Chronic obstructive pulmonary disease and long-term mortality in elderly subjects with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are associated with high rates of mortality in elderly subjects. Concurrent CHF and COPD frequently occur, especially in with advancing age. This study examines long-term mortality in community-dwelling elderly subjects affected by CHF alone, COPD alone, and coexistent CHF and COPD. METHODS: The study evaluated 12-years mortality in 1288 subjects stratified for the presence or absence of CHF or COPD alone, and for coexistence of CHF and COPD. RESULTS: Mortality, at 12 year follow-up, was 46.7% overall, 68.6% in the presence of CHF alone (p < 0.001), 56.9% in the presence of COPD alone (p < 0.01); mortality was 86.2% where CHF and COPD coexisted (p < 0.001) and was significantly higher than in CHF or COPD alone (p < 0.05). Multivariate analysis indicates that CHF (Hazard risk = 1.67, 95% confidence interval 1.15-3.27, p < 0.031) and COPD (Hazard risk = 1.27, 95% confidence interval = 1.08-1.85, p < 0.042) were predictive of long-term mortality. When CHF and COPD simultaneously occurred, the risk dramatically increased up to 3.73 (95% confidence interval = 1.19-6.93, p < 0.001). CONCLUSIONS: Long-term follow-up showed higher mortality among elderly subjects affected by CHF or COPD. Simultaneous presence of CHF and COPD significantly increased the risk of death. Therefore, the presence of COPD in CHF patients should be considered a relevant factor in predicting high risk of mortality.

ß Adrenergic Receptor Kinase C-Terminal Peptide Gene-Therapy Improves ß2-Adrenergic Receptor-Dependent Neoangiogenesis after Hindlimb Ischemia.

After hindlimb ischemia (HI), increased catecholamine levels within the ischemic muscle can cause dysregulation of ß2-adrenergic receptor (ß2AR) signaling, leading to reduced revascularization. Indeed, in vivo ß2AR overexpression via gene therapy enhances angiogenesis in a rat model of HI. G protein-coupled receptor kinase 2 (GRK2) is a key regulator of ßAR signaling, and ß adrenergic receptor kinase C-terminal peptide (ßARKct), a peptide inhibitor of GRK2, has been shown to prevent ßAR down-regulation and to protect cardiac myocytes and stem cells from ischemic injury through restoration of ß2AR protective signaling (i.e., protein kinase B/endothelial nitric oxide synthase). Herein, we tested the potential therapeutic effects of adenoviral-mediated ßARKct gene transfer in an experimental model of HI and its effects on ßAR signaling and on endothelial cell (EC) function in vitro. Accordingly, in this study, we surgically induced HI in rats by femoral artery resection (FAR). Fifteen days of ischemia resulted in significant ßAR down-regulation that was paralleled by an approximately 2-fold increase in GRK2 levels in the ischemic muscle. Importantly, in vivo gene transfer of the ßARKct in the hindlimb of rats at the time of FAR resulted in a marked improvement of hindlimb perfusion, with increased capillary and ßAR density in the ischemic muscle, compared with control groups. The effect of ßARKct expression was also assessed in vitro in cultured ECs. Interestingly, ECs expressing the ßARKct fenoterol, a ß2AR-agonist, induced enhanced ß2AR proangiogenic signaling and increased EC function. Our results suggest that ßARKct gene therapy and subsequent GRK2 inhibition promotes angiogenesis in a model of HI by preventing ischemia-induced ß2AR down-regulation.

The Multidimensional Prognostic Index predicts in-hospital length of stay in older patients: a multicentre prospective study.

BACKGROUND: prediction of length of stay (LOS) may be useful to optimise care plans to reduce the negative outcomes related to hospitalisation. OBJECTIVE: to evaluate whether the Multidimensional Prognostic Index (MPI), based on a Comprehensive Geriatric Assessment (CGA), may predict LOS in hospitalised older patients. DESIGN: prospective multicentre cohort study. SETTING: twenty Geriatrics Units. PARTICIPANTS: patients aged 65 and older consecutively admitted to Geriatrics Units. MEASUREMENT: at admission, the CGA-based MPI was calculated by using a validated algorithm that included information on basal and instrumental activities of daily living, cognitive status, nutritional status, the risk of pressures sores, co-morbidity, number of drugs and co-habitation status. According to validated cut-offs, subjects were divided into three groups of risk, i.e. MPI-1 low risk (value ≤0.33), MPI-2 moderate risk (value 0.34-0.66) and MPI-3 severe risk of mortality (value ≥0.67). RESULTS: two thousand and thirty-three patients were included; 1,159 were women (57.0%). Age- and sex-adjusted mean LOS in patients divided according to the MPI grade was MPI-1 = 10.1 (95% CI 8.6-11.8), MPI-2 = 12.47 (95% CI 10.7-14.68) and MPI-3 = 13.41 (95% CI 11.5-15.7) days (P for trend <0.001). The overall accuracy of the MPI to predict LOS was good (C-statistic 0.74, 95% CI 0.72-0.76). Moreover, a statistically significant trend of LOS means was found even in patients stratified according to their International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) main diagnosis. CONCLUSIONS: the MPI is an accurate predictor of LOS in older patients hospitalised with the most frequent diseases.

Impact of diabetes mellitus on lymphocyte GRK2 protein levels in patients with heart failure.

BACKGROUND: Diabetes mellitus (DM) is associated with impaired prognosis in patients with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated ß-adrenergic receptor (ß-AR) activation by catecholamines causes G-protein-coupled receptor kinase-2 (GRK2) upregulation which is responsible for ß-AR signalling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. Moreover, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signalling. The aim of this study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM. METHODS AND MATERIALS: Patients with a diagnosis of HF were enrolled in the study. All subjects underwent a complete clinical examination (including NYHA functional class assessment and echocardiography) and blood draw for serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lymphocyte GRK2 and plasma norepinephrine (NE) levels. Demographic data including age, sex, medications, cardiovascular risk factors and presence of comorbidities were also collected. RESULTS: Two hundred and sixty-eight patients with HF (left ventricular ejection fraction [LVEF] 30.6 ± 7.6%) with and without DM were enrolled. No differences between the two groups were found in terms of demography, HF aetiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in patients with DM compared to non-DM. At multivariate linear regression analysis, LVEF, NE, NT-proBNP and diabetes came out to be independent predictors of GRK2 levels in the overall study population. CONCLUSION: In HF patients, DM is associated with significantly more elevated lymphocyte GRK2 protein levels, likely reflecting more compromised cardiac ß-AR signalling/function, despite similar hemodynamic status and neuro-hormonal activation compared to patients without DM. These findings contribute to explain the negative prognostic impact of DM in patients with HF.

Long-term mortality in frail elderly subjects with osteoarthritis.

OBJECTIVE: Elderly subjects are characterized by a high prevalence of OA and clinical frailty. This study aimed to examine the predictive role of clinical frailty on long-term mortality in elderly subjects with and without OA. METHODS: Mortality was evaluated after a 12-year follow-up in 698 subjects with and 590 subjects without OA recruited in 1992. Clinical frailty was assessed according to the Frailty Staging System and stratified in tertiles. RESULTS: After a 12-year follow-up, mortality was 42.2% in subjects without and 55.8% in subjects with OA (P = 0.256). With increasing frailty, mortality increased by 30.5% (P for trend < 0.001) in subjects without and by 45.6% in subjects with OA (P for trend < 0.001). Multivariate analysis showed that frailty [hazard ratio (HR) = 1.49 for each unit of increase, 95% CI 1.32, 1.94, P < 0.001) but not OA (HR = 1.28, 95% CI 0.987, 1.39, P = 0.412) was predictive of long-term mortality. Moreover, when Cox regression analysis was performed, frailty enhanced the risk of long-term mortality for each unit of increase by 32% (HR = 1.32, 95% CI 1.06, 1.65, P = 0.03) in the absence of OA and by 98% in the presence (HR = 1.98, 95% CI 1.63, 2.95, P < 0.01) of OA. CONCLUSION: Clinical frailty significantly predicts mortality in subjects without OA and even more in those with OA. Thus clinical frailty may be considered a new prognostic factor to identify subjects with OA at high risk of mortality.

CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy.

Tumor growth requires neoangiogenesis. VEGF is the most potent proangiogenic factor. Dysregulation of hypoxia-inducible factor (HIF) or cytokine stimuli such as those involving the chemokine receptor 4/stromal-derived cell factor 1 (CXCR4/SDF-1) axis are the major cause of ectopic overexpression of VEGF in tumors. Although the CXCR4/SDF-1 pathway is well characterized, the transcription factors executing the effector function of this signaling are poorly understood. The multifunctional Yin Yang 1 (YY1) protein is highly expressed in different types of cancers and may regulate some cancer-related genes. The network involving CXCR4/YY1 and neoangiogenesis could play a major role in cancer progression. In this study we have shown that YY1 forms an active complex with HIF-1alpha at VEGF gene promoters and increases VEGF transcription and expression observed by RT-PCR, ELISA, and Western blot using two different antibodies against VEGFB. Long-term treatment with T22 peptide (a CXCR4/SDF-1 inhibitor) and YY1 silencing can reduce in vivo systemic neoangiogenesis (P < 0.01 and P < 0.05 vs. control, respectively) during metastasis. Moreover, using an in vitro angiogenesis assay, we observed that YY1 silencing led to a 60% reduction in branches (P < 0.01) and tube length (P < 0.02) and a 75% reduction in tube area (P < 0.001) compared with control cells. A similar reduction was observed using T22 peptide. We demonstrated that T22 peptide determines YY1 cytoplasmic accumulation by reducing its phosphorylation via down-regulation of AKT, identifying a crosstalk mechanism involving CXCR4/YY1. Thus, YY1 may represent a crucial molecular target for antiangiogenic therapy during cancer progression.

Role of ventricular rate response on dementia in cognitively impaired elderly subjects with atrial fibrillation: a 10-year study.

BACKGROUND: The role of ventricular rate response (VRr) on the incidence of dementia in elderly subjects with cognitive impairment and atrial fibrillation (AF) is not known. Thus, we examined the ability of VRr to predict dementia in cognitively impaired elderly subjects with and without AF. METHODS: A total of 358 cognitively impaired elderly subjects (MMSE <24) with and without AF were stratified in low/high (<50/>90) and moderate (>50/<90 bpm) VRr. A 10-year follow-up was performed. RESULTS: Cognitively impaired subjects with dementia at the end of the follow-up were 135 (37.7%): 33 in the presence (75.0%) and 102 (32.5%) in the absence of AF (p < 0.001). Multivariate analysis shows that AF is a strong predictor of dementia (hazard ratio, HR = 4.10; 95% confidence interval, CI = 1.80-9.30, p < 0.001). More importantly, low/high VRr (<50/>90 bpm) is predictive of dementia in the presence (HR = 7.70, 95% CI = 1.10-14.20, p = 0.03) but not in the absence (HR = 1.85; 95% CI = 0.78-4.47; p = 0.152) of AF. CONCLUSIONS: This study demonstrates that AF predicts dementia in elderly subjects with cognitive impairment. Moreover, VRr seems to play a key role in the incidence of dementia in cognitively impaired elderly subjects with AF.

Depressive symptoms predict mortality in elderly subjects with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is characterized by a high mortality in the elderly. Moreover, depression status is also related to poor prognosis in advancing age. Thus, we sought to determine whether depressive status predicts long-term mortality in subject with or without CHF. METHODS AND RESULTS: Long-term mortality after 12-year follow-up in 125 elderly subjects with CHF and 1143 elderly subjects without CHF was studied. Depression was evaluated using the Geriatric Depression Scale (GDS), and all subjects were stratified in tertiles according to GDS score (0-10, 11-20 and 21-30). With increasing GDS score, long-term mortality at the end of follow-up increased from 43·4% to 72·0% in subjects without (P < 0·001) and from 52·6% to 83·9% in subjects with (P < 0·007) CHF. In multivariate analysis, GDS appeared to be predictive of long-term mortality in the absence (Hazard ratio = 1·01; confidence interval 95% 1·00-1·05; P = 0·04) and, even more, in the presence of CHF (Hazard ratio = 1·08; confidence interval 95% 1·01-1·15; P < 0·01). CONCLUSIONS: Depression symptoms predict long-term mortality in elderly subjects without and, even more, with CHF. Thus, depression can be considered a strong predictor of death in CHF elderly subjects.

Serum withdrawal after embryoid body formation does not impair cardiomyocyte development from mouse embryonic stem cells.

BACKGROUND AIMS: Procedures for cardiomyocyte differentiation of mouse embryonic stem cells (mESCs) utilize different amounts of serum. Because the serum composition is unknown, unambiguous characterization of the differentiation process is biased. All reported serum-free protocols used for compound testing provide serum throughout the differentiation process. We report on an embryoid body (EB)-based procedure for cardiomyocyte differentiation of mESCs in which serum is provided only in the earliest step (hanging drop, 0-2 days). METHODS: To assess cardiomyocyte differentiation, we generated an mESCs clone that expressed green fluorescence protein (GFP) under the control of the myosin light chain 2v (MLC2v) promoter. To define the lowest serum concentration required for efficient induction of cardiomyocyte differentiation, EBs were formed in presence of 5% (S5), 10% (S10) and 15% (S15) serum until day 2, then switched to a serum-free medium. RESULTS: Analysis of cardiac-specific transcripts on day 6 of differentiation showed that 10% (S10) was the minimum amount of serum for efficient continuation of cultures under serum-free conditions. Spontaneously beating foci were detected in 90.0 ± 5.5% of S10 EBs on day 7 of differentiation, and cardiomyocyte markers were expressed from day 8 of differentiation (MLC2v-driven GFP; α-myosin heavy chain). Dose-response curves to isoproterenol showed that the beating rate increased by 113.0 ± 39.4%, with a concentration for half-maximal effect (EC(50)) of 25.7 nm. CONCLUSIONS: The development of functional cardiomyocytes from mESCs is not affected by serum withdrawal after EBs formation. This culture system represents a new model for cardiomyocyte differentiation of mESCs to assess the effects of compounds on the process of cardiomyogenesis.

Two-year morbidity and mortality in elderly patients with syncope.

BACKGROUND: syncope is a common cause of hospitalisation in the elderly. However, morbidity and mortality in elderly patients with syncope is not well established. METHODS: two-hundred and forty-two patients older than 65 years consecutively referred to the participating centres for evaluation of transient loss of consciousness were enrolled in a multicentre 2-year longitudinal observational study. Mortality and syncope recurrences were recorded and multidimensionally evaluated at 6, 12, 18 and 24 months. FINDINGS: at 24 months, total mortality was 17.2% and syncope recurrence was 32.5%. Cardiac syncope was more frequent in deceased than in survivor patients (21.7 versus 12.3%; P = 0.03), whereas neuro-mediated (62.1 versus 66.2%; P = 0.357) and unexplained syncope (10.8 versus 11.8%; P = 0.397) did not differ between the two groups. Drug-induced and/or multifactorial syncope was less frequent in patients with syncope recurrence (5.7 versus 10.7%; P = 0.02). Kaplan-Meyer curves indicated that mortality and syncope recurrence increased significantly with age (P = 0.006 and P = 0.008, respectively). At multivariate analysis, mortality was significantly predicted by age and comorbidity (hazard ratios: 1.17 and 1.39, and 95% confidence interval 1.01-1.37 and 1.01-1.93, respectively), and syncope recurrence by age and disability (hazard ratio: 1.13 and 1.04, 95% confidence interval 1.01-1.25 and 1.04-2.25, respectively). Depression increased from baseline to the end of follow-up (from 28.3 to 41.4%; P = 0.001). CONCLUSIONS: in our patients, mortality was related to increasing age and comorbidity, whereas recurrence was related to increasing age and disability. Cardiac syncope was more frequent in deceased than in survivor patients, and syncope recurrence was high despite a low incidence of unexplained syncope.

Telemedicine fetal phonocardiography surveillance: an italian satisfactory experience.

In this paper we describe an Italian experience of fetal home monitor, organized using a portable phonocardiography system (product by Pentavox, Hungary), and the method utilized to evaluate its effectiveness in providing quality services and patient satisfaction. Patient satisfaction is an important dimension in the evaluation of quality care delivery. We used phonocardiography technique in our experience of fetal home monitoring as it is non invasive and passive in nature, low-cost and easy to use. A lightweight portable phonocardiograph (Fetaphon-home) was assigned to six selected patients, without effective pregnancy risk to monitor fetal heartbeat, uterine contractions and fetal movements at home or wherever they need it. The selected patients were instructed by trained personnel in the use of the monitoring device. Patients were asked to perform the recording two times a week and to transmit 20-min signal to the reference centre. The home monitoring sessions were performed in addition to the routine surveillance at a gynecologist's office; thus, the home monitoring did not replace clinic visits. The women were requested to fill a satisfaction questionnaire in order to evaluate their quality of life and anxiety state. Preliminary results have shown that home fetal surveillance appreciably reduces the need of travel for patients and consequently their stress. Furthermore, our results suggest that, after a short training, pregnant women are able to record and transmit long traces without troubles. Use of telemedicine system was generally well accepted by pregnant women since it increased the possibility of fetal long-term home surveillance which in turn could increase the efficiency of the service offered to them.

Joint effect of physical activity and body mass index on mortality for acute myocardial infarction in the elderly: role of preinfarction angina as equivalent of ischemic preconditioning.

BACKGROUND: Preinfarction angina (PrA), clinical equivalent of ischemic preconditioning, confers protection against in-hospital mortality for acute myocardial infarction (AMI) in adult but not in elderly patients. This study aims to examine the interaction between physical activity and body mass index (BMI) in preserving the cardioprotective effect of PrA in elderly patients with AMI. DESIGN: Elderly patients (>/=65 years old) with AMI admitted to Coronary Care Unit. METHODS: Elderly patients with AMI were retrospectively stratified for the presence and absence of PrA, and for quartiles of BMI and physical activity. In-hospital outcomes (death, cardiogenic shock, and reinfarction and creatine kinase-MB peak) were evaluated. RESULTS: In-hospital mortality of 1014 elderly patients with AMI was 19.2% in those with PrA and 22.7% in those without (P=0.18, NS). Mortality further decreased with increased physical activity and reduced BMI, a trend that was not observed in patients without PrA. When physical activity and BMI were considered together, lowest in-hospital mortality was observed in patients with highest physical activity and normal BMI (from 18.2 to 9.6%; P<0.01) with the greatest reduction observed in patients with PrA (from 18.3 to 5.1%; P=0.02). Multivariate analysis showed that PrA did not exert a protective effect in all patients irrespective of physical activity and BMI. A protective role was, however, observed in patients with highest physical activity or normal BMI and reached a maximum protective role in patients who showed both highest physical activity and normal BMI [odds ratio=0.08; 95% confidence interval=0.02-0.72; P<0.01]. CONCLUSION: The cardioprotective effect of PrA was preserved in elderly patients who showed the highest physical activity and a normal BMI.

Heart rate variability and drawing impairment in hypoxemic COPD.

We studied 54 patients with hypoxemic chronic obstructive pulmonary disease (COPD). The Mini Mental State Examination and the Mental Deterioration Battery were used for neuropsychological assessment. Heart rate variability (HRV) was assessed based on 24-h Holter ECG recording. Mann-Whitney test was used to compare HRV parameters of patients performing normally or abnormally on individual neuropsychological tasks. Spearman's rho was used to investigate the correlations between HRV parameters and neuropsychological scores, indexes of health status or COPD severity. Patients with defective performance at copying drawings with landmarks (CDL) test (N = 23) had lower very low frequency (VLF) power with respect to patients with normal performance (N = 31) (24 h: median 213; interquartile range 120-282 vs. 309; 188-431 ms2, p = 0.043; daytime: 202; 111-292 vs. 342; 194-397 ms2, p = 0.039). The CDL score correlated with the VLF power (24 h: rho = 0.27, p = 0.049; daytime: rho = 0.30, p = 0.028), and the normalized low frequency/high frequency (LF/HF) ratio (24 h: rho = 0.27, p = 0.05; daytime: rho = 0.33, p = 0.015). Sympathetic modulation decreased for increasing severity of COPD. In conclusion, drawing impairment correlates with depressed sympathetic modulation in patients with COPD, and both might be indexes of COPD severity.

Charlson Comorbidity Index does not predict long-term mortality in elderly subjects with chronic heart failure.

BACKGROUND: comorbidity plays a critical role in the high mortality for chronic heart failure (CHF) in the elderly. Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index. No studies are available on the ability of CCI to predict mortality in CHF elderly subjects. The aim of the present study was to assess if CCI was able to predict long-term mortality in a random sample of elderly CHF subjects. METHODS: long-term mortality after 12-year follow-up in 125 subjects with CHF and 1,143 subjects without CHF was studied. Comorbidity was evaluated using CCI. FINDINGS: in elderly subjects stratified for CCI (1-3 and > or =4), mortality was higher in non-CHF subjects with CCI > or =4 (52.4% versus 70%, P < 0.002) but not in those with CHF (75.9% versus 77.6%, P = 0.498, NS). Cox regression analysis on 12 years mortality indicated that both CCI (HR = 1.15; 95% CI = 1.01-1.31; P = 0.035) and CHF (HR = 1.27; 95% CI = 1.04-8.83; P = 0.003) were predictive of mortality. When Cox analysis was performed by selecting the presence and the absence of CHF, CCI was predictive of mortality in the absence but not in the presence of CHF. CONCLUSION: CCI does not predict long-term mortality in elderly subjects with CHF.

Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart.

AIMS: We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated beta-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. METHODS AND RESULTS: Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 +/- 5%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac beta-adrenergic receptor downregulation and desensitization. CONCLUSIONS: Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

The prevalence of diarrhea and its association with drug use in elderly outpatients: a multicenter study.

OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug use in elderly outpatients. METHODS: The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic data, disability, gastrointestinal symptoms, and current medications were evaluated using a structured interview, including the evaluation of the activities of daily living (ADL), the instrumental activities of daily living (IADL), and the gastrointestinal symptoms rating scale (GSRS). RESULTS: The study included 5,387 elderly subjects who regularly completed the structured interview. In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean age 75.6 +/- 6.2 yr, range 65-100 yr) reported diarrhea, that is, items 11 and 12 of the GSRS, during the 7-day period before the interview. The prevalence of diarrhea significantly increased with older age (P = 0.025), the severity of ADL (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P = 0.0002). A multivariate analysis demonstrated that the presence of diarrhea was significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95% confidence interval [CI] 1.95-10.73), proton pump inhibitors (OR 2.97, 95% CI 2.03-4.35), allopurinol (OR 2.19, 95% CI 1.26-3.81), psycholeptics (OR 1.82, 95% CI 1.26-2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01-2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08-1.99), also accounting for sex, age, and the use of antidiarrheal agents and drugs for functional gastrointestinal disorders. CONCLUSION: Diarrhea is a common problem in elderly outpatients. Its prevalence increases with old age, the severity of disability, and the number of drugs. Monitoring the presence of diarrhea and its complications in elderly patients who need treatments with drugs significantly associated with diarrhea may be clinically useful.

Cognitive training is ineffective in hypoxemic COPD: a six-month randomized controlled trial.

Cognitive impairment is highly prevalent in chronic obstructive pulmonary disease (COPD) complicated by chronic hypoxemia, but the effect of cognitive training in patients with COPD has not been studied. The aim of the present study was to verify whether cognitive training can preserve cognitive abilities of patients with hypoxemic COPD. Our series consisted of 105 COPD patients with at rest (n = 36) or effort (n = 69) hypoxemia and free from concurrent dementing diseases. Neuropsychologic assessment included a screening test, the Mini Mental State Examination (MMSE), and a standardized confirmatory battery of neuropsychological tests, the Mental Deterioration Battery (MDB). After baseline assessment, patients were randomized to receive standardized multidimensional care (standardization of pharmacological therapy, health education, selection of inhalers according to patient's ability, respiratory rehabilitation, nutritional counseling, oxygen therapy, and control visits) with (n = 53) or without (n = 52) cognitive training aimed at stimulating attention, learning, and logical-deductive thinking. Cognitive performance was reassessed after 1.5, 4, and 6 months. The analysis of variance for repeated measures (ANOVA) having the group membership (study vs. control) as grouping factor was used to assess changes in cognitive performance. Both intervention and control groups showed no significant changes in cognitive performance except for a trend toward improvement in verbal fluency and verbal memory, but cognitive intervention had no significant effect. In conclusion, cognitive training seems ineffective in COPD. However, a multidimensional standardized therapeutic approach, as it was indistinctly provided to all patients, could help to slow or prevent cognitive decline.

Transient ischemic attack before nonlacunar ischemic stroke in the elderly.

BACKGROUND: Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age. METHODS: We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale. RESULTS: We evaluated 203 patients (>or=65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 +/- 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge. CONCLUSION: These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly.

Left ventricular hypertrophy as protective factor after bypass grafting.

Left ventricular hypertrophy (LVH) is a well established cardiovascular risk factor, accounting for an increase in cardiovascular morbid-mortality, although how much the magnitude and the kind of LVH could affect cardiovascular outcomes is in large part unknown. We speculate that mild LVH in absence of left ventricular (LV) chamber dilation, could play a protective role towards functional capacity, clinical outcome, cardiovascular and total morbi-mortality in conditions in which LV systolic function is generally reduced. Accordingly to many epidemiological observations, the availability of extra-quote of systolic function could lead to a significative improvement in the final outcome of some kinds of heart patients, as those undergoing bypass-grafting, where the stress for heart and cardiovascular system is always high. We suppose that the functional reserve available for patients with LVH could make the difference with respect to other patients undergoing myocardial revascularization. Similarly, the availability of a contractile reserve warranted by LVH could ensure a little gain in the outcome for patients after other major cardiovascular events (such as myocardial infarction or other heart surgery as surgical valve replacement). However, our hypothesis only involves mild LVH without LV chamber dilation, that is the initial stage of "non-dilated concentric" LVH and "non-dilated eccentric" LVH according to the new four-tiered classification of LVH based on relative wall thickness and LV dilation. Support for our hypothesis derives from the well-known protective role of systolic function that is a major factor in almost all cardiovascular diseases, where LV ejection fraction (LVEF) has shown to significantly improve quality of life, as well as morbidity and mortality. The knowledge that mild LVH in absence of LV chamber dilation is not as harmful in such conditions as believed at present could make avoidable some drugs prescription in some stages of the disease. Furthermore, it may allow a better evaluation of the risk profile of patients with LVH undergoing some cardiovascular major events like bypass grafting, myocardial infarction or surgical heart valve replacement.

An active lifestyle improves outcome of primary angioplasty in elderly patients with acute myocardial infarction.

BACKGROUND: Regular physical activity has been shown to improve outcome of acute myocardial infarction (AMI) in the elderly population. The aim of this study was to evaluate whether the positive role of an active lifestyle on cardiac prognosis extends to elderly patients with AMI who undergo primary percutaneous transluminal coronary angioplasty (PTCA). METHODS: We prospectively studied 180 patients with AMI aged > or = 70 years and treated with primary PTCA. In all patients, physical activity levels before AMI were quantified by a score derived from the Physical Activity Scale for the Elderly (PASE). Cardiac deaths and nonfatal cardiac events were evaluated within 30 days and 1-year from primary PTCA. RESULTS: A high PASE score was significantly associated with a strong reduction of 30-day cardiac deaths (from 23.1% to 4%; P for trend = .021) and overall nonfatal events (from 21.1% to 10%; P for trend = .01). Accordingly, at 1 year of follow-up, the incidence of cardiac mortality and nonfatal events significantly decreased with increasing PASE score (from 28.8% to 8% and from 55.7% to 14.5%, respectively). Logistic regression analysis indicated that physical activity before AMI was an independent predictor of increased survival in those patients that showed the highest PASE scores. In addition, at 6 months of follow-up, although low ejection fraction and recurrent angina strongly predicted 1-year mortality, high PASE scores still predicted a better outcome. CONCLUSIONS: Our data indicate that an active lifestyle may favorably affect early and late outcomes of primary PTCA in the elderly population.