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Journal of the American Academy of... Feb 2023Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis: Efficacy of Pharmacological Interventions for Irritability and Emotional Dysregulation in Autism Spectrum Disorder and Predictors of Response.
OBJECTIVE
Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response.
METHOD
Following a preregistered protocol (PROSPERO: CRD42021235779), we systematically searched multiple databases until January 1, 2021. We included placebo-controlled randomized controlled trials (RCTs) and evaluated the efficacy of pharmacological interventions and predictors of response for emotional dysregulation and irritability. We assessed heterogeneity using Q statistics and publication bias. We conducted subanalyses and meta-regressions to identify predictors of response. The primary effect size was the standardized mean difference. Quality of studies was assessed using the Cochrane Risk of Bias Tool (RoB2).
RESULTS
A total of 2,856 individuals with ASD in 45 studies were included, among which 26.7% of RCTs had a high risk of bias. Compared to placebo, antipsychotics (standardized mean difference = 1.028, 95% CI = 0.824-1.232) and medications used to treat attention-deficit/hyperactivity disorder (ADHD) (0.471, 0.061-0.881) were significantly better than placebo in improving emotional dysregulation and irritability, whereas evidence of efficacy was not found for other drug classes (p > .05). Within individual medications, evidence of efficacy was found for aripiprazole (1.179, 0.838-1.520) and risperidone (1.074, 0.818-1.331). Increased rates of comorbid epilepsy (β = -0.049, p = .026) were associated with a lower efficacy.
CONCLUSION
Some pharmacological interventions (particularly risperidone and aripiprazole) have proved efficacy for short-term treatment of emotional dysregulation and irritability in ASD and should be considered within a multimodal treatment plan, taking into account also the tolerability profile and families' preferences.
Topics: Humans; Risperidone; Aripiprazole; Antipsychotic Agents; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity
PubMed: 35470032
DOI: 10.1016/j.jaac.2022.03.033 -
JACC. Cardiovascular Imaging Mar 2023Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined.
OBJECTIVES
The purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA.
METHODS
A systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes.
RESULTS
A total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59).
CONCLUSIONS
In patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up.
Topics: Female; Humans; Male; Middle Aged; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Magnetic Resonance Spectroscopy; MINOCA; Myocardial Infarction; Myocarditis; Predictive Value of Tests; Prognosis; Risk Factors; Takotsubo Cardiomyopathy
PubMed: 36889851
DOI: 10.1016/j.jcmg.2022.12.029 -
Journal of Personalized Medicine Aug 2021Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD... (Review)
Review
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5-75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.
PubMed: 34442428
DOI: 10.3390/jpm11080784 -
JAMA Pediatrics Apr 2022Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are childhood-onset disorders that may persist into adulthood. Several studies have... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are childhood-onset disorders that may persist into adulthood. Several studies have suggested that they may be associated with an increased risk of mortality; however, the results are inconsistent.
OBJECTIVE
To assess the risk of mortality among persons with ASD or ADHD and their first-degree relatives.
DATA SOURCES
A search of MEDLINE, Embase, Scopus, Web of Science, and PsycINFO (published from inception to April 1, 2021) was supplemented by searching reference lists of the retrieved articles.
STUDY SELECTION
Cohort and case-control studies that reported mortality rate ratios (RRs) in persons with ASD or ADHD and/or their first-degree relatives compared with the general population or those without ASD/ADHD were included.
DATA EXTRACTION AND SYNTHESIS
Screening, data extraction, and quality assessment were performed by at least 2 researchers independently. A random-effects model was used to meta-analyze individual studies and assessed heterogeneity (I2).
MAIN OUTCOMES AND MEASURES
All-cause mortality in association with ASD or ADHD. Secondary outcome was cause-specific mortality.
RESULTS
Twenty-seven studies were included, with a total of 642 260 individuals. All-cause mortality was found to be higher for persons with ASD (154 238 participants; 12 studies; RR, 2.37; 95% CI, 1.97-2.85; I2, 89%; moderate confidence) and persons with ADHD (396 488 participants; 8 studies; RR, 2.13; 95% CI, 1.13-4.02; I2, 98%; low confidence) than for the general population. Among persons with ASD, deaths from natural causes (4 studies; RR, 3.80; 95% CI, 2.06-7.01; I2, 96%; low confidence) and deaths from unnatural causes were increased (6 studies; RR, 2.50; 95% CI, 1.49-4.18; I2, 95%; low confidence). Among persons with ADHD, deaths from natural causes were not significantly increased (4 studies; RR, 1.62; 95% CI, 0.89-2.96; I2, 88%; low confidence), but deaths from unnatural causes were higher than expected (10 studies; RR, 2.81; 95% CI, 1.73-4.55; I2, 92%; low confidence).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that ASD and ADHD are associated with a significantly increased risk of mortality. Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups. The substantial heterogeneity between studies should be explored further.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Case-Control Studies; Child; Humans
PubMed: 35157020
DOI: 10.1001/jamapediatrics.2021.6401 -
Gut microbiota in patients with Alzheimer's disease spectrum: a systematic review and meta-analysis.Aging Jan 2022Gut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain... (Meta-Analysis)
Meta-Analysis
CONTEXT
Gut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain substantially controversial.
OBJECTIVE
A systematic review and meta-analysis were performed to investigate the differences of gut microbiota (GM) between patients with AD spectrum (including mild cognitive impairment [MCI] and AD) and healthy controls (HC).
DATA SOURCES
PubMed, MEDLINE, Scopus, and Cochrane Library from January 2000 to August 2021. Eligibility criteria for study selection: Observational trials and pre-intervention data of intervention trials that investigated the abundance of GM in patients with AD spectrum and HC.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently identified articles, extracted data, and evaluated the risk of bias. The effect sizes were performed by a random-effect, inverse-variance weighted model. The effects of different countries and of clinical stages on GM abundance were also examined.
RESULTS
11 studies consisting of 378 HC and 427 patients with AD spectrum were included in the meta-analysis. Patients with AD, but not MCI, showed significantly reduced GM diversity as compared to HC. We also found more abundance of , and , but less abundance of , , and in patients with AD spectrum as compared with HC. The profiles of abundance of and in HC and AD spectrum were differentially affected by countries. Finally, when considering clinical stage as a moderator, the comparisons of abundance in and showed large effect sizes, with gradient changes from MCI to AD stage.
LIMITATIONS
The inclusion of studies originating only from China and the U.S. was a possible limitation.
CONCLUSIONS
Patients with AD spectrum demonstrated altered GM abundance, which was differentially mediated by countries and clinical stages.
Topics: Aged; Alzheimer Disease; Bacteria; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged
PubMed: 35027502
DOI: 10.18632/aging.203826 -
Frontiers in Psychiatry 2022This study was to investigated the efficacy of music therapy (MT) in children with autism spectrum disorder (ASD) via a meta-analysis that comprehensively evaluated data...
OBJECTIVES
This study was to investigated the efficacy of music therapy (MT) in children with autism spectrum disorder (ASD) via a meta-analysis that comprehensively evaluated data from all eligible research in this field.
DESIGN
Systematic review and meta-analysis.
SETTING
A systematic search of the PubMed, Embase, and Cochrane Library databases from inception to October 2021 to identify studies that administered MT to children with ASD.
RESULTS
Eight randomized controlled trials (RCTs) including 608 participants met the inclusion criteria. The meta-analysis showed that MT was associated with a significant increase in social reactions among children with ASD (standardized mean difference (SMD) = 0.24, 95% confidence interval (CI) [0.03, 0.46], = 0%, = 0.03). However, MT did not elicit a significant increase in symptom severity (SMD = 0.17, 95% CI [-0.04,0.38], = 0%, = 0.12), social adaptive behavior (SMD = 0.02, 95% CI [-0.44,0.48], = 0%, = 0.93) or speech (SMD = 0.04, 95% CI [-0.39, 0.47], = 0%, = 0.86) in children with ASD.
CONCLUSION
MT can improve social skills in children with ASD; however, there does not seem to be a consensus on the persistence of its effects. These findings can inform clinical practice. Promoting the use of MT in children with ASD and improving its symptoms are the ultimate goals.
PubMed: 36276324
DOI: 10.3389/fpsyt.2022.905113 -
Clinical Psychology Review Mar 2017Group-based social skills interventions (GSSIs) are widely used for treating social competence among youth with autism spectrum disorder (ASD), but their efficacy is... (Meta-Analysis)
Meta-Analysis Review
Group-based social skills interventions (GSSIs) are widely used for treating social competence among youth with autism spectrum disorder (ASD), but their efficacy is unclear. Previous meta-analysis of the literature on well-designed trials of GSSIs is limited in size and scope, collapsing across highly heterogeneous sources (parents; youths; teachers; observers; behavioral tasks). The current meta-analysis of randomized control trials (RCTs) was conducted to ascertain overall effectiveness of GSSIs and differences by reporting sources. Nineteen RCTs met inclusion criteria. Results show that overall positive aggregate effects were medium (g=0.51, p<0.001). Effects were large for self-report (g=0.92, p<0.001), medium for task-based measures (g=0.58, p<0.001), small for parent- and observer-report (g=0.47 and 0.40, respectively, p<0.001), and nonsignificant for teacher-report (p=0.11). Moderation analyses of self-report revealed the effect was wholly attributable to youth reporting that they learned about skilled social behaviors (social knowledge; g=1.15, p<0.01), but not that they enacted them (social performance; g=0.28, p=0.31). Social skills interventions presently appear modestly effective for youth with ASD, but may not generalize to school settings or self-reported social behavior.
Topics: Adolescent; Autism Spectrum Disorder; Child; Child, Preschool; Humans; Interpersonal Relations; Psychotherapy, Group; Randomized Controlled Trials as Topic; Social Behavior; Social Skills; Young Adult
PubMed: 28130983
DOI: 10.1016/j.cpr.2017.01.006 -
Psychological Medicine Apr 2020People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic... (Comparative Study)
Comparative Study Meta-Analysis
Comparative meta-analyses of brain structural and functional abnormalities during cognitive control in attention-deficit/hyperactivity disorder and autism spectrum disorder.
BACKGROUND
People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities.
METHODS
Systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods.
RESULTS
Eighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation.
CONCLUSIONS
People with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Brain; Cerebral Cortex; Child; Cognition; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Parietal Lobe; Thalamus; Young Adult
PubMed: 32216846
DOI: 10.1017/S0033291720000574 -
Cells Aug 2022Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and... (Review)
Review
BACKGROUND
Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics.
AIM
To perform a systematic review of optical biomarkers to identify changes in cerebral haemodynamics and metabolism during the pre-ictal, ictal, and post-ictal phases of neonatal seizures.
METHOD
A systematic search was performed in eight databases. The search combined the three broad categories: (neonates) AND (NIRS) AND (seizures) using the stepwise approach following PRISMA guidance.
RESULTS
Fifteen papers described the haemodynamic and/or metabolic changes observed with NIRS during neonatal seizures. No randomised controlled trials were identified during the search. Studies reported various changes occurring in the pre-ictal, ictal, and post-ictal phases of seizures.
CONCLUSION
Clear changes in cerebral haemodynamics and metabolism were noted during the pre-ictal, ictal, and post-ictal phases of seizures in neonates. Further studies are necessary to determine whether NIRS-based methods can be used at the cot-side to provide clear pathophysiological data in real-time during neonatal seizures.
Topics: Brain; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Seizures; Spectroscopy, Near-Infrared
PubMed: 36010678
DOI: 10.3390/cells11162602 -
Sensors (Basel, Switzerland) Aug 2018Autism Spectrum Disorder (ASD) is a neurodevelopmental disease that is specially characterized by impairments in social communication and social skills. ASD has a high...
Autism Spectrum Disorder (ASD) is a neurodevelopmental disease that is specially characterized by impairments in social communication and social skills. ASD has a high prevalence in children, affecting 1 in 160 subjects. Virtual reality (VR) has emerged as an effective tool for intervention in the health field. Different recent papers have reviewed the VR-based treatments in ASD, but they have an important limitation because they only use clinical databases and do not include important technical indexes such as the Web of Science index or the Scimago Journal & Country Rank. To our knowledge, this is the first contribution that has carried out an evidence-based systematic review including both clinical and technical databases about the effectiveness of VR-based intervention in ASD. The initial search identified a total of 450 records. After the exclusion of the papers that are not studies, duplicated articles, and the screening of the abstract and full text, 31 articles met the PICO (Population, Intervention, Comparison and Outcomes) criteria and were selected for analysis. The studies examined suggest moderate evidence about the effectiveness of VR-based treatments in ASD. VR can add many advantages to the treatment of ASD symptomatology, but it is necessary to develop consistent validations in future studies to state that VR can effectively complement the traditional treatments.
Topics: Adolescent; Autism Spectrum Disorder; Child; Communication; Humans; Interpersonal Relations; Virtual Reality
PubMed: 30071588
DOI: 10.3390/s18082486