The treatment of disabling intermittent claudication in patients with superficial femoral artery occlusive disease—Decision analysis

ObjectiveTo determine the preferred approach to superficial femoral artery (SFA) revascularization of Trans-Atlantic Inter-Societal Consensus (TASC) B and C lesions in claudicants requiring intervention based on a review of published data.DesignDecision analysis, Markov state transition model.SubjectsHypothetical cohorts of claudicants with TASC B or TASC C superficial femoral artery lesions considered candidates for either angioplasty with selective stenting (PTA/S) or greater saphenous vein bypass (GSVB).Main outcome measureQuality adjusted life years (QALYs).ResultsFor a 65-year-old man with disabling claudication, percutaneous transluminal angioplasty and selective stenting (PTA/S) was preferred over GSVB for a TASC B SFA lesion. In an otherwise identical patient with a TASC C lesion, bypass was the preferred therapy. Treating PTA/S failures with subsequent bypass increased the utility of PTA/S but bypass remained the preferred initial therapy for TASC C lesions. Sensitivity analysis showed that PTA/S surpasses bypass efficacy for TASC C lesions if PTA/S primary patency is >32% at 5 years, patient age is >80 years, or GSVB operative mortality is > 6%.ConclusionPTA/S is the preferred initial therapy over GSVB for TASC B SFA lesions in patients with disabling intermittent claudication who require intervention. Given contemporary published outcomes for TASC C lesions, GSVB is the preferred therapy in operative candidates. In elderly patients or patients at high risk for bypass, PTA/S should be considered over GSVB. Improved technology that results in a 5-year primary patency of 32% would also justify PTA/S for TASC C SFA lesions

Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1

Acknowledgements This work was supported by grants from the Wellcome Trust (200855/Z/16/Z) to MFN and the BBSRC (BB/V010107/1) to MFN and BV. The authors thank Innes Jarmson for the generation of adeno-associated viruses.Peer reviewedPublisher PD

Development of the Carers’ Alert Thermometer (CAT) to identify family carers struggling with caring for someone dying at home: a mixed method consensus study

Background: There is an increasing international policy direction to promote home death for dying patients which will impact on the demands placed on family carers. The early identification of carer needs and appropriate intervention can help avoid crisis situations for the carer and avoidable hospital admissions which are reported to be a global concern. The aim of the study was to explore what professionals and carers of patients with cancer and advanced progressive illness, in their last year of life, find burdensome and to develop an alert system for use by non-specialist staff. Methods: A mixed-method, multi-phased, consensus study sequentially utilising qualitative and quantitative data to develop and pilot the Carers’ Alert Thermometer (CAT). 245 people (117 carers and 128 professionals) participated in the study across a range of health and social care settings in the North West of England (2011–2014). Results: A number of key domains were identified and prioritised by consensus for inclusion in the CAT. The 8 domains fit within two overarching themes of the reported carer experience; the support needed by the carer to provide care and the support needed for the carer’s own health and well-being. The resultant CAT is an evidence-based alert thermometer consisting of 10 questions, guidance on the possible actions for each alert and space for an action plan to be jointly agreed by the assessor and carer. Preliminary piloting of the CAT has shown it to be valued, fit for purpose and it can be administered by a range of personnel. Conclusions: The CAT enables the identification of current and potential future needs so a proactive approach can be taken to supporting the carer as their role develops over time, with a view to enhancing their well-being and preventing avoidable hospital admissions; ultimately supporting patient choice to remain in their own home

Position statement and considerations for remotely delivered pulmonary rehabilitation services.

Statement and methods of development The challenge of access to pulmonary rehabilitation (PR) and meeting associated service demand is certainly not new. However, the COVID-19 pandemic set an unprecedented challenge evoking rapid adaptation of services. An inherent spotlight has been placed on remotely delivered services. As we look beyond the height of this pandemic, it is important to reflect and consider what has been learnt, and emerging perspectives on the future of PR service delivery. This document updates the ‘ACPRC statement and considerations for the remote delivery of pulmonary rehabilitation services during the COVID-19 pandemic’ (1) and seeks to provide pragmatic practical guidance for remotely delivered models of PR for healthcare professionals that should be used alongside local guidance. The recommendations provided are for guidance only, and may be updated in response to further national guidelines and new evidence. An online survey of PR healthcare professionals (ACPRC pulmonary rehabilitation provision during COVID-19 and beyond!) was conducted in the development of this document to scope current practice in PR services across the U.K. Informed by queries received by the ACPRC, the survey was first conducted in 2020 and repeated in July 2021 with the aim of capturing a snapshot of practice, one-year post onset of the COVID-19 pandemic. The survey was publicised and disseminated via Twitter using the @theACPRC handle, with request that one team member completed on behalf of their service. A summary of the 21 responses can be found in Appendix 1 which served to inform the content of this document. A literature review was undertaken to identify and integrate relevant published trials since the 2021 Cochrane review of telerehabilitation for people with chronic respiratory disease (2). Details of the search strategy can be found in Appendix 2 and summary of study characteristics and outcomes in Appendix 3. Anonymous feedback from four PR services was collated and analysed to identify common themes in experiences of remotely delivered PR services. A summary of this process and collated feedback can be found in Appendix 4. Key terms Remotely delivered models – the delivery of pulmonary rehabilitation services at a distance; the interaction between healthcare professional and participant using communication and information technologies, that may take place in real-time (synchronously) or asynchronously (1). It may be delivered by a virtual platform, an online web application or programme, or referred to as telerehabilitation (note: this terminology is used where studies have reported it). Field walking tests are commonly employed to evaluate exercise capacity, prescribe exercise, and evaluate treatment response in chronic respiratory diseases (3). The most valid, reliable and responsive ones are the six-minute walk test (6MWT), incremental (ISWT) and endurance walk test (ESWT). NACAP – the National Asthma and COPD Audit Programme is commissioned by the Healthcare Quality Improvement Partnership (HQIP), as part of the National Clinical Audit and Patient Outcomes Programme (NCAPOP), and currently covers England and Wales. The programme is led by the Royal College of Physicians (RCP) and includes a pulmonary rehabilitation workstream. PRSAS – the Pulmonary Rehabilitation Services Accreditation Scheme was launched in April 2018, and is run by the Royal College of Physicians (RCP)

Reducing risk with e-based support for adherence to lifestyle change in hypertension (REACH): Protocol for a multicentred randomised controlled trial

Introduction: Web-based lifestyle counselling designed to improve adherence to self-management behaviours for diet, exercise and medication has been shown to reduce blood pressure (BP). However, the long-term clinical outcome of these interventions is not established. Our aim was to establish whether an e-counselling program is independently associated with improved clinical outcomes over a 12-month period, as defined by the following criteria: (1) reduction of systolic BP, diastolic BP, pulse pressure and associated risk factors for cardiovascular events; and (2) adherence to self-management behaviour (diet, exercise, smoke-free living and prescribed medication). Methods and analysis: Reducing risk with e-based support for adherence to lifestyle change in hypertension is a two-parallel group, double-blind randomised controlled trial that will utilise a two (Groups: e-counselling vs control) by three (assessment intervals: baseline, 4-month and 12-month outcome) design. BP, lipoprotein cholesterol, physical activity and dietary behaviours and psychological distress will be measured at each assessment. We plan to recruit 528 participants (35-74 years of age) diagnosed with stage 1 or 2 hypertension (systolic BP, 140-180 mm Hg; diastolic BP 90-110 mm Hg) from three major cities (Toronto, London, Vancouver) and one rural area (Grey Bruce region) across Canada between February 2012 and July 2015. Controls will receive general educational e-messages on heart healthy living and the e-counselling group will receive tailored e-messages that are matched to their stage of readiness for change. For both groups, e-messages will be sent proactively on a weekly basis during months 1-4, then bi-weekly during months 5-8 and then monthly during months 9-12. Ethics and dissemination: Ethical approval has been obtained from all recruitment sites. This will be one of the first studies to evaluate the long-term efficacy of preventive e-counselling strategies for cardiovascular disease prevention in patients with hypertension. Findings from this study will be used to guide the ongoing development of e-counselling services

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen