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Background: Standardised Diagnostic Assessment tools, such as the Development and Well-Being Assessment (DAWBA), may aid detection and diagnosis of emotional disorders but there is limited real-world evidence of their clinical or cost effectiveness., Methods: We conducted a multicentre, two-arm parallel group randomised controlled trial in eight large National Health Service Trusts in England providing multidisciplinary specialist Child and Adolescent Mental Health Services (CAMHS). Participants (5-17 year-olds with emotional difficulties referred to CAMHS) were randomly assigned (1:1), following referral receipt, to either receive the DAWBA and assessment-as-usual (intervention group) or assessment-as-usual (control group). Data were self-reported by participants (parents and/or young person, depending on age) at baseline, 6- and 12-month post-randomisation and collected from clinical records up to 18 months post-randomisation. The primary outcome was a clinician-made diagnosis decision about the presence of an emotional disorder within 12 months of randomisation., Trial Registration: ISRCTN15748675., Results: In total, 1,225 children and young people (58% female sex) were randomised (615 intervention; 610 control). Adherence to the intervention (full/partial completion) was 80% (494/615). At 12 months, 68 (11%) participants in the intervention group received an emotional disorder diagnosis versus 72 (12%) in the control group (adjusted risk ratio (RR) 0.94 [95% CI 0.70, 1.28]). The intervention was not cost effective. There was no evidence of any differences between groups for service-related or participant-reported secondary outcomes, for example, CAMHS acceptance of the index referral (intervention 277 (45%) versus control 262 (43%); RR: 1.06 [95% CI: 0.94, 1.19]) was similar between groups., Conclusions: As delivered in this pragmatic trial, we found no evidence for the effectiveness or cost effectiveness of using a Standardised Diagnostic Assessment tool in aiding the detection of emotional disorders or clinical outcomes in clinically referred children and young people. Despite regular efforts to encourage clinicians to view the DAWBA report and consider its findings as part of assessment and diagnosis, we did not collect data on usage and therefore cannot confirm the extent to which clinicians did this. As a pragmatic trial that aimed to test the effectiveness of incorporating the DAWBA into usual practice and clinical care, our study found that, in the format as delivered in this trial, there was no impact on diagnosis or clinical outcomes., (Journal of Child Psychology and Psychiatry© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Hydrogen peroxide (H 2 O 2 ) is an oxidant produced endogenously by several enzymatic pathways. While it can cause molecular damage, H 2 O 2 also plays a role in regulating cell proliferation and survival through redox signaling pathways. In the vascular system, red blood cells (RBCs) are notably efficient at metabolizing H 2 O 2 . In addition to a robust antioxidant defense, we recently determined that human RBCs also have a high membrane permeability to H 2 O 2 that is independent of aquaporin 1 or aquaporin 3. In this work, we sought to further investigate the permeation mechanism of H 2 O 2 through the membrane of human RBCs. First, we explored the role of other erythrocytic membrane proteins in H 2 O 2 transport, including urea transporter B and ammonia transporter Rh proteins. However, no differences were found in H 2 O 2 permeability in RBCs lacking these proteins compared to control RBCs. We then focused on the hypothesis that H 2 O 2 diffuses through the lipid bilayer. To test this, we studied H 2 O 2 permeability in RBCs from patients with Gaucher disease (GD), which accumulate sphingolipids in the membrane, affecting RBC morphology and deformability. We found that RBCs from GD patients exhibited lower H₂O₂ membrane permeability. In another approach, we treated normal RBCs with hexanol, which fluidizes the lipid fraction of the RBC membrane, and observed an increase in the permeability to H 2 O 2 . In contrast, hexanol had no effect on the rate of water efflux by aquaporin 1. Together, these results support the hypothesis that H 2 O 2 diffusion through the RBC membrane occurs primarily through the lipid fraction., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The BRIGhTMIND study was a double-blind RCT comparing repetitive transcranial magnetic stimulation at a standard simulation site (the "F3" location given by the International 10-20 system, F3-rTMS) versus connectivity-guided intermittent theta burst stimulation (cgiTBS) for treatment-resistant depression. This present study reports the acceptability, safety, and tolerability of F3-rTMS versus cgiTBS., Methods: The present study used quantitative and qualitative methods. Two hundred fifty-four participants were included in the quantitative BRIGhTMIND acceptability and safety analysis (n = 126 F3-rTMS, n = 128 cgiTBS). Qualitative analysis included interviews for 15 participants (n = 7 F3-rTMS, n = 8 cgiTBS) and 582 written comments made by any participant randomised to the BRIGhTMIND trial regarding their experience of TMS and the study. Statistical analyses were used to explore differences between F3-rTMS and cgiTBS, as well as associations between acceptability, impression of change and safety. Qualitative data was analysed using an inductive thematic framework approach., Outcomes: Acceptability, TMS benefits/negative effects and impression of improvement ratings did not differ across the two treatment protocols, with ratings maintained long-term (71.4 % rated TMS acceptable, 48.8 % indicated benefits of TMS outweighed negative effects and 52.2 % feeling somewhat or much better at 26 week follow-up n = 203). Impression of improvement was positively associated with acceptability and TMS benefits. Qualitative themes included participants' TMS experience, TMS response variability, and lay theories of effectiveness. Safety profiles were comparable between F3-rTMS and cgiTBS, with 74.5 % of participants (n = 190/254) experiencing at least one adverse event possibly, probably, or definitely related to TMS. The majority of adverse events were transient and mild, with a sizeable number requiring simple treatments or small adjustments to TMS intensity and coil positioning. The F3-rTMS group had a significantly greater proportion of participants that required small adjustments to TMS to tolerate treatment compared to the cgiTBS group. Serious adverse events were rare, with one serious event in each treatment arm possibly related to TMS (F3-rTMS- psychotic episode, cgiTBS-manic episode)., Conclusion: F3-rTMS and cgiTBS are comparably safe, tolerable and highly acceptable interventions for treatment-resistant depression. BRIGhTMIND systematically collected data from a large sample, providing evidence to meet the information needs of patients, clinicians and policy makers., (Copyright © 2024. Published by Elsevier Inc.)