Dual bronchodilators are recommended as maintenance treatment for patients with symptomatic COPD in the UK; further evidence is needed to evaluate cost-effectiveness versus monotherapy. ...Cost-effectiveness of umeclidinium/vilanterol versus umeclidinium and salmeterol from a UK healthcare perspective in patients without exacerbations in the previous year was assessed using post hoc EMAX trial data.
The validated GALAXY model was populated with baseline characteristics and treatment effects from the non-exacerbating subgroup of the symptomatic EMAX population (COPD assessment test score ≥10) and 2020 UK healthcare and drug costs. Outputs included estimated exacerbation rates, costs, life-years (LYs), and quality-adjusted LYs (QALYs); incremental cost-effectiveness ratio (ICER) was calculated as incremental cost/QALY gained. The base case (probabilistic model) used a 10-year time horizon, assumed no treatment discontinuation, and discounted future costs and QALYs by 3.5% annually. Sensitivity and scenario analyses assessed robustness of model results.
Umeclidinium/vilanterol treatment was dominant versus umeclidinium and salmeterol, providing an additional 0.090 LYs (95% range: 0.035, 0.158) and 0.055 QALYs (-0.059, 0.168) with total cost savings of £690 (£231, £1306) versus umeclidinium, and 0.174 LYs (0.076, 0.286) and 0.204 QALYs (0.079, 0.326) with savings of £1336 (£1006, £2032) versus salmeterol. In scenario and sensitivity analyses, umeclidinium/vilanterol was dominant versus umeclidinium except over a 5-year time horizon (more QALYs at higher total cost; ICER=£4/QALY gained) and at the lowest estimate of the St George's Respiratory Questionnaire treatment effect (fewer QALYs at lower total cost; ICER=£12,284/QALY gained); umeclidinium/vilanterol was consistently dominant versus salmeterol. At willingness-to-pay threshold of £20,000/QALY, probability that umeclidinium/vilanterol was cost-effective in this non-exacerbating subgroup was 95% versus umeclidinium and 100% versus salmeterol.
Based on model predictions from a UK perspective, symptomatic patients with COPD and no exacerbations in the prior year receiving umeclidinium/vilanterol are expected to have better outcomes at lower costs versus umeclidinium and salmeterol.
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary ...disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies. Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components. These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.
The COPD Assessment Test Gupta, Nisha, MSc; Pinto, Lancelot, MD; Benedetti, Andrea, PhD ...
Chest,
November 2016, Letnik:
150, Številka:
5
Journal Article
Recenzirano
Background The COPD Assessment Test (CAT) is a valid disease-specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics ...remains limited. Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups. Methods The Canadian Cohort Obstructive Lung Disease (CanCOLD) is a random-sampled, population-based, multicenter, prospective cohort that includes subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease GOLD classifications 1 to 3). The CAT questionnaire was administered at three visits (baseline, 1.5 years, and 3 years). The CAT total score was determined for sex, age groups, smoking status, GOLD classification, exacerbations, and comorbidities. Results A total of 716 subjects with COPD were included in the analysis. The majority of subjects (72.5%) were not previously diagnosed with COPD. The mean FEV1 /FVC ratio was 61.1 ± 8.1%, with a mean FEV1 % predicted of 82.3 ± 19.3%. The mean CAT scores were 5.8 ± 5.0, 9.6 ± 6.7, and 16.1 ± 10.0 for GOLD 1, 2, and 3+ classifications, respectively. Higher CAT scores were observed in women, current smokers, ever-smokers, and subjects with a previous diagnosis of COPD. The CAT was also able to distinguish between subjects who experience exacerbations vs those who had no exacerbation. Conclusions These results suggest that the CAT, originally designed for use in clinically symptomatic patients with COPD, can also be used in individuals with mild airflow obstruction and newly diagnosed COPD. In addition, the CAT was able to discriminate between sexes and subjects who experience frequent and infrequent exacerbations. Trial Registry ClinicalTrials.gov; No.: NCT00920348 ; Study ID No.: IRO-93326.
Glossopharyngeal breathing Maltais, François
American journal of respiratory and critical care medicine,
08/2011, Letnik:
184, Številka:
3
Journal Article
Active mind-body movement therapies (AMBMTs), including but not limited to yoga, tai chi, and qigong, have been applied as exercise modalities for people with chronic obstructive pulmonary disease ...(COPD). AMBMT strategies have been found to be more effective than usual care; however, whether AMBMT is inferior, equivalent, or superior to pulmonary rehabilitation (PR) in people with COPD remains to be determined.
To assess the effects of AMBMTs compared with, or in addition to, PR in the management of COPD.
We searched the Cochrane Airways Group Specialised Register of trials and major Chinese databases, as well as trial registries from inception to July 2017. In addition, we searched references of primary studies and review articles. We updated this search in July 2018 but have not yet incorporated these results.
We included (1) randomised controlled trials (RCTs) comparing AMBMT (i.e. controlled breathing and/or focused meditation/attention interventions for which patients must actively move their joints and muscles for at least four weeks with no minimum intervention frequency) versus PR (any inpatient or outpatient, community-based or home-based rehabilitation programme lasting at least four weeks, with no minimum intervention frequency, that included conventional exercise training with or without education or psychological support) and (2) RCTs comparing AMBMT + PR versus PR alone in people with COPD. Two independent review authors screened and selected studies for inclusion.
Two review authors independently selected trials for inclusion, extracted outcome data, and assessed risk of bias. We contacted study authors if necessary to ask them to provide missing data. We calculated mean differences (MDs) using a random-effects model.
We included in the meta-analysis 10 studies with 762 participants across one or more comparisons. The sample size of included studies ranged from 11 to 206 participants. Nine out of 10 studies involving all levels of COPD severity were conducted in China with adults from 55 to 88 years of age, a higher proportion of whom were male (78%). Nine out of 10 studies provided tai chi and/or qigong programmes as AMBMT, and one study provided yoga. Overall, the term 'PR' has been uncritically applied in the vast majority of studies, which limits comparison of AMBMT and PR. For example, eight out of 10 studies considered walking training as equal to PR and used this as conventional exercise training within PR. Overall study quality for main comparisons was moderate to very low mainly owing to imprecision, indirectness (exercise component inconsistent with recommendations), and risk of bias issues. The primary outcomes for our review were quality of life, dyspnoea, and serious adverse events.When researchers compared AMBMT versus PR alone (mainly unstructured walking training), statistically significant improvements in disease-specific quality of life (QoL) (St. George's Respiratory Questionnaire (SGRQ) total score) favoured AMBMT: mean difference (MD) -5.83, 95% confidence interval (CI) -8.75 to -2.92; three trials; 249 participants; low-quality evidence. The common effect size, but not the 95% CI around the pooled treatment effect, exceeded the minimal clinically important difference (MCID) of minus four. The COPD Assessment Test (CAT) also revealed statistically significant improvements favouring AMBMT over PR, with scores exceeding the MCID of three, with an MD of 6.58 units (95% CI -9.16 to - 4.00 units; one trial; 74 participants; low-quality evidence). Results show no between-group differences with regard to dyspnoea measured by the modified Medical Research Council Scale (MD 0.00 units, 95% CI -0.37 to 0.37; two trials; 127 participants; low-quality evidence), the Borg Scale (MD 0.44 units, 95% CI -0.88 to 0.00; one trial; 139 participants; low-quality evidence), or the Chronic Respiratory Questionnaire (CRQ) Dyspnoea Scale (MD -0.21, 95% CI -2.81 to 2.38; one trial; 11 participants; low-quality evidence). Comparisons of AMBMT versus PR alone did not include assessments of generic quality of life, adverse events, limb muscle function, exacerbations, or adherence.Comparisons of AMBMT added to PR versus PR alone (mainly unstructured walking training) revealed significant improvements in generic QoL as measured by Short Form (SF)-36 for both the SF-36 general health summary score (MD 5.42, 95% CI 3.82 to 7.02; one trial; 80 participants; very low-quality evidence) and the SF-36 mental health summary score (MD 3.29, 95% CI 1.45 to 4.95; one trial; 80 participants; very low-quality evidence). With regard to disease-specific QoL, investigators noted no significant improvement with addition of AMBMT to PR versus PR alone (SGRQ total score: MD -2.57, 95% CI -7.76 to 2.62 units; one trial; 192 participants; moderate-quality evidence; CRQ Dyspnoea Scale score: MD 0.04, 95% CI -2.18 to 2.26 units; one trial; 80 participants; very low-quality evidence). Comparisons of AMBMT + PR versus PR alone did not include assessments of dyspnoea, adverse events, limb muscle function, exacerbations, or adherence.
Given the quality of available evidence, the effects of AMBMT versus PR or of AMBMT added to PR versus PR alone in people with stable COPD remain inconclusive. Evidence of low quality suggests better disease-specific QoL with AMBMT versus PR in people with stable COPD, and evidence of very low quality suggests no differences in dyspnoea between AMBMT and PR. Evidence of moderate quality shows that AMBMT added to PR does not result in improved disease-specific QoL, and evidence of very low quality suggests that AMBMT added to PR may lead to better generic QoL versus PR alone. Future studies with adequate descriptions of conventional exercise training (i.e. information on duration, intensity, and progression) delivered by trained professionals with a comprehensive understanding of respiratory physiology, exercise science, and the pathology of COPD are needed before definitive conclusions can be drawn regarding treatment outcomes with AMBMT versus PR or AMBMT added to PR versus PR alone for patients with COPD.
Phosphoinositide 3-kinase γ (PI3Kγ) is an attractive target to potentially treat a range of disease states. Herein, we describe the evolution of a reported phenylthiazole pan-PI3K inhibitor into a ...family of potent and selective benzothiazole inhibitors. Using X-ray crystallography, we discovered that compound 22 occupies a previously unreported hydrophobic binding cleft adjacent to the ATP binding site of PI3Kγ, and achieves its selectivity by exploiting natural sequence differences among PI3K isoforms in this region.
Home-based rehabilitation is a promising approach to improve access to pulmonary rehabilitation.
To assess whether self-monitored, home-based rehabilitation is as effective as outpatient, ...hospital-based rehabilitation in patients with chronic obstructive pulmonary disease (COPD).
Randomized, multicenter, noninferiority trial.
10 academic and community medical centers in Canada.
252 patients with moderate to severe COPD.
After a 4-week education program, patients took part in home-based rehabilitation or outpatient, hospital-based rehabilitation for 8 weeks. They were followed for 40 weeks to complete the 1-year study.
The primary outcome was the change in Chronic Respiratory Questionnaire dyspnea subscale score at 1 year. The primary analysis took a modified intention-to-treat approach by using all patients who provided data at the specified follow-up time, regardless of their level of adherence. The analysis used regression modeling that adjusted for the effects of center, sex, and baseline level. All differences were computed as home intervention minus outpatient intervention.
Both interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, -0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention.
The contribution of the educational program to the improvement in health status and exercise tolerance cannot be ascertained.
Home rehabilitation is a useful, equivalent alternative to outpatient rehabilitation in patients with COPD.
Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia.
Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients ...infected with SARS-CoV-2?
The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle.
Twenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 3-10 vs 9 4-12 days; P = .34), median duration of hospitalization (9 6-12 vs 10 6-18 days; P = .20), and median time to clinical improvement (4 3-7 vs 7 3-11 days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 63-67 vs 71 69-72 beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported.
To our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated.
ClinicalTrials.gov; No.: NCT04405102; URL: www.
gov.
In pulmonary arterial hypertension (PAH), the six-minute walk test (6MWT) is believed to be representative of patient's daily life physical activities (DL(PA)). Whether DL(PA) are decreased in PAH ...and whether the 6MWT is representative of patient's DL(PA) remain unknown.
15 patients with idiopathic PAH (IPAH) and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc) were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH. Each subject completed a 6MWT. The mean number of daily steps and the mean energy expenditure and duration of physical activities >3 METs were assessed with a physical activity monitor for seven consecutive days and used as markers of DL(PA).
The mean number of daily steps and the mean daily energy expenditure and duration of physical activities >3 METs were all reduced in PAH patients compared to their controls (all p<0.05). The mean number of daily steps correlated with the 6MWT distance for both IPAH and PAH-SSc patients (r = 0.76, p<0.01 and r = 0.85, p<0.01), respectively.
DL(PA) are decreased in PAH and correlate with the 6MWT distance. Functional exercise capacity may thus be a useful surrogate of DL(PA) in PAH.
The COPD Assessment Test (CAT) is a valid disease-specific questionnaire measuring health status. However, knowledge concerning its use regarding patient and disease characteristics remains limited. ...Our main objective was to assess the degree to which the CAT score varies and can discriminate between specific patient population groups.
The Canadian Cohort Obstructive Lung Disease (CanCOLD) is a random-sampled, population-based, multicenter, prospective cohort that includes subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease GOLD classifications 1 to 3). The CAT questionnaire was administered at three visits (baseline, 1.5 years, and 3 years). The CAT total score was determined for sex, age groups, smoking status, GOLD classification, exacerbations, and comorbidities.
A total of 716 subjects with COPD were included in the analysis. The majority of subjects (72.5%) were not previously diagnosed with COPD. The mean FEV
/FVC ratio was 61.1 ± 8.1%, with a mean FEV
% predicted of 82.3 ± 19.3%. The mean CAT scores were 5.8 ± 5.0, 9.6 ± 6.7, and 16.1 ± 10.0 for GOLD 1, 2, and 3+ classifications, respectively. Higher CAT scores were observed in women, current smokers, ever-smokers, and subjects with a previous diagnosis of COPD. The CAT was also able to distinguish between subjects who experience exacerbations vs those who had no exacerbation.
These results suggest that the CAT, originally designed for use in clinically symptomatic patients with COPD, can also be used in individuals with mild airflow obstruction and newly diagnosed COPD. In addition, the CAT was able to discriminate between sexes and subjects who experience frequent and infrequent exacerbations.
ClinicalTrials.gov; No.: NCT00920348; Study ID No.: IRO-93326.
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