What is the evidence for the management of patients along the pathway from the emergency department to acute admission to reduce unplanned attendance and admission? An evidence synthesis

Background Globally, the rate of emergency hospital admissions is increasing. However, little evidence exists to inform the development of interventions to reduce unplanned Emergency Department (ED) attendances and hospital admissions. The objective of this evidence synthesis was to review the evidence for interventions, conducted during the patient’s journey through the ED or acute care setting, to manage people with an exacerbation of a medical condition to reduce unplanned emergency hospital attendance and admissions. Methods A rapid evidence synthesis, using a systematic literature search, was undertaken in the electronic data bases of MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science, for the years 2000–2014. Evidence included in this review was restricted to Randomised Controlled Trials (RCTs) and observational studies (with a control arm) reported in peer-reviewed journals. Studies evaluating interventions for patients with an acute exacerbation of a medical condition in the ED or acute care setting which reported at least one outcome related to ED attendance or unplanned admission were included. Results Thirty papers met our inclusion criteria: 19 intervention studies (14 RCTs) and 11 controlled observational studies. Sixteen studies were set in the ED and 14 were conducted in an acute setting. Two studies (one RCT), set in the ED were effective in reducing ED attendance and hospital admission. Both of these interventions were initiated in the ED and included a post-discharge community component. Paradoxically 3 ED initiated interventions showed an increase in ED re-attendance. Six studies (1 RCT) set in acute care settings were effective in reducing: hospital admission, ED re-attendance or re-admission (two in an observation ward, one in an ED assessment unit and three in which the intervention was conducted within 72 h of admission). Conclusions There is no clear evidence that specific interventions along the patient journey from ED arrival to 72 h after admission benefit ED re-attendance or readmission. Interventions targeted at high-risk patients, particularly the elderly, may reduce ED utilization and warrant future research. Some interventions showing effectiveness in reducing unplanned ED attendances and admissions are delivered by appropriately trained personnel in an environment that allows sufficient time to assess and manage patients

Blood Eosinophils and outcomes in severe hospitalized exacerbations of COPD

Background Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations. Methods Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was ≥ 200 cells/μL and/or ≥ 2% of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups. Results A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3% (median time to death, 12 days; range, 9-16 days). The median absolute eosinophil count was 100 cells/μL (range, 10-1,500 cells/μL), and 25% met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs 6.5 [range, 1-33]; P = .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months were similar between groups. Conclusions The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used

Determining the minimum important differences for field walking tests in adults with long-term conditions: a systematic review and meta-analysis

• Correction - https://publications.ersnet.org/content/errev/34/176/245198• Supplementary material - https://publications.ersnet.org/content/errev/34/176/240198/DC1/embed/inline-supplementary-material-1.pdfIMPORTANCE: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions. METHODS: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan. RESULTS: 42 studies were included in the analyses, involving n=13 949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25 m (24-26 m) for respiratory conditions, 23 m (8-37 m) for cardiac conditions and 37 m (26-49 m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48 m (39-57 m) for respiratory conditions and 70 m (55-85 m) for cardiac conditions. The MID for ESWT in COPD was 159 s (94-224 s). The pooled MID across conditions within exercise interventions was 26 m (22-40 m) for the 6MWD and 53 m (44-62 m) for the ISWT, with reasonable heterogeneity (I2=48% and I2=47%, respectively). CONCLUSION: We propose new MIDs for exercise interventions using anchor-based methodology in long‑term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta‑analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking

A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) is a chronic, life-limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene leading to abnormal airway surface ion transport, chronic lung infections, inflammation and eventual respiratory failure. With the exception of the small-molecule potentiator, ivacaftor (Kalydeco®, Vertex Pharmaceuticals, Boston, MA, USA), which is suitable for a small proportion of patients, there are no licensed therapies targeting the basic defect. The UK Cystic Fibrosis Gene Therapy Consortium has taken a cationic lipid-mediated CFTR gene therapy formulation through preclinical and clinical development. OBJECTIVE: To determine clinical efficacy of the formulation delivered to the airways over a period of 1 year in patients with CF. DESIGN: This was a randomised, double-blind, placebo-controlled Phase IIb trial of the CFTR gene–liposome complex pGM169/GL67A. Randomisation was performed via InForm™ version 4.6 (Phase Forward Incorporated, Oracle, CA, USA) and was 1 : 1, except for patients in the mechanistic subgroups (2 : 1). Allocation was blinded by masking nebuliser chambers. SETTINGS: Data were collected in the clinical and scientific sites and entered onto a trial-specific InForm, version 4.6 database. PARTICIPANTS: Patients with CF aged ≥ 12 years with forced expiratory volume in the first second (FEV1) between 50% and 90% predicted and any combination of CFTR mutations. The per-protocol group (≥ 9 doses) consisted of 54 patients receiving placebo (62 randomised) and 62 patients receiving gene therapy (78 randomised). INTERVENTIONS: Subjects received 5 ml of nebulised pGM169/G67A (active) or 0.9% saline (placebo) at 28 (±5)-day intervals over 1 year. MAIN OUTCOME MEASURES: The primary end point was the relative change in percentage predicted FEV1 over the 12-month period. A number of secondary clinical outcomes were assessed alongside safety measures: other spirometric values; lung clearance index (LCI) assessed by multibreath washout; structural disease on computed tomography (CT) scan; the Cystic Fibrosis Questionnaire – Revised (CFQ-R), a validated quality-of-life questionnaire; exercise capacity and monitoring; systemic and sputum inflammatory markers; and adverse events (AEs). A mechanistic study was performed in a subgroup in whom transgene deoxyribonucleic acid (DNA) and messenger ribonucleic acid (mRNA) was measured alongside nasal and lower airway potential difference. RESULTS: There was a significant (p = 0.046) treatment effect (TE) of 3.7% [95% confidence interval (CI) 0.1% to 7.3%] in the primary end point at 12 months and in secondary end points, including forced vital capacity (FVC) (p = 0.031) and CT gas trapping (p = 0.048). Other outcomes, although not reaching statistical significance, favoured active treatment. Effects were noted by 1 month and were irrespective of sex, age or CFTR mutation class. Subjects with a more severe baseline FEV1 had a FEV1 TE of 6.4% (95% CI 0.8% to 12.1%) and greater changes in many other secondary outcomes. However, the more mildly affected group also demonstrated benefits, particularly in small airway disease markers such as LCI. The active group showed a significantly (p = 0.032) greater bronchial chloride secretory response. No difference in treatment-attributable AEs was seen between the placebo and active groups. CONCLUSIONS: Monthly application of the pGM169/GL67A gene therapy formulation was associated with an improvement in lung function, other clinically relevant parameters and bronchial CFTR function, compared with placebo. LIMITATIONS: Although encouraging, the improvement in FEV1 was modest and was not accompanied by detectable improvement in patients’ quality of life. FUTURE WORK: Future work will focus on attempts to increase efficacy by increasing dose or frequency, the coadministration of a CFTR potentiator, or the use of modified viral vectors capable of repeated administration. TRIAL REGISTRATION: ClinicalTrials.gov NCT01621867

British Thoracic Society Clinical Statement on pulmonary rehabilitation

Copyright © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.Linked Article: Editorial: Pulmonary rehabilitation marches on: refining, optimising and delivering through the clinical statement, Charlotte E. Bolton, Thorax 2023; 78 (Suppl. 5), pp. s1-s1 Published Online First: 08 Nov 2023. DOI URL: https://doi.org/10.1136/thorax-2023-220581 .The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments

Characterisation of volatile organic compounds in hospital indoor air and exposure health risk determination

Several volatile organic compounds (VOCs) have impacts on human health, but little is known about the concentrations of VOCs in the hospital environment. This study characterised VOCs present in clinical assessment rooms. More than 600 samples of air were collected over 31 months (2017–2020) at two hospital sites in Leicester, United Kingdom, and analysed by comprehensive two-dimensional gas chromatography, making this the largest hospital environment database worldwide on VOCs and first such UK study. The most abundant VOCs found were 2-propanol, ethyl chloride, acetone and hexane, with respective mean concentrations of 696.6 μgm−3, 436.5 μgm−3, 83.9 μgm−3 and 58.5 μgm−3. Acetone, 2-propanol and hexane concentrations were 4, 9 and 30-fold higher respectively compared to similar studies performed in other hospitals. Our results showed that the most frequently detected VOCs, with the highest concentrations, were most likely released by healthcare activities, or related to ingress of vehicle emissions. Hazard quotient (HQ) and cancer risk (CR) were calculated to identify the potential risk of VOCs exposure to the health of healthcare workers. No HQs were measured above 1, compared to inhaled US EPA and OEHHA health guidelines for non-cancer chemicals. For both hospitals, trichloroethylene CR were calculated above 1E-06 by using inhaled US EPA cancer risk values, leading to possible risks to healthcare workers with long-term exposure. More studies of this type, including measurements of VOCs such as formaldehyde that we were unable to include in this study, are needed to better characterise exposures and risks, both to healthcare workers and patients

Accelarated immune ageing is associated with COVID-19 disease severity

Background: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. / Results: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (β = 0.174, p = 0.043), with a major influence being disease severity (β = 0.188, p = 0.01). / Conclusions: Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK:a multicentre, longitudinal cohort study

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty.Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107.Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered.Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required.Funding: UK Research and Innovation and National Institute for Health Research