Role of a multidisciplinary program in improving outcomes in cognitively impaired heart failure older patients.

Background: Cognitive impairment (CI) frequently complicates Heart failure (HF) and is associated with increased mortality and morbidity. Previous studies reported that nurse-lead home-based multidisciplinary program (MP) may not improve the prognosis of this high-risk group. In the present study, we analysed the relative effectiveness of an integrated hospital-based MP in patients with cognitive impairment. Methods: Consecutive (n=173) community-living outpatients aged >70 years (mean 77+6, 48% women) randomized to a MP (n=86) or usual care (UC) (n=87) were enrolled in stable clinical conditions. Cognitive status was assessed by means of Folstein Mini Mental State Examination (MMSE). Results: CI (MMSE<24) was present in 41.6% (42,5% UC vs 40.7% MP p=ns). The variables independently associated to CI were: older age, education level <5 years, anemia and severe renal dysfunction. During a 2-year follow-up, 59 patients died (31.4%) with no significant difference between intervention group. At multivariate analysis, in the entire cohort, CI was independently associated to death (HR 2,077[95%CI 1,097- 3,931]), HF admissions (2,133[1,346-3,381]), death/HF admissions (1,784[1,132-2,811]) and all-cause admissions (1,473[1,008-2,153]. When considered according to intervention groups, CI was independently associated to all-cause death (3,603 [1,553-8,358], death/HF admissions (2,029[1,200-3,432]) and HF admissions (2,474[1,406-4,353]) but not to all-cause admissions. The assignment of patients with CI to MP was associated to a significant reduction in HF admissions vs UC (0,503[0,253-0,999] (all interaction tests p=ns). Conclusions: This study suggests that CI is very common and associated to worse prognosis in heart failure and that hospital-based MP seems to improve outcomes in these patients through reduction of heart failure hospital admission

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

c-Fos expression in preoptic nuclei as a marker of sleep rebound in the rat.

Thermoregulation is known to interfere with sleep, possibly due to a functional interaction at the level of the preoptic area (POA). Exposure to low ambient temperature (T(a)) induces sleep deprivation, which is followed by sleep rebound after a return to laboratory T(a). As two POA subregions, the ventrolateral preoptic nucleus (VLPO) and the median preoptic nucleus (MnPO), have been proposed to have a role in sleep-related processes, the expression of c-Fos and the phosphorylated form of the cAMP/Ca(2+)-responsive element-binding protein (P-CREB) was investigated in these nuclei during prolonged exposure to a T(a) of -10 degrees C and in the early phase of the recovery period. Moreover, the dynamics of the sleep rebound during recovery were studied in a separate group of animals. The results show that c-Fos expression increased in both the VLPO and the MnPO during cold exposure, but not in a specific subregion within the VLPO cluster counting grid (VLPO T-cluster). During the recovery, concomitantly with a large rapid eye movement sleep (REMS) rebound and an increase in delta power during non-rapid eye movement sleep (NREMS), c-Fos expression was high in both the VLPO and the MnPO and, specifically, in the VLPO T-cluster. In both nuclei, P-CREB expression showed spontaneous variations in basal conditions. During cold exposure, an increase in expression was observed in the MnPO, but not in the VLPO, and a decrease was observed in both nuclei during recovery. Dissociation in the changes observed between c-Fos expression and P-CREB levels, which were apparently subject to state-related non-regulatory modulation, suggests that the sleep-related changes observed in c-Fos expression do not depend on a P-CREB-mediated pathway

REM sleep homeostasis: a matter of size?

In different species, REM sleep (REMS) occurrence appears to be finely regulated on either a short (Vivaldi E, 1994) or a long-term basis (Parmeggiani PL, 1980). However, the hypothesis that REMS amount is homeostatically regulated is challenged by data on humans which show that a scarce REMS rebound follows REMS deprivation (Horne J, 2000). Further analysis was carried out on data from an experiment in which 24 male Sprague-Dawley rats (250g) were exposed for 24h to different low ambient temperatures (Tas, ranging from \u201310\ub0C to 10\ub0C) and then allowed to recover for 4 days at normal laboratory Ta (Cerri M, 2005). REMS decreased proportionally with cold exposure, but a quick compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond an \u201calarm\u201d threshold (AT) corresponding to 22% of the REMS daily need. By using data from literature we have calculated that AT for cats (Parmeggiani PL, 1980) and humans (Endo T, 1998) should correspond to 72% and 234% of the REMS daily need. Examining the three species together, AT appears to increase proportionally to the average duration of the REMS episode. It also appears to be positively related to their brain mass (Kg) according to a power function: y = 226.03x 0.36 , r2=0.986. This would suggest that, in analogy to what has been observed regarding the body\u2019s energy needs, small mammals have a smaller capacity to buffer their REMS need than large ones