Study protocol for the use of time series forecasting and risk analyses to investigate the effect of the COVID-19 pandemic on hospital admissions associated with new-onset disability and frailty in a national, linked electronic health data setting.

INTRODUCTION: Older people were at particular risk of morbidity and mortality during COVID-19. Consequently, they experienced formal (externally imposed) and informal (self-imposed) periods of social isolation and quarantine. This is hypothesised to have led to physical deconditioning, new-onset disability and frailty. Disability and frailty are not routinely collated at population level but are associated with increased risk of falls and fractures, which result in hospital admissions. First, we will examine incidence of falls and fractures during COVID-19 (January 2020-March 2022), focusing on differences between incidence over time against expected rates based on historical data, to determine whether there is evidence of new-onset disability and frailty. Second, we will examine whether those with reported SARS-CoV-2 were at higher risk of falls and fractures. METHODS AND ANALYSIS: This study uses the Office for National Statistics (ONS) Public Health Data Asset, a linked population-level dataset combining administrative health records with sociodemographic data of the 2011 Census and National Immunisation Management System COVID-19 vaccination data for England. Administrative hospital records will be extracted based on specific fracture-centric International Classification of Diseases-10 codes in years preceding COVID-19 (2011-2020). Historical episode frequency will be used to predict expected admissions during pandemic years using time series modelling, if COVID-19 had not occurred. Those predicted admission figures will be compared with actual admissions to assess changes in hospital admissions due to public health measures comprising the pandemic response. Hospital admissions in prepandemic years will be stratified by age and geographical characteristics and averaged, then compared with pandemic year admissions to assess more granular changes. Risk modelling will assess risk of experiencing a fall, fracture or frail fall and fracture, if they have reported a positive case of COVID-19. The combination of these techniques will provide insight into changes in hospital admissions from the COVID-19 pandemic. ETHICS AND DISSEMINATION: This study has approval from the National Statistician's Data Ethics Advisory Committee (NSDEC(20)12). Results will be made available to other researchers via academic publication and shared via the ONS website.

Vocational Rehabilitation To Enhance Return to Work After Trauma: Findings From A Non-Randomised Feasibility Study...American Congress of Rehabilitation Medicine (ACRM) Annual Conference, November 8-11, 2022, Chicago, Illinois

To assesses the feasibility of delivering a telehealth vocational rehabilitation (VR) intervention to enhance return to work and improve quality of life and wellbeing in people post-trauma. Non-randomised single-arm mixed-methods feasibility study. Participants were recruited from two UK major trauma centres (MTCs). The intervention was delivered virtually (or face-to-face where necessary) in participants' homes. Adult patients (n=10) 16-69 years, admitted to participating UK MTCs with Injury Severity Score (ISS) >8, recruited ≤12 weeks post-injury. Eligible participants were employed (paid or unpaid) or in full-time education at injury onset. Treating occupational therapists (OTs) and clinical psychologists (CPs) (n=6) trained in ROWTATE VR. ROWTATE is an individually-tailored job retention intervention, delivered by OTs, who act as case-coordinators, and CPs. It commences 12-weeks post-injury and is delivered for up to 12 months. It involves: assessing impact of injury;work-focused rehabilitation;planning/monitoring phased return-to-work;liaising with employers/healthcare team;educating patients/employers about injury impact;early identification, monitoring and support for psychological problems. Due to COVID-19, the intervention was adapted for remote delivery (video/phone call) and OTs/CPs trained in remote delivery. Study completion. Intervention fidelity, barriers and enablers to delivery, acceptability and usefulness;acceptability of remote intervention training. At 6 months: 90% started intervention ≤12 weeks post-injury, 103 OT sessions (M=10.3, range 5-19);99% OT sessions delivered remotely, 6 patients referred to CP;22 sessions (M=3.7, range 1-5), 100% remote. Fidelity: OT: 90%-100% across patients, CP: 82%-100% across patients. No participant withdrawals. Treating therapists and all participants found the intervention acceptable. Remote VR training and delivery is feasible and acceptable to OTs/CPs and trauma survivors. Findings have informed a definitive randomised controlled trial. No conflicting interests.

Vocational Rehabilitation To Enhance Return to Work After Trauma: Findings From A Non-Randomised Feasibility Study

Research Objectives To assesses the feasibility of delivering a telehealth vocational rehabilitation (VR) intervention to enhance return to work and improve quality of life and wellbeing in people post-trauma. Design Non-randomised single-arm mixed-methods feasibility study. Setting Participants were recruited from two UK major trauma centres (MTCs). The intervention was delivered virtually (or face-to-face where necessary) in participants’ homes. Participants Adult patients (n=10) 16-69 years, admitted to participating UK MTCs with Injury Severity Score (ISS) >8, recruited ≤12 weeks post-injury. Eligible participants were employed (paid or unpaid) or in full-time education at injury onset. Treating occupational therapists (OTs) and clinical psychologists (CPs) (n=6) trained in ROWTATE VR. Interventions ROWTATE is an individually-tailored job retention intervention, delivered by OTs, who act as case-coordinators, and CPs. It commences 12-weeks post-injury and is delivered for up to 12 months. It involves: assessing impact of injury;work-focused rehabilitation;planning/monitoring phased return-to-work;liaising with employers/healthcare team;educating patients/employers about injury impact;early identification, monitoring and support for psychological problems. Due to COVID-19, the intervention was adapted for remote delivery (video/phone call) and OTs/CPs trained in remote delivery. Main Outcome Measures Study completion. Intervention fidelity, barriers and enablers to delivery, acceptability and usefulness;acceptability of remote intervention training. Results At 6 months: 90% started intervention ≤12 weeks post-injury, 103 OT sessions (M=10.3, range 5-19);99% OT sessions delivered remotely, 6 patients referred to CP;22 sessions (M=3.7, range 1-5), 100% remote. Fidelity: OT: 90%-100% across patients, CP: 82%-100% across patients. No participant withdrawals. Treating therapists and all participants found the intervention acceptable. Conclusions Remote VR training and delivery is feasible and acceptable to OTs/CPs and trauma survivors. Findings have informed a definitive randomised controlled trial. Author(s) Disclosures No conflicting interests.

Mental health of people with multiple sclerosis during the COVID-19 outbreak: A prospective cohort and cross-sectional case-control study of the UK MS Register.

BACKGROUND: People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor psychological wellbeing during the pandemic. OBJECTIVE: To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbreak in the United Kingdom. METHODS: This is a community-based, prospective longitudinal cohort and cross-sectional case-control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS. RESULTS: The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58-2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04-1.80) reported worse social support (OR: 1.90, 95% CI: 1.18-3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18-2.32) during the outbreak than controls. CONCLUSION: Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.

A randomised controlled trial investigating the clinical and cost-effectiveness of Alpha-Stim AID cranial electrotherapy stimulation (CES) in patients seeking treatment for moderate severity depression in primary care (Alpha-Stim-D Trial).

BACKGROUND: Major depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation. METHODS: The aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions. DISCUSSION: This study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms. TRIAL REGISTRATION: ISRTCN ISRCTN11853110 . Registered on 14 August 2020.

Connectivity-Guided Theta Burst Transcranial Magnetic Stimulation Versus Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Moderate to Severe Depression: Magnetic Resonance Imaging Protocol and SARS-CoV-2-Induced Changes for a Randomized Double-blind Controlled Trial.

BACKGROUND: Depression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment-a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses. OBJECTIVE: The aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment. METHODS: The study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity. RESULTS: Recruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023. CONCLUSIONS: This trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients. TRIAL REGISTRATION: ISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31925.

The predictive value of patient, therapist, and in-session ratings of motivational factors early in remote cognitive behavioural therapy for severe health anxiety.

OBJECTIVES: Remote psychotherapy and the prevalence of Severe Health Anxiety (SHA) are both growing as a result of the COVID-19 pandemic. Remotely delivered Cognitive Behavioural Therapy (rCBT) for SHA is evidenced as effective, but many who seek help do not benefit. Motivational processes can influence outcomes, but it is unclear what assessment methods offer the best clinical utility in rCBT for SHA. DESIGN: This study compared the predictive validity of patient, therapist and in-session ratings of motivational factors taken at session two of rCBT for SHA among high healthcare users experiencing multimorbidity. METHODS: Motivational factors were assessed for 56 participants who attended at least two sessions of CBT for SHA delivered via video-conferencing or telephone. Following session two, therapists and patients completed online assessments of patient motivation. Two trained observers also rated motivational factors and therapeutic alliance from in-session interactions using session two recordings and transcripts. Multilevel modelling was used to predict health anxiety and a range of secondary health outcomes from motivation assessments. RESULTS: Where patients were more actively engaged in discussion of positive changes during session two, greater outcome improvements ensued in health anxiety and all secondary outcomes. Conversely, larger proportions of session two spent describing problems predicted poorer outcomes. Therapist and patient assessments of motivation did not predict health anxiety, but therapist assessments of client confidence and motivation predicted all secondary outcomes. CONCLUSIONS: Motivation remains an important process in CBT when delivered remotely, and motivational factors may predict outcomes more consistently from in-session interactions, compared to self-reports.

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study).

BACKGROUND: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. METHODS: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology - Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. TRIAL REGISTRATION: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

Predicting outcomes and sudden gains from initial in-session interactions during remote cognitive-behavioural therapy for severe health anxiety.

There has been a dramatic increase in remote psychotherapy since the onset of the COVID-19 crisis. There is also expected to be an increase in mental health problems in the wake of the COVID-19 pandemic. An increase in severe health anxiety (SHA) is particularly anticipated, for which cognitive-behavioural therapy (CBT) is a frontline treatment. However, it is unclear what interaction types are associated with outcome-improvement in remote-CBT (rCBT) for SHA. This study aimed to identify interaction types that predict outcomes and sudden gains in rCBT for SHA using initial therapy session content. Forty-eight participants in rCBT for SHA had interactions at their first sessions categorized and rated in terms of patient activation: an individual's confidence and ability to manage their health. Multilevel modelling assessed whether early interaction types predicted session-by-session wellbeing. For participants experiencing sudden gains (n = 12) interactions at the session directly prior to the gain were similarly categorized and rated. The scores were then compared with ratings for the preceding session. A smaller proportion of early sessions was taken up with problem descriptions among those with greater outcome improvements. There was also a significant reduction in the proportion of the session spent describing problems in the session directly prior to a sudden gain, as compared with the previous session. Conversely, clients with better outcomes made more positive evaluations of themselves and therapy, noticed more positive changes and made more contributions to structuring interactions at initial sessions. Specific early interaction types predict session-by-session outcomes and precede sudden gains in rCBT for SHA.

Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND).

INTRODUCTION: The BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus standard repetitive transcranial magnetic stimulation (rTMS) in adults with moderate to severe treatment resistant depression. METHODS AND ANALYSIS: The study is a randomised double-blind controlled trial with 1:1 allocation to either 20 sessions of (1) cgiTBS or (2) neuronavigated rTMS not using connectivity guidance. A total of 368 eligible participants with a diagnosis of current unipolar major depressive disorder that is both treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital Staging Score) and moderate to severe (scoring >16 on the 17-item Hamilton Depression Rating Scale (HDRS-17)), will be recruited from primary and secondary care settings at four treatment centres in the UK. The primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks postrandomisation. Cost-effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined. ETHICS AND DISSEMINATION: Ethical approval was granted by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. The results of the study will be published in relevant peer-reviewed journals, and then through professional and public conferences and media. Further publications will explore patient experience, moderators and mediators of outcome and mechanism of action. TRIAL REGISTRATION NUMBER: ISRCTN19674644.