SPACE FOR COPD© delivered as a maintenance programme on Pulmonary Rehabilitation discharge::protocol of a randomised controlled trial evaluating the long-term effects on exercise tolerance and mental well-being

Introduction The benefits achieved during pulmonary rehabilitation (PR) are known to be sustained for 6–12 months after the initial programme. Several maintenance trials have been conducted but were heterogeneous in terms of duration, frequency and labour cost. There is no consensus on one best strategy. SPACE FOR COPD (Self-management Programme of Activity, Coping and Education for Chronic Obstructive Pulmonary Disease) is a home-based self-management programme, which has been shown previously to be effective in primary and secondary care settings and is to be tested here as a maintenance programme. The aim is to evaluate the efficacy of the SPACE FOR COPD programme (manual and group sessions), on exercise tolerance and mental well-being, compared with usual care following PR in patients with COPD. Methods and analysis A prospective, multicentre, single-blinded randomised controlled trial requiring 116 participants with a clinical diagnosis of COPD who have finished PR within 4 weeks will be randomised 1:1 to either a usual care group or a SPACE FOR COPD programme group. The intervention comprises a home-based manual and 4, 2-hour group sessions adopting motivational interviewing techniques over 12 months. The primary outcome is endurance capacity measured by the Endurance Shuttle Walking Test at 12 months. Secondary outcomes are: maximal exercise capacity, health-related quality of life, mood, patient activation, physical activity, lung function and healthcare costs. The measures will be taken at baseline, 6 and 12 months. Patient interviews and staff focus groups will be conducted to explore barriers, facilitators and views about the intervention at the end of the study. A framework analysis will be used for the interpretation of qualitative data. Ethics and dissemination The trial was granted ethical approval from Health Research Authority and Health and Care Research Wales (HCRW19/EM/0267 on 10 October 2019). Results will be made available to all stakeholders through a dissemination event, conferences and peer-reviewed publications. Trial registration number ISRCTN30110012

Web-based cardiac REhabilitatioN alternative for those declining or dropping out of conventional rehabilitation : results of the WREN feasibility randomised controlled trial

Introduction Cardiac rehabilitation (CR) is typically delivered in hospital-based classes and is recommended to help people reduce their risk of further cardiac events. However, many eligible people are not completing the programme. This study aimed to assess the feasibility of delivering a web-based CR intervention for those who decline/drop out from usual CR. Intervention A web-based CR programme for 6 months, facilitated with remote support. Methods Two-centre, randomised controlled feasibility trial. Patients were randomly allocated to web-based CR/usual care for 6 months. Data were collected to inform the design of a larger study: recruitment rates, quality of life (MacNew), exercise capacity (incremental shuttle walk test) and mood (Hospital Anxiety and Depression Scale). Feasibility of health utility collection was also evaluated. Results 60 patients were randomised (90% male, mean age 62±9 years, 26% of those eligible). 82% completed all three assessment visits. 78% of the web group completed the programme. Quality of life improved in the web group by a clinically meaningful amount (0.5±1.1 units vs 0.2±0.7 units: control). Exercise capacity improved in both groups but mood did not change in either group. It was feasible to collect health utility data. Conclusions It was feasible to recruit and retention to the end of the study was good. The web group reported important improvements in quality of life. This intervention has the opportunity to increase access to CR for patients who would otherwise not attend. Promising outcomes and recruitment suggest feasibility for a full-scale trial. Trial registration number 1072679

Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction:multicentre, open label, randomised controlled trial

OBJECTIVE: To assess the clinical effectiveness of septoplasty.DESIGN: Multicentre, randomised controlled trial.SETTING: 17 otolaryngology clinics in the UK's National Health Service.PARTICIPANTS: 378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score &gt;30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale).INTERVENTIONS: Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex.MAIN OUTCOME MEASURES: The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures.RESULTS: Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P&lt;0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections.CONCLUSIONS: Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum.TRIAL REGISTRATION: ISRCTN Registry ISRCTN16168569.</p

Evidence for exercise-based interventions across 45 different long-term conditions: an overview of systematic reviews

Background: Almost half of the global population face significant challenges from long-term conditions (LTCs) resulting in substantive health and socioeconomic burden. Exercise is a potentially key intervention in effective LTC management. Methods: In this overview of systematic reviews (SRs), we searched six electronic databases from January 2000 to October 2023 for SRs assessing health outcomes (mortality, hospitalisation, exercise capacity, disability, frailty, health-related quality of life (HRQoL), and physical activity) related to exercise-based interventions in adults (aged &gt;18 years) diagnosed with one of 45 LTCs. Methodological quality was assessed using AMSTAR-2. International Prospective Resister of Systematic Reviews (PROSPERO) ID: CRD42022319214. Findings: Forty-two SRs plus three supplementary RCTs were included, providing 990 RCTs in 936,825 people across 39 LTCs. No evidence was identified for six LTCs. Predominant outcome domains were HRQoL (82% of SRs/RCTs) and exercise capacity (66%); whereas disability, mortality, physical activity, and hospitalisation were less frequently reported (≤25%). Evidence supporting exercise-based interventions was identified in 25 LTCs, was unclear for 13 LTCs, and for one LTC suggested no effect. No SRs considered multimorbidity in the delivery of exercise. Methodological quality varied: critically-low (33%), low (26%), moderate (26%), and high (12%). Interpretation: Exercise-based interventions improve HRQoL and exercise capacity across numerous LTCs. Key evidence gaps included limited mortality and hospitalisation data and consideration of multimorbidity impact on exercise-based interventions

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial

Introduction: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes. Methods and analysis: A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention. Ethics and dissemination: The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public. Trial registration number: ISRCTN68786622. Protocol version 2.0 (16 May 2023)

Outcome measures in a combined exercise rehabilitation programme for adults with COPD and chronic heart failure : A preliminary stakeholder consensus event

Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders (n = 18) were asked to (1) rank in order of importance a list of categories, (2) prioritise outcome measures and (3) prioritise baseline patient evaluation measures that should be assessed in a combined COPD and CHF rehabilitation programme. The tasks were completed anonymously and related to clinical rehabilitation programmes and associated research. Health-related quality of life, exercise capacity and symptom evaluation were voted as the most important categories to assess for clinical purposes (median rank: 1, 2 and 3 accordingly) and research purposes (median rank; 1, 3 and 4.5 accordingly) within combined exercise rehabilitation. All stakeholders agreed that profiling symptoms at baseline were 'moderately', 'very' or 'extremely' important to assess for clinical and research purposes in combined rehabilitation. Profiling of frailty was ranked of the same importance for clinical purposes in combined rehabilitation. Stakeholders identified a suite of multidisciplinary measures that may be important to assess in a combined COPD and CHF exercise rehabilitation programme

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Web-Based Self-management Program (SPACE for COPD) for Individuals Hospitalized With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Nonrandomized Feasibility Trial of Acceptability

BackgroundHospital admissions due to the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are costly for individuals and health services. Pulmonary rehabilitation (PR) is known to reduce hospital readmissions when delivered after hospitalization, but the uptake and completion of PR following hospitalization remains poor (<10% of those eligible in the UK audit data). A web-based platform of the SPACE (Self-management Program of Activity Coping and Education) for COPD (chronic obstructive pulmonary disease) has previously shown promising results in patients with stable COPD but has not been tested following an AECOPD. ObjectiveThis study aims to assess the feasibility and acceptability of a web-based self-management program. MethodsA nonrandomized feasibility study for patients with confirmed AECOPD who were deemed web literate was conducted. All patients consented during their hospitalization and received access to the website following discharge in addition to usual care. The program aims to facilitate patients to better understand and manage their condition through education and home-based exercises. Participants were asked to complete the Bristol COPD Knowledge Questionnaire at baseline and after 6 months. A total of 14 participants were also interviewed (n=8 completers; n=6 noncompleters) regarding their experiences with the web-based program and trial. The interviews were analyzed using thematic analysis. ResultsIn total, 2080 patients were screened for eligibility, of which 100 patients (age: mean 71.2 years, SD 9.3 years; male: 55/100, 55%; forced expiratory volume in 1 second/forced vital capacity ratio: mean 0.46, SD 0.14; pack-years: mean 50.2, SD 31.0; current smokers: 35/100, 35%) were recruited (4.8% of those screened). The main reason for ineligibility was a lack of web literacy (1366/1980, 68.98%). In total, 18% (18/100) of patients had completed the web program by 6 months, with others still registered in the program (27/100, 27%), and more than half did not register (55/100, 55%). There was a mean change in Bristol COPD Knowledge Questionnaire scores at 6 months of 7.8 (SD 10.2) points. Qualitative interviews identified three main themes: preparing for, engagement with, and benefits of the study and program. A total of 57% (57/100) accepted a referral to PR on discharge and 19% (19/100) had completed the program after 6 months. ConclusionsOn the basis of the challenges of recruiting, retaining, and engaging participants in a web-based self-management program, it is not a feasible approach to roll out widely. This study acknowledges that this is a challenging time for patients with an AECOPD to engage in exercise and self-management education. However, for patients who were able to engage in such an intervention, the completion rate of PR was double the previous audit estimates from the United Kingdom, disease knowledge improved, and the intervention was of value to patients. Trial RegistrationISRCTN Registry 13081008; https://www.isrctn.com/ISRCTN1308100