Are diabetes self-management interventions delivered in the psychiatric inpatient setting effective?: A protocol for a systematic review

Introduction: Diabetes is a major risk factor for cardiovascular disease, which is the most significant contributor to increased mortality due to natural causes in those with severe mental illness (SMI). Self-management interventions for diabetes have been shown to be effective in the general population, however, effects of these interventions in those with SMI is still unclear. Psychiatric admission could be used opportunistically to deliver interventions of this kind and help improve diabetes self-management. This review aims to assess whether interventions of this kind improve diabetes outcomes and have an effect on reducing cardiovascular risk. Methods and analysis: This review will include studies assessing diabetes self-management interventions designed to be delivered to those aged 18 and over with comorbid type 2 diabetes and SMI during admission to psychiatric inpatient settings. Databases including the Cochrane Library, Medline, Psychinfo, CINAHL, Embase, WHO’s International Clinical Trials Registry Platform, International Health Technology Assessment Database, UK Clinical Research Network and ClinicalTrials.gov will be searched from inception to September 2022. Where possible, meta-analysis of included studies will be conducted. If heterogeneity is high and meta-analysis is not possible, we will use other means of data synthesis and will include a narrative description of included studies. Ethics and dissemination: Ethical approval is not required as the systematic review will only include data from existing studies. The results will be disseminated via peer-reviewed publication and presentation at relevant national and international conferences. PROSPERO registration number: CRD4202235767

Managing diabetes in the psychiatric in-patient setting: knowledge, attitudes and skills of healthcare professionals

Aims and method There is currently a lack of monitoring and standardisation of diabetes care in the National Health Service (NHS) psychiatric in-patient setting. We surveyed healthcare professionals in psychiatric in-patient units across England to understand current diabetes care. A 13-item questionnaire was piloted via think-aloud interviews. The survey was completed by healthcare professionals across 19 wards in 11 NHS mental health trusts. Results were analysed via descriptive statistics and thematic analysis. Results Of 150 respondents, 98% agreed that addressing physical health needs was an important part of the mental health team's role; 68% agreed that they had adequate skills and knowledge to manage diabetes safely. Thematic analysis identified themes relating to individual, organisational and patient-level factors. Clinical implications Psychiatric admission could be used opportunistically to improve the healthcare disparities for people with comorbid diabetes and severe mental illness. This national survey highlights areas that need to be addressed to optimise diabetes care in this setting

Cardiac monitoring in memory clinics: national survey of UK practice

Aims and method People diagnosed with dementia are often started on acetylcholinesterase inhibitors (AChEIs). As AChEIs can be associated with cardiac side-effects, an electrocardiogram (ECG) is sometimes requested before treatment. Previous work has suggested there is little consensus as to when or how ECGs should be obtained. This can create inconsistent practice, with patient safety, economic and practical repercussions. We surveyed 305 UK memory clinic practitioners about prescribing practice. Results More than 84% of respondents completed a pulse and cardiac history before prescribing AChEIs. Opinion was divided as to who should fund and conduct ECGs. It was believed that obtaining an ECG causes patients inconvenience and delays treatment. Despite regularly interpreting ECGs, 76% of respondents did not update this clinical skill regularly. Clinical implications The variation in practice observed has service-level and patient implications and raises potential patient safety concerns. Implementing national guidelines or seeking novel ways of conducting cardiac monitoring could help standardise practice

Robotics and Automated Systems for Environmental Sustainability: Monitoring Terrestrial Biodiversity

It is critical to protect Earth’s biodiversity, not just for its own intrinsic value, but also for the ecosystem services it underpins. Yet biodiversity is in crisis, with up to 1 million animal and plant species at risk of extinction, many within decades. This dire projection has captured world attention and triggered major mitigation efforts, but we are faced with problems in assessing global trends in biodiversity – which species, taxa, habitats and ecosystems are suffering the greatest declines? Are current mitigation measures having any positive impact? To answer key questions such as these, ecologists are seeking the help of robotics and automated systems (RAS) experts in the monumental task of attempting to monitor the state of biodiversity.In this White Paper, we have surveyed recent literature and consulted more than 120 international expert ecologists and engineers working in the fields of biodiversity and robotics. We have done this to evaluate the potential for developing robotic and autonomous systems that could massively extend the scope of terrestrial biodiversity monitoring across habitats globally. The complexities of biodiversity itself, and the many barriers and challenges that must be overcome in monitoring it, are formidable. We assess each of these barriers in turn, highlighting currently available RAS solutions, as well as nascent technologies that may be relevant to future RAS for biodiversity (RAS-BD) monitoring. Using this information, we have drawn up a roadmap of actions needed to address the barriers that should be easiest to overcome. Encouragingly, we find that a variety of existing RAS capabilities may be transferable to a biodiversity monitoring context. Beyond these are the harder barriers, where promising novel ideas being researched at UK universities and research institutes may, in time, become integral parts of future RAS-BD monitoring technology. We believe that RAS-BD technology has great potential to complement and considerably extend the field survey work undertaken by expert human observers. In the UK, we are fortunate in having particular strengths in both biodiversity and robotics research; as a nation we are in an ideal position to integrate them and become a leading force in the development and application of RAS-BD monitoring. To this end, we propose these recommendations that we hope will guide future government strategy in an area that is vital to the future of humanity:● The creation and funding of an integrated multidisciplinary task force, including academics and industry specialists with expertise in RAS and biodiversity, to support technological research and development.● Future UK funding and focus should be prioritised to utilise existing RAS capabilities to develop first generation RAS-BD technology for monitoring biodiversity.● Relevant nascent technologies being researched by numerous UK academic teams need increased and accelerated research and development funding to turn pioneering concepts into enhanced RAS-BD technology suited to overcoming the hardest monitoring barriers that ecologists encounter.● Education strategies should be developed to foster links between aspiring engineers, biologists andcomputer technologists, both in the curriculum of schools, and at later stages in universities and research facilities

Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice

RNA alternative splicing (AS) expands the regulatory potential of eukaryotic genomes. The mechanisms regulating liver-specific AS profiles and their contribution to liver function are poorly understood. Here, we identify a key role for the splicing factor RNA-binding Fox protein 2 (RBFOX2) in maintaining cholesterol homeostasis in a lipogenic environment in the liver. Using enhanced individual-nucleotide-resolution ultra-violet cross-linking and immunoprecipitation, we identify physiologically relevant targets of RBFOX2 in mouse liver, including the scavenger receptor class B type I (Scarb1). RBFOX2 function is decreased in the liver in diet-induced obesity, causing a Scarb1 isoform switch and alteration of hepatocyte lipid homeostasis. Our findings demonstrate that specific AS programmes actively maintain liver physiology, and underlie the lipotoxic effects of obesogenic diets when dysregulated. Splice-switching oligonucleotides targeting this network alleviate obesity-induced inflammation in the liver and promote an anti-atherogenic lipoprotein profile in the blood, underscoring the potential of isoform-specific RNA therapeutics for treating metabolism-associated diseases

Azetidines Kill Multidrug-Resistant <i>Mycobacterium tuberculosis</i> without Detectable Resistance by Blocking Mycolate Assembly

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99 values &lt;10 μM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies. </p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention