RESUMO
The U.S. chronic disease health care system has substantial gaps in delivery of services. New models of care change traditional delivery of care and explore new settings for care. This article describes a new model of diabetes chronic care delivery: nurse-delivered care that includes protocol-based insulin titration and patient education delivered solely in a virtual environment. In phase 1, the clinical outcome of time to achievement of glycated hemoglobin (A(1C)) goals (P < .001; 95% confidence interval, 1.68-2.24) was significantly improved by registered nurse (RN) standing order intervention (n = 24) as compared with historical controls (n = 28). In phase 2, patients who were referred to an RN-managed insulin titration protocol with individualized A(1C) goals had a significant (P < .001; 95% confidence interval, 1.680-2.242) reduction in results from a mean of 9.6% at baseline to 7.7% at completion. Average patient age was 66 years, with a mean duration of 11 years diagnosed with diabetes. Safety was demonstrated by the absence of hypoglycemia related to RN protocol adjustment. There were no admissions or emergency room (ER) visits for hypoglycemia. This study demonstrates safety and efficacy of RN virtual chronic disease management for an older population of patients with long-standing diabetes.
Assuntos
Atenção à Saúde , Diabetes Mellitus Tipo 2/enfermagem , Modelos de Enfermagem , Consulta Remota/organização & administração , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Avaliação de Programas e Projetos de Saúde , Estados Unidos , United States Department of Veterans Affairs , VeteranosRESUMO
CD28 plays crucial costimulatory roles in T cell proliferation, cytokine production, and germinal center response. Mice that are deficient in the inducible costimulator (ICOS) also have defects in cytokine production and germinal center response. Because the full induction of ICOS in activated T cells depends on CD28 signal, the T cell costimulatory capacity of ICOS in the absence of CD28 has remained unclear. We have clarified this issue by comparing humoral immune responses in wild-type, CD28 knockout (CD28 KO), and CD28-ICOS double-knockout (DKO) mice. DKO mice had profound defects in Ab responses against environmental Ags, T-dependent protein Ags, and vesicular stomatitis virus that extended far beyond those observed in CD28 KO mice. However, DKO mice mounted normal Ab responses against a T-independent Ag, indicating that B cell function itself was normal. Restimulated CD4(+) DKO T cells that had been primed in vivo showed decreased proliferation and reduced IL-4 and IL-10 production compared with restimulated CD4(+) T cells from CD28 KO mice. Thus, in the absence of CD28, ICOS assumes the major T cell costimulatory role for humoral immune responses. Importantly, CD28-mediated ICOS up-regulation is not essential for ICOS function in vivo.
Assuntos
Anticorpos Antivirais/biossíntese , Antígenos de Diferenciação de Linfócitos T/fisiologia , Antígenos CD28/genética , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Animais , Antígenos de Diferenciação de Linfócitos T/genética , Antígenos CD28/fisiologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Divisão Celular/genética , Divisão Celular/imunologia , Células Clonais , Cruzamentos Genéticos , Citocinas/biossíntese , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Imunoglobulina A/biossíntese , Switching de Imunoglobulina/genética , Imunoglobulina G/metabolismo , Imunoglobulina M/biossíntese , Proteína Coestimuladora de Linfócitos T Induzíveis , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Rhabdoviridae/genética , Infecções por Rhabdoviridae/imunologia , Células Th2/imunologia , Células Th2/metabolismo , Células Th2/patologia , Vírus da Estomatite Vesicular Indiana/imunologiaRESUMO
Understanding the pathways that signal T cell tolerance versus activation is key to regulating immunity. Previous studies have linked CD28 and protein kinase C-theta (PKCtheta) as a potential signaling pathway that influences T cell activation. Therefore, we have compared the responses of T cells deficient for CD28 and PKCtheta in vivo and in vitro. Here, we demonstrate that the absence of PKCtheta leads to the induction of T cell anergy, with a phenotype that is comparable to the absence of CD28. Further experiments examined whether PKCtheta triggered other CD28-dependent responses. Our data show that CD4 T cell-B cell cooperation is dependent on CD28 but not PKCtheta, whereas CD28 costimulatory signals that augment proliferation can be uncoupled from signals that regulate anergy. Therefore, PKCtheta relays a defined subset of CD28 signals during T cell activation and is critical for the induction of activation versus tolerance in vivo.