Central and North West London NHS Foundation Trust is an NHS Foundation Trust in England. It provides healthcare in London, Milton Keynes, Surrey and elsewhere. It was created in 2002 by a merger between Brent, Kensington & Chelsea and Westminster Mental Health NHS Trust, Harrow and Hillingdon Healthcare Trust, and the substance misuse service component of Hounslow and Spelthorne Community and Mental Health NHS Trust. It subsequently won additional contracts, including Milton Keynes Community Health Services from April 2013. It has substantial contracts for prison health services. CNWL is a member of Imperial College Health Partners.Professor Dorothy Griffiths was appointed as chair of the Trust in January 2014 following the retirement of Dame Ruth Runciman, who served the Trust for more than ten years.In 2017 the trust established a subsidiary company, Quality Trusted Solutions Ltd, to which 35 staff were transferred. The intention was to achieve pay bill savings, by recruiting new staff on less expensive non-NHS contracts.
Importance:The involvement of the serotonin system in the pathophysiology of schizophrenia has been proposed for over 60 years, but there has been no prior study to test if there is altered serotonin release in vivo in schizophrenia (to the authors' knowledge). Objective:To investigate serotonin release in vivo in schizophrenia and its association with negative symptoms. It was hypothesized a priori that frontal cortex serotonin release capacity would be lower in schizophrenia compared with healthy controls and that this would be associated with more severe baseline negative symptoms. Design, Setting, and Participants:This was a single-center case-control neuroimaging study conducted in London, UK. All participants had dynamic 90-minute [11C]Cimbi-36 positron emission tomography (PET) scans at baseline and 3 hours after oral administration of d-amphetamine 0.5mg/kg. Data were collected between 2015 and 2024. Participants included stable adult outpatients with DSM-5 schizophrenia (antipsychotic free or taking antipsychotics with negligible affinity for 5-hydroxytryptamine receptor 2A [5-HT2A] receptors) and healthy controls matched for age, sex, and body mass index. Main Outcomes and Measures:The primary neuroimaging outcome was the group difference in serotonin release capacity, prespecified as the percentage change in frontal cortex [11C]Cimbi-36 binding potential between the baseline and d-amphetamine scans. Results:A total of 54 individuals were included, 26 with DSM-5 schizophrenia (mean [SD] age, 33.3 [9.1] years, 16 male [62%]; 21 not taking antipsychotic medication [81%]) and 28 healthy controls (mean [SD] age, 32.0 [9.5] years, 19 male [68%]). Frontal cortex serotonin release was significantly greater in the group with schizophrenia compared with healthy controls (18.0%; 95% CI, 2.5%-33.6%; P = .02; Cohen d = 0.69). In schizophrenia, greater frontal cortex serotonin release was correlated with more severe baseline negative symptoms (Brief Negative Symptom Scale: Pearson r = 0.42; P = .04) and poorer functioning (Social Functioning Scale: Pearson r = -0.42; P = .04). Exploratory analyses showed significantly greater frontal cortex serotonin release in deficit schizophrenia, characterized by primary and enduring negative symptoms, compared with healthy controls (mean difference = 32.3%; FDR-corrected P value = 0.001; Cohen d = 1.10) and nondeficit schizophrenia (mean difference = 28.9%; FDR-corrected P value = 0.004; Cohen d = 0.89). These findings were all replicated in 21 individuals with schizophrenia not taking antipsychotic medication. Baseline cortical [11C]Cimbi-36 binding (indexing baseline cortical 5-HT2A receptor levels) was unaltered in schizophrenia. Conclusions and Relevance:This case-control study found that serotonergic dysfunction in the pathophysiology of schizophrenia was associated with negative symptoms, suggesting the regulation of serotonin release as a target to treat negative symptoms. Results of the exploratory analysis suggest particularly marked serotonergic dysfunction in the subgroup with deficit schizophrenia.
BACKGROUND:Long-term psychological treatments are recommended for people with personality disorder. Brief interventions are increasingly delivered but are of uncertain benefit. We aimed to investigate the effectiveness of a brief individual psychological intervention for people with probable personality disorder over a 12-month period. METHODS:The Structured Psychological Support (SPS) study was a multicentre, researcher-masked, randomised controlled superiority trial, conducted in seven mental health Trusts in England: Avon and Wiltshire Mental Health Partnership National Health Service (NHS) Trust, Central and North West London NHS Foundation Trust, Coventry and Warwickshire Partnership NHS Trust, Derbyshire Healthcare NHS Foundation Trust, Lincolnshire Partnership NHS Foundation Trust, Mersey Care NHS Foundation Trust, and Oxford Health NHS Foundation Trust. Participants were aged 18 years or older and had probable personality disorder identified by meeting a threshold of 4 or more on the Standardised Assessment of Personality Abbreviated Scale. We excluded those who: did not consent; had a co-existing psychotic disorder; or were already receiving psychological treatment. We assessed whether participants met criteria for borderline personality disorder using the Structured Clinical Interview for Axis II Personality Disorders and whether they had co-existing complex post-traumatic stress disorder using the International Trauma Questionnaire. We randomly assigned participants to up to ten sessions of SPS plus treatment-as-usual or enhanced treatment-as-usual (allocation ratio 1·15:1), using an independent remote system. Researchers assessing outcomes were masked to group allocation. SPS comprises up to ten individual sessions of personalised psychological support, which includes psychoeducation and psychological skills derived from evidence-based treatments (dialectical behaviour therapy and mentalisation-based treatment). Sessions were usually delivered on a fortnightly basis by staff with previous experience of working with people with personality disorder. The primary outcome was social functioning at 12 months measured using the Work and Social Adjustment Scale (WSAS). Data were analysed using multilevel mixed effects general linear regression on an intention-to-treat basis. We used multiple imputation to address missing outcomes. We undertook a parallel health economic evaluation, which included cost-effectiveness and cost-utility analyses. People with lived experience were involved in the design of the research and in the writing process. The trial was prospectively registered (ISRCTN13918289) and is now complete. FINDINGS:Between Feb 7, 2023, and Jan 31, 2024, 569 potential participants were referred for study inclusion, 34 were deemed ineligible, 56 declined to participate, and 127 were not approached. 352 potential participants provided consent, of whom 16 were deemed ineligible or withdrew. 336 participants were randomly assigned to either SPS (n=180) or treatment-as-usual (n=156). 251 (75%) participants were female, 75 (22%) were male, and ten (3%) were non-binary or other. The mean age was 34·8 years (SD 13·2; range 18-68) and 281 (84%) participants were White. 152 (84%) participants in the SPS group and 132 (85%) in the control group completed the 12-month follow-up. There was no difference between groups for the primary outcome of WSAS score (standardised coefficient 0·12 [95% CI -2·14 to 2·38]; p=0·92). The probability that SPS is cost-effective was 0·34-0·39. There were 36 serious adverse events affecting 17 participants in the SPS group and 16 in the treatment-as-usual group. None were judged to be related to study procedures. Two study participants died during the 12-month follow period, both in the SPS group. INTERPRETATION:We found no difference in social functioning over the course of 1 year among people offered a brief psychological intervention, and no evidence of cost-effectiveness. These data highlight the importance of improving access to longer-term evidence-based psychological treatment programmes for people with personality disorder. FUNDING:National Institute for Health and Care Research.
BACKGROUND:Narrative descriptions of HIV and Trypanosoma cruzi, the causative agent of Chagas disease, co-infection exist in the literature but the breadth and depth of the data underlying these descriptions has not been previously thoroughly scrutinised and reactivation is poorly understood. The aim of this systematic review was to identify, synthesise and analyse the published literature on the epidemiology and clinical features of T. cruzi and HIV co-infection. METHODS:A systematic review of published literature on HIV and T. cruzi co-infection was conducted. Six international databases were searched: Medline, Embase, Global Health, Global Index Medicus (including LILACS, AIM, IMEMR, IMSEAR & WPRIM), Web of Science and Scopus. Articles reporting on HIV and T. cruzi co-infection, as defined by the authors, with no restrictions on study type, language or date of publication or reporting were included. RESULTS:152 articles (62% case reports or series) were included, of which 110 reported individual patient data on 352 individuals with HIV and T. cruzi co-infection. Reported prevalence of co-infection varied by region and setting of screening, ranging from 0.2% to 5%. 86% of reactivations were reported in individuals with CD4 < 200 cells/mm3. CNS reactivation, typically presenting with meningoencephalitis and/or central nervous system (CNS) lesions, accounted for 85% of all published cases of reactivation. Myocarditis (accounting for 10% published reactivation cases) was less well characterised. Mortality of all reactivation cases was 67% (79% in those with CNS reactivation). CONCLUSION:T. cruzi reactivation mainly affects those with untreated HIV and lower CD4 counts. CNS reactivation is the most common clinical picture and confers high mortality. Prompt recognition of reactivation and immediate initiation of trypanocidal therapy (with benznidazole or nifurtimox) is recommended. Increased education and better awareness of the risks of co-infection are needed, as is systematic screening of individuals at-risk. TRIAL REGISTRATION:Prospero CRD42020216125.
BACKGROUND: Non-medical ketamine use is becoming increasingly common in the United States (US), but awareness remains limited among US healthcare providers. CASE PRESENTATION: Here we present the case of a young woman who developed severe ketamine use disorder in the setting of an acute exacerbation of chronic post-traumatic stress disorder (PTSD). She also demonstrated symptoms concerning for two known complications of chronic ketamine use: gastrointestinal toxicity and ketamine-induced uropathy. Informed by best practices established by specialists in club drug use from the United Kingdom (UK), a multidisciplinary care plan was implemented. The plan included specialist referrals for suspected physical complications and connection with a psychiatrist and psychologist to address underlying mental health conditions driving ketamine use. With individualized, multidisciplinary support, she was able to significantly reduce ketamine use, for a period of time. CONCLUSIONS: US healthcare providers must be aware of non-medical ketamine use and associated harms, including ketamine use disorder, in order to provide effective counseling and treatment to increasing numbers of people using ketamine. In the UK, a multidisciplinary clinic was established to serve people struggling with ketamine and other club drug use, providing a model for effective, patient-centered care that can inform our approach to building systems of care for people who use ketamine and other club drugs in the US.
Objective Artificial intelligence (AI) is beginning to be used within digital surgical wound monitoring to facilitate implementation at scale. AI acceptability is essential to its success. This study aimed to explore patient and staff acceptability of an AI-based digital surgical wound monitoring platform. Design Qualitative interviews Setting Two hospitals performing cardiac surgery in England. Participants 20 patients undergoing cardiac surgery and 10 clinical staff participating in a randomised feasibility trial of surgical wound monitoring with AI. Interventions Semi-structured interviews were conducted focusing on participants’ experiences or perceptions of AI-based digital surgical wound monitoring. Data were analysed, guided by the theoretical framework of acceptability. Primary measure Patient and staff acceptability of AI within surgical wound monitoring. Results Patients and staff were supportive of the use of AI within surgical wound monitoring and felt safety was improved, access was increased and efficiency was improved. AI monitoring was perceived to allow the early detection and treatment of surgical wound complications and facilitate the implementation of monitoring at scale for all patients. Some participants were concerned about data security risks, staff over-reliance on AI and the loss of human interaction. Conclusion AI-supported digital surgical wound monitoring appeared acceptable to participants within this feasibility study. Further research is needed to evaluate implementation in broader settings. Trial registration number ISRCTN16900119 and NCT06475703 .
