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Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research.

Background: Growing evidence suggests that community-based interventions may be effective for anxiety and depression. This study aimed to describe studies of community interventions delivered to adults and/or young people, either in person or online, evaluated in randomised controlled trials and provide an indication as to their effectiveness, acceptability, quality of data and where possible, mechanisms of action. We included interventions delivered at and/or by museums, art galleries, libraries, gardens, music groups/choirs and sports clubs. Method: We developed and followed a preregistered protocol: PROSPERO CRD42020204471. Randomised controlled trials in adults and young people were identified in an extensive search with no date/time, language, document type and publication status limitations. Studies were selected according to predetermined eligibility criteria and data independently extracted and then assessed using Risk of Bias 1. The studies were deemed too heterogeneous for meta-analysis and were therefore reported using a narrative synthesis. Results: Our analysis included 31 studies, with 2898 participants. Community interventions most studied in randomised controlled trials were community music (12 studies, 1432 participants), community exercise (14 studies, 955 participants) and community gardens/gardening (6 studies, 335 participants). The majority of studies were from high-income countries – many were in specific populations (such as those with physical health problems) and were generally of low quality. Dropout rates across the included studies were low (1 participant on average per 100 participants). The inadequate description of interventions limited identification of potential mechanisms of action. Discussion: The uncertainty of the evidence allows only a weak recommendation in support of community interventions for anxiety and depression. The results suggest community engagement is a promising area for wide-reaching interventions to be implemented and evaluated, but more high-quality trials are needed, especially in young people and under-represented communities.

SummaryAn antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with ‘therapeutic’ (0.50–1.00) versus ‘subtherapeutic’ (0.05–0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69–0.97, P = 0.017) and among patients with ‘therapeutic’ lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67–0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Background: Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. Methods: For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. Findings: Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24–3·16) for intracranial haemorrhage, 6·92% (6·17–7·76) for ischaemic stroke, 0·26% (0·15–0·45) for parkinsonism, 1·74% (1·31–2·30) for dementia, 19·15% (17·90–20·48) for anxiety disorder, and 2·77% (2·31–3·33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40–1·47, for any diagnosis; 1·78, 1·68–1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14–1·17, for any diagnosis; 1·32, 1·27–1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50–1·67, for any diagnosis; 2·87, 2·45–3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events. Interpretation: Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings.

TCUC is a comprehensive real-time web-based programme for UC patients. It monitors multiple parameters via electronic questionnaires: symptoms, quality of life (QoL), and outcomes (eg hospitalisation). Medications are entered and personalised treatment guidance formulated. This information, graphically displayed on a traffic light system, is available to the patient and clinical team via the TCUC website (https://ouh.truecolours.nhs.uk/ibd/en/), and is housed on a secure National Health Service server. The objectives were to assess feasibility, usability and adherence of TCUC.

Conventional follow-up for UC places demands on health services. Demand might be better managed by targeting appointments to those patients who need therapeutic decisions. The aim was to develop a model that would predict the likelihood of escalation of therapy at an appointment.

Introduction. Gabapentin has been extensively prescribed off-label for psychiatric indications, with little established evidence of efficacy. Both gabapentin and pregabalin, a very similar drug with the same mechanism of action, bind to a subunit of voltage dependent calcium channels, which are implicated in the aetiopathogenesis of bipolar disorder, anxiety and insomnia. This systematic review and meta-analysis aims to collect and critically appraise all the available evidence about efficacy and tolerability of gabapentin and pregabalin in the treatment of bipolar disorder, insomnia and anxiety. Methods and analysis. We will include all randomized controlled trials reported as double-blind and comparing gabapentin or pregabalin with placebo or any other active pharmacological treatment (any preparation, dose, frequency, route of delivery or setting) in patients with bipolar disorder, anxiety or insomnia. For consideration of adverse effects (tolerability), single blind or open label RCTs and non-randomised evidence will also be summarised. The main outcomes will be efficacy (measured both as dichotomous and continuous outcome) and acceptability (proportion of patients who dropped out of the allocated treatment). Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random-effects meta-analysis to synthesize all evidence for each outcome. Heterogeneity between studies will be investigated by the I2 statistic. Data from included studies will be entered into a funnel plot for investigation of small-study effects. No subgroup analysis will be undertaken, but we will carry out sensitivity analyses about combination treatment, psychiatric comorbidity, use of rescue medications and fixed versus random-effects model.

BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of chronicity. Treatment resistance persists despite the use of established medications, such as lithium and valproate. New medications are required for the treatment of refractory cases. Some open-label reports have suggested that the anticonvulsant tiagabine may be efficacious in bipolar disorder. There is a need to clarify the evidence available, in the form of randomised controlled trials, for its use in the treatment of acute affective episodes in bipolar disorder OBJECTIVES: To review the evidence for the efficacy and acceptability of tiagabine in the treatment of acute mood episodes in bipolar disorder. SEARCH STRATEGY: The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of mood disorder were searched. Handsearches were done (specialist journals and conference proceedings). Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials, which compared tiagabine with placebo or with active agents in the treatment of any acute mood episodes in bipolar disorder, were selected. Studies of participants with bipolar disorder were to be included. Subjects could be of either sex and of all ages. DATA COLLECTION AND ANALYSIS: Data extraction and methodological quality assessment were performed independently by two reviewers. For analysis, relative risk was used for binary efficacy outcomes and the weighted mean difference or standardised mean differerence was used for continuously distributed outcomes MAIN RESULTS: We did not find any studies which fulfilled the Cochrane criteria of randomised controlled trials. However, one uncontrolled open label study and one case series were found. There were also three case reports/series of acute treatment which were continued into maintenance therapy, and one open non-randomised study with this design. The results of these studies are inconsistent. AUTHORS' CONCLUSIONS: We found no randomised controlled trials of tiagabine in bipolar disorder. In the reported cases, a significant proportion of patients suffered episodes of syncope or seizure. There is a need for randomised controlled trials examining the efficacy and acceptability of tiagabine in the acute treatment of bipolar disorder, after the nature of these episodes has been clarified.

OBJECTIVES: To examine the feasibility of collecting course of illness data from patients with bipolar I and II disorder, using weekly text-messaged mood ratings, and to examine the time trajectory of symptom ratings based on this method of self-report. METHODS: A total of 62 patients with bipolar I (n = 47) or II (n = 15) disorder provided mood data in response to weekly cell phone text messages (n = 54) or e-mail prompts (n = 8). Participants provided weekly ratings using the Altman Self-Rating Mania Scale and the Quick Inventory of Depressive Symptoms-Self Report. Patients with bipolar I and II disorder, and men and women, were compared on percentages of time in depressive or manic mood states over up to two years. RESULTS: Participants provided weekly ratings over an average of 36 (range 1-92) weeks. Compliance with the procedure was 75%. Overall, participants reported depressive symptoms 47.7% of the time compared to 7% of entries reflecting manic symptoms, 8.8% reflecting both depressive and manic symptoms, and 36.5% reflecting euthymic mood. Participants with bipolar I disorder reported more days of depression and were less likely to improve with time than participants with bipolar II disorder. Gender differences observed at the beginning of the study were not observed at follow-up. CONCLUSIONS: The results are similar to those of other longitudinal studies of bipolar disorder that use traditional retrospective, clinician-gathered mood data. Text-message-based symptom monitoring during routine follow-up may be a reliable alternative to in-person interviews.

The classification procedure of streaming data usually requires various ad hoc methods or particular heuristic models. We explore a novel non-parametric and systematic approach to analysis of heterogeneous sequential data. We demonstrate an application of this method to classification of the delays in responding to the prompts, from subjects with bipolar disorder collected during a clinical trial, using both synthetic and real examples. We show how this method can provide a natural and systematic way to extract characteristic features from sequential data., 16 pages, 7 figures

L-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of ”brain-selective” LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.