Supporting patient self-management: A cross-sectional and prospective cohort study investigating Patient Activation Measure (PAM) and Clinician Support for PAM scores as part of a multi-centre haemodialysis breakthrough series collaborative.

BACKGROUND: Patient self-management, measured by the Patient Activation Measure (PAM), is associated with reduced healthcare utilisation and better health-related quality of life. Self-management in haemodialysis (HD) is challenging and may require support from clinicians with positive attitudes towards self-management, measured by the Clinician Support for PAM (CSPAM). OBJECTIVES: To assess whether kidney staff CSPAM scores are: 1) associated with their centre's patient PAM scores and 2) modifiable through staff coaching. METHODS: Baseline PAM and CSPAM and six-month CSPAM were collected from HD patients and kidney staff respectively in seven UK kidney centres as part of a six-month breakthrough series collaborative (BTSC), which trained kidney staff in supporting patient independence with HD tasks. Firstly, multivariable linear regression analyses adjusted for patient characteristics were used to test the baseline association between centre-level staff CSPAM scores and patient PAM scores. Secondly, paired univariate and unpaired multivariable linear regression analyses were conducted to compare staff CSPAM scores at baseline and six months. RESULTS: 236 PAM questionnaires (mean score = 55.5) and 89 CSPAM questionnaires (median score = 72.6) were analysed at baseline. There was no significant association between centre-level mean CSPAM scores and PAM scores in univariate analyses (P = 0.321). After adjusting for patient-level characteristics, increasing centre-level mean CSPAM score by 1 point resulted in a non-significant 0.3-point increase in PAM score (0.328 (95% CI: -0.157 to 0.812; P = 0.184). Paired (n = 37) and unpaired (n = 174) staff analyses showed a non-significant change in CSPAM scores following the BTSC intervention (mean change in CSPAM score in unpaired analysis = 1.339 (95% CI: -1.945 to 4.623; P = 0.422). CONCLUSIONS: Lack of a significant: 1) association between CSPAM and PAM scores and 2) change in CSPAM scores suggest that modifying staff beliefs alone is less likely to influence patient self-management, requiring co-production between patients and staff.

Centre variation in home dialysis uptake: A survey of kidney centre practice in relation to home dialysis organisation and delivery in England.

BACKGROUND: Disparities in home dialysis uptake across England suggest inequity and unexplained variation in access. We surveyed staff at all English kidney centres to identify patterns in service organisation/delivery and explore correlations with home therapy uptake, as part of a larger study ('Inter-CEPt'), which aims to identify potentially modifiable factors to address observed variations. METHODS: Between June and September 2022, staff working at English kidney centres were surveyed and individual responses combined into one centre-level response per question using predetermined data aggregation rules. Descriptive analysis described centre practices and their correlation with home dialysis uptake (proportion of new home dialysis starters) using 2019 UK Renal Registry 12-month home dialysis incidence data. RESULTS: In total, 180 responses were received (50/51 centres, 98.0%). Despite varied organisation of home dialysis services, most components of service delivery and practice had minimal or weak correlations with home dialysis uptake apart from offering assisted peritoneal dialysis and 'promoting flexible decision-making about dialysis modality'. Moderate to strong correlations were identified between home dialysis uptake and centres reporting supportive clinical leadership (correlation 0.32, 95% Confidence Interval (CI): 0.05-0.55), an organisational culture that values trying new initiatives (0.57, 95% CI: 0.34-0.73); support for reflective practice (0.38, 95% CI: 0.11-0.60), facilitating research engagement (0.39, 95% CI: 0.13-0.61) and promoting continuous quality improvement (0.29, 95% CI: 0.01-0.53). CONCLUSIONS: Uptake of home dialysis is likely to be driven by organisational culture, leadership and staff attitudes, which provide a supportive clinical environment within which specific components of service organisation and delivery can be effective.

Identifying individuals at risk of needing CKD associated medications in a European kidney disease cohort.

BACKGROUND: The consequences of chronic kidney disease (CKD) can be addressed with a range of pharmacotherapies primarily prescribed by nephrologists. More accurate information regarding future CKD-related pharmacotherapy requirements could guide clinical decisions including follow-up frequency. METHODS: Following assignment to derivation and validation groups (2,1), variables predicting individually future use of vitamin D receptor agonists (VDRA), phosphate binders, erythropoiesis stimulating agents (ESAs) and iron were identified using logistic regression in a prospective cohort study containing demography, comorbidity, hospitalization, laboratory, and mortality data in patients with CKD stage G4/G5 across six European countries. Discriminative ability was measured using C-statistics, and predicted probability of medication use used to inform follow-up frequency. RESULTS: A total of 2196 patients were included in the analysis. During a median follow-up of 735 days 648 initiated hemodialysis and 1548 did not. Combinations of age, diabetes status and iPTH, calcium, hemoglobin and serum albumin levels predicted the use of ESA, iron, phosphate binder or VDRA, with C-statistics of 0.70, 0.64, 0.73 and 0.63 in derivation cohorts respectively. Model performance in validation cohorts were similar. Sixteen percent of patients were predicted to have a likelihood of receiving any of these medications of less than 20%. CONCLUSIONS: In a multi-country CKD cohort, prediction of ESA and phosphate binder use over a two-year period can be made based on patient characteristics with the potential to reduce frequency of follow-up in individuals with low risk for requiring these medications.

Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial.

OBJECTIVE: Chronic kidney disease-associated pruritus (CKD-aP) can have a substantial negative impact on health-related quality of life (HRQoL), including an increased risk of depression, anxiety and sleep disturbance. This trial aimed to assess the impact of intravenous difelikefalin on HRQoL in haemodialysis patients with moderate-to-severe CKD-aP. METHODS: Post hoc analysis of an open-label, multicentre, single-arm intervention trial assessed pruritus severity and HRQoL at baseline and at 12 weeks of difelikefalin treatment using Worst Itching Intensity Numerical Rating Scale (WI-NRS), Sleep Quality Numeric Rating Scale (SQ-NRS), 5-D itch scale, Skindex-10 scale, EQ-5D-5L with Pruritus Bolt-On (EQ-PSO). RESULTS: A total of 222 patients received ≥ 1 dose of difelikefalin, and 197 patients completed 12 weeks of difelikefalin treatment. Clinically meaningful changes from baseline to 12 weeks were observed in all disease-specific measures: 73.7% of patients achieved a ≥ 3-point reduction in the weekly mean of 24 h WI-NRS scores and 66% of patients experienced ≥ 3-point improvements in SQ-NRS scores. Improvements were also observed in all Skindex-10 scale and 5-D itch scale domain scores. The percentage of patients reporting no problems in all EQ-PSO domains increased from 1.4 to 24.7% (p < 0.001), respectively. Patients' generic HRQoL EQ-5D-5L mean utility and EQ-5D visual analogue scale scores increased from baseline to 12 weeks: mean changes 0.04 (p = 0.001) and 2.8 (p = 0.046), respectively. CONCLUSIONS: Patients undergoing haemodialysis with moderate-to-severe CKD-aP receiving difelikefalin reported experiencing clinically meaningful improvements in both their pruritus symptoms and itch-related QoL. CLINICALTRIALS: gov registration number, NCT03998163; first submitted, 7 May 2019.

Use of Analog and Human Insulin in a European Hemodialysis Cohort With Type 2 Diabetes: Associations With Mortality, Hospitalization, MACE, and Hypoglycemia.

RATIONALE & OBJECTIVE: Poor glycemic control may contribute to the high mortality rate in patients with type 2 diabetes receiving hemodialysis. Insulin type may influence glycemic control, and its choice may be an opportunity to improve outcomes. This study assessed whether treatment with analog insulin compared with human insulin is associated with different outcomes in people with type 2 diabetes and kidney failure receiving hemodialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: People in the Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) study with kidney failure commencing hemodialysis and type 2 diabetes being treated with insulin within 288 dialysis facilities between 2007 and 2009 across 7 European countries. Study participants were followed for 3 years. People with type 1 diabetes were excluded using an established administrative data algorithm. EXPOSURE: Treatment with an insulin analog or human insulin. OUTCOME: All-cause mortality, major adverse cardiovascular events (MACE), all-cause hospitalization, and confirmed hypoglycemia (blood glucose<3.0mmol/L sampled during hemodialysis). ANALYTICAL APPROACH: Inverse probability weighted Cox proportional hazards models to estimate hazard ratios for analog insulin compared with human insulin. RESULTS: There were 713 insulin analog and 733 human insulin users. Significant variation in insulin type by country was observed. Comparing analog with human insulin at 3 years, the percentage of patients experiencing end points and adjusted hazard ratios (AHR) were 22.0% versus 31.4% (AHR, 0.808 [95% CI, 0.66-0.99], P=0.04) for all-cause mortality, 26.8% versus 35.9% (AHR, 0.817 [95% CI, 0.68-0.98], P=0.03) for MACE, and 58.2% versus 75.0% (AHR, 0.757 [95% CI, 0.67-0.86], P<0.001) for hospitalization. Hypoglycemia was comparable between insulin types at 14.1% versus 15.0% (AHR, 1.169 [95% CI, 0.80-1.72], P=0.4). Consistent strength and direction of the associations were observed across sensitivity analyses. LIMITATIONS: Residual confounding, lack of more detailed glycemia data. CONCLUSIONS: In this large multinational cohort of people with type 2 diabetes and kidney failure receiving maintenance hemodialysis, treatment with analog insulins was associated with better clinical outcomes when compared with human insulin. PLAIN-LANGUAGE SUMMARY: People with diabetes who are receiving dialysis for kidney failure are at high risk of cardiovascular disease and death. This study uses information from 1,446 people with kidney failure from 7 European countries who are receiving dialysis, have type 2 diabetes, and are prescribed either insulin identical to that made in the body (human insulin) or insulins with engineered extra features (insulin analog). After 3 years, fewer participants receiving analog insulins had died, had been admitted to the hospital, or had a cardiovascular event (heart attack, stroke, heart failure, or peripheral vascular disease). These findings suggest that analog insulins should be further explored as a treatment leading to better outcomes for people with diabetes on dialysis.

Catheter Event Rates in Medical Compared to Surgical Peritoneal Dialysis Catheter Insertion.

Introduction: How patient, center, and insertion technique factors interact needs to be understood when designing peritoneal dialysis (PD) catheter insertion pathways. Methods: We undertook a prospective cohort study in 44 UK centers enrolling participants planned for first catheter insertion. Sequences of regressions were used to describe the associations linking patient and dialysis unit-level characteristics with catheter insertion technique and their impact on the occurrence of catheter-related events in the first year (catheter-related infection, hospitalization, and removal). Factors associated with catheter events were incorporated into a multistate model comparing the rates of catheter events between medical and surgical insertion alongside treatment modality transitions and mortality. Results: Of 784 first catheter insertions, 466 (59%) had a catheter event in the first year and 61.2% of transitions onto hemodialysis (HD) were immediately preceded by a catheter event. Catheter malfunction was less but infection was more common with surgical compared with medical insertions. Participants at centers with fewer late presenters and more new dialysis patients starting PD, had a lower probability of a catheter event. Adjusting for these factors, the hazard ratio for a catheter event following insertion (medical vs. surgical) was 0.70 (95% confidence interval [CI] 0.43 to 1.13), and once established on PD 0.77 (0.62 to 0.96). Conclusion: Offering both medical and surgical techniques is associated with lower catheter event rates and keeps people on PD for longer.

The trajectory of a range of commonly captured symptoms with standard care in people with kidney failure receiving haemodialysis: consideration for clinical trial design.

BACKGROUND: Despite the recognized high symptom prevalence in haemodialysis population, how these symptoms change over time and its implications for clinical practice and research is poorly understood. METHODS: Prevalent haemodialysis patients in the SHAREHD trial reported 17 POS-S Renal symptoms (none, mild, moderate, severe and overwhelming) at baseline, 6, 12 and 18 months. To assess the prevalence change at population level in people reporting moderate or worse symptoms at baseline, the absolute change in prevalence was estimated using multi-level mixed effects probit regression adjusting for age, sex, time on haemodialysis and Charlson Comorbidity Score. To assess changes at individual level, the proportion of people changing their symptom score every 6 months was estimated. RESULTS: Five hundred fifty-two participants completed 1725 questionnaires at four timepoints. Across all 17 symptoms with moderate or worse symptom severity at baseline, the majority of the change in symptom prevalence at population level occurred in the 'severe' category. The absolute improvement in prevalence of the 'severe' category was ≤ 20% over 18 months in eleven of the seventeen symptoms despite a large degree of relatively balanced movement of individuals in and out of severe category every six months. Examples include depression, skin changes and drowsiness, which had larger proportion (75-80%) moving in and out of severe category each 6 months period but < 5% difference between movement in and out of severe category resulting in relatively static prevalence over time. Meanwhile, larger changes in prevalence of > 20% were observed in six symptoms, driven by a 9 to 18% difference between movement in and movement out of severe category. All symptoms had > 50% of people in severe group changing severity within 6 months. CONCLUSIONS: Changes in the severity of existing symptoms under standard care were frequent, often occurring within six months. Certain symptoms exhibited clinically meaningful shifts at both the population and individual levels. This highlighted the need to consider improvements in symptom severity when determining sample size and statistical power for trials. By accounting for potential symptom improvements with routine care, researchers can design trials capable of robustly detecting genuine treatment effects, distinguishing them from spontaneous changes associated with standard haemodialysis.

Relationship Between Standardized Measures of Chronic Kidney Disease-associated Pruritus Intensity and Health-related Quality of Life Measured with the EQ-5D Questionnaire: A Mapping Study.

Chronic kidney disease-associated pruritus is linked with decreased health-related quality of life assessed using disease-specific instruments. The extent to which worsening pruritus reduces generic quality of life assessed using the EQ-5D instrument is unknown. Prevalent kidney failure patients receiving in-centre haemodialysis from 5 centres completed the EQ-5D-5L quality of life measure, worst Itching Intensity Numerical Rating Scale and 5-D itch pruritus instruments. Latent class models were used to identify clusters of patients with similarly affected body parts, and mixture models were used to map the pruritus measures to the EQ-5D. Data on 487 respondents were obtained. Latent class analysis identified 3 groups of patients who had progressively worsening severity and an increasing number of body parts affected. Although the worst itching intensity numerical rating scale and 5-D itch instruments correlated with each other, only the latter had a strong relationship with EQ-5D. When controlling for age, sex, diabetes and years receiving dialysis, the meanpredicted EQ-5D utility (1: perfect health, 0: dead) decreased progressively from 0.69 to 0.41. These findings suggest that pruritus instruments that include domains capturing how the individual is physically, mentally and socially affected by their pruritus, in addition to severity, more closely approximate the EQ-5D generic quality of life measure.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Barriers and facilitators to the implementation of guidelines in rare diseases: a systematic review.

BACKGROUND: Rare diseases present a challenge to guideline implementation due to a low prevalence in the general population and the unfamiliarity of healthcare professionals. Existing literature in more common diseases references barriers and facilitators to guideline implementation. This systematic review aims to identify these barriers and facilitators in rare diseases from existing literature. METHODS: A multi-stage strategy included searching MEDLINE PubMed, EMBASE Ovid, Web of Science and Cochrane library from the earliest date available to April 2021, Orphanet journal hand-search, a pearl-growing strategy from a primary source and reference/citation search was performed. The Integrated Checklist of Determinants of Practice which comprises of twelve checklists and taxonomies, informed by 57 potential determinants was selected as a screening tool to identify determinants that warrant further in-depth investigation to inform design of future implementation strategies. RESULTS: Forty-four studies were included, most of which were conducted in the United States (54.5%). There were 168 barriers across 36 determinants (37 studies) and 52 facilitators across 22 determinants (22 studies). Fifteen diseases were included across eight WHO ICD-11 disease categories. Together individual health professional factors and guideline factors formed the majority of the reported determinants (59.5% of barriers and 53.8% of facilitators). Overall, the three most reported individual barriers were the awareness/familiarity with the recommendation, domain knowledge and feasibility. The three most reported individual facilitators were awareness/familiarity with the recommendation, agreement with the recommendation and ability to readily access the guidelines. Resource barriers to implementation included technology costs, ancillary staff costs and more cost-effective alternatives. There was a paucity of studies reporting influential people, patient advocacy groups or opinion leaders, or organisational factors influencing implementation. CONCLUSIONS: Key barriers and facilitators to the implementation of clinical practice guidelines in the setting of rare diseases were at the individual health professional and guideline level. Influential people and organisational factors were relatively under-reported and warrant exploration, as does increasing the ability to access the guidelines as a potential intervention.

Cost Effectiveness of Difelikefalin Compared to Standard Care for Treating Chronic Kidney Disease Associated Pruritus (CKD-aP) in People with Kidney Failure Receiving Haemodialysis.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is associated with an increased risk of depression, poor sleep and reduced health-related quality of life. Two phase III studies (KALM-1 and KALM-2) of difelikefalin showed reduced CKD-aP severity and improved itch-related health-related quality of life in patients with moderate and severe CKD-aP receiving haemodialysis for kidney failure. OBJECTIVE: We aimed to estimate the cost effectiveness of difelikefalin for patients with CKD-aP receiving haemodialysis for kidney failure compared to standard care from a UK National Health Service perspective. METHODS: A cohort model was developed with four health states representing levels of pruritus intensity over time, based on the KALM trials augmented with longer term CKD-aP severity data from another haemodialysis trial (SHAREHD) for standard care. Utilities were estimated from a mapping study of 5-D Itch to EQ-5D-5L in 487 patients receiving haemodialysis, costs were estimated based on resource use alongside the SHAREHD and 2018 unit costs, and inflated to 2021 costs. Costs and quality-adjusted life-years were discounted at 3.5% per annum. A de novo economic model was developed in Microsoft Excel with scenario analyses performed using a range of assumptions. RESULTS: In the base-case analysis over a time horizon of 64 weeks, using a placeholder cost of £75 per 28-days for difelikefalin, the incremental cost-effectiveness ratio of difelikefalin compared with standard care was £19,558/quality-adjusted life-year (QALY). Scenario analyses resulted in incremental cost-effectiveness ratios that ranged from £10,154/QALY (severe only) to £16,957/QALY (5-year horizon) for difelikefalin compared to standard care. Probabilistic sensitivity analyses suggested difelikefalin has a 48.6% probability of being cost effective at a threshold of £20,000/QALY and a 57.2% probability of being cost effective at a threshold of £30,000/QALY. CONCLUSIONS: The cost effectiveness of difelikefalin in a range of scenarios could make it an important pharmacotherapy to address the high burden of disease and unmet need for treatments associated with CKD-aP in the UK.

Catheter insertion techniques for improving catheter function and clinical outcomes in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) relies on the optimal functionality of the flexible plastic PD catheter present within the peritoneal cavity to enable effective treatment. As a result of limited evidence, it is uncertain if the PD catheter's insertion method influences the rate of catheter dysfunction and, thus, the quality of dialysis therapy. Numerous variations of four basic techniques have been adopted in an attempt to improve and maintain PD catheter function. This review evaluates the association between PD catheter insertion technique and associated differences in  PD catheter function and post-PD catheter insertion complications OBJECTIVES: Our aims were to 1) evaluate if a specific technique used for PD catheter insertion has lower rates of PD catheter dysfunction (early and late) and technique failure; and 2) examine if any of the available techniques results in a reduction in post-procedure complication rates including postoperative haemorrhage, exit-site infection and peritonitis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 24 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) examining adults and children undergoing PD catheter insertion. The studies examined any two PD catheter insertion techniques, including laparoscopic, open-surgical, percutaneous and peritoneoscopic insertion. Primary outcomes of interest were PD catheter function and technique survival.  DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed the risk of bias for all included studies. Main outcomes in the Summary of Findings tables include primary outcomes - early PD catheter function, long-term PD catheter function, technique failure and postoperative complications. A random effects model was used to perform meta-analyses; risk ratios (RRs) were calculated for dichotomous outcomes, and mean differences (MD) were calculated for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. The certainty of the evidence was evaluated using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.  MAIN RESULTS: Seventeen studies were included in this review. Nine studies were suitable for inclusion in quantitative meta-analysis (670 randomised participants). Five studies compared laparoscopic with open PD catheter insertion, and four studies compared a 'medical' insertion technique with open surgical PD catheter insertion: percutaneous (2) and peritoneoscopic (2). Random sequence generation was judged to be at low risk of bias in eight studies. Allocation concealment was reported poorly, with only five studies judged to be at low risk of selection bias. Performance bias was judged to be high risk in 10 studies. Attrition bias and reporting bias were judged to be low in 14 and 12 studies, respectively. Six studies compared laparoscopic PD catheter insertion with open surgical insertion. Five studies could be meta-analysed (394 participants). For our primary outcomes, data were either not reported in a format that could be meta-analysed (early PD catheter function, long-term catheter function) or not reported at all (technique failure). One death was reported in the laparoscopic group and none in the open surgical group. In low certainty evidence, laparoscopic PD catheter insertion may make little or no difference to the risk of peritonitis (4 studies, 288 participants: RR 0.97, 95% CI 0.63 to 1.48; I² = 7%), PD catheter removal (4 studies, 257 participants: RR 1.15, 95% CI 0.80 to 1.64; I² = 0%), and dialysate leakage (4 studies, 330 participants: RR 1.40, 95% CI 0.49 to 4.02; I² = 0%), but may reduce the risk of haemorrhage (2 studies, 167 participants: RR 1.68, 95% CI 0.28 to 10.31; I² = 33%) and catheter tip migration (4 studies, 333 participants: RR 0.43, 95% CI 0.20 to 0.92; I² = 12%). Four studies compared a medical insertion technique with open surgical insertion (276 participants). Technique failure was not reported, and no deaths were reported (2 studies, 64 participants). In low certainty evidence, medical insertion may make little or no difference to early PD catheter function (3 studies, 212 participants: RR 0.73, 95% CI 0.29 to 1.83; I² = 0%), while one study reported long-term PD function may improve with peritoneoscopic insertion (116 participants: RR 0.59, 95% CI 0.38 to 0.92). Peritoneoscopic catheter insertion may reduce the episodes of early peritonitis (2 studies, 177 participants: RR 0.21, 95% CI 0.06 to 0.71; I² = 0%) and dialysate leakage (2 studies, 177 participants: RR 0.13, 95% CI 0.02 to 0.71; I² = 0%). Medical insertion had uncertain effects on catheter tip migration (2 studies, 90 participants: RR 0.74, 95% CI 0.15 to 3.73; I² = 0%). Most of the studies examined were small and of poor quality, increasing the risk of imprecision. There was also a significant risk of bias therefore cautious interpretation of results is advised. AUTHORS' CONCLUSIONS: The available studies show that the evidence needed to guide clinicians in developing their PD catheter insertion service is lacking. No PD catheter insertion technique had lower rates of PD catheter dysfunction. High-quality, evidence-based data are urgently required, utilising multi-centre RCTs or large cohort studies, in order to provide definitive guidance relating to PD catheter insertion modality.

Treatment inequity in antiplatelet therapy for ischaemic heart disease in patients with advanced chronic kidney disease: releasing the evidence vacuum.

Chronic kidney disease (CKD) is a global health problem and an independent risk factor for cardiovascular morbidity and mortality. Despite evidence-based therapies significantly improving cardiovascular mortality outcomes in the general population and those with non-dialysis-dependent CKD, this risk reduction has not translated to patients with end-stage kidney disease (ESKD). Absent from all major antiplatelet trials, this has led to insufficient safety data for P2Y12 inhibitor prescriptions and treatment inequity in this subpopulation. This review article presents an overview of the progression of research in understanding antiplatelet therapy for ischaemic heart disease in patients with advanced CKD (defined as eGFR <30 mL/min/1.73 m2). Beyond trial recruitment strategies, new approaches should focus on registry documentation by CKD stage, risk stratification with biomarkers associated with inflammation and haemorrhage and building a knowledge base on optimal duration of dual and single antiplatelet therapies.

What is the context? Patients with kidney disease are more likely to experience a heart attack than those without.Those with advanced kidney disease have a higher risk of death following a heart attack.Over the past two decades, advances in treatment following a heart attack have reduced the risk of death, however this has not translated to those with advanced kidney disease.Progression of kidney disease influences antiplatelet (e.g. clopidogrel) treatment efficacy.What is new?This contemporary review analyses registry and trial data to highlight some of the issues surrounding treatment inequity in patients with advanced kidney disease.This article describes potential mechanisms by which progression of kidney disease can influence clotting, bleeding and antiplatelet treatments.What is the impact?Further research into antiplatelet therapy for patients with advanced kidney disease is required.Registry and trial data can improve upon classification of kidney disease for future research.Future trials in antiplatelet therapy for advanced kidney disease are anticipated.

Symptom burden according to dialysis day of the week in three times a week haemodialysis patients.

BACKGROUND: Haemodialysis patients experience significant symptom burden and effects on health-related quality of life. Studies have shown increases in fluid overload, hospitalization and mortality immediately after the long interdialytic interval in thrice weekly in-centre haemodialysis patients, however the relationship between the dialytic interval and patient reported outcome measures (PROMs) has not been quantified and the extent to which dialysis day of PROM completion needs to be standardised is unknown. METHODS: Three times a week haemodialysis patients participating in a stepped wedge trial to increase patient participation in haemodialysis tasks completed PROMs (POS-S Renal symptom score and EQ-5D-5L) at recruitment, six, 12 and 18 months. Time from the long interdialytic interval, HD day of the week, and HD days vs non-HD days were included in mixed effects Linear Regression, estimating severity (none to overwhelming treated as 0 to 4) of 17 symptoms and EQ-5D-5L, adjusting for age, sex, time on HD, control versus intervention and Charlson Comorbidity Score. RESULTS: 517 patients completed 1659 YHS questionnaires that could be assigned HD day (510 on Mon/Tue/Sun, 549 on Wed/Thu/Tue, 308 on Fri/Sat/Thu and 269 on non-HD days). With the exception of restless legs and skin changes, there was no statistically significant change in symptom severity or EQ-5D-5L with increasing time from the long interdialytic interval. Patients who responded on non-HD days had higher severity of poor appetite, constipation, difficulty sleeping, poor mobility and depression (approximately 0.2 severity level), and lower EQ-5D-5L (-0.06, CI -0.09 to -0.03) compared to HD days. CONCLUSIONS: Measuring symptom severity and EQ-5D-5L in haemodialysis populations does not need to account for dialysis schedule, but completion either on HD or non-HD days could introduce bias that may impact evaluation of interventions. Researchers should ensure completion of these instruments are standardized on either dialysis or non-dialysis days.

Propensity Score and Instrumental Variable Techniques in Observational Transplantation Studies: An Overview and Worked Example Relating to Pre-Transplant Cardiac Screening.

Inferring causality from observational studies is difficult due to inherent differences in patient characteristics between treated and untreated groups. The randomised controlled trial is the gold standard study design as the random allocation of individuals to treatment and control arms should result in an equal distribution of known and unknown prognostic factors at baseline. However, it is not always ethically or practically possible to perform such a study in the field of transplantation. Propensity score and instrumental variable techniques have theoretical advantages over conventional multivariable regression methods and are increasingly being used within observational studies to reduce the risk of confounding bias. An understanding of these techniques is required to critically appraise the literature. We provide an overview of propensity score and instrumental variable techniques for transplant clinicians, describing their principles, assumptions, strengths, and weaknesses. We discuss the different patient populations included in analyses and how to interpret results. We illustrate these points using data from the Access to Transplant and Transplant Outcome Measures study examining the association between pre-transplant cardiac screening in kidney transplant recipients and post-transplant cardiac events.

Intervening to eliminate the centre-effect variation in home dialysis use: protocol for Inter-CEPt-a sequential mixed-methods study designing an intervention bundle.

INTRODUCTION: Use of home dialysis by centres in the UK varies considerably and is decreasing despite attempts to encourage greater use. Knowing what drives this unwarranted variation requires in-depth understanding of centre cultural and organisational factors and how these relate to quantifiable centre performance, accounting for competing treatment options. This knowledge will be used to identify components of a practical and feasible intervention bundle ensuring this is realistic and cost-effective. METHODS AND ANALYSIS: Underpinned by the non-adoption, abandonment, scale-up, spread and sustainability framework, our research will use an exploratory sequential mixed-methods approach. Insights from multisited focused team ethnographic and qualitative research at four case study sites will inform development of a national survey of 52 centres. Survey results, linked to patient-level data from the UK Renal Registry, will populate a causal graph describing patient and centre-level factors, leading to uptake of home dialysis and multistate models incorporating patient-level treatment modality history and mortality. This will inform a contemporary economic evaluation of modality cost-effectiveness that will quantify how modification of factors facilitating home dialysis, identified from the ethnography and survey, might yield the greatest improvements in costs, quality of life and numbers on home therapies. Selected from these factors, using the capability, opportunity and motivation for behaviour change framework (COM-B) for intervention design, the optimal intervention bundle will be developed through workshops with patients and healthcare professionals to ensure acceptability and feasibility. Patient and public engagement and involvement is embedded throughout the project. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Health Research Authority reference 20-WA-0249. The intervention bundle will comprise components for all stake holder groups: commissioners, provider units, recipients of dialysis, their caregivers and families. To reache all these groups, a variety of knowledge exchange methods will be used: short guides, infographics, case studies, National Institute for Health and Care Excellence guidelines, patient conferences, 'Getting it Right First Time' initiative, Clinical Reference Group (dialysis).

Measuring quality of life in trials including patients on haemodialysis: methodological issues surrounding the use of the Kidney Disease Quality of Life Questionnaire.

BACKGROUND: Haemodialysis (HD) treatment causes a significant decrease in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up because they die or they receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed. METHODS: A systematic search of electronic databases for trials measuring QoL in HD patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire was conducted. The review was conducted in Covidence version 2. Quantitative analysis was conducted in Stata version 16. RESULTS: We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted a sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used, but are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many articles (70%) amending the validated questionnaires or reporting only statistically significant results. CONCLUSIONS: Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient-reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group. PROSPERO REGISTRATION: CRD42020223869.

The relationship between chronic kidney disease-associated pruritus and health-related quality of life: a systematic review.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is a common and burdensome condition for end-stage kidney disease (ESKD) patients, especially those receiving haemodialysis. High-quality evidence of the relationship between CKD-aP and health-related quality of life (HRQoL) can therefore inform clinicians and policymakers about treatment choice and reimbursement decisions. METHODS: A systematic literature review and narrative synthesis stratified by study design and HRQoL instrument was conducted to evaluate in adult ESKD patients receiving in-centre haemodialysis the relationship between CKD-aP and HRQoL assessed using multi dimensional generic or condition-specific preference- or non-preference-based measures. MEDLINE, Embase, Web of Science, BIOSIS Citation Index, Cochrane Library and PsycINFO from inception to March 2020 were searched, with two reviewers extracting data independently. RESULTS: Searches identified 2684 unique records, of which 20 papers relating to 18 unique studies [5 randomised controlled trials (RCTs) and 13 observational studies] were included. HRQoL was assessed using four generic and eight disease-specific measures. The impact of CKD-aP was assessed by comparison of means, linear regression and correlation. Observational studies employing comprehensively adjusted multivariable linear regression largely found associations between CKD-aP severities and HRQoL. Analyses suggest this relationship is partially mediated by the sleep disturbance caused by CKD-aP. RCTs showing improvements in CKD-aP severity were associated with clinically meaningful improvements in HRQoL. Compared with generic measures, disease-specific HRQoL instruments reported greater changes with reduced CKD-aP. Heterogeneity in study design and reporting precluded meta-analysis. CONCLUSIONS: CKD-aP severity was found to be associated with a worsening of HRQoL in the majority of observational and RCT studies. Parallel improvements in CKD-aP and HRQoL with interventions may support their use (PROSPERO registration 175035).

The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States.

BACKGROUND AND OBJECTIVES: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active-Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan-Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. RESULTS: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. CONCLUSIONS: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.