METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed.
RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity.
CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.
METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports.
RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting.
CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.
METHODS: We conducted a systematic review of published CVD mortality studies that reported ASMR as an indicator for premature mortality measurement. All English articles published as of October 2022 were searched in four electronic databases: PubMed, Scopus, Web of Science (WoS), and the Cochrane Central Register of Controlled Trials (CENTRAL). We computed pooled estimates of ASMR using random-effects meta-analysis. We assessed heterogeneity from the selected studies using the I2 statistic. Subgroup analyses and meta regression analysis was performed based on sex, main CVD types, income country level, study time and age group. The analysis was performed using R software with the "meta" and "metafor" packages.
RESULTS: A total of 15 studies met the inclusion criteria. The estimated global ASMR for premature mortality from total CVD was 96.04 per 100,000 people (95% CI: 67.18, 137.31). Subgroup analysis by specific CVD types revealed a higher ASMR for ischemic heart disease (ASMR = 15.57, 95% CI: 11.27, 21.5) compared to stroke (ASMR = 12.36, 95% CI: 8.09, 18.91). Sex-specific differences were also observed, with higher ASMRs for males (37.50, 95% CI: 23.69, 59.37) than females (15.75, 95% CI: 9.61, 25.81). Middle-income countries had a significantly higher ASMR (90.58, 95% CI: 56.40, 145.48) compared to high-income countries (21.42, 95% CI: 15.63, 29.37). Stratifying by age group indicated that the age groups of 20-64 years and 30-74 years had a higher ASMR than the age group of 0-74 years. Our multivariable meta-regression model suggested significant differences in the adjusted ASMR estimates for all covariates except study time.
CONCLUSIONS: This meta-analysis synthesized a comprehensive estimate of the worldwide burden of premature CVD mortality. Our findings underscore the continued burden of premature CVD mortality, particularly in middle-income countries. Addressing this issue requires targeted interventions to mitigate the high risk of premature CVD mortality in these vulnerable populations.
METHODS: C0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C0 and AUC0-24. An external dataset was used for predictive performance evaluation.
RESULTS: Before starting treatment, C0 can be predicted a priori using the Catboost-based C0-ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C0) in patients have been obtained, AUC0-24 can be further predicted using the Catboost-based AUC-ML model combined with C0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%.
CONCLUSION: C0-based and AUC0-24-based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively.
MATERIALS AND METHODS: A total of 110 nasopharyngeal swabs (NPS) were collected from children aged one month to 12 years old who were admitted with ARI in UKMMC during a one-year period. The two qPCR assays were conducted in parallel.
RESULTS: Ninety-seven samples (88.2%) were positive by QIAstat-Dx RP and 86 (78.2%) by RespiFinder assay. The overall agreement on both assays was substantial (kappa value: 0.769) with excellent concordance rate of 96.95%. Using both assays, hRV/EV, INF A/H1N1 and RSV were the most common pathogens detected. Influenza A/H1N1 infection was significantly seen higher in older children (age group > 60 months old) (53.3%, p-value < 0.05). Meanwhile, RSV and hRV/EV infection were seen among below one-year-old children. Co-infections by two to four pathogens were detected in 17 (17.5%) samples by QIAstat-Dx RP and 12 (14%) samples by RespiFinder, mainly involving hRV/EV. Bacterial detection was observed only in 5 (4.5%) and 6 (5.4%) samples by QIAstat-Dx RP and RespiFinder, respectively, with Mycoplasma pneumoniae the most common detected.
CONCLUSION: The overall performance of the two qPCR assays was comparable and showed excellent agreement. Both detected various clinically important respiratory pathogens in a single test with simultaneous multiple infection detection. The use of qPCR as a routine diagnostic test can improve diagnosis and management.
OBJECTIVES: 1. To assess the effects of CPAP on AoP in preterm infants (this may be compared to supportive care or mechanical ventilation). 2. To assess the effects of different CPAP delivery systems on AoP in preterm infants.
SEARCH METHODS: Searches were conducted in September 2022 in the following databases: Cochrane Library, MEDLINE, Embase, and CINAHL. We also searched clinical trial registries and the reference lists of studies selected for inclusion.
SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials (RCTs) in which researchers determined that CPAP was necessary for AoP in preterm infants (born before 37 weeks). Cross-over studies were also included, provided sufficient data were available for analysis.
DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of risk of bias and extraction of data by at least two review authors. Discrepancies were resolved by involvement of a third author. We used the GRADE approach to assess the certainty of evidence for the following outcomes: 1) failed CPAP; 2) apnoea; 3) adverse effects of CPAP.
MAIN RESULTS: We included four single-centre trials conducted in Malaysia, Spain, Germany, and North America, involving 138 infants with a mean/median gestation of 26 to 28 weeks. Two studies were parallel-group RCTs and two were cross-over trials. None of the studies compared CPAP with supportive care. All trials compared one form of CPAP with another. Two compared a variable flow device with ventilator CPAP, one compared two different variable flow devices, and one compared a variable flow device with bubble CPAP. Interventions were administered for periods ranging between six and 48 hours, with pressures between 4 and 6 cm H2O. We assessed all trials as having a high risk of bias for blinding of participants and personnel, and two studies for blinding of outcome assessors. We found a high risk of a carry-over effect in two studies where the washout period was not adequately described, and a high risk of bias in a study that appeared to use an analysis method not generally accepted for cross-over studies. Comparison 1. CPAP and supportive care compared to supportive care alone We did not identify any study for inclusion in this comparison. Comparison 2. CPAP delivered by different types of devices 2a. Variable flow compared to ventilator CPAP Two studies were included in this comparison. We are very uncertain whether there is any difference in the incidence of failed CPAP, defined as the need for mechanical ventilation (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.01 to 2.90; 1 study, 26 participants; very low-certainty). We are very uncertain whether there is any difference in the frequency of apnoea events (mean difference (MD) per four-hour interval -0.10, 95% CI -1.30 to 1.10; 1 study, 26 participants; very low-certainty). We are uncertain whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. 2b. Variable flow compared to bubble CPAP We included one study in this comparison, but it did not report our pre-specified outcomes. 2c. Infant Flow variable flow CPAP compared to Medijet variable flow CPAP We are very uncertain whether there is any difference in the incidence of failed CPAP (RR 2.62, 95% CI 0.91 to 7.53; 1 study, 80 participants; very low-certainty). The frequency of apnoea was not reported, and we do not know whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. Comparison 3. CPAP compared to mechanical ventilation We did not identify any studies for inclusion in this comparison.
AUTHORS' CONCLUSIONS: Due to the limited available evidence, we are very uncertain whether any CPAP device is more effective than other forms of supportive care, other CPAP devices, or mechanical ventilation for the prevention and treatment of AoP. The devices used in these studies included two types of variable flow CPAP device: bubble CPAP and ventilator CPAP. For each comparison, data were only available from a single study. There are theoretical reasons why these devices might have different effects on AoP, therefore further trials are indicated.
PATIENTS AND METHODS: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts.
RESULTS: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004).
CONCLUSION: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.
METHOD: Data was collected on 1085 CI recipients of as part of a prospective, longitudinal, observational, international, multi-centre, paediatric registry, initiated by Cochlear Ltd (Sydney, NSW, Australia). Outcome data from children (≤10 years old) implanted in routine practice was voluntarily entered into a central, externally hosted, e-platform. Collection occurred prior to initial device activation (baseline) and at six monthly follow-up intervals up to 24 months and then at 3 years post activation. Clinician reported baseline and follow up questionnaires and Categories of Auditory Performance version II (CAP-II) outcomes were collated. Self-reported evaluation forms and patient information were provided by the parent/caregiver/patient via the implant recipient baseline and follow up, Children Using Hearing Implants Quality of Life (CuHIQoL) and Speech Spatial Qualities (SSQ-P) Parents Version questionnaires.
RESULTS: Children were mainly bilaterally profoundly deaf, unilaterally implanted and used a contralateral hearing aid. Prior to implant 60% used signing or total communication as their main mode of communication. Mean age at implant was 3.2 ± 2.2 years (range 0-10 years). At baseline 8.6% were in mainstream education with no additional support and 82% had not yet entered school. After three years of implant use, 52% had entered mainstream education with no additional support and 38% had not yet entered school. In the sub-group of 141 children who were implanted at or after three years of age and were thus old enough to be in mainstream school at the three-year follow up, an even higher proportion (73%) were in mainstream education with no support. Quality of life scores for the child improved statistically significantly post implant compared to baseline and continued to improve significantly at each interval up to 3 years (p
METHODS: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.
RESULTS: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.
CONCLUSIONS: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.
CLINICAL TRIALS REGISTRATION: NCT02654171.
METHODS: This study used data from the National Health and Morbidity Survey 2016: Maternal and Child Health. It includes a sample of 10 686 children, ages 0 to 59 mo, of Malay ethnicity. Height-for-age z score was determined based on the World Health Organization Anthro software. A binary logistic regression model was used to examine the association between the selected social determinants and the occurrence of stunting.
RESULTS: About 22.5% of children aged <5 y of Malay ethnicity were stunted. For those ages 0 to 23 mo, stunting is more prevalent in boys, in rural areas, and in those who have screen exposure, whereas a reduction of stunting was observed for those children whose mothers work in the private sector and in those who consume formula milk and meat. As for those ages 24 to 59 mo, there was a higher prevalence of stunting for those with self-employed mothers and reduced prevalence in children with hygienic waste disposal practices as well as those who play with toys.
CONCLUSIONS: The prevalence of stunting among children of Malay ethnicity aged <5 in Malaysia necessitates immediate intervention. It is pertinent to facilitate early identification of those children at risk of stunting for additional care to promote healthy growth.
MATERIALS AND METHODS: A single-centre, prospective, casecontrol study involving 32 subjects of preterm neonates was conducted at a tertiary care hospital in Malang, East Java, Indonesia between January to June 2022. A total of 15 preterm neonates with NEC and 17 preterm neonates without NEC were enrolled in this study. Data on demographic, clinical and laboratory findings were collected. Multiple logistic regression test was performed to analyse the risk factors for NEC development. Further profiling within 15 subjects with NEC, i.e., NEC grade ≥ II, were conducted to collect systemic, abdominal, laboratory, abdominal x-ray (AXR) and blood culture findings.
RESULTS: The risk factors related to NEC development in preterm infants were multi-morbidity (adjusted OR = 11.96; 95% CI 1.85 168.38; p = 0.046), antibiotic exposure (OR = 15.95; 95% CI 1.54 165.08; p = 0.020) and requiring advanced neonatal resuscitation at birth (OR = 10.04; 95% CI 1.09 92.11; p = 0.041). Further profiling within NEC cohorts highlighted respiratory distress (86.7%), (oro)gastric retention (80.0%), thrombocytopenia (53.3%), gastrointestinal dilatation in AXR (53.3%), and positive blood culture Klebsiella pneumoniae (40.0%) were most common findings.
CONCLUSION: Preterm neonates with multimorbidity, prolonged antibiotic exposure, and requiring advanced resuscitation at birth were more likely to develop NEC. Early detection of the risk factors and determinant factors for survival may help to improve the clinical outcome.
METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records.
RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood.
CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.
METHODS: Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration-time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing.
RESULTS: Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3-12.1% (amikacin), 16.2-19.0% (tobramycin), 12.2-45.8% (gentamicin), and 9.6-19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin).
CONCLUSIONS: Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.
METHODS: This randomized trial was conducted from December 2019-June 2020. 234 nulliparas, 34-36 weeks' gestation with self-reported night sleep