A scoping review on the epidemiology and public significance of Brucella abortus in Chinese dairy cattle and humans.

Brucellosis, caused by Brucella spp., is a re-emerging One Health disease with increased prevalence and incidence in Chinese dairy cattle and humans, severely affecting animal productivity and public health. In dairy cattle, B. abortus is the primary causative agent although infections with other Brucella species occur occasionally. However, the epidemiological and comparative importance of B. abortus in dairy cattle and humans remains inadequately understood throughout China due to the heterogeneity in locations, quality, and study methods. This scoping review aims to describe the changing status of B. abortus infection in dairy cattle and humans, investigate the circulating Brucella species and biovars, and identify factors driving the disease transmission by retrieving publicly accessible literature from four databases. After passing the prespecified inclusion criteria, 60 original articles were included in the final synthesis. Although the reported animal-level and farm-level prevalence of brucellosis in dairy cattle was lower compared to other endemic countries (e.g. Iran and India), it has been reported to increase over the last decade. The incidence of brucellosis in humans displayed seasonal increases. The Rose Bengal Test and Serum Agglutination Test, interpreted in series, were the most used serological test to diagnose Brucella spp. in dairy cattle and humans. B. abortus biovar 3 was the predominant species (81.9%) and biovar (70.3%) in dairy cattle, and B. melitensis biovar 3 was identified as the most commonly detected strain in human brucellosis cases. These strains were mainly clustered in Inner Mongolia and Shannxi Province (75.7%), limiting the generalizability of the results to other provinces. Live cattle movement or trade was identified as the key factor driving brucellosis transmission, but its transmission pattern remains unknown within the Chinese dairy sector. These knowledge gaps require a more effective One Health approach to be bridged. A coordinated and evidence-based research program is essential to inform regional or national control strategies that are both feasible and economical in the Chinese context.

Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study.

BACKGROUND: Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score. This real-world study compared the effectiveness of switching patients with COPD in England from MITT to once-daily SITT with FF/UMEC/VI by evaluating rates of COPD exacerbation, healthcare resource use (HCRU) and associated direct medical costs. METHODS: Retrospective cohort pre-post study using linked primary care electronic health record and secondary care administrative datasets. Patients diagnosed with COPD at age ≥35 years, with smoking history, linkage to secondary care data and continuous GP registration for 12 months pre-switch and 6 months post-switch to FF/UMEC/VI were included. Index date was the first initiation of an FF/UMEC/VI prescription immediately following MITT use from 15 November 2017 to 30 September 2019. Baseline was 12 months prior to index, with outcomes assessed 6/12 months pre-switch and post-switch, and stratified by prior COPD exacerbation status. RESULTS: We included 2533 patients (mean [SD] age: 71.1 [9.9] years; 52.1% male). In the 6 months post-switch, there were significant decreases in the proportion of patients experiencing ≥1 moderate-to-severe (36.2%-28.9%), moderate only (24.4%-19.8%) and severe only (15.4%-11.8%) COPD exacerbation (each, p<0.0001) compared with the 6 months pre-switch. As demonstrated by rate ratios, there were significant reductions in exacerbation rates of each severity overall (p<0.01) and among patients with prior exacerbations (p<0.0001). In the same period, there were significant decreases in the rate of each COPD-related HCRU and total COPD-related costs (-24.9%; p<0.0001). CONCLUSION: Patients with COPD switching from MITT to once-daily SITT with FF/UMEC/VI in a primary care setting had significantly fewer moderate and severe exacerbations, and lower COPD-related HCRU and costs, in the 6 months post-switch compared with the 6 months pre-switch.

Characteristics of Users and New Initiators of Single- and Multiple-Inhaler Triple Therapy for Chronic Obstructive Pulmonary Disease in Germany.

Purpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany. Patients and Methods: Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period. Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period. Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.

Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019. In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years. The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).

Association between Increased Risk of Pneumonia with ICS in COPD: A Continuous Variable Analysis of Patient Factors from the IMPACT Study.

INTRODUCTION: Despite the proven benefits of inhaled corticosteroid (ICS)-containing triple therapy for chronic obstructive pulmonary disease (COPD), clinicians limit patient exposure to ICS due to the risk of pneumonia. However, there are multiple factors associated with the risk of pneumonia in patients with COPD. This post hoc analysis of IMPACT trial data aims to set the risks associated with ICS into a context of specific patient-related factors that contribute to the risk of pneumonia. METHODS: The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI), FF/VI or UMEC/VI. Annual rate of on-treatment pneumonias in the intent-to-treat population associated with age, body mass index (BMI), percent predicted forced expiratory volume in 1 s (FEV1) and blood eosinophil count (BEC) was evaluated. RESULTS: This analysis revealed that the annual rate of pneumonia showed the lowest risk at the age of 50 years. The 95% confidence intervals (CI) between ICS-containing and non-ICS containing treatments diverged in ages > 63 years, suggesting a significantly increased ICS-related risk in older patients. In contrast, the annual rate of pneumonia rose in both groups below BMI of 22.5 kg/m2, but above that, there was no relationship to pneumonia rate and no differential effect between the two groups. The relationship between BEC and pneumonia was flat up to > 300/µL cells with ICS-containing treatment and then rose. In contrast, the rate of pneumonia with non-ICS containing treatment appeared to increase at a lower level of BEC (~ 200/µL). CONCLUSIONS: There was little evidence of a differential effect of older age, lower BMI, lower FEV1 and BEC on the pneumonia rate between ICS-containing and non-ICS containing treatments. This analysis points to the need for a balanced approach to risk versus benefit in the use of ICS-containing treatments in COPD. CLINICAL TRIAL REGISTRATION: IMPACT ClinicalTrials.gov number, NCT02164513.

Understanding the Gaps in the Reporting of COPD Exacerbations by Patients: A Review.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function, poor quality of life, loss of exercise capacity, risk of serious cardiovascular events, hospitalization, and death. However, patients underreport exacerbations, and evidence suggests that unreported exacerbations have similar negative health implications for patients as those that are reported. Whilst there is guidance for physicians to identify patients who are at risk of exacerbations, they do not help patients recognise and report them. Newly developed tools, such as the COPD Exacerbation Recognition Tool (CERT) have been designed to achieve this objective. This review focuses on the underreporting of COPD exacerbations by patients, the factors associated with this, the consequences of underreporting, and potential solutions.

Treatment pathways, economic burden and clinical outcomes in new users of inhaled corticosteroid/long-acting B2-agonist dual therapy with chronic obstructive pulmonary disease in a primary care setting in England: a retrospective cohort study.

OBJECTIVE: Management of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) improves lung function and health status and reduces COPD exacerbation risk versus monotherapy. This study described treatment use, healthcare resource utilisation (HCRU), healthcare costs and outcomes following initiation of single-device ICS/LABA as initial maintenance therapy (IMT). DESIGN: Retrospective cohort study. SETTING: Primary care, England. DATA SOURCES: Linked data from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. PARTICIPANTS: Patients with COPD and ≥1 single-device ICS/LABA prescription between July 2015 and December 2018 were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Treatment pathways, COPD-related HCRU and healthcare costs, COPD exacerbations, time to triple therapy, medication adherence (proportion of days covered ≥80%) and indexed treatment time to discontinuation. Data for patients without prior maintenance therapy history (IMT users) and non-triple users were assessed over a 12-month follow-up period. RESULTS: Of 13 451 new ICS/LABA users, 5162 were IMT users (budesonide/formoterol, n=1056; beclomethasone dipropionate/formoterol, n=2427; other ICS/LABA, n=1679), for whom at 3 and 12 months post-index, 45.6% and 39.4% were still receiving any ICS/LABA. At >6 to ≤12 months, the proportion of IMT users with ≥1 outpatient visit (10.1%) and proportion with ≥1 inpatient stay (12.6%) had increased from those at 3 months (9.0% and 7.4%, respectively). Inpatient stays contributed most to total COPD-related healthcare costs. For non-triple IMT users, at 3 and 12 months post-index, 4.5% and 13.7% had ≥1 moderate-to-severe COPD exacerbation. Time to triple therapy initiation and time to discontinuation of index medication ranged from 45.9 to 50.2 months and 2.3 to 2.8 months between treatments. Adherence was low across all time points (21.5-27.6%). Results were similar across indexed therapies. CONCLUSIONS: In the year following treatment initiation, ICS/LABA adherence was poor and many patients discontinued or switched therapies, suggesting that more consideration and optimisation of treatment is required in England for patients initiating single-device ICS/LABA therapy.

Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

A novel Bayesian Latent Class Model (BLCM) evaluates multiple continuous and binary tests: A case study for Brucella abortus in dairy cattle.

Bovine brucellosis, primarily caused by Brucella abortus, severely affects both animal health and human well-being. Accurate diagnosis is crucial for designing informed control and prevention measures. Lacking a gold standard test makes it challenging to determine optimal cut-off values and evaluate the diagnostic performance of tests. In this study, we developed a novel Bayesian Latent Class Model that integrates both binary and continuous testing outcomes, incorporating additional fixed (parity) and random (farm) effects, to calibrate optimal cut-off values by maximizing Youden Index. We tested 651 serum samples collected from six dairy farms in two regions of Henan Province, China with four serological tests: Rose Bengal Test, Serum Agglutination Test, Fluorescence Polarization Assay, and Competitive Enzyme-Linked Immunosorbent Assay. Our analysis revealed that the optimal cut-off values for FPA and C-ELISA were 94.2 mP and 0.403 PI, respectively. Sensitivity estimates for the four tests ranged from 69.7% to 89.9%, while specificity estimates varied between 97.1% and 99.6%. The true prevalences in the two study regions in Henan province were 4.7% and 30.3%. Parity-specific odds ratios for positive serological status ranged from 1.2 to 2.2 for different parity groups compared to primiparous cows. This approach provides a robust framework for validating diagnostic tests for both continuous and discrete tests in the absence of a gold standard test. Our findings can enhance our ability to design targeted disease detection strategies and implement effective control measures for brucellosis in Chinese dairy farms.

Risk Factors Associated with a First Exacerbation Among Patients with COPD Classified as GOLD A and B in Routine Clinical Practice in the UK.

Purpose: Risk factors for exacerbations of chronic obstructive pulmonary disease (COPD) have been previously characterized for patients with more severe cases of COPD. It is unclear how the risk of first exacerbation may best be identified in patients with less severe disease. This study investigated risk factors for first exacerbation among English patients with COPD classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A or B. Patients and Methods: A retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) AURUM linked to Hospital Episode Statistics. Patients with COPD aged ≥35 years and classified as GOLD group A or B (2020 criteria) from January 2013-December 2019 were eligible. Patients were required to have 24 months history in CPRD (baseline). Two cohorts were defined: cohort 1 included patients with no severe exacerbations during baseline; cohort 2 included patients with no moderate or severe exacerbations during baseline. Risk factors associated with severe, or combined moderate and severe exacerbation were examined for up to 5 years of follow-up. Results: Overall, 194,948 patients were included in cohort 1 (mean age 66.2 years; 55.2% male), and 148,396 patients in cohort 2 (mean age 66.1 years; 56.6% male). Identified risk factors for exacerbation (and associated 1-year absolute risk of severe, or combined moderate and severe exacerbation, respectively) included: Medical Research Council dyspnea scale score (15.9%/28.4%); COPD Assessment Test score (9.6%/25.3%); GOLD grade of airflow limitation (forced expiratory volume in 1 second % predicted; 13.6%/27.5%); and lung cancer (8.1%/23.6%). After adjustment for risk factors, these factors remained independently associated with severe exacerbation at 1, 3, and 5 years of follow-up. Conclusion: The identified risk factors may aid physicians in the early recognition of patients with COPD classified as GOLD group A or B at risk of first exacerbation.

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

This review addresses outstanding questions regarding initial pharmacological management of chronic obstructive pulmonary disease (COPD). Optimizing initial treatment improves clinical outcomes in symptomatic patients, including those with low exacerbation risk. Long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) dual therapy improves lung function versus LAMA or LABA monotherapy, although other treatment benefits have been less consistently observed. The benefits of dual bronchodilation in symptomatic patients with COPD at low exacerbation risk, and its duration of efficacy and cost effectiveness in this population, are not yet fully established. Questions remain on the impact of baseline symptom severity, prior treatment, degree of reversibility to bronchodilators, and smoking status on responses to dual bronchodilator treatment. Using evidence from EMAX (NCT03034915), a 6-month trial comparing the LAMA/LABA combination umeclidinium/vilanterol with umeclidinium and salmeterol monotherapy in symptomatic patients with COPD at low exacerbation risk who were inhaled corticosteroid-naïve, we describe how these findings can be applied in primary care.

Comparative Effectiveness of Umeclidinium/Vilanterol versus Indacaterol/Glycopyrronium on Moderate-to-Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease in Clinical Practice in England.

Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England. Patients and Methods: This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed. Results: In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were <1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and <1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments. Conclusion: UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.

Benefit of prompt initiation of single-inhaler fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) in patients with COPD in England following an exacerbation: a retrospective cohort study.

BACKGROUND: Triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite dual therapy. The optimal timing of triple therapy following an exacerbation of COPD is unknown. The outcomes of prompt (≤ 30 days) vs. delayed (31-180 days) initiation of single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) following an exacerbation of COPD were examined. METHODS: This was a retrospective cohort study of linked English primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Patients aged ≥ 35 years with COPD were indexed on the first and/or earliest date of exacerbation between November 15, 2017 and March 31, 2019 with subsequent FF/UMEC/VI initiation within 180 days. Patients were required to be continuously registered with a general practitioner for ≥ 12 months prior to and following index. Subsequent exacerbations, direct medical costs, and hospital readmissions were compared between prompt and delayed initiators. Inverse probability of treatment weighting was used to adjust for measured confounders between cohorts. RESULTS: Overall, 1599 patients were included (prompt: 393, delayed: 1206). After weighting, prompt initiators had numerically lower moderate/severe exacerbations compared with delayed initiators (rate ratio: 0.87, 95% confidence interval [CI]: 0.76-1.01, p = 0.0587). Both all-cause and COPD-related 30-day hospital readmissions were significantly lower among patients with prompt initiation compared with delayed initiators (all-cause: 23.6% vs. 34.6%, odds ratio [95% CI]: 0.58 [0.36-0.95], p = 0.0293; COPD-related: 20.3% vs. 30.6%, odds ratio [95% CI]: 0.58 [0.35-0.96], p = 0.0347). Prompt initiators also had numerically lower all-cause total costs and significantly lower COPD-related costs per-person-per year compared with delayed initiators (COPD-related: £742 vs. £801, p = 0.0016). CONCLUSION: Prompt initiation of FF/UMEC/VI following a moderate/severe exacerbation was associated with fewer subsequent exacerbations, fewer hospital readmissions, and lower COPD-related medical costs compared with delayed initiation.

Triple therapy with an inhaled corticosteroid (ICS), a long-acting muscarinic antagonist (LAMA), and a long-acting ß2-agonist (LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) who still experience symptoms while taking dual therapy (LABA/LAMA or ICS/LABA). Triple therapy can be taken using single or multiple inhalers. The best time to start triple therapy for patients who may benefit from it following a short-term worsening (flare-up) of their COPD symptoms is unknown. This study assesses the effect of starting treatment with triple therapy sooner compared with later in patients with COPD.Patients who experienced a flare-up of their COPD symptoms were split into two groups ­ those who started taking triple therapy (via a single inhaler) within 30 days of their symptom flare-up and those who started taking triple therapy 31­180 days following their symptom flare-up. Over the 12 months following the initial flare-up, patients who started triple therapy earlier (within 30 days) had fewer subsequent symptom flare-ups, fewer hospital admissions, and lower healthcare costs compared with patients who started triple therapy later (31­180 days). These findings suggest that doctors should consider prescribing triple therapy (via a single inhaler) to their patients with COPD straight away if they experience a flare-up of their symptoms.

Cost-Effectiveness of Single-Inhaler Triple Therapy (FF/UMEC/VI) versus Tiotropium Monotherapy in Patients with Symptomatic Moderate-to-Very Severe COPD in the UK.

Purpose: For patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite maintenance treatment, clinical management guidelines recommend a stepwise escalation from monotherapy to dual therapy, and from dual therapy to triple therapy. However, in clinical practice, patients are often escalated directly from monotherapy to triple therapy based on disease severity. This study evaluated the cost-effectiveness of once-daily, single-inhaler fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) triple therapy compared with long-acting muscarinic antagonist monotherapy with once-daily tiotropium (TIO) in patients with symptomatic moderate-to-very severe COPD, from a UK National Health Service perspective. Patients and Methods: The validated GALAXY-COPD disease progression model was populated with patient baseline characteristics and treatment effect data from the 12-week GSK Study 207626 comparing FF/UMEC/VI with TIO in patients with moderate-to-very severe COPD. UK unit costs and drug costs (British Pound, 2021) were applied to healthcare resource utilization and treatments. The base case analysis was conducted over a lifetime horizon, and costs and health outcomes (except for life years [LYs]) were discounted at 3.5% per year. Model outputs included exacerbation rates, healthcare costs, LYs, quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios. Results: Overall, treatment with FF/UMEC/VI resulted in increased clinical benefit (reduction in total exacerbations and increased overall survival and QALYs), coupled with cost savings (derived from lower maintenance and exacerbation healthcare costs) compared with TIO monotherapy. In the base case analysis, FF/UMEC/VI provided an additional 0.393 LYs (95% range: 0.176, 0.655) and 0.443 QALYs (0.246, 0.648), at a cost saving of £880 (£54, £1608) versus TIO. FF/UMEC/VI remained the cost-effective (dominant) treatment option across sensitivity and scenario analyses. Conclusion: FF/UMEC/VI offers greater clinical benefits and is a cost-effective treatment option compared with TIO for the treatment of adult patients with COPD with persistent symptoms and/or who are at risk of exacerbation in the UK.

Comparison of Rescue Medication Prescriptions in Patients with Chronic Obstructive Pulmonary Disease Receiving Umeclidinium/Vilanterol versus Tiotropium Bromide/Olodaterol in Routine Clinical Practice in England.

Purpose: Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting ß2-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO. Patients and Methods: This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics. Patients with a COPD diagnosis at age ≥35 years were included (indexed) following initiation of single-inhaler UMEC/VI or TIO/OLO between July 1, 2015, and September 30, 2019. Outcomes included the number of rescue medication prescriptions at 12-months (primary), and at 6-, 18- and 24-months (secondary), adherence at 6-, 12-, 18- and 24-months post-index, defined as proportion of days covered ≥80% (secondary), and time-to-initiation of triple therapy (exploratory). Inverse probability of treatment weighting (IPTW) was used to balance potential confounding baseline characteristics. Superiority of UMEC/VI versus TIO/OLO for the primary outcome of rescue medication prescriptions was assessed using an intention-to-treat analysis with a p-value < 0.05. Results: In total, 8603 patients were eligible (UMEC/VI: n = 6536; TIO/OLO: n = 2067). Following IPTW, covariates were well balanced across groups. Patients initiating UMEC/VI had statistically significantly fewer (mean [standard deviation]; p-value) rescue medication prescriptions versus TIO/OLO in both the unweighted (4.84 [4.78] vs 5.68 [5.00]; p < 0.001) and weighted comparison (4.91 [4.81] vs 5.48 [5.02]; p = 0.0032) at 12 months; consistent results were seen at all timepoints. Adherence was numerically higher for TIO/OLO versus UMEC/VI at all timepoints. Time-to-triple therapy was similar between treatment groups. Conclusion: UMEC/VI was superior to TIO/OLO in reducing rescue medication prescriptions at 12 months after treatment initiation in a primary care cohort in England, potentially suggesting improvements in symptom control with UMEC/VI compared with TIO/OLO.

Use of CAPTURE to Identify Individuals Who May or May Not Require Treatment for Chronic Obstructive Pulmonary Disease.

Rationale: The CAPTURE tool (Chronic Obstructive Pulmonary Disease [COPD] Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk) was developed to identify patients with undiagnosed COPD with an FEV1 <60% predicted or risk of exacerbation as treatment criteria. Objectives: To test the ability of CAPTURE to identify patients requiring treatment because of symptoms or risk of exacerbation or hospitalization. Methods: Data were from COMPASS (Clinical, Radiological and Biological Factors Associated with Disease Progression, Phenotypes and Endotypes of COPD in China), a prospective study of COPD, chronic bronchitis without airflow limitation (postbronchodilator FEV1/FVC ratio ≥0.70), and healthy never-smokers. CAPTURE was tested as questions alone and with peak expiratory flow measurement. Sensitivity, specificity, and positive and negative predicted values (PPV and NPV) were calculated for COPD Assessment Test (CAT) scores ⩾10 versus <10, modified Medical Research Council (mMRC) scores ⩾2 versus <2, and at least one moderate exacerbation or hospitalization in the previous year versus none. Measurements and Main Results: Patients with COPD (n = 1,696) had a mean age of 65 ± 7.5 years, and 90% were male, with a postbronchodilator FEV1 of 66.5 ± 20.1% predicted. Control participants (n = 307) had a mean age of 60.2 ± 7.0 years, and 65% were male, with an FEV1/FVC ratio of 0.78 ± 0.04. CAPTURE using peak expiratory flow showed the best combination of sensitivity and specificity. Sensitivity and specificity were 68.5% and 64.0%, respectively, to detect a CAT score ⩾10; 85.6% and 61.0% to detect an mMRC score ⩾2; 63.5% and 55.6% to detect at least one moderate exacerbation; and 70.2% and 59.4% to detect at least one hospitalization. PPVs ranged from 15.6% (moderate exacerbations) to 47.8% (CAT score). NPVs ranged from 80.8% (CAT score) to 95.6% (mMRC score). Conclusions: CAPTURE has good sensitivity to identify patients with COPD who may require treatment because of increased symptoms or risk of exacerbations or hospitalization, including those with an FEV1 >60% predicted. High NPV values show that CAPTURE can also exclude those who may not require treatment. Clinical trial registered with www.clinicaltrials.gov (NCT04853225).

Burden of Disease in Patients with Mild or Mild-to-Moderate Chronic Obstructive Pulmonary Disease (Global Initiative for Chronic Obstructive Lung Disease Group A or B): A Systematic Literature Review.

Background: Patients with mild or mild-to-moderate chronic obstructive pulmonary disease (COPD), defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A/B, are regarded as having a lower risk of experiencing multiple or severe exacerbations compared with patients classified as GOLD group C/D. Current guidelines suggest that patients in GOLD A/B should commence treatment with a bronchodilator; however, some patients within this population who have a higher disease burden may benefit from earlier introduction of dual bronchodilator or inhaled corticosteroid-containing therapies. This study aimed to provide research-based insights into the burden of disease experienced by patients classified as GOLD A/B, and to identify characteristics associated with poorer outcomes. Methods: A systematic literature review (SLR) was conducted to identify evidence (burden of disease and prevalence data) relating to the population of interest (patients with COPD classified as GOLD A/B). Results: A total of 79 full-text publications and four conference abstracts were included. In general, the rates of moderate and severe exacerbations were higher among patients in GOLD group B than among those in group A. Among patients classified as GOLD A/B, the risk of exacerbation was higher in those with more symptoms (modified Medical Research Council or COPD Assessment Test scales) and more severe airflow limitation (forced expiratory volume in 1 second % predicted). Conclusion: Data from this SLR provide clear evidence of a heavier burden of disease for patients in GOLD B, compared with those in GOLD A, and highlight factors associated with worse outcomes for patients in GOLD A/B.

Comparative Effectiveness of Umeclidinium/Vilanterol versus Inhaled Corticosteroid/Long-Acting ß2-Agonist in Patients with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in England.

Purpose: To compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England. Patients and Methods: Active comparator, new-user, retrospective cohort study using CPRD-Aurum primary care data and linked Hospital Episode Statistics secondary care administrative data. Patients without exacerbations in the previous year were indexed on first/earliest prescription date of once-daily UMEC/VI or twice-daily ICS/LABA as initial maintenance therapy between July 2014-September 2019. Primary outcome: medication adherence at 12 months post-index, defined as proportion of days covered (PDC) ≥80%. PDC represented proportion of time over the treatment duration that the patient was theoretically in possession of the medication. Secondary outcomes: adherence at 6, 18, and 24 months post-index, time-to-triple therapy, time-to-first on-treatment COPD exacerbation, COPD-related and all-cause healthcare resource utilization (HCRU), and direct health-care costs. A propensity score was generated and inverse probability of treatment weighting (IPTW) was used to balance potential confounders. Superiority was defined as >0% difference between treatment groups. Results: In total, 6815 eligible patients were included (UMEC/VI:1623; ICS/LABA:5192). At 12 months post-index, weighted odds of a patient being adherent were significantly greater with UMEC/VI versus ICS/LABA (odds ratio [95% CI]: 1.71 [1.09, 2.66]; p=0.0185), demonstrating superiority of UMEC/VI. Patients taking UMEC/VI were statistically significantly more adherent than those taking ICS/LABA at 6, 18, and 24 months post-index (p<0.05). Differences in time-to-triple therapy, time-to-moderate COPD exacerbations, HCRU, and direct medical costs were not statistically significant between treatments after IPTW was applied. Conclusion: At 12 months post-treatment initiation, once-daily UMEC/VI was superior to twice-daily ICS/LABA in medication adherence among patients with COPD without exacerbations in the previous year, newly initiating dual maintenance therapy in England. The finding was consistent at 6, 18, and 24 months.

Two weeks of arm cycling sprint interval training enhances spinal excitability to the biceps brachii.

The present study aimed to investigate whether a 2-wk arm cycling sprint interval training (SIT) program modulated corticospinal pathway excitability in healthy, neurologically intact participants. We employed a pre-post study design with two groups: 1) an experimental SIT group and 2) a nonexercising control group. Transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of corticospinal axons were used at baseline and post-training to provide indices of corticospinal and spinal excitability, respectively. Stimulus-response curves (SRCs) recorded from the biceps brachii were elicited for each stimulation type during two submaximal arm cycling conditions [25 watts (W) and 30% peak power output (PPO)]. All stimulations were delivered during the mid-elbow flexion phase of cycling. Compared with baseline, performance on the time-to-exhaustion (TTE) test at post-testing was improved for members of the SIT group but was not altered for controls, suggesting that SIT improved exercise performance. There were no changes in the area under the curve (AUC) for TMS-elicited SRCs for either group. However, the AUC for TMES-elicited cervicomedullary motor-evoked potential SRCs were significantly larger at post-testing in the SIT group only (25 W: P = 0.012, d = 0.870; 30% PPO: P = 0.016, d = 0.825). This data shows that overall corticospinal excitability is unchanged following SIT, whereas spinal excitability is enhanced. Although the precise mechanisms underlying these findings during arm cycling at post-SIT are unknown, it is suggested that the enhanced spinal excitability may represent a neural adaptation to training.NEW & NOTEWORTHY Two weeks of arm cycling sprint interval training (SIT) improves subsequent aerobic exercise performance and induces changes within the descending corticospinal pathway. Specifically, spinal excitability is enhanced following training, whereas overall corticospinal excitability does not change. These results suggest that the enhanced spinal excitability may represent a neural adaptation to training. Future work is required to discern the precise neurophysiological mechanisms underlying these observations.