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A systematic review was conducted to investigate prevalence, management and outcomes of atrial fibrillation (AF) in people with Serious Mental Illnesses (SMI) versus the general population.MEDLINE, EMBASE, and PsycINFO were searched for primary research written in English and published between 2004 and 2022.A total of 1459 studies were identified in the initial search of which 16 met the inclusion criteria. Studies (n = 4) reporting on ischaemic stroke and major bleeding events were included in the meta-analysis.Two independent reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Scale. Discrepancies were resolved by consulting a third reviewer.Low rates of AF were reported among people with SMI suggesting under-recognition or recording gaps. People with SMI and AF were less likely to receive oral anticoagulation therapy compared to the general population. When receiving warfarin, those with bipolar disorder experienced poor anticoagulation control as measured by time in INR therapeutic range. Pooled analysis of risk estimates showed that in patients with identified AF, SMI was not significantly associated with an increased risk of stroke (HR: 1.09; 95%CI: 0.85 to 1.40; IMore research is needed to examine the prevalence, management and outcomes of AF in this population, and to evaluate the effect of the introduction of the novel anti-coagulants on these metrics over time.

Objective: People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.Methods: An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.Results: Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019.Conclusion: Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.

Background: Clozapine is uniquely effective in treatment-resistant psychosis. In the UK, patients must discontinue clozapine indefinitely if they are placed on the Central Non-Rechallenge Database (CNRD) after their haematological parameters fall below particular thresholds. Under exceptional circumstances, patients can be rechallenged on clozapine under an off-licence agreement. In the USA in 2015, restrictive practice was discontinued to allow greater flexibility for clozapine maintenance. The absolute neutrophil count leading to treatment interruption was lowered from less than 1·5 × 109/L to less than 1·0 × 109/L and platelet and white cell count monitoring were ceased. We aimed to investigate the implications of a similar policy change on clozapine use in the UK. Methods: This was a modelling study of all patients registered on the UK CNRD. First, we determined the proportion of patients placed on the database in the UK who would have had to discontinue clozapine treatment under the US Food and Drug Administration (FDA) criteria. Second, we compared the haematological characteristics of patients who did or did not meet FDA criteria for discontinuing clozapine, including the time to registration from clozapine initiation and the proportion of cases of severe neutropenia at registration. Third, we investigated the success rates of clozapine re-challenge for patients that had been placed on the CNRD. Successful rechallenge was defined as no recurrence of CNRD registration. Findings: Between May 2, 2002 and March 1, 2021, 3731 patients were placed on the CNRD, with a mean age of 47 years (SD 15), including 1420 (38%) women and 2311 (62%) men, of whom 3089 (83%) were White, 360 (10%) were Black, 190 (5%) were Asian, and 92 (2%) were classified as other. 566 (15%) of 3731 patients met the equivalent criteria for clozapine discontinuation under the FDA guidelines. The median time to CNRD registration from clozapine initiation was 1·6 years (IQR 0·2–4·9). Data for 519 rechallenged patients were examined; 419 (81%) were successful. Clozapine rechallenge success rates were broadly similar between individuals who did not meet the US CNRD registration criteria (36 [78%] of 46) and those who did meet the criteria (383 [81%] of 473). Interpretation: Implementing the revised FDA monitoring criteria in the UK would substantially reduce clozapine discontinuation for haematological reasons, which would greatly improve the mental health outcomes of these patients without having a major effect on their physical health. Funding: None.

Serious mental illnesses (SMIs) exert a considerable financial burden on health-care systems. In this study, the resource utilization in mental illness (RUMI) tool was developed and employed to evaluate resource utilization in patients with SMI.Data from 107 patients with SMI treated in four psychiatric outpatient clinics in Sweden were collected. The relationships between costs for physical and psychiatric care, social services, and the justice system, to self-reported health and quality of life, educational level, Global Assessment of Functioning (GAF), the Clinical Global Impressions scale score (CGI), and body mass index (BMI) were studied.Sixteen out of 107 patients accounted for 74% of the total costs. The mean and median cost for 6 months included in the survey for social services, family and social welfare and healthcare, psychiatric and physical treatment interventions, mean 8349 EUR, median 2599 EUR per patient (currency value for 2021). Education and psychosocial function (GAF) were both negatively correlated with costs for the social services (education,The RUMI scale was acceptable and enabled estimation of resource utilization in a comparable manner across different care settings. Such comparable data have potential to provide a basis for budgeting and resource allocation.

BACKGROUND People with severe mental illness (SMI) are more likely to suffer from physical health conditions than the general population, with a lower life expectancy of up to 18 years. Little is known about the experience of people with SMI using digital health interventions (DHIs) to support their physical health, and whether they perceive such interventions as beneficial. OBJECTIVE We explored how people with SMI use DHIs to support their physical health, the acceptability, factors effecting use and any perceived impact on physical health. METHODS A mixed methods approach was used, delivered in three stages. Stage 1 online survey of people with SMI; Stage 2 interviews with a sub-sample of participants from Stage 1; Stage 3 stakeholder workshops with people with SMI, clinical staff, carers, voluntary sector staff and commissioners. Study design, data collection and analyses were co-produced with two Experts by Experience with lived experience of SMI. RESULTS Stage 1 results revealed that participants were generally satisfied with the quality of DHIs available to them. The most popular DHIs were targeted at diet, exercise, and weight management. Stage 2 results suggested participants experienced a number of barriers and facilitators to use of DHIs. Factors that encouraged use included simplicity, passivity, and data-linkage. Concerns included costs, data security and reliability of information. Positive impacts included accountability, encouragement, and tangible physical health benefits. Self-awareness and autonomy of care were also perceived to increase. Mental health impacted engagement with DHIs: low mood often hindered motivation to engage with devices, and information produced by these devices could be perceived as triggering. Findings of stage 2 were corroborated in stage 3: workshop participants reported that DHIs could be a useful tool to monitor physical health but could not replace contact with clinical services. The two could be used in conjunction, to expand the benefit of clinical appointments and encourage service user autonomy. Participants appreciated being able to share physical health data in appointments and suggested that data sharing between service user and care team could be a positive feature. Participants sought clinical guidance and recommendations for which devices they could use to monitor or support their physical health. CONCLUSIONS Popular DHIs for supporting physical health were considered useful and acceptable by people with SMI and may be used as an extension of clinical care, giving people with SMI a sense of control and involvement in their own health. The specific needs and priorities of people with SMI should be considered both in developing and recommending interventions.

Introduction: Despite respiratory disease being a major cause of excess mortality in people with schizophrenia, the prevalence of respiratory conditions in this population is poorly defined. A systematic review and meta-analysis were conducted to establish the prevalence and association of respiratory diseases in people with schizophrenia. Material and methods: Major electronic databases were searched from inception to 27 April 2020 for articles reporting respiratory disease (asthma, chronic obstructive pulmonary disease [COPD], pneumonia, and tuberculosis) in people with schizophrenia and, where possible, a control group. A random-effects meta-analysis was conducted. The study was registered with PROSPERO (CRD42018115137). Results: Of 1569 citations, 21 studies consisting of 619,214 individuals with schizophrenia and 52,159,551 controls were included in the meta-analysis. Compared to the general population, people with schizophrenia had significantly higher rates of COPD (odds ratio [OR]: 1.82, 95% CI: 1.28–2.57), asthma (OR: 1.70, 95% CI: 1.02–2.83), and pneumonia (OR: 2.62, 95% CI: 1.10–6.23). In people with schizophrenia, the prevalence of COPD was 7.7% (95% CI: 4.0–14.4), asthma 7.5% (95% CI: 4.9–11.3), pneumonia 10.3% (95% CI 5.4–18.6), and tuberculosis 0.3% (95% CI 0.1 –0.8). After adjusting for publication bias, the prevalence of COPD increased to 19.9% (95% CI: 9.6–36.7). Discussion: All respiratory diseases examined were significantly more prevalent in people with schizophrenia compared with the general population. Future studies should focus on improving the prevention and management of respiratory disease in this group to reduce associated excess mortality. © 2021 Elsevier B.V.

Severe mental illnesses, such as schizophrenia or bipolar disorder, affect ≈1% of the population who, as a group, experience significant disadvantage in terms of physical health and reduced life expectancy. In this review, we explore the interaction between race, ethnicity, severe mental illness, and cardiovascular disease, with a focus on cardiovascular care pathways. Finally, we discuss strategies to investigate and address disparities in cardiovascular care for patients with severe mental illness.

ObjectivesFatigue is a pervasive clinical symptom in coronaviruses and may continue beyond the acute phase, lasting for several months or years. This systematic review and meta-analysis aimed to incorporate the current evidence for postinfection fatigue among survivors of SARS-CoV-2 and investigate associated factors.MethodsEmbase, PsyINFO, Medline, CINAHL, CDSR, Open Grey, BioRxiv and MedRxiv were systematically searched from January 2019 to December 2021. Eligible records included all study designs in English. Outcomes were fatigue or vitality in adults with a confirmed diagnosis of SARS-CoV-2 measured at >30 days post infection. Non-confirmed cases were excluded. JBI risk of bias was assessed by three reviewers. Random effects model was used for the pooled proportion with 95% CIs. A mixed effects meta-regression of 35 prospective articles calculated change in fatigue overtime. Subgroup analyses explored specific group characteristics of study methodology. Heterogeneity was assessed using Cochran’s Q and I2statistic. Egger’s tests for publication bias.ResultsDatabase searches returned 14 262 records. Following deduplication and screening, 178 records were identified. 147 (n=48 466 participants) were included for the meta-analyses. Pooled prevalence was 41% (95% CI: 37% to 45%, k=147, I2=98%). Fatigue significantly reduced over time (−0.057, 95% CI: −107 to −0.008, k=35, I2=99.3%, p=0.05). A higher proportion of fatigue was found in studies using a valid scale (51%, 95% CI: 43% to 58%, k=36, I2=96.2%, p=0.004). No significant difference was found for fatigue by study design (p=0.272). Egger’s test indicated publication bias for all analyses except valid scales. Quality assessments indicated 4% at low risk of bias, 78% at moderate risk and 18% at high risk. Frequently reported associations were female gender, age, physical functioning, breathlessness and psychological distress.ConclusionThis study revealed that a significant proportion of survivors experienced fatigue following SARS-CoV-2 and their fatigue reduced overtime. Non-modifiable factors and psychological morbidity may contribute to ongoing fatigue and impede recovery.PROSPERO registration numberCRD42020201247.

Background and AimsIn the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom.MethodsThis was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status.ResultsOne hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = −7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria.ConclusionImplementation of the updated FDA’s monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia.

People with severe mental illness and type 2 diabetes have a reduced life expectancy compared to the general population. One factor that contributes to this is the inability to provide optimal management, as the two conditions are typically managed by separate physical and mental health systems. The role of care navigators in coordinating diabetes care in people with severe mental illness may provide a solution to better management.To explore the views of clinicians and people with severe mental illness and type 2 diabetes on an integrated health service model with a focus on the care navigator to identify potential mechanisms of action.Qualitative one-to-one semi-structured interviews and part of a wider pilot intervention study.Community Mental Health Unit in South London.Topic guides explored the perspectives and experiences of both clinicians and people with severe mental illness and diabetes. Data analysis was conducted using Thematic Analysis.From the analysis of 19 participants, five main themes emerged regarding the care navigator role: administrative service; signposting to local services; adhering to lifestyle changes and medication; engaging in social activities; further skills and training needed. The key findings from this study emphasise the benefits that the role of a care navigator has in helping people with severe mental illness to better manage their diabetes i.e. through diet, exercise medication and attending essential health check-ups.This study illustrates that having a care navigator in place empowers those with severe mental illness to improve the management of their diabetes. Future research should focus on the extent to which care navigators are effective in improving specific outcomes.

BackgroundClozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.AimsThe aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.MethodThis was a naturalistic study of community patients recommended for clozapine treatment.ResultsOf 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).ConclusionsThese findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.

Background Improvements to the primary prevention of physical health illnesses like diabetes in the general population have not been mirrored to the same extent in people with serious mental illness (SMI). This work evaluates the technical feasibility of implementing an electronic clinical decision support system (eCDSS) for supporting the management of dysglycaemia and diabetes in patients with serious mental illness in a secondary mental healthcare setting. Methods A stepwise approach was taken as an overarching and guiding framework for this work. Participatory methods were employed to design and deploy a monitoring and alerting eCDSS. The eCDSS was evaluated for its technical feasibility. The initial part of the feasibility evaluation was conducted in an outpatient community mental health team. Thereafter, the evaluation of the eCDSS progressed to a more in-depth in silico validation. Results A digital health intervention that enables monitoring and alerting of at-risk patients based on an approved diabetes management guideline was developed. The eCDSS generated alerts according to expected standards and in line with clinical guideline recommendations. Conclusions It is feasible to design and deploy a functional monitoring and alerting eCDSS in secondary mental healthcare. Further work is required in order to fully evaluate the integration of the eCDSS into routine clinical workflows. By describing and sharing the steps that were and will be taken from concept to clinical testing, useful insights could be provided to teams that are interested in building similar digital health interventions.

Context Excess cardiovascular morbidity and an increased prevalence of sudden cardiac death (SCD) contributes to premature mortality in schizophrenia. Brugada syndrome (BrS) is an important but underrecognized cause of SCD. It is more commonly seen in schizophrenia than in general population controls. Methods We conducted a scoping review to describe the pathogenesis of BrS in schizophrenia and to identify the psychotropic medications that increase the risk of unmasking BrS and associated ventricular arrhythmias resulting in SCD. Findings Schizophrenia and BrS share similar calcium channel abnormalities, which may result in aberrant myocardial conductivity. It remains uncertain if there is a genetic pre-disposition for BrS in a subset of patients with schizophrenia. However, the unmasking of Brugada ECG patterns with the use of certain antipsychotics and antidepressants increases the risk of precipitating SCD, independent of QT prolongation. Conclusions and future directions Specific cardiology assessment and interventions may be required for the congenital or unmasked Brugada ECG pattern in schizophrenia. The current long-term standard of care for BrS is an implantable cardioverter defibrillator (ICD), but post-implantation psychological effects must be considered. Careful use of antipsychotic and other psychotropic medications is necessary to minimize proarrhythmic effects due to impact on cardiac sodium and calcium ion channels. When prescribing such drugs to patients with schizophrenia, clinicians should be mindful of the potentially fatal unmasking of Brugada ECG patterns and how to manage it. We present recommendations for psychiatrists managing this patient population.

Vitamin D deficiency is associated with an increased risk of acute respiratory infection. There is an excess of respiratory infections and deaths in schizophrenia, a condition where vitamin D deficiency is especially prevalent. This potentially offers a modifiable risk factor to reduce the risk for and the severity of respiratory infection in people with schizophrenia, although there is as yet no evidence regarding the risk of COVID-19. In this narrative review, we describe the prevalence of vitamin D deficiency in schizophrenia, report the research examining the relationship between vitamin D levels and COVID-19 and discuss the associations between vitamin D deficiency and respiratory infection, including its immunomodulatory mechanism of action.

Background People with psychotic disorders have reduced life expectancy largely because of physical health problems, especially cardiovascular disease, that are complicated by the use of tobacco and cannabis. Objectives We set out to (1) chart lifestyle and substance use choices and the emergence of cardiometabolic risk from the earliest presentation with psychosis, (2) develop a pragmatic health promotion intervention integrated within the clinical teams to improve the lifestyle choices and health outcomes of people with psychosis and (3) evaluate the clinical effectiveness and cost-effectiveness of that health promotion intervention. Design We performed a longitudinal cohort study of people presenting with their first episode of psychosis in three mental health trusts and followed up participants for 1 year [work package 1, physical health and substance use measures in first episode of psychosis (PUMP)]. We used an iterative Delphi methodology to develop and refine a modular health promotion intervention, improving physical health and reducing substance use in psychosis (IMPaCT) therapy, which was to be delivered by the patient’s usual care co-ordinator and used motivational interviewing techniques and cognitive–behavioural therapy to improve health choices of people with psychosis (work package 2). We then conducted a multicentre, two-arm, parallel-cluster, randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of using the intervention with people with established psychosis (work package 3: IMPaCT randomised controlled trial) in five UK mental health trusts. The work took place between 2008 and 2014. Participants All people aged between 16 and 65 years within 6 months of their first presentation with a non-organic psychosis and who were proficient in English were eligible for inclusion in the PUMP study. Participants in the work package 2 training development were staff selected from a range of settings, working with psychosis. Participants in the phase 3 Delphi consensus and manual development comprised three expert groups of (1) therapists/researchers recruited from the local and national community, (2) clinicians and (3) service users, each of whom took part in two iterative review and feedback sessions. For work package 3, IMPaCT randomised controlled trial, care co-ordinators in participating community mental health teams who were permanently employed and had a minimum of four eligible patients (i.e. aged between 18 and 65 years with a diagnosis of a psychotic disorder) on their caseload were eligible to participate. In studies 1 and 3, patient participants were ineligible if they were pregnant or had a major illness that would have had an impact on their metabolic status or if they had a significant learning disability. All participants were included in the study only after giving written confirmed consent. Main outcome measures Cardiometabolic risk markers, including rates of obesity and central obesity, and levels of glycated haemoglobin (HbA1c) and lipids, were the main outcomes in work package 1 (PUMP), with descriptive data presented on substance use. Our primary outcome measure for the IMPaCT randomised controlled trial was the physical or mental health component Short Form questionnaire-36 items quality-of-life scores at 12 months. Results Obesity rates rose from 18% at first presentation with psychosis to 24% by 1 year, but cardiometabolic risk was not associated with baseline lifestyle and substance use choices. Patterns of increase in the levels of HbA1c over the year following first presentation showed variation by ethnic group. We recruited 104 care co-ordinators, of whom 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) were randomised to deliver treatment as usual, in keeping with our power calculations. Of these 406 participants with established psychosis, 318 (78%) and 301 (74%) participants, respectively, attended the 12- and 15-month follow-ups. We found no significant effect of IMPaCT therapy compared with treatment as usual on the physical or mental health component Short Form questionnaire-36 items scores at either time point in an intention-to-treat analysis [physical health score (‘d’) –0.17 at 12 months and –0.09 at 15 months; mental health score (‘d’) 0.03 at 12 months and –0.05 at 15 months] or on costs. Nor did we find an effect on other cardiovascular risk indicators, including diabetes, except in the case of high-density lipoprotein cholesterol, which showed a trend for greater benefit with IMPaCT therapy than with treatment as usual (treatment effect 0.085, 95% confidence interval 0.007 to 0.16; p = 0.034). Limitations Follow-up in work package 1 was challenging, with 127 out of 293 participants attending; however, there was no difference in cardiometabolic measures or demographic factors at baseline between those who attended for follow-up and those who did not. In work package 3, the IMPaCT randomised controlled trial, care co-ordinators struggled to provide additional time to their patients that was devoted to the health promotion intervention on top of their usual clinical care contact with them. Conclusions Cardiometabolic risk is prominent even soon after first presentation with psychosis and increases over time. Lifestyle choices and substance use habits at first presentation do not predict those who will be most cardiometabolically compromised 1 year later. Training and supervising care co-ordinators to deliver a health promotion intervention to their own patients on top of routine care is not effective in the NHS for improving quality of life or reducing cardiometabolic risk. Future work Further work is needed to develop and evaluate effective, cost-effective and affordable ways of preventing the emergence of and reversing existing cardiometabolic risk indicators in people with psychosis. Trial registration Current Controlled Trials ISRCTN58667926. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 1. See the NIHR Journals Library website for further project information.

Background: Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always suitable, with a proportion of individuals intolerant of side effects or unable to engage in necessary blood monitoring. Given the profound impact TRS can have on those affected, alternative pharmacological approaches to care are needed. Objectives: To review the literature on the efficacy and tolerability of high-dose olanzapine (>20 mg daily) in adults with TRS. Design: This is a systematic review. Data Sources and Methods: We searched for eligible trials published prior to April 2022 in PubMed/MEDLINE, Scopus and Google Scholar. Ten studies met the inclusion criteria [five randomised controlled trials (RCTs), one randomised crossover trial and four open label studies]. Data were extracted for predefined primary outcomes (efficacy, tolerability). Results: Compared with standard treatment, high-dose olanzapine was non-inferior in four RCTs, three of which used clozapine as the comparator. Clozapine was superior to high-dose olanzapine in a double-blind crossover trial. Open-label studies demonstrated tentative evidence in support of high-dose olanzapine use. It was better tolerated than clozapine and chlorpromazine in two respective RCTs, and was generally well tolerated in open-label studies. Conclusion: This evidence suggests high-dose olanzapine is superior for TRS when compared with other commonly used first- and second-generation antipsychotics, including haloperidol and risperidone. In comparison with clozapine, the data are encouraging for the use of high-dose olanzapine where clozapine use is problematic, but larger, better designed trials are needed to assess the comparative efficacy of both treatments. There is insufficient evidence to consider high-dose olanzapine equivalent to clozapine when clozapine is not contraindicated. Overall, high-dose olanzapine was well tolerated, with no serious side effects. Registration: This systematic review was preregistered with PROSPERO [CRD42022312817].

ImportanceLess than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the world.ObjectiveTo compare demographic and clinical profiles of cohorts of cases and rates of untreated psychoses (proxy for incidence) across and within 3 economically and socially diverse settings in the Global South. Two hypotheses were tested: (1) demographic and clinical profiles of cases with an untreated psychotic disorder vary across setting and (2) rates of untreated psychotic disorders vary across and within setting by clinical and demographic group.Design, Setting, and ParticipantsThe International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II) comprises incidence, case-control, and cohort studies of untreated psychoses in catchment areas in 3 countries in the Global South: Kancheepuram District, India; Ibadan, Nigeria; and northern Trinidad. Participants were individuals with an untreated psychotic disorder. This incidence study was conducted from May 1, 2018, to July 31, 2020. In each setting, comprehensive systems were implemented to identify and assess all individuals with an untreated psychosis during a 2-year period. Data were analyzed from January 1 to May 1, 2022.Main Outcomes and MeasuresThe presence of an untreated psychotic disorder, assessed using the Schedules for Clinical Assessment in Neuropsychiatry, which incorporate the Present State Examination.ResultsIdentified were a total of 1038 cases, including 64 through leakage studies (Kancheepuram: 268; median [IQR] age, 42 [33-50] years; 154 women [57.5%]; 114 men [42.5%]; Ibadan: 196; median [IQR] age, 34 [26-41] years; 93 women [47.4%]; 103 men [52.6%]; Trinidad: 574; median [IQR] age, 30 [23-40] years; 235 women [40.9%]; 339 men [59.1%]). Marked variations were found across and within settings in the sex, age, and clinical profiles of cases (eg, lower percentage of men, older age at onset, longer duration of psychosis, and lower percentage of affective psychosis in Kancheepuram compared with Ibadan and Trinidad) and in rates of untreated psychosis. Age- and sex-standardized rates of untreated psychoses were approximately 3 times higher in Trinidad (59.1/100 000 person-years; 95% CI, 54.2-64.0) compared with Kancheepuram (20.7/100 000 person-years; 95% CI, 18.2-23.2) and Ibadan (14.4/100 000 person-years; 95% CI, 12.3-16.5). In Trinidad, rates were approximately 2 times higher in the African Trinidadian population (85.4/100 000 person-years; 95% CI, 76.0-94.9) compared with the Indian Trinidadian (43.9/100 000 person-years; 95% CI, 35.7-52.2) and mixed populations (50.7/100 000 person-years; 95% CI, 42.0-59.5).Conclusions and RelevanceThis analysis adds to research that suggests that core aspects of psychosis vary by historic, economic, and social context, with far-reaching implications for understanding and treatment of psychoses globally.

Background Severe mental illnesses (SMI), including schizophrenia spectrum disorder, bipolar disorder and major depressive disorder, are associated with physical health comorbidities and premature mortality. Physical activity and structured exercise have a beneficial impact on cardiometabolic risk and ameliorate mental health symptomology and cognition. This protocol describes a feasibility study for a high-intensity interval training (HIIT) intervention among inpatients with SMI, to improve their physical and mental health. Methods The feasibility study follows a two-part design owing to COVID-19-related adaptations to project design: (a) a non-blinded randomised controlled trial (RCT) of 12 weeks of bicycle-based HIIT, delivered twice weekly in a face-to-face, one-to-one setting, compared to treatment as usual (TAU) and (b) a naturalistic study of inpatient HIIT; eligible participants will be invited to two sessions of HIIT per week, delivered by the research team remotely or in person. Additionally, participants in the naturalistic study may use the bike to conduct self-directed sessions of their chosen length and intensity. We will measure the feasibility and acceptability of the HIIT intervention as primary outcomes, alongside secondary and tertiary outcomes evaluating the physical, mental and cognitive effects of HIIT. The study aims to recruit 40 patients to the RCT and 6–8 patients to the naturalistic design. Discussion Exercise is a modifiable lifestyle barrier that can reverse cardiometabolic disease risk. If HIIT is found to be feasible and acceptable in inpatients with SMI, there would be scope for large-scale work to evaluate the clinical, cost and implementation effectiveness of HIIT in inpatient mental health settings. Trial registration ClinicalTrials.gov NCT03959735. Registered June 22, 2019.

INTRODUCTION: People with severe mental illness (SMI) are at increased risk of osteoporosis but minimal information is available on their treatment and referral. We investigated differences in these outcomes between patients with/without SMI in linked primary and specialist care data. METHODS: People with SMI aged 18+ at diagnosis with both primary and mental healthcare records between 1st May 2009 and 31st May 2019 from a south London catchment were matched 1:4 to randomly selected controls on gender, age and duration of primary care follow-up. Outcomes included prescription of osteoporosis medications and referrals for osteoporosis, analysed using multivariable logistic regression analyses. RESULTS: The study included 2269 people with SMI and 9069 matched non-SMI controls. People with SMI were more likely to have a recorded prescription of osteoporosis medications (odds ratio [OR] = 3.54, 95% confidence interval [CI] 2.87, 4.35) and be referred for osteoporosis (OR = 1.51, 95% CI 1.09, 2.08) within 2 years after the date of first SMI diagnosis after adjusting for ethnicity, deprivation and Charlson Comorbidity Index. Factors including older age (osteoporosis medications: OR = 1.04, 95% CI 1.03, 1.05; osteoporosis referral: OR = 1.05, 95% CI 1.04, 1.07) and being prescribed with Class A analgesics (osteoporosis medications: OR = 1.91, 95% CI 1.31, 2.77; osteoporosis referral: OR = 1.77, 95% CI 1.02, 3.07) are significant predictors for osteoporosis management pathways within SMI patients. CONCLUSION: People with SMI are more frequently prescribed medications for osteoporosis and referred to osteoporosis screening than the general population. Given the many risk factors for osteoporosis in this group, this increased rate of referrals may well be warranted, and there is need to pay more attention to this at-risk group. Screening studies are needed to determine whether the rate of referral is proportional to the need. ispartof: JOURNAL OF PSYCHIATRIC RESEARCH vol:147 pages:94-102 ispartof: location:England status: published

BackgroundEarly in 2020, mental health services had to rapidly shift from face-to-face models of care to delivering the majority of treatments remotely (by video or phone call or occasionally messaging) due to the COVID-19 pandemic. This resulted in several challenges for staff and patients, but also in benefits such as convenience or increased access for people with impaired mobility or in rural areas. There is a need to understand the extent and impacts of telemental health implementation, and barriers and facilitators to its effective and acceptable use. This is relevant both to future emergency adoption of telemental health, and to debates on its future use in routine mental health care.ObjectiveTo investigate the adoption and impacts of telemental health approaches during the COVID-19 Pandemic, and facilitators and barriers to optimal implementation.MethodsFour databases (PubMed, PsycINFO, CINAHL and Web of Science) were searched for primary research relating to remote working, mental health care, and the COVID-19 pandemic. Preprint servers were also searched. Results of studies were synthesised using framework synthesis.ResultsA total of 77 papers met our inclusion criteria. In most studies, the majority of contacts could be transferred to a remote form during the pandemic, and good acceptability to service users and clinicians tended to be reported, at least where the alternative to remote contacts was interrupting care. However, a range of impediments to dealing optimal care by this means were also identified.ConclusionsImplementation of telemental health allowed some continuing support to the majority of service users during the COVID-19 pandemic and has value in an emergency situation. However, not all service users can be reached by this means, and better evidence is now needed on long-term impacts on therapeutic relationships and quality of care, and on impacts on groups at risk of digital exclusion and how to mitigate these.

BACKGROUND Early in 2020, mental health services had to rapidly shift from face-to-face models of care to delivering the majority of treatments remotely (by video or phone call or occasionally messaging) due to the COVID-19 pandemic. This resulted in several challenges for staff and patients, but also in benefits such as convenience or increased access for people with impaired mobility or in rural areas. There is a need to understand the extent and impacts of telemental health implementation, and barriers and facilitators to its effective and acceptable use. This is relevant both to future emergency adoption of telemental health and to debates on its future use in routine mental health care. OBJECTIVE To investigate the adoption and impacts of telemental health approaches during the COVID-19 pandemic, and facilitators and barriers to optimal implementation. METHODS Four databases (PubMed, PsycINFO, CINAHL, and Web of Science) were searched for primary research relating to remote working, mental health care, and the COVID-19 pandemic. Preprint servers were also searched. Results of studies were synthesized using framework synthesis. RESULTS A total of 77 papers met our inclusion criteria. In most studies, the majority of contacts could be transferred to a remote form during the pandemic, and good acceptability to service users and clinicians tended to be reported, at least where the alternative to remote contacts was interrupting care. However, a range of impediments to dealing optimal care by this means were also identified. CONCLUSIONS Implementation of telemental health allowed some continuing support to the majority of service users during the COVID-19 pandemic and has value in an emergency situation. However, not all service users can be reached by this means, and better evidence is now needed on long-term impacts on therapeutic relationships and quality of care, and on impacts on groups at risk of digital exclusion and how to mitigate these. CLINICALTRIAL PROSPERO International prospective register of systematic reviews CRD42021211025; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021211025

BACKGROUND: There is a paucity of longitudinal research investigating vitamin D in people with early psychosis.METHOD: Vitamin D levels were measured in 168 patients (64% (n = 108) male, mean age 29.3 (9.8) years) with first episode psychosis (FEP), along with measures of clinical state at baseline and at 12 months follow up. We assessed the a) cross sectional, and; b) longitudinal relationships between continuous and categorical 25-hydroxyvitamin D (25(OH)D) levels and clinical symptoms at first contact for psychosis and at 12 months.RESULTS: In FEP, 80% (n = 134) at baseline, and 76% at 12 months follow up, had suboptimal vitamin D levels (CONCLUSION: We identified a prospective association between higher baseline serum Vitamin D levels and lower total psychotic symptoms and negative symptoms of psychosis at 12 months after first contact for psychosis. The results of this study require replication in larger prospective studies, and highlight the need for large randomised trials to assess the effect of vitamin D supplementation on symptoms of psychosis in FEP.

BackgroundMinocycline has neurological anti-inflammatory properties and has been hypothesised to have antipsychotic effects.AimThe aim of this study was to investigate, using routinely collected United Kingdom primary health care data, whether adolescent men and women are more or less likely to receive an urgent psychiatric referral during treatment for acne with minocycline compared with periods of non-treatment.MethodA self-controlled case series using United Kingdom Clinical Practice Research Datalink to calculate the incidence rate ratio of urgent psychiatric referrals for individuals, comparing periods during which minocycline was prescribed with unexposed periods, adjusted for age.ResultsWe found 167 individuals who were at the time exposed to minocycline for a mean of 99 days and who received an urgent psychiatric referral. There was no difference in psychiatric referral risk during periods of exposure compared with periods of non-exposure: incidence rate ratio first 6 weeks of exposure 1.96, 95% confidence interval 0.82–4.71, p=0.132; incidence rate ratio remaining exposure period=1.97, 95% confidence interval 0.86–4.47, p=0.107.ConclusionsWe found no evidence in support of a protective effect of minocycline against severe psychiatric symptoms in adolescence.

BACKGROUND: Metabolic abnormalities and peripheral inflammation have been increasingly reported in patients at the onset of psychosis and associated with important physical health disorders and increased mortality. However, the impact of an abnormal metabolic-inflammatory status on the psychiatric outcome of these patients has not yet been investigated.OBJECTIVES: The aims of this study were 1) to explore whether, in a sample of patients at their first episode of psychosis (FEP), an overall metabolic-inflammatory status may be measured, by combining metabolic and inflammatory variables in metabolic-inflammatory factors; 2) to explore the association between these factors and clinical outcome at 1-year follow-up (FU), in terms of symptoms severity and treatment response.METHODS: In this longitudinal study we recruited 42 FEP patients and 46 healthy controls (HC) matched with patients for age, gender and ethnicity. At baseline (T1) we measured high sensitivity C-reactive protein (hsCRP) as biomarker of inflammation, and body mass index (BMI), lipid profile and gluco-metabolic parameters (glycated hemoglobin (HbA1c) and fasting glucose) as metabolic variables. A principal component analysis (PCA) was then used to reduce the dimensionality of the dataset accounting for both inflammation and metabolic status. In FEP patients, we assessed symptoms severity at T1 and at 1-year FU (T2) as well as treatment response to antipsychotics at T2.RESULTS: at T1, FEP showed higher HbA1c (p = 0.034), triglycerides (TG) (p = 0.045) and BMI (p = 0.026) than HC. PCA identified 3 factors: factor 1 accounting for hsCRP, TG and BMI, factor 2 accounting for LDL and cholesterol, and factor 3 accounting for fasting glucose and HbA1c. Factor 1 was associated with T1 negative symptoms severity (p = 0.021) and predicted T2 positive (p = 0.004) and overall symptoms severity (0.001), as well as general psychopathology (p CONCLUSION: In this sample of FEP patients, inflammation and metabolism, closely correlated at the onset of psychosis, proved to play a key role as predictors of the clinical course of psychosis when combined in a single factor. These findings offer an important potential target for early screening and interventions.

AimsPatients with mental health disorders are known to have worse physical health outcomes. ‘Consultant Connect’ (CC) is an app-based communication platform which aims to improve patient outcomes and experience, by offering clinicians direct access to consultants working in a partnership acute Trust, so they can seek advice and guidance for their patients’ physical health problems. This creates whole system efficiencies by avoiding unnecessary referrals to an Emergency Department or outpatient clinics. This poster describes the implementation of CC in a large UK Mental Health Trust. Initially designed for GPs, this is the first time a UK Mental Health Trust has used CC.MethodsConsultant Connect was launched in the Mental Health Trust's inpatient services in June 2020 as part of a Trust-wide programme of work aiming to improve the physical healthcare of mental health patients. In July 2021 it was rolled out across all services, including all community services. All platform activity was monitored and the implementation team collected data to determine: a) origin of call, b) which specialty was required, c) numbers of calls successfully connected, and in a subset of calls d) outcome of call. In addition, 183 call recordings were analysed, to identify clinical training needs and inform further development of the platform.ResultsIn the period June 2020 – December 2021, there were 1422 use episodes of the CC platform by Mental Health Trust clinicians. There were 401 Trust registered downloads of the CC App by the Trust clinicians. 53 different clinical specialties were contacted, with cardiology (414 calls), diabetes and endocrinology (243 calls), and haematology (124 calls) the most frequently called. 68% of queries received a response. 48% of calls had an outcome recorded, with 70% of these resulting in the physical healthcare being delivered by the mental health team, following the advice received (i.e. referral or admission avoided, or the patient treated out of hospital).ConclusionCC is being progressively embedded into clinical practice and has become a well-used pathway for mental health clinicians seeking immediate clinical advice from acute hospital Consultant colleagues. Further qualitative and quantitative work is planned with mental health clinicians, patients and carers to better understand their experience and determine if it improves care from both the clinicians’ and patients’ perspective.

Background Patients with psychotic disorders show higher rates of the metabolic syndrome (MS) between the cluster of severe mental illnesses. Depressive symptoms can worsen outcomes of individuals with psychotic disorders. However, research on the association between MS and depression in psychotic disorders and their relevance to outcomes is lacking. Methods We investigated the association between depression and cardiometabolic biomarkers in psychotic disorders and the predictive value of depressive symptoms on psychopathological severity and quality of life (QoL). 406 patients with psychotic disorders were recruited as part of the Improving Physical Health and Reducing Substance Use in Severe Mental Illness randomised controlled trial. Depression, psychotic symptoms, QoL, waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure, and fasting glucose of patients were assessed at baseline and 12 months. Sensitivity analyses were conducted to test the effect of treatment. Results More severe baseline symptoms of depression significantly predicted worse 12-month psychotic symptoms and lower mental health related QoL at 12 months. These associations held after controlling for alcohol use, gender, ethnicity, education, and mental health related QoL Baseline. Depressive symptoms also correlated with waist circumference at both baseline and 12 months, after controlling for multiple testing. Conclusion Individuals with psychotic disorders experiencing more severe depressive symptoms are more likely to have larger waist circumference contemporaneously and 12 months later, as well as more severe psychotic symptoms and worse QoL at follow-up. This highlights the need for evaluation of strategies to address depression in the management of psychotic disorders.

Background: Severe mental illnesses (SMI), including schizophrenia spectrum disorder, bipolar disorder and major depressive disorder are associated with physical health comorbidities and premature mortality. Physical activity and structured exercise have a beneficial impact on cardiometabolic risk and ameliorate mental health symptomology and cognition. This protocol describes a feasibility study for a high intensity interval training (HIIT) intervention amongst inpatients with SMI, to improve their physical and mental health. Methods: The feasibility study follows a two-part design owing to Covid-19 related adaptations to project design: a) A non-blinded randomized controlled trial (RCT) of 12 weeks of bicycle-based HIIT, delivered twice weekly in a face-to-face, one-to-one setting, compared to treatment as usual (TAU). b) A naturalistic study of inpatient HIIT; eligible participants will be invited to two sessions of HIIT per week, delivered by the research team remotely or in person. Additionally, participants may use the bike to conduct self-directed sessions of their chosen length and intensity. We will measure feasibility and acceptability of the HIIT intervention as primary outcomes, alongside secondary and tertiary outcomes evaluating the physical, mental and cognitive effects of HIIT. The study aims to recruit 40 patients to the RCT and 6-8 patients to the naturalistic design. Discussion: Exercise is a modifiable lifestyle barrier that can reverse cardiometabolic disease risk. If HIIT is found to be feasible and acceptable in inpatients with SMI there would be scope for large scale work to evaluate the clinical, cost and implementation effectiveness of HIIT in inpatient mental health settings. Trial registration: ClinicalTrials.gov, registration no: NCT03959735, registered 22/05/2019, https://clinicaltrials.gov/ct2/show/NCT03959735

BACKGROUND Telemental health care has been rapidly adopted for maintaining services during the COVID-19 pandemic, and a substantial interest is now being devoted in its future role. Service planning and policy making for recovery from the pandemic and beyond should draw on both COVID-19 experiences and the substantial research evidence accumulated before this pandemic. OBJECTIVE We aim to conduct an umbrella review of systematic reviews available on the literature and evidence-based guidance on telemental health, including both qualitative and quantitative literature. METHODS Three databases were searched between January 2010 and August 2020 for systematic reviews meeting the predefined criteria. The retrieved reviews were independently screened, and those meeting the inclusion criteria were synthesized and assessed for risk of bias. Narrative synthesis was used to report these findings. RESULTS In total, 19 systematic reviews met the inclusion criteria. A total of 15 reviews examined clinical effectiveness, 8 reported on the aspects of telemental health implementation, 10 reported on acceptability to service users and clinicians, 2 reported on cost-effectiveness, and 1 reported on guidance. Most reviews were assessed to be of low quality. The findings suggested that video-based communication could be as effective and acceptable as face-to-face formats, at least in the short term. Evidence on the extent of digital exclusion and how it can be overcome and that on some significant contexts, such as children and young people’s services and inpatient settings, was found to be lacking. CONCLUSIONS This umbrella review suggests that telemental health has the potential to be an effective and acceptable form of service delivery. However, we found limited evidence on the impact of its large-scale implementation across catchment areas. Combining previous evidence and COVID-19 experiences may allow realistic planning for the future implementation of telemental health. CLINICALTRIAL

ObjectivesFatigue is a pervasive clinical symptom for many infected with respiratory viruses such as influenza or coronaviruses. Prior evidence from influenza and coronavirus epidemics suggest that fatigue symptomology may continue beyond the acute phase, lasting for several months to several years post-discharge. This systematic review aimed to examine long-term fatigue prevalence among survivors and among communities, as well as investigate the current evidence for associated factors.DesignSystematic review and meta-analysis.SettingHospitalised and community samples.ParticipantsPatient populations with a confirmed diagnosis of a named influenza virus or coronavirus.Main outcomes measuredFatigue, fatigue syndromesResultsTen studies met the inclusion criteria for a pooled prevalence analysis and five studies were identified as eligible for a means differences analysis. A fatigue prevalence of 41% (95% CI 0.299-0.488) was found among a total population of 1,310. Using the ‘vitality’ subscale of the SF-36 as a proxy for fatigue, the estimate for means differences indicated a lower mean vitality score for survivors compared to population norms (M -1.523, CI -13.53 – 10.48), although this was not significant (p = 0.803). The most common associations with fatigue were PTSD, depression and anxiety, female gender and higher age.ConclusionsThis study reveals that a significant proportion of survivors (41%) experienced fatigue following their recovery from novel respiratory viruses such as SARS, MERS, SARS-CoV2 or influenza and that this fatigue can be long-lasting. Also, some factors such as female gender and psychological factors may contribute to continuing fatigue outcomes for this population.Strengths and limitations(a) this study provides support for long-term fatigue outcomes in people with a confirmed influenza, SARS, MERS, SARS-CoV2 virus infection (b) the study suggests individual, psychological and social factors are associated with fatigue, (c) findings are limited by the availability of fatigue data and lack of pre-morbid fatigue information; (d) a meta-analysis on the associations was prohibited by the small number of studies investigating long-term fatigue correlates and (e) the heterogeneity of the studies (>75%) suggests the pooled estimates should be interpreted with caution.

BackgroundTele-mental health care has been rapidly adopted to maintain services during the pandemic, and there is now substantial interest in its future role. Service planning and policy making for recovery from the pandemic and beyond should draw not only on COVID-19 experiences, but also on the substantial research evidence accumulated prior to this.Aimsto conduct an umbrella review of systematic reviews of research literature and evidence-based guidance on remote working in mental health, including both qualitative and quantitative literature.MethodThree databases were searched between January 2010 and August 2020 for systematic reviews meeting pre-defined criteria. Reviews retrieved were independently screened and those meeting inclusion criteria were synthesised and assessed for risk of bias. Narrative synthesis was used to report findingsResultsNineteen systematic reviews met inclusion criteria. Fifteen examined clinical effectiveness, eight reported on aspects of tele-mental health implementation, ten reported on acceptability to service users and clinicians, two on cost-effectiveness and one on guidance. Most reviews were assessed as low quality. Findings suggested that video-based communication could be as effective and acceptable as face-face formats, at least in the short-term. Evidence was lacking on extent of digital exclusion and how it can be overcome, or on significant context such as children and young people and inpatient settings.ConclusionsThis umbrella review suggests that tele-mental health has potential to be an effective and acceptable form of service delivery. However, we found limited evidence on impacts of large-scale implementation across catchment areas. Combining previous evidence and COVID-19 experiences may allow realistic planning for future tele-mental health implementation.

BackgroundA possible role of vitamin D in the pathophysiology of depression is currently speculative, with more rigorous research needed to assess this association in large adult populations. The current study assesses prospective associations between vitamin D status and depression in middle-aged adults enrolled in the UK Biobank.MethodsWe assessed prospective associations between vitamin D status at the baseline assessment (2006–2010) and depression measured at the follow-up assessment (2016) in 139 128 adults registered with the UK Biobank.ResultsAmongst participants with no depression at baseline (n = 127 244), logistic regression revealed that those with vitamin D insufficiency [adjusted odds ratio (aOR) = 1.14, 95% confidence interval (CI) = 1.07–1.22] and those with vitamin D deficiency (aOR = 1.24, 95% CI 1.13–1.36) were more likely to develop new-onset depression at follow-up compared with those with optimal vitamin D levels after adjustment for a wide range of relevant covariates. Similar prospective associations were reported for those with depression at baseline (n = 11 884) (insufficiency: aOR = 1.11, 95% CI 1.00–1.23; deficiency: aOR = 1.30, 95% CI 1.13–1.50).ConclusionsThe prospective associations found between vitamin D status and depression suggest that both vitamin D deficiency and insufficiency might be risk factors for the development of new-onset depression in middle-aged adults. Moreover, vitamin D deficiency (and to a lesser extent insufficiency) might be a predictor of sustained depressive symptoms in those who are already depressed. Vitamin D deficiency and insufficiency is very common, meaning that these findings have significant implications for public health.

Background People with serious mental illnesses (SMI) such as schizophrenia often also have physical health illnesses and interventions are needed to address the resultant multimorbidity and reduced life expectancy. Research has shown that volunteers can support people with SMI. This protocol describes a feasibility randomised controlled trial (RCT) of a novel intervention involving volunteer ‘Health Champions’ supporting people with SMI to manage and improve their physical health. Methods This is a feasibility hybrid II randomised effectiveness-implementation controlled trial. The intervention involves training volunteers to be ‘Health Champions’ to support individual people with SMI using mental health services. This face-to-face or remote support will take place weekly and last for up to 9 months following initial introduction. This study will recruit 120 participants to compare Health Champions to treatment as usual for people with SMI using secondary community mental health services in South London, UK. We will measure the clinical and cost effectiveness including quality of life. We will measure the implementation outcomes of acceptability, feasibility, appropriateness, fidelity, barriers and enablers, unintended consequences, adoption and sustainability. Discussion There is a need for interventions to support people with SMI with their physical health. If this feasibility trial is successful, a definitive trial will follow to fully evaluate the clinical, cost and implementation effectiveness of Health Champions supporting people with SMI. Trial registration ClinicalTrials.gov, registration no: NCT04124744.

BackgroundClozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.AimsThis was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.MethodSuccessful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.ResultsAmong 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.ConclusionsIntramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

Objectives: The aim of the study was to explore acute care utilisation towards end of life by and the place of death for patients with serious mental disorders and to demonstrate any inequalities in end-of-life care faced by this patient group. Study design: This is a retrospective cohort study using linked, routinely collected data. Methods: This study used linked data extracted from mental health records, Hospital Episode Statistics and mortality data. Adult cases (≥18 years old) were included if they had a serious mental disorder and died between 2007 and 2015. Multiple imputation was used to manage missing data, and generalised linear models were used to assess multiple adjusted associations between sociodemographic and clinical explanatory variables and acute service use at the end of life and in-hospital deaths. Results: A cohort of 1350 adults was analysed. More than half visited the accident and emergency (A&E) department in the last 90 days of life, and a third had a burdensome transition (multiple hospital admissions in the last 90 days of life or at least one in the last three days); the median number of days spent in the hospital was 4 (range: 0–86). Having more comorbidities was a strong correlate of more A&E visits (adjusted odds ratio [OR] = 1.03 [95% confidence interval = 1.02–1.04]), burdensome transitions (adjusted OR = 1.06 [1.04–1.08]) and days spent in the hospital (adjusted OR = 1.04 [1.03–1.05]). Having a diagnosis of schizophrenia spectrum disorder, compared with other serious mental disorder diagnoses, was associated with fewer A&E visits (adjusted OR = 0.78 [0.71–0.88]) and fewer days in the hospital (adjusted OR = 0.77 [0.66–0.89]). Younger age was associated with more A&E visits (adjusted OR = 1.28 [1.07–1.53]) and fewer days spent in the hospital (adjusted OR = 0.70 [0.52–0.95]). Hospital deaths were high (51%), and in a fully adjusted model, they were associated with having more comorbidities (adjusted OR = 1.02 [1.01–1.03]) and accessing acute care at the end of life (including more A&E visits; adjusted OR = 1.07 [1.05–1.10]), burdensome transitions (adjusted OR = 1.53 [1.37–1.71]) and days spent in the hospital (adjusted OR = 2.05 [1.70–247]). Conclusion: People with comorbidities are more likely to use more burdensome acute health care at the end of life and are more likely to die in the hospital. Hospital deaths could be reduced, and end-of-life care could be improved by targeting patients with comorbidities and who are accessing more acute healthcare services.

BackgroundAntipsychotic drug-induced weight gain puts individuals with schizophrenia at increased cardiometabolic risk. As a potential intervention for this problem, we describe the theoretical background and a protocol for a feasibility randomised controlled trial (RCT) of approach bias modification (ABM) training combined with real versus sham (placebo) transcranial direct current stimulation (tDCS). The primary aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of ABM and tDCS in this group of participants. Second, the study will assess the preliminary efficacy of ABM + tDCS in reducing food cravings in people who take antipsychotic medication.MethodsThirty adults with a DSM-V diagnosis of schizophrenia or schizoaffective disorder treated with anti-psychotic medication will be randomly allocated to receive five sessions that will combine ABM and real or sham tDCS, in a parallel group design. In this feasibility study, a broad range of outcome variables will be examined. Measures will include food craving, psychopathology (e.g. symptoms of schizophrenia and depression), neuropsychological processes (such as attentional bias and impulsiveness), and the tolerability and acceptability of tDCS. The feasibility of conducting a large-scale RCT of ABM + tDCS and appropriateness of tDCS as a treatment for antipsychotic drug-induced weight gain will be evaluated by assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up).DiscussionThe effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. In addition, results from this study will provide a preliminary indication of the efficacy of ABM + tDCS treatment for antipsychotic drug-induced weight gain.Trial registrationISRCTN Registry,ISRCTN13280178. Registered on 16 October 2018.

Background Antipsychotic drug induced weight gain puts individuals with schizophrenia at increased cardiometabolic risk. As a potential intervention for this problem we describe the theoretical background and a protocol for a feasibility randomised controlled trial (RCT) of approach bias modification training (ABM) combined with real versus sham (placebo) transcranial direct current stimulation (tDCS). The primary aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of ABM and tDCS in this group of participants. Secondly, the study will assess the preliminary efficacy of [ABM + tDCS] in reducing food cravings in people who take antipsychotic medication. Methods Thirty adults with a DSM-V diagnosis of schizophrenia or schizoaffective disorder treated with anti-psychotic medication will be randomly allocated to receive 5 sessions that will combine ABM and real or sham tDCS, in a parallel group design. In this feasibility study a broad range of outcome variables will be examined. Measures will include food craving, psychopathology (e.g. symptoms of schizophrenia and depression), neuropsychological processes (such as attentional bias, and impulsiveness) and the tolerability and acceptability of tDCS. The feasibility of conducting a large-scale RCT of [ABM + tDCS] and appropriateness of tDCS as a treatment for antipsychotic drug induced weight gain will be evaluated by assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up). Discussion The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. In addition, results from this study will provide a preliminary indication of the efficacy of [ABM + tDCS] treatment for antipsychotic drug induced weight gain.

Low levels of vitamin D are prevalent among patients with schizophrenia and have been linked to the risk and outcome of the disorder. Vitamin D has a regulatory effect on the inflammatory system, which is dysfunctional in schizophrenia. We investigated the association between serum vitamin D levels, inflammatory status, and severity of schizophrenia symptoms. A total of 39 clozapine-treated schizophrenia patients were recruited to the study. Blood samples for biochemical analysis were collected from all participants. Serum levels of vitamin D and cytokines (IL-4, IL-6, IL-10, and TNF-α) were analyzed and the association between biochemical and clinical measures was assessed. Most of the sample (82%) had insufficient levels of vitamin D. There was a significant inverse correlation between serum vitamin D and IL-6 levels (Pearson's r = -0.38, P < 0.05). Vitamin D levels correlated with the severity of positive symptoms (r = 0.39, P < 0.05). These results suggest that within clozapine-treated schizophrenia patients, high levels of vitamin D are associated with lower serum levels of the proinflammatory cytokine IL-6. This relationship may indicate an immunomodulatory effect of vitamin D in treatment-resistant patients with schizophrenia maintained on clozapine.

As employment and relationship status are important long-term outcomes in individuals with a diagnosis of first episode psychosis (FEP) disorders, there is a need to elucidate more accurately the extent of these social deficits in people with FEP. This in turn can aid treatment planning and policy development ultimately ensuring more complete and sustainable recoveries. We carried out a systematic review and meta-analysis of longitudinal studies in FEP reporting on employment and relationship status during the illness course. Random effects meta-analyses and meta-regression analyses were employed. Seventy-four studies were included with a sample totalling 15,272 (range = 20-1724) FEP cases with an average follow-up duration of 8.3 years (SD = 7.2). 32.5% (95%CI = 28.5-36.9) of people with a diagnosis of FEP disorders were employed and 21.3% (95%CI = 16.5-27.1) were in a relationship at the end of follow-up. Studies from high-income countries and Europe had a higher proportion of people in employment at the end of follow-up compared to middle-income nations and non-European countries. The inverse was found for relationship status. The proportion of people with a diagnosis of FEP in employment decreased significantly with longer follow-up. Living with family, being in a relationship at first contact and Black and White ethnicities were identified as significant moderators of these outcomes. These findings highlight marked functional recovery deficits for people with FEP, although cultural factors need to be considered. They support the need for interventions to improve employment opportunities, and social functioning, both in early psychosis and during the longitudinal illness course.

High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a lack of clarity in the totality of the evidence whether HIIT is effective and safe across different populations and outcomes. The aim of this meta-review was to establish the benefits, safety and adherence of HIIT interventions across all populations from systematic reviews and meta-analyses. Major databases were searched for systematic reviews (with/without meta-analyses) of randomisednon-randomised trials that compared HIIT to a control. Thirty-three systematic reviews (including 25 meta-analyses) were retrieved encompassing healthy subjects and people with physical health complications. Evidence suggested HIIT improved cardiorespiratory fitness, anthropometric measures, blood glucose and glycaemic control, arterial compliance and vascular function, cardiac function, heart rate, some inflammatory markers, exercise capacity and muscle mass, versus non-active controls. Compared to active controls, HIIT improved cardiorespiratory fitness, some inflammatory markers and muscle structure. Improvements in anxiety and depression were seen compared to pre-training. Additionally, no acute injuries were reported, and mean adherence rates surpassed 80% in most systematic reviews. Thus, HIIT is associated with multiple benefits. Further large-scale high-quality studies are needed to reaffirm and expand these findings.

PURPOSE/BACKGROUND: Clozapine is the criterion standard in treatment-resistant schizophrenia. We sought to review data on several inflammatory effects associated with clozapine, specifically interstitial nephritis, hepatitis, and pancreatitis.METHODS/PROCEDURES: We conducted a systematic review to identify studies, published up until December 2017, describing clozapine-induced hepatitis, nephritis, and pancreatitis. The primary objective was to characterize the clinical characteristics associated with each of the specific inflammatory reactions to clozapine.FINDINGS/RESULTS: We identified 42 cases of inflammatory reactions associated with clozapine treatment- 20 :cases of clozapine-induced hepatitis, 11 cases of nephritis, and 11 of pancreatitis. The mean (SD) age was 38.8 (11.9) years. The mean (SD) dose of clozapine used was 252.4 (133.7) mg. Time to onset of pancreatitis (17.9 [11.2] days; range 4-35 days) was shorter than that for hepatitis (34.2 [20.1] days; range, 12-90 days) and nephritis (27.9 [27.0]; range, 8-90 days) but was not statistically significant (F = 2.267, P = 0.117). The mean (SD) time to recovery was shorter for cases of pancreatitis (15.7 [18.4] days) compared with cases of hepatitis (25.9 [16.5] days) and nephritis (24.5 [18.9] days). Three cases with hepatitis died. Seven of the cases had a clozapine rechallenge (hepatitis [n = 3], nephritis [n = 1], pancreatitis [n = 3]), with 5 having a recurrence at a mean (SD) onset of 3.5 (2.5) days (range, 1-7 days); 2 hepatitis cases were successfully rechallenged.IMPLICATIONS/CONCLUSIONS: Clozapine-induced hepatitis, nephritis, and pancreatitis are uncommon adverse events, reflected in the paucity of case studies in the literature. Early recognition of the signs and symptoms of clozapine-associated hepatitis, nephritis, and pancreatitis is important, as when identified, clozapine should be urgently discontinued. Clozapine is associated with evidence of benign inflammatory processes; the extent to which hepatitis, and other inflammatory reactions, may be on a continuum with these more benign and self-limiting reactions is unclear, and this can only be resolved by prospectively following cohorts of clozapine-treated patients.