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Background and Aims To assess the risk of hospitalization and mortality within 1 year of severe hypoglycaemia and theirs clinical predictors. Methods and Results We retrospectively examined 399 admissions for severe hypoglycemia in adults with DM at the Emergency Department (ED) of the University Hospital of Novara (Italy) betweeen 2012-2017, and we compared the clinical differences between older (aged ≥ 65 years) and younger individuals (aged 18-64 years). A logistic regression model was used to explore predictors of hospitalization following ED access and 1-year later, according to cardiovascular (CV) or not (no-CV) reasons; 1-year all-cause mortality was also detected. The study cohort comprised 302 patients (median [IQR] age 75 [17] years, 50.3% females, 93.4% white, HbA1c level 7.6% [1.0%]). Hospitalization following ED access occurred in 16.2% of patients and kidney failure (OR .50 [95% CI 1.29-5.03]) was the only predictor of no-CV specific hospitalization; 1-year hospitalization occurred in 24.5% of patients and obesity (OR 3.17 [95% CI 1.20-8.12]) and pre-existing heart disease (OR 3.20 [95% 1.20-9.39]) were associated with CV specific hospitalization; 1-year all-cause mortality occurred in 14.9% of patients and was associated with older age (OR 1.12 [95% CI 1.07-1.18]) and pre-existing heart disease (OR 2.63 [95% CI 1.19-6.14]) Conclusions Severe hypoglycemia is associated with risk of hospitalization and mortality mainly in elderly patients and it may be predictive of future cardiovascular events in diabetic patients with pre-existing heart disease and obesity.

Background We aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event. Methods and Results This was a retrospective cohort study of consecutive patients with preceding established indications for long-term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management-relevant high-risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence-based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70-84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1-12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1-3) days. TTE identified 26 of 191 (14%) patients with 35 management-relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management-relevant pathologies. Most management-relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management-relevant high-risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], C-reactive protein, d-dimer, and troponin levels). Conclusions In patients with established indications for long-term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management-relevant high-risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients.

Staphylococcus aureus is a major human pathogen that utilises a wide array of pathogenic and immune evasion strategies to cause disease. One immune evasion strategy, common to many bacterial pathogens, is the ability of S. aureus to produce a capsule that protects the bacteria from several aspects of the human immune system. To identify novel regulators of capsule production by S. aureus, we applied a genome wide association study (GWAS) to a collection of 300 bacteraemia isolates that represent the two major MRSA clones in UK and Irish hospitals: CC22 and CC30. One of the loci associated with capsule production, the menD gene, encodes an enzyme critical to the biosynthesis of menadione. Mutations in this gene that result in menadione auxotrophy induce the slow growing small-colony variant (SCV) form of S. aureus often associated with chronic infections due to their increased resistance to antibiotics and ability to survive inside phagocytes. Utilising such an SCV, we functionally verified this association between menD and capsule production. Although the clinical isolates with polymorphisms in the menD gene in our collections had no apparent growth defects, they were more resistant to gentamicin when compared to those with the wild-type menD gene. Our work suggests that menadione is involved in the production of the S. aureus capsule, and that amongst clinical isolates polymorphisms exist in the menD gene that confer the characteristic increased gentamicin resistance, but not the major growth defect associated with SCV phenotype.

Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen Staphylococcus aureus . By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance-associated genes, mdeA, mpsB and yycH. Detailed analysis of an MpsB mutant supports its previous association with the slow growing small colony variant (SCV) phenotype of S. aureus , and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion for the ability of S. aureus to cause disease, we believe that these findings explain the role of the mpsB gene as a mortality-associated locus during human disease.

Here we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient’s persistent symptoms and radiological changes.

Little is known on the current global prevalence of atopic dermatitis (AD) in the pediatric population.To estimate the real-world global prevalence of AD in the pediatric population and by disease severity.This international, cross-sectional, web-based survey of children and adolescents (6 months to18 years old) was conducted in the following 18 countries: North America (Canada, United States), Latin America (Argentina, Brazil, Columbia, Mexico), Europe (France, Germany, Italy, Spain, United Kingdom), Middle East and Eurasia (Israel, Saudi Arabia, Turkey, United Arab Emirates, Russia), and East Asia (Japan, Taiwan). Prevalence was determined using the following 2 definitions: (1) diagnosed as having AD according to the International Study of Asthma and Allergies in Childhood (ISAAC) criteria and self- or parent-report of ever being told by a physician that they or their child child had AD (eczema); and (2) reported AD based on the ISAAC criteria only. Severity was assessed using the Patient Global Assessment (PtGA) and Patient-Oriented Eczema Measure (POEM).Among 65,661 responders, the 12-month diagnosed AD prevalence (ISAAC plus self-reported diagnosis) ranged from 2.7% to 20.1% across countries; reported AD (ISAAC only) was 13.5% to 41.9%. Severe AD evaluated with both PtGA and POEM was generally less than 15%; more subjects rated AD as mild on PtGA than suggested by POEM. No trends in prevalence were observed based on age or sex; prevalence was generally lower in rural residential settings than urban or suburban.This global survey in 18 countries revealed that AD affects a substantial proportion of the pediatric population. Although prevalence and severity varied across age groups and countries, less than 15% had severe AD.

Neisseria meningitidis is a strictly human pathogen and is the major cause of septicemia and meningitis worldwide. Factor H binding protein (fHbp) is a meningococcal surface-exposed lipoprotein that binds the human Complement factor H allowing the bacterium to evade the host innate immune response. FHbp is also a key antigen in two vaccines against N. meningitidis serogroup B. Although the fHbp gene is present in most circulating meningococcal strains, level of fHbp expression varies among isolates and has been correlated to differences in promoter sequences upstream of the gene. Here we elucidated the sequence determinants that control fHbp expression in globally circulating strains. We analyzed the upstream fHbp intergenic region (fIR) of more than 5800 strains representative of the UK circulating isolates and we identified eleven fIR sequence alleles which represent 88% of meningococcal strains. By engineering isogenic recombinant strains where fHbp expression was under the control of each of the eleven fIR alleles, we confirmed that the fIR sequence determines a specific and distinct level of expression. Moreover, we identified the molecular basis for variation in expression through polymorphisms within key regulatory regions that are known to affect fHbp expression. We experimentally established three expression groups, high–medium–low, that correlated directly with the susceptibility to killing mediated by anti-fHbp antibodies and the ability of the meningococcal strain to survive within human serum. By using this sequence classification and information about the variant, we predicted fHbp expression in the panel of UK strains and we observed that strains with higher expressing fIR alleles are more likely associated with invasive disease. Overall, our findings can contribute to understand and predict vaccine coverage mediated by fHbp as well as to shed light on the role of this virulence factor in determining an invasive phenotype., Author summary Complement plays a key role in the immunity against Neisseria meningitidis. The meningococcus uses the Factor H binding protein (fHbp), to bind a negative regulator of the alternative complement pathway, factor H, to its surface thus preventing complement deposition and lysis. The use of fHbp as an antigen in two licensed vaccines highlights its public health relevance. Therefore the levels of this antigen produced by the bacterium are pivotal on the one hand for the survival of N. meningitidis in blood and on the other hand for the susceptibility to vaccine-induced killing antibodies. Here, we identify the predominant nucleotide sequences that drive distinct levels of the fHbp antigen in circulating meningococcal strains. We cluster them into distinct groups with increasing levels and observe that strains expressing higher fHbp amounts are associated with invasive disease. Our findings show that the nucleotide sequence of the fHbp promoter can be used for the prediction of antigen levels of any given strain and consequently for both the assessment of its sensitivity to killing by fHbp antibodies and its likelihood to cause invasive disease.

Supplemental Digital Content is available in the text., Background: The HeartLogic algorithm combines multiple implantable cardioverter-defibrillator sensors to identify patients at risk of heart failure (HF) events. We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events. Methods: The HeartLogic feature was activated in 366 implantable cardioverter-defibrillator and cardiac resynchronization therapy implantable cardioverter-defibrillator patients at 22 centers. The median follow-up was 11 months [25th–75th percentile: 6–16]. The HeartLogic algorithm calculates a daily HF index and identifies periods IN alert state on the basis of a configurable threshold. Results: The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients. The time IN alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations, and 8 patients died of HF during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (hazard ratio, 24.53 [95% CI, 8.55–70.38], P

Iron-deficiency anemia (IDA) was the main condition contributing to higher rates of years lived with disabilities in women in 2016. To date, few studies have investigated gender differences in determinants of IDA in Europe. The aim of the present study was to evaluate the determinants of IDA among females and males in four European countries. IDA determinants were estimated using multivariable Cox regression based on information gathered from national primary care databases, namely Italy (for years 2002-2013), Belgium, Germany, and Spain (for years 2007-2012). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) were estimated. Age was significantly associated with IDA in females of childbearing age in all four countries, as well as pregnancy, for which the aHR ranged from 1.20 (95% CI 1.15-1.25) in Italy to 1.88 (95% CI 1.53-2.31) in Germany. In males, the aHR increased with age starting from the 65-69 age group. Menometrorrhagia was associated with IDA in Germany (aHR 2.71, 95% CI 1.96-3.73), Italy (aHR 1.80, 95% CI 1.60-2.03), and Spain (aHR 1.52, 95% CI 1.31-1.76). A greater risk for women with alopecia was also observed. Weakness and headache indicated a higher risk in both men and women. Patients with diseases characterized by blood loss or gastrointestinal malabsorption were also at significantly increased risk. Physicians should encourage women of childbearing age to adhere to dietary recommendations regarding iron intake and regularly prescribe screening of iron status. Upper and lower gastrointestinal investigations should be recommended for patients with a confirmed diagnosis of IDA.

The aim of the study was to identify the main aspects concerning appropriateness and efficacy of Spa therapy for musculoskeletal pathologies.A committee of 8 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Clinicians from Italian medical centers specialized in rheumatology, rehabilitation and thermal medicine took part in a Delphi process aimed at obtaining consensus statements among the participants.Large consensus was obtained for statements grouped under the following main themes: treatment indications; choice of treatment modality and treatment efficacy.The experts developed a number of consensus statements which may be used as a practical reference to guide the choice of physicians to treat musculoskeletal diseases with Spa therapy.

Background Healthcare utilization data are increasingly used for chronic disease surveillance. Nevertheless, no standard criteria for estimating prevalence of high-impact diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, are available. In this study an algorithm for recognizing COPD/asthma cases from HCU data is developed and implemented in the HCU databases of the Italian Lombardy Region (about 10 million residents). The impact of diagnostic misclassification for reliably estimating prevalence was also assessed. Methods Disease-specificdrug codes, hospital discharges together with co-payment exemptions when available, and a combination of them according with patient’s age, were used to create the proposed algorithm. Identified cases were considered for prevalence estimation. An external validation study was also performed in order to evaluate systematic uncertainty of prevalence estimates. Results Raw prevalence of COPD and asthma in 2010 was 3.6 and 3.3% respectively. According to external validation, sensitivity values were 53% for COPD and 39% for asthma. Adjusted prevalence estimates were respectively 6.8 and 8.5% for COPD (among person aged 40 years or older) and asthma (among person aged 40 years or younger). Conclusions COPD and asthma prevalence may be estimated from HCU data, albeit with high systematic uncertainty. Validation is recommended in this setting. Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0362-6) contains supplementary material, which is available to authorized users.

BackgroundMood disorders are managed predominantly in primary care. However, general practitioners’ (GPs) ability to detect and diagnose patients with mood disorders is still considered unsatisfactory. The aim of the present study was to identify predictors for the early recognition of depressive disorder (DD) and bipolar disorder (BD) in general practice.MethodsA cohort of 1,144,622 patients (605,285 women, 539,337 men) was investigated, using the Health Search IMS Health Longitudinal Patient Database. Predictors of DD or BD were identified at baseline encompassing somatization-related features, lifestyle variables, medical and psychiatric comorbidities. Patients were followed up as long as the following events occurred: diagnoses of DD or BD, death, end of the registration with the GP, end of the study period.ResultsWe found an incidence rate of DD or BD of 53.61 and 1.5 per 10,000 person-years, respectively. For both the conditions, the incidence rate grew with age. Most of the lifestyle variables and medical comorbidities increased the risk of mood disorders. The strongest effect was found for migraine/headache (HR [95% CI] = 1.32 [1.26–1.38]), fatigue (1.32 [1.25–1.39]) irritable bowel syndrome (1.15 [1.08-1.23]), and pelvic inflammation disease (1.28 [1.18–1.38]).ConclusionsSeveral predictors, in particular somatic symptoms, could be interpreted as an early sign of a mood disorder, and represent a valid indication for the GPs diagnostic process of mental disorders.

Background The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. Via the colorectal cancer screening program, all average-risk individuals in the 50-74-year age group are invited every 2 years to do a guaiac-based or, since April 2015, an immunochemical fecal occult blood test. Methods The fifth edition of the nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1299 individuals with no history of cancer (age, 50-74 years) was interviewed between 22 November and 7 December 2016. The present analysis focuses on minimum lifetime uptake of screening tests, compliance to recommended repeat-screening intervals, and reasons for non-participation. Results In 2016, 64% survey participants had been screened at least once and 38% had been screened in the previous 2 years, suggesting a trend towards increasing participation rates, particularly in the younger age categories and among men. The 2016 data also suggest that the newly implemented FIT-based screening program has been well perceived by the population. Up to one in four individuals cited ``no risk factors'' as the reason for not undergoing screening. This reveals ignorance of the fact that the colorectal cancer screening program actually targets all average-risk individuals in a given age group, without individual risk factors. Conclusion We suggest the next step should be dedicated to educational approaches to explain exactly what screening involves and to persuasive messages targeting those who to date have remained unreceptive to information campaigns.

Background The general population is nowadays well aware that tobacco smoking dramatically increases the risk of developing lung cancer. We hypothesized that a personal history of smoking and the level of nicotine dependence in current smokers may affect the perception of this risk among healthy individuals. Methods The fourth French nationwide observational survey, EDIFICE 4, was conducted by telephone among a representative sample of individuals (N = 1602) aged between 40 and 75 years. Interviewees were asked about their smoking habits, perception of the risk of lung cancer, and nicotine dependence (Fagerstrom test). Results Regardless of their smoking status or level of nicotine dependence, the majority (96%) of our study population (N = 1463) acknowledged that tobacco smoking is a major risk factor for lung cancer. For 34% of all respondents, smoking

Background Primary prevention of cancer relies on awareness of and consequent identification of risk factors. We investigated knowledge of breast cancer risk factors not only among laywomen but also among female physicians. Methods The EDIFICE 4 nationwide observational survey was conducted by phone interviews of a representative female population (737 laywomen and 105 female physicians) aged 40-75 years, using the quotamethod. This analysis focuses on spontaneous replies to the question ``In your opinion, what are the five main risk factors that increase the risk of breast cancer?''. Results Heredity/Family history of breast cancer was the most widely recognized risk factor in both study populations (98.1% physicians vs. 54.2% laywomen; P

Participation is key to the success of cancer screening. Identifying the reasons for nonparticipation is therefore essential. The present analysis of the EDIFICE (etude sur le depistage des cancers et ses facteurs de compliance [survey on cancer screening and compliance factors]) surveys (n = 1463) found 36.4% of current smokers and 26.3% of former smokers intended to participate in a lung cancer screening program. Discrepancies exist between the screening program target populations and the individuals who actually intend to undergo screening. Background: Lung cancer (LC) screening (LCS) with annual low-dose computed tomography scans has been seen to reduce the specific and overall mortality in selected populations. However, participation is key to successful screening programs. The EDIFICE (etude sur le depistage des cancers et ses facteurs de compliance [survey on cancer screening and compliance factors]) nationwide observational surveys are used to assess behavior related to cancer screening programs in France. Materials and Methods: Using comprehensive multivariate stepwise logistic regression analyses of data from current and former cigarette smokers, we sought to identify the explanatory factors associated with the intention to participate in an LCS program. Results: Of the 1463 respondents with no personal history of cancer, 263 (36.4%) of the current cigarette smokers and 170 (26.3%) of the former cigarette smokers stated their willingness to participate in an LCS program. The explanatory factors differed between current cigarette smokers (already screened for LC: odds ratio PRI, 2.81; < 30 pack-years: OR, 2.69; intention to quit smoking: OR, 1.96; no social vulnerability: OR, 2.15) and former cigarette smokers (comorbidities: OR, 0.31). The usual eligibility criteria were not significantly explanatory. Conclusion: Our findings highlight the discrepancy that exists between target populations and individuals who actually intend to participate in a screening program for LC, with subsequent potential effects on the participation rates and, thus, on the efficacy of screening. (C) 2018 Elsevier Inc. All rights reserved.

Zhihua Julia Qiu has over 20 years post PhD experience in academic institutes, pharmaceutical industry and biotechnology startup settings; focused on novel therapeutics discovery and development and diagnostic tools. She is currently a Scientist in the Bioanalytical Sciences department at Genentech; responsible for developing, evaluating and implementing Bioanalytical strategy to support protein therapeutics development. That includes assay development and validation to evaluate PK, antitherapeutic antibodies as well as biomarkers in both nonclinical and clinical studies for Immunology and Oncology indications. In addition, she has led the evaluation of multiple novel technology platforms and transitioning assay platform to enable continuous support for the development of protein therapeutics and antibody–drug conjugates.

International audience; Background:As conservation of whole blood samples undergoing white blood cell (WBC) differential performed by flow cytometry (Hematoflow) is needed, we evaluated the effects of two commercially available fixatives, namely TransfixTM and Streck Cell PreservativeTM.Methods:We focused on 15 normal samples and on 13 various pathological samples. We compared the two fixatives and cold- or room- temperature effects on various parameters provided by the Hematoflow system.Results:We observed that, even after 2 hours of sample treatment, the conservative methods led to significant modifications of the cell percentages due to substantial variations of the epitope expression.Conclusion:None of the different conservation methods is really reliable for WBC differential performed by flow cytometry and thus samples should be analyzed promptly or stored at 4°C.

The use of palm oil by the food industry is increasingly criticized, especially in Italy, for its purported negative effects on human health and environment. This paper summarizes the conclusions of a Symposium on this topic, gathered by the Nutrition Foundation of Italy, among experts representing a number of Italian Medical and Nutritional Scientific Societies. Toxicological and environmental issues were not considered. Participants agreed that: no evidence does exist on the specific health effects of palm oil consumption as compared to other saturated fatty acids-rich fats; the stereospecific distribution of saturated fatty acids in the triacylglycerol molecule of palm oil limits their absorption rate and metabolic effects; in agreement with International guidelines, saturated fatty acids intake should be kept

Blood pressure ( BP) control remains unsatisfactory worldwide. Better knowledge of BP management in clinical practice is needed to develop more effective improving strategies. Using a large Italian primary care database, we selected the subjects diagnosed with hypertension, and extracted the diagnosis of myocardial infarction, angina pectoris/coronary disease, stroke/transitory ischemic attack (TIA), heart failure, atrial fibrillation, peripheral arterial disease, diabetes mellitus, the serum total cholesterol, HDL cholesterol, triglycerides, creatinine, BP, electrocardiogram, weight, height and the prescription of cardiovascular ( CV) drugs. Hypertension was recorded in 119.065 individuals (prevalence 19.3%), 19.134 (16%) had no ambulatory visit and 33.183 (27.8%) had no BP value recorded. Overall, 14.594 (21.9%) had at least one recorded diagnosis showing high CV risk. BP was controlled (mean of BP values

OBJECTIVE The aim of this study was to assess the accuracy of a risk calculator that includes renal function as compared with that of the traditional Framingham Risk Score (FRS) in predicting the risk of mortality of hypertensive individuals managed in primary care. METHODS From the databases of British and Italian General Practitioners, we retrieved demographic and clinical data for 35 101 UK and 27 818 Italian individuals aged 35-74 years with a diagnosis of hypertension. Then, the 5-year incidence of cardiovascular events as well as all-cause and cardiovascular mortality were recorded for both samples. A comparison analysis of the performance of the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator with that of FRS in predicting 5-year all-cause and cardiovascular mortality risk was made. RESULTS The INDANA calculator was more accurate than the FRS in predicting all-cause [Δc 0.038, 95% confidence interval (CI) 0.026-0.051 for United Kingdom, and 0.018, 95% CI 0.010-0.027 for Italy, both P

OBJECTIVE: The aim of the study was to identify the main aspects involved in patient selection, the choice of therapeutic agents and the safety profile, as well as the medico-legal and organizational aspects of intra-articular injection therapies for osteoarthritis. METHODS: A committee of 10 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Fifty-two clinicians from a large number of Italian medical centers specialized in intra-articular injection therapy took part in a Delphi process aimed at obtaining consensus statements among the participants. RESULTS: Large consensus was obtained for statements grouped under the following main themes: treatment indications; drug/medical device choice; treatment efficacy; and appropriate setting. CONCLUSIONS: The consensus statements developed by a large number of experts may be used as a practical reference tool to help physicians treat osteoarthritis patients by means of intra-articular injection therapies.

BACKGROUND: Stroke represents worldwide the second and seventh cause of death and invalidity, respectively. Patients with ischaemic stroke or transitory ischaemic attack (TIA) are at high risk of recurrence, therefore requiring intensive treatment. Hypercholesterolaemia is a modifiable risk factor for stroke. The general practitioners attitude towards detection and treatment of dyslipidaemia among patients with stroke or TIA in Italy is unknown; we therefore aimed to address this issue taking advantage of the database of The Italian College of General Practitioners. METHODS: Prevalence of the monitored factors (lipid levels, statin prescription, and lipid level control with hypolipidaemic agents prescription) were analysed on a patient population of 465 061. RESULTS: A total of 2555 (49% women and 51% men) patients with a diagnosis of stroke and 2755 patients (52% women and 48% men) with a diagnosis of TIA were included in the study. Total plasma cholesterol (TC) was reported in more than 60% of the patients and low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) in less than half. Total plasma cholesterol and LDLc were controlled in 70.3 and 72.8% of the patients, respectively. The percentage of controlled patients decreased to 64% when both LDLc and TC were considered. Statins and fibrates were prescribed in a small proportion of patients (16.9 and 3.5%, respectively). An acceptable control of blood lipids was achieved in a majority of those patients (60.2%). However a relatively large number of patients (646) with high plasma lipids remained untreated. CONCLUSIONS: Monitoring and intervention strategies on plasma lipid levels in patients with a diagnosis of stroke or TIA need to be improved.

AIMS Although calculation of the global cardiovascular risk is strongly recommended, limited data are available regarding the use and the utility of this tool in clinical practice. We aimed at answering the following questions in the setting of Italian general practice: how many patients are evaluated via the cardiovascular risk algorithm; what are their characteristics; and what happens after their evaluation. METHODS We used the Health Search/CSD Longitudinal Patient Database. The software used by about 800 participating GPs allows the calculation of the global cardiovascular risk in automatic. The following data were yearly extracted from the database within 2004-2008: age, sex, and recorded diagnosis of the main cardiovascular and other information encompassing smoking habits, blood pressure, total cholesterol, high density lipoprotein cholesterol (i.e., variables used to calculate cardiovascular risk), BMI, physical activity, triglycerides, glucose and creatinine; wherever available, current cardiovascular therapy and the automatically computed global cardiovascular risk were also extracted. RESULTS In 2008, the observed population, aged 35-69 years, numbered 438 922 individuals; 78 617 (17.9%) had at least one calculation of cardiovascular risk; 20 181 patients were re-evaluated at least once: 61.1% among high-risk patients, 43.8% among moderate-risk patients, and 27.2% among low-risk patients. The level of cardiovascular risk measured at baseline increased in 6863 (34%), decreased in 11 791 (58.4%), and did not change in 1527 (7.6%) individuals. Overall, mean cardiovascular risk decreased over 4 years in 2.25% (SD 6.41%; P

The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. Of note, clinical evaluations and non-invasive exams are often performed to low risk patients. In the present consensus document, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Three strategies follow-up have been defined and types and timing of clinical and instrumental evaluations are reported. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners, who are in charge to manage post-PCI patients, equally contributed to the creation of the present document.

Background and aims In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry. Methods and results From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m 2 , n = 22,015), and metabolic control (HbA 1c ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA 1c , diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21–26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27–40% of all discontinuations, after excluding lost to follow-up. HbA 1c decreased on average by 0.9–1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0–1.5% with DPP-4 inhibitors. Conclusions In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

Objectives Iron deficiency anaemia (IDA) is a global public health concern, being responsible for about 800 000 deaths per year worldwide. To date, few studies have investigated the epidemiology of IDA in Europe. This study therefore aimed to assess the incidence rate and determinants of IDA in four European countries. Methods Demographic and clinical information was obtained from four national primary care databases, respectively, for Italy, Belgium, Germany and Spain. IDA-related determinants were estimated using multivariable Cox regression. Results The annual incidence rates of IDA ranged between 7.2 and 13.96 per 1000 person-years. The estimates were higher in Spain and Germany. Females, younger and older patients were at greater risk of IDA, as well as those suffering from gastrointestinal diseases, pregnant women and those with history of menometrorrhagia, and aspirin and/or antacids users. A Charlson Index >0 was a significant determinant of IDA in all countries. Conclusions The use of primary care databases allowed us to assess the incidence rate and determinants of IDA in four European countries. Given the crucial role of general practitioners in the diagnosis and management of this condition, our findings may contribute to increase the awareness of IDA among physicians as well as to reduce its occurrence among at-risk patients.

Systemic sclerosis is a multisystem autoimmune disease that causes chronic widespread obliterative vasculopathy of the small arteries associated with various degrees of tissue fibrosis. The prognosis of the disease depends largely on the visceral involvement; however musculoskeletal involvement is an important factor to functional disability. Suffering from a chronic auto-immune disease, such as Systemic Sclerosis, compromises the quality of life and the work ability. The rehabilitative treatment may be a viable option for improving the quality of life, but there are few studies to support this hypothesis in adequate population. (Rehabilitation is still an under- studied field of research). Aim: Proposed personalised rehabilitation programme, with a multilocalized, multidisciplinary approach specifically designed for patients with Systemic Sclerosis.Retrospective study. Setting: Rehabilitation Institute, inpatients. Population: Forty-three patients affected by systemic sclerosis. Methods: Patients underwent a rehabilitation programme of 3 weeks. Three cycles of rehabilitation in 3 consecutive years were administered. The priority outcome measure was the Health Assessment Questionnaire-Disability Index (HAQ-DI). The effectiveness of treatment cycles repeated at 1-year intervals was also compared to the first cycle.Each treatment had an acute beneficial effect, leading to an improvement in the disability score after each of the three cycles (admission vs discharge: 1.2±0.6 vs 0.8±0.6, p minor than 0.0001, 1.3±0.6 vs 1.0±0.6, p minor than 0.0001 and 1.4±0.7 vs 1.1±0.7, p minor than 0.0001). The improvement in HAQ-DI scores after repeated cycles was progressively lower, but the difference in efficacy was not statistically significant (p=0.38 and p=0.17 for the comparison between the second and the first and the third and the first cycles respectively).The multilocalized, multidisciplinary protocol developed by our rehabilitation team led to a significant reduction in disability perceived by patients, independently of the disease duration. The beneficial effects at the end of the first cycle were reproduced in the subsequent cycles. Nevertheless, there was a tendency of progressive efficacy reduction in following cycles, due to increased disability caused by disease stage. Impact of rehabilitation: We believe that our results demonstrate the utility of personalised, multilocalized, multidisciplinary rehabilitation treatment in slowing the evolution of systemic sclerosis.

Background— Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the association of adherence with acute cardiovascular events. Methods and Results— Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18 806 newly diagnosed hypertensive patients ≥35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories—high (proportion of days covered, ≥80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, ≤40%)—and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly ( P P =0.032). Conclusions— The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits.

BACKGROUND Elevated blood pressure (BP) is one of the most important modifiable risk factors for cardiovascular diseases. In this study we assessed the excess of cardiovascular risk attributable to high BP and antihypertensive treatment in a sample of Italian patients enrolled by the 'Cholesterol and Health: Education, Control and Knowledge' (CHECK) study. METHODS CHECK is a large, cross-sectional epidemiological study, which randomly enrolled patients aged 40-79 years from 425 Italian General Practices from March 2002 to April 2004. Among 5731 patients enrolled in the study [49.6% men, mean age (standard deviation) 57.7 (10.3) years], 723 (12.6%) had 'optimal' BP, 1496 (26.1%) had 'high normal' BP, and 1942 (33.9%) were hypertensive. RESULTS According to the European Guidelines stratification of the cardiovascular risk-excess attributable to high BP, 34.7% of the sample had a low added risk and 53.2% had a moderate-to-very high added risk. The pharmacological therapy was prescribed in 22.3, 43.9, 61.4, and 76.9% of the patients with low, moderate, high, and very high added risk, respectively. CONCLUSION Overall dietary and drug therapies are under prescribed, as most of the treated patients would require two additional antihypertensive drugs to meet the recommended BP target. This effort could provide significant individual benefit to moderate/high-risk patients.

The recommendations for the management of osteoarthritis (OA) of the hip were proposed by EULAR in 2005. Among the most important objectives of the expert charged to provide these recommendations were their wide dissemination and implementation. Thus, the information generated can be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. According with that previously executed for the EU-LAR recommendation 2003 for the knee, the Italian Society of Rheumatology (SIR) has organised a Consensus on the EULAR recommendations 2005 for the management of hip OA. To obtain an acceptability as large as possible, the group of experts was composed by many physicians interested in the management of hip OA, including Orthopaedics, Rheumatologists, Physiatrists, and General Practitioners. Main aim of the Consensus was to analyse the acceptability and applicability of the recommendations according to own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that the specialists involved in the management of hip OA strongly encourage the dissemination of the EULAR 2005 recommendations also in Italy.

Objective To describe patterns of persistence and related primary care costs associated with first antihypertensive treatment. Design and setting Retrospective cohort study during 2000–2001, using information from 320 Italian general practitioners. Participants We studied 13 303 patients with newly diagnosed hypertension, who received a first single antihypertensive prescription within 3 months after diagnosis. Main outcome measures Persistence with first-line single treatment, categorized as follows: continuers: patients continuing the first-line medication for at least 1 year; combiners: patients receiving an additional antihypertensive drug and continuing the initial medication; switchers: patients changing from the first-line to another class of antihypertensive drug and discontinuing the initial treatment; discontinuers: patients stopping the first-line treatment without having another prescription until the end of the follow-up. Primary care costs were expressed as the cost of hypertension management per person-year of follow-up. Results In the study cohort, 19.8% were continuers, 22.1% were combiners, 15.4% were switchers, and 42.6% were discontinuers. Continuation was greatest with angiotensin II type 1 receptor blocking agents (25.2%), calcium channel blockers (23.9%) and angiotensin-converting enzyme inhibitors (23.3%). Severe hypertension [hazards ratio 1.30; 95% confidence interval (CI) 1.18 to 1.43] and severe health status (hazards ratio 1.22; 95% CI 1.15 to 1.30) increased the risk of discontinuation. The likelihood of needing an additional antihypertensive drug was associated with mildto- severe baseline blood pressure, diabetes (hazards ratio 1.20; 95% CI 1.06 to 1.36), and familial history of cardiovascular disease (hazards ratio 1.24; 95% CI 1.10 to 1.39). Discontinuers accounted for 22.4% of the total primary care cost. Initial treatment with angiotensin II type 1 receptor blocking agents and b-blockers resulted in incremental primary care costs of s145.2 and s144.2, respectively, compared with diuretics. Combiners and switchers increased the primary care cost by s140.1 and s11.7, compared with continuers. Conclusion Persistence with first-line single antihypertensive drugs is extremely low during the first year of treatment. Potential cost saving should be possible by reducing the high frequency of discontinuation. Diuretics represent the least expensive therapeutic option, although further investigations in the long-term are needed to analyse the effects of persistence on therapeutic effectiveness and related costs. J Hypertens 23:2093–2100

The potential benefit of silymarin (special extract from the fruits of Silybum marianum) in the treatment of liver diseases remains a controversial issue.For this systematic review electronic databases identified 65 papers for the search terms silymarin, silibinin, silicristin or milk thistle and clinical trial. Only 19 complied with the criteria'double-' or 'single-blind'. These publications were analysed from a clinical point of view and meta-analytic calculations were performed.The clinical evidence ofa therapeutic effect of silymarin in toxic liver diseases is scarce. There is no evidence of a favourable influence on the evolution of viral hepatitis, particularly hepatitis C. In alcoholic liver disease, comparing with placebo, aspartate aminotransferase was reduced in the silymarin-treated groups (p = 0.01) while alkaline phosphatase was not. In liver cirrhosis, mostly alcoholic, total mortality was 16.1% with silymarin vs. 20.5% with placebo (n.s.); liver-related mortality was 10.0% with silymarin vs. 17.3% with placebo(p = 0.01).Based on the available clinical evidence it can be concluded - concerning possible risks /probable benefits - that it is reasonable to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning but also (alcoholic and grade Child 'A') liver cirrhosis. A consistent research programme, consolidating existing evidence and exploring new potential uses,would be very welcome.

Recent years have seen an explosion of scientific papers that deal with drugs from the fruits of milk thistle and its active substances silymarin (standardized mixture of flavonolignanes), thus justifying an updated systematic review. Methods: Electronic databases identified silymarin, silibinin, silicristin or milk thistle as descriptors in >700 papers (34% published in last 5 years; 92% dealt with animal pharmacological). Only papers adequately reporting on experimental conditions, dosing, variables tested and statistics were analysed. Results: Silymarin was found to modify specifically the functions related to various transporters and receptors located in the cell membranes; that is, organic anion uptake transporter peptides (OATP), ABC transporters (P-gp), bile salt export pump, as well as TNF-a-dependent and possibly selectin-dependent phenomena. In the cytoplasm, some antioxidant properties and the inhibition of the lipoxygenase pathway seem quite selective and could concur to the antitoxic effects. Some effects like the inhibition of inducible nitric-oxide synthase, of nuclear factor κ B, and reduction of collagen synthesis are indicative of DNA/RNAmediated effects. Several studies using ‘in vitro’ and ‘in vivo’ cancer models suggest a potential of silymarin in such diseases. Topical and systemic silymarin has skin protective properties against UV-induced damage in epidermis and causes an up-regulation of tumour-suppressor genes p53- and p21CIP1. There were no data on hepatic viral replication, viremia or spontaneous tumours in the data examined. Conclusions: Data presented here do not solve the question about the complex mechanism(s) of action of the medicinal herbal drug silymarin. Silymarin may be a natural multi-functional and multi-target drug.

In order to collect information on food intake, lifestyle and health status of the Italian population, a random cohort of about 2000 adults was selected in collaboration with the Italian society of general practitioners’ network (SIMG). Cohort subjects underwent a full clinical evaluation, by their family doctor, who also collected anthropometric data and information on the prevalence of cardiovascular disease risk factors; they were also administered diary forms developed to assess dietary use of simple sugars, of sugar-containing food and of selected food items. Data obtained indicate that the consumption of simple sugars (either added or as natural part of food) by the Italian adult population is, on average, not high (65 and 67 g/day, among women and men, respectively) and mostly derived from food items such as fruit, milk and yogurt. In addition, no correlations were found, in this low-sugar-consuming cohort, between sugar intake and weight, body mass index and waist circumference. Intakes of simple sugars in the LIZ cohort are not associated with weight, BMI and waist circumference. Prospective data, from cohorts like the LIZ one, might shed further light on the contribution of simple sugar intake to health in countries like Italy.

Background: Haiti is a country with a heavy burden of HIV infection in childbearing women. Previous studies have shown that early infant deaths are common in children of HIV-infected women. This study was designed to define the rates of and risk factors for systemic bacterial and mycobacterial infection in such children and to identify the causative agents. Methods: A cohort of 120 children born to HIV-infected mothers between May 2001 and December 2003 were prospectively observed to 15 months of age. They received comprehensive pediatric care at the GHESKIO Centers. Children were assigned to being HIV-infected by serology, RNA detection, and/or defining clinical illnesses. Blood cultures were obtained before giving antibiotics in children who were febrile or chronically ill. Blood cultures also were obtained at selected visits on well children. Results: The mortality rate in the first 15 months was high, 22 of 106 (207/1000 live births) in these children. Sixteen (70%) deaths were within 6 months of birth. Fourty-eight blood cultures had clinically significant organisms of which 38 were Staphylococcus aureus. Blood cultures were more likely to be positive in symptomatic and in HIV-infected children. Conclusions: Despite perinatal HIV treatment, mortality in children born to HIV-infected mothers remained high. Bacteremia, particularly with Staphylococcus aureus, is a partial explanation for excess illness.

Objective: To assess the effect of a calcium carbonate/perlite toothpaste on the levels of extrinsic stain removed at two weeks compared to a silica control toothpaste. Design: In this parallel group, double-blind study, subjects were stratified by natural baseline stain and tobacco use and allocated at random to one of the two study toothpastes. Subjects brushed with their allocated toothpaste twice daily for two weeks before extrinsic tooth stain was again assessed. Setting: The study was performed at 4-Front Research UK Limited, Maldon, UK. Participants: 152 adult subjects with at least eight assessable incisors/ canines with natural extrinsic tooth stain completed the study. Methods: The extrinsic tooth stain on the facial surfaces of incisors and canines was measured using the Macpherson modification of the Lobene Stain Index. Results: Both of the toothpaste groups had significantly less stain after two weeks of use compared to the baseline value (p

Data generated using various immunoassay methods are an integral part of the development of protein therapeutics. These assays are used in clinical and preclinical studies to establish the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics as well as to assess the immunogenicity properties of a therapeutic. PK assays measure therapeutic levels post-administration which is essential for understanding the effective dose and dose regimen for a therapeutic. Anti-OX40L is a fully humanized monoclonal antibody designed for the potential treatment of an autoimmune disease. The anti-OX40L human PK assay is required to be sensitive, robust, and precise. To address challenges due to assay sensitivity and reproducibility, as well as assay technology limitations, during development of the anti-OX40L human PK assay, three different assays, including an MSD-based electrochemiluminescence assay (ECLA), a fluorometric enzyme-linked immunosorbent assay (ELISA), and a colorimetric ELISA, were evaluated. The MSD-based assay was the most sensitive but posed risk of inter-well signal crosstalk. The fluorescence ELISA fell short on reproducibility. The colorimetric ELISA was ultimately chosen for supporting sample analysis. This paper presents characterization data obtained from each of these assay formats, challenges that were encountered in the development of the assay, and the rationale for selecting the ultimate assay format.

The purpose of the study was to investigate the risk of stroke with typical and atypical anti-psychotics in elderly subjects, weighting for a number of known risk factors, including dementia. Data were retrospectively drawn from the primary care setting from the Health Search Database, which stores information on about 1.5% of the total Italian population served by general practitioners. All elderly patients (65+ years) prescribed an anti-psychotic in monotherapy from January 2000 to June 2003 were selected for the study. A cohort of patients not exposed to anti-psychotics was taken from the same database. Subjects who had previously had a stroke were excluded. The main outcome measure was the incidence of first-ever stroke during exposure to an anti-psychotic.The sample included non-users (69,939), users of atypicals (599), butyrophenones (749), phenotiazines (907) and substituted benzamides (1,968). The crude incidence of stroke in subjects not exposed to anti-psychotics was 12.0/1000 person-years. Risk was significantly higher for those on butyrophenones (47.1/1000), phenotiazines (72.7/1000) and in the atypical anti-psychotic group (47.4/1000). Substituted benzamides had an almost significant higher risk (25.0/1000). Cox regression modelling, weighting for demographic and clinical variables with non-users as the reference group, showed that the risk for stroke was 5.79 times for phenotiazines, 3.55 times for butyrophenones, and 2.46 times for atypicals. Clinicians should be cautious in prescribing phenotiazines and butyrophenones in elderly patients, since the risk for stroke would seem comparable or even greater than with atypicals.

To evaluate prevalence of use and prescribing patterns of antiepileptic drugs (AEDs) in Italian general practice. Primary care data were obtained from the Health Search Database, a longitudinal observational database implemented by the Italian College of General Practitioners (GPs). We selected 465 061 subjects registered by the end of 2005 in the lists of 320 GPs, homogeneously distributed throughout Italy. Prevalence of AED use was assessed in the entire sample and by drug type, age group, year and main geographic area (north, centre and south/islands). Overall, 24 383 subjects (5.2%) received at least one AED prescription in the study period. Prevalence of AED use (with 95% confidence interval) increased progressively from 7.1 (6.9–7.3) in 2000 to 11.8 (11.5–12.1) in 2005 for old AEDs and from 1.1 (1.0–1.2) to 12.2 (11.9–12.5) for new AEDs. Carbamazepine, phenobarbital and valproic acid were the most common AEDs until 2003, when gabapentin became first. There were no differences in prescribing patterns in the three main geographic areas. Newer AEDs were mostly used in patients aged 65 years and older. The more widespread use of newer AEDs was for mood disorders or pain. Older AED currently remain first line drugs for epileptic disorders. An increasing use of AEDs has been recently observed over a 6-year period in Italian general practice, mostly explained by newer compounds used for conditions other than epilepsy.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

Objective To collect information on the major risk factors and secondary prevention among patients with myocardial infarction in Italy. Methods Data were obtained from the database of the Italian College of General Practitioners; 3588 patients (mean age 68.7 +/- 11.3 years; 2698 men, 888 women; two unrecorded gender), with an average time from event of 6 +/- 5.7 years, were identified. Results Among the major risk factors, data entry ranged from 50.3% for physical activity to 74.9% for blood pressure. Inadequate blood pressure control was present in 49.2% and elevated plasma cholesterol levels (>5.2 mmol/l) in 57.3%; among the latter group, 65% were on lipid-lowering therapy. Only 47.2% of the treated patients achieved a total cholesterol level of

BACKGROUND: The aim of this study was to compare the prevalence of angina pectoris (AP) using self-reported information and primary care databases. METHODS: A comparison between the prevalence of AP in 730,586 subjects from the Health Search Database (HSD) and 119,799 individuals from a Health Interview Survey (HIS) was performed. The age-specific prevalence was calculated by dividing the detected cases by the total number of individuals in each age group. The age-standardized prevalence was estimated by direct standardization performed using the Italian standard population. RESULTS: The HSD reported a higher crude prevalence of AP than the HIS, both in males (1374/100,000 vs 1006/100,000) and females (1449/100,000 vs 1007/100,000). In the HSD the age-specific prevalence was lower for patients aged

The present study aimed to estimate the incidence of diabetes in general practice patients who were treated with haloperidol, olanzapine, risperidone or quetiapine monotherapy and in subjects who were not exposed to antipsychotics. The design was a retrospective, up to 2 years, cohort study, with age-, sex- and length of observation-matching between subjects who were exposed and not exposed to antipsychotic drugs. Data were taken from the Health Search database, which contains information from 550 Italian general practitioners. Participants comprised 2,071 subjects taking haloperidol, 266 taking olanzapine, 567 taking risperidone and 109 taking quetiapine, in addition to 6,026 age- and sex-matched subjects who were not using antipsychotic drugs during the period of observation. Inclusion was limited to initially non-diabetic and antipsychotic drug-free individuals. The main outcome measure was the incidence of drug-treated diabetes. After age and sex correction by Cox regression analysis, the four groups treated with antipsychotics significantly differed from untreated subjects in hazard ratios for diabetes. The ratios for the haloperidol, olanzapine, risperidone and quetiapine groups were 12.4 (95% confidence interval 6.3-24.5), 20.4 (6.9-60.3), 18.7 (8.2-42.8) and 33.7 (9.2-123.6), respectively, with no significant differences when compared to each other.

OBJECTIVES: To assess the antipsychotic use and the prevalence/incidence of antipsychotic drug users in Italy during the years 1999-2002. To estimate the persistence with antipsychotic medications, and to measure their off-label use. METHODS: We selected 465,061 individuals registered by June 2002 in the lists of 320 general practitioners, homogeneously distributed throughout Italy, from the Health Search Database. We measured the antipsychotic drug consumption, calculated as defined daily dose (DDD) per 1000 inhabitants per day. We also calculated the number of individuals receiving at least one antipsychotic prescription, to estimate the annual prevalence and incidence of antipsychotic users. Among incident users, we evaluated the percentage of patients adherent to drug label indications and the average duration of treatment, estimated as medical possession ratio (MPR). RESULTS: Atypical antipsychotic use has continuously increased from 1999 to 2002. Women, older people and patients affected by psychotic disorders other than schizophrenia were seen to be more likely to receive antipsychotic prescriptions. Persistence with atypical drug treatment (MPR=0.213 in 2002) appeared longer than that of typical drugs (0.169). The percentage of patients adherent to drug label indications was significantly higher among typical antipsychotic users (P

Chronic deficiency of various vitamins can influence the occurrence of some chronic degenerative diseases such as cancer, cardiovascular pathology, cataract, arthritis, disorders of the nervous system and photosensitivity. Similarly, vitamin intake can influence various disorders in infants and elderly people, in burns and in subjects following unbalanced diets or undergoing strenuous physical exercise. Among vitamins, beta-carotene, vitamin E and vitamin C have received most attention, particularly in the prevention of oxidative damage from free radicals. It is supposed that each vitamin plays a different role in the pathogenesis of various diseases, depending on the type of damage relevant to a specific disease. Results from different studies are still far from conclusive and the effects on longevity are not well defined. In industrialized countries, vitamin deficiencies seem to be related only to specific and clearly identifiable groups in the population: therefore, at the moment, it seems more advisable to target vitamin supplementation at risk groups.

OBJECTIVE: To assess patient- and doctor-related variables leading physicians to prescribe antibiotics or parenteral antibiotics for acute respiratory infections (ARIs) and to describe the variability as well as the appropriateness of antibiotic use and its predictive factors in general practice. METHODS: We conducted a cross-sectional study among patients aged 15-85 years with a diagnosis of ARIs, using information from 469 GPs from the Health Search Database. Diagnoses were linked with antibiotic prescriptions and other patients and doctor-related variables. Available scientific evidence was used to establish the appropriateness of first-choice antibiotic treatment. Frequency analyses and logistic regressions were used to identify variables associated with antibiotic use and appropriateness. RESULTS: On 67,761 cases of ARIs, antibiotics were prescribed in 63.2%, varying from 80.9% for acute bronchitis to 43.9% for croup, influenza and common cold. Significant associations with antibiotic use were found for geographic location and number of patients under care. The use of diagnostic tests significantly lowered the risk. Geographic location and living in an urban area were associated with parenteral antibiotic use. Amoxicillin (16.7%) and amoxicillin-clavulanate (17.9%) were the most common antibiotics prescribed. Appropriateness was reported in 39.0% of cases, with geographic location, physician's gender and diagnostic tests being the factors more predictive of appropriate antibiotic use. CONCLUSIONS: There is still excessive antibiotic use for ARIs. Its overuse is influenced by the physicians' characteristics and by the environment in which they practice, whilst diagnostic tests might reduce inappropriateness. Therefore, effective strategies for changing diagnostic and therapeutic behaviour are needed.

Background: The etiology of functional dyspepsia (FD) is multi-factorial. Its prevalence is high and it considerably impairs the patients' quality of life. The treatment options are limited. Padma Digestin, a multi-herbal formula from Tibetan Medicine, is traditionally used in malabsorption and dyspeptic symptoms as they do occur in FD, but as yet no clinical data exist on the formula. The aim of this study was to evaluate the safety, tolerability, and efficacy of Padma Digestin in patients with FD in a prospective, open, clinical phase III trial. Patients and Methods: Patients were recruited by general practitioners, internists, and gastroenterologists and treated with 2 × 3 capsules of Padma Digestin daily for 6 weeks. Dyspeptic symptoms were analyzed using the Domestic/International Gastroenterology Surveillance Study (DIGEST) questionnaire extended by the 2 symptoms stomach cramps and lack of appetite. The quality of life was assessed using the Psychological General Well-Being Index (PGWBI-S) questionnaire (short version). Results: 37 patients were admitted and efficacy could be assessed in 31. In the overall efficacy assessment, the Padma Digestin treatment led to a statistically highly significant reduction of the respective most bothersome symptom scores regarding frequency, severity, and impairment of daily activities (p < 0.01). The treatment also led to significant improvements of the individual symptoms of postprandial fullness, nausea, localized and diffuse epigastric pain, stomach cramps, and lack of appetite. The onset of improvement was after a median of 7 days; time until disappearance of the symptoms was after a median of 22 days. The global efficacy and tolerability were rated as good or very good by the doctors and the patients in 84% and 78%, respectively. The PGWBI-S increased from 55 ± 19.5% to 70.5 ± 15.5%, which is nearly the normal value (73.5 ± 15.4%). As for safety, 11 patients reported a total of 17 adverse events (AE), 1 of which was serious but unrelated to the study medication. The AE were mild or moderate. The safety laboratory data showed no statistically significant or otherwise relevant changes. Conclusions: The results show that the formula Padma Digestin has a high tolerability and efficacy in FD symptoms and positively influences psychological well-being and thus quality of life. It therefore represents a much needed extension of the therapeutic repertoire in FD.