Lingual Ischemia from Prolonged Insertion of a Fastrach Laryngeal Mask Airway

We report a case of lingual ischemia and swelling in an elderly stroke patient from prolonged insertion of a FastrachTM Laryngeal Mask Airway ® following a failed Emergency Department intubation. Simple suggestions to mitigate such injury are provided

(Re)conceptualising physical activity participation as career

Physical activity is increasingly positioned as playing an important role in preventing and mitigating many of the decrements associated with biological ageing. As a result, public health messages encourage older people to remain active in later life. Despite this, physical activity participation rates among older adults are low. This may be in part related to the conventional approach to understanding physical activity participation as a product of motivation. We contend that this approach does not allow for a deeper exploration of the wider structural, historical and discursive contexts in which physical activity participation occurs. Therefore, we propose that physical activity can be reconceptualised as a career. Through a synthesis of findings from four studies exploring physical activity experiences in later life, we demonstrate that beginning and maintaining a physical activity career requires a disposition towards physical activity, the legitimation of physically active practices and dealing with contingencies. In addition, we demonstrate that maintaining a physical activity career requires investment and deliberation to adapt physical activity practices continually within an individual's own personal biography. As such, we conclude that current strategies to promote physical activity to older adults are unlikely to result in increased levels of participation. To promote physical activity to older adults an understanding of how structural, cultural and historical contexts influence participation is needed

The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. Methods: RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Discussion: Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN Registration: ISRCTN14813929 (22/04/2021)

The effect of frailty on survival in patients with COVID-19 (COPE) : a multicentre, European, observational cohort study

Peer reviewedPublisher PD

Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with Covid-19

Acknowledgement We acknowledge the dedication, commitment, and sacrifice of the staff from participating centres across UK and Italy, two among the most severely affected countries in Europe. We gratefully acknowledge the contribution of our collaborators, National Institute of Health Research (NIHR), Health Research Authority (HRA) in the UK and Ethics Committee of Policlinico Hospital Modena, which provided rapid approval of COPE study and respective Institutions’ Research and Development Offices and Caldicott Guardians for their assistance and guidance. We also thank COPE Study Sponsor, Cardiff University, Wales, UK.Peer reviewedPublisher PD

Paternal effect on genomic activation, clinical pregnancy and live birth rate after ICSI with cryopreserved epididymal versus testicular spermatozoa

<p>Abstract</p> <p>Background</p> <p>This study takes an in depth look at embryonic development, implantation, pregnancy and live birth rates with frozen epididymal and testicular sperm from obstructed (OA) and non-obstructed (NOA) patients.</p> <p>Methods</p> <p>Paternal effect of sperm source on zygote formation, embryonic cleavage, and genomic activation were examined. Additional outcome parameters monitored were clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate.</p> <p>Results</p> <p>In this report, we retrospectively analyzed 156 ICSI cycles using cryopreserved epididymal sperm (ES; n = 77) or testicular sperm (TESE; n = 79). The developmental potential of embryos did not appear to be influenced by the type of surgically retrieved sperm. The average number of blastomeres observed on Day 3 was not different among different groups; 7.5 +/- 1.7 (ES), 7.6 +/- 2.1 (TESE-OA) and 6.5 +/- 2.3 (TESE-NOA). Compaction and blastulation rates, both indicators of paternal genomic activation, were similar in embryos derived from ICSI with ES or TESE from OA as well as NOA men. The only parameter significantly affected in NOA-TESE cases was the fertilization rate. CPR and IR with cryopreserved TESE (TESE-OA 59%, 34%, and TESE-NOA 37%, 20%) were also not statistically different, from that achieved with cryopreserved ES (61% and 39%). Live birth rates also appeared to be independent of sperm type. The 87 clinical pregnancies established using cryopreserved TESE and ES, resulted in the birth of 115 healthy infants. No congenital anomalies were noted.</p> <p>Conclusion</p> <p>Zygotic activation seems to be independent of sperm origin and type of azoospermia.</p

The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study

Background The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. Methods This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). Findings Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. Interpretation In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19

The RELIEF feasibility trial: Topical lidocaine patches in older adults with rib fractures

Background: Lidocaine patches, applied over rib fractures, may reduce pulmonary complications in older patients. Known barriers to recruiting older patients in emergency settings necessitate a feasibility trial. We aimed to establish whether a definitive randomised controlled trial (RCT) evaluating lidocaine patches in older patients with rib fracture(s) was feasible. Methods: This was a multicentre, parallel-group, open-label, feasibility RCT in seven hospitals in England and Scotland. Patients aged ≥65 years, presenting to ED with traumatic rib fracture(s) requiring hospital admission were randomised to receive up to 3×700 mg lidocaine patches (Ralvo), first applied in ED and then once daily for 72 hours in addition to standard care, or standard care alone. Feasibility outcomes were recruitment, retention and adherence. Clinical end points (pulmonary complications, pain and frailty-specific outcomes) and patient questionnaires were collected to determine feasibility of data collection and inform health economic scoping. Interviews and focus groups with trial participants and clinicians/research staff explored the understanding and acceptability of trial processes. Results: Between October 23, 2021 and October 7, 2022, 206 patients were eligible, of whom 100 (median age 83 years; IQR 74–88) were randomised; 48 to lidocaine patches and 52 to standard care. Pulmonary complications at 30 days were determined in 86% of participants and 83% of expected 30-day questionnaires were returned. Pulmonary complications occurred in 48% of the lidocaine group and 59% in standard care. Pain and some frailty-specific outcomes were not feasible to collect. Staff reported challenges in patient compliance, unfamiliarity with research measures and overwhelming the patients with research procedures. Conclusion: Recruitment of older patients with rib fracture(s) in an emergency setting for the evaluation of lidocaine patches is feasible. Refinement of data collection, with a focus on the collection of pain, frailty-specific outcomes and intervention delivery are needed before progression to a definitive trial. Trial registration number: ISRCTN14813929

Protocol for the development of a multidisciplinary clinical practice guideline for the care of patients with chronic subdural haematoma

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.</p

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