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Adverse reactions, toxicity, and poor compliance from patients still represent major challenges for conventional chemotherapy treatments. Localized drug delivery would ideally improve therapeutic efficacy, minimizing the side effects. An MSU-type mesoporous silica-based nanodevice (FOL-MSN-BTZ), able to selectively deliver the antineoplastic drug bortezomib (BTZ) to folate receptor over-expressing multiple myeloma (FR+ MM) cells is described. The receptor-specific ligand, folic acid, grafted on the external surface of the nanosystem, allows tumor recognition and cell internalization, while BTZ, mainly linked to the pore internal surface through a covalent pH-sensitive bond, is released in an acidic tumor environment. A detailed investigation showed that only the fine balancing of different functionalities of the nanodevice around the external and internal surfaces of MSN particles shows the absence of toxicity towards healthy cells in vitro and negligible BTZ-release at physiological pH, which are suitable features for applicative purposes in the engineering of therapies. After complete characterization in vitro, an accurate suspendability assessment, which considered the sedimentation process that reduces the particle amount and, consequently, drug content in the suspensions, allowed the development of an injectable formulation of FOL-MSN-BTZ that showed higher antitumor efficacy and an overall tendency to lower toxicity in a MM mice model compared to the conventional bortezomib chemotherapy.

Background To face the second COVID-19 wave, Italy implemented a tiered restriction system with different risk levels (yellow=low; orange=medium, red=high). It is unknown whether the effect of the tiers was equal among provinces with varying levels of socioeconomic deprivation (SED). At each restriction level, we analyzed the impact of the province's SED on the SARS-CoV-2 daily reproduction number (Rt). Methods We considered the Rt (Nov 2020-May 2021) as the dependent variable and the SED as the independent variable. The Rt was estimated using daily incidence data from the Civil Protection Department as the instantaneous Rt. The province SED was measured using the percentage of individuals whose yearly income was less than 10,000€ (2019 data from the Ministry of Economy and Finance). We used multilevel linear regression models with random intercepts stratified by restriction level to estimate the effect of the SED on Rt (β) and its Standard Error (SE). Our analyses adjusted the estimates for the number of days into the tier first and then for other covariates. Results We found different levels and trends of Rt by SED in every restriction. Days-adjusted models found a containing effect for the red and the orange tier, while the Rt had an increasing trend in yellow. Higher SED was associated with higher Rt: β was positive and significant in red (β = 0.004 SE = 0.001) and orange (β = 0.002 SE = 0.001) but not in the lowest tier (β = 0.001 SE = 0.001). We found a significant interaction between the number of days into the restriction and the SED in the complete models. Compared to less deprived, more deprived provinces had slower Rt reduction in the highest tier. However, they had steeper Rt reductions in orange and slower increasing trends in yellow. Conclusions The highest restriction had milder effects in more deprived provinces, while lower tiers were more effective. These results underline the importance of accounting for SED when implementing public health measures. Key messages • Area-level deprivation can modify the effects of public health measures. • Socioeconomic characteristics of the areas should be considered when implementing policies aimed to prevent the spread of epidemics.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Background In Italy there is evidence of a large variability in health care services and health outcomes. This multi-regional project is funded on Ministry of Health and Health Regional Authorities (code NET-2016-02364191). The aims are: 1) To test the effectiveness of Audit and Feedback (A&F) interventions in improving health professional practices and patients' outcomes in different settings using both a quantitative and a qualitative approach. 2) To examine factors that may explain variations in the effectiveness of A&F. 3) To evaluate the impact of A&F in reducing avoidable differences in access to effective health care interventions in socioeconomically disadvantaged populations. Methods In the 7 participating Regions (about 33 million inhabitants) experimental study designs have been implemented in different clinical areas (e.g. before-after controlled study, cluster randomized trial): in Lazio emergency care and chronic diseases care, in Friuli Venezia Giulia emergency care, in Piemonte oncology care, in Emilia Romagna chronic disease care, in Lombardia cardiovascular care, in Calabria deliveries and maternal health, in Sicilia emergency care. The effectiveness of different types of A&F are compared in term of outcomes using health information system databases. Results Preliminary results show large heterogeneity in developing and conducting A&F, in term of team project composition, type of intervention, clinicians' behavior to be changed, outcomes indicators, professionals involved, structure and timing of data reporting, actions to be implemented after the intervention. Limited awareness and interest of clinicians in A&F interventions was found. Conclusions The project represents a unique opportunity to explore how A&F interventions could be better designed. Different A&F strategies will be compared in term of clinical outcomes. The identification of barriers/facilitating factors will supply knowledge on mechanisms and tools to enhance A&F effectiveness. Key messages The project supports providers in reducing gap between knowledge and practice. The project promotes culture of interprofessional collaboration as a key point for high quality care.

BackgroundThe impact of the severe acute respiratory syndrome Coronavirus 2 disease (COVID-19) pandemic on people with systemic autoimmune rheumatic diseases (SARDs) remains to be fully established. It is unclear whether SARDs are an independent risk factor for COVID-19 infection and poor outcome.ObjectivesThe aim of our study is to assess the incidence and prognosis of test-proven SARS-CoV-2 infection during the first COVID-19 wave in a large population of SARD patients of the Lazio Italian region.MethodsWe retrospectively evaluated in a cohort of 4.716.119 subjects aged over 18 years and affiliated to the health system of the Lazio Italian Region, the incidence and 30-day outcomes of COVID-19 infection in 40.490 SARD pts and compared to the affiliated population as incidence rate ratio adjusted for demographics and comorbidities (adjIRR). SARD diagnosis and comorbidities were derived from medical administrative records using the Chronic Related Group classification system. Data on COVID-19 infection were derived from a dedicated regional digital network.ResultsThe risk of COVID-19 infection was increased in patients with Psoriatic Arthritis (adjIRR=1.21, 95% CI 1.10-1.33) and Undifferentiated Connective Tissue Disease (adjIRR=1.26, 95% CI 1.03-1.54). The risk of hospitalisation was higher in patients with Axial Spondylarthritis (adjIRR=2.16, 95% CI 1.45-3.22), and Systemic Vasculitis (adjIRR=1.81, 95% CI 1.07-3.06) while the risk of Intensive care unit admission was higher in Systemic Erythematous Lupus (adjIRR=3.67, 95% CI 1.52-8.83) and primary Sjögren Syndrome (adjIRR=4.13, 95% CI 1.71-9.96) patients. An increased COVID-19 mortality was reported in patients with Rheumatoid Arthritis (adjIRR=1.50, 95% CI 1.04-2.17), Systemic Erythematous Lupus (adjIRR=2.67, 95% CI 1.10-6.44), primary Sjögren Syndrome (adjIRR=2.51, 95% CI 1.12-5.62), and Scleroderma (adjIRR=4.60, 95% CI 2.06-10.29).ConclusionThe incidence of severe COVID-19 is not increased in the same percentage in SARDs. Each SARD presents a peculiar pattern in terms of increased risk of COVID-19 incidence, hospitalisation, intensive care unit admission and death, that is not linked to the immunosuppressive behaviour of the disease.Disclosure of InterestsNone declared

Background Polypharmacy in the elderly is a matter of concern, especially regarding adverse events and drug–drug interactions. Little is known about real world drug use in the elderly in Italy. The present study aimed at describing drug use in the elderly with respect to individual characteristics, performing a cross-sectional population study in Lazio, Italy. Methods From the regional health care assistance file, residents aged 65 years and older (mean age = 75.9 years, SD = 7.4) and alive at the end of 2010 were enrolled. Drug consumption was linked from the drug claims registry for 2010, and hospital admissions were retrieved from the hospital admission registry during 2009–2010. Enrolees were characterised for socio-demographic variables, presence of chronic diseases, and drug consumption, considering large groups, and specific sub-groups. Polypharmacy was defined as use of 6+ drugs (ATC 4th level). Results Of the 1,122,864 elderly residents, 57.9% were women, and 48.8% aged 75+. In the previous two years, 28.3% had been admitted to hospital; most common causes were cerebro- and cardiovascular diseases, diabetes and tumours; 78.9% of the elderly population of the city of Rome lived in low-level socio-economic areas. Only 6.8% had not been prescribed drugs in the 12-months observation period, and 58.8% were exposed to polypharmacy. With respect to the overall population, polypharmacy users were more often females (59.7%), older (54.5% aged 75 + ), had poorer health conditions (37.2% hospitalised), and more often lived in poorer areas (19.9%). Conclusion In Lazio, polypharmacy is an important phenomenon in the elderly population. Female gender, older ages and presence of chronic diseases are related to multiple drug use. The present results offer a useful tool for future initiatives aiming at reducing inappropriate polypharmacy and target interventions to subpopulations at higher risk of being exposed to polypharmacy.

Graphical abstractDisplay Omitted Highlights? Growth of TiO2/CNT composite by an evaporation technique in UHV ambient. ? In the composite growth we observe chemical bonds formation only between oxygen and Ti atoms. ? The TiO2 film appears highly homogeneous and with a thickness of about 1.5micron. ? Absence of luminescence emission from composites indicates the absence of oxygen vacancies defects. In this work we present a method for preparing carbon nanotubes/titanium dioxide (CNTs/TiO2) composites with a simple metal vaporization technique in ultra high vacuum ambient at high temperature. We obtain a composite with a highly uniform layer of Ti/TiO2 on CNT and measure exactly the ratio between composites with X-ray Photoemission Spectroscopy (XPS). The obtained Ti-TiO2 film has a thickness of about 1.5micron and it is perfectly super imposed to carbon nanotubes buckypaper without formation of chemical bonds between tubes and Ti at interface. Comparison between TEM images taken from CNT before and after the treatment indicates the absence of deformation and changes in tube structures. The crystallinity of deposed TiO2 was investigated by Fourier Transform Infrared Spectroscopy (FTIR) which indicate the only presence of anatase. Titanium dioxide is produced by bonds between evaporated Ti atoms and oxygen already adsorbed on carbon nanotubes. Moreover the produced film is very stable and we do not observe changes in Ti percentage after several annealing cycles at high temperatures (500?C).Finally cathode-luminescence measurements indicate the formation of TiO2 film without presence of oxygen vacancies defects.

Background Percutaneous coronary intervention (PCI) reduces mortality in most myocardial infarction (MI) patients but the effect on elderly patients with comorbidities is unclear. Our aim was to analyse the effect of PCI on in-hospital mortality of MI patients, by age, sex, ST elevation on presentation, diabetes mellitus (DM) and chronic kidney disease (CKD). Methods Cohort study of 79,791 MI patients admitted at European hospitals during 2000–2014. The effect of PCI on in-hospital mortality was analysed by age group (18–74, ≥ 75 years), sex, presence of ST elevation, DM and CKD, using propensity score matching. The number needed to treat (NNT) to prevent a fatal event was calculated. Sensitivity analyses were conducted. Results PCI was associated with lower in-hospital mortality in ST and non-ST elevation MI (STEMI and NSTEMI) patients. The effect was stronger in men [Odds ratio (95% confidence interval) 0.30 (0.25–0.35)] than in women [0.46 (0.39–0.54)] aged ≥ 75 years, and in NSTEMI [0.22 (0.17–0.28)] than in STEMI patients [0.40 (0.31–0.5)] aged < 75 years. PCI reduced in-hospital mortality risk in patients with and without DM or CKD (54–72% and 52–73% reduction in DM and CKD patients, respectively). NNT was lower in patients with than without CKD [≥ 75 years: STEMI = 6(5–8) vs 9(8–10); NSTEMI = 10(8–13) vs 16(14–20)]. Sensitivity analyses such as exclusion of hospital stays < 2 days yielded similar results. Conclusions PCI decreased in-hospital mortality in MI patients regardless of age, sex, and presence of ST elevation, DM and CKD. This supports the recommendation for PCI in elderly patients with DM or CKD. © 2017 The Authors

BACKGROUND: Evidence on the association between short-term exposure to desert dust and health outcomes is controversial. OBJECTIVES: We aimed to estimate the short-term effects of particulate matter 0 mu g/m(3)). Most episodes occurred in spring-summer, with increasing gradient of both frequency and intensity north-south and west-east of the Mediterranean basin. We found significant associations of both PM10 concentrations with mortality. Increases of 10 mu g/m(3) in non-desert and desert PM10 (lag 0-1 days) were associated with increases in natural mortality of 0.55% (95% CI: 0.24, 0.87%) and 0.65% (95% CI: 0.24, 1.06%), respectively. Similar associations were estimated for cardio-respiratory mortality and hospital admissions. CONCLUSIONS: PM10 originating from the desert was positively associated with mortality and hospitalizations in Southern Europe. Policy measures should aim at reducing population exposure to anthropogenic airborne particles even in areas with large contribution from desert dust advections.

Objectives: While several studies have reported associations of daily exposures to PM2.5 (particles less than 2.5 μm) with mortality, few studies have examined the impact of its constituents such as black carbon (BC), which is also a significant contributor to global climate change. Methods: We assessed the association between daily concentrations of BC and total, cardiovascular and respiratory mortality in two southern Mediterranean cities. Daily averages of BC were collected for 2 years in Barcelona, Spain and Athens, Greece. We used case-crossover analysis and examined single and cumulative lags up to 3 days. Results: We observed associations between BC and all mortality measures. For a 3-day moving average, cardiovascular mortality increased by 4.5% (95% CI 0.7 to 8.5) and 2.0% (95% CI 0 to 4.0) for an interquartile change in BC in Athens and Barcelona, respectively. Considerably higher effects for respiratory mortality and for those above age 65 were observed. In addition, BC exhibited much greater toxicity per microgram than generic PM2.5. Conclusions: Our findings suggest that BC, derived in western industrialised nations primarily from diesel engines and biomass burning, poses a significant burden to public health, particularly in European cities with high-traffic density.

Background: Few recent studies examined acute effects on health of individual chemical species in the particulate matter (PM) mixture, and most of them have been conducted in North America. Studies in Southern Europe are scarce. The aim of this study is to examine the relationship between particulate matter constituents and daily hospital admissions and mortality in five cities in Southern Europe. Methods: The study included five cities in Southern Europe, three cities in Spain: Barcelona (2003-2010), Madrid (2007-2008) and Huelva (2003-2010); and two cities in Italy: Rome (2005-2007) and Bologna (2011-2013). A case-crossover design was used to link cardiovascular and respiratory hospital admissions and total, cardiovascular and respiratory mortality with a pre-defined list of 16 PM10and PM2.5constituents. Lags 0 to 2 were examined. City-specific results were combined by random-effects meta-analysis. Results: Most of the elements studied, namely EC, SO4 2-, SiO2,Ca, Fe, Zn, Cu, Ti, Mn, V and Ni, showed increased percent changes in cardiovascular and/or respiratory hospitalizations, mainly at lags 0 and 1. The percent increase by one interquartile range (IQR) change ranged from 0.69% to 3.29%. After adjustment for total PM levels, only associations for Mn, Zn and Ni remained significant. For mortality, although positive associations were identified (Fe and Ti for total mortality; EC and Mg for cardiovascular mortality; and NO3 -for respiratory mortality) the patterns were less clear. Conclusions: The associations found in this study reflect that several PM constituents, originating from different sources, may drive previously reported results between PM and hospital admissions in the Mediterranean area. © 2014 Elsevier Ltd.

Background: An association between occurrence of wildfires and mortality in the exposed population has been observed in several studies with controversial results for cause-specific mortality. In the Mediterranean area, forest fires usually occur during spring-summer, they overlap with Saharan outbreaks, are associated with increased temperature and their health effects are probably due to an increase in particulate matter. Aim and methods: We analysed the effects of wildfires and particulate matter (PM10) on mortality in 10 southern European cities in Spain, France, Italy and Greece (2003-2010), using satellite data for exposure assessment and Poisson regression models, simulating a case-crossover approach. Results: We found that smoky days were associated with increased cardiovascular mortality (lag 0-5, 6.29%, 95% CIs 1.00 to 11.85). When the effect of PM10 (per 10 mg/m3) was evaluated, there was an increase in natural mortality (0.49%), cardiovascular mortality (0.65%) and respiratory mortality (2.13%) on smoke-free days, but PM10-related mortality was higher on smoky days (natural mortality up to 1.10% and respiratory mortality up to 3.90%) with a suggestion of effect modification for cardiovascular mortality (3.42%, p value for effect modification 0.055), controlling for Saharan dust advections. Conclusions: Smoke is associated with increased cardiovascular mortality in urban residents, and PM10 on smoky days has a larger effect on cardiovascular and respiratory mortality than on other days.

A cross-sectional survey was carried out between April 1997 and February 1998 among street prostitutes in Rome. The study population (n = 142) consisted of 102 women and 40 transsexuals: 20% from Western Europe, 38% Eastern Europe, 23% Latin America and 17% Africa. Two-thirds of the population had more than 20 clients during the last week and most respondents (95%) reported always using condoms with clients. Eight per cent of the women and 2% of the transsexuals report a history of injecting drug use. Only 38% of the women with a stable partner reported use of contraceptives and 33% of them had undergone a voluntary abortion during the last year. Only 38% of the women had been checked for STDs during the last year, compared with 80% of the transsexuals. The HIV-prevalence was 6% among the women and 20% among the transsexuals. Four out of the six positive women and one of the positive transsexuals had a history of injecting drug use. Five out of the six HIV-positive women were Italian. Transsexual prostitutes seem to pay more attention to their medical wellbeing compared with females who rarely go for medical check-ups and only a minority uses efficient contraceptive methods.

Previous studies reported significant variability of air pollutants across Europe with the lowest concentrations generally found in Northern Europe and the highest in Southern European countries. Within the MED-PARTICLES project the spatial and temporal variations of long-term PM and gaseous pollutants data were investigated in traffic and urban background sites across Southern Europe. The highest PM levels were observed in Greece and Italy (Athens, Thessaloniki, Turin and Rome) while all traffic sites showed high NO2levels, frequently exceeding the established limit value. High PM2.5/PM10ratios were calculated indicating that fine particles comprise a large fraction of PM10, with the highest values found in the urban background sites. It seems that although in traffic sites the concentrations of both PM2.5and PM10are significantly higher than those registered in urban background sites, the coarse fraction PM2.5-10is more important at the traffic sites. This fact is probably due to the high levels of resuspended road dust in sites highly affected by traffic, a phenomenon particularly relevant for Mediterranean countries. The long-term trends of air pollutants revealed a significant decrease of the concentration levels for PM, SO2and CO while for NO2no clear trend or slightly increasing trends were observed. This reduction could be attributed to the effectiveness of abatement measures and strategies and also to meteorological conditions and to the economic crisis that affected Southern Europe. © 2014 Elsevier B.V.

We investigated the short-term effects of particles with aerodynamic diameter less than 2.5μm (PM2.5), between 2.5 and 10μm (PM2.5-10) and less than 10μm (PM10) on deaths from diabetes, cardiac and cerebrovascular causes, lower respiratory tract infections (LRTI) and chronic obstructive pulmonary disease (COPD) in 10 European Mediterranean metropolitan areas participating in the MED-PARTICLES project during 2001-2010.In the first stage of the analysis, data from each city were analyzed separately using Poisson regression models, whereas in the second stage, the city-specific air pollution estimates were combined to obtain overall estimates. We investigated the effects following immediate (lags 0-1), delayed (lags 2-5) and prolonged exposure (lags 0-5) and effect modification patterns by season. We evaluated the sensitivity of our results to co-pollutant exposures or city-specific model choice. We applied threshold models to investigate the pattern of selected associations.For a 10μg/m3 increase in two days' PM2.5 exposure there was a 1.23% (95% confidence interval (95% CI): -1.63%, 4.17%) increase in diabetes deaths, while six days' exposure statistically significantly increased cardiac deaths by 1.33% (95% CI: 0.27, 2.40%), COPD deaths by 2.53% (95% CI: -0.01%, 5.14%) and LRTI deaths by 1.37% (95% CI: -1.94%, 4.78%). PM2.5 results were robust to co-pollutant adjustments and alternative modeling approaches. Stronger effects were observed in the warm season. Coarse particles displayed positive, even if not statistically significant, associations with mortality due to diabetes and cardiac causes that were more variable depending on exposure period, co-pollutant and seasonality adjustment.Our findings provide support for positive associations between PM2.5 and mortality due to diabetes, cardiac causes, COPD, and to a lesser degree to cerebrovascular causes, in the European Mediterranean region, which seem to drive the particles short-term health effects. © 2014 Elsevier Ltd.

Background: Few studies have investigated the independent health effects of different size fractions of particulate matter (PM) in multiple locations, especially in Europe. Objectives: We estimated the short-term effects of PM with aerodynamic diameter ≤ ; 10; μm (PM10), ≤ 2.5; μm (PM2.5), and between 2.5 and 10; μm (PM2.5-10) on all-cause, cardiovascular, and respiratory mortality in 10 European Mediterranean metropolitan areas within the MED-PARTICLES project. Methods: We analyzed data from each city using Poisson regression models, and combined city-specific estimates to derive overall effect estimates. We evaluated the sensitivity of our estimates to co-pollutant exposures and city-specific model choice, and investigated effect modification by age, sex, and season. We applied distributed lag and threshold models to investigate temporal patterns of associations. Results: A 10-μg/m3 increase in PM2.5 was associated with a 0.55% (95% CI: 0.27, 0.84%) increase in all-cause mortality (0-1 day cumulative lag), and a 1.91% increase (95% CI: 0.71, 3.12%) in respiratory mortality (0-5 day lag). In general, associations were stronger for cardiovascular and respiratory mortality than all-cause mortality, during warm versus cold months, and among those ≥ 75 versus < 75 years of age. Associations with PM2.5-10 were positive but not statistically significant in most analyses, whereas associations with PM10 seemed to be driven by PM2.5. Conclusions: We found evidence of adverse effects of PM2.5 on mortality outcomes in the European Mediterranean region. Associations with PM2.5-10 were positive but smaller in magnitude. Associations were stronger for respiratory mortality when cumulative exposures were lagged over 0-5 days, and were modified by season and age.

Background: Evidence on the short-term effects of fine and coarse particles on morbidity in Europe is scarce and inconsistent. Objectives: We aimed to estimate the association between daily concentrations of fine and coarse particles with hospitalizations for cardiovascular and respiratory conditions in eight Southern European cities, within the MED-PARTICLES project. Methods: City-specific Poisson models were fitted to estimate associations of daily concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), ≤ 10 (PM10), and their difference (PM2.5-10) with daily counts of emergency hospitalizations for cardiovascular and respiratory diseases. We derived pooled estimates from random-effects meta-analysis and evaluated the robustness of results to co-pollutant exposure adjustment and model specification. Pooled concentration-response curves were estimated using a meta-smoothing approach. Results: We found significant associations between all PM fractions and cardiovascular admissions. Increases of 10 μg/m3 in PM2.5, 6.3 μg/m3 in PM2.5-10, and 14.4 μg/m3 in PM10 (lag 0-1 days) were associated with increases in cardiovascular admissions of 0.51% (95% CI: 0.12, 0.90%), 0.46% (95% CI: 0.10, 0.82%), and 0.53% (95% CI: 0.06, 1.00%), respectively. Stronger associations were estimated for respiratory hospitalizations, ranging from 1.15% (95% CI: 0.21, 2.11%) for PM10 to 1.36% (95% CI: 0.23, 2.49) for PM2.5 (lag 0-5 days). Conclusions: PM2.5 and PM2.5-10 were positively associated with cardiovascular and respiratory admissions in eight Mediterranean cities. Information on the short-term effects of different PM fractions on morbidity in Southern Europe will be useful to inform European policies on air quality standards.

Adherence to evidence-based drug therapy after acute myocardial infarction has increased over the last decades, but is still unsatisfactory. Our objectives are to set out to analyse patterns of evidence-based drug therapy after acute myocardial infarction (AMI), and evaluating socio-demographic differences.A cohort of 3920 AMI patients discharged from hospital in Rome (2006-2007) was selected. Drugs claimed during the 12 months after discharge were retrieved. Drug utilization was defined as density of use (boxes claimed/individual follow-up; chronic use = 6+ boxes/365 days) and therapeutic coverage, calculated through Defined Daily Doses (chronic use: ≥80% of individual follow-up). Patterns of use of single drugs and their combination were described. The association between poly-therapy and gender, age and socio-economic position (small-area composite index based on census data) was analysed through logistic regression, accounting for potential confounders.Most patients used single drugs: 90·5% platelet aggregation inhibitors (antiplatelets), 60·0%β-blockers, 78·1% agents acting on the renin-angiotensin system (ACEIs/ARBs), 77·8% HMG CoA reductase inhibitors (statins). Percentages of patients with ≥80% of therapeutic coverage were 81·9% for antiplatelets, 17·8% for β-blockers, 64·4% for ACEIs/ARBs and 76·1% for statins. The multivariate analysis showed gender and age differences in adherence to poly-therapy (females: OR = 0·84; 95% CI 0·72-0·99; 71-80 years age-group: OR = 0·82; 95% CI 0·68-0·99). No differences were observed with respect to socio-economic position.The availability of information systems offers the opportunity to monitor the quality of care and identify weaknesses in public health-care systems. Our results identify specific factors contributing to non-adherence and hence define areas for more targeted health-care interventions. Our results suggest that efforts to improve adherence should focus on women and older patients.

Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin.To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning.The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information.Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments.The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity.2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only.No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

By means of both cross-section and layout two-dimensional (2D) numerical simulations, three-dimensional (3D) latch-up interactions are demonstrated to significantly influence the latch-up behavior of a typical CMOS structure. A 3D latch-up test pattern is designed to allow the experimental study of such effects. The first measurement results show complex behaviors that can be overlooked if common 2D test patterns are used. >

Despite widespread use in many countries of tapered methadone for detoxification from opiate dependence, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated.To determine whether tapered methadone is effective to manage withdrawal from opioids.We searched: the Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; Internet (NIDA, Clinical Trials.org, BMJ).All randomised controlled trials which focus on the use of tapered methadone (length of treatment max 30 days) versus all other pharmacological detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal. Trials including patients with additional diagnoses such as benzodiazepine dependence were also eligible.One reviewer (LA) assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between reviewers. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. Where possible analysis was carried out according to the "intention to treat" principles.20 studies were included in the review, with 1357 people randomised. 10 studies compared methadone with adrenergic agonists, 7 studies compared different modalities of methadone detoxification, 2 studies compared methadone with other opioid agonists, 1 study compared methadone with chlordiazepoxide one with placebo. The conclusions of the 10 studies that compared methadone with adrenergic agonists showed no substantial clinical difference of the two treatments in terms of retention in treatment, degree of discomfort and detoxification success rates. The conclusions of the 6 studies that compare different methadone reduction schedules, showed that different types of methadone withdrawal schedule produce different responses in terms of time course of withdrawal, the severity of withdrawal response and possibly in terms of subsequent engagement with treatment. Regarding the studies that compare methadone with other opioid agonists, in Sorensen 1982 methadyl acetate performed similarly to methadone on most process and outcome measures, while in Tennant 1975, methadone reduced severity of withdrawal and had fewer drop-outs than did a propoxyphene group. In Drummond 1989, using chlordiazepoxide vs methadone, the results suggest that the two drugs had similar results in terms of overall effectiveness.San 1992 compared methadone with placebo and found more severe withdrawal and more drop outs in the placebo group. The results indicate that tapered methadone and other medications used in the included studies are effective in the treatment of the heroin withdrawal syndrome, although symptoms experienced by subjects differed according to the medication used and the program adopted. It seems that regardless of which medication is selected for heroin detoxification, the rates of subsequent heroin abstinence are about equal. This suggests that the medications are similar in terms of overall effectiveness. Improvements were achieved when other services such as counseling and other supporting services were offered contemporaneously with detoxification.Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. Results of many outcomes could not be summarised because they were presented either in graphical form or provided only statistical tests and p-values. For most studies standard deviation for continuous variables were not provided. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, accompanied by medicaopioids, accompanied by medical supervision and ancillary medications can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use. However this cannot be considered a goal for a detoxification as heroin dependence is a chronic, relapsing disorder and the goal of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.

Introduction Administrative databases are increasingly used to identify patients with chronic conditions, however the optimal methodology for Chronic Obstructive Pulmonary Disease (COPD) is still debated. Objective To develop and validate an algorithm to identify patients with COPD in Lazio (2 625 102 residents over 45) linking clinical and administrative data. Methods From the regional hospitalisation, drug prescription and outpatient registries, through record linkage, we identified patterns of specific drug use (minimum 2 prescription during 12 months) and COPD hospitalisations during a 9-year period in 428 patients with COPD, who attended an outpatient clinic in 2006, and in 2140 people without COPD. Through a Bootstrap-Stepwise procedure we selected COPD associated factors. We validated the algorithm through internal (cross-validation-bootstrap, jack-knife) and external validation (comparison with external COPD patients with confirmed diagnosis). Results A total of 205 611 (7.8%) COPD patients were identified. Factors associated with COPD were: prescription of β2-agonists, anticholinergics, corticosteroids, oxygen, and previous hospitalisation for COPD and respiratory failure. For each patient we estimated an expected probability to suffer from COPD. Depending on the cut-point of expected probability, sensibility (SE) ranged from 0.15 to 0.87 and specificity (SP) from 0.79 to 0.99. We defined a cut-point of 0.30 (SE=64%; SP=97%) to identify the COPD patients. Applying our algorithm on external COPD patients we succeeded to identify 86%. Conclusion The algorithm showed good performance to identify COPD patients among those individuals registered in the regional healthcare system confirming the strength of administrative data for monitoring chronic diseases.

Introduction Clinical guidelines recommend treatment with evidence-based (EB) drug therapy (antiplatelets, β-blockers, agents acting on the renin-angiotensin system, statins) for patients with acute myocardial infarction (AMI). Results on long term outcomes from observational population studies are scarce. Objectives Analysing the association between EB drug therapy and 2 years mortality in AMI patients. Methods Twothousand-twohundred-and-four AMI patients, discharged in 2006 and resident in Rome were selected from the Hospital Information System, excluding deaths during the first month after discharge. Exposure information was collected from the drug claims data considering EB drug prescriptions at discharge and during the first month; exposure was defined as at least one prescription, comparing different composite treatments (1, 2, 3 or 4 EB drug groups). The association between exposure to EB drug therapy and all-cause mortality during a 24 months follow-up was analysed through logistic regression, adjusting for gender, age and co-morbidities. Results Most patients were treated with EB drug combinations (0: 9.5%, 1: 4.6%, 2: 14.7%, 3: 30.1%, 4: 41.1%); 7.4% of the patients died during follow-up. Mortality risk decreased with increasing number of prescribed EB drugs; combinations of 3 or 4 EB drugs were associated with a significant protective effect vs no EB drugs (4 vs 0 EB drugs: OR adj =0.46; 95% CI 0.27 to 0.78; 3 vs 0 EB drugs: OR adj =0.50; 95% CI 0.29 to 0.86; 2 vs 0 EB drugs: OR adj =0.69; 95% CI 0.39 to 1.23; 1 vs 0 EB drugs: OR adj =0.49; 95% CI 0.21 to 1.13). Conclusions In Rome, most patients are treated with EB drugs after AMI; first-month poly-drug therapy is associated with reduction in 2 years mortality.

Despite widespread use of naltrexone maintenance in many countries for more than a decade, the evidence of its effects has not yet been systematically evaluated.To evaluate the effects of naltrexone maintenance treatment in preventing relapse in opioid addicts after detoxification.We searched MEDLINE (1973-first year of naltrexone use in humans-July 2000), EMBASE (1974-July 2000), Cochrane Controlled Trials Register (Cochrane Library issue 2001.4) and handsearched the "Bolletino per le Farmacodipendenze e l'Alcolismo" (1978 to 1997) and reference lists of relevant articles. We contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups. Date of most recent searches: December 2001.All controlled studies of naltrexone; treatment of heroin addicts after detoxification.Reviewers evaluated data independently and analysed outcome measures taking into consideration adherence to and success of the study intervention. Data were extracted and analysed stratifying for the three categories of study quality. Where possible, meta-analysis was performed.Eleven studies met the criteria for inclusion in this review, even if not all of them were randomised. The methodological quality of the included studies varied, but was generally poor. Meta-analysis could be performed to a very low degree only, because the studies and their outcome measures were very heterogeneous. A statistically significant reduction of (re-)incarcerations was found for patients treated with naltrexone and behaviour therapy in respect to those treated with behaviour therapy only. The other outcomes considered in the meta-analysis did not yield any significant results. Final conclusions on whether naltrexone treatment may be considered effective in maintenance therapy cannot be drawn from the clinical trials available so far.The available trials do not allow a final evaluation of naltrexone maintenance treatment yet. A trend in favour of treatment with naltrexone was observed for certain target groups (particularly people who are highly motivated), as has been previously described in the literature.

The aim of this study was to analyze the pattern of mortality among patients with ulcerative colitis (UC) and compare it with mortality in the general population of the same age and sex. All patients with UC admitted to one of the Inflammatory Bowel Disease Clinics in Rome, from January 1970 to December 31, 1989 were enrolled. Vital status was ascertained through the Registry Office of the last municipality of residence as of July 1, 1990. Cause of death was ascertained through record linkage with the national or regional mortality file and coded using the ninth revision of the International Classification of Diseases. Standardized Mortality Ratios (SMRs) were computed to compare mortality among UC patients with mortality in the general population of the same age and sex. Out of a total of 508 UC patients admitted during the study period, 27 deaths were observed, compared with 27.6 expected (SMR = 98). After excluding prevalent cases, an excess risk of death was observed among newly diagnosed cases in the first year after diagnosis (SMR = 644; p0.001); ulcerative colitis was the main reason for this excess mortality. Mortality for other diseases was close to that expected. In conclusion, ulcerative colitis impairs life expectancy in the first year after diagnosis, while no excess mortality seems to be present afterwards.

In 1991 the Lazio Region set up a surveillance system which collects individual data on each drug user attending Public Treatment Centres (PTCs). The analysis of surveillance system data allows not only to describe the characteristics of treatments but also to analyse determinants of treatment outcomes. In this study the outcome of treatment was evaluated in 5.646 drug users who attended public centres in 1992. The outcome was defined in two categories: positive (subjects who completed the therapeutic program, were referred to different service or were still in treatment) negative (subjects who refused or dropped out treatment, arrested or dead). Drug users usually receive more than one treatment in one year, 60% of them successfully completed. Methadone treatment shows the highest level of compliance while naltrexone the lowest. The negative outcome is highly associated with sex, type of treatment, length of treatment and outcome of previous treatment. Males are more likely to experience a negative outcome than females. Those offered naltrexone are more likely to refuse and drop out than those offered psychosocial treatment. Long term treatments are more successful than shorter ones. Furthermore, drop out is higher among those who have dropped out in the past. Although this observational study might not permit conclusions on the efficacy of each type of treatment, it allows an evaluation of the selection procedures at the treatment centres. Treatment centres for drug users in Lazio tend to select clients according to standard therapeutic treatment protocols instead of making treatments more accessible to drug users.