Plasma proenkephalin A and incident chronic kidney disease and albuminuria in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

BACKGROUND: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S. METHODS: In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design. RESULTS: At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR: 1.29; 95% CI 1.09, 1.53). CONCLUSION: While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.

Plasma Pro-Enkephalin A and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke Cohort.

Background Cardiovascular disease is a risk factor for cognitive impairment. Evidence links both lower and higher concentration of the circulating opioid pro-enkephalin A (PENK-A) with stroke risk. We studied the association of plasma PENK-A with incident cognitive impairment. Methods and Results REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a prospective cohort study of 30 239 adults enrolled from 2003 to 2007. Baseline PENK-A was measured in a nested case-control study of 462 participants who developed cognitive impairment over 4.7 years, and 556 controls. Logistic regression and spline plots adjusted for confounders estimated odds ratios (ORs) of cognitive impairment by baseline PENK-A. Interaction terms tested for differences in associations by age, sex, and race. Baseline PENK-A was comparable between cases and controls. There were significant differences in the association of PENK-A with cognitive impairment by sex and age (adjusted P=0.003 and 0.06, respectively). In women but not men, spline plots showed that higher and lower PENK-A were associated with decreased odds of cognitive impairment (ORs for 10th and 90th percentiles versus median, 0.65 [95% CI, 0.43-0.96] and 0.64 [95% CI, 0.41-0.99]), with no difference by age. In men ≥65 years of age but not younger men, higher PENK-A was associated with decreased odds for cognitive impairment (OR for fourth versus first quartile 0.47 [95% CI, 0.22-0.99]); this pattern was not confirmed with spline plotting. Conclusions High and low levels of circulating opioid PENK-A were associated with decreased odds of future cognitive impairment in specific subgroups. Additional research is warranted to understand the biology underlying this association and the observed differences by sex.

Dietary Patterns, Apolipoprotein L1 Risk Genotypes, and CKD Outcomes Among Black Adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study.

Rationale & Objective: Dietary factors may impact inflammation and interferon production, which could influence phenotypic expression of Apolipoprotein1 (APOL1) genotypes. We investigated whether associations of dietary patterns with kidney outcomes differed by APOL1 genotypes. Study Design: Prospective cohort. Settings & Participants: 5,640 Black participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS). Exposures: Five dietary patterns derived from food frequency questionnaires: Convenience foods, Southern, Sweets and Fats, Plant-based, and Alcohol/Salads. Outcomes: Incident chronic kidney disease (CKD), CKD progression, and kidney failure. Incident CKD was defined as a change in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2 accompanied by a ≥25% decline from baseline eGFR or development of kidney failure among those with baseline eGFR ≥60 mL/1.73 m2 body surface area. CKD progression was defined as a composite of 40% reduction in eGFR from baseline or development of kidney failure in the subset of participants who had serum creatinine levels at baseline and completed a second in-home visit/follow-up visit. Analytical Approach: We examined associations of dietary pattern quartiles with incident CKD (n=4,188), CKD progression (n=5,640), and kidney failure (n=5,640). We tested for statistical interaction between dietary patterns and APOL1 genotypes for CKD outcomes and explored stratified analyses by APOL1 genotypes. Results: Among 5,640 Black REGARDS participants, mean age was 64 years (standard deviation = 9), 35% were male, and 682 (12.1%) had high-risk APOL1 genotypes. Highest versus lowest quartiles (Q4 vs Q1) of Southern dietary pattern were associated with higher adjusted odds of CKD progression (OR, 1.28; 95% CI, 1.01-1.63) but not incident CKD (OR, 0.92; 95% CI, 0.74-1.14) or kidney failure (HR, 1.48; 95% CI, 0.90-2.44). No other dietary patterns showed significant associations with CKD. There were no statistically significant interactions between APOL1 genotypes and dietary patterns. Stratified analysis showed no consistent associations across genotypes, although Q3 and Q4 versus Q1 of Plant-based and Southern patterns were associated with lower odds of CKD progression among APOL1 high- but not low-risk genotypes. Limitations: Included overlapping dietary patterns based on a single time point and multiple testing. Conclusions: In Black REGARDS participants, Southern dietary pattern was associated with increased risk of CKD progression. Analyses stratified by APOL1 genotypes suggest associations may differ by genetic background, but these findings require confirmation in other cohorts.

Risk Factors for Incident CKD in Black and White Americans: The REGARDS Study.

RATIONALE & OBJECTIVE: Little information exists on the incidence of and risk factors for chronic kidney disease (CKD) in contemporary US cohorts and whether risk factors differ by race, sex, or region in the United States. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 4,198 Black and 7,799 White participants aged at least 45 years, recruited from 2003 through 2007 across the continental United States, with baseline estimated glomerular filtration rate (eGFR)>60mL/min/1.73m2 and eGFR assessed again approximately 9 years later. EXPOSURES: Age, sex, race (Black or White), region ("stroke belt" or other), education, income, systolic blood pressure, body mass index, diabetes, coronary heart disease, hyperlipidemia, smoking, and albuminuria. OUTCOMES: (1) eGFR change and (2) incident CKD defined as eGFR<60mL/min/1.73m2 and≥40% decrease from baseline or kidney failure. ANALYTICAL APPROACH: Linear regression and modified Poisson regression were used to determine the association of risk factors with eGFR change and incident CKD overall and stratified by race, sex, and region. RESULTS: Mean age of participants was 63±8 (SD) years, 54% were female, and 35% were Black. After 9.4±1.0 years of follow-up, CKD developed in 9%. In an age-, sex-, and race-adjusted model, Black race (ß =-0.13; P<0.001) was associated with higher risk of eGFR change, but this was attenuated in the fully adjusted model (ß=0.02; P=0.5). Stroke belt residence was independently associated with eGFR change (ß =-0.10; P<0.001) and incident CKD (relative risk, 1.14 [95% CI, 1.01-1.30]). Albuminuria was more strongly associated with eGFR change (ß of-0.26 vs-0.17; P=0.01 for interaction) in Black compared with White participants. Results were similar for incident CKD. LIMITATIONS: Persons of Hispanic ethnicity were excluded; unknown duration and/or severity of risk factors. CONCLUSIONS: Established CKD risk factors accounted for higher risk of incident CKD in Black versus White individuals. Albuminuria was a stronger risk factor for eGFR decrease and incident CKD in Black compared with White individuals. Living in the US stroke belt is a novel risk factor for CKD.

Evolution of Investigating Informed Assent Discussions about CPR in Seriously Ill Patients.

CONTEXT: Outcomes after cardiopulmonary resuscitation (CPR) remain poor. We have spent 10 years investigating an "informed assent" (IA) approach to discussing CPR with chronically ill patients/families. IA is a discussion framework whereby patients extremely unlikely to benefit from CPR are informed that unless they disagree, CPR will not be performed because it will not help achieve their goals, thus removing the burden of decision-making from the patient/family, while they retain an opportunity to disagree. OBJECTIVES: Determine the acceptability and efficacy of IA discussions about CPR with older chronically ill patients/families. METHODS: This multi-site research occurred in three stages. Stage I determined acceptability of the intervention through focus groups of patients with advanced COPD or malignancy, family members, and physicians. Stage II was an ambulatory pilot randomized controlled trial (RCT) of the IA discussion. Stage III is an ongoing phase 2 RCT of IA versus attention control in in patients with advanced chronic illness. RESULTS: Our qualitative work found the IA approach was acceptable to most patients, families, and physicians. The pilot RCT demonstrated feasibility and showed an increase in participants in the intervention group changing from "full code" to "do not resuscitate" within two weeks after the intervention. However, Stages I and II found that IA is best suited to inpatients. Our phase 2 RCT in older hospitalized seriously ill patients is ongoing; results are pending. CONCLUSIONS: IA is a feasible and reasonable approach to CPR discussions in selected patient populations.

Content of Tele-Palliative Care Consultations with Patients Receiving Dialysis.

Background: Little is known about the content of communication in palliative care telehealth conversations in the dialysis population. Understanding the content and process of these conversations may lead to insights about how palliative care improves quality of life. Methods: We conducted a qualitative analysis of video recordings obtained during a pilot palliative teleconsultation program. We recruited patients receiving dialysis from five facilities affiliated with an academic medical center. Palliative care clinicians conducted teleconsultation using a wall-mounted screen with a camera mounted on a pole and positioned mid-screen in the line of sight to facilitate direct eye contact. Patients used an iPad that was attached to an IV pole positioned next to the dialysis chair. Conversations were coded using a preexisting framework of themes and content from the Serious Illness Conversation Guide (SICG) and revised Edmonton Symptom Assessment System-Renal. Results: We recruited 39 patients to undergo a telepalliative care consultation while receiving dialysis, 34 of whom completed the teleconsultation. Specialty palliative care clinicians (3 physicians and 1 nurse practitioner) conducted 35 visits with 34 patients. Median (interquartile range) duration of conversation was 42 (28-57) minutes. Most frequently discussed content included sources of strength (91%), critical abilities (88%), illness understanding (85%), fears and worries (85%), what family knows (85%), fatigue (77%), and pain (65%). Process features such as summarizing statements (85%) and making a recommendation (82%) were common, whereas connectional silence (56%), and emotion expression (21%) occurred less often. Conclusions: Unscripted palliative care conversations in outpatient dialysis units through telemedicine exhibited many domains recommended by the SICG, with less frequent discussion of symptoms. Emotion expression was uncommon for these conversations that occurred in an open setting.

Biomarkers as MEDiators of racial disparities in risk factors (BioMedioR): Rationale, study design, and statistical considerations.

PURPOSE: Relative to White adults, Black adults have a substantially higher prevalence of hypertension and diabetes, both key risk factors for stroke, cardiovascular disease, cognitive impairment, and dementia. Blood biomarkers have shown promise in identifying contributors to racial disparities in many chronic diseases. METHODS: We outline the study design and related statistical considerations for a nested cohort study, the Biomarker Mediators of Racial Disparities in Risk Factors (BioMedioR) study, within the 30,239-person biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) study (2003-present). Selected biomarkers will be assessed for contributions to racial disparities in risk factor development over median 9.4 years of follow-up, with initial focus on hypertension, and diabetes. Here we outline study design decisions and statistical considerations for the sampling of 4,400 BioMedioR participants. RESULTS: The population for biomarker assessment was selected using a random sample study design balanced across race and sex to provide the optimal opportunity to describe association of biomarkers with the development of hypertension and diabetes. Descriptive characteristics of the BioMedioR sample and analytic plans are provided for this nested cohort study. CONCLUSIONS: This nested biomarker study will examine pathways with the target to help explain racial differences in hypertension and diabetes incidence.

Communication Skills Training for Nurses and Social Workers: An Initiative to Promote Interdisciplinary Advance Care Planning and Palliative Care in Patients on Dialysis.

Palliative care initiatives are needed in nephrology, yet implementation is lacking. We created a 6-hour workshop to teach the skills of active listening, responding to emotion, and exploring goals and values to nurses and social workers working in dialysis units. The workshop consisted of interactive didactics and structured role play with trained simulated patients. We assessed preparedness using a Likert scale and utilized paired t tests to measure the impact using a self-assessment survey following the training. Ten nurses and two social workers from six dialysis units completed the training. Mean scores improved in all domains: demonstrating empathic behaviors, responding to emotion and end-of-life concerns, eliciting family's concerns at end-of-life and patient's goals, and discussing spiritual concerns. Further testing in larger samples may help to confirm these results.

Feasibility and Acceptability of Telemedicine-Facilitated Palliative Care Consultations in Rural Dialysis Units.

Background: Patients receiving dialysis have unmet palliative care needs. Limited access to palliative care is a key barrier to its integration into routine dialysis care. Objective: To determine the feasibility and acceptability of telepalliative care in rural dialysis units. Methods: This was a single-arm pilot clinical trial. The target population was patients with kidney failure receiving outpatient dialysis in a rural U.S. state. Feasibility was measured by one-month completion rate. Acceptability was measured using an adapted telemedicine questionnaire. Results: We recruited 39 patients with mean age 71.2 years to undergo a telepalliative care consultation while receiving dialysis. Four specialty palliative care clinicians (three physicians and one nurse practitioner) conducted the visits. The recruitment rate was 40% (39/96), scheduling rate was 100% (39/39), and one-month completion rate was 77% (30/39). Thirty-six patient participants (14 women and 22 men) completed the baseline survey. Audiovisual aspects of the visit were rated highly. More than 80% reported the visit being at least as good as an in-person visit and 41% felt the teleconsult was better. Eighty-one percent of patients felt the appointment was relevant to them, 58% felt they learned new things about their condition, and 27% reported the appointment changed the way they think about dialysis. Discussion: Telepalliative care is acceptable to patients receiving dialysis and is a feasible approach to integrating palliative care in rural dialysis units. The study was registered with Clinicaltrials.gov (NCT03744117).

Dietary Oxidative Balance Scores and Biomarkers of Inflammation among Individuals with and without Chronic Kidney Disease.

BACKGROUND: Oxidative stress and inflammation are proposed mechanisms of nonspecific kidney injury and progressive kidney failure. Higher dietary oxidative balance scores (OBS) are associated with lower prevalence of chronic kidney disease (CKD). METHODS: We investigated the association between OBS and biomarkers of inflammation using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Nutrient estimates from the Block Food Frequency Questionnaires were used to define tertiles of 11 pro- and antioxidant factors. Points for each OBS component were summed, with a higher score indicating predominance of antioxidant exposures. Multivariable linear regression models were used to estimate the association between OBS and biomarkers of inflammation (interleukin-6 [IL-6], interleukin-8 [IL-8], interleukin-10 [IL-10], fibrinogen, C-reactive protein [CRP], white blood cell count, and cystatin C). An interaction term was included to determine if associations between OBS and inflammatory markers differed between individuals with and without CKD. RESULTS: Of 682 participants, 22.4% had CKD. In adjusted models, OBS was associated with CRP and IL-6. For every 5-unit increase in OBS, the CRP concentration was -15.3% lower (95% CI: -25.6, -3.6). The association of OBS with IL-6 differed by CKD status; for every 5-unit increase in OBS, IL-6 was -10.7% lower (95% CI: -16.3, -4.7) among those without CKD, but there was no association among those with CKD (p = 0.03). CONCLUSION: This study suggests that a higher OBS is associated with more favorable levels of IL-6 and CRP, and that the association of OBS and IL-6 may be modified by CKD status.

Venous thromboembolism, factor VIII and chronic kidney disease.

Chronic kidney disease (CKD) affects 30 million Americans and is associated with approximately a two-fold increased risk of venous thromboembolism (VTE). There is a graded increased risk of VTE across declining kidney function, as measured by estimated glomerular filtration rate (eGFR) and albuminuria. When patients with end-stage kidney disease (ESKD) experience VTE they are more likely than the general population to be hospitalized and they have a higher mortality. The incidence and consequences of VTE may also differ depending on the cause of kidney disease. In addition, kidney transplant patients with VTE are at a greater risk for death and graft loss than transplant patients without VTE. The reasons that patients with CKD are at increased risk of VTE are not well understood, but recent data suggest that factor VIII is a mediator. Factor VIII is an essential cofactor in the coagulation cascade and a strong risk factor for VTE in general. It is inversely correlated with eGFR and prospective studies demonstrate that factor VIII activity predicts incident CKD and rapid eGFR decline. The etiology of CKD may also influence factor VIII levels. This review summarizes the epidemiology VTE in CKD and reviews the biochemistry of factor VIII and determinants of its levels, including von Willebrand factor and ABO blood group. We explore mechanisms by which the complications of CKD might give rise to higher factor VIII and suggests future research directions to understand how factor VIII and CKD are linked.

Measures of Kidney Disease and the Risk of Venous Thromboembolism in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study.

BACKGROUND: Kidney disease has been associated with venous thromboembolism (VTE) risk, but results conflict and there is little information regarding blacks. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 30,239 black and white adults 45 years or older enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study 2003 to 2007. PREDICTORS: Estimated glomerular filtration rate (eGFR) using the combined creatinine-cystatin C (eGFRcr-cys) equation and urinary albumin-creatinine ratio (ACR). OUTCOMES: The primary outcome was adjudicated VTE, and secondary outcomes were provoked and unprovoked VTE, separately. Mortality was a competing-risk event. RESULTS: During 4.6 years of follow-up, 239 incident VTE events occurred over 124,624 person-years. Cause-specific HRs of VTE were calculated using proportional hazards regression adjusted for age, sex, race, region of residence, and body mass index. Adjusted VTE HRs for eGFRcr-cys of 60 to <90, 45 to <60, and <45 versus ≥90mL/min/1.73m2 were 1.28 (95% CI, 0.94-1.76), 1.30 (95% CI, 0.77-2.18), and 2.13 (95% CI, 1.21-3.76). Adjusted VTE HRs for ACR of 10 to <30, 30 to <300, and ≥300 versus <10mg/g were 1.14 (95% CI, 0.84-1.56), 1.15 (95% CI, 0.79-1.69), and 0.64 (95% CI, 0.25-1.62). Associations were similar for provoked and unprovoked VTE. LIMITATIONS: Single measurement of eGFR and ACR may have led to misclassification. Smaller numbers of events may have limited power. CONCLUSIONS: There was an independent association of low eGFR (<45 vs ≥90mL/min/1.73m2) with VTE risk, but no association of ACR and VTE.

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative.

BACKGROUND: Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs). PREDICTORS: Categories of eGFR (exposure); race/ethnicity (effect modifier). OUTCOMES: The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death. MEASUREMENTS: We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. RESULTS: During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories. LIMITATIONS: Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. CONCLUSIONS: In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

Menopausal symptoms in women with chronic kidney disease.

OBJECTIVE: This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events. METHODS: CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort. Primary outcomes were presence, severity, and timing/duration of VMS (self-reported hot flashes and night sweats) at baseline. We used polytomous logistic regression to test for associations among CKD and four VMS categories (no VMS; early VMS-present before menopause but not at study baseline; late VMS-present only at study baseline; persistent VMS-present before menopause and study baseline) and Cox regression to determine whether CKD modified associations between late VMS and mortality or cardiovascular events. RESULTS: Women with CKD (1,017 of 17,891; mean estimated glomerular filtration rate, 50.7 mL/min/1.73 m) were more likely to have had menopause before age 45 years (26% vs 23%, P = 0.02) but were less likely to experience VMS (38% vs 46%, P < 0.001) than women without CKD. Women with CKD were not more likely than women without CKD to experience late VMS. Late VMS (hazard ratio, 1.16; 95% CI, 1.04-1.29) and CKD (hazard ratio, 1.74; 95% CI, 1.54-1.97) were each independently associated with increased risk for mortality, but CKD did not modify the association of late VMS with mortality (Pinteraction = 0.53), coronary heart disease (Pinteraction = 0.12), or stroke (Pinteraction = 0.68). CONCLUSIONS: Women with mild CKD experience earlier menopause and fewer VMS than women without CKD.

Virtual reality therapy for adults post-stroke: a systematic review and meta-analysis exploring virtual environments and commercial games in therapy.

BACKGROUND: The objective of this analysis was to systematically review the evidence for virtual reality (VR) therapy in an adult post-stroke population in both custom built virtual environments (VE) and commercially available gaming systems (CG). METHODS: MEDLINE, CINAHL, EMBASE, ERIC, PSYCInfo, DARE, PEDro, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were systematically searched from the earliest available date until April 4, 2013. Controlled trials that compared VR to conventional therapy were included. Population criteria included adults (>18) post-stroke, excluding children, cerebral palsy, and other neurological disorders. Included studies were reported in English. Quality of studies was assessed with the Physiotherapy Evidence Database Scale (PEDro). RESULTS: Twenty-six studies met the inclusion criteria. For body function outcomes, there was a significant benefit of VR therapy compared to conventional therapy controls, G = 0.48, 95% CI = [0.27, 0.70], and no significant difference between VE and CG interventions (P = 0.38). For activity outcomes, there was a significant benefit of VR therapy, G = 0.58, 95% CI = [0.32, 0.85], and no significant difference between VE and CG interventions (P = 0.66). For participation outcomes, the overall effect size was G = 0.56, 95% CI = [0.02, 1.10]. All participation outcomes came from VE studies. DISCUSSION: VR rehabilitation moderately improves outcomes compared to conventional therapy in adults post-stroke. Current CG interventions have been too few and too small to assess potential benefits of CG. Future research in this area should aim to clearly define conventional therapy, report on participation measures, consider motivational components of therapy, and investigate commercially available systems in larger RCTs. TRIAL REGISTRATION: Prospero CRD42013004338.

Prognostic stratification in older adults commencing dialysis.

BACKGROUND: Accurate prognostic models could inform treatment decisions for older adults with end-stage renal disease who are considering dialysis and might identify patients more appropriate for conservative care or hospice. METHODS: In a cohort of patients aged ≥ 67 years commencing dialysis in the United States between January 1, 2008 and June 30, 2009, we compared the discrimination of three existing instruments (the Liu index; the French Renal Epidemiology and Information Network score; and hospice eligibility criteria) for the prediction of 6-month mortality. We estimated the odds of death associated with each prognostic index using logistic regression with and without adjustment for age. Predictive indices were compared using the concordance ("c")-statistic. RESULTS: Of 44,109 eligible patients, 10,289 (23.3%) died within 6 months of dialysis initiation. The c-statistic for the Liu, Renal Epidemiology and Information Network, hospice eligibility criteria, and combined Liu/hospice eligibility criteria scores without and with age were 0.62/0.65, 0.63/0.66, 0.65/0.68, and 0.68/0.70, respectively. Discrimination was poorer at older ages, especially for the Liu and Renal Epidemiology and Information Network scores. Although sensitivity was poor, a Renal Epidemiology and Information Network score ≥ 9 or an hospice eligibility criteria ≥ 3 had relatively high specificity. CONCLUSIONS: Existing prognostic indices based on administrative data perform poorly with respect to prediction of 6-month mortality in older patients with end-stage renal disease commencing dialysis.