ImportanceIntraventricular hemorrhage (IVH) has been described to typically occur during the early hours of life (HOL); however, the exact time of onset is still unknown.ObjectiveTo investigate the temporal distribution of IVH reported in very preterm neonates.Data SourcesPubMed, Embase, Cochrane Library, and Web of Science were searched on May 9, 2024.Study SelectionArticles were selected in which at least 2 cranial ultrasonographic examinations were performed in the first week of life to diagnose IVH. Studies with only outborn preterm neonates were excluded.Data Extraction And SynthesisData were extracted independently by 3 reviewers. A random-effects model was applied. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The Quality in Prognostic Studies 2 tool was used to assess the risk of bias.Main Outcomes And MeasuresThe overall occurrence of any grade IVH and severe IVH among preterm infants was calculated along with a 95% CI. The temporal distribution of the onset of IVH was analyzed by pooling the time windows 0 to 6, 0 to 12, 0 to 24, 0 to 48, and 0 to 72 HOL. A subgroup analysis was conducted using studies published before and after 2007 to allow comparison with the results of a previous meta-analysis.ResultsA total of 21 567 records were identified, of which 64 studies and data from 9633 preterm infants were eligible. The overall rate of IVH did not decrease significantly before vs after 2007 (36%; 95% CI, 30%-42% vs 31%; 95% CI, 25%-36%), nor did severe IVH (10%; 95% CI, 7%-13% vs 11%; 95% CI, 8%-14%). The proportion of very early IVH (up to 6 HOL) after 2007 was 9% (95% CI, 3%-23%), which was 4 times lower than before 2007 (35%; 95% CI, 24%-48%). IVH up to 24 HOL before and after 2007 was 44% (95% CI, 31%-58%) and 25% (95% CI, 15%-39%) and up to 48 HOL was 82% (95% CI, 65%-92%) and 50% (95% CI, 34%-66%), respectively.Conclusion And RelevanceThis systematic review and meta-analysis found that the overall prevalence of IVH in preterm infants has not changed significantly since 2007, but studies after 2007 showed a later onset as compared with earlier studies, with only a small proportion of IVHs occurring before 6 HOL.

BACKGROUND:With the introduction of new therapy modalities and the resulting increase in survival rates, childhood brain cancers have become a focal point of research in pediatric oncology. In current protocols, besides surgical resection and chemotherapy, radiotherapy is required to ensure optimal survival. Our aim was to determine which of the two major irradiation options, proton (PT) or photon (XRT), was the least harmful yet effective for children with brain tumors. METHODS:The protocol was registered on PROSPERO in advance (CRD42022374443). A systematic search was performed in four databases (MEDLINE via (PubMed), Embase, Cochrane Library, and Scopus) on 23 April 2024. Odd ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Survival and six major types of side effects were assessed based on data in the articles and reported using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Heterogeneity was assessed using Higgins and Thompson's I2 statistics. RESULTS:Altogether, 5848 articles were screened, of which 33 were eligible for data extraction. The 5-year overall survival results showed statistically no significant difference between the two radiotherapy modalities (OR = 0.80, 95% CI: 0.51-1.23, p = 0.22, I2 = 0%). In terms of toxicity rates, an advantage was found for PT, particularly in terms of chronic endocrine side effects (hypothyroidism OR: 0.22, 95% CI: 0.10-0428, p = 0.002, I2 = 68%), neurocognitive decline (global IQ level MD: 13.06, 95% CI: 4.97-21.15, p = 0.009, I2 = 68%). As for hematological, acute side effects, neurological changes and ophthalmologic disorders PT can be beneficial for survivors in terms of reducing them. CONCLUSIONS:In comparison with XRT, PT can reduce most side effects, without significantly decreasing the survival rate. There is considerable clinical relevance in the findings, even not all of them are statistically significant, which may facilitate the development of protocols regarding the usage of radiotherapy methods, and may encourage the establishment of more proton centers, where more studies can be done.

IMPORTANCE Intraventricular hemorrhage (IVH) has been described to typically occur during the early hours of life (HOL); however, the exact time of onset is still unknown. OBJECTIVE To investigate the temporal distribution of IVH reported in very preterm neonates. DATA SOURCES PubMed, Embase, Cochrane Library, and Web of Science were searched on May 9, 2024. STUDY SELECTION Articles were selected in which at least 2 cranial ultrasonographic examinations were performed in the first week of life to diagnose IVH. Studies with only outborn preterm neonates were excluded. DATA EXTRACTION AND SYNTHESIS Data were extracted independently by 3 reviewers. A random-effects model was applied. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The Quality in Prognostic Studies 2 tool was used to assess the risk of bias. MAIN OUTCOMES AND MEASURES The overall occurrence of any grade IVH and severe IVH among preterm infants was calculated along with a 95% CI. The temporal distribution of the onset of IVH was analyzed by pooling the time windows 0 to 6, 0 to 12, 0 to 24, 0 to 48, and 0 to 72 HOL. A subgroup analysis was conducted using studies published before and after 2007 to allow comparison with the results of a previous meta-analysis. RESULTS A total of 21567 records were identified, of which 64 studies and data from 9633 preterm infants were eligible. The overall rate of IVH did not decrease significantly before vs after 2007(36%; 95% CI, 30%-42% vs 31%; 95% CI, 25%-36%), nor did severe IVH (10%; 95% CI, 7%-13% vs 11%; 95% CI, 8%-14%). The proportion of very early IVH (up to 6 HOL) after 2007 was 9% (95% CI, 3%-23%), which was 4 times lower than before 2007(35%; 95% CI, 24%-48%). IVH up to 24 HOL before and after 2007 was 44% (95% CI, 31%-58%) and 25% (95% CI, 15%-39%) and up to 48 HOL was 82% (95% CI, 65%-92%) and 50% (95% CI, 34%-66%), respectively. CONCLUSION AND RELEVANCE This systematic review and meta-analysis found that the overall prevalence of IVH in preterm infants has not changed significantly since 2007, but studies after 2007 showed a later onset as compared with earlier studies, with only a small proportion of IVHs occurring before 6 HOL.

ImportanceSignificant advancements in pediatric oncology have led to a continuously growing population of survivors. Although extensive research is being conducted on the short-, medium-, and long-term somatic effects, reports on psychosocial reintegration are often conflicting; therefore, there is an urgent need to synthesize the evidence to obtain the clearest understanding and the most comprehensive answer.ObjectiveTo provide a comprehensive review and analysis of the socioeconomic attainment of childhood cancer survivors (CCSs) compared with their unaffected peers.Data SourcesA systematic review and meta-analysis was conducted using data obtained from a comprehensive search of MEDLINE (via PubMed), Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases on October 23, 2021; the search was updated until July 31, 2023.Study SelectionEligible articles reported on educational attainment, employment, family formation, quality of life (QoL), or health-risk behavior-related outcomes of CCSs, and compared them with their unaffected peers. Study selection was performed in duplicate by 4 blinded independent coauthors.Data Extraction and SynthesisData extraction was performed in duplicate by 4 independent authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcome measures were odds ratios (ORs) and mean differences with 95% CIs; data were pooled using a random-effects model.ResultsThe search identified 43 913 articles, 280 of which were eligible for analysis, reporting data on a total of 389 502 survivors. CCSs were less likely to complete higher levels of education (OR, 0.69; 95% CI, 0.40-1.18), had higher odds of health-related unemployment (OR, 2.94; 95% CI, 1.90-4.57), and showed lower rates of marriage (OR, 0.72; 95% CI, 0.63-0.84) and parenthood (OR, 0.60; 95% CI, 0.49-0.74) compared with population-based controls.Conclusion and RelevanceStudy findings suggest that CCSs face several socioeconomic difficulties; as a result, the next goal of pediatric oncology should be to minimize adverse effects, as well as to provide lifelong survivorship support aimed at maximizing social reintegration.

Importance:Significant advancements in pediatric oncology have led to a continuously growing population of survivors. Although extensive research is being conducted on the short-, medium-, and long-term somatic effects, reports on psychosocial reintegration are often conflicting; therefore, there is an urgent need to synthesize the evidence to obtain the clearest understanding and the most comprehensive answer. Objective:To provide a comprehensive review and analysis of the socioeconomic attainment of childhood cancer survivors (CCSs) compared with their unaffected peers. Data Sources:A systematic review and meta-analysis was conducted using data obtained from a comprehensive search of MEDLINE (via PubMed), Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases on October 23, 2021; the search was updated until July 31, 2023. Study Selection:Eligible articles reported on educational attainment, employment, family formation, quality of life (QoL), or health-risk behavior-related outcomes of CCSs, and compared them with their unaffected peers. Study selection was performed in duplicate by 4 blinded independent coauthors. Data Extraction and Synthesis:Data extraction was performed in duplicate by 4 independent authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcome measures were odds ratios (ORs) and mean differences with 95% CIs; data were pooled using a random-effects model. Results:The search identified 43 913 articles, 280 of which were eligible for analysis, reporting data on a total of 389 502 survivors. CCSs were less likely to complete higher levels of education (OR, 0.69; 95% CI, 0.40-1.18), had higher odds of health-related unemployment (OR, 2.94; 95% CI, 1.90-4.57), and showed lower rates of marriage (OR, 0.72; 95% CI, 0.63-0.84) and parenthood (OR, 0.60; 95% CI, 0.49-0.74) compared with population-based controls. Conclusion and Relevance:Study findings suggest that CCSs face several socioeconomic difficulties; as a result, the next goal of pediatric oncology should be to minimize adverse effects, as well as to provide lifelong survivorship support aimed at maximizing social reintegration.

Background Current paediatric cancer care requires innovative approaches to predict prognosis that facilitates personalised stratification, yet studies on the performance, composition and limitations of contemporary prognostic models are lacking. We aimed to compare the accuracy of traditional and advanced prognostic models. Methods A systematic search for this systematic review and meta-analysis (CRTN42022370251) was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases on 28 June 2024. Studies on the accuracy of prognostic markers or models used in paediatric haematological malignancies, central nervous system (CNS), or non-CNS solid tumours (NCNSST) were included. Three model categories were defined using: 1-clinical parameters, 2-genomic-transcriptomic data, and 3-artificial intelligence (AI). Primary outcomes were area under the receiver operating characteristic curve with a 95% confidence interval (CI) for various overall survival intervals and event-free survival. Two independent groups performed selection and data extraction. We used data published by the authors and publicly available databases. Findings Of 12,982 studies, 358 were included in the meta-analysis and 27 in the systematic review, with limited data on AI-approaches. Most data were reported on NCNSST at 5-year OS, where a statistically significant difference was observed between Category-1 (0.75 CI: 0.72-0.79) and Category-2 (0.85 CI: 0.82-0.88) (p < 0.001), but not between Categories-2 and-3 (p = 0.2834) (0.82 CI: 0.77-0.88). Internal validation studies showed significantly better performance compared to those using external validation, highlighting the high risk of bias (ROB) inherent in internal validation. High ROB was most commonly experienced in the outcomes and statistical analysis domains, assessed using PROBAST and QUIPS. Interpretation It is advisable to introduce Category-2 and-3 models in a clinical setting, especially for NCNSST prognostic for aiding risk-stratification. Although AI-supported predictions in paediatric oncology are at an early stage of development, it is imperative to further explore their potential. This requires structured data collection and ethical sharing from paediatric oncology patients in sufficient quantity and quality. Funding None. 2024;78: 102902 Published Online https://doi.org/10. 1016/j.eclinm.2024. 102902

Background Paediatric patients are often exposed to subtherapeutic levels or treatment failure of beta-lactams, and prolonged infusion may be beneficial. We aimed to investigate the efficacy and safety of extended infusion (EI; defined as >= 3 h) or continuous infusion vs. short, intermittent infusion (SI; defined as <= 60 min) of beta-lactams in patients <21 years of age.Methods A systematic review and meta-analysis was conducted to compare EI and continuous infusion with SI of beta-lactams in children. A systematic search was performed in MEDLINE (via PubMed), Embase, CENTRAL, and Scopus databases for randomised controlled trials (RCTs) and observational studies published from database inception up to August 22, 2023. Any comparative study concerned with mortality, clinical efficacy, adverse events, or plasma concentrations of beta-lactams for any infection was eligible. Case reports, case series, and patients aged >21 years were excluded. Odds ratios (OR) and median differences with 95% confidence intervals (CI) were calculated using a random-effects model. Risk of bias (ROB) was assessed using ROB2 and ROBINS-I tools. The protocol was registered with PROSPERO, CRD42022375397.Findings In total, 19,980 articles were screened, out of which 19 studies (4195 patients) were included in the meta-analysis. EI administration was associated with a significantly lower all-cause mortality in both RCTs and non-RCTs [OR 0.74; CI 0.55-0.99; I-2 = 0%; CI 0-58%]. Early microbiological eradication was higher with EI [OR 3.18; CI 2.24-4.51; I-2 = 0%; CI 0-90%], but the clinical cure did not differ significantly between the two groups [OR 1.20; CI 0.17-8.71; I-2 = 79%; CI 32-93%]. Achieving the optimal plasma level (50-100% fT > MIC) appeared favourable in the EI group compared to the SI. No significant differences were observed in the adverse events. The overall ROB was high because of the small sample sizes and clinically heterogeneous populations.Interpretation Our findings suggest that extended infusion of beta-lactams was associated with lower mortality and increased microbiological eradication and was considered safe compared to short-term infusion.