Evidence-Based Medicine

Research Appraisals

Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.

Showing 7 appraisals

Randomised Controlled TrialEvidence: Moderate
75CEBM

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

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Systematic ReviewEvidence: Weak
70CEBM

Pediatric surgery international

Single-stage versus staged reconstruction for high and intermediate anorectal malformations in neonates: a systematic review and meta-analysis

The surgical approach to high and intermediate anorectal malformations remains controversial. This systematic review compared continence and infection outcomes between the two approaches. MEDLINE, Embase, and Cochrane CENTRAL were searched per a registered protocol (PROSPERO CRD420261291319). Comparative studies of single-stage versus staged repair in neonates with high or intermediate anorectal malformations were included. Risk of bias was assessed using ROBINS-I. Random-effects meta-analysis with prediction intervals was performed. Four comparative studies (746 patients: 399 single-stage, 347 staged) were included. Pooled analysis showed no significant difference in incontinence outcomes (RR 0.93, 95% CI: 0.52-1.66, p = 0.80; 95% prediction interval: 0.28-3.08) with substantial heterogeneity (I²=83%). Infection data could not be pooled due to methodological concerns in outcome reporting. All included studies demonstrated moderate to serious risk of bias. GRADE certainty was LOW for incontinence and VERY LOW for infection. Current evidence does not demonstrate superiority of either approach for bowel continence (LOW certainty). Infection evidence was insufficient for synthesis (VERY LOW). Wide prediction intervals indicate substantial uncertainty; available data cannot confirm or refute inferior outcomes after single-stage repair. Prospective studies with standardized outcomes are needed. Protocol registration: PROSPERO CRD420261291319.

17 July 2026

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Systematic ReviewEvidence: Weak
20CEBM

Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners

Systematic Review of Studies Investigating Infant Feeding Difficulties: Focus on Machine Learning Applications

INTRODUCTION: This study aims to systematically review studies using machine learning for infant feeding difficulties and identify the clinical applicability and limitations of such approaches. METHODS: A literature search was conducted in accordance with the PRISMA guidelines. Studies on the use of machine learning for infants with feeding difficulties were analyzed. RESULTS: We screened 1,104 studies, and 10 were eligible for inclusion. These studies applied machine learning to measure physiological signals during feeding, such as the number of sucking, swallowing and breathing events, to classify or predict feeding difficulties. The most common algorithms in the analyzed studies included support vector machines (SVMs), k-nearest neighbors (KNNs), and decision trees (DTs), which generally achieved high classification accuracy. DISCUSSION: Although all included studies used sensor-based data, only four directly applied machine learning models. Future research should expand the direct applications of machine learning, standardize measurements, and validate algorithms to improve clinical utility.

2 July 2026

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Systematic ReviewEvidence: Weak
60CEBM

Annals of medicine

Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis

BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association. Published studies have identified an association between pRBC transfusion and NEC progression; however, whether this association is causal remains unclear.Despite consistent evidence from observational studies suggesting a potential association between pRBC transfusion and NEC progression, the overall quality of the evidence is low because of the lack of randomized controlled trials to determine causality.

25 May 2026

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Systematic ReviewEvidence: Weak
60CEBM

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

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Systematic ReviewEvidence: Strong
85CEBM

Gut and liver

Global Prevalence of Functional Abdominal Pain Disorder among Children and Adolescents According to the Rome III and IV Criteria: A Systematic Review and Meta-Analysis

BACKGROUND/AIMS: Despite the global burden of functional abdominal pain disorder (FAPD) and its four subtypes (irritable bowel syndrome [IBS], functional dyspepsia [FD], abdominal migraine [AM], and functional abdominal pain not otherwise specified [FAP-NOS]), studies involving an estimation of FAPD prevalence based on the Rome III or IV criteria are limited. Therefore, we aimed to estimate the prevalence of FAPD and its four subtypes. METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library. Studies that were performed with the general population and applied Rome III or IV diagnostic criteria were included. Data were extracted to estimate the prevalence of FAPD using a random-effects model with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. The study protocol was preregistered with PROSPERO (CRD420251004116). RESULTS: The overall prevalence of FAPD was 10.89% (95% CI, 9.51% to 12.48%), with pooled prevalence rates of 11.84% (10.29% to 13.61%) with the Rome III criteria and 8.42% (6.10% to 11.62%) with the Rome IV criteria. With the Rome III criteria, IBS had the highest prevalence, while FD had the lowest. In contrast, with the Rome IV criteria, the prevalence of IBS, AM, and FAP-NOS decreased, whereas FD became the most prevalent, affecting approximately one in 23 individuals, compared to one in 51 individuals affected by IBS, one in 68 individuals affected by AM, and one in 115 individuals affected by FAP-NOS. Additionally, females exhibited higher prevalence rates of FAPD and all its subtypes than males. CONCLUSIONS: The diagnostic criteria of Rome IV are stricter than those of Rome III, which likely affects the estimated prevalence of FAPD and its subtypes.

18 May 2026

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Systematic ReviewEvidence: Weak
55CEBM

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

A meta-analysis of gut microbiome research in malnourished African populations: a natural language processing approach

Malnutrition still affects millions of children in Africa. Changes in the gut microbiome have been implicated in malnutrition, but there has been inconsistent nomenclature of microbes. This meta-analysis reviews the microbiome literature using natural language processing (NLP) methods. We searched PubMed for gut microbiome studies of undernourished children living in low- and middle-income countries (LMICs). The primary analysis focused on continental coverage and study characteristics of microbiome research in sub-Saharan Africa (ss-Africa). We also used an NLP tool for normalizing primary data from full-text publications in ss-Africa compared with other LMICs, and between diseased and healthy children. We identified 16 studies. Most studies were conducted in Malawi and characterized the faecal microbiome using 16S rRNA sequencing. For comparison, 18 studies conducted in Bangladesh, India, Pakistan and Peru were included. With this, we identified frequently reported microbes that were distinctly identified in ss-Africa and highlighted possible signatures of an undernourished faecal microbiome across the globe. The consistent associations between elevated Pseudomonadota levels and severe acute malnutrition provide new insights into host-microbiome interactions in African contexts. However, the overlap between taxa associated with healthy and stunting underscores the need for further research to better inform potential targeted interventions in Africa. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

15 May 2026

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