Management and Long-Term Outcomes of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Drug reaction with eosinophilia and systemic symptoms (DReSS) is known to cause mortality and long-term sequelae in the pediatric population, however there are no established clinical practice guidelines for the management of pediatric DReSS. We conducted a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the currently available data on treatment, mortality, and long-term sequelae of DReSS in children (aged 0-18 years). Data from 644 individuals revealed that various treatment strategies are being used in the management of pediatric DReSS, and strategies were often used in combination. The diversity in treatment approaches cannot be solely attributed to age or disease severity and reflects the lack of evidence-based management guidelines for DReSS. Children are also at risk of developing autoimmune sequelae following DReSS, most commonly thyroid disease and type 1 diabetes mellitus. We found that the eventual development of autoimmune disease was more often associated with DReSS caused by antibiotics, especially minocycline and sulfamethoxazole, in comparison with individuals who did not develop sequelae. In this study, we identify strengths and weaknesses in the currently available literature and highlight that future prospective studies with structured and long-term follow-up of children with DReSS are needed to better understand potential risk factors for mortality and development of sequelae after DReSS.

Clinical Presentation and Diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially challenging in children due to a low incidence rate, heterogeneous clinical presentation, and a lack of (pediatric) diagnostic criteria and clinical practice guidelines. We performed a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the clinical presentation and diagnostic process of DReSS in children (aged 0-18 years). Data from 644 individuals showed that DReSS manifests differently in children compared to adults. Children have a higher number of organs involved, including higher rates of cardiac and respiratory involvement compared to adults. Children < 6 years of age appear more prone to develop neurologic symptoms. Conversely, eosinophilia, edema, and kidney involvement are less frequently observed in children. Anti-seizure medications are by far the most common causative drug class, but the range of implicated drugs increases as children get older. This study highlights that children with DReSS not only differ from adults but also that differences exist between children of different ages. As such, there is a need to establish pediatric-specific diagnostic criteria. These efforts will promote earlier diagnosis of DReSS and likely lead to improved clinical care offered to children and their families.

Pharmacologic Procedural Distress Management During Laceration Repair in Children: A Systematic Review.

OBJECTIVES: To systematically appraise the literature on the relative effectiveness of pharmacologic procedural distress management agents for children undergoing laceration repair. METHODS: Six databases were searched in August 2021, and the search was updated in January 2023. We included completed randomized or quasi-randomized trials involving ( a ) children younger than 15 years undergoing laceration repair in the emergency department; ( b ) randomization to at least one anxiolytic, sedative, and/or analgesic agent versus any comparator agent or placebo; ( c ) efficacy of procedural distress management measured on any scale. Secondary outcomes were pain during the procedure, administration acceptance, sedation duration, additional sedation, length of stay, and stakeholder satisfaction. Cochrane Collaboration's risk-of-bias tool assessed individual studies. Ranges and proportions summarized results where applicable. RESULTS: Among 21 trials (n = 1621 participants), the most commonly studied anxiolytic agents were midazolam, ketamine, and N 2 O. Oral midazolam, oral ketamine, and N 2 O were found to reduce procedural distress more effectively than their comparators in 4, 3, and 2 studies, respectively. Eight studies comparing routes, doses, or volumes of administration of the same agent led to indeterminate results. Meta-analysis was not performed because of heterogeneity in comparators, routes, and outcome measures across studies. CONCLUSIONS: Based on procedural distress reduction, this study favors oral midazolam and oral ketamine. However, this finding should be interpreted with caution because of heterogeneous comparators across studies and minor conflicting results. An optimal agent for procedural distress management cannot be recommended based on the limited evidence. Future research should seek to identify the minimal, essential measures of patient distress during pharmacologic anxiolysis and/or sedation in laceration repair to guide future trials and reviews.

Acute Fluid Biomarkers for Diagnosis and Prognosis in Children with Mild Traumatic Brain Injury: A Systematic Review.

BACKGROUND AND OBJECTIVE: Fluid biomarkers have the potential to improve the accuracy of diagnosis and prognosis in children with mild traumatic brain injury. Our primary objective was to assess the diagnostic and prognostic utility of acute blood and fluid biomarkers in children with mild traumatic brain injury. METHODS: We performed a systematic review of the published literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Fluid biomarker studies assessing pediatric mild traumatic brain injury diagnosis or prognosis were included if blood or fluids were sampled within 24 h of injury. RESULTS: Thirty-two studies involving 4743 patients were included comprising 25 diagnostic studies and ten prognostic studies with three studies assessing both diagnosis and prognosis. Sixteen of the 25 diagnostic studies reported the area under the receiver operating characteristic curve (AUC) for predicting abnormal computed tomography scans of the head; S100 calcium binding protein B (S100B, N = 6 studies, AUC range 0.67-1.00), glial fibrillary acidic protein (N = 5, AUC range 0.41-0.85), ubiquitin C-terminal hydrolase (N = 3, AUC 0.59 and 0.83), neuron specific enolase (N = 1, AUC 0.99), total tau (N = 1, AUC 0.65), and interleukin-6 (N = 1, AUC 0.61). In four of the ten prognostic studies, increased acute serum S100B levels, tumor necrosis factor-α, or interleukin-8 were associated with post-concussive symptoms or fatigue from 3 to 12 months post-injury. CONCLUSIONS: The largest amount of evidence supported the potential use of S100B, glial fibrillary acidic protein, and UCH-L1, but there was mixed accuracy for diagnosis and prognostication for all biomarkers in pediatric mTBI.

Diagnostic test accuracy of ultrasound for orbital cellulitis: A systematic review.

BACKGROUND: Periorbital and orbital cellulitis are inflammatory conditions of the eye that can be difficult to distinguish using clinical examination alone. Computer tomography (CT) scans are often used to differentiate these two infections and to evaluate for complications. Orbital ultrasound (US) could be used as a diagnostic tool to supplement or replace CT scans as the main diagnostic modality. No prior systematic review has evaluated the diagnostic test accuracy (DTA) of ultrasound compared to cross-sectional imaging. OBJECTIVE: To conduct a systematic review of studies evaluating the DTA of orbital ultrasound compared with cross-sectional imaging, to diagnose orbital cellulitis. METHODS: MEDLINE, EMBASE, CENTRAL, and Web of Science were searched from inception to August 10, 2022. All study types were included that enrolled patients of any age with suspected or diagnosed orbital cellulitis who underwent ultrasound and a diagnostic reference standard (i.e., CT or magnetic resonance imaging [MRI]). Two authors screened titles/abstracts for inclusion, extracted data, and assessed the risk of bias. RESULTS: Of the 3548 studies identified, 20 were included: 3 cohort studies and 17 case reports/series. None of the cohort studies directly compared the diagnostic accuracy of ultrasound with CT or MRI, and all had high risk of bias. Among the 46 participants, diagnostic findings were interpretable in 18 (39%) cases which reported 100% accuracy. We were unable to calculate sensitivity and specificity due to limited data. In the descriptive analysis of the case reports, ultrasound was able to diagnose orbital cellulitis in most (n = 21/23) cases. CONCLUSION: Few studies have evaluated the diagnostic accuracy of orbital ultrasound for orbital cellulitis. The limited evidence based on low quality studies suggests that ultrasound may provide helpful diagnostic information to differentiate orbital inflammation. Future research should focus studies to determine the accuracy of orbital US and potentially reduce unnecessary exposure to radiation.

Kidney Ultrasonography After First Febrile Urinary Tract Infection in Children: A Systematic Review and Meta-analysis.

Importance: Controversy exists on the clinical utility of kidney ultrasonography after first febrile urinary tract infection (UTI), and clinical practice guideline recommendations vary. Objective: To determine the prevalence of urinary tract abnormalities detected on kidney ultrasonography after the first febrile UTI in children. Data Sources: The MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials databases were searched for articles published from January 1, 2000, to September 20, 2022. Study Selection: Studies of children with first febrile UTI reporting kidney ultrasonography findings. Data Extraction and Synthesis: Two reviewers independently screened titles, abstracts, and full texts for eligibility. Study characteristics and outcomes were extracted from each article. Data on the prevalence of kidney ultrasonography abnormalities were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was prevalence of urinary tract abnormalities and clinically important abnormalities (those that changed clinical management) detected on kidney ultrasonography. Secondary outcomes included the urinary tract abnormalities detected, surgical intervention, health care utilization, and parent-reported outcomes. Results: Twenty-nine studies were included, with a total of 9170 children. Of the 27 studies that reported participant sex, the median percentage of males was 60% (range, 11%-80%). The prevalence of abnormalities detected on renal ultrasonography was 22.1% (95% CI, 16.8-27.9; I2 = 98%; 29 studies, all ages) and 21.9% (95% CI, 14.7-30.1; I2 = 98%; 15 studies, age <24 months). The prevalence of clinically important abnormalities was 3.1% (95% CI, 0.3-8.1; I2 = 96%; 8 studies, all ages) and 4.5% (95% CI, 0.5-12.0; I2 = 97%; 5 studies, age <24 months). Study recruitment bias was associated with a higher prevalence of abnormalities. The most common findings detected were hydronephrosis, pelviectasis, and dilated ureter. Urinary tract obstruction was identified in 0.4% (95% CI, 0.1-0.8; I2 = 59%; 12 studies), and surgical intervention occurred in 1.4% (95% CI, 0.5-2.7; I2 = 85%; 13 studies). One study reported health care utilization. No study reported parent-reported outcomes. Conclusions and Relevance: Results suggest that 1 in 4 to 5 children with first febrile UTI will have a urinary tract abnormality detected on kidney ultrasonography and 1 in 32 will have an abnormality that changes clinical management. Given the considerable study heterogeneity and lack of comprehensive outcome measurement, well-designed prospective longitudinal studies are needed to fully evaluate the clinical utility of kidney ultrasonography after first febrile UTI.

Financial incentives to promote employment of persons with disabilities: a scoping review of when and how they work best.

PURPOSE: To assess the state of evidence on the use of financial incentives to employ, retain, and promote persons with disabilities. MATERIALS AND METHODS: We completed a scoping review of the peer-reviewed literature published from 1990 to 31 March 2022. Inclusion criteria were - populations with a disability; employment, retention, or promotion; and use of financial incentives targeted at employers. Articles were excluded if incentive was targeted solely at persons with disabilities. RESULTS: Seventeen articles met the inclusion criterion and were collated based on their study designs, type of incentive investigated, employment sector, and jurisdiction. We identified seven common themes that are relevant contextual and situational factors associated with the use of financial incentives to employ, retain, and promote persons with disabilities. CONCLUSIONS: While the literature identified the fact that financial incentives are widely used, the current state of the literature is modest and insufficient to make strong statements about the evidence on how and when financial incentives work well or do not work well. The themes identified allude to a subset of contextual factors requiring consideration for incentive use; however, evaluative research is still required to substantiate best practices for their use.Implications for rehabilitationFinancial incentives for the recruitment, retention, and promotion of workers with disabilities take many different forms and can incent different behaviours based on their form and context.Workers with disabilities are as diverse as workers without disabilities, consequently the supports required will differ from situation to situation.In some cases, a worker with a disability may require several types of supports, at a point in time, or over their employment journey.Employer knowledge and experience are important considerations in the use of financial incentives, as are employer skills in recruitment, retention, and promotion of workers with disabilities.

Clinical Health Outcomes of Siblings of Children with Chronic Conditions: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of the study was to assess clinical mental and physical health outcomes of siblings of children with chronic health condition(s) compared with siblings of healthy children or normative data. STUDY DESIGN: We searched Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL through August 9, 2021. We included English-language studies that reported clinically diagnosable mental or physical health outcomes among siblings of children (<18 years old) with a chronic health condition, included a comparison group, and used an experimental or observational study design. Two reviewers extracted data and independently assessed risk of bias using the Newcastle Ottawa Scale. RESULTS: Of 9899 screened studies, 34 were included; 28 studies reported on mental health, 3 reported on physical health, and 3 reported on mortality. Siblings of children with chronic conditions had greater depression rating scale scores than their comparison groups (standardized mean difference = 0.53; 95% CI = 0.38-0.68; P < .001 [6 studies]), whereas anxiety scores were not substantially increased (standardized mean difference = 0.21; 95% CI = -0.02 to 0.43; P = .07 [7 studies]). The effects for confirmed psychiatric diagnoses (7 studies), mortality (3 studies), or physical health outcomes (3 studies) could not be meta-analyzed given the limited number of studies and between-study heterogeneity. CONCLUSION: Siblings of children with chronic health conditions may be at an increased risk of depression. Our findings suggest the need for targeted interventions to support the psychological well-being of siblings of children with chronic health conditions.

Quality Indicators for Youth Transitioning to Adult Care: A Systematic Review.

BACKGROUND AND OBJECTIVE: Transition from pediatric to adult care is associated with adverse health outcomes for many adolescents with chronic illness. We identified quality indicators for transition to adult care that are broadly applicable across chronic illnesses and health systems. METHODS: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature were searched, covering earliest available date to July 2021. The Gray Matters framework was used to search gray literature. Two independent reviewers screened articles by title and abstract, followed by full-text review. Disagreements were resolved by a third reviewer. Studies were included that identified quality indicators developed via consensus-building methods. Indicators were organized into a framework categorized by illness specificity, level of care, Donabedian model, and Institute of Medicine quality domain. Appraisal of Guidelines for Research and Evaluation tool was used for critical appraisal. RESULTS: The search identified 4581 articles, of which 321 underwent full-text review. Eight peer-reviewed studies and 1 clinical guideline were included, identifying 169 quality indicators for transition. Of these, 56% were illness specific, 43% were at the patient level of care, 44% related to transition processes, and 51% were patient centered and 0% equity focused. Common indicator themes included education (12%), continuity of care (8%), satisfaction (8%), and self-management/self-efficacy (7%). The study was limited by quality indicators developed through consensus-building methodology. CONCLUSIONS: Although most quality indicators for transition were patient-centered outcomes, few were informed by youth and parents/caregivers, and none focused on equity. Further work is needed to prioritize quality indicators across chronic illness populations while engaging youth and parents/caregivers in the process.

Treatment of children with infantile spasms: A network meta-analysis.

AIM: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms. METHOD: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed. RESULTS: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'. INTERPRETATION: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms. WHAT THIS PAPER ADDS: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.

Impact of Project ECHO on Patient and Community Health Outcomes: A Scoping Review.

PURPOSE: Project Extension for Community Healthcare Outcomes (ECHO) is a hub-and-spoke tele-education model that aims to increase health care providers' access to evidence-based guidelines and enhance their capacity to care for complex patients in rural, remote, and underserved communities. The purpose of this scoping review was to examine evidence of the impact of Project ECHO programs on patient and community health outcomes. METHOD: The authors used Arksey and O'Malley's framework and subsequent revisions proposed by Levac and colleagues to guide their review. They searched MEDLINE, EMBASE, CINAHL Plus, and Web of Science for English-language, peer-reviewed articles published between January 2003 and June 2020. Included studies focused on Project ECHO programs and reported either patient or community health outcomes. The authors used a standardized data extraction form to document bibliographical information and study characteristics, including health outcome level(s), as articulated by Moore's evaluation framework for continuing medical education. RESULTS: Of the 597 search results, the authors identified 15 studies describing Project ECHO programs. These programs were implemented in the United States and Australia and facilitated education sessions with health care providers caring for adult patients living with 1 of 7 medical conditions. Included study findings suggest Project ECHO programs significantly changed patient-level outcomes (n = 15) and to a lesser extent changed community-level outcomes (n = 1). Changes in care were observed at the individual patient level, at the practice level, and in objective clinical measures, including sustained virologic response and HbA1c. CONCLUSIONS: This review identified emerging evidence of the effectiveness of Project ECHO as a tele-education model that improves patient health outcomes and has the potential to positively impact community health. The small number of included studies suggests that additional evidence of patient- and community-level impact is required to support the continued adoption and implementation of this model.

Eating Behaviors, Caregiver Feeding Interactions, and Dietary Patterns of Children Born Preterm: A Systematic Review and Meta-Analysis.

Infants born preterm (<37 weeks of gestation) often experience feeding problems during hospitalization. Whether difficulties persist or have long-term sequelae on childhood eating is unclear. We aimed to describe the oromotor eating skills (e.g., chewing/swallowing), eating behaviors (e.g., food neophobia), food parenting practices (e.g., pressure to eat), and dietary patterns of preterm children during late infancy (6-12 mo) and early childhood (>12 mo-7 y) and to determine whether these differed from those of term-born peers. We identified 67 articles (57 unique studies) for inclusion. We used random-effects meta-analysis of proportions to examine the prevalence of oromotor eating skill and eating behavior challenges among preterm children, standard meta-analysis for comparisons with term-born peers, and the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty of evidence. Forty-three percent (95% CI: 24%, 62%) of infants and 25% (95% CI: 17%, 33%) of children born preterm experienced oromotor eating difficulties and 16% (95% CI: 4%, 27%) and 20% (95% CI: 11%, 28%), respectively, exhibited challenging eating behaviors. During late infancy and early childhood, oromotor eating difficulties (OR: 2.86; 95% CI: 1.71, 4.77; I2 = 67.8%) and challenging eating behaviors (OR: 1.52; 95% CI: 1.11, 2.10; I2 = 0.0%) were more common in those born preterm than in those born term: however, the certainty of evidence was very low. Owing to the low number and heterogeneity of studies, we narratively reviewed literature on food parenting and dietary patterns. Mothers of preterm infants appeared to have heightened anxiety while feeding and utilized coercive food parenting practices; their infants reportedly received less human milk, started solid foods earlier, and had poorer diet quality than term-born peers. In conclusion, meta-analyses show preterm children experience frequent oromotor eating difficulties and challenging eating behaviors throughout the early years. Given preterm birth increases risk of later obesity and diet-related chronic disease, research examining the effects of caregiver-child interactions on subsequent diet is warranted. This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020176063.

The Long-term Cardiac and Noncardiac Prognosis of Kawasaki Disease: A Systematic Review.

CONTEXT: It is uncertain if children with Kawasaki Disease (KD) are at risk for non-cardiac diseases and if children with KD but without coronary artery aneurysms (CAA) are at risk for long-term cardiac complications. OBJECTIVE: To determine the long-term mortality and prognosis of children after KD. DATA SOURCES: Medline, Embase, and the Cochrane Central Register. STUDY SELECTION: Controlled trials and observational studies were included if they included children with KD and reported mortality, major adverse cardiovascular events (MACE), chronic cardiac or other disease over an average follow-up of ≥1 year. DATA EXTRACTION: Data extracted included sample size, age at diagnosis, the proportion with coronary artery aneurysms (CAA), follow-up duration, and outcome(s). RESULTS: Seventy-four studies were included. Thirty-six studies reported mortality, 55 reported a cardiac outcome, and 12 reported a noncardiac outcome. Survival ranged from 92% to 99% at 10 years, 85% to 99% at 20 years, and 88% to 94% at 30 years. MACE-free survival, mostly studied in those with CAA, varied from 66% to 91% at 10 years, 29% to 74% at 20 years, and 36% to 96% at 30 years. Seven of 10 studies reported an increased risk in early atherosclerosis. All 6 included studies demonstrated an increased risk in allergic diseases. LIMITATIONS: Our study may have missed associated chronic comorbidities because short-term studies were excluded. The majority of outcomes were evaluated in East-Asian patients, which may limit generalizability. Studies frequently excluded patients without CAA and did not compare outcomes to a comparison group. CONCLUSIONS: Studies demonstrate >90% survival up to 30 years follow-up. MACE is observed in children with CAA, but is not well studied in those without CAA.

Examining Clinical Practice Guidelines for Male Circumcision: A Systematic Review and Critical Appraisal Using AGREE II.

OBJECTIVE: To identify and critically appraise available clinical practice guidelines (CPGs) targeting male circumcision using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. STUDY DESIGN: A literature search was conducted using electronic databases, CPG databases, and national/international societies providing recommendations to guide clinical decision making for male circumcision. We selected pediatric-focused CPGs related to male circumcision published between January 2010 and December 2020. Non-English CPGs and publications involving narrative reviews, primary research, training manuals, patient and allied health professional guidelines, and technical guides were excluded from our search. Complete CPG documents (including full-text articles, supplemental documents, and associated information) were reviewed. Quality appraisal of CPGs was conducted in accordance with the AGREE II manual. RESULTS: A total of 163 CPGs were identified, of which 93 were screened and 13 were reviewed. All AGREE II domains demonstrated good to excellent interrater reliability, with intraclass correlation coefficients ranging from 0.82 (95% CI, 0.72-0.89) to 0.93 (95% CI, 0.90-0.95). Most CPGs performed satisfactorily in the clarity of presentation domain and performed poorly in the applicability and editorial independence domains. The top 3 CPGs identified were those of the American Academy of Pediatrics, Centers for Disease Control and Prevention, and Canadian Urological Association. Consistencies among the CPGs were demonstrated across most recommendations. CONCLUSIONS: Current CPGs are of variable quality, and our findings should be taken into consideration by clinicians and health care professionals when selecting appropriate guidelines for male circumcision.

Parenteral versus enteral fluid therapy for children hospitalised with bronchiolitis.

BACKGROUND: The main focus of treatment for children hospitalised with bronchiolitis is supportive, including oxygen supplementation, respiratory support, and fluid therapy. Up to half of infants hospitalised with bronchiolitis require non-oral fluid therapy due to dehydration or concerns related to the safety of oral feeding. The two main modalities used for non-oral fluid therapy are parenteral (intravenous (IV)) and enteral tube (nasogastric (NG) or orogastric (OG)). However, it is not known which mode is optimal in young children. OBJECTIVES: To systematically review randomised clinical trials (RCTs) of the effectiveness and safety of parenteral and enteral tube fluid therapy for children under two years of age hospitalised with bronchiolitis. SEARCH METHODS: We conducted a search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 8 March 2021. We handsearched conference proceedings, conducted forward and backward searching of citation lists of relevant articles, and contacted experts. SELECTION CRITERIA: We included RCTs and quasi-RCTs of children aged up to two years admitted to hospital with a clinical diagnosis of bronchiolitis who required fluid therapy. The trials compared enteral tube fluid therapy with parenteral fluid therapy. The primary outcome was difference in length of hospital stay in hours after each non-oral fluid therapy modality. As actual time of discharge can be impacted by various factors, we also assessed theoretical length of stay (i.e. time when a patient is safe for discharge). We assessed several secondary outcomes. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  MAIN RESULTS: The searches yielded 615 unique records, of which four articles underwent full-text screening. We included two trials (810 children). Oakley 2013 was an open, non-blinded RCT of infants aged two to 12 months admitted to hospitals in Australia and New Zealand with a clinical diagnosis of bronchiolitis during three bronchiolitis seasons. The trial enrolled 759 children, of which 381 were randomised to NG tube therapy and 378 to IV therapy. Risk of bias was low in most domains. Kugelman 2013 was an open, non-blinded RCT that enrolled infants aged less than six months with a clinical diagnosis of "moderate bronchiolitis" at a single hospital in Israel. The study enrolled 51 infants, of which 31 were assigned to NG or OG tube therapy and 20 to IV therapy. Risk of bias was unclear in most domains. The application of enteral tube fluid therapy compared to IV fluid therapy probably makes little to no difference for actual length of hospital stay (mean difference (MD) 6.8 hours, 95% confidence interval (CI) -4.7 to 18.4 hours; 2 studies, 810 children, moderate certainty evidence). There was also little to no difference for theoretical length of stay (MD 4.4 hours, 95% CI -3.6 to 12.4 hours; 2 studies, 810 children, moderate certainty evidence). For the secondary outcomes, enteral tube fluid therapy probably makes little to no difference for time to resume full oral feeding compared to IV fluid therapy (MD 2.8 hours, 95% CI -3.6 to 9.2 hours; 2 studies, 810 children, moderate certainty evidence). The use of enteral tube for fluid therapy probably results in a large increase in the success of insertion of fluid modality at first attempt (risk ratio (RR) 1.52, 95% CI 1.36 to 1.69; 1 study, 617 children, moderate certainty evidence), and probably largely reduces the chances of change in fluid therapy modality (RR 0.52, 95% CI 0.38 to 0.71; 1 study, 759 children, moderate certainty evidence) compared to IV fluid.  Oakley 2013 reported 47 local complication events after discharge in the IV fluid group compared to 30 events in the NG tube group. They also evaluated parental satisfaction, which was high with both modalities. Enteral tube fluid therapy makes little to no difference to the duration of oxygen supplementation (MD 2.2 hours, 95% CI -5.0 to 9.5 hours; 2 studies, 810 children, moderate certainty evidence). Compared with the IV fluid therapy group, there was a 17% relative reduction in the number of intensive care unit admissions (RR 0.83, 95% CI 0.47 to 1.46; 1 study, 759 children, moderate certainty evidence) and a 19% relative reduction in number of readmissions to hospital (RR 0.81, 95% CI 0.33 to 2.04; 1 study, 678 children, moderate certainty evidence) in the enteral tube fluid therapy group. Adverse events were uncommon in both trials, with likely little to no differences between groups. AUTHORS' CONCLUSIONS: Based on two RCTs, enteral tube feeding likely results in little to no difference in length of hospital stay compared with the IV fluid group. However, enteral tube fluid therapy likely results in a large increase in the success of insertion of fluid modality at first attempt, and a large reduction in change in modality of fluid therapy. It also probably reduces local complications compared to the IV fluid group. Despite bronchiolitis being one of the most prevalent childhood conditions, we identified only two studies with under 1000 participants in total, which highlights the need for multicentre trials. Future studies should explore type of fluid administered, parent-reported outcomes and preferences, and the role of shared decision-making.

A Systematic Review of the Prospective Relationship between Child Maltreatment and Chronic Pain.

OBJECTIVE: The present systematic review aimed to evaluate the association between childhood maltreatment and chronic pain, with specific attention to the temporal nature of the relationship and putative moderators, including, the nature (type), timing of occurrence, and magnitude of maltreatment; whether physical harm or injury occurred; and whether post-traumatic stress disorder (PTSD) subsequently developed. METHOD: We included studies that measured the prospective relationship between child maltreatment and pain. Medline, EMBASE, PsycINFO, and CINAHL were searched electronically up to 28 July 2019. We used accepted methodological procedures common to prognosis studies and preregistered our review (PROSPERO record ID 142169) as per Cochrane review recommendations. RESULTS: Nine studies (17,340 participants) were included in the present review. Baseline participant age ranged from 2 years to more than 65 years. Follow-up intervals ranged from one year to 16 years. Of the nine studies included, three were deemed to have a high risk of bias. With the exception of one meta-analysis of three studies, results were combined using narrative synthesis. Results showed low to very low quality and conflicting evidence across the various types of maltreatment, with the higher quality studies pointing to the absence of direct (non-moderated and non-mediated) associations between maltreatment and pain. PTSD was revealed to be a potential mediator and/or moderator. Evidence was not found for other proposed moderators. CONCLUSIONS: Overall, there is an absence of evidence from high quality studies of an association between maltreatment and pain. Our results are limited by the small number of studies reporting the relationship between child maltreatment and pain using a prospective design. High quality studies, including prospective cohort studies and those that assess and report on the moderators described above, are needed to advance the literature.

A Systematic Review of the Prospective Relationship Between Bullying Victimization and Pain.

OBJECTIVE: This systematic review synthesized evidence about the relationship between childhood bullying victimization and chronic pain, with a focus on the temporal nature of the relationship and moderating factors, such as the type and intensity of victimization. METHOD: We included prospective cohort studies that examined the relationship between childhood bullying victimization and pain measured at least three months later. We conducted electronic searches of Medline, EMBASE, PsycINFO, and CINAHL up to June 30, 2019. Standard methodological procedures consistent with Cochrane reviews of prognosis studies were used (PROSPERO record ID 133146). RESULTS: We included four longitudinal studies (6275 participants) in this review. The mean age of participants at baseline ranged from 10 to 14 years and the follow-up periods ranged from 6 months to 12 years. Two of the four studies were judged as having high risk of bias. Meta-analysis of results from four studies revealed increased risk of pain among victimized compared to non-victimized youth (adjusted OR [95% CI] = 1.45 [1.06-1.97], but the effect size was small and not clinically important. Only one study examined the inverse association (ie, from pain to victimization), and there was not enough evidence to conduct a meaningful analysis of the proposed moderators. CONCLUSIONS: Study findings were limited by few prospective studies. Meta-analytic findings suggested that victimization may incur some risk for later pain, although the evidence was judged to be very low quality. High-quality studies that measure and report the nuances of bullying victimization are needed to test the proposed moderator models.

The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide.

BACKGROUND: The overall global impact of COVID-19 in children and regional variability in pediatric outcomes are presently unknown. METHODS: To evaluate the magnitude of global COVID-19 death and intensive care unit (ICU) admission in children aged 0-19 years, a systematic review was conducted for articles and national reports as of December 7, 2020. This systematic review is registered with PROSPERO (registration number: CRD42020179696). RESULTS: We reviewed 16,027 articles as well as 225 national reports from 216 countries. Among the 3,788 global pediatric COVID-19 deaths, 3,394 (91.5%) deaths were reported from low- and middle-income countries (LMIC), while 83.5% of pediatric population from all included countries were from LMIC. The pediatric deaths/1,000,000 children and case fatality rate (CFR) were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs 1.32 in HIC; p < 0.001 and 0.24% in LMIC vs 0.01% in HIC; p < 0.001, respectively). The ICU admission/1,000,000 children was 18.80 and 1.48 in HIC and LMIC, respectively (p < 0.001). The highest deaths/1,000,000 children and CFR were in infants < 1 year old (10.03 and 0.58% in the world, 5.39 and 0.07% in HIC and 10.98 and 1.30% in LMIC, respectively). CONCLUSIONS: The study highlights that there may be a larger impact of pediatric COVID-19 fatality in LMICs compared to HICs.

Publication Trends of Pediatric and Adult Randomized Controlled Trials in General Medical Journals, 2005-2018: A Citation Analysis.

Policy has been developed to promote the conduct of high-quality pediatric randomized controlled trials (RCTs). Whether these strategies have influenced publication trends in high-impact journals is unknown. We aim to evaluate characteristics, citation patterns, and publication trends of pediatric RCTs published in general medical journals (GMJs) compared with adult RCTs over a 13-year period. Studies were identified using Medline, and impact metrics were collected from Web of Science and Scopus. All RCTs published from 2005-2018 in 7 GMJs with the highest impact factors were identified for analysis. A random sample of matched pediatric and adult RCTs were assessed for publication characteristics, academic and non-academic citation. Citations were counted from publication until June 2019. Among 4146 RCTs, 2794 (67.3%) enrolled adults, 591 (14.2%) enrolled children, and 761 RCTs (18.3%) enrolled adult and pediatric patients. Adult RCTs published in GMJs grew by 5.1 publications per year (95% CI: 3.3-6.9), while the number of pediatric RCTs did not show significant change (-0.4 RCTs/year, 95% CI: -1.4-0.6). Adult RCTs were cited more than pediatric RCTs (median(IQR): 29.9 (68.5-462.8) citations/year vs. 13.2 (6.8-24.9) citations/year; p < 0.001); however, social media attention was similar (median(IQR) Altmetric Attention Score: 37 (13.75-133.8) vs. 26 (6.2-107.5); p = 0.25). Despite policies which may facilitate conduct of pediatric RCTs, the publishing gap in high-impact GMJs is widening.

What is the effect of changing eligibility criteria for disability benefits on employment? A systematic review and meta-analysis of evidence from OECD countries.

BACKGROUND: Restrictions in the eligibility requirements for disability benefits have been introduced in many countries, on the assumption that this will increase work incentives for people with chronic illness and disabilities. Evidence to support this assumption is unclear, but there is a danger that removal of social protection without increased employment would increase the risk of poverty among disabled people. This paper presents a systematic review of the evidence on the employment effects of changes to eligibility criteria across OECD countries. METHODS: Systematic review of all empirical studies from OECD countries from 1990 to June 2018 investigating the effect of changes in eligibility requirements and income replacement level of disability benefits on the employment of disabled people. Studies were narratively synthesised, and meta-analysis was performed using meta-regression on all separate results. The systematic review protocol was registered with the Prospective Register for Systematic Reviews (Registration code: PROSPERO 2018 CRD42018103930). RESULTS: Seventeen studies met inclusion criteria from seven countries. Eight investigated an expansion of eligibility criteria and nine a restriction. There were 36 separate results included from the 17 studies. Fourteen examined an expansion of eligibility; six found significantly reduced employment, eight no significant effect and one increased employment. Twenty-two results examined a restriction in eligibility for benefits; three found significantly increased employment, 18 no significant effect and one reduced employment. Meta-regression of all studies produced a relative risk of employment of 1.06 (95% CI 0.999 to 1.014; I2 77%). CONCLUSIONS: There was no firm evidence that changes in eligibility affected employment of disabled people. Restricting eligibility therefore has the potential to lead to a growing number of people out of employment with health problems who are not eligible for adequate social protection, increasing their risk of poverty. Policymakers and researchers need to address the lack of robust evidence for assessing the employment impact of these types of welfare reforms as well as the potential wider poverty impacts.