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Lisa Jane Brighton,1 Claire M Nolan,2,3 Ruth E Barker,2,4,5 Suhani Patel,2,4 Jessica A Walsh,2 Oliver Polgar,2 Samantha SC Kon,2,4,6 Wei Gao,1 Catherine J Evans,1,7 Matthew Maddocks,1 William DC Man2,4,8,9 1Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, King’s College London, London, UK; 2Harefield Respiratory Research Group, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas NHS Foundation Trust, London, UK; 3Division of Physiotherapy, College of Health, Medicine and Life Sciences, Brunel University London, London, UK; 4National Heart and Lung Institute, Imperial College, London, UK; 5Insight Innovation, Wessex Academic Health Science Network, Southampton, UK; 6Department of Respiratory Medicine, The Hillingdon Hospital NHS Trust, London, UK; 7Brighton General Hospital, Sussex Community NHS Foundation Trust, Brighton, UK; 8Harefield Pulmonary Rehabilitation Unit, Guy’s and St Thomas NHS Foundation Trust, London, UK; 9Faculty of Life Sciences & Medicine, King’s College London, London, UKCorrespondence: Lisa Jane Brighton, Cicely Saunders Institute, Bessemer Road, Denmark Hill, London, SE5 9PJ, UK, Tel +44 020 7848 5041, Email lisa.brighton@kcl.ac.ukBackground: Identifying frailty in people with chronic obstructive pulmonary disease (COPD) is deemed important, yet comparative characteristics of the most commonly used frailty measures in COPD are unknown. This study aimed to compare how the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) characterise frailty in people with stable COPD, including prevalence of and overlap in identification of frailty, disease and health characteristics of those identified as living with frailty, and predictive value in relation to survival time.Methods: Cohort study of people with stable COPD attending outpatient clinics. Agreement between frailty classifications was described using Cohen’s Kappa. Disease and health characteristics of frail versus not frail participants were compared using t-, Mann–Whitney U and Chi-Square tests. Predictive value for mortality was examined with multivariable Cox regression.Results: Of 714 participants, 421 (59%) were male, mean age 69.9 years (SD 9.7), mean survival time 2270 days (95% CI 2185– 2355). Similar proportions were identified as frail using the FFP (26.2%) and SPPB (23.7%) measures; classifications as frail or not frail matched in 572 (80.1%) cases, showing moderate agreement (Kappa = 0.469, SE = 0.038, p < 0.001). Discrepancies seemed driven by FFP exhaustion and weight loss criteria and the SPPB balance component. People with frailty by either measure had worse exercise capacity, health-related quality of life, breathlessness, depression and dependence in activities of daily living. In multivariable analysis controlling for the Age Dyspnoea Obstruction index, sex, BMI, comorbidities and exercise capacity, both the FFP and SPPB had predictive value in relation to mortality (FFP aHR = 1.31 [95% CI 1.03– 1.66]; SPPB aHR = 1.29 [95% CI 0.99– 1.68]).Conclusion: In stable COPD, both the FFP and SPPB identify similar proportions of people living with/without frailty, the majority with matching classifications. Both measures can identify individuals with multidimensional health challenges and increased mortality risk and provide additional information alongside established prognostic variables.Keywords: respiratory disease, chronic obstructive pulmonary disease, frailty, survival

Ruth E Barker,1,2 Lisa J Brighton,3 Matthew Maddocks,3 Claire M Nolan,1,2 Suhani Patel,1 Jessica A Walsh,1 Oliver Polgar,1 Jenni Wenneberg,4 Samantha SC Kon,4 Jadwiga A Wedzicha,2 William DC Man,1,2 Morag Farquhar5 1Harefield Respiratory Research Group, Harefield Hospital, Middlesex, UK; 2National Heart and Lung Institute, Imperial College, London, UK; 3Cicely Saunders Institute of Palliative Care, Policy and Rehabilitation, King’s College London, London, UK; 4The Hillingdon Hospitals NHS Foundation Trust, London, UK; 5School of Health Sciences, University of East Anglia, Norwich, UKCorrespondence: Ruth E BarkerHarefield Respiratory Research Group, Harefield Hospital, Hill End Road, Middlesex, UB9 6JH, United KingdomTel +44 01895 828851Email r.barker2@rbht.nhs.ukBackground: Hospital at home (HaH) schemes allow early discharge of patients hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Traditional outpatient pulmonary rehabilitation (PR) following an AECOPD has an established evidence-base, but there are issues with low referral, uptake and completion. One commonly cited barrier to PR post-hospitalisation relates to poor accessibility. To address this, the aim of this project was to enrol service users (patients with COPD and informal carers) and healthcare professionals to co-design a model of care that integrates home-based exercise training within a HaH scheme for patients discharged from hospital following AECOPD.Methods: This accelerated experience-based co-design project included three audio-recorded stakeholder feedback events, using key “touchpoints” from previous qualitative interviews and a recent systematic review. Audio-recordings were inductively analysed using directed content analysis. An integrated model of care was then developed and finalised through two co-design groups, with the decision-making process facilitated by the tables of changes approach.Results: Seven patients with COPD, two informal carers and nine healthcare professionals (from an existing outpatient PR service and HaH scheme) participated in the stakeholder feedback events. Four key themes were identified: 1) individualisation, 2) progression and transition, 3) continuity between services, and 4) communication between stakeholders. Two patients with COPD, one informal carer and three healthcare professionals participated in the first joint co-design group, with five healthcare professionals attending a second co-design group. These achieved a consensus on the integrated model of care. The agreed model comprised face-to-face supervised, individually tailored home-based exercise training one to three times a week, delivered during HaH scheme visits where possible by a healthcare professional competent to provide both home-based exercise training and usual HaH care.Conclusion: An integrated model of care has been co-designed by patients with COPD, informal carers and healthcare professionals to address low uptake and completion of PR following AECOPD. The co-designed model of care has now been integrated within a well-established HaH scheme.Keywords: COPD, exacerbations, rehabilitation, exercise training, integrated care, co-design

Drug-induced liver injury (DILI) is a problem of increasing significance, but has been a long-standing concern in the treatment of tuberculosis (TB) infection. The liver has a central role in drug metabolism and detoxification, and is consequently vulnerable to injury. The pathogenesis and types of DILI are presented, ranging from hepatic adaptation to hepatocellular injury. Knowledge of the metabolism of anti-TB medications and of the mechanisms of TB DILI is incomplete. Understanding of TB DILI has been hampered by differences in study populations, definitions of hepatotoxicity, and monitoring and reporting practices. Available data regarding the incidence and severity of TB DILI overall, in selected demographic groups, and in those coinfected with HIV or hepatitis B or C virus are presented. Systematic steps for prevention and management of TB DILI are recommended. These include patient and regimen selection to optimize benefits over risks, effective staff and patient education, ready access to care for patients, good communication among providers, and judicious use of clinical and biochemical monitoring. During treatment of latent TB infection (LTBI) alanine aminotransferase (ALT) monitoring is recommended for those who chronically consume alcohol, take concomitant hepatotoxic drugs, have viral hepatitis or other preexisting liver disease or abnormal baseline ALT, have experienced prior isoniazid hepatitis, are pregnant or are within 3 months postpartum. During treatment of TB disease, in addition to these individuals, patients with HIV infection should have ALT monitoring. Some experts recommend biochemical monitoring for those older than 35 years. Treatment should be interrupted and, generally, a modified or alternative regimen used for those with ALT elevation more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms. Priorities for future studies to develop safer treatments for LTBI and for TB disease are presented. [ABSTRACT FROM AUTHOR]

During 1993-2003, incidence of tuberculosis (TB) in the United States decreased 44% and is now occurring at a historic low level (14,874 cases in 2003). The Advisory Council for the Elimination of Tuberculosis has called for a renewed commitment to eliminating TB in the United States, and the Institute of Medicine has published a detailed plan for achieving that goal. In this statement, the American Thoracic Society (ATS), CDC, and the Infectious Diseases Society of America (IDSA) propose recommendations to improve the control and prevention of TB in the United States and to progress toward its elimination. This statement is one in a series issued periodically by the sponsoring organizations to guide the diagnosis, treatment, control, and prevention of TB. This statement supersedes the previous statement by ATS and CDC, which was also supported by IDSA and the American Academy of Pediatrics (AAP). This statement was drafted, after an evidence-based review of the subject, by a panel of representatives of the three sponsoring organizations. AAP, the National Tuberculosis Controllers Association, and the Canadian Thoracic Society were also represented on the panel. This statement integrates recent scientific advances with current epidemiologic data, other recent guidelines from this series, and other sources into a coherent and practical approach to the control of TB in the United States. Although drafted to apply to TB control activities in the United States, this statement might be of use in other countries in which persons with TB generally have access to medical and public health services and resources necessary to make a precise diagnosis of the disease; achieve curative medical treatment; and otherwise provide substantial science-based protection of the population against TB. This statement is aimed at all persons who advocate, plan, and work at controlling and preventing TB in the United States, including persons who formulate public health policy and make decisions about allocation of resources for disease control and health maintenance and directors and staff members of state, county, and local public health agencies throughout the United States charged with control of TB. The audience also includes the full range of medical practitioners, organizations, and institutions involved in the health care of persons in the United States who are at risk for TB. [ABSTRACT FROM AUTHOR]

Context: Isoniazid preventive therapy for latent tuberculosis (TB) infection has been debated because of the risk of hepatotoxicity. The frequency of hepatotoxicity was 0.5% to 2.0% in early studies but may have changed with new criteria for diagnosis and patient selection.Objective: To determine the rate of isoniazid hepatotoxicity in patients managed according to current guidelines and practice standards.Design: Prospective cohort study.Setting: A public health clinic operated by the TB control program of a city-county public health agency.Patients: A total of 11141 consecutive patients who started a regimen of isoniazid preventive therapy for latent TB infection from January 1989 through December 1995.Main Outcome Measures: The rate of developing symptoms and signs of hepatotoxicity among all persons starting isoniazid preventive therapy, among all those completing therapy, and by age, sex, and race.Results: Eleven patients (0.10% of those starting, and 0.15% of those completing treatment) had hepatotoxic reactions to isoniazid during preventive treatment. The rate of hepatotoxicity in persons receiving preventive therapy increased with increasing age (chi2 for linear trend = 5.22, P=.02) and there were trends toward increased rates in women (odds ratio [OR], 3.30; 95% confidence interval [CI], 0.87-12.45; chi2 = 3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; chi2 = 3.08; P=.08).Conclusions: The rate of isoniazid hepatotoxicity during clinically monitored preventive therapy was lower than has been reported previously. Clinicians should have greater confidence in the safety of isoniazid preventive therapy. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle dysfunction is common in COPD. Ultrasound-derived rectus femoris cross-sectional area (RFCSA) is a radiation free, non-invasive measure of muscle bulk that relates to quadriceps strength in people with COPD. However, there are limited longitudinal data for RFCSA, and it is not known whether longitudinal change in RFCSA reflects change in quadricep strength, exercise capacity, lower limb function or muscle mass. We aimed to quantify longitudinal change in ultrasound-derived RFCSA and assess its relationship with change in quadriceps maximal voluntary contraction (QMVC), incremental shuttle walk test (ISWT), five-repetition sit-to-stand (5STS) and fat-free mass (FFM) over 12 months in people with COPD., Methods: We measured ultrasound-derived RFCSA, QMVC, ISWT, 5STS and FFM (measured by bioelectric impedance analysis) at baseline and 12 months in 169 people with stable COPD. Change was correlated using Pearson's or Spearman's coefficients., Results: Baseline characteristics: mean±sd age 70.4±9.4 years; FEV 1 53.3±18.9% predicted. Over the course of 12 months mean RFCSA change was -33.7 mm 2 (99% CI -62.6- -4.9 mm 2 ; p=0.003) representing a mean±sd percentage change of -1.8±33.5%. There was a weak correlation between change in RFCSA and FFM (r=0.205, p=0.009), but not with change in QMVC, ISWT or 5STS., Conclusion: There is a statistically significant decrease in ultrasound-derived RFCSA over 12 months in people with stable COPD, but this decrease does not correlate with change in quadriceps strength, exercise capacity, FFM or lower limb function., Competing Interests: Conflict of interest: T.O. Jenkins reports grants from the Royal Brompton and Harefield Hospital Charity, outside of the submitted work. T.O. Jenkins received funding from the National Institute for Health Research to undertake the submitted work. C.M. Nolan reports grants from the National Institute for Health and Care Research, Royal Brompton and Harefield Hospital Charities, and Brunel University London, outside of the submitted work. M. Maddocks reports grants from the National Institute for Health Research, the European Commission and UKRI Innovate UK, outside of the submitted work. M. Maddocks received funding from the National Institute for Health Research to undertake the submitted work. W.D-C. Man reports grants from the National Institute for Health Research, outside of the submitted work. W.D-C. Man received funding from the Medical Research Council to undertake the submitted work. W-D.C. Man is an Associate Editor of this journal. The remaining authors report no grants outside of the submitted work, or to undertake the submitted work., (Copyright ©The authors 2024.)

Rationale: Standing from a sitting position is an important activity of daily living. The five-repetition sit-to-stand test (5STS) is a simple physical performance test that measures the fastest time taken to stand five times from a chair with arms folded. It can be measured in most healthcare settings and at home, where traditional field walking tests may not be possible. The 5STS has been validated in community-dwelling older adults and people with chronic obstructive pulmonary disease, but data in idiopathic pulmonary fibrosis (IPF) are limited. Objectives: The aims of this cohort study were to establish the construct validity, responsiveness to pulmonary rehabilitation (PR), and minimal important difference (MID) of the 5STS in IPF. Methods: In 149 people with IPF, we compared the 5STS with measures of lung function, exercise capacity, quadriceps strength, breathlessness, and health-related quality of life. Responsiveness and effect sizes were determined by measuring the 5STS before and after PR. The MID was estimated using anchor- and distribution-based methods. Results: The 5STS correlated significantly with incremental shuttle walk test (ISW) ( r  = -0.55), isometric quadriceps maximum voluntary contraction (QMVC) ( r  = -0.45), Medical Research Council dyspnea scale score ( r  = 0.40), Chronic Respiratory Questionnaire-Total ( r  = -0.21), and King's Brief Interstitial Lung Disease Questionnaire-Total ( r  = -0.21) but not forced vital capacity percentage predicted or quadriceps one-repetition maximum (1RM). There was a significant but very weak correlation between change in 5STS and changes in Medical Research Council ( r  = 0.18), ISW ( r  = -0.21), and Chronic Respiratory Questionnaire-Total ( r  = -0.26) but no significant correlation with change in 1RM ( r  = -0.12) or QMVC ( r  = -0.18). 5STS time improved with PR (median [25th percentile, 75th percentile] change, -1.97 [-3.47, -0.62] s; P  < 0.001). The effect size for the 5STS was 0.66 and higher than quadriceps 1RM, QMVC, and ISW. The mean (range) MID estimate was -1.93 (-1.85 to -2.10) seconds. Conclusions: In people with IPF, the 5STS is a valid physical performance measure that is responsive to exercise-based interventions and suitable for use in most healthcare settings.

Background: Remote delivery may improve access to pulmonary rehabilitation (PR). Existing studies are largely limited to individuals with COPD, and the interventions have lacked codesign elements to reflect the needs and experiences of people with chronic respiratory disease, their carers/families and healthcare professionals. The aim of this study was, using experience-based codesign (EBCD), to collaborate with people with interstitial lung disease (ILD), their carers/families and healthcare professionals, to codesign a remote PR programme ready for testing in a future study., Methods: EBCD comprises interviews, stakeholder workshops and codesign meetings. One-to-one videorecorded interviews with purposively selected people with ILD with experience of PR, their carers/families and healthcare professionals, were edited into a 20 min film. The film was shown at three audiorecorded stakeholder feedback events to identify key themes and touchpoints, and short-list key programme components. The programme was finalised at two further codesign workshops., Results: Ten people with ILD, four carers/families and seven healthcare professionals were interviewed. Participants in the codesign workshops included service-user group: n=14 and healthcare professional group: n=11; joint event: n=21. Final refinements were made with small codesign teams, one comprising three people with ILD and one carer/family member, one with five healthcare professionals. The final codesigned model is a group based, supervised programme delivered by videoconference. Key elements of programme specific to ILD include recommendations to ensure participant safety in the context of desaturation risk, dedicated time for peer support and adaption of the education programme for ILD needs, including signposting to palliative care., Conclusion: In this EBCD project, a remote PR programme for people with ILD was codesigned by service-users, their carers/families and multidisciplinary healthcare professionals. Future research should explore the feasibility and acceptability of this intervention., Competing Interests: Competing interests: NS, JG-N, KAI and JH report no competing interests. LJB was funded by an ESRC Post-doctoral fellowship ES/X005259/1 and was supported by the NIHR Applied Research Collaboration South London (NIHR ARC South London) at King’s College Hospital NHS Foundation Trust. CMN reports funding from the Royal Brompton and Harefield Charity, National Institute for Health Research for Patient Benefit and Brunel University London BRIEF award. WD-CM reports grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background and Objective: Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome., Methods: In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event., Results: 4MGS declined over 6 months (mean [95% CI] change: -0.05 [-0.09 to -0.01] m/s; p = 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan-Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >-0.07 m/s versus minor decline/improvers: ≤-0.07 m/s; p = 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23-15.83]). Similar results were observed in multiple imputation analysis., Conclusion: In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Objective: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19., Design: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations., Setting: 64 UK acute hospital Trusts., Participants: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19., Main Outcome Measures: Self-reported swallow, communication, voice and cognitive compromise., Results: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001)., Conclusion: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues., Competing Interests: Competing interests: CEB has a UKRI PHOSP grant through NIHR Nottingham Biomedical Research Centre for support to conduct the PHOSP study, and Nottingham Hospital Trust Charity donations to support her research. JC has grants/contracts with AstraZeneca, Boehringer Ingelheim, Insmed, Gilead Sciences, Grifols and has received consulting fees from AstraZeneca, Boehringer Ingelheim, Insmed, Gilead Sciences, Grifols, Pfizer, Zambon, Antabio, Janssen. LVW holds a UK Research and Innovation GSK/Asthma + Lung UK National Institute of Health Research Grant and Orion Pharma GSK Genentech AstraZeneca research funding and has received consulting fees from Galapagos Boehringer Ingelheim and travel fees from Greentech, is on the advisory board for Galapagos and is the Associate Editor for European Respiratory Journal. MR has received consulting fees from Galapagos Boehringer Ingelheim. ASi received joint funding UKRI & NIHR grant references: MR/V027859/1 and COV031. CB has received UKRI/DHSC PHOSP-COVID grant via NIHR Leicester BRC, grants from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, consultancy paid to institution from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, TEVA. RAE has received NIHR/UKRI/Wolfson Foundation grants, consulting fees from AstraZeneca for long COVID, honoraria payment from Boeringher, support from Chiesi to attend BTS, and is ERS Group 01.02 Pulmonary Rehabilitation Secretary. JKQ is on the Thorax editorial board., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The effect of meditative movement, which includes yoga, tai chi and qi gong, on breathlessness in advanced disease is unknown. This systematic review aims to comprehensively assess the evidence on the effect of meditative movement on breathlessness (primary outcome), health-related quality of life, exercise capacity, functional performance and psychological symptoms (secondary outcomes) in advanced disease. 11 English and Chinese language databases were searched for relevant trials. Risk of bias was assessed using the Cochrane tool. Standardised mean differences (SMDs) with 95% confidence intervals were computed. 17 trials with 1125 participants (n=815 COPD, n=310 cancer), all with unclear or high risk of bias, were included. Pooled estimates (14 studies, n=671) showed no statistically significant difference in breathlessness between meditative movement and control interventions (SMD (95% CI) 0.10 (-0.15-0.34); Chi 2 =30.11; I 2 =57%; p=0.45), irrespective of comparator, intervention or disease category. Similar results were observed for health-related quality of life and exercise capacity. It was not possible to perform a meta-analysis for functional performance and psychological symptoms. In conclusion, in people with advanced COPD or cancer, meditative movement does not improve breathlessness, health-related quality of life or exercise capacity. Methodological limitations lead to low levels of certainty in the results., Competing Interests: Conflict of interest: C.M. Nolan reports personal fees from Novartis, consultancy work (not reimbursed) with Vicore Pharma and grants from the National Institute for Health and Care Research outside the submitted work. W.D-C. Man reports grants from the National Institute for Health and Care Research (NIHR), outside the submitted work. M. Maddocks reports grants from NIHR, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Pulmonary rehabilitation improves mood disorder in COPD, but there are limited data in idiopathic pulmonary fibrosis (IPF). The aims of this cohort study were to investigate whether pulmonary rehabilitation reduces mood disorder in IPF, and estimate the minimal important difference (MID) of the Hospital Anxiety and Depression Scale (HADS)., Methods: HADS and core pulmonary rehabilitation outcomes were measured in 166 participants before and after an 8-week, in-person, outpatient pulmonary rehabilitation programme. Anchor- and distribution-based methods were used to calculate the MID of HADS-Anxiety (A) and HADS-Depression (D)., Results: Suggestive or probable anxiety and depression (HADS ≥8) were present in 35% and 37% of participants, respectively, at baseline, and this reduced significantly following pulmonary rehabilitation (post-pulmonary rehabilitation: HADS-A 23%, HADS-D 26%). Overall, there was a significant reduction in HADS-D (mean change -1.1, 95% CI -1.6- -0.5), but not HADS-A (-0.6, -1.3-0.15) with pulmonary rehabilitation. Subgroup analysis of those with HADS ≥8 revealed significant improvements in HADS domains (mean change: HADS-A -4.5, 95% CI -5.7- -3.4; median change: HADS-D -4.0, interquartile range -6.0- -1.0). The mean (range) MID estimates for HADS-A and HADS-D were -2 (-2.3- -1.7) and -1.2 (-1.9- -0.5), respectively., Conclusion: In people with IPF and suggestive or probable mood disorder, pulmonary rehabilitation reduces anxiety and depression., Competing Interests: Conflict of interest: G.D. Edwards, O. Polgar, S. Patel, R.E. Barker, J.A. Walsh and J. Harvey report no competing interests. Conflict of interest: W.D-C. Man reports personal fees from Jazz Pharmaceuticals, Mundipharma and Novartis, grants from Pfizer, nonfinancial support from GSK, and grants from the National Institute for Health Research and British Lung Foundation, outside the submitted work; and is an associate editor of this journal. Conflict of interest: C.M. Nolan reports personal fees from Novartis and consultancy work (not reimbursed) with Vicore Pharma outside the submitted work., (Copyright ©The authors 2023.)

Introduction: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group., Methods and Analysis: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care., Ethics and Dissemination: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority., (© 2023. The Author(s).)

Like many communities across the United States, St. Louis, Missouri, faces stark inequities in health outcomes, including wellness, quality of life, and life expectancy. These inequities are the result of social systems and policies that have robbed generations of St. Louisans of opportunity. BJC HealthCare's (BJC's) commitment to becoming a catalyst for community health by helping to eliminate health disparities led to the launch of its community health improvement strategy. This article details the community-driven and evidence-informed process that BJC used to create a multiyear, proactive approach to addressing the social and economic factors that are the root causes of health inequities. It examines areas of opportunity through which the strategy will drive change and explores lessons learned and promising practices for other healthcare institutions to consider as they advance health equity., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Foundation of the American College of Healthcare Executives.)

Introduction: Breathing pattern disorder (BPD) is an abnormal breathing pattern associated with biochemical, biomechanical and psychophysiological changes. While physiotherapy is often offered, limited evidence-based therapies for BPD are available. Music therapy-based singing exercises have been shown to improve quality of life for individuals with respiratory conditions and may also be beneficial for individuals living with BPD. No study has previously compared these participatory interventions in the treatment of people living with BPD., Methods and Analysis: This is a study protocol for an assessor blinded 1:1 randomised controlled trial and qualitative interview study. Forty participants aged 18-40 years who score at least 19 on the Nijmegen Questionnaire (NQ) and do not have any underlying respiratory conditions will be recruited. Participants will be randomised to receive either physiotherapy-led or music therapy-led breathing exercises for 6 weeks. The primary outcome will be between-group difference in NQ post-intervention. Semistructured interviews with a purposive sample of participants will be performed. Qualitative data will be analysed using thematic analysis to better understand participants' intervention and trial experiences., Ethics and Dissemination: This study has received ethical approval by Brunel University London College of Health, Medicine and Life Science's Research Ethics Committee (32483-MHR-Mar/2022-38624-3). The anonymised completed dataset will be made available as an open-access file via Brunel University London Figshare and the manuscript containing anonymised patient data will be published in an open-access journal., Trial Registration Number: This trial is registered on the Open Science Framework Registry (https://osf.io/u3ncw)., Competing Interests: Competing interests: CMN declares personal fees from Novartis outside of this work. Other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms., Methods: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators., Results: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes., Conclusions: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant., (© 2022. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison with COPD, remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program and to determine whether pulmonary rehabilitation is associated with survival in IPF., Research Question: Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are noncompletion of or nonresponse to pulmonary rehabilitation, or both, associated with 1-year all-cause mortality in IPF?, Study Design and Methods: Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred for pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over 1 year after pulmonary rehabilitation discharge. Cox proportional hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality., Results: Similar pulmonary rehabilitation completion rates (IPF, 69%; COPD, 63%; P = .24) and improvements in exercise response were observed in both groups with no significant mean between-group differences in incremental shuttle walk test (ISWT) change (mean, 2 m [95% CI, -18 to 22 m]). Pulmonary rehabilitation noncompletion (hazard ratio [HR], 5.62 [95% CI, 2.24-14.08]) and nonresponse (HR, 3.91 [95% CI, 1.54-9.93]) were associated independently with increased 1-year all-cause mortality in IPF., Interpretation: This real-word study demonstrated that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation compared with a matched group of patients with COPD. In IPF, noncompletion of and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Genomic imprinting occurs in therian mammals and is a phenomenon whereby the two alleles of a gene are differentially expressed, based on the sex of the parent from whom the alleles were inherited. The allelic differences in expression are the consequence of different epigenetic modifications that are established in the sperm or oocyte during gametogenesis and transmitted at fertilization to offspring. A small minority of genes is regulated in this way but they have important biological functions, and aberrant regulation of imprinted genes contributes to disease aetiology in humans and other animals. The factors driving the evolution of imprinted genes are also of considerable interest, as these genes appear to forego the benefits of diploidy. To broaden the phylogenetic analysis of genomic imprinting, we began a study of imprinted genes in the domestic dog, Canis familiaris. In this report, we show that canine IGF2 and H19 are imprinted, with parent-of origin-dependent monoallelic expression patterns in neonatal umbilical cord. We identify a putative imprint control region associated with the genes, and provide evidence for differential methylation of this region in a somatic tissue (umbilical cord) and for its hypermethylation in the male germline. Canis familiaris is fast becoming a highly informative system for elucidating disease processes and evolution, and the study of imprinted genes in this species may help in understanding how these genes contribute to the generation of morphological and behavioral diversity., (© 2021 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)

Objective: We previously demonstrated low levels of digital literacy amongst pulmonary rehabilitation service-users prior to the COVID-19 pandemic. We aimed to identify whether the pandemic accelerated digital literacy in this population, resulting in greater acceptance of remote web-based pulmonary rehabilitation programme models., Methods: We surveyed digital access and behaviours and pulmonary rehabilitation delivery preferences of service-users referred to pulmonary rehabilitation in 2021 (cohort 2021) and propensity score-matched them to a cohort who completed the survey in 2020 (cohort 2020)., Results: There were indicators that digital access and confidence were better amongst the Cohort 2021 but no difference was seen in the proportion of patients choosing remote web-based pulmonary rehabilitation as an acceptable method of receiving pulmonary rehabilitation., Conclusion: In an unselected cohort of service-users, remote web-based pulmonary rehabilitation was considered acceptable in only a minority of patients which has implications on healthcare commissioning and delivery of pulmonary rehabilitation.

Background: The 4-m gait speed (4MGS) test is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD)., Methods: 213 participants hospitalised with AECOPD (52% male, mean age 72 years and mean forced expiratory volume in 1 s (FEV 1 ) 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 year after discharge and multivariable Cox proportional hazards regressions were performed. Kaplan-Meier and competing risks analyses were conducted comparing time to all-cause readmission and mortality between 4MGS quartiles., Results: 111 participants (52%) were readmitted and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797-0.945; p=0.001) per 0.1 m·s -1 increase in gait speed, and with all-cause mortality, with an adjusted subdistribution hazard ratio of 0.747 (95% CI 0.622-0.898; p=0.002) per 0.1 m·s -1 increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV 1 % pred alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80, respectively. Kaplan-Meier and competing risks curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log-rank, both p<0.001)., Conclusions: 4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support., Competing Interests: Conflict of interest: R.E. Barker has nothing to disclose. Conflict of interest: S.S.C. Kon has nothing to disclose. Conflict of interest: S.E. Jones has nothing to disclose. Conflict of interest: W. Banya has nothing to disclose. Conflict of interest: C.M. Nolan reports personal fees from Novartis, outside the submitted work. Conflict of interest: S. Patel has nothing to disclose. Conflict of interest: O. Polgar has nothing to disclose. Conflict of interest: B.M. Haselden has nothing to disclose. Conflict of interest: M.I. Polkey reports personal fees for consultancy from Philips and JFD, grants from GSK, outside the submitted work. Conflict of interest: P. Cullinan has nothing to disclose. Conflict of interest: W.D-C. Man reports grants from the Medical Research Council UK, during the conduct of the study; grants from the National Institute for Health Research, British Lung Foundation and Pfizer, personal fees from Jazz Pharmaceuticals, Mundipharma and Novartis, nonfinancial support from GSK, outside the submitted work. Conflict of interest: J.A. Walsh has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Pulmonary rehabilitation (PR), an exercise and education programme for people with chronic lung disease, aims to improve exercise capacity, breathlessness and quality of life. Most evidence to support PR is from trials that use specialist exercise equipment, for example, treadmills (PR-gym). However, a significant proportion of programmes do not have access to specialist equipment with training completed with minimal exercise equipment (PR-min). There is a paucity of robust literature examining the efficacy of supervised, centre-based PR-min. We aim to determine whether an 8-week supervised, centre-based PR-min programme is non-inferior to a standard 8-week supervised, centre-based PR-gym programme in terms of exercise capacity and health outcomes for patients with chronic lung disease., Methods and Analysis: Parallel, two-group, assessor-blinded and statistician-blinded, non-inferiority randomised trial. 436 participants will be randomised using minimisation at the individual level with a 1:1 allocation to PR-min (intervention) or PR-gym (control). Assessment will take place pre-PR (visit 1), post-PR (visit 2) and 12 months following visit 1 (visit 3). Exercise capacity (incremental shuttle walk test), dyspnoea (Chronic Respiratory Questionnaire (CRQ)-Dyspnoea), health-related quality of life (CRQ), frailty (Short Physical Performance Battery), muscle strength (isometric quadriceps maximum voluntary contraction), patient satisfaction (Global Rating of Change Questionnaire), health economic as well as safety and trial process data will be measured. The primary outcome is change in exercise capacity between visit 1 and visit 2. Two sample t-tests on an intention to treat basis will be used to estimate the difference in mean primary and secondary outcomes between patients randomised to PR-gym and PR-min., Ethics and Dissemination: London-Camden and Kings Cross Research Ethics Committee and Health Research Authority have approved the study (18/LO/0315). Results will be submitted for publication in peer-reviewed journals, presented at international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders., Trial Registration Number: ISRCTN16196765., Competing Interests: Competing interests: CMN reports fees from Novartis outside of this research. MM consultancy fees from Fresenius Kabi and Helsinn, grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work. WM reports personal fees from Jazz Pharmaceuticals, personal fees from Mundipharma, personal fees from Novartis, grants from Pfizer, non-financial support from GSK, grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Total thyroxine (T4) concentrations are lower in healthy greyhounds compared to most other non-sighthound breeds. In humans, variations in the structure or concentration of the major thyroid hormone binding proteins are responsible for most reported differences between total T4 concentrations in healthy individuals from different ethnic groups or other subpopulations. The aim of this study was to determine if such variations are also responsible for the lower total T4 concentrations in greyhounds. The predicted protein sequences of thyroxine-binding globulin (TBG), transthyretin and albumin were determined in liver tissue from a euthyroid greyhound with decreased T4 concentration and a Jack Russell terrier using reverse-transcriptase PCR. Sequences were compared to each other and online reference sequences. Serum proteins from 21 greyhounds and 21 non-sighthound dogs were separated by denaturing electrophoresis and immunoblots probed with polyclonal antibodies to human TBG and transthyretin. Reactive bands were quantified by densitrometry, expressed relative to the mean of reference samples included in each gel. Serum albumin concentrations were measured using a commercially-available assay. Several SNPs were identified but none was thought likely to explain the lower total T4 concentrations in greyhounds. There was no significant difference between the quantity of any of the binding proteins in serum from greyhounds and non-sighthound dogs. However, total T4 and transthyretin concentrations were highly correlated in the greyhound group (r = 0.73, P = 0.0002). Variation in the sequence of thyroid hormone binding proteins is not responsible for low greyhound total T4 concentrations. Further evaluation of the role of transthyretin is warranted., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the acceptability of neuromuscular electrical stimulation (NMES) of the quadriceps muscles in people with idiopathic pulmonary fibrosis (IPF) and to identify whether a future definitive trial is feasible., Design: A randomised, parallel, two-group, participant and assessor-blinded, placebo-controlled feasibility trial with embedded qualitative interviews., Setting: Outpatient department, Royal Brompton and Harefield Hospitals., Participants: Twenty-two people with IPF: median (25th, 75th centiles) age 76 (74, 82) years, forced vital capacity 62 (50, 75) % predicted, 6 min walk test distance 289 (149, 360) m., Interventions: Usual care (home-based exercise, weekly telephone support, breathlessness management leaflet) with either placebo or active NMES for 6 weeks, with follow-up at 6 and 12 weeks., Primary Outcome Measures: Feasibility of recruitment and retention, treatment uptake and adherence, outcome assessments, participant and outcome assessor blinding and adverse events related to interventions., Secondary Outcome Measures: Outcome measures with potential to be primary or secondary outcomes in a definitive clinical trial. In addition, purposively sampled participants were interviewed to capture their experiences and acceptability of the trial., Results: Out of 364 people screened, 23 were recruited: 11 were allocated to each group and one was withdrawn prior to randomisation. Compared with the control group, a greater proportion of the intervention group completed the intervention, remained in the trial blinded to group allocation and experienced intervention-related adverse events. Assessor blinding was maintained. The secondary outcome measures were feasible with most missing data associated with the accelerometer. Small participant numbers precluded identification of an outcome measure suitable for a definitive trial. Qualitative findings demonstrated that trial process and active NMES were acceptable but there were concerns about the credibility of placebo NMES., Conclusions: Primarily owing to recruitment difficulties, a definitive trial using the current protocol to evaluate NMES in people with IPF is not feasible., Trial Registration Number: NCT03499275., Competing Interests: Competing interests: CMN reports receiving fees from Novartis, outside of this work. PMG reports fees, honoraria and grants from Roche Pharmaceuticals, Boehringer Ingelheim, Cippla and Brainomix. EAR reports lecture and/or advisory board fees and/or grants from Roche Pharmaceuticals and Boehringer Ingelheim. AUW reports speaking and consultancy fees from Roche and Boehringer Ingelheim. PLM reports receiving fees from AstraZeneca, Boehringer Ingelheim and Hoffman-La Roche, outside the submitted work. VK reports fees from Roche, outside the submitted work. FC reports fees from Boehringer Ingelheim and Roche, outside the submitted work. TMM has, via his institution, received industry-academic funding from AstraZeneca and GlaxoSmithKline R&D and has received consultancy or speaker fees from AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, Galecto, GlaxoSmithKline R&D, Indalo, IQVIA, Pliant, Respivant, Roche and Theravance. WDCM reports personal fees from Jazz Pharmaceuticals, personal fees from Mundipharma, personal fees from Novartis, grants from Pfizer, non-financial support from GSK, grants from National Institute for Health Research, grants from British Lung Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)