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Background and Objectives: Fibromyalgia syndrome (FMS) is a multifaceted disease with a strong preference for the female sex. It is characterised by chronic widespread pain, sleep-wake disorders, fatigue, cognitive disturbances, and several other somatic symptoms. Materials and Methods: In this prospective observational study, we analysed data regarding 302 patients who were referred to our pain centre for a first clinical assessment evaluation and were then inspected for the physician-based 2016 revision of the ACR diagnostic criteria for FMS, regardless of the final diagnosis previously made by the pain therapist. Results: Among the 280 patients who adhered to the 2016 ACR questionnaire, 20.3% displayed positive criteria for FMS diagnosis. The level of agreement between the FMS discharge diagnosis made by the pain clinician and the ACR 2016 criteria-positivity was moderate (kappa = 0.599, with moderate agreement set at a kappa value of 0.6). Only four patients (1.7%) diagnosed as suffering from FMS at discharge did not satisfy the minimal 2016 ACR diagnostic criteria. Conclusions : This prospective observational study confirmed the diagnostic challenge with FMS, as demonstrated by the moderate grade of agreement between the FMS diagnosis at discharge and the positivity for 2016 ACR criteria. In our opinion, the use of widely accepted diagnostic guidelines should be implemented in clinical scenarios and should become a common language among clinicians who evaluate and treat patients reporting widespread pain and FMS-suggestive symptoms. Further methodologically stronger studies will be necessary to validate our observation.

Background: The aim of the present study was to examine the prevalence of dementia, related comorbidities, and mortality rates in hospitalized elderly patients in Italy., Methods: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged 65 years or above admitted to acute Internal Medicine during 2 years (n=3,695,278 admissions). Discharge diagnoses were re-classified into 24 clusters, each including homogeneous diseases by the ICD-9-CM code classification. Dementia was identified by the presence of ICD-9-CM codes 290, 294, or 331 series., Results: Patients with dementia represented 7.5% of the sample; compared with those without dementia, they were older and more often female, had a greater length of hospital stay and higher mortality rate. Besides delirium [odds ratio (OR): 54.20], enthesopaties (OR: 2.19), diseases of fluids and electrolytes (OR:1.96), diseases of arteries (OR: 1.69), skin diseases (OR: 1.64), and pneumonia and pleurisy (OR: 1.53) were the diseases more strongly associated with the diagnosis of dementia, independent of other clusters, age, sex, and length of stay., Conclusions: Some comorbidities are specifically associated with the diagnosis of dementia among hospitalized elderly patients. Overall, these comorbidities describe the typical clinical profile of the patient with advanced dementia and could be treated in the context of the primary care, since they do not require specific skills belonging to hospital settings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This study is a meta-analysis of the published studies on the relationship between methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and the risk of late- onset Alzheimer 's disease (LOAD) in Italian cohorts., Evidence Acquisition: We conducted a search on the electronic databases PubMed/Medline, Web of Science and Scopus. All cohort and case-control studies investigating the association between MTHFR 677T polymorphism and LOAD in Italian population published any time to May 8, 2020 were included in the analysis., Evidence Synthesis: From an initial screening of 136 articles, 4 were included into the systemic review. The pooled analysis based on the co-dominant model revealed that the MTHFR C677T polymorphism was associated with a significant risk of LOAD among Italian cohorts (TC vs. CC: OR=1.20, 95% CI=1.06-1.36, P=0.004, I 2 =0%). Conversely, the pooled analysis based on the allelic model demonstrated a non-significant relationship between the MTHFR C677T polymorphism and susceptibility to LOAD in Italians (OR: 1.25, 95% CI: 0.99-1.59, P=0.060, I 2 =14.6%). Moreover, Italian subjects with MTHFR 677TT genotype resulted to have a significantly increased susceptibility to LOAD (OR=1.75, 95% CI=1.23-2.50, P=0.002, I 2 =0%)., Conclusions: The present meta-analysis showed only trend of association between MTHFR C677T polymorphism and LOAD in Italian population; however, it also demonstrated an increased susceptibility of LOAD in patients having MTHFR 677TT genotype. Further studies are needed to establish whether MTHFR polymorphisms can be used as non-invasive biomarker for LOAD.

Objective: SARS-CoV-2 has been compared with other strains of coronaviruses, SARS-CoV and MERS-CoV, and with the flu viruses: all of them manifest themselves with respiratory symptoms and, although their genetic patterns are similar, the spread of SARS-CoV-2 infection has quickly reached global dimensions, demonstrating that SARS-CoV-2 is a virus with greater spreading capacity, albeit less lethal. Compared with influenza viruses, coronaviruses have a longer incubation period and the patients with coronaviruses' syndromes develop more severe diseases requiring frequent hospitalizations and intensive care admissions. The aim was to explore the relationships between seasonal influenza vaccination and coronavirus infection and to understand whether this hypothetic role by the flu vaccines modifies SARS-CoV-2 infection's outcomes., Patients and Methods: In this retrospective, multicenter study, we enrolled 952 patients diagnosed with SARS-CoV-2 infection; 448 were admitted to our two main hospitals in Ferrara territory, while the remaining 504 were isolated at home. We compared the group of patients who had been vaccinated for influenza in the previous 12 months to that of unvaccinated patients., Results: Significant differences were found for both the need for hospitalization and 30-day mortality between vaccinated and unvaccinated patients. We found age to be the only independent risk factor for a worse 30-day prognosis, while gender, influenza vaccinations and age itself were independent risk factors for undergoing hospitalization., Conclusions: In our groups of patients, we found a relationship between seasonal influenza vaccinations and SARS-CoV-2 infection. Age seems to be the main risk factor for short-term mortality in COVID-19 inpatients, while the influenza vaccination is, together with gender and age itself, a determining factor in predicting the need for hospitalization.

Objective: Clinical outcomes in patients hospitalized for severe acute respiratory syndrome due to coronavirus (SARS-CoV-2) infection seems to be closely related with burden of comorbidities. A comorbidity score could help in clinical stratification of patients admitted to internal medicine units. Our aim was to assess a novel modified Elixhauser index (mEi) and the Charlson Comorbidity Index (CCI) for predicting in-hospital mortality (IHM) in internal medicine patients with SARS-CoV-2 infection., Patients and Methods: This single-center retrospective study enrolled all consecutive patients discharged from internal medicine unit with confirmed SARS-CoV-2 infection. Both the mEi and CCI were easily calculated from administrative data. Comorbidity scores were tested using receiver operating characteristic (ROC) analysis, and the respective area under the curve (AUC)., Results: The total sample consisted of 151 individuals, and 30 (19.9%) died during their hospital stay. Deceased subjects were older (82.8±10.8 vs. 63.3±18.1 years; p<0.001) and had a higher burden of comorbidities: the mEi and CCI were 29.9±11 vs. 8.8±9.2 and 4.6±2.6 vs. 1.2±2 (p<0.001), respectively. Only the mEi was independently associated with IHM (OR 1.173), and ROC curves analysis showed that the AUCs were 0.863 and 0.918 for the CCI and for mEi, respectively., Conclusions: In patients admitted to internal medicine wards with SARS-CoV-2 infection, the mEi showed a better performance in predicting IHM than CCI.

Objective: SARS-CoV-2 can reportedly exist on inanimate surfaces for a long duration, but there is limited data available from Italian COVID-19 hospital wards, especially for non-intensive care units hosting patients that do not require mechanical ventilation. Identification of the extent of environmental contamination can help in understanding possible virus transmission routes, limit hospital infections and protect healthcare workers. Thus, we investigated virus contamination on surfaces of the acute COVID-19 ward of an Italian hospital., Materials and Methods: Ward surfaces, including four points inside and six points outside the patients' rooms were sampled by swabs, seven hours after routine sanitation. To minimize the risk of underestimation of virus detection, two different sensitive molecular methods were used comparatively, and specific internal controls were added to enhance the efficiency of all the analysis steps., Results: SARS-CoV-2 contamination was detected in only three out of all the collected samples, i.e., on two floors and one-bathroom sink, likely reflecting aerosol and saliva contamination, respectively. The overall level of contamination was low, and the floors exhibited a very low level of SARS-CoV-2 presence, evidenced by only one of the two methods used., Conclusions: The existence of SARS-CoV-2 on hospital surfaces may be limited, although it was reported to persist for a longer duration on surfaces under controlled laboratory conditions. Thus, effective transmission of SARS-CoV-2 by surfaces/fomites within the hospital ward may be a rare event. However, the results highlight the importance of assessing method sensitivity and including controls when investigating low-level virus contamination so as to avoid the risk of underestimation of virus presence.

Background: Data regarding pulmonary embolism (PE)-related mortality in Italy are scarce. We assessed PE-related mortality and its time trend in Italy by using the World Health Organization (WHO) Mortality Database., Methods: The vital registration data of Italy from the WHO Mortality Database were analyzed for the period between 2003 and 2015, and compared with time trends in Southern Europe. Death was defined as PE-related when classified with specific codes for PE or limb vein thrombosis listed as the primary cause of death. This coding was based on the International Classification of Diseases, tenth revision., Results: Overall, 28 647 PE-related deaths (10 178 men and 18 469 women) were recorded between 2003 and 2015. The observed age-standardized annual PE-related mortality rates were 2.5 per 100 000 men and 2.8 per 100 000 women. Moreover, PE-related mortality increased with age with a seemingly exponential distribution. Joinpoint regression analysis demonstrated a statistically significant linear decrease in age-standardized PE-related mortality of -0.21 (95% confidence interval -0.27; -0.15) and -0.22 (95% confidence interval -0.28; -0.16) deaths per 100 000 population for men and women, respectively., Conclusions: The Italian age-adjusted mortality rates appeared lower compared to overall Southern Europe, despite a similar decreasing trend over time.

Objective: At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients., Patients and Methods: We retrospectively evaluated all patients admitted to COVID internal medicine units with confirmed SARS-CoV-2 infection, and treated with darunavir-ritonavir (single daily dose, for seven days). Age, sex, length of stay (LOS), pharmacological treatment, and timing of antiviral administration (morning or evening), were recorded. Outcome indicators were death or LOS, and laboratory parameters, e.g., variations in C-reactive protein (CRP) levels, ratio of arterial oxygen partial pressure (PaO2, mmHg) to fractional inspired oxygen (FiO2) (PaO2/FiO2), and leucocyte count., Results: The total sample consisted of 151 patients, 33 (21.8%) of whom were selected for antiviral treatment. The mean age was 61.8±18.3 years, 17 (51.5%) were male, and the mean LOS was 13.4±8.6 days. Nine patients (27.3%) had their antiviral administration in the morning, and 24 (72.7%) had antiviral administration in the evening. No fatalities occurred. Despite the extremely limited sample size, morning group subjects showed a significant difference in CRP variation, compared to that in evening group subjects (-65.82±33.26 vs. 83.32±304.89, respectively, p<0.032). No significant differences were found for other parameters., Conclusions: This report is the first study evaluating temporized morning vs. evening antiviral administration in SARS-CoV-2 patients. The morning regimen was associated with a significant reduction in CRP values. Further confirmations with larger and multicenter samples of patients could reveal novel potentially useful insights.

Background and Aims: Increased uric acid levels correlate with cardiovascular disease and cardiovascular/overall mortality. To identify a uric acid threshold above which cardiovascular mortality rises, we studied the relationship between uric acid concentration and overall/cardiovascular mortality., Methods and Results: We analyzed data from the InCHIANTI study, a cohort study of Italian community-dwelling people with 9 years of follow-up. We selected a sample of 947 individuals over 64 years of age, free from cardio-cerebrovascular disease and with available uric acid measurement at baseline. The sample was divided according to plasma uric acid tertiles. The Hazard ratio (HR) for mortality was calculated by multivariate Cox proportional hazard model. Mean age of participants was 75.3 ± 7.3 years; the mean value of uric acid was 5.1 ± 1.4 mg/dl. Over 9-years of follow-up, 342 (36.1%) participants died, 143 deaths (15.1%) were due to cardiovascular disease. Subjects with higher uric acid concentrations presented a higher cardiovascular mortality [II (4.6-5.5 mg/dl) vs I (1.8-4.5 mg/dl) tertile HR: 1.98, 95%C.I. 1.22-3.23; III (≥5.6 mg/dl) vs I tertile HR: 1.87, 95%C.I. 1.13-3.09]. We found a non-linear association between uric acid concentrations and cardiovascular mortality with the lowest mortality for values of about 4.1 mg/dl and a significant risk increment for values above 4.3 mg/dl., Conclusion: In community-dwelling older individuals free from cardio-cerebrovascular events, the lowest 9-year cardiovascular mortality was observed for uric acid values far below current target values. If confirmed, these data might represent the background for investigating the efficacy of uric acid levels reduction in similar populations., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To define the prevalence of dysphagia and its associated factors and to investigate the influence of dysphagia and nutritional therapies performed in dysphagic subjects on clinical outcomes, including nutritional status, pressure ulcers, hospitalization, and mortality., Design: A prospective observational study., Setting and Participants: Thirty-one Italian nursing homes participating in the ULISSE project and 1490 long-stay nursing home residents, older than 65 years, assessed at baseline and reassessed after 6 and 12 months., Measures: All participants underwent a standardized comprehensive assessment using the Italian version of the nursing home Minimum Data Set. The activities of daily living Long-Form scale was used to evaluate functional status. Health care professionals assessed dysphagia by means of clinical evaluation. Nutritional status was assessed using the information on weight loss., Results: The prevalence of dysphagia was 12.8%, and 16% of the subjects were treated with artificial nutrition. The mortality rate in subjects with dysphagia was significantly higher compared with that of nondysphagic subjects (27.7% vs 16.8%; P = .0001). The prevalence of weight loss and pressure ulcers was also higher in dysphagic subjects. At variance, dysphagia was not associated with a higher hospitalization risk., Conclusion/implications: Dysphagia is common in nursing home residents, and it is associated with higher mortality. Therefore, early diagnosis and optimal management of dysphagia should become a priority issue in nursing homes., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia is associated with increased risk of adverse outcomes in older people. Aim of the study was to explore the predictive value of the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic algorithm in terms of disability, hospitalization, and mortality and analyze the specific role of grip strength and walking speed as diagnostic criteria for sarcopenia., Methods: Longitudinal analysis of 538 participants enrolled in the InCHIANTI study. Sarcopenia was defined as having low muscle mass plus low grip strength or low gait speed (EWGSOP criteria). Muscle mass was assessed using bioimpedance analysis. Cox proportional and logistic regression models were used to assess risk of death, hospitalization, and disability for sarcopenic people and to investigate the individual contributions of grip strength and walking speed to the predictive value of the EWGSOP's algorithm., Results: Prevalence of EWGSOP-defined sarcopenia at baseline was 10.2%. After adjusting for potential confounders, sarcopenia was associated with disability (odds ratio 3.15; 95% confidence interval [CI] 1.41-7.05), hospitalization (hazard ratio [HR] 1.57; 95% CI 1.03-2.41), and mortality (HR 1.88; 95% CI 0.91-3.91). The association between an alternative sarcopenic phenotype, defined only by the presence of low muscle mass and low grip strength, and both disability and mortality were similar to the association with the phenotypes defined by low muscle mass and low walking speed or by the EWGSOP algorithm., Conclusions: The EWGSOP's phenotype is a good predictor of incident disability, hospitalization and death. Assessment of only muscle weakness, in addition to low muscle mass, provided similar predictive value as compared to the original algorithm., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine the association between hyperhomocysteinemia and cognitive function, taking into account the effect of B group vitamin (BGV) deficiency., Design: Cross-sectional., Setting: Memory Clinic, S. Anna University Hospital, Ferrara, Italy., Participants: Elderly individuals (≥65) (N = 318; 44 normal cognition, 127 with cognitive impairment, 147 with dementia) divided into four groups according to plasma homocysteine (high vs normal) and BGV (normal vs deficit) levels., Measurements: Cognitive, clinical, biochemical, functional, and neuroimaging parameters were evaluated., Results: Hyperhomocysteinemia (>15 μmol/L) was associated with a higher prevalence of cognitive and functional impairment and dementia (odds ratio (OR) = 1.98, 95% confidence interval (CI) = 1.13-3.48), independent of BGV status and other confounders. Participants with hyperhomocysteinemia with normal BGV status had the worst functional status and the highest prevalence of dementia (high homocysteine/normal BGV vs normal homocysteine/normal BGV: OR = 3.20, 95% CI = 1.65-6.21). Homocysteine levels were correlated negatively with folate and vitamin B12 levels and glomerular filtration rate and positively with free thyroxine and uric acid levels (model coefficient of determination = 0.43)., Conclusion: Hyperhomocysteinemia was associated with worse cognitive and functional status and dementia independently of BGV levels. Approximately half of participants with hyperhomocysteinemia had normal BGV levels, suggesting that other unmeasured factors might be associated with high homocysteine levels., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Background: Muscle impairment is a common condition in older people and a powerful risk factor for disability and mortality. The aim of this study was to apply the European Working Group on Sarcopenia in Older People criteria to estimate the prevalence and investigate the clinical correlates of sarcopenia, in a sample of Italian community-dwelling older people., Methods: Cross-sectional analysis of 730 participants (74% aged 65 years and older) enrolled in the InCHIANTI study. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People criteria using bioimpedance analysis for muscle mass assessment. Logistic regression analysis was used to identify the factors independently associated with sarcopenia., Results: Sarcopenia defined by the European Working Group on Sarcopenia in Older People criteria increased steeply with age (p < .001), with 31.6% of women and 17.4% of men aged 80 years or older being affected by this condition. Higher education (odds ratio: 0.85; 95% CI: 0.74-0.98), lower insulin-like growth factor I (lowest vs highest tertile, odds ratio: 3.89; 95% CI: 1.03-14.1), and low bioavailable testosterone (odds ratio: 2.67; 95% CI: 1.31-5.44) were independently associated with the likelihood of being sarcopenic. Nutritional intake, physical activity, and level of comorbidity were not associated with sarcopenia., Conclusions: Sarcopenia identified by the European Working Group on Sarcopenia in Older People criteria is a relatively common condition in Italian octogenarians, and its prevalence increases with aging. Correlates of sarcopenia identified in this study might suggest new approaches for prevention and treatment of sarcopenia.

Aim: Increasing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment. The aim of the present study was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older nursing home residents., Methods: We used data from the database of the U.L.I.S.S.E project (Un Link Informatico sui Servizi Sanitari Esistenti per l'Anziani), a prospective multicenter observational study. Patients from 31 facilities in Italy were assessed at baseline and at 6 and 12 months by trained personnel, using the Minimum Data Set for Nursing Home (MDS-NH). The only exclusion criterion was age younger than 65 years. The Anticholinergic Risk Scale (ARS), a list of commonly prescribed drugs with potential anticholinergic effects, was used to calculate the anticholinergic load., Results: A total population of 1490 patients was analyzed; almost half of the sample (48%) was using drugs with anticholinergic properties. The population of patients with ARS 1 or higher had a higher comorbidity index (P < .003) and greater cognitive impairment (CPS 5-6) (P < .007). They were more likely to suffer from heart failure, Parkinson disease, depression, anxiety, and schizophrenia. In multivariate analysis, a higher score in the ARS scale was associated with a greater likelihood of functional decline (described as the loss of ≥1 ADL point) (odds ratio [OR] 1.13; confidence interval [CI] 1.03-1.23), to a higher rate of falls (OR 1.26; CI 1.13-1.41), and to a higher incidence of delirium (OR 1.16; CI 1.02-1.32) during a 1-year follow-up., Conclusions: The use of medications with anticholinergic properties is common among older nursing home residents. Our results suggest that among older nursing home residents the use of anticholinergic drugs is associated with important negative outcomes, such as functional decline, falls, and delirium.

Background: In older individuals, acute medical illnesses and admission to hospital are often associated with a deterioration of cognitive status, also in the absence of dementia and full-blown delirium. We evaluated the prevalence of subsyndromal delirium (SSD) and its correlates in a sample of elderly medical inpatients., Methods: From 763 consecutive inpatients, 325 participants with known dementia or delirium were excluded, whereas 438 (mean age: 80.6 years; female participants: 60.1%) were enrolled. SSD was diagnosed within 48 hour from admission, when at least two DSM-IV delirium criteria including disorientation, attention or memory deficit, altered level of consciousness, or perceptual disturbances were present. Cognitive performance was evaluated by Mini Mental Status Examination (MMSE). General, clinical, and laboratory parameters were also registered., Results: One hundred and sixty-six patients (37%) had SSD. Compared with controls, SSD patients were older individuals, had less formal education, higher comorbidity, lower hemoglobin/lymphocytes counts, and higher creatinine levels. A trend toward higher prevalence of previous stroke and widowhood was observed. A MMSE score of less than 24/30 identified SSD with 88% sensitivity and 78% specificity. In SSD patients, MMSE independently correlated with years of education, high-sensitivity C reactive protein levels, and O2 arterial saturation (model adjusted r (2) = 0.30, p = .001); conversely, only years of education were associated with MMSE in controls (adjusted r (2) = 0.06, p = .01)., Conclusions: Our data suggest that SSD is common in hospitalized older medical inpatients, and low MMSE score might be useful for identification of participants at risk of SSD. Current inflammatory response and reduced O2 arterial saturation were the only independent determinants of cognitive performance in SSD patients.

Objective: To determine the prevalence of dementia diagnoses and the use of antidementia drugs in a cohort of Italian older nursing home (NH) residents., Design: Cross-sectional study., Setting: The NH residents participating in 2 studies: the U.L.I.S.S.E. study and the Umbria Region survey., Participants: A total of 2215 nursing home residents., Measurement: Each resident underwent a comprehensive geriatric assessment at baseline by means of the RAI MDS 2.0. Dementia diagnosis was based on ICD-9 codes., Results: The prevalence of dementia diagnosis according to ICD-9 codes was 50.7% (n = 1123), whereas 312 subjects had cognitive impairment with a cognitive performance scale score ≥3 without a diagnosis of dementia. Only 56 NH residents were treated (5% of the sample) and the main drugs used were cholinesterase inhibitor, whereas only 1 subject was treated with memantine. Limiting our analysis to patients with mild to moderate Alzheimer's disease, who are those reimbursed by the public health care system for receiving antidementia drugs, the percentage rose to 11.3%., Conclusion: These findings demonstrate a high rate of underdiagnosis and undertreatment of dementia in Italian NH residents. Potential explanations include the lack of systematic assessment of cognitive functions, the limitations to antidementia drug reimbursement, the complexity of the reimbursement procedure itself, and the high prevalence of patients with severe dementia. Older NH residents still lack proper access to state-of-the-art diagnosis and treatment for a devastating condition such as dementia., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the principal discharge diagnosis and related comorbidity in hospitalized older patients affected by dementia., Methods: Data from 51,838 consecutive computerized discharge records of the St. Anna University Hospital (Ferrara, Italy) were analyzed. Records included only subjects aged ≥60 years. Number of admissions, length of stay in hospital, primary and secondary discharge diagnosis (by ICD-9-CM code), number of procedures, and possible death were evaluated., Results: Demented patients represented 8.6% of the sample (4466 individuals) and were older and more likely to be female patients compared with controls (47,372 individuals); they were characterized by higher number of admissions to hospital, instrumental clinical investigations, secondary diagnoses, and mortality rate. Among the primary diagnoses, a higher prevalence of cerebrovascular disease, pneumonia, and hip fracture was observed in demented patients. Furthermore, pulmonary embolism, renal failure, septicemia, and urinary infections were frequently reported in demented patients, but not in controls. As regards secondary diagnoses, dementia was associated with an increased risk of delirium, muscular atrophy and immobilization, dehydration, cystitis, and pressure ulcers, whereas the risk for other conditions, including cancer, was reduced., Conclusions: Among older patients, dementia was associated with higher rate of admissions to hospital and mortality. Discharge diagnoses were sensibly different according to the presence of dementia; in particular, a greater load and a different kind of comorbidity were observed in demented patients. On the whole, our data suggest that the adequate management of demented outpatients might help to reduce hospitalization., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits biological activity on vascular cells in vitro. Rapid variation of circulating TRAIL levels occurs during acute coronary ischemia, suggesting that biological pathways involving TRAIL may be activated during ischemic heart disease. However, whether differential levels of soluble TRAIL in normal individuals are associated with adverse health outcomes has not been investigated. We tested the hypothesis that TRAIL levels predict mortality in a population based sample of community dwelling men and women., Methods: Plasma TRAIL level was measured by ELISA at baseline in 1282 adults (mean age 68 years) enrolled in the InCHIANTI study. Vital status was ascertained over the six-year follow-up., Results: In multivariable Cox regression analysis adjusted for potential confounders including prevalent cardiovascular diseases (CVD), ankle-brachial index, electrocardiogram abnormalities, and inflammatory markers, baseline TRAIL levels were inversely related to all-cause mortality (p=0.008). In stratified analyses, the prognostic effect of TRAIL level was strong and highly significant in participants with prevalent CVD (N=321), (lowest versus highest quartile: HR 3.1; 95% CI 1.5-6.5) while it was negligible in those free of CVD (p value for the interaction term between CVD status and TRAIL levels=0.038). Similar findings were obtained when CVD mortality was considered as the outcome of interest., Conclusions: In older patients with CVD, low levels of TRAIL were associated with increased risk of death over a period of 6 years. Lower concentration of circulating TRAIL may be related to the clinical evolution of older adults with CVD., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals., Methods: A total of 1051 older community-dwelling individuals (age >/=65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years., Results: At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis, HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93-0.99), but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle-brachial index., Conclusions: Among community-dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels.

Background: The biological action of uric acid (UA) in humans is controversial. UA is considered an antioxidant compound, but preclinical evidence suggests a proinflammatory action. Epidemiological studies found that hyperuricemia is associated with conditions leading to dementia. Our aim is to investigate the relationship between UA levels and dementia in older persons., Methods: Cross-sectional study performed in 1,016 community-dwelling older persons participating in the InCHIANTI study. Participants underwent determination of circulating UA levels and neuropsychological evaluation. A multivariate logistic regression model was used to estimate the probability of participants belonging to the highest and middle UA tertile to be affected by dementia compared to those in the lowest tertile., Results: Demented persons had higher UA levels (p = 0.001) and the prevalence of persons affected by dementia increased across UA tertiles (p < 0.0001). Independent of several confounders, persons belonging to the highest UA tertile had a threefold (OR = 3.32; 95% CI: 1.06-10.42) higher probability to suffer from a dementia syndrome while those in the middle UA tertile tended to have a higher probability of being demented compared to those in the lowest tertile., Conclusion: In a population-based sample, high circulating UA levels are associated with an increased likelihood to be affected by a dementia syndrome.

Objectives: To evaluate the independent association between high-density lipoprotein cholesterol (HDL-C) levels and objective measures of lower extremity performance., Design: Cross-sectional cohort study., Setting: Community-based., Participants: Eight hundred thirty-six nondisabled women and men aged 65 and older enrolled in the Invecchiare in Chianti study., Measurements: Lower extremity performance was assessed using 4-m walking speed at fast pace, 400-m walking speed, and knee extension torque. Fasting HDL-C levels were determined using commercial enzymatic tests., Results: The mean age of participants was 73.7 (65-92), and 55.6% were women. After adjusting for potential confounders (sociodemographic factors, smoking, physical activity, body composition, and clinical conditions including cardiovascular and cerebrovascular disease, inflammatory markers, and serum testosterone) HDL-C levels were significantly associated with knee extension torque in men and women and with 4-m and 400-m walking speed in men. Men in the highest tertile of the HDL-C distribution (>55 mg/dL) had, on average, a three times greater probability of belonging to the best tertile of all indexes of lower extremity performance, including 4-m fast walking speed (odds ratio (OR)=2.57, 95%=confidence interval (CI)=1.07-6.17), 400-m walking speed (OR=3.74, 95% CI=1.20-11.7), and knee extension torque (OR=3.63, 95%=CI 1.41-9.33). Path analysis suggested a direct relationship between HDL-C and knee extension torque., Conclusion: In older nondisabled persons, HDL-C levels are highly correlated with knee extension torque and walking speed. Further research should focus on the biological mechanism of this association.

Background: Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased incidence of coronary heart disease (CHD). A better understanding of the mechanisms leading to low HDL-C and CHD is essential for planning treatment strategies. Clinical studies have demonstrated that cytokines might affect both concentration and composition of plasma lipoproteins, including HDLs., Methods: We investigated the possible association between low HDL-C levels, defined as < or =10th gender specific percentile, and circulating markers of inflammation (IL-1beta, TNF-alpha, IL-6, IL-10, IL-18, and CRP) in a population of 1044 community dwelling older Italian subjects from the InChianti study., Results: Using logistic regression analysis we demonstrated that IL-6 levels (III versus I tertile, OR: 2.10; 1.10-3.75), TG (III versus I tertile OR: 27.45; 8.47-88.93), fasting insulin (III versus I tertile OR: 2.84; 1.50-5.42), and age (OR: 1.038; 1.002-1.075) were associated with low HDL-C independent of smoking, BMI, waist circumference, hypertension, diabetes, physical activity, alcohol intake, oral hypoglycaemics, CRP, IL-18, and TNF-alpha levels. The adjusted attributable risk of low HDL-C in the exposed group (III tertile of IL-6) was 54%., Conclusions: The present study provides the epidemiological evidence that besides triglycerides, fasting insulin, and age, IL-6 is one of the main correlates of low HDL-C levels in older individuals.

Background and Aims: In older persons, anemia is a common medical disorder and is often associated with comorbidity and poor health outcomes. We evaluated the relationship between anemia and physical disability in a sample of older hospitalized patients, taking into account the role of comorbidity., Methods: Cross-sectional analysis of the baseline data of the Italian Group of Pharmacoepidemiology in the Elderly Study. Patients aged 65 years or older (n=10,903), admitted to participating centers in the 1993-1998 survey period, were included. Anemia was defined according to the World Health Organization (WHO) criteria; physical disability was defined as need for assistance in performing at least one Activity of Daily Living (ADL) in the week before admission. Comorbidity was ascertained using the Charlson Index., Results: Prevalence of anemia was 41.1%. In the unadjusted analysis, anemia was associated with increased likelihood of disability, in both women (Odds Ratio [OR]: 1.54; 95% Confidence Interval [CI]: 1.38-1.71) and men (OR 1.70; CI 1.52-1.90). After inclusion of demographics and life-style factors in multivariate analysis, the strength of association was only modestly attenuated, whereas nutritional factors and disease-related variables resulted in a greater reduction of the strength of association. In analyses stratified by comorbidity severity, the association between anemia and disability was statistically significant only in patients with the lowest comorbidity levels (p for anemia Charlson Index interaction term <0.05, in both women and men)., Conclusions: Among hospitalized subjects, anemia is associated with ADL disability. The disablement process associated with anemia may be partially explained by nutritional and disease-related factors. However, anemia appears to have an independent effect, particularly in subjects with low comorbidity.

Background: Stroke is the third cause of death in older individuals living in Western Countries. The identification of predictors for mortality after stroke has a major importance for clinicians in order to allow the implementation of therapeutic and preventive strategies., Objective: To evaluate the association between clinical and laboratory parameters and 30-days total mortality in a large sample of older patients with stroke., Methods: 469 older patients (median age: 80.0 years) consecutively hospitalized for acute ischemic stroke were enrolled. The data recorded included: (1) clinical features of stroke; (2) routine clinical chemistry analyses; (3) medical history, and (4) 12-lead ECG. All patients underwent computed tomography scan of the brain. Stroke type was classified by the Oxfordshire Community Stroke Project system., Results: 130 subjects died within 30 days after stroke, with an overall mortality of 27.7%. At univariate analysis, altered levels of consciousness (ALC), congestive heart failure, atrial fibrillation, previous stroke, high blood glucose, fibrinogen and blood sedimentation rate levels, higher white blood cell count, lower serum albumin and iron levels were associated with mortality. Multivariate logistic regression analysis indicated that short-term mortality was associated with ALC (OR: 11.80; CI 95%: 5.50-24.00), congestive heart failure (OR: 3.06; CI 95%: 1.04-8.80), and age (OR: 1.04; CI 95%: 1.002-1.09) independent of gender, previous stroke, AF, fasting blood glucose, serum albumin, serum iron, and white blood cell count. In patients with ALC (high-mortality rate: 63.6%), only hyperglycemia (III vs. I tertile, OR: 9.60; CI 95%: 1.65-52.50) was associated with mortality after multivariate adjustment., Conclusion: Our study highlights the role of ALC and congestive heart failure in the short-term prognostic stratification of older patients with acute ischemic stroke. Furthermore, our results support the value of post-stroke hyperglycemia as a marker for short-term mortality also in advanced age, and particularly in the presence of ALC and in nondiabetic individuals.

Objectives: To study the association between performance on psychological tests of executive function and performance on lower extremity tasks with different attentional demands in a large sample of nondemented, older adults., Design: Cross-sectional study., Setting: Community-based., Participants: Nine hundred twenty-six persons aged 65 and older, without dementia, stroke, parkinsonism, visual impairment, or current treatment with neuroleptics, enrolled in a large epidemiological study., Measurements: Trail Making Test (TMT) parts A and B and two performance-based measures of lower extremity function that require different executive/attentional-demanding skills: walking speed on a 4-m course at usual pace and walking speed on a 7-m obstacle course at fast pace. A difference score (Delta TMT), obtained by subtracting time to perform part A from time to perform part B of the TMT, was used as an indicator of executive function. Based on Delta TMT, subjects were divided into poor performance, intermediate performance, and good performance., Results: After adjustment, no association between Delta TMT and 4-m course usual-pace walking speed was found. Participants with poor Delta TMT and with intermediate Delta TMT performance were more likely to be in the lowest tertile for 7-m obstacle course walking speed., Conclusion: In nondemented older persons, executive function is independently associated with tasks of lower extremity function that require high attentional demand.

Background and Aim: Inherited hypercholesterolemias are common disorders characterised by elevated LDL-C levels and premature coronary heart disease. We have recently described a recessive form of hypercholesterolemia (autosomal recessive hypercholesterolemia, ARH) in which LDL catabolism is reduced because of a mutation in the gene coding for an adaptor protein that impairs LDL-receptor (LDL-R) activity in the liver. The aim of this study was to characterise in detail the phenotypes of subjects with homozygous and heterozygous ARH., Methods and Results: We have so far identified six Italian families with ARH and studied the clinical and biochemical characteristics of 11 homozygotes (age 13-47 years) and 12 obligate heterozygotes (age 42-83 years). The study protocol included an evaluation of the lipoprotein profile, LDL-R activity in fibroblasts, LDL binding activity, and apo E genotype; a structured questionnaire (CHD risk factors, medical history, current medications); a physical examination, resting and stress ECG, ultrasound examinations (heart, carotid arteries, Achilles tendons) and coronary angiography. The pedigrees were characterised by the absence of vertical transmission; consanguinity was documented in two families. Only the two previously described Sardinian mutations, ARH1 (c.432insA) and ARH2 (c.65G > A), were identified in the probands. All of the ARH homozygotes had large tendinous xanthomas, two had exertional angina, and four a positive stress ECG. None had experienced myocardial infarction or stroke. More than half had instrumental signs of atherosclerosis such as a positive stress ECG or positive carotid echo-doppler examination. The ARH heterozygotes were consistently normal and had a normal lipid profile., Conclusions: The ARH phenotype resembles that of familial hypercholesterolemia (FH) homozygotes, but ARH may be a less serious illness. The absence of vertical transmission, and the presence of mild coronary heart disease and consanguinity, can suggest a possible diagnosis of ARH. ARH might be considered a phenocopy of FH but heterozygous subjects seem to have a consistently normal phenotype.

Background: Autosomal recessive hypercholesterolaemia (ARH) is caused by mutations in a putative adaptor protein called ARH. This recessive disorder, characterised by severe hypercholesterolaemia, xanthomatosis, and premature coronary artery disease, is rare except on the island of Sardinia, Italy. Our aim was to ascertain why ARH is more common on Sardinia than elsewhere., Methods: We obtained detailed medical histories, did physical examinations, measured concentrations of lipoproteins, and harvested genomic DNA from 28 Sardinians with ARH from 17 unrelated families. We sequenced the coding regions and consensus splice sites of ARH in probands from these families, and from 40 individuals of non-Sardinian origin who had an autosomal recessive form of hypercholesterolaemia of unknown cause., Findings: Two ARH mutations, a frameshift mutation (c432insA) in exon 4 (ARH1) and a nonsense mutation (c65G-->A) in exon 1 (ARH2), were present in all of the 17 unrelated families with ARH. Three of the ARH alleles contained both mutations, as a result of an ancient recombination between ARH1 and ARH2. No regional clustering of the three mutant alleles within Sardinia was apparent. Furthermore, four Italians from the mainland with autosomal recessive hypercholesterolaemia were homozygous for ARH1., Interpretation: The small number, high frequency, and dispersed distribution of ARH mutations on Sardinia are consistent with these mutations being ancient and maintained in the Sardinian population because of geographic isolation.

Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to an approximately 1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.

Objectives: To assess whether systemic oxidative stress can predict the risk of first myocardial infarction, ischemic stroke, and congestive heart failure., Design: A longitudinal study started in 1992 and completed in 1997., Setting: Community-based, outpatient., Participants: 102 apparently healthy, community-dwelling subjects age 80 and older from the Vibrata valley, Teramo, Italy., Measurements: Plasma vitamin E, beta-carotene, vitamin C, fluorescent products of lipid peroxidation (FPLPs), and serum lipids were determined at enrollment., Results: Thirty-two cardiovascular events were recorded in 47.4 months of follow-up. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile (relative risk (RR) = 0.16; 95% confidence interval (CI) = 0.04-0.55). The subjects with FPLPs in the highest quartile had a risk seven times greater than those with FPLPs in the lowest quartile (RR = 7.61; 95% CI = 2.23-25.96). No association was observed for vitamin C, beta-carotene, or total cholesterol. Multivariate adjustment for known risk factors did not significantly change the results., Conclusions: Our results suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E and FPLPs predicts the risk of future cardiovascular events. We confirm previous data showing that total cholesterol is not a predictor of cardiovascular disease in people age 80 and older.

Besides functional impairment, several factors have been associated with mortality in institutionalized older subjects, including advanced age, gender, comorbidity, and malnutrition. We investigated the possible association of a large number of factors, including functional, anthropometric, nutritional, metabolic, clinical, and demographic variables, with two-year all-cause mortality in a sample of 344 institutionalized older subjects (> or = 65 years) without evidence of acute illness at the time of observation. Although a number of factors were associated with mortality risk, multivariate analysis showed that only severe disability (6 vs 0-1 lost ADL, O.R.: 3.37, C.I. 95%: 1.76-7.3) and low albumin levels (lowest vs highest tertile: O.R.: 3.0, C.I. 95%: 1.65-5.43) were independent predictors of outcome. Moreover, in the analysis stratified for degree of disability and albumin tertiles, we found a strong gradient in mortality risk with increasing disability and decreasing albumin levels. These results further support the value of these two simple parameters in identifying frail institutionalized older individuals.

Background: The total cholesterol concentration decreases with age in older people. The reasons for this phenomenon are controversial. This study investigated the hypothesis that poor health status is a determinant of the inverse association between age and cholesterol in older persons., Methods: Cross-sectional study of 2,486 (53% women) older medical patients (> or =65 years) admitted at 35 centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study in Italy. Total cholesterol was measured on the first day after admission to the hospital. Disease burden and comorbidity were assessed by the Charlson index; low serum albumin and iron were considered markers of frailty and poor health., Results: In men there was a significant, inverse age-cholesterol relationship (-0.97 mg/dl per year, p<0.001). In women the association was nonlinear and cholesterol significantly decreased after the age of 75 (-0.95 mg/dl per year, p<0.005). In multiple linear regression analysis, indicators of poor health accounted for almost two thirds of the crude effect of age on the cholesterol level in both men and women (adjusted coefficients for age were: for men, -0.38 mg/dl per year, p = 0.044; for women after the age of 75, -0.37 mg/dl per year, p = 0.205). The unadjusted probability of having low cholesterol significantly increased with age among men (p for trend <0.005). In multiple logistic regression, indicators of poor health were strongly associated with low cholesterol in both men and women. After adjusting for indicators of poor health, the association between age and low cholesterol in men was no longer present., Conclusion: These findings suggest that the age-dependent reduction of cholesterol often observed in clinical and epidemiologic studies is substantially explained by the effect of poor health status. Low cholesterol in older persons may be a marker of poor health., (Copyright 2001 S. Karger AG, Basel.)

In recent years, the use of benzodiazepines has been recognized as an independent risk factor for falls among the elderly. To evaluate the role of different types of benzodiazepines in determining falls in a hospitalized geriatric population, we conducted a prospective study among 7908 patients consecutively admitted in 58 clinical centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA), during an 8-month observation period (1991 and 1993). Over 70% of the patients were older than 65 years, 50% were women, and 23. 6% had a benzodiazepine prescription during hospital stay. The number of patients who experienced one or more falls during follow-up was 174 (2.2%). Sixty falls occurred among patients taking benzodiazepines (3.2%) and 114 (1.9%) among those who did not use benzodiazepines; the crude odds ratio for users versus non-users was 1.7 (95% CI 1.2-2.3). Multivariate logistic regression analysis showed that benzodiazepines with very short (OR 1.9; CI 1.03-3.3) and short half-life (OR 1.8; CI 1.2-2.8) were positively associated with falls during hospital stay. Patients who used other psychotropic agents (OR 2.3; CI 1.7-3.4), antidiabetic agents (OR 1. 5; CI 1.03-2.2), patients with presence of cognitive impairment (OR 1.6; CI 1.08-2.3), high level of comorbidity (OR 1.7; CI 1.05-2.9), more advanced age (>80 years, OR 2.7; CI 1.5-4.7) and those who stayed in the hospital for 17 days or more (OR 2.1; CI 1.4-3.3) were also at a greater risk. These findings suggest that benzodiazepines with short and very short half-life are an important and independent risk factor for falls and their prescription to elderly hospitalized patients should be carefully evaluated.

High serum cholesterol is an established risk factor for cardiovascular disease and is the prime target for therapeutic intervention in large groups of patients. The development of modern treatments for this major risk factor was propelled by the early realization that forms of severe hypercholesterolemia could be caused by dominantly inherited defects in the LDL receptor or in the APOB gene. Further understanding of the mechanisms contributing to early atherosclerosis will allow for new targets for therapy. We therefore identified and investigated the genetics of families from Sardinia that have recessive inheritance of precocious hypercholesterolemia. We used five families in an analysis of linkage of the autosomal recessive hypercholesterolemia locus, termed "ARH1," to chromosome 15q25-q26. A genomewide search mapped the disease-causing gene with a LOD score of 3.3 and excluded major contributions to the phenotype of other genes. A candidate gene present in the mapped chromosome region-the ligand-activated liver-transcription-factor gene ARP1 (apolipoprotein regulatory-protein gene)-has been excluded after DNA sequencing. The close-bred nature of the Sardinian population offers unique opportunities for isolation of this hypercholesterolemia-causing gene.

Background: Several epidemiological studies have documented the presence of a 'J' or 'U' association between total cholesterol levels and total mortality. Not only the mechanism underlying the association between increased mortality and low total cholesterol values is not completely clear, but the relationship itself also appears to be complex in the elderly., Objective: The aim of the study was to evaluate the possible association between some biohumoral markers of the acute phase, comorbidity, disability, and reduced levels of some lipoprotein parameters in a sample of hospitalized elderly subjects., Methods: 341 patients over 65 years of age (185 males, 156 females; mean age 76.2 years), consecutively admitted to our department from 1994 to 1995, were studied. Acute phase was defined as the simultaneous presence of: (1) increased alpha2-plasma protein on electrophoresis (>12%); (2) high fibrinogen concentration (>450 mg/dl), and (3) increased blood sedimentation rate (>15 and >20 mm 1 h in males and females, respectively)., Results: The prevalence of signs of acute phase was higher in males and in the youngest patients, but did not change with the level of comorbidity. Patients with signs of acute phase were characterized by lower total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol levels compared to subjects without signs of acute phase; this difference was significant even after adjustment for indicators of comorbidity, disability, and nutritional status. Multivariate logistic regression analysis evidenced that the simultaneous presence of these three markers of acute phase was independently associated with low levels of total cholesterol [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1 - 3.9], and HDL-cholesterol (OR 2.3, 95% CI 1.2 - 4.2), considered as the sex-specific first quintile., Conclusion: The findings of this study demonstrate an independent association between acute phase markers and low levels of total and HDL-cholesterol, suggesting that recognized or subclinical diseases in elderly patients may determine a reduction in these plasma lipids. Low level of total and HDL-cholesterol should be considered as possible clinical markers of an underlying state of acute phase rather than a sign of malnutrition. Given the high prevalence of chronic diseases in the elderly, epidemiological studies addressing the lipid profile in this age group should take into account the possible confounding effect of the presence of signs of acute phase.

Circulating thyroid autoantibodies were assessed in a sample of Italian octo-nonagenarians living in a restricted area (Val Vibrata, Abruzzo), and selected according to the absence or presence of chronic illness and disability. The study groups included: Group A ("Successful aging"), 98 free-living healthy, fully independent, octo-nonagenarians (57 males and 41 females, average age +/-SD 83.9+/-3 years); Group B ("Unsuccessful aging"), 62 highly disabled octo-nonagenarians (24 males and 38 females; average age 86.5+/-3.4 years), and Group C (Controls), 91 randomly selected healthy adult controls (42 males and 49 females; age 53.7+/-16.6 SD years, range 20-70). Serum autoantibodies to thyroglobulin (anti-Tg) and to thyroid peroxidase (anti-TPO) were measured by passive hemagglutination and radioimmunoassays (RIA); serum free thyroxine and thyrotropin by RIA. The prevalence of positive thyroid autoantibody tests was not significantly increased in the elderly groups compared to the controls, with the remarkable exception of anti-Tg detected by RIA which were increased in disabled elderly, compared to free-living elderly and controls. Two/62 disabled elderly had subclinical (1) or mild (1) primary hypothyroidism, and one free-living woman aged 90 years was hyperthyroid (toxic nodular goiter). No correlation was found between serum thyroid autoantibodies, thyroid hormones and TSH and serum lipoprotein fractions. The higher prevalence of thyroid autoantibodies found only in disabled, but not in free-living Italian octo-nonagenarians suggests that thyroid autoimmune phenomena in the elderly may be an expression of age-associated disease rather than related to the aging process in itself.

Several factors, such as disability, malnutrition, weight loss, and the interactive effect of diseases and aging have been associated with morbidity and mortality in the elderly population. Nevertheless, the relationship between disability and biological parameters has not been extensively investigated as a primary focus. In a cross sectional survey, 344 institutionalized elderly subjects were evaluated. Disability was measured according to the Katz index, and patients were divided into three groups: low (0-1 lost ADL), mild (2-4 lost ADL), and severe (5-6 lost ADL). Anthropometric, metabolic, and nutritional parameters were assessed; age, gender, number of pathologies, and number of drugs were also recorded. Data were analyzed by multiple comparison of means according to Scheffé, and by multivariate logistic regression analysis. An impairment in functional status was associated with several modifications in biological parameters. Logistic regression analysis showed that severe disability (5-6 lost ADL) was associated with low waist/hip ratio (< 0.9 vs > 0.9, OR: 1.56, CI 95%: 1.08-2.25), high body resistance (> 625 vs < 575 omega, OR: 1.39, CI 95%: 1.38-1.39), low plasma albumin levels (< 3.5 vs > 4.0 g/dL, OR: 6.02, CI 95%: 5.18-6.85), and low plasma transferrin levels (< 200 vs > 250 mg/dL, OR: 5.47, CI 95%: 4.56-4.58) independently of age, gender, comorbidity, and other confounding factors. Our results indicate that severe disability in ADL is strongly associated with anthropometric and biohumoral parameters suggesting the presence of malnutrition. A careful evaluation of the nutritional state appears to be of primary importance, and efforts to improve nutritional status are needed in approaching disabled elderly patients.

We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with similar characteristics was identified. Probands showed severe hypercholesterolemia, whereas their parents and grandparents were normolipidemic. FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester storage disease were excluded by in vitro studies. We addressed the metabolic basis of this inherited disorder by studying the in vivo metabolism of LDL in 3 probands from these 2 families. 125I-LDL turnover studies disclosed a marked reduction in the fractional catabolic rate (0.19+/-0.01 versus 0.36+/-0.03 pools per day, respectively; P<0.001) and a significant increase in the production rate [20.7+/-4.4 versus 14. 0+/-2.4 mg. kg-1. d-1, respectively; P<0.01] of LDL apoB in the probands compared with normolipidemic controls. We then studied the in vivo biodistribution and tissue uptake of 99mtechnetium-labeled LDL in the probands and compared them with those in normal controls and 1 FH homozygote. The probands showed a significant reduction in hepatic LDL uptake, similar to that observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen was also observed in all patients. Our findings suggest that this recessive form of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism. This appears to be caused by a selective reduction in hepatic LDL uptake. We propose that in this new lipid disorder, a recessive defect causes a selective impairment of LDL receptor function in the liver.

Cardiovascular diseases are the leading cause of disability and mortality in western countries. Lipoprotein(a) [Lp(a)] is now considered an independent risk factor for atherosclerosis, and might consequently be related to longevity and/or disability. In the context of a study on metabolic and anthropometric parameters in a sample of Italian octo-nonagenarians, Lp(a) and apo(a) isoforms were evaluated. One-hundred and fifty Italian octo-nonagenarians were classified as free-living or disabled, according to Katz's index, and compared to 91 healthy control adults. All the study subjects were recruited from a valley (Val Vibrata valley) near Teramo, in the central part of Italy. The median Lp(a) concentration of the whole group was 17 mg/dL (range 1-161 mg/dL), which is much higher than the values observed in Caucasian populations. No differences were detected between the octo-nonagenarian group (median 16 mg/dL, range 1-126 mg/dL) and the control group (median 19.5 mg/dL, range 1-161 mg/dL), nor between the free-living and the disabled groups. Apo(a) isoforms were similarly distributed among free-living, disabled and control subjects. While our findings suggest that Lp(a) plasma levels and apo(a) isoforms are not factors associated with longevity or disability, we cannot exclude that the low incidence of other major risk factors for atherosclerosis in our free-living octo-nonagenarians hampered the full expression of the lipoprotein(a) atherogenic potential, and thus allowed the achievement of a very old age in a good healthy status, even in carriers of high Lp(a) levels or small apo(a) isoforms.

A family presenting several cases of severe primary hypercholesterolaemia and/or premature sudden death was studied. This family is characterized by consanguinity, absence of vertical transmission, bimodal distribution of plasma cholesterol values, and reduction of reproductive fitness in affected individuals. The probands have clinical traits of homozygous familial hypercholesterolaemia, including hypercholesterolaemia, xanthomas and early coronary atherosclerosis, while the parents and grandparents are clinically normal. Eight relatives on the mother's side experienced premature sudden death, and in four cases hypercholesterolaemia was diagnosed. Haplotype segregation analysis of the inheritance of the LDL receptor and apo B genes in the probands' family excluded the involvement of these two genes in the pathogenesis of the disease. LDL receptor activity, as well as the ability of LDL to bind to the LDL receptor, and plasma vegetal sterols were within normal limits both in probands and in their relatives. The study of this pedigree suggests that hypercholesterolaemia is not produced by defects in the LDL receptor or LDL particles, and disease inheritance is consistent with an autosomal recessive trait.

This retrospective study concerns 537 adolescent pregnant patients followed at the 1st Dep. of Obst. and Gyn. during the time period 1984-87. Preeclampsia, preterm labor and neonatal mortality were more frequent than in the general population.

"Multiple Correspondence Analysis was used to describe the complex structure formed by those sociodemographic variables, whose association with the occurrence of prenatal and neonatal deaths and diseases has been most frequently stressed in literature: social class, prenatal care, maternal age and parity. The study regards 41,537 women included in a multicentre survey of perinatal preventive medicine, which was carried out, between 1973 and 1979, in six Italian centres...." It is found that "in all centres there are distinct groups of women characterized by a set of unfavourable factors closely interrelated: low social class implies lower prenatal care, higher occurrence of precocious or belated childbearing and higher number of pregnancies, often unintended." (SUMMARY IN FRE AND ITA), (excerpt)

Fetal risk related to cordocentesis has been analyzed on a series of 222 ultrasound-guided fetal blood samplings for prenatal diagnosis of fetal diseases during the second trimester of pregnancy. Affected and malformed fetuses were excluded. Seven intrauterine deaths (3.2%) and 2 spontaneous abortions (0.9%) were observed. These figures proved higher than those observed in non-homogeneous series which consider the second and third trimester altogether. The fetal risk was significantly correlated with gestational age (less than 18 weeks 7.6% vs greater than 18 weeks 0.7% p = .02) and duration of the procedure (greater than 10'11.4% vs = less than 10'0.9% p = .0029). The number of abdominal insertions resulted in different death rates (greater than 1 ins. = 6.5% vs 1 ins. = 1.4%). It is likely that different developmental, anatomical and neurovegetative mechanism play a significant role in the risk rate found in the second trimester cordocentesis. These findings and the specific risk factors observed within the different technical conditions reported, must be taken into consideration for prenatal counseling.