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Competing Interests: Competing interests: CV is a PhD student in the OSIRIS (Open Science to Increase Reproducibility in Science) project. The OSIRIS project has received funding from the European Union’s Horizon Europe research and innovation programme under the grant agreement number 101094725. SH has received funding from the European Union’s Horizon Europe programme, the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) and the LMUExcellent. CP received funding from NIH (NIEHS R01ES0324702 and NIA RF1AG074372). NJD has received funding from the European Union’s Horizon Europe programme, also via the OSIRIS project, the Naji Foundation, the German Federal Ministry of Education and Research (BMBF) and the Fetzer Franklin Memorial Fund, and has been employed on grants from the Mohn-Westlake Foundation, Laura and John Arnold Foundation, Elsevier and the Good Thinking Society in the last 5 years. BT is compensated for consulting with Seed Health and Enzymetrics Biosciences on microbiome study design. FN received funding from the French National Research Agency (ANR-17-CE36-0010), the French Ministry of Health and the French Ministry of Research. He is a work package leader in the OSIRIS project. He is a work package leader for the doctoral network MSCA-DN SHARE-CTD (HORIZON-MSCA-2022-DN-01 101120360), funded by the EU. The work of JPAI has been supported by an unrestricted gift from Sue and Bob O’Donnell to Stanford University.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members towards one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but non-financial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analysing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated towards COVID-19 elimination (zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases towards advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Psychotherapies are first-line treatments for most mental disorders, but their absolute outcomes (i.e., response and remission rates) are not well studied, despite the relevance of such information for health care users, providers and policy makers. We aimed to examine absolute and relative outcomes of psychotherapies across eight mental disorders: major depressive disorder (MDD), social anxiety disorder, panic disorder, generalized anxiety disorder (GAD), specific phobia, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and borderline personality disorder (BPD). We used a series of living systematic reviews included in the Metapsy initiative (www.metapsy.org), with a common strategy for literature search, inclusion of studies and extraction of data, and a common format for the analyses. Literature search was conducted in major bibliographical databases (PubMed, PsycINFO, Embase, and the Cochrane Register of Controlled Trials) up to January 1, 2023. We included randomized controlled trials comparing psychotherapies for any of the eight mental disorders, established by a diagnostic interview, with a control group (waitlist, care-as-usual, or pill placebo). We conducted random-effects model pairwise meta-analyses. The main outcome was the absolute rate of response (at least 50% symptom reduction between baseline and post-test) in the treatment and control conditions. Secondary outcomes included the relative risk (RR) of response, and the number needed to treat (NNT). Random-effects meta-analyses of the included 441 trials (33,881 patients) indicated modest response rates for psychotherapies: 0.42 (95% CI: 0.39-0.45) for MDD; 0.38 (95% CI: 0.33-0.43) for PTSD; 0.38 (95% CI: 0.30-0.47) for OCD; 0.38 (95% CI: 0.33-0.43) for panic disorder; 0.36 (95% CI: 0.30-0.42) for GAD; 0.32 (95% CI: 0.29-0.37) for social anxiety disorder; 0.32 (95% CI: 0.23-0.42) for specific phobia; and 0.24 (95% CI: 0.15-0.36) for BPD. Most sensitivity analyses broadly supported these findings. The RRs were significant for all disorders, except BPD. Our conclusion is that most psychotherapies for the eight mental disorders are effective compared with control conditions, but absolute response rates are modest. More effective treatments and interventions for those not responding to a first-line treatment are needed., (© 2024 World Psychiatric Association.)

Background: Psychological interventions that are efficacious as treatments for depression could indirectly affect suicide-related outcomes. We examined suicidal thoughts and behaviours as eligibility criteria, outcomes, and adverse events across trials of psychotherapy for depression., Methods: We used a publicly available meta-analytic database developed through systematic searches (updated as of May 1, 2023) to identify randomised controlled trials in which a psychological intervention for depression was compared with an inactive or non-specific control condition in adults with depression and in which any suicide-related outcomes were reported. We also identified studies in which suicide risk was an exclusion criterion. We excluded inpatient studies and trials of unguided digital interventions or collaborative care that included a psychological component. Pairs of reviewers worked independently to select studies and extract data. In a random-effects meta-analysis with robust variance estimation, we assessed the effect of the psychological intervention on suicide outcomes in trials in which suicide was explicitly assessed as an outcome with clinical scales with established psychometric properties. Risk of bias was assessed with the Cochrane risk-of-bias tool (version 2)., Findings: Of the 469 randomised trials we identified in which a psychological intervention was compared with an inactive control in people with depression, 251 excluded people judged at risk of suicide. Any assessment of suicide was included in only 45 trials, 12 of which assessed suicidal ideation or risk as an outcome. These 12 trials included 3930 participants, 2795 (71%) of whom were female and 1135 (29%) of whom were male; data for age and ethnicity were not consistently reported. Psychological interventions for depression were associated with a small reduction in suicidal ideation and risk in 11 trials (one trial reported only follow-up data) after the intervention (standardised mean difference -0·31 [95% CI -0·60 to -0·03]) but not at follow-up (-0·49 [-1·31 to 0·32]). Suicide-related adverse events were reported in 25 trials, and suicide-related serious adverse events (eg, suicide attempts, deaths by suicide) were reported in 13 trials. Heterogeneity was substantial across all analyses, and prediction intervals crossed zero., Interpretation: Trials of psychological interventions for depression rarely report assessments of suicide. Psychological interventions might reduce suicidal ideation in patients with depression, but more randomised controlled trials are required to clarify this effect. Monitoring and reporting of suicide-related adverse events should be improved in trials of psychological interventions for depression, and future trials should incorporate outcomes related to suicidal thoughts or behaviours., Funding: None., Translation: For the Spanish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: FN received funding from the French National Research Agency (ANR-17-CE36-0010), the French Ministry of Health and the French Ministry of Research. He is a work package leader in the OSIRIS project (Open Science to Increase Reproducibility in Science), which has received funding from the European Union’s Horizon Europe research and innovation programme under the grant agreement No. 101094725. He is a work package leader for the doctoral network MSCA-DN SHARE-CTD (HORIZON-MSCA-2022-DN-01 101120360), funded by the EU. CJP received funding from National Institutes for Health (NIEHS R01ES0324702 and NIA RF1AG074372). NJD has received funding from the Horizon Europe programme, the OSIRIS project, the Naji Foundation, the German Federal Ministry of Education and Research, and the Fetzer Franklin Memorial Fund and has been employed on grants from the Mohn-Westlake Foundation, Laura and John Arnold Foundation, Elsevier, and the Good Thinking Society in the past five years. SH has received funding from Horizon Europe, the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection, and from LMUExcellent.

Competing Interests: Declaration of competing interest None declared. The Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) is supported by the Foundation Clinical Neuroimmunology and Neuroscience Basel (Switzerland).

Objectives: This descriptive study of registered trials aimed to identify large clinical trials on antidepressants for mental disorders: (1) to assess what proportion could be labelled as 'seeding trials' (trials for marketing purposes) and (2) to describe their methodological characteristics and outcomes., Design: A search was conducted across all trials registered on ClinicalTrials.gov by drug name in March 2017., Setting: All trials registered in the database of ClinicalTrials.gov were screened. Large registered studies were received and studies focusing prospectively on the effects of antidepressants in mental health disorders. Specific data items were extracted automatically, and subsequently inspected, corrected and completed by hand., Participants: Prospective studies were selected focusing on the effects of antidepressants in any mental health disorder with 800 participants or more planned for inclusion., Main Outcome Measures: Three members from the study team independently assessed the following 'seeding trial' characteristics in each registered study: a high level of involvement of the product manufacturer in the study design, in the data analysis and reporting of the study, an abnormally low ratio of patient numbers to study site, spin and/or omissions of clinically relevant findings in the abstracts, and conclusions that focused on secondary endpoints and surrogate markers. Secondary outcomes were the exploration of a functional outcome and suicidality., Results: 31 trials were identified from clinical trials database. 18/31 were published (58%). 8 of these 18 (44%) studies were identified as possible seeding trials. 13/31 (42%) large trials planned to explore functioning and 5/31 (16%) suicidality., Conclusions: Large trials are rare in the field of antidepressant research. Some could be 'seeding trials'. Few explored suicidality. Identifying seeding trials from incomplete data entries in registries, especially when almost half of the studies were still unpublished, posed considerable challenges. The delay between our research and publication limits the strength of our conclusions., Prospero Registration Number: CRD42017065591., 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.)

A broad range of psychotherapies have been proposed and evaluated in the treatment of borderline personality disorder (BPD), but the question which specific type of psychotherapy is most effective remains unanswered. In this study, two network meta-analyses (NMAs) were conducted investigating the comparative effectiveness of psychotherapies on (1) BPD severity and (2) suicidal behaviour (combined rate). Study drop-out was included as a secondary outcome. Six databases were searched until 21 January 2022, including RCTs on the efficacy of any psychotherapy in adults (⩾18 years) with a diagnosis of (sub)clinical BPD. Data were extracted using a predefined table format. PROSPERO ID:CRD42020175411. In our study, a total of 43 studies ( N = 3273) were included. We found significant differences between several active comparisons in the treatment of (sub)clinical BPD, however, these findings were based on very few trials and should therefore be interpreted with caution. Some therapies were more efficacious compared to GT or TAU. Furthermore, some treatments more than halved the risk of attempted suicide and committed suicide (combined rate), reporting RRs around 0.5 or lower, however, these RRs were not statistically significantly better compared to other therapies or to TAU. Study drop-out significantly differed between some treatments. In conclusion, no single treatment seems to be the best choice to treat people with BPD compared to other treatments. Nevertheless, psychotherapies for BPD are perceived as first-line treatments, and should therefore be investigated further on their long-term effectiveness, preferably in head-to-head trials. DBT was the best connected treatment, providing solid evidence of its effectiveness.

Background: The treatment of depression in patients with somatic disorders is crucial, given its negative impact on quality of life (QoL), functioning, and even on the somatic disease prognosis. We aimed to examine the most updated evidence on the effects of psychotherapy in patients with depression and somatic disorders, including HIV, oncological, cardiometabolic, and neurological disorders., Methods: We conducted a meta-analysis of 75 randomized trials (8209 participants) of psychotherapy for adults with somatic disorders and a diagnosis or elevated symptoms of depression. Outcomes included depression, QoL, somatic health-related outcomes, and mortality., Results: Psychotherapy significantly reduced the severity of depression at post-treatment across all categories of somatic disorders (Hedges' g = 0.65; 95% CI 0.52-0.79), with sustained effects at 6-11 months ( g = 0.38; 95% CI 0.22-0.53) and at 12 months follow-up or longer ( g = 0.13; 95% CI 0.04-0.21). Psychotherapy also showed significant effects on QoL ( g = 0.26; 95% CI 0.17-0.35), maintained up to 11 months follow-up ( g = 0.25; 95% CI 0.16-0.34). No significant effects were observed on the most frequently reported somatic health-related outcomes (glycemic control, pain), and neither on mortality. Heterogeneity in most analyses was very high, and only 29 (38%) trials were rated at low risk of bias (RoB)., Conclusions: Psychotherapy may be an effective treatment option for patients with depression and somatic disorders, with long-term effects on depression severity and QoL. However, these results should be interpreted with caution due to heterogeneity and RoB.

Competing Interests: We declare no competing interests.

Objectives: The effectiveness of pharmacologic prophylaxis against catheter-associated thrombosis in children is unclear. We evaluated the compliance and outcomes associated with a prophylactic enoxaparin protocol in postoperative cardiac children., Design: The protocol was implemented as a quality improvement initiative and then analyzed using interrupted time series method. Data collected from November 2014 to December 2018 were divided into preprotocol (period 1), protocol implementation (period 2), and protocol revision (period 3)., Setting: A 12-bed academic pediatric cardiac ICU., Patients: Children less than or equal to 18 years old with congenital heart disease admitted postoperatively with central venous catheter in situ for greater than or equal to 1 day., Interventions: Before 2016, prophylactic enoxaparin was administered according to physician preference. In January 2016, an enoxaparin protocol was implemented with a goal anti-Xa range of 0.25-0.49 international units/mL. Protocol was revised in February 2017 to increase the starting dose by 25% for infants less than 1 year old., Measurements and Main Results: We analyzed 780 hospitalizations from 636 children. Median percentage of catheter-days on prophylactic enoxaparin was 33% (interquartile range [IQR], 23-47%), 42% (IQR, 30-51%), and 38% (IQR, 35-52%) in periods 1-3, respectively. Percentage of catheter-days on enoxaparin showed immediate increase of 90% (95% CI, 17-210%) between periods 1 and 2 and sustained increase of 2% (95% CI, 0.3-4%) between periods 2 and 3. Median rates of thrombosis per 1,000 catheter-days were 5.8 (IQR, 0-9.3), 3.8 (IQR, 0-12), and 0 (IQR, 0-5.3) in periods 1-3, respectively. Rate of thrombosis showed immediate decrease of 67% (95% CI, 12-87%) between periods 1 and 2 and sustained decrease of 11% (95% CI, 2-18%) between periods 1 and 3., Conclusions: The temporal association between increase in percentage of catheter-days on enoxaparin and decrease in rate of thrombosis suggests the effectiveness of prophylactic enoxaparin., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Data sharing is gradually becoming a requirement across all fields of science, owing to its key benefits in verifying the reproducibility of findings and reusing existent data for new purposes. Although metaresearch studies are complex, time-consuming, and hinge on the availability of data produced and curated by others, there has been little focus on how they make their own data available. This is in stark contrast to the heightened attention data sharing has received in clinical research. Yet, as secondary data users par excellence, metaresearchers are ethically bound to both improving and evaluating data sharing practices and correctly sharing their own data. We contrast particularities of data sharing in metaresearch and clinical research, such as benefits, barriers, and inadequate and potentially pervasive sharing practices. We conclude with an array of concrete and tailored recommendations for improvement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data., Aims: This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602)., Method: Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes., Conclusions: To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.

Introduction: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge., Methods: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart review. Surveys for clinical outcomes were administered to caregivers., Results: Of the 470 subjects included in this study, 249 (53.0%) received employer-based insurance coverage and 221 (47.0%) received Medicaid as sole coverage at least once between 0 and 3 years of age. The Medicaid group was twice as likely to have sick visits (adjusted odd ratio [OR]: 2.06; p = 0.009) and emergency department visits (aOR: 2.09; p = 0.028), and three times more likely to be admitted for respiratory reasons (aOR: 3.04; p = 0.001) than those in the employer-based group. Additionally, those in the Medicaid group were more likely to have nighttime respiratory symptoms (aOR: 2.62; p = 0.004)., Conclusions: Children with BPD who received Medicaid coverage were more likely to utilize acute care and have nighttime respiratory symptoms during the first 3 years of life. More comprehensive studies are needed to determine whether the use of Medicaid represents a barrier to accessing care, lower socioeconomic status, and/or a proxy for detrimental environmental exposures., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

During the COVID-19 pandemic, the rush to scientific and political judgements on the merits of hydroxychloroquine was fuelled by dubious papers which may have been published because the authors were not independent from the practices of the journals in which they appeared. This example leads us to consider a new type of illegitimate publishing entity, 'self-promotion journals' which could be deployed to serve the instrumentalisation of productivity-based metrics, with a ripple effect on decisions about promotion, tenure and grant funding, but also on the quality of manuscripts that are disseminated to the medical community and form the foundation of evidence-based medicine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Though aberrant face processing is a hallmark of autistic spectrum disorder (ASD), findings on accompanying brain activity are divergent. Therefore, we conducted an activation likelihood estimation (ALE) meta-analysis of studies examining brain activity during face processing., Methods: We searched PubMed and PsycINFO using combinations of terms as 'fMRI', 'Autism Spectrum Disorder', 'Face Perception'. Eligible studies reported on DSM-diagnosed ASD individuals, compared to controls (HC), using face stimuli presented in fMRI and reporting whole-brain analysis coordinates. We compared two approaches: 'convergence of differences' (primary analysis) using study-level coordinates from ASD vs. HC contrasts, and 'differences in convergence' (secondary) pooling coordinates within each group separately, and contrasting the resultant ALE maps., Results: Thirty-five studies (655 ASD and 668 HC) were included. Primary analysis identified a cluster in amygdala/parahippocampus where HC showed greater convergence of activation. Secondary analysis yielded no significant results., Conclusions: Results suggest that ASD dysfunction in face processing relies on structures involved in emotional processing rather than perception. We also demonstrate that the two ALE methodologies lead to divergent results., (© 2021 Association for Child and Adolescent Mental Health.)

Alongside the growing concerns regarding predatory journal growth, other questionable editorial practices have gained visibility recently. Among them, we explored the usefulness of the Percentage of Papers by the Most Prolific author (PPMP) and the Gini index (level of inequality in the distribution of authorship among authors) as tools to identify journals that may show favoritism in accepting articles by specific authors. We examined whether the PPMP, complemented by the Gini index, could be useful for identifying cases of potential editorial bias, using all articles in a sample of 5,468 biomedical journals indexed in the National Library of Medicine. For articles published between 2015 and 2019, the median PPMP was 2.9%, and 5% of journal exhibited a PPMP of 10.6% or more. Among the journals with the highest PPMP or Gini index values, where a few authors were responsible for a disproportionate number of publications, a random sample was manually examined, revealing that the most prolific author was part of the editorial board in 60 cases (61%). The papers by the most prolific authors were more likely to be accepted for publication within 3 weeks of their submission. Results of analysis on a subset of articles, excluding nonresearch articles, were consistent with those of the principal analysis. In most journals, publications are distributed across a large number of authors. Our results reveal a subset of journals where a few authors, often members of the editorial board, were responsible for a disproportionate number of publications. To enhance trust in their practices, journals need to be transparent about their editorial and peer review practices., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: IAC collaborates with two of the authors of the main article (CB and TF) on research projects unrelated to the current work. DMN declares no competing interests.

Florian Naudet and co-authors propose a pathway involving registered criteria for evaluation and approval of new drugs., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: ET is a former reviewer at the US Food and Drug Administration (1998-2001).

The effects of psychotherapies for depression have been examined in several hundreds of randomized trials, but no recent network meta-analysis (NMA) has integrated the results of these studies. We conducted an NMA of trials comparing cognitive behavioural, interpersonal, psychodynamic, problem-solving, behavioural activation, life-review and "third wave" therapies and non-directive supportive counseling with each other and with care-as-usual, waiting list and pill placebo control conditions. Response (50% reduction in symptoms) was the primary outcome, but we also assessed remission, standardized mean difference, and acceptability (all-cause dropout rate). Random-effects pairwise and network meta-analyses were conducted on 331 randomized trials with 34,285 patients. All therapies were more efficacious than care-as-usual and waiting list control conditions, and all therapies - except non-directive supportive counseling and psychodynamic therapy - were more efficacious than pill placebo. Standardized mean differences compared with care-as-usual ranged from -0.81 for life-review therapy to -0.32 for non-directive supportive counseling. Individual psychotherapies did not differ significantly from each other, with the only exception of non-directive supportive counseling, which was less efficacious than all other therapies. The results were similar when only studies with low risk of bias were included. Most therapies still had significant effects at 12-month follow-up compared to care-as-usual, and problem-solving therapy was found to have a somewhat higher long-term efficacy than some other therapies. No consistent differences in acceptability were found. Our conclusion is that the most important types of psychotherapy are efficacious and acceptable in the acute treatment of adult depression, with few significant differences between them. Patient preference and availability of each treatment type may play a larger role in the choice between types of psychotherapy, although it is possible that a more detailed characterization of patients with a diagnosis of depression may lead to a more precise matching between individual patients and individual psychotherapies., (© 2021 World Psychiatric Association.)

Though a plethora of functional magnetic resonance imaging (fMRI) studies explored the neurobiological underpinnings of borderline personality disorder (BPD), findings across different tasks were divergent. We conducted a systematic review and activation likelihood estimation (ALE) meta-analysis on the fMRI studies conducted in BPD patients compared to healthy controls (HC). We systematically searched PubMed and PsychINFO from inception until July 9th 2020 using combinations of database-specific terms like 'fMRI', 'Neuroimaging', 'borderline'. Eligible studies employed task-based fMRI of the brain in participants of any age diagnosed with BPD compared to HC, during any behavioral task and providing a direct contrast between the groups. From 762 entries, we inspected 92 reports full-texts and included 52 studies (describing 54 experiments). Across all experiments, the HC > BPD and BPD > HC meta-analyses did not yield any cluster of significant convergence of differences. Analyses restricted to studies of emotion processing revealed two significant clusters of activation in the bilateral hippocampal/amygdala complex and anterior cingulate for the BPD > HC meta-analysis. Fail-safe N and single study sensitivity analysis suggested significant findings were not robust. For the subgroup of emotional processing experiments, on a restricted number of experiments providing results for each group separately, another meta-analysis method (difference of convergence) showed a significant cluster in the insula/inferior frontal gyrus for the HC > BPD contrast. No consistent pattern of alteration in brain activity for BPD was evidenced suggesting substantial heterogeneity of processes and populations studied. A pattern of amygdala dysfunction emerged across emotion processing tasks, indicating a potential pathophysiological mechanism that could be transdiagnostic.

Background: Care-as-usual (CAU) is often used as a control condition in psychotherapy research, but it may vary considerably what that entails, ranging from no treatment, to routine treatment in primary care, general medical care, perinatal care, and specialized mental health care., Methods: We conducted a meta-analysis of trials comparing psychotherapy for depression to CAU, with a focus on the different categories of CAU and countries where the studies were conducted. We used an existing database of randomized trials on psychotherapy for depression that is updated every year., Results: A total of 140 studies with 15 419 patients were included. We found no significant differences in effects between categories of CAU (effect sizes ranging from g = 0.43 for CAU in primary care to g = 0.73 for no treatment), but heterogeneity was high in all CAU categories. After stratifying effects across specific countries (within CAU categories) we found that heterogeneity was considerably lower and there were several significant differences between countries. Overall, effects were larger in non-Western countries (g = 0.84 to 1.28) compared to those in Western countries (g = 0.52; p for difference = 0.002). Effects were smaller in studies with risk of bias (p = 0.01)., Conclusions: There are no significant differences between major categories of CAU when compared to psychotherapy conditions in randomized trials. However, effects of psychotherapy differ considerably across CAU conditions in specific countries. CAU therefore is a heterogeneous control condition in psychotherapy research.

Background: Mindfulness applications are popular tools for improving well-being, but their effectiveness is unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) that employed a mindfulness meditation app as the main intervention to improve users' well-being and mental-health related outcomes., Methods: A systematic search was conducted in PsycINFO, PubMed, Web of Science, ProQuest Dissertations and Theses Global, the Cochrane Library, Open Grey and ResearchGate through June, 2020. Effects were calculated as standardized mean difference (Hedges' g) between app-delivered mindfulness interventions and control conditions at post-test and pooled with a random-effects model., Results: From 2637 records, we selected 34 trials (N = 7566). Significant effect sizes were found at post-test for perceived stress (n = 15; g = 0.46, 95% CI [0.24, .68], I 2 = 68%), anxiety (n = 15; g = 0.28, 95% CI [0.16, .40], I 2 = 35%), depression (n = 15; g = 0.33, 95% CI [0.24, .43], I 2 = 0%), and psychological well-being (n = 5; g = 0.29, 95% CI [0.14, .45], I 2 = 0%). No significant effects were found for distress at post-test (n = 6; g = 0.10, 95% CI [-0.02, .22], I 2 = 11%) and general well-being (n = 5; g = 0.14, 95% CI [-0.02, 0.29], I 2  = 14%)., Conclusion and Limitations: Mindfulness apps seem promising in improving well-being and mental-health, though results should be interpreted carefully due to the small number of included studies, overall uncertain risk of bias and heterogeneity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In the coronavirus disease 2019 (COVID-19) pandemic, a large number of non-pharmaceutical measures that pertain to the wider group of social distancing interventions (e.g. public gathering bans, closures of schools, workplaces and all but essential business, mandatory stay-at-home policies, travel restrictions, border closures and others) have been deployed. Their urgent deployment was defended with modelling and observational data of spurious credibility. There is major debate on whether these measures are effective and there is also uncertainty about the magnitude of the harms that these measures might induce. Given that there is equipoise for how, when and if specific social distancing interventions for COVID-19 should be applied and removed/modified during reopening, we argue that informative randomised-controlled trials are needed. Only a few such randomised trials have already been conducted, but the ones done to-date demonstrate that a randomised trials agenda is feasible. We discuss here issues of study design choice, selection of comparators (intervention and controls), choice of outcomes and additional considerations for the conduct of such trials. We also discuss and refute common counter-arguments against the conduct of such trials.

Background: Virtual reality (VR) may enhance the effectiveness of psychological interventions for acute pain. We conducted a meta-analysis to assess the efficacy and safety of VR-based interventions for pain associated with medical procedures., Methods: We searched PubMed, EMBASE, the Cochrane Library, and PsycINFO until June 17th 2018. We identified randomized controlled trials (RCTs), comparing VR-based psychological interventions to usual care, for pain intensity (primary outcome) or affective and cognitive components of pain (secondary outcomes), assessed real-time or retrospectively. Two independent reviewers performed study selection and data extraction. Risk of bias was independently evaluated by three raters using the revised Cochrane Collaboration tool. A random-effects model using the Paule and Mandel estimator was used for pooling effect sizes., Results: 27 RCTs (1452 patients) provided enough data for meta-analysis. Compared to usual care, VR-based interventions reduced pain intensity both real-time (9 RCTs, Hedges' g = 0.95, 95% CI 0.32-1.57) and retrospectively (22 RCTs, g = 0.87, 95% CI 0.54-1.21). Results were similar for cognitive (8 RCTs, g = 0.82, 95% CI 0.39-1.26) and affective pain components (14 RCTs, g = 0.55, 95% CI 0.34-0.77). There was marked heterogeneity, which remained similarly high in sensitivity analyses. Across domains, few trials were rated as low risk of bias and there was evidence of publication bias. Adverse events were rare., Conclusions: Though VR-based interventions reduced pain for patients undergoing medical procedures, inferring clinical effectiveness is precluded by the predominance of small trials, with substantial risk of bias, and by incomplete reporting.

We aimed to assess whether Nobel prizes (widely considered the most prestigious award in science) are clustering in work done in a few specific disciplines. We mapped the key Nobel prize-related publication of each laureate awarded the Nobel Prize in Medicine, Physics, and Chemistry (1995-2017). These key papers mapped in only narrow sub-regions of a 91,726-cluster map of science created from 63 million Scopus-indexed published items. For each key Nobel paper, a median of 435 (range 0 to 88383) other Scopus-indexed items were published within one year and were more heavily cited than the Nobel paper. Of the 114 high-level domains that science can be divided into, only 36 have had a Nobel prize. Five of the 114 domains (particle physics [14%], cell biology [12.1%], atomic physics [10.9%], neuroscience [10.1%], molecular chemistry [5.3%]) have the lion's share, accounting in total for 52.4% of the Nobel prizes. Using a more granular classification with 849 sub-domains shows that only 71 of these sub-domains (8.3%) have at least one Nobel-related paper. Similar clustering was seen when we mapped all the 40,819 Scopus-indexed publications representing the career-long output of all the Nobel laureates. In conclusion, work resulting in Nobel prizes is concentrated in a small minority of scientific disciplines., Competing Interests: KWB is an employee of SciTech, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Cognitive bias modification (CBM) therapies, including attention bias modification, interpretation bias modification, or approach and avoidance training, are prototypical examples of mechanistically derived treatments, but their effectiveness is contentious. We aimed to assess the relative effectiveness of various CBM interventions for anxious and depressive symptomatology., Methods: For this systematic review and network meta-analysis, we searched PubMed, PsycINFO, Embase, and Cochrane Central Register from database inception up until Feb 7, 2020. We included randomised controlled trials of CBM versus control conditions or other forms of CBM for adults aged 18 years and older with clinical or subclinical anxiety or depression measured with a diagnostic interview or a validated clinical scale. We excluded studies comparing CBM with a non-CBM active intervention. Two researchers independently selected studies and evaluated risk of bias with the Cochrane Collaboration tool. Primary outcomes encompassed anxiety and depressive symptoms measured with validated clinical scales. We computed standardised mean differences (SMDs) with a restricted maximum likelihood random effects model. This study is registered with PROSPERO, CRD42018086113., Findings: From 2125 records we selected 85 trials, 65 (n=3897) on anxiety and 20 (n=1116) on depression. In a well connected network of anxiety trials, interpretation bias modification outperformed waitlist (SMD -0·55, 95% CI -0·91 to -0·19) and sham training (SMD -0·30, -0·50 to -0·10) for the primary outcome. Attention bias modification showed benefits only in post-hoc sensitivity analyses excluding post-traumatic stress disorder trials. Prediction intervals for all findings were large, including an SMD of 0. Networks of depression trials displayed evidence of inconsistency. Only four randomised controlled trials had low risk of bias on all six domains assessed., Interpretation: CBM interventions showed consistent but small benefits; however heterogeneity and risk of bias undermine the reliability of these findings. Larger, definitive trials for interpretation bias modification for anxiety might be warranted, but insufficient evidence precludes conclusions for depression., Funding: Romanian Ministry of Research and Innovation, The National Council for Scientific Research-The Executive Agency for Higher Education, Research, Development and Innovation Funding., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

There is no comprehensive meta-analysis of randomised trials examining the effects of Eye Movement Desensitization and Reprocessing (EMDR) on post-traumatic stress disorder (PTSD) and no systematic review at all of the effects of EMDR on other mental health problems. We conducted a systematic review and meta-analysis of 76 trials. Most trials examined the effects on PTSD (62%). The effect size of EMDR compared to control conditions was g = 0.93 (95% CI: 0.67-.18), with high heterogeneity ( I 2 = 72%). Only four of 27 studies had low risk of bias, and there were indications for publication bias. EMDR was more effective than other therapies (g = 0.36; 95% CI: 0.14-0.57), but not in studies with low risk of bias. Significant results were also found for EMDR in phobias and test anxiety, but the number of studies was small and risk of bias was high. EMDR was examined in several other mental health problems, but for none of these problems, sufficient studies were available to pool outcomes. EMDR may be effective in the treatment of PTSD in the short term, but the quality of studies is too low to draw definite conclusions. There is not enough evidence to advise it for the use in other mental health problems.

Background: In November 2017, the Food and Drug Administration (FDA) approved a version of a second-generation antipsychotic, aripiprazole, embedded with a sensor (Abilify MyCite)., Objective: To systematically review the evidence supporting the FDA's approval of digital aripiprazole and how that evidence was disseminated in the scientific literature and news reports., Study Selection: Prospective, double-blind, randomised controlled trials (RCTs), non-randomised and non-comparative studies were included if they focused on the use of digital aripiprazole. All scientific publications citing the trials were included if written in English. For the news reports, all languages were included if an English translation was available, and all records that were published after FDA approval were included., Findings: In the primary evidence search, no RCT comparing digital aripiprazole with a non-digital formulation, other active comparators or placebo was found. Only three non-comparative uncontrolled cohorts were found. No study provided data on remission, quality of life or any efficacy outcome. Fourteen scientific papers were identified that cited the trials and 70 news stories met the inclusion criteria. Almost 80% (11/14) of the scientific papers and three-fourths (52/70) of the news stories conveyed an unsupported impression of benefit., Conclusions: Regulatory approval for this first-ever digital drug was based on weak evidence, and there was no evidence of better adherence with the digital version of aripiprazole compared with the non-digital version. The possibilities afforded by this technology make room for a new type of evergreening (ie, patenting of older drugs with a sensor as a 'new invention'). Both the scientific literature and news reports conveyed an unsupported impression of benefit., Trial Registration Number: CRD42018089515., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)