D'Onofrio G.,Geriatric Unit |
Panza F.,Geriatric Unit |
Frisardi V.,Geriatric Unit |
Solfrizzi V.,University of Bari |
And 6 more authors.
Expert Opinion on Drug Discovery | Year: 2012
Introduction: In an attempt of altering the natural history of Alzheimer's disease (AD), several compounds have been developed with the aim of inhibiting γ-secretase, the enzymatic complex generating β-amyloid (Aβ) peptides (Aβ1 40 and Aβ1 42), from amyloid precursor protein (APP). APP is believed to be involved in the pathophysiological cascade of AD. Areas covered: This article briefly reviews the profile of γ-secretase inhibitors that have reached the clinic. The paper reviews studies from the primary English literature on γ-secretase inhibitors published before November 2011, searching through the PubMed database of NCBI by author and the following keywords: drugs targeting β-amyloid, γ-secretase inhibitors, dementia syndromes and Alzheimer's disease. Expert opinion: Studies in both transgenic and non-transgenic animal models of AD have indicated that γ-secretase inhibitors, administered by the oral route, are able to lower brain Aβ concentrations. However, scanty data are available on the effects of these compounds on brain Aβ deposition after prolonged administration. γ-Secretase inhibitors may cause significant toxicity in experimental animals and in humans believed to be associated with the inhibition of the cleavage of Notch, a transmembrane receptor involved in regulating cell-fate decisions. Unfortunately, two large Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effects of the drug, possibly due to its lack of selectivity on APP processing. New APP-selective γ-secretase inhibitors are being developed with the hope of overcoming the previous setbacks. © 2012 Informa UK, Ltd.
Artaza-Artabe I.,Igurco Servicios Socio Sanitarios |
Saez-Lopez P.,Geriatrics Unit |
Sanchez-Hernandez N.,Unit of Orthopaedics Surgery |
Fernandez-Gutierrez N.,Igurco Servicios Socio Sanitarios |
Malafarina V.,Clinica Los Manzanos
Maturitas | Year: 2016
Background: Frailty is a geriatric syndrome that predicts the onset of disability, morbidity and mortality in elderly people; it is a state of pre-disability and is reversible.The aim of this review is to assess how nutrition influences both the risk of developing frailty and its treatment. Data sources: We searched two databases, PubMed and Web of Science. We included epidemiologic studies and clinical trials carried out on people aged over 65 years. We included 32 studies with a total of over 50,000 participants. Results: The prevalence of frailty is ranges from 15% among elderly people living in the community to 54% among those hospitalized. Furthermore, the prevalence of frailty is disproportionately high among elderly people who are malnourished. Malnutrition, which is very prevalent in geriatric populations, is one of the main risk factors for the onset of frailty.A good nutritional status and, wherever necessary, supplementation with macronutrients and micronutrients reduce the risk of developing frailty. Physical exercise has been shown to improve functional status, helps to prevent frailty and is an effective treatment to reverse it. Despite the relatively large number of studies included, this review has some limitations. Firstly, variability in the design of the studies and their different aims reduce their comparability. Secondly, several of the studies did not adequately define frailty. Conclusions: Poor nutritional status is associated with the onset of frailty. Screening and early diagnosis of malnutrition and frailty in elderly people will help to prevent the onset of disability. Effective treatment is based on correction of the macro- and micronutrient deficit and physical exercise. © 2016 Elsevier Ireland Ltd.
PubMed | Clinica Los Manzanos, Unit of Orthopaedics Surgery, Igurco Servicios Socio Sanitarios and Geriatrics Unit
Type: | Journal: Maturitas | Year: 2016
Frailty is a geriatric syndrome that predicts the onset of disability, morbidity and mortality in elderly people; it is a state of pre-disability and is reversible. The aim of this review is to assess how nutrition influences both the risk of developing frailty and its treatment.We searched two databases, PubMed and Web of Science. We included epidemiologic studies and clinical trials carried out on people aged over 65 years. We included 32 studies with a total of over 50,000 participants.The prevalence of frailty is ranges from 15% among elderly people living in the community to 54% among those hospitalized. Furthermore, the prevalence of frailty is disproportionately high among elderly people who are malnourished. Malnutrition, which is very prevalent in geriatric populations, is one of the main risk factors for the onset of frailty. A good nutritional status and, wherever necessary, supplementation with macronutrients and micronutrients reduce the risk of developing frailty. Physical exercise has been shown to improve functional status, helps to prevent frailty and is an effective treatment to reverse it. Despite the relatively large number of studies included, this review has some limitations. Firstly, variability in the design of the studies and their different aims reduce their comparability. Secondly, several of the studies did not adequately define frailty.Poor nutritional status is associated with the onset of frailty. Screening and early diagnosis of malnutrition and frailty in elderly people will help to prevent the onset of disability. Effective treatment is based on correction of the macro- and micronutrient deficit and physical exercise.
Pilotto A.,S Antonio Hospital |
Noale M.,CNR Institute of Neuroscience |
Maggi S.,CNR Institute of Neuroscience |
Addante F.,Geriatrics Unit |
And 4 more authors.
BioMed Research International | Year: 2014
Aim. To identify the characteristics associated with multidimensional impairment, evaluated through the Multidimensional Prognostic Index (MPI), a validated predictive tool for mortality derived from a standardized Comprehensive Geriatric Assessment (CGA), in a cohort of elderly diabetic patients treated with oral hypoglycemic drugs. Methods and Results. The study population consisted of 1342 diabetic patients consecutively enrolled in 57 diabetes centers distributed throughout Italy, within the Metabolic Study. Inclusion criteria were diagnosis of type 2 diabetes mellitus (DM), 65 years old or over, and treatment with oral antidiabetic medications. Data concerning DM duration, medications for DM taken during the 3-month period before inclusion in the study, number of hypoglycemic events, and complications of DM were collected. Multidimensional impairment was assessed using the MPI evaluating functional, cognitive, and nutritional status; risk of pressure sores; comorbidity; number of drugs taken; and cohabitation status. The mean age of participants was 73.3 ± 5.5 years, and the mean MPI score was 0.22 ± 0.13. Multivariate analysis showed that advanced age, female gender, hypoglycemic events, and hospitalization for glycemic decompensation were independently associated with a worse MPI score. Conclusion. Stratification of elderly diabetic patients using the MPI might help to identify those patients at highest risk who need better-tailored treatment. © 2014 A. Pilotto et al.
Lubrano E.,University of Molise |
Spadaro A.,University of Rome La Sapienza |
Amato G.,U.O. of Rheumatology |
Benucci M.,Hospital Sgiovanni Of Dio |
And 13 more authors.
Seminars in Arthritis and Rheumatism | Year: 2015
Objectives: To systematically review the evidence for a synergistic effect of combining rehabilitation with biological anti-tumour necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS). Methods: Data were analysed to identify the most effective rehabilitation programmes, the best endpoints for effectiveness, and patient subgroups most likely to benefit from combination therapy. Systematic MEDLINE and Embase searches were performed to identify studies evaluating rehabilitation programmes and biological therapy in patients with AS. Evidence was categorised by study type, and efficacy, adverse effects and other outcomes were summarised. Results: Of the 75 studies identified, 13 investigated the combination of a rehabilitation programme with TNF inhibitor therapy, while the remainder studied rehabilitation with standard therapy (often not specified). Data from these few studies suggest that combined rehabilitation plus anti-TNF therapy is more effective in terms of symptom severity, disease activity, disability and quality-of-life indices versus biologic alone or rehabilitation with standard medical therapy, or, in non-comparative studies, compared with baseline. The most effective rehabilitation appears to be supervised or in-patient programmes with an educational component. Available data do not provide guidance on most appropriate endpoints or identify patients most likely to benefit from combination therapy. Combined, TNF inhibitor and rehabilitation therapy appear to have a synergistic effect, possibly due to increased adherence to exercise. Exercise regimes are more effective if supervised and include an education component. Conclusions: Further randomized, controlled trials comparing endpoints and investigating longer-term benefits of combining TNF inhibitors with rehabilitation in different AS subgroups are needed. © 2014 Elsevier Inc.
Liem I.S.,Innsbruck Medical University |
Kammerlander C.,Innsbruck Medical University |
Suhm N.,University of Basel |
Blauth M.,Innsbruck Medical University |
And 13 more authors.
Injury | Year: 2013
Background and purpose: Osteoporotic fractures are an increasing problem in the world due to the ageing of the population. Different models of orthogeriatric co-management are currently in use worldwide. These models differ for instance by the health-care professional who has the responsibility for care in the acute and early rehabilitation phases. There is no international consensus regarding the best model of care and which outcome parameters should be used to evaluate these models. The goal of this project was to identify which outcome parameters and assessment tools should be used to measure and compare outcome changes that can be made by the implementation of orthogeriatric co-management models and to develop recommendations about how and when these outcome parameters should be measured. It was not the purpose of this study to describe items that might have an impact on the outcome but cannot be influenced such as age, co-morbidities and cognitive impairment at admission. Methods Based on a review of the literature on existing orthogeriatric co-management evaluation studies, 14 outcome parameters were evaluated and discussed in a 2-day meeting with panellists. These panellists were selected based on research and/or clinical expertise in hip fracture management and a common interest in measuring outcome in hip fracture care. Results: We defined 12 objective and subjective outcome parameters and how they should be measured: mortality, length of stay, time to surgery, complications, re-admission rate, mobility, quality of life, pain, activities of daily living, medication use, place of residence and costs. We could not recommend an appropriate tool to measure patients' satisfaction and falls. We defined the time points at which these outcome parameters should be collected to be at admission and discharge, 30 days, 90 days and 1 year after admission. Conclusion: Twelve objective and patient-reported outcome parameters were selected to form a standard set for the measurement of influenceable outcome of patients treated in different models of orthogeriatric co-managed care. © 2013 Elsevier Ltd. All rights reserved.
D'Onofrio G.,Geriatric Unit and Laboratory of Gerontology and Geriatrics |
Sancarlo D.,Geriatric Unit and Laboratory of Gerontology and Geriatrics |
Addante F.,Geriatric Unit and Laboratory of Gerontology and Geriatrics |
Ciccone F.,Geriatric Unit and Laboratory of Gerontology and Geriatrics |
And 10 more authors.
International Journal of Geriatric Psychiatry | Year: 2015
Objective To evaluate in a pilot single-blind randomized controlled clinical trial the efficacy of an integrated treatment with rivastigmine transdermal patch (RTP) and cognitive stimulation (CS) in Alzheimer's disease (AD) patients at 6-month follow-up. Methods We enrolled 90 patients with an age ≥65years admitted to the outpatient Alzheimer's Evaluation Unit with diagnosis of AD. Patients were randomized to enter in the Group-1 (RTP+CS) or in the Group-2 (RTP). All patients at baseline and after 6months were evaluated with the following tools: Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression (HAM-D), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-Distress (NPI-D), and a standardized Comprehensive Geriatric Assessment, including also activities of daily living (ADL), instrumental activities of daily living (IADL), and the Mini Nutritional Assessment (MNA). Mortality risk was assessed using the Multidimensional Prognostic Index (MPI). Results At baseline no significant difference was shown between the two groups. After 6months of follow-up, there were significant differences between Group-1 and Group-2 in: MMSE: +6.39% vs. +2.69%, CDR: +6.92% vs. +1.54%, HDRS-D=-60.7% vs. -45.8%, GDS: -60.9% vs. -7.3%, NPI: -55.2% vs. -32.7%%, NPI-D: -55.1% vs. -18.6%, ADL: +13.88% vs. +5.95%, IADL: +67.59% vs. +18.28%, MNA: +12.02% vs. +5.91%, and MPI: -29.03% vs. -12.90%. Conclusion The integrated treatment of RTP with CS in AD patients for 6months improved significantly cognition, depressive and neuropsychiatric symptoms, functional status, and mortality risk in comparison with a group of AD patients receiving only RTP. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
Volpato S.,University of Ferrara |
Bazzano S.,Geriatrics Unit |
Bazzano S.,Geriatric Gerontology Research Unit |
Fontana A.,Scientific Institute for Research and Care |
And 3 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2015
Background: The Multidimensional Prognostic Index (MPI) is a validated predictive tool for long-term mortality based on information collected in a standardized Comprehensive Geriatric Assessment. We investigated whether the MPI is an effective predictor of intrahospital mortality and length of hospital stay after admission to acute geriatric wards. Methods: Prospective study of 1,178 older patients (702 women and 476 men, 85.0 ± 6.8 years) admitted to 20 geriatrics units. Within 48 hours from admission, the MPI, according to an earlier validated algorithm, was calculated. Subjects were divided into three groups of MPI score, low-risk (MPI-1 value. 0.33), moderate-risk (MPI-2 value 0.34.0.66), and severe-risk of mortality (MPI-3 value. 0.67), on the basis of earlier established cut-offs. Associations with in-hospital mortality and length of stay were examined using multivariable Cox regression models and adjusted Poisson linear mixed-effects models, respectively. Results: At admission, 23.6% subjects had a MPI-1 score, 33.8% had a MPI-2 score, and 42.6% had a MPI-3 score. Subjects with higher MPI score at admission were older (p <.001), more frequently women (p <.001) and had higher prevalence of common chronic conditions. After adjustment for age, gender, and diseases, patients included in the MPI-2 and MPI-3 groups had a significantly higher risk for intrahospital mortality (hazard ratio: 3.48, 95% confidence intervals: 1.02.11.88, p =.047; hazard ratio: 8.31, 95% confidence intervals: 18.104.22.168, p <.001) than patients included in the MPI-1 group, respectively. In multivariable model, length of stay significantly increased across the three MPI groups (11.29 [0.5], 13.73 [1.3], and 15.30 [1.4] days, respectively [p <.0001]). Conclusions: In older acute care inpatients, MPI score assessed at hospital admission is an independent predictor of in-hospital mortality and the length of hospital stay. © the Author 2014.
PubMed | Medical Oncology, Radiology, Geriatrics Unit, Sloan Kettering Cancer Center and 4 more.
Type: | Journal: Radiation oncology (London, England) | Year: 2016
A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [(18)F]Choline ([(18)F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa).Twenty-nine pts with oligometastatic PCa (3 synchronous active lesions detected with [(18)F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [(18)F]FMCHPET/CT.A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded.Repeated salvage [(18)F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa.
PubMed | Obesity and Digestive Diseases Unit and Geriatrics Unit
Type: Journal Article | Journal: Geriatric orthopaedic surgery & rehabilitation | Year: 2014
There are risk factors associated with mortality in patients older than 70 years with hip fracture, including kidney function. However, indirect formulas to calculate glomerular filtration rate are not validated in patients older than 70 years. We analyzed whether the formula hematocrit, urea, and gender (HUGE) can be used as a prognostic factor.A retrospective cohort study of 88 patients older than 70 years with a diagnosis of hip fracture. At admission, clinical and biochemical parameters were measured and glomerular filtration rate by Cockcroft-Gault, Modification Of Diet In Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and HUGE value. Accuracy to assess long-term mortality was analyzed with receiver-operating curve analysis. Cox regression analysis was performed to identify risk factor for mortality.Sample included 88 patients; overall mortality was 13.63%, 17.85%, 28.57%, and 75.85% at 6 months, 1, 2, and 3 years, respectively. There was no significant difference in glomerular filtration rate by different formulas, contrary to HUGE, with higher values in the mortality group (1.83 6.38 vs -2.61 2.70, P = .0001). Survival was lower in patients with higher HUGE values (22.7 months, 95% confidence interval [CI] 16.1-29.5 vs 32.9 months, 95% CI 30.2-35.7; P .001). In the Cox regression analysis, a negative HUGE value is associated with lower mortality (hazards ratio = 0.238; 95% CI 0.568-0.099).The HUGE formula is an independent risk factor for mortality in elderly patients with hip fracture, but not the glomerular filtration rate determined by Cockcroft-Gault, MDRD, and CKD-EPI.