Cognitive functioning and clinical characteristics of children with non-syndromic orofacial clefts: A case-control study.

Introduction: The higher rate of neuropsychiatric disorders in individuals with non-syndromic orofacial clefts has been well documented by previous studies. Our goal was to identify children with non-syndromic orofacial clefts that are at risk for abnormal neurodevelopment by assessing their developmental history and present cognitive functioning. Materials and methods: A single-center, case-controlled study was carried out at the Department of Pediatrics of the University of Pécs in Hungary. The study consisted of three phases including questionnaires to collect retrospective clinical data and psychometric tools to assess IQ and executive functioning. Results: Forty children with non-syndromic oral clefts and 44 age-matched controls participated in the study. Apgar score at 5 min was lower for the cleft group, in addition to delays observed for potty-training and speech development. Psychiatric disorders were more common in the cleft group (15%) than in controls (4.5%), although not statistically significant with small effect size. The cleft group scored lower on the Continuous Performance Test. Subgroup analysis revealed significant associations between higher parental socio-economic status, academic, and cognitive performance in children with non-syndromic orofacial clefts. Analyzes additionally revealed significant associations between early speech and language interventions and higher scores on the Verbal Comprehension Index of the WISC-IV in these children. Discussion: Children with non-syndromic orofacial clefts seem to be at risk for deficits involving the attention domain of the executive system. These children additionally present with difficulties that affect cognitive and speech development. Children with non-syndromic orofacial clefts show significant skill development and present with similar cognitive strengths as their peers. Longitudinal studies with larger sample sizes are needed to provide more conclusive evidence on cognitive deficits in children with non-syndromic orofacial clefts at risk for neurodevelopmental difficulties.

Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses.

Inulin-type fructans are considered to stimulate the growth of beneficial microorganisms, like Bifidobacterium in the gut and support health. However, both the fructan source and chemical structure may modify these effects. A systematic review was conducted to assess the effects of chicory-derived inulin-type fructans consumed either in specific foods or as dietary supplements on abundance of Bifidobacterium in the gut and on health-related outcomes. Three electronic databases and two clinical trial registries were systematically searched until January 2021. Two authors independently selected randomized controlled trials that investigated with a protocol of minimum seven days supplementation the effect of chicory-derived inulin-type fructans on Bifidobacterium abundance in any population. Meta-analyses with random-effects model were conducted on Bifidobacterium abundance and bowel function parameters. We evaluated risk of bias using Cochrane RoB tool. Chicory-derived inulin-type fructans at a dose of 3-20 g/day significantly increased Bifidobacterium abundance in participants with an age range from 0 to 83 years (standardized mean difference: 0.83, 95% CI: 0.58-1.08; p < 0.01; 50 studies; 2525 participants). Significant bifidogenic effects were observed in healthy individuals and in populations with health impairments, except gastrointestinal disorders. Significant beneficial effects on bowel function parameters were observed in healthy subjects. Chicory-derived inulin-type fructans may have significant bifidogenic effects and may beneficially influence bowel function in healthy individuals. PROSPERO registration number CRD42020162892.

Complex management of children affected with cleft lip and palate associated with genetic syndromes / Ajak- és szájpadhasadékkal társult genetikai szindrómás gyermekek komplex ellátása

Introduction: The majority of facial clefts are isolated developmental anomalies. In a minority of the cases, however, facial clefts may occur as part of particular genetic syndromes. Objective: We aimed to analyse the treatment of the syndromic patients and determine whether the algorithm of complex treatment ­ used in non-syndromic patients ­ has changed in patients who had syndromes. Method: Documentation of the patients, treated by the Pecs Cleft Team between 1999 and 2015, were obtained and analysed retrospectively. These included surgical and genetical data as well. Epidemiological data from the national registry of birth were also used. Results: 607 patients were treated by the Cleft Team in the given period. Among these patients, 25 (4.11%) were found to have associated anomalies. Sixteen patients (2.6%) were identified as having a particular syndrome. 8 different syndromes occurred. Robin sequence represented 50% of this cohort. In 13 patients, the usual treatment algorithm had to be modified. The modifications were necessary due to the given genetic syndromes. Conclusion: Genetic syndromes significantly may affect the treatment algorithm in children born with cleft lip and palate. The (surgical) treatment of associated anomalies have priority over the reconstruction of cleft lip and palate.

Publication of clinical trials on medicinal products: follow-up on trials authorized in Hungary.

BACKGROUND: Clinical research should provide reliable evidence to clinicians, health policy makers, and researchers. The reliability of evidence will be assured once study planning, conducting, and reporting of results are transparent. The present research investigates publication rates, time until publication, and characteristics of clinical trials on medicinal products associated with timely publication of results, measures of scientific impact, authorship, and open access publication. METHODS: Clinical trials authorized in Hungary in 2012 were followed until publication and/or June 2020. Corresponding scientific publications were searched via clinical trial registries, PubMed (MEDLINE), and Google. RESULTS: Overall, 330 clinical trials were authorized in 2012 of which 232 trials were completed for more than 1 year in June 2020. The proportion of industry initiation was high (97%). Time to publication was 21 (22) months [median (IQR)]. Time to publication was significantly shorter when trials involved both European and non-European countries (26 vs 69 months [median]; hazard ratio = 0.38, 95% CI 0.22-0.66, p< 0.001), and were registered in both EU CTR and clinicaltrials.gov (27 vs 88 months; hazard ratio = 0.24, 95% CI 0.11-0.54; p< 0.001) based on survival analyses. A significant amount (24.1%) of unpublished clinical trial results were accessible in a trial register. The majority of available publications were published "open access" (70.93%). A minority of identified publications had a Hungarian author (21.5%). CONCLUSIONS: We encourage academic researchers to plan, register and conduct trials on medicinal products. Registries should be considered as an important source of information of clinical trial results. Publications with domestic co-authors contribute to the research output of a country. Measurable domestic scientific impact of trials on medicinal products needs further improvement.

Compassionate use of remdesivir in children with COVID-19.

Children represent a minority of total COVID-19 cases, but studies have reported severe disease and death in pediatric patients. Remdesivir (RDV) has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in children.A nationwide multicenter observational study was conducted on children with confirmed SARS-CoV-2 receiving compassionate treatment with RDV in Spain. Eight patients were included in the study, four infants and four older children [median age 5 years old; IQR 4 months-11.6 years old]. Half of them had complex underlying medical conditions, and the rest were mostly infants (3/4). Six out of eight children needed Pediatric Intensive Care Unit Admission. No RDV-related adverse outcomes were observed in our patients. Seven have reached successful clinical outcome, but one patient with serious clinical status died due to complications. However, she received RDV very late after the first COVID-19 symptom.Conclusions: In our cohort, most of the patients achieved successful clinical outcome, without observing adverse events. Clinical trials of RDV therapy for children with COVID-19 are urgently needed, to assess the safety, tolerability, efficacy, and pharmacokinetics of RDV in children, as this could be an effective treatment in severe cases. What is Known: • Remdesivir has not been approved to treat COVID-19 in children under 12 years old, although the drug is currently being prescribed in critically ill children. • Remdesivir has recently demonstrated promising results in adults with COVID-19, but few data have been reported to date in paediatric population. What is New: • We report a multicentre cohort of children with confirmed SARS-CoV-2 and severe COVID-19 disease receiving remdesivir during the first month of the pandemic in Spain. • No remdesivir-related adverse outcomes were observed in most of the cases. Seven patients reached successful clinical outcome, and one died due to complications (bacterial sepsis).

The Influence of Genetic Syndromes on the Algorithm of Cleft Lip and Palate Repair - A Retrospective Study.

Introduction: This study aimed to determine if the treatment algorithm used for nonsyndromic cleft patients required alteration to manage syndromic cleft lip and/or palate patients. Methods: The records of patients managed by the Pécs Cleft Team between January 1999 and December 2015 were analyzed retrospectively. The sources of the data included clinical and genetic records. Results: A total of 607 patients were managed by the cleft team during the study. Sixteen patients (2.6%) were noted to be afflicted with a particular identifiable syndrome. Seven different genetic syndromes and one sequence were present in the study. The Pierre Robin sequence occurred most often, comprising 50% of the cohort. The treatment algorithm used in managing nonsyndromic clefts required modification in 13 of the 16 syndromic patients. Discussion: The presence of a genetic syndrome may notably affect the treatment algorithm in children born with cleft lip and/or palate. The surgical treatment of certain associated anomalies has by necessity, priority over the timing of the reconstruction of the cleft lip and/or cleft palate in syndromic patients.