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Neuroscience and Biobehavioral Reviews Jun 2023We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and... (Review)
Review
The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.
We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.
Topics: Humans; Child; Adolescent; Psychopharmacology; Randomized Controlled Trials as Topic; Attention Deficit Disorder with Hyperactivity; Prader-Willi Syndrome; Clinical Trials, Phase II as Topic
PubMed: 37001575
DOI: 10.1016/j.neubiorev.2023.105149 -
European Archives of... May 2024Prader-Willi syndrome is a serious genetic condition, capable of causing endocrinological imbalance, which has as one of its main treatments the growth hormone therapy.... (Review)
Review
PURPOSE
Prader-Willi syndrome is a serious genetic condition, capable of causing endocrinological imbalance, which has as one of its main treatments the growth hormone therapy. However, this therapy still causes some uncertainty concerning its effects on the respiratory parameters of those patients, especially in cases of obstructive sleep apnea, therefore, presenting a need for the analysis of the relationship between the therapy and the otolaryngologic condition.
METHODS
A systematic review following the PRISMA model was developed, with searches for keywords made in the databases PubMed (MEDLINE), Scopus, and Web of Science and registration in the PROSPERO platform (CRD42023404250).
RESULTS
Three randomized controlled trials were considered eligible for inclusion in the review. None of the studies demonstrated statistically significant modifications in the obstructive sleep apnea parameters of Prader-Willi patients related to the growth hormone administration.
CONCLUSIONS
Growth hormone therapy is safe for Prader-Willi syndrome patients when analyzing their obstructive sleep apnea parameters.
Topics: Humans; Prader-Willi Syndrome; Growth Hormone; Sleep Apnea, Obstructive; Human Growth Hormone; Pharynx
PubMed: 38133808
DOI: 10.1007/s00405-023-08406-x -
Journal of the American Academy of... Sep 2020The behavioral phenotype of neurogenetic disorders associated with intellectual disability often includes psychiatric comorbidity. The objectives of this systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The behavioral phenotype of neurogenetic disorders associated with intellectual disability often includes psychiatric comorbidity. The objectives of this systematic review and meta-analysis were to systematically review the prevalence of psychiatric disorders and symptoms in children and adolescents with these disorders and compare phenotypic signatures between syndromes.
METHOD
MEDLINE and PsycINFO databases were searched for articles from study inception to December 2018. Eligible articles were peer reviewed, were published in English, and reported prevalence data for psychiatric disorders and symptoms in children and adolescents aged 4 to 21 years using a formal psychiatric assessment or a standardized assessment of mental health symptoms. Pooled prevalence was determined using a random-effects meta-analysis in studies with sufficient data. Prevalence estimates were compared with general population data using a test of binomial proportions.
RESULTS
Of 2,301 studies identified for review, 39 articles were included in the final pool, which provided data on 4,039 children and adolescents. Ten syndromes were represented, and five were predominant: Down syndrome, 22q11.2 deletion syndrome, fragile X syndrome, Williams syndrome, and Prader-Willi syndrome. The Child Behavior Checklist was the most commonly used assessment tool for psychiatric symptoms. The pooled prevalence with total scores above the clinical threshold was lowest for Down syndrome (32% [95% confidence interval, 19%-44%]) and highest for Prader-Willi syndrome (74% [95% CI, 65%-82%]) with each syndrome associated with significantly higher prevalence than in the general population. Parallel trends were observed for the internalizing and externalizing domains and social subscale scores.
CONCLUSION
Differential vulnerability for psychiatric phenotype expression across the disorders was observed. Syndromes with higher levels of social ability or competence appear to offer relative protection against developing psychopathology. This preliminary finding merits further exploration.
Topics: Adolescent; Adult; Child; Child, Preschool; Comorbidity; Humans; Intellectual Disability; Mental Disorders; Mental Health; Prader-Willi Syndrome; Prevalence; Young Adult
PubMed: 31945412
DOI: 10.1016/j.jaac.2020.01.006 -
Childhood Obesity (Print) Apr 2023Probiotics have been proposed as a prevention or treatment for pediatric overweight and obesity. Conduct a scoping review on probiotic use in children and adolescents... (Review)
Review
Probiotics have been proposed as a prevention or treatment for pediatric overweight and obesity. Conduct a scoping review on probiotic use in children and adolescents with overweight or obesity and those with weight-related conditions and to identify knowledge gaps and research priorities. Seven databases using keywords and medical subject heading terms for articles reporting probiotic use in children or adolescents with overweight or obesity published from database conception until initiation of the study. Articles reporting primary data on probiotics use in children or adolescents with overweight or obesity. We utilized the Arksey and O'Malley framework, PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, followed a predetermined study protocol for level-one abstract and level-two full-text screenings, synthesized information into subject-area domains, and identified research gaps. Heterogeneity of probiotic interventions, host factors, and genomics. Database search yielded 1356 unique articles with 19 randomized placebo-controlled studies, 945 participants, duration of interventions from 8 weeks to 9 months. Disease indications included Nonalcoholic Fatty Liver Disease, insulin resistance, hypercholesterolemia, Prader-Willi Syndrome, metabolic syndrome, and obesity. Limited and heterogeneous evidence for probiotic use in children and adolescents with weight-related conditions noted. Heterogeneity among published articles in probiotic strains, doses, design, biomarkers, confirmation, and outcomes observed. Despite complex existing and limited data, studies to date of children and adolescents with overweight and obesity demonstrate potential beneficial treatment effects of probiotics on BMI, adiposity, metabolic parameters, inflammatory markers, fatty liver, transaminase levels, and glucose metabolism. Clinical trials to address heterogeneous results are needed.
Topics: Child; Humans; Adolescent; Overweight; Pediatric Obesity; Probiotics; Adiposity; Metabolic Syndrome
PubMed: 35723657
DOI: 10.1089/chi.2022.0059 -
BMC Medical Research Methodology May 2023There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of...
BACKGROUND
There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification.
METHODS
Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of > 1.50 was considered acceptable.
RESULTS
Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier's gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barré syndrome) had one study with an acceptable match, and four diseases (Behcet's syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington's disease, Sjogren's syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence.
CONCLUSIONS
Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.
Topics: Humans; Rare Diseases; Endpoint Determination; Clinical Studies as Topic
PubMed: 37210484
DOI: 10.1186/s12874-023-01947-z -
Pediatric Obesity May 2023A systematic review of value and preference studies conducted in children and their caregivers related to the estimated benefits and harms of interventions for managing... (Review)
Review
OBJECTIVE
A systematic review of value and preference studies conducted in children and their caregivers related to the estimated benefits and harms of interventions for managing paediatric obesity.
METHODS
We searched Ovid Medline (1946-2022), Ovid Embase (1974-2022), EBSCO CINAHL (inception to 2022), Elsevier Scopus (inception to 2022), and ProQuest Dissertations & Theses (inception to 2022). Reports were eligible if they included: behavioural and psychological, pharmacological, or surgical interventions; participants between (or had a mean age within) 0-18 years old with overweight or obesity; systematic reviews, primary quantitative, qualitative, or mixed/multiple methods studies; and values and preferences as main study outcomes. At least two team members independently screened studies, abstracted data, and appraised study quality.
RESULTS
Our search yielded 11 010 reports; eight met the inclusion criteria. One study directly assessed values and preferences based on hypothetical pharmacological treatment for hyperphagia in individuals with Prader-Willi Syndrome. Although not having reported on values and preferences using our a priori definitions, the remaining seven qualitative studies (n = 6 surgical; n = 1 pharmacological) explored general beliefs, attitudes, and perceptions about surgical and pharmacological interventions. No studies pertained to behavioural and psychological interventions.
CONCLUSION
Future research is needed to elicit the values and preferences of children and caregivers using the best available estimates of the benefits and harms for pharmacological, surgical, and behavioural and psychological interventions.
Topics: Child; Humans; Infant, Newborn; Infant; Child, Preschool; Adolescent; Pediatric Obesity; Overweight; Hyperphagia
PubMed: 36810978
DOI: 10.1111/ijpo.13006 -
Journal of Pediatric Endocrinology &... Jun 2022Registries are considered valuable data sources for identification of pediatric conditions treated with growth hormone (GH), and their follow-up. Currently, there is no... (Review)
Review
BACKGROUND
Registries are considered valuable data sources for identification of pediatric conditions treated with growth hormone (GH), and their follow-up. Currently, there is no systematic literature review on the scope and characteristics of pediatric GH registries. Therefore, the purpose of this systematic review is to identify worldwide registries reported on pediatric GH treatment and to provide a summary of their main characteristics.
CONTENT
Pediatric GH registries were identified through a systematic literature review. The search was performed on all related literature published up to January 30th, 2021. Basic information on pediatric GH registries, their type and scope, purpose, sources of data, target conditions, reported outcomes, and important variables were analyzed and presented.
SUMMARY
Twenty two articles, reporting on 20 pediatric GH registries, were included in this review. Industrial funding was the most common funding source. The main target conditions included in the pediatric GH registries were: growth hormone deficiency, Turner syndrome, Prader Willi syndrome, small for gestational age, idiopathic short stature, and chronic renal insufficiency. The main objectives in establishing and running pediatric GH registries were assessing the safety and effectiveness of the treatment, describing the epidemiological aspects of target growth conditions and populations, serving public health surveillance, predicting and measuring treatment outcomes, exploring new and useful aspects of GH treatment, and improving the quality of patient care.
OUTLOOK
This systematic review provides a global perspective on pediatric GH registries which can be used as a basis for the design and development of new GH registry systems at both national and international levels.
Topics: Child; Dwarfism, Pituitary; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Registries
PubMed: 35567286
DOI: 10.1515/jpem-2022-0045 -
Journal of Pediatric Endocrinology &... Jun 2010Genotropin (somatropin) is licensed for the treatment of children with growth hormone deficiency, Prader-Willi syndrome, Turner syndrome, chronic renal insufficiency and... (Review)
Review
Genotropin (somatropin) is licensed for the treatment of children with growth hormone deficiency, Prader-Willi syndrome, Turner syndrome, chronic renal insufficiency and in children born small for gestational age. This systematic review (SR) evaluated the clinical efficacy and effectiveness of Genotropin in these conditions to inform a NICE Technology Appraisal of growth hormone for the treatment of growth failure in children. Search terms were used to search seven databases, including Medline and Embase, for English language studies. Randomised controlled trials (RCTs) or observational studies investigating Genotropin in children were included. Out of 30 RCTs identified, one reported final height data. Eleven observational studies reported final height and seven were based on the Pfizer International Growth Survey (KIGS). This SR highlights the lack of long-term RCTs reporting final height data and other important qualitative outcomes, such as quality of life. Observational data, such as those from KIGS, remain vital for informing therapy.
Topics: Adolescent; Body Height; Child; Clinical Trials, Phase III as Topic; Databases, Bibliographic; Female; Growth Disorders; Human Growth Hormone; Humans; Male; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 20662327
DOI: 10.1515/jpem.2010.092 -
Journal of Neural Transmission (Vienna,... Jan 2017Invasive and non-invasive vagus nerve stimulation (VNS) is a promising add-on treatment for treatment-refractory depression, but is also increasingly evaluated for its... (Review)
Review
Invasive and non-invasive vagus nerve stimulation (VNS) is a promising add-on treatment for treatment-refractory depression, but is also increasingly evaluated for its application in other psychiatric disorders, such as dementia, schizophrenia, somatoform disorder, and others. We performed a systematic review aiming to give a detailed overview of the available evidence of the efficacy of VNS for the treatment of psychiatric disorders. Data derived from animal models, experimental trials without health-related outcomes, case reports, single-session studies, and reviews were excluded. From 1292 publications, 33 records were included for further analyses: 25 focused on VNS as treatment of unipolar or bipolar major depressive disorder and one investigated the neurocognitive improvement after VNS in major depressive disorder. Seven focused on the improvement of cognitive function in Alzheimer´s disease, improvement of schizophrenia symptoms, treatment of obsessive compulsive disorder (OCD), panic disorder (PD) and post-traumatic stress disorder (PTSD), treatment resistant rapid-cycling bipolar disorder, treatment of fibromyalgia, and Prader-Willi syndrome. A total of 29 studies used invasive VNS, while four studies used non-invasive, transcutaneous VNS. Only 7 out of 33 studies investigated conditions other than affective disorders. The efficacy data of VNS in affective disorders is promising, whereas more in controlled and naturalistic studies are needed. In other conditions like schizophrenia, Alzheimer's disease, OCD, PD, PTSD, and fibromyalgia, either no effects or preliminary data on efficacy were reported. At this point, no final conclusion can be made regarding the efficacy of VNS to improve symptoms in psychiatric disorders other than in affective disorders.
Topics: Evidence-Based Medicine; Humans; Mental Disorders; Psychiatry; Vagus Nerve Stimulation
PubMed: 27848034
DOI: 10.1007/s00702-016-1642-2 -
Sleep Medicine Reviews Jun 2021Individuals with Rare Genetic Neurodevelopmental Disorders (RGND) present with significant sleep problems and circadian rhythm abnormalities of uncertain aetiology.... (Review)
Review
Individuals with Rare Genetic Neurodevelopmental Disorders (RGND) present with significant sleep problems and circadian rhythm abnormalities of uncertain aetiology. Abnormal melatonin secretion may play a role in sleep disturbance in individuals with higher incidence developmental disabilities, however, RGND research is limited. This review compared the melatonin profiles in a range of RGND with that of the general population and considered the impact of any differences on sleep. A systematic search identified 19 studies that met inclusion criteria. Each study was examined to extract data relating to the study design, participant characteristics, objectives, sleep measures and results, and melatonin measures and findings. Studies were evaluated using the BIOCROSS quality appraisal tool. Nine studies focussed on Smith-Magenis syndrome (SMS), the rest included individuals with Angelman (AS), Fragile-X (FXS), Prader-Willi (PWS), septo-optic dysplasia, PAX6/WAGR and Williams (WS) syndromes (N = 349). Individuals with RGND present with a range of sleep problems, particularly dyssomnias. The melatonin profile varied within and between RGND, with low nocturnal melatonin levels commonly reported. Understanding the relationship between specific sleep and melatonin parameters within RGND may help inform sleep intervention.
Topics: Humans; Melatonin; Neurodevelopmental Disorders; Sleep; Sleep Wake Disorders; Smith-Magenis Syndrome
PubMed: 33561678
DOI: 10.1016/j.smrv.2021.101433