Short- and Long-Term Impact of Prior Chronic Obstructive Pulmonary Disease Exacerbations on Healthcare Resource Utilization and Related Costs: An Observational Study (SHERLOCK).

The observational retrospective cohort Study on HEalthcare Resource utiLization (HCRU) related to exacerbatiOns in patients with COPD (SHERLOCK; D5980R00014) evaluated exacerbation-related HCRU and costs using the U.K. National Health Service Greater Glasgow and Clyde Health Board data. Patients (≥40 years) with COPD were stratified by exacerbations one year before the index date: Group A (none), B (1 moderate), C (1 severe) and D (≥2 moderate and/or severe). All-cause and COPD-related HCRU and costs were assessed over 36 months. Adjusted rate ratios (RRs) or relative costs versus Group A were estimated using generalized linear models with appropriate distributions and link functions. The study included 22 462 patients (Group A, n = 7788; B, n = 5151; C, n = 250 and D, n = 9273). At 12 months, RRs (95% CI) versus Group A for all-cause and COPD-related HCRU, respectively, were highest in Groups C (1.28 [1.18, 1.39] and 1.18 [1.09, 1.29]) and D (1.26 [1.23, 1.28] and 1.29 [1.26, 1.31]). General practitioner and outpatient visits, and general ward stays/days accounted for the greatest COPD-related HCRU. All-cause and COPD-related relative costs (95% CI) versus Group A at 12 months, respectively, were 1.03 (0.94, 1.12) and 1.06 (0.99, 1.13) in Group B; 1.47 (1.07, 2.01) and 1.54 (1.20, 1.97) in Group C; 1.47 (1.36, 1.58) and 1.63 (1.54, 1.73) in Group D. Increased HCRU and costs in patients with exacerbation histories persisted at 36 months, demonstrating the sustained impact of exacerbations. The study suggests the importance of management and prevention of exacerbations through intervention optimization and budgeting by payers for exacerbation-related costs.

Cost-Effectiveness of Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate versus Dual Therapies in Moderate-to-Very Severe Chronic Obstructive Pulmonary Disease: United Kingdom Analysis Using the ETHOS Study.

Background: In the 52-week ETHOS study (NCT02465567), fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) reduced moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations versus fixed-dose long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA dual therapies. Here, ETHOS data were used to estimate the long-term cost-effectiveness of BGF versus LAMA/LABA and ICS/LABA dual therapies in the United Kingdom. Methods: Costs, exacerbations, quality-adjusted life-years (QALYs), and LYs were extrapolated using a Markov model that considered disease severity progression, risk of moderate and severe exacerbations, adverse events, and treatment discontinuation in patients with moderate-to-very severe COPD receiving BGF 320/14.4/10 µg, the LAMA/LABA glycopyrronium/formoterol fumarate dihydrate 14.4/10 µg (GFF), or the ICS/LABA budesonide/formoterol fumarate dihydrate 320/10 µg (BFF). Utilities for COPD severity states were estimated using EuroQol 5-dimension 5-level data from ETHOS. Exacerbation disutilities were sourced from published literature. Healthcare resource utilization was based on ETHOS data, published literature, key external experts' input, and informed assumptions. Unit costs came from the UK National Health Service Schedule of Reference Costs, Unit Costs of Health and Social Care from the Personal Social Services Research Unit, and published literature. A lifetime horizon was considered, with costs, QALYs, and LYs discounted at 3.5% per annum. Results: The incremental cost-utility ratio (ICUR; per QALY gained) was £9901 for BGF versus GFF and £2164 for BGF versus BFF. The probability of treatments being cost-effective at the conventional UK-adopted willingness-to-pay threshold of ICUR <£20,000 was 85.1% for BGF, 14.3% for GFF, and 0.6% for BFF. Conclusion: Based on ETHOS data, BGF was demonstrated to be cost-effective versus LAMA/LABA and ICS/LABA dual therapies at the conventional UK-adopted willingness-to-pay threshold (ICUR <£20,000). The main cost-effectiveness driver for BGF versus LAMA/LABA and ICS/LABA therapies was reduction in rate of exacerbations, which reduced costs and preserved quality of life.

Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung function, increased disease burden, and mortality, and, therefore, preventing their occurrence is an important goal of COPD management. This review was conducted to identify the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD. METHODS: A literature review was performed in Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials (CENTRAL). Searches were conducted from January 2015 to July 2019. Eligible publications were peer-reviewed journal articles, published in English, that reported risk factors or predictors for the occurrence of moderate-to-severe exacerbations in adults age ≥ 40 years with a diagnosis of COPD. RESULTS: The literature review identified 5112 references, of which 113 publications (reporting results for 76 studies) met the eligibility criteria and were included in the review. Among the 76 studies included, 61 were observational and 15 were randomized controlled clinical trials. Exacerbation history was the strongest predictor of future exacerbations, with 34 studies reporting a significant association between history of exacerbations and risk of future moderate or severe exacerbations. Other significant risk factors identified in multiple studies included disease severity or bronchodilator reversibility (39 studies), comorbidities (34 studies), higher symptom burden (17 studies), and higher blood eosinophil count (16 studies). CONCLUSIONS: This systematic literature review identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Prior exacerbation history was confirmed as the most important predictor of future exacerbations. These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the global burden of COPD, including morbidity and mortality.

The long-term clinical impact of COPD exacerbations: a 3-year observational study (SHERLOCK).

BACKGROUND AND AIMS: Exacerbations of chronic obstructive pulmonary disease (COPD) drive disease progression and can lead to an accelerated decline in lung function and a burden on healthcare systems. The retrospective, observational cohort Study on HEalthcare Resource utiLization related to exacerbatiOns in patients with COPD (SHERLOCK; D5980R00014) evaluated the associations between exacerbation history and rates of subsequent COPD exacerbations in primary care patients from the National Health Service in Greater Glasgow and Clyde, United Kingdom. METHODS: Patients were stratified into four groups according to exacerbation history in the year before the index date: Group A (no exacerbations), Group B (1 moderate exacerbation only), Group C (1 severe exacerbation only), and Group D (⩾2 moderate or severe exacerbations). The frequencies of moderate and/or severe exacerbations were recorded over 36 months of follow-up and compared with reference Group A, using generalized linear models. RESULTS: Over 36 months of follow-up, the adjusted rate ratios (RRs, 95% confidence interval) of moderate or severe exacerbations relative to Group A were 1.60 (1.53, 1.67), 1.75 (1.50, 2.04), 1.61 (1.54, 1.68), and 3.61 (3.48, 3.74) for Groups B, C, B + C, and D, respectively. Compared with Group A, patients in Group C exhibited an increased rate of moderate (RR, 1.58 (1.35, 1.85)) and severe exacerbations (RR, 3.13 (2.20, 4.46)). CONCLUSION: SHERLOCK highlights that even one moderate exacerbation increases the risk for subsequent exacerbations compared with having no recent prior exacerbations. Reviewing recent exacerbation history to ascertain future exacerbation risk and inform COPD management may reduce hospitalizations and improve patient outcomes.

A Systematic Literature Review of the Humanistic Burden of COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, causing substantial economic and social burden. OBJECTIVE: This review assessed the patient-reported humanistic burden associated with moderate to very severe COPD, specifically the impact on health-related quality of life (HRQoL), symptoms, limitations in daily life, and emotional implications, through the use of HRQoL instruments. METHODS: A systematic review was conducted to retrieve relevant clinical data from published literature using a representative sample of countries where healthcare systems provide wide availability of COPD medications and/or universal coverage includes respiratory medicines (Australia, Canada, China, France, Germany, Italy, Spain, the UK, and the USA). The primary inclusion criteria were patients with moderate to very severe COPD. HRQoL was quantified with non-disease-specific and disease-specific questionnaires. RESULTS: In total, 82 studies from 95 publications presented HRQoL data from patients with moderate to very severe COPD. Patient-reported HRQoL declined with worsening airflow limitation, advancing GOLD group, and increasing exacerbation frequency. Both increasing frequency of hospitalization for COPD exacerbations and recurrent hospitalization adversely impacted HRQoL. Comorbidity incidence was higher in patients with increased airflow limitation. It was associated with a further decline in HRQoL and increased depression and anxiety, particularly as disease-associated pain worsened. Physical activity improved HRQoL over time. CONCLUSION: This review highlighted the impact of exacerbations and associated hospitalizations on the humanistic burden of COPD. These findings underline the importance of managing COPD actively, including prompt and appropriate use of pharmacological and non-pharmacological therapies that can improve symptoms and reduce the risk of exacerbations, thereby lessening the humanistic burden. Future reviews could consider a broader range of countries and publications to further assess the humanistic impact of COPD in low- and middle-income economies.

Efficacy and Safety of Budesonide/Glycopyrronium/Formoterol Fumarate versus Other Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis.

In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 µg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.

Prescribing pathways to triple therapy in patients with chronic obstructive pulmonary disease in the United States.

BACKGROUND: Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend triple therapy (TT) for chronic obstructive pulmonary disease (COPD) patients based on severity. TT utilization by severity is infrequently studied in real-world settings and may deviate significantly from current clinical recommendations. This study describes prescribing pathways to TT among patients with COPD in the United States. METHODS: This study analyzed Geisinger Health System electronic medical records from 1 January 2004 to 30 November 2016. Two retrospective cohorts of COPD patients were included: (1) incident COPD, and (2) incident TT users. COPD treatment patterns, including time to TT, were summarized. Time to TT was estimated using Kaplan-Meier methods. Predictors of the relative hazard for TT among incident COPD patients were estimated using Cox proportional hazards regressions. RESULTS: Incident COPD and TT cohorts included 57,141 and 8173 patients, respectively. TT was used by 9.6% of incident COPD patients. In the year before TT, 34.3% of incident TT patients received treatment combinations recommended before TT according to GOLD recommendations, which mainly included: long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs) + LAMAs, and inhaled corticosteroids + LABAs. Among incident TT patients, median time from COPD diagnosis to TT exceeded 2 years. The hazard for TT over time was associated with lower forced expiratory volume in 1 s values, more frequent exacerbations, current/previous smoking, and comorbid lung conditions such as pulmonary vascular disease, acute respiratory failure, and lung cancer. About 15-20% of the incident TT patients stepped down to a one- or two-drug regimen. Median time to TT discontinuation or step-down were 2 and 9 months, respectively. CONCLUSION: The study has revealed discrepancies in the treatment of COPD patients between GOLD guidelines and actual clinical practices in the United States. Pathways to TT differed from recommended therapy regimes. Further studies are needed to understand barriers to the use of guideline-recommended TTs by healthcare providers.The reviews of this paper are available via the supplemental material section.

Development and Validation of a Method to Estimate COPD Severity in Multiple Datasets: A Retrospective Study.

INTRODUCTION: Outcomes in chronic obstructive pulmonary disease (COPD) such as symptoms, hospitalisations and mortality rise with increasing disease severity. However, the heterogeneity of electronic medical records presents a significant challenge in measuring severity across geographies. We aimed to develop and validate a method to approximate COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 classification scheme, which categorises patients based on forced expiratory volume in 1 s, hospitalisations and the modified Medical Research Council dyspnoea scale or COPD Assessment Test. METHODS: This analysis was part of a comprehensive retrospective study, including patients sourced from the IQVIA Medical Research Data [IMRD; incorporating data from The Health Improvement Network (THIN), a Cegedim database] and the Clinical Practice Research Datalink (CPRD) in the UK, the Disease Analyzer in Germany and the Longitudinal Patient Data in Italy, France and Australia. Patients in the CPRD with the complete set of information required to calculate GOLD 2011 groups were used to develop the method. Ordinal logistic models at COPD diagnosis and at index (first episode of triple therapy) were then used to validate the method to estimate COPD severity, and this was applied to the full study population to estimate GOLD 2011 categories. RESULTS: Overall, 4579 and 12,539 patients were included in the model at COPD diagnosis and at index, respectively. Models correctly classified 74.4% and 75.9% of patients into severe and non-severe categories at COPD diagnosis and at index, respectively. Age, gender, time between diagnosis and start of triple therapy, healthcare resource use, comorbid conditions and prescriptions were included as covariates. CONCLUSION: This study developed and validated a method to approximate disease severity based on GOLD 2011 categories that can potentially be used in patients without all the key parameters needed for this calculation.

Prescribing Pathways to Triple Therapy: A Retrospective Observational Study of Adults with Chronic Obstructive Pulmonary Disease in the UK.

Purpose: Treatment guidance for chronic obstructive pulmonary disease (COPD) recommends inhaled corticosteroid (ICS)+long-acting muscarinic antagonist+long-acting ß2-agonist (LABA) triple therapy for patients who experience recurrent exacerbations, persistent breathlessness, or exercise limitation on dual therapy. However, information is limited on pathways to triple therapy in the UK. Patients and Methods: A retrospective cohort study was conducted using de-identified patient-level data from UK primary care electronic medical records from January 1, 2005 to May 1, 2016. Data were included from patients who had their first triple therapy regimen (index date) recorded during the study period and a minimum of 12 months' pre-index data. Treatment pathways to triple therapy were recorded, and the proportion of patients on triple therapy before their COPD diagnosis was determined. Adherence to triple therapy was estimated using the proportion of days covered (PDC). Results: After applying eligibility criteria, 82,300 patients were included, with a mean age at COPD diagnosis of 64.7 years. The major treatment pathway (27.9%) was the first initiation of ICS+LABA prior to triple therapy. Following COPD diagnosis, the median time to triple therapy was approximately 3.5 years. The estimated mean adherence to triple therapy was 81.8% PDC. Multivariate analysis showed that the following groups were more likely to have received previous therapy prior to triple therapy: females (versus males), patients with asthma (versus those without asthma), severe COPD (versus those with non-severe COPD), or fewer exacerbations (versus those with more exacerbations). Conclusion: Treatment pathways to triple therapy in the UK are diverse, highlighting the need to better understand factors involved in clinical decision-making.

Prescribing Pathways to Triple Therapy: A Multi-Country, Retrospective Observational Study of Adult Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Maintenance treatment strategies in COPD recommend inhaled corticosteroid (ICS) + long-acting muscarinic antagonist (LAMA) + long-acting ß2-agonist (LABA) triple therapy after initial dual therapy. Little is known about how treatment pathways to triple therapy vary across countries in clinical practice. METHODS: This multi-country, retrospective cohort study (conducted 1 January 2005-1 May 2016) included patients with a COPD diagnosis, and (UK only) evidence of smoking history, or (France, Italy, Germany, and Australia) an indicator confirming COPD diagnosis, a first instance of triple therapy recorded during the study period and ≥ 12 months of data prior to this date. Treatment pathways to triple therapy were analyzed in patients whose first instance of triple therapy was on or after the initial COPD diagnosis. The proportion of patients who initiated triple therapy prior to initial COPD diagnosis was also estimated. Meta-analyses of the main results were performed. RESULTS: In 130,729 patients across all countries, mean age (standard deviation) ranged from 63.4 (10.4) years (Germany) to 69.8 (9.9) years (Italy), and median time (interquartile range) from initial COPD diagnosis to first prescription of triple therapy ranged from 16.9 (5.7-36.2) months (Australia) to 42.5 (13.9-87.4) months (UK). ICS + LABA was the most common treatment pathway prior to triple therapy in the UK, Germany, and Italy (27.3%-31.6%); no previous maintenance therapy prior to triple therapy was the most common pathway in France and Australia (32.5% and 37.9%, respectively). Meta-analyses provided a pooled estimate of 20.4% (95% confidence interval: 13.8%-29.1%) for the proportion of patients initiating triple therapy at or before initial COPD diagnosis. CONCLUSIONS: In this retrospective cohort study, treatment pathways to triple therapy were diverse within and between countries. The differing impact of treatments may affect quality of life and disease control in patients with COPD. Further analyses should investigate factors influencing pathways to triple therapy.

Efficacy of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Versus Other Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting ß2-Agonist (ICS/LAMA/LABA) Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis.

INTRODUCTION: Triple inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) combination therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations/symptoms on dual LAMA/LABA or ICS/LABA therapy. The relative efficacy of budesonide/glycopyrronium/formoterol fumarate metered dose inhaler 320/18/9.6 µg (BGF MDI) in COPD was compared with other ICS/LAMA/LABA fixed-dose and open combination therapies in a network meta-analysis (NMA). METHODS: A systematic literature review was conducted to identify randomized controlled trials of at least 10-week duration, including at least one fixed-dose or open combination triple therapy arm, in patients with moderate to very severe COPD. Studies were assessed for methodological quality and risk of bias. A three-level hierarchical Bayesian NMA model was used to determine the exacerbation rate per patient per year as well as the following outcomes at week 24: changes from baseline in pre-dose trough forced expiratory volume in 1 s (FEV1), post-dose peak FEV1, and St. George's Respiratory Questionnaire (SGRQ) total score; proportion of SGRQ responders; and Transition Dyspnea Index focal score. Change from baseline in rescue medication use over weeks 12-24 was also analyzed. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. RESULTS: Eighteen studies (n = 29,232 patients) contributed to the NMA. ICS/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes, there were no statistically significant differences between BGF MDI and other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium/formoterol fumarate) and open combinations with data available within the network. Results from sensitivity analyses and meta-regression were consistent with the base-case scenario. CONCLUSION: This NMA suggested that BGF MDI has comparable efficacy to other ICS/LAMA/LABA fixed-dose and open triple combination therapies in reducing exacerbations and improving lung function and symptoms in patients with moderate to very severe COPD. Further research is warranted as additional evidence regarding triple therapies, especially fixed-dose combinations, becomes available.

Maintenance inhaler preference, attribute importance, and satisfaction in prescribing physicians and patients with asthma, COPD, or asthma-COPD overlap syndrome consulting for routine care.

Background: In respiratory disorders, patient- and physician-perceived satisfaction with the maintenance inhaler device is an important factor driving treatment compliance and outcomes. We examine inhaler preferences in asthma and COPD from patient and physician perspectives, particularly focusing on the relative importance of individual device attributes and patient characteristics guiding inhaler choice. Materials and methods: Real-world data from >7,300 patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS) consulting for routine care were derived from respiratory Disease Specific Programs conducted in Europe, USA, Japan, and China. Outcome variables included current pattern of inhaled maintenance therapy and device type, physician preference, patient-reported device attribute importance, and satisfaction. Results: The most commonly prescribed inhalers for maintenance therapy of asthma, COPD, and ACOS were dry powder inhalers (62.8%-88.5% of patients) and pressurized metered dose inhalers (18.9%-35.3% of patients). One-third of physicians stated no preference for maintenance device when prescribing treatment, and less than one-third of patients reported being "extremely satisfied" with any attribute of their device. Instructions being "simple and easy to follow" was the inhaler attribute most commonly selected as important. For approximately one-third of patients across all groups, "ease of use/suitability of inhaler device" was a reason for the prescribing decision, as stated by the physician. Device characteristics were more likely to impact the prescribing decision in older patients (in asthma and COPD; P<0.01) and those with worse disease severity (in COPD; P<0.001). Conclusion: A relatively high proportion of physicians had no preference for inhaler type across asthma, COPD, and ACOS. Simplicity of use was the most important inhaler attribute from a patient's perspective. Physicians appeared to place most importance on ease of use and device suitability when selecting inhalers for older patients and those with more severe disease, particularly in COPD.

A cross-sectional survey of current treatment and symptom burden of patients with COPD consulting for routine care according to GOLD 2014 classifications.

BACKGROUND: As part of the Respiratory Disease Specific Program (DSP) conducted to provide observations of clinical practice from a physician and matched patient viewpoint, this study aimed to establish how patients with COPD are treated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system and to quantify the symptom burden. METHODS: Data were obtained from the Respiratory DSP, a cross-sectional survey of patients with a diagnosis of COPD consulting for routine care in France, Germany, Italy, Spain, the UK, and the USA during the third quarter of 2013. Patients' exacerbation risk and symptom data were used for classification into GOLD groups A-D based on GOLD 2014 criteria. Prescribing practices were stratified by physician type and time since patient diagnosis. RESULTS: A total of 903 physicians participated in the Respiratory DSP, with data from 1,641 patients included in this analysis. Most patients were classified into GOLD groups B (n=742; 45.2%) and D (n=704; 42.9%). Patients in groups A and D were most likely to be treated in line with GOLD recommendations (61.5% and 77.5%, respectively), compared with 40.1% for group B. Patients with a diagnosis within the past 12 months were more likely to be treated according to recommendations. Inhaled corticosteroids (ICSs) in combination with one or more long-acting bronchodilator were prescribed across all GOLD groups. Patterns of treatment were, in general, similar for patients treated by a primary care physician or a pulmonologist. COPD assessment test scores ≥10 indicating a high symptom burden were reported for >80% of patients. CONCLUSION: This analysis confirmed a high symptom burden among patients with COPD and indicates some misalignment of prescribing with GOLD recommendations, particularly regarding the role of ICS/long-acting ß2-agonist (LABA) and ICS/LABA + long-acting muscarinic antagonist combinations across the different GOLD groups.

A cross-sectional survey of night-time symptoms and impact of sleep disturbance on symptoms and health status in patients with COPD.

BACKGROUND: Sleep disturbance has been termed the forgotten dimension of chronic obstructive pulmonary disease (COPD), but it is clinically important as most patients are affected. This study examined the incremental burden of illness associated with sleep disturbance in COPD, with reference to health status and disease impact, and the degree of concordance between physicians and patients in reporting night-time COPD symptoms. METHODS: Real-world data from >2,500 patients with COPD consulting for routine care were derived from respiratory Disease-Specific Programs conducted in Europe, the USA, and China. Night-time COPD symptom burden was assessed from patient and physician perspectives. Patients completed the Jenkins Sleep Evaluation Questionnaire (JSEQ), COPD assessment test (CAT), and EuroQol five-dimension questionnaire (EQ-5D). A regression approach was used to analyze the relationship between sleep disturbance (JSEQ score) and health status (EQ-5D score), adjusting for confounding variables. RESULTS: Frequency of night-time symptoms was high and was higher when reported by patients than physicians (69.7% and 65.7%, respectively). According to the JSEQ, 73.3% of patients had trouble falling asleep, 75.3% experienced night-time awakenings, 70.6% had trouble staying asleep, and 67.7% woke after a usual amount of sleep feeling worn out. Over half (52.7%) of patients received maintenance treatment where night-time symptom relief was stated by the physician as a treatment aim. A one unit increase in JSEQ score was associated with increased CAT score (0.7 units in Europe and the USA; 0.2 units in China). Sleep disturbance was significantly associated with worse health status (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.18, 1.36, P<0.001 for Europe; OR: 1.23, 95% CI: 1.12, 1.38, P<0.001 for the USA; and OR: 1.19, 95% CI: 1.10, 1.28, P<0.001 for China). CONCLUSIONS: Night-time symptoms and sleep disturbance are common among patients with COPD, and sleep disturbance has a detrimental impact on COPD symptoms and health status.

COPD symptom burden: impact on health care resource utilization, and work and activity impairment.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) can greatly impact the quality of life by limiting patients' activities. However, data on impact of symptomatic burden on the health care resource utilization (HCRU) and employment in COPD are lacking. We examined the association between COPD Assessment Test (CAT) score and direct/indirect costs associated with HCRU and work productivity. METHODS: Data from >2,100 patients with COPD consulting for routine care were derived from respiratory disease-specific programs in Europe, the USA and China. Questionnaires, including CAT and Work Productivity and Activity Impairment (WPAI), were used to collect the past and current disease status data and HCRU characteristics from physicians (general practitioners/specialists) and patients. A regression approach was used to quantify the association of CAT with HCRU and WPAI variables. CAT score was modeled as a continuous independent variable (range: 0-40). RESULTS: Ninety percent of patients with COPD had a CAT score ≥10. Short-acting therapy and maintenance bronchodilator monotherapy, respectively, were currently prescribed to patients with CAT scores of 10-19 (5.8% and 27.6%), 20-29 (5.1% and 13.1%) and 30-40 (2.8% and 6.6%). Prescribing of maintenance bronchodilator dual therapy was low across the CAT score groups (0-9, 7.8%; 10-19, 6.4%; 20-29, 5.9%; 30-40, 4.4%), whereas maintenance triple combination therapy was prescribed more commonly in patients with higher CAT scores (0-9, 16.1%; 10-19, 23.2%; 20-29, 25.9%; 30-40, 35.5%). Increasing CAT scores were significantly associated with a higher frequency of primary care physician visits (P<0.001), pulmonologist visits (P=0.007), exacerbations requiring hospitalization (P<0.001) and WPAI scores (P<0.001). CONCLUSION: Most patients with COPD presented with high symptom levels, despite being treated for COPD. Increasing symptom burden was associated with increasing HCRU and had a detrimental impact on work productivity.

A cross-sectional assessment of the burden of COPD symptoms in the US and Europe using the National Health and Wellness Survey.

INTRODUCTION: Past research has suggested significant relationships between symptoms and health outcomes among patients with COPD. However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment. As a result, the aim of this study was to document the burden of COPD symptoms among those who are currently treated with the standard-of-care (SOC) medications in both the US and Western Europe. METHODS: Data from the 2013 US (N=75,000) and 2011 (N=57,512)/2013 (N=62,000) European (France, Germany, Italy, Spain, and UK; 5EU) National Health and Wellness Survey (NHWS) were used. The NHWS is a health survey administered to a demographically representative sample of the adult population in each country. A total of 1,666 and 2,006 patients with self-reported physician diagnosis of COPD in the 5EU and US, respectively, were being treated with the appropriate SOC (based on self-reported medication use) and were included in the analyses. Symptoms (eg, dyspnea, coughing, wheezing) were reported descriptively and summed to create a symptom score (with higher score indicating more frequent symptoms). The relationships between the symptom score and patient outcomes (eg, health status using the Short Form-36 version 2 [SF-36v2], work productivity and activity impairment [WPAI], and self-reported health care resource use) were explored using regression modeling. RESULTS: Nearly all patients (99.7% and 99.8% in the 5EU and US, respectively) reported experiencing symptoms and >80% reported experiencing at least one symptom "often". Increasing symptom scores were associated with poorer health status (unstandardized beta [b] =-0.87 and -0.78 for mental component summary and physical component summary, respectively, in the US and b =-0.67 and -0.79 in the 5EU, respectively; all P<0.05). Increasing symptom scores were also associated with greater work impairment (b =0.09 and 0.06 for the US and 5EU, respectively), activity impairment (b =0.05 and 0.06, respectively), and health care resource utilization (eg, hospitalizations: b =0.05 and 0.06, respectively) (all P<0.05). Approximately 70% of patients reported some level of non-adherence. Greater non-adherence was significantly associated with more frequent symptoms, poorer health status, and greater work impairment and health care resource use (all P<0.05). CONCLUSION: Patients with COPD who are using the appropriate SOC still experience symptoms, which have a significant effect on both humanistic and economic outcomes.

Non-invasive and microinvasive electrical impedance spectra of skin cancer - a comparison between two techniques.

BACKGROUND/PURPOSE: Bio-electrical impedance spectra of skin cancer and other lesions can be assessed using both regular non-invasive probes and a novel type of microinvasive electrode system with a surface furnished with tiny spikes that penetrate stratum corneum. The aim of the study was to compare the accuracy of detection for various types of skin cancer using impedance spectra measured with these two different electrode systems in an objective way without optimising the power of discrimination. METHODS: Impedance spectra of 99 benign nevi, 28 basal cell carcinomas (BCC), and 13 malignant melanomas (MM) were measured using the two electrode systems. Classification of the lesions was made using Fisher's linear discriminant, and the sensitivities and specificities of the techniques were estimated using cross-validation. RESULTS: The best separation between nevi and BCC was achieved using the regular non-invasive probe (96% sensitivity and 86% specificity), whereas the best separation between nevi and MM was achieved using the microinvasive electrodes (92% sensitivity and 80% specificity). CONCLUSIONS: Our results indicate that the choice of electrode system is application dependent.

Skin cancer identification using multifrequency electrical impedance--a potential screening tool.

Electrical bio-impedance can be used to assess skin cancers and other cutaneous lesions. The aim of this study was to distinguish skin cancer from benign nevi using multifrequency impedance spectra. Electrical impedance spectra of about 100 skin cancers and 511 benign nevi were measured. Impedance of reference skin was measured ipsi-laterally to the lesions. The impedance relation between lesion and reference skin was used to distinguish the cancers from the nevi. It was found that it is possible to separate malignant melanoma from benign nevi with 75% specificity at 100% sensitivity, and to distinguish nonmelanoma skin cancer from benign nevi with 87% specificity at 100% sensitivity. The power of skin cancer detection using electrical impedance is as good as, or better than, conventional visual screening made by general practitioners.

Assessment of skin lesions and skin cancer using simple electrical impedance indices.

BACKGROUND/AIMS: Purpose of this investigation was to assess benign pigmented cellular nevus (BEN), basal cell carcinoma (BCC), dermatofibroma (DER), dysplastic nevus (DYS), and seborrheic keratoses (SEB) using in vivo non- invasive electrical impedance technique. METHODS: Electrical impedance was measured at 258 BEN, 34 BCC, 17 DER, 35 DYS, and 26 SEB lesions. Controls were measured at healthy skin close to the lesions. The impedance was measured between 1 kHz and 1 MHz at five depth settings. After the impedance measurements the lesions were histopathologically diagnosed. The impedance spectra were parameterized to four indices prior to the statistical analysis of the data. RESULTS: There were significant differences between the lesions and their controls for BEN (P < 0.001), BCC (P < 0.001), DYS (P < 0.01), and SEB (P < 0.01). CONCLUSIONS: There are clear statistical differences between impedance of common lesions and control skin. With some further developments, the impedance technique can be useful as a diagnostic decision support tool for skin cancer assessment.