Showing papers by "Montreal Children's Hospital published in 2020"

Diagnostic Testing for Severe Acute Respiratory Syndrome-Related Coronavirus 2: A Narrative Review.

Abstract: Diagnostic testing to identify persons infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction-based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS-CoV-2 infection. Here, the authors review the current array of tests for SARS-CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.

Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project.

Abstract: Importance There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. Objective To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. Process Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. Evidence Synthesis Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. Recommendations Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH Conclusions and Relevance This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus 2 : A Narrative Review.

Abstract: Accurate serologic tests to detect host antibodies to SARS-CoV-2 will be critical for the public health response to the COVID-19 pandemic. This article discusses key use cases for SARS-CoV-2 antibo...

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy

Abstract: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients’ needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. This innovative CPG methodology was guided by patients’ perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Trajectories of Growth Associated With Long-Term Stimulant Medication in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder

Abstract: Objective To estimate long-term stimulant treatment associations on standardized height, weight, and body mass index trajectories from childhood to adulthood in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (MTA). Method Of 579 children with DSM-IV ADHD−combined type at baseline (aged 7.0–9.9 years) and 289 classmates (local normative comparison group [LNCG]), 568 and 258 respectively, were assessed 8 times over 16 years (final mean age = 24.7). Parent interview data established subgroups with self-selected Consistent (n = 53, 9%), Inconsistent (n = 374, 66%), and Negligible (n = 141, 25%) stimulant medication use, as well as patients starting stimulants prior to MTA entry (n = 211, 39%). Height and weight growth trajectories were calculated for each subgroup. Results Height z scores trajectories differed among subgroups (F = 2.22, p Conclusion Compared with those negligibly medicated and the LNCG, 16 years of consistent stimulant treatment of children with ADHD in the MTA was associated with changes in height trajectory, a reduction in adult height, and an increase in weight and body mass index. Clinical trial registration information Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); https://clinicaltrials.gov/ ; NCT00000388 .

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial.

Abstract: Importance Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia–free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks’ postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures The primary outcome was bronchopulmonary dysplasia–free survival in infants at 36 weeks’ postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, –5.0% [95% CI, –11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04],P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, –3.9% [95% CI, –6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13],P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73],P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia–free survival at 36 weeks’ postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration ClinicalTrials.gov Identifier:NCT02371460

Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing.

Abstract: Characterizing the developmental trajectory of oligodendrocyte progenitor cells (OPC) is of great interest given the importance of these cells in the remyelination process. However, studies of human OPC development remain limited by the availability of whole cell samples and material that encompasses a wide age range, including time of peak myelination. In this study, we apply single cell RNA sequencing to viable whole cells across the age span and link transcriptomic signatures of oligodendrocyte-lineage cells with stage-specific functional properties. Cells were isolated from surgical tissue samples of second-trimester fetal, 2-year-old pediatric, 13-year-old adolescent, and adult donors by mechanical and enzymatic digestion, followed by percoll gradient centrifugation. Gene expression was analyzed using droplet-based RNA sequencing (10X Chromium). Louvain clustering analysis identified three distinct cellular subpopulations based on 5,613 genes, comprised of an early OPC (e-OPC) group, a late OPC group (l-OPC), and a mature OL (MOL) group. Gene ontology terms enriched for e-OPCs included cell cycle and development, for l-OPCs included extracellular matrix and cell adhesion, and for MOLs included myelination and cytoskeleton. The e-OPCs were mostly confined to the premyelinating fetal group, and the l-OPCs were most highly represented in the pediatric age group, corresponding to the peak age of myelination. Cells expressing a signature characteristic of l-OPCs were identified in the adult brain in situ using RNAScope. These findings highlight the transcriptomic variability in OL-lineage cells before, during, and after peak myelination and contribute to identifying novel pathways required to achieve remyelination.

Letter: The Risk of COVID-19 Infection During Neurosurgical Procedures: A Review of Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) Modes of Transmission and Proposed Neurosurgery-Specific Measures for Mitigation.

Abstract: To the Editor: The novel coronavirus disease of 2019 (COVID-19) is a disease caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). It was first reported inDecember 2019 as a series of cases of pneumonia with an unknown etiology clustered around a food market in Wuhan City, China.1 The infection spread quickly and was declared a pandemic by the World Health Organization (WHO) on March 11, 2019.2 By March 30, more than 782 365 confirmed cases were reported and a third of the world population were living in confinement to try to contain the virus.3 While the disease itself is often mild, approximately 11% of cases require acute medical care, and this cohort quickly overwhelmed healthcare systems around the world.4 In anticipation of such a demand, hospitals in many countries quickly stopped all nonurgent visits, procedures, and surgeries, freeing up beds, equipment, and workforce.5 While neurosurgeons are not on the frontline of COVID-19 management and treatment, they commonly care for critically ill patients who will continue to present with subarachnoid hemorrhages, subdural hematomas, brain tumors, traumatic brain injuries, spinal cord injuries, and compressive myelopathies while the pandemic occurs. While public health measures such as quarantine and social distancing are proving effective at slowing the spread,6,7 surgeons remain in direct contact with their patients throughout their operations. Protecting the surgical team from contracting COVID-19 is of utmost importance as they are both a potential vector for patient contamination and a scarce resource that cannot be easily replaced. The goal of this paper is to briefly review how SARS-CoV-2 is transmitted and propose measures that could be implemented to minimize the risk of contaminating the operating room (OR) personnel during the most common neurosurgical procedures. Methods and ethical considerations are discussed in the Supplemental Digital Content.

The Roles of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography in the Evaluation and Treatment of Chronic Pancreatitis in Children: A Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee.

Abstract: Introduction Pediatric chronic pancreatitis is increasingly diagnosed. Endoscopic methods [endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP)] are useful tools to diagnose and manage chronic pancreatitis. Pediatric knowledge and use of these modalities is limited and warrants dissemination. Methods Literature review of publications relating to use of ERCP and EUS for diagnosis and/or management of chronic pancreatitis with special attention to studies involving 0--18 years old subjects was conducted with summaries generated. Recommendations were developed and voted upon by authors. Results Both EUS and ERCP can be used even in small children to assist in diagnosis of chronic pancreatitis in cases where cross-sectional imaging is not sufficient to diagnose or characterize the disease. Children under 15 kg for EUS and 10 kg for ERCP can be technically challenging. These procedures should be done optimally by appropriately trained endoscopists and adult gastroenterology providers with appropriate experience treating children. EUS and ERCP-related risks both include perforation, bleeding and pancreatitis. EUS is the preferred diagnostic modality over ERCP because of lower complication rates overall. Both modalities can be used for management of chronic pancreatitis -related fluid collections. ERCP has successfully been used to manage pancreatic duct stones. Conclusion EUS and ERCP can be safely used to diagnose chronic pancreatitis in pediatric patients and assist in management of chronic pancreatitis-related complications. Procedure-related risks are similar to those seen in adults, with EUS having a safer risk profile overall. The recent increase in pediatric-trained specialists will improve access of these modalities for children.

Genome sequencing in persistently unsolved white matter disorders

Abstract: Genetic white matter disorders have heterogeneous etiologies and overlapping clinical presentations. We performed a study of the diagnostic efficacy of genome sequencing in 41 unsolved cases with prior exome sequencing, resolving an additional 14 from an historical cohort (n = 191). Reanalysis in the context of novel disease-associated genes and improved variant curation and annotation resolved 64% of cases. The remaining diagnoses were directly attributable to genome sequencing, including cases with small and large copy number variants (CNVs) and variants in deep intronic and technically difficult regions. Genome sequencing, in combination with other methodologies, achieved a diagnostic yield of 85% in this retrospective cohort.

Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of Allergy and Clinical Immunology.

Abstract: The vast majority of individuals labelled as allergic are not deemed truly allergic upon appropriate assessment by an allergist. A label of beta-lactam allergy carries important risks for individual and public health. This article provides an overview of beta-lactam allergy, implications of erroneous beta-lactam allergy labels and the impact that can be provided by structured allergy assessment. We provide recommendations on how to stratify risk of beta-lactam allergy, beta lactam challenge protocols as well as management of patients at high risk of beta-lactam allergy.

Assessment of Extubation Readiness Using Spontaneous Breathing Trials in Extremely Preterm Neonates.

Abstract: Importance Spontaneous breathing trials (SBTs) are used to determine extubation readiness in extremely preterm neonates (gestational age ≤28 weeks), but these trials rely on empirical combinations of clinical events during endotracheal continuous positive airway pressure (ET-CPAP). Objectives To describe clinical events during ET-CPAP and to assess accuracy of comprehensive clinical event combinations in predicting successful extubation compared with clinical judgment alone. Design, Setting, and Participants This multicenter diagnostic study used data from 259 neonates seen at 5 neonatal intensive care units from the prospective Automated Prediction of Extubation Readiness (APEX) study from September 1, 2013, through August 31, 2018. Neonates with birth weight less than 1250 g who required mechanical ventilation were eligible. Neonates deemed to be ready for extubation and who underwent ET-CPAP before extubation were included. Interventions In the APEX study, cardiorespiratory signals were recorded during 5-minute ET-CPAP, and signs of clinical instability were monitored. Main Outcomes and Measures Four clinical events were documented during ET-CPAP: apnea requiring stimulation, presence and cumulative durations of bradycardia and desaturation, and increased supplemental oxygen. Clinical event occurrence was assessed and compared between extubation pass and fail (defined as reintubation within 7 days). An automated algorithm was developed to generate SBT definitions using all clinical event combinations and to compute diagnostic accuracies of an SBT in predicting extubation success. Results Of 259 neonates (139 [54%] male) with a median gestational age of 26.1 weeks (interquartile range [IQR], 24.9-27.4 weeks) and median birth weight of 830 g (IQR, 690-1019 g), 147 (57%) had at least 1 clinical event during ET-CPAP. Apneas occurred in 10% (26 of 259) of neonates, bradycardias in 19% (48), desaturations in 53% (138), and increased oxygen needs in 41% (107). Neonates with successful extubation (71% [184 of 259]) had significantly fewer clinical events (51% [93 of 184] vs 72% [54 of 75],P = .002), shorter cumulative bradycardia duration (median, 0 seconds [IQR, 0 seconds] vs 0 seconds [IQR, 0-9 seconds],P Conclusions and Relevance The findings suggest that extremely preterm neonates commonly show signs of clinical instability during ET-CPAP and that the accuracy of multiple clinical event combinations to define SBTs is low. Thus, SBTs may provide little added value in the assessment of extubation readiness.

Environmentally sustainable perioperative medicine: simple strategies for anesthetic practice

Abstract: This continuing professional development module aims to inform anesthesiologists about the magnitude of healthcare-related waste and its contribution to global warming, as well as providing general strategies to improve environmental sustainability in daily anesthesia practice in a Canadian context. Global warming is considered to be the biggest global health threat of the 21st century. Healthcare is not only adversely impacted by but also a significant contributor to global warming and environmental degradation. Healthcare provision produces 4.6% of the total national greenhouse gas emissions in Canada, while healthcare waste has increased unabated in recent years, largely because of increased use of disposable medical supplies. Operating rooms are highly energy-intensive and produce up to 33% of total hospital waste. Increasingly, attention in healthcare is being focused on environmental sustainability by exploring evidence-based approaches to more sustainable delivery of healthcare. Key to environmental sustainability research is the life-cycle assessment methodology, which measures the cradle-to-grave impact of products on various environmental outcomes and empowers purchasing departments to make environmentally conscious decisions. By using the “reduce, reuse, recycle” hierarchy of waste reduction, several easily implementable evidence-based strategies are proposed to reduce the environmental footprint of everyday anesthesia practice. These recommendations focus on informed decisions on volatile anesthetic use, reduced drug waste, limited use of single-use devices, and meticulous waste segregation and recycling strategies. Anesthesiologists have a unique opportunity to be champions of environmental sustainability through evidence-based practices, while simultaneously reaping significant synergistic health, cost, and quality co-benefits.

International expert recommendations of clinical features to prompt referral for diagnostic assessment of cerebral palsy.

Abstract: Aim To establish international expert recommendations on clinical features to prompt referral for diagnostic assessment of cerebral palsy (CP). Method An online Delphi survey was conducted with international experts in early identification and intervention for children with CP, to validate the results obtained in two previous consensus groups with Canadian content experts and knowledge users. We sent two rounds of questionnaires by e-mail. Participants rated their agreement using a 4-point Likert scale, along with optional open-ended questions for additional feedback. Additionally, a panel of experts and knowledge-users reviewed the results of each round and determined the content of subsequent surveys. Results Overall, there was high-level of agreement on: (1) six clinical features that should prompt referral for diagnosis; (2) two 'warning sign' features that warrant monitoring rather than immediate referral for diagnosis; and (3) five referral recommendations to other healthcare professionals to occur simultaneously with referral for diagnosis. Interpretation There was high agreement among international experts, suggesting that the features and referral recommendations proposed for primary care physicians for early detection of CP were broadly generalizable. These results will inform the content of educational tools to improve the early detection of CP in the primary care context. What this paper adds International experts provide strong agreement on clinical features to detect cerebral palsy. Consensus on clinical 'warning signs' to monitor over time. Referral recommendations from primary care to specialized health services are identified.

DGCR8 microprocessor defect characterizes familial multinodular goiter with schwannomatosis

Abstract: BACKGROUNDDICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions. Other susceptibility genes for familial forms of MNG likely exist.METHODSWhole-exome sequencing of a kindred with early-onset MNG and schwannomatosis was followed by investigation of germline pathogenic variants that fully segregated with the disease. Genome-wide analyses were performed on 13 tissue samples from familial and nonfamilial DGCR8-E518K-positive tumors, including MNG, schwannomas, papillary thyroid cancers (PTCs), and Wilms tumors. miRNA profiles of 4 tissue types were compared, and sequencing of miRNA, pre-miRNA, and mRNA was performed in a subset of 9 schwannomas, 4 of which harbor DGCR8-E518K.RESULTSWe identified c.1552G>A;p.E518K in DGCR8, a microprocessor component located in 22q, in the kindred. The variant identified is a somatic hotspot in Wilms tumors and has been identified in 2 PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the DGCR8 locus, was found in all 13 samples harboring c.1552G>A;p.E518K. miRNA profiling of PTCs, MNG, schwannomas, and Wilms tumors revealed a common profile among E518K hemizygous tumors. In vitro cleavage demonstrated improper processing of pre-miRNA by DGCR8-E518K. MicroRNA and RNA profiling show that this variant disrupts precursor microRNA production, impacting populations of canonical microRNAs and mirtrons.CONCLUSIONWe identified DGCR8 as the cause of an unreported autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter with schwannomatosis.FUNDINGCanadian Institutes of Health Research, Compute Canada, Alex's Lemonade Stand Foundation, the Mia Neri Foundation for Childhood Cancer, Cassa di Sovvenzioni e Risparmio fra il Personale della Banca d'Italia, and the KinderKrebsInitiative Buchholz/Holm-Seppensen.

An eHealth decision-support tool to prioritize referral practices for genetic evaluation of patients with Wilms tumor.

Abstract: Over 10% of children with Wilms tumor (WT) have an underlying cancer predisposition syndrome (CPS). Cognizant of increasing demand for genetic evaluation and limited resources across health care settings, there is an urgent need to rationalize genetic referrals for this population. The McGill Interactive Pediatric OncoGenetic Guidelines study, a Canadian multi-institutional initiative, aims to develop an eHealth tool to assist physicians in identifying children at elevated risk of having a CPS. As part of this project, a decisional algorithm specific to WT consisting of five tumor-specific criteria (age 1 overgrowth feature was strongly associated with Beckwith-Wiedemann syndrome. Stromal-predominant histology did not contribute to CPS identification. We recommend the incorporation of the WT algorithm in the routine assessment of children with WT to facilitate prioritization of genetic referrals in a sustainable manner.

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

Abstract: OBJECTIVES The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). METHODS Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. RESULTS Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. CONCLUSIONS In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy.

Abstract: Glycosylphosphatidylinositol (GPI)-anchored proteins are critical for embryogenesis, neurogenesis, and cell signaling. Variants in several genes participating in GPI biosynthesis and processing lead to decreased cell surface presence of GPI-anchored proteins (GPI-APs) and cause inherited GPI deficiency disorders (IGDs). In this report, we describe 12 individuals from nine unrelated families with 10 different bi-allelic PIGK variants. PIGK encodes a component of the GPI transamidase complex, which attaches the GPI anchor to proteins. Clinical features found in most individuals include global developmental delay and/or intellectual disability, hypotonia, cerebellar ataxia, cerebellar atrophy, and facial dysmorphisms. The majority of the individuals have epilepsy. Two individuals have slightly decreased levels of serum alkaline phosphatase, while eight do not. Flow cytometric analysis of blood and fibroblasts from affected individuals showed decreased cell surface presence of GPI-APs. The overexpression of wild-type (WT) PIGK in fibroblasts rescued the levels of cell surface GPI-APs. In a knockout cell line, transfection with WT PIGK also rescued the GPI-AP levels, but transfection with the two tested mutant variants did not. Our study not only expands the clinical and known genetic spectrum of IGDs, but it also expands the genetic differential diagnosis for cerebellar atrophy. Given the fact that cerebellar atrophy is seen in other IGDs, flow cytometry for GPI-APs should be considered in the work-ups of individuals presenting this feature.

Predicting Acute Postoperative Pain Trajectories and Long-Term Outcomes of Adolescents after Spinal Fusion Surgery.

Abstract: Objectives Acute pain trajectories are associated with long-term outcomes such as persistent pain and functional disability in adults. However, there are limited data on acute postoperative pain trajectories in the pediatric population. The aims of this study were to investigate acute postoperative pain trajectories, their predictors, and their impact on long- term outcomes in adolescents with idiopathic scoliosis. Methods We evaluated the preoperative pain intensity, use of analgesics, psychosocial measures and physical functioning of adolescents scheduled to undergo spinal fusion, and their average 6-hour self-reported pain intensity scores for their entire hospital stay. Six months after surgery, baseline variables were reassessed. We used growth mixture modeling to conduct acute postoperative pain trajectory analysis and to identify predictors of pain trajectories. Generalized linear models were conducted to determine whether acute pain trajectories predict long-term outcomes. Results One hundred and six patients were included in the best-fitted acute pain trajectory model that included four classes that differed in initial pain intensity and rates of change over time. Preoperative pain catastrophizer status and use of analgesics significantly predicted pain trajectory membership. Furthermore, at the 6-month follow-up, patients experiencing moderate-to-severe pain in the acute postoperative period were more likely to report higher levels of pain severity, use pain medication, and miss a greater number of school/work days due to back pain in the last three months. Discussion. Preoperative assessment and analyzing the progression of pain in the acute postoperative period can help identify those at risk of negative long-term outcomes after surgery.

Airway ultrasound: Point of care in children-The time is now.

Abstract: Background Point-of-care ultrasonography of the airway is becoming a first-line noninvasive adjunct assessment tool of the pediatric airway. It is defined as a focused and goal-directed portable ultrasonography brought to the patient and performed and interpreted on the spot by the provider. Successful use requires a thorough understanding of airway anatomy and ultrasound experience. Aims To outline the many benefits, and some limitations, of airway ultrasonography in the clinical and perioperative setting. Materials and methods Expert review of the recent literature. Results Ultrasound assessment of the airway may provide the clinician with valuable information that is specific to the individual airway static and dynamic anatomy of the patient. Ultrasound can help identify vocal cord dysfunction and pathology, assess airway size, predict the appropriate diameter of endotracheal and tracheostomy tubes, differentiate tracheal from esophageal intubation, localize the cricothyroid membrane for emergency airway access and identify tracheal rings for US-guided tracheostomy. Ultrasonography is also a great tool for the intraoperative diagnosis of a pneumothorax, the visualization of the movement of the diaphragms, and quantifying the amount of gastric content. Ultrasonography signs, tips, and pearls that allow these diagnoses are highlighted. The major disadvantage of ultrasonography remains interobserver variability, and operator dependence, as it requires specific training and experience. Conclusion Although it is not standard of care yet, there is significant potential for the integration of ultrasound technology into the routine care of the airway.

Low-Cost Polyester-Tipped Three-Dimensionally Printed Nasopharyngeal Swab for the Detection of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2).

Abstract: Case identification, isolation, and contact tracing are fundamental strategies used to control the spread of coronavirus disease 2019 (COVID-19). This has led to widespread testing that interrupted the supply chain for testing materials around the world. A prospective study was conducted to compare inexpensive and easily sourced 3-dimensionally (3D)-printed polylactic acid and polyester nasopharyngeal swabs to commercially manufactured swabs for the detection of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). During the study period, 287 laboratory-confirmed hospitalized COVID-19 patients, at multiple stages of their illness, were enrolled. The median age for the study population was 47.6 years (interquartile range [IQR], 34.4 to 56.6 years), and two-thirds (67.6%) of the subjects were male. The median duration of hospitalization, at the time of sampling, was 13 days (IQR, 10 to 16 days). Overall concordance between the prototype and control swabs was 80.8% (Cohen's kappa coefficient, 0.61). Most discrepant results were due to prototype-positive control-negative results. When considering all positive results to be true positives, the prototype swab had a higher sensitivity (90.6% versus 80.8%; 95% confidence interval [CI], 85.7% to 94.0% and 74.7% to 85.7%, respectively; P < 0.015). The cost to produce the prototype swab was estimated to be $0.05 per swab. Polylactic acid 3D-printed polyester-tipped swabs were shown to be effective for nasopharyngeal sample collection. We believe that this design can easily be adopted in countries where commercial swabs are not readily available and can play a vital role in public health efforts for disease control in low-income countries.

Long-term survival and costs following extracorporeal membrane oxygenation in critically ill children—a population-based cohort study

Abstract: Extracorporeal membrane oxygenation (ECMO) is used to provide temporary cardiorespiratory support to critically ill children. While short-term outcomes and costs have been evaluated in this population, less is known regarding long-term survival and costs. Population-based cohort study from Ontario, Canada (October 1, 2009 to March 31, 2017), of pediatric patients (< 18 years of age) receiving ECMO, identified through the use of an ECMO procedural code. Outcomes were identified through linkage to provincial health databases. Primary outcome was survival, measured to hospital discharge, as well as at 1 year, 2 years, and 5 years following ECMO initiation. We evaluated total patient costs in the first year following ECMO. We analyzed 342 pediatric patients. Mean age at ECMO initiation was 2.9 years (standard deviation [SD] = 5.0). Median time from hospital admission to ECMO initiation was 5 days (interquartile range [IQR] = 1–13 days). Overall survival to hospital discharge was 56.4%. Survival at 1 year, 2 years, and 5 years was 51.5%, 50.0%, and 42.1%, respectively. Among survivors, 99.5% were discharged home. Median total costs among all patients in the year following hospital admission were $147,957 (IQR $70,571–$300,295). Of these costs, the large proportion were attributable to the inpatient cost from the index admission (median $119,197, IQR $57,839–$250,675). Children requiring ECMO continue to have a significant in-hospital mortality, but reassuringly, there is little decrease in long-term survival at 1 year. Median costs among all patients were substantial, but largely reflect inpatient hospital costs, rather than post-discharge outpatient costs. This information provides value to providers and health systems, allowing for prognostication of short- and long-term outcomes, as well as long-term healthcare-related expenses for pediatric ECMO survivors.

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

Abstract: 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...

Individual-patient prediction of meningioma malignancy and survival using the Surveillance, Epidemiology, and End Results database.

Abstract: Meningiomas are known to have relatively lower aggressiveness and better outcomes than other central nervous system (CNS) tumors. However, there is considerable overlap between clinical and radiological features characterizing benign, atypical, and malignant tumors. In this study, we developed methods and a practical app designed to assist with the diagnosis and prognosis of meningiomas. Statistical learning models were trained and validated on 62,844 patients from the Surveillance, Epidemiology, and End Results database. We used balanced logistic regression-random forest ensemble classifiers and proportional hazards models to learn multivariate patterns of association between malignancy, survival, and a series of basic clinical variables-such as tumor size, location, and surgical procedure. We demonstrate that our models are capable of predicting meaningful individual-specific clinical outcome variables and show good generalizability across 16 SEER registries. A free smartphone and web application is provided for readers to access and test the predictive models (www.meningioma.app). Future model improvements and prospective replication will be necessary to demonstrate true clinical utility. Rather than being used in isolation, we expect that the proposed models will be integrated into larger and more comprehensive models that integrate imaging and molecular biomarkers. Whether for meningiomas or other tumors of the CNS, the power of these methods to make individual-patient predictions could lead to improved diagnosis, patient counseling, and outcomes.