Does Celecoxib Prescription for Pain Management Affect Post-tonsillectomy Hemorrhage Requiring Surgery? A Retrospective Observational Cohort Study.

BACKGROUND: Adenotonsillectomy and tonsillectomy (referred to as tonsillectomy hereafter) are common pediatric surgeries. Postoperative complications include hemorrhage requiring surgery (2 to 3% of cases) and pain. Although nonsteroidal anti-inflammatory drugs are commonly administered for postsurgical pain, controversy exists regarding bleeding risk with cyclooxygenase-1 inhibition and associated platelet dysfunction. Preliminary evidence suggests selective cyclooxygenase-2 inhibitors, for example celecoxib, effectively manage pain without adverse events including bleeding. Given the paucity of data for routine celecoxib use after tonsillectomy, this study was designed to investigate the association between postoperative celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery using chart-review data from the Children's Hospital of Eastern Ontario. METHODS: After ethics approval, a retrospective single-center observational cohort study was performed in children less than 18 yr of age undergoing tonsillectomy from January 2007 to December 2017. Cases of adenoidectomy alone were excluded due to low bleed rates. The primary outcome was the proportion of patients with post-tonsillectomy hemorrhage requiring surgery. The association between a celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery was estimated using inverse probability of treatment weighting based on propensity scores and using generalized estimating equations to accommodate clustering by surgeon. RESULTS: An initial patient cohort of 6,468 was identified, and 5,846 children with complete data were included in analyses. Median (interquartile range) age was 6.10 (4.40, 9.00) yr, and 46% were female. In the cohort, 28.1% (n = 1,644) were prescribed celecoxib. Among the 4,996 tonsillectomy patients, 1.7% (n = 86) experienced post-tonsillectomy hemorrhage requiring surgery. The proportion with post-tonsillectomy hemorrhage requiring surgery among patients who had a tonsillectomy and were or were not prescribed celecoxib was 1.94% (30 of 1,548; 95% CI, 1.36 to 2.75) and 1.62% (56 of 3,448; 95% CI, 1.25 to 2.10), respectively. Modeling did not identify an association between celecoxib prescription and increased odds of post-tonsillectomy hemorrhage requiring surgery (odds ratio = 1.4; 95% CI, 0.85 to 2.31; P = 0.20). CONCLUSIONS: Celecoxib does not significantly increase the odds of post-tonsillectomy hemorrhage requiring surgery, after adjusting for covariates. This large pediatric cohort study of celecoxib administered after tonsillectomy provides compelling evidence for safety but requires confirmation with a multisite randomized controlled trial.

Global trends and decision-making in the management of arachnoid cysts.

OBJECTIVE: In pediatric patients, middle cranial fossa (MCF) arachnoid cysts are often discovered incidentally on imaging in asymptomatic patients during workup for other indications. This study aims to describe current management gestalt and threshold for surgical intervention by surveying an international cohort of neurosurgeons. METHODS: A web-based survey was circulated via email list of attendants of the 2019 Canadian Pediatric Neurosurgery Study Group (CPNSG) and International Society of Pediatric Neurosurgery (ISPN) mailing list. The survey consisted of 8 clinical scenarios involving patients with MCF arachnoid cysts. Demographic variables of respondents and their decisions regarding management for each scenario were analyzed using R computing software. RESULTS: A total of 107 respondents were included. Cysts in asymptomatic patients (92%), younger age at diagnosis (81%), and presence of a mild learning delay were predominantly managed non-surgically (80.7 ± 9.4%). Patients with cyst enlargement, headaches, new seizures, or hemorrhage were divided between non-surgical (55.8 ± 3.3%) and surgical (44.2 ± 2.9%) management. Patients with contralateral hemiparesis were treated predominantly surgically (67%). For both Galassi I and II, papilledema was favored as the primary indication for surgical intervention in 54% of patients. Those inclined to surgery (n = 17) were more likely to practice and train outside North America compared to those not pro-surgical (adjusted P = 0.092). CONCLUSION: Incidental MCF arachnoid cysts in asymptomatic patients and younger age of diagnosis are predominantly managed non-surgically. Mild learning delay was not considered an indication to intervene. In contrast, radiological progression, hemorrhagic evolution, or non-focal neurological deficits lead to uncertainty in management, while focal neurological deficits and papilledema with MCF cysts were favored to be intervened surgically. Among the provider level factors, only location of training and practice trended towards a pro-surgery approach.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Assent in Pediatric Critical Care Research: A Cross-Sectional Stakeholder Survey of Canadian Research Ethics Boards, Research Coordinators, Pediatric Critical Care Researchers, and Nurses.

OBJECTIVES: Survey of four stakeholder groups involved in defining and obtaining assent for research in Canadian PICUs to better understand their perspectives and perceived barriers to assent. DESIGN: Cross-sectional survey. SETTING: Fourteen tertiary-care pediatric hospitals in Canada. PARTICIPANTS: Research Ethics Board Chairs, pediatric critical care nurses, research coordinators, and researchers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 193 participants responded. Thirty-seven percent (59/159) thought it was "Never/Almost Never" (59/159, 37%) feasible to obtain assent during the first 48 hours of PICU admission, and 112 of 170 (66%) indicated there are unique barriers to assent at the time of enrollment in PICU studies. Asking children for assent was most frequently rated as Important/Very Important for interviews/focus groups with the child (138/180, 77%), blood sample collection with a needle poke for research (137/178, 77%), and studies involving genetic testing with results communicated to the child/legal guardian (134/180, 74%). In two scenarios where a child and legal guardian disagreed about study participation, most respondents indicated that whether the child should still be enrolled would depend on the patient's age (34-36%), and/or the risk of the study (24-28%). There was a lack of consensus over how the assent process should be operationalized, and when and for how long children should be followed to seek assent for ongoing study participation. Most stakeholders (117/158, 74%) thought that children should have the opportunity to decide if their samples could stay in a biobank once they are old enough to do so. CONCLUSIONS: There was an overall lack of consensus on the feasibility of, and challenges associated with, obtaining assent at the time of study enrollment and on how key aspects of the assent process should be operationalized in the PICU. This highlights the need for guidelines to clarify the assent process in pediatric critical care research.

Skin morbidity in Indigenous children in relation to housing conditions in remote communities in Northwestern Ontario, Canada.

BACKGROUND: Elevated rates of eczema and skin infections in Canadian First Nation (FN) communities are of concern to families, community leaders and healthcare professionals. AIM: To determine whether skin morbidity was associated with indoor environmental quality factors in Canadian FN children living in remote communities. METHODS: We quantified indoor environmental quality (IEQ) in the homes of FN children aged < 4 years of age living in four remote communities in the Sioux Lookout region of Northwestern Ontario, Canada. We conducted a quantitative housing inspection, including measuring surface area of mould (SAM), and monitored air quality for 5 days in each home, including carbon dioxide and relative humidity and quantified endotoxin in settled floor dust. We reviewed the medical charts of participating children for skin conditions and administered a health questionnaire. Relationships between IEQ and skin infections or eczema were evaluated using multivariable regression. RESULTS: In total, 98 children were included in the descriptive analyses, of whom 86 had complete data and were evaluated in multivariate analyses for dermatological outcomes (mean age 1.6 years). Of these 86 children, 55% had made ≥ 1 visits to the local health centre (HC) for skin and soft tissue infections and 25.5% for eczema. Unexpectedly, annualized eczema visits were inversely associated with SAM (RR = 0.14; 95% CI 0.01-0.93). There was a trend suggesting an inverse relationship between endotoxin and HC encounters for eczema and skin and soft tissue infections. CONCLUSION: Skin infections were common in this population of FN children. IEQ did not appear to be associated with skin infections or eczema. Mould exposure appeared to be inversely associated with HC encounters for eczema, possibly related to complex microorganism-host interactions occurring early in life.

Return to the Emergency Department Within 3 Months Following Pediatric Acute Concussion.

OBJECTIVE: To determine the proportion of concussed children returning to the emergency department (ED) for a concussion-related reason within 3 months of initial presentation and to determine which clinical composite score (5P or Post-Concussion Symptom Inventory) best predicts a return visit. SETTING, DESIGN, AND PARTICIPANTS: We combined a secondary analysis of data from the prospectively collected 5P study with a retrospective medical record review of children aged 5 to 18 years who returned to the Children's Hospital of Eastern Ontario (CHEO) ED for a concussion-related reason within 3 months of an acutely diagnosed concussion. Among 770 eligible participants, 632 children (median age: 11.8 [interquartile range (IQR), 9.0-14.5] years; 58.9% male) were included in the study. MAIN MEASURES: The primary outcome was the number of patients who returned to CHEO ED for a concussion-related reason within 3 months of an acute concussion diagnosed at CHEO ED. The secondary outcome was number of patients who returned within 14 days. RESULTS: Forty-seven children (7.4%; 95% confidence interval [CI]: 5.6-9.7) had a concussion-related return to the ED within 3 months, the majority of which occurred in the first 14 days (29/47; 61.7%; 95% CI: 47.4-74.2). History of migraines (21.3% vs 9.7%; P = .03) were more common in those with a return visit. Headache was the most frequently reported symptom (87.2%) on revisit. Females aged 13 to 18 years had the highest return rate (survival rate: 85.8% [95% CI: 79.8-92.3]) compared with males and younger age groups. In multivariable Cox hazards regression modeling, inclusion of risk scores improved prognostication (pseudo R2 = 8%). The difference in pseudo R2 between 5P and Post-Concussion Symptom Inventory is small. CONCLUSION: Most children and adolescents do not return to the ED following an acute concussion. Female youth with medium to high 5P scores at the index concussion visit may benefit from early referral to interdisciplinary specialty concussion care to guide treatment in anticipation of prolonged symptoms. By identifying these risk factors at the initial ED visit, healthcare and patient burden may be reduced.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU. METHODS: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial. RESULTS: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%). CONCLUSIONS: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up. CLINICALTRIALS: gov NCT02452762 Registered 25/05/2015.

Housing conditions and respiratory morbidity in Indigenous children in remote communities in Northwestern Ontario, Canada.

BACKGROUND: Rates of lower respiratory tract infection (LRTI) among First Nations (FN) children living in Canada are elevated. We aimed to quantify indoor environmental quality (IEQ) in the homes of FN children in isolated communities and evaluate any associations with respiratory morbidity. METHODS: We performed a cross-sectional evaluation of 98 FN children (81 with complete data) aged 3 years or younger, living in 4 FN communities in the Sioux Lookout region of Northern Ontario. We performed medical chart reviews and administered questionnaires. We performed a housing inspection, including quantifying the interior surface area of mould (SAM). We monitored air quality for 5 days in each home and quantified the contaminant loading of settled floor dust, including endotoxin. We analyzed associations between IEQ variables and respiratory conditions using univariable and multivariable analyses. RESULTS: Participants had a mean age of 1.6 years and 21% had been admitted to hospital for respiratory infections before age 2 years. Houses were generally crowded (mean occupancy 6.6 [standard deviation 2.6, range 3-17] people per house). Serious housing concerns were frequent, including a lack of functioning controlled ventilation. The mean SAM in the occupied space was 0.2 m2. In multivariable modelling, there was evidence of an association of LRTI with log endotoxin (p = 0.07) and age (p = 0.02), and for upper respiratory tract infections, with SAM (p = 0.07) and age (p = 0.03). Wheeze with colds was associated with log endotoxin (p = 0.03) and age (p = 0.04). INTERPRETATION: We observed poor housing conditions and an association between endotoxin and wheezing in young FN children living in Northern Ontario.

Development of a Multiparametric Renal CT Algorithm for Diagnosis of Clear Cell Renal Cell Carcinoma Among Small (≤ 4 cm) Solid Renal Masses.

BACKGROUND. The MRI clear cell likelihood score predicts the likelihood that a renal mass is clear cell renal cell carcinoma (ccRCC). A CT-based algorithm has not yet been established. OBJECTIVE. The purpose of our study was to develop and evaluate a CT-based algorithm for diagnosing ccRCC among small (≤ 4 cm) solid renal masses. METHODS. This retrospective study included 148 patients (73 men, 75 women; mean age, 58 ± 12 [SD] years) with 148 small (≤ 4 cm) solid (> 25% enhancing tissue) renal masses that underwent renal mass CT (unenhanced, corticomedullary, and nephrographic phases) before resection between January 2016 and December 2019. Two radiologists independently evaluated CT examinations and recorded calcification, mass attenuation in all phases, mass-to-cortex corticomedullary attenuation ratio, and heterogeneity score (score on a 5-point Likert scale, assessed in corticomedullary phase). Features associated with ccRCC were identified by multivariable logistic regression analysis and then used to create a five-tiered CT score for diagnosing ccRCC. RESULTS. The masses comprised 53% (78/148) ccRCC and 47% (70/148) other histologic diagnoses. The mass-to-cortex corticomedullary attenuation ratio was higher for ccRCC than for other diagnoses (reader 1: 0.84 ± 0.68 vs 0.68 ± 0.65, p = .02; reader 2: 0.75 ± 0.29 vs 0.59 ± 0.25, p = .02). The heterogeneity score was higher for ccRCC than other diagnoses (reader 1: 4.0 ± 1.1 vs 1.5 ± 1.6, p < .001; reader 2: 4.4 ± 0.9 vs 3.3 ± 1.5, p < .001). Other features showed no difference. A five-tiered diagnostic algorithm including the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score had interobserver agreement of 0.71 (weighted κ) and achieved an AUC for diagnosing ccRCC of 0.75 (95% CI, 0.68-0.82) for reader 1 and 0.72 (95% CI, 0.66-0.82) for reader 2. A CT score of 4 or greater achieved sensitivity, specificity, and PPV of 71% (95% CI, 59-80%), 79% (95% CI, 67-87%), and 79% (95% CI, 67-87%) for reader 1 and 42% (95% CI, 31-54%), 81% (95% CI, 70-90%), and 72% (95% CI, 56-84%) for reader 2. A CT score of 2 or less had NPV of 85% (95% CI, 69-95%) for reader 1 and 88% (95% CI, 69-97%) for reader 2. CONCLUSION. A five-tiered renal CT algorithm, including the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score, had substantial interobserver agreement, moderate AUC and PPV, and high NPV for diagnosing ccRCC. CLINICAL IMPACT. The CT algorithm, if validated, may represent a useful clinical tool for diagnosing ccRCC.

Balanced Versus Unbalanced Fluid in Critically Ill Children: Systematic Review and Meta-Analysis.

OBJECTIVES: The ideal crystalloid fluid bolus therapy for fluid resuscitation in children remains unclear, but pediatric data are limited. Administration of 0.9% saline has been associated with hyperchloremic metabolic acidosis and acute kidney injury. The primary objective of this systematic review was to compare the effect of balanced versus unbalanced fluid bolus therapy on the mean change in serum bicarbonate or pH within 24 hours in critically ill children. DATA SOURCES: We searched MEDLINE including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, CENTRAL Trials Registry of the Cochrane Collaboration, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. STUDY SELECTION: Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols guidelines, we retrieved all controlled trials and observational cohort studies comparing balanced and unbalanced resuscitative fluids in critically ill children. The primary outcome was the change in serum bicarbonate or blood pH. Secondary outcomes included the prevalence of hyperchloremia, acute kidney injury, renal replacement therapy, and mortality. DATA EXTRACTION: Study screening, inclusion, data extraction, and risk of bias assessments were performed independently by two authors. DATA SYNTHESIS: Among 481 references identified, 13 met inclusion criteria. In the meta-analysis of three randomized controlled trials with a population of 162 patients, we found a greater mean change in serum bicarbonate level (pooled estimate 1.60 mmol/L; 95% CI, 0.04-3.16; p = 0.04) and pH level (pooled mean difference 0.03; 95% CI, 0.00-0.06; p = 0.03) after 4-12 hours of rehydration with balanced versus unbalanced fluids. No differences were found in chloride serum level, acute kidney injury, renal replacement therapy, or mortality. CONCLUSIONS: Our systematic review found some evidence of improvement in blood pH and bicarbonate values in critically ill children after 4-12 hours of fluid bolus therapy with balanced fluid compared with the unbalanced fluid. However, a randomized controlled trial is needed to establish whether these findings have an impact on clinical outcomes before recommendations can be generated.

Consent models in Canadian critical care randomized controlled trials: a scoping review.

PURPOSE: Our primary objective was to describe consent models used in Canadian-led adult and pediatric intensive care unit (ICU/PICU) randomized controlled trials (RCTs). Our secondary objectives were to determine the consent rate of ICU/PICU RCTs that did and did not use an alternate consent model to describe consent procedures. SOURCE: Using scoping review methodology, we searched MEDLINE, Embase, and CENTRAL databases (from 1998 to June 2019) for trials published in English or French. We included Canadian-led RCTs that reported on the effects of an intervention on ICU/PICU patients or their families. Two independent reviewers assessed eligibility, abstracted data, and achieved consensus. PRINCIPAL FINDINGS: We identified 48 RCTs of 17,558 patients. Included RCTs had ethics approval to use prior informed consent (43/48; 90%), deferred consent (13/48; 27%), waived consent (5/48; 10%), and verbal consent (1/48; 2%) models. Fifteen RCTs (15/48; 31%) had ethics approval to use more than one consent model. Twice as many trials used alternate consent between 2010 and 2019 (13/19) than between 2000 and 2009 (6/19). The consent rate for RCTs using only prior informed consent ranged from 54 to 91% (ICU) and 43 to 94% (PICU) and from 78 to 100% (ICU) and 74 to 87% (PICU) in trials using an alternate/hybrid consent model. CONCLUSION: Alternate consent models were used in the minority of Canadian-led ICU/PICU RCTs but have been used more frequently over the last decade. This suggests that Canadian ethics boards and research communities are becoming more accepting of alternate consent models in ICU/PICU trials.

RéSUMé: OBJECTIF: Notre objectif principal était de décrire les modèles de consentement utilisés dans les études randomisées contrôlées (ERC) menées par des chercheurs canadiens dans les unités de soins intensifs adultes et pédiatriques (USI/USIP). Nos objectifs secondaires étaient de déterminer le taux de consentement aux ERC à l'USI et l'USIP qui utilisaient et n'utilisaient pas un autre modèle de consentement pour décrire les processus de consentement. SOURCES: À l'aide d'une méthodologie d'étude de portée, nous avons effectué des recherches dans les bases de données MEDLINE, Embase et CENTRAL (de 1998 à juin 2019) pour en tirer les études publiées en anglais ou en français. Nous avons inclus des ERC dirigées par des chercheurs canadiens qui rapportaient les effets d'une intervention sur les patients à l'USI/USIP ou leurs familles. Deux examinateurs indépendants ont évalué l'admissibilité, résumé les données et atteint un consensus. RéSULTATS PRINCIPAUX: Nous avons identifié 48 ERC portant sur 17 558 patients. Les ERC incluses avaient obtenu l'approbation du comité d'éthique pour l'utilisation de modèles de consentement éclairé préalable (43/48; 90 %), de consentement différé (13/48; 27 %), de renoncement au consentement (5/48; 10 %) et de consentement verbal (1/48; 2 %). Quinze ERC (15/48; 31 %) avaient reçu l'approbation du comité d'éthique pour utiliser plus d'un modèle de consentement. Deux fois plus d'études ont utilisé un autre type de consentement entre 2010 et 2019 (13/19) qu'entre 2000 et 2009 (6/19). Le taux de consentement pour les ERC utilisant uniquement un consentement éclairé préalable variait de 54 à 91 % (USI) et de 43 à 94 % (USIP), contre 78 à 100 % (USI) et 74 à 87 % (USIP) pour les études utilisant un modèle de consentement alternatif/hybride. CONCLUSION: Des modèles de consentement alternatif ont été utilisés dans une minorité des ERC en USI/USIP dirigées par des chercheurs canadiens, mais ils ont été utilisés plus fréquemment au cours de la dernière décennie. Cela donne à penser que les comités d'éthique et les communautés de recherche canadiens acceptent de plus en plus les modèles de consentement alternatifs dans les études réalisées en USI et en USIP.

Genetic and metabolic investigations for individuals with neurodevelopmental disorders: A survey of Canadian geneticists' practices.

Neurodevelopmental disorders (NDDs) are genetically heterogeneous. There are many possible etiological investigations for NDDs, and a lack of clear and current guidelines for such testing. Here we characterize the practices of genetic and metabolic physicians in Canada as it pertains to etiological investigation of patients with NDDs, by means of an online questionnaire. The survey response rate was 30% (n = 46). The most commonly ordered first-line tests for patients with non-syndromic NDDs are chromosomal microarray (98%) and Fragile X testing (85%). The most commonly ordered second-line test for non-syndromic NDDs is a multi-gene panel (78%) or exome sequencing (29%). Biochemical screening is ordered as a first line test by 33% of respondents, second line by 31%, and rarely or never by 36% of respondents. Those respondents with metabolics fellowship training were more likely to order biochemical screening than those without. The number of years of clinical experience generally did not affect the types of tests ordered. For patients with NDDs, test-ordering practice among Canadian clinical geneticists is highly variable, in particular with respect to biochemical screening and use of next-generation sequencing technologies. Evidence-based guidelines should be developed to facilitate best practices in Canada.

Evaluating the relationship between citation set size, team size and screening methods used in systematic reviews: a cross-sectional study.

BACKGROUND: Standard practice for conducting systematic reviews (SRs) is time consuming and involves the study team screening hundreds or thousands of citations. As the volume of medical literature grows, the citation set sizes and corresponding screening efforts increase. While larger team size and alternate screening methods have the potential to reduce workload and decrease SR completion times, it is unknown whether investigators adapt team size or methods in response to citation set sizes. Using a cross-sectional design, we sought to understand how citation set size impacts (1) the total number of authors or individuals contributing to screening and (2) screening methods. METHODS: MEDLINE was searched in April 2019 for SRs on any health topic. A total of 1880 unique publications were identified and sorted into five citation set size categories (after deduplication): < 1,000, 1,001-2,500, 2,501-5,000, 5,001-10,000, and > 10,000. A random sample of 259 SRs were selected (~ 50 per category) for data extraction and analysis. RESULTS: With the exception of the pairwise t test comparing the under 1000 and over 10,000 categories (median 5 vs. 6, p = 0.049) no statistically significant relationship was evident between author number and citation set size. While visual inspection was suggestive, statistical testing did not consistently identify a relationship between citation set size and number of screeners (title-abstract, full text) or data extractors. However, logistic regression identified investigators were significantly more likely to deviate from gold-standard screening methods (i.e. independent duplicate screening) with larger citation sets. For every doubling of citation size, the odds of using gold-standard screening decreased by 15 and 20% at title-abstract and full text review, respectively. Finally, few SRs reported using crowdsourcing (n = 2) or computer-assisted screening (n = 1). CONCLUSIONS: Large citation set sizes present a challenge to SR teams, especially when faced with time-sensitive health policy questions. Our study suggests that with increasing citation set size, authors are less likely to adhere to gold-standard screening methods. It is possible that adjunct screening methods, such as crowdsourcing (large team) and computer-assisted technologies, may provide a viable solution for authors to complete their SRs in a timely manner.

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis.

Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020 Online supplemental material is available for this article.

Obstructive sleep apnea and hypertension in pediatric chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for obstructive sleep apnea (OSA) and hypertension. The objectives of this study were to explore associations between OSA severity using the apnea-hypopnea-index(AHI) and obstructive apnea-hypopnea-index(OAHI) on polysomnography (PSG), OSA symptoms, and measures of hypertension in children with CKD. METHODS: One-night in-laboratory PSGs and 24-h ambulatory blood pressure monitoring (ABPM) were performed on children with CKD stages 2-5 (non-dialysis dependent). Sleep questionnaires, including the modified Epworth Sleepiness Scale (ESS) and the Pediatric Sleep Questionnaire (PSQ), were administered during the sleep study. RESULTS: Nineteen children and adolescents completed a PSG and questionnaires and thirteen completed ABPMs. Mean (standard deviation) age at the time of the sleep study was 14.1 (3.2) years. Eleven (58%) participants had CKD stage two, and eight (42%) had stage 3-4. None of the participants were found to have OSA on PSG. One participant had a positive ESS score (≥ 11) and five participants had positive PSQ scores (≥  eight). Night systolic and diastolic pressures were strongly correlated with the OAHI (r = 0.67 and r = 0.69, respectively, p < 0.05), while the AHI was not correlated with any blood pressure measures. CONCLUSIONS: Our study did not find OSA on PSG in children with predominantly mild to moderate CKD. The OAHI was found to be strongly correlated with nighttime blood pressures. Future prospective studies with a larger sample size are needed to monitor for potential progression of symptoms and findings on PSG in pediatric patients as they evolve across the spectrum of CKD.

Updated Clinical Practice Guideline on Use of Gadolinium-Based Contrast Agents in Kidney Disease Issued by the Canadian Association of Radiologists.

In 2017, the Canadian Association of Radiologists issued a clinical practice guideline (CPG) regarding the use of gadolinium-based contrast agents (GBCAs) in patients with acute kidney injury (AKI), chronic kidney disease (CKD), or on dialysis due to mounting evidence indicating that nephrogenic systemic fibrosis (NSF) occurs with extreme rarity or not at all when using Group II GBCAs or the Group III GBCA gadoxetic acid (compared to first generation Group I linear GBCAs). One of the goals of the work group was to re-evaluate the CPG after 24 months to determine the effect of more liberal use of GBCA on reported cases of NSF in patients with AKI, CKD Stage 4 or 5 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2), or those that are dialysis-dependent. A comprehensive review of the literature was conducted by a subcommittee of the initial CPG panel between the dates of January 1, 2017-December 31, 2018 to identify new unconfounded cases of NSF linked to Group II or Group III GBCAs and an updated CPG developed. To our knowledge, when using a Group II or Group III GBCA between 2017-2018, only a single unconfounded case report of a fibrosing dermopathy has been reported in a patient who received gadobenate dimeglumine with Stage 2 CKD. No other unconfounded cases of NSF have been reported with Group II or III agents in during this timeframe. The subcommittee concluded that the main recommendations from the 2017 CPG should remain unaltered, but agreed that screening for renal disease in the outpatient setting is no longer justifiable, cost-effective or recommended. Patients on hemodialysis (HD) should, however, be identified prior to GBCA administration to arrange timely HD to optimize gadolinium clearance, although there remains no evidence that HD reduces the risk of NSF. When administering Group II or III GBCAs to patients with AKI, on dialysis or with severe CKD, informed consent relating to NSF is also no longer explicitly recommended.

Gadolinium-Based Contrast Agents in Kidney Disease: Comprehensive Review and Clinical Practice Guideline Issued by the Canadian Association of Radiologists.

Use of gadolinium-based contrast agents (GBCAs) in renal impairment is controversial, with physician and patient apprehension in acute kidney injury (AKI), chronic kidney disease (CKD), and dialysis because of concerns regarding nephrogenic systemic fibrosis (NSF). The position that GBCAs are absolutely contraindicated in AKI, CKD stage 4 or 5 (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) and dialysis-dependent patients is outdated, and may limit access to clinically necessary contrast-enhanced MRI examinations. Following a comprehensive review of the literature and reported NSF cases to date, a committee of radiologists and nephrologists developed clinical practice guidelines to assist physicians in making decisions regarding GBCA administrations. In patients with mild-to-moderate CKD (eGFR ≥30 and <60 mL/min/1.73 m2), administration of standard doses of GBCA is safe and no additional precautions are necessary. In patients with AKI, with severe CKD (eGFR <30 mL/min/1.73 m2), or on dialysis, administration of GBCAs should be considered individually and alternative imaging modalities utilized whenever possible. If GBCAs are necessary, newer GBCAs may be administered with patient consent obtained by a physician (or their delegate), citing an exceedingly low risk (much less than 1%) of developing NSF. Standard GBCA dosing should be used; half or quarter dosing is not recommended and repeat injections should be avoided. Dialysis-dependent patients should receive dialysis; however, initiating dialysis or switching from peritoneal to hemodialysis to reduce the risk of NSF is unproven. Use of a macrocyclic ionic instead of macrocyclic nonionic GBCA or macrocyclic instead of newer linear GBCA to further prevent NSF is unproven. Gadopentetate dimeglumine, gadodiamide, and gadoversetamide remain absolutely contraindicated in patients with AKI, with stage 4 or 5 CKD, or on dialysis. The panel agreed that screening for renal disease is important but less critical when using macrocyclic and newer linear GBCAs. Monitoring for and reporting of potential cases of NSF in patients with AKI or CKD who have received GBCAs is recommended.

Hand hygiene knowledge and practices of family caregivers in inpatient pediatrics.

Family caregivers are essential inpatient pediatric care partners, yet their handwashing knowledge and compliance are rarely studied. Through hand hygiene audits and self-administered questionnaires, we observed 9% compliance, significantly lower than self-reported practice. We suggest interventions to improve caregiver handwashing behaviors to decrease infection transmission risk to hospitalized children.

Hybrid immunity after BNT162b2 Covid-19 vaccine administration in children aged 5 to 11 years.

BACKGROUND: The immune response to coronavirus disease 2019 (COVID-19) vaccination is stronger among adults with prior infection (hybrid immunity). It is important to understand if children demonstrate a similar response to better inform vaccination strategies. Our study investigated the humoral response after BNT162b2 COVID-19 vaccine doses in SARS-CoV-2 naïve and recovered children (5-11 years). METHODS: A multi-institutional, longitudinal, prospective cohort study was conducted. Children were enrolled in a case-ascertained antibody surveillance study in Ottawa, Ontario from September/2020-March/2021; at least one household member was severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive on RT-PCR. In November 2021, BNT162b2 COVID-19 vaccine was authorized for children aged 5-11 in Canada. Children enrolled in the surveillance study intending to receive two vaccine doses were invited to participate in this study from November 2021-April 2022. Main exposure was prior SARS-CoV-2 infection, defined by positive RT-PCR or SARS-CoV-2 anti-N IgG antibody presence. Primary outcome was spike IgG antibody levels measured following the first vaccine dose (2-3 weeks) and second vaccine dose (3-4 weeks). RESULTS: Of the 153 eligible children, 75 participants (median age 8.9 IQR (7.4, 10.2) years; 38 (50.7 %) female; 59 (78.7 %) Caucasian) had complete follow-up. Fifty-four (72 %) children had prior SARS-COV-2 infection. Spike IgG antibody levels are significantly higher in SARS-CoV-2 recovered participants after receiving the first dose (p < 0.001) and the second (p = 0.01) compared to infection naïve children. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 recovered children (5-11 years) demonstrated higher antibody levels following first BNT162b2 vaccine dose compared with naïve children. Most reached antibody saturation two to three weeks after the first dose; a second dose didn't change the saturation level. A single vaccine dose in SARS-CoV-2 recovered children may be equivalent or superior to a 2-dose primary series in naïve children. Further research is needed on the durability and quality of a single vaccine dose in this population.