Reporting adverse drug reactions on a geriatric ward: a pilot project

OBJECTIVE: To test a method for registration of adverse drug reactions (ADRs) resulting in hospital admission and of ADRs occurring during hospital stay. Spontaneous reporting was compared with data from patient interview. METHODS: Spontaneous reporting of ADRs by nurses and physicians, as well as patient interviews by pharmacists. This pilot project was carried out in the geriatric ward of the Ghent University Hospital over a period of 8 months in order to develop suitable registration forms and to test feasibility. Causality, severity, type and level of intervention of the reported ADRs were analysed. Reports from physicians and nurses were compared with the data obtained by patient interviews. RESULTS: During the 8 months, for 168 patients, 12 spontaneous reports were received from physicians and nurses. Fifty-six of these patients were interviewed and 32 ADRs were reported. Only 2 ADRs detected by patient interview were also reported spontaneously. The interviews of the 56 geriatric patients indicated that 20% of them were admitted to the hospital because of an ADR. ADRs occurred during hospital stay in another 20% of those patients. CONCLUSION: Spontaneous reporting by physicians and nurses revealed considerably fewer ADRs than patient interview by pharmacists. Physicians and nurses reported the more serious ADRs that occurred during hospital stay, whereas the interviews revealed more ADRs that caused hospital admission. Our data confirm that ADRs are an important cause of hospital admission of geriatric patients and occur frequently during their hospital stay.     

Personality, Individual Differences, and Preferences for the Sexual Media

The extent to which personality and individual differences predict preferences for and choices of various forms of sexual media was examined. Personality (e.g., intelligence, aggression) and individual difference factors (e.g., prior sexual experience) were assessed in 160 undergraduate men. These men also indicated their preferences for and choices of various forms of sexual media (e.g., erotic, female insatiability, violent). As expected, individual differences were predictive, with, for example, men lower in intelligence and higher in aggressive/antisocial tendencies having a higher preference for violent sexual stimuli than men higher in intelligence and lower in aggressive/antisocial tendencies had. In addition, as much as 50% of the variation in the preference for violent sexual materials was accounted for by an additive combination of individual differences and self-report arousal to these materials. Finally, the results indicated that, when given a choice to view different media materials, the men chose a broad range of media materials, although the female insatiability films were more popular than the other sexual films (e.g., erotic or violent). Results are discussed in relation to recent research and psychological theories that view adults as active in choosing their own social environments.     

Oral vasoactive medication in intermittent claudication: utile or futile?

Objective: To evaluate the role of orally administered vasoactive medication in the management of intermittent claudication. Setting: We limited our study to the products on the market in Belgium: cinnarizine, cyclandelate, isoxsuprine, naftidrofuryl, pentoxifylline, xanthinol nicotinate and buflomedil. Data sources: We conducted a systematic literature search involving Medline, International Pharmaceutical Abstracts, the Cochrane Library, direct contact with marketing companies and key authors, snowballing and Science Citation Index search. We looked for randomised placebo-controlled trials (RCTs) in patients with Fontaine stage II, in which pain-free and/or maximal walking distance were measured using a standardised exercise test. For isoxsuprine and xanthinol nicotinate, no trials conforming to these criteria were found. Thirty-six trials on cinnarizine, cyclandelate, buflomedil, naftidrofuryl and pentoxifylline met our inclusion criteria. Study selection: After quality assessment, 26 trials were excluded, mainly because of short trial duration (less than 12 weeks), small sample size (less than 30 patients) and/or failure to report details on variability (standard deviation or confidence limits). For cinnarizine and cyclandelate, none of the three selected RCTs was included. Data extraction: For buflomedil, of six published RCTs, two were included after quality assessment, each showing a marginally positive effect of buflomedil versus placebo. For naftidrofuryl, nine RCTs were selected; six were included of which five showed a significant positive result. The likelihood of publication bias and the heterogeneity of the results within and between trials precluded a meta-analysis. For pentoxifylline, of the 18 selected RCTs, only two could be included, both with inconclusive results. Conclusion: A national consensus conference, based on this review, concluded that health resources should be allocated to prevention and rehabilitation of intermittent claudication rather than to reimbursement of these products with doubtful efficacy. Received: 11 November 1999 / Accepted in revised form: 10 February 2000     

Prognosis and treatment of idiopathic thrombocytopenic purpura in children]

The following conclusions can be drawn from the study of 55 cases of I.T.P. of childhood. 1. I.T.P. evolving more than 6 months must always be considered as chronic, the disease having in these cases few chances of recovery without splenectomy. After 6 months evolution, it is probably possible to establish a prognosis and a therapeutic approach with little risk of error. 2. Among the clinical and biological criteria noted at the onset of the disease, the intensity of thrombopenia alone is statistically different in acute and chronic I.T.P. Consequently, there are few criteria allowing the early recognition of evolution to chronic I.T.P. 3. The corticoids have no curative value in I.T.P. Prolonged corticotherapy is therefore useless in this disease. 4. As a palliative, the value of the corticoids can only be statisfactorily demonstrated in chronic I.T.P. Here it is certain in 6 cases on 16. 5. The value of corticoids for capillary resistance is evident, even in small doses. 6. Splenectomy must be considered in all cases of severe or corticodependant chronic I.T.P. Cure is obtained in most cases. 7. The contribution of immunosuppressive agents and in particular azathioprine, cannot be usefully assessed on the basis of the series studied. In the absence of decisive results, it would be worthwhile to evaluate this treatment by means of a greater number of clinical trials.     

Influence of enhanced alpha-1-acid glycoprotein concentration on protein binding, pharmacokinetics and antiarrhythmic effect of lidocaine in the dog

The pharmacokinetics and the antiarrhythmic effect of lidocaine were studied in healthy dogs on three occasions: before administration of rifampicin, on the 14th day of treatment with rifampicin and 4 weeks after stopping rifampicin treatment. On each occasion a loading and a maintenance infusion of lidocaine were given to obtain steady-state concentrations. Blood and plasma concentrations of lidocaine, alpha-1-acid glycoprotein plasma concentrations and percentage of free lidocaine in plasma were determined at the end of the maintenance infusion. The antiarrhythmic effect of lidocaine was evaluated by measuring the arrhythmogenic dose of epinephrine. Blood concentrations and, consequently, the total blood clearance of lidocaine were comparable on the three occasions. Total plasma concentrations were significantly higher after rifampicin administration as compared to the two control periods. Percentage of free lidocaine decreased from about 50 to about 30%, accompanied by a nearly 3-fold increase of alpha-1-acid glycoprotein concentrations. Free plasma concentrations were slightly lower after rifampicin treatment. The epinephrine dose ratio (before/after) paralleled the changes in free lidocaine concentrations. The correlation between free plasma concentrations and epinephrine dose ratio was much stronger than between total plasma concentrations and epinephrine dose ratio. The plasma elimination half-life of lidocaine was markedly shortened after rifampicin treatment, due to a diminished volume of distribution. It is concluded that, under steady-state conditions, marked increases in the protein binding of lidocaine are accompanied by only slight decreases of free plasma concentrations and of antiarrhythmic effect.     

Plasma concentrations and haemodynamic effects of nimodipine in patients resuscitated after cardiac arrest

Summary As the pharmacokinetics of a drug may be altered in haemodynamically compromised patients, the plasma concentrations and haemodynamic effects of the calcium entry blocker nimodipine have been examined in patients resuscitated after out-of-hospital cardiac arrest.In 7 patients nimodipine was infused at increasing rates up to 30 µg·kg^–1·h^–1. The plasma concentrations increased with increasing dose; at the highest dose a mean steady-state plasma concentration of 22.1 ng·ml^–1 was obtained, and the mean plasma clearance was 1.4 l·kg^–1·h^–1. There were no marked changes in mean arterial blood pressure or heart rate.In 9 other patients nimodipine was given as a bolus infusion of 10 µg·kg^–1 over 3 min, followed by a continuous infusion of 30 µg·kg^–1·h^–1. A mean steady-state plasma concentration of 17.6 ng·ml^–1 was obtained and the mean plasma clearance was 1.9 l·kg^–1·h^–1. Heart rate did not change significantly, but the mean arterial blood pressure fell.The data indicate that in patients resuscitated after cardiac arrest, the pharmacokinetics of nimodipine are not markedly different from patients with other conditions, e.g. subarachnoid haemorrhage. However, if a loading dose is given to obtain a steady-state concentration sooner, there will be a fall in arterial blood pressure.     

Postoperative immunological response against contractile proteins after coronary bypass surgery

The pathogenesis of post-cardiac injury syndrome was studied prospectively in 62 patients who underwent coronary bypass grafting. Preoperative and serial postoperative titres of actin and myosin antibodies were measured by an enzyme linked immunosorbent assay. Perioperative cumulative release of serum aspartate and alanine aminotransferases, lactate dehydrogenase, and creatine kinase was calculated by approximation formulas that are used to estimate infarct size. Complete post-cardiac injury syndrome developed in eight (13%) patients and an incomplete syndrome developed in 16 (26%). There was a significant correlation between frequency and intensity of the syndrome and the ratio of postoperative to preoperative titres of actin and myosin antibodies. Furthermore, there was a significant correlation between the cumulative release of lactate dehydrogenase, serum aspartate aminotransferase, and creatine kinase and the number of coronary vessels that were grafted, but no correlation was found between the incidence of post-cardiac injury syndrome and the number of coronary bypasses grafted or between the cumulative enzyme release and the postoperative immunological response against the major contractile proteins, actin and myosin. The amount of enzymes released during coronary bypass surgery seems to be a good indicator of the extent of myocardial damage during operation but it does not determine either the incidence of post-cardiac injury syndrome or the postoperative immunological response against the main contractile proteins actin and myosin.     

In-vitro biotransformation of antipyrine, lignocaine and propranolol in the liver of rats with turpentine-induced inflammation

In rats with inflammation induced by turpentine injection, changes in drug disposition occur in-vivo and in the perfused isolated liver. Therefore the biotransformation of a low extraction drug, antipyrine, and of two high extraction drugs, lignocaine and propranolol, has been evaluated in the 9000g supernatant fraction of the liver of turpentine-treated rats. Aminopyrine N-demethylase activity and cytochrome P450 content were also measured. Turpentine treatment significantly reduced the in-vitro breakdown of the three drugs; aminopyrine N-demethylase activity and cytochrome P450 content were also decreased. Similar results were found in the proadifen-treated rats, except that in those, the cytochrome P450 content was slightly increased. The changes in drug disposition seen after turpentine-induced inflammation, could therefore be due in part to a change in hepatic enzymatic activity.