To investigate frailty state transitions in a cohort of older Italian adults to identify factors exacerbating or improving frailty conditions. Design: Population-based longitudinal study with mean follow-up of 4.4 years. Setting: Community. Participants: Individuals enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,925; n = 1,179 male, n = 1,746 female; mean age 74.4 ± 7.3). Measurements: Frailty was identified at baseline and follow-up based on the presence of at least three Fried criteria; prefrailty was defined as the presence of one or two Fried criteria. Anthropometric, socioeconomic, and clinical characteristics were assessed at baseline in a personal interview and clinical examination using validated scales and medical history. During the study period, 1,114 (38.1%) subjects retained their baseline frailty status, 1,066 (36.4%) had a transition in frailty status, and the remainder of the sample died. Older age, female sex, obesity, cardiovascular disease, osteoarthritis, smoking, loss of vision, low levels of self-sufficiency and physical performance, cognitive impairment, hypovitaminosis D, hyperuricemia, and polypharmacy were associated with increasing frailty and greater mortality. Conversely, overweight, low to moderate drinking, high educational level, and living alone were associated with decreasing frailty. Frailty was confirmed as a dynamic syndrome, with socioeconomic and clinical factors that could be targets of preventive actions influencing transitions to better or worse frailty status

Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 ؎ 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n ‫؍‬ 360) or therapeutic (n ‫؍‬ 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.

No abstract

The prevalence of edentulism among the elderly Italian population studied was at the high end among Western countries, and higher in women than in men. In women, tooth loss correlated with aging, female events (pregnancies, menopausal status), and living alone. In men, aging and smoking are important determinants of edentulism, which is associated with the risk condition of hypoalbuminemia. Difficulty in chewing was associated with dentition type. In our study, the high prevalence of edentulous subjects without prostheses suggests a need for educational and social measures to improve patients' attitudes to dental care and to encourage the use of prostheses among the elderly.

Our findings suggest that pre-frailty, which is potentially reversible, is independently associated with a higher risk of older adults developing CVD. Among the physical domains of pre-frailty, low gait speed seems to be the best predictor of future CVD.

High prevalence and low female/male ratio for validated centenarians are observed in Sardinia and these findings appear to be thus far unique to this island. Moreover a specific region on the island is characterized by exceptional male longevity. We calculated the extreme longevity index (ELI), defined as the percentage of persons born in Sardinia between 1880 and 1900, who became centenarians. A gaussian smoothing method was used in order to identify the so-called 'Blue Zone', where longevity is concentrated in the central-eastern part of the island and covers all the mountainous areas of central Sardinia. The estimated life expectancy in the 'Blue Zone' is longer than in the remaining territory of the island especially for men and the male to female ratio among centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia. The specific mechanism by which persons living in this territory were more likely to reach extreme longevity remains unknown but it is interesting to note that most of the 'longevity hot spots' identified in various regions of the world over the years have been located in mountainous geographical areas even if none of these longevity regions have been fully validated. An alternative and interesting hypothesis is that the high rate of inbreeding determined by frequent marriages between consanguineous individuals and low immigration rates have progressively decreased the variability of the genetic pool and facilitated the emergence of genetic characteristics that protect individuals from diseases that are major causes of mortality particularly in older individuals. Given the exceptionally high prevalence of male centenarians in the 'Blue Zone', it is reasonable to assume that either the environmental characteristics or the genetic factors, or both, exert their favorable effect more strongly in men than in women. Thus, the mechanism involved may be modulated by the hormonal milieu, or may be associated with genes located in the sex chromosomes.

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene–environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases.

Gender-specific medicine is the study of how diseases differ between men and women in terms of prevention, clinical signs, therapeutic approach, prognosis, psychological and social impact. It is a neglected dimension of medicine. In this review we like to point out some major issues in five enormous fields of medicine: cardiovascular diseases (CVDs), pharmacology, oncology, liver diseases and osteoporosis.CVDs have been studied in the last decades mainly in men, but they are the first cause of mortality and disability in women. Risk factors for CVD have different impacts in men and women; clinical manifestations of CVD and the influence of drugs on CVD have lot of gender differences. Sex-related differences in pharmacokinetics and pharmacodynamics are also emerging. These differences have obvious relevance to the efficacy and side effect profiles of various medications in the two sexes. This evidence should be considered for drug development as well as before starting any therapy. Gender disparity in cancer incidence, aggressiveness and prognosis has been observed for a variety of cancers and, even if partially known, is underestimated in clinical practice for the treatment of the major types of cancer. It is necessary to systematize and encode all the known data for each type of tumor on gender differences, to identify where this variable has to be considered for the purposes of the prognosis, the choice of treatment and possible toxicity. Clinical data suggest that men and women exhibit differences regarding the epidemiology and the progression of certain liver diseases , i.e., autoimmune conditions, genetic hemochromatosis, non-alcoholic steatohepatitis and chronic hepatitis C. Numerous hypotheses have been formulated to justify this sex imbalance including sex hormones, reproductive and genetic factors. Nevertheless, none of these hypothesis has thus far gathered enough convincing evidence and in most cases the evidence is conflicting. Osteoporosis is an important public health problem both in women and men. On the whole, far more epidemiologic, diagnostic and therapeutic studies have been carried out in women than in men. In clinical practice, if this disease remains underestimated in women, patients ' and physicians ' awareness is even lower for male osteoporosis, for which diagnostic and therapeutic strategies are at present less defined.In conclusion this review emphasizes the urgency of basic science and clinical research to increase our understanding of the gender differences of diseases.