Improving the management of chronic kidney disease in primary care by enhancing laboratory reports with additional information and follow-up procedures.

Identifying people at risk for progressive chronic kidney disease and connecting them with recommended care is crucial for providing timely and optimal treatment. The ASSIST-CKD (A programme to Spread eGFR [estimated glomerular filtration rate] graph Surveillance for the early identification, Support and Treatment of people with progressive CKD [chronic kidney disease]) trial evaluated the effect of graphical eGFR reporting to primary care physicians on late presentation to a nephrologist in the United Kingdom. Trial data were obtained from the UK Renal Registry. Although the results were neutral, the data generated from the ASSIST-CKD trial are informative and provide useful estimates of the intervention effect. The trial also provides valuable insights into the challenges of implementing complex interventions in busy health care environments, which can be used to guide the designs of future interventions.

Predictors of Delayed Diagnosis of Pediatric CNS Tumors in the Emergency Department.

OBJECTIVE: Central nervous system (CNS) tumor diagnoses are frequently delayed in children, which may lead to adverse outcomes and undue burdens on families. Examination of factors associated with delayed emergency department (ED) diagnosis could identify approaches to reduce delays. STUDY DESIGN: We performed a case-control study using data from 2014 to 2017 for 6 states. We included children aged 6 months to 17 years with a first diagnosis of CNS tumor in the ED. Cases had a delayed diagnosis, defined as 1 or more ED visits in the 140 days preceding tumor diagnosis (the mean prediagnostic symptomatic interval for pediatric CNS tumors in the United States). Controls had no such preceding visit. RESULTS: We included 2828 children (2139 controls, 76%; 689 cases, 24%). Among cases, 68% had 1 preceding ED visit, 21% had 2, and 11% had 3 or more. Significant predictors of delayed diagnosis included presence of a complex chronic condition (adjusted odds ratio [aOR], 9.73; 95% confidence interval [CI], 6.67-14.20), rural hospital location (aOR, 6.37; 95% CI, 1.80-22.54), nonteaching hospital status (aOR, 3.05, compared with teaching hospitals; 95% CI, 1.94-4.80), age younger than 5 years (aOR, 1.57; 95% CI, 1.16-2.12), public insurance (aOR, 1.49, compared with private; 95% CI, 1.16-1.92), and Black race (aOR, 1.42, compared with White; 95% CI, 1.01-1.98). CONCLUSIONS: Delayed ED diagnosis of pediatric CNS tumors is common and frequently requires multiple ED encounters. Prevention of delays should focus on careful evaluation of young or chronically ill children, mitigating disparities for Black and publicly insured children, and improving pediatric readiness in rural and nonteaching EDs.

Domain 3a of Munc18-1 plays a crucial role at the priming stage of exocytosis.

Munc18-1 is believed to prime or stimulate SNARE-mediated membrane fusion/exocytosis through binding to the SNARE complex, in addition to chaperoning its cognate syntaxins. Nevertheless, a Munc18-1 mutant that selectively loses the priming function while retaining the syntaxin chaperoning activity has not been identified. As a consequence, the mechanism that mediates Munc18-1-dependent priming remains unclear. In the course of analyzing the functional outcomes of a variety of point mutations in domain 3a of Munc18-1, we discovered insertion mutants (K332E/K333E with insertions of 5 or 39 residues). These mutants completely lose their ability to rescue secretion whereas they effectively restore syntaxin-1 expression at the plasma membrane as well as dense-core vesicle docking in Munc18-1 and Munc18-2 double-knockdown PC12 cells. The mutants can bind syntaxin-1A in a stoichiometric manner. However, binding to the SNARE complex is impaired compared with the wild type or the hydrophobic pocket mutant (F115E). Our results suggest that the domain 3a of Munc18-1 plays a crucial role in priming of exocytosis, which is independent of its syntaxin-1 chaperoning activity and is downstream of dense-core vesicle docking. We also suggest that the priming mechanism of Munc18-1 involves its domain-3a-dependent interaction with the SNARE complex.

Living kidney donor estimated glomerular filtration rate and recipient graft survival.

BACKGROUND: Kidney transplants from living donors with an estimated glomerular filtration rate (eGFR) < 80 mL/min per 1.73 m(2) may be at risk for increased graft loss compared with a recipient who receives a kidney from a living donor with a higher eGFR. METHODS: This retrospective cohort study considered 2057 living kidney donors and their recipients from July 1993 to March 2010 at five centres in Ontario, Canada, and linked them to population-based, universal healthcare databases. Recipients were divided into five groups based on their donor's baseline eGFR. The median (inter-quartile range) for the lowest eGFR group was 73 (68-77) mL/min per 1.73 m(2). Subjects were followed for a median of 6 years (IQR: 3-10 years). RESULTS: There was no significant difference in the adjusted hazard ratio (HR) for graft loss when comparing recipients in each eGFR category to the referent group (≥110 mL/min per 1.73 m(2)). The adjusted HRs (95% CI) from the lowest (<80 mL/min per 1.73 m(2)) to highest (100-109.9 mL/min per 1.73 m(2)) eGFR categories were 1.27 (0.84-1.92), 1.43 (0.96-2.14), 1.23 (0.86-1.77) and 1.23 (0.85-1.77), respectively. Similar results were observed when dichotomizing the baseline donor eGFR using a cut-point of 80 mL/min per 1.73 m(2)-adjusted HR 1.01 [95% confidence interval (95% CI) (0.76-1.44)]. CONCLUSIONS: Further research in this setting should clarify whether additional tests (i.e. measured GFR) should be performed in potential donors whose eGFR is considered borderline, whether eGFR values should be standardized to body surface area, and the outcomes for donors after nephrectomy.

Public and patient perspectives on the use of clinical and administrative health data to identify and contact people at risk of future illness-The case of chronic kidney disease.

For decades, researchers have used linkable administrative health data for evaluating the health care system, subject to local privacy legislation. In Ontario, Canada, the relevant privacy legislation permits some organizations (prescribed entities) to conduct this kind of research but is silent on their ability to identify and contact individuals in those datasets. Following consultation with the Office of the Information and Privacy Commissioner of Ontario, we developed a pilot study to identify and contact by mail a sample of people at high risk for kidney failure within the next 2 years, based on laboratory and administrative data from provincial datasets held by ICES, to ensure they receive needed kidney care. Before proceeding, we conducted six focus groups to understand the acceptability to the public and people living with chronic kidney disease of direct mail outreach to people at high risk of developing kidney failure. While virtually all participants indicated they would likely participate in the study, most felt strongly that the message should come directly from their primary care provider or whoever ordered the laboratory tests, rather than from an unknown organization. If this is not possible, they felt the health care provider should be made aware of the concern related to their kidney health. Most agreed that, if health authorities could identify people at high risk of a treatable life-threatening illness if caught early enough, there is a social responsibility to notify people. While privacy laws allow for free flow of health information among health care providers who provide direct clinical care, the proposed case-finding and outreach falls outside that model. Enabling this kind of information flow will require greater clarity in existing laws or revisions to these laws. This also requires adequate notification and culture change for health care providers and the public around information uses and flows.

Cardiovascular disease after Escherichia coli O157:H7 gastroenteritis.

BACKGROUND: Escherichia coli O157:H7 is one cause of acute bacterial gastroenteritis, which can be devastating in outbreak situations. We studied the risk of cardiovascular disease following such an outbreak in Walkerton, Ontario, in May 2000. METHODS: In this community-based cohort study, we linked data from the Walkerton Health Study (2002-2008) to Ontario's large healthcare databases. We included 4 groups of adults: 3 groups of Walkerton participants (153 with severe gastroenteritis, 414 with mild gastroenteritis, 331 with no gastroenteritis) and a group of 11 263 residents from the surrounding communities that were unaffected by the outbreak. The primary outcome was a composite of death or first major cardiovascular event (admission to hospital for acute myocardial infarction, stroke or congestive heart failure, or evidence of associated procedures). The secondary outcome was first major cardiovascular event censored for death. Adults were followed for an average of 7.4 years. RESULTS: During the study period, 1174 adults (9.7%) died or experienced a major cardiovascular event. Compared with residents of the surrounding communities, the risk of death or cardiovascular event was not elevated among Walkerton participants with severe or mild gastroenteritis (hazard ratio [HR] for severe gastroenteritis 0.74, 95% confidence interval [CI] 0.38-1.43, mild gastroenteritis HR 0.64, 95% CI 0.42-0.98). Compared with Walkerton participants who had no gastroenteritis, risk of death or cardiovascular event was not elevated among participants with severe or mild gastroenteritis. INTERPRETATION: There was no increase in the risk of cardiovascular disease in the decade following acute infection during a major E. coli O157:H7 outbreak.

Living donor age and kidney transplant outcomes: an assessment of risk across the age continuum.

Detailed data on living donor age, and its interplay with recipient age, in predicting allograft and recipient outcomes are wanting. We used the Scientific Registry of Transplant Recipients (2000-2009, n = 49 589) to assess the effect of living donor age on delayed graft function (DGF), total graft failure, death-censored graft failure, death with graft function, and graft failure with death as a competing risk using logistic and Cox proportional hazards models. Potential nonlinear associations were modeled using fractional polynomial functions. There was a significant 1.87-fold increase in the adjusted odds of DGF in the oldest versus youngest age groups. The 10-year adjusted hazard ratios (HR) for total graft failure, death-censored graft failure, and death with graft function increased in a nonlinear fashion across the range of living donor age studied. Graft failure was most accentuated in the youngest recipient age groups in competing risk models. Adjustment for renal function at 6- and 12-months post-transplant markedly attenuated the association between living donor age and graft/patient outcomes. Our findings confirm the important influence of living donor age on transplant outcomes and provide detailed estimates of risk across the living donor age continuum.

Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation.

BACKGROUND: Living kidney donation offers a unique setting to study changes in phosphate and vitamin D homeostasis attributable to mild isolated decreases in estimated glomerular filtration rate (eGFR). STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 198 living kidney donors and 98 nondonor controls from 9 transplant centers across 3 countries. For donors, median time after donation was 5.3 years. At assessment, donors had a lower eGFR than controls (73 vs 98 mL/min/1.73 m(2)). PREDICTOR: Living kidney donation (mildly decreased eGFR). OUTCOMES: Biochemical markers of chronic kidney disease-mineral and bone disorder. MEASUREMENTS: Serum creatinine, total serum calcium, serum and urine inorganic phosphate, plasma intact parathyroid hormone, serum calcidiol and calcitriol, renal fractional excretion of inorganic phosphate, and intact serum fibroblast growth factor 23 (FGF-23). RESULTS: Serum FGF-23 levels were significantly higher in donors (38.1 vs 29.7 pg/mL; P < 0.001). For every 10-mL/min/1.73 m(2) decrease in eGFR, FGF-23 level was higher by 3.2 (95% CI, 2.0-4.4) pg/mL. Compared with controls, donors showed higher renal tubular fractional excretion of inorganic phosphate (17.8% vs 12.3%; P < 0.001), lower serum phosphate (0.97 vs 1.02 mmol/L; P = 0.03), and lower serum calcitriol values (63 vs 77 pmol/L; P < 0.001). Serum calcium levels were not significantly different between the 2 groups. Plasma intact parathyroid hormone levels were significantly higher in donors (5.7 vs 5.0 pmol/L; P = 0.03), but were not correlated with FGF-23 or calcitriol levels. LIMITATIONS: Enrollment of a small proportion of past donors at participating centers; assessment of only postdonation values; unable to assess seasonal variation or other temporal patterns in biochemical markers; assessment of kidney function was based on eGFR, not measured GFR. CONCLUSIONS: The FGF-23 pathway may be activated in living kidney donors who show early biochemical changes compatible with chronic kidney disease-mineral and bone disorder. Whether these changes influence bone mineral density and fracture rates warrants consideration.

Fracture risk in living kidney donors: a matched cohort study.

BACKGROUND: Chronic kidney disease increases the risk of bone fragility fractures (osteoporotic fractures). Living kidney donors lose 50% of their renal mass and show changes in calcium homeostasis. We studied whether living kidney donation increases the risk of fragility fracture. DESIGN: Retrospective matched-cohort study. SETTING & PARTICIPANTS: We reviewed the medical charts of all 2,015 adults in Ontario, Canada, who donated a kidney between 1992 and 2009 (surgeries performed across 5 transplant programs). We linked this information to health care databases and randomly selected 20,150 matched nondonors from the healthiest portion of the general population. Median age was 43 (95% CI, 24-50) years at study enrollment. Donors and nondonors were then followed up for a median of 6.6 years and a maximum of 17.7 years. PREDICTOR: Living donor nephrectomy. OUTCOMES: The primary outcome was lower- and upper-extremity fragility fractures. Individuals who reached 66 years or older in follow-up had bisphosphonate prescriptions recorded. RESULTS: The rate of fragility fracture was no higher in donors compared with nondonors (16.4 vs 18.7 events/10,000 person-years; rate ratio, 0.88; 95% CI, 0.58-1.32). Results were similar in multiple additional analyses. There was little difference in the proportion of older adults in follow-up who received a bisphosphonate prescription (17.1% vs 15.2%; P = 0.4). LIMITATIONS: These are interim results. Ongoing surveillance of this and other donor cohorts is warranted to be sure an association does not manifest with longer follow-up. CONCLUSIONS: To date, there is no evidence of increased fragility fracture risk in living kidney donors. Our results meet an information need and are reassuring for the safety of the practice.

Acute dialysis risk in living kidney donors.

BACKGROUND: Reduced kidney function confers a higher risk of acute kidney injury at the time of an inciting event, such as sepsis. Whether the same is true in those with reduced renal mass from living kidney donation is unknown. METHODS: We conducted a population-based matched cohort study of all living kidney donors in the province of Ontario, Canada who underwent donor nephrectomy from 1992 to 2009. We manually reviewed the medical records of these living kidney donors and linked this information to provincial health care databases. Non-donors were selected from the healthiest segment of the general population. RESULTS: There were 2027 donors and 20 270 matched non-donors. The median age was 43 years (interquartile range 34-50) and individuals were followed for a median of 6.6 years (maximum 17.7 years). The primary outcome was acute dialysis during any hospital stay. Reasons for hospitalization included infectious diseases, cardiovascular diseases and hematological malignancies. Only one donor received acute dialysis in follow-up (6.5 events per 100 000 person-years), a rate which was statistically no different than 14 non-donors (9.4 events per 100 000 person-years). CONCLUSIONS: These results are reassuring for the practice of living kidney donation. Longer follow-up of this and other donor cohorts will provide more precise estimates about this risk.

Rapid Cycle Deliberate Practice Improves Retention of Pediatric Resuscitation Skills Compared With Postsimulation Debriefing.

INTRODUCTION: Rapid cycle deliberate practice (RCDP) for teaching team-based resuscitation is associated with similar improvements in immediate performance as compared with postsimulation debriefing (PSD). Limited studies compare skill retention between these 2 modalities. Our objective was to compare retention of team leader performance in residents trained with RCDP versus PSD. METHODS: This was a cluster-randomized trial comparing RCDP and PSD from January 2018 to April 2019. Pediatric and emergency medicine residents participated in simulation-based pediatric resuscitation education, and teams were randomized to undergo either RCDP or PSD. Each participant's team leader performance was assessed 1 to 12 months after training via a simulated cardiac arrest. The primary outcome was time to defibrillation. Secondary outcomes included overall team leader performance and time to chest compressions. RESULTS: Thirty-two residents (90.6% pediatrics, 9.4% emergency medicine) met inclusion criteria (16 RCDP, 16 PSD). Of the 32 residents, 40% returned in 1 to 3 months, 25% 3 to 6 months, 16% 6 to 9 months, and 19% 10 to 12 months. Participants in RCDP had more than 5 times the odds of achieving defibrillation versus those in the PSD group (odds ratio = 5.57, 95% confidence interval = 1.13-27.52, P = 0.04). The RCDP group had a higher mean Resident Team Leader Evaluation score (0.54 ± 0.19) than the PSD group (0.34 ± 0.16, P < 0.001). CONCLUSIONS: This study shows significant differences in subsequent performance in the team leader trained with RCDP and suggests that RCDP may improve retention of pediatric resuscitation skills compared with PSD. Future studies should focus on best applications for RCDP with attention to knowledge and skill decay.

Informing the debate: rates of kidney transplantation in nations with presumed consent.

BACKGROUND: The kidney is the most common transplanted organ, accounting for almost all living donor transplantations and most deceased donor organ transplantations. The organ shortage has caused policymakers in many nations to debate the merits of adopting presumed consent legislation as a way to increase donor organ donation from deceased donors. OBJECTIVE: To compare characteristics and kidney transplantation rates for countries with presumed consent for deceased organ donation with countries with explicit consent. DESIGN: A longitudinal study of international kidney transplantation from 1997 to 2007. SETTING: 44 nations performing kidney transplantation. PATIENTS: Recipients of deceased and living kidney donor transplants. MEASUREMENTS: Rates of transplantation of kidneys from deceased and living donors. RESULTS: National characteristics, such as population size, proportion of the population self-identified as Catholic, per capita gross domestic product, health expenditures, and physician density, varied widely for the 22 nations with presumed consent and the 22 nations with explicit consent. Deceased donor kidney transplantation rates were higher in nations with presumed consent (median, 22.6 transplantations per million population [pmp]; interquartile range [IQR], 9.3 to 33.8) versus nations with explicit consent (median, 13.9 transplantations pmp; IQR, 3.6 to 23.1). Living donor kidney transplantation rates were lower in nations with presumed consent (median, 2.4 transplantations pmp; IQR, 1.7 to 4.3) versus nations with explicit consent (median, 5.9 transplantations pmp; IQR, 2.3 to 12.2). The findings were consistent when nations were classified according to per capita gross domestic product, health expenditures, and physician density. LIMITATION: As with any observational study, associations may not be causal. CONCLUSION: Nations with presumed consent have higher rates of deceased donor kidney transplantation than nations with explicit consent. Any nation deciding to adopt presumed consent should carefully consider and reduce any negative effect on rates of living donation. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Lawson Health Research Institute.

Evolving Medical Imaging Techniques for the Assessment of Delayed Graft Function: A Narrative Review.

PURPOSE OF REVIEW: Delayed graft function (DGF) is a significant complication that contributes to poorer graft function and shortened graft survival. In this review, we sought to evaluate the current and emerging role of medical imaging modalities in the assessment of DGF and how it may guide clinical management. SOURCES OF INFORMATION: PubMed, Google Scholar, and ClinicalTrial.gov up until February 2021. METHODS: This narrative review first examined the pathophysiology of DGF and current clinical management. We then summarized relevant studies that utilized medical imaging to assess posttransplant renal complications, namely, DGF. We focused our attention on noninvasive, evolving imaging modalities with the greatest potential for clinical translation, including contrast-enhanced ultrasound (CEUS) and multiparametric magnetic resonance imaging (MRI). KEY FINDINGS: A kidney biopsy in the setting of DGF can be used to assess the degree of ischemic renal injury and to rule out acute rejection. Biopsies are accompanied by complications and may be limited by sampling bias. Early studies on CEUS and MRI have shown their potential to distinguish between the 2 most common causes of DGF (acute tubular necrosis and acute rejection), but they have generally included only small numbers of patients and have not kept pace with more recent technical advances of these imaging modalities. There remains unharnessed potential with CEUS and MRI, and more robust clinical studies are needed to better evaluate their role in the current era. LIMITATIONS: The adaptation of emerging approaches for imaging DGF will depend on additional clinical trials to study the feasibility and diagnostic test characteristics of a given modality. This is limited by access to devices, technical competence, and the need for interdisciplinary collaborations to ensure that such studies are well designed to appropriately inform clinical decision-making.

MOTIF DE LA REVUE: La reprise retardée de la fonction du greffon (RRFG) est une complication importante susceptible d'affecter négativement la fonction du greffon et de réduire sa survie. Dans cette revue, nous cherchions à évaluer le rôle actuel et grandissant des modalités d'imagerie médicale dans l'évaluation de la RRFG et la façon dont cela pourrait orienter la prise en charge clinique. SOURCES: PubMed, Google Scholar et ClinicalTrial.gov jusqu'à février 2021. MÉTHODOLOGIE: Notre revue narrative portait d'abord sur la physiopathologie de la RRFG et la prise en charge clinique actuelle. Nous avons par la suite résumé les études pertinentes ayant utilisé l'imagerie médicale pour évaluer les complications rénales post- transplantation, notamment la RRFG. Nous avons concentré notre attention sur les modalités d'imagerie non effractives et évolutives présentant le plus grand potentiel d'application clinique, notamment l'échographie de contraste (CEUS) et l'imagerie par résonance magnétique (IRM) multiparamétrique. PRINCIPAUX RÉSULTATS: Dans les cas de RRFG, une biopsie du rein peut être utilisée pour évaluer l'ampleur des lésions rénales ischémiques et pour exclure le rejet aigu. Les biopsies s'accompagnent de complications et pourraient être limitées par des biais d'échantillonnage. Des études préliminaires examinant les CEUS et l'IRM ont montré que ces modalités permettaient une distinction entre les deux causes les plus fréquentes de la RRFG (nécrose tubulaire aiguë et rejet aigu), mais ces études portaient généralement sur de petits nombres de patients et n'avaient pas suivi les plus récents progrès techniques de ces modalités d'imagerie. Il subsiste un potentiel non exploité avec les CEUS et l'IRM. Des études cliniques plus robustes sont nécessaires pour mieux évaluer leur rôle à l'heure actuelle. LIMITES: L'adaptation des approches émergentes pour l'imagerie en contexte de RRFG dépendra d'essais cliniques supplémentaires qui examineront la faisabilité et les caractéristiques des tests diagnostiques d'une modalité donnée. Cela est limité par l'accès aux appareils, la compétence technique et la nécessité de collaborations interdisciplinaires afin de s'assurer que ces études sont bien conçues et qu'elles puissent éclairer adéquatement la prise de décisions cliniques.

Video-Based Telemedicine for Kidney Disease Care: A Scoping Review.

BACKGROUND AND OBJECTIVES: Video-based telemedicine provides an alternative health care delivery model for patients with CKD. The objective was to provide an overview of the available evidence on the implementation and outcomes of adopting video-based telemedicine in nephrology. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL were searched in December 2019 and again in January 2021 for studies using video-based telemedicine for adults across the spectrum of kidney disease. Study types included peer-reviewed clinical trials, observational studies, and descriptive studies available in full text. Search results were independently screened by two authors, who then independently reviewed and extracted data from the eligible studies. Results were synthesized in tabular format, summarizing study characteristics by area within nephrology; the video-based interventions used; and clinical, health care utilization, and patient-reported outcomes. RESULTS: After reviewing 1870 unique citations, 24 studies were included (four randomized controlled trials, six cohort studies, five pre-post intervention studies, seven case series, and two qualitative studies). Video-based technology was used to facilitate care across all stages of CKD. Although earlier studies used a range of institution-specific technologies that linked main hospital sites to more remote health care locations, more recent studies used technology platforms that allowed patients to receive care in a location of their choice. Video-based care was well received, with the studies reporting high patient satisfaction and acceptable clinical outcomes. CONCLUSIONS: Video-based telemedicine is being used for kidney care and has evolved to be less reliant on specialized telemedicine equipment. As its use continues to grow, further primary studies and systematic reviews of outcomes associated with the latest innovations to video-based care in nephrology can address knowledge gaps, such as approaches to sustainable integration and minimization of barriers to access.

Rapid-cycle deliberate practice improves time to defibrillation and reduces workload: A randomized controlled trial of simulation-based education.

BACKGROUND: The optimal structure of simulation to train teams to perform pediatric advanced life support (PALS) requires further research. Most simulation is structured with an uninterrupted scenario with postsimulation debriefing (PSD). Rapid-cycle deliberate practice (RCDP) is structured with a series of simulations with microdebriefing quickly switching within action targeting specific performance goals. OBJECTIVE: The objective was to compare team performance immediately after training, as well as learner workload, for teams trained using either PSD or RCDP. METHODS: In 2018-2019, a total of 41 interprofessional teams of 210 residents and nurses were recruited from 250 eligible participants (84%) and randomized into either arm (RCDP or PSD) teaching the same objectives of resuscitation of a patient in PEA arrest, in the same time frame. The structure of the simulation varied. Demographic surveys were collected before training, the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) was administered immediately after training to assess workload during training and performance was assessed immediately after training using a pulseless ventricular tachycardia arrest with the primary outcome being time to defibrillation. RESULTS: Thirty-nine teams participated over a 16-month time span. Performance of teams randomized to RCDP showed significantly better time to defibrillation, 100 s (95% confidence interval [CI] = 90-111), compared to PSD groups, 163 s (95% CI = 120-201). The workload of the groups also showed a lower total NASA-TLX score for the RCDP groups. CONCLUSIONS: For team-based time-sensitive training of PALS, RCDP outperformed PSD. This may be due to a reduction in the workload faced by teams during training.

Workload of learners during simulated paediatric cardiopulmonary resuscitation.

Introduction: Learner workload during simulated team-based resuscitations is not well understood. In this descriptive study, we measured the workload of learners in different team roles during simulated paediatric cardiopulmonary resuscitation. Methods: Paediatric emergency nurses and paediatric and emergency medicine residents formed teams of four to eight and randomised into roles to participate in simulation-based, paediatric resuscitation. Participant workload was measured using the NASA Task Load Index, which provides an average workload score (from 0 to 100) across six subscores: mental demand, physical demand, temporal demand, performance, frustration and mental effort. Workload is considered low if less than 40, moderate if between 40 and 60 and high if greater than 60. Results: There were 210 participants representing 40 simulation teams. 138 residents (66%) and 72 nurses (34%) participated. Team lead reported the highest workload at 65.2±10.0 (p=0.001), while the airway reported the lowest at 53.9±10.8 (p=0.001); team lead had higher scores for all subscores except physical demand. Team lead reported the highest mental demand (p<0.001), while airway reported the lowest. Cardiopulmonary resuscitation coach and first responder reported the highest physical demands (p<0.001), while team lead and nurse recorder reported the lowest (p<0.001). Conclusions: Workload for learners in paediatric simulated resuscitation teams was moderate to high and varied significantly based on team role. Composition of workload varied significantly by team role. Measuring learner workload during simulated resuscitations allows improved processes and choreography to optimise workload distribution.

Cancer pain: part 2: physical, interventional and complimentary therapies; management in the community; acute, treatment-related and complex cancer pain: a perspective from the British Pain Society endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners.

OBJECTIVE: This discussion document about the management of cancer pain is written from the pain specialists' perspective in order to provoke thought and interest in a multimodal approach to the management of cancer pain, not just towards the end of life, but pain at diagnosis, as a consequence of cancer therapies, and in cancer survivors. It relates the science of pain to the clinical setting and explains the role of psychological, physical, interventional and complementary therapies in cancer pain. METHODS: This document has been produced by a consensus group of relevant healthcare professionals in the United Kingdom and patients' representatives making reference to the current body of evidence relating to cancer pain. In the second of two parts, physical, invasive and complementary cancer pain therapies; treatment in the community; acute, treatment-related and complex cancer pain are considered. CONCLUSIONS: It is recognized that the World Health Organization (WHO) analgesic ladder, whilst providing relief of cancer pain towards the end of life for many sufferers world-wide, may have limitations in the context of longer survival and increasing disease complexity. To complement this, it is suggested that a more comprehensive model of managing cancer pain is needed that is mechanism-based and multimodal, using combination therapies including interventions where appropriate, tailored to the needs of an individual, with the aim to optimize pain relief with minimization of adverse effects.

DAMPAned Methotrexate: A Case Report and Review of the Management of Acute Methotrexate Toxicity.

RATIONALE: Consensus guidelines on the management of methotrexate-induced nephrotoxicity using glucarpidase (Voraxaze) may be relatively unfamiliar to the nephrology community. PRESENTING CONCERNS OF THE PATIENT: A 61-year-old man with intravascular large B-cell lymphoma was admitted for cycle #1 of high-dose methotrexate (HDMTX) following 2 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. On admission, he was clinically euvolemic and had a creatinine clearance of 98 mL/min. He received standard HDMTX toxicity prophylaxis with volume expansion, urinary alkalinization, and leucovorin rescue. DIAGNOSES: Despite prophylactic efforts, he developed a severe acute kidney injury, creatinine 63 to 226 µmol/L (2.56 mg/dL), following HDMTX, impaired methotrexate clearance, and neurotoxicity manifested by status epilepticus. INTERVENTIONS: He was given glucarpidase to convert extracellular methotrexate into its inactive metabolites, glutamate and DAMPA (4-deoxy-4-amino-N 10-methylpteroic acid) at 52 hours post-HDMTX. Cross-reactivity between commercial methotrexate immunoassays with DAMPA led to falsely elevated methotrexate concentrations for much longer than expected based on the current guideline (5 days instead of <48 hours). This required ongoing monitoring of methotrexate concentration by mass spectrometry. OUTCOMES: The patient remained nonoliguric and did not develop acute indications for dialysis. Serum creatinine peaked at 608 µmol/L (6.88 mg/dL) 6 days after HDMTX. He ultimately had a full renal and neurologic recovery. LESSONS LEARNED: Glucarpidase is an effective option for nonrenal elimination of methotrexate-induced nephrotoxicity. Timing of methotrexate concentration monitoring to assess for toxicity, how to access the drug, and the need for ongoing monitoring by mass spectrometry beyond the guideline recommendation are highlighted for centers where HDMTX therapy may be used.

JUSTIFICATION: Les lignes directrices consensuelles sur la prise en charge de la néphrotoxicité induite par le méthotrexate par l'administration de glucarpidase (VoraxazeMD) sont possiblement mal connues en néphrologie. PRÉSENTATION DU CAS: Nous présentons le cas d'un patient de 61 ans atteint d'un lymphome intravasculaire à grandes cellules B qui avait été admis pour un cycle de traitement à dose élevée de méthotrexate (HDMTX) après deux cycles de chimiothérapie par R-CHOP. À l'admission, le patient était cliniquement euvolémique et présentait une clairance de la créatinine à 98 mL/min. Le patient a reçu la prophylaxie standard pour une toxicité à HDMTX avec expansion volumique, alcalinisation urinaire et sauvetage par leucovorine. DIAGNOSTIC: Malgré les mesures prophylactiques, l'état du patient a évolué vers une grave insuffisance rénale aigüe (créatinine initiale de 63 à 226 µmol/L [2,56 mg/dL]) après le traitement au HDMTX, de même qu'une altération de la clairance du méthotrexate et une neurotoxicité manifestée par un status epilepticus. INTERVENTIONS: Le patient a reçu du glucarpidase pour convertir le méthotrexate extracellulaire en ses métabolites inactifs, le glutamate et le DAMPA (acide 4-déoxy-4-amino-N 10-méthylptéroïque) 52 heures après le traitement au HDMTX. La réactivité croisée entre les immunoessais commerciaux au méthotrexate et le DAMPA a entraîné des concentrations faussement élevées de méthotrexate pour beaucoup plus longtemps que prévu selon la recommandation actuelle (5 jours plutôt que < 48 heures). Cette situation a nécessité une surveillance continue de la concentration du méthotrexate par spectrométrie de masse. RÉSULTATS: Le patient est demeuré non oligurique et n'a pas nécessité de dialyse. Le taux de créatinine sérique a culminé à 608 µmol/L (6,88 mg/dL) six jours après l'administration de HDMTX. Les fonctions rénale et neurologique du patient se sont finalement rétablies complètement. LEÇONS TIRÉES: La glucarpidase est une option efficace pour éliminer de façon non rénale la néphrotoxicité induite par le méthotrexate. Le moment de mesurer la concentration de méthotrexate pour évaluer la toxicité, la façon d'accéder au médicament et la nécessité d'une surveillance continue par spectrométrie de masse au-delà de la recommandation actuelle sont clarifiés pour les centres où un traitement par HDMTX pourrait être administré.

Validation of Living Donor Nephrectomy Codes.

BACKGROUND: Use of administrative data for outcomes assessment in living kidney donors is increasing given the rarity of complications and challenges with loss to follow-up. OBJECTIVE: To assess the validity of living donor nephrectomy in health care administrative databases compared with the reference standard of manual chart review. DESIGN: Retrospective cohort study. SETTING: 5 major transplant centers in Ontario, Canada. PATIENTS: Living kidney donors between 2003 and 2010. MEASUREMENTS: Sensitivity and positive predictive value (PPV). METHODS: Using administrative databases, we conducted a retrospective study to determine the validity of diagnostic and procedural codes for living donor nephrectomies. The reference standard was living donor nephrectomies identified through the province's tissue and organ procurement agency, with verification by manual chart review. Operating characteristics (sensitivity and PPV) of various algorithms using diagnostic, procedural, and physician billing codes were calculated. RESULTS: During the study period, there were a total of 1199 living donor nephrectomies. Overall, the best algorithm for identifying living kidney donors was the presence of 1 diagnostic code for kidney donor (ICD-10 Z52.4) and 1 procedural code for kidney procurement/excision (1PC58, 1PC89, 1PC91). Compared with the reference standard, this algorithm had a sensitivity of 97% and a PPV of 90%. The diagnostic and procedural codes performed better than the physician billing codes (sensitivity 60%, PPV 78%). LIMITATIONS: The donor chart review and validation study was performed in Ontario and may not be generalizable to other regions. CONCLUSIONS: An algorithm consisting of 1 diagnostic and 1 procedural code can be reliably used to conduct health services research that requires the accurate determination of living kidney donors at the population level.

CONTEXTE: Les professionnels de la santé se fient de plus en plus aux données administratives pour évaluer l'issue de l'opération chez les donneurs de rein vivants, étant donné la rareté des complications et les défis posés par la perte des patients au cours du suivi. OBJECTIF: Nous souhaitions évaluer la validité des données de néphrectomies sur donneur vivant rapportées dans les bases de données administratives en santé comparativement à la norme de référence qui consiste à consigner les données manuellement dans les dossiers médicaux. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective. CADRE DE L'ÉTUDE: L'étude a été menée dans l'un des cinq principaux centres de transplantation d'Ontario, au Canada. PARTICIPANTS: La cohorte était composée de donneurs de rein vivants dont la néphrectomie a eu lieu entre 2003 et 2010. MESURES: Sensibilité et valeur prédictive positive (VPP). MÉTHODOLOGIE: Dans le cadre d'une étude rétrospective menée à l'aide de bases de données administratives, nous avons examiné la validité des codes de diagnostic et des codes d'intervention dans les cas de néphrectomie sur donneur vivant. Les données de l'organisme ontarien d'approvisionnement en organes, vérifiées manuellement par analyse des dossiers médicaux, ont servi de norme de référence. On a déterminé les paramètres fonctionnels (la sensibilité et la VPP) de plusieurs algorithmes basés sur les codes de diagnostic, les codes d'intervention et les codes de facturation. RÉSULTATS: Il y a eu 1 199 néphrectomies sur donneur vivant pendant la période couverte par l'étude. Globalement, le meilleur algorithme de repérage des donneurs de rein vivants combinait i) un code de diagnostic attribué à un donneur de rein (ICD-10 Z52.4) et ii) un code d'intervention attribué à l'ablation ou au prélèvement rénal (1PC58, 1PC89, 1PC91). En comparaison avec la norme de référence, cet algorithme présente une sensibilité de 97 % et une VPP de 90 %. Les codes de diagnostic et d'intervention se sont avérés de meilleurs indicateurs que les codes de facturation du médecin (sensibilité de 60 %; VPP de 78 %). LIMITES DE L'ÉTUDE: L'examen des dossiers médicaux des donneurs et l'étude de validation ayant été menés en Ontario, ses conclusions peuvent ne pas être transposables à d'autres régions. CONCLUSION: Un algorithme combinant un code de diagnostic et un code d'intervention s'est avéré fiable pour le dénombrement des donneurs de rein vivants dans la population générale en contexte de recherche en santé.

Is the Kidney Donor Risk Index a Useful Tool in Non-US Patients?

BACKGROUND: Deceased donor kidney allocation in the United States is guided by the Kidney Donor Risk Index (KDRI). The generalizability of the KDRI beyond the United States has not been widely studied. OBJECTIVE: To assess the generalizability of the KDRI in a cohort of non-US (Canadian) deceased donor kidney transplant recipients. DESIGN: Population-based retrospective cohort study. SETTING: Ontario, Canada. PATIENTS: Recipients of deceased donor kidneys from January 1, 2005, to March 31, 2011. METHODS: Using administrative data, we analyzed a cohort of deceased donor kidney recipients in Ontario, Canada. The Kaplan-Meier method and Cox proportional hazards models were used to assess the relationship between KDRI and the outcomes of graft loss and death. KDRI was modeled continuously and categorically. The ability of models with KDRI to predict recipient outcomes beyond donor age was also explored. Model discrimination was assessed using c-statistics, evaluated at 5 years of follow-up. RESULTS: A total of 1299 consecutive deceased donor kidney transplant recipients were included. The median follow-up was 5.5 years. Mean donor age increased from 27 to 64 years across ascending KDRI quintiles. The adjusted relative hazards (95% confidence interval) for total graft loss from Q2 to Q5 (referent = Q1) were 1.27 (0.89-1.80), 1.58 (1.13-2.22), 1.43 (1.01-2.02), and 2.15 (1.54-2.99), respectively. Increased relative hazards across KDRI quintiles were also observed for death-censored graft loss, but not death with graft function. All-cause mortality was increased for the highest KDRI quintile only. In this cohort, a model with KDRI performed better than a model with donor age alone (P = .009). LIMITATIONS: Large health care databases may have precluded the complete capture of covariate data. CONCLUSIONS: In conclusion, the KDRI is generalizable to Canadian patients in Ontario and may help inform risk assessment beyond donor age. The performance of KDRI in other non-US settings, and the need for additional model refinement, warrants further study.

CONTEXTE: Aux États-Unis, l'attribution des reins provenant de donneurs décédés est guidée par l'indice Kidney Donor Risk Index (KDRI). La généralisation de cet indice hors des États-Unis a toutefois été peu étudiée. OBJECTIF DE L'ÉTUDE: Déterminer s'il est possible de généraliser l'indice KDRI à une cohorte canadienne de receveurs d'un rein provenant d'un donneur décédé. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective. CADRE: La province de l'Ontario, au Canada. SUJETS: Les patients ayant reçu un rein provenant d'un donneur décédé entre le 1er janvier 2005 et le 31 mars 2011. MÉTHODOLOGIE: À l'aide des données administratives provinciales de l'Ontario (Canada), nous avons analysé une cohorte de receveurs d'un rein provenant d'un donneur décédé. Des modèles des risques proportionnels de Cox et la méthode de Kaplan-Meier ont été employés pour quantifier la relation entre l'indice KDRI et le risque de perte du greffon ou de décès du patient. L'indice KDRI a été modélisé de façon continue et par quintiles. On a également étudié la validité prédictive des modèles employant l'indice KDRI concernant les résultats du receveur au-delà d'une prédiction basée uniquement sur l'âge du donneur. Le pouvoir discriminant des modèles a été analysé par la surface sous la courbe à cinq ans post-intervention. RÉSULTATS: Un total de 1 299 receveurs d'une greffe de rein provenant d'un donneur décédé ont été inclus dans l'étude. La durée médiane du suivi s'établissait à 5,5 ans. L'âge moyen des donneurs passait de 27 ans au quintile inférieur à 64 ans au quintile supérieur. Le risque relatif corrigé (IC 95 %) de perte totale du greffon du Q2 au Q5 (référence = Q1) s'établissait respectivement à 1,27 (0,89; 1,80), 1,58 (1,13; 2,22), 1,43 (1,01; 2,02), et 2,15 (1,54; 2,99). Une augmentation du risque relatif a également été observée pour tous les quintiles dans les cas de perte du greffon censurée au décès du patient, mais pas dans les cas de décès du patient dont le greffon était toujours fonctionnel. Le taux de mortalité toutes causes confondues s'est accru dans le quintile supérieur seulement. Au sein de cette cohorte, le modèle basé sur l'indice KDRI a mieux prédit l'issue des patients que le modèle basé uniquement l'âge du donneur (p=0,009). LIMITES DE L'ÉTUDE: Vu la grande taille des bases de données en santé, il est possible que la saisie des covariables soit incomplète. CONCLUSION: L'indice KDRI est généralisable aux patients ontariens et pourrait contribuer à éclairer l'évaluation des risques plus efficacement qu'en ne considérant que l'âge du donneur. La valeur prédictive de l'indice KDRI hors des États-Unis et la nécessité de perfectionner le modèle justifient des études plus approfondies.