Transition of continuous subcutaneous insulin infusion systems in a very short time frame as a consequence of a public tender process

AIM: The procurement of pumps/supplies through a tender process is common practice among public services. A report is presented on the feasibility and safety of the transition from one continuous subcutaneous insulin infusion (CSII) system to another within a very short time frame (4-weeks) as the consequence of a public tender. METHODS: The program consisted of: Session-1 was a system start-up training session. Patient satisfaction was evaluated. Session-2 consisted of a call from technical staff 72 h after Session- 1 to provide support regarding the programming or the change of infusion set. Session-3 was a training session regarding the use of therapy management software. During and 2 months after Session-2, clinical events, technical issues, and training reinforcement incidents were registered. HbA1c data were collected retrospectively. RESULTS: A total of 219 patients were enrolled. During the second week, 81% of patients weretransferred to the new system. Patient overall satisfaction scored 9.4/10 (none <7). There were 30 training reinforcement events and 7 technical issues, with all 37 of them being were sorted out over the telephone. There were 31 additional clinical events (infusion set issues). Twentyfour were considered mild, and were solved by phone technical support. Medical assistance was needed in six (five unexpected hyperglycemia, one ketosis). There was only one severe event (ketoacidosis requiring hospitalization). HbA1c did not deteriorate during the transition process. One hundred twenty-eight patients attended the therapy management software training. CONCLUSIONS: With the assistance of a specific program, a complete switch to a new insulin pump in a large population of patients with T1D in the context of a public tender in a very short time was carried out safely and without deterioration of metabolic control

INTRODUCCIÓN: El sistema público de salud financia la utilización de infusores subcutáneos de insulina (ISCI) como tratamiento no convencional en pacientes con diabetes mellitus tipo 1 (DT1). En este contexto, y con el fin de mejorar la eficiencia, es frecuente que los centros encargados de este tipo de terapia utilicen procedimientos de licitación. Nuestro objetivo fue evaluar la eficacia y la seguridad de un proceso de recambio de dispositivos ISCI a llevar a cabo en un breve periodo (4 semanas) en un procedimiento de concurso público. PACIENTES Y MÉTODOS: El proceso de recambio incluyó 3 sesiones precedidas por la presentación y la justificación del mismo: sesión 1: adiestramiento en la utilización del nuevo dispositivo ISCI y administración de una encuesta de satisfacción; sesión 2: contacto telefónico de soporte a las 72 h de iniciado el programa a la búsqueda de incidencias, y sesión 3: a los 3 meses, sesión de refuerzo/consolidación de los conocimientos y adiestramiento en el uso de programa informático de gestión del tratamiento. Durante 2 meses se recogieron todas las incidencias clínicas y técnicas. Retrospectivamente, se obtuvo la HbA1c más cercana al inicio y la primera una vez finalizado el programa. RESULTADOS: Se efectuó el recambio en 219 pacientes, el 81% de los recambios se efectuó en las 2 primeras semanas. En la encuesta de satisfacción realizada se obtuvo una puntuación media de 9,4 sobre 10. Se efectuaron un total de 30 llamadas telefónicas extra con el fin de reforzar aspectos educativos y en 7 ocasiones se atendieron incidencias técnicas que fueron resueltas de manera inmediata. Veinticuatro de 31 eventos clínicos registrados fueron considerados de carácter leve. Seis de ellos fueron moderados (5 hiperglucemias simples/1 cetosis). Un evento fue catalogado como grave (cetoacidosis diabética). Todos los eventos se relacionaron con el equipo de infusión (recambio) y en todos se resolvieron de manera satisfactoria. La HbA1c tras el recambio no cambió significativamente. Ciento veintiocho pacientes acudieron al adiestramiento en el uso del programa informático de gestión del tratamiento. CONCLUSIONES: En el contexto de un proceso de licitación y bajo un programa diseñado específicamente, el recambio de dispositivos ISCI puede realizarse de manera segura y sin deterioro alguno en el control metabólico en un considerable número de pacientes y en un corto periodo

Membrane trafficking at the ER/Golgi interface: functional implications of RhoA and Rac1.

N-WASP and Arp2/3, the components of the actin nucleation/polymerization signaling pathway governed by Cdc42, are located in Golgi membranes and regulate ER/Golgi interface protein transport. In the present study, we examined whether RhoA and Rac1, like Cdc42, are also involved in this early secretory pathway. Unlike Cdc42, RhoA and Rac1 were not observed in the Golgi complex of different clonal cell lines nor were they present in isolated Golgi membranes. Expression of constitutively active or inactive mutants of RhoA or Rac1 proteins in HeLa cells did not alter either the disassembly or the assembly of the Golgi complex following the addition or withdrawal of BFA, respectively, the ER-to-Golgi VSV-G transport or the Sar1(dn)-induced ER accumulation of Golgi proteins. Moreover, unlike Cdc42-expressing cells, the 15 degrees C-induced subcellular redistribution of the KDEL receptor remained unaltered. Only cells that constitutively express the activated Cdc42 mutant (Cdc42Q61L), or that were microinjected with activated Cdc42Q61L protein, exhibited a significant change in Golgi complex morphology. Collectively, our results demonstrate that RhoA and Rac1 are not located in the Golgi complex, nor do they directly or indirectly regulate membrane trafficking at the ER/Golgi interface. This finding, in turn, confirms that Cdc42 is the only Rho GTPase to have a specific function on the Golgi complex.

Association of Cdc42/N-WASP/Arp2/3 signaling pathway with Golgi membranes.

Recent findings indicate that Cdc42 regulates Golgi-to-ER (endoplasmic reticulum) protein transport through N-WASP and Arp2/3 (Luna et al. 2002, Mol. Biol. Cell, 13:866-879). To analyse the components of the Cdc42-governed signaling pathway in the secretory pathway, we localized Cdc42, N-WASP and Arp2/3 in the Golgi complex by cryoimmunoelectron microscopy. Cdc42 is found throughout the Golgi stack, particularly in cis/middle cisternae, whereas N-WASP and Arp3 (a component of the Arp2/3 complex) are restricted to cis cisternae. Arp3 also colocalized in peri-Golgi tubulovesicular structures with either KDEL receptor or GM130. Even though Arp3 is not found in TGN46-positive cisternal elements, a small fraction of Arp3-labeled tubulo-vesicular elements showed TGN46 labeling. Active Cdc42 (GTP-bound form) induced relocation of N-WASP and Arp3 to the lateral rims of Golgi cisternae. These results show that the actin nucleation and polymerization signaling pathway governed by Cdc42/N-WASP/Arp operates in the Golgi complex of mammalian cells, further implicating actin dynamics in Golgi-associated membrane trafficking.

Regulation of protein transport from the Golgi complex to the endoplasmic reticulum by CDC42 and N-WASP.

Actin is involved in the organization of the Golgi complex and Golgi-to-ER protein transport in mammalian cells. Little, however, is known about the regulation of the Golgi-associated actin cytoskeleton. We provide evidence that Cdc42, a small GTPase that regulates actin dynamics, controls Golgi-to-ER protein transport. We located GFP-Cdc42 in the lateral portions of Golgi cisternae and in COPI-coated and non-coated Golgi-associated transport intermediates. Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]). Coexpression of wild-type or activated Cdc42 and N-WASP also inhibited Golgi-to-ER transport, but this was not the case in cells expressing Cdc42V12 and N-WASP(Delta WA), a mutant form of N-WASP that lacks Arp2/3 binding. Furthermore, Cdc42V12 recruited GFP-N-WASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP-dependent manner.