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      Effect of multidose drug dispensing on the time in therapeutic range in patients using vitamin‐K antagonists: A randomized controlled trial

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          Abstract

          Background

          A high number of vitamin K antagonist (VKA) users have a low proportion of time in therapeutic range (TTR) resulting in a high number of bleeding and thromboembolism events.

          Objective

          Can the quality of anticoagulation be improved by dispensing VKAs via multidose drug dispensing (MDD).

          Method

          A randomized controlled trial in the Netherlands. Patients who used VKAs, ≥65 years of age with a TTR <65% were eligible for inclusion. All oral drugs were dispensed via MDD. In MDD systems, all oral chronic medication intended for one dosing moment is packed in plastic disposable pouches. Controls received VKAs by manual dispensing. The difference in TTR between the 6 months after‐ and 6 months before the index date. A mixed‐effects model with the intervention, TTR before the index date, MDD system at baseline as covariates, and pharmacy as random effect. A per‐protocol analysis was performed with all patients who completed the study as intended.

          Results

          One hundred and seventy‐nine patients were included. Mean age was 80.0 (SD 6.9) years. Mean TTR during the study was 79.2 ± 18.0% in the intervention group and 72.5 ± 20.1% in the control group. The intervention resulted in a 5.6% (95% CI: 0.1‐11.1) increase in TTR compared to the control group. Per‐protocol analysis resulted in an 8.3% (95% CI: 0.99‐15.61) increase in TTR compared to the control group. No differences in reduction were observed between the intervention and control group.

          Conclusion

          The quality of anticoagulation can be improved with the use of MDD systems.

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          Most cited references20

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          2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

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            Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism.

            The efficacy and safety of vitamin K antagonists (VKA) are related to the actual level of anticoagulation (given as the international normalized ratio, INR). It is often difficult to maintain an optimal INR over time. We assessed the clinical impact of the individual time spent within INR target range (ITTR) in 2304 consecutive patients with venous thromboembolism. Annual incidences of recurrent thromboembolism and major bleeding were 6.2% and 2.8% respectively. The relative risk (RR) of thromboembolism was 4.5 [95% confidence interval (CI) 3.1-6.6, P 5.0, compared with INR 2.0-3.0. Patients with ITTR 65% (RR 2.8, 1.9-4.3, P 65% (RR 1.2, 0.7-1.8, P = 0.54). Annual incidences of recurrent thromboembolism were 16.0%, 4.9% and 4.6% at ITTR 65% respectively. For major bleeding these were 8.7%, 2.1% and 1.9% respectively. ITTR < 37% during the first 30 treatment days was highly predictive for the total treatment time ITTR < 45% (RR 24.2, 13.5-43.1, P < 0.001). In conclusion, ITTR can be used to identify patients on VKA at risk of recurrent thromboembolism or major bleeding. Since the 30-d ITTR is highly predictive for total treatment ITTR, these patients can be identified soon after start of treatment.
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              Practical Problems with Medication Use that Older People Experience: A Qualitative Study

              Objectives To identify the practical problems that older people experience with the daily use of their medicines and their management strategies to address these problems and to determine the potential clinical relevance thereof. Design Qualitative study with semistructured face-to-face interviews. Setting A community pharmacy and a geriatric outpatient ward. Participants Community-dwelling people aged 70 and older (N = 59). Measurements Participants were interviewed at home. Two researchers coded the reported problems and management strategies independently according to a coding scheme. An expert panel classified the potential clinical relevance of every identified practical problem and associated management strategy using a 3-point scale. Results Two hundred eleven practical problems and 184 management strategies were identified. Ninety-five percent of the participants experienced one or more practical problems with the use of their medicines: problems reading and understanding the instructions for use, handling the outer packaging, handling the immediate packaging, completing preparation before use, and taking the medicine. For 10 participants, at least one of their problems, in combination with the applied management strategy, had potential clinical consequences and 11 cases (5% of the problems) had the potential to cause moderate or severe clinical deterioration. Conclusion Older people experience a number of practical problems using their medicines, and their strategies to manage these problems are sometimes suboptimal. These problems can lead to incorrect medication use with clinically relevant consequences. The findings pose a challenge for healthcare professionals, drug developers, and regulators to diminish these problems.
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                Author and article information

                Contributors
                b.j.mertens@uu.nl
                Journal
                J Thromb Haemost
                J. Thromb. Haemost
                10.1111/(ISSN)1538-7836
                JTH
                Journal of Thrombosis and Haemostasis
                John Wiley and Sons Inc. (Hoboken )
                1538-7933
                1538-7836
                19 September 2019
                January 2020
                : 18
                : 1 ( doiID: 10.1111/jth.v18.1 )
                : 70-78
                Affiliations
                [ 1 ] SIR Institute for Pharmacy Practice and Policy Leiden the Netherlands
                [ 2 ] Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical Sciences University Utrecht Utrecht the Netherlands
                [ 3 ] Department of Thrombosis and Hemostasis Leiden University Medical Center Leiden the Netherlands
                [ 4 ] Department of General Practice and Elderly Care Medicine EMGO Institute for Health and Care Research VU University Medical Center Amsterdam the Netherlands
                Author notes
                [*] [* ] Correspondence

                Bram J. Mertens, SIR Institute for Pharmacy Practice and Policy, Leiden, the Netherlands

                Email: b.j.mertens@ 123456uu.nl

                Author information
                https://orcid.org/0000-0001-6863-8180
                Article
                JTH14625
                10.1111/jth.14625
                6972487
                31469508
                b8dafcc0-9934-4870-891f-56415bde160c
                © 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 04 April 2019
                : 26 August 2019
                Page count
                Figures: 2, Tables: 3, Pages: 9, Words: 6211
                Funding
                Funded by: Pluripack
                Funded by: The Royal Dutch Pharmacists Association (KNMP)
                Funded by: Verpakapotheek
                Funded by: SPITS BV
                Funded by: 5 Sterrenapotheek
                Funded by: Apotheek Voorzorg BV
                Funded by: Brocacef Maatmedicatie BV
                Categories
                Original Article
                HAEMOSTASIS
                Original Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:21.01.2020

                Hematology
                atrial fibrillation,community pharmacy,medication adherence,multidose drug dispensing,ttr

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