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.