Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial

Background The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. Aims To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. Method Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. Results Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76–0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69–0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. Conclusions These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting

5-HT₄ Receptor Agonist Effects on Functional Connectivity in the Human Brain:Implications for Procognitive Action

Background: Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT4 receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown.Methods: We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT4 receptor agonist) and 25 received placebo in a randomized double-blind design.Results: Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions.Conclusions: Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT4 receptor agonists in humans and supports the potential for 5-HT4 receptor agonists to be used in clinical psychiatric populations

Trial of Affordable Bone Conduction Headphones to Support a Deaf Child's Education in Malawi.

Peer reviewed: TrueA 13-year-old child with hearing loss secondary to chronic serous otitis media and bilateral tympanic perforations had been unable to hear the teacher at school and unable to pass end-of-year exams. In 2020, she trialed a bone conduction headset paired by Bluetooth to a remote microphone and used this to support her hearing at school, socializing with friends and in the family home. Due to the COVID (COronaVIrus Disease) pandemic and a cholera epidemic, she was followed up 3 years later. The child (now 16 years old) reported using the headset every day for 3 years. Able to hear the teacher, she reported having passed school exams every year since using the device, and now had ambitions to study medicine

Are neurocognitive factors associated with repetition of self-harm? A systematic review

Background: Prediction of self-harm is limited clinically. Early identification of individuals likely to repeat self-harm could improve outcomes and reduce suicide risk. Various neurocognitive deficits have been found in people who self-harm, but the ability of these to predict repetition has yet to be established Aims: Identify neurocognitive factors that may predict repetition of self-harm. Methods: Systematic narrative review of English language publications assessing neurocognitive functioning and self-harm repetition, searching multiple databases from inception to March 2015. Quality of studies was appraised. A narrative synthesis was performed. Results: 7026 unique records were identified, and 169 full-texts assessed. 15 unique studies provided data. No imaging studies could be included. Most studies assessed cognitive control or problem solving, but neither factor was consistently associated with repetition. However, specific tasks may show promise. Two studies in adolescents suggest that value-based decision-making impairments could be predictive of repetition. There were too few results for memory to draw specific conclusions. Conclusions: Selected studies suggest promise for particular neurocognitive factors and specific cognitive tasks in terms of repetition of self-harm

Data

Questionnaire and fMRI behavioural data for the 7 day prucalopride stud

A Multicenter Validity Study of Four Smartphone Hearing Test Apps in Optimized and Home Environments

Publication status: PublishedObjectivePure tone audiometry (PTA) is the gold standard for hearing assessment. However, it requires access to specialized equipment. Smartphone audiometry applications (apps) have been developed to perform automated threshold audiometry and could allow patients to perform self‐administered screening or monitoring. This study aimed to assess the validity and feasibility of patients using apps to self‐assess hearing thresholds at home, with comparison to PTA.MethodsA multi‐center, prospective randomized study was conducted amongst patients undergoing PTA in clinics. Participants were randomly allocated to one of four publicly‐available apps designed to measure pure tone thresholds. Participants used an app once in optimal sound‐treated conditions and a further three times at home. Ear‐specific frequency‐specific thresholds and pure tone average were compared using Pearson correlation coefficient. The percentage of app hearing tests with results within ±10 dB of PTA was calculated. Patient acceptability was assessed via an online survey.ResultsOne hundred thirty‐nine participants submitted data. The results of two at‐home automated smartphone apps correlated strongly/very strongly with PTA average and their frequency‐specific median was within ±10 dB accuracy. Smartphone audiometry performed in sound‐treated and home conditions were very strongly correlated. The apps were rated as easy/very easy to use by 90% of participants and 90% would be happy/very happy to use an app to monitor their hearing.ConclusionJudicious use of self‐performed smartphone audiometry was both valid and feasible for two of four apps. It could provide frequency‐specific threshold estimates at home, potentially allowing assessments of patients remotely or monitoring of fluctuating hearing loss.Level of Evidence2 Laryngoscope, 2024</jats:sec

Qualtrics template files

The Master Template file includes the following questionnaires: • BDI (Beck Depression Inventory - 21Q)* • EPQ (Eysenck Personality Questionnaire 90Q)* • Locus of Control (29Q)* • STAI-T (State-Trait Anxiety Inventory - Trait 20Q)* • STAI-S (State-Trait Anxiety Inventory - State 20Q)* • PANAS (Positive and Negative Affect Scale 20Q)* • SHAPS (Snaith-Hamilton Pleasure Scale 14Q)* • VAS (Visual Analogue Scales -combined 6Q) • VAS (Visual Analogue Scales -individual 16Q) • EHI (Edinburgh Handedness Inventory) • BIS (Barratt Impulsiveness Scale 30Q) • AGQ (Buss Perry Aggression Questionnaire 29Q) • ASEC (Anti-depressant Side Effect Checklist 18Q) • PHQ-9 (Patient Health Questionnaire 9Q) • GAD-7 (Generalised Anxiety Disorder 7Q) • BFNE (Brief Fear of Negative Evaluation 8Q) • FPES (Fear of Positive Evaluation 10Q) • BFIN (Big Five Inventory 8Q) • RESES (Rosenberg Self Esteem 10Q) • DAS24 (Derriford Appearance - short 24Q) • STAXI-S (State-Trait Anger Expression Inventory - State) • STAXI-T (State-Trait Anger Expression Inventory - Trait) • STAXI-AEC (State-Trait Anger Expression Inventory - Anger Expression and Control) • AMI (Apathy Motivation Index 18Q) • Epworth Sleepiness Scale (8Q) • HADS (Hospital Anxiety and Depression Scale 14Q) • PDQ (Perceived Deficits Questionnaire 20Q) • QUIP (Questionnaire for Impulsive-compulsive disorders in Parkinson's 15Q) • UDPRS Part I nM-EDL (Unified Parkinson's disease rating scale) Part 1 - Non Motor Aspects Experiences of Daily Living (7Q) • UDPRS Part II M-EDL (Unified Parkinson's disease rating scale) Part 2 - Non Motor Aspects Experiences of Daily Living (13Q) • PDQ (Perceived Deficits Questionnaire 20Q) • RBDSQ (REM Sleep Behaviour Disorder Screening 16Q) • BADS (behavioural activation for depression scale 25Q) • EROS (environmental reward observation scale 10Q) • MSPSS (multidimension scale of perceived social support 12Q) * = with scoring To use, download the file, then on qualtrics choose to Create a Project from Existing, select From a File and then navigate to select the Master Template file. This will be added to your library, and you can then rename it and remove or add questionnaires to suit your study. If you would like to to help add to the Master Template, feel free to do the above, and then add additional blocks of questions, and re-upload here (keeping the same file name as the download). The UDPRS III Motor Examination template is seperate, as an examiner rated scale - all the others are completed by participants