Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Disfunción Cognitiva/diagnóstico , Evaluación Preclínica de Medicamentos/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Pruebas Neuropsicológicas , Factores de Edad , Animales , Conducta Animal/efectos de los fármacos , Niño , Conducta Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Ensayos Clínicos como Asunto , Cognición/efectos de los fármacos , Cognición/fisiología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/psicología , Congresos como Asunto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/psicología , Humanos , Modelos Animales , Factores de TiempoRESUMEN
OBJECTIVES: In 2003, the US Food and Drug Administration issued warnings about hyperglycemia and diabetes with second-generation antipsychotics (SGAs); guidelines have recommended metabolic screening since 2004. However, little is known of contemporary practices of glucose screening among youth initiating SGAs. Our objective was to evaluate baseline glucose assessment among youth in the Mini-Sentinel Distributed Database starting an SGA. METHODS: The cohort included youth ages 2 through 18 newly initiating SGAs January 1, 2006, through December 31, 2011, across 10 sites. Baseline glucose was defined as fasting/random glucose or hemoglobin A1c (GLU) measurement occurring relative to first SGA dispensing. Differences in GLU assessment were evaluated with χ(2) tests and logistic regression. RESULTS: The cohort included 16,304 youth; 60% boys; mean age 12.8 years. Risperidone was most commonly started (43%). Eleven percent (n = 1858) had GLU assessed between 90 days before and 3 days after first dispensing. Assessment varied across SGAs (olanzapine highest), sites (integrated health care systems higher), ages (16-18 highest), years (2007 highest), and gender (female higher; all P < .001). GLU assessment among those starting olanzapine was more likely than among those starting quetiapine (odds ratio [OR]: 1.72 [95% confidence interval (CI): 1.37-2.18]), aripiprazole (OR: 1.49 [95% CI: 1.18-1.87]), or risperidone (OR: 1.61 [95% CI: 1.28-2.03]). CONCLUSIONS: Few children and adolescents starting SGA have baseline glucose assessed. This is concerning because those at high diabetes risk may not be identified. Further, lack of screening impedes determining the contribution of SGAs to hyperglycemia development.
Asunto(s)
Antipsicóticos/efectos adversos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Guías de Práctica Clínica como Asunto/normas , Adolescente , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus/sangre , Diabetes Mellitus/inducido químicamente , Femenino , Humanos , Hiperglucemia/sangre , Hiperglucemia/inducido químicamente , Masculino , Estudios RetrospectivosRESUMEN
Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic.