The Netherlands

De bescherming van fundamentele rechten in een integrerend Europ

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

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

Effect of fatigue on stroking characteristics in an arms-only 100-m front-crawl race

Purpose: Race analyses during swimming provide information on the time-dependent values of, among other variables, a swimmer's clean swimming speed (v), stroke rate (SR), and stroke length (SL). The effect of fatigue on changes in v, SR, and SL was investigated. Methods: Lap-averaged values of v, SR, and SL while swimming 100 m all out with arms only (trial 1) were related to the decline in mechanical power output measured during an all-out 100-m swim on the MAD system (trial 2), with legs immobilized in both trials. Results: Swimming a 100-m front-crawl sprint using arms only led to a significant 24% decrease in lap-averaged mechanical power output (from 200 to 153 W, P < 0.01). This reduction in power-generating capacity led to a 12.4% decrease in v̄ when lap 1 was compared with lap 4 (from 1.69 to 1.48 m-