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      Association between poor therapy adherence to inhaled corticosteroids and tiotropium and morbidity and mortality in patients with COPD

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          Abstract

          Aim

          The aim of this study was to analyze the association between therapy adherence to inhaled corticosteroids (ICSs) and tiotropium on the one hand and morbidity and mortality in COPD on the other hand.

          Methods

          Therapy adherence to ICSs and tiotropium over a 3-year period of, respectively, 635 and 505 patients was collected from pharmacy records. It was expressed as percentage and deemed optimal at ≥75–≤125%, suboptimal at ≥50%–<75%, and poor at <50% (underuse) or >125% (overuse). The association between adherence and time to first hospital admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community acquired pneumonia (CAP), and mortality was analyzed, with optimal use as the reference category.

          Results

          Suboptimal use and underuse of ICSs and tiotropium were associated with a substantial increase in mortality risk: hazard ratio (HR) of ICSs was 2.9 (95% CI 1.7–5.1) and 5.3 (95% CI 3.3–8.5) and HR of tiotropium was 3.9 (95% CI 2.1–7.5) and 6.4 (95% CI 3.8–10.8) for suboptimal use and underuse, respectively. Suboptimal use and overuse of tiotropium were also associated with an increased risk of CAP, HR 2.2 (95% CI 1.2–4.0) and HR 2.3 (95% CI 1.2–4.7), respectively. Nonadherence to tiotropium was also associated with an increased risk of severe AECOPD: suboptimal use HR 3.0 (95% CI 2.01–4.5), underuse HR 1.9 (95% CI 1.2–3.1), and overuse HR 1.84 (95% CI 1.1–3.1). Nonadherence to ICSs was not related to time to first AECOPD or first CAP.

          Conclusion

          Poor adherence to ICSs and tiotropium was associated with a higher mortality risk. Furthermore, nonadherence to tiotropium was associated with a higher morbidity. The question remains whether improving adherence can reduce morbidity and mortality.

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          Most cited references 18

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          Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results.

          Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated infections. In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analysed and identified potential risk factors for adverse event reports of pneumonia in this randomised, double-blind trial comparing twice-daily inhaled salmeterol (SAL) 50 microg, fluticasone propionate (FP) 500 microg, and the combination (SFC) with placebo in 6,184 patients with moderate-to-severe COPD over 3 yrs. Despite a higher withdrawal rate in the placebo arm, after adjusting for time on treatment, a greater rate of pneumonia was reported in the FP and SFC treatment arms (84 and 88 per 1,000 treatment-yrs, respectively) compared with SAL and placebo (52 and 52 per 1,000 treatment-yrs, respectively). Risk factors for pneumonia were age > or =55 yrs, forced expiratory volume in 1 s <50% predicted, COPD exacerbations in the year prior to the study, worse Medical Research Council dyspnoea scores and body mass index <25 kg.m(-2). No increase in pneumonia deaths with SFC was observed; this could not be concluded for FP. Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies.
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            Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy.

            To evaluate the validity of patient report, pharmacy dispensing records, and pill counts as measures of antihypertensive adherence using electronic monitoring as the validation standard. The study was conducted among 286 members of Harvard Pilgrim Health Care, a managed care organization, who were at least 18 years of age, on monotherapy for hypertension, and had prescription drug coverage. Prescription refill adherence during the 12 months before enrollment was determined from their automated pharmacy dispensing records. Participants were interviewed about their medication adherence before and after a 3-month electronic monitoring period during which pill counts were also performed. Adherence to both recommended number and timing of doses was estimated from electronic monitoring data. Data analysis was based on statistical correlation and analysis of variance. Electronic adherence monitoring revealed that the proportion of prescribed doses consumed was higher (0.92) than the proportion of doses taken on time (0.63). The correlation between adherence to quantity and timing of doses was 0.32. Concurrent pill counts and earlier refilling patterns were moderately correlated with electronic monitoring (pill count: r = .52 with quantity and r = .17 with timing; refill adherence r = .32 with quantity and r = .22 with timing). There was considerable misclassification of adherence reported by patients, although nonadherence was generally accurately reported. Deviation from recommended timing of doses appears to be greater than from prescribed number of doses. Pharmacy dispensing records demonstrate predictive validity as measures of cumulative exposure and gaps in medication supply. Adherence levels determined from pill counts and pharmacy dispensing records correlate more closely with quantity than with timing of doses. Nonadherence reported by patients can serve as a qualitative indicator and predictor of reduced adherence.
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              Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia.

              Inhaled corticosteroids are commonly prescribed to patients with chronic obstructive pulmonary disease (COPD). To examine whether these medications might be associated with an excess risk of pneumonia. We conducted a nested case-control study within a cohort of patients with COPD from Quebec, Canada, over the period 1988-2003, identified on the basis of administrative databases linking hospitalization and drug-dispensing information. Each subject hospitalized for pneumonia during follow-up (case subjects) was age and time matched to four control subjects. The effect of the use of inhaled corticosteroids was assessed by conditional logistic regression, after adjusting for comorbidity and COPD severity. The cohort included 175,906 patients with COPD of whom 23,942 were hospitalized for pneumonia during follow-up, for a rate of 1.9 per 100 per year, and matched to 95,768 control subjects. The adjusted rate ratio of hospitalization for pneumonia associated with current use of inhaled corticosteroids was 1.70 (95% confidence interval [CI], 1.63-1.77) and 1.53 (95% CI, 1.30-1.80) for pneumonia hospitalization followed by death within 30 days. The rate ratio of hospitalization for pneumonia was greatest with the highest doses of inhaled corticosteroids, equivalent to fluticasone at 1,000 microg/day or more (rate ratio, 2.25; 95% CI, 2.07-2.44). All-cause mortality was similar for patients hospitalized for pneumonia, whether or not they had received inhaled corticosteroids in the recent past (7.4 and 8.2%, respectively). The use of inhaled corticosteroids is associated with an excess risk of pneumonia hospitalization and of pneumonia hospitalization followed by death within 30 days, among elderly patients with COPD.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                24 May 2018
                : 13
                : 1683-1690
                Affiliations
                [1 ]Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands
                [2 ]Department of Health Technology and Services Research, University of Twente, Enschede, the Netherlands
                [3 ]Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, the Netherlands
                [4 ]Medical School Twente, Medisch Spectrum Twente, Enschede, the Netherlands
                [5 ]Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands
                Author notes
                Correspondence: Kirsten Koehorst-ter Huurne, Department of Pulmonary Medicine, Medisch Spectrum Twente, PO Box 50000, 7500 KA Enschede, the Netherlands, Tel +31 53 487 2643, Fax +31 53 487 2676, Email kirstenterhuurne@ 123456gmail.com
                Article
                copd-13-1683
                10.2147/COPD.S161374
                5973470
                © 2018 Koehorst-ter Huurne et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                hospitalization, copd, exacerbation, pneumonia, mortality, morbidity, adherence

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