Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.     

Risk of infectious complications in well-appearing children with transient neutropenia

To determine whether well-appearing children found incidentally to be neutropenic are at risk for an infectious complication, 44 consecutive months of hematology laboratory records were reviewed. One hundred nineteen patients had medical record documentation regarding clinical course, serial white blood cell counts, and the absence of serious infections, chronic illnesses, or a family history known to be associated with neutropenia. The median duration of documented neutropenia was 13 days (range, 1 to 491 days). Infectious complications occurred in 4 of the 36 patients who had neutropenia for more than 30 days (2 with stomatitis, 1 with cellulitis, and 1 with pneumonia) but in none with shorter durations of neutropenia. There were no significant associations between the development of an infectious complication and either the initial absolute neutrophil count or the lowest documented absolute neutrophil count, nor was there a correlation between the initial absolute neutrophil count and the duration of neutropenia. These data indicate that infectious complications occur in otherwise well children with unexplained neutropenia that persists, but these infections are infrequent and usually are superficial.     

Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases

We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia (CLL). Cases were subclassified as morphologically typical and atypical CLL according to the criteria of the FAB proposal. Typical CLL cases were mostly diagnosed at a low-risk stage (Binet A/Rai 0), required no immediate treatment and expected a long survival; atypical CLL cases mostly presented at a more advanced risk stage (Binet B/Rai I–II), usually required immediate treatment and their survival was shorter. Moreover, clinical staging was of prognostic significance in typical but not in atypical cases.   In typical CLL, del(11q) was the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12 was found in about 65% of the cases documented with an abnormal karyotype. Although chromosomal abnormalities were associated with a poor survival in typical CLL, they are of no prognostic significance in atypical CLL.   Based on these data, we conclude that subtyping CLL by morphology enables the identification of two groups of cases, each characterized by a specific clinical presentation, different cytogenetic abnormalities and prognostic parameters. We speculate that these two groups may represent two related, but different, diseases with different prognostic parameters and a different survival.     

Severe ciguatera poisoning in Madagascar: A case report

In a single outbreak on the East coast of Madagascar, more than 500 people, 98 of whom died, were poisoned by the flesh of a shark, Carcharhinus amboinensis. From clinical symptoms it can be concluded that this poisoning is due to ciguatera toxins. It is the first case of a severe outbreak caused by a shark, and it is the first case with a mortality rate of 20%.     

Outbreak of measles in a teenage school population: the need to immunize susceptible adolescents.

An outbreak of measles occurred in a community school and the surrounding area in Crowborough, East Sussex, UK, from December 1992 to February 1993. There were 96 suspected cases reported: 66 cases among 1673 students at one school and 30 community cases. The majority of suspected cases were in those aged 11-17 (78%), 2 cases occurred in infants < 1 year old and 8 cases in adults aged 18 years or over. Data collected on 60 (91%) of the 66 suspect school cases showed 56 (93%) had an illness which met a case definition of measles. Eighteen had confirmatory IgM measles antibody. Two cases were hospitalized. The local percentage uptake for measles immunization for the school age years affected varied between 64% and 84%. A survey of parents showed that approximately 74% of the students attending the school had a history of measles immunization. The immunization rates reported by parents for children who developed measles was 21%, (29% based on GP records) compared with 77% for those who remained well. Vaccine efficacy was estimated to be 92%. This outbreak, along with others recently reported in older unimmunized children in the UK, reinforces the need for catch-up immunization programmes to reach this susceptible group of adolescents.     

Rubella virus strains show no major antigenic differences.

To determine whether antigenic differences occur among rubella virus strains, five wild-type strains of rubella virus isolated in the UK, the USA, and in Japan between 1964 and 1987 and four attenuated vaccine strains were compared employing a panel of 28 monoclonal antibodies in neutralization, haemagglutination-inhibition, enzyme immunoassay, and indirect immunofluorescence assays. No antigenic differences were detected which confirms that rubella vaccines will protect against circulating strains and that rubella antigens used in serological tests for screening and diagnosis will detect antibodies induced by all strains.