Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
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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 →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
Congenital cytomegalovirus screening by dried blood spot: a systematic review
UNLABELLED: Congenital human cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss and neurological sequelae in children. Although newborn screening strategies remain controversial, dried blood spots (DBS) collected for routine metabolic screening have been proposed as a low-cost method for large-scale detection. This systematic review assessed studies that evaluated the accuracy of DBS testing for screening newborns for cCMV infection. A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and reported in accordance with PRISMA-DTA. The PIRT strategy included the following: Population (newborns undergoing screening for cCMV), Index test (detection of cCMV using DBS samples), Reference standard (confirmatory testing using saliva or urine PCR collected within 21 days of life), Target condition (cCMV infection). Searches were performed in PubMed/MEDLINE, Scopus, Bireme, Embase, LILACS, SciELO, and CENTRAL. The search identified 365 articles; after removing 210 duplicates, 155 were screened by title and abstract, and 9 studies were included. The included studies tested between 1174 and 551,034 DBS samples each. Confirmatory testing used PCR in urine (seven studies) or saliva (two studies). Three studies used paired samples for screening; sensitivity ranged from 28.3% to 79.3%, specificity from 99.9% to 100%. Positive predictive value (PPV) ranged from 39 to 100%, and negative predictive value (NPV) from 99.6% to 99.9%. CONCLUSION: Neonatal screening for congenital cytomegalovirus using DBS samples is promising, since it would allow early identification for timely interventions to reduce sequelae. WHAT IS KNOWN: • Congenital CMV is a leading cause of sensorineural hearing loss and neurodevelopmental sequelae, with many cases asymptomatic at birth. Diagnosis relies on early viral detection, and while saliva/urine PCR is sensitive, newborn screening lacks consensus and feasibility is unknown in many settings. WHAT IS NEW: • DBS PCR emerges as a scalable, feasible low-cost screening alternative for cCMV screening. A few states in the USA and provinces in Canada have implemented newborn cCMV screening programs using DBS, but the sensitivity appears lower than in research studies. Improving DNA extraction and PCR methods are required as well as assessing feasibility of using other specimens (e.g., urine or saliva) for screening.
28 June 2026
Read appraisal →The Journal of infectious diseases
Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial
BACKGROUND: Cerebral malaria (CM) is a common cause of febrile coma among African children. Despite treatment with highly efficacious intravenous artesunate, CM remains associated with high mortality and neurologic sequelae. In a mouse CM model, the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) demonstrated robust efficacy as a potential adjuvant therapy. Before testing DON in children with CM, we investigated tolerability in African adults, including individuals with malaria. METHODS: We conducted an open-label, prospective, dose-escalation, phase 1 clinical trial of single-dose intravenous DON in Blantyre, Malawi. Participants included healthy adults and adults with uncomplicated malaria, enrolled in dose-cohorts of 10 and administered DON at 0.1, 1.0, 5.0, or 10 mg/kg. We assessed adverse events (AEs) and plasma pharmacokinetics. RESULTS: Forty healthy adults and 38 adults with uncomplicated malaria received DON. Transient, asymptomatic creatinine elevation occurred 12 hours postinfusion in 18% of all participants. Nausea and vomiting were uncommon at 0.1 and 1.0 mg/kg but occurred more frequently at 5.0 and 10 mg/kg DON. All DON-related AEs resolved rapidly, without sequelae, and did not significantly differ between healthy and uncomplicated malaria participants. In healthy adults, maximum plasma concentrations increased proportional to dose, but adults with malaria had greater than dose-proportional increases. Terminal half-life ranged from 1.7 to 4.1 hours. CONCLUSIONS: DON was well tolerated in healthy adults and adults with uncomplicated malaria. Higher doses were associated with transient gastrointestinal AEs. Pharmacokinetics were minimally influenced by malaria disease. These results provide critical data to guide dosing strategies for adjunctive DON in children with CM. Clinical Trials Registration. NCT05478720.
18 May 2026
Read appraisal →European journal of pediatrics
7-days versus 14-days antibiotic therapy in uncomplicated culture proven neonatal sepsis: a randomized control assessor-blinded trial
UNLABELLED: The trial aimed to establish the non-inferiority of a 7-day antibiotic therapy for uncomplicated neonatal sepsis when compared to the standard 14-day therapy. This study was a parallel-group, randomized non-inferiority assessor-blinded trial conducted in a tertiary Neonatal Intensive Care Unit in Central India. Neonates weighing ≥ 1000 g with suspected sepsis were screened and those meeting criteria were enrolled. Exclusions included babies with CNS (central nervous system) infections, septic arthritis, and life-threatening congenital malformations. Participants were observed for 7 days on antibiotics and re-evaluated; those with positive blood cultures were then randomized to receive either 7 or 14 days of antibiotics. The primary outcome was the relapse of sepsis, and a sample size of 70 in each arm was calculated based on a non-inferiority margin. Follow-ups were conducted for 48 h post-antibiotic treatment and weekly for 35 days to monitor any recurrence of illness. During the study, 917 babies with suspected sepsis were admitted, of which 256 had culture-positive sepsis. After excluding those with meningitis, staphylococcus, and fungal infections, 140 babies showed improvement at day 5 and were randomized into two groups: one receiving antibiotics for 7 days and the other for 14 days, each consisting of 70 babies. Klebsiella pneumoniae was the prevalent organism. The 7-day group had a shorter hospital stay (p < 0.05) and less respiratory support (p < 0.05). Outcomes revealed a low incidence of probable relapse in both groups, with no fatalities or definitive relapses recorded. CONCLUSIONS: A 7-day antibiotic regimen for uncomplicated neonatal sepsis is not inferior to a 14-day regimen. WHAT IS KNOWN: • Unregulated use of antibiotics can lead to a myriad of problems, especially in neonates. • There is some evidence that uncomplicated neonatal sepsis can be treated with short-course antibiotics. WHAT IS NEW: • Data is lacking-especially from Central India. • This trial checks if it is possible to reduce the duration of antibiotic therapy in uncomplicated neonatal sepsis.
16 Apr 2026
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