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Numerous recommendations have been made to address the high rates of mental health disorders among justice-involved youth. Few data are available on the use, quality, appropriateness, or availability of services to address these needs. This study examined the relationship between trauma-informed mental health screening, other referral pathways for diagnostic evaluation, subsequent DSM-5 diagnoses, and treatments for evaluated youth. Eligible participants were all youth admitted to New York City secure juvenile detention facilities from September 17, 2015 to October 30, 2016 who remained in the facility for at least five days ( N = 786). Of those, 581 (73.9%) were voluntarily screened and 309 (53.2%) later received a diagnostic evaluation. Youth who screened positive for depression, posttraumatic stress disorder, and problematic substance use were more likely to be evaluated. Treatment received was related to diagnosis rather than reason for referral. For youth who were referred for behavioral or emotional concerns, 99.1 percent (114 of 115) of those diagnosed with a neurodevelopmental disorder had attention-deficit/hyperactivity disorder (ADHD). These data are among the first to describe DSM-5 diagnoses and treatment among youth detainees. They highlight the prevalence of ADHD in detained youth and argue for the coordination of universal trauma-informed mental health screening and a structured referral system for this population., (© 2024 American Academy of Psychiatry and the Law.)

Introduction: Promoting mental health, preventing and treating mental disorders are critically important in public health, and many randomised controlled trials (RCTs) evaluate intervention strategies for these objectives. However, distinguishing promotion from prevention and from treatment RCTs is challenging. A tool to place studies along the promotion-to-treatment continuum in mental health research does not exist, leaving it to researchers and policymakers to decide on how to classify individual RCTs, which hinders evidence synthesis., Methods and Analysis: We present a protocol for the development of a new tool to assist researchers in distinguishing RCTs along the promotion-to-treatment continuum. We will establish a Tool Development Group, and use the Population, Intervention, Comparison and Outcome framework to define constructs. We will generate, define, categorise and reduce the items in the tool using qualitative methods, including cognitive interviews and a Delphi exercise. Psychometric evaluation-including unidimensionality, local independence, monotonicity and item homogeneity-will include data collection, scoring, internal consistency checks and factor analysis of the tool's indicators for available RCTs. We will use standard Cohen's kappa statistics to assess the reliability of the tool., Ethics and Dissemination: This study involves data collection from the already published literature. However, this protocol has been approved by the ethics committee of the Università della Svizzera Italiana (CE 2024 04). The results of the present project will be disseminated in peer-reviewed journals and at international and national scientific meetings. Training materials for the application of the tool will also be developed and disseminated to the scientific community. The tool and all related implementation materials will be published on a website and will be freely accessible to the public., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare second-generation antipsychotics (SGAs) and mood stabilizers (MSs) in youth with a bipolar disorder type I (BD-I) manic/mixed episode., Method: A systematic PubMed/Embase/PsycInfo literature search until December 31, 2023, for randomized trials of SGAs or MSs in patients ≤18 years of age with BD-I manic/mixed episode was conducted. The study included a network meta-analysis comparing treatments regarding mania symptoms and mania response (co-primary outcomes), and secondary efficacy and tolerability outcomes., Results: Eighteen studies (n = 2844, mean age = 11.74, female participants = 48.0%, mean study duration = 5.4 weeks) comparing 6 SGAs (aripiprazole, asenapine, olanzapine, quetiapine, risperidone, and ziprasidone) and 4 MSs (lithium, oxcarbazepine, topiramate, and valproate) were meta-analyzed. All 6 SGAs outperformed placebo in reducing manic symptomatology, including risperidone (standardized mean difference [SMD] = -1.18, 95% CI = -0.92, -1.45, Confidence in Network Meta-Analysis [CINeMA] = moderate confidence), olanzapine (SMD = -0.77, 95% CI = -0.36, -1.18, low confidence), aripiprazole (SMD = -0.67, 95% CI = -0.33, -1.01, moderate confidence), quetiapine (SMD = -0.60, 95% CI = -0.32, -0.87, high confidence), asenapine (SMD = -0.54, 95% CI = -0.19, -0.89, moderate confidence), and ziprasidone (SMD = -0.43, 95% CI = -0.17, 0.70, low confidence), whereas no mood stabilizer outperformed placebo. Concerning mania response, risperidone (Risk ratio [RR] = 2.58, 95% CI = 1.88, 3.54, low confidence), olanzapine (RR = 2.42, 95% CI = 1.33, 3.54, very low confidence), aripiprazole (RR = 2.05, 95% CI = 1.44, 2.92, low confidence), quetiapine (RR = 1.89, 95% CI = 1.45n 2.47, moderate confidence), asenapine (RR = 1.81, 95% CI = 1.28, 2.55, very low confidence) and lithium (RR = 1.35, 95% CI = 1.00, 1.83, p = .049, very low confidence) outperformed placebo, without superiority of other MSs vs placebo. Individually, risperidone was more efficacious in reducing manic symptomatology than all other comparators, except olanzapine and topiramate, yet with low/very low confidence, and was associated with increased prolactin and glucose. Pooled together, SGAs outperformed both placebo and MSs for mania symptom reduction (SMD = -0.68, 95% CI = -0.86, -0.51 and SMD = -0.61, 95% CI = -0.82, -0.40, moderate confidence), and mania response (RR = 1.85, 95% CI = 1.53, 2.24 and RR = 1.65, 95% CI = 1.33, 2.04, moderate confidence) without differences between MSs and placebo. There were no significant treatment-placebo differences for all-cause discontinuation, whereas lithium, ziprasidone, and oxcarbazepine were associated with more adverse event-related drop-outs than placebo. Most SGAs were associated with more sedation, weight gain, and metabolic issues vs placebo and MSs., Conclusion: SGAs were more efficacious than placebo and MSs in treating acute mania symptoms, however, their use must be carefully weighed against important side effects., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Moderating the pool of active ribosomal subunits is critical for maintaining global translation rates. A factor crucial for modulating the 60S ribosomal subunits is eukaryotic translation initiation factor 6. Release of eIF6 from 60S is essential to permit 60S interactions with 40S. Here, using the N106S mutant of eIF6, we show that disrupting eIF6 interaction with 60S leads to an increase in vacant 80S. It further highlights a dichotomy in the anti-association activity of eIF6 that is distinct from its role in 60S biogenesis and shows that the nucleolar localization of eIF6 is not dependent on uL14-BCCIP interactions. Limiting active ribosomal pools markedly deregulates translation especially in mitosis and leads to chromosome segregation defects, mitotic exit delays and mitotic catastrophe. Ribo-Seq analysis of the eIF6-N106S mutant shows a significant downregulation in the translation efficiencies of mitotic factors and specifically transcripts with long 3'UTRs. eIF6-N106S mutation also limits cancer invasion, and this role is correlated with the overexpression of eIF6 only in high-grade invasive cancers suggesting that deregulation of eIF6 is probably not an early event in cancers. Thus, this study highlights the segregation of eIF6 functions and its role in moderating 80S availability for mitotic translation and cancer progression.

Plant-microbe symbioses require intense interaction and genetic coordination to successfully establish in specific cell types of the host and symbiont. Traditional RNA-seq methodologies lack the cellular resolution to fully capture these complexities, but single-cell and spatial transcriptomics (ST) are now allowing scientists to probe symbiotic interactions at an unprecedented level of detail. Here, we discuss the advantages that novel spatial and single-cell transcriptomic technologies provide in studying plant-microbe endosymbioses and highlight key recent studies. Finally, we consider the remaining limitations of applying these approaches to symbiosis research, which are mainly related to the simultaneous capture of both plant and microbial transcripts within the same cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 versus 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 ( n  = 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, p  = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, p  = 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 versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed., Trial Registration: CRD42023407120 (PROSPERO)., (© The Author(s), 2024.)

(1) Background: Lower socioeconomic status increases psychiatric service use, exacerbated during the COVID-19 pandemic by environmental stressors like air pollution and limited green spaces. This study aims to assess the influence of sociodemographic and environmental factors on mental health service utilisation. (2) Methods: This retrospective study uses an administrative database focusing on community mental health services in Northeast Italy. Spatial and temporal analyses were used to address space-time dependencies. (3) Results: Findings showed that sociodemographic factors like living in rented apartments and lower education levels predicted higher mental health service use. Environmental factors, such as elevated NO 2 levels and, before the pandemic, lower solar radiation and tree cover, correlated with increased service utilisation. COVID-19 reduced most of the pre-existing differences associated with these factors across census blocks with a different composition of sociodemographic and environmental factors. (4) Conclusions: These findings contribute to a better understanding of the impact of the environment on public mental health., Competing Interests: The authors declare no conflicts of interest.

Importance: Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified., Objective: To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD., Data Sources: MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD., Study Selection: RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion., Data Extraction and Synthesis: This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results., Main Outcomes and Measures: Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated., Results: Data from 65 RCTs were included. Effect size estimates on data from 5048 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.76 [95% CI, -1.15 to -0.36]; certainty, moderate), CBT (SMD, -0.74 [95% CI, -1.09 to -0.38]; certainty, moderate), and relaxation therapy (SMD, -0.59 [95% CI, -1.07 to -0.11]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.04 [95% CI, 0.64-1.67] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.47; 95% CI, -1.18 to 0.23). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.60; 95% CI, -0.99 to -0.21)., Conclusions and Relevance: Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.

Refugees are at increased risk for developing psychological impairments due to stressors in the pre-, peri- and post-migration periods. There is limited knowledge on how everyday functioning is affected by migration experience. In a secondary analysis of a study in a sample of refugees and asylum seekers, it was examined how aspects of psychological functioning were differentially affected. 1,101 eligible refugees and asylum seekers in Europe and Türkiye were included in a cross-sectional analysis. Gender, age, education, number of relatives and children living nearby, as well as indicators for depressive and posttraumatic symptoms, quality of life, psychological well-being and functioning, and lifetime potentially traumatic events were assessed. Correlations and multiple regression models with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version's total and six subdomains' scores ('mobility', 'life activities', 'cognition', 'participation', 'self-care', 'getting along') as dependent variables were calculated. Tests for multicollinearity and Bonferroni correction were applied. Participants reported highest levels of impairment in 'mobility' and 'participation', followed by 'life activities' and 'cognition'. Depression and posttraumatic symptoms were independently associated with overall psychological functioning and all subdomains. History of violence and abuse seemed to predict higher impairment in 'participation', while past events of being close to death were associated with fewer issues with 'self-care'. Impairment in psychological functioning in asylum seekers and refugees was related to current psychological symptoms. Mobility and participation issues may explain difficulties arising after resettlement in integration and exchange with host communities in new contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baumgartner, Renner, Wochele-Thoma, Wehle, Barbui, Purgato, Tedeschi, Tarsitani, Roselli, Acartürk, Uygun, Anttila, Lantta, Välimäki, Churchill, Walker, Sijbrandij, Cuijpers, Koesters, Klein, White, Aichberger and Wancata.)

Background: Scalable psychological interventions such as the WHO's Self-Help Plus (SH+) have been developed for clinical and non-clinical populations in need of psychological support. SH+ has been successfully implemented to prevent common mental disorders among asylum seekers and refugees who are growing in number due to increasing levels of forced migration. These populations are often exposed to multiple, severe sources of traumatisation, and evidence of the effect of such events on treatment is insufficient, especially for non-clinical populations. Objective: We aim to study the effect of potentially traumatic experiences (PTEs) and the mediating role of symptoms of posttraumatic stress disorder (PTSD) on the improvement following SH+. Method: Participants allocated to SH+ who received at least three sessions ( N  = 345) were extracted from two large, randomised, European prevention trials involving asylum seekers and refugees. Measures of distress, depression, functional impairment, and post-traumatic stress symptoms were administered at baseline and 6 months post-intervention, together with measures of well-being and quality of life. Adjusted models were constructed to examine the effect of PTEs on post-intervention improvement. The possible mediating role of PTSD symptoms in this relationship was then tested. Results: Increasing numbers of PTEs decreased the beneficial effect of SH+ for all measures. This relationship was mediated by symptoms of PTSD when analysing measures of well-being and quality of life. However, this did not apply for measures of mental health problems. Conclusions: Exposure to PTEs may largely reduce benefits from SH+. PTSD symptomatology plays a specific, mediating role on psychological well-being and quality of life of participants who experienced PTE. Healthcare professionals and researchers should consider the role of PTEs and PTSD symptoms in the treatment of migrants and refugees and explore possible feasible add-on solutions for cases exposed to multiple PTEs.

Legume-rhizobium signaling during establishment of symbiotic nitrogen fixation restricts rhizobium colonization to specific cells. A limited number of root hair cells allow infection threads to form, and only a fraction of the epidermal infection threads progress to cortical layers to establish functional nodules. Here we use single-cell analysis to define the epidermal and cortical cell populations that respond to and facilitate rhizobium infection. We then identify high-confidence nodulation gene candidates based on their specific expression in these populations, pinpointing genes stably associated with infection across genotypes and time points. We show that one of these, which we name SYMRKL1, encodes a protein with an ectodomain predicted to be nearly identical to that of SYMRK and is required for normal infection thread formation. Our work disentangles cellular processes and transcriptional modules that were previously confounded due to lack of cellular resolution, providing a more detailed understanding of symbiotic interactions., (© 2023. The Author(s).)

Introduction: Common mental disorders, including depression, anxiety and related somatic health symptoms, are leading causes of disability worldwide. Especially in low-resource settings, psychosocial interventions delivered by non-specialist providers through task-sharing modalities proved to be valid options to expand access to mental healthcare. However, such interventions are usually eclectic multicomponent interventions consisting of different combinations of evidence-based therapeutic strategies. Which of these various components (or combinations thereof) are more efficacious (and for whom) to reduce common mental disorder symptomatology is yet to be substantiated by evidence., Methods and Analysis: Comprehensive search was performed in electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Register of Controlled Trials-CENTRAL from database inception to 15 March 2023 to systematically identify all randomised controlled trials that compared any single component or multicomponent psychosocial intervention delivered through the task-sharing modality against any active or inactive control condition in the treatment of adults suffering from common mental disorders. From these trials, individual participant data (IPD) of all measured outcomes and covariates will be collected. We will dismantle psychosocial interventions creating a taxonomy of components and then apply the IPD component network meta-analysis (IPD-cNMA) methodology to assess the efficacy of individual components (or combinations thereof) according to participant-level prognostic factors and effect modifiers., Ethics and Dissemination: Ethics approval is not applicable for this study since no original data will be collected. Results from this study will be published in peer-reviewed journals and presented at relevant conferences., Competing Interests: Competing interests: TAF reports personal fees from Boehringer-Ingelheim, DT Axis, Kyoto University Original, Shionogi and SONY, and a grant from Shionogi, outside the submitted work. In addition, TAF has patents 2020-548587 and 2022-082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic has negatively affected the mental health of international migrant workers (IMWs). IMWs experience multiple barriers to accessing mental health care. Two scalable interventions developed by the World Health Organization (WHO) were adapted to address some of these barriers: Doing What Matters in times of stress (DWM), a guided self-help web application, and Problem Management Plus (PM +), a brief facilitator-led program to enhance coping skills. This study examines whether DWM and PM + remotely delivered as a stepped-care programme (DWM/PM +) is effective and cost-effective in reducing psychological distress, among Polish migrant workers with psychological distress living in the Netherlands., Methods: The stepped-care DWM/PM + intervention will be tested in a two-arm, parallel-group, randomized controlled trial (RCT) among adult Polish migrant workers with self-reported psychological distress (Kessler Psychological Distress Scale; K10 > 15.9). Participants (n = 212) will be randomized into either the intervention group that receives DWM/PM + with psychological first aid (PFA) and care-as-usual (enhanced care-as-usual or eCAU), or into the control group that receives PFA and eCAU-only (1:1 allocation ratio). Baseline, 1-week post-DWM (week 7), 1-week post-PM + (week 13), and follow-up (week 21) self-reported assessments will be conducted. The primary outcome is psychological distress, assessed with the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS). Secondary outcomes are self-reported symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), resilience, quality of life, and cost-effectiveness. In a process evaluation, stakeholders' views on barriers and facilitators to the implementation of DWM/PM + will be evaluated., Discussion: To our knowledge, this is one of the first RCTs that combines two scalable, psychosocial WHO interventions into a stepped-care programme for migrant populations. If proven to be effective, this may bridge the mental health treatment gap IMWs experience., Trial Registration: Dutch trial register NL9630, 20/07/2021, https://www.onderzoekmetmensen.nl/en/trial/27052., (© 2023. The Author(s).)

The eIF4E family of translation initiation factors bind 5' methylated caps and act as the limiting step for mRNA translation. The canonical eIF4E1A is required for cell viability, yet other related eIF4E families exist and are utilized in specific contexts or tissues. Here, we describe a family called Eif4e1c, for which we find roles during heart development and regeneration in zebrafish. The Eif4e1c family is present in all aquatic vertebrates but is lost in all terrestrial species. A core group of amino acids shared over 500 million years of evolution forms an interface along the protein surface, suggesting that Eif4e1c functions in a novel pathway. Deletion of eif4e1c in zebrafish caused growth deficits and impaired survival in juveniles. Mutants surviving to adulthood had fewer cardiomyocytes and reduced proliferative responses to cardiac injury. Ribosome profiling of mutant hearts demonstrated changes in translation efficiency of mRNA for genes known to regulate cardiomyocyte proliferation. Although eif4e1c is broadly expressed, its disruption had most notable impact on the heart and at juvenile stages. Our findings reveal context-dependent requirements for translation initiation regulators during heart regeneration., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Introduction: Evidence-based and scalable prevention and promotion focused mental health and psychosocial support interventions are needed for conflict-affected populations in humanitarian settings. This study retrospectively assessed whether participation in Self Help Plus (SH+) versus enhanced usual care (EUC) resulted in reduced incidence of probable mental disorder and increased positive mental health and well-being post-intervention among South Sudanese refugee women in Uganda., Methods: This study used secondary data from treatment-oriented pilot (n=50) and fully-powered cluster randomised controlled trials (cRCT)s (n=694) of SH+ versus EUC. Data from baseline and post-intervention assessments were combined. A composite latent indicator for mental health problems was generated using mental health and well-being measures included in both cRCTs. In order to assess incidence, a binary variable approximating probable mental disorder was created to exclude those with probable mental disorder from the analysis sample and as the primary prevention outcome. The promotive effects of SH+ relative to EUC were examined in the same sample by assessing subjective well-being and psychological flexibility scale scores., Results: A single factor for mental health problems was identified with all factor loadings >0.30 and acceptable internal consistency (α=0.70). We excluded 161 women who met criteria for probable mental disorder at baseline. Among those with at least moderate psychological distress but without probable mental disorder at baseline and with follow-up data (n=538), the incidence of probable mental disorder at post-intervention was lower among those who participated in SH+ relative to EUC (Risk ratio =0.16, 95% CI: 0.05 to 0.53). Participation in SH+ versus EUC was also associated with increased subjective well-being (β=2.62, 95% CI: 1.63 to 3.60) and psychological flexibility (β=4.55, 95% CI: 2.92 to 6.18) at post-intervention assessment., Conclusions: These results support the use and further testing of SH+ as a selective and indicated prevention and promotion focused psychosocial intervention in humanitarian settings., Trial Registration Number: ISRCTN50148022., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Question: Refugees and asylum seekers are at high risk of mental disorders due to various stressors before, during and after forceful displacement. The WHO Self-Help Plus (SH+) intervention was developed to manage psychological distress and a broad range of mental health symptoms in vulnerable populations. This study aimed to examine the effects and moderators of SH+ compared with Enhanced Care as Usual (ECAU) in reducing depressive symptoms among refugees and asylum seekers., Study Selection and Analysis: Three randomised trials were identified with 1795 individual participant data (IPD). We performed an IPD meta-analysis to estimate the effects of SH+, primarily on depressive symptoms and second on post-traumatic stress, well-being, self-identified problems and functioning. Effects were also estimated at 5-6 months postrandomisation (midterm)., Findings: There was no evidence of a difference between SH+ and ECAU+ in reducing depressive symptoms at postintervention. However, SH+ had significantly larger effects among participants who were not employed (β=1.60, 95% CI 0.20 to 3.00) and had lower mental well-being levels (β=0.02, 95% CI 0.001 to 0.05). At midterm, SH+ was significantly more effective than ECAU in improving depressive symptoms (β=-1.13, 95% CI -1.99 to -0.26), self-identified problems (β=-1.56, 95% CI -2.54 to -0.59) and well-being (β=6.22, 95% CI 1.60 to 10.90)., Conclusions: Although SH+ did not differ significantly from ECAU in reducing symptoms of depression at postintervention, it did present benefits for particularly vulnerable participants (ie, unemployed and with lower mental well-being levels), and benefits were also evident at midterm follow-up. These results are promising for the use of SH+ in the management of depressive symptoms and improvement of well-being and self-identified problems among refugees and asylum seekers., Competing Interests: Competing interests: RGW acted as a consultant reviewer to the WHO in the development of the SH+ intervention, and I am an author on the papers reporting on the RCTs in the EU and Uganda. The rest of the authors have nothing to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Resource competition can be the cause of unintended coupling between co-expressed genetic constructs. Here we report the quantification of the resource load imposed by different mammalian genetic components and identify construct designs with increased performance and reduced resource footprint. We use these to generate improved synthetic circuits and optimise the co-expression of transfected cassettes, shedding light on how this can be useful for bioproduction and biotherapeutic applications. This work provides the scientific community with a framework to consider resource demand when designing mammalian constructs to achieve robust and optimised gene expression., (© 2023. The Author(s).)

Background: In asylum seekers and refugees, the frequency of mental disorders, such as depression, anxiety and post-traumatic stress disorder, is higher than the general population, but there is a lack of data on risk factors for the development of mental disorders in this population., Aim: This study investigated the risk factors for mental disorder development in a large group of asylum seekers and refugees resettled in high- and middle-income settings., Methods: Participant-level data from two randomized prevention studies involving asylum seekers and refugees resettled in Western European countries and in Turkey were pooled. The two studies randomized participants with psychological distress, but without a diagnosis of mental disorder, to the Self-Help Plus psychological intervention or enhanced care as usual. At baseline, exposure to potentially traumatic events was measured using the Harvard Trauma Questionnaire-part I, while psychological distress and depressive symptoms were assessed with the General Health Questionnaire and the Patient Health Questionnaire. After 3 and 6 months of follow-up, the proportion of participants who developed a mental disorder was calculated using the Mini International Neuropsychiatric Interview., Results: A total of 1,101 participants were included in the analysis. At 3- and 6-month follow-up the observed frequency of mental disorders was 13.51% (115/851) and 24.30% (207/852), respectively, while the frequency estimates after missing data imputation were 13.95% and 23.78%, respectively. After controlling for confounders, logistic regression analysis showed that participants with a lower education level ( p  = .034), a shorter duration of journey ( p  = .057) and arriving from countries with war-related contexts ( p  = .017), were more at risk of developing mental disorders. Psychological distress ( p  = .004), depression ( p  = .001) and exposure to potentially traumatic events ( p  = .020) were predictors of mental disorder development., Conclusions: This study identified several risk factors for the development of mental disorders in asylum seekers and refugees, some of which may be the target of risk reduction policies. The identification of asylum seekers and refugees at increased risk of mental disorders should guide the implementation of focused preventative psychological interventions.

Competition for intracellular resources, also known as gene expression burden, induces coupling between independently co-expressed genes, a detrimental effect on predictability and reliability of gene circuits in mammalian cells. We recently showed that microRNA (miRNA)-mediated target downregulation correlates with the upregulation of a co-expressed gene, and by exploiting miRNAs-based incoherent-feed-forward loops (iFFLs) we stabilise a gene of interest against burden. Considering these findings, we speculate that miRNA-mediated gene downregulation causes cellular resource redistribution. Despite the extensive use of miRNA in synthetic circuits regulation, this indirect effect was never reported before. Here we developed a synthetic genetic system that embeds miRNA regulation, and a mathematical model, MIRELLA, to unravel the miRNA (MI) RolE on intracellular resource aLLocAtion. We report that the link between miRNA-gene downregulation and independent genes upregulation is a result of the concerted action of ribosome redistribution and 'queueing-effect' on the RNA degradation pathway. Taken together, our results provide for the first time insights into the hidden regulatory interaction of miRNA-based synthetic networks, potentially relevant also in endogenous gene regulation. Our observations allow to define rules for complexity- and context-aware design of genetic circuits, in which transgenes co-expression can be modulated by tuning resource availability via number and location of miRNA target sites., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI continuers and discontinuers through Mann-Whitney U test, Kaplan-Meier survival curves, regression for interval-censored data, and a maximum-likelihood mixed-model with individual random-effect and time as predictor. Of the 261 participants analyzed, 71.3% had schizophrenia-spectrum disorders, and 29.5% discontinued the LAI before 1 year. At baseline, LAI discontinuers had a shorter illness duration, lower attitude and adherence scores. The mirror-image analysis showed reduced hospital admissions only for LAI continuers. Over time, continuers spent less days hospitalized, but had more adverse events and more antipsychotics prescribed, with higher overall doses. In conclusion, this study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained. LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time. Therefore, the choice of initiating and maintaining a LAI should be carefully weighed on a case-by-case basis., (© 2023. The Author(s).)

Aims: WHO declared that mental health care should be considered one essential health service to be maintained during the coronavirus disease 2019 (COVID-19) pandemic. This study aims to describe the effect of lockdown and restrictions due to the COVID-19 pandemic in Italy on mental health services' utilisation, by considering psychiatric diagnoses and type of mental health contacts., Methods: The study was conducted in the Verona catchment area, located in the Veneto region (northeastern Italy). For each patient, mental health contacts were grouped into: (1) outpatient care , (2) social and supportive interventions , (3) rehabilitation interventions , (4) multi-professional assessments , (5) day care . A 'difference in differences' approach was used: difference in the number of contacts between 2019 and 2020 on the weeks of lockdown and intermediate restrictions was compared with the same difference in weeks of no or reduced restrictions, and such difference was interpreted as the effect of restrictions. Both a global regression on all contacts and separate regressions for each type of service were performed and Incidence Rate Ratios (IRRs) were calculated., Results: In 2020, a significant reduction in the number of patients who had mental health contacts was found, both overall and for most of the patients' characteristics considered (except for people aged 18-24 years for foreign-born population and for those with a diagnosis of schizophrenia. Moreover, in 2020 mental health contacts had a reduction of 57 096 (-33.9%) with respect to 2019; such difference remained significant across the various type of contacts considered, with rehabilitation interventions and day care showing the greatest reduction. Negative Binomial regressions displayed a statistically significant effect of lockdown, but not of intermediate restrictions, in terms of reduction in the number of contacts. The lockdown period was responsible of a 32.7% reduction (IRR 0.673; p -value <0.001) in the overall number of contacts. All type of mental health contacts showed a reduction ascribable to the lockdown, except social and supportive interventions., Conclusions: Despite the access to community mental health care during the pandemic was overall reduced, the mental health system in the Verona catchment area was able to maintain support for more vulnerable and severely ill patients, by providing continuity of care and day-by-day support through social and supportive interventions.

Several in-person and remote delivery formats of cognitive-behavioural therapy (CBT) for panic disorder are available, but up-to-date and comprehensive evidence on their comparative efficacy and acceptability is lacking. Our aim was to evaluate the comparative efficacy and acceptability of all CBT delivery formats to treat panic disorder. To answer our question we performed a systematic review and network meta-analysis of randomised controlled trials. We searched MEDLINE, Embase, PsycINFO, and CENTRAL, from inception to 1st January 2022. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO. We found a total of 74 trials with 6699 participants. Evidence suggests that face-to-face group [standardised mean differences (s.m.d.) -0.47, 95% confidence interval (CI) -0.87 to -0.07; CINeMA = moderate], face-to-face individual (s.m.d. -0.43, 95% CI -0.70 to -0.15; CINeMA = Moderate), and guided self-help (SMD -0.42, 95% CI -0.77 to -0.07; CINeMA = low), are superior to treatment as usual in terms of efficacy, whilst unguided self-help is not (SMD -0.21, 95% CI -0.58 to -0.16; CINeMA = low). In terms of acceptability (i.e. all-cause discontinuation from the trial) CBT delivery formats did not differ significantly from each other. Our findings are clear in that there are no efficacy differences between CBT delivered as guided self-help, or in the face-to-face individual or group format in the treatment of panic disorder. No CBT delivery format provided high confidence in the evidence at the CINeMA evaluation.

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry out several of its methodological and statistical steps is still lacking. Therefore, different working groups might often make different methodological choices based on their clinical and research experience, with possible advantages and shortcomings. In this contribution, we will critically assess two network meta-analyses on the topic of pharmacological prevention of relapse in schizophrenia, carried out by two different research groups. We will highlight the implications of different methodological choices on the analysis results and their clinical-epidemiological interpretation. Moreover, we will discuss some of the most relevant technical issues of network meta-analyses for which there is not a broad methodological agreement, including the assessment of transitivity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. Published by BMJ.)

Introduction: Migrant populations, including workers, undocumented migrants, asylum seekers, refugees, internationally displaced persons, and other populations on the move, are exposed to a variety of stressors and potentially traumatic events before, during, and after the migration process. In recent years, the COVID-19 pandemic has represented an additional stressor, especially for migrants on the move. As a consequence, migration may increase vulnerability of individuals toward a worsening of subjective wellbeing, quality of life, and mental health, which, in turn, may increase the risk of developing mental health conditions. Against this background, we designed a stepped-care programme consisting of two scalable psychological interventions developed by the World Health Organization and locally adapted for migrant populations. The effectiveness and cost-effectiveness of this stepped-care programme will be assessed in terms of mental health outcomes, resilience, wellbeing, and costs to healthcare systems., Methods and Analysis: We present the study protocol for a pragmatic randomized study with a parallel-group design that will enroll participants with a migrant background and elevated level of psychological distress. Participants will be randomized to care as usual only or to care a usual plus a guided self-help stress management guide (Doing What Matters in Times of Stress, DWM) and a five-session cognitive behavioral intervention (Problem Management Plus, PM+). Participants will self-report all measures at baseline before random allocation, 2 weeks after DWM delivery, 1 week after PM+ delivery and 2 months after PM+ delivery. All participants will receive a single-session of a support intervention, namely Psychological First Aid. We will include 212 participants. An intention-to-treat analysis using linear mixed models will be conducted to explore the programme's effect on anxiety and depression symptoms, as measured by the Patient Health Questionnaire-Anxiety and Depression Scale summary score 2 months after PM+ delivery. Secondary outcomes include post-traumatic stress disorder symptoms, resilience, quality of life, resource utilization, cost, and cost-effectiveness., Discussion: This study is the first randomized controlled trial that combines two World Health Organization psychological interventions tailored for migrant populations with an elevated level of psychological distress. The present study will make available DWM/PM+ packages adapted for remote delivery following a task-shifting approach, and will generate evidence to inform policy responses based on a more efficient use of resources for improving resilience, wellbeing and mental health., Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04993534., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Purgato, Turrini, Tedeschi, Serra, Tarsitani, Compri, Muriago, Cadorin, Ostuzzi, Nicaise, Lorant, Sijbrandij, Witteveen, Ayuso-Mateos, Mediavilla, Haro, Felez-Nobrega, Figueiredo, Pollice, McDaid, Park, Kalisch, Petri-Romão, Underhill, Bryant, Nosè and Barbui.)

In Argentina, despite the important studies conducted on the prevalence of infection and the antibiotic resistance of Helicobacter pylori, there are no reports simultaneously analyzing a profile of virulence factors of the bacterium and polymorphisms in cytokine genes in patients with different alterations in the gastric mucosa (including intestinal metaplasia, IM). Our aim was to evaluate H. pylori genotypes in 132 adult patients with chronic gastritis presenting three different histological findings (inactive chronic gastritis, active chronic gastritis IM- and active chronic gastritis IM+) along with SNP-174 G>C in the IL-6 gene. cagA, vacA and babA2 genes were analyzed by multiplex PCR. The -174 G>C SNP IL-6 gene was analyzed by PCR-RFLP. Patients with active chronic gastritis IM+ showed the highest proportion of the cagA(+)/IL-6GG, cagA(+)/vacAm1s1/IL-6GG and cagA(+)/vacAm1s1/babA2(+)/IL-6GG combinations (p<0.05). There was 4-5 times greater probability of finding patients presenting the GG genotype for SNP-174 G>C IL-6, which in turn were infected with the most virulent H. pylori genotypes -cagA(+), cagA(+)/vacAm1s1 and cagA(+)/vacAm1s1/babA2- in the ACGIM+ group in comparison to the ICG group. Our results provide regional data to the idea that the transition towards severe alterations in the gastric mucosa would be the result of a balance between specific factors of H. pylori and inherent host factors. This fact can be useful to identify patients at greater risk and to select those individuals requiring appropriate eradication treatment to prevent progression to gastric cancer., (Copyright © 2022 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Vocal disorders are frequent in people with multiple sclerosis (MS). Cognitive impairment, fatigue, depression, and other clinical characteristics can be associated with treatment effectiveness in rehabilitation. Finding baseline characteristics that identify those who are responding to treatment can help the clinical decision-making process, which can then help improve the effectiveness of voice treatment. We developed a model to identify factors associated with treatment-related improvement on voice intensity in people with MS., Methods: Data are from a randomized controlled trial of the effects of voice therapy. Forty-four people with MS were enrolled and randomized to receive Lee Silverman Voice Treatment LOUD, specifically addressing voice intensity, or conventional speech-therapy group. Voice intensity (dB) was measured during monologue before and after treatment and was used to differentiate those who responded (posttreatment voice intensity > 60 dB) from those who did not. Possible associated factors were cognitive impairment, fatigue, depression, disability, and disease duration. Associations were assessed by univariate logistic regression and univariate and multivariate linear regressions., Results: Mean ± SD monologue voice intensity is improved in the whole sample (before rehabilitation: 51.8 ± 4.2 dB; and after rehabilitation 57.0 ± 6.5 dB; P < .001), and 11 people with MS (27.5%) responded to treatment. Specificity of treatment was associated with the return to normal voice intensity (OR, 14.28; 95% CI, 12.17-309.56) and we found a linear association between voice improvement and the specificity of treatment (6.65 [SE = 1.54] dB; P < .05). Moreover, the analysis revealed a nonlinear association between improvement and fatigue, suggesting increased benefits for people with MS with moderate fatigue. Other factors were not significantly associated with treatment effectiveness., Conclusions: Moderate fatigue and the specificity of the intervention seem to be key factors associated with clinically relevant improvement in voice intensity even in people with MS with a high level of disability and long disease duration., Competing Interests: FINANCIAL DISCLOSURES: The authors declare no conflicts of interest., (© 2023 Consortium of Multiple Sclerosis Centers.)

Purpose of Review: Epinephrine autoinjectors (EAIs) are recommended to all patients previously experiencing anaphylaxis reaction in order to prevent further reactions and fatalities. Under that perspective, EAI prescription could be considered as a proxy of anaphylaxis epidemiology. Nevertheless EAI prescription rates are still unacceptably low., Recent Findings: The review focuses on potential determinants, in addition to clinical indications, which might impact EAI prescription rates by exploring the scientific literature published within the past 18 months, wherever available. Although some controversial results, age, sex, ethnicity, geographical setting and socioeconomic conditions might influence both physician prescription behaviour and EAIs' accessibility from the patient's side, which hampers the accuracy of EAI prescription as a proxy of anaphylaxis. Low EAI prescription and refill rates have been recorded even in the absence of significant socioeconomic barriers, suggesting that economical limitations only partially account for the issue, and cultural restrictions have also to be considered and addressed., Summary: In addition to providing the same opportunities in terms of EAI availability in all countries worldwide, implementing the resources for anaphylaxis management in terms of practical knowledge, education, and allergy specialist networks is an urgent need, even in the absence of socioeconomic barriers., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Heterogeneous Nuclear Ribonucleoprotein K (hnRNPK) is a multifunctional RNA binding protein (RBP) localized in the nucleus and the cytoplasm. Abnormal cytoplasmic enrichment observed in solid tumors often correlates with poor clinical outcome. The mechanism of cytoplasmic redistribution and ensuing functional role of cytoplasmic hnRNPK remain unclear. Here we demonstrate that the SCF Fbxo4 E3 ubiquitin ligase restricts the pro-oncogenic activity of hnRNPK via K63 linked polyubiquitylation, thus limiting its ability to bind target mRNA. We identify SCF Fbxo4 -hnRNPK responsive mRNAs whose products regulate cellular processes including proliferation, migration, and invasion. Loss of SCF Fbxo4 leads to enhanced cell invasion, migration, and tumor metastasis. C-Myc was identified as one target of SCF Fbxo4 -hnRNPK. Fbxo4 loss triggers hnRNPK-dependent increase in c-Myc translation, thereby contributing to tumorigenesis. Increased c-Myc positions SCF Fbxo4 -hnRNPK dysregulated cancers for potential therapeutic interventions that target c-Myc-dependence. This work demonstrates an essential role for limiting cytoplasmic hnRNPK function in order to maintain translational and cellular homeostasis., (© 2022. The Author(s).)

Background: Longitudinal studies examining mental health trajectories in refugees and asylum seekers are scarce. Objectives: To investigate trajectories of psychological symptoms and wellbeing in refugees and asylum seekers, and identify factors associated with these trajectories. Method: 912 asylum seekers and refugees from the control arm of three trials in Europe ( n  = 229), Turkey ( n  = 320), and Uganda ( n  = 363) were included. We described trajectories of psychological symptoms and wellbeing, and used trauma exposure, age, marital status, education, and individual trial as predictors. Then, we assessed the bidirectional interactions between wellbeing and psychological symptoms, and the effect of each predictor on each outcome controlling for baseline values. Results: Symptom improvement was identified in all trials, and for wellbeing in 64.7% of participants in Europe and Turkey, versus 31.5% in Uganda. In Europe and Turkey domestic violence predicted increased symptoms at post-intervention ( ß  = 1.36, 95% CI 0.17-2.56), whilst murder of family members at 6-month follow-up ( ß  = 1.23, 95% CI 0.27-2.19). Lower wellbeing was predicted by murder of family member ( ß  = -1.69, 95% CI -3.06 to -0.32), having been kidnapped ( ß  = -1.67, 95% CI -3.19 to -0.15), close to death ( ß  =  -1.38, 95% CI -2.70 to -0.06), and being in the host country ≥2 years ( ß  =  -1.60, 95% CI -3.05 to -0.14). In Uganda at post-intervention, having been kidnapped predicted increased symptoms ( ß  = 2.11, 95% CI 0.58-3.65), and lack of shelter ( ß  = -2.51, 95% CI -4.44 to -0.58) and domestic violence predicted lower wellbeing ( ß  = -1.36, 95% CI -2.67 to -0.05). Conclusion: Many participants adapt to adversity, but contextual factors play a critical role in determining mental health trajectories., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background and Aims: The coronavirus disease 2019 pandemic has challenged health services worldwide, with a worsening of healthcare workers' mental health within initial pandemic hotspots. In early 2022, the Omicron variant is spreading rapidly around the world. This study explores the effectiveness and cost-effectiveness of a stepped-care programme of scalable, internet-based psychological interventions for distressed health workers on self-reported anxiety and depression symptoms., Methods: We present the study protocol for a multicentre (two sites), parallel-group (1:1 allocation ratio), analyst-blinded, superiority, randomised controlled trial. Healthcare workers with psychological distress will be allocated either to care as usual only or to care as usual plus a stepped-care programme that includes two scalable psychological interventions developed by the World Health Organization: A guided self-help stress management guide (Doing What Matters in Times of Stress) and a five-session cognitive behavioural intervention (Problem Management Plus). All participants will receive a single-session emotional support intervention, namely psychological first aid. We will include 212 participants. An intention-to-treat analysis using linear mixed models will be conducted to explore the programme's effect on anxiety and depression symptoms, as measured by the Patient Health Questionnaire - Anxiety and Depression Scale summary score at 21 weeks from baseline. Secondary outcomes include post-traumatic stress disorder symptoms, resilience, quality of life, cost impact and cost-effectiveness., Conclusions: This study is the first randomised trial that combines two World Health Organization psychological interventions tailored for health workers into one stepped-care programme. Results will inform occupational and mental health prevention, treatment, and recovery strategies., Registration Details: ClinicalTrials.gov Identifier: NCT04980326., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Backgrounds: Individuals with chronic medical conditions are considered highly exposed to COVID-19 pandemic stress, but emerging evidence is demonstrating that resilience is common even among them. We aimed at identifying sustained resilient outcomes and their predictors in chronically ill people during the first year of the pandemic., Methods: This international 4-wave 1-year longitudinal online survey included items on socio-demographic characteristics, economic and living situation, lifestyle and habits, pandemic-related issues, and history of mental disorders. Adherence to and approval of imposed restrictions, trust in governments and in scientific community during the pandemic were also investigated. The following tools were administered: the Patient Health Questionnaire, the Generalized Anxiety Disorder scale, the PTSD Checklist DSM-5, the Oslo Social Support Scale, the Padua Inventory, and the Portrait Values Questionnaire., Results: One thousand fifty-two individuals reporting a chronic condition out of 8011 total participants from 13 countries were included in the study, and 965 had data available for the final model. The estimated probability of being "sustained-resilient" was 34%. Older male individuals, participants employed before and during the pandemic or with perceived social support were more likely to belong to the sustained-resilience group. Loneliness, a previous mental disorder, high hedonism, fear of COVID-19 contamination, concern for the health of loved ones, and non-approving pandemic restrictions were predictors of not-resilient outcomes in our sample., Conclusions: We found similarities and differences from established predictors of resilience and identified some new ones specific to pandemics. Further investigation is warranted and could inform the design of resilience-building interventions in people with chronic diseases., (© 2022. The Author(s).)

Background: Psychotherapies are the treatment of choice for panic disorder, but which should be considered as first-line treatment is yet to be substantiated by evidence., Aims: To examine the most effective and accepted psychotherapy for the acute phase of panic disorder with or without agoraphobia via a network meta-analysis., Method: We conducted a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the most effective and accepted psychotherapy for the acute phase of panic disorder. We searched MEDLINE, Embase, PsycInfo and CENTRAL, from inception to 1 Jan 2021 for RCTs. Cochrane and PRISMA guidelines were used. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO (CRD42020206258)., Results: We included 136 RCTs in the systematic review. Taking into consideration efficacy (7352 participants), acceptability (6862 participants) and the CINeMA confidence in evidence appraisal, the best interventions in comparison with treatment as usual (TAU) were cognitive-behavioural therapy (CBT) (for efficacy: standardised mean differences s.m.d. = -0.67, 95% CI -0.95 to -0.39; CINeMA: moderate; for acceptability: relative risk RR = 1.21, 95% CI -0.94 to 1.56; CINeMA: moderate) and short-term psychodynamic therapy (for efficacy: s.m.d. = -0.61, 95% CI -1.15 to -0.07; CINeMA: low; for acceptability: RR = 0.92, 95% CI 0.54-1.54; CINeMA: moderate). After removing RCTs at high risk of bias only CBT remained more efficacious than TAU., Conclusions: CBT and short-term psychodynamic therapy are reasonable first-line choices. Studies with high risk of bias tend to inflate the overall efficacy of treatments. Results from this systematic review and network meta-analysis should inform clinicians and guidelines.

Background: Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on different maintenance treatment strategies, including continuing the antipsychotic at standard doses, reducing the dose, switching to another antipsychotic, or even stopping the antipsychotic. We aimed to compare the effectiveness of these maintenance treatment strategies, hypothesising the superiority of all strategies over stopping, and of continuing at standard doses over both switching and reducing the dose., Methods: We did a systematic review and network meta-analysis of randomized controlled trials (RCTs) that investigated antipsychotics for relapse prevention in adults with schizophrenia-spectrum disorders who were clinically stable, and which compared four treatment strategies: continuing the current antipsychotic at standard doses recommended for acute treatment; reducing the current antipsychotic dose; switching to a different antipsychotic; and stopping the antipsychotic and replacing it with placebo. We excluded RCTs with fewer than 25 individuals, a prerandomisation washout period greater than 4 weeks, a follow-up shorter than 6 weeks, and those recruiting treatment-resistant individuals. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, and online trial registers for published and unpublished RCTs from inception to Sept 1, 2021, combining terms describing all available antipsychotics, and terms describing continuation, maintenance, or long-term treatment for schizophrenia-spectrum disorders. Relative risks (RRs) and standardised mean differences were pooled using random-effects pairwise and network meta-analyses. We assessed risk of bias of each RCT with the Cochrane Risk-of-Bias 2 tool, and confidence of pooled estimates with CINeMA. The primary outcome was relapse prevention. The study protocol was registered in advance in the Open Science Forum registry., Findings: Of 3936 records identified, 119 records, reporting on 101 RCTs, were eligible, 98 of which (including 13 988 individuals) provided data that could be meta-analysed for at least one outcome. The mean proportion of female participants per study was 38% (range 0-100; median 39%, IQR 29-50), whereas for male participants it was 62% (range 0-100; median 61%, IQR 50-71), and the overall mean age was 38·8 years (range 23·2-63·9; median 39·3, IQR 35·0-43·9). Of the 98 RCTs meta-analysed, 89·8% were done in high-income and upper-middle-income countries. The ethnic group White or so-called Caucasian was the most represented (mean 56% participants per study), although this information was relatively scarce. All continuation strategies were significantly more effective in preventing relapse than stopping antipsychotic treatment, with a large risk reduction for continuing at standard doses (RR 0·37, 95% CI 0·32-0·43; number-needed-to-treat [NNT] 3·17, 95% CI 2·94-3·51) and antipsychotic switching (RR 0·44, 0·37-0·53; NNT 3·57, 3·17-4·25), and moderate risk reduction for dose reduction (RR 0·68, 0·51-0·90; NNT 6·25, 4·08-20·00). Continuing and switching antipsychotics did not differ significantly (RR 0·84, 0·69-1·02; with lower values favouring continuing), whereas reducing antipsychotic dose was outperformed by both continuing (RR 0·55, 0·42-0·71; NNT 4·44, 3·45-6·90) and switching (RR 0·65, 0·47-0·89; NNT 5·17, 3·77-18·18). Results were supported by moderate confidence of evidence and confirmed by secondary analyses and by several sensitivity and subgroup analyses, including removing studies with abrupt antipsychotic discontinuation or fast tapering (≤4 weeks). No tolerability differences emerged between treatment strategies. According to the Cochrane Risk-of-Bias tool, version 2, 16·8% of included RCTs had an overall high risk of bias for the primary outcome. We found moderate heterogeneity (τ 2 =0·13; I 2 =61%) and no overall incoherence for the primary analysis. Results were supported by moderate confidence of evidence and confirmed by secondary analyses., Interpretation: Contrary to our original hypothesis, we found that continuing antipsychotic treatment at standard doses or switching to a different antipsychotic are similarly effective treatment strategies, whereas reducing antipsychotic doses below standard doses is associated with higher risk of relapse than the other two maintenance treatment strategies and should therefore be limited to selected cases. Despite limitations, including moderate heterogeneity and moderate certainty of evidence, these results are of pragmatic relevance for clinicians, and should support the update of evidence-based guidelines., Funding: None., Competing Interests: Declaration of interests CUC has been a consultant, advisor, or both to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Cardio Diagnostics, Compass, Damitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen Johnson & Johnson, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Relmada, Reviva, Rovi, Seqirus, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, and Viatris. CUC provided expert testimony for Janssen and Otsuka. CUC served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, and Teva. CUC has received grant support from Janssen and Takeda. CUC received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, and LB Pharma. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe., Methods: Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ⩾ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes., Results: Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p -value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p -value = 0.230). SH + was associated with improvements at 12 months in psychological distress ( p -value = 0.004), depressive symptoms ( p -value = 0.011) and wellbeing ( p -value = 0.001)., Conclusions: The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.

Background: Hypophonia is a prevailing problem in people with multiple sclerosis (PwMS). However, evidence supporting the effectiveness of voice rehabilitation is lacking., Objective: The aim of this study was to identify the most effective method to reduce hypophonia., Methods: In this randomized controlled trial, 44 PwMS were randomized to intensive and high-effort voice treatment groups, the LSVT-LOUD ® , and conventional treatment group. Subjects received 16 treatments (4 sessions/week) lasting 45 minutes. The primary outcome was voice intensity (dB) in monologue, vocalization, and sentences while voice handicap index (VHI) measured voice self-perception. Outcomes were assessed by a blinded observer at baseline, post-treatment, and 15-month follow-up (FU)., Results: Linear models revealed a significant post-intervention between-group mean difference in favor of LSVT-LOUD for monologue: +6.3 dB (95% CI: 2.5 to 10.1); vocalization: +7.4 dB (95% CI: 2.3 to 12.5); and sentences: +9.5 dB (95% CI: 4.7 to 14.3). However, 43.7% PwMS in the LSVT-LOUD and 10% in the conventional treatment group obtained a full recovery of voice intensity (>60 dB) post-treatment, Fisher's test = 13.3, p  < 0.01. However, these improvements were not maintained at FU. Between-group differences at VHI were -10.8 (95% CI: -21.2 to -0.4) and -11.3 (95% CI: -24.3 to -1.7) in favor of LSVT-LOUD at post and FU., Conclusion: LSVT-LOUD can be a valid treatment to increase voice intensity in PwMS. However, results suggest the need for FU interventions targeting maintenance.

According to current evidence and guidelines, continued antipsychotic treatment is key for preventing relapse in people with schizophrenia-spectrum disorders, but evidence-based recommendations for the choice of the individual antipsychotic for maintenance treatment are lacking. Although oral antipsychotics are often prescribed first line for practical reasons, long-acting injectable antipsychotics (LAIs) are a valuable resource to tackle adherence issues since the earliest phase of disease. Medline, EMBASE, PsycINFO, CENTRAL and CINAHL databases and online registers were searched to identify randomized controlled trials comparing LAIs or oral antipsychotics head-to-head or against placebo, published until June 2021. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse and dropout due to adverse events. We used the Cochrane Risk of Bias tool to assess study quality, and the CINeMA approach to assess the confidence of pooled estimates. Of 100 eligible trials, 92 (N=22,645) provided usable data for meta-analyses. Regarding relapse prevention, the vast majority of the 31 included treatments outperformed placebo. Compared to placebo, "high" confidence in the results was found for (in descending order of effect magnitude) amisulpride-oral (OS), olanzapine-OS, aripiprazole-LAI, olanzapine-LAI, aripiprazole-OS, paliperidone-OS, and ziprasidone-OS. "Moderate" confidence in the results was found for paliperidone-LAI 1-monthly, iloperidone-OS, fluphenazine-OS, brexpiprazole-OS, paliperidone-LAI 1-monthly, asenapine-OS, haloperidol-OS, quetiapine-OS, cariprazine-OS, and lurasidone-OS. Regarding tolerability, none of the antipsychotics was significantly worse than placebo, but confidence was poor, with only aripiprazole (both LAI and OS) showing "moderate" confidence levels. Based on these findings, olanzapine, aripiprazole and paliperidone are the best choices for the maintenance treatment of schizophrenia-spectrum disorders, considering that both LAI and oral formulations of these antipsychotics are among the best-performing treatments and have the highest confidence of evidence for relapse prevention. This finding is of particular relevance for low- and middle-income countries and constrained-resource settings, where few medications may be selected. Results from this network meta-analysis can inform clinical guidelines and national and international drug regulation policies., (© 2022 World Psychiatric Association.)

Importance: The cost-effectiveness of the Self-Help Plus (SH+) program, a group-based, guided, self-help psychological intervention developed by the World Health Organization for people affected by adversity, is unclear., Objective: To investigate the cost-utility of providing the SH+ intervention combined with enhanced usual care vs enhanced usual care alone for Syrian refugees or asylum seekers hosted in Turkey., Design, Setting, and Participants: This economic evaluation was performed as a prespecified part of an assessor-blinded randomized clinical trial conducted between October 1, 2018, and November 30, 2019, with 6-month follow-up. A total of 627 adults with psychological distress but no diagnosed psychiatric disorder were randomly assigned to the intervention group or the enhanced usual care group., Interventions: The SH+ program was a 5-session (2 hours each), group-based, stress management course in which participants learned self-help skills for managing stress by listening to audio sessions. The SH+ sessions were facilitated by briefly trained, nonspecialist individuals, and an illustrated book was provided to group members. Th intervention group received the SH+ intervention plus enhanced usual care; the control group received only enhanced usual care from the local health care system. Enhanced usual care included access to free health care services provided by primary and secondary institutions plus details on nongovernmental organizations and freely available mental health services, social services, and community networks for people under temporary protection of Turkey and refugees., Main Outcomes and Measures: The primary outcome measure was incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the Turkish health care system. An intention-to-treat analysis was used including all participants who were randomized and for whom baseline data on costs and QALYs were available. Data were analyzed September 30, 2020, to July 30, 2021., Results: Of 627 participants (mean [SD] age, 31.3 [9.0] years; 393 [62.9%] women), 313 were included in the analysis for the SH+ group and 314 in the analysis for the enhanced usual care group. An incremental cost-utility ratio estimate of T£6068 ($1147) per QALY gained was found when the SH+ intervention was provided to groups of 10 Syrian refugees. At a willingness to pay per QALY gained of T£14 831 ($2802), the SH+ intervention had a 97.5% chance of being cost-effective compared with enhanced usual care alone., Conclusions and Relevance: This economic evaluation suggests that implementation of the SH+ intervention compared with enhanced usual care alone for adult Syrian refugees or asylum seekers hosted in Turkey is cost-effective from the perspective of the Turkish health care system when both international and country-specific willingness-to-pay thresholds were applied.

Refugees are at high risk of developing mental disorders. There is no evidence from randomized controlled trials (RCTs) that psychological interventions can prevent the onset of mental disorders in this group. We assessed the effectiveness of a self-help psychological intervention developed by the World Health Organization, called Self-Help Plus, in preventing the development of mental disorders among Syrian refugees experiencing psychological distress in Turkey. A two-arm, assessor-masked RCT was conducted in two Turkish areas. Eligible participants were adult Syrian refugees experiencing psychological distress (General Health Questionnaire ≥3), but without a diagnosis of mental disorder. They were randomly assigned either to the Self-Help Plus arm (consisting of Self-Help Plus combined with Enhanced Care as Usual, ECAU) or to ECAU only in a 1:1 ratio. Self-Help Plus was delivered in a group format by two facilitators over five sessions. The primary outcome measure was the presence of any mental disorder assessed by the Mini International Neuropsychiatric Interview at six-month follow-up. Secondary outcome measures were the presence of mental disorders at post-intervention, and psychological distress, symptoms of post-traumatic stress disorder and depression, personally identified psychological outcomes, functional impairment, subjective well-being, and quality of life at post-intervention and six-month follow-up. Between October 1, 2018 and November 30, 2019, 1,186 refugees were assessed for inclusion. Five hundred forty-four people were ineligible, and 642 participants were enrolled and randomly assigned to either Self-Help Plus (N=322) or ECAU (N=320). Self-Help Plus participants were significantly less likely to have any mental disorders at six-month follow-up compared to the ECAU group (21.69% vs. 40.73%; Cramer's V = 0.205, p<0.001, risk ratio: 0.533, 95% CI: 0.408-0.696). Analysis of secondary outcomes suggested that Self-Help Plus was not effective immediately post-intervention, but was associated with beneficial effects at six-month follow-up in terms of symptoms of depression, personally identified psychological outcomes, and quality of life. This is the first prevention RCT ever conducted among refugees experiencing psychological distress but without a mental disorder. Self-Help Plus was found to be an effective strategy for preventing the onset of mental disorders. Based on these findings, this low-intensity self-help psychological intervention could be scaled up as a public health strategy to prevent mental disorders in refugee populations exposed to ongoing adversities., (© 2022 World Psychiatric Association.)

Polystyrene (PS) is a plastic polymer extensively used for food packaging. PS is difficult to decompose and has low recycling rates, resulting in its accumulation in the environment, in the form of microplastic particles causing pollution and harming oceans and wildlife. Degradation of PS by mealworms ( Tenebrio molitor ) has been suggested as a possible biological strategy for plastic contamination; however, the biodegradation mechanism of PS by mealworms is poorly understood. It is hypothesized that the gut microbiome plays an important role in the degradation of PS by mealworms. This study carried out a comparative analysis of the gut microbiome of Tenebrio molitor larvae under different feeding strategies, and of the formation of degradation compounds (monomers, oligomers). A diet of bran:PS at 4:1 and 20:1 ratios was tested. The diet with the low ratio of bran:PS led to the presence of higher amounts of these compounds, compared to that with the high ratio. In addition, it was demonstrated that the addition of H 2 O significantly improved the biodegradation of PS monomer and oligomer residues, which could be identified only in the frass. The protein and nitrogen contents in insects' biomass and frass varied amongst treatments. The diets resulted in differences in the gut microbiota, and three potential bacterial strains were identified as candidates involved in the biodegradation of PS.

This article describes a randomized controlled trial to evaluate the effectiveness of a supervised online delivery of self-help plus (SH+), during the second wave of COVID-19 contagions in Northern Italy. The SH+ is a psychological intervention developed by the World Health Organization to increase a person's ability to deal with stress. In this trial, it was tested primarily as a tool to reduce anxiety and post-traumatic symptomatology in workers of residential nursing and care homes. In order to partial out non-specific effects of the intervention, the SH+ was compared to an equally supervised and structured alternative activity. Secondarily, in view of future emergencies, the potential of SH+ as a tool to reduce perceived stress, increase subjective well-being and foster individual resilience was explored. At post-intervention, the preregistered analysis revealed no difference in self-reported anxiety and/or post-traumatic symptomatology between the group receiving the SH+ and the group engaged in an alternative activity. Some specific and positive effects of the SH+ intervention were only found on self-reported intervention effectiveness and engagement in exploratory analyses. These findings raise the question whether the previously documented effectiveness of the SH+ on self-reported symptomatology and on the prevention of psychiatric conditions could be attributed mostly to non-specific rather than specific factors connected with participant enrolment in a psychological intervention. Indeed, the effects of the SH+ had been previously compared only to the effects of not being engaged in any alternative activity (often described in the literature as 'treatment as usual'-or 'enhanced treatment as usual', when some relevant information is given to the control group as a one-off). Given the negative findings of this study, before the SH+ is implemented in clinical practice, further studies should be conducted to examine its short- and long-term beneficial effects, by means of randomized studies that employ alternative but similarly structured interventions as control conditions, aiming to minimize the confounding effect of non-specific factors., (© 2021 The Authors.)

The majority of youth in the juvenile justice system have experienced multiple traumatic events in their lives, including community violence, physical abuse, neglect, and traumatic loss. These high prevalence rates, coupled with the known negative consequences of trauma in childhood and adolescence, have led to a greater emphasis on implementing trauma-informed services and practices within juvenile justice settings. However, although many stakeholders and government entities have expressed support for creating more trauma-informed juvenile justice systems, there is still limited empirical knowledge about which interventions are most effective at improving outcomes, particularly at the organizational or facility level. In an effort to fill this gap, the current study evaluated the impact of a trauma-informed milieu intervention, including skills training for youth and training for staff, on rates of violence at two secure juvenile detention facilities ( N = 14,856) located in a large Northeastern city. The analyses revealed that the intervention was significantly related to a reduction of violent incidents in Facility A, with no impact on incidents in Facility B. Follow-up analyses revealed that a larger proportion of eligible youth in Facility A completed the skills group program as compared with eligible youth in Facility B (16% vs. 9%). This finding has important implications for the implementation of trauma-informed interventions for youth in juvenile detention settings, as it suggests that to impact outcomes at the facility level, a minimum threshold of youth may need to be exposed to the intervention. In addition, reductions in violence at Facility A were only realized after both staff training and youth skills components were implemented, suggesting that both components are necessary to create change at the facility level. Future research is needed to further explore the impact of organizational and implementation-level factors on trauma-informed care outcomes in juvenile justice settings.

Background: Refugees and asylum seekers face various stressors due to displacement and are especially vulnerable to common mental disorders. To effectively manage psychological distress in this population, innovative interventions are required. The World Health Organization (WHO) Self-Help Plus (SH+) intervention has shown promising outcomes in reducing symptoms of common mental disorders among refugees and asylum seekers. However, individual participant differences in response to SH+ remain largely unknown. The Individual Participant Data (IPD) meta-analysis synthesizes raw datasets of trials to provide cutting-edge evidence of outcomes that cannot be examined by conventional meta-analytic approaches., Objectives: This protocol outlines the methods of a series of IPD meta-analyses aimed at examining the effects and potential moderators of SH+ in (a) reducing depressive symptoms at post-intervention and (b) preventing the six-month cumulative incidence of mental disorders in refugees and asylum seekers., Method: RCTs on SH+ have been identified through WHO and all authors have agreed to share the datasets of the trials. The primary outcomes of the IPD meta-analyses are (a) reduction in depressive symptoms at post-intervention, and (b) prevention of six-month cumulative incidence of mental disorders. Secondary outcomes include post-traumatic stress disorder symptoms, well-being, functioning, quality of life, and twelve-month cumulative incidence of mental disorders. One-stage IPD meta-analyses will be performed using mixed-effects linear/logistic regression. Missing data will be handled by multiple imputation., Conclusions: These results will enrich current knowledge about the response to SH+ and will facilitate its targeted dissemination. The results of these IPD meta-analyses will be published in peer-reviewed journals., Competing Interests: Dr. Ross White acted as a consultant reviewer to the WHO in the development of the SH+ intervention, and I am an author on the papers reporting on the RCTs in the EU and Uganda., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses., Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors., Methods: The STAR Network 'Depot Study' was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively., Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4-44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3-43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4-84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6-40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6-27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742-0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003-4.634; p = 0.049)., Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation.

Introduction: Refugees and asylum seekers are vulnerable to common mental disorders, including post-traumatic stress disorder (PTSD). Using a network meta-analysis (NMA) approach, the present systematic review compared and ranked psychosocial interventions for the treatment of PTSD in adult refugees and asylum seekers., Methods: Randomised studies of psychosocial interventions for adult refugees and asylum seekers with PTSD were systematically identified. PTSD symptoms at postintervention was the primary outcome. Standardised mean differences (SMDs) and ORs were pooled using pairwise and NMA. Study quality was assessed with the Cochrane Risk of Bias (RoB) tool, and certainty of evidence was assessed through the Confidence in Network Meta-Analysis application., Results: A total of 23 studies with 2308 participants were included. Sixteen studies were conducted in high-income countries, and seven in low-income or middle-income countries. Most studies were at low risk of bias according to the Cochrane RoB tool. NMA on PTSD symptoms showed that cognitive behavioural therapy (CBT) (SMD=-1.41; 95% CI -2.43 to -0.38) and eye movement desensitisation and reprocessing (EMDR) (SMD=-1.30; 95% CI -2.40 to -0.20) were significantly more effective than waitlist (WL). CBT was also associated with a higher decrease in PTSD symptoms than treatment as usual (TAU) (SMD -1.51; 95% CI -2.67 to -0.36). For all other interventions, the difference with WL and TAU was not significant. CBT and EMDR ranked best according to the mean surface under the cumulative ranking. Regarding acceptability, no intervention had less dropouts than inactive interventions., Conclusion: CBT and EMDR appeared to have the greatest effects in reducing PTSD symptoms in asylum seekers and refugees. This evidence should be considered in guidelines and implementation packages to facilitate dissemination and uptake in refugee settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses., Methods: The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation)., Results: Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone)., Conclusions: LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.

Background: Coercive treatment comprises a broad range of practices, ranging from implicit or explicit pressure to accept certain treatment to the use of forced practices such as involuntary admission, seclusion and restraint. Coercion is common in mental health services., Aims: To evaluate the strength and credibility of evidence on the efficacy of interventions to reduce coercive treatment in mental health services. Protocol registration: https://doi.org/10.17605/OSF.IO/S76T3., Method: Systematic literature searches were conducted in MEDLINE, Cochrane Central, PsycINFO, CINAHL, Campbell Collaboration, and Epistemonikos from January 2010 to January 2020 for meta-analyses of randomised studies. Summary effects were recalculated using a common metric and random-effects models. We assessed between-study heterogeneity, predictive intervals, publication bias, small-study effects and whether the results of the observed positive studies were more than expected by chance. On the basis of these calculations, strength of associations was classified using quantitative umbrella review criteria, and credibility of evidence was assessed using the GRADE approach., Results: A total of 23 primary studies (19 conducted in European countries and 4 in the USA) enrolling 8554 participants were included. The evidence on the efficacy of staff training to reduce use of restraint was supported by the most robust evidence (relative risk RR = 0.74, 95% CI 0.62-0.87; suggestive association, GRADE: moderate), followed by evidence on the efficacy of shared decision-making interventions to reduce involuntary admissions of adults with severe mental illness (RR = 0.75, 95% CI 0.60-0.92; weak association, GRADE: moderate) and by the evidence on integrated care interventions (RR = 0.66, 95% CI 0.46-0.95; weak association, GRADE: low). By contrast, community treatment orders and adherence therapy had no effect on involuntary admission rates., Conclusions: Different levels of evidence indicate the benefit of staff training, shared decision-making interventions and integrated care interventions to reduce coercive treatment in mental health services. These different levels of evidence should be considered in the development of policy, clinical and implementation initiatives to reduce coercive practices in mental healthcare, and should lead to further studies in both high- and low-income countries to improve the strength and credibility of the evidence base.

Introduction: Self-Help Plus (SH+) is a group-based psychological intervention developed by the World Health Organization for managing stress., Objective: To assess the effectiveness of SH+ in preventing mental disorders in refugees and asylum seekers in Western Europe., Methods: We conducted a randomized controlled trial in 5 European countries. Refugees and asylum seekers with psychological distress (General Health Questionnaire score ≥3), but without a Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or ICD/10 diagnosis of mental disorder, as assessed with the Mini International Neuropsychiatric Interview (MINI), were randomized to SH+ or enhanced treatment as usual (ETAU). The primary outcome was the frequency of mental disorders with the MINI at 6 months. Secondary outcomes included the frequency of mental disorders at postintervention, self-identified problems, psychological symptoms, and other outcomes., Results: Four hundred fifty-nine individuals were randomly assigned to SH+ or ETAU. For the primary outcome, we found no difference in the frequency of mental disorders at 6 months (Cramer V = 0.007, p = 0.90, RR = 0.96; 95% CI 0.52-1.78), while the difference significantly favored SH+ at after the intervention (secondary outcome, measured within 2 weeks from the last session; Cramer V = 0.13, p = 0.01, RR = 0.50; 95% CI 0.29-0.87)., Conclusions: This is the first randomized indicated prevention study with the aim of preventing the onset of mental disorders in asylum seekers and refugees in Western Europe. As a prevention effect of SH+ was not observed at 6 months, but rather after the intervention only, modalities to maintain its beneficial effect in the long term need to be identified., (© 2021 The Author(s) Published by S. Karger AG, Basel.)