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Since the outbreak of SARS-CoV-2, also known as COVID-19, conflicting theories have circulated on the influence of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID-19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID-19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID-19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARSCoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19.

Background: Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods: The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiat

Aims: To study community pharmacists' level of knowledge on medication safety in patients with hepatic impairment and their practice in caring for these patients. Methods: Pharmacists from Dutch community pharmacies (n = 1545) were invited to participate in an online survey. The survey consisted of 27 questions covering 2 main topics: knowledge and current practice. The level of knowledge was measured by a 6-item knowledge test. Multiple linear regression was used to identify predictors of correctly answered responses. Results: In total, 338 pharmacists (22%) completed the questionnaire. The mean knowledge score was 2.8 (standard deviation 1.6). Only 30.3% of respondents were able to appropriately advise on use of analgesics in severe cirrhosis. Postgraduate education on hepatic impairment, knowledge of recently developed practical guidance, and fewer years of practice were associated with a higher level of knowledge. In total, 70.4% indicated to evaluate medication safety in a patient with hepatic impairment at least once weekly. In the past 6 months, 83.3% of respondents consulted a prescriber about a patient with hepatic impairment. Frequently encountered barriers in practice were insufficient knowledge on the topic and a lack of essential patient information (i.e. diagnosis and severity of the impairment). Conclusion: Community pharmacists regularly evaluate the safety of medication in patients with hepatic impairment, yet their level of knowledge was insufficient and additional education is needed. Pharmacists experienced several difficulties in providing pharmaceutical care. If these issues are resolved, pharmacists can play a more active role in ensuring medication safety in their patients with hepatic impairment.

Background: In 2005, the European Medicines Agency (EMA) released guidance on pharmacokinetic studies in patients with hepatic impairment. This guidance describes the design of these studies and what information should be presented in the Summary of Product C

Introduction: Patients with cirrhosis are at risk for adverse drug reactions (ADRs) due to altered pharmacokinetics and pharmacodynamics. We aimed to determine the prevalence of drug prescriptions and the potential safety of these prescriptions in a real-world cohort of patients with cirrhosis. Methods: This was a retrospective cohort study based on linked real-world data from the Out-patient Pharmacy Database and the Hospitalisation Database of the PHARMO Database Network. Patients with a diagnosis of cirrhosis between January 1998 and December 2015 were included. Follow-up ended when the patient underwent a liver transplant, died, transferred out of the database, or on 31 December 2015. Prescription data were derived from a community pharmacy database and were compared with our previously developed safety recommendations for 209 drugs. Results: In total, 5618 patients were included and followed for a median of 3 years (interquartile range [IQR] 1–7). In the first year after the diagnosis, patients used a median of nine drugs (IQR 5–14), with proton pump inhibitors (prevalence 53.9%), aldosterone antagonists (43.6%), and sulfonamide diuretics (41.3%) being the most commonly used drug groups. Almost half (48.3%) of 102,927 prescripti

Introduction Drug confusion is thought to be the most common type of dispensing error. Several strategies can be implemented to reduce the risk of medication errors. One of these are alerts in the pharmacy information system. Objective To evaluate the experiences of pharmacists and pharmacy technicians with alerts for drug name and strength confusion. Methods In May 2017, a cross-sectional survey of pharmacists and pharmacy technicians was performed in community pharmacies in the Netherlands using an online questionnaire. Results Of the 269 respondents, 86% (n = 230) had noticed the alert for drug name confusion, and 26% (n = 67) for drug strength confusion. Of those 230, 9% (n = 20) had experienced that the alert had prevented dispensing the wrong drug. For drug strength confusion, this proportion was 12% (n = 8). Respondents preferred to have an alert for drug name and strength confusion in the pharmacy information system. ‘Alert fatigue’ was an important issue, so alerts should only be introduced for frequent confusions or confusions with serious consequences. Conclusion Pharmacists and pharmacy technicians were positive about having alerts for drug confusions in their pharmacy information system and experienced that alerts contributed to the prevention of dispensing errors. To prevent alert fatigue, it was considered important not to include all possible confusions as a new alert: the potential contribution to the prevention of drug confusion should be weighed against the risk of alert fatigue.

Aims: Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis. Methods: A systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child–Turcotte–Pugh (CTP) classification. Results: A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having ‘no additional risks known’. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. Conclusions: We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients.

Introduction: The presence of liver cirrhosis can have a major impact on pharmacodynamics and pharmacokinetics, but guidance for prescribing is lacking. Objective: The aim of this study is to provide an overview of evidence-based recommendations developed for the safe use of drugs in liver cirrhosis. Methods: Recommendations were based on a systematic literature search combined with expert opinion from a panel of 10 experts. The safety of each drug was classified as safe, no additional risks known, additional risks known, unsafe, unknown or the safety class was dependent on the severity of liver cirrhosis (Child–Pugh classification). If applicable, drug-specific dosing advice was provided. All recommendations were implemented in clinical decision support systems and on a website. Results: We formulated 218 recommendations for a total of 209 drugs. For nine drugs, two recommendations were formulated for different administration routes or indications. Drugs were classified as ‘safe’ in 29 recommendations (13.3%), ‘no additional risks known’ in 60 (27.5%), ‘additional risks known’ in 3 (1.4%), and ‘unsafe’ in 30 (13.8%). In 57 (26.1%) of the recommendations, safety depended on the severity of liver cirrhosis and was ‘unknown’ in 39 (17.9%) recommendations. Large alt

Background To improve continuity of care at hospital admission and discharge and to decrease medication errors pharmaceutical care programs are developed. This study aims to determine the cost-effectiveness of the COACH program in comparison with usual care from a societal perspective. Methods A controlled clinical trial was performed at the Internal Medicine department of a general teaching hospital. All admitted patients using at least one prescription drug were included. The COACH program consisted of medication reconciliation, patient counselling at discharge, and communication to healthcare

Introduction: Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. Methods and analysis: For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of ) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Ethics and dissemination: Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings.

BACKGROUND: Medication reconciliation aims to correct discrepancies in medication use between health care settings and to check the quality of pharmacotherapy to improve effectiveness and safety. In addition, medication reconciliation might also reduce costs. OBJECTIVE: To evaluate the effect of medication reconciliation on medication costs after hospital discharge in relation to hospital pharmacy labor costs. METHODS: A prospective observational study was performed. Patients discharged from the pulmonology department were included. A pharmacy team assessed medication errors prevented by medication reconciliation. Interventions were classified into 3 categories: correcting hospital formulary-induced medication changes (eg, reinstating less costly generic drugs used before admission), optimizing pharmacotherapy (eg, discontinuing unnecessary laxative), and eliminating discrepancies (eg, restarting omitted preadmission medication). Because eliminating discrepancies does not represent real costs to society (before hospitalization, the patient was also using the medication), these medication costs were not included in the cost calculation. Medication costs at 1 month and 6 months after hospital discharge and the associated labor costs were assessed using descriptive statistics and scenario analyses. For the 6-month extrapolation, only medication intended for chronic use was included. RESULTS: Two hundred sixty-two patients were included. Correcting hospital formulary changes saved?1 €63/patient (exchange rate: EUR 1 = USD 1.3443) in medication costs at 1 month after discharge and?9 €79 at 6 months. Optimizing pharmacotherapy saved?20 euro;13/patient in medication costs at 1 month and? €86.86 at 6 months. The associated labor costs for performing medication reconciliation were? €41.04/patient. Medication cost savings from correcting hospital formularyinduced changes and optimizing of pharmacotherapy?(€96.65/patient) outweighed the labor costs at 6 months extrapolation by

Objective: To investigate the needs of Dutch general practitioners on discharge medication, both regarding content, timing and the appreciation of pharma-cotherapeutic advices from clinical pharmacists. Setting: A general teaching hospital in Amsterdam, the Netherlands. Method: A prospective observational study was performed. A questionnaire with regard to the content, optimal timing (including way of information transfer) and appreciation of pharmacotherapeutic advices was posted to 464 general practitioners. One reminder was sent. Main outcome measure: Description of the needs of general practitioners was assessed. For each question and categories of comments frequency tables were made. The Fisher-exact test was used to study associations between the answers to the questions. Results: In total, 149 general practitioners (32%) responded. Most gener

BACKGROUND: Hospital admissions are a risk factor for the occurrence of unintended medication discrepancies between drugs used before admission and after discharge. To diminish such discrepancies and improve quality of care, medication reconciliation has been developed. The exact contribution of patient counseling to the medication reconciliation process is unknown, especially not when compared with community pharmacy medication records, which are considered reliable in the Netherlands. OBJECTIVE: To examine the effect of medication reconciliation with and without patient counseling among patients at the time of hospital discharge on the number and type of interventions aimed at preventing drug-related problems. METHODS: A prospective observational study in a general teach

More than 10,000 Caspian seals (Phoca caspica) were reported dead in the Caspian Sea during spring and summer 2000. We performed necropsies and extensive laboratory analyses on 18 seals, as well as examination of the pattern of strandings and variation in weather in recent years, to identify the cause of mortality and potential contributory factors. The monthly stranding rate in 2000 was up to 2.8 times the historic mean. It was preceded by an unusually mild winter, as observed before in mass mortality events of pinnipeds. The primary diagnosis in 11 of 13 seals was canine distemper, characterized by broncho-interstitial pneumonia, lymphocytic necrosis and depletion in lymphoid organs, and the presence of typical intracytoplasmic inclusion bodies in multiple epithelia. Canine distemper virus infection was confirmed by phylogenetic analysis of reverse transcriptase-polymerase chain reaction products. Organochlorine and zinc concentrations in tissues of seals with canine distemper were comparable to those of Caspian seals in previous years. Concurrent bacterial infections that may have contributed to the mortality of the seals included Bordetella bronchiseptica (4/8 seals), Streptococcus phocae (3/8), Salmonella dublin (1/8), and S. choleraesuis (1/8). A newly identified bacterium, Corynebacterium caspium, was associated with balanoposthitis in one seal. Several infectious and parasitic organisms, including poxvirus, Atopobacter phocae, Eimeria- and Sarcocystis-like organisms, and Halarachne sp. were identified in Caspian seals for the first time.