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Past studies showed that hospital characteristics affect hospital performance in terms of 30-day unplanned readmissions, proving the existence of a “hospital effect”. However, the stability over time of this effect has been under-investigated. This study offers new evidence about the stability over time of the hospital effect on 30-day unplanned readmissions. Using 78,907 heart failure (HF) records collected from 116 hospitals in the Lombardy Region (Northern Italy) over three years (2010-2012), this study analysed hospital performance in terms of 30-day unplanned readmissions. Hospitals with unusually high and low readmission rates were identified through multi-level regression that combined both patient and hospital covariates in each year. Our results confirm that although hospital covariates – and the connected managerial choices – affect the 30-day unplanned readmissions of a specific year, their effect is not stable in the short-term (3 years). This has important implications for pay-for-performance schemes and quality improvement initiatives.

Background Controlling the quality of care through readmissions and mortality for patients with heart failure (HF) is a national priority for healthcare regulators in developed countries. In this longitudinal cohort study, using administrative data such as hospital discharge forms (HDFs), emergency departments (EDs) accesses, and vital statistics, we test new covariates for predicting mortality and readmissions of patients hospitalized for HF and discuss the use of combined outcome as an alternative. Methods Logistic models, with a stepwise selection method, were estimated on 70% of the sample and validated on the remaining 30% to evaluate 30-day mortality, 30-day readmissions, and the combined outcome. We followed an extraction method for any-cause mortality and unplanned readmission within 30 days after incident HF hospitalization. Data on patient admission and previous history were extracted by HDFs and ED dataset. Results Our principal findings demonstrate that the model's discriminant ability is consistent with literature both for mortality (AUC=0.738, CI (0.729-0.748)) and readmissions (AUC=0.578, CI (0.562-0.594)). Additionally, the discriminant ability of the composite outcome model is satisfactory (AUC=0.675, CI (0.666-0.684)). Conclusion Hospitalization characteristics and patient history introduced in the logistic models do not improve their discriminant ability. The composite outcome prediction is led more by mortality than readmission, without improvements for the comprehension of the readmission phenomenon.

Objective To evaluate the risk factors for recurrence of high‐grade disease after cervical excision in women living with HIV (WLWH), with a specific interest in the role of high‐risk (HR‐) HPV positivity. Methods Multicentric retrospective study conducted on WLWH who underwent cervical excision between January 1987 and June 2017 in six Italian institutions. The rate of high‐grade recurrence was determined. Risk factors for recurrence and HR‐HPV positivity were determined with the Log‐rank test and Cox proportional hazards regression models. Results A total of 271 WLWH were included in the final analysis. A high‐grade recurrence was found in 58 (21.4%) patients. Age 41 years or more at inclusion and HR‐HPV positivity during follow up were independently associated with a higher risk of disease recurrence with relative risks of 4.15 (95% confidence interval [CI] 2.01–8.58, P, Synopsis High‐risk‐HPV positivity during long‐term follow up is a risk factor for high‐grade disease recurrence after cervical excisional treatment in women living with HIV.

Con la statistica descrittiva vogliamo rilevare, classificare, sintetizzare e rappresentare le informazioni raccolte su una data popolazione. Da un lato, essa si distingue dalla statistica matematica per il suo scopo decisamente piu limitato, e dall’altro per l’attenzione ad alcuni problemi delle applicazioni che di solito non sono trattati nell’ambito piu matematico, come ad esempio i tipi di variabili o i diversi tipi di grafici che possiamo usare per rappresentare i dati. Gli obiettivi di questo capito los ono quindi: Il primo scopo della statistica descrittiva e quello di riassumere i dati. L’ideale e di permettere al lettore di individuare a prima vista le caratteristiche di un gruppo di valori, risparmiandogli il tempo per mettere ordine dove sembra esserci soltanto caos.

Summary The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono-infected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV mono-infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real-time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P

Iron supplementation is associated with side effects and overload risk. We compared different regimens of iron supplementation on maternal hematological status and pregnancy outcome in a cohort of healthy pregnant women.Eighty non-anemic women with a normal singleton pregnancy were recruited at 11-13 weeks and randomized into controls (C; n = 20) and groups supplemented with ferrous iron 30 mg (FI; n = 20), liposomal iron 14 mg (Sideral® Pharmanutra, Pisa PI, Italy) (LI14; n = 20) and liposomal iron 28 mg/daily (LI28; n = 20) up to 6 weeks post-partum. Longitudinal maternal blood samples for iron markers were collected. Data on birth outcome were recorded. The treatment effect was evaluated using a mixed-effect regression model.Both LI28 and LI14 groups showed significantly higher hemoglobin and ferritin concentrations compared with controls. Birth weight showed a trend to increase with supplementation, resulting in higher birth weight in the LI28 group compared with controls (3499 ± 464.1 g and 3092 ± 469.5 g, respectively, p 0.01).Our data show the effectiveness of 28 mg and 14 mg LI on maternal anemia prevention, as previously reported with FI 40 mg. LI has similar effects of higher doses of ferrous iron on maternal hematological parameters, thus allowing to reduce iron doses and side effects.

This study investigates the stability of the “hospital effect” on performance over time by administrative health data as a source of evidence. Using 78,907 heart failure adult records from 117 hospitals in the Lombardy Region (Northern Italy) over three years (2010–2012), we analyzed hospital performance in terms of 30-day mortality and 30-day unplanned readmissions to gather evidence about the stability of the “hospital effect.” Best/worst performers were identified through multi-level models that combine both patient and hospital covariates. Our results confirm that managerial choices affect hospital performance, and that the “hospital effect” is not, contrary to expectations, stable over the short term. Performance improvement/worsening over the three years has been also analyzed.

Changes in the incidence, clinical features and microbiology of infective endocarditis (IE) observed in a single center in Italy were compared between the period 2003-2010 and 2011-2015.All cases of IE, defined as definite or possible according to the modified Duke criteria, observed at the 'L. Sacco' Hospital in Milan, Italy between 2003 and 2015 were retrospectively reviewed.366 episodes of IE were identified in 325 patients. The mean number of incident IE over the period 2003-2015 was 1.43 (range: 0.6-2.1) cases per 1000 admissions, with a significantly increasing trend from a mean of 1.28-1.72 cases per 1000 admissions/year in 2003-2010 and 2011-2015, respectively (+34%; p = .04). Staphylococci remain the leading pathogens causing IE (29%) with a relative increase of methicillin-resistant Staphylococcus aureus between the two periods. Streptococci and enterococci account for 26% and 18% of IE, respectively. We found an increase in the proportion of cases due to enterococci (from 14% in 2003-2010 to 22% in 2011-2015). The rate of in-hospital mortality was 19%, similar in the two periods studied.The incidence of IE continuously increased in our cohort over the past decade and, along with the aging of the population, a raise in the incidence of health care-associated infections and a change in the distribution of prevalent pathogens were observed. Surgery was independently associated with higher in-hospital survival (AOR, 95% CI: 0.38, 0.19-0.74; p = .005). A constant surveillance is required to guide the optimal management of the changing epidemiology of IE.

Aims Triplet chemotherapy with fluoropyrimidines, oxaliplatin and irinotecan is a standard therapy for metastatic colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in DPYD and UGT1A1 influence fluoropyrimdines and irinotecan adverse events (AEs). Low frequency DPYD variants (c.1905 + 1G > A, c.1679 T > G, c.2846A > T) are validated but more frequent ones (c.496A > G, c.1129-5923C > G and c.1896 T > C) are not. rs895819 T > C polymorphism in hsa-mir-27a is associated with reduced DPD activity. In this study, we evaluated the clinical usefulness of a pharmacogenetic panel for patients receiving triplet combinations.

Complex drug-drug interactions have been reported with concurrent administration of telaprevir (TVR) and human immunodeficiency virus (HIV) protease inhibitors (PIs), leading to relevant limitations of the therapeutic options for patients coinfected with hepatitis C virus (HCV) and HIV. However, little is known about the pharmacokinetics and drug interactions between TVR and antiretrovirals in HIV/HCV-coinfected patients with advanced liver fibrosis. Here we report the pharmacokinetics of TVR and antiretrovirals in a cohort of HIV/HCV genotype 1-coinfected patients with advanced liver fibrosis treated with TVR-based triple anti-HCV therapy. No significant differences were observed in the pharmacokinetics of atazanavir, amprenavir or tenofovir at baseline and at Day 15 of TVR, whereas the AUC0-4h of darunavir was 36% lower in the presence of TVR (AUC0-4h 15007ngh/mL and 9563ngh/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4h, Cmin and Cmax of raltegravir were reduced by 61%, 50% and 64%, respectively. However, none of the patient's plasma levels of tenofovir, atazanavir, amprenavir or raltegravir declined below their minimum effective concentrations even in association with TVR, and no HIV treatment failure occurred. A non-significant trend for lower TVR exposure was seen in patients concomitantly given amprenavir versus those given atazanavir (AUC0-4h, 9840ngh/mL and 13345ngh/mL, respectively). In conclusion, this study highlighted the feasibility of maintaining the current antiretroviral regimen in HIV/HCV-coinfected patients, even when significant interactions with TVR are predictable, whenever a change of HIV PIs is not deemed appropriate.

Chronic hepatitis C is one of the most important causes of liver disease, leading to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Recently some important advances in therapy have been achieved with the introduction of first wave, first generation direct acting antiviral agents (DAAs) such as boceprevir (BOC), in combination with pegylated interferon (Peg-IFN) and ribavirin (RBV). The superior rate of sustained virological response with this treatment is accompanied by an elevated frequency of anaemia. Several studies have evidenced the importance of single nucleotide polymorphisms (SNPs) in inosine triphosphatase (ITPA) and solute carrier family 29, member 1 (SLC29A1) genes in the development of this adverse event. Here, we investigated haemoglobin levels and the best-known functional SNPs in ITPA and SLC29A1 genes in 22 patients treated with triple therapy with BOC/Peg-IFN/RBV. The identification of ITPA protective and SLC29A1 risk genotypes still appears to be a current methodology in RBV dosing during hepatitis C virus therapy with DAAs.

The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting.HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons.Patients were given TDF with protease inhibitors/ritonavir (n = 212), non-nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation.Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out.

A new meningococcal serogroup B vaccine (4 CMenB) has recently been licensed. This study assessed the acceptability of 4 CMenB vaccine among parents and healthcare workers (HCWs). From May to July 2013 in Milan, Italy, self-administered questionnaires were distributed to 2050 parents of infants presenting at immunization clinics for the mandatory hexavalent vaccination and submitted to 350 HCWs involved in immunization practices. 1842 parents (89.1%) responded to the survey; 64.4% of parents wanted their child to receive the 4 CMenB vaccine and 5.1% would not vaccinate their children. Multivariate analysis showed that recognition of the severity of meningitis [a life threatening vs a mild or unthreatening disease (Odds ratio (OR): 2.3; confidence interval (CI): 1.4-3.6], awareness of vaccination as a beneficial preventive measure (very beneficial vs not beneficial OR = 6.4; CI 3.0-13.7) and knowledge of the Meningococcal C vaccine (OR = 1.4; CI 1.1-1.8) were strongly associated to willingness to receive 4 CMenB vaccine. On the contrary, level of education was associated with refusal of immunization (university vs education level lower than middle school OR = 0.68; CI 0.47-0.97). Among the parents who were willing to immunize their children, 66.9% would agree with three injections to be administered during the same visit. A total of 291 HCWs (83.1%) agreed to participate in the survey; 73% considered 4 CMenB vaccine a priority in infants' immunization schedule; 26.8% of HCWs suggested the concomitant administration with routine infant immunization. Parental and HCWs acceptability of 4 CMenB vaccine was high. Increasing knowledge about meningitis and vaccine prevention might further increase the acceptability of this vaccine.

The aim of this study was to assess recent trends in hospital mortality and in the treatment techniques for patients with ST-segment elevation myocardial infarction according to gender. Data on hospitalizations for ST-segment elevation myocardial infarction from 2000 to 2010 were extracted from hospital discharge record databases (International Classification of Diseases, Ninth Revision, Clinical Modification, codes) in the Lombardy Region of Italy. The impact of female gender on in-hospital mortality was assessed by multivariable regression after adjusting for invasive approach use (i.e., coronary angiography, angioplasty or coronary artery bypass graft), age, and co-morbidities. A total of 89,562 patients, men (66.5%) and women (33.5%), were enrolled. The use of an invasive approach increased over time in both sexes although it was higher in men (from 54.9% in 2000 to 91.9% in 2010 in men; from 36.8% in 2000 to 72.0% in 2010 in women). This pattern was driven by the subgroup of patients aged ≥75 years, whereas differences between sexes were not observed in patients65 years and were small in patients aged 65 to 74 years. In-hospital mortality presented a small decrease from 7.6% in 2000 to 6.2% in 2010 in men (p for trend = 0.004), whereas it remained higher and substantially constant over time in women (16.6% in 2000, 15.5% in 2010, p for trend = 0.09). At multivariable regression, female gender did not emerge as an independent predictor of mortality (p = 0.13). However, a significant gender-age interaction was found, with female gender being a significant predictor of increased mortality in patients aged ≥75 years (odds ratio [OR] 1.33) while predicting a reduced mortality in patients aged75 years (OR 0.93, p for interaction0.0001). The use of an invasive approach was an independent predictor of mortality (OR 0.23, p0.0001), the magnitude of mortality reduction being higher in men than in women and in patients aged75 years than in those aged ≥75 years. In conclusion, a weak temporal trend in mortality reduction is observed in men only, which is driven by patients aged ≥75 years. In-hospital mortality remains higher in women than in men, although female gender is not a significant predictor of mortality. Despite temporal increases in the use of an invasive approach, women are more often treated conservatively.

Candida species represent the fourth leading cause of nosocomial bloodstream infections (BSI) worldwide. However, candidaemia rates and species involved vary geographically. To evaluate the epidemiological pattern, risk factors for mortality and antifungal therapy of Candida BSI over a 5-year period (2008–2012) in a university hospital in northern Italy together with a review of the recent literature concerning candidaemia. A retrospective cohort study cross-linked with microbiology database was performed. A total of 89 Candida BSI were identified in 42 males (47 %) and 47 females (52.8 %). The median age was 69 years (interquartile range 55–78) with 61.8 % of patients being older than 65 years. Considering all hospitalized patients, the overall incidence rate of candidaemia increased significantly from 2008 to 2012 (from 0.4 to 1.68 episodes per 10,000 patient/days) (p = 0.0001) with a mean linear increase in 5 new cases per year. Candida albicans was the predominant species isolated (64 %) followed by C. glabrata (19.1 %). The latter species was observed with significantly higher frequency in Internal Medicine and Intensive Care Units (ICU). In-hospital crude mortality was 41.6 %. Candidaemia is an increasing BSI in our university hospital, in accordance with that observed in northern Italy, and it is still associated with high in-hospital crude mortality.

This study was undertaken to evaluate trends in heat failure hospitalizations (HFHs) and 1-year mortality of HFH in Lombardy, the largest Italian region, from 2000 to 2012.Hospital discharge forms with HF-related ICD-9 CM codes collected from 2000 to 2012 by the regional healthcare service (n=699797 in 370538 adult patients), were analyzed with respect to in-hospital and 1-year mortality; Group (G) 1 included most acute HF episodes with primary cardiac diagnosis (70%); G2 included cardiomyopathies without acute HF codes (17%); and G3 included non-cardiac conditions with HF as secondary diagnosis (13%). Patients experiencing their first HFH since 2005 were analyzed as incident cases (n=216782).Annual HFHs number (mean 53830) and in-hospital mortality (9.4%) did not change over the years, the latter being associated with increasing age (p0.0001) and diagnosis Group (G1 9.1%, G2 5.6%, G3 15.9%, p0.0001). Incidence of new cases decreased over the years (3.62 [CI 3.58-3.67] in 2005 to 3.13 [CI 3.09-3.17] in 2012, per 1000 adult inhabitants/year, p0.0001), with an increasing proportion of patients aged ≥85y (22.3% to 31.4%, p0.0001). Mortality lowered over time in75y incident cases, both in-hospital (5.15% to 4.36%, p0.0001) and at 1-year (14.8% to 12.9%, p=0.0006).The overall burden and mortality of HFH appear stable for more than a decade. However, from 2005 to 2012, there was a reduction of new, incident cases, with increasing age at first hospitalization. Meanwhile, both in-hospital and 1-year mortality decreased in patients aged75y, possibly due to improved prevention and treatment.

Background Administrative data are increasingly used in healthcare research. However, in order to avoid biases, their use requires careful study planning. This paper describes the methodological principles and criteria used in a study on epidemiology, outcomes and process of care of patients hospitalized for heart failure (HF) in the largest Italian Region, from 2000 to 2012. Methods Data were extracted from the administrative data warehouse of the healthcare system of Lombardy, Italy. Hospital discharge forms with HF-related diagnosis codes were the basis for identifying HF hospitalizations as clinical events, or episodes. In patients experiencing at least one HF event, hospitalizations for any cause, outpatient services utilization, and drug prescriptions were also analyzed. Results Seven hundred one thousand, seven hundred one heart failure events involving 371,766 patients were recorded from 2000 to 2012. Once all the healthcare services provided to these patients after the first HF event had been joined together, the study database totalled about 91 million records. Principles, criteria and tips utilized in order to minimize errors and characterize some relevant subgroups are described. Conclusions The methodology of this study could represent the basis for future research and could be applied in similar studies concerning epidemiology, trend analysis, and healthcare resources utilization.

Prior to 2000 a network of conventional ozone (O 3 ) analysers existed in the Province of Firenze (Tuscany, central Italy). Between 2000 and 2004 the network was extended to incorporate a newly designed bioindicator network of tobacco plants ( Nicotiana tabacum Bel W3). The objective was to set-up an integrated monitoring system to obtain estimates of ground-level O 3 concentrations over the whole study area (3513 km 2 ) in order to fill data gaps and cover reporting requirements. The existing conventional monitors were purposefully located mainly in urban areas. A total of 45 biomonitoring sites were selected using a systematic design to cover the target area. Two to five additional biomonitoring sites were co-located with conventional O 3 analysers for calibration purposes, and five more sites for independent validation of modelled O 3 concentrations. Visible Leaf Injury Index (LII) on the tobacco plants was significantly correlated ( P : 0.018 ÷ 0.0014) with a series of O 3 exposure variables (mean of weekly 1-hour maxima, M1; mean of 7-hour means, M7; 24-hour mean, M24; and weekly AOT40). LII was found to be a significant predictor of weekly means of the O 3 exposure variables with a standard error of estimates between 13.6 and 24.3 μg m − 3 (absolute values). LII was mapped with an ad-hoc spatial model over the study area at a 2 ⁎ 2 km grid resolution, and mapped values were used to predict O 3 concentrations by means of a first order linear model. Results showed that high estimates of O 3 (up to 188 μg m − 3 as mean of weekly maxima, M1) occurred more frequently in hilly and mountainous areas, with a spatial pattern changing on an annual basis. Predicted O 3 concentrations were not significantly different from the measured concentrations ( P : 0.34), although marked differences were observed for individual sites and years. The study provided evidence that integration of monitoring networks using different methods can be a viable option to obtain estimates of O 3 concentrations over large areas.

Chronic hepatitis C is one of the most important causes of liver disease, leading to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Recently some important advances in therapy have been achieved with the introduction of first wave, first generation direct acting antiviral agents (DAAs) such as boceprevir (BOC), in combination with pegylated interferon (Peg-IFN) and ribavirin (RBV). The superior rate of sustained virological response with this treatment is accompanied by an elevated frequency of anaemia. Several studies have evidenced the importance of single nucleotide polymorphisms (SNPs) in inosine triphosphatase (ITPA) and solute carrier family 29, member 1 (SLC29A1) genes in the development of this adverse event. Here, we investigated haemoglobin levels and the best-known functional SNPs in ITPA and SLC29A1 genes in 22 patients treated with triple therapy with BOC/Peg-IFN/RBV. The identification of ITPA protective and SLC29A1 risk genotypes still appears to be a current methodology in RBV dosing during hepatitis C virus therapy with DAAs.

ObjectivesThe equilibrative nucleoside transporter 1 (ENT1) is the main protein involved in ribavirin cellular uptake. Polymorphisms at the SLC29A1 gene, encoding ENT1, may influence ribavirin-associated anaemia, which is observed at a higher incidence with telaprevir in combination with pegylated-IFNα and ribavirin than with pegylated-IFNα and ribavirin alone. In this study, we investigated the role of the rs760370 SLC29A1 variant in ribavirin-induced anaemia in chronic hepatitis C patients treated with telaprevir-based triple therapy.MethodsForty patients infected with hepatitis C virus (HCV) genotype 1 and starting anti-HCV therapy with telaprevir in combination with pegylated-IFN/ribavirin were prospectively evaluated for SNPs at the SLC29A1 gene and inosine triphosphatase (ITPA) genes using a real-time PCR system.Results40% of patients developed severe anaemia with a haemoglobin (Hb) decline ≥5 g/dL from the pretreatment value. The SLC29A1 rs760370 GG genotype was associated with the severity of Hb decrease as expressed by the median (IQR) Hb nadir change from baseline [−5.4 (−5.6; −5.0) g/dL in GG versus −4.2 (−5.1; −3.4) in AA/AG genotype; P = 0.05] and by the Hb decrease ≥5 g/dL by week 12 (77.8% of GG carriers versus 24% of AA/AG; P ConclusionsIn patients with chronic hepatitis C receiving telaprevir-based therapy, SNP rs760370A>G at the SLC29A1 gene influences the severity of ribavirin-induced anaemia, possibly mirroring the erythrocyte uptake of ribavirin.

Advantages and criticisms in using administrative data for clinical and epidemiological research are well discussed. These databases were originally designed for administrative aims rather than for clinical research. Several choices are necessary to make these databases suitable for clinical and epidemiological research. The choices have to be explicit and clearly declared, to let the reader know their possible effects. In this work we discuss methodological issues concerning the preliminary work on data from a regional project.

Passive samplers (diffusion tubes with organic reagent, produced by Passam of Switzerland) were used in a sampling campaign for the detection of weekly mean ozone concentrations in 15 sites over a domain of 80 x 40 km on the southern side of the European Alps from May to August 1998. The area is characterized by vast natural terrain of complex topography, with conifer and broadleaf forests. It is difficult to access and monitor air quality there with continuous analysers. By applying geostatistical techniques (ordinary kriging), and correcting the interpolated ozone concentrations according to the altitude of each single grid cell (2 x 2 km), maps of weekly ozone concentrations were produced. The weekly ozone data were used to assess daily and hourly data by means of an iterative procedure based on a functional dependence of ozone concentrations both on altitude and on the time of day. This allowed the estimation of values with an exposure index such as AOT40 (accumulated exposure over the threshold of 40 ppb) in all 800 cells of the domain. This also allowed the mapping of risk assessment related to the effects of ozone on the regional forest vegetation. Results obtained show values that exceed the exposure standards adopted in the Kuopio protocol (1996). Excess exposure values also match values calculated over a wider territorial domain by using hourly data on ozone concentration derived from continuous automatic analysers.

Health research based on administrative data and the availability of regional or national administrative databases has been increasing in recent years. We will discuss the general characteristics of administrative data and specific aspects of their use for health research purposes, indicating their advantages and disadvantages. Some fields of application will be discussed and described through examples.

Background This study aimed to provide a contemporary picture of the epidemiologic, clinical, microbiologic characteristics and in-hospital outcome of infective endocarditis (IE) observed in a single center in Italy. Methods We performed a retrospective study of patients with definite or probable IE observed at the “L. Sacco” Hospital in Milan, Italy, from January 1, 2003 through December 31, 2010. Results 189 episodes of IE in 166 patients were included. The mean number of incident IE in the study period was of 1.27 (range 0.59-1.76) cases per 1000 patients admitted. The median age of the cohort was 57 (interquartile range, 43-72) years, 63% were male and 62.5% had native valve IE. Twenty-six percent were active intravenous drug users (IVDU), 29% had a health care-associated IE and 5% chronic rheumatic disease. Twenty-nine percent of the cases occurred in patients affected by chronic liver disease and 19% in HIV positive subjects. Staphylococcus aureus was the most common pathogen (30%), followed by streptococci. The mitral (34%) and aortic (31%) valves were involved most frequently. The following complications were common: stroke (19%), non-stroke embolizations (25%), heart failure (26%) and intracardiac abscess (9%). Surgical treatment was frequently employed (52%) but in hospital mortality remained high (17%). Health care-associated IE and complications were independently associated with an increased risk of in-hospital death, while surgery was associated with decreased mortality. Conclusion S. aureus emerged as the leading causative organism of IE in a University hospital in northern Italy. Our study confirmed the high in-hospital mortality of IE, particularly if health care associated, and the protective role of surgery.

The present study aims to promote incidence and prevalence estimates, to evaluate potential benefits and harms of specific health policies and to evaluate adherence to best practice by quality indicators based on administrative and textual databases (DB).

The industrialized world is undergoing epidemiologic variations in acute coronary syndrome and the female gender is particularly involved in these changes. Our study was designed based on administrative databases of all hospital admissions in the Lombardy region during the years 2000–2010 which enabled us to obtain complete and updated information regarding the gender-related epidemiologic situation.

The long-term impact of pegylated-interferon plus ribavirin (Peg-IFN-RBV) treatment outcome on CD4 T cell course in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is unknown. The aim of this study was to investigate the impact of HCV-RNA clearance by standard anti-HCV therapy on long-term CD4 cells recovery in HIV/HCV patients on successful combined antiretroviral therapy (cART). We retrospectively enrolled HIV/HCV-coinfected patients on stable cART, treated with Peg-IFN-RBV between 2005 and 2009. CD4(+) T cell counts were registered at baseline (pre-Peg-IFN-RBV), after 6, 12, and 24 months of follow-up from therapy discontinuation. Multiple linear regression analysis was performed to identify independent predictors of CD4(+) T cell change following the anti-HCV treatment outcome. Of the 116 patients enrolled, 54 (46.6%) reached a sustained virological response (SVR) and 62 (53.4%) did not. Throughout a median follow-up of 24 months, the SVR group showed a mean annual increase in CD4(+) T cell from baseline of 84 cells/μl at 1 year and of a further 38 cells/μl within the second year (p=0.01, 0.001, respectively). A nonsignificant mean increase of 77 cells/μl occurred in the non-SVR group within month 24 (p=0.06). Variables associated with greater CD4 gains were higher nadir and lower pre-interferon CD4 counts, and lower body mass index (BMI). The achievement of SVR was not significantly associated with the change in CD4(+) count. The clearance of HCV replication did not affect the CD4(+) changes after Peg-IFN-RBV therapy in coinfected patients on efficient cART. Liver fibrosis and higher BMI were negative determinants of immune recovery.

Objectives: Low 25-Hydroxyvitamin D (25[OH]D) was associated with severe fibrosis and low sustained virological response (SVR) after interferon (IFN)-based therapy in chronic hepatitis C. Furthermore, hypovitaminosis D was reported in HIV-infected individuals, but its role in liver disease progression in HIV/HCV coinfection is unknown. Methods: 25(OH)D was retrospectively measured in 237 HIV-infected patients (93 with HCV coinfection) and 76 healthy controls. Multivariate analysis included season, immuno-virological data, combined antiretroviral therapy (cART) and, in a subgroup of 51 HIV/HCV-genotype 1 coinfected patients, factors influencing SVR to pegylated-IFN and ribavirin. In a group of 20 patients, liver expression of cytochrome (CY)-P27A1 and CYP2R1, 25-hydroxylating enzymes, was assessed by immunohistochemistry. Results: Median 25(OH)D levels were 23.4 (interquartile range 16.7-33.7) ng/mL in the HIV-infected population and 24 ng/mL (18.3-29.5) in healthy controls (p=0.9). At multiple regression analysis, only winter/spring measurements correlated with lower 25(OH)D levels. No correlation with HCV coinfection, nor with cART regimens was found. Low 25(OH)D was independently associated with advanced fibrosis in HIV/HCV coinfected patients (p=0.023), whereas no association emerged with SVR to IFN-based therapy. CYP27A1 and CYP2R1 expression was associated neither with 25(OH)D serum levels nor with HCV-infection, liver histology, or cART. Conclusions: In our experience, despite the high prevalence of 25(OH)D insufficiency, HIV and HCV-infection did not seem to influence vitamin D status. The role of HIV, HCV and cART on hypovitaminosis D needs further validation in larger cohorts that account for the vitamin levels in general populations and for seasonal and regional variability.

Background & Aims It is uncertain whether mucosal healing after the first course of corticosteroids therapy predicts outcome in patients with ulcerative colitis (UC). We evaluated whether early clinical and endoscopic responses to this therapy are associated with late outcomes in UC. Methods Patients with newly diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed up for 5 years. They were evaluated using clinical (Powel–Tuck [PT]) and endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at month 3 (early response) were used to identify patients with complete (group A: PT, 0–1; Baron, 0), partial (group B: PT, 0–1; Baron, 1–3), or no response (group C: persistence of clinical and endoscopic activity). The association between early and late outcomes was assessed. Results After 5 years, there were significant differences between complete and partial responders in the rates of hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.21–6.72), immunosuppression therapy (5% in group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67–25.67), colectomy (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24–32.37), and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61; 95% CI, 1.12–6.11). After multivariate analysis, lack of mucosal healing was the only factor associated with negative outcomes at 5 years (immunosuppressors: hazard risk [HR], 10.581; 95% CI, 2.193–51.039; P = .0033; hospitalization: HR, 3.634; 95% CI, 1.556–8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278–55.186; P = .0268). Conclusions No mucosal healing after corticosteroid therapy is associated with a more aggressive disease course.

OBJECTIVES Recent reports demonstrated in vitro the efficacy of fluvastatin in inhibiting hepatitis C virus (HCV) replication and a synergistic effect in association with interferon-alpha (IFN-alpha). In vivo the inhibition of HCV replication by statins has not been demonstrated. We evaluated in this open-label, randomized controlled study the efficacy of fluvastatin as adjuvant to pegylated-(PEG)-IFN and ribavirin in HIV/HCV genotype 1 co-infected patients. PATIENTS AND METHODS Forty-four HIV/HCV co-infected patients were randomized to receive, in addition to PEG-IFN-alpha 2b and ribavirin, 80 mg of fluvastatin once daily or no medication. Primary and secondary endpoints were the achievement of sustained virological response (SVR) and rapid virological response (RVR), respectively. RESULTS By intent-to-treat analysis, 25% of the patients achieved an SVR. An SVR was observed in 8/21 patients in the fluvastatin arm and in 3/23 patients in the standard therapy arm (P = 0.08). A significantly higher RVR rate was obtained in the fluvastatin arm compared with the standard therapy [7/21 (33%) and 1/23 (4%), respectively; P = 0.02]. Baseline alanine aminotransferase (ALT) values and fluvastatin treatment arm were the only predictors of RVR at the univariate analysis; however, no predictors were independently associated with RVR or SVR at the multivariate analysis. CONCLUSIONS Fluvastatin addition to standard therapy did not significantly increase the SVR rate in HIV/HCV genotype 1 co-infected patients; however, it did significantly improve the RVR. Further studies are needed to confirm these promising results and to investigate the mechanisms of action of statins in HCV infection.

Women are at high risk for mortality after ST-elevation acute myocardial infarction (STEMI). Whether sex-disparities still exist in the treatment and mortality of patients after STEMI remains controversial. The aim of this study was to assess recent trends in hospital mortality and in treatment

In recent years multidisciplinary surveys examining the impact of pollutants on forest ecosystems have been carried out in the Valtellina (Northern Italy, Alpine region). A large part of the activity of these surveys has involved the study of ozone and its distribution in the area, development of the exceedances maps (AOT40) and their validation by means of field observation of visible foliar symptoms in the indigenous and sensitive forest vegetation. The present paper reports the results of a field survey carried out in 1998 on the visible symptoms expressed by several native species (trees, shrubs and herbs). A non-systematic grid of 81 plots was assessed throughout the valley. Due to the high variability of the physical (altitude, slope, exposure, etc.) and vegetational (species assemblage, tree age, forest structure) features, the comparability among the plots was found to be very weak, so only the presence or absence of leaf injuries was assessed. Results do not show any correlation between the distribution of foliar symptoms in Valtellina and ozone levels. Rather, leaf injuries follow the same distribution of environmental modifying factors (such as depth and moisture of the soil) and tree sensitivity.

Ozone is the most harmful air pollutant for plant ecosystems in the Mediterranean and Alpine areas due to its biological and economic damage to crops and forests. In order to evaluate the relation between ozone exposure and vegetation injury under on-field conditions, suitable ozone monitoring techniques were investi-gated. In the framework of a 5-year research project aimed at ozone risk assessment on forests, both continuous analysers and passive samplers were employed during the summer seasons (1994�1998) in different sites of a wide mountain region (80 x 40 km2) on the southern slope of the European Alps. Continuous analysers allowed the recording of ozone hourly concentration means necessary both to calculate specific exposure indexes (such as AOT, SUM, W126) and to record daily time-courses. Passive samplers, even though supplied only weekly mean concentration values, made it possible to estimate the altitude concentration gradient useful to correct the altitude dependence of ozone concentrations to be inserted into exposure indexes. In-canopy ozone profiles were also determined by placing passive samplers at different heights inside the forest canopy. Vertical ozone soundings by means of tethered balloons (kytoons) allowed the measurement of the vertical concentration gradient above the forest canopy. They also revealed ozone reservoirs aloft and were useful to explain the ozone advection dynamic in mountain slopes where ground measurement proved to be inadequate. An intercomparison between passive (PASSAM, CH) and continuous measurements highlighted the necessity to accurately standardize all the exposure operations, particularly the pre- and postexposure conservation at cold temperature to avoid dye (DPE) activity. Advantages and disadvantages from each mentioned technique are discussed.

Background Injury is a public health problem in terms of mortality, morbidity and disability. The implementation of a regionalised trauma system has been proved to significantly reduce the social impact of severe trauma on population. A population-based registry may be useful to obtain reliable epidemiologic data. Aim To perform an exhaustive analysis of severe trauma patients hospitalised in Lombardia, a region of northern Italy. Materials and methods The regional Hospital Discharge Registry (HDR) was used to retrieve data of all patients who suffered from serious injuries from 2008 to 2010. ICD9-CM codes of discharge diagnoses were analysed and patients coded from 800.0 to 939.9 or from 950.0 to 959.9 have been retrieved. Femur fractures in elderly and patients with length of hospital stay less than 2 days were excluded. Patients have been considered seriously injured if discharged dead or any of followings: admission or transit in ICU, need of mechanical ventilation, tracheotomy, invasive hemodynamic monitoring. Average reimbursement based on DRG has been evaluated. Statistics Student’s t test, ANOVA for continuous data, chi-square test for categorical data were used, and a p value less than 0.05 was considered significant. Results The severely injured patients hospitalised in Lombardia in three years were 11704, 391 per million per year. Overall mortality was 24.17% and increased with age. Males aging from 18 to 64 years had more occupational injuries, trauma on the road and violence by others. Females were more susceptible to domestic injuries and self inflicted violence, mostly in older ages. Acute mortality was higher after traffic accidents, while late mortality was increased in domestic trauma. Pediatric cases were unusual. A significant increase (+10.18%) in domestic trauma, with a concomitant decrease (-17.76%) in road-related accidents was observed in the three years study period. Reimbursement paid to hospitals for seriously injured was insufficient with regard to estimated costs of care. Conclusion Serious injury requiring hospitalisation in Lombardia is still an healthcare problem, with a trend toward a decrease of traffic accidents, increase in domestic trauma and involvement of older people. These results may help to plan a new regionalised Trauma System.