Using ChatGPT in Psychiatry to Design Script Concordance Tests in Undergraduate Medical Education: Mixed Methods Study.

Background: Undergraduate medical studies represent a wide range of learning opportunities served in the form of various teaching-learning modalities for medical learners. A clinical scenario is frequently used as a modality, followed by multiple-choice and open-ended questions among other learning and teaching methods. As such, script concordance tests (SCTs) can be used to promote a higher level of clinical reasoning. Recent technological developments have made generative artificial intelligence (AI)-based systems such as ChatGPT (OpenAI) available to assist clinician-educators in creating instructional materials. Objective: The main objective of this project is to explore how SCTs generated by ChatGPT compared to SCTs produced by clinical experts on 3 major elements: the scenario (stem), clinical questions, and expert opinion. Methods: This mixed method study evaluated 3 ChatGPT-generated SCTs with 3 expert-created SCTs using a predefined framework. Clinician-educators as well as resident doctors in psychiatry involved in undergraduate medical education in Quebec, Canada, evaluated via a web-based survey the 6 SCTs on 3 criteria: the scenario, clinical questions, and expert opinion. They were also asked to describe the strengths and weaknesses of the SCTs. Results: A total of 102 respondents assessed the SCTs. There were no significant distinctions between the 2 types of SCTs concerning the scenario (P=.84), clinical questions (P=.99), and expert opinion (P=.07), as interpretated by the respondents. Indeed, respondents struggled to differentiate between ChatGPT- and expert-generated SCTs. ChatGPT showcased promise in expediting SCT design, aligning well with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, albeit with a tendency toward caricatured scenarios and simplistic content. Conclusions: This study is the first to concentrate on the design of SCTs supported by AI in a period where medicine is changing swiftly and where technologies generated from AI are expanding much faster. This study suggests that ChatGPT can be a valuable tool in creating educational materials, and further validation is essential to ensure educational efficacy and accuracy.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Differences in medication adherence by sex and organ type among adolescent and young adult solid organ transplant recipients.

BACKGROUND: Identification of differences in medication adherence by sex or organ type may help in planning interventions to optimize outcomes. We compared immunosuppressive medication adherence between males and females, and between kidney, liver and heart transplant recipients. METHODS: This multicenter study of prevalent kidney, liver and heart transplant recipients 14-25 years assessed adherence 3 times (0, 3, 6 months post-enrollment) with the BAASIS self-report tool. At each visit, participants were classified as adherent if they missed no doses in the prior 4 weeks and non-adherent otherwise. Adherence was also assessed using the coefficient of variation (CV) of tacrolimus trough levels; CV < 30% was classified as adherent. We used multivariable mixed effects logistic regression models adjusted for potential confounders to compare adherence by sex and by organ. RESULTS: Across all visits, males (n = 150, median age 20.4 years, IQR 17.2-23.3) had lower odds of self-reported adherence than females (n = 120, median age 19.8 years, IQR 17.1-22.7) (OR 0.41, 95% CI 0.21-0.80) but higher odds of adherence by tacrolimus CV (OR 2.50, 95% CI 1.30-4.82). No significant differences in adherence (by self-report or tacrolimus CV) were noted between the 184 kidney, 58 liver, and 28 heart recipients. CONCLUSION: Females show better self-reported adherence than males but greater variability in tacrolimus levels. Social desirability bias, more common in females than males, may contribute to better self-reported adherence among females. Higher tacrolimus variability among females may reflect biologic differences in tacrolimus metabolism between males and females rather than sex differences in adherence. There were no significant differences in adherence by organ type.

Association of Nonrecovery of Kidney Function After Pediatric Acute Kidney Injury With 5-Year Kidney and Nonkidney Outcomes.

Acute kidney injury is common in critically ill children, but the long-term outcomes are not well defined. OBJECTIVES: Evaluated whether nonrecovery of kidney function, following acute kidney injury, was associated with postdischarge mortality, healthcare utilization, and chronic kidney disease. DESIGN: Retrospective, two-center, observational study. SETTING: Two ICUs at tertiary children's hospitals in Montreal, QC. PARTICIPANTS: Pediatric patients (age ≤ 18 yr) with index admission to intensive care between January 1, 2003, and March 31, 2005. Children were excluded if they 1) died during admission, 2) did not have serum creatinine or urine output measured, 3) did not develop acute kidney injury, 4) could not be linked to administrative health data, and 5) (for chronic kidney disease outcome) had pre-existing renal disease by chart review, baseline estimated glomerular filtration rate measurement, or administrative health data codes. MAIN OUTCOMES AND MEASURES: Three-hundred seventy-eight patients' data were included for long-term mortality and healthcare utilization outcomes; 316 patients for long-term chronic kidney disease outcome. Outcomes were defined using provincial administrative healthcare data diagnosis, procedure, and billing codes. MAIN RESULTS: Nonrecovery of kidney function, defined as serum creatinine greater than or equal to 1.5× baseline at ICU discharge, occurred in 51 patients (13%). Nonrecovery of kidney function was not associated with long-term mortality (at 5-7 yr following hospital discharge), increased hospitalizations or emergency department visits (at 30-days, 1-year, and 5-yr follow-up), or increased physician visits (at 1- and 5-yr follow-up). Nonrecovery was associated with increased 30-day physician visits (adjusted relative risk, 1.40; 95% CI, 1.13-1.73) and chronic kidney disease diagnosis within 5 years of discharge (adjusted hazard ratio, 4.92, 95% CI, 1.77-13.70). CONCLUSIONS AND RELEVANCE: Nonrecovery of kidney function following an episode of acute kidney injury in critically ill children is associated with nearly five-fold increased risk for long-term chronic kidney disease. Acute kidney injury nonrecovery may be a useful marker to identify patients that are particularly important to follow-up post discharge for chronic kidney disease detection.

Acute kidney injury in the pediatric intensive care unit: outpatient follow-up.

BACKGROUND: Few studies have characterized follow-up after pediatric acute kidney injury (AKI). Our aim was to describe outpatient AKI follow-up after pediatric intensive care unit (PICU) admission. METHODS: Two-center retrospective cohort study (0-18 years; PICU survivors (2003-2005); noncardiac surgery; and no baseline kidney disease). Provincial administrative databases were used to determine outcomes. EXPOSURE: AKI (KDIGO (Kidney Disease: Improving Global Outcomes) definitions). OUTCOMES: post-discharge nephrology, family physician, pediatrician, and non-nephrology specialist visits. Regression was used to evaluate factors associated with the presence of nephrology follow-up (Cox) and the number of nephrology and family physician or pediatrician visits (Poisson), among AKI survivors. RESULTS: Of n = 2041, 355 (17%) had any AKI; 64/355 (18%) had nephrology; 198 (56%) had family physician or pediatrician; and 338 (95%) had family physician, pediatrician, or non-nephrology specialist follow-up by 1 year post discharge. Only 44/142 (31%) stage 2-3 AKI patients had nephrology follow-up by 1 year. Inpatient nephrology consult (adjusted hazard ratio (aHR) 7.76 [95% confidence interval (CI) 4.89-12.30]), kidney admission diagnosis (aHR 4.26 [2.21-8.18]), and AKI non-recovery by discharge (aHR 2.65 [1.55-4.55]) were associated with 1-year nephrology follow-up among any AKI survivors. CONCLUSIONS: Nephrology follow-up after AKI was uncommon, but nearly all AKI survivors had follow-up with non-nephrologist physicians. This suggests that AKI follow-up knowledge translation strategies for non-nephrology providers should be a priority. IMPACT: Pediatric AKI survivors have high long-term rates of chronic kidney disease (CKD) and hypertension, justifying regular kidney health surveillance after AKI. However, there is limited pediatric data on follow-up after AKI, including the factors associated with nephrology referral and extent of non-nephrology follow-up. We found that only one-fifth of all AKI survivors and one-third of severe AKI (stage 2-3) survivors have nephrology follow-up within 1 year post discharge. However, 95% are seen by a family physician, pediatrician, or non-nephrology specialist within 1 year post discharge. This suggests that knowledge translation strategies for AKI follow-up should be targeted at non-nephrology healthcare providers.

Age- and sex-mediated differences in T lymphocyte populations of kidney transplant recipients.

BACKGROUND: Graft failure rates increase through childhood and adolescence, decline in adulthood, and are higher in female than male kidney transplant recipients (KTR) until middle age. We aimed to describe age- and sex-related differences in T-cell subsets among KTR to determine which differences may help to explain the differences in kidney graft failure rates. METHODS: Effector T (Teff)-cell and regulatory T (Treg)-cell phenotypes in PBMCs from healthy controls and KTR, who were at least 1 year post-transplant with stable graft function under immunosuppression, were analyzed by flow cytometry. The effects of age, sex, and status (KTR or control) were analyzed using linear regressions. RESULTS: We enrolled 20 male and 21 female KTR and 20 male and 20 female controls between 3 and 29 years of age. CD3+ T-cell frequencies were not associated with age or sex but were higher in KTR than controls. There were no differences in CD4+ and CD8+ frequencies. Th1 (IFNγ+ IL-4- IL-17A-) and Th17 (IL-17A+) frequencies within the CD4+ T-cell population were higher at older ages. The frequencies of FOXP3 + Helios + Treg cells in CD4+ CD25+ CD127- T cells were lower in females than males and in KTR than controls. CONCLUSIONS: Increasing frequencies of Th1 and Th17 cells with increasing age mirrors the increasing graft failure rates from childhood to young adulthood. Importantly, sex differences in frequencies of circulating Treg cells may suggest a role in the sex differences in graft failure rates.

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

BACKGROUND: We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients. METHODS: We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada. Patients were enrolled between June 2015 and March 2018 and followed for 6 months. Adherence was assessed at baseline, 3, and 6 months using the BAASIS© self-report tool. Patients were classified as adherent if no doses were missed in the prior 4 weeks. Transplant program directors and nurses completed questionnaires regarding care organization and processes. RESULTS: Of the 270 participants, 99 were followed in pediatric programs and 171 in adult programs. Median age was 20.3 years, and median time since transplant was 5 years. At baseline, 71.5% were adherent. Multivariable mixed effects logistic regression models with program as a random effect identified two program-level factors as independently associated with better adherence: minimum number of prescribed blood draws per year for those >3 years post-transplant (per 1 additional) (OR 1.12 [95% CI 1.00, 1.26]; p = .047), and average time nurses spend with patients in clinic (per 5 additional minutes) (OR 1.15 [1.03, 1.29]; p = .017). CONCLUSION: Program-level factors including protocols with a greater frequency of routine blood testing and more nurse time with patients were associated with better medication adherence. This suggests that interventions at the program level may support better adherence.

Association of pediatric cardiac surgery-associated acute kidney injury with post-discharge healthcare utilization, mortality and kidney outcomes.

BACKGROUND: Acute kidney Injury (AKI) in children undergoing cardiac surgery (CS) is strongly associated with hospital morbidity. Post-discharge CS AKI outcomes are less clear. We evaluated associations between AKI and post-discharge (a) healthcare utilization, (b) chronic kidney disease (CKD) or hypertension and (c) mortality. METHODS: This is a retrospective two-centre cohort study of children surviving to hospital discharge after CS. Primary exposures were post-operative ≥Stage 1 AKI and ≥Stage 2 AKI defined by Kidney Disease Impoving Global Outcomes. Association of AKI with time to outcomes was determined using multivariable Cox-Proportional Hazards analysis. RESULTS: Of 350 participants included (age 3.1 (4.5) years), 180 [51.4%] developed AKI and 60 [17.1%] developed ≥Stage 2 AKI. Twenty-eight (9%) participants developed CKD or hypertension (composite outcome), and 17 (5%) died within 5 years of discharge. Post-operative ≥Stage 1 and ≥Stage 2 AKI were not associated with post-discharge hospitalizations, emergency room (ER) visits, physician visits or CKD or hypertension in adjusted analyses. A trend was observed between ≥Stage 2 AKI and mortality but was not statistically significant. In unadjusted stratified analyses, AKI was associated with post-discharge hospitalizations in children with RACHS-1 score ≥3, complex chronic disease classification and children living in urban areas. CONCLUSIONS: Post-CS AKI is not associated with post-discharge healthcare utilization, death and CKD or hypertension, though it may be associated with healthcare utilization in more complex paediatric CS children. Studies should aim to better understand post-CS healthcare utilization patterns and non-AKI risk factors for CKD, hypertension and mortality, to reduce adverse long-term outcomes after CS.

Canadian Association of Paediatric Nephrologists COVID-19 Rapid Response: Guidelines for Management of Acute Kidney Injury in Children.

PURPOSE: This article provides guidance on managing acute kidney injury (AKI) and kidney replacement therapy (KRT) in pediatrics during the COVID-19 pandemic in the Canadian context. It is adapted from recently published rapid guidelines on the management of AKI and KRT in adults, from the Canadian Society of Nephrology (CSN). The goal is to provide the best possible care for pediatric patients with kidney disease during the pandemic and ensure the health care team's safety. INFORMATION SOURCES: The Canadian Association of Paediatric Nephrologists (CAPN) COVID-19 Rapid Response team derived these rapid guidelines from the CSN consensus recommendations for adult patients with AKI. We have also consulted specific documents from other national and international agencies focused on pediatric kidney health. We identified additional information by reviewing the published academic literature relevant to pediatric AKI and KRT, including recent journal articles and preprints related to COVID-19 in children. Finally, our group also sought expert opinions from pediatric nephrologists across Canada. METHODS: The leadership of the CAPN, which is affiliated with the CSN, solicited a team of clinicians and researchers with expertise in pediatric AKI and acute KRT. The goal was to adapt the guidelines recently adopted for Canadian adult patients for pediatric-specific settings. These included specific COVID-19-related themes relevant to AKI and KRT in a Canadian setting, as determined by a group of kidney disease experts and leaders. An expert group of clinicians in pediatric AKI and acute KRT reviewed the revised pediatric guidelines. KEY FINDINGS: (1) Current Canadian data do not suggest an imminent threat of an increase in acute KRT needs in children because of COVID-19; however, close coordination between nephrology programs and critical care programs is crucial as the pandemic continues to evolve. (2) Pediatric centers should prepare to reallocate resources to adult centers as needed based on broader health care needs during the COVID-19 pandemic. (3) Specific suggestions pertinent to the optimal management of AKI and KRT in COVID-19 patients are provided. These suggestions include but are not limited to aspects of fluid management, KRT vascular access, and KRT modality choice. (4) Considerations to ensure adequate provision of KRT if resources become scarce during the COVID-19 pandemic. LIMITATIONS: We did not conduct a formal systematic review or meta-analysis. We did not evaluate our specific suggestions in the clinical environment. The local context, including how the provision of care for AKI and acute KRT is organized, may impede the implementation of many suggestions. As knowledge is advancing rapidly in the area of COVID-19, suggestions may become outdated quickly. Finally, most of the literature for AKI and KRT in COVID-19 comes from adult data, and there are few pediatric-specific studies. IMPLICATIONS: Given that most acute KRT related to COVID-19 is likely to be required in the pediatric intensive care unit initial setting, close collaboration and planning between critical care and pediatric nephrology programs are needed. Our group will update these suggestions with a supplement if necessary as newer evidence becomes available that may change or add to the recommendations provided.

Educators and practitioners' perspectives in the development of a learning by concordance tool for medical clerkship in the context of the COVID pandemic.

BACKGROUND: The COVID-19 pandemic has forced medical schools to create educational material to palliate the anticipated and observed decrease in clinical experiences during clerkships. An online learning by concordance (LbC) tool was developed to overcome the limitation of students' experiences with clinical cases. However, knowledge about the instructional design of an LbC tool is scarce, especially the perspectives of collaborators involved in its design: 1- educators who wrote the vignettes' questions and 2- practitioners who constitute the reference panel by answering the LbC questions. The aim of this study was to describe the key elements that supported the pedagogical design of an LbC tool from the perspectives of educators and practitioners. METHODS: A descriptive qualitative research design has been used. Online questionnaires were used, and descriptive analysis was conducted. RESULTS: Six educators and 19 practitioners participated in the study. Important to the educators in designing the LbC tool were prevalent or high-stake situations, theoretical knowledge, professional situations experienced and perceived difficulties among students, and that the previous workshop promoted peer discussion and helped solidify the writing process. Important for practitioners was standards of practice and consensus among experts. However, they were uncertain of the educational value of their feedback, considering the ambiguity of the situations included in the LbC tool. CONCLUSIONS: The LbC tool is a relatively new training tool in medical education. Further research is needed to refine our understanding of the design of such a tool and ensure its content validity to meet the pedagogical objectives of the clerkship.

CONTEXTE: Face à la pandémie de la COVID-19, les facultés de médecine ont été contraintes à créer du matériel pédagogique pouvant pallier la diminution prévue et avérée de l'exposition clinique pendant les stages d'externat. Un outil numérique de formation par concordance (FpC) a été développé pour combler le manque d'exposition à des cas cliniques. Cependant, les connaissances sur la conception pédagogique des outils de FpC sont limitées, en particulier en ce qui concerne les perspectives des collaborateurs participant à leur réalisation : 1 ­ les éducateurs qui rédigent les questions des vignettes et 2 ­ les praticiens composant le groupe d'experts qui fournissent les réponses de référence aux questions de FpC. L'objectif de cette étude était de décrire les éléments clés qui ont étayé la conception pédagogique d'un outil FpC du point de vue des éducateurs et des praticiens. MÉTHODES: Il s'agit d'une recherche qualitative de type descriptif, pour laquelle on s'est servi de questionnaires en ligne et d'une méthode d'analyse descriptive. RÉSULTATS: Six éducateurs et 19 praticiens ont participé à l'étude. Dans la conception de l'outil FpC, les éducateurs ont attribué une importance particulière aux situations courantes ou à enjeu élevé, aux connaissances théoriques, aux situations professionnelles vécues par les étudiants et aux difficultés qu'ils ont perçues chez eux. Ils ont également tenu à faire en sorte que l'atelier qui précédait la conception favorise le débat entre pairs et contribue à solidifier le processus de rédaction. Les praticiens ont privilégié les normes de pratique et l'existence d'un consensus entre experts. Cependant, ils doutaient de la valeur pédagogique de leurs commentaires, compte tenu de l'ambiguïté des situations décrites dans l'outil FpC. CONCLUSIONS: Les outils FpC sont relativement nouveaux en éducation médicale. Des recherches plus poussées sont nécessaires pour affiner notre compréhension de la conception d'un tel outil et pour nous assurer de sa validité de contenu, pour bien répondre aux objectifs pédagogiques de l'externat.

Management of Pediatric Kidney Transplant Patients During the COVID-19 Pandemic: Guidance From the Canadian Society of Transplantation Pediatric Group.

PURPOSE OF THE PROGRAM: To provide guidance on the management of pediatric kidney transplant patients during the COVID-19 pandemic. SOURCES OF INFORMATION: Program-specific documents, preexisting, and related to COVID-19; documents from provincial, national, and international kidney transplant societies/agencies and organ procurement agencies; national and international webinars, including webinars that we hosted for input and feedback; with additional information from formal and informal review of published academic literature. METHODS: Challenges in the care of pediatric kidney transplant patients during the COVID-19 pandemic were highlighted within the Canadian Society of Transplantation (CST) Pediatric Group. It identified pediatric kidney transplant nephrologists (including a pediatric nephrologist ethicist) across the country and formed a workgroup. The initial guidance document was drafted and members of the workgroup reviewed and discussed all suggestions in detail via e-mail and virtual meetings. Disagreements were resolved by consensus. The document was reviewed by the CST Kidney Transplant Working Group, by the Canadian Society of Nephrology (CSN) COVID-19 Rapid Response Team (RRT), and an infectious disease expert. The suggestions were presented at an interactive webinar sponsored by CSN in collaboration with the CST and Canadian Association of Pediatric Nephrologists (CAPN), and attended by pediatric kidney health care professionals for further peer input. Final revisions were made based on feedback received. CJKHD editors reviewed the parallel process peer review and edited the manuscript for clarity. KEY FINDINGS: We identified 8 key areas of pediatric kidney transplant care that may be affected by the COVID-19 pandemic: (1) transplant activity, (2) outpatient clinic activity, (3) monitoring, (4) multidisciplinary care, (5) medications (immunosuppression and others), (6) patient/family education/support, (7) school and employment, and (8) management of pediatric kidney transplant patients who are COVID-19 positive. We make specific suggestions for each of these areas. LIMITATIONS: A full systematic review of available literature was not undertaken for the sake of expediency in development of this guideline. There is a paucity of literature to support evidence-based recommendations at this time. Instead, these guidelines were formulated based on expert opinion derived from available knowledge/experience and are subject to the biases associated with this level of evidence. The parallel review process that was created to expedite the publication of this work may not be as robust as standard arms' length peer review processes. IMPLICATIONS: These recommendations are meant to serve as a guide to pediatric kidney transplant directors, clinicians, and administrators for providing the best patient care in the context of limited resources while protecting patients and health care providers wherever possible by limiting exposure to COVID-19. We recognize that recommendations may not be applicable to all provincial/local health authority practices and that they may not be delivered to all patients given the time and resource constraints affecting the individual provincial/local health jurisdiction.

Management of Canadian Pediatric Patients With Glomerular Diseases During the COVID-19 Pandemic: Recommendations From the Canadian Association of Pediatric Nephrologists COVID-19 Rapid Response Team.

PURPOSE: The goal of these recommendations is to provide guidance on the optimal care of children with glomerular diseases during the COVID-19 pandemic. Patients with glomerular diseases are known to be more susceptible to infection. Risk factors include decreased vaccine uptake, urinary loss of immunoglobulins, and treatment with immunosuppressive medications. The Canadian Society of Nephrology (CSN) recently published guidelines on the care of adult glomerulonephritis patients. This guideline aims to expand and adapt those recommendations for programs caring for children with glomerular diseases. SOURCES OF INFORMATION: We used the CSN COVID-19 Rapid Response Team adult glomerulonephritis recommendations, published in the Canadian Journal of Kidney Health and Disease, as the foundation for our guidelines. We reviewed documents published by nephrology and non-nephrology societies and health care agencies focused on kidney disease and immunocompromised populations. Finally, we conducted a formal literature review of publications relevant to pediatric and adult glomerular disease, chronic kidney disease, hypertension, and immunosuppression in the context of the COVID-19 pandemic. METHODS: The leadership of the Canadian Association of Pediatric Nephrologists (CAPN), which is affiliated with the CSN, identified a team of clinicians and researchers with expertise in pediatric glomerular diseases. The aim was to adapt Canadian adult glomerulonephritis guidelines to make them applicable to children and discuss pediatric-specific considerations. The updated guidelines were peer-reviewed by senior clinicians with expertise in the care of childhood glomerular diseases. KEY FINDINGS: We identified a number of key areas of glomerular disease care likely to be affected by the COVID-19 pandemic, including (1) clinic visit scheduling, (2) visit types, (3) provision of multidisciplinary care, (4) blood work and imaging, (5) home monitoring, (6) immunosuppression, (7) other medications, (8) immunizations, (9) management of children with suspected COVID-19, (10) renal biopsy, (11) patient education and support, and (12) school and child care. LIMITATIONS: There are minimal data regarding the characteristics and outcomes of COVID-19 in adult or pediatric glomerular disease patients, as well as the efficacy of strategies to prevent infection transmission within these populations. Therefore, the majority of these recommendations are based on expert opinion and consensus guidance. To expedite the publication of these guidelines, an internal peer-review process was conducted, which may not have been as rigorous as formal journal peer-review. IMPLICATIONS: These guidelines are intended to promote optimal care delivery for children with existing or newly diagnosed glomerular diseases during the COVID-19 pandemic. The implications of modified care delivery, altered immunosuppression strategies, and limited access to existing resources remain uncertain.

Acute kidney injury in critically ill children and 5-year hypertension.

BACKGROUND: To develop a pediatric-specific hypertension algorithm using administrative data and use it to evaluate the association between acute kidney injury (AKI) in the intensive care unit (ICU) and hypertension diagnosis 5 years post-discharge. METHODS: Two-center retrospective cohort study of children (≤ 18 years old) admitted to the pediatric ICU in Montreal, Canada, between 2003 and 2005 and followed until 2010. Patients with a valid healthcare number and without end-stage renal disease were included. Patients who could not be merged with the provincial database, did not survive admission, underwent cardiac surgery, had pre-existing renal disease associated with hypertension or a prior diagnosis of hypertension were excluded. AKI defined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Using diagnostic codes and medications from administrative data, novel pediatric-specific hypertension definitions were designed. Both the evaluation of the prevalence of hypertension diagnosis and the association between AKI and hypertension occurred. RESULTS: Nineteen hundred and seventy eight patients were included (median age at admission [interquartile range] 4.3 years [1.1-11.8], 44% female, 325 (16.4%) developed AKI). Of these patients, 130 (7%) had a hypertension diagnosis 5 years after discharge. Patients with AKI had a higher prevalence of hypertension diagnosis [non-AKI: 84/1653 (5.1%) vs. AKI: 46/325 (14.2%), p < .001]. Children with AKI had a higher adjusted risk of hypertension diagnosis (hazard ratio [95% confidence interval] 2.19 [1.47-3.26]). CONCLUSIONS: Children admitted to the ICU have a high prevalence of hypertension post-discharge and children with AKI have over two times higher risk of hypertension compared to those with no AKI.

Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury. METHODS: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up. RESULTS: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed. CONCLUSIONS: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

Mixed-methods evaluation of a transition and young adult clinic for kidney transplant recipients.

The aims of the present study were to describe the experiences of kidney transplant patients attending a young adult clinic or a regular adult clinic, to explore similarities and differences between the groups, and to conduct an evaluation of the clinical and psychosocial outcomes of the young adult clinic, by comparing these outcomes to those of the regular adult clinic. A mixed-methods design combining qualitative and quantitative data was used. Empirically validated questionnaires measuring self-determination theory variables, quality of life, and adherence were distributed to all consenting patients attending the YAC (n = 17) and RAC (n = 16). Semi-structured interviews were conducted with a subsample of the first (n = 10) and second group (n = 8), and analyzed using thematic analysis. Clinical outcomes were retrieved from medical records. Descriptive, correlational, and comparative analyses were performed. We found clinically significant differences on tacrolimus blood levels variability, self-reported adherence, and physical quality of life. Small and medium effect sizes were detected. No statistical differences were found. Statistically significant correlations were found between self-determination theory variables and both physical quality of life and different measures of adherence. Four themes characterized patients' experiences: resilience; relational needs and the therapeutic alliance; quest for balance; and quest for normalcy. The young adult clinic seems to meet its initial objectives and to make a difference particularly in the early period post-transition, but over time what matters most for patients is therapeutic alliance. Mental health issues need to be better addressed, and special attention should be paid to youths transplanted in an adult setting.

A Validation Study of Administrative Health Care Data to Detect Acute Kidney Injury in the Pediatric Intensive Care Unit.

BACKGROUND: Large studies evaluating pediatric acute kidney injury (AKI) epidemiology and outcomes are lacking, partially due to underuse of large administrative health care data. OBJECTIVE: To assess the diagnostic accuracy of administrative health care data-defined AKI in children admitted to the pediatric intensive care unit (PICU). DESIGN: Retrospective cohort study utilizing chart and administrative data. SETTING: Children admitted to the PICU at 2 centers in Montreal, QC. PATIENTS: Patients between 0 and 18 years old with a provincial health insurance number, without end-stage renal disease and admitted to the PICU between January 1, 2003, and March 31, 2005, were included. MEASUREMENTS: The AKI was defined from chart data using the Kidney Disease: Improving Global Outcomes (KDIGO) definition (Chart-AKI). The AKI defined using administrative health data (Admin-AKI) was based on International Classification of Disease, Ninth Revision (ICD-9) AKI codes. METHODS: Data available from retrospective chart review, including baseline and PICU patient characteristics, and serum creatinine (SCr) and urine output (UO) values during PICU admission, were merged with provincial administrative health care data containing diagnostic and procedure codes used for ascertaining Admin-AKI. Sensitivity, specificity, positive, and negative predictive value of Admin-AKI compared with Chart-AKI (reference standard) were calculated. Univariable associations between Admin-AKI and hospital mortality were evaluated. RESULTS: A total of 2051 patients (55% male, mean age at admission 6.1 ± 5.8 years, 355 cardiac surgery, 1696 noncardiac surgery) were included. The AKI defined by SCr or UO criteria occurred in 52% of cardiac surgery patients and 24% of noncardiac surgery patients. Overall, Admin-AKI detected Chart-AKI with low sensitivity, but high specificity in cardiac and noncardiac surgery patients. Sensitivity increased by 1.5 to 2 fold with each increase in AKI severity stage. Admin-AKI was associated with hospital mortality (13% in Admin-AKI vs 2% in non-AKI, P < .001). LIMITATIONS: These data were generated in a PICU population; future research should study non-PICU populations. CONCLUSIONS: Use of administrative health care data to define AKI in children leads to AKI incidence underestimation. However, for detecting more severe AKI, sensitivity is higher, while maintaining high specificity.

CONTEXTE: On dispose de peu d'études à grande échelle évaluant l'épidémiologie et l'évolution de l'insuffisance rénale aigüe (IRA) chez les enfants, notamment en raison d'une sous-utilisation des données administratives du système de santé. OBJECTIF: Évaluer la précision diagnostique de l'IRA définie à partir des données administratives en santé chez des enfants admis aux unités de soins intensifs pédiatriques (USIP). TYPE D'ÉTUDE: Une étude de cohorte rétrospective utilisant des données administratives et les données provenant des dossiers médicaux. CADRE: Les USIP de deux centres hospitaliers de Montréal, au Canada. SUJETS: Ont été inclus les patients âgés de 0 à 18 ans possédant un numéro d'assurance-maladie provincial qui ont été admis aux USIP entre le 1er janvier 2003 et le 31 mars 2005 avec une insuffisance rénale non terminale. MESURES: L'IRA-Dos a été définie à partir des dossiers médicaux en utilisant les critères du KDIGO (Kidney Disease: Improving Global Outcomes). L'IRA-Admin a été définie à partir des données administratives en santé avec les codes d'IRA de la neuvième révision de la Classification internationale des maladies (CIM-9). MÉTHODOLOGIE: Les données tirées de l'examen rétrospectif des dossiers médicaux, soit les valeurs de créatinine sérique (SCr) et de diurèse pendant le séjour aux USIP et les caractéristiques des patients, initiales et à l'admission, ont été fusionnées aux données administratives provinciales en santé contenant les codes de diagnostic et de procédure utilisés pour établir l'IRA-Admin. La sensibilité, la spécificité et les valeurs prédictives négative et positive de l'IRA-Admin, en comparaison à l'IRA-Dos (standard de référence), ont été calculées. L'association univariée entre l'IRA-Admin et la mortalité à l'hôpital a également été évaluée. RÉSULTATS: Un total de 2 051 patients ont été inclus (355 ayant subi une cardiochirurgie et 1 696 non opérés). L'âge moyen des sujets à l'admission était de 6,1 ± 5,8 ans et 55 % étaient des garçons. L'IRA définie par les critères de SCr et de diurèse a été diagnostiquée chez 52 % des patients opérés et chez 24 % des patients non opérés. Pour l'ensemble de la cohorte (patients opérés ou non), l'IRA-Admin a détecté l'IRA-Dos avec une faible sensibilité, mais avec une spécificité élevée. La sensibilité s'est accrue de 1,5 à 2 fois pour chaque passage à un stade supérieur de gravité de l'IRA. Enfin, l'IRA-Admin a été associée à un taux plus élevé de mortalité à l'hôpital (13 % des patients IRA-Admin contre 2 % des patients sans IRA, p<0,001). LIMITATIONS: Ces résultats concernent une population de patients hospitalisés aux USIP. Des études futures devraient inclure des populations non admises aux USIP. CONCLUSIONS: L'utilisation des données administratives en santé pour définir l'IRA chez les enfants a mené à une sous-estimation de son incidence. Cependant, la méthode montre une plus grande sensibilité dans la détection des cas plus graves d'IRA, tout en conservant une spécificité élevée.

Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy (POSITIVE Study): The Collaboration and Design of a National Transplant Precision Medicine Program.

BACKGROUND: Despite age-related differences in biology, physiology, and behavior, transplant immunosuppression is not tailored by age. This likely contributes to high graft failure and posttransplant complications. We present the aims, design, and methods of the Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy Study aimed at personalizing posttransplant immunosuppression in children and young adults. METHODS: In this prospective observational cohort study, we recruited pediatric and young adult solid organ transplant, pediatric allogeneic hematopoietic stem cell transplant recipients, and matched living and deceased organ donors from 14 transplant centers across Canada. Clinical data, questionnaires, biospecimens, and pharmacy records were collected at serial time points: (1) to identify genetic and host immune factors that influence immunosuppression dose requirements across different ages and transplant types, (2) to identify viral-host interactions that increase susceptibility to Epstein-Barr virus infection, and (3) to define care processes and structures associated with medication adherence in adolescents and young adults. RESULTS: From 2015 to 2018, 1662 new and prevalent transplant recipients were screened, 1166 were recruited for the various aims, including 370 liver, 445 kidney, 277 heart, 19 lung, 19 multiple, and 36 hematopoietic stem cell transplant transplants. Twelve percent were younger than 2 years, 30% were 2 to 10 years, 42% were 10 to 18 years, and 16% were 18 to 24 years at enrollment. Nine hundred thirty-one consented to participation in aims 1 and 2 (90% consent rate), 287 to aim 3 (82% consent rate). Biospecimens collected included 898 for DNA, 276 for immunoassays, and 717 for biomarker studies. Seventy percent participants have completed follow-up; 30% are pending study completion. CONCLUSIONS: The design of this national multicenter cross-organ network helped maximize recruitment of a large patient cohort for studying age and organ-related differences in immunosuppression needs that would not otherwise be feasible. Leveraging the unique clinical, biological, environmental, and behavioral characteristics of this cohort will help develop precision medicine strategies for individualizing posttransplant immunosuppression.

Long-term Mortality After Acute Kidney Injury in the Pediatric ICU.

OBJECTIVES: (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)-defined AKI alters the association. METHODS: A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS: The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46-6.57] and 3.38 [1.63-7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS: AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships.

Healthcare Utilization after Acute Kidney Injury in the Pediatric Intensive Care Unit.

BACKGROUND AND OBJECTIVES: Little is known about the long-term burden of AKI in the pediatric intensive care unit. We aim to evaluate if pediatric AKI is associated with higher health service use post-hospital discharge. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective cohort study of children (≤18 years old) admitted to two tertiary centers in Montreal, Canada. Only the first admission per patient was included. AKI was defined in two ways: serum creatinine alone or serum creatinine and/or urine output. The outcomes were 30-day, 1-year, and 5-year hospitalizations, emergency room visits, and physician visits per person-time using provincial administrative data. Univariable and multivariable Poisson regression were used to evaluate AKI associations with outcomes. RESULTS: A total of 2041 children were included (56% male, mean admission age 6.5±5.8 years); 299 of 1575 (19%) developed AKI defined using serum creatinine alone, and when urine output was included in the AKI definition 355 of 1622 (22%) children developed AKI. AKI defined using serum creatinine alone and AKI defined using serum creatinine and urine output were both associated with higher 1- and 5-year hospitalization risk (AKI by serum creatinine alone adjusted relative risk, 1.42; 95% confidence interval, 1.12 to 1.82; and 1.80; 1.54 to 2.11, respectively [similar when urine output was included]) and higher 5-year physician visits (adjusted relative risk, 1.26; 95% confidence interval, 1.14 to 1.39). AKI was not associated with emergency room use after adjustments. CONCLUSIONS: AKI is independently associated with higher hospitalizations and physician visits postdischarge.

A Randomized Trial of a Multicomponent Intervention to Promote Medication Adherence: The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).

BACKGROUND: Poor adherence to immunosuppressive medications is a major cause of premature graft loss among children and young adults. Multicomponent interventions have shown promise but have not been fully evaluated. STUDY DESIGN: Unblinded parallel-arm randomized trial to assess the efficacy of a clinic-based adherence-promoting intervention. SETTING & PARTICIPANTS: Prevalent kidney transplant recipients 11 to 24 years of age and 3 or more months posttransplantation at 8 kidney transplantation centers in Canada and the United States (February 2012 to May 2016) were included. INTERVENTION: Adherence was electronically monitored in all participants during a 3-month run-in, followed by a 12-month intervention. Participants assigned to the TAKE-IT intervention could choose to receive text message, e-mail, and/or visual cue dose reminders and met with a coach at 3-month intervals when adherence data from the prior 3 months were reviewed with the participant. "Action-Focused Problem Solving" was used to address adherence barriers selected as important by the participant. Participants assigned to the control group met with coaches at 3-month intervals but received no feedback about adherence data. OUTCOMES: The primary outcomes were electronically measured "taking" adherence (the proportion of prescribed doses of immunosuppressive medications taken) and "timing" adherence (the proportion of doses of immunosuppressive medications taken between 1 hour before and 2 hours after the prescribed time of administration) on each day of observation. Secondary outcomes included the standard deviation of tacrolimus trough concentrations, self-reported adherence, acute rejection, and graft failure. RESULTS: 81 patients were assigned to intervention (median age, 15.5 years; 57% male) and 88 to the control group (median age, 15.8 years; 61% male). Electronic adherence data were available for 64 intervention and 74 control participants. Participants in the intervention group had significantly greater odds of taking prescribed medications (OR, 1.66; 95% CI, 1.15-2.39) and taking medications at or near the prescribed time (OR, 1.74; 95% CI, 1.21-2.50) than controls. LIMITATIONS: Lack of electronic adherence data for some participants may have introduced bias. There was low statistical power for clinical outcomes. CONCLUSIONS: The multicomponent TAKE-IT intervention resulted in significantly better medication adherence than the control condition. Better medication adherence may result in improved graft outcomes, but this will need to be demonstrated in larger studies. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01356277.