Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers.

BACKGROUND AND OBJECTIVE: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. METHOD: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. RESULTS: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. CONCLUSIONS: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD.

"Can do, don't do" are not the lazy ones: a longitudinal study on physical functioning in patients with COPD.

BACKGROUND AND OBJECTIVE: Reduced physical capacity (PC) and physical activity (PA) are common in COPD patients and associated with poor outcome. However, they represent different aspects of physical functioning and interventions do not affect them in the same manner. To address this, a new PC-PA quadrant concept was recently generated to identify clinical characteristics of sub-groups of physical functioning. The objective of this study was to I) proof the new concept and to verify their differentiating clinical characteristics, II) evaluate the consistency of the concept over time, III) assess whether patients changed their quadrant affiliation over time, IV) and to test if changes in quadrant affiliations are associated with changes in clinical characteristics. METHODS: In a longitudinal, prospective, non-interventional cohort with mild to very severe COPD patients, PC and PA as well as respiratory variables, COPD-specific health status, comorbidities, survival, and exacerbations were yearly assessed. RESULTS: Data from 283 patients were analysed at baseline. Mean (min/max) follow-up time was 2.4 (0.5/6.8) years. The PC-PA quadrants could be characterized as follows: I) "can't do, don't do": most severe and symptomatic, several comorbidities II) "can do, don't do": severe but less symptomatic, several comorbidities III) "can't do, do do": few patients, severe and symptomatic, less comorbidities IV) "can do, do do": mildest and less symptomatic, less comorbidities, lowest exacerbation frequency. Of the 172 patients with at least one follow-up, 58% patients never changed their quadrant affiliation, while 17% declined either PC, PA or both, 11% improved their PC, PA or both, and 14% showed improvement and decline in PC, PA or both during study period. None of the clinical characteristics or their annual changes showed consistent significant and relevant differences between all individual sub-groups. CONCLUSION: Our findings suggest that there are no clinical characteristics allowing to distinguish between the PC-PA quadrants and the concept seems not able to illustrate disease process. However, the already low PA but preserved PC in the "can do, don't do" quadrant raises the question if regularly assessment of PA in clinical practice would be more sensitive to detect progressive deterioration of COPD compared to the commonly used PC. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01527773.

Handgrip Strength Seems Not to Be Affected by COPD Disease Progression: A Longitudinal Cohort Study.

Skeletal muscle dysfunction, functional exercise capacity impairment and reduced physical activity are characteristic features in patients with chronic obstructive pulmonary disease (COPD). Assessments addressing muscle strength of the upper limb, such as measurement of handgrip strength (HGS), are rarely performed and reported. We aimed to analyze the course of HGS and possible predictors of changes in HGS over time in COPD. Yearly assessments of various disease markers were performed for a follow-up of up to seven years in a cohort of COPD patients to assess the longitudinal disease process. Data of 194 patients with at least one follow-up measurement were analyzed. HGS decreased significantly by B = -0.86 (95% CI -1.09/-0.62, p < 0.001) over time. The multivariate mixed effects model showed an independent association between greater annual declines in HGS and lower numbers of steps per day by B = 0.11 (95% CI 0.03/0.18, p = 0.006) and an enhanced change in COPD Assessment Test scores by B = -0.01 (95% CI -0.01/-0.00, p = 0.034). No evidence for an independent association between annual decline in HGS and FEV1% pred. by B = -0.01 (95% CI -0.03/0.01, p = 0.297) was shown. Patients who died during follow-up did not exhibit greater declines in HGS compared to survivors (p = 0.884). Although HGS significantly decreased over time, no pathophysiological link with COPD disease progression could be demonstrated. Previous cross-sectional associations between HGS and mortality could not be confirmed in this longitudinal setting. Our data suggests that repeated monitoring of HGS in clinical settings seems not to be helpful to predict COPD specific disease progression.

[Pulmonary Rehabilitation]. / Pulmonale Rehabilitation.

Pulmonary Rehabilitation Abstract. Pulmonary rehabilitation is a comprehensive therapeutic approach for patients with advanced chronic lung diseases which leads to a decline of dyspnea, an increase of exercise capacity and an increase of quality of life. Further effects are a reduction of frequency of hospitalisations and an increase of physical activity, if a self management education program is integrated. Pulmonary rehabilitation incorporates an individualised training program with focus on endurance, strength and mobility, further a disease specific education with the goal to improve self efficacy and self management of the patients, specially with the goal to improve their daily physical activity. Due to the good evidence of pulmonary rehabilitation, the accredited programs are accepted and paid by the swiss insurances.

Diagnosis, Prevention and Treatment of Stable COPD and Acute Exacerbations of COPD: The Swiss Recommendations 2018.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update.

A multicentre validation of the 1-min sit-to-stand test in patients with COPD.

Our aim was to comprehensively validate the 1-min sit-to-stand (STS) test in chronic obstructive pulmonary disease (COPD) patients and explore the physiological response to the test.We used data from two longitudinal studies of COPD patients who completed inpatient pulmonary rehabilitation programmes. We collected 1-min STS test, 6-min walk test (6MWT), health-related quality of life, dyspnoea and exercise cardiorespiratory data at admission and discharge. We assessed the learning effect, test-retest reliability, construct validity, responsiveness and minimal important difference of the 1-min STS test.In both studies (n=52 and n=203) the 1-min STS test was strongly correlated with the 6MWT at admission (r=0.59 and 0.64, respectively) and discharge (r=0.67 and 0.68, respectively). Intraclass correlation coefficients (95% CI) between 1-min STS tests were 0.93 (0.83-0.97) for learning effect and 0.99 (0.97-1.00) for reliability. Standardised response means (95% CI) were 0.87 (0.58-1.16) and 0.91 (0.78-1.07). The estimated minimal important difference was three repetitions. End-exercise oxygen consumption, carbon dioxide output, ventilation, breathing frequency and heart rate were similar in the 1-min STS test and 6MWT.The 1-min STS test is a reliable, valid and responsive test for measuring functional exercise capacity in COPD patients and elicited a physiological response comparable to that of the 6MWT.

Unravelling Contaminants in the Anthropocene Using Statistical Analysis of Liquid Chromatography-High-Resolution Mass Spectrometry Nontarget Screening Data Recorded in Lake Sediments.

The significant increase in traces of human activity in the environment worldwide provides evidence of the beginning of a new geological era, informally named the Anthropocene. The rate and variability of these human modifications at the local and global scale remain largely unknown, but new analytical methods such as high-resolution mass spectrometry (HRMS) can help to characterize chemical contamination. We therefore applied HRMS to investigate the contamination history of two lakes in Central Europe over the preceding 100 years. A hierarchical clustering analysis (HCA) of the collected time series data revealed more than 13 000 profiles of anthropogenic origin in both lakes, defining the beginning of large-scale human impacts during the 1950s. Our results show that the analysis of temporal patterns of nontarget contaminants is an effective method for characterizing the contamination pattern in the Anthropocene and an important step in prioritizing the identification of organic contaminants not yet successfully targeted by environmental regulation and pollution reduction initiatives. As proof of the concept, the success of the method was demonstrated with the identification of the pesticide imazalil, which probably originated from imported fruits. This new approach applicable to palaeoarchives can effectively be used to document the time and rate of change in contamination over time and provide additional information on the onset of the Anthropocene.

Determinants of annual change in physical activity in COPD.

BACKGROUND AND OBJECTIVE: Daily physical activity (PA) is reduced in patients with COPD. Previous cross-sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co-morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co-morbidities is scant. METHODS: In a heterogeneous cohort of COPD patients, we annually assessed the number of steps per day over 1 week and potential determinants including lung function, exacerbations and co-morbidities. Univariable and multivariable mixed effect models were used to investigate associations between the change in steps per day (dependent variable) and possible predictors and their annual changes. RESULTS: A total of 177 COPD patients (46% GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 1/2, 38% stage 3 and 16% stage 4) with a mean (min/max) follow-up time of 2.7 (1/5) years were annually assessed. The number of steps per day decreased significantly over time (P < 0.001) with a mean annual change of -508 steps. The decrease in activity was significantly associated with forced expiratory volume in 1 s (FEV1 ) % predicted (P = 0.020) but not with annual changes in FEV1 . Hyperinflation, exacerbations, co-morbidities and their annual changes, and survival did not significantly affect change in PA. CONCLUSION: COPD patients have a substantial decrease of PA over time. This decrease seems to be determined by the degree of airflow limitation. However, patients with a greater annual decline in lung function did not show a greater decrease in PA. The rate of decline in PA did not differ between survivors and non-survivors in this cohort.

Diagnostic accuracy of methacholine challenge tests assessing airway hyperreactivity in asthmatic patients - a multifunctional approach.

BACKGROUND: There are few studies comparing diagnostic accuracy of different lung function parameters evaluating dose-response characteristics of methacholine (MCH) challenge tests (MCT) as quantitative outcome of airway hyperreactivity (AHR) in asthmatic patients. The aim of this retrospectively analysis of our database (Clinic Barmelweid, Switzerland) was, to assess diagnostic accuracy of several lung function parameters quantitating AHR by dose-response characteristics. METHODS: Changes in effective specific airway conductance (sGeff) as estimate of the degree of bronchial obstruction were compared with concomitantly measured forced expiratory volume in 1 s (FEV1) and forced expiratory flows at 50% forced vital capacity (FEF50). According to the GINA Guidelines the patients (n = 484) were classified into asthmatic patients (n = 337) and non-asthmatic subjects (n = 147). Whole-body plethysmography (CareFusion, Würzburg, Germany) was performed using ATS-ERS criteria, and for the MCTs a standardised computer controlled protocol with 3 consecutive cumulative provocation doses (PD1: 0.2 mg; PD2: 1.0 mg; PD3: 2.2 mg) was used. Break off criterion for the MCTs were when a decrease in FEV1 of 20% was reached or respiratory symptoms occurred. RESULTS: In the assessment of AHR, whole-body plethysmography offers in addition to spirometry indices of airways conductance and thoracic lung volumes, which are incorporated in the parameter sGeff, derived from spontaneous tidal breathing. The cumulative percent dose-responses at each provocation step were at the 1st level step (0.2 mg MCH) 3.7 times, at the 2nd level step (1 mg MCH) 2.4 times, and at the 3rd level step (2.2 mg MCH) 2.0 times more pronounced for sGeff, compared to FEV1. A much better diagnostic odds ratio of sGeff (7.855) over FEV1 (6.893) and FEF50 (4.001) could be found. Moreover, the so-called dysanapsis, and changes of end-expiratory lung volume were found to be important determinants of AHR. CONCLUSIONS: Applying plethysmographic tidal breathing analysis in addition to spirometry in MCTs provides relevant advantages. The absence of deep and maximal inhalations and forced expiratory manoeuvres improve the subject's cooperation and coordination, and provide sensitive and differentiated test results, improving diagnostic accuracy. Moreover, by the combined assessment, pulmonary hyperinflation and dysanapsis can be respected in the differentiation between "asthmatics" and "non-asthmatics".

Sedation during bronchoscopy: data from a nationwide sedation and monitoring survey.

BACKGROUND: There is limited knowledge on practice patterns in procedural sedation and analgesia (PSA), the use of propofol, and monitoring during flexible bronchoscopy (FB). The purpose of this study was to assess the current practice patterns of FBs and to focus on the use of propofol, the education of the proceduralist, and the involvement of anaesthesiologists during FB. METHODS: An anonymous questionnaire was sent to 299 pulmonologists. Only respondents who were active physicians in adult respiratory medicine performing FB were subsequently analysed. RESULTS: The response rate was 78 % and 27,149 FB in the previous 12 months were analysed. The overall sedation-related morbidity rate was 0.02 % and mortality was 7/100'000 FB. Sedation was used in 95 % of bronchoscopies. The main drugs used for PSA were propofol (77 %) and midazolam (46 %). In 84 % of PSAs propofol was used without the attendance of an anaesthesiologist. The use of propofol was associated with high volume bronchoscopists (p < 0.010) and career-young pulmonologists (p < 0.001). While monitoring vital parameters has become standard practice, pulmonologists reported a very low rate of systematic basic education and training in the field of PSA (50 %). CONCLUSIONS: In Switzerland, PSA during FB is mostly performed with propofol without the attendance of an anaesthesiologist and the use of this drug is expected to increase in the future. While monitoring standards are very high there is need for policies to improve education, systematic training, and support for pulmonologists for PSA during FB.

Impact of comorbidities on physical activity in COPD.

BACKGROUND AND OBJECTIVE: Both comorbidities and physical inactivity have been shown to impair quality of life and contribute to hospital admissions and mortality in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that the comorbid status predicts the level of daily physical activity (PA) in COPD. METHODS: In 228 patients with COPD (76% men; median (quartiles) age: 64 (59/69) years; percentage of predicted forced expiratory volume in 1 s (FEV1 % pred): 44 (31/63)), comorbidities were assessed by medical history, clinical interviews, examination and blood analysis. PA level (PAL) was measured by an activity monitor (SenseWear Pro, Bodymedia Inc., Pittsburgh, PA, USA). The association between PAL and comorbidities was investigated by univariate and multivariate regression analysis. RESULTS: Seventy-nine percent of the COPD patients had at least one additional chronic comorbidity, 56% had two or more comorbidities and 35% had three or more comorbidities. In univariate analysis body mass index, the number of pack years and having at least one additional comorbidity was negatively associated with PAL while there was a positive nonlinear association between FEV1 and PAL. The presence of at least one additional comorbidity was independently associated with PAL irrespective of airflow limitation. CONCLUSIONS: In this cohort, almost 80% of COPD patients had at least one additional chronic comorbidity. The level of daily PA seems to be significantly impaired by the presence of comorbidities irrespective of the type of comorbidity and independent of the degree of airflow limitation. CLINICAL TRIAL REGISTRATION: NCT01527773 at http://www.clinicalTrials.gov.

Are Predictors for Overall Mortality in COPD Patients Robust over Time?

(1) Background: Mortality is a major outcome in research on chronic obstructive pulmonary disease (COPD) with various predictors described. However, the dynamic courses of important predictors over time are disregarded. This study evaluates if longitudinal assessment of predictors provides additional information on the mortality risk in COPD when compared with a cross-sectional analysis.; (2) In a longitudinal, prospective, non-interventional cohort study including mild to very severe COPD patients, mortality and its various possible predictors were annually assessed up to seven years.; (3) Results: 297 patients were analysed. Mean (SD) age was 62.5 (7.6) years and 66% males. Mean (SD) FEV1 was 48.8 (21.4)%. A total of 105 events (35.4%) happened with a median (95% CI) survival time of 8.2 (7.2/NA) years. No evidence for a difference between the raw variable and the variable history on the predictive value for all tested variables over each visit was found. There was no evidence for changing effect estimates (coefficients) across the study visits due to the longitudinal assessment; (4) Conclusions: We found no evidence that predictors of mortality in COPD are time dependent. This implies that cross-sectional measured predictors show robust effect estimates over time and multiple assessments seem not to change the predictive value of the measure.

Early versus late pulmonary rehabilitation in chronic obstructive pulmonary disease patients with acute exacerbations: a randomized trial.

BACKGROUND: Around the world, the timing of referral of chronic obstructive pulmonary disease (COPD) patients for pulmonary rehabilitation differs from immediately after exacerbation (early) to later on when patients are in a stable state (late). There are no trials comparing the different time points of referral for pulmonary rehabilitation. OBJECTIVES: Our aim was to compare the effects of early and late pulmonary rehabilitation on exacerbation rates and health-related quality of life (HRQOL) in COPD patients with exacerbations. METHODS: We randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages II-IV) with a recent exacerbation to early (within 2 weeks) or late pulmonary rehabilitation (starting 6 months after randomization and in a stable state). The primary outcome was the exacerbation rate over 18 months, and secondary outcomes included HRQOL and mortality. We used multivariate analyses and an intention-to-treat analysis approach. RESULTS: We randomized 36 patients to pulmonary rehabilitation. On average, patients with early rehabilitation (n = 19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43-1.63; p = 0.60). Over the 18-month period, patients with late rehabilitation experienced more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74 and on the Medical Research Council dyspnea scale 0.37), but neither these differences nor any difference in HRQOL domains reached statistical significance. CONCLUSIONS: We did not find any statistically significant differences between early and late pulmonary rehabilitation. However, our trial indicates that early rehabilitation may lead to faster recovery of HRQOL after exacerbations compared to rehabilitation later on when patients are in a stable state.

Contemporary mass balance on a cold Eastern Alpine ice cap as a potential link to the Holocene climate.

Alpine cold ice caps are sensitive indicators of local climate. The adequate interpretation of this information in an ice core requires detailed in situ glaciological and meteorological records, of which there are few. The Weißseespitze summit ice cap (3499 m) presents an ideal case to compare past and present climate and mass balance, with limited ice flow, but close to 6000 years locked into about 10 m of ice. First-ever meteorological observations at the ice dome have revealed that over 3 years of observation most of the accumulation took place between October and December and from April to June. In the colder winter months, between January and March, wind erosion prevents accumulation. Melt occurred between June and September, ice was only affected during short periods, mainly in August, which caused ice losses of up to 0.6 m (i.e. ~ 5% of the total ice thickness). Historical data points at a loss of of 34.9 ± 10.0 m between 1893 and 2018 and almost balanced conditions between 1893 and 1914. The local evidence of ice loss lays the basis for the interpretation of past gaps in the ice core records as past warm/melt events.

Functional Predictors Discriminating Asthma-COPD Overlap (ACO) from Chronic Obstructive Pulmonary Disease (COPD).

Background: A significant proportion of patients with obstructive lung disease have clinical and functional features of both asthma and chronic obstructive pulmonary disease (COPD), referred to as the asthma-COPD overlap (ACO). The distinction of these phenotypes, however, is not yet well-established due to the lack of defining clinical and/or functional criteria. The aim of our investigations was to assess the discriminating power of various lung function parameters on the assessment of ACO. Methods: From databases of 4 pulmonary centers, a total of 540 patients (231 males, 309 females), including 372 patients with asthma, 77 patients with ACO and 91 patients with COPD, were retrospectively collected, and gradients among combinations of explanatory variables of spirometric (FEV1, FEV1/FVC, FEF25-75), plethysmographic (sReff, sGeff, the aerodynamic work of breathing at rest; sWOB), static lung volumes, including trapped gases and measurements of the carbon monoxide transfer (DLCO, KCO) were explored using multiple factor analysis (MFA). The discriminating power of lung function parameters with respect to ACO was assessed using linear discriminant analysis (LDA). Results: LDA revealed that parameters of airway dynamics (sWOB, sReff, sGeff) combined with parameters of static lung volumes such as functional residual capacity (FRCpleth) and trapped gas at FRC (VTG FRC) are valuable and potentially important tools discriminating between asthma, ACO and COPD. Moreover, sWOB significantly contributes to the diagnosis of obstructive airway diseases, independent from the state of pulmonary hyperinflation, whilst the diffusion capacity for carbon monoxide (DLCO) significantly differentiates between the 3 diagnostic classes. Conclusion: The complexity of COPD with its components of interaction and their heterogeneity, especially in discrimination from ACO, may well be differentiated if patients are explored by a whole set of target parameters evaluating, interactionally, flow limitation, airway dynamics, pulmonary hyperinflation, small airways dysfunction and gas exchange disturbances assessing specific functional deficits.

Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index.

BACKGROUND: The BODE index (including body-mass index, airflow obstruction, dyspnoea, and exercise capacity) was an important contribution to the prognostic assessment of patients with chronic obstructive pulmonary disease (COPD). However, no study has assessed whether the risk of mortality predicted by the BODE index matches the observed mortality in different populations. We assessed the calibration of the BODE index, updated it to improve its calibration, and developed and validated a simplified index for use in primary-care settings. METHODS: We included 232 patients from the Swiss Barmelweid cohort with longstanding and severe COPD and 342 patients from the Spanish Phenotype and Course of COPD cohort study who had had their first hospital admission due to moderate-to-severe COPD. In both cohorts we compared the observed 3-year risk of all-cause mortality with the risk predicted by the BODE index. We then updated the BODE index and developed a simplified ADO index (including age, dyspnoea, and airflow obstruction) from the Swiss cohort, and validated both in the Spanish cohort. FINDINGS: Calibration of the BODE index was poor, with relative underprediction of 3-year risk of mortality by 36% in the Swiss cohort (median predicted risk 21.7% [IQR 12.7-31.7] vs 34.1% observed risk; p=0.013) and relative overprediction by 39% in the Spanish cohort (16.7% [12.7-31.7] vs 12.0%; p=0.035). The 3-year risk of mortality predicted by both the updated BODE (median 10.7% [8.1-13.8]) and ADO indices (11.8% [9.1-14.3]) matched the observed mortality in the Spanish cohort well (p=0.99 and p=0.98, respectively). INTERPRETATION: Both the updated BODE and ADO indices could lend support to the prognostic assessment of patients with COPD in specialised and primary-care settings. Such assessment enhances the targeting of treatments to individual patients. FUNDING: Swiss National Science Foundation; Klinik Barmelweid; Fondo de Investigación Sanitaria Ministry of Health, Spain; Agència d'Avaluació de Tecnologia i Recerca Mèdiques, Catalonia Government; Spanish Society of Pneumology and Thoracic Surgery; Catalan Foundation of Pneumology; Red RESPIRA; Red RCESP; Fondo de Investigación Sanitaria; Fondo de Investigación Sanitaria; Fundació La Marató de TV3; Novartis Farmacèutica, Spain.

Compliance of Pharmacotherapy with GOLD Guidelines: A Longitudinal Study in Patients with COPD.

Objective: To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting. Methods: This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland. Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016. For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline. We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication. Groups were compared via ANOVA. Results: Data of 305 patients (62±7 years, 66% men) were analysed. In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline. Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines. Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively. Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%). Conclusion: The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups. The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement.

Recruitment barriers in a randomized controlled trial from the physicians' perspective: a postal survey.

BACKGROUND: The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment. METHODS: We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier) to 7 (no agreement with statement = no recruitment barrier). RESULTS: 38 of 55 recruiting physicians returned questionnaires (69% response rate), of which 35 could be analyzed (64% useable response rate). Recruiting physicians reported that "time constraints" (median agreement of 3, interquartile range 2-5) had the most negative impact on recruitment followed by "difficulties including identified eligible patients" (median agreement of 5, IQR 3-6). Other barriers such as "trial design barriers", "lack of access to treatment", "individual barriers of recruiting physicians" or "insufficient training of recruiting physicians" were perceived to have little or no impact on patient recruitment. CONCLUSION: Physicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be developed and tested in randomized trials. TRIAL REGISTRATION: ISRCTN84612310.

Influence of morphology of monolithic sulfur-poly(acrylonitrile) composites used as cathode materials in lithium-sulfur batteries on electrochemical performance.

Solvent-induced phase separation (SIPS) and thermally-induced phase separation (TIPS) derived poly(acrylonitrile) (PAN) based monoliths with different morphology and specific surface area were prepared and thermally converted into monolithic sulfur-poly(acrylonitrile) (SPAN) materials for use as active cathode materials in lithium-sulfur batteries. During thermal processing, the macroscopic monolithic structure fully prevailed while significant changes in porosity were observed. Both the monomer content in the precursor PAN-based monoliths and the tortuosity of the final monolithic SPAN materials correlate with the electrochemical performance of the SPAN-based cathodes. Overall, percolation issues predominate. In percolating SPAN-based cathode materials, the specific capacity of the SPAN-based cells increases with decreasing tortuosity. All monolithic SPAN materials provided highly reversible and cycle stable cathodes reaching reversible discharge capacities up to 1330 mA h gsulfur -1 @ 0.25C, 900 mA h gsulfur -1 @ 2C and 420 mA h gsulfur -1 @ 8C.