A CIBIS III alvizsgálatának eredményei

L

Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232]

BACKGROUND: Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets. A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population. DESIGN: MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study

Site-specific labeling of nucleotides for making RNA for high resolution NMR studies using an E. coli strain disabled in the oxidative pentose phosphate pathway

Escherichia coli (E. coli) is a versatile organism for making nucleotides labeled with stable isotopes (13C, 15N, and/or 2H) for structural and molecular dynamics characterizations. Growth of a mutant E. coli strain deficient in the pentose phosphate pathway enzyme glucose-6-phosphate dehydrogenase (K10-1516) on 2-13C-glycerol and 15N-ammonium sulfate in Studier minimal medium enables labeling at sites useful for NMR spectroscopy. However, 13C-sodium formate combined with 13C-2-glycerol in the growth media adds labels to new positions. In the absence of labeled formate, both C5 and C6 positions of the pyrimidine rings are labeled with minimal multiplet splitting due to 1JC5C6 scalar coupling. However, the C2/C8 sites within purine rings and the C1′/C3′/C5′ positions within the ribose rings have reduced labeling. Addition of 13C-labeled formate leads to increased labeling at the base C2/C8 and the ribose C1′/C3′/C5′ positions; these new specific labels result in two- to three-fold increase in the number of resolved resonances. This use of formate and 15N-ammonium sulfate promises to extend further the utility of these alternate site specific labels to make labeled RNA for downstream biophysical applications such as structural, dynamics and functional studies of interesting biologically relevant RNAs

Tendencias de la cultura y cambio organizacional: estudio de caso

La imagen corporativa en relación con el medio se evidencia en el informe de Deloitte (2018) sobre tendencias del capital humano, en donde se reportan alrededor de 11.000 cuestionarios aplicados a gerentes de 140 países y 150 líderes de empresas colombianas, el planteamiento realizado sugiere que el capital social cobra tanto importancia como el físico y el financiero. Estos aspectos están relacionados con la identidad corporativa y cómo se relaciona a su vez con la cultura y la gestión del en la organización. La cultura y la gestión del cambio han cobrado mucho interés para las personas que guían las organizaciones, los estudios realizados por Deloitte en 2017 se focalizaron en la relación de la cultura y el compromiso como elementos importantes del empleado; los resultados del estudio dejan en evidencia cómo la habilidad de las organizaciones para afrontar inconvenientes de compromiso y cultura tenían una reducción del 14% con respecto al año anterior, estos datos permiten entender la complejidad del ambiente en el ámbito laboral y dan cuenta de la importancia de desarrollar conocimiento válido que oriente a académicos y empresarios para que puedan abordar de una manera adecuada estos aspectos.1a edició

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The effect of treatment with bisoprolol-first versus enalapril-first on cardiac structure and function in heart failure

Background: In CIBIS III, initiating chronic heart failure (CHF) treatment with bisoprolol (target dose 10 mg q.d.) followed by combination therapy with enalapril (target dose 10 mg b.i.d.), compared to the opposite order, showed similar effects on survival and hospitalization. By echocardiography, we evaluated the effects of these treatment strategies on cardiac structure and function. Methods: In a single-centre substudy, we compared the impact on left ventricular (LV) dimensions and ejection fraction (EF) of treatment with bisoprolol-first (n = 21) and enalapril-first (n = 19) in 40 beta-blocker and angiotensin-converting-enzyme-inhibitor naive patients, with stable, mild or moderate CHF (NYHA II-III) and LVEF <= 35%. Echocardiography was performed at baseline, after the 6-month monotherapy phase and after 12 months, i.e. after 6 months combination therapy. Results: Baseline characteristics were similar across treatment groups. After 6 months LVEF increased by 5.1 +/- 4.0 EF-% (P<0.0001) with Bisoprolol and 4.0 +/- 4.0 EF-% (P = 0.0005), with enalapril (between-group P = 0.47). LV end-diastolic volume (LVEDV) decreased by 8.1 +/- 4.7 ml (P<0.0001) with bisoprolol and by 4.6 +/- 8.2 ml (P = 0.03) with enalapril (between-group P = 0.16). Mean wall thickness (WT) decreased by 0.31 +/- 0.43 mm (P = 0.004) with bisoprolol and by 0.18 +/- 0.48 mm (P = 0.11) with enalapril (between-group P = 0.29). From baseline to 12 months, LVEF increased by 7.5 +/- 4.0 EF-% (P<0.0001) in Bisoprolol first group and 6.0 +/- 4.6 EF-% (P<0.0001), in the enalapril first group (between-group P = 0.31). LVEDV decreased by 12.9 +/- 6.3 ml (P<0.0001) with bisoprolol-first and by 7.9 +/- 7.7 ml (P = 0.0006) with enalapril-first (between-group P = 0.16) and WT decreased by 0.38 +/- 0.44 mm (P = 0.0008) and 0.59 +/- 0.54 mm (P = 0.0004), respectively (between-group P = 0.10). Conclusion: During both monotherapy and combined therapy, bisoprolol-first and enalapril-first similarly reversed cardiac remodelling and improved LVEF. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Nurse practitioner care improves renal outcome in patients with CKD

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m2 per year less than in the control group (P=0.01). Inconclusion, additionalsupport by nurse practitioners attenuatedthe declineof kidney function and improved renal outcome in patients with CKD. Copyrigh