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

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

Medicatiescreening met Beers-criteria en STOPP/START-criteria bij de oudere patiënt: associatie tussen potentieel ongewenst geneesmiddelengebruik en geneesmiddelgerelateerde ziekenhuisopnamen

OBJECTIVE To assess the risk of medication-related hospital admissions associated with inappropriate medication use applying the Beers and the STOPP/START criteria. There are multiple screening methods to detect and reduce potentially inappropriate medication [PIM] and prescribing omissions (PPOs). Whether this will result in less medication-related hospitalisations is unknown. DESIGN A nested case-control study was conducted with a subset of patients of the Hospital Admissions Related to Medication (HARM) study. METHODS Cases were defined as patients ≥65 years with a potentially preventable medication-related hospital admission. For each case one control was selected, matched on age and sex. The primary determinant was defined as the presence of one or more PlMs and/or PPOs according to the Beers 2012 and the STOPP/START criteria. The strength of the association between a PIM/PPO and a medication-related hospital admission was evaluated with multivariate logistic regression and expressed as odds ratios with 95% confidence intervals (Cl95). RESULTS PlMs and PPOs detected with the STOPP/START criteria are associated with medication-related hospital admissions [OR 3.47; CI95 1.70-7.09], while for the presence of PIMs according to the Beers 2012 criteria a non-significant trend was visible (ORadj 1.49; CI95 0.90-2.47). CONCLUSION Both the STOPP/START criteria and the Beers 2012 criteria can be used to identify older people at risk for medication-related problems. The choice which set of criteria should be used is more dependent on other factors (e.g. national guidelines, practical considerations) than on the association of each set with ADR-related hospital admission

The effect of ICU-tailored drug-drug interaction alerts on medication prescribing and monitoring: Protocol for a cluster randomized stepped-wedge trial

Background: Drug-drug interactions (DDIs) can cause patient harm. Between 46 and 90% of patients admitted to the Intensive Care Unit (ICU) are exposed to potential DDIs (pDDIs). This rate is twice as high as patients on general wards. Clinical decision support systems (CDSSs) have shown their potential to prevent pDDIs. However, the literature shows that there is considerable room for improvement of CDSSs, in particular by increasing the clinical relevance of the pDDI alerts they generate and thereby reducing alert fatigue. However, consensus on which pDDIs are clinically relevant in the ICU setting is lacking. The primary aim of this study is to evaluate the effect of alerts based on only clinically relevant interactions for the ICU setting on the prevention of pDDIs among Dutch ICUs. Methods: To define the clinically relevant pDDIs, we will follow a rigorous two-step Delphi procedure in which a national expert panel will assess which pDDIs are perceived clinically relevant for the Dutch ICU setting. The intervention is the CDSS that generates alerts based on the clinically relevant pDDIs. The intervention will be evaluated in a stepped-wedge trial. A total of 12 Dutch adult ICUs using the same patient data management system, in which the CDSS will operate, were invited to participate in the trial. Of the 12 ICUs, 9 agreed to participate and will be enrolled in the trial. Our primary outcome measure is the incidence of clinically relevant pDDIs per 1000 medication administrations. Discussion: This study will identify pDDIs relevant for the ICU setting. It will also enhance our understanding of the effectiveness of alerts confined to clinically relevant pDDIs. Both of these contributions can facilitate the successful implementation of CDSSs in the ICU and in other domains as well. Trial registration: Nederlands Trial register Identifier: NL6762. Registered November 26, 2018

Clinically relevant potential drug-drug interactions in intensive care patients: a large retrospective observational multicenter study

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when con -sidering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients. ? 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine: A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients

[Does it still make sense? Deprescribing in the frail elderly]

Elderly patients with multimorbidity often take several chronically used medicines. A large part of this polypharmacy is preventive in intention. Although one would expect that, at the end of life, the ratio of preventive therapy, would decrease in proportion to symptomatic treatment, this appears often not to be the case in practice. Although patients seem to be open to stopping medication, physicians seem to find it difficult to deprescribe preventive medication in particular. One of the major reasons for this is uncertainty about the potential clinical consequences of deprescribing. Since frail elderly people seldom participate in clinical drug trials, clear information is not available for this patient group on the balance between the chance of efficacy and the risk of harm of drug therapy. Discussion with the patient about his or her preferences and options with respect to drug therapy is the basis for all subsequent steps and must form part of the periodic reviews of medication

[Does it still make sense? Deprescribing in the frail elderly]

Item does not contain fulltextElderly patients with multimorbidity often take several chronically used medicines. A large part of this polypharmacy is preventive in intention. Although one would expect that, at the end of life, the ratio of preventive therapy, would decrease in proportion to symptomatic treatment, this appears often not to be the case in practice. Although patients seem to be open to stopping medication, physicians seem to find it difficult to deprescribe preventive medication in particular. One of the major reasons for this is uncertainty about the potential clinical consequences of deprescribing. Since frail elderly people seldom participate in clinical drug trials, clear information is not available for this patient group on the balance between the chance of efficacy and the risk of harm of drug therapy. Discussion with the patient about his or her preferences and options with respect to drug therapy is the basis for all subsequent steps and must form part of the periodic reviews of medication