Why there is a need for pharmacovigilance.

Not everything is known about a medicine when it receives its licence for marketing. The merits of a new drug, balancing its beneficial and its untoward effects, become only established after sufficient experience has been gained from its use in real practice. Part of the reason for this is that our extensive phase III clinical trials fail to detect some side-effects.

Coming full circle in pharmacovigilance: communicating safety information to patients through patient package inserts.

Optimal drug therapy requires that the patient should be informed adequately, unequivocally and in timely fashion. Patient package inserts (PPIs) have an important facilitating role to play in this respect. Patients' confidence in the benefit of a drug treatment and their fear of its side effects are strong determinants of their adherence to that treatment.

Post-marketing cohort study comparing the safety and efficacy of flunarizine and propranolol in the prophylaxis of migraine.

A comparative post-marketing surveillance study of the safety and efficacy of flunarizine and propranolol in the treatment of migraine was carried out. General practitioners in Belgium and the Netherlands each recruited patients for whom they would prescribe one of the study medications in the normal course of their treatment and recorded all medical events on follow-up forms for up to 8 months. A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort and 763 in the propranolol cohort.

Postmarketing study of the use of flunarizine in vestibular vertigo and in migraine.

Objective: This international postmarketing observational study of flunarizine was designed to evaluate, in routine clinical practice, the risk/benefit ratio of flunarizine in its approved indications, namely prophylaxis of migraine and treatment of vertigo. Comparator drugs were propranolol in migraine and betahistine in vertigo. The study was carried out by 498 general practitioners in Belgium, The Netherlands and Germany, whose participation had been requested by mail.

Risk of selected serious cardiac events among new users of antihistamines.

This retrospective cohort study examined the risk of selected serious cardiac events in new users of either astemizole or sedating antihistamines identified from the COMPASS Ohio Medicaid population of approximately 1 million active lives per year (1986-1992). (COMPASS is an automated claims database.) There were 15,585 patients in the astemizole group and 30,105 in the sedating antihistamines group.

QTc-measurements: a case-control study on serum electrolytes.

This is a report on a prospective case-control study, in which a group of patients with an electrocardiographic diagnosis of QTc-prolongation (cases) was compared with a group of patients with a normal QTc (controls) for the presence of potential causative factors. Twelve cases and twelve carefully-matched controls were entered during a 1-year recruitment period. Ventricular arrhythmias were more frequent amongst the cases than amongst the controls (7/12 the cases, only 2/12 controls).

Reproducibility of QTc-measurements in healty volunteers.

To assess the potential time-dependency and the reproducibility of the QTc-interval, ECG's from 84 healthy volunteers, recorded between 8 a.m. and 4 p.

Levamisole, the story and the lessons.

The history of the use of levamisole in man is summarized, from its start as an anthelmintic in the early sixties, through its world-wide recognition as an immunotropic agent especially in the seventies and early eighties, and its return to clinical prominence in 1989-90 as an effective adjuvant treatment for operable colon cancer. The knowledge accumulated from experimental tumour models and from clinical use in various types of cancer, supplemented with the recent evidence obtained from large-scale controlled trials in resectable colon cancer is reviewed. It is speculated that we may not have seen the end of levamisole story yet; also, the role of serendipidity in drug research is emphasized.

The role of the gut in migraine: the oral 51-Cr EDTA test in recurrent abdominal pain.

Sixteen children with recurrent abdominal pain (or: "recurrent syndrome"), regarded as migraine equivalent in childhood, were submitted to the 51-Cr EDTA gut permeability test. The results were compared with those obtained in 10 healthy young adults and in 11 control children. The gut permeability in the recurrent syndrome was significantly higher than in healthy adults and control children (p less than 0.

Prophylactic and curative treatment of migraine with calcium antagonists.

The present review discusses the available clinical information dealing with the treatment of migraine with calcium entry blocking agents. The data on prophylactic therapy are limited to 3 compounds, of which flunarizine is the most extensively studied and the only substance whose activity is well established. Clinical experience with these agents in the acute treatment of migraine attacks is still very limited.

Aromatase inhibition by R 76713: experimental and clinical pharmacology.

R 76713 is a new non-steroidal compound which inhibits aromatase in vitro and in vivo with a potency of at least 1000-fold that of aminoglutethimide. In male cynomolgus monkeys peripheral conversion of labeled androstenedione to estrone is decreased by 85%, 4-5 h after a single intravenous dose of 0.003 mg/kg of R 76713, without altering steroid metabolic clearance rates.

The sensorium of the migraineur.

The occurrence of perceptual disturbances in migraineurs, particularly during the headache-free interval, has been scrutinized rather rarely. This subject was studied via a mail survey in 134 patients presenting perceptual changes before or during their migraine attacks. The patients had to complete a 5-part questionnaire covering history, events before, during as well as after the attack, and the attack-free interval.

Hepatic cytochrome P450-mediated oxidation function in migraine.

Hepatic cytochrome P450-dependent oxidation is deficient in 5% to 10% of the Caucasian population. A similar percentage seems to suffer from migraine. The hypothesis was tested that an oxidation deficiency possibly relevant to potential dietary triggers plays a role in the pathogenesis of migraine.

Employee attitude surveys in the medical group practice.

Employee attitude surveys offer the potential for augmenting a progressive, participatory approach to management of medical groups. They can be used in many ways to understand and improve the environment within an organization. Upward communication, downward communication, morale boosting, education, management motivation--in these and many other areas, an effective survey can lead to positive results.

Onset of action of various migraine prophylactics.

Four studies were pooled to study the onset of action of three pharmacologically different migraine prophylactics: flunarizine, pizotifen and propranolol. Inter-drug differences in reduction of baseline attack frequency were subjected to analysis of variance. At months 1, 2, and 3 the inter-drug differences in number of patients showing a first 50% decrease in attack rate were subjected to the Chi-square test.

The effect of sabeluzole (R 58735) on memory retrieval functions.

In a first double-blind, placebo-controlled parallel experiment, 20 volunteers with a median age of 45 years were treated for 1 week with either sabeluzole (R 58735) or placebo. Before and after the treatment period, they were subjected to a Selective Reminding Procedure in which a 20-word list had to be learned. No differences between the two groups were seen for total recall, short-term retrieval, total long-term retrieval, random long-term retrieval and long-term storage.

The effect of R 58 735 (Sabeluzole) on memory functions in healthy elderly volunteers.

The effects of chronic treatment (5 mg b.i.d.