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BackgroundSeveral long-term chronic illnesses are known to be associated with an increased risk of dementia independently, but little is known how combinations or clusters of potentially interacting chronic conditions may influence the risk of developing dementia.Methods447 888 dementia-free participants of the UK Biobank cohort at baseline (2006–2010) were followed-up until 31 May 2020 with a median follow-up duration of 11.3 years to identify incident cases of dementia. Latent class analysis (LCA) was used to identify multimorbidity patterns at baseline and covariate adjusted Cox regression was used to investigate their predictive effects on the risk of developing dementia. Potential effect moderations by C reactive protein (CRP) and Apolipoprotein E (APOE) genotype were assessed via statistical interaction.ResultsLCA identified four multimorbidity clusters representingMental health,Cardiometabolic,Inflammatory/autoimmuneandCancer-related pathophysiology, respectively. Estimated HRs suggest that multimorbidity clusters dominated byMental health(HR=2.12, pCardiometabolicconditions (2.02, pInflammatory/autoimmunecluster was intermediate (1.56, pCancercluster was least pronounced (1.36, pConclusionsEarly identification of older adults at higher risk of accumulating multimorbidity of specific pathophysiology and tailored interventions to prevent or delay the onset of such multimorbidity may help prevention of dementia.

Global cognitive changes in older age impact driving behaviour and road safety, but how spatial orientation changes impact driving behaviours is unknown on a population level, despite clear implications for driving policy and evaluation during ageing. The present study aimed to establish how spatial navigation changes impact driving behaviour and road safety within a large cohort of older adults. 804 participants (mean age: 71.05) were recruited for a prospective cohort study. Participants self-reported driving behaviour followed by spatial orientation (allocentric & egocentric) testing and a broader online cognitive battery (visuomotor speed, processing speed, executive functioning, spatial working memory, episodic memory, visuospatial functioning). It was found that spatial orientation performance significantly predicted driving difficulty and frequency. Experiencing more driving difficulty was associated with worse allocentric spatial orientation, processing speed, and source memory performance. Similarly, avoiding challenging driving situations was associated with worse spatial orientation and episodic memory. Allocentric spatial orientation was the only cognitive domain consistently affecting driving behaviour in under 70 and over 70 age groups, a common age threshold for driving evaluation in older age. In conclusion, we established for the first time that worse spatial orientation performance predicted increased driving difficulty and avoidance of challenging situations within an older adult cohort. Deficits in spatial orientation emerge as a robust indicator of driving performance in older age, which should be considered in future ageing driving assessments, as it is has clear relevance for road safety within the ageing population.

Aim: To investigate the prevalence of cognitive impairment and its predictors among the elderly in Bangladesh. Subject and Methods: We use a cross-sectional survey of 1015 older people (≥60 years) in Bangladesh collected jointly by the Sir William Beveridge Foundation (SWBF) and Aging Support Forum (ASF), Bangladesh. The Mini-Mental State Examination (MMSE) scale, adapted to the Bengali language, was used for assessing cognitive impairment, which was available for 111 participants. Logistic regression analysis was used to identify predictors of cognitive impairment. Multiple imputation under the missing-at-random (MAR) mechanism was used to deal with missing data. Results: Overall, 31 out of 111 (27.9%) participants had mild, moderate or severe cognitive impairment, with a higher proportion among women (33.3%, 17 out of 51) than men (23.3%, 14 out of 60). More precisely, 24 out of 111 (21.6%) and 7 out of 111 (6.3%) had mild/moderate and severe cognitive impairment, respectively, with a higher percentage among women (mild/moderate: 25.5%, severe: 7.8%) than men (mild/moderate: 18.3%, severe: 5.0%). Age (odds ratio, OR = 1.06, p = 0.046, 95% CI: 1.001 to 1.119) and social engagement (OR = 0.25, p = 0.033, 95% CI: 0.072 to 0.898) were found to be statistically significant predictors of cognitive impairment in this group of people. The effect of physical disability fell short of statistical significance at the 5% level but was significant at the 10% level (OR = 2.89, p = 0.099, 90% CI: 0.999 to 8.370). Conclusion: The prevalence of cognitive impairment in Bangladesh is alarming and is comparatively higher among elderly women, which seems to increase with age and the presence of any physical disability. Also, prevalence appears to be lower in people who are more socially engaged or active.

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, among patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. Among those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this.•schizophrenia•clozapine•Antipsychotic agents•COVID-19•SARS-CoV-2

IntroductionThe increasingly ageing population is associated with greater numbers of people living with dementia (PLwD) and mild cognitive impairment (MCI). There are an estimated 55 million PLwD and approximately 6% of people over 60 years of age are living with MCI, with the figure rising to 25% for those aged between 80 and 84 years. Sleep disturbances are common for this population, but there is currently no standardised approach within UK primary care to manage this. Coined as a ‘wicked design problem’, sleep disturbances in this population are complex, with interventions supporting best management in context.Methods and analysisThe aim of this realist review is to deepen our understanding of what is considered ‘sleep disturbance’ in PLwD or MCI within primary care. Specifically, we endeavour to better understand how sleep disturbance is assessed, diagnosed and managed. To co-produce this protocol and review, we have recruited a stakeholder group comprising individuals with lived experience of dementia or MCI, primary healthcare staff and sleep experts. This review will be conducted in line with Pawson’s five stages including the development of our initial programme theory, literature searches and the refinement of theory. The Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) quality and reporting standards will also be followed. The realist review will be an iterative process and our initial realist programme theory will be tested and refined in response to our data searches and stakeholder discussions.Ethics and disseminationEthical approval is not required for this review. We will follow the RAMESES standards to ensure we produce a complete and transparent report. Our final programme theory will help us to devise a tailored sleep management tool for primary healthcare professionals, PLwD and their carers. Our dissemination strategy will include lay summaries via email and our research website, peer-reviewed publications and social media posts.PROSPERO registration numberCRD42022304679.

BackgroundStudies show ethnic inequalities in rates of involuntary admission and types of clinical care (such as psychological therapies). However, few studies have investigated if there is a relationship between clinical care practices and ethnic inequalities in involuntary admission.AimsThis study investigated the impact of ethnicity and clinical care on involuntary admission and the potential mediation effects of prior clinical care.MethodIn this retrospective cohort study, we used data from the electronic records of the South London and Maudsley NHS Foundation Trust and identified patients with a first hospital admission between January 2008 and May 2021. Logistic regression and mediation analyses were used to investigate the association between ethnicity and involuntary admission, and whether clinical care, in the 12 months preceding admission, mediates the association.ResultsCompared with White British people, higher odds of involuntary admission were observed among 10 of 14 minority ethnic groups; with more than twice the odds observed among people of Asian Chinese, of Asian Bangladeshi and of any Black background. There were some ethnic differences in clinical care prior to admission, but these had a minimal impact on the inequalities in involuntary admission. More out-patient appointments and home treatment were associated with higher odds of involuntary admission, whereas psychological therapies and having a care plan were associated with reduced odds of involuntary admission.ConclusionsEthnic inequalities in involuntary admission persist after accounting for potential mediating effects of several types and frequencies of clinical care. Promoting access to psychological therapies and ensuring that care plans are in place may reduce involuntary admissions.

Introduction: People with Dementia (PwD)'s performance of activities of daily living (ADLs) has been associated with apathy, cognitive deficits, carers' depression and burden. However, it is not known if the carers' management style affects ADL performance, particularly alongside PwD's cognitive deficits and apathy. Thus, the aim of this study was to explore the contribution of intrinsic (cognition, apathy) and extrinsic (carer management styles) dementia factors to ADL performance. Methods: PwD (n = 143) were assessed on global cognition (ACE-III); apathy (CBI-R); ADLs (Disability Assessment for Dementia-DAD). Carers' (n = 143) criticism, encouragement and active-management styles were assessed with the Dementia Management Strategy Scale (DMSS). Multiple linear regression analysis investigated contributions of carer styles, cognition, apathy (independent variables) on ADLs (dependent variable). Results: The best model explaining the variance of the DAD scores included cognition (β = 0.413, t (142) = 4.463, p = 0.001), apathy (β = –0.365, t (142) = –5.556, p = 0.001), carer criticism (β = –0.326, t (142) = –2.479, p = 0.014) and carer encouragement styles (β = 0.402, t (142) = 2.941, p = 0.004) accounting for 40% of the variance of the DAD scores. Conclusions: This novel study demonstrated that PwD's level of apathy and the carer's use of criticism negatively affected ADL performance while PwD's cognitive abilities and carer encouragement style improved ADL performance. These findings have critical implications for the development of novel multi-component non-pharmacological interventions to maintain function and delay disease progression in dementia, as well as direct relevance to current carers and families.

BACKGROUND: People with dementia sometimes refuse assistance with personal care activities such as washing or dressing. We aimed to investigate the factors associated with refusals of care in advanced dementia. METHODS: a cross-sectional study using informant-based measures. Participants were people with advanced dementia and their caregivers (family carers or care-home staff) (n=260, 130 dyads) in the UK. Mixed effects linear models were used to examine the effects of neuropsychiatric behaviours, ability with activities of daily living, professional input, co-morbidities, psychotropic medications, environment modifications, and caregiver factors including type and training status on refusals of care. The Refusal of Care Informant Scale was used, range 1-13; higher scores indicate more refusal behaviours. RESULTS: higher independence in activities of daily living was associated with less refusal behaviours (coefficient = -0.11, p

Background: The identification and understanding of the discrepancy between caregivers’ reports of people with dementia’s (PwD) performance of activities of daily living (ADLs) and observed performance, could clarify what kind of support a PwD effectively needs when completing tasks. Strategies used by caregivers have not been included in the investigation of this discrepancy. Objective: To (1) investigate if caregivers’ report of PwD’s ADL performance are consistent with PwD’s observed performance; (2) explore if caregiver management styles, depression, and anxiety, contribute to this discrepancy. Methods: PwD (n = 64) were assessed with standardized performance-based (Assessment of Motor and Process Skills, AMPS) and informant-based (Disability Assessment for Dementia, DAD) ADL assessments. Caregivers completed depression (PHQ-9), anxiety (GAD-7), and dementia management style (DMSS: criticism, active-management, and encouragement) questionnaires. Cohen’s kappa determined agreement/disagreement in ADL performance. To investigate the potential discrepancy between the DAD and AMPS, a continuous variable was generated: comparative ADL score. Multiple linear regression analysis explored whether caregivers’ management styles, depression or anxiety could explain the ADL discrepancy. Results: Poor level of agreement between observed and reported ADL performance [k = –0.025 (95% CI –0.123 –0.073)] was identified, with most caregivers underestimating ADL performance. The combined model explained 18% (R2 = 0.18, F (5,55) = 2.52, p≤0.05) of the variance of the comparative ADL score. Active-management (β= –0.037, t (60) = –3.363, p = 0.001) and encouragement (β= 0.025, t (60) = 2.018, p = 0.05) styles made the largest and statistically significant contribution to the model. Conclusion: Encouragement style could be advised for caregivers who underestimate ADL performance, while active management style for those who overestimate it. Findings have scope to increase caregivers’ abilities to support PwD activity engagement in daily life.

The role of anxiety on the quality of life of family carers of people with dementia is somewhat neglected in the carer literature. The current study aimed to investigate the impact of common risk factors (i.e., care recipient's neuropsychiatric symptoms, carer depression, and burden) and anxiety on QoL. This cross-sectional study recruited 89 family carers. Most of the participants were looking after a spouse with Alzheimer's or mixed dementia. A multiple regression analysis was conducted with carer QoL as a dependent variable. All risk factors (i.e., people with dementia's neuropsychiatric symptoms, carer depression, anxiety, and burden) were entered into the model simultaneously as independent variables. The model's R2 was 33%. The results demonstrated that anxiety was the only significant independent variable predicting carer QoL (β = - 0.34, p = 0.03, 95% CI: - 0.64 to - 0.04). These results indicated that having more symptoms of anxiety was associated with worse QoL as measured by the ICEpop CAPability measure for Older people (ICECAP-O). These findings suggested that improving carer's anxiety may be particularly important in promoting QoL among family carers of people with dementia. Future interventions should target this variable to achieve the desired result of improving carer QoL.

Background High baseline pain self-efficacy (PSE) predicts a better outcome for people attending physiotherapy for musculoskeletal shoulder pain. A potential contributing factor is that PSE moderates the relationship between some treatment modalities and outcome. Our aim was to investigate whether there is a difference in outcome between participants with high compared to low PSE receiving manual therapy, acupuncture, and electrotherapy. Methods Participants were stratified into high or low baseline (i) PSE, (ii) shoulder pain and disability index (SPADI), and (iii) did or did not receive the treatment. Whether the effect of treatment differs for people with high compared to low PSE was assessed using the 95% confidence interval of the difference of difference (DoD) at a 5% significance level ( p Results Six-month SPADI scores were consistently lower (less pain and disability) for those who did not receive passive treatments compared to those who did (statistically significant less pain and disability in 7 of 24 models). However, DoD was statistically insignificant. Conclusion PSE did not moderate the relationship between treatment and outcome. However, participants who received passive treatment experienced equal or more pain and disability at 6 months compared to those who did not. Results are subject to confounding by indication but do indicate the need for further appropriately designed research. Level of Evidence Level of evidence II-b.

The objectives of this randomized, cross-over pilot study were to determine whether isometric plantarflexion exercises resulted in an immediate change in Achilles tendon pain during a loading task, and whether this differed in knee extension or flexion. Eleven participants with mid-portion Achilles tendinopathy were recruited from NHS community physiotherapy services and local running clubs. Participants were then randomized to complete an isometric calf muscle exercise with the knee fully extended or flexed to 80°. Participants switched to the alternate exercise after a minimum seven-day period. Achilles tendon pain during a specific, functional load test was measured on a 11-point numeric pain rating scale (NPRS) pre- and post-intervention. There was a small, immediate, mean reduction in pain following isometric plantar flexion performed in both knee extension (1.6, 95%CI 0.83 to 2.45, p=0.001) and knee flexion (1.3, 95%CI 0.31 to 2.19, p=0.015). There were no significant differences between the two positions. A non-significant, potentially clinically relevant finding was a 20% larger reduction in symptoms in knee extension versus flexion (p=0.110). In conclusion, isometric plantarflexion holds gave an approximately 50% immediate reduction in Achilles tendon pain with a functional load test. There were no significant differences between the two positions and both were well tolerated.The objectives of this randomized, cross-over pilot study were to determine whether isometric plantarflexion exercises resulted in an immediate change in Achilles tendon pain during a loading task, and whether this differed in knee extension or flexion. Eleven participants with mid-portion Achilles tendinopathy were recruited from NHS community physiotherapy services and local running clubs. Participants were then randomized to complete an isometric calf muscle exercise with the knee fully extended or flexed to 80°. Participants switched to the alternate exercise after a minimum seven-day period. Achilles tendon pain during a specific, functional load test was measured on a 11-point numeric pain rating scale (NPRS) pre- and post-intervention. There was a small, immediate, mean reduction in pain following isometric plantar flexion performed in both knee extension (1.6, 95%CI 0.83 to 2.45, p=0.001) and knee flexion (1.3, 95%CI 0.31 to 2.19, p=0.015). There were no significant differences between the two positions. A non-significant, potentially clinically relevant finding was a 20% larger reduction in symptoms in knee extension versus flexion (p=0.110). In conclusion, isometric plantarflexion holds gave an approximately 50% immediate reduction in Achilles tendon pain with a functional load test. There were no significant differences between the two positions and both were well tolerated.

Background: Different dementia syndromes display different patterns of everyday functioning. This article explored different patterns of functioning at baseline and trajectories of change in behavioral variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD). Methods: Data from the Uniform Data Set of the National Alzheimer’s Coordinating Centre were employed. The Functional Assessment Questionnaire assessed functioning at up to 7 follow-up visits. Independent t tests assessed variations in functioning between syndromes at baseline. Linear mixed-effect modeling explored longitudinal functional trajectories between syndromes. Results: Data from 3351 patients (306 bvFTD and 3,045AD) were analyzed. At baseline, patients with bvFTD performed all daily activities poorer than AD dementia. Linear mixed models showed a significant effect of syndrome and time on functioning, and evidence of interaction between syndrome and time, with bvFTD showing a steeper decline for using the stove and travel. Conclusions: Findings can help in the effective care planning of everyday functioning for bvFTD and AD dementia.

Background: The relationship between the physical environment and the person with dementia’s (PwD) activities of daily living (ADLs) task performance is controversial. Although the general assumption is that this population benefits from their home environment when performing ADLs, very few experimental studies have been conducted to date. Objectives: The aim was to investigate the influence of the environment (home vs. Research-lab) and the role of clutter on ADL performance. Methods: Sixty-five PwD were evaluated with a performance-based ADL assessment (at home and clutter-free Research-lab). Paired t tests compared ADL performance and level of clutter in both environments. Multiple regression analysis investigated factors associated with better ADL performance. Results: Overall, PwD performed better at home even though clutter was significantly lower in the Research-lab. When stratified by dementia stage, PwD in the moderate stage of the disease performed better at home. Conclusion: Absence of clutter in the Research-Lab did not appear to play a beneficial role in ADLs. When stratified by dementia stage, only PwD in the moderate stage appeared to benefit from their home environment when performing ADL tasks. Future studies are required to elucidate the wider role of the environment in supporting engagement in daily activities in different dementia stages.

Background Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation. Methods A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources. Results The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12 months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE = 0.316) or cohort data only (1.56, SE = 0.240) overestimated this compared with the estimate using data from both sources (0.86, SE = 0.327). Conclusions It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.

Summary We describe the incidence of suicidality (2007–2017) in people with depression treated by secondary mental healthcare services at South London and Maudsley NHS Trust (n = 26 412). We estimated yearly incidence of ‘suicidal ideation’ and ‘high risk of suicide’ from structured and free-text fields of the Clinical Record Interactive Search system. The incidence of suicidal ideation increased from 0.6 (2007) to 1 cases (2017) per 1000 population. The incidence of high risk of suicide, based on risk forms, varied between 0.06 and 0.50 cases per 1000 adult population (2008–2017). Electronic health records provide the opportunity to examine suicidality on a large scale, but the impact of service-related changes in the use of structured risk assessment should be considered.

Background and objectives Research indicates the value of targeting emotional regulation (ER) skills in psychological interventions for psychosis. These skills can be delivered in a group format, thereby increasing access to therapy. This pilot study examined the acceptability and clinical effects of teaching ER skills in The Living Through Psychosis (LTP) group programme. Methods Patients with a psychotic illness were offered the LTP programme, comprising eight sessions over four weeks. Measures were completed by 55 participants. Acceptability was assessed by attendance rates and group cohesion. Measures of intervention targets, recovery and clinical outcomes were completed at baseline, pre-group, post-group, and one-month follow-up. Results High group attendance and cohesion support the acceptability of the group. Participants reported less difficulty with ER (Coeff. = −8.29, 95% CI: −13.40 to −3.18, within participant uncontrolled effect size (ES) d = 0.29), increased mindful relating to distressing symptoms (Coeff. = 11.20, 95% CI: 7.02 to 15.38, d = 0.65), and improvements in recovery dimensions (Coeff. = 10.07, 95% CI: 5.6 to 14.54, d = 0.42) from pre-to post-intervention, and maintained at one-month follow-up. Participants’ hallucinations and delusions reduced from pre-intervention to follow-up (t(18) = 4.64, p < 0.001; t(18) = 5.34, p < 0.001). There was no change in fear of relapse. Limitations The uncontrolled, pre-post design precluded blinded assessments, and may have inflated effect sizes. Other factors may have contributed to the improvements. Conclusions The LTP programme was acceptable to people with psychosis. The preliminary findings indicate the potential utility of teaching ER and mindfulness skills in a brief group programme. Findings require replication in a randomized controlled trial.

OBJECTIVES: To provide baseline cohort descriptives and assess change in health behaviours since the UK COVID-19 lockdown. DESIGN: A prospective cohort (N = 1,044) of people recruited online, purposively targeting vulnerable populations. METHODS: After a baseline survey (April 2020), participants completed 3 months of daily ecological momentary assessments (EMA). Dietary, physical activity, alcohol, smoking, vaping and substance use behaviours collected retrospectively for the pre-COVID-19 period were compared with daily EMA surveys over the first 30 days during early lockdown. Predictors of behaviour change were assessed using multivariable regression models. RESULTS: 30% of the cohort had a COVID-19 at risk health condition, 37% were classed as deprived and 6% self-reported a mental health condition. Relative to pre-pandemic levels, participants ate almost one portion of fruit and vegetables less per day (vegetables mean difference -0.33, 95% CI -0.40, -0.25; fruit -0.57, 95% CI -0.64, -0.50), but showed no change in high sugar portions per day (-0.03, 95% CI -0.12, 0.06). Participants spent half a day less per week doing ≥30 min of moderate to vigorous physical activity (-0.57, 95% CI -0.73, -0.40) but slightly increased days of strength training (0.21, 95% CI 0.09, 0.34), increased alcohol intake (AUDIT-C score change 0.25, 95% CI 0.13, 0.37), though did not change smoking, vaping or substance use behaviour. Worsening health behaviour change was associated with being younger, female and higher body mass index. CONCLUSIONS: The cohort reported worsening health behaviours during early lockdown. Longer term changes will be investigated using further waves of data collection.

BackgroundClozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics.AimsTo investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation and intensive care treatment, and death, among patients taking antipsychotics with schizophrenia-spectrum disorders.MethodUsing data from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics at the time of the COVID-19 pandemic in the UK, and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores.ResultsIn the 157 individuals who developed COVID while on antipsychotics, there were 44 COVID-related hospitalisations, 13 COVID-related intensive care treatments and 13 deaths of any cause during the follow-up period. In the unadjusted analysis, there was no significant association between clozapine and any of the outcomes and there remained no associations following adjusting for the confounding variables.ConclusionsIn our sample of patients with COVID-19 and schizophrenia-spectrum disorders, we found no evidence that clozapine treatment puts patients at increased risk of hospitalisation, intensive care treatment or death, compared to any other antipsychotic treatment. However, further research should be considered in larger samples to confirm this.Conflict of interestRDH has received research funding from Roche, Pfizer, Janssen, and Lundbeck. DFF has received research funding from Janssen and Lundbeck. JHM has received research funding from Lundbeck. JTT has received research funding from Bristol-Meyers-Squibb. RS declares research support in the last 36 months from Janssen, GSK and Takeda.Ethics statementThe research was conducted under ethical approval reference 18/SC/0372 from Oxfordshire Research Ethics Committee C.

Implementation of evidence-based cognitive behavioural therapy for psychosis (CBTp) remains low in routine services. The United Kingdom Improving Access to Psychological Therapies for people with Severe Mental Illness (IAPT-SMI) initiative aimed to address this issue. The project evaluated whether existing services could improve access to CBTp and demonstrate effectiveness using a systematic approach to therapy provision and outcome monitoring (in a similar way to the Improving Access to Psychological Therapies (IAPT) model for people with anxiety and depression). We report the clinical outcomes and key learning points from the South London and Maudsley NHS Foundation Trust IAPT-SMI demonstration site for psychosis. Additional funding enabled increased therapist capacity within existing secondary care community mental health services. Self-reported wellbeing and psychotic symptom outcomes were assessed, alongside service use and social/occupational functioning. Accepted referrals/year increased by 89% (2011/12: n = 106/year; 2012–2015: n = 200/year); 90% engaged (attended ≥5 sessions) irrespective of ethnicity, age and gender. The assessment protocol proved feasible, and pre-post outcomes (n = 280) showed clinical improvements and reduced service use, with medium effects. We conclude that, with appropriate service structure, investment allocated specifically for competent therapy provision leads to increased and effective delivery of CBTp. Our framework is replicable in other settings and can inform the wider implementation of psychological therapies for psychosis.

Background: older people with frailty are particularly high users of healthcare services, however a lack of standardised recording of frailty in different healthcare electronic datasets has limited investigations into healthcare service usage and demand of the older frail population. Objectives: to investigate the community service demand of frail patients using the electronic frailty index (eFI) as a measure of frailty. Study design and setting: a retrospective cohort study using anonymised linked healthcare patient data from primary care, community services and acute hospitals in Norfolk. Participants: patients aged 65 and over who had an eFI assessment score established in their primary care electronic patient record in Norwich based General Practices. Results: we include data from 22,859 patients with an eFI score. Frailty severity increased with age and was associated with increased acute hospital admission within a 6-month window. Patients with a frail eFI score were also more likely to have a community service referral within a 6-month window of frailty assessment, with a RR of 1.84 (1.76–1.93) for mild frailty, 1.96 (1.83–2.09) for moderate frailty and 2.95 (2.76–3.14) for severe frailty scores. We also found that frail patients had more community referrals per patient then those classified as fit and required more care plans per community referral. Conclusions: eFI score was an indicator of community service use, with increasing severity of frailty being associated with higher community healthcare requirements. The eFI may help planning of community services for the frail population.

The relationship between the physical environment and the person with dementia's (PwD) activities of daily living (ADLs) task performance is controversial. Although the general assumption is that this population benefits from their home environment when performing ADLs, very few experimental studies have been conducted to date.The aim was to investigate the influence of the environment (home vs. Research-lab) and the role of clutter on ADL performance.Sixty-five PwD were evaluated with a performance-based ADL assessment (at home and clutter-free Research-lab). Paired t tests compared ADL performance and level of clutter in both environments. Multiple regression analysis investigated factors associated with better ADL performance.Overall, PwD performed better at home even though clutter was significantly lower in the Research-lab. When stratified by dementia stage, PwD in the moderate stage of the disease performed better at home.Absence of clutter in the Research-Lab did not appear to play a beneficial role in ADLs. When stratified by dementia stage, only PwD in the moderate stage appeared to benefit from their home environment when performing ADL tasks. Future studies are required to elucidate the wider role of the environment in supporting engagement in daily activities in different dementia stages.

Background Cognitive decline is a common complaint in menopause. Alzheimer disease(AD) has higher incidence in women and early menopause increases risk for AD. Studies of cognitive change at menopause have had mixed results. Navigational ability declines early in the course of AD. No studies have looked at changes in navigational ability around menopause. Objective: Determine the effect of menopause on navigation. Method Participants were 200,999 persons aged 35‐65 who downloaded the Sea Hero Quest app and completed enough levels to analyze navigation. Measures of navigation examined included distance traveled and time spent to complete levels as well as accuracy in determining one’s starting point after completing a maze. These scores were normalized based on early, simple levels in order to control for video game ability. Each measure was analyzed by splitting male and female participants into ages 35‐45 and ages 55‐65 in order to look at persons before and after menopause. Groups were analyzed using a 2‐way ANOVA with gender and age as independent variables. Additionally, piecewise linear modeling was applied to the entire population aged 35 to 65 to test whether there was a significant change in the slope of decline in navigational ability at age 51, the average age of menopause. Result Female gender and advancing age were both predictive of worse performance on all measures. ANOVA found significant(p

OBJECTIVE:Psychological interventions reduce the impact of psychosis, but widescale implementation is problematic. We tested the feasibility of group acceptance and commitment therapy for Psychosis (G-ACTp), delivered by frontline staff, and co-facilitated by service-user experts-by-experience (SU-EbyE), for service-users and informal caregivers (ISRCTN: 68540929). We estimated recruitment/retention rates and outcome variability for future evaluation. METHODS:Staff and SU-EbyE facilitators completed 1-day workshops, then delivered closely supervised G-ACTp, comprising four sessions (weeks 1-4) and two boosters (10 and 12 weeks). Participants recruited from adult community psychosis services were randomized to receive G-ACTp immediately or after 12 weeks, completing outcome assessments at 0, 4, and 12 weeks. Service-use/month was calculated for 1-year pre-randomization, weeks 0-12, and 5-year uncontrolled follow-up. RESULTS:Of 41 facilitators trained (29 staff, 12 SU-EbyE), 29 (71%; 17 staff, 12 SU-EbyE) delivered 18 G-ACTp courses. Participant refusal rates were low (9% of service-users [10/112]; 5% of caregivers [4/79]); 60% of those invited to participate attended ≥1 G-ACTp session (64% of service-users [39/61]; 56% of caregivers [35/63]). Randomization of facilitators and participants proved problematic and participant follow-up was incomplete (78% [66/85]; 82% of service-users [36/44]; 73% of caregivers [30/41]). Effect sizes ranged from very small to large mostly favouring treatment. Service-use reductions require cautious interpretation, as very few participants incurred costs. CONCLUSIONS:Implementation appears feasible for service-users; for caregivers, retention needs improving. Outcome variability indicated n = 100-300/arm followed up (α = 0.05, 90% power). Methodological limitations' mean replication is needed: identified sources of potential bias may be reduced in a cluster randomized design with sessional outcome completion. PRACTITIONER POINTS:Group acceptance and commitment therapy can be successfully adapted for people with psychosis and their caregivers. Implementation (training and delivery) is possible in routine community mental health care settings. Clinical and economic outcomes are promising, but replication is needed. Recommendations are made for future studies.

Supplemental Material, Additional_File_Table_A1 for Distinguishing Frontotemporal Dementia From Alzheimer Disease Through Everyday Function Profiles: Trajectories of Change by Clarissa M. Giebel, David Knopman, Eneida Mioshi and Mizanur Khondoker in Journal of Geriatric Psychiatry and Neurology

Background The density of information in digital health records offers new potential opportunities for automated prediction of cost-relevant outcomes. Aims We investigated the extent to which routinely recorded data held in the electronic health record (EHR) predict priority service outcomes and whether natural language processing tools enhance the predictions. We evaluated three high priority outcomes: in-patient duration, readmission following in-patient care and high service cost after first presentation. Method We used data obtained from a clinical database derived from the EHR of a large mental healthcare provider within the UK. We combined structured data with text-derived data relating to diagnosis statements, medication and psychiatric symptomatology. Predictors of the three different clinical outcomes were modelled using logistic regression with performance evaluated against a validation set to derive areas under receiver operating characteristic curves. Results In validation samples, the full models (using all available data) achieved areas under receiver operating characteristic curves between 0.59 and 0.85 (in-patient duration 0.63, readmission 0.59, high service use 0.85). Adding natural language processing-derived data to the models increased the variance explained across all clinical scenarios (observed increase in r2 = 12–46%). Conclusions EHR data offer the potential to improve routine clinical predictions by utilising previously inaccessible data. Of our scenarios, prediction of high service use after initial presentation achieved the highest performance.

Summary Trends in detention under the Mental Health Act 1983 in two major London secondary mental healthcare providers were explored using patient-level data in a historical cohort study between 2007–2008 and 2016–2017. An increase in the number of detention episodes initiated per fiscal year was observed at both sites. The rise was accompanied by an increase in the number of active patients; the proportion of active patients detained per year remained relatively stable. Findings suggest that the rise in the number of detentions reflects the rise of the number of people receiving secondary mental healthcare.

Clustering algorithms group data items based on clearly defined similarity between the items aiming to minimize the intracluster differences and maximize the intercluster distances. A wealth of efficient and good quality clustering algorithms are already available for traditional data, but there are challenges for applying them to big data due to the overwhelming volume and complexities of such data. Data volume is getting bigger at an incredible pace due to growing access to Internet, social media, mobile devices, and technological innovations, and improving clustering algorithms, their computational cost and scalability have been the focus of much of the research in this area. This article provides an introduction to the characteristics of big data, and an overview of available algorithms and the current improvement trend of clustering algorithms for dealing with the challenges of big data.

Aims: To investigate clustering of all-cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid-dependent individuals in specialist addiction treatment. Design, Setting and Participants: Mortality data were identified within a sample of 5,445 patients with opioid use disorder who had received OST treatment between 1st April 2008 and 31st December 2013 from a large mental healthcare provider in United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n=103) after a planned discharge, drop-out and transfer between services. Measurements: Crude mortality rates for overdose mortality 7/14/28/180 days after the end of treatment/transfer for overdose mortality. Findings: Of 47 individuals who died from overdose after having been transferred between services, 9 died in the first 2 weeks (crude mortality rate [CMR] 136.4, 64.3 – 243.1 95% CI) and a further 5 died in the first month post-transfer (CMR 79.5, 44.2 – 129.7 95% CI). Of the 32 individuals who died from overdose after planned OST cessation, 5 died in the first 2 weeks (CMR 151.5, 51.1 – 319.0 95% CI) and a further 4 died in the first month post discharge (CMR 82.6, 38.4 – 151.0 95% CI). Conclusions: In the UK, opioid-dependent people who are transferred to an alternative treatment provider for continuation of their opioid substitution therapy experience high overdose mortality rates, with substantially higher rates in the first month (especially first 14 days) following transfer.

Background As mortality from coronary heart disease (CHD) falls, years lived with disability increase. Depression and anxiety are known indicators of poor outcomes in CHD, but most research has measured distress symptoms at one time point, often following acute events. Here we consider the long-term trajectories of these symptoms in established CHD, and examine their association to distinct measures of disability and impact on costs. Methods and results 803 patients with diagnosis of CHD were recruited from primary care, and completed detailed assessments every 6 months for 3 years. Latent class growth analysis (LCGA) was used to identify 5 distinct symptom trajectories based on the Hospital Anxiety and Depression Questionnaire (HADS): ‘stable low’, ‘chronic high’, ‘improving’, ‘worsening’, and ‘fluctuating’. The ‘chronic high’ group had highest association with reporting of chest pain (RRR 5.8, CI 2.9 to 11.7), smoking (2.9, 1.1 to 6.3), and poorer physical (0.88, 0.83–0.93) and mental (0.78, 0.73–0.84) quality of life. The ‘chronic high’ and ‘worsening’ trajectories had significantly higher health-care costs over the ‘stable low’ trajectory (107.2% and 95.5% increase, respectively). In addition, our trajectories were the only significant variable associated with increased health-care costs across the 3 years. Conclusions Symptoms of depression and anxiety are highly prevalent in stable CHD patients, and their long-term trajectories are the single biggest driver of health care costs. Managing morbidity in these patients, in which depression and anxiety play a key role in, should become the primary focus of policy makers and future clinical trials.

Aims.Within acute psychiatric inpatient services, patients exhibiting severely disturbed behaviour can be transferred to a psychiatric intensive care unit (PICU) and/or secluded in order to manage the risks posed to the patient and others. However, whether specific patient groups are more likely to be subjected to these coercive measures is unclear. Using robust methodological and statistical techniques, we aimed to determine the demographic, clinical and behavioural predictors of both PICU and seclusion.Methods.Data were extracted from an anonymised database comprising the electronic medical records of patients within a large South London mental health trust. Two cohorts were derived, (1) a PICU cohort comprising all patients transferred from general adult acute wards to a non-forensic PICU ward between April 2008 and April 2013 (N = 986) and a randomly selected group of patients admitted to general adult wards within this period who were not transferred to PICU (N = 994), and (2) a seclusion cohort comprising all seclusion episodes occurring in non-forensic PICU wards within the study period (N = 990) and a randomly selected group of patients treated in these wards who were not secluded (N = 1032). Demographic and clinical factors (age, sex, ethnicity, diagnosis, admission status and time since admission) and behavioural precursors (potentially relevant behaviours occurring in the 3 days preceding PICU transfer/seclusion or random sample date) were extracted from electronic medical records. Mixed effects, multivariable logistic regression analyses were performed with all variables included as predictors.Results.PICU cases were significantly more likely to be younger in age, have a diagnosis of bipolar disorder and to be held on a formal section compared with patients who were not transferred to PICU; female sex and longer time since admission were associated with lower odds of transfer. With regard to behavioural precursors, the strongest predictors of PICU transfer were incidents of physical aggression towards others or objects and absconding or attempts to abscond. Secluded patients were also more likely to be younger and legally detained relative to non-secluded patients; however, female sex increased the odds of seclusion. Likelihood of seclusion also decreased with time since admission. Seclusion was significantly associated with a range of behavioural precursors with the strongest associations observed for incidents involving restraint or shouting.Conclusions.Whilst recent behaviour is an important determinant, patient age, sex, admission status and time since admission also contribute to risk of PICU transfer and seclusion. Alternative, less coercive strategies must meet the needs of patients with these characteristics.

International audience; Spatial navigation is emerging as a critical factor in identifying preclinical Alzheimer's disease (AD). However, the impact of interindi-vidual navigation ability and demographic risk factors (e.g., APOE, age, and sex) on spatial navigation make it difficult to identify persons "at high risk" of AD in the preclinical stages. In the current study, we use spatial navigation big data (n = 27,108) from the Sea Hero Quest (SHQ) game to overcome these challenges by investigating whether big data can be used to benchmark a highly phenotyped healthy aging laboratory cohort into high-vs. low-risk persons based on their genetic (APOE) and demographic (sex, age, and educational attainment) risk factors. Our results replicate previous findings in APOE e4 carriers, indicative of grid cell coding errors in the entorhinal cortex, the initial brain region affected by AD pathophysiology. We also show that although baseline navigation ability differs between men and women, sex does not interact with the APOE genotype to influence the manifestation of AD-related spatial disturbance. Most importantly, we demonstrate that such high-risk preclinical cases can be reliably distinguished from low-risk participants using big-data spatial navigation benchmarks. By contrast, participants were undistinguishable on neuropsychological episodic memory tests. Taken together, we present evidence to suggest that, in the future, SHQ normative benchmark data can be used to more accurately classify spatial impairments in at-high-risk of AD healthy participants at a more individual level, therefore providing the steppingstone for individualized diagnostics and outcome measures of cognitive symptoms in preclinical AD. Alzheimer's disease | spatial navigation | personalized health care | APOE genotype | preclinical diagnosis S patial navigation is a promising cognitive fingerprint for underlying Alzheimer's disease (AD) pathophysiology (1-8) and has been adopted by many high-profile clinical trials (such as the European Prevention of Alzheimer's Dementia Consortium) to improve the sensitivity of neurocognitive testing and assess the efficacy of potentially disease-modifying treatments. In fact, brain areas affected by AD pathophysiology in the preclinical stage (including the entorhinal cortex, posterior cingulate cortex, and precuneus) form the key nodes in the spatial navigation network (6, 9-13). Recent evidence suggests that abnormal spatial navigation patterns may be present before episodic memory deficits, which are the current gold standard for AD diagnosis (6, 14, 15). A major challenge at this stage, however, is to understand how interindividual and demographic factors affect spatial navigation to identify earliest pathological spatial navigation changes in AD (16-19). Understanding diversifying factors that influence variability in spatial ability in the healthy population and individuals at risk to develop AD will advance the diagnostic power of the spatial tests and support more personalized diagnostic and treatment approaches (17, 20-23). Among factors underlying navigation, age is a well-documented predictor of declining spatial abilities, as older adults show a strong bias toward egocentric rather than allocentric strategies (24, 25) leading to suboptimal navigation performance (26). Age-related decline in allocentric process are due to changes in coding patterns of place, grid, border, and head direction cells that underpin our ability to form cognitive maps of the environment and intergrate environmental and self-motion cues to optimize navigational performance (27-29). However, decline in other cognitive domains such as general planning and cognitive control abilities (30) also contribute to spatial deficits in old age, suggesting that, like most diagnostic tests, age-range normative cutoff scores are required (30, 31). Similarly, sex differences in navigation behavior and underlying neuroanatomy have generated arguments for sex-specific clinico-pathological AD phenotypes (17, 21, 32-35). Rodent models of the Morris water maze have shown that male rats consistently outper-form females (36), and human studies display similar sex differences favoring males (37-40) across 57 countries in both map-dependent allocentric and map-independent egocentric navigational strategies (41). Therefore, although spatial navigation tools must retain sensitivity and specificity to preclinical AD pathophysiology, it will be critical to develop diagnostic tools that can adjust for underlying sex differences. Finally, one of the biggest challenges in preclinical AD studies is to identify those who are at high risk to develop symptomatic AD in the future. Genetic variation in the apolipoprotein E 4 allele carriers is currently the strongest known genetic risk factor for sporadic AD (7, 42-44). Compared with the e3e3 carriers, those with the e3e4 show a threefold to fourfold increased risk for AD (44, 45). Phenotypic characteristics of apoE e4 allele show that the cognitive profile of e4 carriers changes over the life span, with some cognitive advantage seen in young adulthood (39) and cognitive disturbances in mnemonic and spatial process in mid-adulthood (46-48). Recent findings also show that temporal grid cell-like representation in the

Objective/Background: Our aim was to qualitatively explore the experiences of people who attended a one-day sleep workshop six years previously. Participants: Of the 95 people who originally attended the workshop and a three-month follow-up, 14 individuals (mean age = 63.6 years) participated. Methods: Semi-structured interviews were used to explore: participants’ experiences of insomnia since the workshop, memories of the techniques and information provided and the perceived impact of the workshop on their lives. Qualitative data were analyzed using the principles of Framework Analysis. Results: Interviews produced rich accounts of attributions of changes in sleep, the application of taught strategies and general experiences of the workshop. Conclusions: This research highlights which aspects of a large-scale intervention may be most helpful for individuals experiencing sleep difficulties and what factors may contribute to changes in sleep over time.

ObjectivesTo (i) identify predictors of outcome for the physiotherapy management of shoulder pain and (ii) enable clinicians to subgroup people into risk groups for persistent shoulder pain and disability.Methods1030 people aged ≥18 years, referred to physiotherapy for the management of musculoskeletal shoulder pain were recruited. 810 provided data at 6 months for 4 outcomes: Shoulder Pain and Disability Index (SPADI) (total score, pain subscale, disability subscale) and Quick Disability of the Arm, Shoulder and Hand (QuickDASH). 34 potential prognostic factors were used in this analysis.ResultsFour classification trees (prognostic pathways or decision trees) were created, one for each outcome. The most important predictor was baseline pain and/or disability: higher or lower baseline levels were associated with higher or lower levels at follow-up for all outcomes. One additional baseline factor split participants into four subgroups. For the SPADI trees, high pain self-efficacy reduced the likelihood of continued pain and disability. Notably, participants with low baseline pain but concomitant low pain self-efficacy had similar outcomes to patients with high baseline pain and high pain self-efficacy. Cut-off points for defining high and low pain self-efficacy differed according to baseline pain and disability. In the QuickDASH tree, the association between moderate baseline pain and disability with outcome was influenced by patient expectation: participants who expected to recover because of physiotherapy did better than those who expected no benefit.ConclusionsPatient expectation and pain self-efficacy are associated with clinical outcome. These clinical elements should be included at the first assessment and a low pain self-efficacy response considered as a target for treatment intervention.