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Design: This randomised crossover trial compared nocturnal auto-adjusting continuous positive airway pressure (APAP) and nocturnal oxygen therapy (NOT) in adults and children with sickle cell anaemia, with patient acceptability as the primary outcome. Secondary outcomes included pulmonary physiology (adults), safety, and daily pain during interventions and washout documented using tablet technology.Methods: Inclusion criteria were age > 8 years and the ability to use an iPad to collect daily pain data. Trial participation was 4 weeks; week 1 involved baseline data collection and week 3 was a washout between interventions, which were administered for 7 days each during weeks 2 and 4 in a randomised order. Qualitative interviews were transcribed verbatim and analysed for content using a funnelling technique, starting generally and then gaining more detailed information on the experience of both interventions. Safety data included routine haematology and median pain days between each period. Missing pain day values were replaced using multiple imputation.Results: Ten adults (three female, median age 30.2 years, range 18-51.5 years) and eleven children (five female, median age 12 years, range 8.7-16.9 years) enrolled. Nine adults and seven children completed interviews. Qualitative data revealed that the APAP machine was smaller, easier to handle, and less noisy. Of 16 participants, 10 preferred APAP (62.5%, 95% confidence interval (CI) 38.6-81.5%). Haemoglobin decreased from baseline on APAP and NOT (mean difference -3.2 g/L (95% CI -6.0 to -0.2 g/L) and -2.5 g/L (95% CI -4.6 to 0.3 g/L), respectively), but there was no significant difference between interventions (NOT versus APAP, 1.1 (-1.2 to 3.6)). Pulmonary function changed little. Compared with baseline, there were significant decreases in the median number of pain days (1.58 for APAP and 1.71 for NOT) but no significant difference comparing washout with baseline. After adjustment for carry-over and period effects, there was a non-significant median difference of 0.143 (95% CI -0.116 to 0.401) days additional pain with APAP compared with NOT.Conclusion: In view of the point estimate of patient preference for APAP, and no difference in haematology or pulmonary function or evidence that pain was worse during or in washout after APAP, it was decided to proceed with a Phase II trial of 6 months APAP versus standard care with further safety monitoring for bone marrow suppression and pain.Trial Registration: ISRCTN46078697 . Registered on 18 July 2014. [ABSTRACT FROM AUTHOR]

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations., Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings., Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care., Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size., Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions., Competing Interests: The study design, data gathering, data analysis, results and interpretation were carried out independently by the authors who declare that the source of funding has not led to any competing or conflicting interests. AstraZeneca reviewed the manuscript for medical and scientific accuracy. EA reports that Aquarius received funding for their company to do the research and their company has received funding for other projects relating to COPD and respiratory conditions from grants and commercial contracts (including AstraZeneca which funded the project in question). Outside of the submitted work, TW reports receiving consulting fees and/or fees for attending lectures, meetings and conferences and/or travel expenses and/or research grants from My mhealth, AstraZeneca, GlaxoSmithKline, Synairgen, Bergenbio, UCB, UKRI, NIHR, Valneva, OM Pharma, Boehringer Ingelheim, Roche, Chiesi, Teva and Nutricia. TW is a founder, director and shareholder of My mhealth. TW has served on monitoring boards for trials sponsored by Synairgen and Valneva, and has applied for patents with GlaxoSmithKline and My mhealth. HW reports receiving consulting fees and/or fees/honoraria for attending/presenting lectures, meetings and conferences and/or travel expenses and/or grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Bayer, GlaxoSmithKline and Veronapharma. HW has served on monitoring boards for AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Bayer and GlaxoSmithKline. MB reports receiving consulting fees and/or fees/honoraria for attending/presenting lectures, meetings and conferences and/or travel expenses and/or grants from AstraZeneca, GlaxoSmithKline, Pfizer, Sanofi, Covis, Grifols, Boehringer Ingelheim, Valeo, The Lung Association of Saskatchewan, Alberta Lung and NWT, CIHR, Alberta Innovates, Novartis and Mereo. MB has a leadership or fiduciary role in the Canadian Thoracic Society and Alberta Health Services. CL reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, and Pfizer, grants from Ontario Ministry of Health and Canadian Institutes of Health Research and personal fees from GSK, Valeo, Teva and Covis, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Adams et al.)

Background: Sickle cell anaemia (SCA) is an inherited disorder of haemoglobin. Patients experience long-term health care problems, affecting quality of life (QOL) including frequent acute pain, which is difficult to document in trials except as hospital admissions. Pilot data suggests that overnight respiratory support, either supplementary oxygen or auto-adjusting continuous positive airways pressure (APAP), is safe and may have clinical benefit. This pilot trial aims to determine which intervention is more acceptable to participants and whether there are other advantages of one over the other, e.g. in respiratory function or haematological parameters, before conducting the Phase 2 trial of overnight respiratory support funded by the National Institutes of Health Research., Methods/design: This is a pilot cross-over interventional trial with the order of interventions decided by simple randomization. Ten adults (age over 18 years) and 10 children (aged between 8 and 18 years) with homozygous sickle cell disease (haemoglobin SS, HbSS), recruited regardless of symptoms of sleep-disordered breathing, will undergo overnight pulse oximetry and will have two interventions, overnight oxygen and APAP, for a week each in randomised order with a washout week between interventions. Participants will complete online diaries via an iPad throughout the 29 days of the study and will complete QOL questionnaires and have measurement of haematology, biochemistry, spirometry and lung volumes (adults only) at 3 time points, at baseline and after each intervention, as well as in-depth semi-structured qualitative interviews after each intervention, carried out by an experienced psychologist. Both qualitative and statistical methods will be used to analyze the data. The primary outcome is qualitative data looking at participant experience from the transcribed interviews after each intervention. The participant's view on feasibility, acceptability and preference will specifically be explored. The QOL, laboratory and lung function data will be compared with baseline for each arm., Discussion: Patient and public involvement is an integral part of this trial and the key outcome is the qualitative result, which is dependent on obtaining good quality data to advise on participant feasibility, acceptability and preference. This is being addressed by using a standard interview. The development of a pain endpoint is another important outcome and collecting daily measurements is likely to be challenging. Research results will be used to inform design of the Phase 2 trial., Trial Registration: ISRCTN46078697 18 July 2014.