Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales:a routine data linkage study 2003-2018

OBJECTIVE: To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents. METHODS: Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality. RESULTS: There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8–90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1–17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9–17.9) in 2010 to 17.0% (16.1–18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17–1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11–1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36–1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22–1.34], P < 0.001). CONCLUSIONS: Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy

Homeostatic apoptosis prevents competition-induced atrophy in follicular B cells

While the intrinsic apoptosis pathway is thought to play a central role in shaping the B cell lineage, its precise role in mature B cell homeostasis remains elusive. Using mice in which mature B cells are unable to undergo apoptotic cell death, we show that apoptosis constrains follicular B (FoB) cell lifespan but plays no role in marginal zone B (MZB) cell homeostasis. In these mice, FoB cells accumulate abnormally. This intensifies intercellular competition for BAFF, resulting in a contraction of the MZB cell compartment, and reducing the growth, trafficking, and fitness of FoB cells. Diminished BAFF signaling dampens the non-canonical NF-κB pathway, undermining FoB cell growth despite the concurrent triggering of a protective p53 response. Thus, MZB and FoB cells exhibit a differential requirement for the intrinsic apoptosis pathway. Homeostatic apoptosis constrains the size of the FoB cell compartment, thereby preventing competition-induced FoB cell atrophy.Stéphane Chappaz, Kate McArthur, Liam Kealy, Charity W. Law, Maximilien Tailler, Rachael M. Lane ... et al

GP/GPN partner* perspectives on clinical placements for student nurses in general practice: can a community of practice help to change the prevailing culture within general practice?

Background: The UK Government document 5 year forward view describes the need to move chronic disease management from secondary to primary care, which will require a significant increase in the numbers of General Practice Nurses (GPNs). Until recently, there has been no specific recruitment strategy to address this increased need. In recent times, a number of solutions have been suggested to address this impending GPN recruitment crisis. For example, Health Education England (HEE) commission General Practitioners (GPs), who are members of the Advanced Training Practice Scheme (ATPS), to provide placements for student nurses within general practice. Methods: A descriptive qualitative study was undertaken, in which data were collected using semi-structured interviews with 16 GPs and 2 GPN partners∗. Qualitative analysis used a framework approach and themes were cross-checked within the team and member checking was undertaken with a convenience sample of GPs. The research had ethical approval and anonymity and confidentiality were maintained. Results: From the GP perspective, there were two key themes that emerged from the data. The first theme of 'fishing in the same small pond' included succession planning for the general practice workforce, the 'merry go round' of poaching staff from other practices, and the myths and misunderstandings that have grown up around general practice nursing. The second theme, 'growing your own', looked at the impact of the student nurse placements as a means to address the crisis in GPN recruitment. There was recognition of the need for cultural change in the way that GPNs are recruited, and that the ATPS was one way of helping to achieve that change. There were however a number of challenges to sustaining this cultural shift, such as the financial constrains placed upon the GP practice, and the need to function as a 'small business'. Conclusions: Despite all the challenges, the evidence is that, through the Community of Practice (CoP), the ATPS scheme is beginning to 'bear fruit', and there is a subtle but discernible move by GPs from a 'why would we?' to 'why wouldn't we?' invest in education and training for nurses in general practice. N.B. The term GPN partner∗denotes a GPN who is a 'full partner' in the practice business, holding the same NHS contracts and the same status as a GP. For the purposes of the paper itself, the term GP will be used to denote both types of partner

Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study

Aim: To explore factors associated with OAC prescription. Design and Setting: Retrospective cohort study set in care homes in Wales, United Kingdom, listed in the Care Inspectorate Wales Registry 2017/18. Method: Analysis of anonymised individual-level electronic health and administrative data on people aged ≥65 years entering a care home between 1st January 2003 and 31st December 2018, provisioned from the Secure Anonymised Information Linkage Databank. Results: Between 2003 and 2018, 14,493 people with AF aged ≥65 years became new residents in care homes in Wales and 7,057 (48.7%) were prescribed OAC (32.7% in 2003 compared to 72.7% in 2018) within six months prior to care entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per one year age increase [95% confidence interval [CI] 0.95 to 0.96] and aOR 0.91 [0.84 to 0.98], respectively). Conversely, prior venous thromboembolism (aOR 4.06 [3.17 to 5.20]), advancing frailty (mild: aOR 4.61 [3.95 to 5.38]; moderate: aOR 6.69 [5.74 to 7.80]; severe: aOR 8.42 [7.16 to 9.90]) and year of care home entry from 2011 onwards (aOR 1.91 [1.76 to 2.06]) were associated with higher odds of OAC prescription. Conclusions: There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population

Effects of a demand-led evidence briefing service on the uptake and use of research evidence by commissioners of health services: protocol for a controlled before and after study

Background Clinical Commissioning Groups (CCGs) are mandated to use research evidence effectively to ensure optimum use of resources by the National Health Service (NHS), both in accelerating innovation and in stopping the use of less effective practices and models of service delivery. We intend to evaluate whether access to a demand-led evidence service improves uptake and use of research evidence by NHS commissioners compared with less intensive and less targeted alternatives. Methods/design This is a controlled before and after study involving CCGs in the North of England. Participating CCGs will receive one of three interventions to support the use of research evidence in their decision-making: 1) consulting plus responsive push of tailored evidence; 2) consulting plus an unsolicited push of non-tailored evidence; or 3) standard service unsolicited push of non-tailored evidence. Our primary outcome will be changed at 12 months from baseline of a CCGs ability to acquire, assess, adapt and apply research evidence to support decision-making. Secondary outcomes will measure individual clinical leads and managers’ intentions to use research evidence in decision making. Documentary evidence of the use of the outputs of the service will be sought. A process evaluation will evaluate the nature and success of the interactions both within the sites and between commissioners and researchers delivering the service. Discussion The proposed research will generate new knowledge of direct relevance and value to the NHS. The findings will help to clarify which elements of the service are of value in promoting the use of research evidence. Those involved in NHS commissioning will be able to use the results to inform how best to build the infrastructure they need to acquire, assess, adapt and apply research evidence to support decision-making and to fulfil their statutory duties under the Health and Social Care Act

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Modulation of Neutrophil Function by a Secreted Mucinase of Escherichia coli O157∶H7

Escherichia coli O157∶H7 is a human enteric pathogen that causes hemorrhagic colitis which can progress to hemolytic uremic syndrome, a severe kidney disease with immune involvement. During infection, E. coli O157∶H7 secretes StcE, a metalloprotease that promotes the formation of attaching and effacing lesions and inhibits the complement cascade via cleavage of mucin-type glycoproteins. We found that StcE cleaved the mucin-like, immune cell-restricted glycoproteins CD43 and CD45 on the neutrophil surface and altered neutrophil function. Treatment of human neutrophils with StcE led to increased respiratory burst production and increased cell adhesion. StcE-treated neutrophils exhibited an elongated morphology with defective rear detachment and impaired migration, suggesting that removal of the anti-adhesive capability of CD43 by StcE impairs rear release. Use of zebrafish embryos to model neutrophil migration revealed that StcE induced neutrophil retention in the fin after tissue wounding, suggesting that StcE modulates neutrophil-mediated inflammation in vivo. Neutrophils are crucial innate effectors of the antibacterial immune response and can contribute to severe complications caused by infection with E. coli O157∶H7. Our data suggest that the StcE mucinase can play an immunomodulatory role by directly altering neutrophil function during infection. StcE may contribute to inflammation and tissue destruction by mediating inappropriate neutrophil adhesion and activation

Defective germline reprogramming rewires the spermatogonial transcriptome.

Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia. In both Miwi2-/- and Dnmt3l-/- spermatogonia, the intracisternal-A particle (IAP) family of endogenous retroviruses is derepressed, but, in contrast to meiotic cells, DNA damage is not observed. Instead, we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring genes. Finally, spermatogonial numbers, proliferation and differentiation are altered in Miwi2-/- and Dnmt3l-/- mice. In summary, defective reprogramming deregulates the spermatogonial transcriptome and may underlie spermatogonial dysfunction

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700