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Pediatric Rheumatology Online Journal Aug 2023To review whether the current COVID-19 vaccines can prevent the occurrence of multisystem inflammatory syndrome in children (MIS-C) and adolescents. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To review whether the current COVID-19 vaccines can prevent the occurrence of multisystem inflammatory syndrome in children (MIS-C) and adolescents.
METHODS
A systematic literature review and meta-analysis were performed. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Primary outcome was the efficacy of COVID-19 vaccination in preventing MIS-C development. The search was performed in PubMed and Embase.
RESULTS
The review yielded 13 studies, which were included for critical appraisal and data extraction. The available studies showed a reduced incidence of MIS-C after mRNA COVID-19 vaccination in children aged 12-18 years. Four studies were eligible for meta-analysis and the pooled odds ratio for MIS-C in vaccinated children compared to unvaccinated children was 0.04 (95% confidence interval: 0.03-0.06). Additionally, the risk of MIS-C as an adverse effect of vaccination was much lower compared to the risk of MIS-C post-infection.
CONCLUSIONS
Our systematic review highlights the current available evidence on the efficacy of COVID-19 vaccination in preventing MIS-C. The published studies so far - mainly conducted during the Delta wave - indicate that (original strain) COVID-19 mRNA vaccines in children are safe and associated with significantly less development of MIS-C. These findings further reinforce the recommendation for COVID-19 vaccination in children, which should be promoted and largely supported.
Topics: Adolescent; Child; Humans; COVID-19 Vaccines; COVID-19; Systemic Inflammatory Response Syndrome; Child Development
PubMed: 37550719
DOI: 10.1186/s12969-023-00848-1 -
British Journal of Clinical Pharmacology Jul 2023New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial... (Review)
Review
AIM
New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial literature and concisely report the updated safety and adverse effects of topical medications used to treat atopic dermatitis in children.
METHODS
A systematic search of Cochrane Library, Embase, PubMed and ClinicalTrials.gov from inception to March 2022 was conducted for trials of topical medications used to treat AD in patients <18 years (PROSPERO #CRD42022315355). Included records were limited to English-language publications and studies of ≥3 weeks duration. Phase 1 studies and those that lacked separate paediatric safety reporting were excluded.
RESULTS
A total of 5005 records were screened; 75 records met inclusion criteria with 15 845 paediatric patients treated with tacrolimus, 12 851 treated with pimecrolimus, 3539 with topical corticosteroid (TCS), 700 with crisaborole and 202 with delgocitinib. Safety data was well reported in tacrolimus trials with the most frequently reported adverse events being burning sensation, pruritus and cutaneous infections. Two longitudinal cohort studies were included, one for tacrolimus and one for pimecrolimus, which found no significant increased risk of malignancy with topical calcineurin inhibitor (TCI) use in children. Skin atrophy was identified as an adverse event in TCS trials, which other medications did not. Systemic adverse events for the medications were largely common childhood ailments.
CONCLUSION
Data discussed here support the use of steroid-sparing medications (tacrolimus, pimecrolimus, crisaborole, delgocitinib) as safe options with minimal adverse events for managing paediatric AD, although a larger number of TCI studies reported burning and pruritus compared to TCS studies. TCS was the only medication class associated with reports of skin atrophy in this review. The tolerability of these adverse events should be considered when treating young children. This review was limited to English-language publications and the variable safety reporting of trial investigators. Many newer medications were not included due to pooled adult and paediatric safety data that did not meet inclusion criteria.
Topics: Adult; Child; Humans; Child, Preschool; Dermatitis, Atopic; Tacrolimus; Longitudinal Studies; Calcineurin Inhibitors; Dermatologic Agents; Pruritus; Treatment Outcome
PubMed: 37075252
DOI: 10.1111/bcp.15751 -
European Journal of Medical Genetics Nov 2023The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical,...
The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5-6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the striking features of achondroplasia.
Topics: Adolescent; Humans; Child; Adult; Quality of Life; Chronic Pain; Achondroplasia
PubMed: 37758167
DOI: 10.1016/j.ejmg.2023.104850 -
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 -
Children (Basel, Switzerland) Oct 2022The SARS-CoV-19 (COVID-19) pandemic has become a global problem but has affected the paediatric population less so than in adults. The clinical picture in paediatrics... (Review)
Review
INTRODUCTION
The SARS-CoV-19 (COVID-19) pandemic has become a global problem but has affected the paediatric population less so than in adults. The clinical picture in paediatrics can be different to adults but nonetheless both groups have been subject to frequent imaging. The overall aim of this study was to comprehensively summarise the findings of the available literature describing the chest radiograph (CXR) findings of paediatric patients with confirmed COVID-19. The COVID-19 landscape is rapidly changing, new information is being constantly brought to light, it is therefore important to appraise clinicians and the wider scientific community on the radiographic features of COVID-19 in children.
METHODS
Four databases, which included, PubMed; Medline; CINAHL; ScienceDirect were searched from the 30 November 2020 to the 5 March 2021. The review was conducted using the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis, PRISMA" guidelines. Studies were included for (1) publications with full text available, (2) patients with confirmed COVID-19 diagnoses, (3) CXR imaging features of COVID-19 were reported, (4) the age of patients was 0-18 years, (5) studies were limited to human subjects and (6) a language restriction of English was placed on the search. Quality assessment of included articles used the National of Health Quality Assessment Tool for Case Series Studies.
RESULTS
Eight studies met our criteria for inclusion in the review. All eight studies documented the number of CXRs obtained, along with the number of abnormal CXRs. Seven out of the eight studies noted greater than 50% of the CXRs taken were abnormal. Opacification was the number one feature that was recorded in all eight studies, followed by pleural effusion which was seen in six studies. Consolidation and peri-bronchial thickening features were both evident in four studies. Opacification was sub-divided into common types of opacities i.e., consolidation, ground glass opacities, interstitial, alveolar and hazy. Consolidation was reported in half of the studies followed by ground glass opacities and interstitial opacities which was seen in three out of the eight studies.
CONCLUSION
This systematic review provides insight into the common COVID-19 features that are seen on CXRs in paediatric patients. Opacification was the most common feature reported, with consolidation, ground glass and interstitial opacities the top three opacifications seen. Peri-bronchial thickening is reported. in the paediatric population but this differs from the adult population and was not reported as a common radiographic finding typically seen in adults.
ADVANCES IN KNOWLEDGE
This systematic review highlights the CXR appearances of paediatric patients with confirmed SARS-CoV-19, to gain insight into the disease pathophysiology and provide a comprehensive summary of the features for clinicians aiding optimal management.
PubMed: 36360348
DOI: 10.3390/children9111620 -
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 -
Frontiers in Pharmacology 2021Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile,... (Review)
Review
Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6-68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96513, identifier CRD42018096513.
PubMed: 35185536
DOI: 10.3389/fphar.2021.777498 -
Scandinavian Journal of Trauma,... Dec 2021Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not... (Review)
Review
BACKGROUND
Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not received sufficient attention. The present systematic review therefore aims to perform a comprehensive search of databases to examine the preferable drugs for prehospital pain relief in paediatric patients with acute pain, irrespective of aetiology.
METHODS
The systematic review includes studies from 2000 and up to 2020 that focus on children's prehospital pain management. The study protocol is registered in PROSPERO with registration no. CRD42019126699. Pharmacological pain management using any type of analgesic drug and in all routes of administration was included. The main outcomes were (1) measurable pain reduction (effectiveness) and (2) no occurrence of any serious adverse events. Searches were conducted in PubMed, Medline, Embase, CINAHL, Epistemonikos and Cochrane library. Finally, the risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist and a textual narrative analysis was performed due to the heterogeneity of the results.
RESULTS
The present systematic review on the effectiveness and safety of analgesic drugs in prehospital pain relief in children identified a total of eight articles. Most of the articles reviewed identified analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The effects of fentanyl, morphine and methoxyflurane were examined and all of the included analgesic drugs were evaluated as effective. Adverse events of fentanyl, methoxyflurane and ketamine were also reported, although none of these were considered serious.
CONCLUSION
The systematic review revealed that fentanyl, morphine, methoxyflurane and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported following the administration of fentanyl, methoxyflurane and ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, the level of evidence (LOE) in the included studies was only three or four, and further studies are therefore necessary.
Topics: Acute Pain; Analgesics; Analgesics, Opioid; Child; Emergency Medical Services; Fentanyl; Humans
PubMed: 34895311
DOI: 10.1186/s13049-021-00974-3 -
International Journal of Molecular... Jun 2023Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral... (Meta-Analysis)
Meta-Analysis Review
A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis.
Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60-75% but fall to 5-15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.
Topics: Adult; Aged; Child; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Meta-Analysis as Topic; Neoplasm Recurrence, Local
PubMed: 37298623
DOI: 10.3390/ijms24119667 -
Anales de Pediatria Sep 2021We present the summary of a critical appraisal document of the available evidence on COVID-19, developed with a clinical practice guide format following GRADE... (Meta-Analysis)
Meta-Analysis
We present the summary of a critical appraisal document of the available evidence on COVID-19, developed with a clinical practice guide format following GRADE methodology. The document tries to provide answers to a series of structured clinical questions, with an explicit definition of the population, intervention / exposure, comparison and outcome, and a rating of the clinical relevance of the outcome measures. We conducted a systematic review of the literature to answer the questions, grouped into six chapters: epidemiology, clinical practice, diagnosis, treatment, prevention, and vaccination. We assessed the risk of bias of the selected studies with standard instruments (RoB-2, ROBINS-I, QUADAS and Newcastle-Ottawa). We constructed evidence tables and, when necessary and possible, meta-analysis of the of the most relevant outcome measures. We followed the GRADE system to synthesise the evidence, assessing its quality, and, when appropriate, giving recommendations, rated according to the quality of the evidence, the values and preferences, the balance between benefits, risks and costs, equity and feasibility.
Topics: COVID-19; Child; Evidence-Based Medicine; Female; Humans; Infant; Infant, Newborn; Pediatrics; Pregnancy; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 34380606
DOI: 10.1016/j.anpede.2021.05.003