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Epilepsia Oct 2023Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed... (Meta-Analysis)
Meta-Analysis
Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.
Topics: Infant, Newborn; Humans; Anticonvulsants; Levetiracetam; Phenytoin; Consensus; Epilepsy; Seizures
PubMed: 37655702
DOI: 10.1111/epi.17745 -
Journal of Neurotrauma Nov 2023Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last... (Review)
Review
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.
Topics: Adult; Child; Humans; Young Adult; Anticoagulants; Brain Injuries, Traumatic; Erythrocyte Transfusion; Hypopituitarism; Venous Thromboembolism; Practice Guidelines as Topic
PubMed: 37341019
DOI: 10.1089/neu.2023.0149 -
Annals of the Rheumatic Diseases Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Child; Adult; Humans; United States; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Rheumatology; Consensus
PubMed: 37487610
DOI: 10.1136/ard-2023-224123 -
European Respiratory Review : An... Dec 2023We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo.
METHODS
Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model.
RESULTS
Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36).
CONCLUSIONS
The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.
Topics: Adolescent; Humans; Child; Quality of Life; Asthma; Rhinitis, Allergic; Adrenal Cortex Hormones
PubMed: 37852659
DOI: 10.1183/16000617.0124-2023 -
Arthritis & Rheumatology (Hoboken, N.J.) Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Adult; Child; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Consensus; Physicians; Advisory Committees
PubMed: 37486733
DOI: 10.1002/art.42636 -
The Journal of Allergy and Clinical... Aug 2023Allergic rhinitis (AR) is associated with significant clinical and socioeconomic burdens. It is a frequent risk factor for other atopic diseases, such as asthma. Thus, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic rhinitis (AR) is associated with significant clinical and socioeconomic burdens. It is a frequent risk factor for other atopic diseases, such as asthma. Thus, a comprehensive updated description of the epidemiology of AR in the pediatric population is needed to understand its implications better.
OBJECTIVE
To determine the incidence, prevalence, and epidemiology of AR among children over the past 10 years.
METHODS
We conducted a systematic review and meta-analysis using a protocol registered and published with the International Prospective Register of Systematic Reviews (Register No. CRD42022332667). We searched databases, registers, and Web sites for cohort or cross-sectional studies published between 2012 and 2022, evaluating the epidemiology (incidence or prevalence) of AR in the pediatric population. We assessed study quality of and risk for bias using items derived from the Strengthening the Reporting of Observational Studies in Epidemiology statement.
RESULTS
Twenty-two studies were included in the analysis. The overall prevalence of physician-diagnosed AR was 10.48%, the overall prevalence of self-reported current (past 12 months) AR was 18.12%, and the overall prevalence of self-reported lifetime AR was 19.93%. The incidence could not be determined. The analysis of prevalence of AR over time showed a rising trend in physician-diagnosed AR over the years (8.39% in 2012 to 2015 vs 19.87% in 2016 to 2022).
CONCLUSIONS
Allergic rhinitis has significant impacts on the pediatric population, with an increasing trend for diagnosed AR over the years. Further investigations concerning the incidence, comorbidities, diagnosis, and treatment are needed to provide a complete overview of the disease as well as its burden and management.
Topics: Humans; Child; Cross-Sectional Studies; Rhinitis, Allergic; Asthma; Comorbidity; Risk Factors; Prevalence
PubMed: 37236349
DOI: 10.1016/j.jaip.2023.05.016 -
Journal of Thrombosis and Haemostasis :... Oct 2023Direct oral anticoagulants (DOACs) represent a cornerstone of adult venous thromboembolism (VTE) treatment. Recently, randomized controlled trials (RCTs) investigating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct oral anticoagulants (DOACs) represent a cornerstone of adult venous thromboembolism (VTE) treatment. Recently, randomized controlled trials (RCTs) investigating DOACs in pediatrics have been performed.
OBJECTIVES
To evaluate the efficacy and safety of DOACs in the pediatric population.
METHODS
We systematically searched MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov from initiation up to August 20, 2022, for RCTs comparing DOACs to standard of care (SOC) in patients aged <18 years according to PRISMA guidelines (PROSPERO registration CRD42022353870). The primary analysis was performed according to the anticoagulation intensity and clinical setting (ie, prophylaxis in cardiac disease or treatment in VTE). Efficacy outcomes were all-cause mortality and VTE. Safety outcomes were major bleeding (MB), clinically relevant non-MB, any bleeding, serious adverse events, and discontinuation due to adverse events (AEs).
RESULTS
Seven RCTs were included in the systematic review and 6 in the meta-analysis (3 prophylaxis in cardiac disease and 3 treatment in VTE). DOACs showed a significant reduction of VTE recurrence for treatment (odds ratio [OR] = 0.42; 95% CI, 0.19-0.94) and a nonsignificant reduction in VTE occurrence in prophylaxis (OR = 0.22; 95% CI, 0.03-1.55). No differences were observed for any bleeding, serious AEs, and MB in prophylaxis. Nonsignificant trends were observed for clinically relevant non-MB, MB in treatment, and discontinuation due to AE in prophylaxis. We found a significant increase in discontinuation due to AE in treatment.
CONCLUSIONS
DOAC treatment seems to reduce VTE compared with SOC without major safety issues in the pediatric population, whereas DOAC prophylaxis seems at least comparable to SOC.
Topics: Humans; Child; Anticoagulants; Venous Thromboembolism; Hemorrhage; Blood Coagulation; Heart Diseases; Administration, Oral
PubMed: 37481075
DOI: 10.1016/j.jtha.2023.07.011 -
Allergy Feb 2024The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the... (Meta-Analysis)
Meta-Analysis Review
The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.
Topics: Female; Animals; Cattle; Humans; Child; Middle Aged; Egg Hypersensitivity; Food Hypersensitivity; Skin Tests; Immunoglobulin E; Allergens; Arachis; Diagnostic Tests, Routine; Randomized Controlled Trials as Topic
PubMed: 38009299
DOI: 10.1111/all.15939 -
JAMA Pediatrics Aug 2023Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support... (Meta-Analysis)
Meta-Analysis
Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children: A Systematic Review and Network Meta-Analysis.
IMPORTANCE
Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown.
OBJECTIVE
To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT).
DATA SOURCES
MEDLINE, Embase, and CINAHL Complete through May 2022.
STUDY SELECTION
Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA).
MAIN OUTCOMES AND MEASURES
The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury.
RESULTS
A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension.
CONCLUSIONS AND RELEVANCE
The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF.
Topics: Infant; Child; Humans; Child, Preschool; Continuous Positive Airway Pressure; Oxygen; Cannula; Airway Extubation; Bayes Theorem; Critical Illness; Network Meta-Analysis; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic
PubMed: 37273226
DOI: 10.1001/jamapediatrics.2023.1478 -
Clinical Gastroenterology and... Aug 2023Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of 4 major dietary treatment regimens in EoE, updating the evidence presented in a meta-analysis from 2014.
METHODS
Electronic databases such as PubMed, Scopus, and Web of Science, and other sources were searched up to September 2022 to identify studies on dietary treatment of EoE. Based on histologic remission criteria, the efficacy of these treatments was pooled and analyzed with respect to the type of dietary regimen: 6-food elimination diet (SFED), 4-food elimination diet (FFED), 1-food elimination diet (OFED), and a targeted elimination diet (TED). Clinical response rates, food sensitization, and efficacies for a pediatric subpopulation were calculated. Influencing variables on efficacies were estimated via meta-regression analyses.
RESULTS
Thirty-four studies with 1762 patients met the inclusion criteria. The overall rate of histologic remission was 53.8% (95% CI, 48.0%-59.6%), and in the individual dietary groups was 61.3% (95% CI, 53.0%-69.3%) for SFED, 49.4% (95% CI, 32.5%-66.3%) for FFED, 51.4% (95% CI, 42.6%-60.1%) for OFED, and 45.7% (95% CI, 32.0%-59.7%) for TED. Dietary regimen and patient age did not significantly affect rates of histologic remission. The overall rate of clinical response was 80.8% (95% CI, 72.3%-88.2%), with response rates of 92.8% (95% CI, 81.2%-99.6%) for SFED, 74.1% (95% CI, 49.8%-92.6%) for FFED, 87.1% (95% CI, 58.4%-99.9%) for OFED, and 69.0% (95% CI, 50.2%85.3%) for TED.
CONCLUSIONS
Dietary therapy is an effective treatment for EoE patients of any age. The current results could support a trend toward less-restrictive dietary regimens as a primary treatment option.
Topics: Child; Humans; Allergens; Diet; Elimination Diets; Eosinophilic Esophagitis; Food; Treatment Outcome
PubMed: 36731591
DOI: 10.1016/j.cgh.2023.01.019