Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 23 appraisals
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Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review
BACKGROUND: Approximately 10%-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulins (IVIG) and are at increased risk of developing coronary artery aneurysms (CAA). A potential therapeutic role of anakinra (ANK) in refractory KD has been suggested. The aim of this work is to systematically review and critically appraise the available clinical evidence on the use of ANK in the treatment of IVIG-resistant KD, focusing on treatment indications, timing, dosage, efficacy on fever, inflammation, CAA and safety. METHODS: A systematic literature search was conducted across PubMed, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar from inception to 9 October 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included all study designs reporting outcomes of patients with KD treated with ANK. RESULTS: Thirty-two publications (31 identified through database search and one by cross-referencing) describing 81 patients were included. Most reports were single cases or small series, with two early-phase clinical trials. Treatment with ANK was associated with resolution of fever and systemic inflammation in 94.9% of patients. Complete CAA resolution was reported in 32% and stabilisation/dimensional reduction in 56.3%. No serious safety concerns were identified. However, these findings derive from heterogeneous and low-quality evidence and should be interpreted with caution. CONCLUSIONS: In IVIG-resistant KD, ANK was effective in controlling systemic inflammation, although more data are needed to assess its efficacy on coronary outcomes. While these findings are encouraging in supporting consideration of ANK for refractory KD, larger randomised clinical studies are warranted to define optimal ANK timing of introduction and dosing, and to evaluate its long-term efficacy on cardiac outcomes. PROSPERO REGISTRATION NUMBER: CRD420252129435.
31 July 2026
Read appraisal →Sleep & breathing = Schlaf & Atmung
Upper airway dimensions in pediatric obstructive sleep-disordered breathing: a systematic review and meta-analysis
PURPOSE: This review aimed to highlight the association between upper airways dimensions and pediatric obstructive sleep-disordered breathing (oSDB). METHODS: We conducted a systematic review and meta-analysis of the published literature on upper airways dimensions in oSDB children compared with controls. We examined publications focusing on children aged up to 9 years old whose oSDB diagnosis was based on polysomnographic exams, identification of mouth breathing rather than normal nasal breathing, or snoring. To be included, these publications should evaluate differences in mean values of upper airways dimensions between oSDB children and controls. The risk of bias and certainty of evidence were assessed. This review followed the protocols recommended by the Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA-2020) guidelines. RESULTS: 17 studies were selected identified from the initial 489 publications identified. Children with oSDB symptoms showed a reduced cross-sectional area of the global airway and its nasopharyngeal and oropharyngeal subsections, a smaller minimum cross-section, and a shorter anteroposterior dimension of the upper part of the pharynx compared with controls, whatever the method used to image the upper airways. All the included studies were considered at low risk of bias even though some limitations were noted. CONCLUSION: These findings have clinical implications as they help facilitate diagnosis and treatment of children with oSDB. More specifically, they indicate that the management of the pathology should focus on increasing the nasopharyngeal space and strongly support early adeno-/tonsillectomy as the primary treatment option in pediatric oSDB.
31 July 2026
Read appraisal →European journal of pediatrics
Health-related quality of life and associated factors in children with bronchiectasis: A systematic review
UNLABELLED: This systematic review aimed to summarize the current evidence on health-related quality of life (HRQoL) and its associated factors in children with bronchiectasis. Following the PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, ScienceDirect, CINAHL, CENTRAL, CNKI, WanFang, VIP, and CBM published from inception to October 2025. Two reviewers independently screened studies, extracted data, and assessed quality using standardized tools. Descriptive synthesis was performed. Nine studies were included, with overall moderate to high quality. HRQoL scores in children with bronchiectasis were significantly lower than those in healthy controls across most scales, though findings varied across physical and psychosocial domains. Parent-proxy scores were generally lower than child self-reports. Lower HRQoL was associated with impaired lung function, frequent exacerbations, higher symptom burden, and anxiety/depression. CONCLUSION: HRQoL is substantially impaired in children with bronchiectasis. Routine assessment of HRQoL and integrated interventions addressing both physical and psychosocial aspects are warranted in clinical practice. WHAT IS KNOWN: • Bronchiectasis is a chronic respiratory disease that causes coughing and breathing difficulties in children. • Previous studies have reported inconsistent findings on quality of life in children with bronchiectasis. WHAT IS NEW: • This systematic review consolidates evidence from nine studies, confirming that children with bronchiectasis have significantly lower quality of life than healthy children. • Poor lung function, frequent exacerbations, and anxiety/depression are key determinants; parents tend to rate their child's quality of life lower than the children themselves, underscoring the need for integrated care including psychological support.
31 July 2026
Read appraisal →JAMA
Prone Positioning in Infants With Acute Bronchiolitis: The PROPOSITIS Randomized Clinical Trial
IMPORTANCE: Prone positioning has been shown to improve respiratory mechanics and oxygenation, but its clinical benefit in infants with acute viral bronchiolitis receiving high-flow nasal cannula (HFNC) support remains unknown. OBJECTIVE: To investigate whether prone positioning in infants with moderate to severe acute bronchiolitis and HFNC support reduces escalation to noninvasive or invasive ventilation. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, open-label trial conducted in 15 pediatric intermediate or intensive care units in France. Infants aged 6 months or younger admitted for 24 hours or less with a diagnosis of acute bronchiolitis with moderate to severe respiratory distress requiring HFNC support were enrolled between January 2021 and November 2023 and followed up until hospital discharge (last patient discharged on December 11, 2023). INTERVENTIONS: Participants were randomly assigned to the prone position (n = 221) or supine position (n = 230). Infants in the prone position group received prone positioning for 24 hours or longer during the first 48 hours. All participants received standardized HFNC support at 2 L/kg/min. MAIN OUTCOMES AND MEASURES: The primary outcome was the need for escalation of care to noninvasive or invasive ventilation within the first 72 hours, according to prespecified criteria. Secondary outcomes included treatment failure, determined by an independent clinical adjudication committee; tolerance of prone positioning; length of hospital stay; duration of respiratory support; infant comfort; and adverse events. RESULTS: Among 451 infants randomized, 446 were included in the primary analysis (median age, 41 [IQR, 19-72] days; 54% male). Escalation of care occurred in 80 infants (17.9%), with no significant difference between the prone position (33/220 [15.0%]) and supine position (47/226 [20.8%]) groups (adjusted odds ratio, 0.66 [95% CI, 0.40-1.07]; P = .09). Secondary outcomes did not differ significantly between the 2 groups. In the safety analysis, serious adverse events occurred in 2 of 180 infants (1.1%) in the prone position group and 2 of 264 (0.8%) in the supine position group. CONCLUSIONS AND RELEVANCE: Prone positioning in infants with moderate to severe bronchiolitis receiving HFNC support did not significantly reduce escalation of care. However, the wide 95% confidence interval around the observed odds ratio suggests that this study was not definitive and further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03976895.
30 July 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Shorter Antitubercular Regimens Versus 9 Months of Isoniazid for Latent Tuberculosis in Children: A Systematic Review and Meta-Analysis
BACKGROUND: We conducted a systematic review and meta-analysis to compare effectiveness and safety of 9 months of isoniazid (9H) versus shorter rifamycin-containing regimens for treating latent tuberculosis infection (TBI) in children. METHODS: We systematically searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to June 2025 for randomized, controlled trials (RCTs) and cohort studies that compared regimens that were shorter than 9 months of isoniazid in children aged 1-18 years. Outcomes were development of TB disease, treatment completion, and adverse events. Risk of bias was assessed using RoB 2.0 and the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool; certainty of evidence was graded using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Five RCTs and 7 nonrandomized studies that enrolled approximately 2950 children in trials and >25 000 in observational cohorts were included. In pooled analysis of 3 RCTs, shorter rifamycin-containing regimens resulted in little to no difference in development of TB disease compared with 9H (odds ratio [OR], 0.19; 95% confidence interval [CI], .03-1.12; moderate-certainty evidence). Treatment completion was probably higher with shorter regimens (OR, 0.51; 95% CI, .42-0.62; moderate-certainty evidence). Adverse events were similar between groups, but evidence is uncertain (low-certainty evidence). Observational data were consistent with these findings, showing higher completion rates and lower hepatotoxicity with shorter treatments. CONCLUSIONS: Shorter rifamycin-containing regimens for pediatric TBI probably increase treatment completion and have similar safety outcomes, with no important difference in development of TB disease compared with the standard regimen. These findings support current guideline recommendations that favor shorter regimens in children.
25 July 2026
Read appraisal →European journal of pediatrics
Probiotics in pediatric functional abdominal pain disorders: a systematic review and meta-analysis
UNLABELLED: Functional abdominal pain disorders (FAPDs), currently referred to as abdominal pain-related disorders of gut-brain interaction (AP-DGBIs), are characterized by recurrent abdominal discomfort in children that cannot be fully explained by an identifiable organic disorder. Probiotics are increasingly used as microbiota-targeted treatments, although their true clinical benefit remains uncertain. The objective of this study is to evaluate the efficacy and safety of probiotic supplementation compared with placebo in children with AP-DGBIs. PubMed, Embase, Web of Science and Scopus were searched from the start of each database to April 2026; the review followed PRISMA guidelines. Randomized controlled trials in patients < 18 years with FAPDs (IBS, FAP-NOS, functional dyspepsia, abdominal migraine) diagnosed by Rome II-IV, in which probiotic supplementation was evaluated. Two reviewers independently extracted data and assessed risk of bias using RoB2 tool. Meta-analyses and network meta-analyses were used to synthesize the data; the certainty of the evidence was evaluated using GRADE and CINeMA. This review covers 21 trials (2005-2025) with 1899 patients treatments completed. Probiotics modestly reduced pain intensity and weekly pain episodes, and modestly increased the rate of complete symptom resolution compared with placebo. Treatment with probiotics was associated with complete symptom resolution in 35.3% versus 22.8% of placebo-treated patients, corresponding to a number needed to treat (NNT) of 7 (95%CI = 3.97-29.04). However, the certainty of evidence was rated as low to moderate across outcomes. Moreover, from a clinical perspective, when success was defined as an improvement in symptoms according to an author-defined threshold, probiotic supplementation was not associated with different response rates compared with placebo. CONCLUSION: Probiotics provide modest symptom relief in pediatric FAPDs and may be considered a safe adjunctive therapy rather than a stand-alone treatment. While these findings are in line with the ESPGHAN/NASPGHAN 2025 guidelines, larger standardized trials are required to define optimal strain selection, dosage and treatment duration. TRIAL REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251149947 , identifier CRD420251149947. WHAT IS KNOWN: • AP-DGBIs (formerly FAPDs) are common childhood disorders characterized by recurrent abdominal pain without identifiable organic disease. • Probiotics are increasingly used to restore gut microbial balance, but their clinical benefit remains uncertain. WHAT IS NEW: • Our meta-analysis showed that probiotic supplementation reduced pain intensity and weekly pain episodes and increased symptom resolution versus placebo. • Benefi ts were modest, with substantial heterogeneity across studies and low-to-moderate certainty of evidence.
21 July 2026
Read appraisal →Renal failure
Novel biomarkers for acute kidney injury in high-risk pediatric populations: a systematic review
Acute Kidney Injury (AKI) is currently diagnosed in pediatric patients by measuring rises in serum creatinine. The objective of this systematic review is to determine the diagnostic accuracy of novel biomarkers for early detection or prediction of pediatric AKI across a variety of high-risk pediatric populations. Relevant studies were searched in PubMed, Cochrane Library, and Web of Science databases. Observational studies and randomized trials assessing diagnostic biomarkers for AKI in high-risk pediatric populations were included, while studies limited to traditional biomarkers, adult populations, or non-original research were excluded. Risk of bias was assessed using the QUADAS-2 tool. The review was prospectively registered in PROSPERO (CRD420261293432). Diagnostic accuracy outcomes included AUC, sensitivity, specificity, and other performance measures. 53 total studies were included and grouped into 1 of 5 categories based on the specific population of pediatric patients studied and the general etiology of their AKI. Of note, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and cystatin-C were among the most studied biomarkers and showed significant promise as reliable indicators of kidney injury. The product of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein-7, interleukin-18, and others showed some evidence of being predictive, early markers of AKI and warrant additional investigation. The review further discusses the integration of novel biomarkers within existing clinical detection frameworks, including validated risk stratification tools and emerging FDA-approved biomarker assays, to contextualize their translational potential in high-risk pediatric populations. Future advances in precision medicine may lead to earlier diagnosis and better prognosis for pediatric patients suffering from AKI. What is known: Acute kidney injury in children is associated with significant morbidity, and serum creatinine often detects kidney injury only after substantial damage has occurred.This study adds: This systematic review summarizes current evidence on emerging pediatric acute kidney injury biomarkers and highlights those with the greatest potential for earlier diagnosis across multiple high-risk populations.Potential impact: Earlier identification of acute kidney injury using novel biomarkers may enable more timely intervention and improve outcomes, although further validation is needed before widespread clinical implementation.
17 July 2026
Read appraisal →Blood advances
I-STRONG: an integrative, multicomponent treatment approach for chronic pain in pediatric sickle cell disease
Chronic pain affects ∼20% of adolescents living with sickle cell disease (SCD). There is a critical unmet need for evidence-based interdisciplinary approaches for chronic SCD pain treatment. We aimed to (1) use community engagement to adapt an integrative multicomponent treatment program designed to meet the unique needs of chronic SCD pain (ie, Integrative Strong Body and Mind Training [I-STRONG] for SCD), and (2) optimize feasibility and acceptability of I-STRONG through a proof-of-concept trial. Modifications to an existing cognitive behavioral therapy (CBT) and neuromuscular treatment program for chronic widespread pain were informed by semistructured qualitative interviews with adolescents (aged 12-18 years) with chronic SCD pain (n = 12) and their caregivers (n = 12), community advisory boards, and interdisciplinary experts to develop I-STRONG. I-STRONG is a virtual 8-week, 16-session, group intervention combining CBT and neuromuscular exercise training, co-led by experts in psychology and physical therapy. A pilot clinical trial of I-STRONG (n = 12 adolescents; n = 9 caregivers) was conducted to iteratively optimize intervention feasibility and acceptability. Community engagement strategies informed systematic adaptations for access, engagement, relevance, satisfaction, and sense of belonging to meet the unique needs of youth experiencing chronic SCD pain. Pilot testing demonstrated high levels of feasibility (95% completion, 97% intervention fidelity, 92% retention), moderate to high acceptability, and safety. Over 82% of adolescents reported improvements in pain after treatment and at 3-month follow-up. Preliminary evidence suggests that I-STRONG is a promising approach for management of chronic pain in pediatric SCD. A planned multicenter, randomized controlled trial will evaluate I-STRONG's efficacy for pain reduction. This trial was registered at www.clinicaltrials.gov as #NCT06110754.
14 July 2026
Read appraisal →Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
A systematic review of long-term outcomes (>10-year follow-up) of paediatric craniopharyngioma
PURPOSE: Adamantinomatous craniopharyngiomas (ACP) in children are rare benign tumours. Relatively few publications have addressed the long-term impact of this tumour and its treatment. We undertake a systemic review of the existing literature aiming to define the outcome of ACP beyond 10 years' follow-up. METHODS: Ovid MEDLINE, Embase and Google Scholar were used to search the literature. The search criteria were children (aged under 18 at diagnosis), any intervention for and outcomes of ACP. Publications with less than 10 years' follow-up and single case reports were excluded. RESULTS: Twenty-one studies were included reporting on 1152 children, with a mean age of 8.8 years at diagnosis. Mean follow-up was 14 years. The most common presenting symptom was headache. The mean overall survival at 5, 10, 15 and 20 years post-diagnosis was 91.6%, 84.4%, 77.5% and 68.0%, respectively. In children undergoing gross total resection only or radiotherapy only, survival was higher than with combined treatments. Seventy-five percent of children had endocrine dysfunction after intervention; the most prevalent was hypothyroidism (81.9%). The prevalence of endocrinopathies was similar across all treatment groups. Lower QoL was reported than the general population, predominantly related to the effects of hypothalamic injury. One in ten patients suffered a late complication related to radiotherapy with vasculopathy being the most prevalent. CONCLUSIONS: The long-term morbidity and mortality for paediatric ACP remain high. The impact from hypothalamic injury cannot be understated and is likely the cause for this finding. As surgical treatment advances, less hypothalamic injury may arise and improved outcomes may follow. Gross total resection, if felt achievable without hypothalamic injury, should form the mainstay of treatment due to the late radiotherapy-related complications that arise.
10 July 2026
Read appraisal →World journal of urology
Non-operative management of early onset small urethrocutaneous fistula post hypospadias repair: a systematic review
BACKGROUND: Urethrocutaneous fistulas (UCF) after hypospadias repair are typically managed surgically, but conservative approaches may offer a less invasive, cost-effective alternative. While surgical repair remains the standard, non-operative strategies may eliminate anesthesia exposure, shorten recovery time, and lower healthcare costs. However, systematic evidence regarding these approaches remains limited. METHODS: This narrative systematic review evaluates non-operative management for small (typically ≤ 2 mm) UCFs. A comprehensive search was conducted across PubMed, Cochrane, ScienceDirect, Wiley, and Google Scholar up to April 2025. The study followed PRISMA guidelines and is registered in PROSPERO (CRD420251069870). We included randomized controlled trials (RCTs), comparative trials, case series, and anecdotal reports involving children (< 18 years). Risk of bias was assessed using Cochrane RoB-2, ROBINS-I, and JBI Critical Appraisal tools. RESULTS: Five studies involving 73 patients were included for analysis. Due to significant clinical heterogeneity in fistula characteristics and interventions, a pooled closure rate was not calculated. Reported individual study closure rates ranged from 53.8% to 62.5% in the primary series, with one anecdotal report (n = 1) showing 100% success. Success was more frequently observed in early-onset UCFs (diagnosed within 14 days post-catheter removal) and those with a diameter ≤ 2 mm. Minor adverse events included localized heat (42.8%) and transient dysuria (4.7%). Cost-analysis from one RCT indicated that non-operative adhesive application cost approximately 9.3% compared to total operative costs. Most included studies were classified as having a high risk of bias. CONCLUSION: Non-operative approaches using tissue adhesives, fibrin glue, or recatheterization may be viable for small (≤ 2 mm), early-onset UCFs. However, the current evidence is limited, heterogeneous, and carries a high risk of bias. These findings should be considered hypothesis-generating, and further high-quality comparative studies are required to establish definitive clinical protocols. TRIAL REGISTRATION: PROSPERO CRD420251069870.
19 June 2026
Read appraisal →European journal of pediatrics
Pentoxifylline in children with acute encephalitis syndrome: a randomized control trial
Because of the excessive endogenous inflammatory mediators, acute encephalitis syndrome (AES) results in death, or sequelae in survivors. Pentoxifylline, a modulator of inflammation, can have beneficial role in AES. The primary objective was to assess the efficacy of pentoxifylline in terms of time taken for improvement in Glasgow coma scale (GCS) from baseline, in children with AES. The secondary objectives were adverse effects of pentoxifylline and frequency of sequelae among the survivors. This open-label randomized controlled trial (RCT) was conducted in a tertiary care teaching institution for 2 years (January 2022 to December 2023). Children aged 1 month to 14 years with a clinical diagnosis of AES were randomized to receive either standard treatment along with pentoxifylline or standard treatment alone. The data were recorded in case record forms. Forty-four children were randomized (median age, 77 months; male 72.7%). There was no significant difference in the time (median, IQR) taken for improvement of Glasgow coma scale (GCS) by 3 points or normalization between the pentoxifylline group [26 (19-50) hours] and control group [28 (16-52) hours] (p = 0.92). Other outcomes like requirement of mechanical ventilation, mortality, and sequalae were not significantly different between the two groups. The adverse event rate was also not different. Conclusion: Adjunctive pentoxifylline did not provide significant clinical benefit in children with AES, although it was safe and well tolerated. Larger, adequately powered multicenter trials with etiological stratification and biomarker integration are needed to identify potential subgroup benefits. What is Known: • Acute encephalitis syndrome (AES) is associated with high mortality and significant neurological sequelae, largely driven by host-mediated inflammatory responses. • No immunomodulatory adjunct therapy has yet shown proven benefit in pediatric AES. What is New: • Adjunctive pentoxifylline did not significantly improve neurological recovery or clinical outcomes in children with AES. • Pentoxifylline was safe and well tolerated, supporting further evaluation in larger, etiology-stratified trials.
29 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
The evolution of scientific knowledge in childhood asthma over time
Paediatric asthma management has undergone a significant transformation from rudimentary assessments in the early 20th century to sophisticated diagnostic and therapeutic approaches today. Early clinical observations lacked paediatric specificity, but mid-20th-century studies introduced functional assessments, spirometry and recognition of asthma as a chronic inflammatory condition. The introduction of inhaled corticosteroids transformed long-term management, offering targeted control with reduced systemic risks. Advances in noninvasive diagnostics, such as fractional exhaled nitric oxide, induced sputum analysis, exhaled breath condensate and electronic nose technology, have improved inflammation monitoring, phenotype classification and therapeutic responsiveness. The integration of omics technologies, i.e. genomics, proteomics and metabolomics, has enabled deeper insights into disease mechanisms and facilitated early, individualised interventions. Concurrently, artificial intelligence (AI) and machine learning are emerging as tools for predicting exacerbations, identifying clinical subtypes and enhancing decision-making through large-scale data integration. Despite these advancements, challenges remain around standardisation, data quality and ensuring equitable access. This narrative review synthesises decades of progress in paediatric asthma care, emphasising the transition from empirical treatment to personalised, biomarker-driven strategies. It highlights current gaps, particularly in algorithm transparency, paediatric-specific validation and holistic care integration. As asthma management enters an era of digital health and AI-assisted precision medicine, future success will depend on interdisciplinary collaboration, real-world validation and policies that close care disparities.
29 May 2026
Read appraisal →Neurology
Efficacy of Levetiracetam in Patients With Pediatric Epilepsy: A Systematic Review and Meta-Analysis
BACKGROUND AND OBJECTIVES: Levetiracetam (LEV) is widely used in pediatric epilepsies because of its favorable pharmacokinetics, ease of administration, and perceived tolerability. However, its comparative efficacy relative to established antiseizure medications (ASMs) in children remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate LEV efficacy in pediatric epilepsies and compare outcomes vs placebo and active comparators. METHODS: We systematically searched PubMed/MEDLINE and Embase (2000-6 August 2025) for RCTs enrolling patients 16 years or younger with epilepsy and reporting seizure freedom and/or ≥50% responder rate. Trials including both pediatric and adult patients were eligible if pediatric participants were represented. Comparisons included LEV vs placebo or active ASMs as monotherapy or adjunctive therapy. Primary outcomes were seizure freedom and responder rate at the trial's primary endpoint or, if not specified, longest reported follow-up. We assessed risk of bias using Cochrane Risk of Bias 2. We pooled risk differences (RDs) with 95% CIs using random-effects models, stratified by comparator and epilepsy subtype. RESULTS: We included 25 RCTs (4,070 participants): 23 contributed to pooled meta-analyses. Across 25 trials, the mean age ranged from 0.4 to 39.3 years, reflecting pediatric-only and mixed-age RCTs; 43.8% were female. In placebo/no-therapy-controlled trials (mainly add-on studies), LEV was associated with higher seizure freedom (RD 11.0%; 95% CI 5.3%-16.7%) and responder rates (RD 24.3%; 95% CI 19.1%-29.4%). In active-comparator-controlled trials (mainly monotherapy head-to-head studies), LEV showed no overall advantage vs active comparators for seizure freedom (RD -2.4%; 95% CI -5.6% to 0.7%) or responder rate (RD -7.4%; 95% CI -23.0% to 8.1%). Fourteen trials were at high risk of bias. Sensitivity analyses confirmed benefit vs placebo but showed significant disadvantage vs active comparators in low risk-of-bias trials. Findings in pediatric-only trials (16 RCTs; 1,380 participants) were consistent with the overall results. DISCUSSION: LEV confers benefit vs placebo, mostly as adjunctive therapy, but does not consistently outperform established ASMs in pediatric epilepsies and may be inferior in some subgroups when higher-quality evidence is considered. Limitations include substantial heterogeneity, frequent high risk of bias, variable follow-up durations, publication bias, and limited pediatric-only comparative data.
28 May 2026
Read appraisal →The Cochrane database of systematic reviews
Gastrostomy plus fundoplication or gastro-jejunal tube or gastrostomy alone for treating or preventing gastro-esophageal reflux in children and adolescents with neurological impairment
RATIONALE: Children with neurological impairment (NI) represent a vulnerable pediatric population who often experience multiple co-occurring chronic conditions and may develop worsening comorbidities over time due to primary dysfunctions of the nervous system. Among the most significant of these are gastro-esophageal reflux (GER) and dysphagia, which likely account for much of the associated morbidity and mortality. There is substantial variation in the management of GER, and few studies have been conducted to evaluate the effects of antireflux procedures in preventing and improving outcomes in this population. OBJECTIVES: To assess the benefits and harms of the two most common enteral feeding tubes and associated antireflux procedures. We aimed to compare: 1) gastrostomy tube (GT) plus fundoplication, 2) gastrostomy plus insertion of a gastro-jejunal (GJ) tube, and 3) GT alone for treating or preventing GER in children and adolescents with NI. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers, together with reference checking and contact with two experts in the field, to identify studies for inclusion in the review. There were no restrictions on language. The latest search date was 17 September 2024. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) in children with NI, with or without GER, comparing the three interventions. We excluded studies of neurologically normal children. OUTCOMES: Our critical outcomes were symptoms of GER and mortality. Important outcomes included major surgical complications (perforation or peritonitis), length of stay (LOS), number of hospitalizations for respiratory morbidity (pneumonia), number of emergency department (ED) visits, and child's quality of life (QoL). RISK OF BIAS: We used the ROBINS-I tool to assess bias in NRSIs. We did not find any RCTs. SYNTHESIS METHODS: We meta-analyzed the results for each outcome where possible (inverse-variance, random-effects). Where this was precluded by the nature of the data, we synthesized results according to Synthesis Without Meta-analysis (SWiM) guidelines. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: We included 11 NRSIs with a total of 3122 children with NI. Among these, seven cohort studies compared GT plus fundoplication versus GT alone (2654 participants); one cohort study compared GJ tubes versus GT alone (50 participants); and three cohort studies compared GT plus fundoplication versus GJ tubes (418 participants). SYNTHESIS OF RESULTS: GT plus fundoplication compared to GT alone for GER in children with NI The evidence is very uncertain about the effect of GT plus fundoplication on symptoms of GER (odds ratio [OR] 2.02, 95% confidence interval [CI] 0.64 to 6.44; 3 NRSIs, 180 participants; very low-certainty evidence); mortality (OR 2.62, 95% CI 0.41 to 16.80; 3 NRSIs, 415 participants; very low-certainty evidence); major surgical complications (OR 2.61, 95% CI 0.46 to 14.87; 3 NRSIs, 412 participants; very low-certainty evidence); and LOS (1 NRSI with no comparison, 130 participants; very low-certainty evidence). GT plus fundoplication may result in little to no difference in the number of hospitalizations for pneumonia (mean difference [MD] 0.04 higher, 95% CI 0.01 lower to 0.09 higher; 1 NRSI, 2054 participants; low-certainty evidence). The evidence is very uncertain about the effect of GT plus fundoplication on the number of ED visits (OR 1.82, 95% CI 0.78 to 4.27; 1 NRSI, 130 participants; very low-certainty evidence). Child's QoL was not reported. GJ tubes compared to GT alone for GER in children with NI The evidence is very uncertain about the effect of GJ tubes on mortality (OR 5.38, 95% CI 0.40 to 73.09; 1 NRSI, 50 participants; very low-certainty evidence) and child's QoL (effect estimate not reported; no effect of the type of tube on quality of life; 1 prospective NRSI, 50 participants; very low-certainty evidence). Symptoms of GER, major surgical complications, LOS, number of hospitalizations for respiratory morbidity (pneumonia), and number of ED visits were not reported. GT plus fundoplication compared to GJ tubes for GER in children with NI The evidence is very uncertain about the effect of GT plus fundoplication on symptoms of GER (3 NRSIs with conflicting results, including 1 unmatched cohort, 1531 participants; very low-certainty evidence); mortality (OR 1.12, 95% CI 0.52 to 2.41; 3 NRSIs, 418 participants; very low-certainty evidence); major surgical complications (OR 2.84, 95% CI 0.45 to 17.82; 2 NRSIs, 190 participants; very low-certainty evidence); and LOS (1 NRSI with no comparison, 79 participants; very low-certainty evidence). GT plus fundoplication may result in little to no difference in the number of hospitalizations for pneumonia (MD 0.05 lower, 95% CI 0.21 lower to 0.11 higher; 1 NRSI, 228 participants; low-certainty evidence). Number of ED visits and child's QoL were not reported. We downgraded the certainty of evidence for risk of bias and imprecision. Most studies were at serious risk of bias due to confounding, except for hospitalizations for pneumonia for the comparisons of GT plus fundoplication versus GT alone and versus GJ tubes. AUTHORS' CONCLUSIONS: In children with NI, the evidence is very uncertain about the effect of GT plus fundoplication on symptoms of GER, mortality, major surgical complications, and LOS, when compared to GT alone or GJ tubes (very low-certainty evidence). GT plus fundoplication may result in little to no difference in the number of hospitalizations for pneumonia when compared to GT alone or GJ tubes (low-certainty evidence). The evidence is very uncertain about the effect of GT plus fundoplication on the number of ED visits when compared to GT alone (very low-certainty evidence). The evidence is very uncertain about the effect of GJ tubes on mortality and child's QoL when compared to GT alone (very low-certainty evidence). We found no RCTs, and our results should be interpreted with caution due to the limited number of studies and the limitations of NRSIs. Additional research is necessary. It is likely that RCTs will be difficult to conduct; however, better-designed NRSIs could improve the quality of evidence in this area. FUNDING: This review was funded by Foundation Fresno, Universidad Católica de Chile, for librarian support only. The foundation had no role in the design or conduct of this review. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD015007.
21 May 2026
Read appraisal →JMIR formative research
Complication Risk Classification in Children and Adolescents With Type 1 Diabetes: Interpretable Machine Learning Study Based on Saudi Clinical Guidelines
BACKGROUND: Complication risks in children and adolescents with type 1 diabetes (T1D) can lead to serious health outcomes if not detected early. Despite the availability of clinical data, there remains a gap in interpretable tools that support risk stratification in this age group, particularly in alignment with local clinical guidelines. OBJECTIVE: The purpose of this study is to develop a clinically interpretable model that classifies the risk levels of T1D complications-acute, chronic, and low-using real-world data and expert clinical rules derived from the Saudi Diabetes Clinical Practice Guidelines. METHODS: A pediatric T1D dataset comprising of 306 patients was preprocessed through structured cleaning and feature engineering. Risk labels were constructed using Saudi Diabetes Clinical Practice Guidelines-derived rules. Feature selection was performed using a hybrid approach that combined the SHAP (Shapley Additive Explanations) analysis with exhaustive feature selection. A decision tree model was trained and optimized via cross-validation, using the F1-score as the primary performance metric. RESULTS: The final model achieved a high mean F1-score of 0.9876 with a low variance of 0.0189, using only 5 clinical features: BMI, hypoglycemia, disease duration, hemoglobin A1c, and impaired glucose metabolism. These features were consistently ranked as the most influential. The resulting decision tree offered a transparent logic path, enhancing its clinical interpretability and usability. CONCLUSIONS: This study demonstrates that a simple and interpretable model, guided by national clinical guidelines, can effectively predict the risk levels of T1D complications in children and adolescents. Its strong performance, clarity, and reliance on a small number of clinically meaningful features make it a promising candidate for integration into clinical decision support systems. This supports a shift toward predictive and personalized diabetes care.
17 May 2026
Read appraisal →BMJ open
Regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes: a systematic review with meta-analysis and trial sequential analysis
OBJECTIVES: To assess the beneficial and harmful effects of regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes. DESIGN: Systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. DATA SOURCES: CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to 30 January 2026. STUDY SELECTION: Randomised clinical trials comparing regular human insulins versus rapid-acting insulin analogues (insulin aspart, lispro, glulisine) in children and adolescents with type 1 diabetes. ANALYSES: Data were analysed using meta-analysis and trial sequential analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool, V.2, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. PRIMARY OUTCOMES: Severe hypoglycaemia, ketoacidosis and serious adverse events. RESULTS: 10 trials randomising 1107 participants were included. The certainty of evidence was very low mainly due to high risk of bias and small sample sizes. Meta-analysis showed no evidence of a difference between regular human insulins and rapid-acting insulin analogues on severe hypoglycaemia (risk ratio (RR) 1.28, 95% CI 0.81 to 2.03; I2=0.0%; p=0.2851; nine trials), ketoacidosis (RR 0.88, 95% CI 0.26 to 2.93; I2=0.0%; p=0.8593; two trials) and serious adverse events (RR 1.00, 95% CI 0.44 to 2.25; I2=0.0%; p=0.9958; two trials). Trial sequential analysis showed that all meta-analyses of primary outcomes were underpowered. CONCLUSIONS: Current research shows no differential effects between regular human insulins and rapid-acting insulin analogues for children and adolescents with type 1 diabetes, but the evidence is very uncertain. PROSPERO REGISTRATION NUMBER: CRD42024508625.
16 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Normal polysomnography parameters in healthy children: a systematic review and meta-analysis
INTRODUCTION: There is a lack of normative values for polysomnographic parameters in childhood. This study presents a comprehensive meta-analysis of paediatric polysomnography parameters scored using recent criteria to establish normative values adjusted for age and sex. METHODOLOGY: A systematic search was conducted in Web of Science and Scopus for studies that performed overnight polysomnography in healthy children and reported polysomnographic parameters scored using the American Academy of Sleep Medicine criteria (2007 or 2012). Children with previously diagnosed health conditions were excluded. Estimates for sleep, arousals and cardiorespiratory parameters were pooled using a random-effects meta-analysis and the influence of sex and age was assessed using meta-regression. RESULTS: Of 3612 articles, 66 studies were eligible, resulting in a sample size of 2947 healthy children. Pooled estimates and 95% confidence intervals for 34 polysomnographic parameters were established. Meta-regression revealed age-related decrease in total sleep time (TST), sleep period time, TST in stage N3 and REM, number of sleep cycles, total arousals, total leg movements, periodic leg movement index, central apnoea index, apnoea-hypopnoea index (AHI), mean peripheral oxygen saturation (S pO2 ), mean heart rate in sleep and REM, while the number of awakenings, TST in stage N2, number of stage shifts, and S pO2 nadir increased with age. Sleep latency was the only parameter influenced by sex (change of -1.27 min per 10% increase in the proportion of males). CONCLUSION: This meta-analysis provides normative polysomnographic data for the paediatric population that can be used as control values in both clinical and research context.
15 May 2026
Read appraisal →Current pain and headache reports
Addressing the Treatment Gap for Pediatric Headache in Underserved Regions
PURPOSE OF REVIEW: This review explores innovative strategies to address the treatment gap for pediatric headache disorders in underserved regions worldwide. RECENT FINDINGS: Global Burden of Disease studies indicate that the fastest growth in pediatric headache burden occurs in low- and middle-income countries, where reported prevalence likely underestimates true disease burden due to healthcare access barriers. Telemedicine demonstrates comparable efficacy, safety, and satisfaction to in person care. Artificial intelligence based diagnostic models achieve high accuracy for pediatric migraine identification. School-based interventions leveraging existing educational infrastructure improve headache knowledge and coping behaviors. Task shifting and integrated care delivery models are increasingly recognized as essential components of sustainable care. Telemedicine, artificial intelligence, school-based interventions, task shifting, and integrated care networks represent scalable solutions for extending headache care to underserved pediatric populations. Realizing their potential requires integrating technological innovation with workforce capacity building, community engagement, and policy advocacy.
14 May 2026
Read appraisal →BMJ open
Multimodal personalised executive function intervention (E-Fit) for school-aged children with complex congenital heart disease in Switzerland: a randomised controlled feasibility study
OBJECTIVE: To explore the feasibility of a novel multimodal executive function intervention in school-aged children with complex congenital heart disease (cCHD). DESIGN: Single-centre, single-blinded, randomised-controlled 8-week multimodal personalised executive function intervention (E-Fit) study. Outcomes were measured throughout the intervention, post-intervention (T1) and at 4-month follow-up (T2). SETTING: Tertiary care centre between May 2022 and May 2024. PARTICIPANTS: Children 10 to 12 years (M=11.0, SD=0.9) with cCHD without a genetic diagnosis with infant open-heart surgery and reported difficulties (T-scores ≥60) on any of the summary scales of the parent- or teacher-reported Behavior Rating Inventory for Executive Function (BRIEF). INTERVENTIONS: Children with cCHD were randomly assigned to one of two groups: the intervention or the control group. The 8-week intervention was multimodal including three modalities: (1) computerised executive function (EF) training 3×20 min/week with CogniFit; (2) a weekly, remote standardised 1:1 individual EF strategy coaching; (3) analogue games played at convenience. The control group completed activity logs. FEASIBILITY MEASURES: Acceptability: Acceptance and Feasibility Scale (AFS) and coach-rated engagement during coaching sessions. Demand: Number of completed computerised training, strategy coaching and analogue game sessions. IMPLEMENTATION: E-Fit Fidelity Measurement System, assessing adherence to core components. Practicality: Retention rate. Integration: AFS integration items. Exploratory efficacy: BRIEF, neuropsychological EF testing and psychosocial variables at baseline, post-intervention (8 weeks) and at 4-month follow-up. RESULTS: We recruited 42 participants (Nfemale=20). Acceptability: The intervention was acceptable, with moderate observed engagement. Demand: median number of computerised training sessions completed was 16 of 24 sessions (67%, (IQR; 6 to 19)), all children attended all scheduled coaching sessions, analogue games were played in total a median of 9 times (IQR 4 to 14). IMPLEMENTATION: Coaching sessions could be implemented by the coaches as intended. Practicality: Overall retention rate was 90%. Integration: E-Fit was well integrable into the home setting. Exploratory efficacy favoured the intervention group with improvements in the parent-rated Behavioral Regulation Index of the BRIEF (adjusted Hedge's (gA1) = -0.408 to -0.903) and in social responsiveness (gA1 = -0.427 to -0.521) at T1 and at T2. CONCLUSIONS: E-Fit is a feasible intervention suggesting EF and social responsiveness improvements in children with cCHD. Motivational strategies to improve adherence to computerised training should be refined before a full-scale efficacy trial. TRIAL REGISTRATION NUMBER: NCT05198583.
12 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Oscillometry for the diagnosis of asthma in children: a systematic review
BACKGROUND: Diagnosing asthma in children and young people (CYP) remains challenging. Oscillometry is a promising tool and is feasible from 2 years of age. European Respiratory Society (ERS) technical standards and bronchodilator response (BDR) oscillometry thresholds have been published, but diagnostic accuracy is not established. METHODS: We systematically reviewed studies comparing oscillometry and spirometry in CYP under investigation for asthma. Reference standards were positive BDR or positive methacholine challenge test (MCT). Primary aims were to investigate the sensitivity and specificity of current ERS oscillometry thresholds (>40% decrease in resistance at 5 Hz (R 5), >50% increase in reactance at 5 Hz (X 5) or >80% decrease in the area under the reactance curve); secondary aims were to identify oscillometry threshold values optimising both sensitivity and specificity. RESULTS: 11 studies were included; six (n=992 CYP) utilised BDR and five (n=531 CYP) MCT as reference standard. Meta-analysis was not possible due to heterogeneity of results reported. In two studies using current ERS BDR thresholds, zero sensitivity and high specificity (>85%) were observed. In weighted regression analyses of BDR studies, a 17.0% decrease in resistance at 5-6 Hz had sensitivity and specificity of 71.6% (95% CI 69.7-73.7%); a 20.2% increase in X 5 had sensitivity and specificity of 68.6% (95% CI 66.6-70.8%). Similarly, 27.7% increase in R 5 had sensitivity and specificity of 73.6% (95% CI 71.9-75.3%) for MCT. CONCLUSION: Currently recommended ERS thresholds for oscillometry BDR have low sensitivity. Proposed thresholds for defining positive BDR and MCT by oscillometry require prospective validation and adoption of standards for measuring and reporting oscillometry parameters in future diagnostic comparative studies.
3 May 2026
Read appraisal →European journal of pediatrics
Efficacy and safety of vosoritide in children with achondroplasia: a systematic review and meta-analysis
UNLABELLED: Achondroplasia is caused by a gain-of-function mutation in the FGFR3 gene. Vosoritide activates the NPR-B receptor to inhibit the overactive FGFR3 signaling pathway. We aim to pool the efficacy and safety outcomes of vosoritide in children with genetically confirmed achondroplasia who are receiving the approved dose of 15 μg/kg/day. We searched five databases up to February 10, 2026. A systematic review and single-arm meta-analysis were conducted in accordance with the PRISMA guidelines. The primary outcomes were annualized growth velocity (AGV), height gain, and change in height Z-score. Three quality assessment tools were used to assess different study designs of the included studies. All analyses were conducted using OnlineMeta V1.1. Thirteen studies on vosoritide treatment in children with achondroplasia were included, comprising randomized controlled trials, cohort studies, case reports, and case series. A meta-analysis showed that vosoritide was associated with an AGV of 5.72 cm/year (95% CI: 5.51-5.94) at 12 months. The mean height Z-score improvement at 12 months after sensitivity analysis was 0.28 (95% CI: 0.16-0.4), with no significant difference between sexes. Overall, the most common adverse events were injection site reactions (51%) and gastrointestinal symptoms (50%). CONCLUSION: One-year treatment with vosoritide is associated with increased growth velocity, height gain, and a modest improvement in height Z-score, accompanied by a high incidence of mild to moderate adverse events. Larger, longer-term studies are necessary to confirm the treatment's safety and efficacy. WHAT IS KNOWN: • Achondroplasia is a skeletal dysplasia caused by a mutation in the FGFR3 gene, which leads to inhibit endochondral ossification and bone growth. • Vosoritide is a recombinant C-type natriuretic peptide analogue designed to counteract overactive FGFR3 signaling and was approved by the FDA and EMA. WHAT IS NEW: • One-year treatment with vosoritide in achondroplasia children is associated with increased growth velocity and improvement in height Z-score with reported minor adverse events.
26 Apr 2026
Read appraisal →Archives of disease in childhood
How accurate is point-of-care ultrasound for detecting paediatric appendicitis? A systematic review and meta-analysis.
OBJECTIVES: Primary: To evaluate the diagnostic accuracy of point-of-care ultrasound (POCUS) in the diagnosis of appendicitis in paediatric patients presenting with suspected appendicitis.Secondary: To investigate how the use of POCUS affects length of stay in the paediatric emergency department and CT utilisation. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) up until February 2025 for studies involving patients presenting to the paediatric emergency department with suspected appendicitis, who underwent POCUS. Studies were assessed for risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies framework. The primary outcome of interest was the ability of POCUS to detect appendicitis in terms of sensitivity and specificity. RESULTS: Eight studies were included encompassing 993 patients. Calculated pooled sensitivity was 85.6% (95% CI 68.9% to 94.1%) with a specificity of 90.2% (95% CI 86.5% to 93.0%). There was a wide range of reported sensitivities for POCUS, ranging from 53% to 100%. There was less variation in reported specificities that ranged from 82% to 95.2%. The studies analysed were of variable quality with the reference standard and flow and timing being the main areas subject to bias. CONCLUSIONS: Based on the findings of this systematic review and meta-analysis, it is reasonable to conclude that POCUS can be used as an effective tool to diagnose paediatric appendicitis. With a moderately high sensitivity, it may not be recommended to be used to exclude appendicitis based on POCUS findings alone. Further prospective studies evaluating the reliability of POCUS in excluding appendicitis, either alone or when combined with a clinical prediction rule, are required. Secondary findings from this study demonstrate that POCUS may result in a reduced length of stay in the paediatric emergency department and lead to a reduction in CT utilisation, though insufficient data were available to draw firm conclusions in relation to this.
19 Apr 2026
Read appraisal →European journal of pediatrics
The impact of growth hormone therapy on ocular structural parameters in idiopathic short stature: a systematic review and meta-analysis
This study aimed to conduct a systematic review and meta-analysis of the effects of growth hormone (GH) therapy on ocular structures and biometric parameters in children with idiopathic short stature (ISS), synthesizing existing evidence for future research. We systematically searched PubMed, EMBASE, the Cochrane Library, CNKI, Wanfang, and VIP databases from inception to September 2025. Randomized controlled trials and observational studies comparing the effects of GH therapy versus control on ocular biometric and refractive outcomes in children with ISS were included. Study quality was assessed using the Cochrane Risk of Bias Tool (RoB 2) and the NOS. Meta-analysis was performed using R software version 4.3.2, with effect sizes expressed as MD or SMD and 95% CI. Nine studies were included (4 RCTs, 5 cohort studies). Meta-analysis showed no significant association of GH therapy with corneal curvature (SMD = 0.13, 95% CI: -0.34 to 0.61). For axial length, the random-effects model showed no significant difference (MD = 0.72, 95% CI: -0.36 to 1.81), with high heterogeneity (I2 = 91.7%). Similarly, no significant association was found for intraocular pressure (MD = 1.38, 95% CI: -0.66 to 3.43; I2 = 95.9%). However, a significant association was observed for refractive status (MD = 0.53, 95% CI: 0.20 to 0.86; I2 = 0.0%). Sensitivity analysis showed robust results for corneal curvature and refractive outcomes, while axial length and intraocular pressure results were influenced by individual studies. Funnel plots and Egger's test indicated no significant publication bias.Conclusion: The associations between GH therapy and ocular biometric parameters in children with ISS remain uncertain. Current evidence suggests a possible link with refractive changes but shows no significant associations with axial length or intraocular pressure when accounting for high heterogeneity. The findings are inconsistent and should be regarded as hypothesis-generating, insufficient to recommend changes in clinical monitoring practice. Future large-sample, long-term studies are required.
17 Apr 2026
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