Search

Prisco Piscitelli,1,2 Giovanni Iolascon,3 Alberto Argentiero,2 Giovanna Chitano,2 Cosimo Neglia,2 Gemma Marcucci,1 Manuela Pulimeno,2 Marco Benvenuto,2 Santa Mundi,2 Valentina Marzo,2 Daniela Donato,4 Angelo Baggiani,4 Alberto Migliore,5 Mauro Granata,6 Francesca Gimigliano,3 Raffaele Di Blasio,7 Alessandra Gimigliano,3 Lorenzo Renzulli,7 Maria Luisa Brandi,1 Alessandro Distante,2,4 Raffaele Gimigliano3,71University of Florence, Florence Italy; 2ISBEM Research Centre, Brindisi, Italy; 3Second University of Naples, Naples, Italy; 4University of Pisa, Pisa, Italy; 5Fatebenefratelli St Peter’s Hospital, Rome, Italy; 6St Filippo Neri Hospital, Rome, Italy; 7Casa di Cura Santa Maria del Pozzo, Somma Vesuviana, ItalyObjectives: As osteoporotic fractures are becoming a major health care problem in countries characterized by an increasing number of older adults, in this study we aimed to compare the incidence and costs of hip fragility fractures in Italian elderly people versus those of major cardiovascular diseases (strokes and acute myocardial infarctions [AMI]) occurring in the whole adult population.Methods: We analyzed hospitalization records maintained at the national level by the Italian Ministry of Health for the diagnosis of hip fractures (ICD-9-CM codes 820–821), AMI (code 410), hemorrhagic (codes 430, 431, 432) and ischemic strokes (codes 433–434), and TIA (code 435) between 2001–2005. Cost analyses were based on diagnosis-related groups.Results: The incidence of hip fractures in elderly people has increased (+12.9% between 2001 and 2005), as well as that of AMI (+20.2%) and strokes (hemorrhagic: +9.6%; ischemic: +14.7) occurring in the whole adult population; conversely, hospitalization due to TIA decreased by a rate of 13.6% between 2001 and 2005. In 2005, the hospital costs across the national health care system that were associated with hip fragility fractures in the elderly were comparable to those of strokes (both hemorrhagic and ischemic), which occurred in the whole Italian adult population. Moreover, these costs were higher than those generated by AMI and TIA. Rehabilitation costs following strokes reached about 3 billion Euros in 2005, but rehabilitative costs of hip fractures and AMI were comparable (about 530 million Euros in 2005).Conclusion: The burden of hip fragility fractures in Italy is comparable to that of AMI and strokes.Keywords: hip fractures, strokes, acute myocardial infarction, incidence, hospital costs, rehabilitation costs

Early atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress. Mostly as a consequence of the activation of enzymatic systems leading to ROS overproduction, proatherogenic factors lead to a pro-inflammatory status that translates in changes in gene expression and functional rearrangements, including changes in the transendothelial transport of molecules, leading to the deposition of low-density lipoproteins (LDL) and the subsequent infiltration of circulating leucocytes in the intima. In this review, we focus on such early changes in atherogenesis and on the concept that proatherogenic stimuli and risk factors for cardiovascular disease, by altering the endothelial barrier properties, co-ordinately trigger the accumulation of LDL in the intima and ultimately plaque formation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

The severity of side effects that may occur with vitamin K antagonists due to their narrow therapeutic window requires great attention in finding out the most appropriate dose for these drugs. Pharmacogenetic research has now considerably helped clarifying the relationships between genetic variants and sensitivity to such therapy, paving the ground to predictive algorithms that include clinical and genetic variables to establish the best doses to start and maintain an adequate anticoagulation. Pharmacogenetic algorithms indeed aim at identifying tailored regimens, reducing adverse drug reactions and subsequent hospitalizations, optimizing therapeutic efficacy and containing costs. Here we describe the results so far achieved in pharmacogenetic research with vitamin K antagonists, analyzing studies that have assessed the usefulness of such algorithms.

The narrow therapeutic index, the large interindividual variability, and the severity of adverse drug reactions connected with vitamin K antagonists, together with their ample use in medical therapy, have prompted the search for strategies to better assist doctors in the choice of the safest and most effective dose of these drugs. The molecular mechanism by which oral anticoagulants exert their effect is an interference with the bioactivation of vitamin K. This mechanism is therefore the subject of numerous pharmacogenetic studies, aimed at finding the relationship between genetic variants influencing the metabolism or action of the drug and therapeutic outcomes. However, genes involved in the metabolism or action of vitamin K antagonists are many, and the role of some of them has not yet been fully understood. In this review we present and discuss current knowledge about the relationship between genotypes and the development of adverse drug reactions, focusing on gene variants that appear to influence dosing and clinical endpoints, and aiming at clarifying the usefulness of pharmacogenetic approaches as applied to this treatment.

Background: More than 320 000 hip fractures occur annually in North America. An estimated 30% of this population have cognitive impairment. We sought to determine the extent to which patients with cognitive impairment or dementia have been included in randomized controlled trials (RCTs) assessing hip fracture management., Methods: We conducted a systematic search of 3 electronic journal databases of articles published between January 2000 and June 2010. Studies were screened in duplicate to collect English-language RCTs assessing operative interventions for femoral head, neck or intertrochanteric fractures. We systematically collected descriptive data and used the χ(2) test for comparison between groups as appropriate., Results: We screened 1201 abstracts, 72 of which were eligible for inclusion in our review. Femoral neck and intertrochanteric fractures were equally represented. Thirty-three (46%) studies did not report the inclusion or exclusion of patients with cognitive impairment. Nineteen (26%) studies explicitly included cognitively impaired patients, whereas 20 (28%) excluded them. Only 2 trials (3%) reported outcomes specific to cognitively impaired patients. Fourteen trials (19.4%) reported the use of a validated cognitive assessment tool. None of the trials that reported inclusion of cognitively impaired patients were from North American centres., Conclusion: One in 3 patients with hip fractures have concomitant cognitive impairment, yet 8 of 10 hip fracture trials excluded or ignored this population. The ambiguity or exclusion of these patients misses an opportunity to study outcomes and identify factors associated with improved prognosis.

Background: Over 320,000 hip fractures occur in North America each year and they are associated with a mortality rate ranging from 14% to 36% within 1 year of surgery. We assessed whether mortality and reoperation rates have improved in hip fracture patients over the past 31 years., Methods: 3 electronic databases were searched for randomized controlled trials on hip fracture management, published between 1950 and 2013. Articles that assessed the surgical treatment of intertrochanteric or femoral neck fractures and measured mortality and/or reoperation rates were obtained. We analyzed overall mortality and reoperation rates, as well as mortality rates by fracture type, comparing mean values in different decades. Our primary outcome was the change in 1-year postoperative mortality., Results: 70 trials published between 1981 and 2012 were included in the review. Overall, the mean 1-year mortality rate changed from 24% in the 1980s to 23% in the 1990s, and to 21% after 1999 (p = 0.7). 1-year mean mortality rates for intertrochanteric fractures diminished from 34% to 23% in studies published before 2000 and after 1999 (p = 0.005). Mean mortality rates for femoral neck fractures were similar over time (~20%). Reoperation rates were also similar over time., Interpretation: We found similar mortality and reoperation rates in surgically treated hip fracture patients over time, with the exception of decreasing mortality rates in patients with intertrochanteric fractures.

Structural changes as a result of variations in pH value and salt concentration were determined for purified vicilin, the major globular protein in kidney beans using intrinsic fluorescence and circular dichroism (CD). The vicilin consisted of two polypeptide chains of about 43 and 45 kDa in size when analysed under reducing SDS-PAGE. Amino acid analysis showed that the vicilin had high contents of acidic amino acids and a low lysine/arginine ratio. Intrinsic fluorescence measurements were performed to measure exposure of tyrosine and tryptophan as a means of estimating protein conformational changes. Generally, the vicilin showed an unfolded structure at pH 3.0, 5.0, 7.0, and 9.0 as evident by the extensive red shift (>350 nm) of the wavelength of maximum tryptophan fluorescence intensity. At pH 3.0 and 5.0, the fluorescence intensity (FI) was greater than values obtained at pH 7.0 and 9.0, which suggests that the microenvironment of tryptophan was less hydrophilic at acidic pH. Addition of NaCl also led to increased FI, an indication of structural changes of tryptophan in response to the hydrophilic environment. These changes in FI were due mostly to tryptophan emission because tyrosine emission (at 303 nm) was suppressed. The far-UV CD spectra showed that vicilin had minimal measurable secondary structures at pH 3.0 and 5.0 when compared to pH 7.0 and 9.0. Addition of NaCl led to an increase in the tertiary structure conformation of vicilin as determined from the near-UV CD spectra., (Copyright © 2013 Elsevier Ltd. All rights reserved.)