RESUMO
BACKGROUND: Accurate estimates of the incidence of anaphylaxis are limited. Current International Classification of Diseases, Ninth Revision (ICD-9) codes complicate accurate diagnosis of anaphylaxis and assessment of appropriate epinephrine prescribing. OBJECTIVE: To quantify the incidence and demographic character of patients with anaphylaxis-related ICD-9 codes in a large health maintenance organization and analyze epinephrine prescribing and dispensing rates. METHODS: All patients included had at least 12 months of continuous membership over a 4-year period from January 1, 2008 to December 31, 2012 and were selected based on anaphylaxis-related ICD-9 codes (N = 159,172). This algorithm was extrapolated from a previous study that used expanded ICD-9 codes to identify more cases of anaphylaxis. Individual chart reviews found that many expanded ICD-9 codes represented unconfirmed cases of anaphylaxis and therefore were excluded, resulting in analysis of 52,405 patients. RESULTS: Incidence of anaphylaxis over 4 years was 2.07%, with female predominance (56.5%) over male predominance (43.5%). Epinephrine was prescribed in 16.2% of total cases. Highest rates of epinephrine prescription were for traditional ICD-9 codes 995.0 (other anaphylactic shock) and 995.60 to 995.69 (anaphylactic shock caused by food) at 49.3% and 58.6%, respectively. Of the cases in which an epinephrine auto-injector was prescribed, it was dispensed 95.9% of the time, independent of copayment amount. CONCLUSION: Low epinephrine auto-injector prescribing rates in cases of anaphylaxis suggest the continued difficulty in the diagnosis of anaphylaxis and could result in suboptimal treatment of potential future episodes.
Assuntos
Anafilaxia/epidemiologia , Sistemas Pré-Pagos de Saúde , Algoritmos , Anafilaxia/diagnóstico , Anafilaxia/terapia , California/epidemiologia , Custos de Medicamentos , Prescrições de Medicamentos , Epinefrina/administração & dosagem , Feminino , Sistemas Pré-Pagos de Saúde/estatística & dados numéricos , Humanos , Incidência , Classificação Internacional de Doenças , Masculino , Vigilância da População , Padrões de Prática Médica , Estudos Retrospectivos , AutoadministraçãoRESUMO
The pyruvate dehydrogenase complex (PDC) oxidizes pyruvate to acetyl CoA and is critically important in maintaining normal cellular energy homeostasis. Loss-of-function mutations in PDC give rise to congenital lactic acidosis and to progressive cellular energy failure. However, the subsequent biochemical consequences of PDC deficiency that may contribute to the clinical manifestations of the disorder are poorly understood. We postulated that altered flux through PDC would disrupt mitochondrial electron transport, resulting in oxidative stress. Compared to cells from 4 healthy subjects, primary cultures of skin fibroblasts from 9 patients with variable mutations in the gene encoding the alpha subunit (E1α) of pyruvate dehydrogenase (PDA1) demonstrated reduced growth and viability. Superoxide (O(2)(.-)) from the Qo site of complex III of the electron transport chain accumulated in these cells and was associated with decreased activity of manganese superoxide dismutase. The expression of uncoupling protein 2 was also decreased in patient cells, but there were no significant changes in the expression of cellular markers of protein or DNA oxidative damage. The expression of hypoxia transcription factor 1 alpha (HIF1α) also increased in PDC deficient fibroblasts. We conclude that PDC deficiency is associated with an increase in O(2)(.-) accumulation coupled to a decrease in mechanisms responsible for its removal. Increased HIF1α expression may contribute to the increase in glycolytic flux and lactate production in PDC deficiency and, by trans-activating pyruvate dehydrogenase kinase, may further suppress residual PDC activity through phosphorylation of the E1α subunit.