Breathing Out Completely Before Inhalation: The Most Problematic Step in Application Technique in Patients With Non-Mild Chronic Obstructive Pulmonary Disease

Background: Patient adherence to an inhaled medication application technique (A-ApplT) represents a major health-care issue in patients with chronic obstructive pulmonary disease (COPD). However, there is a lack of studies evaluating this issue thoroughly. The aim of our study was to introduce a universal easy-to-use method of assessing the A-ApplT to chronic medication in moderate to very severe COPD individuals.Methods: The Czech Multicenter Research Database of COPD (COPD CMRD), a large observational prospective study, was used as a source of clinical data. A-ApplT was evaluated using our Five Steps Assessment. This measure is based on dichotomous evaluation of each of five predefined consecutive application technique steps and can be used in all settings for all currently available inhalation systems in COPD subjects.Results: A total of 546 participants (75.0% men; mean age 66.7 years; mean forced expiratory volume in 1s 44.7%) were available for analysis. This represents 69.6% of all patients recruited in the COPD CMRD. Less than one third of patients presented their application technique without any erroneous steps. The most problematic steps were breathing out completely in one breath immediately before inhalation (step No. 3), and the actual inhalation maneuver (step No. 4). The total number of errors was similar for dry powder inhalers and pressurized metered-dose inhalers.Conclusion: Our novel instrument, Five Steps Assessment, is comfortable for use in routine clinical practice to explore A-ApplT. The A-ApplT in real-life patients with non-mild COPD was inadequate and patients should be repeatedly trained by properly (re-)educated medical staff

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Real-life GOLD 2011 implementation: the management of COPD lacks correct classification and adequate treatment.

Chronic obstructive pulmonary disease (COPD) is a serious, yet preventable and treatable, disease. The success of its treatment relies largely on the proper implementation of recommendations, such as the recently released Global Strategy for Diagnosis, Management, and Prevention of COPD (GOLD 2011, of late December 2011). The primary objective of this study was to examine the extent to which GOLD 2011 is being used correctly among Czech respiratory specialists, in particular with regard to the correct classification of patients. The secondary objective was to explore what effect an erroneous classification has on inadequate use of inhaled corticosteroids (ICS). In order to achieve these goals, a multi-center, cross-sectional study was conducted, consisting of a general questionnaire and patient-specific forms. A subjective classification into the GOLD 2011 categories was examined, and then compared with the objectively computed one. Based on 1,355 patient forms, a discrepancy between the subjective and objective classifications was found in 32.8% of cases. The most common reason for incorrect classification was an error in the assessment of symptoms, which resulted in underestimation in 23.9% of cases, and overestimation in 8.9% of the patients' records examined. The specialists seeing more than 120 patients per month were most likely to misclassify their condition, and were found to have done so in 36.7% of all patients seen. While examining the subjectively driven ICS prescription, it was found that 19.5% of patients received ICS not according to guideline recommendations, while in 12.2% of cases the ICS were omitted, contrary to guideline recommendations. Furthermore, with consideration to the objectively-computed classification, it was discovered that 15.4% of patients received ICS unnecessarily, whereas in 15.8% of cases, ICS were erroneously omitted. It was therefore concluded that Czech specialists tend either to under-prescribe or overuse inhaled corticosteroids

Introducing a new prognostic instrument for long-term mortality prediction in COPD patients: the CADOT index

Objectives. The BODE (BMI, Obstruction - FEV1, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV1) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients. Methods and Participants. The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality. These were entered into the ROC analysis and reclassification analysis. Those with the strongest discriminative power were used to construct the new index (CADOT). The new index was validated on 187 patients of the CIROCO+ cohort (Netherlands; the validation cohort). Results. The CADOT was constructed by adding two newly identified prognosis-determining factors, chronic heart failure (CHF) and TLCO, to the ADO index. In a head-to-head comparison, the CADOT index showed highest c-statistic values compared to the BODE and ADO indices (0.701 vs 0.677 vs 0.644, respectively). The prognostic power was more definitive when applied to the Dutch validation (CIROCO+) cohort (0.842 vs 0.799 vs 0.825, respectively). Conclusions. The CADOT index has comparable prognostic power to the BODE and ADO indices. The CADOT is complementary/an alternative to the BODE (if 6-MWT is not feasible) and ADO (with less dependence on the age factor) indices. Trial registration: ClinicalTrials.gov (NCT01923051)

Introducing a new prognostic instrument for long-term mortality prediction in COPD patients: the CADOT index

Objectives. The BODE (BMI, Obstruction - FEV1, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV1) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients. Methods and Participants. The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality. These were entered into the ROC analysis and reclassification analysis. Those with the strongest discriminative power were used to construct the new index (CADOT). The new index was validated on 187 patients of the CIROCO+ cohort (Netherlands; the validation cohort). Results. The CADOT was constructed by adding two newly identified prognosis-determining factors, chronic heart failure (CHF) and TLCO, to the ADO index. In a head-to-head comparison, the CADOT index showed highest c-statistic values compared to the BODE and ADO indices (0.701 vs 0.677 vs 0.644, respectively). The prognostic power was more definitive when applied to the Dutch validation (CIROCO+) cohort (0.842 vs 0.799 vs 0.825, respectively). Conclusions. The CADOT index has comparable prognostic power to the BODE and ADO indices. The CADOT is complementary/an alternative to the BODE (if 6-MWT is not feasible) and ADO (with less dependence on the age factor) indices. Trial registration: ClinicalTrials.gov (NCT01923051)

Use of ICS in monotherapy or combination therapy.

<p>Use of ICS in monotherapy or combination therapy.</p