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Alimentary Pharmacology & Therapeutics Jan 2023The effects of early feeding practices on the risk of coeliac disease (CD) remain debated. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effects of early feeding practices on the risk of coeliac disease (CD) remain debated.
AIMS
To update evidence on these practices on the risk of CD and/or CD-related autoimmunity (CDA), defined as anti-transglutaminase or anti-endomysial antibody positivity METHODS: We searched MEDLINE, EMBASE and the Cochrane Library to May 2022 for randomised controlled trials (RCTs) and observational studies.
RESULTS
We included 36 publications (30 studies). In the population at genetic risk of developing CD (HLA DQ2/DQ8-positive), exclusive or any breastfeeding and longer breastfeeding duration did not reduce the risk of developing CD/CDA during childhood. While a meta-analysis of four case-control studies showed a decreased risk for CD when gluten was introduced during breastfeeding, this was not shown in RCTs and cohort studies. Age at gluten introduction was not associated with cumulative CD/CDA risk, although two RCTs suggested that earlier gluten introduction was associated with earlier CDA appearance. Evidence from six observational studies suggests that consumption of a higher amount of gluten at weaning and/or thereafter may increase CD risk. There is insufficient evidence to determine the amount of gluten associated with an increased CD/CDA risk. Regarding whether infant feeding practices modulate the risk conferred by different HLA genotypes results were inconsistent.
CONCLUSIONS
For the population at genetic risk of CD, breastfeeding and age at gluten introduction have no effect on its cumulative incidence during childhood. There is some evidence for an effect of the amount of gluten consumed at weaning and/or thereafter on CD/CDA risk.
Topics: Humans; Celiac Disease; Evidence Gaps
PubMed: 36411726
DOI: 10.1111/apt.17290 -
Graefe's Archive For Clinical and... Apr 2022Recently, endothelial keratoplasty (EK) has been increasingly considered the first intervention in pediatrics with isolated corneal endothelial dysfunction. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recently, endothelial keratoplasty (EK) has been increasingly considered the first intervention in pediatrics with isolated corneal endothelial dysfunction. This systematic review aims to investigate the current evidence about the advantages, disadvantages, technical challenges, and clinical outcomes of EK in the pediatric group.
METHOD
All the English literature relevant to pediatric EK was searched in PubMed, Embase, Scopus, and Cochrane databases with appropriate keywords. Relevant data were pooled to conduct an individual participant data meta-analysis.
RESULTS
Of 1646 articles found initially, 35 articles were finally eligible to be included in our study. A total of 154 eyes of 107 patients underwent Descemet's stripping automated endothelial keratoplasty (DSAEK). Congenital hereditary endothelial dystrophy (CHED) was the most reported indication for pediatric DSAEK (108 eyes). Descemet's membrane endothelial keratoplasty (DMEK) was performed in 2 eyes of 2 cases, one with PPCD and another one in a patient with Kearns-Sayre syndrome. Owing to some specific anatomical and physiological pediatric characteristics, some modifications in a standard procedure were suggested. The average follow-up period was 23.80 ± 20.18 months (3 months to 8.5 years). Seventy-six eyes who had a mean best-corrected visual acuity (BCVA) of 1.36 ± 0.70 (0.49 to 3) logMAR preoperatively found mean BCVA of 0.51 ± 0.33 (0.04 to 2) logMAR postoperatively. Graft dislocation was the most reported complication (26 eyes). The rate of other complications was low. Endothelial cell loss was reported from 8.3 to 63.7% after pediatric EK with follow-up duration from 3 months to 8.3 years.
CONCLUSION
EK procedures, despite some technical challenges, are feasible surgical techniques with acceptable visual and anatomical outcomes in the management of pediatrics with corneal endothelial dysfunction and minimal stromal involvement.
Topics: Child; Descemet Membrane; Descemet Stripping Endothelial Keratoplasty; Endothelium, Corneal; Fuchs' Endothelial Dystrophy; Humans; Pediatrics; Retrospective Studies; Visual Acuity
PubMed: 34709453
DOI: 10.1007/s00417-021-05459-8 -
BMC Pediatrics Apr 2022Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children...
BACKGROUND
Vedolizumab use in pediatrics is still off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD).
METHODS
PubMed, EMBASE and Cochrane databases were systematically searched for studies of vedolizumab in children and adolescents with IBD reporting clinical remission, response, corticosteroid-free (CS-free) remission, mucosal healing, or safety up to December 3 2021.
RESULTS
Ten studies, comprising 455 patients were included. For CD, the pooled clinical remission rates were 25% (19/75) at 6 weeks, 28% (25/85) at 14 weeks, 32% (17/53) at 22 weeks, and 46% (43/92) at 1 year. For UC/IBD-U, the pooled clinical remission rates were 36% (25/70) at 6 weeks, 48% (52/101) at 14 weeks, 53% (24/45) at 22 weeks, and 45% (50/112) at 1 year. Mucosal healing was found in 17%-39% of CD and 15%-34% of UC/IBD-U respectively. Six percent of patients reported serious adverse events.
CONCLUSIONS
According to low-quality evidence based on case series, approximately one-third and one-half of patients for CD and UC/IBD-U respectively achieved remission within 22 weeks, and about half of patients achieved remission at 1 year with reasonable safety profile. Long-term benefit profile data and high quality evidence are still needed.
Topics: Adolescent; Antibodies, Monoclonal, Humanized; Child; Humans; Inflammatory Bowel Diseases; Pediatrics; Remission Induction
PubMed: 35379216
DOI: 10.1186/s12887-022-03229-x -
Resuscitation Mar 2021To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest. (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest.
METHODS
We searched Medline, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL) for human randomized clinical trials and observational studies including comparative cohorts. Two investigators reviewed relevance of studies, extracted the data, conducted meta-analyses and assessed the risk of bias using the GRADE and CLARITY frameworks. Authors of the eligible studies were contacted to obtain additional data. Critically important outcomes included return of spontaneous circulation, survival to hospital discharge and survival with good neurological outcome.
RESULTS
We identified 7 observational studies suitable for meta-analysis and no randomized clinical trials. The overall certainty of evidence was very low. For the critically important outcomes, the earlier administration of epinephrine was favorable for both in-hospital and out-of-hospital cardiac arrest. Because of a limited number of eligible studies and the presence of severe confounding factors, we could not determine the optimal interval of epinephrine administration.
CONCLUSIONS
Earlier administration of the first epinephrine dose could be more favorable in non-shockable pediatric cardiac arrest. The optimal interval for epinephrine administration remains unclear.
Topics: Child; Epinephrine; Humans; Infant; Out-of-Hospital Cardiac Arrest; Patient Discharge
PubMed: 33529645
DOI: 10.1016/j.resuscitation.2021.01.015 -
BMJ Supportive & Palliative Care Jun 2020To review literature relating to evidence, context and facilitation to describe knowledge translation in paediatric palliative care. Paediatric palliative care requires...
OBJECTIVES
To review literature relating to evidence, context and facilitation to describe knowledge translation in paediatric palliative care. Paediatric palliative care requires competences including both paediatric specialists as well as services that are developed for this purpose, and there is a need to facilitate paediatric palliative care knowledge translation. Promoting Action on Research Implementation in the Health Services (PARiHS) is a framework for knowledge translation, which highlights the relationships between evidence, context and facilitation. PARiHS framework has been revised and updated in a new version called i-PARiHS.
METHODS
The electronic databases AgeLine, CINAHL, The Cochrane Library, PsycINFO, PubMed and Scopus were searched. Papers included were limited to English and Swedish publications and restricted to publications dated between 1993 and August 2019. All types of observational and experimental studies using any research design were included.
RESULTS AND CONCLUSIONS
Thirty-eight articles were included and there was a common vision about how and when palliative care should be offered to children. The i-PARiHS was used as a lens to describe the knowledge translation in paediatric palliative care. Symptom relief was the most commonly described evidence-based strategy, and the hospital environment was the most commonly described context. Different types of education were the most commonly used strategies to facilitate knowledge translation. The results mainly focused on increasing knowledge of palliative care in paediatric care. To sum up, the results report strategies to achieve knowledge translation of paediatric palliative care, and these can be interpreted as a guideline for how this process can be facilitated.
TRIAL REGISTRATION NUMBER
CRD42018100663.
Topics: Child; Female; Health Services Research; Humans; Male; Palliative Care; Pediatrics; Translational Research, Biomedical
PubMed: 31836595
DOI: 10.1136/bmjspcare-2019-001934 -
The Lancet. Oncology Sep 2023Approximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 90% of children with cancer live in low-income and middle-income countries (LMICs), where 5-year survival is lower than 20%. Treatment-related mortality in high-income countries is approximately 3-5%; however, in LMICs, treatment-related mortality has been reported in up to 45% of children with cancer. This study aimed to systematically explore the burden of treatment-related mortality in children with cancer in LMICs and to explore the association between country income level and treatment-related mortality.
METHODS
For this systematic review and meta-analysis we identified articles published between Jan 1, 2010, and June 22, 2021, describing treatment-related mortality in paediatric patients (aged 0-21 years) with cancer in LMICs. We searched PubMed, Trip, Web of Science, Embase, and the WHO Global Metric Index databases. The search was limited to full-text articles and excluded case reports (<10 patients) and haematopoietic stem-cell transplantation recipients. Two reviewers independently screened studies for eligibility, extracted data from included publications, and evaluated data quality. Random and mixed-effects models were used to estimate treatment-related mortality burden and trends. The Cochran-Q statistic was used to assess heterogeneity between studies. This study is registered on PROSPERO (CRD42021264849).
FINDINGS
Of 13 269 identified abstracts, 501 studies representing 68 351 paediatric patients with cancer were included. The treatment-related mortality estimate was 6·82% (95% CI 5·99-7·64), accounting for 30·9% of overall mortality (4437 of 14 358 deaths). Treatment-related mortality was inversely related to country income. Treatment-related mortality was 14·19% (95% CI 9·65-18·73) in low-income countries, 9·21% (7·93-10·49) in lower-middle-income countries, and 4·47% (3·42-5·53) in upper-middle-income countries (Cochran-Q 42·39, p<0·0001). In upper-middle-income countries, the incidence of treatment-related mortality decreased over time (slope -0·002, p=0·0028); however, outcomes remained unchanged in low-income (p=0·21) and lower-middle-income countries (p=0·16).
INTERPRETATION
Approximately one in 15 children receiving cancer treatment in LMICs die from treatment-related complications. Although treatment-related mortality has decreased in upper-middle-income countries over time, it remains unchanged in LMICs. There is an urgent need for targeted supportive care interventions to reduce global disparities in childhood cancer survival.
FUNDING
American Lebanese Syrian Associated Charities and National Cancer Institute.
Topics: Humans; Child; Developing Countries; Income; Poverty; Neoplasms
PubMed: 37517410
DOI: 10.1016/S1470-2045(23)00318-2 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk... (Meta-Analysis)
Meta-Analysis Review
Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.
Topics: Humans; Child; Masked Hypertension; Hypertrophy, Left Ventricular; Blood Pressure Monitoring, Ambulatory; Carotid Intima-Media Thickness; Prevalence; Pulse Wave Analysis; Hypertension; Blood Pressure
PubMed: 37737026
DOI: 10.1161/HYPERTENSIONAHA.123.20967 -
Dialogues in Clinical Neuroscience 2021Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better... (Review)
Review
Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better understanding of brain function, both normal and abnormal, throughout developmental stages. The degree to which childhood epilepsies exert a significant effect on brain network organisation and cognition remains unclear. The hypothesis suggests that the formation of abnormal networks associated with epileptogenesis early in life causes a disruption in normal brain network development and cognition, reflecting abnormalities in later life. Neurological diseases with onset during critical stages of brain maturation, including childhood epilepsy, may threaten this orderly neurodevelopmental process. According to the hypothesis that the formation of abnormal networks associated with epileptogenesis in early life causes a disruption in normal brain network development, it is then mandatory to perform a proper examination of children with new-onset epilepsy early in the disease course and a deep study of their brain network organisation over time. In regards, graph theoretical analysis could add more information. In order to facilitate further development of graph theory in childhood, we performed a systematic review to describe its application in functional dynamic connectivity using electroencephalographic (EEG) analysis, focussing on paediatric epilepsy.
Topics: Brain; Brain Mapping; Child; Cognition; Electroencephalography; Epilepsy; Humans; Magnetic Resonance Imaging; Nerve Net; Neurodevelopmental Disorders
PubMed: 35860177
DOI: 10.1080/19585969.2022.2043128 -
Epilepsia Dec 2023Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based... (Review)
Review
Scoping review and expert-based consensus recommendations for assessment and management of psychogenic non-epileptic (functional) seizures (PNES) in children: A report from the Pediatric Psychiatric Issues Task Force of the International League Against Epilepsy.
Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based recommendations to fill this gap. The members of the International League Against Epilepsy (ILAE) Task Force on Pediatric Psychiatric Issues conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SR) standards. This was supplemented with a Delphi process sent to pediatric PNES experts. Consensus was defined as ≥80% agreement. The systematic search identified 77 studies, the majority (55%) of which were retrospective (only one randomized clinical trial). The primary means of PNES identification was video electroencephalography (vEEG) in 84% of studies. Better outcome was associated with access to counseling/psychological intervention. Children with PNES have more frequent psychiatric disorders than controls. The Delphi resulted in 22 recommendations: Assessment-There was consensus on the importance of (1) taking a comprehensive developmental history; (2) obtaining a description of the events; (3) asking about potential stressors; (4) the need to use vEEG if available parent, self, and school reports and video recordings can contribute to a "probable" diagnosis; and (5) that invasive provocation techniques or deceit should not be employed. Management-There was consensus about the (1) need for a professional with expertise in epilepsy to remain involved for a period after PNES diagnosis; (2) provision of appropriate educational materials to the child and caregivers; and (3) that the decision on treatment modality for PNES in children should consider the child's age, cognitive ability, and family factors. Comorbidities-There was consensus that all children with PNES should be screened for mental health and neurodevelopmental difficulties. Recommendations to facilitate the assessment and management of PNES in children were developed. Future directions to fill knowledge gaps were proposed.
Topics: Humans; Child; Retrospective Studies; Consensus; Seizures; Epilepsy; Mental Disorders; Electroencephalography; Randomized Controlled Trials as Topic
PubMed: 37804168
DOI: 10.1111/epi.17768 -
The European Respiratory Journal Mar 2023Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.
METHODS
We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC) and peak plasma concentration ( ) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC and were assessed with linear mixed-effects models.
RESULTS
Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC for isoniazid and pyrazinamide. -acetyltransferase 2 rapid acetylators had lower isoniazid AUC and slow acetylators had higher isoniazid AUC than intermediate acetylators. Determinants of were generally similar to those for AUC.
CONCLUSIONS
This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.
Topics: Child; Adolescent; Humans; Child, Preschool; Antitubercular Agents; Isoniazid; Pyrazinamide; Ethambutol; Rifampin
PubMed: 36328357
DOI: 10.1183/13993003.01596-2022