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.

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.

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.

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.

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.

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.

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.

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

PURPOSE OF REVIEW: Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps. SOURCES OF INFORMATION: Peer-reviewed articles. METHODS: We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist. KEY FINDINGS: The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia. LIMITATIONS: Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.

CONTEXTE MOTIVANT LA REVUE: Les stratégies visant à atténuer les crampes musculaires sont parmi les principales priorités de recherche des patients hémodialysés. L'hypomagnésémie étant un possible facteur de risque, nous avons procédé à une revue de la littérature afin de mieux en comprendre l'épidémiologie, et d'examiner la physiologie et l'épidémiologie des crampes musculaires. Nous souhaitions également examiner les données probantes issues d'études interventionnelles portant sur l'effet des thérapies à base de dialysat de magnésium et de magnésium oral sur les crampes musculaires. SOURCES: Articles examinés par les pairs. MÉTHODOLOGIE: Nous avons cherché les articles pertinents dans les principales bases de données bibliographiques, notamment MEDLINE et EMBASE. La qualité méthodologique a été évaluée à l'aide d'une version modifiée des critères de contrôle de la qualité des études de Downs et Black. PRINCIPAUX RÉSULTATS: L'étiologie des crampes musculaires chez les patients hémodialysés est mal comprise et il n'existe aucune stratégie de prévention ou traitement clairement fondé sur des données probantes. Plusieurs facteurs pourraient jouer un rôle, notamment de faibles concentrations sériques de magnésium. La prévalence de l'hypomagnésémie (concentration inférieure à 0,7 mmol/L) chez les patients hémodialysés variait de 10 à 20 %. Une faible consommation de magnésium dans l'alimentation, la prise de médicaments inhibant l'absorption du magnésium (ex. les inhibiteurs de la pompe à protons), l'excrétion accrue du magnésium (ex. dose élevée de diurétiques de l'anse) et une faible concentration de dialysat de magnésium figuraient parmi les causes d'hypomagnésémie. Un taux de dialysat de magnésium inférieur ou égal à 0,5 mmol/L pourrait être associé à une diminution de la concentration sérique de magnésium au fil du temps. Les résultats préliminaires de certaines études observationnelles et interventionnelles suggèrent qu'une concentration sérique plus élevée de magnésium dans le dialysat augmenterait les concentrations sériques de magnésium et pourrait réduire la fréquence et la sévérité des épisodes de crampes musculaires. La qualité des preuves appuyant ce bienfait est cependant limitée. Des essais multicentriques et à plus vaste échelle sont nécessaires pour juger si un traitement à base de magnésium peut véritablement réduire les crampes musculaires chez les patients hémodialysés. Dans les études menées jusqu'à maintenant, l'augmentation de la concentration de dialysat de magnésium semblait bien tolérée et a été associée à un faible risque d'hypermagnésémie symptomatique. LIMITES: Peu d'études interventionnelles ont examiné l'effet de la prise de magnésium sur les crampes musculaires des patients hémodialysés, et la plupart de celles-ci constituaient des plans pré- ou post-études non randomisées.

Major Outcomes With Personalized Dialysate TEMPerature (MyTEMP): Rationale and Design of a Pragmatic, Registry-Based, Cluster Randomized Controlled Trial.

BACKGROUND: Small randomized trials demonstrated that a lower compared with higher dialysate temperature reduced the average drop in intradialytic blood pressure. Some observational studies demonstrated that a lower compared with higher dialysate temperature was associated with a lower risk of all-cause mortality and cardiovascular mortality. There is now the need for a large randomized trial that compares the effect of a low vs high dialysate temperature on major cardiovascular outcomes. OBJECTIVE: The purpose of this study is to test the effect of outpatient hemodialysis centers randomized to (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol for 4 years on cardiovascular-related death and hospitalizations. DESIGN: The design of the study is a pragmatic, registry-based, open-label, cluster randomized controlled trial. SETTING: Hemodialysis centers in Ontario, Canada, were randomized on February 1, 2017, for a trial start date of April 3, 2017, and end date of March 31, 2021. PARTICIPANTS: In total, 84 hemodialysis centers will care for approximately 15 500 patients and provide over 4 million dialysis sessions over a 4-year follow-up. INTERVENTION: Hemodialysis centers were randomized (1:1) to provide (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol of 36.5°C. For the personalized protocol, nurses set the dialysate temperature between 0.5°C and 0.9°C below the patient's predialysis body temperature for each dialysis session, to a minimum dialysate temperature of 35.5°C. PRIMARY OUTCOME: A composite of cardiovascular-related death or major cardiovascular-related hospitalization (a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) captured in Ontario health care administrative databases. PLANNED PRIMARY ANALYSIS: The primary analysis will follow an intent-to-treat approach. The hazard ratio of time-to-first event will be estimated from a Cox model. Within-center correlation will be considered using a robust sandwich estimator. Observation time will be censored on the trial end date or when patients die from a noncardiovascular event. TRIAL REGISTRATION: www.clinicaltrials.gov; identifier: NCT02628366.

CONTEXTE: De petits essais à répartition aléatoire ont montré que l'utilisation d'un dialysat à basse température réduisait le risque d'hypotension intra-dialytique. De même, certaines études observationnelles ont démontré qu'un dialysat à basse température était associé à un plus faible risque de mortalité toute cause ou d'origine cardiovasculaire. Le temps est venu de procéder à un vaste essai à répartition aléatoire comparant les effets d'un dialysat à basse température et à température standard sur les principaux résultats cardiovasculaires. OBJECTIF: Répartir aléatoirement des centres d'hémodialyse ambulatoire pour qu'ils suivent pendant quatre ans (i) un protocole personnalisé de dialysat à basse température ou (ii) un protocole de dialysat à température standard, et tester l'effet sur les hospitalisations et la mortalité attribuables à des événements cardiovasculaires. TYPE D'ÉTUDE: Un essai clinique à répartition aléatoire en grappes. CADRE: Le 1er février 2017, des centres d'hémodialyse de l'Ontario (Canada) ont été répartis aléatoirement en vue d'un essai qui a débuté le 3 avril 2017 et qui se poursuivra jusqu'au 31 mars 2021. PARTICIPANTS: Quatre-vingt-quatre centres d'hémodialyse qui prendront en charge environ 15 500 patients pendant les quatre ans de suivi. INTERVENTION: Les centres d'hémodialyse ont été répartis aléatoirement (1:1) pour offrir (i) un protocole personnalisé de dialysat à température réduite ou (ii) un protocole de dialysat à 36,5°C. Pour le protocole personnalisé, les infirmières règlent la température du dialysat entre 0,5 et 0,9°C sous la température corporelle du patient mesurée avant la dialyse, jusqu'à une température minimale de 35,5°C. PRINCIPAUX RÉSULTATS: Un ensemble d'hospitalisations attribuables à un événement cardiovasculaire majeur (accident ischémique cérébral non fatal, infarctus du myocarde ou insuffisance cardiaque congestive) et de décès d'origine cardiovasculaire consignés dans les bases de données de santé de l'Ontario. PRINCIPALE ANALYSE ENVISAGÉE: L'analyse primaire adoptera une approche fondée sur l'intention de traiter. Un modèle de Cox servira à estimer le rapport de risque du temps écoulé jusqu'au premier événement. La corrélation intra-centre sera prise en compte à l'aide d'un estimateur sandwich robuste. Le temps d'observation sera censuré à la date de fin de l'essai ou au moment d'un décès non lié à un événement cardiovasculaire.

Validity of administrative database code algorithms to identify vascular access placement, surgical revisions, and secondary patency.

BACKGROUND:: We assessed the validity of physician billing codes and hospital admission using International Classification of Diseases 10th revision codes to identify vascular access placement, secondary patency, and surgical revisions in administrative data. METHODS:: We included adults (≥18 years) with a vascular access placed between 1 April 2004 and 31 March 2013 at the University Health Network, Toronto. Our reference standard was a prospective vascular access database (VASPRO) that contains information on vascular access type and dates of placement, dates for failure, and any revisions. We used VASPRO to assess the validity of different administrative coding algorithms by calculating the sensitivity, specificity, and positive predictive values of vascular access events. RESULTS:: The sensitivity (95% confidence interval) of the best performing algorithm to identify arteriovenous access placement was 86% (83%, 89%) and specificity was 92% (89%, 93%). The corresponding numbers to identify catheter insertion were 84% (82%, 86%) and 84% (80%, 87%), respectively. The sensitivity of the best performing coding algorithm to identify arteriovenous access surgical revisions was 81% (67%, 90%) and specificity was 89% (87%, 90%). The algorithm capturing arteriovenous access placement and catheter insertion had a positive predictive value greater than 90% and arteriovenous access surgical revisions had a positive predictive value of 20%. The duration of arteriovenous access secondary patency was on average 578 (553, 603) days in VASPRO and 555 (530, 580) days in administrative databases. CONCLUSION:: Administrative data algorithms have fair to good operating characteristics to identify vascular access placement and arteriovenous access secondary patency. Low positive predictive values for surgical revisions algorithm suggest that administrative data should only be used to rule out the occurrence of an event.

Definitions and End Points for Interventional Studies for Arteriovenous Dialysis Access.

This paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access' evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1-patent arteriovenous access, stage 2-physiologically mature arteriovenous access, and stage 3-clinically functional arteriovenous access. Once the requirements of a stage 3-clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.