RESUMO
OBJECTIVE: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. METHODS: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. RESULTS: We report an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10-11; odds ratio [95% confidence interval] 7 [3.2-16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. CONCLUSIONS: The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H-related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.
Assuntos
Anticonvulsivantes/efeitos adversos , Apolipoproteínas/genética , Toxidermias/genética , Variação Genética , Fenitoína/efeitos adversos , Anticonvulsivantes/uso terapêutico , Povo Asiático/genética , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Estudos de Casos e Controles , Fator H do Complemento/genética , Toxidermias/etnologia , Toxidermias/etiologia , Epilepsia/tratamento farmacológico , Epilepsia/genética , Estudo de Associação Genômica Ampla , Antígenos HLA-A/genética , Humanos , Desequilíbrio de Ligação , Mutação de Sentido Incorreto , Variantes Farmacogenômicos , Fenitoína/uso terapêutico , Estudos Retrospectivos , População Branca/genéticaRESUMO
OBJECTIVE: To assess the influence of an educational intervention on the knowledge, attitude, behavior and intention to use safe patient handling and movement (SPHM) of radiation therapy students during their initial clinical education experience. METHOD: Seventeen first-year students in a 2-year radiation therapy baccalaureate program received education on traditional manual patient handling and SPHM through 2 1-hour lectures and a 2-hour skills laboratory. Questionnaires and a group discussion were used to collect data on the students' knowledge, attitude, behavior and intention to use SPHM in clinical practice. RESULTS: Although students' patient handling knowledge improved following the educational intervention, their overall knowledge, attitude and intention to use SPHM did not change. However, fewer students perceived patient handling injuries to be a problem in radiation therapy after their initial clinical education. CONCLUSION: A gap exists between students' SPHM knowledge and their performance of the techniques. Educators should incorporate SPHM into their curriculum because the information helped students achieve high levels of perceived behavioral control, increased patient handling knowledge and positive attitudes regarding SPHM.