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Scientific Reports Jun 2024A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for... (Meta-Analysis)
Meta-Analysis
A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for Parkinson's disease (PD). We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases from the date of database inception to April 30th, 2024. Two researchers independently screened studies of NIBS treatment in patients with PD based on inclusion and exclusion criteria. Two researchers independently performed data extraction of the included studies using an Excel spreadsheet and assessed the quality of the literature according to the Cochrane Risk of Bias Assessment Tool (RoB2). Network meta-analysis was performed in StataMP 17.0. A total of 28 studies involving 1628 PD patients were included. The results showed that HF-rTMS over the SMA (SMD = - 2.01; 95% CI [- 2.87, - 1.15]), HF-rTMS over the M1 and DLPFC (SMD = - 1.80; 95% CI [- 2.90, - 0.70]), HF-rTMS over the M1 (SMD = - 1.10; 95% CI [- 1.55, - 0.65]), a-tDCS over the DLPFC (SMD = - 1.08; 95% CI [- 1.90, - 0.27]), HF-rTMS over the M1 and PFC (SMD = - 0.92; 95% CI [- 1.71, - 0.14]), LF-rTMS over the M1 (SMD = - 0.72; 95% CI [- 1.17, - 0.28]), and HF-rTMS over the DLPFC (SMD = - 0.70; 95% CI [- 1.21, - 0.19]) were significantly improved motor function compared with sham stimulation. The SUCRA three highest ranked were HF-rTMS over the SMA (95.1%), HF-rTMS over the M1 and DLPFC (89.6%), and HF-rTMS over the M1 (73.0%). In terms of enhanced cognitive function, HF-rTMS over the DLPFC (SMD = 0.80; 95% CI [0.03,1.56]) was significantly better than sham stimulation. The SUCRA three most highly ranked were a-tDCS over the M1 (69.8%), c-tDCS over the DLPFC (66.9%), and iTBS over the DLPFC (65.3%). HF-rTMS over the M1 (SMD = - 1.43; 95% CI [- 2.26, - 0.61]) and HF-rTMS over the DLPFC (SMD = - 0.79; 95% CI [- 1.45, - 0.12)]) significantly improved depression. The SUCRA three highest ranked were HF-rTMS over the M1 (94.1%), LF-rTMS over the M1 (71.8%), and HF-rTMS over the DLPFC (69.0%). HF-rTMS over the SMA may be the best option for improving motor symptoms in PD patients. a-tDCS and HF-rTMS over the M1 may be the NIBS with the most significant effects on cognition and depression, separately.Trial registration: International Prospective Register of Systematic Review, PROSPERO (CRD42023456088).
Topics: Parkinson Disease; Humans; Network Meta-Analysis; Transcranial Magnetic Stimulation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38902308
DOI: 10.1038/s41598-024-64196-0 -
Journal of Neuroengineering and... Jun 2024Body weight support (BWS) training devices are frequently used to improve gait in individuals with neurological impairments, but guidance in selecting an appropriate... (Review)
Review
BACKGROUND
Body weight support (BWS) training devices are frequently used to improve gait in individuals with neurological impairments, but guidance in selecting an appropriate level of BWS is limited. Here, we aim to describe the initial BWS levels used during gait training, the rationale for this selection and the clinical goals aligned with BWS training for different diagnoses.
METHOD
A systematic literature search was conducted in PubMed, Embase and Web of Science, including terms related to the population (individuals with neurological disorders), intervention (BWS training) and outcome (gait). Information on patient characteristics, type of BWS device, BWS level and training goals was extracted from the included articles.
RESULTS
Thirty-three articles were included, which described outcomes using frame-based (stationary or mobile) and unidirectional ceiling-mounted devices on four diagnoses (multiple sclerosis (MS), spinal cord injury (SCI), stroke, traumatic brain injury (TBI)). The BWS levels were highest for individuals with MS (median: 75%, IQR: 6%), followed by SCI (median: 40%, IQR: 35%), stroke (median: 30%, IQR: 4.75%) and TBI (median: 15%, IQR: 0%). The included studies reported eleven different training goals. Reported BWS levels ranged between 30 and 75% for most of the training goals, without a clear relationship between BWS level, diagnosis, training goal and rationale for BWS selection. Training goals were achieved in all included studies.
CONCLUSION
Initial BWS levels differ considerably between studies included in this review. The underlying rationale for these differences was not clearly motivated in the included studies. Variation in study designs and populations does not allow to draw a conclusion on the effectiveness of BWS levels. Hence, it remains difficult to formulate guidelines on optimal BWS settings for different diagnoses, BWS devices and training goals. Further efforts are required to establish clinical guidelines and to experimentally investigate which initial BWS levels are optimal for specific diagnoses and training goals.
Topics: Humans; Gait Disorders, Neurologic; Body Weight; Gait
PubMed: 38849899
DOI: 10.1186/s12984-024-01389-8 -
Therapeutic Advances in... 2024Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with...
Efficacy and safety of long-acting injectable oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.
BACKGROUND
Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear.
OBJECTIVES
To assess the relative medium- and long-term efficacy and safety of LAIs OAPs in the maintenance treatment of patients with early-phase SSDs.
METHOD
We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs.
DESIGN
Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs.
RESULTS
Across 11 head-to-head RCTs ( = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99).
CONCLUSION
LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed.
TRIAL REGISTRATION
CRD42023407120 (PROSPERO).
PubMed: 38831918
DOI: 10.1177/20451253241257062 -
Translational Psychiatry Jun 2024Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one... (Review)
Review
Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.
Topics: Humans; Brain; Mental Disorders; Autism Spectrum Disorder; Depressive Disorder, Major; Canonical Correlation Analysis; Attention Deficit Disorder with Hyperactivity; Least-Squares Analysis
PubMed: 38824172
DOI: 10.1038/s41398-024-02954-4 -
Journal of Anxiety Disorders Jun 2024Given the growth in research examining the effects of psychotherapy on social anxiety disorder (SAD), an up-to-date comprehensive meta-analysis in this field is needed. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given the growth in research examining the effects of psychotherapy on social anxiety disorder (SAD), an up-to-date comprehensive meta-analysis in this field is needed.
METHODS
We selected studies from a database of randomized trials (RCTs) on psychotherapies for anxiety disorders (last updated search of PubMed, PsycINFO, Embase, and Cochrane (CENTRAL): 1 January 2024) We included RCTs comparing psychotherapy to a control condition for adults with SAD and conducted random effects meta-analyses to examine the efficacy of psychotherapy compared to control conditions at post-treatment.
RESULTS
Sixty-six RCTs were included with 5560 participants and 98 comparisons between psychotherapy and control groups. Psychotherapy was effective in reducing SAD symptoms, with a large effect size (g = 0.88; 95 % CI: 0.76 to 1.0; I = 74 %; 95 % CI: 69 to 79, NNT = 3.8). Effects remained robust across sensitivity analyses. However, there was evidence for significant risk of bias in the included trials. The multivariable meta-regression indicated significant differences in treatment delivery formats, type of recruitment strategy, target group, and number of sessions.
CONCLUSION
Psychotherapy is an effective treatment for SAD, with moderate to large effect sizes across all treatment types and formats. Future research is needed to determine the long-term effects.
Topics: Humans; Phobia, Social; Psychotherapy; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38815481
DOI: 10.1016/j.janxdis.2024.102881 -
International Journal of Molecular... May 2024Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required.... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Given its prevalence, reliable biomarkers for early diagnosis are required. Exosomal proteins within extracellular nanovesicles are promising candidates for diagnostic, screening, prognostic, and disease monitoring purposes in neurological diseases such as PD. This review aims to evaluate the potential of extracellular vesicle proteins or miRNAs as biomarkers for PD. A comprehensive literature search until January 2024 was conducted across multiple databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, to identify relevant studies reporting exosome biomarkers in blood samples from PD patients. Out of 417 articles screened, 47 studies were selected for analysis. Among exosomal protein biomarkers, α-synuclein, tau, Amyloid β 1-42, and C-X-C motif chemokine ligand 12 (CXCL12) were identified as significant markers for PD. Concerning miRNA biomarkers, miRNA-24, miR-23b-3p, miR-195-3p, miR-29c, and mir-331-5p are promising across studies. α-synuclein exhibited increased levels in PD patients compared to control groups in twenty-one studies, while a decrease was observed in three studies. Our meta-analysis revealed a significant difference in total exosomal α-synuclein levels between PD patients and healthy controls (standardized mean difference [SMD] = 1.369, 95% confidence interval [CI] = 0.893 to 1.846, < 0.001), although these results are limited by data availability. Furthermore, α-synuclein levels significantly differ between PD patients and healthy controls (SMD = 1.471, 95% CI = 0.941 to 2.002, < 0.001). In conclusion, certain exosomal proteins and multiple miRNAs could serve as potential biomarkers for diagnosis, prognosis prediction, and assessment of disease progression in PD.
Topics: Humans; Parkinson Disease; Exosomes; Biomarkers; MicroRNAs; alpha-Synuclein; Amyloid beta-Peptides
PubMed: 38791346
DOI: 10.3390/ijms25105307 -
International Journal of Molecular... May 2024The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated... (Review)
Review
The gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.
Topics: Humans; Epilepsy; Nuclear Receptor Subfamily 4, Group A, Member 2; Developmental Disabilities; Intellectual Disability
PubMed: 38791237
DOI: 10.3390/ijms25105198 -
Toxins May 2024Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's... (Review)
Review
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments' effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson's disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts.
Topics: Humans; Parkinson Disease; Botulinum Toxins; Neuromuscular Agents; Spinal Curvatures; Posture
PubMed: 38787080
DOI: 10.3390/toxins16050228 -
BMJ Mental Health May 2024Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the...
BACKGROUND
Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the literature on HS in patients with neurological disorders. We conducted a systematic review to identify studies that reported HS in neurological disorders. HS was defined as a condition characterized by excessive and persistent preoccupation with sexual thoughts, urges, and behaviors that cause significant distress or impairment in personal, social, or occupational functioning. Data on demographics, assessment techniques, associated elements, phenotypic manifestations, and management strategies were also extracted. The final analysis included 79 studies on HS, encompassing 32 662 patients across 81 cohorts with neurological disorders. Parkinson's disease was the most frequently studied condition (55.6%), followed by various types of dementia (12.7%). Questionnaires were the most common assessment approach for evaluating HS, although the techniques varied substantially. Alterations in the dopaminergic pathways have emerged as contributing mechanisms based on the effects of medication cessation. However, standardized treatment protocols still need to be improved, with significant heterogeneity in documented approaches. Critical deficiencies include risks of selection bias in participant sampling, uncontrolled residual confounding factors, and lack of blinded evaluations of reported outcomes. Despite growth in the last decade, research on HS remains limited across neurological conditions, with lingering quality and methodological standardization deficits. Key priorities include advancing assessment tools, elucidating the underlying neurobiology, and formulating management guidelines.
PROSPERO REGISTRATION NUMBER
CRD42017036478.
Topics: Humans; Nervous System Diseases; Sexual Dysfunctions, Psychological; Male; Female; Parkinson Disease; Sexual Behavior
PubMed: 38777563
DOI: 10.1136/bmjment-2024-300998 -
The Cochrane Database of Systematic... May 2024Because of wars, conflicts, persecutions, human rights violations, and humanitarian crises, about 84 million people are forcibly displaced around the world; the great... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Because of wars, conflicts, persecutions, human rights violations, and humanitarian crises, about 84 million people are forcibly displaced around the world; the great majority of them live in low- and middle-income countries (LMICs). People living in humanitarian settings are affected by a constellation of stressors that threaten their mental health. Psychosocial interventions for people affected by humanitarian crises may be helpful to promote positive aspects of mental health, such as mental well-being, psychosocial functioning, coping, and quality of life. Previous reviews have focused on treatment and mixed promotion and prevention interventions. In this review, we focused on promotion of positive aspects of mental health.
OBJECTIVES
To assess the effects of psychosocial interventions aimed at promoting mental health versus control conditions (no intervention, intervention as usual, or waiting list) in people living in LMICs affected by humanitarian crises.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and seven other databases to January 2023. We also searched the World Health Organization's (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify unpublished or ongoing studies, and checked the reference lists of relevant studies and reviews.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing psychosocial interventions versus control conditions (no intervention, intervention as usual, or waiting list) to promote positive aspects of mental health in adults and children living in LMICs affected by humanitarian crises. We excluded studies that enrolled participants based on a positive diagnosis of mental disorder (or based on a proxy of scoring above a cut-off score on a screening measure).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were mental well-being, functioning, quality of life, resilience, coping, hope, and prosocial behaviour. The secondary outcome was acceptability, defined as the number of participants who dropped out of the trial for any reason. We used GRADE to assess the certainty of evidence for the outcomes of mental well-being, functioning, and prosocial behaviour.
MAIN RESULTS
We included 13 RCTs with 7917 participants. Nine RCTs were conducted on children/adolescents, and four on adults. All included interventions were delivered to groups of participants, mainly by paraprofessionals. Paraprofessional is defined as an individual who is not a mental or behavioural health service professional, but works at the first stage of contact with people who are seeking mental health care. Four RCTs were carried out in Lebanon; two in India; and single RCTs in the Democratic Republic of the Congo, Jordan, Haiti, Bosnia and Herzegovina, the occupied Palestinian Territories (oPT), Nepal, and Tanzania. The mean study duration was 18 weeks (minimum 10, maximum 32 weeks). Trials were generally funded by grants from academic institutions or non-governmental organisations. For children and adolescents, there was no clear difference between psychosocial interventions and control conditions in improving mental well-being and prosocial behaviour at study endpoint (mental well-being: standardised mean difference (SMD) 0.06, 95% confidence interval (CI) -0.17 to 0.29; 3 RCTs, 3378 participants; very low-certainty evidence; prosocial behaviour: SMD -0.25, 95% CI -0.60 to 0.10; 5 RCTs, 1633 participants; low-certainty evidence), or at medium-term follow-up (mental well-being: mean difference (MD) -0.70, 95% CI -2.39 to 0.99; 1 RCT, 258 participants; prosocial behaviour: SMD -0.48, 95% CI -1.80 to 0.83; 2 RCT, 483 participants; both very low-certainty evidence). Interventions may improve functioning (MD -2.18, 95% CI -3.86 to -0.50; 1 RCT, 183 participants), with sustained effects at follow-up (MD -3.33, 95% CI -5.03 to -1.63; 1 RCT, 183 participants), but evidence is very uncertain as the data came from one RCT (both very low-certainty evidence). Psychosocial interventions may improve mental well-being slightly in adults at study endpoint (SMD -0.29, 95% CI -0.44 to -0.14; 3 RCTs, 674 participants; low-certainty evidence), but they may have little to no effect at follow-up, as the evidence is uncertain and future RCTs might either confirm or disprove this finding. No RCTs measured the outcomes of functioning and prosocial behaviour in adults.
AUTHORS' CONCLUSIONS
To date, there is scant and inconclusive randomised evidence on the potential benefits of psychological and social interventions to promote mental health in people living in LMICs affected by humanitarian crises. Confidence in the findings is hampered by the scarcity of studies included in the review, the small number of participants analysed, the risk of bias in the studies, and the substantial level of heterogeneity. Evidence on the efficacy of interventions on positive mental health outcomes is too scant to determine firm practice and policy implications. This review has identified a large gap between what is known and what still needs to be addressed in the research area of mental health promotion in humanitarian settings.
Topics: Humans; Randomized Controlled Trials as Topic; Mental Health; Developing Countries; Quality of Life; Adult; Child; Psychosocial Intervention; Adaptation, Psychological; Altruism; Adolescent; Refugees; Bias; Health Promotion; Psychosocial Functioning; Female; Stress Disorders, Post-Traumatic; Mental Disorders
PubMed: 38770799
DOI: 10.1002/14651858.CD014300.pub2