytic anemia, manifested by elevated mean corpuscular volume (MCV), which has been associated with worse outcomes in CKD patients. However, it is unknown whether elevated MCV is associated with higher mortality risk in incident hemodialysis (HD) patients.MethodsThis retrospective observational cohort study examined all-cause, cardiovascular, and infectious mortality associations with both baseline and time-varying MCV in 109,501 incident HD patients using Cox proportional hazards models with 3 levels of hierarchical multivariable adjustment. Odds ratios of high versus low baseline MCV were evaluated using logistic regression.ResultsThe mean age of patients was 65 ± 15 (standard deviation) years and the cohort was 44% female, 58% diabetic, and 31% African American. Higher MCV was associated with older age, female sex, non-Hispanic White race-ethnicity, alcohol consumption, and having a decreased albumin or protein intake. Patients with higher MCV levels (> 98 fL) had a higher all-cause, cardiovascular, and infectious mortality risk in both baseline and time varying models, and across all levels of adjustment. In the fully adjusted models, compared to a reference of MCV 92-< 94 fL, patients with a baseline MCV > 100+ fL had a 28% higher risk of all-cause mortality (hazard ratio [HR] 1.28, 95% CI 1.22-1.34), 27% higher risk of cardiovascular mortality (HR 1.27, 95% CI 1.18-1.36), and 18% higher risk of infectious mortality (HR 1.18, 95% CI 1.02-1.38). Associations of higher MCV with these adverse outcomes persisted across all examined subgroups of clinical characteristics.ConclusionsHigher MCV was associated with higher all-cause, cardiovascular, and infectious mortality in HD patients. Further investigation is necessary to understand the underlying nature of the observed association.

Background: There are approximately 42 million licensed drivers aged 65 years or older in the United States, who face unique age-related risks while driving. While physical activity affects several chronic conditions thought to be associated with motor vehicle crashes (MVCs), it is unclear if increased physical activity leads to fewer MVCs. This study explores whether self-reported vigorous and moderate physical activity is associated with MVCs in the previous year. Methods: Using cross-sectional data from the LongROAD study, a large multisite prospective cohort study of 2990 older adult drivers, we examined variables related to physical activity and performed a multivariate regression analysis to examine the association of physical activity health behaviors with self-reported MVCs. Results: Overall, 41.2% of participants reported vigorous and 69.6% of participants reported moderate exercise at least once per week. Eleven percent of participants reported at least 1 MVC in the previous year. Neither vigorous nor moderate physical activity was significantly associated with self-reported MVCs in the previous year. Select variables that were significantly associated with self-reported MVC included self-reported unsafe driving practices (odds ratio [OR] 1.55, confidence interval [CI] 1.05-2.29), and fall in the past 12 months (OR 1.46, CI 1.14-1.85). Conclusions: We were unable to detect a significant association between self-reported physical activity and MVCs in the past year among this group of older drivers. Use of objective measures of activity may better clarify this relationship.

BACKGROUND: Older adult drivers may experience decreases in driving safety with age or health status change. Discussing driving safety may help them plan for driving restriction and eventual cessation. Here, we sought to examine conversations between older adults and their family members and physicians. METHODS: In this multi-site cross-sectional analysis of baseline data from the AAA Longitudinal Research on Aging Drivers (LongROAD) cohort study, we measured the prevalence and characteristics of family and physician driving discussions. We examined associations between having driving discussions and participant characteristics using multivariate logistic regression. RESULTS: Of 2990 current drivers aged 65 to 79 years (53% female, 85.5% White), only 14.2% reported discussing driving safety with family and 5.5% had discussions with physicians. Men (adjusted OR, 1.32; 95% CI, 1.05 to 1.66) and those with Masters degrees or higher (adjusted OR, 1.65; 95% CI, 1.27 to 2.13) more often had family discussions. Those with at least a Masters degree were also more likely to speak with their physician (adjusted OR, 1.77; 95% CI, 1.17 to 2.68). CONCLUSION: Few older adults had driving safety conversations with their family or physicians. Practical and effective interventions are needed to engage family and physicians in assisting older adults with risk assessment and driving cessation planning to maintain mobility and well-being.

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.

ObjectiveTo examine whether chronic insomnia is associated with an increased risk of adverse renal outcomes and all-cause mortality.Patients and methodsWe examined associations of chronic insomnia (defined as the presence of both International Classification of Diseases, Ninth Revision codes 307.42, 307.49, and 780.52 and long-term use of insomnia medications) with adverse renal outcomes (end-stage renal disease, incidence of estimated glomerular filtration rate [eGFR] ≤45 mL/min per 1.73 m2, and eGFR slopes

Rationale & objectiveDiabetic patients with declining kidney function are at heightened risk for hypoglycemia. We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post-end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes.Study designObservational cohort study.Setting & participantsUS veterans from the national Veterans Affairs database with diabetes and chronic kidney disease transitioning to dialysis therapy from October 2007 to September 2011.ExposureHypoglycemia-related hospitalizations during the pre-ESRD period and antidiabetic medication regimens.OutcomeThe outcome of post-ESRD all-cause mortality was evaluated relative to pre-ESRD hypoglycemia. The outcome of pre-ESRD hypoglycemia-related hospitalization was evaluated relative to antidiabetic medication regimens.Analytic approachWe examined whether the occurrence and frequency of pre-ESRD hypoglycemia-related hospitalizations are associated with post-ESRD mortality using Cox regression models adjusted for case-mix covariates. In a subcohort of patients prescribed 0 to 2 oral antidiabetic drugs and/or insulin, we examined the 12 most commonly prescribed antidiabetic medication regimens and risk for pre-ESRD hypoglycemia-related hospitalization using logistic regression models adjusted for case-mix covariates.ResultsAmong 30,156 patients who met eligibility criteria, the occurrence of pre-ESRD hypoglycemia-related hospitalization(s) was associated with higher post-ESRD mortality risk: adjusted HR (aHR), 1.25; 95% CI, 1.17-1.34 (reference group: no hypoglycemia hospitalization). Increasing frequency of hypoglycemia-related hospitalizations was independently associated with incrementally higher mortality risk: aHRs of 1.21 (95% CI, 1.12-1.30), 1.47 (95% CI, 1.19-1.82), and 2.07 (95% CI, 1.46-2.95) for 1, 2, and 3 or more hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia hospitalization). Compared with patients who were prescribed neither oral antidiabetic drugs nor insulin, medication regimens that included sulfonylureas and/or insulin were associated with higher risk for hypoglycemia.LimitationsResidual confounding cannot be excluded.ConclusionsAmong incident patients with ESRD with diabetes, a dose-dependent relationship between frequency of pre-ESRD hypoglycemia-related hospitalizations and post-ESRD mortality was observed. Further study of diabetic management strategies that prevent hypoglycemia as patients with chronic kidney disease transition to ESRD are warranted.

ImportanceDe novo statin therapy in patients receiving chronic dialysis has failed to demonstrate cardiovascular (CV) protection in randomized clinical trials and thus is not recommended by current guidelines. However, current guidelines recommend the continuation of statin therapy if initiated before transition to dialysis.ObjectiveTo investigate whether the continuation of statins from advanced chronic kidney disease into the dialysis therapy period is associated with improved survival.Design, setting, and participantsRetrospective cohort study of US veterans transitioning to dialysis between October 1, 2007, and March 30, 2014. Participants were 14 298 US veterans who were receiving statins during the 12-month period before transition to dialysis and survived the first year of dialysis. Data analysis was conducted between August 2, 2017, and June 28, 2018.ExposuresPatients were characterized as statin continuers (n = 11 936) if statin therapy was continued for at least 6 months during the first year after dialysis initiation and as statin discontinuers (n = 2362) if therapy with statins was stopped or no statin therapy was received in the year posttransition.Main outcomes and measuresAssociations of statin continuation with 12-month all-cause mortality and CV mortality after 1 year of dialysis initiation were examined using Cox proportional hazards regression models adjusted for demographics and comorbidities.ResultsThe mean (SD) age of the cohort was 71 (10) years; the cohort was 96.7% (n = 13 828) male and 21.3% (n = 3043) African American, and 74.6% (n = 10 627) had diabetes. The 12-month all-cause mortality and CV mortality rates after 1 year of transition to dialysis were lower in statin continuers: deaths per 100 person-years were 21.9 (95% CI, 20.9-22.8) and 8.1 (95% CI, 7.5-8.6) in statin continuers vs 30.3 (95% CI, 27.8-32.8) and 9.8 (95% CI, 8.3-11.2) in statin discontinuers. Moreover, lower all-cause mortality and CV mortality risks with statin continuation persisted in adjusted analyses, with hazard ratios of 0.72 (95% CI, 0.66-0.79) and 0.82 (95% CI, 0.69-0.96), respectively. Associations were similar across subgroups, including age, race, and diabetes status.Conclusions and relevanceIn this study, the continuation of statin therapy after transition to dialysis was associated with reduced all-cause mortality and CV mortality. The study findings suggest that future studies are needed to examine potential CV benefits of continuing statin therapy after dialysis initiation.

ObjectiveTo develop and validate a risk prediction model that would help individualize treatment and improve the shared decision-making process between clinicians and patients.Patients and methodsWe developed a risk prediction tool for mortality during the first year of dialysis based on pre-end-stage renal disease characteristics in a cohort of 35,878 US veterans with incident end-stage renal disease who transitioned to dialysis treatment between October 1, 2007, and March 31, 2014 and then externally validated this tool among 4284 patients in the Kaiser Permanente Southern California (KPSC) health care system who transitioned to dialysis treatment between January 1, 2007, and September 30, 2015.ResultsTo ensure model goodness of fit, 2 separate models were selected for patients whose last estimated glomerular filtration rate (eGFR) before dialysis initiation was less than 15 mL/min per 1.73 m2 or 15 mL/min per 1.73 m2 or higher. Model discrimination in the internal validation cohort of veterans resulted in C statistics of 0.71 (95% CI, 0.70-0.72) and 0.66 (95% CI, 0.65-0.67) among patients with eGFR lower than 15 mL/min per 1.73 m2 and 15 mL/min per 1.73 m2 or higher, respectively. In the KPSC external validation cohort, the developed risk score exhibited C statistics of 0.77 (95% CI, 0.74-0.79) in men and 0.74 (95% CI, 0.71-0.76) in women with eGFR lower than 15 mL/min per 1.73 m2 and 0.71 (95% CI, 0.67-0.74) in men and 0.67 (95% CI, 0.62-0.72) in women with eGFR of 15 mL/min per 1.73 m2 or higher.ConclusionA new risk prediction tool for mortality during the first year after transition to dialysis (available at www.DialysisScore.com) was developed in the large national Veterans Affairs cohort and validated with good performance in the racially, ethnically, and gender diverse KPSC cohort. This risk prediction tool will help identify high-risk populations and guide management strategies at the transition to dialysis.

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG.

AIMS:Secretory Immunoglobulin A (SIgA) plays a critical role in immune functioning by preventing pathogens from adhering to epithelial mucosa. Most infectious agents enter the body via mucosal surfaces, thus SIgA serves in the defense against respiratory, intestinal, and urinogenitary infections, as well as periodontal disease and caries. This study examined the possibility that pre- and postnatal exposure to cigarette and cannabis is associated with individual differences in Secretory Immunoglobulin A (SIgA) levels in early childhood. METHODS:Participants were 50 mother/infant (29 boys; 35% Caucasian) dyads recruited at their first prenatal appointment in a large northeastern community hospital in the United States. Repeated assessments of pre- and postnatal cigarette and cannabis were conducted beginning in the first trimester of pregnancy, using multiple methods (i.e., saliva, meconium, self-report). Infants were grouped into those prenatally exposed to either cigarette only (n = 19), cigarette and cannabis (n = 19), or with no prenatal substance exposure (n = 12). At age 5 years, the children's saliva was collected and assayed for SIgA. RESULTS:There were group differences in SIgA levels as a function of prenatal exposure to cigarette and cannabis - children in the cigarette only and the cigarette and cannabis groups had higher SIgA levels compared to the non-exposed children. Children who experienced the combination of postnatal exposure to cigarette and cannabis had higher levels of SIgA, even after accounting for prenatal exposures and other covariates relevant to immune system functioning. CONCLUSIONS:Prenatal and postnatal exposure to cigarette and cannabis may be associated with hyperactivity of mucosal immunity in early childhood. Links between cigarette and cannabis exposure and health problems in early childhood may be partially explained by prenatal and postnatal exposure-related changes in mucosal immunity.

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 arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 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/1.73m2) and change in eGFR (

History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models. Post-transplant medication nonadherence was assessed using proportion of days covered (PDC) for tacrolimus and mycophenolic acid in both groups. The mean ± SD age of the cohort at baseline was 61 ± 11 years, 92% were male, and 66% and 27% of patients were white and African-American, respectively. Compared to patients without history of psychosis/mania, patients with a history of psychosis/mania had similar risk of death with functioning graft [subhazard ratio (SHR) (95% confidence interval (CI)): 0.94(0.42-2.09)], all-cause death [hazard ratio (95% CI): 1.04 (0.51-2.14)], graft loss [SHR (95% CI): 1.07 (0.45-2.57)], and rejection [odds ratio(95% CI): 1.23(0.60-2.53)]. Moreover, there was no difference in immunosuppressive drug PDC in patients with and without history of psychosis/mania (PDC: 76 ± 21% vs. 78 ± 19%, P = 0.529 for tacrolimus; PDC: 78 ± 17% vs. 79 ± 18%, P = 0.666 for mycophenolic acid). After careful selection, pretransplantation psychosis/mania is not associated with adverse outcomes in kidney transplant recipients.

BackgroundPrevious studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients.MethodsIn all, 23 089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52 172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models.ResultsWhen entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3) years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9) mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24 months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15 303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24 months compared with 2-≤4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively.ConclusionsMore frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

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 17 732 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 (

BACKGROUND: Partial nephrectomy is considered the preferred care for localized kidney tumors and may yield better patient and kidney survival and similar oncological outcomes compared with radical nephrectomy. We sought to reexamine these hypotheses in a large nationally representative cohort of US veterans who underwent radical or partial nephrectomy. METHODS: We identified 7073 US veterans who had a partial or radical nephrectomy between 2004 and 2013. We collected data on estimated glomerular filtration rate (eGFR) prior to admission for nephrectomy surgery, immediately after surgery and 180 days postsurgery. We evaluated the association of nephrectomy type and eGFR at different time points with long-term mortality risk in adjusted survival models. RESULTS: Patients who underwent radical (compared to partial) nephrectomy had a 2-fold greater decline in eGFR (-21.8 ± 17.7 versus -10.3 ± 17.4 mL/min/1.73 m2) immediately after surgery. This larger drop in eGFR resulted in a larger proportion of radical nephrectomy patients having an eGFR

BackgroundPartial nephrectomy is considered the preferred care for localized kidney tumors and may yield better patient and kidney survival and similar oncological outcomes compared with radical nephrectomy. We sought to reexamine these hypotheses in a large nationally representative cohort of US veterans who underwent radical or partial nephrectomy.MethodsWe identified 7073 US veterans who had a partial or radical nephrectomy between 2004 and 2013. We collected data on estimated glomerular filtration rate (eGFR) prior to admission for nephrectomy surgery, immediately after surgery and 180 days postsurgery. We evaluated the association of nephrectomy type and eGFR at different time points with long-term mortality risk in adjusted survival models.ResultsPatients who underwent radical (compared to partial) nephrectomy had a 2-fold greater decline in eGFR (-21.8 ± 17.7 versus -10.3 ± 17.4 mL/min/1.73 m2) immediately after surgery. This larger drop in eGFR resulted in a larger proportion of radical nephrectomy patients having an eGFR

Background and objectivesAlbuminuria 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.Design, setting, participants, & measurementsIn a nationwide cohort of 56,946 United States veterans with an eGFR≥60 ml/min per 1.73 m2, we examined the associations of 1-year fold changes in albuminuria with subsequent incident CKD (>25% decrease in eGFR reaching

Background and objectivesDepression 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, & measurementsFrom 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.ResultsPatients 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.ConclusionPre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis.

BackgroundRecent studies suggest that potassium levels may differ by race. The basis for these differences and whether associations between potassium levels and adverse outcomes differ by race are unknown.Study designObservational study.Setting & participantsAssociations between race and potassium level and the interaction of race and potassium level with outcomes were investigated in the Racial and Cardiovascular Risk Anomalies in Chronic Kidney Disease (RCAV) Study, a cohort of US veterans (N=2,662,462). Associations between African ancestry and potassium level were investigated in African Americans in the Atherosclerosis Risk in Communities (ARIC) Study (N=3,450).PredictorsRace (African American vs non-African American and percent African ancestry) for cross-sectional analysis; serum potassium level for longitudinal analysis.OutcomesPotassium level for cross-sectional analysis; mortality and end-stage renal disease for longitudinal analysis.ResultsThe RCAV cohort was 18% African American (N=470,985). Potassium levels on average were 0.162mmol/L lower in African Americans compared with non-African Americans, with differences persisting after adjustment for demographics, comorbid conditions, and potassium-altering medication use. In the ARIC Study, higher African ancestry was related to lower potassium levels (-0.027mmol/L per each 10% African ancestry). In both race groups, higher and lower potassium levels were associated with mortality. Compared to potassium level of 4.2mmol/L, mortality risk associated with lower potassium levels was lower in African Americans versus non-African Americans, whereas mortality risk associated with higher levels was slightly greater. Risk relationships between potassium and end-stage renal disease were weaker, with no difference by race.LimitationsNo data for potassium intake.ConclusionsAfrican Americans had slightly lower serum potassium levels than non-African Americans. Consistent associations between potassium levels and percent African ancestry may suggest a genetic component to these differences. Higher and lower serum potassium levels were associated with mortality in both racial groups.

ObjectiveAlthough early trials suggested that intensive glycemic targets reduce the number of complications with diabetes, contemporary trials indicate no cardiovascular benefit and potentially higher mortality risk. As patients with advanced chronic kidney disease (CKD) transitioning to treatment with dialysis were excluded from these studies, the optimal glycemic level in this population remains uncertain. We hypothesized that glycemic status, defined by hemoglobin A1c (HbA--1c) and random glucose levels, in the pre-end-stage renal disease (ESRD) period is associated with higher 1-year post-ESRD mortality among patients with incident diabetes who have ESRD.Research design and methodsAmong 17,819 U.S. veterans with diabetic CKD transitioning to dialysis from October 2007 to September 2011, we examined the association of mean HbA--1c and random glucose levels averaged over the 1-year pre-ESRD transition period with mortality in the first year after dialysis initiation. All-cause mortality hazard ratios (HRs) were estimated using multivariable survival models. Secondary analyses examined cardiovascular mortality using competing risks methods.ResultsHbA--1c levels ≥8% (≥64 mmol/mol) were associated with higher mortality in the first year after dialysis initiation (reference value 6% to

BackgroundMortality 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.Study designObservational study.Setting & participants17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years.PredictorSystolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (

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 < 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 < 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.

BackgroundHeart 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 resultsAmong 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.ConclusionsHF 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.

BackgroundMost current scoring tools to predict allograft and patient survival upon kidney transplantion are based on variables collected posttransplantation. We developed a novel score to predict posttransplant outcomes using pretransplant information including routine laboratory data available before or at the time of transplantation.MethodsLinking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 15 125 hemodialysis patients who underwent first deceased transplantion. Prediction models were developed using Cox models for (a) mortality, (b) allograft loss (death censored), and (c) combined death or transplant failure. The cohort was randomly divided into a two thirds set (Nd = 10 083) for model development and a one third set (Nv = 5042) for validation. Model predictive discrimination was assessed using the index of concordance, or C statistic, which accounts for censoring in time-to-event models (a-c). We used the bootstrap method to assess model overfitting and calibration using the development dataset.ResultsPatients were 50 ± 13 years of age and included 39% women, 15% African Americans, and 36% persons with diabetes. For prediction of posttransplant mortality and graft loss, 10 predictors were used (recipients' age, cause and length of end-stage renal disease, hemoglobin, albumin, selected comorbidities, race and type of insurance as well as donor age, diabetes status, extended criterion donor kidney, and number of HLA mismatches). The new model (www.TransplantScore.com) showed the overall best discrimination (C-statistics, 0.70; 95% confidence interval [95% CI], 0.67-0.73 for mortality; 0.63; 95% CI, 0.60-0.66 for graft failure; 0.63; 95% CI, 0.61-0.66 for combined outcome).ConclusionsThe new prediction tool, using data available before the time of transplantation, predicts relevant clinical outcomes and may perform better to predict patients' graft survival than currently used tools.

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

Study objectivesThe association between restless legs syndrome (RLS) and Parkinson's disease (PD) has been extensively studied with inconclusive results; therefore, we prospectively examined the associations of the presence of RLS with development of incident PD.MethodsFrom a nationally representative prospective cohort of almost 3.5 million US veterans (age: 60 ± 14 years, 93% male, median follow-up time of 7.8 years [interquartile range: 6.4-8.4 years]), we created a propensity-matched cohort of 100882 PD-free patients and examined the association between prevalent RLS and incident PD. This association was also assessed in the entire cohort. Associations were examined using Cox models.ResultsThere were 68 incident PD events (0.13%, incidence rate 1.87 [1.48-2.37]/10000 patient-years) in the RLS-negative group, and 185 incident PD events (0.37%, incidence rate 4.72 [4.09-5.45]/10000 patient-years) in the RLS-positive group in the propensity-matched cohort. Prevalent RLS was associated with more than twofold higher risk of incident PD (hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.95-3.39) compared to RLS-negative patients. Qualitatively similar results were found when we examined the entire 3.5 million cohort: Prevalent RLS was associated with more than twofold higher risk of incident PD (multivariable adjusted HR: 2.81, 95%CI: 2.41-3.27).ConclusionRLS and PD share common risk factors. In this large cohort of US veterans, we found that prevalent RLS is associated with higher risk of incident PD during 8 years of follow-up, suggesting that RLS could be an early clinical feature of incident PD.

BackgroundMortality 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.MethodsWe 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.ResultsA 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.ConclusionsTransition 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.