Abstract:The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.

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Our results strongly suggest that 6-hydroxylation, the main metabolic pathway of melatonin, is mediated mainly, but not exclusively, by CYP1A2, the high-affinity enzyme involved in melatonin metabolism, confirming the observation that a single oral dose of fluvoxamine increases nocturnal serum melatonin levels in healthy subjects. Furthermore, the results indicate that there is a potential for interaction with drugs metabolised by CYP1A2 both at physiological levels and after oral administration of melatonin, while CYP2C19 and CYP2C9 are assumed to be less important.

Marked species differences in xenobiotics metabolism in the liver seriously limit extrapolations from animals to man. Because access to human liver is limited and periodic, we have set up a human "liver bank" available fur metabolic studies. The liver tissue is obtained shortly after circulatory arrest from cadaveric (cerebral infarction) kidney transplant donors. Postmortem changes are minimal. Subcellular liver fractions are prepared immediately and part uf this is used directly for assay. Intact pieces and subcellular fractions are stored in different media at -80°. Each liver is characterized by light and electron microscopy. Several enzymes, including cytochromes P-450 and b; NADPH-cytochrome c reductase, demethylation of aminopyrine and amitriptyline, epoxidation of carbamazepine, oxidation of acetaminophen, and benzo [a ]pyrene, were tested with freshly prepared fractions so that each liver got a "drug metabolic profile." This "test battery" was repeated after storing to evaluate the effect of storage. Our preparation technique gave a well-preserved microsomal fraction with m~nimal contamination. In freshly prepared micro somes the following activities (levels) were oiiserved: cytochrome P-450, 0.13 to 0.73 nmole/mg protein; NADPH-cytochrome c reductase, 70 to 426 nmole/mg protein; demethylation of aminopyrine, 0.9 to 4.1, and of amitriptyline, O.ll to 0.92 nmole/mg protein; carbamazepine-lC.l l epoxidation, 0.03 to 0.46 nmole/mg protein; oxidation of acetaminophen, 0.48 to 2. l l , and of benzo[a]pyrene, 0.04 to O.ll nmole/mg June 1980 protein' min. These values are generally higher than in the literature. Our storage conditions were efficient: most of the activities were well preserved during storage for at least 6 mo. When pairs of enzyme activities (levels) were plotted against each other with fresh tissue there was good correlation between some but not all activities.

DRPs were common. Potential drug interactions and adverse drug reactions dominated. Hospital-based medication review by a clinical pharmacologist was not associated with reduced rates of re-hospitalisation and/or death. The clinical relevancy of DRPs might be overestimated as a risk for re-hospitalisation or death. It is of great importance to clarify if and how drug-related problems can be prevented. In designing such studies, one should consider choosing inclusion criteria that accumulate risk.