Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

<p>Abstract</p> <p>Background</p> <p>Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.</p> <p>Methods/Design</p> <p>This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.</p> <p>Discussion</p> <p>The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00827021</p

Monitoring of lifestyle and cognitive status in seniors at risk of dementia: the SmartAging program

Lifestyle and risk factors affect the development of diseases, cognitive decline and loss of autonomy during ageing. In the Italian Smart Health 2.0 project, we developed the SmartAging program offering innovative ICT solutions, grounded upon the Italian Telecom platform (“Nuvola Italian Home Doctor”), to contrast cognitive decline and support “active” ageing. Specifically, the SmartAging program includes tools for daily telemonitoring at subjects’ home of: (i) eating behaviour, (ii) physical exercise, (iii) tobacco consumption, (iv) cultural, social and relational activities, (v) cognitive functions, (vi) weight, temperature, and blood pressure. Furthermore, a Point of Care device and a Self- Assessment Health Station (i.e. health medical equipment), in proximity to the subjects’ home, allowed periodic measures of blood biomarkers and physiological indices. To demonstrate the feasibility of this program, we performed a clinical proof of concept study for 16 weeks on 10 elderly subjects (5 being oncological long-term survivors). All subjects expressed a need for education and assistance concerning a healthy lifestyle. Most of them expressed a preference for ICT-based home programs to improve the lifestyle over institutional programs. All expressed satisfaction with the SmartAging program in terms of simplicity, clarity, adequacy and reported a positive impact on their quality of life. These results suggest that the SmartAging program fulfills all the requirements to be considered an innovative technological approach for the lifestyle education and telemonitoring of seniors, to prevent dementing disorders. Some concepts of the SmartAging program have been further developing in the H2020-MSCA-ITN-ETN BBDiag project

Different Abnormalities of Cortical Neural Synchronization Mechanisms in Patients with Mild Cognitive Impairment due to Alzheimer's and Chronic Kidney Diseases: An EEG Study

This study tested whether resting state alpha rhythms (8-13 Hz) may characterize mild cognitive impairment due to Alzheimer's disease (ADMCI) compared with MCI due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45 cognitively normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were matched in the three groups, and Mini-Mental State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta (&lt;4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) cortical sources were estimated by eLORETA freeware and classified across individuals by area under the receiver operating characteristic curve (AUROCC). Compared with Nold group, posterior alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In contrast, widespread delta source activities were greater in CKDMCI than ADMCI group. These source activities correlated with the MMSE score and correctly classified between Nold and all MCI individuals (AUROCC = 0.8-0.85) and between ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD affects cortical neural synchronization at alpha frequencies underpinning brain arousal and low vigilance in the quiet wakefulness. In contrast, CKD may principally affect cortical neural synchronization at the delta frequencies. Future prospective cross-validation studies will have to test these candidate rsEEG markers for clinical applications and drug discovery

The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial

Background The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear.Methods In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting B

The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial

The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear