RESUMEN
We aimed to examine pharmacologic, demographic and medical comorbidity risk factors for opioid-related mortality among patients currently receiving methadone for an opioid use disorder. We conducted a population-based, nested case-control study linking healthcare and coroner's records in Ontario, Canada, from January 31, 1994 to December 31, 2010. We included social assistance recipients receiving methadone for an opioid use disorder. Within this group, cases were those who died of opioid-related causes. For each case, we identified up to 5 controls matched on calendar quarter. The primary analysis examined the association between use of psychotropic drugs (benzodiazepines, antidepressants or antipsychotics) and opioid-related mortality. Secondary analyses examined the associations between baseline characteristics, health service utilization, comorbidities and opioid-related mortality. Among 43,545 patients receiving methadone for an opioid use disorder, we identified 175 (0.4%) opioid-related deaths, along with 873 matched controls. Psychotropic drug use was associated with a two fold increased risk of opioid-related death (adjusted odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2 to 3.5). Specifically, benzodiazepines (adjusted OR 1.6; 95% CI 1.1 to 2.5) and antipsychotics (adjusted OR 2.3; 95% CI 1.5 to 3.5) were independently associated with opioid-related death. Other associated factors included chronic lung disease (adjusted OR 1.7; 95% CI 1.2 to 2.6), an alcohol use disorder (adjusted OR 1.9; 95% CI 1.2 to 3.2), mood disorders (adjusted OR 1.8; 95% CI 1.0 to 3.2), and a history of heart disease (adjusted OR 5.3; 95% CI 2.0 to 14.0). Psychotropic drug use is associated with opioid-related death in patients receiving methadone. Mindfulness of these factors may reduce the risk of death among methadone recipients.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Trastornos Relacionados con Opioides/mortalidad , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Factores de RiesgoRESUMEN
cDNAs encoding for preproTRH and preproorexin were cloned in winter flounder, a species that undergoes a period of natural fasting during the winter. For both peptides, the deduced amino acid structure of the hormone precursor shows 30-70% similarities with their homologs in other fish species. RT-PCR studies show that these peptides are present not only in the brain, but also in several peripheral tissues, including gastrointestinal tract and testes. Fasting induced increases in both preproorexin and preproTRH expressions in the hypothalamus, but did not affect their expression levels in the telencephalon/preoptic area. In addition, the mRNA expressions of both preproorexin and preproTRH were higher in the winter than in the summer in both hypothalamus and telencephalon/preoptic area. Our results suggest that orexin and thyrotropin-releasing hormone (TRH) might have a role in the seasonal regulation of food intake in winter flounder.
Asunto(s)
Regulación del Apetito/fisiología , Proteínas de Peces/metabolismo , Lenguado/metabolismo , Péptidos y Proteínas de Señalización Intracelular/química , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuropéptidos/química , Neuropéptidos/metabolismo , Precursores de Proteínas/química , Precursores de Proteínas/metabolismo , Hormona Liberadora de Tirotropina/química , Hormona Liberadora de Tirotropina/metabolismo , Secuencia de Aminoácidos , Animales , Clonación Molecular , ADN Complementario , Femenino , Proteínas de Peces/química , Proteínas de Peces/genética , Lenguado/genética , Privación de Alimentos , Regulación de la Expresión Génica , Hipotálamo/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Datos de Secuencia Molecular , Neuropéptidos/genética , Orexinas , Especificidad de Órganos , Filogenia , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/química , Estaciones del Año , Alineación de Secuencia , Telencéfalo/metabolismo , Hormona Liberadora de Tirotropina/genéticaRESUMEN
cDNAs encoding for neuropeptide Y (NPY), cocaine and amphetamine regulated transcript (CART) and cholecystokinin (CCK) were cloned in winter flounder, a species that undergoes a period of natural fasting during the winter. Tissue distribution studies show that these peptides are present in several peripheral tissues, including gut and gonads, as well as within the brain. We assessed the effects of season and fasting on the expression of these peptides. Our results show that NPY and CCK, but not CART, show seasonal differences in expression with higher hypothalamic NPY and lower gut CCK expression levels in the winter. In the summer, fasting induced an increase in hypothalamic NPY expression levels and a decrease in gut CCK levels, but did not affect hypothalamic CART expression levels. None of the peptides examined was affected by fasting in the winter. Our results suggest that NPY and CCK, but maybe not CART, might have a major role in the regulation of feeding in winter flounder and might contribute to the seasonal fluctuations in appetite in this species.