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Masahiro Shinoda,1 Osamu Hataji,2 Motohiko Miura,3 Masaharu Kinoshita,4 Akira Mizoo,5 Kazunori Tobino,6 Toru Soutome,7 Takanobu Nishi,7 Takeo Ishii,7 Bruce E Miller,8 Ruth Tal-Singer,8 Ryan Tomlinson,8 Taizo Matsuki,7 Paul W Jones,9 Yoko Shibata10 1Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Shinagawa, Tokyo, Japan; 2Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan; 3Department of Respiratory Medicine, Tohoku Rosai Hospital, Sendai, Miyagi, Japan; 4Department of Respiratory Medicine, Nagata Hospital, Yanagawa, Fukuoka, Japan; 5Department of Pulmonary Medicine Japan, Japan Community Healthcare Organization Tokyo Shinjuku Medical Center, Shinjuku, Tokyo, Japan; 6Department of Respiratory Medicine, Iizuka Hospital, Iizuka, Fukuoka, Japan; 7Japan Medical & Development, GSK K.K, Minato-Ku, Tokyo, Japan; 8GSK Pharma R&D, Collegeville, PA, USA; 9General Medicine, GSK, Brentford, Middlesex, UK; 10Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, JapanCorrespondence: Taizo Matsuki, Value Evidence Outcomes, Japan Medical & Development, GSK K.K, Akasaka Intercity AIR 1-8-1 Akasaka, Minato-Ku, Tokyo, 107-0052, Japan, Tel +81-8036928935, Email taizo.2.matsuki@gsk.comBackground: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan.Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥ 40 years of age with COPD or asthma-COPD overlap. Participants underwent training to use YaDoc, a telemedicine smartphone App, which included seven daily symptom questions and weekly COPD Assessment Test (CAT) questions. The primary endpoint was participant compliance for required question completion. The secondary endpoint was participant and physician/facility staff acceptability of YaDoc based on questionnaires completed at Week 52. The impact of the Japanese COVID-19 pandemic state of emergency on results was also assessed.Results: Of the 84 participants enrolled (mean age: 68.7 years, 88% male), 72 participants completed the study. Completion was high in the first six months but fell after that. Median (interquartile range [IQR]) compliance for daily questionnaire entry was 66.6% (31.0– 91.8) and 81.0% (45.3– 94.3) for weekly CAT entry. Positive participant responses to the exit questionnaire were highest regarding YaDoc ease of use (83.8%), positive impact on managing health (58.8%), and overall satisfaction (53.8%). Of the 26 physicians and facility staff enrolled, 24 completed the study. Of these, the majority (66.7%) responded positively regarding app facilitation of communication between physicians and participants to manage disease. Compliance was similar before and after the first COVID-19 state of emergency in Japan.Conclusion: Daily telemedicine monitoring is potentially feasible and acceptable to both patients and physicians in the management of COPD. These results may inform potential use of telemedicine in clinical practice and design of future studies.Clinical Trial Registration: JapicCTI-194916.Keywords: Japan, patient-reported outcome measure, feasibility, acceptability, telemonitoring, smartphone

BackgroundHeart Rate Score (HRSc), the percent of all atrial paced and sensed event in the largest 10 bpm rate histogram bin of a pacemaker, predicts survival in patients with cardiac devices. No correlation between HRSc and development of atrial fibrillation (AF) has been reported.ObjectiveTo evaluate the relationship between pacemaker post-implantation HRSc and newly-developed AF incidence.MethodsPatients with dual-chamber pacemakers, implanted 2013-2017, with ALTITIUDE remote monitoring data with ≥600,000 beats of histogram data collected at baseline were included (N=34,543). HRSc was determined from the post-implantation histogram data during the initial 3 months. Patients were excluded if they had AF, defined as atrial high-rate episodes >5 minutes or >1% of right atrial beats >170 bpm during the initial 3-months post-implantation. New AF, after the baseline period, was defined by each of the following: >1%, >10% or >25% of atrial beats >170 bpm or Atrial Tachycardia Response (ATR) events >24 hr.ResultsPatients were followed a median of 2.8 (1.0-4.0) years. Patients with initial HRSc≥70% were older, had higher %RA pacing, had lower %RV pacing and were more likely programmed with rate-response vs subjects with HRScConclusionHRSc predicts subsequent AF independent of well-known risk factors in pacemaker patients.

Background Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. Research Question Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? Study Design and Methods This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. Results A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). Interpretation Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT02147015; URL: www.clinicaltrials.gov

Hyun-Il Gil,1,* Sungmin Zo,2,* Paul W Jones,3,4 Bo-Guen Kim,2 Noeul Kang,2 Yeonseok Choi,5 Hyun Kyu Cho,6 Danbee Kang,7 Juhee Cho,7 Hye Yun Park,2 Sun Hye Shin2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Institute For Infection and Immunity, St George’s University of London, London, UK; 4Value Evidence and Outcomes, Global Medical R&D, GlaxoSmithKline, Uxbridge, UK; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea; 7Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Sun Hye Shin; Hye Yun ParkDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaTel +82-2-3410-3429Fax +82-2-3410-3849Email freshsunhye@gmail.com; hyeyunpark@skku.eduPurpose: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is widely used to assess the impact of COPD symptoms on health status. Whilst the CAT consists of eight different items, details on the distribution of each item are limited. This study aimed to investigate the distribution and clinical implication of each CAT item, stratified by CAT severity group, in stable COPD patients.Patients and Methods: This was a cross-sectional study at a single referral hospital in South Korea. Spirometry confirmed COPD patients with CAT measured at the first clinical visit were retrospectively identified. Patients were categorized into three groups: low (0 ≤ CAT < 10), medium (10 ≤ CAT < 20), and high (20 ≤ CAT ≤ 40) impact group. For the purpose of this analysis, the first four items (cough, sputum, chest tightness, and dyspnea) and the remaining four items (activities, confidence, sleep and energy) were also grouped as “pulmonary” and “extra-pulmonary”, respectively.Results: A total of 815 patients were included, and mean (SD) forced expiratory volume in 1 s (FEV1) was 62.8 (17.4) % pred. Among them, 300 patients (36.8%) were in the high impact group and had a greater exacerbation history and lower lung function. The proportion of “extra-pulmonary” items score was greater in patients with higher total CAT scores, with the activity and confidence items showing higher scores.Conclusion: In our study, in addition to dyspnea, activity limitation is a particular problem in individual patients with higher CAT total scores, for which physicians need to pay more attention. Our study suggests that whilst CAT total score captures the overall impact of COPD, each item of the CAT contains potentially useful information in understanding the patient’s symptom burden.Keywords: COPD, COPD assessment test, patient reported outcome, symptom

OBJECTIVE: Daily inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) combinations comprising either regular maintenance therapy with ICS/LABA plus as-needed short-acting beta-2-agonist (SABA) or ICS-formoterol combinations used as maintenance and reliever therapy (MART) are recommended for moderate asthma. This analysis compares the direct costs of twice-daily fluticasone propionate/salmeterol (FP/salm) and budesonide/formoterol MART in three Southeast Asian countries. METHODS: A literature review identified three randomized trials in patients with asthma (≥ 12 years) comparing regular twice-daily FP/salm with as-needed SABA versus MART in moderate asthma: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-039-0735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Economic analyses, conducted from a healthcare sector perspective (medication costs + healthcare utilization costs), applied unit costs from countries where healthcare costs are publicly available: Indonesia, Thailand and Vietnam. Results are expressed in British pound sterling (GBP/patient/year). RESULTS: Annual exacerbation rates were low and differences between treatment strategies were small (range, FP/salm: 0.31-0.38, MART: 0.24-0.25) although statistically significant in favor of MART. Total average (minimum-maximum) direct costs (in GBP/patient/year) across the three studies were £187 (£137-£284), £158 (£125-£190), and £151 (£141-£164) for those who used FP/salm, and £242 (£217-£267), £284 (£237-£340) and £266 (£224-£315) for MART in Indonesia, Thailand and Vietnam, respectively. On average, total direct costs/patient/year with FP/salm were 22.8%, 44.6% and 43.0% lower than with MART for Indonesia, Thailand and Vietnam, respectively. CONCLUSIONS: In the three countries evaluated, total treatment costs with regular twice-daily FP/salm were consistently lower than with budesonide/formoterol MART due to lower direct healthcare costs.

BACKGROUND Limited studies are available on the clinical significance of left ventricular (LV) lead polarity in patients undergoing cardiac resynchronization therapy (CRT), with a recent study suggesting better outcomes with LV true bipolar pacing. OBJECTIVE We aimed to determine whether true bipolar LV pacing is associated with reduced mortality in a large, real-life CRT cohort, followed by remote monitoring. METHODS We analyzed de-identified device data from CRT patients followed by the Boston Scientific LATITUDE remote monitoring database system. Patients with LV bipolar leads paced between the LV ring and LV tip were identified as true bipolar and those with LV bipolar leads paced between LV tip or LV ring and right ventricular (RV) coil were identified as extended bipolar. Patients with unipolar leads were identified as unipolar. RESULTS Of the 59 046 patients included in the study, 2927 had unipolar pacing, 34 390 had extended bipolar pacing, and 21 729 had true bipolar pacing. LV true bipolar pacing was associated with a significant 30% lower risk of all-cause mortality as compared to unipolar pacing (hazards ratio [HR] = 0.70, 95% CI: 0.62-0.79, P

Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a large, multicentre, multi-national, randomised, double-blind, 24-week trial. EMAX evaluated the efficacy and safety of dual bronchodilator therapy with umeclidinium bromide (UMEC)/vilanterol (VI) versus monotherapy with either UMEC or salmeterol (SAL) in symptomatic patients with chronic obstructive pulmonary disease (COPD) at low exacerbation risk who were not taking concomitant inhaled corticosteroid (ICS). EMAX generated evidence covering a wide range of patient-centred endpoints in COPD in addition to measures of lung function, clinical deterioration and safety. In addition, prospective and post hoc secondary analyses have generated clinically valuable information regarding the effects of baseline patient characteristics on treatment outcomes. Importantly, as concomitant ICS use was not permitted in this study, EMAX compared dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy with LAMA or LABA monotherapy without potential confounding due to concurrent ICS use or withdrawal. EMAX demonstrated beneficial treatment effects of UMEC/VI over UMEC or SAL monotherapy as maintenance treatment across a range of different patient characteristics, with no forfeit in safety. Thus, the trial provided novel insights into the role of LAMA/LABA versus LABA and LAMA monotherapies as maintenance therapy for patients with symptomatic COPD at low risk of exacerbations. This article will explore the clinical implications of the main findings to date of the EMAX trial and consider the key learnings this trial offers for future trial design in COPD.

Dear Editors,We read with interest the review article by Ritondo et al. on triple therapy in chronic obstructive pulmonary disease (COPD),1 but disagree with some of the points raised by the author...

Key Points Question What are the long-term health outcomes associated with COVID-19 infection 1 year after hospital discharge? Findings In this cohort study of 2433 patients who had been hospitalized with COVID-19, the most common symptoms at 1 year after discharge were fatigue, sweating, chest tightness, anxiety, and myalgia. Patients with severe disease had more postinfection symptoms and higher chronic obstructive pulmonary disease assessment test scores. Meaning This study reported prolonged symptoms of COVID-19 and found that severe disease during hospitalization was a risk factor for more symptoms and higher chronic obstructive pulmonary disease assessment test scores., This cohort study investigates 1-year health outcomes and their associated risk factors among COVID-19 survivors in Wuhan, China., Importance The long-term health outcomes and symptom burden of COVID-19 remain largely unclear. Objective To evaluate health outcomes of COVID-19 survivors 1 year after hospital discharge and to identify associated risk factors. Design, Setting, and Participants This retrospective, multicenter cohort study was conducted at 2 designated hospitals, Huoshenshan Hospital and Taikang Tongji Hospital, both in Wuhan, China. All adult patients with COVID-19 discharged between February 12 and April 10, 2020, were screened for eligibility. Of a consecutive sample of 3988 discharged patients, 1555 were excluded (796 declined to participate and 759 were unable to be contacted) and the remaining 2433 patients were enrolled. All patients were interviewed via telephone from March 1 to March 20, 2021. Statistical analysis was performed from March 28 to April 18, 2021. Exposures COVID-19. Main Outcomes and Measures All patients participated in telephone interviews using a series of questionnaires for evaluation of symptoms, along with a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Logistic regression models were used to evaluate risk factors for fatigue, dyspnea, symptom burden, or higher CAT scores. Results Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02; P

BACKGROUND Heart rate score (HRSc), the percentage of atrial sensed and paced beats in the largest 10 beat/min bin of a device histogram and mean intrinsic heart rate (MIHR), predicted survival in nonrandomized studies of implantable defibrillator (ICD) patients. We evaluated whether HRSc and MIHR independently predicted mortality and heart failure (HF) hospitalization in the prospective, randomized, controlled INTRINSIC RV trial. METHODS AND RESULTS The INTRINSIC RV trial enrolled 1530 patients receiving dual-chamber ICDs. This analysis involves patients (n = 1471) for whom MIHR and HRSc data were available. Mean follow-up was 10.4 months. The relationship between pre-randomization MIHR and HRSc on the primary endpoint of all-cause mortality and HF hospitalization was assessed using multivariate regression and Cox modeling. As categorical variables, MIHR > 70 bpm and HRSc > 70% were considered high. RESULTS The median baseline MIHR and HRSc were 74 (IQR = 16) and 50% (IQR = 20) respectively. As a continuous variable, for every 1% increase in HRSc, death/HF hospitalization increased by 1% (95%CI: 1.002-1.017; p = 0.01). Regression analysis showed baseline MIHR was associated with HRSc (p = 0.01); for every 1 beat/min increase in MIHR, HRSc increased by 1.8%. A MIHR > 70 bpm and HRSc ≥ 70% predicted, but were independently associated with, the primary endpoint (HR: 1.39; 95%CI: 1.10-1.76, p = 0.005 for MIHR and HR: 1.654; 95%CI: 1.11-2.46, p = 0.01 for HRSc). Male gender (HR: 0.75), history of HF (HR: 1.29), and atrial fibrillation (HR: 1.37) also predicted death/hospitalization in the Cox model. CONCLUSIONS In this large, prospectively studied ICD population, HRSc was a robust and independent predictor of death/HF hospitalization. High MIHR and high HRSc were associated but each predicted outcomes independently.

Background Brain damage and cardiovascular disease are extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD). Cardiovascular risk factors and smoking are contributors to neurodegeneration. This study investigates whether there is a specific, COPD-related deterioration in brain structure and function independent of cardiovascular risk factors and smoking. Materials and methods Neuroimaging and clinical markers of brain structure (micro- and macro-) and function (cognitive function and mood) were compared between 27 stable COPD patients (age: 63.0±9.1 years, 59.3% male, forced expiratory volume in 1 second [FEV1]: 58.1±18.0% pred.) and 23 non-COPD controls with >10 pack years smoking (age: 66.6±7.5 years, 52.2% male, FEV1: 100.6±19.1% pred.). Clinical relationships and group interactions with brain structure were also tested. All statistical analyses included correction for cardiovascular risk factors, smoking, and aortic stiffness. Results COPD patients had significantly worse cognitive function (p=0.011), lower mood (p=0.046), and greater gray matter atrophy (p=0.020). In COPD patients, lower mood was associated with markers of white matter (WM) microstructural damage (p

Objective: To assess the effect of asthma exacerbations and mepolizumab treatment on health status of patients with severe asthma using the St George’s Respiratory Questionnaire (SGRQ).Meth...

Background Remote monitoring of implantable cardioverter‐defibrillators has been associated with reduced rates of all‐cause rehospitalizations and mortality among device recipients, but long‐term economic benefits have not been studied. Methods and Results An economic model was developed using the PREDICT RM database comparing outcomes with and without remote monitoring. The database included patients ages 65 to 89 who received a Boston Scientific device from 2006 to 2010. Parametric survival equations were derived for rehospitalization and mortality to predict outcomes over a maximum time horizon of 25 years. The analysis assessed rehospitalization, mortality, and the cost‐effectiveness (expressed as the incremental cost per quality‐adjusted life year) of remote monitoring versus no remote monitoring. Remote monitoring was associated with reduced mortality; average life expectancy and average quality‐adjusted life years increased by 0.77 years and 0.64, respectively (6.85 life years and 5.65 quality‐adjusted life years). When expressed per patient‐year, remote monitoring patients had fewer subsequent rehospitalizations (by 0.08 per patient‐year) and lower hospitalization costs (by $554 per patient year). With longer life expectancies, remote monitoring patients experienced an average of 0.64 additional subsequent rehospitalizations with increased average lifetime hospitalization costs of $2784. Total costs of outpatient and physician claims were higher with remote monitoring ($47 515 vs $42 792), but average per patient‐year costs were lower ($6232 vs $6244). The base‐case incremental cost‐effectiveness ratio was $10 752 per quality‐adjusted life year, making remote monitoring high‐value care. Conclusion Remote monitoring is a cost‐effective approach for the lifetime management of patients with implantable cardioverter‐defibrillators.

INTRODUCTION Insertable cardiac monitors (ICMs) provide a minimally invasive method of continuous monitoring for abnormal heart rhythms. While the benefits of ICMs are clear, current algorithm performance can be improved. The objective of this study is to assess the performance of a novel adaptive atrial fibrillation (AF) detection algorithm and separately programmable atrial tachycardia (AT) algorithm. METHODS A dual-stage detect-and-verify AF algorithm and separately programmable AT algorithm were developed. Sensitivity and PPV across a range of settings were determined in silico by comparison with an adjudicated Holter data set (n = 1966 with 229 patient days). Finally, the ability to improve performance through simulated remote programming was assessed. RESULTS The dual-stage algorithm detected AF in all true AF patients (76/76) resulting in a patient-level sensitivity of 100%. Episode-level sensitivity and PPV ranged from 97.6% to 100% and 79.1% to 98.5%, respectively. Thirty-six false-positive episodes were observed and 32 (88.9%) of these were corrected with programming changes. Decoupling of AF and AT durations improved PPV from a range of 10%-22% to a range of 95%-100%. CONCLUSIONS AF and AT algorithms were designed with novel features including an adaptive morphology assessment for AF detection and separately programmable durations for AT detection. In silico performance yielded improved PPVs while maintaining high sensitivity across a range of settings. Importantly, programming changes that may be made remotely with this system reduced false positives. These algorithms allow clinicians to individualize arrhythmia detection settings thereby improving data management and reducing clinic burden.

No real-world large database associates lower rate limit (LRL) programming and survival of subjects with cardiac resynchronization therapy-defibrillators (CRT-Ds).The purpose of this study was to test the hypothesis that lower LRL programming is independently associated with survival, and that LRL and heart rate score (HrSc) are associated.All dual-chamber CRT-D devices in the Remote Patient Monitoring (RPM) ALTITUDE database (2006-2011) were queried. Baseline HrSc was defined as the percentage of all atrial sensed and paced beats in the tallest 10-beat histogram bin postimplant. LRL was assessed during repeated RPM uploads. Using a Cox model multivariable analysis, relationships between LRL, survival, HrSc, and other variables were evaluated. Survival was determined by query of death indices.Data analyzed included 61,881 subjects (mean follow-up 2.9 years). LRL ranged from 40 to 85 bpm. Baseline lower LRL was associated with younger age, less atrial fibrillation, female sex, and lower HrSc (P.001 for all covariates). Lower LRL was associated with improved survival, with LRL 40 associated with the largest survival benefit. This was significant for all 3 HrSc subgroups (P .001). An interaction between HrSc and LRL was observed, with the largest survival difference between HrSc groups observed at LRL-40 (P.001).LRL programming and HrSc were associated, and lower values of both were associated with improved survival in a large database of CRT-D subjects. Relationships between survival, LRL programming, and HrSc merit further study.

This study sought to investigate the temporal association between changes in physiologic heart failure (HF) sensors, atrial fibrillation (AF) progression, and clinical HF in patients with cardiac resynchronization therapy implantable defibrillators (CRT-D) designed to monitor AF and HF daily.AF is a common comorbidity in HF; however, it is unclear if HF triggers AF, or vice-versa. Current implantable cardiac devices have sensors capable of quantifying HF status, which permits a greater understanding of the impact of AF on HF status and may help guide treatment.The MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) study collected multiple sensor data indicative of HF status in patients with CRT-D followed for up to 12 months. Patients were grouped according to their longest daily AF burden: 1) at least 24 hours of AF (HIGH AF); 2) between 6 minutes and 24 hours (MID AF); and 3)6 minutes (NO AF). Sensor data were aligned to the first qualifying AF event or a randomly selected day for patients in the NO AF group.Among 869 patients with daily AF data available, 98 patients had HIGH AF, 141 patients MID AF, and 630 patients NO AF. At baseline, history of AF, N-terminal pro hormone B-type natriuretic peptide and device-measured S3 were associated with development of AF. HeartLogic index increased before AF onset (Δ HeartLogic = 9.83 ± 2.49; P 0.001). Multivariable time-dependent Cox regression showed an increased risk for HF events following a 24-hour AF episode compared with no 24-hour AF (hazard ratio: 1.96; 95% confidence interval: 1.03-3.74).Device-measured HF indicators worsened before AF onset, whereas clinical HF deterioration only became apparent after AF occurred. Thus, the sensitivity of methods to ascertain AF and HF status appear to influence the direction of perceived causality. (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients [MultiSENSE]; NCT01128166).

Hospitalizations for acute cardiac conditions have markedly declined during the coronavirus disease 2019 (COVID-19) pandemic, yet the cause of this decline is not clear. Using remote monitoring data of 4,029 patients with implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed changes in markers of cardiac status among these patients and compared thoracic impedance and arrhythmia burden in 2019 and 2020 from January through August. We found no change in several key disease decompensation markers among patients with implanted ICD devices during the first phase of COVID-19 pandemic, suggesting that the decrease in cardiovascular hospitalizations in this period is not reflective of a true population-level improvement in cardiovascular health.

Introduction Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the most critical events for patients with COPD that have a negative impact on patients’ quality of life, accelerate disease progression, and can result in hospital admissions and death. Although there is no distinct definition or detailed knowledge about AECOPD, it is commonly used as primary outcome in clinical studies. Furthermore, it may be difficult in clinical practice to differentiate the worsening of symptoms due to an AECOPD or to the development of heart failure. Therefore, it is of major clinical importance to investigate the underlying pathophysiology, and if possible, predictors of an AECOPD and thus to identify patients who are at high risk for developing an acute exacerbation. Methods and analysis In total, 355 patients with COPD will be included prospectively to this study during a 3-week inpatient pulmonary rehabilitation programme at the Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee (Germany). All patients will be closely monitored from admission to discharge. Lung function, exercise tests, clinical parameters, quality of life, physical activity and symptoms will be recorded, and blood samples and exhaled air will be collected. If a patient develops an AECOPD, there will be additional comprehensive diagnostic assessments to differentiate between cardiac, pulmonary or cardiopulmonary causes of worsening. Follow-up measures will be performed at 6, 12 and 24 months. Exploratory data analyses methods will be used for the primary research question (screening and identification of possible factors to predict an AECOPD). Regression analyses and a generalised linear model with a binomial outcome (AECOPD) will be applied to test if predictors are significant. Ethics and dissemination This study has been approved by the Ethical Committee of the Philipps University Marburg, Germany (No. 61/19). The results will be presented in conferences and published in a peer-reviewed journal. Trial registration number NCT04140097.

Introduction COVID-19 presents with acute symptoms of cough, phlegm and pyrexia and can cause severe acute respiratory distress. Little is known about the symptoms patients face following an acute admission for COVID-19 and there is no validated questionnaire to assess patients. This cross sectional study aims to explore the symptoms patients display following an admission with COVID-19 using the COPD Assessment Test (CAT). Methods This was an observational cohort study following patients who recovered from COVID-19. Participants were called after discharge to assess their ongoing symptoms including the CAT and their rehabilitation needs. Correlations between characteristics and CAT scores were performed using Spearman’s rank test. Results 131 patients were assessed following their admission (77 (59%) male, mean [SD] age 60[14]). 31% had a pre-existing respiratory condition. Their mean [SD] hospital stay was 10[12] days and 21 (16%) participants required mechanical ventilation. The mean[SD] time to follow up call was 32[18] days post-discharge. Total CAT scores ranged from 0 to 34 with mean of 11.4[7.8]. 52% of patients had a CAT score ≥10 with scores highest for the breathlessness, activities, sleep, confidence and energy items. Of the patients without a pre-existing respiratory condition 42% had a score of ≥10 and in patients with a pre-existing respiratory condition this proportion was 75%. Breathlessness, activity limitations and energy and were the highest reported symptoms for both groups. There were no statistically significant correlations for the CAT with length of stay, number of days ventilated, self-reported physical activity or time from discharge. Conclusion The CAT total and item scores can provide insight into the severity of symptom burden for patients following a hospitalisation from COVID-19. This may be a useful tool to identify rehabilitation needs. References Jones PW, Harding G, Berry P, et al. Development and first validation of the COPD Assessment test. Eur Respir J 2009:34(3):648–54 Raghavan N, Lam Y, Webb K, et al. Components of the COPD Assessment Test (CAT) associated with a diagnosis of COPD in a random population sample. Journal of Chronic Obstructive Pulmonary Disease 2012:9:175–183

The role of cardiovascular implantable electronic device (CIED)-derived activity to predict implantable cardioverter-defibrillator (ICD) therapy or death is not known.We aimed to assess CIED-derived activity to predict clinical outcomes.In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily, then averaged for the first 30 days following randomization to predict inappropriate/appropriate therapy or death. Kaplan-Meier analysis and Cox proportional regression models were used to evaluate inappropriate/appropriate therapy, heart failure, or death by 30-day CIED-derived patient activity quintiles.There were 1463 patients with CIED activity data (98%). Patients in the highest quintile (Q5) of activity (more active) had the highest rate of inappropriate therapy, 21% at 2 years, as compared to 7%-11% in the other 4 quintiles (P.001), a 1.75 times higher risk (95% confidence interval [CI]: 1.23-2.50, P = .002). However, patients in the lowest quintile of activity (Q1, 1 hour/day) had the highest risk of mortality, 15% in 2 years, as compared to Q2-3 (1-2 hours/day, 8%-7% mortality), and Q4-5 (2 hours/day, 2%-3% mortality) (P.001). Patients with the lowest level of activity (Q1) had a 2.02 times higher risk of mortality (95% CI: 1.21-3.38, P = .007), and they had an 82% higher risk of heart failure hospitalization (95% CI: 1.28-2.57, P = .001).High CIED-derived 30-day median patient activity predicted inappropriate therapy, while low patient activity predicted mortality and heart failure in ICD and cardiac resynchronization therapy with defibrillator patients enrolled in MADIT-RIT. Device-derived activity assessment could serve as a useful predictor of outcomes.

Background: Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy. Implantable Cardioverter Defibrillator (ICD) is important for prevention of sudden cardiac death (SCD) in patients at high risk. In recent years the subcutaneous ICD (S-ICD) has emerged as a viable alternative to the transvenous ICD (TV-ICD). The S-ICD does not require intravascular access, but cannot provide antitachycardia pacing therapy (ATP). Objective: To assess the real world incidence of ICD therapy in patients with HCM implanted with TV-ICD versus S-ICD.Methods: We compared the incidence of ATP and shock therapies between all HCM patients with S-ICD and TV-ICD enrolled in the Boston Scientific ALTITUDE database. Cumulative Kaplan Meier incidence was used to compare therapy free survival and Cox proportional hazard ratios were calculated. We performed an unmatched as well as propensity match analysis. Results: We included 2462 patients with TV-ICD and 716 patients with S-ICD followed for an average of 1348 {plus minus} 989 days. Patients with HCM and TV-ICD had significantly higher rate of device therapy as compared to those with S-ICD (31.1 vs. 14.7 therapies /100 patient year; p

Rationale: Symptom relief is a key treatment goal in patients with chronic obstructive pulmonary disease (COPD). However, there are limited data available on the response to bronchodilator therapy in patients at low risk of exacerbations with different levels of symptom severity. This study compared treatment responses in patients with a range of symptom severities as indicated by baseline COPD assessment test (CAT) scores. Methods: The 24-week EMAX trial evaluated the benefits of umeclidinium/vilanterol versus umeclidinium or salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids. This analysis assessed lung function, symptoms, health status, and short-term deterioration outcomes in subgroups defined by a baseline CAT score [

This chapter focuses on several common techniques for intraframe coding (removing spatial redundancy in single images). It outlines techniques for hierarchical coding (coding images in such a way that different resolutions or quality levels are easily accessible). The chapter describes the fundamental concepts of arithmetic coding by examining Elias' code and briefly discusses its practical implementations. It discusses two key elements in designing a codebook: determining what vectors should be included in the codebook for best performance, and structuring the codebook to allow for efficient searching. The chapter provides a brief overview of some popular compression techniques and describes how all three components can work together to provide useful and efficient compression of digital images. The downside to representing images in digital form is that a large number of bits is required to represent even a single digital image, and with the rapid advances in sensor technology and digital electronics, this number grows larger with each new generation of products.

Objective: The amygdala is a brain region comprised of a group of functionally distinct nuclei that play a central role in social behavior. In homeless and precariously housed individuals, high rates of multimorbidity, and structural aspects of the environment may dysregulate social functioning. This study examined the neurobiological substrates of social connection in homeless and precariously housed persons by examining associations between amygdala nuclei volumes and social network size. Methods: Sixty participants (mean age 43.6 years; 73.3% male) were enrolled from an ongoing study of homeless and precariously housed adults in Vancouver, Canada. Social network size was assessed using the Arizona Social Support Interview Schedule. Amygdala nuclei volumes were extracted from anatomic T1-weighted MRI data. The central and basolateral amygdala nuclei were selected as they are implicated in anxiety-related and social behaviors. The hippocampus was included as a control brain region. Multivariable regression analysis investigated the relationship between amygdala nuclei volumes and social network size. Results: After controlling for age, sex, and total brain volume, individuals with the larger amygdala and central nucleus volumes had a larger network size. This association was not observed for the basolateral amygdala complex, though subsequent analysis found the basal and accessory basal nuclei of the basolateral amygdala were significantly associated with social network size. No association was found for the lateral amygdala nucleus or hippocampus. Conclusions: These findings suggest that select amygdala nuclei may be differentially involved in the social connections of persons with multimorbid illness and social marginalization.

Background Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. Methods The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 μg, once-daily umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, 1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. Results At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59–74 mL; p p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: − 0.56 [p p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use Conclusions In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. Funding GlaxoSmithKline (study number 201749 [NCT03034915]).

The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items against a panel of comorbidities, lung function, or CT characteristics (qualitative score, 15th percentile of mean lung density), with age, BMI and gender as covariates. This was supported by exploratory factor analysis. Regarding the relationship to comorbidities and emphysema, there were marked differences between CAT items, especially items 1 and 2 versus 3 to 8. This grouping was basically confirmed by factor analysis. Items 4 and 5, and to a lower degree 1, 2 and 6, appeared to be informative regarding the presence of emphysema, whereas the total score was not or less informative. Regarding comorbidities, similar findings as for the total CAT score were obtained for the modified Medical Research Council scale (mMRC) which was also informative regarding emphysema. Our findings suggest that the usefulness of the CAT can be increased if evaluated on the basis of single items which may be indicating the presence of comorbidities and emphysema.

Oligosaccharides are important components of milk, serving as substrates for the intestinal microbiota, acting as antimicrobials that prevent pathogen colonization, and supporting the developing gastrointestinal immune system of neonates. Nutrient composition of canine and feline milk samples has been described previously, but little is known about the oligosaccharide content. Therefore, the objective of this study was to characterize canine and feline milk samples using a high-throughput glycomics approach. 23 dogs (9 Labrador retriever and 14 Labrador retriever x golden retriever crossbreed) and 6 domestic shorthair cats were recruited to the study. Milk samples were collected by manual expression at time points after parturition. Samples were collected across 2 phases per species, differentiated by maternal diet. Following extraction, oligosaccharide content was determined by liquid chromatography-mass spectrometry (LC-MS). In canine milk samples, 3 structures accounted for over 90% of all oligosaccharides detected across two diet groups. These were 3’-sialyllactose, 6’-sialyllactose, and 2’-fucosyllactose. In feline samples, a more diverse range of oligosaccharides was detected, with up to 16 structures present at relative abundance >1% of the total. Difucosyllactose-N-hexaose b, 3’-sialyllactose and lacto-N-neohexaose were all detected at abundances >10% in feline milk samples. Statistically significant differences (p

Heart rate score (HRSc) ≥70%, a novel parameter, predicts risk of mortality in patients with implantable cardioverter-defibrillators and identifies patients who have survival benefit with DDDR vs DDD pacing.The purpose of this study was to determine if DDDR pacing lowers HRSc, and a blended sensor with minute ventilation (MV) and accelerometer (XL) improves HRSc more than accelerometer (XL) alone in patients requiring pacemakers (PMs).HRSc, the percentage of all beats in the tallest 10-beat/min device histogram bin, was calculated. Data from the Limiting Chronotropic Incompetence for Pacemaker Recipients Study, a prospective randomized trial of PM patients, comparing XL to blended-sensor (XL + MV) rate-responsive pacing, were analyzed retrospectively for HRSc changes from baseline. The relationship of patient activity (sensor-detected from device memory) to HRSc was examined.Of the 501 randomized patients, 215 (43%) patients had HRSc ≥70% during DDD pacing at baseline. In these patients, HRSc decreased after DDDR programming by 14.2%, while it increased by 0.4% in those with baseline HRSc70% (n = 286) (HRSc ≥70% vs HRSc70%; P.01). No differences were detected between the 2 randomized sensor-based groups at baseline. Blended-sensor (MV + XL) programming reduced HRSc more than the XL sensor alone (MV + XL: 18% vs XL: 10%; P.001). No correlation was observed between patient activity and HRSc (correlation = -0.14; P = .07).HRSc improved (reduced) with rate-response (DDDR) programming in PM patients with high HRSc during DDD pacing. Blended sensors (MV + XL) improved HRSc more than XL alone. HRSc does not correlate with patient activity levels, suggesting that other patient factors determine this parameter. This programming approach needs to be investigated prospectively in a PM outcomes trial.

Background Much controversy persists regarding the place of statin drugs in the treatment of patients with COPD. This systematic review and meta-analysis sought to determine the clinical efficacy of statin therapy in COPD. Methods We searched MEDLINE, EMBASE, the Cochrane Database, and PubMed for relevant clinical studies. Randomized controlled trials (RCTs) comparing the effects of statin drugs with placebo in COPD populations were included. Pooled estimates were calculated using a random-effects model. Heterogeneity was determined using the I2 statistic. Results Ten trials with a total of 1,471 patients were included. Statin treatment was associated with a larger improvement in exercise capacity, lung function, and St. George's Respiratory Questionnaire score compared with placebo, but there were no statistically significant differences in inflammatory markers, all-cause mortality, and safety outcomes; however, subgroup analysis indicated that statin drugs improved clinical outcomes in the subjects from trials enrolling patients with overt cardiovascular disease (CVD), elevated baseline C-reactive protein levels, or a high cholesterol level. Conclusions The findings from this systematic review suggest a role for statin drugs in patients with COPD and coexisting CVD, evidence of increased systemic inflammation, or hyperlipidemia with respect to improving exercise tolerance and pulmonary function. These findings need to be confirmed by RCTs specifically designed to test this hypothesis and identify appropriate patients for statin use. Trial Registry PROSPERO: CRD42017060594; https://www.crd.york.ac.uk/PROSPERO/

Background The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to defibrillate ventricular arrhythmias, avoiding drawbacks of transvenous leads. The global EFFORTLESS S-ICD (Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD) registry is collecting outcomes in 985 patients during a 5-year follow-up. Objectives The primary goal of the EFFORTLESS registry is to determine the safety of the S-ICD by evaluating complications and inappropriate shock rate. Methods This is the first report on the full patient cohort and study endpoints with follow-up ≥1 year. The predefined endpoints are 30- and 360-day complications, and shocks for atrial fibrillation or supraventricular tachycardia. Results Patients were followed for 3.1 ± 1.5 years and 82 completed the study protocol 5-year visit. Average age was 48 years, 28% were women, ejection fraction was 43 ± 18%, and 65% had a primary prevention indication. The S-ICD system and procedure complication rate was 4.1% at 30 days and 8.4% at 360 days. The 1-year complication rate trended toward improvement from the first to last quartile of enrollment (11.3% [quartile 1]) to 7.8% [quartile 2], 6.6% [quartile 3], and 7.4% [quartile 4]; quartile 1 vs. quartiles 2 to 4; p = 0.06). Few device extractions occurred due to need for antitachycardia (n = 5), or biventricular (n = 4) or bradycardia pacing (n = 1). Inappropriate shocks occurred in 8.1% at 1 year and 11.7% after 3.1 years. At implant, 99.5% of patients had a successful conversion of induced ventricular tachycardia or ventricular fibrillation. The 1- and 5-year rates of appropriate shock were 5.8% and 13.5%, respectively. Conversion success for discrete spontaneous episodes was 97.4% overall. Conclusions This registry demonstrates that the S-ICD fulfills predefined endpoints for safety and efficacy. Midterm performance rates on complications, inappropriate shocks, and conversion efficacy were comparable to rates observed in transvenous implantable cardioverter-defibrillator studies. (Evaluation oF Factors ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD [The EFFORTLESS S-ICD Registry]; NCT01085435 )

Purpose Limited data exist on the quantitative validity of the St George's Respiratory Questionnaire (SGRQ) in asthma populations. This study evaluated the psychometric properties of the SGRQ in patients with severe asthma. Methods This was a post-hoc analysis of pooled data from MENSA (N = 576; NCT01691508) and SIRIUS (N = 135; NCT01691521), two randomized, placebo controlled trials of mepolizumab in patients with severe asthma. Patients completed the SGRQ at Baseline and Exit (MENSA Week 32; SIRIUS Week 24). Distributional characteristics, internal consistency reliability, test-retest reliability, convergent and discriminant validity, known-groups validity and responsiveness were assessed. Results Internal consistency reliability was acceptable for the total and domain scores at Baseline and Exit (Cronbach's α was 0.92 and 0.94 at Baseline and Exit, respectively, for the Total score). Test-retest reliability was demonstrated (intraclass correlation coefficients >0.7) for Total score and the Activity and Impacts domains. Convergent and discriminant validity were demonstrated with measures associated or not associated with respiratory-related health status. Known groups validity based on baseline FEV 1 % predicted, Asthma Control Questionnaire (ACQ)-5 score, exacerbations and eosinophil counts was demonstrated for the SGRQ total and domain scores. Responses to therapy based on clinician-rated response, patient-rated response, ACQ-5 change score and exacerbations generally correlated with improvements in SGRQ scores. Conclusions This analysis demonstrated that the SGRQ has acceptable psychometric properties in patients with severe asthma, exceeding the thresholds for adequate reliability, validity and responsiveness. The SGRQ appears to be a good instrument for identifying response to therapy in patients with severe asthma.

Purpose Content validity is the extent to which a patient-reported outcome measure evaluates the concepts most relevant to a patient's condition and treatment. The St George's Respiratory Questionnaire (SGRQ) has been validated in a range of respiratory conditions. This study evaluated the content validity of the SGRQ in patients with severe asthma. Methods A qualitative study, guided by a protocol, which included concept elicitation and cognitive debriefing of the SGRQ, was conducted in patients aged ≥18 years with history of severe asthma and blood eosinophil counts of ≥150/μL (past month) or ≥300/μL (past 12 months). Patients were recruited until saturation for concept elicitation was achieved (i.e. no additional concepts identified). Concepts identified by the patients were then mapped to the SGRQ. Results 18 patient interviews provided concept saturation. Concept elicitation confirmed that the SGRQ includes the commonly reported asthma symptoms and their impact on daily life. In total, 89–100% of patients routinely experienced cough, nighttime awakenings, shortness of breath, chest tightness, sleep difficulty, phlegm/mucus, and wheezing. Patients reported asthma impacting daily and physical activities, mood and sleep. Cognitive interviewing confirmed that patients understood the instructions, items and response options in the SGRQ. Nearly half of the concepts in the SGRQ were endorsed by ≥12 patients; of the 17 items with scoring weights ≥85, 11 were mentioned by ≥12 patients. Conclusions This study demonstrates that the SGRQ is a relevant, comprehensive and content-valid instrument to assess health status in patients with severe asthma.

Background:We hypothesized that survival in implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients is predicted by baseline Heart Rate Score.Methods:Heart Rate Score is determined from the atrial paced and sensed histogram of a DDD ICD or CR

Objectives Vitamin D deficiency and Chronic Obstructive Pulmonary Disease (COPD) are both under-recognized health problems, world-wide. Although Vitamin D has long been known for calcemic effects it also has less known noncalcemic effects. Recent data have shown that Vitamin D deficiency is highly prevalent in patients with COPD and correlates with forced expiratory volume in one second (FEV1) and FEV1 decline. The objective of this work was to review the current literature on vitamin D deficiency in relation with COPD. Data source A literature search, using the words “vitamin D” and “COPD”, was undertaken in Pubmed database. Results The noncalcemic effects of vitamin D relating with COPD may be summarised as increasing antimicrobial peptide production, regulation of inflammatory response and airway remodelling. Vitamin D inhibits the production of several proinflammatory cytokines and leads to suppression Th1 and Th17 responses which may be involved in the pathogenesis of COPD. Vitamin D insufficiency may also contribute to chronic respiratory infections and airway colonization so returning vitamin D concentrations to an optimal range in patients with COPD might reduce bacterial load and concomitant exacerbations.Vitamin D is also important for COPD-related comorbodities such as osteoporosis, muscle weakness and cardiovascular diseases. Data about the effect of Vitamin D supplementation on those comorbidities in relation with COPD are been scarce. Conclusion Improving the blood level of Vitamin D into the desired range may have a beneficial effect bones and muscles, but more studies are needed to test to test that hypothesis.

Background: Patient-reported outcomes data in clinical trials are usually reported as mean values, interpreted in comparison to a minimum clinically important difference (MCID) and ignoring the possibility of a sizable proportion of patients experiencing a worthwhile benefit when the majority did not. This analysis tested the reliability of calculated responder rates (from chronic obstructive pulmonary disease [COPD] patients) with the St George's Respiratory Questionnaire (SGRQ) using a range of responder cut-points above and below the MCID (4 units). Methods: Individual patient data (i.e., data from long-acting bronchodilator [LAB] and inhaled corticosteroids [ICS]/long-acting beta2-agonist [LABA] randomized clinical studies) in the COPD Biomarker Qualification Consortium database were used: short-term (≤1-year duration; 14,814 patients,) and medium-term (2-4 years; 12,043 patients). Responder rates versus placebo across SGRQ score change thresholds ranging from -1.5 to -8.0 were tested; differences were expressed as the odds ratio (OR) of a patient exceeding the threshold versus no change or deterioration. Results: The ORs measuring benefit of active treatment were similar across thresholds in short-term studies (LAB, ORs 1.40-1.42; LABA/ICS, 1.50-1.56) and medium-term LAB studies (ORs 1.34-1.43), whereas ORs in medium-term studies with LABA/ICS intervention showed a trend for higher response rates at higher values of threshold cut-points (1.64-1.79). In short-term studies, different thresholds had little effect on the OR between active drugs versus a trend for lower ORs with lower thresholds in medium-term studies. Conclusions: The OR for a treatment effect compared with placebo appears consistent across a range of responder cut-points. In medium-term trials, the treatment difference between active drugs suggests that use of a lower threshold would not increase the odds of observing a measured treatment difference.

Background: Randomized controlled trials (RCTs) often recruit patients from low and high socioeconomic status (SES) countries, but little is known about the effect of SES on clinical outcomes, particularly patient-centered measures of symptomatic benefit. Methods: Combined individual chronic obstructive pulmonary disease (COPD) patient data from the placebo and long-acting bronchodilator arms of 17 RCTs (from the COPD Biomarkers Qualification Consortium database) were analyzed. Health status was measured using the St George's Respiratory Questionnaire (SGRQ) (minimum clinically important difference [MCID]: 4 units). Trials were grouped into short-term (≤12 months) and medium-term (>12 months to 48 months). A participant's country of residence was categorized into Low/Medium or High SES using World Health Organization criteria. Results: Data from 19765 individuals (6109 Low/Medium SES) were available. Patients in Low/Medium SES countries had more severe disease at baseline. Improvement in SGRQ score with placebo was ≈2 units greater in Low/Medium than in High SES countries; at its greatest, the improvement from baseline exceeded the MCID in Low/Medium countries. This difference was maintained for at least 1 year. Improvement with bronchodilator was also greater in Low/Medium versus High SES countries; overall there was no evidence that the treatment effect versus placebo was different between countries of different SES status. Conclusions: Participants in Low/Medium SES countries experienced significantly larger treatment effects, irrespective of treatment group (placebo and bronchodilator). Despite this, COPD patients in Low/Medium SES countries experienced a health status gain from long-acting bronchodilator treatment that is similar to that seen in High SES countries.

Introduction Les bronchodilatateurs (BD) beta 2-agonistes de longue duree d’action (LABA) et/ou les anticholinergiques de longue duree d’action (LAMA) sont recommandes en traitement de 1re intention chez les patients atteints de BPCO. Leur association peut ameliorer les symptomes par rapport a la monotherapie. Cependant, les essais comparatifs n’ont pas exclu les patients sous corticoides inhales (CSI) ou deja traites par LAMA/LABA. L’etude Early MAXimisation of bronchodilation for improving COPD stability (EMAX) a compare umeclidinium/vilanterol (UMEC/VI), UMEC et salmeterol (SAL) chez des patients BPCO GOLD B symptomatiques ne recevant pas de CSI, ayant eu ≤ 1 exacerbation (E) moderee lors de la derniere annee et recevant ≤ 1 BD LA. Methodes Cette etude de 24 semaines en double aveugle, double placebo et a groupes paralleles a randomise les patients a UMEC/VI 62,5/25 μg 1/jour, UMEC 62,5 μg 1/jour ou SAL 50 μg 2/jour (ratio 1/1/1). Le critere d’evaluation principal etait le VEMS residuel a la semaine 24, comparant UMEC/VI a UMEC. Les criteres secondaires comprenaient la CI, la CVF, le TDI, le E-RS, le SGRQ, le CAT et le SGRSI. Le recours au salbutamol, le risque de 1re E moderee/severe et les effets indesirables (EI) ont ete notes. Des comparaisons entre UMEC/VI et les 2 monotherapies ont ete faites par la methode de la moyenne des moindres carres (MMC) en variation par rapport a la valeur initiale et en reponses cliniquement pertinentes. Resultats A l’inclusion, la population en ITT (N = 2425 [UMEC/VI 812 ; UMEC 804 ; SAL 809]) avait un VEMS post-BD moyen de 55 %, 50 % etaient des fumeurs actuels et 16 % ont eu 1 E moderee de BPCO au cours des 12 derniers mois. UMEC/VI a apporte des ameliorations plus grandes que UMEC (p Tableau 1 ). Conclusion UMEC/VI 1/jour apporte des ameliorations concordantes de la fonction pulmonaire et des symptomes, en particulier de la dyspnee par rapport a UMEC ou SAL chez les patients BPCO symptomatiques a faible risque d’E et sans CSI. Ces donnees soutiennent l’utilisation precoce de LAMA/LABA chez ces patients. Financement GSK, NCT03034915 .