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Background: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. Aim: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. Methods: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Results: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17–1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08–2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62–2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10–1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02–1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68–3.36, p value < 0.0001). Conclusion: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Objectives: The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods: Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993–2015, incidence rates, survival median period and prognostic factors have been evaluated. A case–control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results: Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85–7.31 and OR 3.42, 95% CI 1.93–6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions: For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

Background: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD). Research design and methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug–drug interactions. Outcome occurrence was evaluated 180 days after AP initiation. Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27–1.39) for conventional APs. There was no increased mortality risk with single drug–drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00–1.67)). Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.

Objectives Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition. Design This is a cross-sectional study nested in the 2017 Delirium Day project. Setting and Participants The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium. Methods Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity. Results The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults. Conclusions and Implications Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis.

Anna Maria Bargagli, Silvia Cascini, Nera Agabiti, Ursula Kirchmayer, Claudia Marino, Marina Davoli Department of Epidemiology, Regional Health Service Lazio Region, Rome, ItalyCorrespondence: Silvia CasciniDepartment of Epidemiology, Regional Health Service Lazio Region, Via Cristoforo Colombo, Rome 112 - 00147, ItalyTel +39 06 9972 2130Fax +39 06 9972 2111Email s.cascini@deplazio.itIntroduction: Despite recommendations from associations of geriatric and psychiatry societies and warnings from drug agencies, antipsychotic (AP) drugs are frequently used to control behavioral and psychological symptoms of dementia. APs are associated with a range of potential adverse events, including increased risk of cerebrovascular events and mortality. Evidence suggests limited efficacy of APs for aggression and psychosis. Our objectives were to investigate patterns and predictors for prescription of APs among older adults with dementia residing in a large region of central Italy, and to identify patient characteristics related to typical or atypical APs prescribing.Methods: This is a retrospective population-based cohort study using data from regional health information systems (HIS). We included dementia patients aged ≥65 years residing in the Lazio region. The exposure was defined as new use vs non-use of APs. Dementia patients with incident use of APs during 2015 were followed-up from the date of first prescription to the earliest among discontinuation of use, death, or end of study (December 31, 2016).Results: We enrolled 24,735 dementia patients, 1727 (6.7%) new users and 23,008 non-users of APs. Forty-four percent of AP users were treated for more than 3 months, and among these about 60% received APs continuously for at least 12 months. Individuals using antidepressant or anti-dementia drugs had higher odds of being prescribed with APs (OR: 1.67 and OR: 1.86, respectively). Patients exposed to polypharmacy were less likely to receive APs (OR: 0.82). Cardiovascular risk factors and comorbidities were not associated with APs use. Low socio-economic position was associated with lower odds of atypical AP prescribing (OR: 0.57).Conclusion: The study showed that a not negligible proportion of patients had a period of AP use longer than recommended by guidelines. We identified socio-demographic and clinical factors associated with first use of APs, providing insight into prescribing practices in a community setting and useful information to address areas of potential inappropriateness.Keywords: dementia, antipsychotics, health information systems, older adults

Citizen‐science projects vary extensively in subject matter, objectives, activities, and scale, but there is always one common goal: to collect reliable data that can be used for scientific and policy purposes. The quality of data collected by non-professional volunteers in citizen science programs is crucial to produce data that are usable by stakeholders to implement environmental management and protection plans. The aim of this study was to assess the quality of data collected by non-specialist volunteers during the citizen science project SCUBA Tourism for the Environment (STE), carried out in three touristic resorts of the Red Sea between 2007 and 2015. The project was based on the Recreational citizen science protocol that differs from the Traditional one because it does not change dives features (i.e. dive place, depth, etc.), do not require to follow a training course and to pass a final exam before participating in the project. For the recreational protocol, scuba instructors and divemasters were briefly trained during public events about project aims, methods and expected results and then they had directly involved volunteers in the project. STE project involved more than 14,000 volunteer recreational divers in data collection on biodiversity. Through a specifically designed questionnaire, volunteers indicated which of the seventy-two target marine taxa were sighted during their recreational dive, giving an estimate of their abundance. To assess the validity of collected data, a reference researcher randomly dove with the volunteers and independently filled in the project questionnaire. Correlation analyses between the records of the reference researcher and those of the volunteers were performed to assess their quality. The study was performed based on 513 sample dives (dives in which was present our reference researcher with at least three volunteers) with a total number of 3138 volunteers tested. Different parameters were used to analyze data reliability 1) Accuracy, the similarity between data collected by volunteers and those collected by the reference researcher, obtained with Spearman’s rank correlation coefficient; 2) Consistency, obtained correlating data collected only by volunteers during the same dive, without the reference researcher, using Spearman’s rank correlation coefficient; 3) Percentage of identified that is the percentage of taxa registered by volunteers compared to the taxa observed by the reference researcher; 4) Correct identification that is the percentage of volunteers that correctly identified individual taxa when the taxon was present; 5) Correctness of abundance ratings (CAR) that is the correctness in abundance ratings made by volunteers compared to those collected by the reference researcher; 6) Reliability obtained with correlation between data collected by volunteers and those collected by the reference researcher, using Cronbach’s alpha correlation; 7) measure of similarity between each volunteer and the reference researcher, using Czekanowski’s proportional similarity index). The influence of independent variables date, depth, dive time, diving certification level and group size of participants on volunteers’ accuracy was also analyzed. The lowest mean score (mean score 51.6%, 95% Confidence Interval CI 44.1-59.2%) was obtained for Consistency, indicating that, depending on personal interests, volunteers could give attention to different taxa and the highest one for the Reliability parameter (mean score 69.8%, 95% CI 62.8 – 76.9) indicating that volunteers are able to collect good quality data. A positive correlation was found between Accuracy and Correctness of Abundance Ratings (CAR) score and date indicating that long-term projects could achieve a higher quality of data collected by volunteers. Diving certification level and dive time resulted positively correlated with all parameters except for CAR indicating that more expert divers could collect better quality data than less expert ones and that spending more time underwater could have benefits on data quality. Overall, data quality in this study was comparable to that obtained in Traditional citizen science projects where strict training activities and protocols were followed. Independent variables revealed that long-term projects could achieve a higher Accuracy and CAR, this could be due to an improvement of the project with time, in terms of public training events, more clear description of tasks requested to instructors and divemasters and their consequent improvement in volunteers involvement. We also found that expert scuba divers (volunteers with higher diving certification level) were more reliable than the less expert, this could be due to their familiarity, not only with the marine environment, but also with the diving equipment, which allows them focus on the surrounding environment rather than on their balance or equipment. Finally, more time volunteers spent underwater the more reliable their data became. This study showed that Recreational citizen science could significantly support conventional research methods in monitoring biodiversity, notwithstanding careful planning for volunteer skills according to each specific project. The use of the Recreational citizen science protocol could enhance massive volunteers participation in citizen science projects because it do not require changes to the recreational activity in order to participate; this could also allow the collection of huge amount of data in a short period of time.

Aims Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown. Methods We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged >= 75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis. Results France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m euro); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m euro). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 euro/quality adjusted life year gained for German males to 6324.3 euro/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 euro/quality adjusted life year gained for all scenarios in the six countries, in males and females. Conclusion Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy.

Background although frailty and delirium are among the most frequent and burdensome geriatric syndromes, little is known about their association and impact on short-term mortality. Objective to examine, in hospitalized older persons, whether frailty is associated with delirium, and whether these two conditions, alone or in combination, affect these patients’ 30-day survival. Design observational study nested in the Delirium Day project, with 30-day follow-up. Setting acute medical wards (n = 118) and rehabilitation wards (n = 46) in Italy. Subjects a total of 2,065 individuals aged 65+ years hospitalized in acute medical (1,484 patients, 71.9%) or rehabilitation (581 patients, 28.1%) wards. Methods a 25-item Frailty Index (FI) was created. Delirium was assessed using the 4AT test. Vital status was ascertained at 30 days. Results overall, 469 (22.7%) patients experienced delirium on the index day and 82 (4.0%) died during follow-up. After adjustment for potential confounders, each FI score increase of 0.1 significantly increased the odds of delirium (odds ratio, OR: 1.66 [95% CI: 1.45–1.90]), with no difference between the acute (OR: 1.65 [95% CI: 1.41–1.93]) and rehabilitation ward patients (OR: 1.71 [95% CI: 1.27–2.30]). The risk of dying during follow-up also increased significantly for every FI increase of 0.1 in the overall population (OR: 1.65 [95% CI: 1.33–2.05]) and in the acute medical ward patients (OR: 1.61 [95% CI: 1.28–2.04]), but not in the rehabilitation patients. Delirium was not significantly associated with 30-day mortality in either hospital setting. Conclusions in hospitalized older patients, frailty is associated with delirium and with an increased risk of short-term mortality.

BACKGROUND: there has been a long-standing, consistent use worldwide of Healthcare Administrative Databases (HADs) for epidemiological purposes, especially to identify acute and chronic health conditions. These databases are able to reflect health-related conditions at a population level through disease-specific case-identification algorithms that combine information coded in multiple HADs. In Italy, in the past 10 years, HAD-based case-identification algorithms have experienced a constant increase, with a significant extension of the spectrum of identifiable diseases. Besides estimating incidence and/or prevalence of diseases, these algorithms have been used to enroll cohorts, monitor quality of care, assess the effect of environmental exposure, and identify health outcomes in analytic studies. Despite the rapid increase in the use of case-identification algorithms, information on their accuracy and misclassification rate is currently unavailable for most conditions. OBJECTIVES: to define a protocol to systematically review algorithms used in Italy in the past 10 years for the identification of several chronic and acute diseases, providing an accessible overview to future users in the Italian and international context. METHODS: PubMed will be searched for original research articles, published between 2007 and 2017, in Italian or English. The search string consists of a combination of free text and MeSH terms with a common part on HADs and a disease-specific part. All identified papers will be screened for eligibility by two independent reviewers. All articles that used/defined an algorithm for the identification of each disease of interest using Italian HADs will be included. Algorithms with exclusive use of death certificates, pathology register, general practitioner or pediatrician data will be excluded. Pertinent papers will be classified according to the objective for which the algorithm was used, and only articles that used algorithms with "primary objectives" (I disease occurrence; II population/cohort selection; III outcome identification) will be considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms will be collected. Further information on specific accuracy measures from external validations, sensitivity analyses, and the contribution of each source will be recorded. This protocol will be applied for 16 different systematic reviews concerning eighteen diseases (Hypothyroidism, Hyperthyroidism, Diabetes mellitus, Type 1 diabetes mellitus, Acute myocardial infarction, Ischemic heart disease, Stroke, Hypertension, Heart failure, Congenital heart anomalies, Parkinson's disease, Multiple sclerosis, Epilepsy, Chronic obstructive pulmonary disease, Asthma, Inflammatory bowel disease, Celiac disease, Chronic kidney failure). CONCLUSION: this protocol defines a standardized approach to extensively examine and compare all experiences of case identification algorithms in Italy, on the 18 abovementioned diseases. The methodology proposed may be applied to other systematic reviews concerning diseases not included in this project, as well as other settings, including international ones. Considering the increasing availability of healthcare data, developing standard criteria to describe and update characteristics of published algorithms would be of great use to enhance awareness in the choice of algorithms and provide a greater comparability of results.

Background Autism Spectrum Disorder (ASD) is a neuro-developmental disorder that affects communication and behavior with a prevalence of approximately 1% worldwide. Health outcomes of interventions for ASD are largely Participant Reported Outcomes (PROs). Specific guidelines can help support the best care for people with ASD to optimize these health outcomes but they have to adhere to standards for their development to be trustworthy. Objective The goal of this article is to describe the new methodological standards of the Italian National Institute of Health and novel aspects of this guideline development process. This article will serve as a reference standard for future guideline development in the Italian setting. Methods We applied the new standards of the Italian National Institute of Health to the two guidelines on diagnosis and management of children/adolescents and adults with ASD, with a focus on the scoping, panel composition, management of conflict of interest, generation and prioritization of research questions, early stakeholders’ involvement, and PROs. Recommendations are based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision frameworks. Results Following a public application process, the ISS established two multidisciplinary panels including people with ASD and/or their caregivers. Seventy-nine research questions were identified as potentially relevant for the guideline on children and adolescents with ASD and 31 for the one on adults with ASD. Questions deemed to have the highest priority were selected for inclusion in the guidelines. Other stakeholders valued their early involvement in the process which will largely focus on PROs. The panels then successfully piloted the development of recommendations using the methodological standards and process set by the ISS with a focus on PROs. Conclusions In this article, we describe the development of practice guidelines that focus on PROs for the diagnosis and management of ASD based on novel methods for question prioritization and stakeholder involvement. The recommendations allow for the adoption or adaptation to international settings.

Riccardo Di Domenicantonio,1 Francesco Trotta,1 Silvia Cascini,1 Nera Agabiti,1 Anna Kohn,2 Antonio Gasbarrini,3 Marina Davoli,1 Antonio Addis1 1Department of Epidemiology, Lazio Regional Health Service, Rome, Italy; 2IBD Unit, AO San Camillo Forlanini, Rome, Italy; 3Department of Internal Medicine, Agostino Gemelli University Hospital, Catholic University of Sacred Heart, Rome, Italy Background: The comparison of effectiveness and safety of anti-tumor necrosis factor-alpha agents for the treatment of inflammatory bowel disease (IBD) is relevant for clinical practice and stakeholders. Objective: The objective of this study was to compare the risk of abdominal surgery, steroid utilization, and hospitalization for infection in Crohn’s disease (CD) or ulcerative colitis (UC) patients newly treated with infliximab (IFX) or adalimumab (ADA). Methods: A retrospective population-based cohort study was performed using health information systems data from Lazio region, Italy. Patients with CD or UC diagnosis were enrolled at first prescription of IFX or ADA during 2008–2014 (index date). Only new drug users were followed for 2 years from the index date. IFX versus ADA adjusted hazard ratios were calculated applying “intention-to-treat” approach, controlling for several characteristics and stratifying the analysis on steroid use according to previous drug utilization. Sensitivity analyses were performed according to “as-treated” approach, adjusting for propensity score, censoring at switching or discontinuation, and evaluating different lengths of follow-up periods. Results: We enrolled 1,432 IBD patients (42% and 83% exposed to IFX for CD and UC, respectively). In both diseases, treatment effects did not differ in any outcome considered, and sensitivity analyses confirmed the results from the main analysis. Conclusion: In our population-based cohort study, effectiveness and safety data in new users of ADA or IFX with CD or UC were comparable for the outcomes we tested. Keywords: biologics, real-world effectiveness, inflammatory bowel disease

Objective: The objective of this study was to investigate the relationship between adherence to statin therapy and the risk of exacerbation among elderly individuals affected by chronic obstructive pulmonary disease and cardiovascular disease. Methods: Using the healthcare utilisation databases of five Italian territorial units accounting for nearly 35% of the Italian population, we recruited a cohort of 6263 elderly persons (i.e. aged 65 years or older) with co-existing chronic obstructive pulmonary disease and cardiovascular disease who initiated statin therapy. Exposure was adherence to statins measured by the proportion of days of follow-up covered. Outcome was the first hospital admission for chronic obstructive pulmonary disease occurring in the period of observation. A proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals for the exposure–outcome association, after adjusting for several covariates. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. Results: During an average follow-up of about 4 years, 1307 cohort members experienced the outcome. Compared with patients with low adherence (proportion of days of follow-up covered ≤ 40%), those with intermediate (proportion of days of follow-up covered 41–80%) and high (proportion of days of follow-up covered > 80%) adherence exhibited a lower risk of exacerbation of 16% (95% confidence interval 3–27) and 23% (95% confidence interval 10–34). Conclusions: In a real-world setting, we observed evidence that adherence to statin therapy markedly reduced the risk of chronic obstructive pulmonary disease exacerbations in elderly patients with co-existing chronic obstructive pulmonary disease and cardiovascular disease. Given the limited and controversial evidence from trials, more randomised controlled trials are urgently needed to better examine the potential benefits of statins as adjunct therapy in chronic obstructive pulmonary disease.

Objectives To describe NSAID utilization for musculoskeletal conditions in a large cohort of Italian elderly with cerebro/cardiovascular disease, a population in which NSAIDs should be generally avoided due to the prothrombotic potential. Methods Administrative data from five Italian geographic areas were analyzed. Patients aged ≥ 65 with a cerebro/cardiovascular event recorded between 2008 and 2011 (cohort entry) were selected. Prescription NSAIDs reimbursed for musculoskeletal conditions and dispensed during 1 year follow-up were retrieved to describe (i) prevalence of use, (ii) average amount of defined daily doses of NSAIDs claimed by users per day of follow-up, and (iii) distribution of the received daily dose (RDD) among patients with ≥ 2 dispensings. Among new users, i.e., patients without NSAID dispensings during 2 years before cohort entry, the first dispensed NSAID molecule was observed. Results Overall, 511,989 patients were selected. Across the five geographic areas, prevalence of use ranged from 48 to 21% and average consumption ranged between 30 and 67 DDD/1000 users/day. Around 10% of patients in the overall cohort had a RDD > 1. Nimesulide (9.6%) and diclofenac (7.5%) had the highest prevalence of use. The most consumed NSAIDs were nimesulide and coxibs with 10.6 and 7.5 DDD/1000 users/day, respectively. Among new users recruited in 2011, 30% had diclofenac or a coxibs as the first prescription. Conclusions NSAID use was common in the study cohort, particularly in central-southern areas. In contrast with current recommendations, coxibs and diclofenac were among the most prescribed active principles, even in new users. Interventions to promote appropriateness of use are warranted. Electronic supplementary material The online version of this article (10.1007/s00228-018-2411-y) contains supplementary material, which is available to authorized users.

Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15–20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009–2015. A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009–2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use. Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching. Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.

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Introduction Real-world data on the comparative effectiveness and safety of switching among different epoetins (including originators and biosimilars) are limited. In light of current debate about interchangeability, prescribers, some patient groups and decision makers are calling for additional post-marketing evidence on the clinical effects of switching between originator and biosimilar epoetins in chronic kidney disease (CKD) patients. Objective The objective of this study was to evaluate the effectiveness and safety of switching versus non-switching and of switching from originator/biosimilar epoetin alpha (ESA α) to any other epoetin in CKD patients. Methods An observational, record-linkage, multi-database, retrospective cohort study was carried out in four Italian geographical areas. All subjects with at least one ESA α dispensing between 1 January 2009 and 31 December 2015 were retrieved. Switching was defined as any transition between originator/biosimilar ESA α to any other epoetin in a series of two consecutive prescriptions up to 2 years. Switchers were matched 1:1 with non-switchers by baseline propensity score and by duration of ESA α treatment. Switchers and non-switchers were followed up from switching date to a maximum of 1 year. Lack of effectiveness and safety of switching versus non-switching were evaluated through Cox regression models (hazard ratio [HR], 95% confidence interval [CI]). A direct comparison between the two switcher categories (switchers from originator/biosimilar ESA α to any other epoetin) was also performed. Results Overall, 14,400 incident users of ESA α for anaemia due to CKD (61.4% originator, 38.6% biosimilar) were available for analysis. During the follow-up, we found no differences on effectiveness (HR 1.02, 95% CI 0.79–1.31 originators; HR 1.16, 95% CI 0.75–1.79 biosimilars) and safety outcomes (HR 1.08, 95% CI 0.77–1.50 originators; HR 1.20, 95% CI 0.66–2.21 biosimilars) between switchers and non-switchers of ESA α. Cumulative probabilities of recording an adverse event, either in terms of lack of effectiveness or safety issue, were the same for two switching categories Conclusions In this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA α to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes. Electronic supplementary material The online version of this article (10.1007/s40264-019-00845-y) contains supplementary material, which is available to authorized users.

Background and Objectives: Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Methods: Three case–control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Results: Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84–0.91)], hospitalization [0.90 (0.88–0.93)] and mortality [0.48 (0.47–0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84–0.90), 0.86 (0.83–0.90), 0.55 (0.54–0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13–2.78) for short-acting DHPs; 1.19 (1.07–1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96–3.51) and 1.23 (1.08–1.42)]. Conclusions: The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

Background and Objective: Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality. Methods: The cohort included 29,845 individuals aged ≥ 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008–2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012–2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered ≥ 75%) and outcome, by adjusting and stratifying for several covariates. Results: Patients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3–14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (− 1–38), 14% (7–20), 20% (13–26) and 13% (7–19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively. Conclusions: Better adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.

IntroductionThe epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.MethodsIncident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.ResultsIn the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.ConclusionsThe consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.

The purpose of SENTIERI-ReNaM Project is to describe mesothelioma incidence in the Italian National Priority Contaminated Sites (NPCSs). The present report deals with 39 NPCSs (20 in Northern Italy, 8 in Central Italy and 11 in Southern Italy). Asbestos is specifically mentioned in the regulatory acts of recognition for 10 NPCSs and it is the only agent that has determined environmental contamination in 3 of them (Casale Monferrato, Broni, and Bari). The timeframe of the study is 2000-2011 for 34 out of 39 sites. The corresponding reference periods for the sites of Latium, Campania, Umbria, and Bolzano Province are, respectively, 2001-2011, 2005-2011, and 2006-2011. Standardized Incidence Ratios (SIRs) for mesothelioma, with their corresponding 90% Confidence Intervals, have been estimated for all sites. The interpretation of the study findings has been based on anamnestic information made available by the Italian National Mesothelioma Registry (ReNaM), and completed thanks to knowledge derived from the international scientific literature. In men, mesothelioma incidence has shown excesses in 27/39 sites and defects in the remaining 12; in women, excesses have been reported in 20 sites, defects in 15, and no cases have been detected in the remaining 4 sites. The highest annual incidence rates have been observed in the sites characterized only by the presence of asbestos- cement factories (Broni and Casale Monferrato): respectively, 98.0 and 68.6 per 100,000 per year in men, 72.1 and 45.8 in women. Besides these two sites, the highest rates have been observed in the sites with naval shipyards: 13.2 in men and 2.5 in women. Excesses of mesothelioma incidence have been confirmed (with respect to previous observations) in the sites of Broni, Casale Monferrato, Balangero, and in the coastal areas of Trieste, La Spezia, Venice, and Leghorn. Balangero has been the major European chrysotile quarry, while the other sites are characterized by the presence of naval shipyards with demonstrated use of asbestos before it was banned in 1992. An excess of mesothelioma incidence has also been confirmed in the site of Biancavilla, characterized by the presence of the fluoro-edenite fibrous amphibole, classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC). An increased incidence of mesothelioma was also observed in the areas where no direct use of asbestos had previously been documented, like Cengio and Saliceto (chemical industry), Falconara on Sea (oil refinery), and Litorale Domizio Flegreo and Agro Aversano (a large area including multiple hazardous waste dumping sites). These findings show that a relevant proportion of Italian mesothelioma cases is concentrated in NPCSs. About 1,500 extra cases of mesothelioma have been estimated in the overall series of 39 sites (2000-2011), corresponding to 125 extra cases per year. The excess has concerned the sites with manufacture of asbestos-cement products, but also the areas with asbestos quarries, naval shipyards, illegal hazardous waste dumping sites with asbestos-containing materials, petrochemical industries, refineries and steel plants. In some sites, particularly Casale Monferrato and Broni, analytical epidemiological studies have shown the causal role of not only occupational, but also environmental exposures, with special reference to paving of gardens and courtyards with asbestos-cement industry by-products. The main novelty generated by the collaborative SENTIERI-ReNaM Project concerns the detection of significant mesothelioma excesses not only in sites where asbestos is explicitly reported as a source of contamination, but also in a number of areas defined "of national interest" for environmental cleanup due to other sources of pollution. This confirms that the range of economic activities and working and living environments affected by asbestos exposure is very wide and it is not restricted to the industrial sectors characterized by the direct use of this material.

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

SENTIERI-ReNaM Project analysed the incidence of malignant mesothelioma (MM) for the period 2000-2011 in 39 National Priority Contaminated Sites (NPCSs), and assessed the overall impact of mesothelioma in different types of NPCSs. In the study period, 2,683 incident cases of malignant mesothelioma were recorded: 1,998 males (74.5%), 685 females (25.5%). Excluding cases with non attributable exposure and those non interviewed, exposure was identified in 1,926 cases (70% of all cases): 1,541 males (occupational exposure: 1,414; environmental exposure: 82), 385 females (occupational exposure: 103; environmental exposure: 141). Women experienced mainly environmental and domestic exposures to asbestos. Standard Incidence Ratio (SIR) excesses were observed in men in 27 out of 39 NPCSs and defects in the remaining 12; in women, 20 NPCSs showed SIR excesses, defects in 15; in 4 NPCSs no MM cases occurred among female population. The highest rates were found in NPCSs with asbestos-cement plants (Broni and Casale Monferrato), respectively, 98 per 100,000 per year and 68.6 in men, 72.1 and 45.8 in women. Excluding these two sites, the highest incidence rates were found in the group with harbours and shipyards, where the rates were, respectively, 13.2 among men and 2.5 among women. The results of this report will be communicated to national and local institutions, as well as to NPCSs resident populations.

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.

Mesothelioma incidence has been analyzed in National Priority Contaminated Sites (NPCSs) to estimate the health impact of asbestos exposure on resident people. The burden of professional and environmental exposures has been identified through data of the Regional Operational Centres (CORs), made available by the Italian National Mesothelioma Registry (ReNaM). An excess of mesothelioma incidence is confirmed in sites with a known past history of direct use of asbestos, such as Balangero, Casale Monferrato, Broni, Bari-Fibronit, and in coastal areas, where shipyards, harbours and other industries that involved a wide use of asbestos are represented (e.g., Trieste, La Spezia, Venice, and Leghorn). An excess of mesothelioma has been observed in settings where the asbestos is not mentioned as contaminant in the decree that included these sites among NPCSs, such as Cengio and Saliceto in Northern Italy; Falconara Marittima and the Bacino Idrografico Fiume Sacco in the Central Italy; the Litorale Domizio Flegreo and Agro Aversano, Milazzo, and Gela in the Southern Italy. Observed excess in the various NPCSs confirms the large-scale occurrence in contaminated Italian sites of a significant amount of total mesothelioma cases observed at national level. The analysis of occupational risk in epidemiological studies with an ecological design helps in defining the contribution of different factors to the overall risk.

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 PM10 and PM2.5 constituents. 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. The research described in this article was conducted under the grant agreement European Commission, Environment LIFE10/IT/327. We thank the Instituto Nacional de Estadística and the Agència de Salut Pública de Barcelona for providing the mortality data, the Consorci Sanitari de Barcelona (Cat-Salut) for providing hospitalization data for Barcelona and the Agencia Estatal de Meteorologia (Ministerio de Agricultura, Alimentación y Medio Ambiente) for providing the weather data for Spain. Sí

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.

Il teatro Goldoni di Bagnacavallo, progettato da F. Antolini, è stato ultimato e inaugurato nel 1845. Negli ultimi anni viene utilizzato per rappresentazioni di prosa, prove di tour e concerti amplificati. Nonostante lo scarso utilizzo per esecuzioni operistiche e sinfoniche, il teatro presenta caratteristiche strutturali e volumetriche che lo rendono un riferimento indicativo per la verifica di alcune prescrizioni della ISO 3382-2 e della letteratura tecnica relativa. Sulla base di un numero consistente di risposte all’impulso della sala, misurate nel gennaio 2012, è stata sviluppata un'analisi statistica dei descrittori acustici. Nel presente lavoro i risultati di tale analisi sono confrontati con quanto proposto dalla letteratura di riferimento e se ne traggono conclusioni di interesse generale. Misurazioni ed elaborazioni numeriche sono state svolte nell'ambito del progetto sui teatri storici dell'Emilia Romagna del C.I.R.I. Edilizia e Costruzioni dell’Università di Bologna.

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: Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality. METHODS: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for 10,208 person-years in treatment and 2,914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment. RESULTS: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 95% confidence interval (CI) 2.8-5.4 and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period. CONCLUSIONS: We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use. Language: en