Personalised Care Interprofessional Education Framework (PerCIE): Social prescribing placement curriculum document and guiding principles for undergraduate/postgraduate health and social care students

This Personalised Care Interprofessional Education (PerCIE) Framework has been designed to guide and support HEIs, and PEFs to enable health and social care students to learn about strengths-based approaches to health and wellbeing delivered by services that provide a social prescribing offer. It has been co-created by a network of experts from a broad range of professional backgrounds from seven universities (HEIs), Private Independent and Voluntary Organisations (PIVO sector also known as Voluntary Community Social Enterprise VCSE), National Social Prescribing Network Special Interest Group (SigSpn), Health Education England (Greater Manchester) and the NHS England (NHSe) Personalised Care team. It is underpinned by contemporary practice-based theory and evidence of impact from a range of successful UK projects. The PerCIE Framework is designed to enable universities to work in partnership with VCSE/PIVO partners to create collaborative and inclusive test beds for social action. It can help to support the generation of new socially connected learning opportunities that could provide rich and meaningful insight into health and health inequalities, our BAME communities and marginalised groups. It builds on and recognises the power of community resilience through asset-based working

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

The London Times and the American Civil War.

The Times in the 1860's was the most powerful newspaper in Britain and the world. Through the labours of its exceptionally talented staff in London, the provinces, and abroad, it provided readers with vital information on major questions of the day, and instructed them on its editorial page as to the opinions they should hold. This thesis examines the record of The Times in covering and commenting on the American Civil War. When war threatened in America, Times editor John Delane quickly sent his experienced foreign correspondent, William Howard Russell, to supplement his regular correspondent in New York. Russell was in place to report the beginning of the war, the retreat from the first battle of Bull Run, and the Trent Crisis of November/December 1861. Refused permission in the spring of 1862 to accompany Northern armies on the first major campaign of the war, he angrily returned to England, In this period of just over a year. The Times moved from being the foreign newspaper most educated Americans wanted to read, to being the foreign newspaper most Americans vehemently disliked. Contemporary observers charged then and later that The Times's coverage of the war poisoned relations between Britain and the United States for a generation. This study analyzes this remarkable charge by exploring the private opinions of key players in the drama. The Times is unique among newspapers in possessing an unusually complete archive of letters written by its editors and correspondents. In addition to these letters and Russell's diaries, the papers of William Seward, American Secretary of State, and two of his diplomats, John Bigelow and Henry Sanford, the papers of Times correspondent Bancroft Davis and the diaries of American Minister Charles Francis Adams have been tapped to document American reactions to The Times. Lord Palmerston's papers have been consulted to determine the relationship between the policies advocated by The Times and those of Palmerston and his foreign secretary, Lord Russell. The major concentration of the study has been on the period just before the war up to the time of the Trent crisis, for it was then that The Times's policy was forged. While it has not been possible to examine every issue that was debated in The Times during this four year war, the study goes beyond Russell's tour to describe the reportage of the five other Times correspondents in America, and the part they played in ruining or rescuing The Times's reputation

Healthcare understanding of COVID-19 antibody

Objective: : The SARS-CoV-2 pandemic has shed light on the difficulties in spreading uniform information. We rely on national and international organizations to provide scientifically accurate information to the public at large. With so many different sources of information, often not scientific, there appears to be an incomplete understanding of many aspects of SARS-CoV-2 infection. We sought to gain information about healthcare worker understanding of the implications of a positive serum COVID-19 antibody test result. We identified a broad range of responses among all categories of healthcare workers in our facility. Most notably we found that there was not complete understanding that there can be asymptomatic spread of COVID-19 infection. Methods: : We provided health literacy and opinion questions to the healthcare workers of our facility. Results: : Upon analysis of the data, we identified many differences in level of understanding among our healthcare workers. Conclusion: : We identified a lack of consensus on important details leading to potentially growing uncertainty with respect to SARS-COV-2 antibody. A diminished health literacy with respect to antibody testing could potentially suggest future issues with understanding the importance of vaccination benefits

Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis

Background: Excess body weight is a risk factor for obstructive sleep apnoea (OSA). The aim of the systematic review was to establish whether weight loss via lifestyle interventions such as diet and exercise are useful in the treatment of OSA.Methods: A literature search was conducted between 1980 and February 2012. Systematic reviews and randomised controlled trials (RCTs) with participants who had OSA, were overweight or obese, and who had undergone lifestyle interventions with the aim of improving sleep apnoea were included. Meta analyses were conducted for a subset of RCTs with appropriate data.Results: Two systematic reviews and eight RCTs were included. Meta-analyses were conducted for four RCTs comparing intensive lifestyle interventions to a control. The overall weighted mean differences for weight change, change in apnoea -hypopnoea index (AHI) and change in oxygen desaturation index of >= 4% were as follows: -13.76 kg (95% confidence interval (CI) -19.21, -8.32), -16.09 (95% CI -25.64, -6.54) and -14.18 (95% CI -24.23, -4.13), respectively. Although high heterogeneity within the meta analyses, all studies favoured the interventions. Long-term follow-up data from three RCTs suggest that improvements in weight and AHI are maintained for up to 60 months.Conclusions: Intensive lifestyle interventions are effective in the treatment of OSA, resulting in significant weight loss and a reduction in sleep apnoea severity. Weight loss via intensive lifestyle interventions could be encouraged as a treatment for mild to moderate OSA. (C) 2014 Published by Elsevier B.V

Sleeping Well Trial: Increasing the effectiveness of treatment with continuous positive airway pressure using a weight management program in overweight adults with obstructive sleep apnoea-A stepped wedge randomised trial protocol

Background The majority of adults diagnosed with obstructive sleep apnoea (OSA) are overweight or obese. Continuous positive airway pressure (CPAP) is the most common effective therapy for OSA. However, adherence declines over time with only 50% of patients prescribed CPAP continuing to use it long term. Furthermore, a recent prospective analysis indicated that those more adherent with CPAP therapy have enhanced weight gain trajectories which in turn may negatively impact their OSA. Aim The Sleeping Well Trial aims to establish whether the timing of starting a lifestyle weight loss intervention impacts on weight trajectory in those with moderate-severe OSA treated at home with CPAP, while testing the potential for smart phone technology to improve adherence with lifestyle interventions. Methods A stepped wedge design with randomisation of individuals from 1 to 6 months post-enrolment, with 5 months of additional prospective follow up after completion of the stepped wedge. This design will investigate the effect of the 6-month lifestyle intervention on people undergoing CPAP on body weight, body composition and health-related quality of life. Discussion This trial tests whether the timing of supporting the patient through a weight loss intervention is important in obtaining the maximum benefit of a lifestyle change and CPAP usage, and identify how best to support patients through this critica