Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes

Dapagliflozin is associated with greater reductions in HbA1c and weight than saxagliptin in management of type 2 diabetes mellitus (T2DM). The present post hoc analyses compared the durability of these effects over short- and long-term follow-up in patients with T2DM who were inadequately controlled with metformin (≥1500 mg/day) and who were receiving either dapagliflozin (10 mg/day) or saxagliptin (5 mg/day). Failure of glycaemiccontrol was assessed using the slope of the change in HbA1c from baseline-over-time regression line (coefficient of failure [CoF]). CoF was compared directly (dapagliflozin vs saxagliptin) over the short term (NCT01606007, 24 weeks) and indirectly (placebo-adjusted) over the long term (NCT00528879 and NCT00121667, 102 weeks). A low CoF value indicated greater durability. CoF was lower for dapagliflozin versus saxagliptin over 18–24 weeks (−1.38%/year; 95% CI, −2.41 to −0.35; P =.009) and 20–102 weeks (−0.37%/year; 95% CI, −0.73 to −0.02; P =.04). Fewer dapagliflozin-treated patients versus saxagliptin-treated patients required rescue medication or discontinued the study because of failure to achieve glycaemic control at 24 weeks (3.4% vs 9.4%; P =.0191). In patients with T2DM who were inadequately controlled with metformin, dapagliflozin was associated with greater durability of glycaemic control than saxagliptin over 18–24 and 20–102 weeks

Isolation of DNA markers from a region between incontinentia pigmenti 1 (IP1) X-chromosomal translocation breakpoints by a comparative PCR analysis of a radiation hybrid subclone mapping panel

A strategy based on the use of human-specific interspersed repetitive sequence (IRS)-PCR amplification was used to isolate regional DNA markers in the vicinity of the incontinentia pigmenti 1 (IP1) locus. A radiation hybrid (RH) resulting from a fusion of an irradiated X-only somatic cell hybrid (C12D) and a thymidine kinase deficient (TK-) hamster cell line (a23) was identified as containing multiple X chromosome fragments, including DNA markers spanning IP1 X-chromosomal translocation breakpoints within region Xp11.21. From this RH, a panel of subclones was constructed and analyzed by IRS-PCR amplification to (a) identify subclones containing a reduced number of X chromosome fragments spanning the IP1 breakpoints and (b) construct a mapping panel to assist in identifying regional DNA markers in the vicinity of the IP1 locus. By using this strategy, we have isolated three different IRS-PCR amplification products that map to a region between IP1 X chromosome translocation breakpoints. A total of nine DNA sequences have now been mapped to this region; using these DNA markers for PFGE analyses, we obtained a probe order DXS14-DXS422-MTHFDL1-DXS705. These DNA markers provide a starting point for identifying overlapping genomic sequences spanning the IP1 translocation breakpoints; the availability of IP1 translocation breakpoints should assist the molecular analysis of this locus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29765/1/0000103.pd

ANÁLISE DE EQUAÇÕES ESTRUTURAIS. RELAÇÃO DAS VARIÁVEIS QUE INCIDEM NA GESTÃO DA INOVAÇÃO

O objetivo deste artigo é estabelecer um modelo de equações estruturais que resuma o grau de incidência das variáveis relacionadas à gestão da inovação das organizações. Primeiramente identificaram-se as variáveis a analisar, segundo a literatura e aquelas que foram comprovadas segundo a consulta a expertos. Logo foram construídos instrumentos para a medição destas variáveis.   Estas variáveis foram avaliadas em 111 empresas de diferentes sectores produtivos. Com isto, foi feito uma análise fatorial confirmatório a fim de verificar a incidência das variáveis na gestão da inovação. Foi construído um modelo que mostra a relação entre as diferentes variáveis que contribuem ao processo da gestão da inovação, confirmando, com isto, a natureza multifatorial da inovação. Os dados que facilitaram a geração do modelo permitiram estabelecer a lógica da gestão da inovação desde a gestão integrada das dimensões que os condicionam, assegurando uma correta gestão dos recursos humanos, de processos e comercial

European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

The 2017 European LeukemiaNet (ELN 2017) guidelines for the diagnosis and management of acute myeloid leukemia (AML) have become fundamental guidelines to assess the prognosis and postremission therapy of patients. However, they have been retrospectively validated in few studies with patients included in different treatment protocols. We analyzed 861 patients included in the Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias-12 risk-adapted protocol, which indicates cytarabine-based consolidation for patients allocated to the ELN 2017 favorable-risk group, whereas it recommends allogeneic stem cell transplantation (alloSCT) as a postremission strategy for the ELN 2017 intermediateand adverse-risk groups. We retrospectively classified patients according to the ELN 2017, with 327 (48%), 109 (16%), and 245 (36%) patients allocated to the favorable-, intermediate-, and adverse-risk group, respectively. The 2- and 5-year overall survival (OS) rates were 77% and 70% for favorable-risk patients, 52% and 46% for intermediate-risk patients, and 33% and 23% for adverse-risk patients, respectively. Furthermore, we identified a subgroup of patients within the adverse group (inv(3)/t(3;3), complex karyotype, and/or TP53 mutation/17p abnormality) with a particularly poor outcome, with a 2-year OS of 15%. Our study validates the ELN 2017 risk stratification in a large cohort of patients treated with an ELN-2017 risk-adapted protocol based on alloSCT after remission for nonfavorable ELN subgroups and identifies a genetic subset with a very poor outcome that warrants investigation of novel strategies

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Características de las crisis epilépticas en niños con insuficiencia renal crónica terminal.

Las crisis epilépticas son complicaciones frecuentes en niños que padecen de Insuficiencia Renal Crónica Terminal (IRC-T). Objetivo: Describir la frecuencia y características de las crisis epilépticas en niños con IRC-T. Material y Métodos: Estudio retrospectivo, tipo serie de casos. Se incluyeron 24 pacientes menores de 14 años de ambos sexos con IRC-T que presentaron al menos un episodio de crisis epiléptica, atendidos en el Hospital Nacional Cayetano Heredia entre enero de 1998 y marzo de 2006. Resultados: La frecuencia encontrada de crisis epiléptica en esta población fue de 24/188 (12,7%); 18/24 (75%) se econtraban en tratamiento dialítico crónico al momento de presentarse la primera crisis epiléptica; las glomerulopatías fueron la etiología más frecuente de la IRC-T; la mayoría de niños (41,6%) presentaron crisis parciales, y el hallazgo tomográfico más frecuente fue la hemorragia intraparenquimal. Conclusiones: La frecuencia de crisis epilépticas en esta serie de niños con IRC-T es menor que la descrita en la literatura revisada

Características de las crisis epilépticas en niños con insuficiencia renal crónica terminal.

Las crisis epilépticas son complicaciones frecuentes en niños que padecen de Insuficiencia Renal Crónica Terminal (IRC-T). Objetivo: Describir la frecuencia y características de las crisis epilépticas en niños con IRC-T. Material y Métodos: Estudio retrospectivo, tipo serie de casos. Se incluyeron 24 pacientes menores de 14 años de ambos sexos con IRC-T que presentaron al menos un episodio de crisis epiléptica, atendidos en el Hospital Nacional Cayetano Heredia entre enero de 1998 y marzo de 2006. Resultados: La frecuencia encontrada de crisis epiléptica en esta población fue de 24/188 (12,7%); 18/24 (75%) se encontraban en tratamiento dialítico crónico al momento de presentarse la primera crisis epiléptica; las glomerulopatías fueron la etiología más frecuente de la IRC-T; la mayoría de niños (41,6%) presentaron crisis parciales, y el hallazgo tomográfico más frecuente fue la hemorragia intraparenquimal. Conclusiones: La frecuencia de crisis epilépticas en esta serie de niños con IRC-T es menor que la descrita en la literatura revisada. (Rev Med Hered 2008;19:1-4)

Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): a randomised, double-blind, placebo-controlled trial

Background In patients with type 2 diabetes, intensive glucose control can be renoprotective and albuminuria-lowering treatments can slow the deterioration of kidney function. We assessed the albuminuria-lowering effect of the sodium-glucose co-transporter-2 inhibitor dapagliflozin with and without the dipeptidyl peptidase-4 inhibitor saxagliptin, and the effect of dapagliflozin-saxagliptin on glycaemic control in patients with type 2 diabetes and moderate-to-severe chronic kidney disease. Methods In this double-blind, placebo-controlled trial (DELIGHT), we enrolled patients at 116 research centres in Australia, Canada, Japan, South Korea, Mexico, South Africa, Spain, Taiwan, and the USA. We included patients with a known history of type 2 diabetes, increased albuminuria (urine albumin-to-creatinine ratio [UACR] 30-3500 mg/g), an estimated glomerular filtration rate of 25-75 mL/min per 1.73 m(2), and an HbA(1c) of 7. 0-11. 0% (53-97 mmol/mol), who had been receiving stable doses of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy and glucose-lowering treatment for at least 12 weeks. After a 4-week, single-blind placebo run-in period, participants were randomly assigned (1:1:1; via an interactive voice-web response system) to receive dapagliflozin (10 mg) only, dapagliflozin (10 mg) and saxagliptin (2.5 mg), or placebo once-daily for 24 weeks. Primary endpoints were change from baseline in UACR (dapagliflozin and dapagliflozin-saxagliptin groups) and HbA(1c) (dapagliflozin-saxagliptin group) at week 24 in all randomly allocated patients with available data (full analysis set). This study is registered with ClinicalTrials.gov , number NCT02547935 and is completed. Findings The study took place between July 14,2015, and May 18,2018.1187 patients were screened, of whom 461 were randomly assigned: 145 to the dapagliflozin group, 155 to the dapagliflozin-saxagliptin group, and 148 to the placebo group (13 patients were excluded because of data integrity issues). Dapagliflozin and dapagliflozin-saxagliptin reduced UACR versus placebo throughout the study period. At week 24, the difference (vs placebo; n=134 patients with available data) in mean UACR change from baseline was -21.0% (95% CI -34.1 to -5.2; p=0.011) for dapagliflozin (n=132) and -38.0% (-48.2 to -25.8; p Interpretation Dapagliflozin with or without saxagliptin, given in addition to angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment, is a potentially attractive option to slow the progression of kidney disease in patients with type 2 diabetes and moderate-to-severe chronic kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved