Maternal Vitamin D Supplementation and Infantile Rickets: Secondary Analysis of a Randomized Trial.

BACKGROUND: The role of maternal vitamin D supplementation in the prevention of infantile rickets is unknown, particularly in low- and middle-income countries without routine infant vitamin D supplementation. Through secondary analysis of a randomized, placebo-controlled trial in Bangladesh, we examined the dose-ranging effects of maternal vitamin D supplementation on the risk of biochemical rickets at 6 to 12 months of age. METHODS: Pregnant women (n = 1300) were randomized into 5 groups: placebo, or vitamin D 4200 IU/week, 16 800 IU/week, or 28 000 IU/week from second trimester to delivery and placebo until 6 months postpartum; or 28 000 IU/week prenatally and until 6 months postpartum. Infants underwent biochemical rickets screening from 6 to 12 months of age (n = 790). Relative risks (RR) and 95% confidence intervals (95% CI) of biochemical rickets were estimated for each group versus placebo. RESULTS: Overall, 39/790 (4.9%) infants had biochemical rickets. Prevalence was highest in the placebo group (7.8%), and the risk was significantly lower among infants whose mothers received combined prenatal and postpartum vitamin D at 28 000 IU/week (1.3%; RR, 0.16; 95% CI, 0.03-0.72). Risks among infants whose mothers received only prenatal supplementation (4200 IU, 16 800 IU, 28 000 IU weekly) were not significantly different from placebo: 3.8% (RR, 0.48; 95% CI, 0.19-1.22), 5.8% (RR, 0.74; 95% CI, 0.33-1.69), and 5.7% (RR, 0.73; 95% CI, 0.32-1.65), respectively. CONCLUSIONS: Maternal vitamin D supplementation (28 000 IU/week) during the third trimester of pregnancy until 6 months postpartum reduced the risk of infantile biochemical rickets. Further research is needed to define optimal postpartum supplementation dosing during lactation.

COVID-19 vaccine acceptance and uptake among caregivers of children aged 5-11 years in Ontario, Canada: A cross-sectional survey.

INTRODUCTION: Although COVID-19 vaccine safety in 5-11-year-old children has been documented, half of Ontarian children this age remain unvaccinated. This study aimed to assess caregivers' vaccine acceptance for 5-11-year-old children and identify factors associated with vaccine non-acceptance. METHODS: A multi-language self-administered survey was sent to caregivers of 5-11-year-old children through schools and community health centers within the Greater Toronto Area from April-July 2022. Sociodemographic characteristics and immunization behaviours were collected for caregivers, their 5-11-year-old children, and any older siblings. The primary outcome, COVID-19 vaccine acceptance, was previous uptake of COVID-19 vaccine or caregiver intent to vaccinate for their 5-11-year-old child. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: In total, 807 caregivers were included in analysis. Although 93 % of caregivers had received two doses of COVID-19 vaccine, 77 % had a 5-11-year-old child who received at least one dose of vaccine. Caregivers age was associated with vaccine acceptance (vs. < 40 years; adjusted odds ratio [aOR] 2.1, 95 % confidence interval [CI] 1.4-3.1 for ages 40-49; aOR 2.8, 95 % CI 1.1-7.1 for ages ≥50 years). Immunization factors associated with vaccine acceptance included caregiver COVID-19 vaccination (aOR 38.1 vs. unvaccinated caregivers; 95 % CI 15.8-92.3), older siblings COVID-19 vaccination (aOR 49.2 vs. unvaccinated siblings; 95 % CI 18.3-132.3), and recent influenza vaccination for the child (aOR 6.9 vs. no influenza vaccine; 95 % CI 4.6-10.5). Among 189 caregivers with unvaccinated 5-11-year-old children, the most common reasons for non-acceptance were concerns about long-term side effects (59 %), lack of experience vaccinating children (41 %), and concerns that vaccines were developed too quickly (39 %). CONCLUSION: Acceptance of COVID-19 vaccination for 5-11-year-old children were associated with caregiver vaccine behaviors and sociodemographic factors. These findings highlight groups of caregivers that can be targeted for educational interventions and concerns that may be addressed to increase vaccine confidence.

Clinical prediction models in children that use repeated measurements with time-varying covariates: a scoping review

BACKGROUND: Emerging evidence suggests that clinical prediction models that use repeated (time-varying) measurements within each patient may have higher predictive accuracy than models that use patient information from a single measurement. OBJECTIVE: To determine the breadth of the published literature reporting the development of clinical prediction models in children that use time-varying predictors. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases. ELIGIBILITY CRITERIA: We included studies reporting the development of a multivariable clinical prediction model in children, with or without validation, to predict a repeatedly measured binary or time-to-event outcome and utilizing at least one repeatedly measured predictor. SYNTHESIS METHODS: We categorized included studies by the method used to model time-varying predictors. RESULTS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27 (27%) used methods that incorporated the repeated measurements as time-varying predictors in a single model. Among these 27 time-varying prediction model studies, we grouped model types into nine categories: time-dependent Cox regression, generalized estimating equations, random effects model, landmark model, joint model, neural network, K-nearest neighbor, support vector machine and tree-based algorithms. Where there was comparison of time-varying models to single measurement models, using time-varying predictors improved predictive accuracy. CONCLUSIONS: Various methods have been used to develop time-varying prediction models in children, but there is a paucity of pediatric time-varying models in the literature. Incorporating time-varying covariates in pediatric prediction models may improve predictive accuracy. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy.

Association of maternal, obstetric, fetal, and neonatal mortality outcomes with Lady Health Worker coverage from a cross-sectional survey of >10,000 households in Gilgit-Baltistan, Pakistan.

Pakistan has among the highest rates of maternal, perinatal, and neonatal mortality globally. Many of these deaths are potentially preventable with low-cost, scalable interventions delivered through community-based health worker programs to the most remote communities. We conducted a cross-sectional survey of 10,264 households during the baseline phase of a cluster randomized controlled trial (cRCT) in Gilgit-Baltistan, Pakistan from June-August 2021. The survey was conducted through a stratified, two-stage sampling design with the objective of estimating the neonatal mortality rate (NMR) within the study catchment area, and informing implementation of the cRCT. Study outcomes were self-reported and included neonatal death, stillbirth, health facility delivery, maternal death, postpartum hemorrhage (PPH), and Lady Health Worker (LHW) coverage. Summary statistics (proportions and rates) were weighted according to the sampling design, and mixed-effects Poisson regression was conducted to explore the relationship between LHW coverage and maternal/newborn outcomes. We identified 7,600 women who gave birth in the past five years, among whom 13% reported experiencing PPH. The maternal mortality ratio was 225 maternal deaths per 100,000 live births (95% confidence interval [CI] 137-369). Among 12,376 total births, the stillbirth rate was 41.4 per 1,000 births (95% CI 36.8-46.7) and the perinatal mortality rate was 53.0 per 1,000 births (95% CI 47.6-59.0). Among 11,863 live births, NMR was 16.2 per 1,000 live births (95% CI 13.6-19.3) and 65% were delivered at a health facility. LHW home visits were associated with declines in PPH (risk ratio [RR] 0.89 per each additional visit, 95% CI 0.83-0.96) and late neonatal mortality (RR 0.80, 95% CI 0.67-0.97). Intracluster correlation coefficients were also estimated to inform the planning of future trials. The high rates of maternal, perinatal, and neonatal death in Gilgit-Baltistan continue to fall behind targets of the 2030 Sustainable Development Goals.

A Canadian children's hospital's experience with cystic echinococcosis over 30 years: A case series.

Background: Cystic echinococcosis (CE) or hydatid disease caused by the cestode Echinococcus granulosus sensu lato is an uncommon infection in Canada especially among children. There are limited reports describing the clinical presentation and management in Canadian children. Methods: The medical records of all children diagnosed with CE at a quaternary paediatric centre in Ontario between January 1988 and August 2021 were retrospectively reviewed. The clinical course, management, and outcomes of each case were summarized. Results: We report two paediatric cases of cystic echinococcosis (CE) in detail and review four additional cases seen at our institution over 33.5 years. The first case was a previously healthy 12-year-old boy with pulmonary CE resulting in unilateral lung collapse and mediastinal shift, who was presumedly infected while living in the Middle East. The second case was a previously healthy 3-year-old girl with pulmonary CE acquired locally in southern Ontario. Four other cases of CE with hepatic involvement (median age 12.5 years) were identified during the study period. Five out of six patients received both surgical and medical therapy. Conclusion: CE is a rare but serious disease seen in southern Canada that has historically been associated with travel or migration. Due to changes in urban wildlife landscapes and increased global migration, CE may become more prevalent in Canadian children. We describe the first locally acquired case in rural southern Ontario diagnosed at our centre. Prompt recognition of this infection in children by health care providers is important to prevent morbidity and mortality.

Historique: L'échinococcose kystique (ÉK), ou hydatidose, causée par le cestode Echinococcus granulosus sensu lato, est une infection peu courante au Canada, particulièrement chez les enfants. Peu de rapports en décrivent la présentation clinique et la prise en charge chez les enfants canadiens. Méthodologie: Les auteurs ont procédé à l'analyse rétrospective des dossiers médicaux de tous les enfants ayant reçu un diagnostic d'ÉK dans un centre pédiatrique de soins quaternaires ontarien entre janvier 1988 et août 2021. Ils ont résumé l'évolution clinique, la prise en charge et le résultat clinique de chaque cas. Résultats: Les auteurs font un compte rendu détaillé de deux cas pédiatriques d'ÉK et analysent quatre autres cas observés à leur établissement sur une période de 33,5 ans. Le premier cas d'ÉK pulmonaire a touché un garçon de 12 ans auparavant en santé, probablement infecté alors qu'il habitait au Moyen-Orient, et a entraîné un collapsus pulmonaire unilatéral et une déviation médiastinale. Le deuxième cas d'ÉK pulmonaire a été observé chez une fillette de trois ans auparavant en santé qui a été infectée dans le sud de l'Ontario. Les auteurs ont relevé quatre autres cas d'ÉK comportant une atteinte hépatique (âge médian de 12,5 ans) pendant la période de l'étude. Cinq des six patients ont reçu à la fois un traitement chirurgical et médical. Conclusion: L'ÉK est une maladie rare, mais grave dans le sud du Canada. Elle était auparavant associée à un voyage ou une migration. En raison des changements aux paysages fauniques urbains et de la migration mondiale accrue, elle pourrait devenir plus prévalente chez les enfants canadiens. Les auteurs décrivent les premiers cas d'acquisition dans les régions rurales du sud de l'Ontario, diagnostiqués à leur centre. Il est important que les dispensateurs de soins dépistent cette infection rapidement chez les enfants pour éviter la morbidité et la mortalité.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Bloodstream Infections in Children Hospitalized for Influenza, the Canadian Immunization Monitoring Program Active.

BACKGROUND: We aimed to estimate the proportion of children hospitalized for influenza whose illness was complicated by bloodstream infection, describe their clinical course, and identify the factors associated with bloodstream infection. METHODS: We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from the 2010-2011 to 2020-2021 influenza seasons. Factors associated with bloodstream infection were identified using multivariable logistic regression analyses. RESULTS: Among 9179 laboratory-confirmed influenza hospital admissions, bloodstream infection occurred in 87 children (0.9%). Streptococcus pyogenes (22%), Staphylococcus aureus (18%) and Streptococcus pneumoniae (17%) were the most common bloodstream infection pathogens identified. Children with cancer [adjusted odds ratio (aOR): 2.78; 95% confidence interval (CI): 1.23-5.63], a laboratory-confirmed nonbloodstream bacterial infection (aOR: 14.1; 95% CI: 8.04-24.3) or radiographically-confirmed pneumonia (aOR: 1.87; 95% CI: 1.17-2.97) were more likely to experience a bloodstream infection, whereas children with chronic lung disorders were less likely (aOR: 0.41; 95% CI: 0.19-0.80). Disease severity markers such as intensive care unit admission (aOR: 2.11; 95% CI: 1.27-3.46), mechanical ventilation (aOR: 2.84; 95% CI: 1.63-4.80) and longer hospital length of stay (aOR: 1.02; 95% CI: 1.01-1.03) were associated with bloodstream infection. Bloodstream infection also increased the odds of death (aOR: 13.0; 95% CI: 4.84-29.1) after adjustment for age, influenza virus type and the presence of any at-risk chronic condition. CONCLUSIONS: Bloodstream infections, although infrequent, are associated with intensive care unit admission, mechanical ventilation, increased hospital length of stay and in-hospital mortality, thus requiring increased levels of care among pediatric influenza hospitalizations.

Ethical and cultural implications for conducting verbal autopsies in South and Southeast Asia: a qualitative study.

INTRODUCTION: Causes of deaths often go unrecorded in lower income countries, yet this information is critical. Verbal autopsy is a questionnaire interview with a family member or caregiver to elicit the symptoms and circumstances preceding a death and assign a probable cause. The social and cultural aspects of verbal autopsy have gotten less attention than the technical aspects and have not been widely explored in South and Southeast Asia settings. METHODS: Between October 2021 and March 2023, prior to implementing a verbal autopsy study at rural sites in Bangladesh, Cambodia, Laos, Myanmar and Thailand, focus group discussions were conducted with village heads, religious leaders and community members from varied demographic backgrounds. Thematic analysis elucidated customs and traditional views surrounding death to understand local ethnocultural sensitivities. RESULTS: We found that death rituals varied greatly among religions, ethnicities and by socioeconomic status. Mourning periods were reported to last 3-100 days and related to the cause of death, age and how close the deceased person was to the family. Participants advised that interviews should happen after mourning periods to avoid emotional distress, but not long after so as to avoid recall bias. Interviewers should be introduced to respondents by a trusted local person. To provide reassurance and confidentiality, a family's residence is the preferred interview location. Interview questions require careful local language translation, and community sensitisation is important before data collection. CONCLUSION: Verbal autopsy is acceptable across a wide range of cultural settings in Southeast Asia, provided that local norms are preidentified and followed.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

BACKGROUND: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. METHODS: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 µg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. DISCUSSION: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. TRIAL REGISTRATION: NCT04798833, March 15, 2021.

Antibiotic use in children hospitalised for influenza, 2010-2021: the Canadian Immunization Monitoring Program Active (IMPACT).

PURPOSE: To determine characteristics associated with inappropriate antibiotic use amongst children hospitalised for influenza. METHODS: We performed active surveillance for laboratory-confirmed influenza hospitalizations amongst children ≤ 16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, from September 2010 to August 2021. Antibiotic use was presumed appropriate if any of the following indications were met: age < 1 month, immunocompromised, hemoglobinopathy, laboratory-confirmed bacterial infection, radiographically confirmed pneumonia, admission to an intensive care unit and mechanical ventilation. Regression analyses were used to identify baseline and clinical characteristics associated with antibiotic use amongst patients without an appropriate indication. RESULTS: Amongst 8971 children, 6424 (71.6%) received any antibiotics during their hospitalisation. Amongst the 4429 children without an appropriate indication, 2366 (53.2%) received antibiotics. Antibiotic use amongst children without appropriate indication differed between study centres, ranging from 33.2% to 66.1% (interquartile range [IQR] 50.6-56.3%); it did not change significantly over time (p-value for trend = 0.28). In multivariable analyses, older age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.96-0.99), presence of any high-risk condition (aOR 0.80, 95% CI 0.70-0.92), influenza virus type B (aOR 0.8, 95% CI 0.70-0.91) and croup (aOR 0.64, 95% CI 0.49-0.83) were associated with less, whilst fever ≥ 38.5 °C (aOR 1.82, 95% CI 1.42-2.35) and hospitalisation duration (aOR 1.12, 95% CI 1.09-1.15) were associated with more inappropriate antibiotic use. CONCLUSIONS: Over two-third of children hospitalised for influenza received antibiotics, including over half of those without an appropriate indication for antibiotic treatment. Differences amongst study centres suggest the importance of contextual determinants of antibiotic use.

Pediatric RSV-Associated Hospitalizations Before and During the COVID-19 Pandemic.

Importance: Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. Objective: To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included. Main Outcomes and Measures: The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons. Results: Among 11 014 RSV-associated hospitalizations in children and adolescents (6035 hospitalizations among male patients [54.8%]; 5488 hospitalizations among patients aged <6 months [49.8%]), 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2% (95% CI, 3.1%-3.3%) before the pandemic to 4.5% (95% CI, 4.3%-4.6%) in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces (difference range, 2.5 percentage points; 95% CI, 1.4-3.6 percentage points for Quebec to 2.9 percentage points; 95% CI, 1.4-3.5 percentage points for Alberta; all corrected P < .001). Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May. Conclusions and Relevance: This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children.

Area-based determinants of outreach vaccination for reaching vulnerable populations: A cross-sectional study in Pakistan.

The objective of this study is to gain a comparative understanding of spatial determinants for outreach and clinic vaccination, which is critical for operationalizing efforts and breaking down structural biases; particularly relevant in countries where resources are low, and sub-region variance is high. Leveraging a massive effort to digitize public system reporting by Lady and Community Health Workers (CHWs) with geo-located data on over 4 million public-sector vaccinations from September 2017 through 2019, understanding health service operations in relation to vulnerable spatial determinants were made feasible. Location and type of vaccinations (clinic or outreach) were compared to regional spatial attributes where they were performed. Important spatial attributes were assessed using three modeling approaches (ridge regression, gradient boosting, and a generalized additive model). Consistent predictors for outreach, clinic, and proportion of third dose pentavalent vaccinations by region were identified. Of all Penta-3 vaccination records, 86.3% were performed by outreach efforts. At the tehsil level (fourth-order administrative unit), controlling for child population, population density, proportion of population in urban areas, distance to cities, average maternal education, and other relevant factors, increased poverty was significantly associated with more in-clinic vaccinations (ß = 0.077), and lower proportion of outreach vaccinations by region (ß = -0.083). Analyses at the union council level (fifth-administrative unit) showed consistent results for the differential importance of poverty for outreach versus clinic vaccination. Relevant predictors for each type of vaccination (outreach vs. in-clinic) show how design of outreach vaccination can effectively augment vaccination efforts beyond healthcare services through clinics. As Pakistan is third among countries with the most unvaccinated and under-vaccinated children, understanding barriers and factors associated with vaccination can be demonstrative for other national and sub-national regions facing challenges and also inform guidelines on supporting CHWs in health systems.

Parent and healthcare provider views of live varicella vaccination of pediatric solid organ transplant recipients.

BACKGROUND: Live attenuated varicella vaccine (LAVV) has historically been contraindicated in children who are immunocompromised due to solid organ transplant (SOT) because of safety concerns. Recently, clinical guidelines were developed that support post-transplant varicella vaccination in selected SOT recipients based on emerging evidence of LAVV safety. This qualitative study sought to explore barriers and facilitators to implementing the new guidelines, as well as acceptability of LAVV among healthcare providers (HCPs) and parents. METHODS: HCPs and parents of transplant recipients were recruited from four sites using purposive sampling. Data from semi-structured interviews were analyzed using an Interpretive Description approach that incorporated data from the interviews, academic knowledge and clinical experience, and drew from Grounded Theory and Thematic Analysis. The theoretical framework used was Adaptive Leadership. RESULTS: Thirty-four participants (16 HCPs and 18 parents) were included in the analysis. Parents developed skills in adaptive leadership that included strategies to protect their child against infectious diseases. Foundational information that live vaccines were absolutely contraindicated post-transplant "stuck" with parents and led them to develop strategies other than vaccination to keep their child safe. Some parents struggled to understand that information previously presented as a certainty (contraindication of LAVV) could change. Their approach to adaptive leadership informed their appraisal of the new vaccination guidelines and willingness to accept vaccination. CONCLUSIONS: HCPs should adopt a family-centered approach to communicating changing guidelines that considers parents' approach to adaptive leadership and discusses the changing nature of medical evidence. Trust between HCPs and parents can facilitate these conversations.

Factors associated with intention for revaccination among patients with adverse events following immunization.

OBJECTIVES: Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. METHODS: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. RESULTS: Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08-0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04-0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07-0.65]), high impact (aOR: 0.08 [95% CI: 0.02-0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03-0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04-0.42]). CONCLUSION: Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs.

Alternative Antimicrobial Irrigation Strategies for the Treatment of Infections in Children: A Review of the Existing Literature.

As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, avoiding potentially toxic systemic levels and bypassing anatomical and physiological barriers, local irrigation or infusion of antibiotics may effectively shorten the antimicrobial therapy course and reduce both infection-related and systemic therapy-related complications. Although evidence from the adult population supports its use in selected patients with an acceptable safety profile, data specifically focused on the pediatric population are limited. To provide a rapid and easily accessible tool for clinical practice, we synthesized the most relevant evidence on the use of local antimicrobial agents in common severe infections in children: meningitis, mediastinitis, pleural infections, recurrent urinary infections, and peritonitis. A literature search was performed using predefined combined keywords through an electronic research database (PubMed). Described molecules, dosages, routes, treated age groups, and related efficacy have been summarized for prompt application to clinical practice. It should, however, be noted that the evidence for the pediatric population remains limited, and the local administration of several molecules remains off-label. A careful multidisciplinary and patient-tailored evaluation, as well as a rational use of available guidelines, should always be the basis of clinical decision making in settings where local administration of antibiotics may be considered.

Case Report: A Case of Bone Marrow Necrosis and Hyperinflammation in a 10-Year-Old Boy after Plasmodium falciparum Infection.

A 10-year-old boy with sickle cell disease (SCD) type SC presented with fever and abdominal pain after travel to Ghana and was diagnosed with Plasmodium falciparum infection. Despite adequate antimalarial treatment, he developed evidence of hyperinflammation with marked elevated ferritin, C-reactive protein, and triglycerides and subsequent bone marrow necrosis, characterized by elevated nucleated red blood cells and significant bone pain. This case report highlights the possible association between malaria and bone marrow necrosis in patients with SCD. Important considerations in treatment and workup of patients presenting with malaria and hyperinflammation are discussed.

Safety and immunogenicity of the live-attenuated varicella vaccine in pediatric solid organ transplant recipients: A systematic review and meta-analysis.

This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.

Immunological effects and safety of live rotavirus vaccination after antenatal exposure to immunomodulatory biologic agents: a prospective cohort study from the Canadian Immunization Research Network.

BACKGROUND: People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6-12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network. METHODS: In this prospective cohort study, infants exposed to biologic agents in utero were referred to one of six SIC sites in Canada for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or older than 15 weeks were excluded. Clinical and laboratory evaluations were conducted according to a standard clinical pathway. Data were collected for relevant medical history, pregnancy outcomes, biologic agent exposure history, physical examination, laboratory results of the child, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunisation. After parental consent, deidentified data were transferred to a central database for analysis. Children recommended for rotavirus vaccination were followed up for 8 months after series initiation to ascertain severe and serious adverse events, including severe diarrhoea, vomiting, and intussusception. FINDINGS: Between May 1, 2017, and Dec 31, 2021, 202 infants were assessed and 191 eligible infants were enrolled (97 [51%] were female and 94 [49%] were male). When including those exposed to multiple agents, the most common biologic agents to which infants were exposed were infliximab (67 [35%] of 191), adalimumab (49 [26%]), ustekinumab (18 [9%]), and vedolizumab (17 [9%]). Biologic agent exposure continued into the third trimester for 178 (93%) infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. After SIC assessment, rotavirus vaccination was recommended for 187 (98%) of 191 infants, all of whom were followed up. By end of follow-up on Aug 19, 2022, 168 (90%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious adverse events after immunisation were reported, but three (2%) infants required medical attention, one for vomiting and change in stools who was subsequently diagnosed with gastroesophageal reflux disease, one for rash on labia unrelated to vaccination, and one for vomiting and diarrhoea associated with a milk allergy. INTERPRETATION: Findings from this study suggest that lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination can be offered to infants exposed to anti-TNF agents in utero. FUNDING: Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network.

Paediatric inflammatory multisystem syndrome in Canada: population-based surveillance and role of SARS-CoV-2 linkage.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.