Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: A prospective cohort study.

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.

Twenty-seven-gauge vitrectomy: a consecutive, single-centre case series with exclusive use over a 4-year period.

BACKGROUND: To assess the safety and effectiveness of the exclusive use of 27-gauge instruments for all vitreoretinal diseases requiring vitrectomy. METHODS: In this retrospective study, 1020 consecutive surgeries were performed on 958 eyes of 848 patients using 27-gauge instruments from March 2017 to June 2021. Patients with a minimum follow-up of 3 months were included. Surgical case-mix, best-corrected visual acuity (BCVA), intraocular pressure (IOP), intra- and post-operative complications, and surgery times were recorded. RESULTS: The study patients were followed up for averagely 11 months. Of the 1020 vitrectomies, 958 were primary procedures. Of the 148 retinal detachment (RD) cases, 138 (93%) required a single vitrectomy. Primary macular hole closure was achieved in 143 of 145 (99%) cases. The average surgical times were 55 and 38 min for RD surgeries and for all other indications, respectively. BCVA improved significantly at the final visit (20/49) compared with the pre-operative visit (20/78) (p < 0.01). IOP was similar at the pre-operative (14.8mmHg) and final (14.3mmHg) visits. Complications recorded include transient hypotony in 39 eyes, iatrogenic retinal breaks in 2 eyes, and a vitreous bleed in 1 other eye. CONCLUSION: This study revealed that 27-gauge vitrectomy instruments can be used for a wide range of indications, with exclusive use in certain settings. The outcomes were similar to other gauges, including for rhegmatogenous retinal detachment, with minimal complications.

Exploration of Novel Scaffolds Targeting Cytochrome b of Pyricularia oryzae.

The fulfilment of the European "Farm to Fork" strategy requires a drastic reduction in the use of "at risk" synthetic pesticides; this exposes vulnerable agricultural sectors-among which is the European risiculture-to the lack of efficient means for the management of devastating diseases, thus endangering food security. Therefore, novel scaffolds need to be identified for the synthesis of new and more environmentally friendly fungicides. In the present work, we employed our previously developed 3D model of P. oryzae cytochrome bc1 (cyt bc1) complex to perform a high-throughput virtual screening of two commercially available compound libraries. Three chemotypes were selected, from which a small collection of differently substituted analogues was designed and synthesized. The compounds were tested as inhibitors of the cyt bc1 enzyme function and the mycelium growth of both strobilurin-sensitive (WT) and -resistant (RES) P. oryzae strains. This pipeline has permitted the identification of thirteen compounds active against the RES cyt bc1 and five compounds that inhibited the WT cyt bc1 function while inhibiting the fungal mycelia only minimally. Serendipitously, among the studied compounds we identified a new chemotype that is able to efficiently inhibit the mycelium growth of WT and RES strains by ca. 60%, without inhibiting the cyt bc1 enzymatic function, suggesting a different mechanism of action.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

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.

Digital habits of pulmonary rehabilitation service-users following the COVID-19 pandemic.

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.

COPD discharge bundle and pulmonary rehabilitation referral and uptake following hospitalisation for acute exacerbation of COPD.

Pulmonary rehabilitation (PR) following hospitalisations for acute exacerbation of COPD (AECOPD) is associated with improved exercise capacity and quality of life, and reduced readmissions. However, referral for, and uptake of, post-hospitalisation PR are low. In this prospective cohort study of 291 consecutive hospitalisations for AECOPD, COPD discharge bundles delivered by PR practitioners compared with non-PR practitioners were associated with increased PR referral (60% vs 12%, p<0.001; adjusted OR: 14.46, 95% CI: 5.28 to 39.57) and uptake (40% vs 32%, p=0.001; adjusted OR: 8.60, 95% CI: 2.51 to 29.50). Closer integration between hospital and PR services may increase post-hospitalisation PR referral and uptake.

Supervised pulmonary rehabilitation using minimal or specialist exercise equipment in COPD: a propensity-matched analysis.

BACKGROUND: Many trials supporting the benefits of pulmonary rehabilitation (PR) have used specialist exercise equipment, such as treadmills and cycle ergometers. However, access to specialist equipment may not be feasible in some settings. There is growing interest in delivering PR programmes with minimal, low-cost equipment, but uncertainty remains regarding their efficacy compared with programmes using specialist equipment. METHODS: Using propensity score matching, 318 consecutive patients with COPD undergoing supervised PR using minimal equipment (PR-min) were compared 1:1 with a control group of 318 patients with COPD who underwent supervised PR using specialist equipment (PR-gym). A non-inferiority analysis was performed for the primary outcome (incremental shuttle walk (ISW)) and secondary outcomes (Chronic Respiratory Disease Questionnaire (CRQ)-domain and total scores). RESULTS: Similar improvements in ISW and CRQ-domains were observed in PR-min and PR-gym groups (mean difference ISW: 3 m (95% CI -16 to 9); CRQ-total: 0.9 (95% CI -2.7 to 4.5)). The 95% CI between group differences for ISW and CRQ-total did not cross the predefined non-inferiority margins. However, completion rates were lower in PR-min compared with PR-gym (64% vs 73%; p=0.014). CONCLUSIONS: In patients with COPD, PR delivered using minimal equipment produces clinically significant benefits in exercise capacity and health-related quality of life that are non-inferior to rehabilitation delivered using specialist equipment. This study provides support for the provision of PR using minimal exercise equipment, particularly in areas where access to specialist exercise equipment is limited.

Gait speed and adverse outcomes following hospitalised exacerbation of COPD.

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 (FEV1) 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 FEV1 % 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.

The Effects of a Video Intervention on Posthospitalization Pulmonary Rehabilitation Uptake. A Randomized Controlled Trial.

Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted.Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake.Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV1 % predicted, frailty, transport availability, and previous PR experience.Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV1% predicted, 36 [interquartile range, 27-48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively (P = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video.Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion.

Digital habits of PR service-users: Implications for home-based interventions during the COVID-19 pandemic.

Remote models of pulmonary rehabilitation (PR) are vital with suspension of face-to-face activity during the COVID-19 pandemic. We surveyed digital access and behaviours and PR delivery preferences of current PR service users. There was significant heterogeneity in access to and confidence in using the Internet with 31% having never previously accessed the Internet, 48% confident using the Internet and 29% reporting no interest in accessing any component of PR through a Web-based app. These data have implications for the remote delivery of PR during the COVID-19 pandemic and raise questions about the current readiness of service users to adopt Web-based delivered models of PR.

Anxiety and depression in bronchiectasis: Response to pulmonary rehabilitation and minimal clinically important difference of the Hospital Anxiety and Depression Scale.

The aims of the study were to evaluate the responsiveness of Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale and HADS-Depression (HADS-D) subscale to pulmonary rehabilitation (PR) in patients with bronchiectasis compared to a matched group of patients with chronic obstructive pulmonary disease (COPD) and provide estimates of the minimal clinically important difference (MCID) of HADS-A and HADS-D in bronchiectasis. Patients with bronchiectasis and at least mild anxiety or depression (HADS-A ≥ 8 or/and HADS-D ≥ 8), as well as a propensity score-matched control group of patients with COPD, underwent an 8-week outpatient PR programme (two supervised sessions per week). Within- and between-group changes were calculated in response to PR. Anchor- and distribution-based methods were used to estimate the MCID. HADS-A and HADS-D improved in response to PR in both patients with bronchiectasis and those with COPD (median (25th, 75th centile)/mean (95% confidence interval) change: HADS-A change: bronchiectasis -2 (-5, 0), COPD -2 (-4, 0); p = 0.43 and HADS-D change: bronchiectasis -2 (-2 to -1), COPD -2 (-3 to -2); p = 0.16). Using 26 estimates, the MCID for HADS-A and HADS-D was -2 points. HADS-A and HADS-D are responsive to PR in patients with bronchiectasis and symptoms of mood disorder, with an MCID estimate of -2 points.

Home versus outpatient pulmonary rehabilitation in COPD: a propensity-matched cohort study.

Home-based exercise has been proposed as an equivalent treatment strategy to supervised outpatient pulmonary rehabilitation (PR), but it is not known whether its implementation into clinical practice produces similar benefits to those observed in trials. We compared the real-world responses of 154 patients with COPD undergoing home-based exercise with a matched group attending supervised PR. We observed smaller improvements in exercise capacity with home-based exercise compared with PR, but similar improvements in quality of life. We propose that supervised PR remains the standard of care, with home-based exercise a less effective alternative for those unable to attend PR.

Gait speed and prognosis in patients with idiopathic pulmonary fibrosis: a prospective cohort study.

The 4-m gait speed (4MGS), a simple physical performance measure and surrogate marker of frailty, consistently predicts adverse prognosis in older adults. We hypothesised that 4MGS could predict all-cause mortality and nonelective hospitalisation in patients with idiopathic pulmonary fibrosis (IPF).4MGS and lung function were measured at baseline in 130 outpatients newly diagnosed with IPF. Survival status and nonelective hospital admissions were recorded over 1 year. We assessed the predictive value of 4MGS (as a continuous variable and as a binary variable: slow versus preserved 4MGS) by calculating hazard ratios using Cox proportional regression, adjusting for potential confounding variables. Receiver operating characteristic curves assessed discrimination between the multivariable regression models and established prognostic indices.Continuous 4MGS and slow 4MGS were independent predictors of all-cause mortality (4MGS: HR 0.03, 95% CI 0.01-0.31; p=0.004; slow 4MGS: 2.63, 95% CI 1.01-6.87; p=0.049) and hospitalisation (4MGS: HR 0.02, 95% CI 0.01-0.14; p<0.001; slow 4MGS: 2.76, 95% CI 1.16-6.58; p=0.02). Multivariable models incorporating 4MGS or slow 4MGS had better discrimination for predicting mortality than either the gender, age and lung physiology index or Composite Physiologic Index.In patients with IPF, 4MGS is an independent predictor of all-cause mortality and nonelective hospitalisation.

Pulmonary rehabilitation in bronchiectasis: a propensity-matched study.

International guidelines recommend pulmonary rehabilitation for patients with bronchiectasis, supported by small trials and data extrapolated from chronic obstructive pulmonary disease (COPD). However, it is unknown whether real-life data on completion rates and response to pulmonary rehabilitation are similar between patients with bronchiectasis and COPD.Using propensity score matching, 213 consecutive patients with bronchiectasis referred for a supervised pulmonary rehabilitation programme were matched 1:1 with a control group of 213 patients with COPD. Completion rates, change in incremental shuttle walk (ISW) distance and change in Chronic Respiratory Disease Questionnaire (CRQ) score with pulmonary rehabilitation were compared between groups.Completion rate was the same in both groups (74%). Improvements in ISW distance and most domains of the CRQ with pulmonary rehabilitation were similar between the bronchiectasis and COPD groups (ISW distance: 70 versus 63 m; CRQ-Dyspnoea: 4.8 versus 5.3; CRQ-Emotional Function: 3.5 versus 4.6; CRQ-Mastery: 2.3 versus 2.9; all p>0.20). However, improvements in CRQ-Fatigue with pulmonary rehabilitation were greater in the COPD group (bronchiectasis 2.1 versus COPD 3.3; p=0.02).In a real-life, propensity-matched control study, patients with bronchiectasis show similar completion rates and improvements in exercise and health status outcomes as patients with COPD. This supports the routine clinical provision of pulmonary rehabilitation to patients with bronchiectasis.

King's Brief Interstitial Lung Disease questionnaire: responsiveness and minimum clinically important difference.

Health status is increasingly used in clinical practice to quantify symptom burden and as a clinical trial end-point in patients with interstitial lung disease (ILD). The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a brief, validated 15-item, disease-specific, health-related quality of life questionnaire that is increasingly used in clinical trials, but little data exist regarding the minimum clinically important difference (MCID). Using pulmonary rehabilitation as a model, we aimed to determine the responsiveness of KBILD and provide estimates of the MCID.KBILD scores, Chronic Respiratory Questionnaire (CRQ) scores, Medical Research Council (MRC) Dyspnoea score and incremental shuttle walk test (ISWT) distance were measured in 209 patients with ILD (105 with idiopathic pulmonary fibrosis (IPF)) before and after an outpatient pulmonary rehabilitation programme. Changes with intervention and Cohen's effect size were calculated. Anchor-based (linear regression and receiver operating characteristic plots) or distribution-based approaches (0.5 sd and standard error of measurement) were used to estimate the MCID of KBILD domain and total scores.KBILD, CRQ, MRC Dyspnoea and ISWT improved with intervention, and the effect sizes of KBILD domain and total scores ranged from 0.28 to 0.38. Using anchor-based estimates, the MCID estimates for KBILD-Psychological, KBILD-Breathlessness and activities, and KBILD-Total were 5.4, 4.4 and 3.9 points, respectively. Using distribution-based methods, the MCID estimate for KBILD-Chest symptoms was 9.8 points. The MCID estimates for KBILD in IPF patients were similar.In patients with ILD and IPF, KBILD is responsive to intervention with an estimated MCID of 3.9 points for the total score.

Exercise Training Modalities for People with Chronic Obstructive Pulmonary Disease.

Exercise training confers health benefits for people with chronic obstructive pulmonary disease (COPD). This article reviews the evidence for several exercise training modalities shown to be beneficial among individuals with COPD. These modalities include aerobic, resistance, nonlinear periodized, upper limb and balance training, as well as yoga, Tai Chi, inspiratory muscle training, whole body vibration training and neuromuscular electrical stimulation. The literature pertaining to each modality was critically reviewed, and information on the rationale, mechanism(s) of action (where known), benefits, and exercise prescription is described to facilitate easy implementation into clinical practice.

Gait speed and pedestrian crossings in COPD.

The assumed minimum walking speed at pedestrian crossings is 1.2 m/s. In this prospective cohort study, usual walking speed was measured over a 4 m course in 926 community-dwelling, ambulatory patients with stable COPD. Mean (SD) walking speed was 0.91 (0.24) m/s with only 10.7% walking at a speed equal or greater than 1.2 m/s. In order for 95% of this cohort to safely negotiate a pedestrian cross, traffic lights would have to assume a minimum walking speed of 0.50 m/s (2.4 times longer than current times). The current assumed normal walking speed for pedestrian crossings is inappropriate for patients with COPD.The studies were registered on clinicaltrials.gov and these data relate to the pre-results stage: NCT01649193, NCT01515709 and NCT01507415.

Phenotypic characteristics associated with slow gait speed in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Usual gait speed over 4 m (4MGS) is an established functional performance measure in older adults that consistently predicts adverse health outcomes, but few data exist in idiopathic pulmonary fibrosis (IPF). We assessed the reliability of 4MGS, its relationship with established outcome measures and its responsiveness to pulmonary rehabilitation. METHODS: In four prospective IPF cohorts, 4MGS inter-observer (n = 46) and test-retest (n = 46) reliability, concurrent validity (n = 65 and n = 62) and responsiveness (n = 60) were determined. The phenotypic characteristics of all patients stratified according to slow 4MGS (<0.8 m/s) were compared, including lung function parameters, HRCT of the chest, 6-min walking distance (6MWD), Medical Respiratory Council (MRC) dyspnoea score, King's Brief Interstitial Lung Disease (KBILD) questionnaire and Gender, Age and lung Physiology (GAP) prognostic index. RESULTS: Intra-class correlation coefficients for inter-observer and test-retest reliability were 0.996 and 0.983, respectively. There was a strong association between 4MGS and 6MWD (r = 0.76; P < 0.0001) and moderate correlations with MRC (r = -0.56), KBILD (r = 0.44) and GAP index (r = -0.41); all P < 0.005. 4MGS improved significantly with pulmonary rehabilitation (mean (95% CI) change: 0.16 (0.12-0.20) m/s), effect size 0.65. Patients with slow 4MGS had significantly worse exercise performance (6MWD: -167 (-220 to -133) m), dyspnoea, health status and prognosis index than those with preserved 4MGS, despite similar lung function and HRCT parameters. CONCLUSION: 4MGS is a simple, reliable, valid and responsive tool that may detect a patient phenotype with worse exercise performance, dyspnoea, health status and prognosis index in stable IPF.