Enhancing the Cardiovascular Safety of Hemodialysis Care Using Multimodal Provider Education and Patient Activation Interventions: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: End-stage kidney disease (ESKD) is treated with dialysis or kidney transplantation, with most patients with ESKD receiving in-center hemodialysis treatment. This life-saving treatment can result in cardiovascular and hemodynamic instability, with the most common form being low blood pressure during the dialysis treatment (intradialytic hypotension [IDH]). IDH is a complication of hemodialysis that can involve symptoms such as fatigue, nausea, cramping, and loss of consciousness. IDH increases risks of cardiovascular disease and ultimately hospitalizations and mortality. Provider-level and patient-level decisions influence the occurrence of IDH; thus, IDH may be preventable in routine hemodialysis care. OBJECTIVE: This study aims to evaluate the independent and comparative effectiveness of 2 interventions-one directed at hemodialysis providers and another for patients-in reducing the rate of IDH at hemodialysis facilities. In addition, the study will assess the effects of interventions on secondary patient-centered clinical outcomes and examine factors associated with a successful implementation of the interventions. METHODS: This study is a pragmatic, cluster randomized trial to be conducted in 20 hemodialysis facilities in the United States. Hemodialysis facilities will be randomized using a 2 × 2 factorial design, such that 5 sites will receive a multimodal provider education intervention, 5 sites will receive a patient activation intervention, 5 sites will receive both interventions, and 5 sites will receive none of the 2 interventions. The multimodal provider education intervention involved theory-informed team training and the use of a digital, tablet-based checklist to heighten attention to patient clinical factors associated with increased IDH risk. The patient activation intervention involves tablet-based, theory-informed patient education and peer mentoring. Patient outcomes will be monitored during a 12-week baseline period, followed by a 24-week intervention period and a 12-week postintervention follow-up period. The primary outcome of the study is the proportion of treatments with IDH, which will be aggregated at the facility level. Secondary outcomes include patient symptoms, fluid adherence, hemodialysis adherence, quality of life, hospitalizations, and mortality. RESULTS: This study is funded by the Patient-Centered Outcomes Research Institute and approved by the University of Michigan Medical School's institutional review board. The study began enrolling patients in January 2023. Initial feasibility data will be available in May 2023. Data collection will conclude in November 2024. CONCLUSIONS: The effects of provider and patient education on reducing the proportion of sessions with IDH and improving other patient-centered clinical outcomes will be evaluated, and the findings will be used to inform further improvements in patient care. Improving the stability of hemodialysis sessions is a critical concern for clinicians and patients with ESKD; the interventions targeted to providers and patients are predicted to lead to improvements in patient health and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03171545; https://clinicaltrials.gov/ct2/show/NCT03171545. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46187.

Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.

Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis.

Background: Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity. Methods: From August to November 2020, we enrolled patients on maintenance dialysis with SARS-CoV-2 infections from outpatient dialysis facilities in Atlanta, Georgia. We followed participants for approximately 42 days. We assessed COVID-19 symptoms and collected specimens. Oropharyngeal (OP), anterior nasal (AN), and saliva (SA) specimens were tested for the presence of SARS-CoV-2 RNA, using RT-PCR, and sent for viral culture. Serology, including neutralizing antibodies, was measured in blood specimens. Results: Fifteen participants, with a median age of 58 (range, 37‒77) years, were enrolled. Median duration of RT-PCR positivity from diagnosis was 18 days (interquartile range [IQR], 8‒24 days). Ten participants had at least one, for a total of 41, positive RT-PCR specimens ≥10 days after symptoms onset. Of these 41 specimens, 21 underwent viral culture; one (5%) was positive 14 days after symptom onset. Thirteen participants developed SARS-CoV-2-specific antibodies, 11 of which included neutralizing antibodies. RT-PCRs remained positive after seroconversion in eight participants and after detection of neutralizing antibodies in four participants; however, all of these samples were culture negative. Conclusions: Patients with ESKD on maintenance dialysis remained persistently and intermittently SARS-CoV-2-RT-PCR positive. However, of the 15 participants, only one had infectious virus, on day 14 after symptom onset. Most participants mounted an antibody response, including neutralizing antibodies. Participants continued having RT-PCR-positive results in the presence of SARS-CoV-2-specific antibodies, but without replication-competent virus detected.

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

BACKGROUND: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established. METHODS: To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients. RESULTS: The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care. CONCLUSIONS: Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.

Development and content validity of a hemodialysis symptom patient-reported outcome measure.

PURPOSE: To describe the process and preliminary qualitative development of a new symptom-based patient-reported outcome measure (PROM) intended to assess hemodialysis treatment-related physical symptoms. METHODS: Experienced interviewers conducted concept elicitation and cognitive debriefing interviews with individuals receiving in-center hemodialysis in the United States. Concept elicitation interviews involved eliciting spontaneous reports of symptom experiences and probing to further explore and confirm concepts. We used patient-reported concepts to generate a preliminary symptom PROM. We conducted 3 rounds of cognitive debriefing interviews to evaluate symptom relevance, item interpretability, and draft item structure. We iteratively refined the measure based on cognitive interview findings. RESULTS: Forty-two adults receiving in-center hemodialysis participated in the concept elicitation interviews. A total of 12 symptoms were reported by > 10% of interviewees. We developed a 13-item initial draft instrument for testing in 3 rounds of cognitive interviews with an additional 52 hemodialysis patients. Participant responses and feedback during cognitive interviews led to changes in symptom descriptions, division of the single item "nausea/vomiting" into 2 distinct items, removal of daily activity interference items, addition of instructions, and clarification about the recall period, among other changes. CONCLUSIONS: Symptom Monitoring on Renal Replacement Therapy-Hemodialysis (SMaRRT-HD™) is a 14-item PROM intended for use in hemodialysis patents. SMaRRT-HD™ uses a single treatment recall period and a 5-point Likert scale to assess symptom severity. Qualitative interview data provide evidence of its content validity. SMaRRT-HD™ is undergoing additional testing to assess measurement properties and inform measure scoring.

Depressive affect in incident hemodialysis patients.

BACKGROUND: The prevalence of depressive affect is not well defined in the incident hemodialysis (HD) population. We investigated the prevalence of and associated risk factors and hospitalization rates for depressive affect in incident HD patients. METHODS: We performed a prospective investigation using the Patient Health Questionnaire 2 (PHQ2) depressive affect assessment. From January to July of 2013 at 108 in-center clinics randomly selected across tertiles of baseline quality measures, we contacted 577 and 543 patients by telephone for depressive affect screening. PHQ2 test scores range from 0 to 6 (scores ≥3 suggest the presence of depressive affect). The prevalence of depressive affect was measured at 1-30 and 121-150 days after initiating HD; depressive affect risk factors and hospitalization rates by depressive affect status at 1-30 days after starting HD were computed. RESULTS: Of 1120 contacted patients, 340 completed the PHQ2. In patients screened at 1-30 or 121-150 days after starting HD, depressive affect prevalence was 20.2% and 18.5%, respectively (unpaired t-test, P = 0.7). In 35 patients screened at both time points, there were trends for lower prevalence of depressive affect at the end of incident HD, with 20.0% and 5.7% of patients positive for depressive affect at 1-30 and 121-150 days, respectively (paired t-test, P = 0.1). Hospitalization rates were higher in patients with depressive affect during the first 30 days, exhibiting 1.5 more admissions (P < 0.001) and 10.5 additional hospital days (P = 0.008) per patient-year. Females were at higher risk for depressive affect at 1-30 days (P = 0.01). CONCLUSIONS: The prevalence of depressive affect in HD patients is high throughout the incident period. Rates of hospital admissions and hospital days are increased in incident HD patients with depressive affect.

Right TraC™ Post-Hospitalization Care Transitions Program to Reduce Readmissions for Hemodialysis Patients.

BACKGROUND: Hemodialysis (HD) patients have high hospitalization rates. This nonrandomized trial tested the effect of a bundle of renal-specific "Right TraC™" strategies on 30-day all-cause readmission rates and, secondarily, 90-day readmissions and overall admissions among HD patients. METHODS: Twenty-six Fresenius clinics in West Virginia, Ohio, and Kentucky participated in the interventions. Eighteen matched clinics served as controls; intervention clinics also served as their own controls. We deployed the intervention in 3 incremental phases focused on patient information exchange, post-hospital follow-up, and telephonic case management. Thirty-day hospital readmissions per patient year (ppy) were calculated by dividing the total number of readmissions within 30 days of index admission by the total number of patient-years in baseline (2012) and remeasurement (2014) periods. We also compared readmission rates from 2010 to 2015. We used repeated measures Poisson regression to compare outcomes between groups and time periods. RESULTS: From 2012 to 2014, 30-day all-cause readmissions ppy declined for Right TraC clinics (from 0.88 to 0.66 [p < 0.001]; for controls, from 0.73 to 0.61 [p = 0.16]). Difference in change between groups was nonsignificant (p = 0.26). Overall admissions ppy declined: for Right TraC clinics from 2.51 to 1.97 (p < 0.001); for controls from 2.14 to1.92 (p = 0.21); difference in change between groups was significant (p = 0.01). For 2010, 2011, and 2012, Right TraC clinic 30-day readmissions ppy were unchanged: 0.89, 1.00, 0.88 (p = 0.61 and p = 0.49); they declined to 0.66 (p < 0.001) in 2014 (intervention year); rose to 0.70 (p = 0.06) in 2015 (interventions discontinued). CONCLUSION: We conclude that Right TraC interventions may have been helpful in reducing hospital readmission rates.

Outcomes associated with intradialytic oral nutritional supplements in patients undergoing maintenance hemodialysis: a quality improvement report.

BACKGROUND: Insufficient clinical data exist to determine whether provision of oral nutritional supplements during dialysis can improve survival in hypoalbuminemic maintenance hemodialysis patients. STUDY DESIGN: Retrospective matched-cohort study. SETTING & PARTICIPANTS: All oral nutritional supplement program-eligible in-center maintenance hemodialysis patients with albumin level ≤3.5 g/dL in quarter 4 of 2009 without oral nutritional supplements in the prior 90 days at Fresenius Medical Care, North America facilities. QUALITY IMPROVEMENT PLAN: Monitored intradialytic oral nutritional supplements were provided to eligible maintenance hemodialysis patients upon physician order, to continue for a year or until serum albumin level was ≥4.0 g/dL. OUTCOME: Mortality (including deaths and withdrawals), followed up until December 31, 2010. MEASUREMENTS: Both an intention-to-treat (ITT) and an as-treated analysis was performed using a 1:1 geographic region and propensity score-matched study population (using case-mix, laboratory test, access type, 30-day prior hospitalization, and incident patient status) comparing patients treated with intradialytic oral nutritional supplements with usual-care patients. Cox models were constructed, unadjusted and adjusted for facility standardized mortality ratio and case-mix and laboratory variables. RESULTS: The ITT and as-treated analyses both showed lower mortality in the oral nutritional supplement group. The conservative ITT models with 5,227 matched pairs had 40% of controls subsequently receiving oral nutritional supplements after January 1, 2010 (because many physicians delayed participation), with comparative death rates of 30.1% versus 30.4%. The corresponding as-treated (excluding crossovers) death rates for 4,289 matched pairs were 30.9% versus 37.3%. The unadjusted ITT mortality HR for oral nutritional supplement use was 0.95 (95% CI, 0.88-1.01), and the adjusted HR was 0.91 (95% CI, 0.85-0.98); the corresponding as-treated HRs were 0.71 (95% CI, 0.66-0.76) and 0.66 (95% CI, 0.61-0.71) before and after adjustment, respectively. LIMITATIONS: Limited capture of oral nutritional supplement intake outside the facility and potential residual confounding from unmeasured variables, such as dietary intake. CONCLUSIONS: Maintenance hemodialysis patients with albumin levels ≤3.5 g/dL who received monitored intradialytic oral nutritional supplements showed survival significantly better than similar matched patient controls, with the as-treated analysis highlighting the potentially large effect of this strategy in clinical practice.

RightReturn. Partnering to reduce the high rate of hospital readmission for dialysis-dependent patients.

The rate of rehospitalization is at a critical level. Twenty percent of all Medicare patients are rehospitalized within 30 days of discharge, and this rate is even higher (36%) for end-stage renal disease patients. Dialysis-dependent patients are commonly discharged from the hospital with a decline in various health measures (such as hemoglobin, albumin, and estimated dry weight) when compared to pre-hospital values, making the common response to resume previous orders" in the outpatient setting inadequate. Both quality of care and financial penalties by the Centers for Medicare & Medicaid Services have set the stage for partnerships between dialysis providers and hospitals to develop strategies to reduce readmissions for ESRD patients, and provide for the "RightReturn" to the outpatient setting with resumption of their daily lives at home in optimal health.

Low health literacy associates with increased mortality in ESRD.

Limited health literacy is common in the United States and associates with poor clinical outcomes. Little is known about the effect of health literacy in patients with advanced kidney disease. In this prospective cohort study we describe the prevalence of limited health literacy and examine its association with the risk for mortality in hemodialysis patients. We enrolled 480 incident chronic hemodialysis patients from 77 dialysis clinics between 2005 and 2007 and followed them until April 2008. Measured using the Rapid Estimate of Adult Literacy in Medicine, 32% of patients had limited (<9th grade reading level) and 68% had adequate health literacy (≥9th grade reading level). Limited health literacy was more likely in patients who were male and non-white and who had fewer years of education. Compared with adequate literacy, limited health literacy associated with a higher risk for death (HR 1.54; 95% CI 1.01 to 2.36) even after adjustment for age, sex, race, and diabetes. In summary, limited health literacy is common and associates with higher mortality in chronic hemodialysis patients. Addressing health literacy may improve survival for these patients.

The "right" of passage: surviving the first year of dialysis.

Mortality risk for dialysis patients is highest in the first year. We previously showed a 41% mortality benefit associated with a pilot case management program for incident hemodialysis patients (n = 918). The RightStart Program (RSP) provided prompt medical management and self-management education and was recently expanded to more facilities. We conducted a matched cohort analysis to validate the expanded program's continued effectiveness. Death risk was reduced for RS patients (n = 4308) versus matched controls (C; n = 4308) by 34% (hazard ratio = 0.66, P < 0.0001) at 120 d and 22% at 1 yr (hazard ratio = 0.78, P < 0.0001). RS patients had lower hospitalization during the first year (RS = 15.5 days per patient year versus C = 16.9, P < 0.01). At 120 d, more RS patients achieved hemoglobin 11 to 12 g/dl (RS = 22.4% versus C = 19.7%, P < 0.01), eKt/V > or = 1.2 (RS = 66% versus C = 53.5%, P < 0.01), albumin > or = 4.0 g/dl (RS = 26% versus C = 22%, P < 0.01), and phosphorus 3.5 to 5.5 mg/dl (RS = 52.4% versus C = 45.4%). At 120 d, RS patients had a greater reduction in catheter use (RS = 32% versus C = 25%, P < 0.01) and more vitamin D orders (RS = 60% versus C = 55%, P < 0.01). Expansion of RS to a larger incident patient population results in significant reduction of morbidity and mortality associated with improvement of intermediate outcomes.

Association between repeat hospitalization and early intervention in dialysis patients following hospital discharge.

Dialysis patients have a greater number of hospitalization events compared to patients without renal failure. Here we studied the relationship between different post-discharge interventions and repeat hospitalization in over 126,000 prevalent hemodialysis patients to explore outpatient strategies that minimize the risk of repeat hospitalization. The primary outcome was repeat hospitalization within 30 days of discharge. Compared to pre-hospitalization values, the levels of hemoglobin, albumin, phosphorus, calcium, and parathyroid hormone and weight were significantly decreased after hospitalization. Using covariate-adjusted models, those patients whose hemoglobin was monitored within the first 7 days after discharge, followed by modification of their erythropoietin dose had a significantly reduced risk for repeat-hospitalization when compared to the patients whose hemoglobin was not checked, nor was the dose of erythropoietin changed. Similarly, administration of vitamin D within the 7 days following discharge was significantly associated with reduced repeat hospitalization when compared to patients on no vitamin D. Therefore, it appears that immediate re-evaluation of anemia management orders and resumption of vitamin D soon after discharge may be an effective way to reduce repeat hospitalization.

Patient dialysis knowledge is associated with permanent arteriovenous access use in chronic hemodialysis.

BACKGROUND AND OBJECTIVES: Patient knowledge about chronic hemodialysis (CHD) is important for effective self-management behaviors, but little is known about its association with vascular access use. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective cohort of adult incident CHD patients from May 2002 until November 2005 and followed for 6 mo after initiation of hemodialysis (HD). Patient knowledge was measured using the Chronic Hemodialysis Knowledge Survey (CHeKS). The primary outcome was dialysis access type at: baseline, 3 mo, and 6 mo after HD initiation. Secondary outcomes included anemia, nutritional, and mineral laboratory measures. RESULTS: In 490 patients, the median (interquartile range) CHeKS score (0 to 100%) was 65%[52% to 78%]. Lower scores were associated with older age, fewer years of education, and nonwhite race. Patients with CHeKS scores 20 percentage points higher were more likely to use an arteriovenous fistula or graft compared with a catheter at HD initiation and 6 mo after adjustment for age, sex, race, education, and diabetes mellitus. No statistically significant associations were found between knowledge and laboratory outcome measures, except for a moderate association with serum albumin. Potential limitations include residual confounding and an underpowered study to determine associations with some clinical measures. CONCLUSIONS: Patients with less dialysis knowledge may be less likely to use an arteriovenous access for dialysis at initiation and after starting hemodialysis. Additional studies are needed to explore the impact of patient dialysis knowledge, and its improvement after educational interventions, on vascular access in hemodialysis.

Reducing early mortality in patients on dialysis: lessons from the RightStart program.

RightStart, a specially designed program for patients new to dialysis, incorporates case manager-driven patient education, encouragement, and empowerment in conjunction with facilitation of prompt and appropriate care provided by the interdisciplinary team. Compared with patients who were not in RightStart, participants exhibited a 41% decrease in the risk of death within the first 90 days of dialysis (hazard ratio 0.59, P < 0.001). The results suggest that a program targeted to new patients on dialysis can significantly reduce early mortality and morbidity while increasing job satisfaction for professionals in the case manager role.

Early intervention improves mortality and hospitalization rates in incident hemodialysis patients: RightStart program.

BACKGROUND AND OBJECTIVES: Annualized mortality rates of chronic hemodialysis (CHD) patients in their first 90 d of treatment range from 24 to 50%. Limited studies also show high hospitalization rates. It was hypothesized that a structured quality improvement program (RightStart), focused on medical needs and patient education and support, would improve outcomes for incident CHD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 918 CHD incident patients were prospectively enrolled in a multicenter RightStart Program, and compared with a time-concurrent group of 1020 control patients from non-RightStart clinics. RightStart patients received 3 mo of intervention in management of anemia, dosage of dialysis, nutrition, and dialysis access and a comprehensive educational program. Outcomes were tracked for up to 12 mo. RESULTS: At 3 mo, RightStart patients had higher albumin and hematocrit values. Dose of dialysis and permanent access placement were not statistically significantly different from control subjects. Compared with baseline, Mental Composite Score for RightStart patients improved significantly. Mean hospitalization days per patient year were reduced with RightStart versus control subjects. Mortality rates at 3, 6, and 12 mo were 20, 18, and 17 for RightStart patients versus 39, 33, and 30 deaths per 100 patient-years for control subjects, respectively. CONCLUSIONS: A structured program of prompt medical and educational strategies in incident CHD patients results in improved morbidity and mortality that last up to 1 yr.

Patient education and the nursing process: meeting the patient's needs.

The ultimate goal of patient educational programs is to achieve long-lasting changes in behavior by providing patients with the knowledge to allow them to make autonomous decisions to take ownership of their care as much as possible and improve their own outcomes. Patient education is an integral part of the nursing process, and nephrology nurses can use this process to assess, plan, implement, and evaluate an effective and individualized patient education program.