Sally J. Singh

Background: There are known benefits for National Health Service (NHS) organisations when staff are research-active including better patient outcomes, positive staff experience and retention. However there are known individual and organisational barriers which may hinder participation in research. The aim of this work was to baseline research culture in National Institute for Health and Care Research (NIHR) infrastructure staff (and wider partners) in Leicester and to specifically: - Identify training needs to develop a responsive training programme.- Map career pathways and development opportunities.- Explore barriers to research. Methods: This study received approval from the local audit team and comprised of two surveys conducted; across two separate data collection periods, Survey 1: specifically for directly funded NIHR Leicester Biomedical Research Centre (BRC) and Clinical Research Facility (CRF) staff. Survey 2: open to all staff at BRC partner organisations. The survey was sent via email/ posters and contained a link to a Research Electronic Data Capture (REDCap) data collection tool. The data were extracted from REDCap for descriptive analysis and reported as frequencies/ percentages. Results: 111 individuals completed survey 1 in full and 287 completed survey 2. Nearly 80% of respondents either agreed or strongly agreed that there was good access to training and development opportunities from survey 1 respondents. However, 35% of respondents either disagreed or strongly disagreed that there were opportunities for funding to attend conferences and external meetings. Employer support was largely positive for survey 2 responses with only 9% saying that their employer did not support training/ development. Career pathway data was variable with around a third disagreeing that research career pathways were clear. Around 20% of people wanted to pursue a clinical academic career in the future. Respondents reported that they would like training in similar areas in both surveys (e.g. securing research funding and analysing qualitative research data). Conclusions: Our results show that academic or clinical academic roles feature in many respondents’ career aspirations. However, career pathway responses and development opportunities were variable. Many barriers to research were evident including intrinsic and extrinsic factors, which are consistent with current literature. Trial registration: n/a

Background: Acute COVID-19 alters the airway microbiota. Whether these changes persist post-COVID-19 and contribute to long COVID is unknown. We aimed to describe the microbiota by long COVID severity and subtype, and identify links with inflammation. Methods: Adults were prospectively recruited to the longitudinal UK Post-hospitalisation COVID-19 study (PHOSP-COVID). Patients were grouped by previously described “severity clusters” (of ongoing health impairments) and symptom subgroups. Oral and sputum microbiota (at 6 months post-discharge) were characterised through 16S ribosomal RNA gene amplicon sequencing, and microbiota diversity was assessed. Co-occurrence network analysis identified keystone taxa. Associations between keystone taxa and plasma inflammatory proteins were assessed through Spearman's rank correlations. Results: 771 participants had their microbiota assessed. Of participants with oral rinses and “severity cluster” assignment (mean age 57.5 years), 278 out of 722 (38.5%) were women. The “very severe” cluster, in which disease was predominantly pulmonary in nature, was associated with a distinct microbiota profile post-COVID-19. Reduced lung function was associated with a distinct oral microbiota profile. Persistent neurocognitive symptoms were associated with a distinct oral microbiota profile, while gastrointestinal symptoms were associated with a distinct sputum microbiota profile. Microbiota keystone taxa shifted to a higher prevalence of lactic acid bacteria associated with worse health outcomes. Lactic acid bacteria abundance was associated with elevated blood inflammatory proteins. Conclusion: Distinct oral and sputum microbiota profiles were associated with pulmonary function and with neurocognitive and gastrointestinal symptoms in long COVID. Shifts in keystone microbiota taxa linked with inflammation, based on worse health outcomes, suggest a potential role change for lactic acid bacteria, which may be associated with the host immune response.

The purpose of the document is to provide commissioners, service providers and individuals with a guide to the minimum standards of care that participants attending pulmonary rehabilitation should expect, together with measures of good practice.

Introduction: Multiple long-term conditions (MLTCs), defined as the co-existence of two or more chronic health conditions, are increasingly prevalent across all age groups and disproportionately affect socioeconomically disadvantaged and ethnic minority populations. Trials targeting MLTCs face methodological challenges due to patient heterogeneity, variation in selection of conditions and limitations in design and analysis. These challenges may contribute to the lack of evidence to inform effective interventions for people with MLTCs. This study aims to systematically identify and prioritise key methodological uncertainties in the design, conduct and analysis of future trials aiming to improve health outcomes for people with MLTCs. Methods: We will conduct a four-round modified Delphi study involving key interest groups including methodologists, trialists, MLTC researchers, research funders, commissioners, regulators, people with MLTC lived experience and MLTC carers. The process will include two rounds of online questionnaires, one lived-experience meeting (in-person or virtual) and a final virtual consensus meeting. To promote inclusivity and diversity of input, participants may join at any stage. Responses from each round will be analysed and summarised to inform the next stage, with final priorities agreed through structured consensus voting. Expected Outcomes: This consensus study will produce a ranked list of methodological research uncertainties to guide future research and clinical trial design, conduct and analysis in MLTCs. Findings will be disseminated through a facilitated online dissemination workshop, academic channels and targeted public engagement activities to support inclusive and relevant MLTC research.

Background: Physical inactivity is a risk factor for severe COVID-19 and often worsens after hospitalisation. Clinicians need quick, accurate assessments to target interventions. We aimed to assess the validity of the General Practice Physical Activity Questionnaire (GPPAQ) in adults recovering one year after COVID-19 hospitalisation . Methods: Post-hospitalisation for COVID-19, adults attended a one-year-visit and completed the GPPAQ Physical Activity Index (PAI-4 active), 14-day wrist-worn accelerometry (Moderate-Vigorous PA [MVPA]- active), and other health outcomes. Validity was examined via : (i) internal consistency (factor analysis); (ii) measurement invariance across sex, age, and ethnicity using differential item functioning (DIF); (iii) convergent validity (GPPAQ sensitivity/specificity versus accelerometry); and (iv) construct validity (correlations with health outcomes). Results: 752 participants had GPPAQ and accelerometry (265 female, mean± sd age 60.9±11.6 years, MVPA 18.75 min·day ⁻¹ (IQR 7.55, 36.11), PAI-1 46.8%, PAI-2 15.6%, PAI-3 19.4%, PAI-4 18.2%. Factor analyses supported good internal consistency with two factors (daily activities, physical exercise). Confirmatory factor Index (CFI) showed excellent fit (CFI 0.965). DIF indicated moderate variability by sex and age. GPPAQ-PAI showed limited sensitivity (26.3%) for correctly classifying physically active individuals, but higher specificity (88.4%) for classifying physical inactivity, and weak-to-moderate correlations with health outcomes. Conclusions: GPPAQ demonstrates internal consistency, with construct and convergent validity in adults 1-year post-COVID-19 hospitalisation. GPPAQ effectively identifies inactive individuals to support clinical care; however, its sensitivity suggests underestimation of activity relative to accelerometry. Future pathways should combine GPPAQ with device-based assessment to optimise evaluation of physical activity to guide pulmonary rehabilitation and targeted interventions.

Introduction The benefits of pulmonary rehabilitation (PR) decline after 6–12 months. Previous studies of maintenance in the literature have been labour-intensive and concentrated on secondary care healthcare utilisation only. We aimed to investigate whether Self-management Programme of Activity, Coping and Education (SPACE) for chronic obstructive pulmonary disease (COPD), a light-touch self-management programme, was clinically and cost-effective following PR. Methods We conducted a prospective, multicentre, assessor-blind randomised controlled trial. Patients with COPD were randomised 1:1 to usual care (control) or SPACE. The intervention included a home-based manual and four facilitated group sessions, delivered over 12 months. Primary outcome: Endurance Shuttle Walking Test at 12 months. Secondary outcomes: maximal exercise capacity, mood, patient activation, physical activity, healthcare costs and health-related quality-of-life (HRQoL). Results 116 participants were recruited (October 2019–June 2022). Baseline characteristics: SPACE (65% male, aged 71.8 years, median Medical Research Council (MRC) 3, mean pack years 41.1, mean body mass index (BMI) 29.1), control (51% male, aged 71.8 years, median MRC 3, mean pack years 44.5, mean BMI 28.3). SPACE completion rate=83% and intervention fidelity (assessed via checklist) was excellent. No statistically significant differences at 12 months for primary and secondary outcomes. Economic analysis at 12 months shows a positive HRQoL difference between groups of 0.0871 quality adjusted life years (QALY) and reduced National Health Service (NHS) costs of £139 per participant, driven primarily by a reduction in general practitioner visits in favour of SPACE. Conclusions Endurance exercise tolerance was maintained in both groups. The programme improved HRQoL at 12 months in the intervention group (above control) and was cost-effective, driven by reduced primary care costs.

Purpose: Pulmonary rehabilitation (PR) is recommended internationally for individuals with chronic obstructive pulmonary disease (COPD), but there is limited evidence and practice of PR in Sri Lanka. Key challenges for PR such as poor accessibility, uptake and completion need to be addressed when designing and delivering new PR programmes. Accordingly, this study determined the feasibility and acceptability of culturally adapted PR for adults with COPD in Sri Lanka. Patients and Methods: A randomized controlled feasibility trial was conducted with 50 adults living with COPD in Colombo, Sri Lanka. A culturally adapted PR comprised a 6-week rolling programme with sessions conducted twice every week. Sessions involved endurance and resistance exercise training, education and cultural adaptations of nutritional support and group singing. The control group received usual care, which did not include any form of PR or exercise training. Feasibility was determined by uptake (≥ 60% of eligible participants consented) and completion (≥ 70% of recruited participants). Acceptability was explored by focus group discussions (FGDs) analysed thematically. Results: Seventy-nine eligible individuals (94% of screened) were referred in order to recruit 50 participants (63% uptake). The majority of participants in both intervention (72%, n=18) and control (64%, n=16) groups completed the study. Based on qualitative focus group discussions four themes emerged: (1) Increased knowledge following PR, including dispelling misbeliefs about COPD and improving medication adherence; (2) Perceived improvements in health following PR, including improved walking ability and reduced breathlessness (3) Enjoyment and benefits of cultural adaptations to PR, and (4) Challenges during PR, including adherence to exercise and travel requirements. Conclusion: Culturally adapted PR was feasible and acceptable to adults with COPD in Sri Lanka. A fully powered trial is warranted for evaluating clinical and cost-effectiveness of culturally adapted PR.

Introduction: Following completion of Pulmonary Rehabilitation (PR), the biopsychosocial benefits often decline. PR maintenance is recommended to extend the benefits; however, detail lacks on what this should entail. SPACE for COPD© is a light touch, evidenced-based self-management intervention which we tested as a maintenance strategy during the COVID-19 pandemic. We explored the acceptability of SPACE for COPD© as a maintenance option following PR for both patients and facilitators using qualitative research methods. Methods: We conducted semi-structured interviews and focus groups with patients and intervention facilitators involved in the SPACE for COPD© maintenance study. These were audio recorded, transcribed verbatim and analysed using Framework Analysis. Results: Seventeen patients were interviewed; 13 (76.5%) of which were programme completers: five (29.4%) received a group-based intervention, four (23.5%) received one-to-one, and eight (47.1%) received hybrid. Two focus groups were conducted with eight facilitators; six (75%) were physiotherapists, one (12.5%) was a nurse, and one (12.5%) was a health psychologist. Analysis generated six themes: (1) the changing structure of maintenance SPACE for COPD©; (2) the integral role of the facilitator; (3) engagement with the manual required time and commitment from patients; (4) staying active on maintenance SPACE for COPD© was facilitated by goal setting and exercise; (5) biopsychosocial outcomes of maintenance SPACE for COPD©; and (6) the future of maintenance SPACE for COPD©. Conclusion: Maintenance SPACE for COPD© was acceptable and could be implemented into the PR healthcare pathway during the COVID-19 pandemic. It helped patients to adopt and integrate new exercise habits if they could adapt and personalise these to their home lives. Adaptions made during the COVID-19 pandemic created a menu of options. Building upon this personalisation is required to ensure the intervention is accessible and patient-centred.

Background: In primary ciliary dyskinesia (PCD), impaired mucociliary clearance leads to respiratory infections. Whilst forced expiratory volume in 1 s (FEV ₁ ) is commonly used to evaluate lung function in PCD its sensitivity to detect abnormalities in mild disease is limited. This study explores the utility of ¹²⁹ Xe ventilation and ¹ H anatomical magnetic resonance imaging (MRI) to assess lung health in children with PCD. Methods: This prospective cohort study assessed clinically stable children with PCD (aged 5–18 years) using ¹²⁹ Xe MRI, ¹ H MRI and spirometry during one session. Ventilation defect percentage (VDP) was the primary metric calculated from ¹²⁹ Xe MRI. Results: 35 children were assessed (mean± sd age 12.3±3.3 years, FEV ₁ z-score −1.5±1.7). Most children had visible ventilation abnormalities and 82.8% had an abnormal ¹²⁹ Xe VDP (median (interquartile range) ¹²⁹ Xe VDP 6.3% (1.3–16.1%)). 16 participants had a normal FEV ₁ (z-score > −1.6); however, 12 of these individuals had abnormal ¹²⁹ Xe VDP. ¹ H MRI found 55.9% participants had a region of collapse, 61.3% had bronchiectasis and 50.0% had evidence of air trapping. Conclusions: ¹²⁹ Xe MRI can identify early lung function abnormalities in children with PCD and demonstrates that the extent of ventilation distribution abnormalities in PCD varies between individuals. ¹ H MRI provides complementary diagnostic information on structural abnormalities.

Rationale: Tuberculosis (TB) is a major worldwide cause of disability, with TB survivors experiencing significant and often under-recognised burden, and approximately half going on to develop post-tuberculosis lung disease (PTLD). Pulmonary rehabilitation may offer effective disease management but there is a lack of evidence in PTLD populations. Objectives: We aimed to determine the clinical and cost effectiveness of pulmonary rehabilitation for adults living with PTLD in Kyrgyzstan. Methods: A single-blind randomised controlled trial, conducted March 2021 to June 2022 in Bishkek, Kyrgyzstan, compared supervised PR to usual care for adults living with PTLD. Participants were randomised (1:1) to receive either usual care (control) or culturally adapted pulmonary rehabilitation (intervention), comprising individually prescribed and tailored exercise and self-management education. The primary outcome was change in maximal exercise capacity, measured by the incremental shuttle walking test (ISWT), from baseline to the end of 6-weeks of pulmonary rehabilitation, analysed by intention-to-treat analysis. Secondary outcomes included health-related quality of life (HRQoL) and cost-effectiveness analysis. Results: 114 participants (mean ± SD 43.3 ± 15.2 years, 57% male) received either supervised pulmonary rehabilitation or usual care. Compared with the control group, changes in exercise capacity and HRQoL from baseline were significantly greater in the intervention group (ISWT: 123.0 m, 95%CI 81.2-164.8, P < .001; EQ-5D-5L VAS: 20.2, 95% CI 15.5-24.9, P < .0001). The intervention group saw a significant increase in quality-adjusted life years (QALYs) over the control group (0.2 [95%CI 0.1-0.2]). We calculated a total programme cost of U.S.$5,686.5 (U.S.$95 per patient who received pulmonary rehabilitation), giving a programme cost, after adjusting for purchasing power, of U.S.$2,143.2 per QALY [95%CI 1,621.9-2,663.9]. Conclusions: In adults with PTLD in Kyrgyzstan, a culturally adapted pulmonary rehabilitation programme significantly improved exercise capacity and HRQoL compared with usual care and was both clinically and cost effective.