Impact of out-of-pocket expenses on discontinuation of statin therapy: a cohort study in Finland.

WHAT IS KNOWN AND OBJECTIVE: Out-of-pocket expenses of drug therapy may negatively affect adherence. We aimed to analyse 1-year discontinuation rates between cohorts initiating therapy with either generic simvastatin or non-generic atorvastatin. METHODS: Statin-naìve initiators of atorvastatin and generic simvastatin in April-June 2003, and corresponding cohorts in 2005, were identified through the nationwide Finnish prescription register. Persistence with statin therapy was followed for 365 days, considering the treatment to have been discontinued when the tablet-free gap between two consecutive refills exceeded 90 days. Using multivariate-adjusted logistic regression, odds ratios (OR) for discontinuation associated with initiating with simvastatin vs. atorvastatin were estimated separately for each year. RESULTS AND DISCUSSION: In the year 2003, 5838 persons initiated treatment with atorvastatin and 5644 with generic simvastatin. In the year 2005, the respective numbers were 5228 and 10 987. Soon after the introduction of generic substitution in 2003, there was no difference in the risk of discontinuation between the comparator groups [OR 0·97, 95% confidence interval (CI) 0·89-1·05]. Two years later, persons initiating with generic simvastatin were 20% less likely to discontinue statin therapy (OR 0·80; 95% CI 0·74-0·83). Among persons whose medicinal costs were almost completely reimbursed towards the end of the initiation year, the OR was 1·14 (95% CI 0·76-1·64, P = 0·033 for interaction). WHAT IS NEW AND CONCLUSIONS: We found that lower out-of-pocket expenses associated with the initiating statin had a positive impact on persistence with therapy. The finding does not seem to apply to persons with minor copayments towards the end of the initiation year.

Bleomycin-detectable iron and phenanthroline-detectable copper in the cerebrospinal fluid of patients with neuronal ceroid-lipofuscinoses.

The neuronal ceroid-lipofuscinoses (NCLs) are a group of recessively inherited neurodegenerative lysosomal storage diseases, the pathogenesis of which is unknown. In the present study, we have measured iron and cooper in cerebrospinal fluids (CSF) using methods that detect these metals in a "loosely bound" form, complexable to the chelators bleomycin and 1,10-phenanthroline. We studied 25 children with NCL, 21 children with encephalopathy of some other type, and 5 control children without neurological complications. The CSF concentrations of loosely bound iron at neutral pH values and of loosely bound copper did not correlate with the clinical diagnosis of the patients, nor did they parallel degenerative symptoms in NCL, such as mental impairment, visual loss, motor handicap, and epilepsy. However, the concentrations of loosely bound iron and copper increased significantly with the age of the patient; this is a novel finding and may represent increasing tissue destruction with age. Our present findings do not support a major role for primary iron toxicity in the development of neuronal degeneration. To investigate any secondary pathological role for malplaced transition metals, further research is required.

Dose-response of tubocurarine in patients with and without renal failure.

Different initial doses of tubocurarine (0.1, 0.2, 0.3 and 0.4 mg kg-1) were given to 20 patients with and 20 patients without renal failure (RF) during standard anaesthesia. Neuromuscular blockade was registered with a device based on electromyography. A fluorescent technique was used to measure plasma tubocurarine concentrations, for which blood samples were drawn during induction and at reversal of neuromuscular block. The dose-response curves for the induction period were slightly steeper in patients with RF. A linear correlation between tubocurarine concentration and twitch response was found in both groups, although the curve had shifted to the left in RF patients. The total amount of tubocurarine used for surgical relaxation was lower in the RF than in the non-RF patients.

Effect of ethanol and pH on the adsorption of drugs to activated charcoal: studies in vitro and in man.

The effect of ethanol on the adsorption of aspirin, quinidine and amitriptyline to activated charcoal was studied in vitro at pH 1.2 and 7.0. The adsorption of these drugs was greatly dependent on the charcoal-drug ratio and on the pH. Ethanol (10%) significantly (P less than 0.001) increased the percentage of their unadsorbed fraction at both pHs in vitro. In six healthy volunteers activated charcoal (50 g), ingested 5 min. after aspirin (1000 mg) and quinidine sulfate (200 mg), reduced their bioavailability by about 70% (aspirin) and 99% (quinidine). A significant desorption of aspirin but not that of quinidine from charcoal was obvious on the second and third days and seemed to be related to the effect of pH. The absorption of ethanol was not significantly prevented by charcoal. The concomitant ingestion of alcohol (50 g) with drugs antagonized only slightly the ability of charcoal to reduce the absorption of aspirin and quinidine.