Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study.

This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.

Interaction profile and tolerability of barnidipine.

INTRODUCTION: Barnidipine is a new dihydropyridine calcium antagonist that is presented in modified-release capsules containing a single S-S optical isomer of the molecule. Its characteristics are of interest, as there is evidence of differences in kinetics, dynamics, interactions and safety of individual enantiomers in traditional racemic preparations of calcium antagonists. The safety of barnidipine and its interaction profile are reviewed. SAFETY: Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I and occur in the early phase of treatment. Furthermore, safety results in elderly patients are comparable with those in the general population, indicating that barnidipine can be used without dose adjustment in elderly hypertensive patients. INTERACTIONS: Barnidipine has a pharmacokinetic interaction profile that compares favourably with those from other calcium antagonists. The pharmacokinetic properties of barnidipine are unaffected by food. Minor increases in its availability may occur with concomitant use of alcohol or grapefruit juice, but these are unlikely to have clinical relevance. In contrast with several other calcium antagonists, barnidipine does not affect the steady-state kinetics of digoxin, whereas, like other calcium antagonists its bioavailability may be increased by the concomitant administration of cimetidine. In addition, the potential of barnidipine and its major metabolites to affect the metabolism of concomitant medication is unlikely to be of clinical relevance. CONCLUSION: The interaction and tolerability profile of barnidipine is well established in all age groups.

Diversity and intensity of adverse events in the treatment of hypertension with barnidipine.

Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.

Subsequent development of acute non-lymphocytic leukemia in patients treated for Hodgkin's disease.

A nested case control study was carried out to investigate the association between treatment of patients with Hodgkin's disease (HD) and the risk of developing acute non-lymphocytic leukemia (ANLL). Seven Cancer Centers of the International Cancer Patient Data Exchange System of the UICC participated. A study cohort was selected consisting of 1,681 nonpretreated patients with HD, diagnosed from 1972 through 1978, and followed up through 1984. The median follow-up time was 66 months. Eighteen cases of leukemia were observed in the cohort. The risk of development of ANLL was significantly greater for male than for female patients. The treatment characteristics associated with an increased risk of developing ANLL were extensive radiotherapy, splenectomy and the chemotherapy combination of vincristine, procarbazine and mechlorethamine.

To perfuse or not to perfuse? A retrospective comparative study to evaluate the effect of adjuvant isolated regional perfusion in patients with stage I extremity melanoma with a thickness of 1.5 mm or greater.

The use of isolated regional perfusion in an adjuvant setting for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 20 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (a region of West Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which tumor thickness was the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (P = .61), time to regional lymph node metastasis (P = .11), time to distant metastasis (P = .73), disease-free interval (P = .42), and survival (P = .90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.

A pilot study on the quality of data management in a cancer clinical trial.

Twelve institutional data managers were asked to independently code the data from a patient chart of one patient in an ovarian cancer trial. They abstracted data from the medical record and filled out three types of trial forms (on-study, chemotherapy, and summary forms). The analysis of the processed data revealed that the median rate of errors was 13% for the 12 data managers. The error rate differed among the types of trial forms. The factors causing these errors were mistakes in interpretation, documentation, and coding. The level of experience of the data managers proved to be an important factor. It became clear that the documentation in the medical record was inadequate. We conclude that data managers as well as physicians involved in cancer clinical trials need specific training and that the quality of data management in cancer clinical trials is an important issue for further investigation.

Effects of maternal glucose ingestion on human fetal breathing movements at weeks 24 and 28 of gestation.

The incidence of human fetal breathing movements was studied in normal pregnancies before and after administration of 50 g glucose or a placebo (water) at 24 and 28 weeks. Glucose or water was given to the same women on two separate days in a randomised order. No significant differences were present among the results on the placebo-day and the control period of the glucose-day at either gestational age. On the glucose-day, the incidence rose significantly from 3.6 to a maximum of 11.6% at 24 weeks, and from 6.7 to 30.2% at 28 weeks. At both ages the maximum was found 90-120 min after the intake of glucose. It is concluded that already at 24 weeks gestation the human fetus reacts with an increase of fetal breathing movements after the administration of glucose to the mother.

The incidence of herpes zoster in patients with Hodgkin's disease. An analysis of prognostic factors.

The incidence of zoster in 717 patients with Hodgkin's disease was determined by a retrospective chart review. All patients had been treated and followed in one of six cancer centers. Prognostic factors that might predict the subsequent incidence of zoster were examined by univariate and multivariate analytic techniques. Intensity of treatment was a key factor in the incidence of zoster. Thirty-six months after initiation of treatment, patients receiving chemotherapy-radiation-chemotherapy had twice the attack rate (27.3%) of those receiving radiation alone (11.5%). The pediatric age group had a significantly higher attack rate (26.6%) than did adults (18.7%). Stage, histology, and laparotomy did not influence the incidence of zoster.