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ABSTRACT: The Black Swan Theory was described by Nassim Nicholas Taleb in his book "The Black Swan". This theory refers to "high-impact, hard-to-predict, and rare events beyond the realm of normal expectations". According to Taleb's criteria, a Black Swan Event is a surprise, it has a major impact and after the fact, the event is rationalized by hindsight, as if it had been expected. For most of human history centenarians were a rare and unpredictable phenomenon. The improvements of the social-environmental conditions, of medical care, and the quality of life caused a general improvement of the health status of the population and a consequent reduction of the overall morbidity and mortality, resulting in an overall increase of life expectancy. The study of centenarians and supercentenarians had the objective to consider this black swan and to evaluate the health, welfare, social and economic consequences of this phenomenon.
BMC Surgery 11/2012; 12 Suppl 1:S36. · 1.33 Impact Factor
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ABSTRACT: Authors perform a critical revision of the concept of frailty in elderly going back to its first indication (1978). It is a particular phenotypic condition, characterized by advanced age, clinically unstable polypathologies in evolution, with cognitive disturbances, often very severe, loss of auto sufficiency and the critical socio-economic conditions. The diagnostic validity, both in the definition of the deficits and in the evaluation of the declines in the fundamental functions should be underlined. The first ones are needed particularly for the epidemiological and population studies, and the second one, at the individual level. Today, first of all in the geriatric field, the method of multidimensional evaluation (MDE) is the first choice for the early diagnosis of "elderly frailty" (EF), in order to determine the biological, functional, cognitive and clinical aspects of the elderly subjects, and also for the application of adequate programs of intervention at the sanitary-assistential-social levels.
Archives of gerontology and geriatrics 10/2012; · 1.36 Impact Factor
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ABSTRACT: Osteoblastoma is a rare benign tumor of bone that accounts for approximately 1% of primary skeletal neoplasms, with around 90% of cases diagnosed in the second and third decades of life. Cervical spine is an usual localization of osteoblastoma. The main clinical manifestation in case of cervical spine location is a progressive and resistant pain, possibly accompanied by stiffness, scoliosis or other ailments, including severe neurological deficits. Owing to a non-specific clinical presentation of osteoblastoma, the delay in diagnosis is common. Osteoblastomas may have an aggressive behavior, tend to enlarge and damage the bone and adjacent structures. The treatment of choice is, therefore, a wide and complete surgical excision of the lesion in order to achieve full recovery and prevent recurrence or, in some cases, malignant transformation. In the case of persistent neck pain, not readily relieved by aspirin and possibly accompanied by stiffness, scoliosis or neurological deficits, especially in young subjects, osteoblastoma of cervical spine may be one of the diagnostic options to be considered, in order to avoid delay in diagnosis. We report the case of a 41-year-old male affected by cervical spine osteoblastoma causing a lasting neck pain.
European review for medical and pharmacological sciences 10/2012; 16 (4 Suppl):17-20. · 1.04 Impact Factor
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Marisa Palmeri,
Gabriella Misiano,
Mariano Malaguarnera,
Giusi Irma Forte,
Loredana Vaccarino,
Salvatore Milano,
Letizia Scola,
Calogero Caruso, Massimo Motta,
Domenico Maugeri,
Domenico Lio
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ABSTRACT: The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-γ) and IL-2 levels are unmodified, suggesting a substantial maintenance of relevant T cell functions. In addition, a significant increase of IL-12 serum levels in nonagenarians versus young controls that might be related to the increase of natural killer (NK) cell functions characterizing aging processes was observed. The analysis of Th2 cytokines show an increase of IL-13 and a reduction of IL-4 levels mirroring the maintenance of some effector's mechanisms of the immunoresponse in advanced ages. Our results suggest that the multiplex analysis of cytokine levels might be useful in defining a successful aging profile.
Journal of Immunoassay and Immunochemistry 01/2012; 33(1):82-90. · 0.69 Impact Factor
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ABSTRACT: To evaluate the efficacy of L-carnitine on alleviating anemia, thrombocytopenia and leukopenia, and minimizing dose reductions in patients with chronic hepatitis C virus (HCV) in treatment with Interferon α (IFN-α) plus ribavirin.
Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups. group A (n = 35) received Peg-IFN-α 2b plus ribavirin plus L-carnitine, and group B (n = 34) received Peg-IFN-α and ribavirin for 12 mo. All patients underwent laboratory investigations including: red cell count, hemoglobin, white cell count, platelets, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viremia.
After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8 (IU/L; P < 0.001), ALT 137.9 vs 112.3 (IU/L; P < 0.001), viremia 4.04 vs 2.36 (× 10(6) copies/mL; P < 0.001), Hb 1 vs 3.5 (g/dL; P < 0.05), red blood cells 0.3 vs 1.1 (× 10(12)/L; P < 0.001), white blood cells 1.5 vs 3 (× 10(9)/L; P < 0.001) and platelets 86 vs 85 (× 10(9)/L; P < 0.001). The end treatment responders were 18 vs 12 (60% vs 44%) and the non responders were 12 vs 15 (40% vs 50%) [odds ratio (OR) 1.65, 95% CI = 0.65-5.37, P < 0.05]. In group A compared to group B there was a significant improvement of sustained virological response in 15 vs 7 patients (50% vs 25%), while the relapsers were 3 vs 5 (10% vs 18%) (OR 3.57, 95% CI = 0.65-19.3, P < 0.001).
L-carnitine supplementations modulate erythropoiesis, leucopoiesis and thrombocytopoiesis, and may be useful in patients treated for HCV. L-carnitine treatment offers the possibility of achieving a sustained virological response while preventing overtreatment.
World Journal of Gastroenterology 10/2011; 17(39):4414-20. · 2.47 Impact Factor
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ABSTRACT: Epidemiological studies carried out on a large sample (3191 elderly and 640 centenarians) with identical criteria and applying the actual diagnostic standards, have evidenced a high, statistically significant prevalence of diabetes mellitus type 2 (DMT2) (18.84%) in the elderly, as compared to the centenarians (7.50%). This aspect is correlated with the major frequency of maturity onset diabetes in elderly (MODE), compared to the centenarians, correlated also to the mortality of diabetes mellitus (DM) of long duration. The DMT2 and the aging interact in the determinism of vascular alterations, i.e., of the hypertension, and related cardio-cerebrovascular complications. The most frequently occurring hypertension in both the elderly and centenarians was always the systolic-isolated one. The prevalence of hypertension and acute myocardial infarction (AMI) was statistically significantly higher in diabetics, compared to the normoglycemic patients, in both the elderly and the centenarians. In addition, in a group of 914 elderly patients, being diabetics or normoglycemic at the start of the studies, but having neither AMI nor stroke at the baseline studies, after 5 years, these complications were more prevalent, significantly in statistical terms, in the diabetic subjects, compared to the normoglycemic ones. The increase of life-span causes an increase of the age when the aging phenomena appear, resulting in that the equal-age elderly people today are of better clinical conditions, compared to the previous periods. The increased life span with a consequent progressive aging of the population causes a worse general clinical state of the elderly population, characterized by polypathologies, frailty, and appearance of cognitive deficits or incapabilities for performing manual or instrumental activities.
Archives of gerontology and geriatrics 09/2011; 55(2):221-5. · 1.36 Impact Factor
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Michele Malaguarnera,
Marco Vacante,
Gaetano Bertino,
Sergio Neri,
Mariano Malaguarnera,
Maria Pia Gargante, Massimo Motta,
Lorenzo Lupo,
Giuseppe Chisari,
Cosimo Marcello Bruno,
Giovanni Pennisi,
Rita Bella
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ABSTRACT: The aim of this study was to evaluate whether supplementation of acetyl-L-carnitine (ALC) to pegylated-interferon-α 2b (Peg-IFN-α 2b) and ribavirin (RBV) improves the health-related quality of life during the treatment for chronic hepatitis C, thereby decreasing the risk of treatment discontinuation. Sixty patients with chronic hepatitis C underwent treatment with Peg-IFN-α 2b + RBV (group A; n = 29) or Peg-IFN-α 2b + RBV + ALC (group B; n = 31) for 12 months. At the end of the study, the comparison between group A and group B showed significant differences in aspartate aminotransferase (AST) (-80.9 versus -110.3; P < 0.001), alanine aminotransferase (-111.6 versus -134.7; P < 0.001), Viremia (-3.26 versus -3.82; P < 0.05), mental health (0 versus 11; P < 0.001), physical functioning (-1 versus 8; P < 0.001), role-physical (1 versus 13; P < 0.001), bodily pain (1 versus 12; P < 0.001), general health (3 versus 12; P < 0.001), vitality (3 versus 13; P < 0.001), social functioning (3 versus 10; P < 0.001), physical fatigue (2.1 versus -5.4; P < 0.001), mental fatigue (-0.7 versus -2.7; P < 0.001), and fatigue severity scale (-3.4 versus -12; P < 0.001). ALC supplementation reduced both mental and physical fatigue, improved health-related quality of life, and, therefore, has the potential to increase patient adherence to the combination regimen. This, in turn, may increase the percentage of patients achieving a sustained virological response.
Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 09/2011; 31(9):653-9. · 1.63 Impact Factor
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ABSTRACT: The aim of this study was to investigate the effects of ALC treatment on cognitive functions in patients with severe hepatic encephalopathy. This was a randomized, double-blind, placebo-controlled study. 61 patients with severe hepatic encephalopathy were recruited to the study. The 2 groups received either 2 g ALC twice a day (n = 30) or placebo (n = 30) for 90 days. Clinical and laboratory assessment, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. At the end of the study period, between the 2 groups we observed a significant difference in Everyday Memory Questionnaire -23.9 vs 4.4 (p < 0.001), Logical Memory (Paragraph recall) test 22.3 vs 0.7 (p < 0.001), Trail Making Test A -7.5 vs -2.6 (p < 0.001), Trail Making Test B -10.5 vs -3.1 (p < 0.001), Controlled Oral Word Association Test 4.2 vs 0.5 (p < 0.001), Hooper test 2.6 vs 0.1 (p < 0.05), Judgement of line orientation 2.8 vs 0.3 (p < 0.001), Digit Cancellation time -24.5 vs -2.4 (p < 0.001), NH₄⁺ 30.5 vs 13.5 (p < 0.001), prothrombin time 2 vs 2.4 (p < 0.05), alanine transaminase -10.7 vs -13.6 (p < 0.001). 88% of patients treated with ALC vs 72% of patients treated with placebo showed a significant improvement in EEG. The improvement of cognitive deficits, the reduction of ammonia, and the modification of EEG in patients treated with ALC suggest that ALC could represent a new tool in the treatment of severe hepatic encephalopathy.
Metabolic Brain Disease 08/2011; 26(4):281-9. · 2.20 Impact Factor
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ABSTRACT: The residual liver function is a major clinical index in hepatocellular carcinoma (HCC) patients. As the liver plays a crucial role in lipid and lipoprotein metabolism, the significant impairment of the hepatic function occurring during chronic liver diseases, such as HCC, can influence plasma lipoprotein profiles. Although, lipoprotein(a) (Lp(a)) circulating concentrations are mostly determined by genetic factors, in the majority of reports they have shown a correlation with the hepatic status and a significant decrease in HCC and liver cirrhosis patients than among the controls. In such a way, Lp(a) may represent a new additional and useful marker for a more complete assessment and monitoring of the liver function in patients with HCC and liver cirrhosis. Further studies are needed in order to evaluate the clinical significance of Lp(a) in HCC.
Indian journal of medical and paediatric oncology 04/2011; 32(2):71-5.
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ABSTRACT: Minimal hepatic encephalopathy (MHE) represents a common complication present in well-compensated cirrhotic patients that impairs patients' daily functioning and health-related quality of life (HRQL). Acetyl-L-carnitine (ALC) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE.
This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE.
This was a randomized, double-blind, placebo-controlled study. Sixty-seven patients with MHE were recruited to the study. They were randomly assigned to two groups and received either 2 g acetyl-L-carnitine twice a day (n = 33) or placebo (n = 34) for 90 days. The primary efficacy measures were changes in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl-transpeptidase, albumin, alkaline phosphatase, prothrombin time, and ammonia. Clinical and laboratory assessments, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients.
At the end of the study period, between the two groups, we observed a significant difference in physical function (p < 0.001), role physical (p < 0.001), general health (p < 0.001), social function (p < 0.05), role emotional (p < 0.05), mental health (p < 0.05), Beck Depression Inventory (p < 0.001), TMT-B s (p < 0.001), State Trait Inventory (p < 0.001), urea (p < 0.05), NH(4)(+) (p < 0.001), and bilirubin (p < 0.001).
This study shows that ALC treatment is associated with significant improvement in patient energy levels, general functioning and well-being. The improvement of quality of life is associated with reduction of anxiety and depression.
Scandinavian journal of gastroenterology 03/2011; 46(6):750-9. · 2.08 Impact Factor
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The Indian journal of medical research 01/2010; 131:4-6. · 1.84 Impact Factor
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ABSTRACT: Lipoprotein(a) (also called Lp(a)) is a lipoprotein subclass. Different studies have identified Lp(a) as a putative risk factor for atherosclerotic diseases such as coronary artery disease and stroke. The physiological role of Lp(a) in humans is still unclear, but it seems that individuals with low concentrations of plasma Lp(a) manifest no deficiency syndrome or disease. Because of the high homology between plasminogen and apo(a) it is conceivable that Lp(a) plays a role in the coagulation system, especially in to thrombosis and impaired fibrinolysis processes. It can also contribute to coronary disease and can accumulate in the arterial walls and cerebral vessels. Lp(a) seems to play an active role in acute inflammation promoting the enhancement of intercellular adhesion molecules; that way it can contribute to develop atherosclerosis. Finally, we underline the relationship among Lp(a) levels and others inflammations molecules such as fibrinogen, fibronectin and TGF- beta.
Frontiers in bioscience (Scholar edition) 01/2010; 2:866-75.
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ABSTRACT: The observation of neuroendocrine (NE) activity during clinical course of hepatocellular carcinoma (HCC), suggested the use of NE serum markers to detect it. Thus we have evaluated the usefulness of serum measurements of CgA in monitoring disease activity of HCC. We investigated the role of serum concentrations of CgA, alpha-fetoprotein (AFP) and des-gamma-carboxyl-prothrombin (DCP) in 55 patients with HCC, 27 patients with cirrhosis, 22 patients with chronic hepatitis and a control group of 20 volunteers and the relationship between the pre-treatment serum CgA and clinical stages of the disease. CgA was significantly higher in the patients affected by HCC as compared with those affected by either hepatitis or cirrhosis (p<0.001). We also observed significant differences, comparing CgA serum levels in the tumor classes T1-T4: T1 vs. T2 (p<0.001), T1 vs. T3 (p<0.001), T1 vs. T4 (p<0.001), T2 vs. T3 (p<0.001), T2 vs. T4 (p<0.001) and T3 vs. T4 (p<0.001). CgA levels were significantly higher in poorly differentiated HCC vs. well differentiated (p<0.05) and medium differentiated ones (p<0.001). Also the comparison between Child-Pugh degree A and C showed a significant difference in CgA levels (p<0.001). Thereby, patients with higher CgA level had poor survival and showed poor prognosis, compared to those with lower CgA level, i.e., the CgA is useful in monitoring progression of disease and may assist as a prognostic indicator.
Archives of gerontology and geriatrics 09/2009; 51(1):81-5. · 1.36 Impact Factor
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ABSTRACT: Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients. This study evaluated the efficacy of L-carnitine on the size of LDL particles in type 2 diabetes mellitus patients treated with simvastatin. Eighty diabetic patients were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups received either simvastatin monotherapy 20 mg (n = 40) or L-carnitine 2 g/d and simvastatin 20 mg (n = 40). The following variables were assessed at baseline; after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2 groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05). Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P < .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8% vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 A, P < .001) and HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated with carnitine and simvastatin showed a reduction in small-sized LDL proportion and an increase in LDL particle size.
Metabolism: clinical and experimental 07/2009; 58(11):1618-23. · 2.59 Impact Factor
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ABSTRACT: The diabetes mellitus of type 2 (DMT2) is a disease of the elderly with multifactorial pathogenesis, characterized by interactions of genetic variations suspect for diabetes, as well as of the longevity and aging genes. Since today it is still not possible to obtain the diagnosis with laboratory methods of clinical genetics, we tried to identify the subjects of risk of future diabetes on the basis of a combined measurement of glycemia, the glycosylated hemoglobin (HbA1c) and the waist circumference (WC). The studied population consisted of 2603 elderly subjects of 65-84 years of age, involved in the epidemiological study called ILSA (Italian Longitudinal Study on Aging). The subjects who displayed at the baseline an impaired fasting glucose (IFG) accompanied by HbA1c and WC values above the normal cut-points proved to be diabetic after a 3-year follow-up in 18.96%, while the subjects with normal fasting glucose (NFG) accompanied by normal HbA1c and WC values were found to be diabetic only in 1.34%. It means that the presence of abnormal values of these 3 parameters in the elderly does not allow the identification of the risks for future diabetes in the great majority of subjects. We conclude that the results of prospective studies may gain particular significance not only regarding the glycemia, but also the other 2 risk factors, if we wish to reach not only a predictive diagnosis of risk for diabetes, but also to prevent the chronic degenerative complications of it.
Archives of gerontology and geriatrics 06/2009; 50(1):105-9. · 1.36 Impact Factor
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ABSTRACT: Given the relevance of hyperuricaemia in the development of several diseases, we evaluated rasburicase, generally used in tumor lysis syndrome for uric acid treatment. Our purpose was to evaluate the reduction of serum uric acid and the improvement in renal function.
This is a pilot randomized clinical trial. The study was performed as an 8-week, placebo-controlled group comparison of rasburicase and placebo. Thirty-eight patients were randomly assigned to administration of a single dose of rasburicase (4.5 mg in 100-cc physiological solution versus only physiological solution in 15 min).
We observed in the first week a fast decrease in uric acid value. Two months after rasburicase administration we saw a significant reduction of urate (p < 0.05) and creatinine (p < 0.001) and an increase in creatinine clearance (p < 0.001) and urate clearance (p < 0.001).
In hyperuricaemic elderly patients, a single dose of rasburicase is very effective in lowering serum uric acid levels. Moreover, in patients treated with rasburicase we noted an improvement of renal function. We conclude that rasburicase is an alternative resource for treating those patients who are allopurinol intolerant, have renal dysfunction or have multiple polypharmacy problems in which drug-drug interaction may be of concern.
Expert Opinion on Pharmacotherapy 04/2009; 10(5):737-42. · 3.20 Impact Factor
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ABSTRACT: Patients with type 2 diabetes are under high oxidative stress, and levels of hyperglycemia correlate strongly with levels of LDL oxidation. Carnitine favorably modulates oxidative stress.
This objective of this study was to evaluate the efficacy of L-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes.
Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g L-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B-100, oxidized LDL cholesterol, thiobarbituric acid-reactive substances, and conjugated dienes.
At the end of the study period, the L-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers: oxidized LDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001); LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001); apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05); apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid-reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001).
Our study indicates that oral administration of L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.
American Journal of Clinical Nutrition 01/2009; 89(1):71-6. · 6.67 Impact Factor
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The Indian journal of medical research 10/2008; 128(3):225-7. · 1.84 Impact Factor
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ABSTRACT: The increase in life expectancy, the decrease of birth rate, and of the death rate in advanced ages caused, particularly in the industrialized countries, a progressive demographic transformation of the society, characterized by an increased proportion of the elderly. We assist an inevitable increase of morbidity and disability, not only due to the global aging of the population, but mainly to the increase of the age class above 80 years. For this reason, it is necessary to create and/or effort, especially in the Western countries, an adequate health-caring network. This should integrate and interact between the hospitals and the territories, offering all sanitary services (e.g., assisted sanitary residences, day hospitals (DHs), hospices, Alzheimer centers, diurnal centers, integrated domiciliary care (IDC), general practitioners), required by the elderly, and particularly by the oldest old people. All this should be maintained by an adequate financial support of the social-economic sources, which are necessary not only to activate the health-care services, but also to favor the economic and fiscal stimulation toward the families maintaining the elderly patients.
Archives of gerontology and geriatrics 10/2008; 49(1):32-4. · 1.36 Impact Factor
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ABSTRACT: In an elderly pool of 3288 subjects (65-84 years of age), taking part in the Italian Longitudinal Studies on Aging (ILSA). We evaluated the prevalence of acute myocardial infarction (AMI), the stroke, the non-fatal AMI+stroke cases in relation to the larger or smaller values of the apolipoprotein-B (Apo-B) level considered as cutoff point of normality (150 mg/100 ml). In addition, during the follow-up of 3 years, we observed the prevalence of all these pathologies (AMI, stroke, non-fatal AMI+stroke) in the subjects who had none of these syndromes at the start of the study period. At last, we studied the percentual occurrence of the parameters indicated by the IDF as signs of the metabolic syndrome (MS), and compared them between the subjects displaying higher or lower values of Apo-B of the normal level. Our results revealed that the Apo-B value may be considered as a predictive factor of lipidemic, atherogenic alterations, and it merits in this sense to be included in the diagnostic criteria of MS. However, it cannot be considered as an independent factor of preventive diagnosis of the non-fatal cardio-cerebrovascular complications.
Archives of gerontology and geriatrics 09/2008; 49(1):162-4. · 1.36 Impact Factor