Ethical Issues in Pragmatic Cluster-Randomized Trials in Dialysis Facilities.

A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides general ethical guidance for CRTs, the dialysis setting raises additional considerations. In this article, we outline ethical issues raised by pragmatic CRTs in dialysis facilities. These issues may be divided into 7 key domains: justifying the use of cluster randomization, adopting randomly allocated individual-level interventions as a facility standard of care, conducting benefit-harm analyses, gatekeepers and their responsibilities, obtaining informed consent from research participants, patient notification, and including vulnerable participants. We describe existing guidelines relevant to each domain, illustrate how they were considered in the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (a prototypical pragmatic hemodialysis CRT), and highlight remaining areas of uncertainty. The following is the first step in an interdisciplinary mixed-methods research project to guide the design and conduct of pragmatic CRTs in dialysis facilities. Subsequent work will expand on these concepts and when possible, argue for a preferred solution.

Complications of the Arteriovenous Fistula: A Systematic Review.

The implementation of patient-centered care requires an individualized approach to hemodialysis vascular access, on the basis of each patient's unique balance of risks and benefits. This systematic review aimed to summarize current literature on fistula risks, including rates of complications, to assist with patient-centered decision making. We searched Medline from 2000 to 2014 for English-language studies with prospectively captured data on ≥100 fistulas. We assessed study quality and extracted data on study design, patient characteristics, and outcomes. After screening 2292 citations, 43 articles met our inclusion criteria (61 unique cohorts; n>11,374 fistulas). Median complication rates per 1000 patient days were as follows: 0.04 aneurysms (14 unique cohorts; n=1827 fistulas), 0.11 infections (16 cohorts; n>6439 fistulas), 0.05 steal events (15 cohorts; n>2543 fistulas), 0.24 thrombotic events (26 cohorts; n=4232 fistulas), and 0.03 venous hypertensive events (1 cohort; n=350 fistulas). Risk of bias was high in many studies and event rates were variable, thus we could not present pooled results. Studies generally did not report variables associated with fistula complications, patient comorbidities, vessel characteristics, surgeon experience, or nursing cannulation skill. Overall, we found marked variability in complication rates, partly due to poor quality studies, significant heterogeneity of study populations, and inconsistent definitions. There is an urgent need to standardize reporting of methods and definitions of vascular access complications in future clinical studies to better inform patient and provider decision making.

Second-Generation Antidepressants and Hyponatremia Risk: A Population-Based Cohort Study of Older Adults.

BACKGROUND: Hyponatremia may occur after initiation of a second-generation antidepressant drug. However, the magnitude of this risk among older adults in routine care is not well characterized. STUDY DESIGN: Retrospective, population-based, matched-cohort study. SETTING & PARTICIPANTS: In Ontario, Canada, 2003 to 2012, we compared older adults with a mood or anxiety disorder who were dispensed 1 of 9 second-generation antidepressant drugs with matched adults with comparable indicators of baseline health who were not dispensed an antidepressant drug (n=138,246 per group). A similar comparison was made in a subpopulation with available laboratory data (n=4,186 per group). PREDICTOR: Second-generation antidepressant prescription versus no antidepressant prescription. OUTCOMES: The primary outcome was hospitalization with hyponatremia. A secondary outcome was hospitalization with both hyponatremia and delirium. MEASUREMENTS: We assessed hospitalization with hyponatremia using a diagnosis code and, in the subpopulation, serum sodium values. We assessed hospitalization with hyponatremia and delirium using a combination of diagnosis codes. RESULTS: Second-generation antidepressant use versus nonuse was associated with higher 30-day risk for hospitalization with hyponatremia (450/138,246 [0.33%] vs 84/138,246 [0.06%]; relative risk [RR], 5.46 [95% CI, 4.32-6.91]). This association was consistent in the subpopulation with serum sodium values (73/4,186 [1.74%] vs 18/4,186 [0.43%]; RR, 4.23 [95% CI, 2.50-7.19]; absolute risk increase, 1.31% [95% CI, 0.87%-1.75%]). Second-generation antidepressant use versus nonuse was also associated with higher 30-day risk for hospitalization with both hyponatremia and delirium (28/138,246 [0.02%] vs 7/138,246 [0.005%]; RR, 4.00 [95% CI, 1.75-9.16]). LIMITATIONS: Measures of serum sodium could be ascertained in only a subpopulation. CONCLUSIONS: Use of a second-generation antidepressant in routine care by older adults is associated with an approximate 5-fold increase in 30-day risk for hospitalization with hyponatremia compared to nonuse. However, the absolute increase in 30-day incidence is low.

The role of plasma exchange in treating post-transplant focal segmental glomerulosclerosis: A systematic review and meta-analysis of 77 case-reports and case-series.

BACKGROUND: Evidence on the role of plasma exchange for treating recurrent post-transplant focal segmental glomerulosclerosis (FSGS) comes largely from individual cases and uncontrolled series. We conducted a systematic review and meta-analysis to estimate the remission rate after treatment with plasma exchange, and to determine if remission varied with patient or treatment characteristics. METHODS: We searched MEDLINE, EMBASE, Science Citation Index Expanded, and the Conference Proceedings Citation Index (Science and BIOSIS) for studies of patients with post-transplant recurrent FSGS who were treated with plasma exchange after recurrence (1950-2012). Of 678 studies screened, 77 met our inclusion criteria: 34 case reports (45 patients) and 43 case series (378 patients). We extracted patient-level data from each study and used random-effects models to calculate remission, defined as proteinuria <3.5 g/day (partial) or <0.5 g/day (complete). RESULTS: The overall remission rate in 423 patients with outcome data was 71 % (95 % CI: 66 % to 75 %). In 235 patients with data on age, remission was similar for adults and children: 69.1 % (95 % CI: 59.6 % to 77.2 %) and 70.2 % (95 % CI: 61.1 % to 77.9 %). Males were more likely to achieve remission (OR = 2.85; 95 % CI: 1.44 to 5.62) and patients treated within 2 weeks of recurrence showed a trend towards higher likelihood of remission (OR = 2.16; 95 % CI: 0.93 to 5.01). Proteinuria >7 g/day at recurrence was inversely associated with remission (OR = 0.43; 95 % CI: 0.19 to 0.97). Age and type of kidney transplant (living vs. deceased) did not associate with remission. CONCLUSION: In this systematic review of patients with recurrent post-transplant FSGS, 71 % of patients achieved full or partial remission after treatment with plasma exchange; however, extensive missing data and lack of a control group limit any conclusions on causality.

Repeated Diagnostic Imaging Studies in Ontario and the Impact of Health Information Exchange Systems.

Health information exchange systems can link the results of diagnostic imaging tests across hospitals and geographic areas. One of the potential benefits of these systems is a reduction in imaging studies ordered by physicians who do not know about or have access to the previous imaging results. We used administrative data from Ontario, Canada (from the year 2013), to measure how frequently the same cross-sectional imaging study is repeated in a patient. Overall, 12.8% of the specified imaging tests were repeated within 90 days. An area of Southwestern Ontario with a health information exchange system for diagnostic imaging tests had a 13% lower rate of repeat cross-sectional imaging compared with the rest of the province (11.2 vs 12.8%, p < 0.01). The use of linked radiology systems may be able to reduce the number of repeated imaging tests and improve patient safety and hospital efficiency.

Hemodialysis Arteriovenous Vascular Access Creation After Kidney Transplant Failure.

BACKGROUND: Little is known about vascular access in patients starting hemodialysis therapy after kidney transplant failure. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult patients (aged ≥18 years) who started hemodialysis therapy in Ontario, Canada, from January 1, 2001, through December 31, 2010, after kidney transplant failure. PREDICTOR: Patient clinical and demographic characteristics. OUTCOMES: Proportion and timing of arteriovenous (AV) vascular access creation (fistula or graft) 12 months prior and up to 24 months after starting hemodialysis therapy. MEASUREMENTS: Event rates and outcome predictors. RESULTS: Our cohort included 683 patients with a mean age of 48 years and >50% with comorbidity index score < 3. In the 12 months predialysis and 24 months postdialysis, 16% and 47% of patients had an AV access created, respectively. In the postdialysis period, 13%, 26%, and 38% of patients had an AV access creation at 3, 6, and 12 months, respectively. History of coronary artery disease, diabetes mellitus, and peritoneal dialysis use prior to transplantation were associated with a lower likelihood of AV access creation. LIMITATIONS: Residual selection bias from unmeasured variables beyond the data elements. CONCLUSIONS: In Ontario, AV access creation, both before and after starting hemodialysis therapy, is low in patients with kidney transplant failure despite their being younger and healthier compared to the overall hemodialysis population. This highlights the need for a predialysis care pathway in the transplantation clinic and an active strategy to identify this patient cohort receiving hemodialysis to align modality and access choices.

Preoperative vascular access evaluation for haemodialysis patients.

BACKGROUND: Haemodialysis treatment requires reliable vascular access. Optimal access is provided via functional arteriovenous fistula (fistula), which compared with other forms of vascular access, provides superior long-term patency, requires few interventions, has low thrombosis and infection rates and cost. However, it has been estimated that between 20% and 60% of fistulas never mature sufficiently to enable haemodialysis treatment. Mapping blood vessels using imaging technologies before surgery may identify vessels that are most suitable for fistula creation. OBJECTIVES: We compared the effect of conducting routine radiological imaging evaluation for vascular access creation preoperatively with standard care without routine preoperative vessel imaging on fistula creation and use. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 14 April 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled adult participants (aged ≥ 18 years) with chronic or end-stage kidney disease (ESKD) who needed fistulas (both before dialysis and after dialysis initiation) that compared fistula maturation rates relating to use of imaging technologies to map blood vessels before fistula surgery with standard care (no imaging). DATA COLLECTION AND ANALYSIS: Two authors assessed study quality and extracted data. Dichotomous outcomes, including fistula creation, maturation and need for catheters at dialysis initiation, were expressed as risk ratios (RR) with 95% confidence intervals (CI). Continuous outcomes, such as numbers of interventions required to maintain patency, were expressed as mean differences (MD). We used the random-effects model to measure mean effects. MAIN RESULTS: Four studies enrolling 450 participants met our inclusion criteria. Overall risk of bias was judged to be low in one study, unclear in two, and high in one.There was no significant differences in the number of fistulas that were successfully created (4 studies, 433 patients: RR 1.06, 95% CI 0.95 to 1.28; I² = 76%); the number of fistulas that matured at six months (3 studies, 356 participants: RR 1.11, 95% CI 0.98 to 1.25; I² = 0%); number of fistulas that were used successfully for dialysis (2 studies, 286 participants: RR 1.12, 95% CI 0.99 to 1.28; I² = 0%); the number of patients initiating dialysis with a catheter (1 study, 214 patients: RR 0.66, 95% CI 0.42 to 1.04); and in the rate of interventions required to maintain patency (1 study, 70 patients: MD 14.70 interventions/1000 patient-days, 95% CI -7.51 to 36.91) between the use of preoperative imaging technologies compared with standard care (no imaging). AUTHORS' CONCLUSIONS: Based on four small studies, preoperative vessel imaging did not improve fistula outcomes compared with standard care. Adequately powered prospective studies are required to fully answer this question.

Patency rates of the arteriovenous fistula for hemodialysis: a systematic review and meta-analysis.

BACKGROUND: Advantages of the arteriovenous fistula (AVF), including long patency and few complications, were ascertained more than 2 decades ago and may not apply to the contemporary dialysis population. STUDY DESIGN: Systematic review and meta-analysis. Estimates were pooled using a random-effects model and sources of heterogeneity were explored using metaregression. SETTING & POPULATION: Patients treated with long-term hemodialysis using an AVF. SELECTION CRITERIA FOR STUDIES: English-language studies indexed in MEDLINE between 2000 and 2012 using prospectively collected data on 100 or more AVFs. PREDICTOR: Age, AVF location, and study location. OUTCOMES: Outcomes of interest were primary AVF failure and primary and secondary patency at 1 and 2 years. RESULTS: 7,011 citations were screened and 46 articles met eligibility criteria (62 unique cohorts; n = 12,383). The rate of primary failure was 23% (95% CI, 18%-28%; 37 cohorts; 7,393 AVFs). When primary failures were included, the primary patency rate was 60% (95% CI, 56%-64%; 13 studies; 21 cohorts; 4,111 AVFs) at 1 year and 51% (95% CI, 44%-58%; 7 studies; 12 cohorts; 2,694 AVFs) at 2 years. The secondary patency rate was 71% (95% CI, 64%-78%; 10 studies; 11 cohorts; 3,558 AVFs) at 1 year and 64% (95% CI, 56%-73%; 6 studies; 11 cohorts; 1,939 AVFs) at 2 years. In metaregression, there was a significant decrease in primary patency rate in studies that started recruitment in more recent years. LIMITATIONS: Low quality of studies, variable clinical settings, and variable definitions of primary AVF failure. CONCLUSIONS: In recent years, AVFs had a high rate of primary failure and low to moderate primary and secondary patency rates. Consideration of these outcomes is required when choosing a patient's preferred access type.

Fistula eligibility: a work in progress.

Effective hemodialysis requires a reliable vascular access. Clinical practice guidelines strongly recommend the fistula as the preferred option followed by arteriovenous (AV) grafts, with central venous catheters being least preferred. Recently, there has been a growing awareness of the limitations of the fistula, its high rate of primary failure and that a fistula may not be appropriate for all patients initiating or on hemodialysis. However, determinates for fistula eligibility have not been clearly defined. The creation and use of a fistula requires the complex integration of patient, biological, and surgical factors, none of which can be easily predicted or planned. There have been several successful initiatives over the last decade addressing patient suitability for AV access, but none have validated defined criteria for fistula eligibility. We discuss these initiatives by addressing: 1) process of care, 2) radiological and nonradiological tests and procedures, and 3) alternative surgical approaches. Careful clinical judgment, appropriate vascular access assessment and placement, and an individualized approach to the risks and benefits will optimize patient health outcomes while minimizing prolonged catheter dependence among hemodialysis patients.

Functional difficulties in children and youth with autism spectrum disorder: analysis of the 2019 Canadian Health Survey on Children and Youth. / Difficultés fonctionnelles chez les enfants et les jeunes atteints d'un trouble du spectre de l'autisme : une analyse de l'Enquête canadienne sur la santé des enfants et des jeunes de 2019.

INTRODUCTION: This study examined the prevalence of functional difficulties and associated factors in Canadian children/youth aged 5 to 17 years diagnosed with autism spectrum disorder (ASD). METHODS: We analyzed data from the 2019 Canadian Health Survey on Children and Youth (CHSCY), a nationally representative survey of Canadian children/youth that used the Washington Group Short Set on Functioning (WG-SS) to evaluate functioning in six daily tasks. For each functional domain, binary outcomes were derived (no/some difficulty, a lot of difficulty/no ability). We used logistic regression to identify associations between demographic characteristics, educational experiences, and perceived mental and general health and the most common functional difficulties, namely those related to remembering/concentrating, communication and self-care. All estimates were weighted to be representative of the target population. The bootstrap method was used to calculate variance estimates. RESULTS: Analysis of the records of 660 children/youth with ASD revealed that the most common functional difficulties were remembering/concentrating (22%; 95% CI: 18-27), communicating (19%; 95% CI: 15-23) and self-care (13%; 95% CI: 10-17). Lower perceived mental health was associated with increased functional difficulties with remembering/concentrating. ASD diagnosis at a lower age and lower perceived general health were associated with increased functional difficulty with communication. Parental expectations for postsecondary education were associated with decreased functional difficulty for self-care. CONCLUSION: One or more functional difficulties from the WG-SS was present in 39% of Canadian children/youth aged 5 to 17 years with ASD. Functional difficulties with remembering/concentrating, communication and self-care were most common.

Assessing the impact of the COVID-19 pandemic on the mental health-related hospitalization rate of youth in Canada: an interrupted time series analysis. / Évaluation de l'effet de la pandémie de COVID-19 sur le taux d'hospitalisation pour des raisons de santé mentale chez les jeunes au Canada : analyse de séries chronologiques interrompues.

INTRODUCTION: This study evaluated the effect of the COVID-19 pandemic on temporal trends in mental health and addiction-related inpatient hospitalization rates among youth (aged 10-17 years) in Canadian provinces and territories (excluding Quebec) from 1 April 2018 to 5 March 2022. METHODS: We conducted an interrupted time series analysis across three periods: T0 (pre-pandemic: 1 April 2018 to 15 March 2020); T1 (early pandemic: 15 March 2020 to 5 July 2020); and T2 (later pandemic: 6 July 2020 to 5 March 2022). RESULTS: Pre-pandemic mental health and addiction-related hospitalization rates had significant regional variability, with weekly rates from 6.27 to 85.59 events per 100 000 persons in Manitoba and the territories combined, respectively. During T1, the national (excluding Quebec) weekly hospitalization rate decreased from a pre-pandemic level of 12.82 (95% CI: 12.14 to 13.50) to 5.11 (95% CI: 3.80 to 6.41) events per 100 000 persons. There was no statistically significant change in the mental health and addiction- related hospitalization rate across provinces and territories in T2 compared to T0. However, there was a significant increase in the rate of self-harm-related hospitalizations among females Canada-wide and in most provinces during this period. CONCLUSION: Although several Canadian studies have reported increases in mental health and addiction-related outpatient and emergency department visits among youth during the COVID-19 pandemic, this did not correspond to an increase in the inpatient hospital burden, with the notable exception of self-harm among young females.

Education in vascular access.

The successful creation and use of an arteriovenous vascular access (VA) requires a coordinated, educated multidisciplinary team to ensure an optimal VA for each patient. Patient education programs on VA are associated with increased arteriovenous VA use at dialysis initiation. Education should be tailored to patient goals and preferences with the understanding that experiential education from patient to patient is far more influential than that provided by the healthcare professional. VA education for the nephrologist should focus on addressing the systematic and patient-level barriers in achieving a functional VA, with specific components relating to VA creation, maturation, and cannulation that consider patient goals and preferences. A deficit in nursing skills in the area of assessment and cannulation can have devastating consequences for hemodialysis patients. Delivery of an integrated education program increases nurses' knowledge of VA and development of simulation programs or constructs to assist in cannulation of the VA will greatly facilitate the much needed skill transfer. Adequate VA surgical training and experience are critical to the creation and outcomes of VA. Simulations can benefit nephrologists, dialysis nurses surgeons, and interventionalists though aiding in surgical creation, understanding of the physiology and anatomy of a dysfunctional VA, and practicing cannulation techniques. All future educational initiatives must emphasize the importance of multidisciplinary care to attain successful VA outcomes.

Health Services Use and Outcomes for Hospital Admissions With a Major Cardiovascular Event Recorded in Health Care Administrative Data in Patients Receiving Maintenance Hemodialysis: A Retrospective Cohort Study.

Background: Administrative data are used in studies of hemodialysis care to report cardiovascular-related hospitalizations. Showing recorded events are associated with significant health care resource use and poor outcomes would confirm that administrative data algorithms identify clinically meaningful events. Objective: The objective of this study was to describe the 30-day health service use and outcomes when a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke is recorded in administrative databases. Design: This is a retrospective review of linked administrative data. Patients and Setting: Patients receiving maintenance in-center hemodialysis in Ontario, Canada, between April 1, 2013, and March 31, 2017, were included. Measurements: Records from linked health care databases at ICES in Ontario, Canada were considered. We identified hospital admission with the most responsible diagnosis recorded as myocardial infarction, congestive heart failure, or ischemic stroke. We then assessed the frequency of common tests, procedures, consultations, post-discharge outpatient drug prescriptions, and outcomes within 30 days following the hospital admission. Methods: We used descriptive statistics to summarize results using counts and percentages for categorical variables and means with standard deviations or medians with quartile ranges for continuous variables. Results: There were 14 368 patients who received maintenance hemodialysis between April 1, 2013, and March 31, 2017. The number of events per 1000 person-years was 33.5 for hospital admissions with myocardial infarction, 34.2 for congestive heart failure, and 12.9 for ischemic stroke. The median (25th, 75th percentile) duration of hospital stay was 5 (3-10) days for myocardial infarction, 4 (2-8) days for congestive heart failure, and 9 (4-18) days for ischemic stroke. The chance of death within 30 days was 21% for myocardial infarction, 11% for congestive heart failure, and 19% for ischemic stroke. Limitations: Events, procedures, and tests recorded in administrative data can be misclassified compared with medical charts. Conclusions: In patients receiving maintenance hemodialysis, hospital admissions of major cardiovascular events routinely recorded in health administrative databases are associated with significant use of health service resources and poor health outcomes.

Contexte: Les données administratives sont utilisées pour signaler les hospitalisations liées aux maladies cardiovasculaires dans les études portant sur les soins en hémodialyse. Montrer que les événements signalés sont associés à une utilisation importante des ressources en santé et à une évolution défavorable confirmerait que les algorithmes de données administratives identifient les événements cliniquement significatifs. Objectif: Décrire les interventions et l'évolution de l'état de santé sur une période de 30 jours lorsqu'une hospitalisation pour infarctus du myocarde, insuffisance cardiaque congestive ou accident vasculaire cérébral (AVC) ischémique est enregistrée dans les bases de données administratives. Type d'étude: Revue rétrospective de bases de données administratives couplées. Sujets et cadre de l'étude: Patients sous hémodialyse chronique en milieu hospitalier en Ontario (Canada) entre le 1er avril 2013 et le 31 mars 2017. Mesures: Les dossiers provenant des bases de données couplées de l'ICES en Ontario (Canada). Nous avons répertorié les hospitalisations dont le diagnostic principal enregistré était un infarctus du myocarde, une insuffisance cardiaque congestive ou un AVC ischémique. Nous avons ensuite évalué la fréquence des examens, des procédures, des consultations, des ordonnances de médicaments en consultation externe après la sortie de l'hôpital et des résultats dans les 30 jours suivant l'hospitalisation. Méthodologie: Nous avons utilisé des statistiques descriptives pour résumer les résultats. Des décomptes et pourcentages ont été utilisés pour les variables catégoriques; des moyennes avec écarts-types ou des médianes avec des intervalles de quartiles ont été utilisées pour les variables continues. Résultats: En tout, il y avait 14 368 patients sous hémodialyse chronique entre le 1er avril 2013 et le 31 mars 2017. Le nombre d'événements par 1 000 années-personnes était de 33,5 pour les hospitalisations avec infarctus du myocarde, de 34,2 avec insuffisance cardiaque congestive et de 12,9 pour AVC ischémique. La durée médiane (25e, 75e percentile) de l'hospitalisation était de 5 (3 à 10) jours pour l'infarctus du myocarde, de 4 (2 à 8) jours pour l'insuffisance cardiaque congestive et de 9 (4 à 18) jours pour l'AVC ischémique. Le risque de décès dans les 30 jours était de 21 % pour l'infarctus du myocarde, de 11 % pour l'insuffisance cardiaque congestive et de 19 % pour l'AVC ischémique. Limites: Les événements, les procédures et les examens enregistrés dans les bases de données administratives peuvent être sujets à des erreurs de classification par rapport aux dossiers médicaux. Conclusion: Chez les patients sous hémodialyse chronique, les hospitalisations enregistrées dans les bases de données administratives à la suite d'événements cardiovasculaires majeurs sont associées à une utilisation importante des ressources en santé et à une évolution défavorable de l'état de santé.

Health equity considerations in pragmatic trials in Alzheimer's and dementia disease: Results from a methodological review.

Introduction: To improve dementia care delivery for persons across all backgrounds, it is imperative that health equity is integrated into pragmatic trials. Methods: We reviewed 62 pragmatic trials of people with dementia published 2014 to 2019. We assessed health equity in the objectives; design, conduct, analysis; and reporting using PROGRESS-Plus which stands for Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and other factors such as age and disability. Results: Two (3.2%) trials incorporated equity considerations into their objectives; nine (14.5%) engaged with communities; 4 (6.5%) described steps to increase enrollment from equity-relevant groups. Almost all trials (59, 95.2%) assessed baseline balance for at least one PROGRESS-Plus characteristic, but only 10 (16.1%) presented subgroup analyses across such characteristics. Differential recruitment, attrition, implementation, adherence, and applicability across PROGRESS-Plus were seldom discussed. Discussion: Ongoing and future pragmatic trials should more rigorously integrate equity considerations in their design, conduct, and reporting. Highlights: Few pragmatic trials are explicitly designed to inform equity-relevant objectives.Few pragmatic trials take steps to increase enrollment from equity-relevant groups.Disaggregated results across equity-relevant groups are seldom reported.Adherence to existing tools (e.g., IMPACT Best Practices, CONSORT-Equity) is key.

Recognition of Obesity and Perceptions of Weight Loss Management in Patients With Chronic Kidney Disease: A Retrospective Cross-Sectional Study.

Background: Obesity is, directly and indirectly, linked to the progression of chronic kidney disease (CKD). However, nephrologists' recognition of obesity and willingness to address and manage obesity are unknown. Objectives: The aim of this article is to investigate if obesity is recognized and documented in the clinical encounter and to examine nephrologists' perceptions of obesity and comfort with weight loss management. Design: We conducted a 2-part study. Part I used a retrospective chart review and part II used an anonymous online survey of practicing nephrologists (n = 14) in our center. Setting: The study took place in the Multi-care Kidney Clinic (MCKC) at London Health Sciences Centre in London, Ontario, Canada. Patients: In part I, we conducted a retrospective chart review of 10 random patients with advanced CKD and obesity (body mass index [BMI] > 30 kg/m2) from each of the nephrologists between January and December 2019. Methods: In part I, charts were assessed for documentation of obesity and/or a treatment plan (lifestyle counseling, pharmacologic intervention, and specialist referral). In part II, a survey completed by the nephrologists explored their current experience and perceptions of obesity and comfort with weight loss management. Responses were ranked on a 5-point Likert scale. Results: In all, 140 patient charts were reviewed. The median age was 69 (interquartile range [IQR] = 60-77) years, estimated glomerular filtration rate (eGFR) was 17 (IQR = 12-20) ml/min/1.73 m2, weight was 99 (IQR = 90-116) kg, and BMI was 36 (IQR = 33-40) kg/m2. Obesity with a BMI was documented in 36 (26%) charts, and only 2 (1%) documented a weight loss plan, which only included non-pharmacologic strategies. There were 13 survey responses (93% response rate). All nephrologists agreed that obesity negatively affects the health of patients with CKD. Twelve (92%) reported discussing obesity with patients, but none felt that they had time to treat it. All reported discussions of obesity would evoke a negative patient response, while 5 (38%) thought patients actually want to discuss obesity. Regarding treatment, 8 (62%) nephrologists felt comfortable with non-pharmacologic treatment, but only 1 respondent was comfortable with pharmacologic treatments. Twelve (92%) nephrologists thought patients should be referred to a specialist. Limitations: There was limited generalizability as this was a single center study. The BMI may reflect hypervolemia rather than body mass. Conclusion: In our study, nephrologists rarely document and manage obesity in patients with advanced CKD, despite their perception of treatment benefits. Improved outcomes of obesity management for patients with CKD will require increased knowledge and clinical tools to efficiently address obesity with patients.

Contexte: L'obésité est directement et indirectement liée à la progression de l'insuffisance rénale chronique (IRC). La reconnaissance de l'obésité par les néphrologues et leur volonté de la prendre en charge demeurent toutefois mal connues. Objectifs: Vérifier si l'obésité est reconnue et documentée lors de la rencontre clinique. Examiner les perceptions des néphrologues quant à l'obésité et leur confort face à la gestion du poids. Conception: Notre étude était constituée de deux parties. La première consistait en un examen rétrospectif des dossiers et la deuxième en un sondage anonyme mené en ligne auprès des néphrologues praticiens (n = 14) de notre centre. Cadre: La clinique multidisciplinaire en santé rénale (CMSR) du London Health Sciences Centre de London, en Ontario (Canada). Sujets: Dans la première partie, nous avons examiné rétrospectivement les dossiers de dix patients aléatoires atteints d'IRC de stade avancé et jugés obèses (IMC > 30 kg/m2) pour chacun des néphrologues participants entre janvier et décembre 2019. Méthodologie: Dans la première partie, les dossiers ont été examinés à la recherche d'une mention de l'obésité et/ou d'un plan de traitement (conseils sur le mode de vie, intervention pharmacologique, aiguillage vers un spécialiste). Dans la deuxième partie, un sondage réalisé auprès des néphrologues a exploré leur expérience et leurs perceptions actuelles sur l'obésité et leur confort quant à la gestion de la perte de poids. Les réponses ont été classées sur une échelle Likert de 5 points. Résultats: En tout, 140 dossiers patients ont été examinés. L'âge médian s'établissait à 69 ans (ÉIQ: 60-77), le DFGe médian à 17 ml/min/1,73 m2 (ÉIQ: 12-20), le poids médian à 99 kg (ÉIQ: 90-116) et l'IMC médian à 36 kg/m2 (ÉIQ: 33-40). L'obésité avec IMC était documentée dans 36 dossiers (26%) et seulement deux dossiers (1%) comportaient un plan de perte de poids, lequel ne comprenait que des stratégies non pharmacologiques. Treize néphrologues ont répondu au sondage (taux de réponse: 93%). Tous ont convenu que l'obésité affecte négativement la santé des patients atteints d'IRC; douze (92%) ont mentionné discuter d'obésité avec leurs patients, mais aucun ne pensait avoir le temps de la traiter. Tous les répondants ont indiqué que les discussions abordant l'obésité recevaient un accueil négatif de la part du patient; seuls 5 néphrologues (38%) étaient d'avis que les patients sont réellement ouverts à discuter d'obésité. Quant à son traitement, huit néphrologues (62%) se sont dits à l'aise avec un traitement non pharmacologique; un seul répondant était à l'aise avec les traitements pharmacologiques. Selon douze répondants (92%), les patients devraient être dirigés vers un spécialiste. Limites: Étude dans un seul centre, ce qui limite la généralisabilité. L'IMC pourrait refléter une hypervolémie plutôt que la masse corporelle. Conclusion: Dans notre étude, les néphrologues ont rarement documenté et pris en charge l'obésité de leurs patients atteints d'IRC de stade avancé, et ce, bien qu'ils croient aux avantages de son traitement. Pour améliorer la prise en charge de l'obésité chez les patients atteints d'IRC, il faudra améliorer les connaissances et les outils cliniques permettant de la traiter efficacement chez ces patients.

Machine learning algorithms to identify cluster randomized trials from MEDLINE and EMBASE.

BACKGROUND: Cluster randomized trials (CRTs) are becoming an increasingly important design. However, authors of CRTs do not always adhere to requirements to explicitly identify the design as cluster randomized in titles and abstracts, making retrieval from bibliographic databases difficult. Machine learning algorithms may improve their identification and retrieval. Therefore, we aimed to develop machine learning algorithms that accurately determine whether a bibliographic citation is a CRT report. METHODS: We trained, internally validated, and externally validated two convolutional neural networks and one support vector machine (SVM) algorithm to predict whether a citation is a CRT report or not. We exclusively used the information in an article citation, including the title, abstract, keywords, and subject headings. The algorithms' output was a probability from 0 to 1. We assessed algorithm performance using the area under the receiver operating characteristic (AUC) curves. Each algorithm's performance was evaluated individually and together as an ensemble. We randomly selected 5000 from 87,633 citations to train and internally validate our algorithms. Of the 5000 selected citations, 589 (12%) were confirmed CRT reports. We then externally validated our algorithms on an independent set of 1916 randomized trial citations, with 665 (35%) confirmed CRT reports. RESULTS: In internal validation, the ensemble algorithm discriminated best for identifying CRT reports with an AUC of 98.6% (95% confidence interval: 97.8%, 99.4%), sensitivity of 97.7% (94.3%, 100%), and specificity of 85.0% (81.8%, 88.1%). In external validation, the ensemble algorithm had an AUC of 97.8% (97.0%, 98.5%), sensitivity of 97.6% (96.4%, 98.6%), and specificity of 78.2% (75.9%, 80.4%)). All three individual algorithms performed well, but less so than the ensemble. CONCLUSIONS: We successfully developed high-performance algorithms that identified whether a citation was a CRT report with high sensitivity and moderately high specificity. We provide open-source software to facilitate the use of our algorithms in practice.

Simple compared to covariate-constrained randomization methods in balancing baseline characteristics: a case study of randomly allocating 72 hemodialysis centers in a cluster trial.

BACKGROUND AND AIM: Some parallel-group cluster-randomized trials use covariate-constrained rather than simple randomization. This is done to increase the chance of balancing the groups on cluster- and patient-level baseline characteristics. This study assessed how well two covariate-constrained randomization methods balanced baseline characteristics compared with simple randomization. METHODS: We conducted a mock 3-year cluster-randomized trial, with no active intervention, that started April 1, 2014, and ended March 31, 2017. We included a total of 11,832 patients from 72 hemodialysis centers (clusters) in Ontario, Canada. We randomly allocated the 72 clusters into two groups in a 1:1 ratio on a single date using individual- and cluster-level data available until April 1, 2013. Initially, we generated 1000 allocation schemes using simple randomization. Then, as an alternative, we performed covariate-constrained randomization based on historical data from these centers. In one analysis, we restricted on a set of 11 individual-level prognostic variables; in the other, we restricted on principal components generated using 29 baseline historical variables. We created 300,000 different allocations for the covariate-constrained randomizations, and we restricted our analysis to the 30,000 best allocations based on the smallest sum of the penalized standardized differences. We then randomly sampled 1000 schemes from the 30,000 best allocations. We summarized our results with each randomization approach as the median (25th and 75th percentile) number of balanced baseline characteristics. There were 156 baseline characteristics, and a variable was balanced when the between-group standardized difference was ≤ 10%. RESULTS: The three randomization techniques had at least 125 of 156 balanced baseline characteristics in 90% of sampled allocations. The median number of balanced baseline characteristics using simple randomization was 147 (142, 150). The corresponding value for covariate-constrained randomization using 11 prognostic characteristics was 149 (146, 151), while for principal components, the value was 150 (147, 151). CONCLUSION: In this setting with 72 clusters, constraining the randomization using historical information achieved better balance on baseline characteristics compared with simple randomization; however, the magnitude of benefit was modest.

MyTEMP: Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial.

BACKGROUND: Major Outcomes with Personalized Dialysate TEMPerature (MyTEMP) is a 4-year cluster-randomized clinical trial comparing the effect of using a personalized, temperature-reduced dialysate protocol versus a dialysate temperature of 36.5°C on cardiovascular-related death and hospitalization. Randomization was performed at the level of the dialysis center ("the cluster"). OBJECTIVE: The objective is to outline the statistical analysis plan for the MyTEMP trial. DESIGN: MyTEMP is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized trial. SETTING: A total of 84 dialysis centers in Ontario, Canada. PATIENTS: Approximately 13 500 patients will have received in-center hemodialysis at the 84 participating dialysis centers during the trial period (April 3, 2017, to March 1, 2021, with a maximum follow-up to March 31, 2021). METHODS: Patient identification, baseline characteristics, and study outcomes will be obtained primarily through Ontario administrative health care databases held at ICES. Covariate-constrained randomization was used to allocate the 84 dialysis centers (1:1) to the intervention group or the control group. Centers in the intervention group used a personalized, temperature-reduced dialysate protocol, and centers in the control group used a fixed dialysate temperature of 36.5°C. OUTCOMES: The primary outcome is a composite of cardiovascular-related death or major cardiovascular-related hospitalization (defined as a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) recorded in administrative health care databases. The key secondary outcome is the mean drop in intradialytic systolic blood pressure, defined as the patients' predialysis systolic blood pressure minus their nadir systolic blood pressure during the dialysis treatment. Anonymized data on patients' predialysis and intradialytic systolic blood pressure were collected at monthly intervals from each dialysis center. ANALYSIS PLAN: The primary analysis will follow an intent-to-treat approach. The primary outcome will be analyzed at the patient level as the hazard ratio of time-to-first event, estimated from a subdistribution hazards model. Within-center correlation will be accounted for using a robust sandwich estimator. In the primary analysis, patients' observation time will end if they experience the primary outcome, emigrate from Ontario, or die of a noncardiovascular cause (which will be treated as a competing risk event). The between-group difference in the mean drop in intradialytic systolic blood pressure obtained during the dialysis sessions throughout the trial period will be analyzed at the center level using an unadjusted random-effects linear mixed model. TRIAL STATUS: The MyTEMP trial period is April 3, 2017, to March 31, 2021. We expect to analyze and report results by 2023 once the updated data are available at ICES. TRIAL REGISTRATION: MyTEMP is registered with the US National Institutes of Health at clincaltrials.gov (NCT02628366). STATISTICAL ANALYTIC PLAN: Version 1.1 June 15, 2021.

CONTEXTE: L'essai MyTEMP (Major Outcomes with Personalized Dialysate Temperature) est un essai clinique randomisé en grappes d'une durée de 4 ans comparant l'effet d'un protocole de dialysat personnalisé à température réduite par rapport au dialysat à 36,5 °C sur les hospitalisations et les décès dus à des problèmes cardiovasculaires. La répartition aléatoire des sujets a été effectuée au niveau du centre de dialyse (ci-après appelé « groupe ¼). OBJECTIFS: Exposer les grandes lignes du plan d'analyse statistique de l'essai MyTEMP. TYPE D'ÉTUDE: MyTEMP est un essai clinique pragmatique ouvert, à deux bras, en groupes parallèles, basé sur un registre, et randomisé en grappes. CADRE: L'essai est mené dans 84 centres de dialyse en Ontario (Canada). SUJETS: On estime qu'environ 13 500 patients auront reçu des soins d'hémodialyse dans les 84 centres de dialyse participants au cours de la période de l'essai (3 avril 2017 au 1er mars 2021; suivi maximal jusqu'au 31 mars 2021). MÉTHODOLOGIE: Les résultats et les données concernant l'identification des patients et leurs caractéristiques initiales seront principalement tirés des bases de données administratives du système de santé ontarien tenues par l'ICES. Une répartition aléatoire restreinte par les covariables a été employée pour classer les 84 centres de dialyse (1:1) dans le groupe d'intervention ou le groupe témoin. Le groupe d'intervention a utilisé un protocole personnalisé de dialysat à température réduite et le groupe témoin un dialysat à température fixe (36,5 °C). RÉSULTATS: Le principal critère d'évaluation est la combinaison d'un décès d'origine cardiovasculaire ou d'une hospitalisation majeure liée à la santé cardiovasculaire (définie comme une hospitalisation pour un infarctus du myocarde, une insuffisance cardiaque congestive ou un AVC ischémique) enregistrée dans les bases de données administratives du système de santé. Le principal critère d'évaluation secondaire est la baisse moyenne de la tension artérielle systolique intradialytique, laquelle est définie comme la tension artérielle systolique du patient avant la dialyse moins la tension artérielle systolique minimale pendant la dialyse. Les données anonymisées sur la tension artérielle systolique initiale et la tension artérielle systolique intradialytique des patients ont été colligées à intervalles mensuels dans chaque centre de dialyse. PLAN D'ANALYSE: L'analyse primaire adoptera une approche fondée sur l'intention de traiter. Le principal critère d'évaluation sera analysé au niveau du patient comme le risque relatif de survenue d'un premier événement, estimé à partir d'un modèle de risques de sous-distribution. La corrélation intracentre sera prise en compte à l'aide d'un robuste estimateur sandwich. Dans l'analyse primaire, le temps d'observation des patients prendra fin s'ils présentent le principal critère d'évaluation, s'ils déménagent hors de l'Ontario ou s'ils décèdent d'une cause non cardiovasculaire (qui sera traitée comme un événement à risque concurrentiel). La différence entre les groupes quant à la baisse moyenne de la tension artérielle systolique intradialytique, obtenue pendant les séances de dialyse tout au long de l'essai, sera analysée au niveau du centre avec un modèle linéaire mixte à effets aléatoires non corrigé. STATUT DE L'ESSAI: L'essai MyTEMP couvre la période du 3 avril 2017 au 31 mars 2021. Nous comptons analyser et rendre compte des résultats d'ici 2023, dès que les données mises à jour seront disponibles à l'ICES. ENREGISTREMENT DE L'ESSAI: MyTEMP est enregistré auprès du National Institute of Health des États-Unis sur clincaltrials.gov (NCT02628366).

Reporting of key methodological and ethical aspects of cluster trials in hemodialysis require improvement: a systematic review.

BACKGROUND: The hemodialysis setting is suitable for trials that use cluster randomization, where intact groups of individuals are randomized. However, cluster randomized trials (CRTs) are complicated in their design, analysis, and reporting and can pose ethical challenges. We reviewed CRTs in the hemodialysis setting with respect to reporting of key methodological and ethical issues. METHODS: We conducted a systematic review of CRTs in the hemodialysis setting, published in English, between 2000 and 2019, and indexed in MEDLINE or Embase. Two reviewers extracted data, and study results were summarized using descriptive statistics. RESULTS: We identified 26 completed CRTs and five study protocols of CRTs. These studies randomized hemodialysis centers (n = 17, 55%), hemodialysis shifts (n = 12, 39%), healthcare providers (n = 1, 3%), and nephrology units (n = 1, 3%). Trials included a median of 28 clusters with a median cluster size of 20 patients. Justification for using a clustered design was provided by 15 trials (48%). Methods that accounted for clustering were used during sample size calculation in 14 (45%), during analyses in 22 (71%), and during both sample size calculation and analyses in 13 trials (42%). Among all CRTs, 26 (84%) reported receiving research ethics committee approval; patient consent was reported in 22 trials: 10 (32%) reported the method of consent for trial participation and 12 (39%) reported no details about how consent was obtained or its purpose. Four trials (13%) reported receiving waivers of consent, and the remaining 5 (16%) provided no or unclear information about the consent process. CONCLUSION: There is an opportunity to improve the conduct and reporting of essential methodological and ethical issues in future CRTs in hemodialysis. REVIEW REGISTRATION: We conducted this systematic review using a pre-specified protocol that was not registered.