Guy's and St Thomas' NHS Foundation Trust

Catheters have been widely used to deal with heart valve diseases. However, the diversity in handle structures and bending curvatures imposes significant complexities in safe delivery and positioning. In this work, we designed a module for single knob actuation assembled coaxially on the catheter handle, composed of a chuck for universal clamping of diameters from 15 to 45 mm and a position-adjustable shaft to accommodate various spacing between knobs. In addition, we proposed a two-curvature with pseudo joints (TC-PJ) model for bending control of bendable sections (BSs) in catheters. The verification was decoupled into two steps based on the other three deformation patterns. Firstly, comparing the two-curvature (TC) model with pseudo-rigid-body (PRB), constant curvature (CC), and Euler spiral (ES) models to simulate planar bending and elongation, the results showed a more accurate shape representation. Then, five distinct catheters were employed to test the clamping universality of the module and tip positioning precision of the TC-PJ model which took torsion and shear strain into consideration. The root-mean-square error (RMSE) and the standard deviation (SD) of tip position and direction were analysed. Results indicated the module's suitability for clamping these catheters, with the large guide sheath exhibiting minimal position RMSE (SD) of around 0.10 (0.051) mm and 0.049 (2.15) degrees, while the puncture catheter demonstrated the highest position and direction RMSE (SD) extending to about 1.16 (0.53) mm and 0.70 (31.33) degrees, primarily attributed to the coupling of two sequential bendable components. Overall, the proposed actuation module and kinematic model showed the ability of universal manipulation and an average tip position and direction RMSE of 0.65 mm and 0.23 degrees in free space.

Approximately 30–49% of heart failure (HF) patients are living with obesity. The recommended body mass index (BMI) for the general population is 18.5–24.9 kg/m ² . The obesity paradox suggests that HF patients with obesity (HFpwO) have a better prognosis compared to normal BMI. Guideline recommendations on ideal BMI for HFpwO are limited. This systematic review aims to examine the evidence base for intentional weight loss in HFpwO on the following parameters: mortality, hospitalization, symptoms, quality of life (QOL), effects on left ventricular ejection fraction (LVEF) and adverse events. A total of 22 studies were identified: lifestyle intervention ( n = 9), pharmacotherapy ( n = 3), bariatric surgery ( n = 10). Mortality and hospitalization, symptoms, QOL, and LVEF were reported in 8, 15 and 14 studies, respectively. All studies had moderate to high risk of bias except one randomized controlled trial (RCT) which evaluated semaglutide in HF with preserved ejection fraction (HFpEF) patients. Semaglutide resulted in weight loss with improvement in QOL. Lifestyle intervention led to weight loss, minimal adverse events, and improvement in symptoms in both HF with reduced ejection fraction (HFrEF) and HFpEF patients. In six observational studies, bariatric surgery in HFrEF patients achieved weight loss and improvement in LVEF safely in most patients but some patients developed worsening HF perioperatively. There is a need for high‐quality adequately powered RCTs on intentional weight loss in HFpwO with survival and hospitalization outcomes. All forms of weight loss intervention studied in this review were likely to result in significant weight loss, improved symptoms and QOL. Careful monitoring is required due to an increase in certain adverse events.

Objective The aim of the project was to reduce the risk of patients using the estrogen only part of their hormone replacement therapy (HRT) inadvertently in Banstead PCN. Although understanding about the risk of unopposed estrogen is well understood by prescribers, there are numerous flash points where this exposure can occur which was highlighted by several cases encountered during a study period of 3 months. Study design Cases encountered revealed numerous reasons for this exposure which were split into three areas: Prescribing factors, dispensing checks and patient understanding. Main outcome measures Quality improvement suggestions were tailored to the factors involved. IT system changes to EMIS, our main computer software provider, were proposed to enable safer prescribing. Following discussion with key stakeholders, increased education for pharmacists was proposed alongside an alert sticker system at the dispensing end point. Patient understanding and education for all parties was delivered through various routes. Results The IT system alterations required are complex and still awaited. Funding was obtained and stickers distributed. The results from a re-audit from this intervention are awaited. Interim education measures at an individual level were meantime explored and the impact of them assessed. Patient education and the role of social media were explored. I produced a short video which was circulated to doctors with the plan to distribute via other clinician social media accounts. Conclusions A key discovery through this study is that many of the flash points identified can be difficult to detect and many are not measurable. The increasing number of HRT prescriptions, time pressures in primary care and the known risk from using unopposed estrogen of endometrial cancer means these changes are of potential great value.

Achondroplasia is a lifelong condition requiring lifelong management. There is consensus that infants and children with achondroplasia should be managed by a multidisciplinary team experienced in the condition. However, many people are lost to follow-up after the transition from paediatric to adult care, and there is no standardised approach for management in adults, despite the recent availability of international consensus guidelines. To address this, the European Achondroplasia Forum has developed a patient-held checklist to support adults with achondroplasia in managing their health. The checklist highlights key symptoms of spinal stenosis and obstructive sleep apnoea, both among the most frequent and potentially severe medical complications in adults with achondroplasia. The checklist acts as a framework to support individuals and their primary care provider in completing a routine review. General advice on issues such as blood pressure, pain, hearing, weight, adaptive aids, and psychosocial aspects are also included. The checklist provides key symptoms to be aware of, in addition to action points so that people can approach their primary care provider and be directed to the appropriate specialist, if needed. Additionally, the European Achondroplasia Forum offers some ideas on implementing the checklist during the transition from paediatric to adult care, thus ensuring the existing multidisciplinary team model in place during childhood can support in engaging individuals and empowering them to take responsibility for their own care as they move into adulthood.

We investigated autistic children’s generalisation of social communication over time across three settings during a play-based assessment with different adults and explore the potential moderating effects on generalisation of age, nonverbal IQ and level of restricted and repetitive behaviours. The social communication abilities of 248 autistic children (2–11 years, 21% female, 22% single parent, 60% white) from three UK sites were assessed from 1984 video interactions in three contexts with three different interaction partners (parent/home, teaching assistant/school, researcher/clinic) at baseline, midpoint (+ 7m) and endpoint (+ 12m) within the Paediatric Autism Communication Trial-Generalised (PACT-G), a parent-mediated social communication intervention. Children’s midpoint social communication at home generalised to school at midpoint and to clinic at endpoint. Generalisation was stronger from home to school and clinic than school to home and clinic. Generalisation was not moderated by age, nonverbal IQ or restricted and repetitive behaviour. Broader child development did not explain the pattern of results. The current study is the largest study to date to explore generalisation with autistic children and provides novel insight into their generalisation of social communication skills. Further research is needed to gain a more comprehensive understanding of facilitators of generalisation across settings and interaction partners in order to develop targeted strategies for interventions to enhance outcomes for young autistic children.

Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.

Background Granulomatosis with Polyangiitis (GPA) is a rare multi-system autoimmune disorder that may present with cardiac manifestations that are often under-recognized. In this report, we discuss a usual case of a patient who presented as a cardiac emergency with recurrent ST elevation and discuss the approach and management. Case summary A 44-year-old man presented with two episodes of chest pain associated with ST-segment elevation on 12-lead ECG. Under investigation over the past several weeks for fatigue, nasal congestion, and red eyes, his first presentation was associated with widespread ST-segment elevation and an echogenic myocardium suggestive of myocarditis that was confirmed on cardiac MRI. A week later, the development of chest pain, antero-lateral ST elevation, and regional wall motion abnormalities suggested an acute coronary syndrome and he proceeded to primary percutaneous intervention that treated a lesion in the distal left anterior descending artery secondary to coronary arteritis. Diagnosed with GPA, he was started on immunosuppression and has had a resolution of his cardiac involvement at follow-up. Discussion This case report describes an unusual case of myocarditis and coronary arteritis presenting acutely in the same patient and emphasizes the importance of considering systemic autoimmune conditions when encountering primarily cardiac presentations. Early recognition and diagnosis of cardiac involvement will improve the long-term outcomes in these patients.

Background Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. Objectives To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. Methods We developed a cohort study using Swedish national registers 2013–2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. Results We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0–109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9–102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43–1.35). The IR for major bleeding was 23.5 (95% CI 8.6–51.1) for rivaroxaban versus 49.2 (95% CI 42.3–56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26–1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9–201.5) for rivaroxaban and 565.6 (95% CI 541.8–590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34–0.67). Conclusions Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. Trial registration number NCT05150938 (Registered 9 December 2021).

Background People living with HIV are disproportionately represented among people with severe mpox. Mild and self‐limiting conjunctival involvement has been well‐documented, and severe ocular complications, including keratitis, corneal scarring, and the associated loss of vision, are increasingly recognized. Tecovirimat is the first‐line antiviral therapy for severe mpox, but data around the efficacy of systemic antiviral agents for mpox are limited, particularly in cases of ocular mpox. Case Report Here, we describe a case of sight‐threatening necrotic blepharokeratoconjunctivitis in a person with advanced HIV, requiring an extended course of tecovirimat due to persistent mpox viral shedding for nearly 5 months.

BACKGROUND Increased arterial stiffness and pulse wave velocity (PWV) of the aorta and large arteries impose adverse hemodynamic effects on the heart and other organs. Antihypertensive treatment reduces PWV, but it is unknown whether this results from an unloading of stiffer elements in the arterial wall or is due to an alternate functional or structural change that might differ according to class of antihypertensive drug. METHODS We performed a systematic review and meta-analysis of the effects of different antihypertensive drug classes and duration of treatment on PWV with and without adjustment for change in mean arterial blood pressure (BP; study 1) and compared this to the change in PWV after an acute change in transmural pressure, simulating an acute change in BP (study 2). RESULTS A total of 83 studies involving 6200 subjects were identified. For all drug classes combined, the reduction of PWV was 0.65 (95% CI, 0.46–0.83) m/s per 10 mm Hg reduction in mean arterial BP, a change similar to that induced by an acute change in transmural pressure in a group of hypertensive subjects. When adjusted for change in mean arterial BP, the reduction in PWV after treatment with beta-blockers or diuretics was less than that after treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists or calcium channel antagonists. CONCLUSIONS Reduction in PWV after antihypertensive treatment is largely explained by the reduction in BP, but there are some BP-independent effects. These might increase over time and contribute to better outcomes over the long term, but this remains to be demonstrated in long-term clinical trials.

Background Disability marginalises a large portion of Bangladesh’s population. Global pre- and post-pandemic research evidently states that, this group is more prone to develop mental health problems, which increases the risk of self-harm and suicide among them. It is crucial to comprehend and mitigate the mental health challenges among the people with disabilities which in turn can promote their greater participation in community, and in national socioeconomic development. However, currently there is limited information available, regarding the suicidal behaviour of this group in Bangladesh. Therefore, this study aimed to investigate the prevalence and contributing factors of suicidal behaviour among people with disabilities. Method A cross-sectional survey was conducted during September and October 2022, among the participants who had selected disabilities, by using probability proportional to size sampling technique across all eight divisions of Bangladesh. A semi-structured questionnaire comprising information about sociodemographic, lifestyle, health; and Suicidal Behaviour Questionnaire-Revision (SBQ-R) was used. The association between the determinants and mental health outcome was investigated using the Chi-square test, and the contributing factors were investigated using the multiple binary logistic regression. Result About 10.45% of the participants reported to have suicidal behaviour (e.g., suicidal ideation, attempts, completed suicide), considering the cut-off score as 7 for the SBQ-R in the study period. Approximately, 40% respondents mentioned suicidal ideation in their lifetime, whereas, 9.01% had suicidal ideation over the past 12 months. Additionally, 8.87% of the person with disabilities, mentioned about their suicidal intent to the family members, and 5.94% reported the likelihood of suicide in the future. Being female, having multiple disabilities, and not being connected with family and friends were found to be significantly associated with suicidal behaviour. Conclusion This research demonstrates the significance of treating mental health issues and expanding accessibility to pre-existing services to lessen the impact of the limitations generated by disabilities. Policymakers can utilize this baseline findings to design large scale research and develop measures for suicide prevention, and management for at-risk groups.

describes a case of the growth of a serous borderline tumour recurrence and cyst to papillary projection ratio with associated ultrasound images. The aetiology, presentation and management of such cases are explored and compared to the literature.

PURPOSE Open-label phase II study (RELATIVITY-060) to investigate the efficacy and safety of first-line nivolumab, a PD-1–blocking antibody, plus relatlimab, a lymphocyte-activation gene 3 (LAG-3)–blocking antibody, plus chemotherapy in patients with previously untreated advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC). METHODS Patients with unresectable, locally advanced or metastatic GC/GEJC were randomly assigned 1:1 to nivolumab + relatlimab (fixed-dose combination) + chemotherapy or nivolumab + chemotherapy. The primary end point was objective response rate (ORR; per RECIST v1.1 by blinded independent central review [BICR]) in patients whose tumors had LAG-3 expression ≥1%. RESULTS Of 274 patients, 138 were randomly assigned to nivolumab + relatlimab + chemotherapy and 136 to nivolumab + chemotherapy. Median follow-up was 11.9 months. In patients with LAG-3 expression ≥1%, BICR-assessed ORR (95% CI) was 48% (38 to 59) in the nivolumab + relatlimab + chemotherapy arm and 61% (51 to 71) in the nivolumab + chemotherapy arm; median progression-free survival (95% CI) by BICR was 7.0 months (5.8 to 8.4) versus 8.3 months (6.9 to 12.1; hazard ratio [HR], 1.41 [95% CI, 0.97 to 2.05]), and median overall survival (95% CI) was 13.5 months (11.9 to 19.1) versus 16.0 months (10.9 to not estimable; HR, 1.04 [95% CI, 0.70 to 1.54]), respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 69% and 61% of all treated patients, and 42% and 36% of patients discontinued because of any-grade TRAEs in the nivolumab + relatlimab + chemotherapy and nivolumab + chemotherapy arms, respectively. CONCLUSION RELATIVITY-060 did not meet its primary end point of improved ORR in patients with LAG-3 expression ≥1% when relatlimab was added to nivolumab + chemotherapy compared with nivolumab + chemotherapy. Further studies are needed to address whether adding anti–LAG-3 to anti–PD-1 plus chemotherapy can benefit specific GC/GEJC patient subgroups.

Objectives Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. Methods In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. Results All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. Conclusions It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. Trial registration number NCT04039854 .

Background Outpatient care for patients with heart valve disease (HVD) is best provided by valve clinics delivered by specialists. Modern day practice in the United Kingdom (UK) is currently poorly understood and has not been evaluated for nearly a decade. Furthermore, the COVID 19 pandemic changed the management of many chronic diseases, and how this has impacted patients with heart valve disease is unclear. Methods A British Heart Valve Society survey was sent to 161 hospitals throughout the UK. Results There was a general valve clinic in 46 of the 68 hospitals (68%), in 19 of 23 Heart Centres (83%) and 29 of 45 DGHs (64%). Across all settings, 3824 new patients and 17,980 follow up patients were seen in valve clinics per annum. The mean number of patients per hospital were 197 (median 150, range 48–550) for new patients and 532 (median 400, range 150–2000) for follow up. On the day echocardiography was available in 55% of valve clinics. In patients with severe HVD, serum brain natriuretic peptide (BNP) was measured routinely in 39% of clinics and exercise testing routinely performed in 49% of clinics. A patient helpline was available in 27% of clinics. 78% of centres with a valve clinic had a valve multidisciplinary team meeting (MDT). 45% centres had an MDT co-ordinator and MDT outcomes were recorded on a database in 64%. COVID-19 had a major impact on valve services in 54 (95%) hospitals. Conclusions There has been an increase in the number of valve clinics since 2015 from 21 to 68% but the penetration is still well short of the expected 100%, meaning that valve clinics only serve a small proportion of patients requiring surveillance for HVD. COVID-19 had a major impact on the care of patients with HVD in the majority of UK centres surveyed.