Explore the vast range of titles available.

In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55–0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40–0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported. Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. St Jude Medical Inc.

Macrophage activation is, in part, regulated via hydrolysis of oxidised low density lipoproteins by Lipoprotein-Associated phospholipase A2 (Lp-PLA2), resulting in increased macrophage migration, pro-inflammatory cytokine release and chemokine expression. In uveitis, tissue damage is mediated as a result of macrophage activation; hence inhibition of Lp-PLA2 may limit macrophage activation and protect the tissue. Utilising Lp-PLA2 gene-deficient (KO) mice and a pharmacological inhibitor of Lp-PLA2 (SB-435495) we aimed to determine the effect of Lp-PLA2 suppression in mediating retinal protection in a model of autoimmune retinal inflammation, experimental autoimmune uveoretinitis (EAU). Following immunisation with RBP-3 (IRBP) 1-20 or 161-180 peptides, clinical disease was monitored and severity assessed, infiltrating leukocytes were enumerated by flow cytometry and tissue destruction quantified by histology. Despite ablation of Lp-PLA2 enzyme activity in Lp-PLA2 KO mice or wild-type mice treated with SB-435495, the number of infiltrating CD45+ cells in the retina was equivalent to control EAU animals, and there was no reduction in disease severity. Thus, despite the reported beneficial effects of therapeutic Lp-PLA2 depletion in a variety of vascular inflammatory conditions, we were unable to attenuate disease, show delayed disease onset or prevent progression of EAU in Lp-PLA2 KO mice. Although EAU exhibits inflammatory vasculopathy there is no overt defect in lipid metabolism and given the lack of effect following Lp-PLA2 suppression, these data support the hypothesis that sub-acute autoimmune inflammatory disease progresses independently of Lp-PLA2 activity.

IntroductionObjective risk stratification based is recommended in all patients with a new diagnosis of stable ischaemic heart disease. However, more than half of patients with chronic coronary syndromes who have a future myocardial infarct do not have obstructive coronary disease on coronary imaging, or the ischaemic substrate to enable effective risk stratification with functional testing. There is need for an effective risk stratification tool that can be applied to all patients with chronic coronary syndrome to help guide management decisions.PurposeTo evaluate the role of cardiac troponin testing in the risk stratification of patients with chronic coronary syndrome.Method: Consecutive patients attending a tertiary cardiac centre for investigation of chronic coronary syndrome with coronary angiography were eligible for enrolment into this prospective observational study. High-sensitivity cardiac troponin I was measured in all patients immediately prior to angiography with clinicians blinded to the results. Troponin concentrations were log transformed and evaluated as a continuous variable in adjusted Cox regression models, and categorised as low (<5 ng/L), intermediate (5 ng/L - 99th centile), or high (>99th centile). The primary outcome was a composite of myocardial infarction or cardiovascular death over a median follow-up of 2.5 years.ResultsIn total, 4,344 consecutive patients were enrolled (median age 66 years (IQR 59 - 73), 32.4% female). The majority had obstructive coronary disease on angiography (62.4%, 2,712/4,344), with fewer having non-obstructive disease (27.4%, 1,193/4,344) or angiographically normal coronary arteries (10.2%, 442/4,344). Patients with obstructive disease had higher troponin levels (median 4.0 ng/L, IQR 2.1 - 8.6) than those with non-obstructive disease (2.7 ng/L, IQR 1.4 - 5.1; P<0.001). Patients with the highest troponin concentration were most likely to have a primary outcome (62.8 events per 1,000 patient-years) as compared to those with intermediate (45.5 per 1,000 patient-years) or low troponin levels (15.1 per 1,000 patient-years). In patients with obstructive disease, the incidence of the primary outcome was highest in those with the highest troponin (64.5 per 1,000 patient-years) as compared to those with obstructive disease and either intermediate or low troponin levels (53.2 and 21.2 per 1,000 patient-years, respectively). After adjusting for coronary disease severity, troponin remained an important independent predictor of the primary outcome (aHR 3.1 95%CI 2.4–3.9).Abstract 167 Figure 1Cumulative incidence of the primary outcome (myocardial infarction or cardiovascular death) in patients with obstructive coronary disease, stratified by cardiac troponin concentration [low (green, <5 ng/), intermediate (orange, 5 ng/L - 99th centile), or high (red, >99th centile)ConclusionIn patients with chronic coronary syndrome, cardiac troponin can reliably identify individuals at the highest risk of myocardial infarction or cardiovascular death. Combined with angiographic indices of disease severity, troponin testing in the chronic coronary syndrome could augment current risk stratification strategies and may inform optimised treatment decisions.Conflict of InterestNone

In order to achieve high intensity beams for Fermilab’s neutrino program, slip stacking is used in the Recycler in which bunches overlap and slip through other bunches multiple times. As the bunch intensity is increased in the future, space charge effects during the overlap periods become more detrimental. In order to investigate the size of these space charge effects, the beam simulation program Synergia has been extended to allow copropagation of bunch trains at different momenta.

The addition of rituximab to standard combination chemotherapy in children with high-grade (mainly Burkitt’s) lymphoma improved 3-year event-free survival (94% vs. 82%). The incidence of myelotoxic effects was somewhat higher, without a higher incidence of death from toxic effects; the incidence of hypogammaglobulinemia was higher.

In July 2021, Public Health Wales received two notifications of salmonella gastroenteritis. Both cases has attended the same barbecue to celebrate Eid al–Adha, two days earlier. Additional cases attending the same barbecue were found and an outbreak investigation was initiated. The barbecue was attended by a North African community’s social network. On same day, smaller lunches were held in three homes in the social network. Many people attended both a lunch and the barbecue. Cases were defined as someone with an epidemiological link to the barbecue and/or lunches with diarrhoea and/or vomiting with date of onset following these events. We undertook a cohort study of 36 people attending the barbecue and/or lunch, and a nested case-control study using Firth logistic regression. A communication campaign, sensitive towards different cultural practices, was developed in collaboration with the affected community. Consumption of a traditional raw liver dish, ‘marrara’, at the barbecue was the likely vehicle for infection (Firth logistic regression, aOR: 49.99, 95%CI 1.71–1461.54, p = 0.02). Meat and offal came from two local butchers (same supplier) and samples yielded identical whole genome sequences as cases. Future outbreak investigations should be relevant to the community affected by considering dishes beyond those found in routine questionnaires.

Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive lateral flow test (cases) and a sample of negatives (controls). A total of 199 cases and 2621 controls completed a questionnaire (response rates: 27.1 and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR 3.39, 95% CI 1.43–8.03), social care (aOR 2.63, 1.22–5.67) or healthcare (aOR 2.31, 1.29–4.13), live with someone self-isolating due to contact with a case (aOR 3.07, 2.03–4.62), visit a pub (aOR 2.87, 1.11–7.37) and smoke or vape (aOR 1.54, 1.02–2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (population-attributable fraction: 0.2). As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.

Cell transplantation is one way of limiting the progress of retinal degeneration in animal models of blinding diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Here we transplanted a human retinal pigment epithelial (RPE) cell line into the subretinal space of one such model, the Royal College of Surgeons (RCS) rat, and showed, using head tracking to moving stripes and pattern discrimination in conjunction with single-unit cortical physiology, that cortically mediated vision can be preserved with this treatment.

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures. We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission. Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%). Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.

Background The population of adult residential care homes has been shown to have high morbidity and mortality in relation to COVID‐19. Methods We examined 3115 hospital discharges to a national cohort of 1068 adult care homes and subsequent outbreaks of COVID‐19 occurring between 22 February and 27 June 2020. A Cox proportional hazards regression model was used to assess the impact of time‐dependent exposure to hospital discharge on incidence of the first known outbreak, over a window of 7‐21 days after discharge, and adjusted for care home characteristics, including size and type of provision. Results A total of 330 homes experienced an outbreak, and 544 homes received a discharge over the study period. Exposure to hospital discharge was not associated with a significant increase in the risk of a new outbreak (hazard ratio 1.15, 95% CI 0.89, 1.47, P = .29) after adjusting for care home characteristics. Care home size was the most significant predictor. Hazard ratios (95% CI) in comparison with homes of <10 residents were as follows: 3.40 (1.99, 5.80) for 10‐24 residents; 8.25 (4.93, 13.81) for 25‐49 residents; and 17.35 (9.65, 31.19) for 50+ residents. When stratified for care home size, the outbreak rates were similar for periods when homes were exposed to a hospital discharge, in comparison with periods when homes were unexposed. Conclusion Our analyses showed that large homes were at considerably greater risk of outbreaks throughout the epidemic, and after adjusting for care home size, a discharge from hospital was not associated with a significant increase in risk.