Digitally augmented, parent-led CBT versus treatment as usual for child anxiety problems in child mental health services in England and Northern Ireland: a pragmatic, non-inferiority, clinical effectiveness and cost-effectiveness randomised controlled trial.

BACKGROUND: Anxiety problems are common in children, yet few affected children access evidence-based treatment. Digitally augmented psychological therapies bring potential to increase availability of effective help for children with mental health problems. This study aimed to establish whether therapist-supported, digitally augmented, parent-led cognitive behavioural therapy (CBT) could increase the efficiency of treatment without compromising clinical effectiveness and acceptability. METHODS: We conducted a pragmatic, unblinded, two-arm, multisite, randomised controlled non-inferiority trial to evaluate the clinical effectiveness and cost-effectiveness of therapist-supported, parent-led CBT using the Online Support and Intervention (OSI) for child anxiety platform compared with treatment as usual for child (aged 5-12 years) anxiety problems in 34 Child and Adolescent Mental Health Services in England and Northern Ireland. We examined acceptability of OSI plus therapist support via qualitative interviews. Participants were randomly assigned (1:1) to OSI plus therapist support or treatment as usual, minimised by child age, gender, service type, and baseline child anxiety interference. Outcomes were assessed at week 14 and week 26 after randomisation. The primary clinical outcome was parent-reported interference caused by child anxiety at week 26 assessment, using the Child Anxiety Impact Scale-parent report (CAIS-P). The primary measure of health economic effect was quality-adjusted life-years (QALYs). Outcome analyses were conducted blind in the intention-to-treat (ITT) population with a standardised non-inferiority margin of 0·33 for clinical analyses. The trial was registered with ISRCTN, 12890382. FINDINGS: Between Dec 5, 2020, and Aug 3, 2022, 706 families (706 children and their parents or carers) were referred to the study information. 444 families were enrolled. Parents reported 255 (58%) child participants' gender to be female, 184 (41%) male, three (<1%) other, and one (<1%) preferred not to report their child's gender. 400 (90%) children were White and the mean age was 9·20 years (SD 1·79). 85% of families for whom clinicians provided information in the treatment as usual group received CBT. OSI plus therapist support was non-inferior for parent-reported anxiety interference on the CAIS-P (SMD 0·01, 95% CI -0·15 to 0·17; p<0·0001) and all secondary outcomes. The mean difference in QALYs across trial arms approximated to zero, and OSI plus therapist support was associated with lower costs than treatment as usual. OSI plus therapist support was likely to be cost effective under certain scenarios, but uncertainty was high. OSI plus therapist support acceptability was good. No serious adverse events were reported. INTERPRETATION: Digitally augmented intervention brought promising savings without compromising outcomes and as such presents a valuable tool for increasing access to psychological therapies and meeting the demand for treatment of child anxiety problems. FUNDING: Department for Health and Social Care and United Kingdom Research and Innovation Research Grant, National Institute for Health and Care (NIHR) Research Policy Research Programme, Oxford and Thames Valley NIHR Applied Research Collaboration, Oxford Health NIHR Biomedical Research Centre.

Specialist healthcare services for concussion/mild traumatic brain injury in England: a consensus statement using modified Delphi methodology.

OBJECTIVE: To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome. DESIGN: This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%. SETTING: Specialist outpatient services. PARTICIPANTS: Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England. PRIMARY OUTCOME MEASURE: A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England. RESULTS: 55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics. CONCLUSIONS: This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.

Right BA 10 lesions impair performance on real-world planning but are not sensitive to problem novelty or tower tasks.

The prefrontal cortex (PFC) is associated with many cognitive functions, including planning. In the neuropsychology literature planning is reduced to "look ahead" ability and most extensively studied with the "tower" tasks. The most influential theoretical explanation is that planning is required in the absence of a routine solution and PFC patients have difficulty coping with novelty. There is an alternate view of planning that emphasizes the distinction between real world tasks and laboratory tower tasks. This account focuses on the structure of problem spaces and why patients with lesions to right PFC have difficulty navigating ill-structured problem spaces. To further explore these issues we administered two real world travel planning tasks to 56 Vietnam War veterans with penetrating brain lesions and 14 matched normal controls. One planning task involved familiar knowledge while the other involved knowledge unfamiliar to our participants. Participants also completed the D-KEFS tower task. A subset of 18 patients-with lesions to right anterior prefrontal cortex (BA 10)-were impaired in the travel planning task compared to normal controls. The task familiarity/novelty dimension affected performance across participant groups (familiar-task scores were higher than unfamiliar-task scores), but it did not differentially affect any group. An examination of cognitive strategies utilized by participants revealed that the impaired patient group had difficulty maintaining a sufficient level of abstraction and engaged the task at a much more concrete level than other participants. Interestingly, patients impaired in the real-world planning tasks were not impaired in the tower tasks. We conclude that patients with lesions to right BA 10 have difficulty in real-world planning tasks that can be attributed to difficulties in engaging problems at the appropriate level of abstraction.

Education is power: preserving cognition in the UK biobank.

Introduction: Dementia is a debilitating syndrome characterized by the gradual loss of memory and cognitive function. Although there are currently limited, largely symptomatic treatments for the diseases that can lead to dementia, its onset may be prevented by identifying and modifying relevant life style risk factors. Commonly described modifiable risk factors include diet, physical inactivity, and educational attainment. Importantly, however, to maximize the utility of our understanding of these risk factors, tangible and meaningful changes to policy must also be addressed. Objectives: Here, we aim to identify the mechanism(s) by which educational attainment influences cognition. Methods: We investigated data from 502,357 individuals (Mage = 56.53, SDage = 8.09, 54.40% female) from the UK Biobank cohort via Structural Equation Modelling to illustrate links between predictor variables (i.e., Townsend Deprivation Index, coastal distance, greenspace, years of education), covariates (i.e., participant age) and cognitive function as outcome variables (i.e., pairs-matching, trail-making task B, fluid intelligence). Results: Our model demonstrated that higher education was associated with better cognitive performance (ps < 0.001), and this relationship was mediated by indices of deprivation, and coastal distance. Conclusion: Accordingly, our model evinces the mediating effect of socioeconomic and environmental factors on the relationship between years of education and cognitive function. These results further demonstrate the utility and necessity of adapting public policy to encourage equitable access to education and other supports in deprived areas.

Artificial intelligence for dementia prevention.

INTRODUCTION: A wide range of modifiable risk factors for dementia have been identified. Considerable debate remains about these risk factors, possible interactions between them or with genetic risk, and causality, and how they can help in clinical trial recruitment and drug development. Artificial intelligence (AI) and machine learning (ML) may refine understanding. METHODS: ML approaches are being developed in dementia prevention. We discuss exemplar uses and evaluate the current applications and limitations in the dementia prevention field. RESULTS: Risk-profiling tools may help identify high-risk populations for clinical trials; however, their performance needs improvement. New risk-profiling and trial-recruitment tools underpinned by ML models may be effective in reducing costs and improving future trials. ML can inform drug-repurposing efforts and prioritization of disease-modifying therapeutics. DISCUSSION: ML is not yet widely used but has considerable potential to enhance precision in dementia prevention. HIGHLIGHTS: Artificial intelligence (AI) is not widely used in the dementia prevention field. Risk-profiling tools are not used in clinical practice. Causal insights are needed to understand risk factors over the lifespan. AI will help personalize risk-management tools for dementia prevention. AI could target specific patient groups that will benefit most for clinical trials.

Oxford brain health clinic: protocol and research database.

INTRODUCTION: Despite major advances in the field of neuroscience over the last three decades, the quality of assessments available to patients with memory problems in later life has barely changed. At the same time, a large proportion of dementia biomarker research is conducted in selected research samples that often poorly reflect the demographics of the population of patients who present to memory clinics. The Oxford Brain Health Clinic (BHC) is a newly developed clinical assessment service with embedded research in which all patients are offered high-quality clinical and research assessments, including MRI, as standard. METHODS AND ANALYSIS: Here we describe the BHC protocol, including aligning our MRI scans with those collected in the UK Biobank. We evaluate rates of research consent for the first 108 patients (data collection ongoing) and the ability of typical psychiatry-led NHS memory-clinic patients to tolerate both clinical and research assessments. ETHICS AND DISSEMINATION: Our ethics and consenting process enables patients to choose the level of research participation that suits them. This generates high rates of consent, enabling us to populate a research database with high-quality data that will be disseminated through a national platform (the Dementias Platform UK data portal).

Understanding and managing the long-term cognitive consequences of traumatic brain injuries.

This editorial critically evaluates the current data on traumatic brain injuries and their effects on cognitive function. It discusses management strategies and clinical considerations to improve patient outcomes in light of these findings.

A systematic review and meta-analysis of long COVID symptoms.

BACKGROUND: Ongoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as "long COVID" (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres. METHODS: A systematic protocol was developed, peer reviewed, and published in PROSPERO. The systematic review included publications from the 1st of December 2019-30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analyzed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified. RESULTS: Of the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11,598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported. CONCLUSIONS: The quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.

Lifetime Traumatic Brain Injury and Cognitive Domain Deficits in Late Life: The PROTECT-TBI Cohort Study.

Traumatic brain injury (TBI) causes cognitive impairment but it remains contested regarding which cognitive domains are most affected. Further, moderate-severe TBI is known to be deleterious, but studies of mild TBI (mTBI) show a greater mix of negative and positive findings. This study examines the longer-term cognitive effects of TBI severity and number of mTBIs in later life. We examined a subset (n = 15,764) of the PROTECT study, a cohort assessing risk factors for cognitive decline (ages between 50 and 90 years). Participants completed cognitive assessments annually for 4 years. Cognitive tests were grouped using a principal components analysis (PCA) into working memory, episodic memory, attention, processing speed, and executive function. Lifetime TBI severity and number were retrospectively recalled by participants using the Brain Injury Screening Questionnaire (BISQ). Linear mixed models (LMMs) examined the effect of severity of head injury (non-TBI head strike, mTBI, and moderate-severe TBI) and number of mTBI at baseline and over time. mTBI was considered as a continuous and categorical variable (groups: 0 mTBI, 1 mTBI, 2 mTBIs, 3 mTBIs, and 4+ mTBIs). Of the participants 5725 (36.3%) reported at least one mTBI and 510 (3.2%) at least one moderate-severe TBI, whereas 3711 (23.5%) had suffered at worst a non-TBI head strike and 5818 (32.9%) reported no head injuries. The participants had suffered their last reported head injury an average (standard deviation, SD) of 29.6 (20.0) years prior to the study. Regarding outcomes, there was no worsening in longitudinal cognitive trajectories over the study duration but at baseline there were significant cognitive deficits associated with TBI. At baseline, compared with those without head injury, individuals reporting at least one moderate-severe TBI had significantly poorer attention (B = -0.163, p < 0.001), executive scores (B = -0.151, p = 0.004), and processing speed (B = -0.075, p = 0.033). Those who had suffered at least a single mTBI also demonstrated significantly poorer attention scores at baseline compared with the no head injury group (B = -0.052, p = 0.001). Compared with those with no mTBI, those in the 3 mTBI group manifested poorer baseline executive function (B = -0.149, p = 0.025) and attention scores (B = -0.085, p = 0.015). At baseline, those who had suffered four or more mTBIs demonstrated poorer attention (B = -0.135, p < 0.001), processing speed (B = -0.072, p = 0.009), and working memory (B = -0.052, p = 0.036), compared with those reporting no mTBI. TBI is associated with fixed, dose, and severity-dependent cognitive deficits. The most sensitive cognitive domains are attention and executive function, with approximately double the effect compared with processing speed and working memory. Post-TBI cognitive rehabilitation should be targeted appropriately to domain-specific effects. Significant long-term cognitive deficits were associated with three or more lifetime mTBIs, a critical consideration when counseling individuals post-TBI about continuing high-risk activities.

New Therapeutics in Alzheimer's Disease Longitudinal Cohort study (NTAD): study protocol.

INTRODUCTION: With the pressing need to develop treatments that slow or stop the progression of Alzheimer's disease, new tools are needed to reduce clinical trial duration and validate new targets for human therapeutics. Such tools could be derived from neurophysiological measurements of disease. METHODS AND ANALYSIS: The New Therapeutics in Alzheimer's Disease study (NTAD) aims to identify a biomarker set from magneto/electroencephalography that is sensitive to disease and progression over 1 year. The study will recruit 100 people with amyloid-positive mild cognitive impairment or early-stage Alzheimer's disease and 30 healthy controls aged between 50 and 85 years. Measurements of the clinical, cognitive and imaging data (magnetoencephalography, electroencephalography and MRI) of all participants will be taken at baseline. These measurements will be repeated after approximately 1 year on participants with Alzheimer's disease or mild cognitive impairment, and clinical and cognitive assessment of these participants will be repeated again after approximately 2 years. To assess reliability of magneto/electroencephalographic changes, a subset of 30 participants with mild cognitive impairment or early-stage Alzheimer's disease will also undergo repeat magneto/electroencephalography 2 weeks after baseline. Baseline and longitudinal changes in neurophysiology are the primary analyses of interest. Additional outputs will include atrophy and cognitive change and estimated numbers needed to treat each arm of simulated clinical trials of a future disease-modifying therapy. ETHICS AND DATA STATEMENT: The study has received a favourable opinion from the East of England Cambridge Central Research Ethics Committee (REC reference 18/EE/0042). Results will be disseminated through internal reports, peer-reviewed scientific journals, conference presentations, website publication, submission to regulatory authorities and other publications. Data will be made available via the Dementias Platform UK Data Portal on completion of initial analyses by the NTAD study group.

Adapting UK Biobank imaging for use in a routine memory clinic setting: The Oxford Brain Health Clinic.

The Oxford Brain Health Clinic (BHC) is a joint clinical-research service that provides memory clinic patients and clinicians access to high-quality assessments not routinely available, including brain MRI aligned with the UK Biobank imaging study (UKB). In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) explored the alignment of measures from BHC patients to the largest brain MRI study in the world (ultimately 100,000 participants). Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences (i.e., additional imaging modalities) to improve patients' tolerance for the MRI assessment. We adapted the UKB structural MRI analysis pipeline to take into account the characteristics of a memory clinic population (e.g., high amount of white matter hyperintensities and hippocampal atrophy). We then compared the imaging derived phenotypes (IDPs) extracted from the structural scans to visual ratings from radiology reports, non-imaging factors (age, cognition) and to reference distributions derived from UKB data. Of the first 108 BHC attendees (August 2020-November 2021), 92.5 % completed the clinical scans, 88.0 % consented to use of data for research, and 43.5 % completed the additional research sequences, demonstrating that the protocol is well tolerated. The high rates of consent to research makes this a valuable real-world quality research dataset routinely captured in a clinical service. Modified tissue-type segmentation with lesion masking greatly improved grey matter volume estimation. CSF-masking marginally improved hippocampal segmentation. The IDPs were in line with radiology reports and showed significant associations with age and cognitive performance, in line with the literature. Due to the age difference between memory clinic patients of the BHC (age range 65-101 years, average 78.3 years) and UKB participants (44-82 years, average 64 years), additional scans on elderly healthy controls are needed to improve reference distributions. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.

A randomised controlled trial to compare clinical and cost-effectiveness of an online parent-led treatment for child anxiety problems with usual care in the context of COVID-19 delivered in Child and Adolescent Mental Health Services in the UK (Co-CAT): a study protocol for a randomised controlled trial.

BACKGROUND: In the context of COVID-19, NHS Child and Adolescent Mental Health Services (CAMHS) and other children's mental health services have faced major challenges in providing psychological treatments that (i) work when delivered remotely and (ii) can be delivered efficiently to manage increases in referrals as social distancing measures have been relaxed. Anxiety problems are a common reason for referral to CAMHS, children with pre-existing anxiety problems are particularly vulnerable in the context of COVID-19, and there were concerns about increases in childhood anxiety as schools reopened. The proposed research will evaluate the clinical and cost-effectiveness of a brief online parent-led cognitive behavioural treatment (CBT) delivered by the OSI (Online Support and Intervention for child anxiety) platform with remote support from a CAMHS therapist compared to 'COVID-19 treatment as usual' (C-TAU) in CAMHS and other children's mental health services throughout the COVID-19 pandemic. METHODS: We will conduct a two-arm, multi-site, randomised controlled non-inferiority trial to evaluate the clinical and cost-effectiveness of OSI with therapist support compared to CAMHS and other child mental health services 'COVID-19 treatment as usual' (C-TAU) during the COVID-19 outbreak and to explore parent and therapists' experiences. DISCUSSION: If non-inferiority is shown, the research will provide (1) a solution for efficient psychological treatment for child anxiety disorders while social distancing (for the COVID-19 context and future pandemics); (2) an efficient means of treatment delivery as 'normal service' resumes to enable CAMHS to cope with the anticipated increase in referrals; and (3) a demonstration of rapid, high-quality evaluation and application of online interventions within NHS CAMHS to drive forward much-needed further digital innovation and evaluation in CAMHS settings. The primary beneficiaries will be children with anxiety disorders and their families, NHS CAMHS teams, and commissioners who will access a potentially effective, cost-effective, and efficient treatment for child anxiety problems. TRIAL REGISTRATION: ISRCTN ISRCTN12890382 . Registered prospectively on 23 October 2020.

A systematic review and meta-analysis of digital application use in clinical research in pain medicine.

Importance: Pain is a silent global epidemic impacting approximately a third of the population. Pharmacological and surgical interventions are primary modes of treatment. Cognitive/behavioural management approaches and interventional pain management strategies are approaches that have been used to assist with the management of chronic pain. Accurate data collection and reporting treatment outcomes are vital to addressing the challenges faced. In light of this, we conducted a systematic evaluation of the current digital application landscape within chronic pain medicine. Objective: The primary objective was to consider the prevalence of digital application usage for chronic pain management. These digital applications included mobile apps, web apps, and chatbots. Data sources: We conducted searches on PubMed and ScienceDirect for studies that were published between 1st January 1990 and 1st January 2021. Study selection: Our review included studies that involved the use of digital applications for chronic pain conditions. There were no restrictions on the country in which the study was conducted. Only studies that were peer-reviewed and published in English were included. Four reviewers had assessed the eligibility of each study against the inclusion/exclusion criteria. Out of the 84 studies that were initially identified, 38 were included in the systematic review. Data extraction and synthesis: The AMSTAR guidelines were used to assess data quality. This assessment was carried out by 3 reviewers. The data were pooled using a random-effects model. Main outcomes and measures: Before data collection began, the primary outcome was to report on the standard mean difference of digital application usage for chronic pain conditions. We also recorded the type of digital application studied (e.g., mobile application, web application) and, where the data was available, the standard mean difference of pain intensity, pain inferences, depression, anxiety, and fatigue. Results: 38 studies were included in the systematic review and 22 studies were included in the meta-analysis. The digital interventions were categorised to web and mobile applications and chatbots, with pooled standard mean difference of 0.22 (95% CI: -0.16, 0.60), 0.30 (95% CI: 0.00, 0.60) and -0.02 (95% CI: -0.47, 0.42) respectively. Pooled standard mean differences for symptomatologies of pain intensity, depression, and anxiety symptoms were 0.25 (95% CI: 0.03, 0.46), 0.30 (95% CI: 0.17, 0.43) and 0.37 (95% CI: 0.05, 0.69), respectively. A sub-group analysis was conducted on pain intensity due to the heterogeneity of the results (I 2 = 82.86%; p = 0.02). After stratifying by country, we found that digital applications were more likely to be effective in some countries (e.g., United States, China) than others (e.g., Ireland, Norway). Conclusions and relevance: The use of digital applications in improving pain-related symptoms shows promise, but further clinical studies would be needed to develop more robust applications. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.

Mental health impact on Black, Asian and Minority Ethnic populations with preterm birth: A systematic review and meta-analysis.

BACKGROUND: Preterm birth (PTB) is one of the main causes of neonatal deaths globally, with approximately 15 million infants are born preterm. Women from the Black, Asian, and Minority Ethnic (BAME) populations maybe at higher risk of PTB, therefore, the mental health impact on mothers experiencing a PTB is particularly important, within the BAME populations. AIM: To determine the prevalence of mental health conditions among BAME women with PTB as well as the methods of mental health assessments used to characterise the mental health outcomes. METHODS: A systematic methodology was developed and published as a protocol in PROSPERO (CRD42020210863). Multiple databases were used to extract relevant data. I 2 and Egger's tests were used to detect the heterogeneity and publication bias. A trim and fill method was used to demonstrate the influence of publication bias and the credibility of conclusions. RESULTS: Thirty-nine studies met the eligibility criteria from a possible 3526. The prevalence rates of depression among PTB-BAME mothers were significantly higher than full-term mothers with a standardized mean difference of 1.5 and a 95% confidence interval (CI) 29%-74%. The subgroup analysis indicated depressive symptoms to be time sensitive. Women within the very PTB category demonstrated a significantly higher prevalence of depression than those categorised as non-very PTB. The prevalence rates of anxiety and stress among PTB-BAME mothers were significantly higher than in full-term mothers (odds ratio of 88% and 60% with a CI of 42%-149% and 24%-106%, respectively). CONCLUSION: BAME women with PTB suffer with mental health conditions. Many studies did not report on specific mental health outcomes for BAME populations. Therefore, the impact of PTB is not accurately represented in this population, and thus could negatively influence the quality of maternity services they receive.

Mental health impact of the Middle East respiratory syndrome, SARS, and COVID-19: A comparative systematic review and meta-analysis.

BACKGROUND: Over the last few decades, 3 pathogenic pandemics have impacted the global population; severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2. The global disease burden has attributed to millions of deaths and morbidities, with the majority being attributed to SARS-CoV-2. As such, the evaluation of the mental health (MH) impact across healthcare professionals (HCPs), patients and the general public would be an important facet to evaluate to better understand short, medium and long-term exposures. AIM: To identify and report: (1) MH conditions commonly observed across all 3 pandemics; (2) Impact of MH outcomes across HCPs, patients and the general public associated with all 3 pandemics; and (3) The prevalence of the MH impact and clinical epidemiological significance. METHODS: A systematic methodology was developed and published on PROSPERO (CRD42021228697). The databases PubMed, EMBASE, ScienceDirect and the Cochrane Central Register of Controlled Trials were used as part of the data extraction process, and publications from January 1, 1990 to August 1, 2021 were searched. MeSH terms and keywords used included Mood disorders, PTSD, Anxiety, Depression, Psychological stress, Psychosis, Bipolar, Mental Health, Unipolar, Self-harm, BAME, Psychiatry disorders and Psychological distress. The terms were expanded with a 'snowballing' method. Cox-regression and the Monte-Carlo simulation method was used in addition to I 2 and Egger's tests to determine heterogeneity and publication bias. RESULTS: In comparison to MERS and SARS-CoV, it is evident SAR-CoV-2 has an ongoing MH impact, with emphasis on depression, anxiety and post-traumatic stress disorder. CONCLUSION: It was evident MH studies during MERS and SARS-CoV was limited in comparison to SARS-CoV-2, with much emphasis on reporting symptoms of depression, anxiety, stress and sleep disturbances. The lack of comprehensive studies conducted during previous pandemics have introduced limitations to the "know-how" for clinicians and researchers to better support patients and deliver care with limited healthcare resources.

The Impact of Social Isolation Due to COVID-19 on Symptom Progression in People With Dementia: Findings of the SOLITUDE Study.

Background: People with dementia (PWD) are vulnerable to abrupt changes to daily routines. The lockdown enforced on the 23rd of March 2020 in the UK to contain the expansion of the COVID-19 pandemic limited opportunities for PWD to access healthcare services and socialise. The SOLITUDE study explored the potential long-term effects of lockdown on PWD's symptoms and carers' burden. Methods: Forty-five carers and 36 PWD completed a telephone-based assessment at recruitment (T0) and after 3 (T1) and 6 months (T2). PWD completed measures validated for telephonic evaluations of cognition and depression. Carers completed questionnaires on their burden and on PWD's health and answered a customised interview on symptom changes observed in the initial months of lockdown. Longitudinal changes were investigated for all outcome variables with repeated-measures models. Additional post hoc multiple regression analyses were carried out to investigate whether several objective factors (i.e., demographics and time under social restrictions) and carer-reported symptom changes observed following lockdown before T0 were associated with all outcomes at T0. Results: No significant changes were observed in any outcomes over the 6 months of observations. However, post hoc analyses showed that the length of social isolation before T0 was negatively correlated with episodic and semantic memory performance at T0. Carers reporting worsening of neuropsychiatric symptoms and faster disease progression in PWD also reported higher burden. Moreover, carer-reported worsening of cognitive symptoms was associated with poorer semantic memory at T0. Conclusion: PWD's symptoms and carers' burden remained stable over 6 months of observation. However, the amount of time spent under social restrictions before T0 appears to have had a significant detrimental impact on cognitive performance of patients. In fact, carer-reported cognitive decline during social isolation was consistent with the finding of poorer semantic memory, a domain sensitive to progression in Alzheimer's disease. Therefore, the initial stricter period of social isolation had greater detrimental impact on patients and their carers, followed then by a plateau. Future interventions may be designed to maintain an optimal level of social and cognitive engagement for PWD in challenging times, to prevent abrupt worsening of symptoms and associated detrimental consequences on patients' carers.

The impact of social isolation due to the COVID-19 pandemic on patients with dementia and caregivers.

OBJECTIVE: Social distancing to limit COVID-19 transmission has led to extensive lifestyle changes, including for people with dementia (PWD). The aim of this study, therefore, was to assess the impact of lockdown on the mental health of PWD and their carers. METHODS: Forty-five carers of PWD completed a telephone interview during the baseline assessment of the SOLITUDE study to gather information on life conditions and changes in symptoms of PWD during lockdown. Associations between changes in symptoms of PWD and carers' concerns and mental health were investigated. RESULTS: About 44% of carers experienced anxiety and irritability and reported changes in behavioural and cognitive symptoms in PWD. These changes were associated with worse carers' mental health and concerns about faster disease progression (χ2 = 13.542, p < 0.001). CONCLUSION: COVID-19-related social isolation has had a negative impact on patients' and carers' mental health. Potential long-term neurocognitive consequences require further investigation.

Alwyn Lishman's contribution to the neuropsychiatry of head injury (traumatic brain injury); two key papers.

INTRODUCTION: Alwyn Lishman appreciated that if we are to understand the psychological consequences of cerebral disorder we must study the interaction between organic disease and psychological processes. METHODS: We have reviewed Lishman's two major publications on the neuropsychiatry of head injury, published in 1968 and 1988, and considered their conclusions in the light of current knowledge. RESULTS: In his 1968 paper on the psychiatric sequelae of open head injuries sustained in World War II Lishman demonstrated associations between the type of psychiatric sequelae and the location of the injury. He also found that those with "somatic complaints", such as fatigue or sensitivity to light, showed less evidence of organic injury. In his 1988 paper, he attempted to explain why a mild head injury may be followed by long-lasting symptoms. He suggested that in the absence of complications early, organic, symptoms (physiogenesis) should recover quickly. However, this healthy recovery could be jeopardised by psychological factors (psychogenesis), resulting in long-lasting symptoms. This model of physiogenesis and psychogenesis remains relevant today. CONCLUSIONS: The ideas Lishman developed in these two papers were the basis for his huge contribution to the field of neuropsychiatry, and remain relevant today.

Patient attitudes towards remote memory clinic assessment.

BACKGROUND: Due to demand on UK memory clinic services, most patients have limited consultant interaction before diagnosis/discharge. Technology offers an opportunity for remote assessment, from telephone/video-based consultations to fully digitised cognitive assessments with potential to track disease progression. Whilst many acute services utilise remote assessment, there are perceived barriers in memory clinic populations. However, COVID-19 and related national restrictions may have altered patients' attitudes towards and experience with remote assessment tools. We aimed to investigate attitudes including confidence and perceived challenges towards remote assessment as well as access and experience with technology amongst Oxfordshire memory clinic patients. METHOD: Between June and September 2020, all patients awaiting initial memory clinic assessment were asked to participate in a standardised semi-quantitative survey as part of an Oxford Health NHS Foundation Trust service evaluation. Designed with service-user input, questions aimed to capture availability, experience and confidence using technology and patients' comfort with assessment, diagnosis and future care discussions being conducted remotely, as well as any concerns or comments. RESULT: Amongst 73 respondents (average age=79.1 years), access to technology was high; 82% reported telephone access and 58% to a laptop, tablet, smartphone or combination of the three. 17% reported previous use of web-based video conferencing tools, and although confidence using these tools was 7%, this increased with written instruction or relative assistance. Similarly, whilst under half of the respondents felt comfortable with assessments, diagnosis or future care discussions occurring remotely, this increased to approximately two thirds with relative presence (67%, 69% and 66%, respectively). Qualitative analysis of patient's comments regarding remote assessment also revealed concerns over wait times/urgent need for assessment. However, 62% preferred to wait for an in-person visit, rather than an immediate remote appointment. CONCLUSION: This survey demonstrates availability of technology in this population but a disparity in willingness to engage in remote assessment. Consequently, there is a need to diverge from one-size-fits-all models to a tiered approach that helps facilitate individual choice based on the availability/confidence with technology and level of relative support. The Oxford Brain Health Centre, an integrated clinical-research service, provides an opportunity to research this tiered approach in clinical practice.

Genetic Therapies for Alzheimer's Disease: A Scoping Review.

Effective, disease modifying therapies for Alzheimer's disease (AD) remain a quandary, following a panoply of expensive failures in human clinical trials. Given the stagnation in therapeutics, alternative approaches are needed. Recent successes of genetic therapies in other neurodegenerative diseases may highlight the way forward. This scoping review explores suggested targets of genetic therapy in AD, with a focus on vector-based approaches in pre-clinical and clinical trials. Putative targets of genetic therapies tested in pre-clinical trials include amyloid pathway intermediates and enzymes modulation, tau protein downregulation, APOE4 downregulation and APOE2 upregulation, neurotrophin expression (nerve growth factor (NGF) and brain-derived neurotrophic factor), and inflammatory cytokine alteration, among several other approaches. There have been three completed human clinical trials for genetic therapy in AD patients, all of which upregulated NGF in AD patients, showing some mixed evidence of benefit. Several impediments remain to be surpassed before genetic therapies can be successfully applied to AD, including the challenge of delivering monogenic genetic therapies for complex polygenic disorders, risks in the dominant delivery method (intracranial injection), stability of genetic therapies in vivo, poor translatability of pre-clinical AD models, and the expense of genetic therapy production. Genetic therapies represent an exciting opportunity within the world of AD therapeutics, but clinical applications likely remain a long term, rather than short term, possibility.