Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study.

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

Rapid Response to Remdesivir in Hospitalised COVID-19 Patients: A Propensity Score Weighted Multicentre Cohort Study.

INTRODUCTION: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients' respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. METHODS: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. RESULTS: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79-1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48-1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07-7.56). CONCLUSION: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.

Drug-induced Liver Injury in a Patient With Coronavirus Disease 2019: Potential Interaction of Remdesivir With P-Glycoprotein Inhibitors.

We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.

Development of a multivariable prediction model for identification of patients at risk for medication transfer errors at ICU discharge.

INTRODUCTION: Discharge from the intensive care unit (ICU) is a high-risk process, leading to numerous potentially harmful medication transfer errors (PH-MTE). PH-MTE could be prevented by medication reconciliation by ICU pharmacists, but resources are scarce, which renders the need for predicting which patients are at risk for PH-MTE. The aim of this study was to develop a prognostic multivariable model in patients discharged from the ICU to predict who is at increased risk for PH-MTE after ICU discharge, using predictors of PH-MTE that are readily available at the time of ICU discharge. MATERIAL AND METHODS: Data for this study were derived from the Transfer ICU Medication reconciliation study, which included ICU patients and scored MTE at discharge of the ICU. The potential harm of every MTE was estimated with a validated score, where after MTE with potential for harm were indicated as PH-MTE. Predictors for PH-MTE at ICU discharge were identified using LASSO regression. The c statisticprovided a measure of the overall discriminative ability of the prediction model and the prediction model was internally validated by bootstrap resampling. Based on sensitivity and specificity, the cut-off point of the prediction model was determined. RESULTS: The cohort contained 258 patients and six variables were identified as predictors for PH-MTE: length of ICU admission, number of home medications and patient taking one of the following medication groups at home: vitamin/mineral supplements, cardiovascular medication, psycholeptic/analeptic medication and medication for obstructive airway disease. The c of the final prediction model was 0.73 (95%CI 0.67-0.79) and decreased to 0.62 according to bootstrap resampling. At a cut-off score of two the prediction model yielded a sensitivity of 70% and a specificity of 61%. CONCLUSIONS: A multivariable prediction model was developed to identify patients at risk for PH-MTE after ICU discharge. The model contains predictors that are available on the day of ICU discharge. Once external validation and evaluation of this model in daily practice has been performed, its incorporation into clinical practice could potentially allow institutions to identify patients at risk for PH-MTE after ICU discharge, on the day of ICU discharge, thus allowing for efficient, patient-specific allocation of clinical pharmacy services. TRIAL REGISTRATION: Dutch trial register: NTR4159, 5 September 2013, retrospectively registered.

The effect of a medication reconciliation program in two intensive care units in the Netherlands: a prospective intervention study with a before and after design.

BACKGROUND: Medication errors occur frequently in the intensive care unit (ICU) and during care transitions. Chronic medication is often temporarily stopped at the ICU. Unfortunately, when the patient improves, the restart of this medication is easily forgotten. Moreover, temporal ICU medication is often unintentionally continued after ICU discharge. Medication reconciliation could be useful to prevent such errors. Therefore, the aim of this study was to determine the effect of medication reconciliation at the ICU. METHODS: This prospective 8-month study with a pre- and post-design was carried out in two ICU settings in the Netherlands. Patients were included when they used ≥ 1 chronic medicine and when the ICU stay exceeded 24 h. The intervention consisted of medication reconciliation by pharmacists at the moment of ICU admission and prior to ICU discharge. Medication transfer errors (MTEs) were collected and the severity of potential harm of these MTEs was measured, based on a potential adverse drug event score (pADE = 0; 0.01; 0.1; 0.4; 0.6). Primary outcome measures were the proportions of patients with ≥ 1 MTE at ICU admission and after discharge. Secondary outcome measures were the proportions of patients with a pADE score ≥ 0.01 due to these MTEs, the severity of the pADEs and the associated costs. Odds ratio and 95% confidence intervals were calculated, by using a multivariate logistic regression analysis. RESULTS: In the pre-intervention phase, 266 patients were included and 212 in the post-intervention phase. The proportion of patients with ≥ 1 MTE at ICU admission was reduced from 45.1 to 14.6% (ORadj 0.18 [95% CI 0.11-0.30]) and after discharge from 73.9 to 41.2% (ORadj 0.24 [95% CI 0.15-0.37]). The proportion of patients with a pADE ≥ 0.01 at ICU admission was reduced from 34.8 to 8.0% (ORadj 0.13 [95% CI 0.07-0.24]) and after discharge from 69.5 to 36.2% (ORadj 0.26 [95% CI 0.17-0.40]). The pADE reduction resulted in a potential net cost-benefit of € 103 per patient. CONCLUSIONS: Medication reconciliation by pharmacists at ICU transfers is an effective safety intervention, leading to a significant decrease in the number of MTE and a cost-effective reduction in potential harm. Trial registration Dutch trial register: NTR4159, 5 September 2013, retrospectively registered.

Reliability of a shuttle run test for children with cerebral palsy who are classified at Gross Motor Function Classification System level III.

For children and adolescents with cerebral palsy (CP) classified as Gross Motor Function Classification System (GMFCS) level III there is no running-based field test available to assess their cardiorespiratory fitness. The current study investigated whether a shuttle run test can be reliably (test-retest) performed in a group of children with spastic diplegia (eight male, five female) classified as GMFCS level III. Thirteen children (mean age 12 y, SD 3 y) had to walk/run in squares of 7.5m delimited by cones. The auditory signals from the GMFCS II compact disc (as used in a previous reliability and validation study) were used during the test, resulting in a starting speed of 1.5 km/hour with a graded increase in speed of 0.19 km/hour per minute (shuttle). Intraclass correlation coefficients (two-way mixed) for achieved shuttles were 0.98. The standard error of measurement was 0.48 levels and the smallest detectable change was 1.32 shuttles. The results are the first indication that the shuttle run test protocol could be reliably performed in this population.

Evaluation of pharmacist clinical interventions in a Dutch hospital setting.

OBJECTIVE: Assessing the relevance of a clinically active pharmacist method compared to the traditional working method. METHOD: The study was carried out in a general internal/gastro-enterology unit during two 8-weeks periods in 2004. It was an observational, non-randomized prospective study. Outcome measures were compared before and during the intervention. The intervention was the active presence of a junior hospital pharmacist on the unit. The pharmacist focused on the pharmacotherapy of the individual patient. Patients were included when they used 5 or more medicines on day 1 or 2 of their stay at the ward and/or used at least 1 high-risk drug. Clinical pharmacist interventions were counted and classified. A hospital pharmacist and an internal medicine specialist assessed the clinical relevance of all clinical pharmacist interventions retrospectively. The degree of acceptance of the interventions by physicians was measured. Finally, time associated with the clinical activities was measured. MAIN OUTCOME MEASURES: Number of interventions (related to number of medication orders), clinical relevance and degree of acceptance. RESULTS: In the pre-intervention period 79 patients were included versus 84 in the during-intervention period. About 82 interventions in the pre-intervention period were made compared to 173 during the during-intervention period. There was little agreement between the professional raters (weighted kappa(A-E)=0.30 and weighted kappa(1-5)=0.20). Nevertheless both ratings showed a substantial increase of clinically relevant interventions. The number of interventions accepted by the physician increased from 16 in the pre-intervention period to 75 in the during-intervention period. Working with this method took over 4 h a day. CONCLUSION: Clinical pharmacy services provided by a junior hospital pharmacist on an internal medicine ward contribute to rationalization of drug therapy and are therefore likely to increase medication safety.