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Anaphylaxis is an acute systemic and potentially fatal allergic reaction. In this study, we evaluated trends in yearly rates of anaphylaxis in a pediatric Emergency Department (ED) in Montreal, Canada.A prospective and retrospective recruitment process was used to find families of children who had presented with anaphylaxis at the Montreal Children's Hospital between April 2011 and April 2021. Using a uniform recruitment form, data were collected. Anaphylaxis patterns were compared to clinical triggers using descriptive analysis.Among 830,382 ED visits during the study period, 2726 (26% recruited prospectively) presented with anaphylaxis. The median age was 6 years (IQR: 0.2, 12.00), and 58.7% were males. The relative frequency of anaphylaxis cases doubled between 2011-2015, from 0.22% (95% CI, 0.19, 0.26) to 0.42 March 2020, the total absolute number of anaphylaxis cases and relative frequency declined by 24 cases per month (p0.05) and by 0.5% of ED visits (p0.05).The rate of anaphylaxis has changed over the years, representing modifications in food introduction strategies or lifestyle changes. The observed decrease in the frequency of anaphylaxis presenting to the ED during the COVID pandemic may reflect decreased accidental exposures with reduced social gatherings, the school closed, and reluctance to present to ED.

Prompt epinephrine autoinjector (EAI) use is the primary treatment for anaphylaxis. However, limited Canadian data exist on the impact of reaction location on EAI use for food-induced anaphylaxis (FIA).We sought to investigate the setting, management, and severity of pediatric FIA.We recruited children presenting with FIA from 11 Canadian emergency departments. Patient demographics and the setting, management, and symptoms of FIA were collected by standardized questionnaire. Factors associated with prehospital EAI use and reaction severity were determined by logistic regression.We recruited 3,604 children; 60.2% were male and the median age was 5.0 years (interquartile range 1.8-11.0). Among cases with a known location of FIA (85.0%), home was the most common setting (68.1%), followed by school/daycare (12.8%), other locations (11.4%; eg, park, car), and restaurants (7.4%). In the prehospital setting, EAI was administered in 36.7% of reactions at home, 66.7% in school/daycare, 40.2% in other locations, and 44.5% in restaurants. Relative to reactions occurring at school/daycare, prehospital EAI use was less likely at home (adjusted odds ratio [aOR] 0.80; 95% CI 0.76-0.84), in restaurants (aOR 0.81; 95% CI 0.75-0.87), and in other settings (aOR 0.77; 95% CI 0.73-0.83), when data were adjusted for reaction severity, sex, age, comorbidities, and province. The FIA setting was not associated with reaction severity or hospitalization.Prehospital EAI use was higher at school/daycare than in other settings, potentially owing to the presence of policies and training on FIA. Setting-specific interventions including educational programs and policies/laws mandating training and stocking an EAI may improve anaphylaxis recognition and treatment.

Data are sparse regarding tree nut-induced anaphylaxis (TNA).To characterize rate, clinical characteristics, and management of TNA in children (0-17 years old) across Canada and evaluate factors associated with severe reactions and epinephrine use.Between April 2011 and May 2020, data were collected on children presenting to 5 emergency departments in Canada. Multivariate logistic analysis was used to evaluate factors associated with severe reactions (stridor, cyanosis, circulatory collapse, or hypoxia) and epinephrine use.Among 3096 cases of anaphylaxis, 540 (17%) were induced by tree nut. The median age was 5.2 (interquartile range, 2.5-9.5) years and 65.4% were of male sex. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew (32.8%), hazelnut (20.0%), and walnut (11.5%). Cashew-induced anaphylaxis was more common in British Columbia (14.0% difference [95% confidence interval (CI), 1.6-27.6]) vs Ontario and Quebec, whereas pistachio-induced anaphylaxis was more common in Ontario and Quebec (6.3% difference [95% CI, 0.5-12.2]). Prehospital and emergency department intramuscular epinephrine administration was documented in only 35.2% and 52.4% of cases, respectively. Severe reactions were more likely among of male sex (adjusted odds ratio [aOR], 1.05 [95% CI, 1.01-1.10]), older children (aOR, 1.00 [95% CI, 1.00-1.01]), and in reactions triggered by macadamia (aOR, 1.27 [95% CI, 1.03-1.57]).Different TNA patterns in Canada may be because of differences in lifestyle (higher prevalence of Asian ethnicity in British Columbia vs Arabic ethnicity in Ontario and Quebec). Intramuscular epinephrine underutilization urges for epinephrine autoinjector stocking in schools and restaurants, patient education, and consistent policies across Canada.

Sesame can cause severe allergic reactions and is a priority allergen in Canada.To assess clinical characteristics and management of pediatric sesame-induced anaphylaxis and identify factors associated with epinephrine treatment.Between 2011 and 2021, children with sesame-induced anaphylaxis presenting to 7 emergency departments (ED) in 4 Canadian provinces and 1 regional emergency medical service were enrolled in the Cross-Canada Anaphylaxis Registry. Standardized recruitment forms provided data on symptoms, severity, triggers, and management. Multivariate logistic regression evaluated associations with epinephrine treatment pre-ED and multiple epinephrine dosages.Of all food-induced anaphylactic reactions (n = 3279 children), sesame accounted for 4.0% (n = 130 children), of which 61.5% were boys, and the average (SD) age was 5.0 (4.9) years. Hummus containing sesame paste triggered 58.8% of reactions. In the pre-ED setting, 32.3% received epinephrine, and it was more likely to be used in boys (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.08-1.50) and those with a known food allergy (aOR, 1.36; 95% CI, 1.11-1.68]). In the ED, 47.7% of cases received epinephrine, with older children more likely to receive multiple epinephrine doses (aOR, 1.00; 95% CI, 1.00-1.02).In Canada, hummus is the major trigger of sesame-induced anaphylaxis. Knowledge translation focused on prompt epinephrine use and product-labeling policies are required to limit sesame reactions in communities.

Intermediate filaments (IFs) are integral components of the cytoskeleton. They provide cells with tissue-specific mechanical properties and are involved in numerous cellular processes. Due to their intricate architecture, a 3D structure of IFs has remained elusive. Here we use cryo-focused ion beam milling, cryo-electron microscopy and tomography, to obtain a 3D structure of vimentin IFs (VIFs). VIFs assemble into a modular, densely-packed and highly-ordered helical symmetric structure of 40 α-helices in cross-section, organized into 5 protofibrils. Surprisingly, the intrinsically disordered head domains form an amyloid-like fiber in the center of VIFs, while the intrinsically disordered tails form lateral connections between the protofibrils. Our findings demonstrate how protein domains of low sequence complexity can complement well-folded protein domains to construct a biopolymer with striking strength and stretchability.

The discovery and characterization of antigen-specific CD8+ T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then construct SCT libraries to capture SARS-CoV-2 specific CD8+ T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes is validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease.

Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunotherapy or other immunosuppressive cancer treatments, we summarize the evidence on outcomes from COVID-19; address the safety, immunogenicity, and efficacy of COVID-19 vaccination; and review COVID-19 antiviral therapeutics for the patient with cancer. Despite higher mortality for patients with cancer, treatment with immune checkpoint inhibitors does not seem to increase mortality risk based on observational evidence. Inhibitory therapies directed toward B-cell lineages, including monoclonal antibodies against CD20 and CAR T-cell therapies, are associated with poor outcomes in COVID-19; however, the data are sparse. Regarding vaccination in patients receiving immune checkpoint inhibitors, clinical efficacy comparable to that in the general population can be expected. In patients undergoing B-cell–depleting therapy, immunogenicity and clinical efficacy are curtailed, but vaccination is not futile, which is thought to be due to the cellular response. Vaccine reactogenicity and toxicity in all groups of patients with cancer are comparable to that of the general population. Preexposure prophylaxis with monoclonal antibodies directed against the viral spike may provide passive immunity for those not likely to mount an adequate vaccine response. If infected, prompt treatment with monoclonal antibodies or oral small molecule antivirals is beneficial, though with oral antiviral therapies, care must be taken to avoid drug interactions in patients with cancer.

Background: Caregiver hesitancy for their children to receive the COVID-19 vaccine remains due to concerns regarding safety and efficacy, but also due to fear of vaccine administration-related pain and distress. Study objectives were to determine caregivers’ perceptions regarding both their personal and child’s COVID-19 vaccine administration-related stress and fear and relate this to their likelihood to allow their child to receive COVID-19 vaccinations. Methods: This study was a secondary data analysis of a multicentre, cross-sectional survey of caregivers presenting to four Canadian pediatric emergency departments. Caregivers were surveyed between December 2020 and March 2021 and completed a digital survey on their own smartphones. Results: 331 caregivers responded to the survey (mean age 39.9 years [SD 7.71]); 74.2% (245/331) were mothers. Children’s mean age was 8.8 years [SD 5.4]; 49.8% (165/331) were female. 64.1% (209/326) of caregivers were willing to vaccinate their child against COVID-19, while 35.9% (117/326) were not. Greater perceived COVID-19 vaccine administration-related pain (0.88 [0.80; 0.95], p = .003) and stress (0.82 [0.76; 0.89], p = Conclusions: During the time period between COVID-19 pandemic waves 2 and 3, and after the vaccine had been federally approved for adults, one-third of Canadian caregivers surveyed reported being unwilling to vaccinate their child against COVID-19 in the future. Managing children’s and caregivers’ vaccine administration-related fear and stress may improve vaccine uptake for children.

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.

QUESTION: Ear piercing is one of the most common forms of body modification seen in children and adolescents presenting to my office. Parents of my younger pediatric patients inquire about potential post-piercing complications and risk factors associated with earlobe infections. What guidance should I give them? Also, are there any specific post-piercing complications to consider for older pediatric patients seeking second piercings in the upper cartilage area? ANSWER: Piercing the earlobe or auricular cartilage continues to be a popular procedure among children and adolescents. Despite its widespread practice, improper aseptic piercing technique, insufficient training, and trauma to the soft tissue during high-pressure piercing (eg, use of spring-loaded ear-piercing instruments) can increase one’s susceptibility to infections, bleeding, and microfractures. Other post-piercing complications include embedded earrings, keloids, hypertrophic scarring, and cutaneous hypersensitivity. Early recognition and treatment of infections and perichondritis secondary to transcartilaginous piercings can prevent the progression of severe ear deformities requiring reconstructive surgical interventions.

QUESTION: Un enfant de 1 an s’est présenté à ma clinique après être tombé du sofa et avoir atterri sur la tête. À la clinique, l’enfant était asymptomatique et agissait normalement. Cet enfant a-t-il besoin d’une imagerie de la tête? Si oui, comment décider entre une radiographie du crâne ou une tomodensitométrie (TDM) à l’hôpital? RÉPONSE: La règle de décision clinique du Pediatric Emergency Care Applied Research Network (PECARN) pour les TDM aide à identifier les enfants de moins de 2 ans qui présentent un risque élevé de blessure intracrânienne. L’application de la règle, qui a une sensibilité de 100% et une spécificité de 53,8% pour les lésions cérébrales traumatiques cliniquement importantes chez les enfants, est la première étape de l’évaluation des enfants qui présentent un traumatisme crânien mineur. Si la TDM d’urgence n’est pas nécessaire, il est recommandé que les enfants de moins de 2 ans reçoivent une radiographie du crâne seulement si une fracture du crâne est soupçonnée. La présence et le type de fracture du crâne déterminent si une TDM de la tête et une consultation en neurochirurgie sont justifiées.

COVID-19 affects family life world-wide. Determinants of hesitancy around vaccinating children against COVID-19 are critical in guiding public health campaigns. Gender differences among parents may determine willingness to vaccinate children against COVID-19.Secondary analysis of the COVID-19 Parental Attitude Study (COVIPAS) surveying care givers of children presenting for emergency care in 17 sites in 6 countries during peak pandemic (March-June, 2020). We assessed risk perceptions, vaccination history and plans to vaccinate children against COVID-19 once available. We compared responses given by father or mother and used multivariable logistic regression.A total of 2025 (75.4%) surveys were completed by mothers and 662 (24.6%) by fathers, 60 did not respond to question about future vaccination. Of 2627, 1721 (65.5%) were willing to vaccinate their children. In the multivariable analysis, both fathers and mothers were more willing to vaccinate their child if the parent was older and believed that social distancing is worthwhile, and if their child was up-to-date on childhood vaccines (odds ratio (OR) of 1.02, 3.90, 1.65 for mothers and 1.04, 4.76, 2.87 for fathers, respectively). Mothers (but not fathers) were more willing if they had more than a high school education (OR 1.38), and fathers (but not mothers) were more willing to vaccinate their male children (OR 1.62), compared to female children.Unique differences between mothers and fathers underscore the need to view vaccine hesitancy as an acceptable parental response. Public health should plan targeted educational information for parents about a COVID-19 vaccine for children.

The aim was to determine the impact of time to diagnosis (TTD) on morbidity and mortality and to identify factors associated with overall survival (OS) in pediatric patients with malignant central nervous system (CNS) tumors.This is a retrospective review of all malignant CNS tumors presenting to 2 tertiary care pediatric hospitals from 2000 to 2019. Cox proportional hazard model analysis outcomes included TTD and OS as well as morbidity; stratified by tumor category, age, relapse, and presence of metastatic disease.There were 197 children with malignant CNS tumors (mean age 8.7 y, 61% male). Tumors included medulloblastoma (N=58, 29.4%), ependymoma (N=27, 13.7%), high-grade glioma (N=42, 21.3%), germ cell tumors (N=47, 23.9%), and other embryonal tumors (N=23, 11.7%). Median TTD from symptom onset was 62 (interquartile range: 26.5 to 237.5 d) and 28% had metastatic disease. Three-year progression free survival was 55% and 3-year OS was 73.1%. Increased OS was associated with increased TTD (parameter estimate 0.12; confidence interval [CI]: 0.019-7.06; P=0.019), high-grade glioma (hazard ratio [HR]: 2.46; CI [1.03-5.86]; P=0.042), other embryonal tumor (HR: 2.84; CI [1.06-7.56]; P=0.037), relapse (HR: 10.14; CI: 4.52-22.70; P0.001) and metastatic disease (HR: 3.25; CI: 1.51-6.96; P=0.002). Vision change (HR: 0.58; CI: 0.313-1.06; P=0.078), hearing loss (HR: 0.71; CI: 0.35-1.42; P=0.355), and cognitive impairment (HR: 0.73; CI: 0.45-1.19; P=0.205) were not associated with TTD in this model.Increased median TTD is associated with higher OS in pediatric patients treated for malignant CNS tumors. Tumor biology and treatment modality are more important factors than TTD for predicting morbidity and long-term outcomes in pediatric patients with CNS tumors.

Type 2 diabetes is a chronic, progressive disease, and its management results in a high emotional burden on patents. Eventually many patients require and can benefit from the use of insulin. This article reports results of a survey of patients and health care providers regarding their experiences of and challenges with the use of basal insulin. Health care providers can play a key role in helping people with type 2 diabetes overcome the challenges associated with the use of basal insulin, including connecting with their emotional needs and understanding the stressors associated with managing diabetes.

QUESTION: Au mois de février, un bébé de 9 mois est amené à ma clinique d’urgence rurale après un épisode de 2 jours de toux et de congestion, et de 1 jour de difficultés respiratoires. Une auscultation des poumons révèle des sons diffus, de faibles sibilances et des crépitants. En tenant compte de l’âge du bébé, de la symptomatologie et de la saison hivernale, le diagnostic probable est une bronchiolite. Les β(2)-agonistes inhalés sont-ils un traitement approprié pour un tel patient? RÉPONSE: Il n’est pas indiqué d’utiliser des β(2)-agonistes inhalés chez les enfants de 2 ans et moins souffrant de bronchiolite. La sibilance fait le plus souvent partie des critères diagnostiques d’une bronchiolite, qui est une infection virale des voies respiratoires inférieures chez les jeunes enfants. Au contraire de l’asthme, la bronchiolite ne compte pas parmi ses symptômes la contraction des muscles lisses du poumon. Le traitement de la bronchiolite exige des soins de soutien, et il n’a pas été démontré que les interventions pharmacologiques, comme les β(2)-agonistes, les corticostéroïdes et les antibiotiques, raccourcissaient la durée de la maladie, diminuaient sa gravité ou réduisaient les taux d’hospitalisation. Il pourrait y avoir un sous-groupe de nourrissons souffrant de bronchiolite qui répondraient à un traitement aux β(2)-agonistes; toutefois, ce groupe n’a pas encore été entièrement défini dans la littérature jusqu’ici.

QUESTION: A 30-month-old patient in our clinic has had 4 episodes of acute otitis media (AOM) in the past 6 months. Should I refer the child and family to an ear, nose, and throat surgeon to consider tympanostomy tube placement, or should we continue medical management with antibiotics? ANSWER: Acute otitis media is common among children in Canada, particularly those younger than 3 years of age. Recurrent AOM (3 or more episodes of AOM in a 6-month period or 4 or more episodes of AOM in a 12-month period) is also common in this age group. Routine immunization of infants and children in Canada with pneumococcal conjugate vaccines (initially the 7-valent PCV7 and more recently the 13-valent PCV13) considerably reduced the overall incidence of AOM. Tympanostomy tube placement decreases the incidence of AOM compared with medical management. However, the procedure is no longer superior to medical management after a 2-year period. Both tympanostomy tube placement and medical management are valid options for children with recurrent AOM, and shared decision making with caregivers is recommended.

QUESTION: Infectious mononucleosis (IM) is a common viral infection year round, and we see patients with it in our family medicine clinic frequently. With fatigue, fever, pharyngitis, and cervical or generalized lymphadenopathy causing prolonged illness and school absences, we always look for treatments that will shorten the duration of symptoms. Does treatment with corticosteroids benefit these children? ANSWER: Current evidence points to small and inconsistent benefits when using corticosteroids for symptom relief in children with IM. Corticosteroids alone or in combination with antiviral medications should not be given to children for common symptoms of IM. Corticosteroids should be reserved for those with impending airway obstruction, autoimmune complications, or other severe circumstances.

BACKGROUND Mohs micrographic surgery (MMS) for cutaneous melanoma is becoming more prevalent, but surgical technique varies. OBJECTIVE To define variations in published techniques for MMS for melanoma. METHODS AND MATERIALS A systematic review was performed of PubMed, EMBASE, and Scopus databases to identify all articles describing surgical techniques for MMS for melanoma. Technical details were recorded for the preoperative, intraoperative, and postoperative phases of MMS. RESULTS Twenty-four articles were included. Mohs surgeons vary in how they assess clinical margins, how wide a margin they excise on the first MMS layer, and how they process tissue to determine tumor stage and margin clearance during MMS for melanoma. CONCLUSION Mohs micrographic surgery for melanoma is performed with varied surgical techniques. To establish best practices, additional research is necessary to determine how different techniques affect outcomes.

CE Information Activity Available Online: To access the article, post-test, and evaluation online, go to https://www.highmarksce.com/mscare. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, pharmacists, and other health care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: 1) Describe the characteristic factors of MS disease that can confound the identification of symptomatic urinary tract infection (UTI). 2) Distinguish appropriate, potentially appropriate, and inappropriate testing and treatment practices for the diagnosis and treatment of UTIs in patients with MS. Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Delaware Media Group. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physician Credit: The CMSC designates this journal-based activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Credit: The CMSC designates this enduring material for 0.5 contact hour of nursing continuing professional development (NCPD) (none in the area of pharmacology). Pharmacist Credit: This knowledge-based activity (UAN # JA4008165-9999-21-021-H01-P) qualifies for 0.5 contact hour (0.05 CEUs) of continuing pharmacy education credit. Disclosures: Francois Bethoux, MD, Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has disclosed relationships with Springer Publishing (royalty); Qr8 (receipt of intellectual property rights/patent holder); Biogen (receipt of intellectual property rights/patent holder, speakers' bureau); MedRhythms (consulting fee, contracted research); GW Pharmaceuticals, Genentech, Helius Medical Technologies, Osmotica, Ipsen (consulting fee); and Adamas Pharmaceuticals (contracted research). Alissa Mary Willis, MD, Associate Editor of IJMSC, has disclosed relationships with Greenwich Biosciences (consulting fee); Alexion (consulting fee, speakers' bureau, contracted research); Genentech (consulting fee, speakers' bureau); and Biogen, Bristol Myers Squibb (speakers' bureau). Nicole C. Griffith, PharmD, has disclosed no relevant financial relationships. Brandon K. Hill, PharmD, has disclosed no relevant financial relationships. Myla D. Goldman, MD, has disclosed relationships with Adamas Pharmaceuticals, Biogen, Brainstorm Cell Therapeutics Ltd, EMD Serono, Genentech, Greenwich Biosciences, Immunic, MedDay, and Sanofi Genzyme (consulting fees). S. Ross Tingen, PharmD, has disclosed a relationship with Novartis (advisory board). The staff at IJMSC, CMSC, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Laurie Scudder, DNP, NP, Continuing Education Director CMSC, has served as Reviewer for this activity. She has disclosed no relevant financial relationships. One peer reviewer for IJMSC has disclosed relationships with EMD Serono, Novartis, Bristol Myers Squibb, and Genentech (consulting fees). The other peer reviewer has disclosed no relevant financial relationships. Note: Financial relationships may have changed in the interval between listing these disclosures and publication of the article. Method of Participation: Release Date: October 1, 2021 Valid for Credit Through: October 1, 2022 In order to receive CME/NCPD/CPE credit, participants must: 1) Review the continuing education information, including learning objectives and author disclosures.2) Study the educational content.3) Complete the post-test and evaluation, which are available at https://www.highmarksce.com/mscare. Statements of Credit are awarded upon successful completion of the evaluation and the post-test with a passing score of >70%. The post-test may be retaken if necessary. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. The CMSC and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

QUESTION: A young infant seen in our practice was diagnosed with profound congenital hearing loss. Their parents want to pursue cochlear implant surgery for their child, but they are concerned about language acquisition before and after the surgery. What should they know about the procedure, and how can they improve language outcomes? ANSWER: Congenital hearing loss is often identified on newborn screening hearing tests. Cochlear implants may lead to overall improved spoken language skills among children with profound hearing loss. Some factors associated with successful language acquisition in children after cochlear implant surgery include having the procedure at an earlier age and family engagement in early intervention programs. Learning sign language before cochlear implant surgery may improve subsequent language outcomes and support the child’s cognitive and socioemotional success.

The chromatin associated with the nuclear lamina (NL) is referred to as lamina-associated domains (LADs). Here, we present an adaptation of the tyramide-signal amplification sequencing (TSA-seq) protocol, which we call chromatin pull down-based TSA-seq (cTSA-seq), that can be used to map chromatin regions at or near the NL from as little as 50 000 cells. The cTSA-seq mapped regions are composed of previously defined LADs and smaller chromatin regions that fall within the Hi-C defined B-compartment containing nuclear peripheral heterochromatin. We used cTSA-seq to map chromatin at or near the assembling NL in cultured cells progressing through early G1. cTSA-seq revealed that the distal ends of chromosomes are near or at the reassembling NL during early G1, a feature similar to those found in senescent cells. We expand the use of cTSA-seq to the mapping of chromatin at or near the NL from fixed-frozen mouse cerebellar tissue sections. This mapping reveals a general conservation of NL-associated chromatin and identifies global and local changes during cerebellar development. The cTSA-seq method reported here is useful for analyzing chromatin at or near the NL from small numbers of cells derived from both in vitro and in vivo sources.

A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied.Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3-5 conditions. Logistic regression was used to estimate the risk of grade 3-4 conditions in BMT recipients who were alive at the time of this study compared with siblings.The median age at transplantation was 11.3 years (range, 0.4-22.0 years), and the median length of follow-up was 11.7 years (range, 2.0-45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3-4 condition was 53.8% (95% CI, 46.7%-60.3%). The adjusted odds ratio of a grade 3-4 condition was 15.1 in survivors (95% CI, 9.5-24.0) compared with siblings. The risk of a grade 3-5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01-1.05) and was higher among females (HR, 1.27; 95% CI, 1.02-1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27-2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09-1.74).Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3-4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.

Onsite and in-person experiential education has been well established to prepare practice-ready healthcare professionals, such as pharmacists. From COVID-19, the integration of remote educational delivery has occurred. As healthcare disciplines adjust to new experiential styles and innovate traditional methods, this paper highlights key areas for remote experiential education that can influence student experiences. Factors that are of importance to continuous quality improvement are described. A survey, utilizing the cloud-based software platform Qualtrics® headquartered in the United States, was developed to evaluate whether remote rotation delivery was comparable to traditional onsite experiential education, to assist with quality improvement for virtual experiential education, and to ensure the redesigned educational model meets accreditation standards for two schools of pharmacy. Numerous factors including work, time zone, Office of Experiential Education and preceptor responsiveness, and technology, were examined. Chi-Square test, t-test for proportions and odds ratios were utilized to evaluate results. Students with technology concerns throughout a remote rotation had a more than two-fold increase in identifying the virtual experience as worse than most/all other in-person rotations (p = 0.01). Preceptor responsiveness to questions and concerns significantly impact student perceptions of educational quality (p < 0.05). The majority of students perceived remote experiential education is equal to onsite experiences. Since continuous quality improvement is required by pharmacy accreditors and many other healthcare programs offering clinical opportunities, identifying factors is of importance to make future interventions in the remote experiential education delivery. This type of experiential learning became essential with COVID-19 impacting onsite clinical placements, and information can be used across health science disciplines at large.

Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortium's (PIDTC's) prospective and retrospective studies of SCID.Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed.We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes.According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (0.05 × 10The PIDTC 2022 Definitions describe SCID and its subtypes more precisely than before, facilitating analyses of SCID characteristics and outcomes.

QUESTION: Several physicians in our family medicine clinic noted a recent increase in the number of children with nonspecific symptoms after having had COVID-19. Based on the assumption that these children may have long COVID syndrome, what is the recommended treatment? ANSWER: Lockdowns and isolation during the COVID-19 pandemic have affected the physical and mental health of children and adolescents. A recognized complication of COVID-19 is a post–COVID-19 syndrome (long COVID) that was initially reported in adults with an estimated prevalence of 10%. More recent reports on long COVID in children suggest a prevalence of 8% to 10%, but small cohorts, a range of symptoms, and challenges in defining the syndrome make accurately estimating the prevalence difficult. Furthermore, providers may find it challenging to differentiate between neuropsychiatric symptoms that are consequences of COVID-19 infection versus those that are a result of stress, anxiety, or changes in behaviour owing to restrictions associated with the pandemic. Until more evidence is available, management includes obtaining a detailed history, performing a comprehensive physical examination, and aiming to relieve symptoms while following up every 2 to 4 months.

QUESTION: A 1-year-old child presented to my clinic after falling from a couch and landing on his head. In the clinic, the child was asymptomatic and acting normally. Does this child need imaging of his head? If so, how do I decide between sending the child for a skull x-ray scan and sending him to the hospital for a computed tomography (CT) scan? ANSWER: The Pediatric Emergency Care Applied Research Network clinical decision rule for CT scans helps identify children younger than 2 years of age at high risk of intracranial injury. Application of the rule, which has 100% sensitivity and 53.8% specificity for clinically important traumatic brain injury in children, is the first step to assessing children with minor head injury. If a CT scan is not needed urgently, it is recommended that children younger than 2 years get a skull x-ray scan only if a skull fracture is suspected. The presence and type of skull fracture can determine if a CT scan of the head and consultation with a neurosurgeon is warranted.

QUESTION: Several parents have recently asked me if oxytocin would be helpful for treating their children with autism spectrum disorder (ASD). What do we currently know about the use of oxytocin for the treatment of children with ASD? ANSWER: Autism spectrum disorder is prevalent among children in Canada, with most affected children experiencing difficulties with social function. Behavioural and educational interventions are the first-line treatments for children with ASD. Multiple studies of oxytocin in children with ASD from the past 2 decades provide equivocal results related to social functioning, and a recent large study did not show benefit from treatment with oxytocin. Small sample sizes and differences in participant age, oxytocin formulation and dose, treatment duration, outcome measures, and analytic methods may help explain some of these disparities. The fact that ASD has a range of clinical presentations may also contribute to mixed results. The use of oxytocin has limited benefit in changing social function in children with ASD and there is no support for its current use in the treatment of this population.

QUESTION: Plusieurs parents m’ont récemment demandé si l’ocytocine serait utile pour traiter leur enfant atteint du trouble du spectre de l’autisme (TSA). Que savons-nous sur l’ocytocine pour le traitement des enfants atteints du TSA? RÉPONSE: Le trouble du spectre de l’autisme est fréquent chez les enfants canadiens, et la plupart des enfants atteints éprouvent des difficultés à fonctionner socialement. Les interventions comportementales et éducatives sont les traitements de première intention pour les enfants atteints du TSA. De nombreuses études menées depuis 20 ans sur l’ocytocine chez les enfants atteints du TSA ont donné des résultats équivoques en matière de fonctionnement social, et une récente étude d’envergure n’a pas montré que le traitement par l’ocytocine était bénéfique. Certaines de ces disparités pourraient s’expliquer par la taille réduite des échantillons et les différences d’âge entre les participants, la préparation et la dose d’ocytocine, la durée du traitement, les paramètres d’évaluation et les méthodes analytiques. Le fait que le tableau clinique du TSA soit si vaste contribue également aux résultats mitigés. L’utilisation de l’ocytocine a des bienfaits limités sur la modification du fonctionnement social chez les enfants atteints de TSA, et rien n’appuie son emploi courant pour le traitement de cette population.

Background Virtual reality has been used to alleviate pain and anxiety in a variety of medical procedures. The authors sought to explore the effects of virtual reality in common awake minor plastic surgery procedures where children may experience discomfort. Methods A randomized controlled trial compared virtual reality to standard-of-care distraction among children aged 6 to 16 years undergoing awake minor plastic surgery procedures at a quaternary children's hospital. Primary outcome was change in Faces Pain Scale-Revised pain score, and secondary outcomes included change in Venham Situational Anxiety Scale score, procedure duration, administration of local anesthetic, and pain/anxiety management satisfaction. Results Mean pain and anxiety scores were similar in both groups (p = 0.60 and p = 0.18, respectively), and procedure duration was shorter with virtual reality (22 minutes versus 29 minutes; p = 0.002). Duration remained shorter in a linear regression model accounting for procedure type (p = 0.01). Similar proportions of children received additional local anesthetic after the initial dose (virtual reality, n = 6; standard of care, n = 9; p = 0.19) and median pain management satisfaction was similar (virtual reality, 9 of 10; standard of care, 9 of 10; p = 0.41). Median anxiety management satisfaction was similar (virtual reality, 9 of 10; standard of care, 9 of 10; p = 0.05). Younger children reported more "fun" than older children with virtual reality (p = 0.02). Surgeons reported interest "using virtual reality again" in 83 percent of cases. Conclusions The use of virtual reality for awake pediatric plastic surgery reduced procedure time but not pain or anxiety compared to standard of care in children aged 6 to 16 years. Virtual reality was safe and well-liked and should be considered as an additional tool. Increased efficiency may allow more cases to be performed. Clinical question/level of evidence Therapeutic, II.

QUESTION: Un enfant atteint du syndrome du côlon irritable (SCI) s’est présenté à la clinique pour des symptômes gastro-intestinaux persistants comme principale raison de consulter. Les parents ont indiqué que les modifications alimentaires n’avaient pas amélioré l’état de leur enfant, et ils ne sont pas intéressés à ce qu’il reçoive des médicaments. La thérapie cognitivo-comportementale (TCC) est-elle efficace pour le traitement du SCI chez les enfants? RÉPONSE: La TCC classique et ses sous-types, y compris la TCC en ligne et l’hypnothérapie pour le syndrome du côlon irritable, sont plus efficaces pour soulager la douleur et les symptômes gastro-intestinaux que le traitement standard ou l’absence de traitement chez les enfants et les adolescents atteints du SCI. Cette thérapie devrait être recommandée aux patients et aux parents.

QUESTION: A child with irritable bowel syndrome (IBS) presented to the clinic with a chief concern of ongoing gastrointestinal symptoms. The parents reported no improvement despite dietary modifications and are not interested in any medications. Is cognitive-behavioural therapy (CBT) an effective treatment for IBS in children? ANSWER: Traditional CBT and its subtypes, including Internet-based CBT and gut-directed hypnotherapy, are more effective in reducing pain and gastrointestinal symptoms in children and adolescents with IBS compared with standard treatment or no treatment. This therapy should be recommended to patients and parents.

Restoring forest cover is a key action for mitigating climate change. Although monoculture plantations dominate existing commitments to restore forest cover, we lack a synthetic view of how carbon accumulates in these systems. Here, we assemble a global database of 4756 field-plot measurements from monoculture plantations across all forested continents. With these data, we model carbon accumulation in aboveground live tree biomass and examine the biological, environmental, and human drivers that influence this growth. Our results identify four-fold variation in carbon accumulation rates across tree genera, plant functional types, and biomes, as well as the key mediators (e.g., genus of tree, endemism of species, prior land use) of variation in these rates. Our nonlinear growth models advance our understanding of carbon accumulation in forests relative to mean annual rates, particularly during the next few decades that are critical for mitigating climate change.