Real-World Biomarkers for Pediatric Takayasu Arteritis.

Childhood-onset Takayasu arteritis (TA) is a rare, heterogeneous disease with limited diagnostic markers. Our objective was to identify and classify all candidates for biomarkers of TA diagnosis in children reported in the literature. A systematic literature review (PRISMA) of MEDLINE, EMBASE, Wiley Cochrane Library, ClinicalTrias.gov, and WHO ICTRP for articles related to TA in the pediatric age group between January 2000 and August 2023 was performed. Data on demographics, clinical features, laboratory measurements, diagnostic imaging, and genetic analysis were extracted. We identified 2026 potential articles, of which 52 studies (81% case series) met inclusion criteria. A total of 1067 TA patients were included with a peak onset between 10 and 15 years. Childhood-onset TA predominantly presented with cardiovascular, constitutional, and neurological symptoms. Laboratory parameters exhibited a low sensitivity and specificity. Imaging predominantly revealed involvement of the abdominal aorta and renal arteries, with magnetic resonance angiography (MRA) being the preferred imaging modality. Our review confirms the heterogeneous presentation of childhood-onset TA, posing significant challenges to recognition and timely diagnosis. Collaborative, multinational efforts are essential to better understand the natural course of childhood-onset TA and to identify accurate biomarkers to enhance diagnosis and disease management, ultimately improving patient outcomes.

Management of Shiga toxin producing Escherichia coli-infected children: A multi-national, multi-specialty survey.

AIM: Research has highlighted the potential role that hydration status may play in predicting outcomes in Shiga toxin-producing Escherichia coli (STEC)-infected children. Because little is known about the management of STEC-infected children in the pre-haemolytic uremic syndrome phase, we compared paediatric emergency medicine and nephrologist-stated management approaches to STEC-infected children. METHODS: Members of the Pediatric Emergency Research Canada (PERC; n = 228), the Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC; n = 221) and the Canadian Association of Pediatric Nephrologists (CAPN; n = 66) were surveyed. Five individualised e-mail requests containing a link to a 42-question web-based survey were sent to eligible participants. RESULTS: Of 496 potentially eligible participants, 276 (56%) submitted complete survey responses. In children with classic features of STEC infection, baseline haemoglobin/haematocrit is obtained by 54% of PERC, 41% of PEM CRC and 83% of CAPN members (P < 0.001), and baseline renal function is obtained by 51% of PERC, 38% of PEM CRC and 83% of CAPN members (P < 0.001). Intravenous fluids are more often recommended by nephrologists (28%) compared with PEM physicians (7%), P < 0.001. In children with known E. coli O157:H7 infection, nephrologists more commonly recommend clinical follow-up (P = 0.003), complete blood counts (P < 0.001) and renal function/electrolyte testing (P < 0.001). Intravenous fluid administration and admission are more commonly recommended by nephrologists (P = 0.03 and P < 0.001, respectively). CONCLUSION: Compared with paediatric nephrologists, paediatric emergency medicine physicians are less likely to perform baseline and follow-up blood tests and to administer intravascular volume expansion in children at risk of, and with confirmed, E. coli O157:H7 infection.

Blood pressure in children with attention deficit/hyperactivity disorder.

OBJECTIVES: Children with attention deficit/hyperactivity disorder (ADHD) are frequently treated with psycho-stimulant agents causing a modest but significant increase in blood pressure and heart rate. The objective of this study was to define blood pressure characteristics in children with ADHD treated with a variety of medications in a community setup. METHODS: Children registered at a large paediatric clinic in Calgary, AB with documented histories of ADHD were randomly contacted. Consenting participants had standardized office BP measurements, ambulatory blood pressure monitoring (ABPM) studies and were asked to complete the sleep disturbance scale for children (SDSC) questionnaire. Findings were compared with data from the Canadian Health Measures Survey (CMHS). RESULTS: Fifty-five children (47 males) aged 7 to 17 years (average 11.6 ± 2.5 years) with an average BMI z-score of -0.37 ± 1.22 completed the study. All children were medicated, the majority (82%), with various types of stimulant agents. Elevated office BP values were more prevalent than in the CMHS; >90th percentile in 5 (9.1%) and >95th percentile in 3 (5.5%). ABPM confirmed 'white coat hypertension' in 3 (5.5%), masked hypertension in 2 (3.6%) and nondipping in 28 (51%). The SDSC score suggested that 43 (78%) children had disturbed sleep. Logistic regression modelling indicated that nondipping correlated with disturbed sleep. CONCLUSION: The 'white coat' phenomenon may be responsible for increased prevalence of elevated rest/office BP values in children with ADHD. Prevalent sleep 'non-dipping' in this population is associated with sleep disturbances but clinical significance of this finding requires further investigation.

A longitudinal retrospective analysis of left ventricular mass in a cohort of pediatric kidney transplant recipients.

Childhood end-stage kidney disease is associated with increased risk for early adulthood cardiovascular (CV) morbidity and mortality. Increased LVM is an early indicator of CV disease. Previous studies have suggested that LVM decreases after kidney transplantation; however, trends have been inconsistent. A single center retrospective longitudinal cohort analysis of LVM, documented annually, starting before kidney transplantation for up to 10 yr after transplantation was performed. BP documented by annual 24-h ambulatory monitoring studies, and BMI values were also reviewed. Twenty-seven children followed for a mean period of 5.3 yr were included. Depending on definition of LVH, its prevalence pretransplant and in the first years post-transplant was up to 33% dropping to 0-25% thereafter. Individual longitudinal LVM z-score trends were highly variable but generally trended toward the mean immediately after transplant and toward negative values in the following years. BP was stable during the follow-up period while mean annual BMI increased in the first-year post-transplant but declined thereafter. In a cohort of pediatric renal transplant recipients, prevalence of LVH decreased after transplant; however, individual longitudinal LVM trends were highly variable among patients. Prospective studies are needed to correlate individual LVM trends with outcomes.

Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review.

BACKGROUND: In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies. METHODS: A systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria. Studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cohort, case-control and cross-sectional studies and the Risk of Bias Assessment tool for Non-randomised Studies, or the Cochrane Risk of Bias tool 2.0 for randomised controlled trials. A descriptive synthesis of the data for non-invasive (blood-based or urinary) biomarkers of AAV-related disease activity and organ damage was performed. RESULTS: Twenty-two high quality studies were included. These articles reported the value of blood-based and urinary biomarkers including anti-neutrophil cytoplasmic antibodies, immune cells, complement factors, gene expression profiles, cytokines, chemokines and other proteins in the assessment of disease activity and/or organ damage in patients with AAV. Many of these biomarkers involve the alternative complement pathway, neutrophil activation and macrophage activation. CONCLUSION: This is the first contemporary systematic review synthesising the value of non-invasive biomarkers of AAV-related disease activity and organ damage. The incorporation of individual markers in combined biomarker profiles might enhance clinical decision-making. Many unmet needs were identified; few studies involve oeosinophilic granulomatosis with polyangiitis and patients with childhood-onset AAV. Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision health to systemic vasculitis.

Substantial practice variation exists in the management of childhood nephrotic syndrome.

BACKGROUND: Practice variation is common for nephrotic syndrome (NS) treatment. METHODS: A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS. RESULTS: Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices. CONCLUSIONS: There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.

Comparison of a Rapid Multiplex Gastrointestinal Panel with Standard Laboratory Testing in the Management of Children with Hematochezia in a Pediatric Emergency Department: Randomized Controlled Trial.

Advances in diagnostic microbiology allow for the rapid identification of a broad range of enteropathogens; such knowledge can inform care and reduce testing. We conducted a randomized, unblinded trial in a tertiary-care pediatric emergency department. Participants had stool (and rectal swabs if stool was not immediately available) tested using routine microbiologic approaches or by use of a device (BioFire FilmArray gastrointestinal panel), which identifies 22 pathogens with a 1-h instrument turnaround time. Participants were 6 months to <18.0 years and had acute bloody diarrhea. Primary outcome was performance of blood tests within 72 h. From 15 June 2018 through 7 May 2022, 60 children were randomized. Patients in the BioFire FilmArray arm had a reduced time to test result (median 3.0 h with interquartile range [IQR] of 3.0 to 4.0 h, versus 42.0 h (IQR 23.5 to 47.3 h); difference of -38.0 h, 95% confidence interval [CI] of -41.0 to -22.0 h). Sixty-five percent (20/31) of participants in the BioFire FilmArray group had a pathogen detected-most frequently enteropathogenic Escherichia coli (19%), Campylobacter (16%), and Salmonella (13%). Blood tests were performed in 52% of children in the BioFire FilmArray group and 62% in the standard-of-care group (difference of -10.5%, 95% CI of -35.4% to 14.5%). There were no between-group differences in the proportions of children administered intravenous fluids, antibiotics, hospitalized, or who had diagnostic imaging performed. Testing with the BioFire FilmArray reduced the time to result availability by 38 h. Although statistical significance was limited by study power, BioFire FilmArray use was not associated with clinically meaningful reductions in health care utilization or improved outcomes. IMPORTANCE Advances in diagnostic microbiology now allow for the faster and more accurate detection of an increasing number of pathogens. We determined, however, that in children with acute bloody diarrhea, these advances did not necessarily translate into improved clinical outcomes. While a greater number of pathogens was identified using a rapid turnaround multiplex stool diagnostic panel, with a reduction in the time to stool test result of over 1.5 days, this did not alter the practice of pediatric emergency medicine physicians, who continued to perform blood tests on a large proportion of children. While our conclusions may be limited by the relatively small sample size, targeted approaches that educate clinicians on the implementation of such technology into clinical care will be needed to optimize usage and maximize benefits.

Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. coli Infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial).

BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis. METHODS: We will conduct a pragmatic, embedded, cluster-randomized, crossover trial in 26 pediatric institutions to determine if hyperhydration, compared to conservative fluid management, improves outcomes in 1040 children with high-risk STEC infections. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite measure that includes death, initiation of new renal replacement therapy, or persistent kidney dysfunction. Secondary outcomes include life-threatening, extrarenal complications, and development of HUS. Pathway eligible children will be treated per institutional allocation to each pathway. In the hyperhydration pathway, all eligible children are hospitalized and administered 200% maintenance balanced crystalloid fluids up to targets of 10% weight gain and 20% reduction in hematocrit. Sites in the conservative fluid management pathway manage children as in- or outpatients, based on clinician preference, with the pathway focused on close laboratory monitoring, and maintenance of euvolemia. Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome. With 26 clusters enrolling a mean of 40 patients each with an intraclass correlation coefficient of 0.11, we will have 90% power to detect a 5% absolute risk reduction. DISCUSSION: HUS is a devastating illness with no treatment options. This pragmatic study will determine if hyperhydration can reduce morbidity associated with HUS in children with high-risk STEC infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05219110 . Registered on February 1, 2022.

[Not Available]. / Les recommandations de prise en charge des complications métaboliques associées aux antipsychotiques de deuxième génération chez les enfants et les adolescents.

BACKGROUND: Second-generation antipsychotics are commonly associated with metabolic complications. These medications are being used more frequently for the treatment of mental health disorders in children, which has stimulated the need for creating formal guidelines on monitoring their safety and effectiveness. Previous guidelines have been developed for monitoring metabolic and neurological complications. To assist practitioners who perform these monitoring procedures, a complementary set of treatment recommendations have been created for situations in which abnormal measurements or results are encountered. OBJECTIVE: To create evidence-based recommendations to assist in managing metabolic complications in children being treated with second-generation antipsychotics. METHODS: A systematic review of the literature on metabolic complications of second-generation antipsychotic medications in children was conducted. Members of the consensus group evaluated the information gathered from the systematic review of the literature and used a nominal group process to reach a consensus on treatment recommendations. Wherever possible, references were made to existing guidelines on the evaluation and treatment of metabolic abnormalities in children. RESULTS: Evidence-based recommendations are presented to assist in managing metabolic complications including weight gain; increased waist circumference; elevation in prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function tests; and abnormal thyroid studies. CONCLUSION: The use of second-generation antipsychotics requires proper monitoring procedures. The present treatment guideline provides guidance to clinicians on the clinical management of metabolic complications if they occur.

Outcomes of kidney transplantation in children with nephronophthisis: an analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry.

NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub-analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five-yr follow-up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non-NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.

Iatrogenic Dysnatremias in Children with Acute Gastroenteritis in High-Income Countries: A Systematic Review.

BACKGROUND: Acute gastroenteritis (AGE) causing dehydration with or without dysnatremias is a common childhood health challenge. While it is accepted that oral rehydration therapy is preferred, clinical factors or parent and healthcare provider preferences may lead to intravenous rehydration (IVR). Isotonic solutions are increasingly recommended in most scenarios requiring IVR. Nevertheless, children with AGE, having ongoing losses of water and electrolytes, represent a unique population. OBJECTIVES: To evaluate the association between acquired dysnatremias and IVR in children with AGE. METHODS: A systematic search of MEDLINE database was conducted through September 14, 2016. Observational studies and clinical trials conducted in high-income countries were included. The Grades of Recommendation, Assessment, Development, and Evaluation approach was used to evaluate the overall quality of evidence for each outcome. RESULTS: 603 papers were identified of which 6 were included (3 randomized controlled trials and 3 observational studies). Pooling of patient data was not possible due to significantly different interventions or exposures. Single studies results demonstrated that within 24 h, administration of isotonic saline was not associated with a significant decline in serum sodium while hypotonic solutions (0.2-0.45% saline) were associated, in one study, with mean serum sodium declines from 1.3 mEq/L (139.2, SD 2.9-137.9, SD 2.5) in 133 young infants (aged 1-28 months), to 5.7 (SD 3.1) mEq/L in a subgroup of 18 older children (age mean 5.8, SD 2.7 years). Both isotonic and hypotonic saline were shown to be associated with improvement of baseline hyponatremia in different studies. Baseline hypernatremia was corrected within 4-24 h in 81/83 (99.6%) children using hypotonic saline IVR. CONCLUSION: There is a paucity of publications assessing the risk for acquired dysnatremias associated with IVR in children with AGE. Current high-quality evidence suggests that, short-term use of isotonic solutions is safe and effective in most children with AGE; hypotonic solutions may also be appropriate in some subpopulations, however, the quality of available evidence is low to very low. Further research investigating outcomes associated with IVR use beyond 24 h focusing on specific age groups is required.

Glomerular Filtration Rate Trends During Follow-up in Children With Steroid-Sensitive Nephrotic Syndrome.

BACKGROUND: Overall prognosis of children with steroid-sensitive nephrotic syndrome (SSNS) is regarded as generally favorable. However, only a few recent studies have evaluated changes in kidney function and blood pressure over time in children with SSNS. OBJECTIVES: We describe clinical features of SSNS patients and characterize changes in calculated estimated glomerular filtration rate (eGFR) and use of antihypertensive medications during follow-up. DESIGN: This is a retrospective cohort study. SETTING: This study was conducted in a Canadian pediatric nephrology center. PATIENTS: This study included patients aged 1 to 18 years with SSNS. MEASUREMENTS: eGFR was calculated from recorded serum creatinine and height measurements using the modified Schwartz equation. METHODS: eGFR was calculated at yearly intervals, and the trend of eGFR was assessed using linear mixed effects model. Patients were also evaluated for use of antihypertensive medications during follow-up. RESULTS: Seventy-eight patients-median age, 3.2 years (interquartile range [IQR], 2.65) and median follow-up of 4.37 (IQR, 5.6)-were evaluated. Sixty-three (80.8%) had at least 1 relapse. Twenty-two (28.2%) and 20 (25.6%) were steroid dependent and frequently relapsing, respectively. Forty-three patients (55.1%) received at least 1 steroid-sparing agent, and of these, 18 (41.8%) received a calcineurin inhibitor. One patient had eGFR ≤90 mL/min/1.73 m2 during observation. eGFR remained unchanged over the follow-up period in this cohort of patients. Four patients (5.1%) were on antihypertensive medications at the end of follow-up. LIMITATIONS: Patients who had frequent relapses had more measurements available for serum creatinine and height, creating a sampling bias. The number of eGFR measurements was overall small, making it difficult to ascertain eGFR trend. CONCLUSION: eGFR remained unchanged over time in this cohort, and a small proportion of patients required antihypertensive therapy at the end of follow-up. Our study highlights the needs for carefully constructed long-term observational studies of children with nephrotic syndrome.

MISE EN CONTEXTE: De manière générale, on considère le pronostic du syndrome néphrotique stéroïdosensible chez l'enfant comme favorable. Toutefois, seules quelques études récentes ont mesuré les changements dans la fonction rénale et la pression sanguine au fil du temps chez les enfants atteints du syndrome néphrotique stéroïdosensible. OBJECTIFS DE L'ÉTUDE: Décrire les manifestations cliniques du syndrome néphrotique stéroïdosensible, de même que caractériser les changements dans le débit de filtration glomérulaire estimé (DFGe) et la prise de médicaments contre l'hypertension au cours de la période de suivi. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte prospective qui s'est tenue dans un centre de néphrologie pédiatrique canadien. PATIENTS: Des enfants âgés de 1 à 18 ans atteints du syndrome néphrotique stéroïdosensible. MESURES: On a utilisé l'équation de Schwartz modifiée pour calculer le DFGe des participants à partir de leur taille et de mesures de créatinine sérique déjà enregistrées. MÉTHODOLOGIE: On a procédé au calcul du DFGe chaque année et on en a évalué la tendance à l'aide d'un modèle linéaire à effets mixtes. La prise de médicaments contre l'hypertension a également été évaluée au cours de la période du suivi. RÉSULTATS: Un total de 78 patients, dont l'âge médian se situait à 3,2 ans (écart interquartile = 2,65 ans), ont été évalués sur une période de 4,37 ans (EI = 5,6 ans) en moyenne, desquels 80,8% (63 patients) ont fait au moins une rechute. Des patients évalués, 28,2% (n = 22) étaient dépendants des stéroïdes et 25,6% (n = 20) faisaient des rechutes fréquentes. Quarante-trois patients (55,1%) ont reçu au moins un agent de préservation de stéroïdes, dont dix-huit (41,8%) ont reçu un inhibiteur de la calcineurine. Un seul patient a présenté une valeur de DFGe de plus de 90 ml/min/1,73 m2 au cours de la période d'observation. Le DFGe est demeuré inchangé tout au long de la période de suivi pour cette cohorte. À la fin de la période de suivi, quatre patients (5,1%) prenaient des médicaments contre l'hypertension. LIMITES DE L'ÉTUDE: Un biais d'échantillonnage est introduit par le fait qu'un nombre plus élevé de mesures de taille et de DFGe étaient disponibles pour les patients ayant fait plusieurs rechutes. Par ailleurs, l'établissement de tendances en regard des valeurs de DFGe s'avère difficile étant donné le nombre relativement faible de mesures disponibles. CONCLUSIONS: Les valeurs de DFGe sont demeurées inchangées tout au long de la période de suivi pour cette cohorte de patients, et seulement quatre d'entre eux ont dû être traités pour l'hypertension à la fin du suivi. Cette étude met en lumière le besoin pour la tenue d'études observationnelles à long terme et judicieusement élaborées chez les enfants atteints du syndrome néphrotique stéroïdosensible.

Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin-Producing Escherichia coli: A Systematic Review and Meta-analysis.

Importance: The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear. Objective: To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. Study Selection: Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. Data Extraction and Synthesis: Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. Main Outcomes and Measures: Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). Results: Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]). Conclusions and Relevance: Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

Management of hemolytic-uremic syndrome in children.

Acute renal failure associated with a fulminant, life-threatening systemic disease is rare in previously healthy young children; however, when it occurs, the most common cause is hemolytic-uremic syndrome (HUS). In most cases (90%), this abrupt and devastating illness is a result of ingestion of food or drink contaminated with pathogens that produce very potent toxins. Currently, there are no proven treatment options that can directly inactivate the toxin or effectively interfere with the cascade of destructive events triggered by the toxin once it gains access to the bloodstream and binds its receptor. However, HUS is self-limited, and effective supportive management during the acute phase is proven to be a life saver for children affected by HUS. A minority of childhood HUS cases, approximately 5%, are caused by various genetic mutations causing uncontrolled activation of the complement system. These children, who used to have a poor prognosis leading to end-stage renal disease, now have access to exciting new treatment options that can preserve kidney function and avoid disease recurrences. This review provides a summary of the current knowledge on the epidemiology, pathophysiology, and clinical presentation of childhood HUS, focusing on a practical approach to best management measures.

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: overview of design and methods.

BACKGROUND: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. OBJECTIVES: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. DESIGN: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). SETTING: National study, comprised of all 13 Canadian pediatric nephrology clinics. PATIENTS: 400 patients under 18 years of age to be recruited over 2.5 years. MEASUREMENTS: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. METHODS: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. LIMITATIONS: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. CONCLUSIONS: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres.

CONTEXTE: Le syndrome néphrotique est une néphropathie fréquente chez l'enfant, qui cause une morbidité considérable en raison de la récurrence d'épisodes de protéinurie importante. La gestion du syndrome néphrotique de l'enfant varie énormément d'un médecin et d'un centre de soins à l'autre. OBJECTIFS: L'objectif principal de cette étude est de déterminer les caractéristiques associées à l'exposition et la durée du traitement aux stéroïdes, liées au centre, au médecin et au patient. En deuxième lieu, nous déterminerons la corrélation entre la dose et la durée du traitement aux stéroïdes, puis la durée avant la première rechute. À cette étude s'ajoutera une étude qualitative avec des groupes de discussion composés de professionnels de la santé qui viendra enrichir les résultats quantitatifs en favorisant une meilleure compréhension des attitudes, des croyances et des facteurs contextuels locaux qui entraînent des variations dans les soins. TYPE D'ÉTUDE: Une étude méthodologique mixte; étude d'observation de cohorte prospective (composante quantitative), combinée avec des groupes de discussion semi-structurés composés de professionnels de la santé (composante qualitative). CONTEXTE/ÉCHANTILLON: Étude nationale, constituée des 13 cliniques canadiennes de néphrologie pédiatrique. PARTICIPANTS: 400 patients âgés de moins de 18 ans, à recruter sur une période de 2,5 années. MESURES: Suivi des doses de stéroïdes pour chacun des épisodes (première présentation, première rechute et suivantes), tout au long de l'étude. Catalogage des caractéristiques liées au médecin ou au centre, et attestation des raisons justifiant les préférences de traitement au cours des séances avec les groupes de discussion. MÉTHODES: Tous les patients suivis de manière prospective dans le cadre de l'étude, dont les données constituent un registre prospectif. Un groupe de discussion à chaque endroit, afin d'enrichir la compréhension des variations dans les soins. LIMITES DE L'ÉTUDE: La contamination des protocoles de traitement entre les médecins peut se produire en raison de la tenue simultanée de groupes de discussions. CONCLUSIONS: Les résultats quantitatifs et qualitatifs seront intégrés à la fin de l'étude et permettront de mettre en place des stratégies de développement et de mise en œuvre de protocoles normalisés et fondés sur des données probantes.

Ambulatory Blood Pressure Monitoring in a Cohort of Children Referred with Suspected Hypertension: Characteristics of Children with and without Attention Deficit Hyperactivity Disorder.

Childhood hypertension's increasing prevalence has generally been linked to the obesity epidemic. We observed that a significant proportion of children referred to our pediatric center with documented office hypertension are nonobese and have a history of attention deficit hyperactivity disorder (ADHD). To define the extent of this anecdotal observation, we performed a retrospective analysis of ambulatory blood pressure monitoring (ABPM) tests which in our center are routinely performed in newly referred children suspected of hypertension. Twenty-one percent (48 of 227 new referrals) had a history of ADHD, and 81% of them were treated with psychostimulant medications at the time of their ABPM test. Children in this group had a significantly lower average BMI z-score compared with the rest of the children (0.18 versus 0.75) and were significantly more likely to have abnormally elevated wake systolic loads on ABPM (38% versus 4%). The overall proportion of children with any abnormality on ABPM was comparable in both groups (46% versus 40%). Conclusion. A significant proportion of children suspected of hypertension have ADHD which may be related to higher wake systolic BP values. The prevalence of hypertension among children with ADHD will have to be determined in prospective studies.

Management recommendations for metabolic complications associated with second-generation antipsychotic use in children and youth.

BACKGROUND: Second-generation antipsychotics are commonly associated with metabolic complications. These medications are being used more frequently for the treatment of mental health disorders in children, which has stimulated the need for creating formal guidelines on monitoring their safety and effectiveness. Previous guidelines have been developed for monitoring metabolic and neurological complications. To assist practitioners who perform these monitoring procedures, a complementary set of treatment recommendations have been created for situations in which abnormal measurements or results are encountered. OBJECTIVE: To create evidence-based recommendations to assist in managing metabolic complications in children being treated with second-generation antipsychotics. METHODS: A systematic review of the literature on metabolic complications of second-generation antipsychotic medications in children was conducted. Members of the consensus group evaluated the information gathered from the systematic review of the literature and used a nominal group process to reach a consensus on treatment recommendations. Wherever possible, references were made to existing guidelines on the evaluation and treatment of metabolic abnormalities in children. RESULTS: Evidence-based recommendations are presented to assist in managing metabolic complications including weight gain; increased waist circumference; elevation in prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function tests and abnormal thyroid studies. CONCLUSION: The use of second-generation antipsychotics requires proper monitoring procedures. The present treatment guideline provides guidance to clinicians on the clinical management of metabolic complications if they occur.

Management recommendations for metabolic complications associated with second generation antipsychotic use in children and youth.

BACKGROUND: Second generation antipsychotics (SGAs) are commonly associated with metabolic complications. These medications are being used more frequently for the treatment of mental health disorders in children, which has stimulated the need for creating formal guidelines on monitoring their safety and effectiveness. Previous guidelines have been developed for monitoring for metabolic and neurological complications. In order to assist practitioners who perform these monitoring procedures, we have created a complementary set of treatment recommendations if abnormal measurements or results are encountered. OBJECTIVE: To create evidence-based recommendations to assist in managing metabolic complications in children being treated with second generation antipsychotics. METHODS: A systematic review of the literature on metabolic complications of second generation antipsychotic medications in children was conducted. Members of the consensus group evaluated the information gathered from the systematic review of the literature and used a nominal group process to come to consensus on treatment recommendations. Wherever possible, references were made to existing guidelines on the evaluation and treatment of metabolic abnormalities in children. RESULTS: Evidence-based recommendations are presented to assist in managing metabolic complications, including weight gain, increased waist circumference, elevation in cholesterol, triglycerides and glucose, liver function tests, abnormal thyroid studies, and elevation in prolactin. CONCLUSION: The use of SGAs requires proper monitoring procedures. This treatment guideline provides guidance to clinicians on clinical management of metabolic complications if they occur.

Diarrhea-associated hemolytic uremic syndrome in southern Alberta: A long-term single-centre experience.

BACKGROUND: Reports of long-term incidence trends of endemic diarrhea-associated hemolytic uremic syndrome (D+HUS) are few and inconclusive. OBJECTIVE: To define and analyze the incidence and outcomes of D+HUS over a period of approximately 25 years in a highly endemic region of southern Alberta. METHODS: Annual incidence rates of confirmed cases of D+HUS were compared between two 12-year periods (1980 to 1992 and 1994 to 2006). Differences in therapies used, and some short- and long-term complications observed were also compared between the two periods. RESULTS: The absolute yearly number of D+HUS cases was highly variable. The comparison between the 1980 to 1992, and 1994 to 2006 periods demonstrated a modest 8.8% decrease in the total number of cases. The population-based average annual incidence rates were not significantly different between the two time periods (3.33 cases versus 2.58 cases per 100,000 population per year, respectively; P=0.30). Only supportive care measures were used in the latter period. A mortality rate of lower than 1% in the latter period was one of the lowest ever reported for a large cohort of D+HUS patients. CONCLUSION: The present long-term retrospective study of D+HUS in a highly endemic area documented a modest decrease in the absolute number of cases but no difference in the average annual incidence over an extended period of time.