Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort.

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.

Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group.

BACKGROUND: There has been some concern that vaccination may precipitate the onset of multiple sclerosis or lead to relapses. Since the recent hepatitis B vaccination program in France, there have been new reports of an increased risk of active multiple sclerosis after vaccination. METHODS: We conducted a case-crossover study to assess whether vaccinations increase the risk of relapse in multiple sclerosis. The subjects were patients included in the European Database for Multiple Sclerosis who had a relapse between 1993 and 1997. The index relapse was the first relapse confirmed by a visit to a neurologist and preceded by a relapse-free period of at least 12 months. Information on vaccinations was obtained in a standardized telephone interview and confirmed by means of medical records. Exposure to vaccination in the two-month risk period immediately preceding the relapse was compared with that in the four previous two-month control periods for the calculation of relative risks, which were estimated with the use of conditional logistic regression. RESULTS: Of 643 patients with relapses of multiple sclerosis, 15 percent reported having been vaccinated during the preceding 12 months. The reports of 94 percent of these vaccinations were confirmed. Of all the patients, 2.3 percent had been vaccinated during the preceding two-month risk period as compared with 2.8 to 4.0 percent who were vaccinated during one or more of the four control periods. The relative risk of relapse associated with exposure to any vaccination during the previous two months was 0.71 (95 percent confidence interval, 0.40 to 1.26). There was no increase in the specific risk of relapse associated with tetanus, hepatitis B, or influenza vaccination (range of relative risks, 0.22 to 1.08). Analyses based on risk periods of one and three months yielded similar results. CONCLUSIONS: Vaccination does not appear to increase the short-term risk of relapse in multiple sclerosis.

Cost of varicella in France: a study in day care centers.

To assess the cost of varicella in young children in France, a prospective study was done in day care centers. Children (1263), who were 3 months to 3 years old and attending day care, were followed over a varicella season. For every child who developed varicella (n = 200), detailed information was obtained by use of parental questionnaires. Questions concerned medical care, days missed from work for parents, and the need for extra baby-sitting. On average, each sick child had one consultation with a physician and received three medications. In half of the families (52%), at least 1 parent had to miss work an average of 4.5 days to care for a sick child. Total costs to society were estimated to be US$352 per family, with medical costs accounting for 22% of the cost. The average eventual cost to parents was $89 per family, including $80 of non-medical costs. This study emphasizes the important socioeconomic impact of varicella in the day care setting in France.

[Proposal of guidelines for the set-up of pharmaco-epidemiologic studies in drug surveillance]. / Propositions de procédures pour la mise en place d'études pharmaco-épidémiologiques en pharmacovigilance.

In the light of recent experiences and anticipating an increase in similar requests in the future, it seemed very interesting to a drug safety executives' group from the pharmaceutical industry to propose guidelines for the set-up and follow-up of pharmacoepidemiological studies requested by Health Authorities for the assessment of drug risk. The scope of these guidelines is to establish the responsibility of the teams and structures involved in the study, to define the necessary stages set-up, and to determine the rules in order to ensure its smooth running from the drafting of the protocole to the final use of the data.

Risk of cancer from azathioprine therapy in multiple sclerosis: a case-control study.

An increased risk of cancer has been reported in patients treated with azathioprine. To assess the long-term risk of neoplasia in azathioprine-treated multiple sclerosis (MS) patients, we conducted a case-control study using the Lyon Multiple Sclerosis Database. From the 1,191 MS patients included in the database, we identified patients who developed cancer before December 31, 1991. Each case was then matched to three cancer-free MS controls by gender, date of birth, and date of MS onset. A matched analysis was performed to compare cases and controls for exposure to azathioprine therapy during the same follow-up period. Twenty-three MS patients with cancer were identified: 17 solid tumors, 2 skin carcinomas, 4 hematopoietic cancers. Cases had a mean age of 34.5 years +/- 10.2 (+/- SD) at clinical onset of MS and have been followed up for an average 13.8 years +/- 8.1 before being diagnosed with cancer. Fourteen cases (61%) and 34 controls (49%) had been treated with azathioprine for at least 1 month after being diagnosed with MS (adjusted odds ratio = 1.7; 95% confidence interval [CI], 0.6 to 4.6). When assessing risk associated with different durations of azathioprine therapy compared with no treatment at all, we found that MS patients had an increase in cancer risk of 1.3 (95% CI, 0.4 to 4.0) when treated less than 5 years, of 2.0 (95% CI, 0.4 to 9.1) when treated 5 to 10 years, and of 4.4 (95% CI 0.9 to 20.9) when treated more than 10 years. Similar results were obtained when assessing cancer risk associated with cumulative doses of azathioprine ever taken. This case-control study suggests that the overall long-term risk of cancer from azathioprine is low in MS patients. The results are suggestive of a dose-response relationship with no significant risk during the first years of treatment and a possible increased risk after about 10 years of continuous therapy. Further studies are needed to better assess the risk-benefit ratio of azathioprine in MS.

Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses.

Nocturnal melatonin excretion was studied throughout a complete menstrual cycle in 10 women with migraine without aura attacks associated with menses and 9 women controls. Urine melatonin was determined by radioimmunoassay. The mean nocturnal melatonin excretion throughout the cycle was significantly lower in the migraine patients than in controls. In the control group, melatonin excretion increased significantly from the follicular to the luteal phase, whereas no difference was observed in the migraine group. Results are discussed in view of the role of the pineal gland in the organization of biological rhythms and homeostasis in relation to environmental conditions.