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The South-East of Sicily is characterized by a complex system of coastal lagoons. The site, is considered of great naturalistic value, as it hosts a rich biodiversity and represents an important stop for bird species that migrates through the Northern European-African route. According to recent studies, the site is subject to an ever-increasing climate related coastal erosion and flooding risk, with an estimated potential land loss of 6.2 km2 by 2100 (Antonioli et al. 2020). In the present work, the effectiveness of a dune revegetation is investigated, in order to understand the role played by environmental restoration in reducing coastal risk. A SWAN+XBeach (Booji et al. 1996; Roelvink et al., 2009) numerical modeling chain is developed, aimed to simulating the hydraulic and transport processes that characterize a coastal area, in order to evaluate the effectiveness of the dune revegetation intervention. Results show a reduction of coastal flooding risk due to extreme wave events as an effect of the extended vegetated dune strip. Presence of the vegetation drastically improve coastal protection to the city area. Specifically, a reduction up to 42% of the flooded city area is observed. References Antonioli, F., Defalco, G., Moretti, L., Anzidei, M., Bonaldo, D., Carniel, S., ... & Schicchitano, G. (2019). Relative sea level rise and potential flooding risk for 2100 on 15 coastal plains of the Mediterranean Sea. In Geophysical Research Abstracts (Vol. 21). Booij, N., Holthuijsen, L.H. and R.C. Ris, 1996, The SWAN wave model for shallow water, Proc. 25th Int. Conf. Coastal Engng., Orlando, USA, Vol. 1, pp. 668-676. Roelvink, D., Reniers, A., van Dongeren, A., van Thiel de Vries, J., McCall, R., & Lescinski, J. , 2009. Modelling storm impacts on beaches, dunes and barrier islands. Coastal Engineering, 56(11-12), 1133-1152. doi:10.1016/j.coastaleng.2009.08.006

To determine the occurrence and clustering of complications in subjects restored with fixed implant-supported prostheses.In the present retrospective case series, 241 subjects treated at one clinical centre and provided with 729 implants were included. A clinical and radiographic examination was performed after a mean follow-up period of 4.8 ± 2.0 years. Additional information on occurrence of technical (chipping, loss of retention, fracture of components) and biological complications (marginal bone loss, implant loss) during follow-up was extracted from patient records. For each type of complication and complications overall, regression analyses were performed to identify potential risk factors. Cox regression analyses were used to evaluate time to event for implant loss and technical complications.In all, 30% of the 241 patients presented with at least one complication of technical and/or biological character during the follow-up period. Technical complications affected 19.5% of subjects, while 14.1% presented with marginal bone loss2 mm. Implant loss occurred in 4.6% of subjects. While technical complications were noted already early during the maintenance period (1200 days), implant loss typically occurred during a later phase. A small subgroup of subjects (7.9%) experienced more than one type of complication.Complications occurred frequently and the most common type of complication was of technical character. Technical and biological complications occurred independently of each other.

Introduction COVID-19 case fatality rate in hospitalized patients varies across countries and studies. Reliable estimates, specific for age, sex, and comorbidities, are needed to monitor the epidemic, to compare the outcome in different settings, and to correctly design trials for COVID-19 interventions. The aim of this study was to provide population-based survival curves of hospitalized COVID-19 patients. Materials and methods A cohort study was conducted in three areas of Northern Italy, heavily affected by SARS-CoV-2 infection (Lombardy and Veneto Regions, and Reggio Emilia province), using a loco-regional COVID-19 surveillance system, linked to hospital discharge databases. We included all patients testing positive for SARS-CoV-2 RNA by RT-PCR on nasopharyngeal/throat swab samples who were hospitalized from 21 February to 21 April 2020. Kaplan-Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex, and the Charlson Index. Results Overall, 42,926 hospitalized COVID-19 patients were identified. Patients' median age was 69 years (IQR: 57-79), 62.6% were males, and 6.0% had a Charlson Index ≥3. Survival curves showed that 22.0% (95% CI 21.6-22.4) of patients died within 14 days and 27.6% (95% CI 27.2-28.1) within 30 days from hospitalization. Survival was higher in younger patients and in females. The negative impact of comorbidities on survival was more pronounced in younger age groups. Conclusion The high fatality rate observed in the study (28% at 30 days) suggests that studies should focus on death as primary endpoint during a follow-up of at least one month.

An assessment of formulas to recover wave surface elevation from pressure measurements was carried out in the present study. The investigation focused on the formulas’ performance in the shoaling region, i.e. where the wave nonlinearity gradually increases as the wave travels towards shallower waters. Formulas based on linear wave theory alongside nonlinear reconstructions were considered. Experiments in a large-scale wave flume provided with a concrete beach profile were performed, in which regular waves were generated and surface elevation was measured with acoustic, resistive and pressure gauges. The considered formulas require the application of a cutoff frequency to the wave signal in order to avoid high frequencies amplification that progressively arise as wave shoaling occur. A simple but effective method to obtain a reference cutoff frequency is proposed in the present work; the method is based on a polynomial fitting of the unfiltered wave energy spectrum. A sensitivity analysis of each formula to the variation of this cutoff frequency was carried out. Results showed that all the investigated formulas recover wave elevation fairly well for low-nonlinearity waves, whereas overestimating wave crest height as nonlinearity increases. Wave reconstruction of the linear formulation performance was comparable to nonlinear formulations in terms of wave crest height reconstruction, although tending to amplify frequencies in the wave trough. Moreover, the performance of the formulas to correctly recover the asymmetry and flatness of the surface elevation distribution was assessed by analysing third- and fourth-order moment statistics. In this sense, nonlinear reconstruction formulas performed better in recovering the asymmetric distribution of the wave elevation, with the formula based on linear wave theory underestimating skewness and kurtosis for large nonlinearity waves. This work was funded by the projects: “ISYPORT - Integrated System for navigation risk mitigation in PORTs” funded under the PNR 2015-2020 program, REST-COAST - Large scale RESToration of COASTal ecosystems through rivers to sea connectivity (call: H2020-LC-GD-2020; Proposal no. 101037097) and “VARIO - VAlutazione del Rischio Idraulico in sistemi cOmplessi” of the University of Catania.

Objectives To review the evidence of the effects of centralization of cancer surgery on postoperative mortality. Methods We searched Medline, Embase, Cinahl, Cochrane and Scopus (up to November 2019) for studies that (i) assessed the effects of centralization of cancer surgery policies on in-hospital or 30-day mortality, or (ii) described changes in both postoperative mortality for a surgical intervention and degree of centralization using reduction in the number of hospitals or increases in the proportion of patients undergoing cancer surgery at high volume hospitals as proxy. PRISMA guidelines were followed. We estimated pooled odds ratios (OR) and conducted meta-regression to assess the relationship between degree of centralization and mortality. Results A total of 41 studies met our inclusion criteria of which 15 evaluated the effect of centralization policies on postoperative mortality after cancer surgery and 26 described concurrent changes in the degree of centralization and postoperative mortality. Policy evaluation studies mainly used before-after designs (n = 13) or interrupted time series analysis (n = 2), mainly focusing on pancreatic, oesophageal and gastric cancer. All but one showed some degree of reduction in postoperative mortality, with statistically significant effects demonstrated by six studies. The pooled odds ratio for centralization policy effect was 0.68 (95% Confidence interval: 0.54–0.85; I2 = 80%). Meta-regression analysis of the 26 descriptive studies found that an increase of the proportion of patients treated at high volume hospitals was associated with greater reduction in postoperative mortality. Conclusions Centralization of cancer surgery is associated with reduced postoperative mortality. However, existing evidence tends to be of low quality and estimates of the effect size are likely inflated. There is a need for prospective studies using more robust approaches, and for centralization efforts to be accompanied by well-designed evaluations of their effectiveness.

In the present work, an investigation on the hydrodynamics of waves and currents interacting at right angle over rough beds has been carried out. The work focuses on the effects of wave motion superposed on the current steady boundary layer, and on how the oscillatory flow affects the current velocity distribution, in the presence of gravel and sand beds.A laboratory experimental campaign on wave-current orthogonal interaction has been carried out in a shallow water basin at DHI Water and Environment (Hørsholm, Denmark).Mean flow has been investigated by computing time- and space-averaged velocity profiles. Friction velocity and equivalent roughness have been inferred from the velocity profiles by best fit technique, in order to measure the shear stress experienced by the current mean flow.Tests in the presence of only current, only waves and combined flow have been performed.Instantaneous velocities have been Reynolds-averaged to obtain turbulent fluctuations time series and compute turbulence related quantities, such as turbulence intensities and Reynolds stresses.The analysis of the mean flow revealed a complex interaction of the waves and currents combined flow. Depending on the relative strength of the current with respect to the waves, the superposition of the oscillatory flow may determine an increase or a decrease of the bottom friction experienced by the current.The superposition of waves always induces an increase of turbulence intensity, except over gravel bed in which a decrease is observed in the very proximity of the bottom. Over gravel bed, the presence of the oscillatory flow determines a decrease of the turbulent intensity gradient, which may be related to the decrease of bottom friction observed in the mean flow analysis.A turbulence quadrant analysis has been performed and showed that, in the presence of a lone current over a flat gravel bed, the turbulent ejection-sweep mechanism reaches parts of the water column closer to the water surface, similar to what has been observed in the turbulence intensity profiles.The superposition of the oscillatory flow appears to induce an increment of ejections and sweeps intensity, which is associated with the shear stress increase at the bottom observed in the mean flow analysis. Moreover, a decrease of the number of ejection and sweep events has been recorded, which suggests a suppression of the ejection-sweep events alongside an enhancement of their intensity.

BackgroundCOVID-19 case fatality rate in hospitalized patients varies across countries and studies, but reliable estimates specific for age, sex, and comorbidities are needed to design trials for COVID-19 interventions. Aim of this study is to provide population-based survival curves of hospitalized COVID-19 patients.MethodsA cohort study was conducted in Lombardy, Veneto, and Reggio Emilia using COVID-19 registries linked to hospital discharge databases containing patient clinical histories. All patients with positive SARS-CoV-2 RT-PCR test on oral/nasopharyngeal swabs hospitalized from 21st February to 21st April 2020 were identified. Kaplan Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex and Charlson Index.FindingsOverall, 42,926 hospitalized COVID-19 patients were identified. Patients’ median age was 69 years (IQR: 57-79), 62·6% were males, 69·4% had a Charlson Index of 0. In total, 11,205 (26·1%) patients died over a median follow-up of 24 days (IQR: 10-35). Survival curves showed that 22·0% of patients died within 14 days and 27·6% within 30 days of hospitalization. Survival was higher in younger patients and in females. Younger patients with comorbidities had a lower survival than older ones with comorbidities.InterpretationOver 27% of hospitalized COVID-19 patients died within one month in three areas of Northern Italy that were heavily affected by SARS-CoV-2 infection. Such a high fatality rate suggests that trials should focus on survival and have follow-up of at least one month.FundingThe study did not receive any external funding.Research in contextEvidence before this studyTwo recent systematic reviews with meta-analyses report case fatality rates of three to four percent in COVID-19 patients. Most studies on hospitalized cohorts report only slightly higher figures. These figures do not correspond to those derived from routinely collected clinical data in most European countries, reporting a 10% case fatality rate which has been increasing over time since the epidemic started.Robust and precise survival estimates of hospitalized COVID-19 patients which take into account prognostic factors such as age, sex and burden of comorbidities are needed to design appropriate phase II and phase III clinical studies of drugs targeting COVID-19.Added value of this studyIn this study we present the first survival estimates by age, sex and Charlson index for a large population-based cohort of Italian hospitalized COVID-19 patients.Implications of all the available evidenceOver 27% of COVID-19 patients died within one month from hospital admission. Such a high fatality rate suggests that studies should prioritize mortality as primary outcome. Furthermore, we found that the fatality rate reaches a plateau 30 days after hospitalization, suggesting that studies should have at least one month of follow up to observe deaths; shorter follow-up could lead to overestimation of treatment benefits.

ObjectivesTo describe the age- and sex-specific prevalence of SARS-CoV-2 disease (COVID-19) and its prognostic factors.DesignPopulation-based prospective cohort study on archive data.SettingPreventive services and hospital care in the province of Reggio Emilia, Northern Italy.ParticipantsAll 2653 symptomatic patients who tested positive for SARS-CoV-2 from February 27 to April 2, 2020 in the province of Reggio Emilia.Main outcome measuresHospitalization and death up to April 2, 2020.ResultsFemales had higher prevalence of infection than males below age 50 (2.61 vs. 1.84 ‰), but lower in older ages (16.49 vs. 20.86 ‰ over age 80). Case fatality rate reached 20.7% (22/106) in cases with more than 4 weeks follow up. After adjusting for age and comorbidities, men had a higher risk of hospitalization (hazard ratio (HR) 1.4 95% confidence interval (95% CI) 1.2 to 1.6) and of death (HR 1.6, 95% CI 1.2 to 2.1). Patients over age 80 compared to < age 50 had HR 7.1 (95% CI 5.4 to 9.3) and HR 27.8 (95% CI 12.5 to 61.7) for hospitalization and death, respectively. Immigrants had a higher risk of hospitalization (HR 1.3, 95% CI 0.99 to 1.81) than Italians and a similar risk of death. Risk of hospitalization and of death were higher in patients with heart failure (HR 1.6, 95% CI 1.2 to 2.1and HR 2.3, 95% CI 1.6 to 3.2, respectively), arrhythmia (HR 1.5, 95% CI 1.2 to 1.9 and HR 1.8, 95% CI 1.3 to 2.5, respectively), dementia (HR 1.2, 95% CI 0.9 to 1.8 and HR 1.8, 95% CI 1.1 to 2.8, respectively), ischemic heart disease (HR 1.3, 95% CI 1.0 to 1.7 and HR 1.7, 95% CI 1.2 to 2.5, respectively), diabetes (HR 1.5, 95% CI 1.3 to 1.9 and HR 1.6, 95% CI 1.1 to 2.2, respectively), and hypertensions(HR 1.4, 95% CI 1.2 to 2.6 and HR 1.6, 95% CI 1.2 to 2.1, respectively), while COPD increased the risk of hospitalization (HR 1.9, 95% CI 1.4 to 2.5) but not of death (HR 1.1, 95% CI 0.7 to 1.7). Previous use of ACE inhibitors has no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34)ConclusionsThe mechanisms underlying these associations are mostly unknown. A deeper understanding of the causal chain from infection, disease onset, and immune response to outcomes may explain how these prognostic factors act.

In the present work, an investigation on the hydrodynamics of wave-current orthogonal combined flow has been carried out. The work focuses on the effects of the oscillatory flow superposed on the current steady boundary layer, and on how the oscillatory flow affects the current velocity distribution. A laboratory experimental campaign of wave-current orthogonal interaction has been carried out in a shallow water basin at DHI Water and Environment (Horsholm, Denmark), in order to investigate the orthogonal combined flow in the presence of different roughness beds. Mean flow has been investigated by computing time- and space-averaged velocity profiles. Friction velocity and equivalent roughness have been inferred from the velocity profiles by best fit technique, in order to quantify the shear stress experienced by the current mean flow. Tests in the presence of only current, only waves and combined flow have been performed. Instantaneous velocities have been Reynolds-averaged in order to obtain turbulent fluctuations time series and compute turbulence related quantities, such as Reynolds stresses. The mean current velocity profiles have been also compared with a selection of analytical models in order to assess their validity for the case of wave-current orthogonal flow for the considered wave and current condition ranges. The analysis of the mean flow revealed a complex interaction of the waves and currents combined flow. Depending on the relative strength of the current with respect to the waves, the superposition of the oscillatory flow may determine an increase or a decrease of the bottom friction experienced by the current. Such a behavior is also strictly related to the bed physical roughness. Analysis of the turbulence Reynolds stresses seems to confirm the results of the mean flow investigation.Recorded Presentation from the vICCE (YouTube Link): https://youtu.be/GbtOgeLlVTU

It has been hypothesized that bacille Calmette-Guerin (BCG), the anti-tuberculosis vaccine, can be protective against Covid-19. Using data of performed swabs and RT-PCR results for SARS-CoV-2 in the Reggio Emilia province (Emilia-Romagna Region, Northern Italy) from March 6th to March 26th, 2020, we computed age, gender, and place of birth (Italy or abroad) specific risk of being tested, prevalence of positive tests, and probability of testing positive given that a swab has been taken during the epidemic peak. We report that immigrants resident in Reggio Emilia province, mostly coming from Countries with high BCG vaccination coverage, and Italians had a similar prevalence of infection (odds ratio - OR 0.99; 95%CI 0.82-1.20) and similar probability of being tested (OR 0.93; 95%CI 0.81-1.10). Our data do not support the hypothesis that immigrants from Countries where BCG vaccination is recommended have a lower risk of Covid-19 infection.

In the present work, an experimental investigation on the hydrodynamics of shoaling waves superposed on a steady orthogonal current is carried out. An experimental campaign in a wave tank has been performed, with waves and current interacting at a right angle over a sloping planar beach. Velocity data have been gathered during the experiments in order to investigate mean, phase and turbulent flow. A detailed preliminary analysis of the time- and space-variability of the experiments is presented. Results show that a complex interaction between waves and current occurs as the wave shoals, in terms of sheer production, momentum transfer and turbulent mixing. Superposition of waves determines a shear increase at the bottom due to an enhanced turbulence mixing, nonetheless as depth decreases and the current velocity consequently increases, shoaling waves may be less efficient in enhancing shear at the bottom. Moreover, the superposition of waves determines the current to oscillate around its mean velocity value. Nevertheless, as wave shoals and simultaneously current velocity increases with decreasing depth, waves and current oscillatory motion experience a phase lag, as a response of the larger momentum of the current to the changing of the shoaling waves acceleration distribution along the wave phase. Moreover, the turbulent bursting events of the combined flow in proximity of the bed have been investigated by means of quadrant analysis, showing an increase of the turbulent ejections and sweeps due to the superposition of the shoaling waves.

Orthogonal wave-current interaction often occurs in coastal regions, when waves approach the shoreline near-orthogonally and longshore currents are present. Notwithstanding its wide relevance, this phenomenon is far from being understood to a full extent, especially in the presence of bed roughness. Indeed the effects on the apparent roughness due to the combination of steady currents and surface waves propagating at right angles are still a matter of debate, both in the current and in the wave dominated cases. To this aim, the hydrodynamic effects of an orthogonal regular wave on a current propagating over a rough bed were investigated; two different rough beds, one sandy and one made of gravel, were considered. Both surface elevation and velocity profiles were acquired by means of an array of wave gauges and Micro Acoustic Doppler Velocimeters positioned within the tank. Here the range of the investigated parameters was significantly enlarged with respect to the existing literature studies. The present paper focuses on the analysis of the mean velocity profiles. More specifically, observation of velocity profiles shows that the current to wave velocity ratio and the bed roughness play an important role, by impacting the value of the apparent roughness. Indeed it was found that as far as the flow is current dominated the addition of waves on the current increases the flow resistance. The opposite happens when the flow is wave dominated, irrespective of the bed roughness type. In particular, the apparent roughness increases as far as the wave plus current to current only friction velocity ratio increases. The increase is more rapid if the wave plus current prevails on the current only friction velocity.

Beta-blockers (BB), ACE inhibitors/angiotensin receptor blockers(ACEi/ARBs) and aldosterone antagonists (AA) do represent diseasemodifying drugs and have become the cornerstone of heart failure(HF) pharmacological therapy [1]. However, it is never safe to assumethat treatments of proven efficacy in younger, healthier patients willprovide equivalent benefit in older patients [2] but current guidelinesrarely distinguish the use of these therapies on the basis of age [3].To help clarify these issues a retrospective cohort study was under-taken byidentifyingall patients hospitalized for HF and never hospital-ized for HFin theprevious 10 years, discharged from 1 January 2009 to31December 2010in theEmilia–Romagna, 4.3 million resident inhabi-tants in the Italian region. Inclusion criteria were one of the followingICD9-CM codes as principal discharge diagnosis: 428.0, 428.1, 428.2x,428.3x, 428.4x, 428.9x, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11,404.13, 404.91, 404.93, and 398.91. Exclusion criteria were: age≤75 years,residenceoutsideEmilia–Romagnaregionanddeathwithin90 days of discharge. Accordingly, the eventual HF disease-modifyingdrug was prescribed away from the known clinically “vulnerable”phase regardless of standard medical therapy [4].Theeligiblecohortwascategorizedin6groupsofpatientsbasedonadrugprescriptionwithin90daysfromhospitaldischarge:1)noBB/ACEi/ARBs/AA (“No drug”); 2) single ACEi/ARBs (“only ACEi/ARBs”); 3) singleBB (“only BB”); 4) ACEi/ARBs plus BB (“double therapy”); 5) BB plusACEi/ARBs plus AA (“triple therapy”); and 6) other different combina-tions between BB and/or ACEi/ARBs and/or AA ( “other combinations”).Data were collected from the Emilia–Romagna Region administra-tive healthcare databases, which capture information about health ser-vice utilization from the entire region. Patients' information wasretrievedfromtheregionaldatabaseofhospitaldischarges,theregionaloutpatient and inpatient drug prescription database and the regionalmortality registry. The following ATC classes were used: C07 class(BB); C09A' 'C09B' 'C09C' 'C09D class (ACEi/ARBs); and C03DA class(AA). Individuals were linked across data files with anonymous patientidentifiers and were followed for 1 year.Foreachpatient,informationonage,gender,comorbiditiesandproce-dures was retrieved from the previous 10 years of hospitalization fromindex admission. The study outcomes were 1-year all-cause mortality,HFrehospitalizationandall-causerehospitalizationfromindexdischarge.All the outcomes were calculated crude and adjusted. Continuous vari-ables were expressed as mean ± SD a nd median and compared using aK-sample equality of median test. Categorical variables were expressedas percentages and the Chi-squar e test was used for comparison.IncidenceofeventswasestimatedbytheKaplan–Meiermethodandcompared using the Log-rank test. Observations were censored at thetime of the event or at the end of follow-up. One-year adjusted risk ofevents was evaluated by using Cox's proportional hazards modelsadjusting for all variables reported in Table 1. We used a multivariatestepwise Cox regression analysis for variable selection with entry andstay probability of 0.1 (10%). Results are reported as Hazard Ratios(HR) with 95% confidence intervals.Allstatisticaltestsweretwo-sided(p-valueb0.05wasconsideredtobe significant). All analyses were performed with the SAS 9.1.3 version(Service Pack 4, SAS Institute Inc., Cary, NC, USA) (SAS Institute, Cary,NC,USA)andtheSTATA12.1(STATACorpLP,CollegeStation,TX,USA).Clinical baseline and demographic characteristics of patients areshownin Table1.After1-yearfollow-upperiodfromindexHFhospital-ization,1690(18.1%)deathand5273(56.4%)hospitalreadmissionshadoccurred. The 1-year HF-related hospital readmissions were 1686 (31%of the total hospital readmissions).

The adoption of a surgical checklist is strongly recommended worldwide as an effective practice to improve patient safety; however, several studies have reported mixed results and a number of issues are still unresolved. The main objective of this study was to explore the impact of the first 5-year period of a surgical checklist-based intervention in a large regional health care system in Italy (4 500 000 inhabitants). We conducted a retrospective longitudinal study on 1 166 424 patients who underwent surgery in 48 public hospitals between 2006 and 2014. The adherence to the checklist was measured between 2011 and 2013 through a computerized database. The effects of the intervention were explored through multivariable logistic regression and difference-in-differences (DID) approaches, based on current administrative data sources. In-hospital and 30-days mortality, 30-days readmissions and length-of-stay (LOS) ⩾8 days were the observed outcomes. Adherence to the checklist showed marked variations across hospitals (0%-93.3%). A pre/post analysis detected statistically significant differences between surgical interventions performed in hospitals with higher adherence to the checklist (⩾75% of the surgeries) and those performed in other hospitals, as for the 30-days readmissions rate (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.94-0.98) and LOS ⩾ 8 days rate (OR: 0.88; 95% CI: 0.87-0.89). These findings were confirmed after risk adjustment and DID analysis. No association was observed with mortality outcomes. On the whole, our study attained mixed results. Although a protective effect of the surgical checklist use could not be proved over the first 5 years of this regional implementation experience, our research offers some methodological insights for practical use in the evaluation process of large-scale implementation projects.

Aim of the study was to compare four different strategies of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) treated with PCI. DAPT with Clopidogrel, Ticagrelor and Prasugrel has proved to be effective in patients with ACS treated with percutaneous coronary intervention (PCI) by reducing major adverse cardiovascular outcomes (MACE). However, the effect of the different strategies in a real-world population deserves further verification. A retrospective analysis of 2404 discharged ACS patients treated with PCI was performed, with a median follow-up of 1 year. The study population was stratified in four drug treatment cohorts: ASA + Clopidogrel (A-C), ASA + Plavix (A-PLx), ASA + Ticagrelor (A-T), ASA + Prasugrel (A-P). We assessed the incidence of net adverse cardiovascular events (NACE): all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stroke and bleeding during follow-up. At 1-year, the use of A-C and A-PLx was associated with the highest cumulative incidence of NACE in comparison with A-T and A-P therapies (respectively 14.8 and 29.6% vs. 9.2 and 6%). This difference was mainly driven by the mortality and TVR outcomes. Considering selection bias and differences in the patients baseline characteristics, the association of A-T and A-P seems to be superior in comparison with a DAPT strategy of A-C and A-PLx in low risk ACS-PCI patients from real world. In our Region the prescription is consistent with guidelines recommendations and Clopidogrel and Plavix are still predominantly used in older patients with more comorbidities, and this could partially explain the inferiority of this association.

ObjectiveTo evaluate cross-sectional patient distribution and standardised 30-day mortality in the intensive care units (ICU) of an inclusive hub and spoke trauma system.SettingICUs of the Integrated System for Trauma Patient Care (SIAT) of Emilia-Romagna, an Italian region with a population of approximately 4.5 million.Participants5300 patients with an Injury Severity Score (ISS) >15 were admitted to the regional ICUs and recorded in the Regional Severe Trauma Registry between 2007 and 2012. Patients were classified by the Abbreviated Injury Score as follows: (1) traumatic brain injury (2) multiple injuriesand (3) extracranial lesions. The SIATs were divided into those with at least one neurosurgical level II trauma centre (TC) and those with a neurosurgical unit in the level I TC only.ResultsA higher proportion of patients (out of all SIAT patients) were admitted to the level I TC at the head of the SIAT with no additional neurosurgical facilities (1083/1472, 73.6%) compared with the level I TCs heading SIATs with neurosurgical level II TCs (1905/3815; 49.9%). A similar percentage of patients were admitted to level I TCs (1905/3815; 49.9%) and neurosurgical level II TCs (1702/3815, 44.6%) in the SIATs with neurosurgical level II TCs. Observed versus expected mortality (OE) was not statistically different among the three types of centre with a neurosurgical unit; however, the best mean OE values were observed in the level I TC in the SIAT with no neurosurgical unit.ConclusionThe Hub and Spoke concept was fully applied in the SIAT in which neurosurgical facilities were available in the level I TC only. The performance of this system suggests that competition among level I and level II TCs in the same Trauma System reduces performance in both. The density of neurosurgical centres must be considered by public health system governors before implementing trauma systems.

The current cardiovascular literature advocates an overall beneficial balance between the advantages of oral anticoagulants and antiplatelet drugs in preventing and treating thromboembolic events and their disadvantages in promoting hemorrhage. However, traumatic injuries have usually received little attention despite several studies from the surgical literature showing worse outcomes in anticoagulated trauma registry patients. To quantify at population level too this seemingly deleterious impact, we investigated the effects of anticoagulants and antiplatelet use on the risk for hospital admission for acute traumatic causes.A population-based, case-control study in an Italian region with 4.5 million inhabitants was conducted. Cases were all the 59,348 adult residents admitted to the hospital for traumatic injuries in the years 2010 and 2011. Controls were age- and sex-matched residents selected by incidence density sampling. By conditional logistic regression adjusted for comorbidities, we estimated the risk for traumatic hospital admission while on anticoagulant, antiplatelet, and combined medications.The odds ratios (ORs) for anticoagulation and combined medications were 1.21 (95% confidence interval [CI], 1.15-1.28) and 1.39 (95% CI, 1.21-1.62). These effects were generally consistent across subgroups of demographic and clinical characteristics and particularly important in the head injured (e.g., OR for anticoagulation, 2.00; 95% CI, 1.77-12.27). Antiplatelets alone had no overall effect (OR, 1.02; 95% CI, 0.99-1.05). The number-needed-to-harm of anticoagulation was 595.Oral anticoagulation increased the population risk for traumatic hospital admission, with a further increase in case of concurrent antiplatelet use. Because this effect is most likely to derive from the prohemorrhagic properties of these drugs, injured patients should be included in the future evaluations of the cost-benefit profiles of these medications.Epidemiologic/prognostic study, level III.

SUMMARY What is known and objective: Since 2005, a mounting base of evidence has identified that conventional antipsychotic medications are associated with an increased risk of mortality among elderly patients when compared to atypical antipsychotics. This study sought to explore the feasibility of using the EmiliaRomagna Region (RER) database for comparative safety analyses by replicating and refining risk estimates of this well-known drug safety example through meta-analysis. Methods: We identified a cohort of 23 681 Italian RER patients (aged ≥65) who initiated treatment with a conventional or atypical antipsychotic between 1 July 2009 and 30 June 2011. We compared 180-day mortality using Cox proportional hazards models adjusted for risk factors for death, use of other medications and measures of health services utilization intensity, all measured before antipsychotic initiation. We conducted a metaanalysis of studies with similar methods against which to compare our results. Results: Among 14 462 and 9219 patients prescribed conventional and atypical antipsychotics, respectively, we observed 2402 (166%) and 821 (89%) deaths during follow-up. Conventional antipsychotic initiators were older and generally had higher prevalence of outcome risk factors and higher baseline health service use intensity. The crude hazard ratio (HR) was 195 [95% confidence interval (CI), 180–211], which decreased to 147 (95% CI, 135–160) after full adjustment. We identified seven published studies that examined this association using similar methods. The pooled HR from these studies was 134 (95% CI, 128–139). Including our study, the meta-analysis yielded a summary estimate of 135 (95% CI, 131– 140) and did not introduce any heterogeneity (I 2 = 0%; P = 0455). What is new and conclusions: Our results support the use of the RER database for pharmacoepidemiological studies and provide an up-to-date and pooled estimate of the magnitude of the association between mortality and conventional vs. atypical antipsychotics.

Background Some studies have indicated that marginal bone loss at implants and at teeth are similar, while results from other studies showed that implants lost more bone than teeth in the same dentition. Aim To determine the amount of progressive marginal bone loss that had occurred at implants and teeth in the same segment of the dentition following implant placement in partially dentate subjects. Material and Methods A total of 217 patients with a total of 573 implants and 318 teeth present in the same segments of the dentition were included. Radiographs were available from 1 year (baseline) and ≥3 years after loading. Results The mean bone loss that occurred between the two examinations was at implants 0.42 ± 0.68 mm and at teeth 0.44 ± 0.52 mm. Thirty-eight subjects (18%) had ≥1 implant exhibiting >1 mm bone loss. Bone loss at the 148 implants in this category of patients was 1.30 ± 1.04 mm with a corresponding loss at the 69 teeth of 0.53 ± 0.62 mm. Eighteen subjects (8%) had ≥1 tooth that exhibited >1 mm bone loss. The mean amount of bone loss in this sample was 1.37 ± 0.87 mm (38 teeth) and 0.29 ± 0.31 mm (56 implants). Conclusions This study showed that marginal bone loss at implants and teeth in many partially dentate subjects might be independent phenomena.

TMPM-ICD9 is the latest injury-severity measure based on empirical estimation from ICD-9-CM codes. It is candidate to replace expert-based AIS measures worldwide because of easier accessibility and better predictive performances. In Italy and other countries administrative ICD coding is generally less complete than dedicated AIS coding. We attempted to ascertain how this affects TMPM performances.Discrimination (c statistics) and calibration (calibration curves, Akaike's criterion) of hierarchical logistic regression models for hospital mortality comprising TMPM or ISS were compared using trauma-registry data on 3570 patients of years 2007-2009. The completeness of AIS vs. ICD-9-CM coding was also investigated through the ratio of the respective numbers of codes per patient. Model discrimination was further analyzed after stratification according to the above ratio (1 and ≤ 1).The models with TMPM showed worse performances. The differences, concerned calibration (graphical evidence) in univariate models and discrimination (-1.2% of area under the ROC curve, p0.05) in models completed with age, gender, mechanism of injury, motor GCS and systolic pressure. In parallel, ICD coding was less complete than AIS, as expected: 68% of patients had a ratio1. The discrimination of TMPM vs. ISS models improved when the ratio changed from1 to ≤ 1.The predictive performances of TMPM-ICD9 vs. ISS were lower than in the previous studies; the sub-optimal quality of ICD coding was a main cause. Imperfect administrative coding may hence hamper the TMPM-ICD9 revolution, although in our setting the negligible differences and the ready availability of administrative data may still give reason for adopting TMPM-ICD9.

We sought to: (1) estimate the proportion of patients who initiated beta-blocker therapy after acute myocardial infarction (AMI) in Regione Emilia-Romagna (RER); (2) examine predictors of post-AMI beta-blocker initiation; and (3) assess adherence to such therapy.Using healthcare claims data covering all of RER, we identified a cohort of 24,367 patients with a hospitalization for AMI between 2004 and 2007, who were discharged from the hospital alive and without contraindications to beta-blocker therapy. We estimated the proportion of eligible patients with at least one prescription for a beta-blocker following discharge and performed a multivariable logistic regression analysis to identify independent predictors of post-AMI beta-blocker initiation. We computed the proportion of days covered (PCD) as a measure of medication adherence at 6 and 12 months post-discharge. Following discharge, 16,383 (67%) cohort members initiated beta-blocker therapy. Independent predictors of beta-blocker initiation included age and receipt of invasive procedures during hospitalization, such as coronary artery bypass graft surgery (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.00-2.81), percutaneous transluminal coronary angioplasty (OR, 1.42; 95% CI, 1.31-1.54), and cardiac catheterization (OR, 1.21; 95% CI, 1.11-1.32). Among initiators, adherence to beta-blocker treatment at 6 and 12 months was low and decreased in each study year.Overall, use of and adherence to post-AMI beta-blocker therapy was suboptimal in RER between 2004 and 2007. Older patients and those with indicators of frailty were less likely to initiate therapy. The proportion of patients adherent at 6 and 12 months decreased over time.

A comparison between a range of transfer functions to recover wave height from pressure sensors data is presented. The analysis is carried out by means of a large-scale wave flume experimental dataset, in which resistive, acoustic and pressure gauges recovered wave height are compared as the waves travel from intermediate waters, to the shoaling region and finally into the surf zone. All the considered transfer functions result adequate in recovering wave height in intermediate waters, becoming gradually less accurate as the steepness of the wave increases in the shoaling region and in the surf zone. The accuracy of the compared transfer functions is assessed by means of an ensemble wave height based deviation.

Aims International and national consensus guidelines define appropriate indications for implantable cardioverter–defibrillators (ICDs), but the variability in implant rates in ‘real world’ clinical practice is still unknown. Methods and results In Emilia-Romagna, an Italian region with around 4.3 million inhabitants, a web-based registry was instituted to collect data for all ICDs implanted. Between January 2006 and December 2008, data from all consecutive patients resident in this region who underwent first implant of an ICD or a biventricular ICD were collected and standardized, considering each regional area (i.e. each of the nine provinces). The overall number of implanted ICDs had an increase in years 2007 and 2008, with a relative increase in comparison to 2006, by 14 and 48% respectively, reaching an average value of 16.2 per 100 000 inhabitants in 2008. Most of the increase was due to a rise in ICDs for primary prevention. The ratio between the implant rates of the provinces with the highest and the lowest implant rates, respectively, was around 2 in 2008. Conclusion Implant rates for ICDs, considering both primary and secondary prevention of sudden death, show up to two-fold variations even in a geographical region where the general level of health care is advanced and well appreciated by the population. The lack of a common strategy for sudden death prevention, approved by both physicians and institutional regional authorities, together with some degree of variability in translating guidelines into clinical practice, were identified as the main factors explaining the heterogeneity in ICD implant rates.

e18842Background: After specific treatments, patients may be transferred to other non-acute wards, discharged to home or entrust to local care facilities. This process is frequently hampered by soc...

High residual platelet reactivity (RPR) on clopidogrel treatment has been associated with increased risk for ischemic events during follow-up in patients with acute coronary syndromes. The aim of this study was to assess the incidence, predictors, and clinical consequences of high RPR in a large population of patients with non-ST-segment elevation acute coronary syndromes who underwent percutaneous coronary intervention and stenting. Overall, 833 patients received point-of-care testing of platelet inhibition 30 days after percutaneous coronary intervention. High RPR was diagnosed on the basis of P2Y₁₂ reaction units >230. The incidence and predictors of death, myocardial infarction, stroke, and serious bleeding events were assessed up to 1 year from the day of testing. P2Y₁₂ reaction units were normally distributed, and 264 patients were classified as poor responders (31.7%). Independent predictors of response to clopidogrel were male gender (odds ratio [OR] 1.51), age (OR 0.96), diabetes mellitus (OR 0.51), and use of proton pump inhibitors (OR 0.59). At 1 year, poor responders showed higher rates of death (4.6% vs 1.9%, p = 0.032) and serious bleeding events (4.9% vs 1.8%, p = 0.009) compared with good responders. After adjustment for confounders, high RPR did not emerge as an independent predictor of mortality (OR 0.57, 95% confidence interval [CI] 0.23 to 1.42, p = 0.23) or serious bleeding events (OR 0.61, 95% CI 0.25 to 1.52, p = 0.29). The results did not change using the a cut-off value for P2Y₁₂ reaction units of 208. In conclusion, 1/3 of patients with acute coronary syndromes who underwent percutaneous coronary intervention and stenting showed high on-treatment RPR on bedside monitoring. They had a worse prognosis, but the level of platelet inhibition was not independently associated with the incidence of ischemic or bleeding events.

Aims In accordance with current guidelines, patients discharged after acute myocardial infarction (AMI) are usually prescribed agents acting on the renin–angiotensin system (ACE-I/ARB). However, adherence to prescribing medications is a recognized problem and most studies demonstrating the value of adherence were limited by their non-randomized design and by ‘healthy-adherer’ bias. Herein we sought to evaluate the relationship between adherence to ACE-I/ARB and risk of subsequent AMIs, by using the self-controlled case-series design which virtually eliminates interpersonal confounding, being based on intrapersonal comparisons. Methods and results We linked data from three longitudinal registries containing information about hospitalizations, drug prescriptions, and vital status of all residents in an Italian region. From 30 089 patients hospitalized for AMI in the years 2009–11, we enrolled the 978 with non-fatal re-AMIs at Days 31–365 after discharge, receiving at least one ACE-I/ARB prescription collected at any of the regional pharmacies. Using information on prescriptions, each individual's observation time was then divided into periods exposed or unexposed to ACE-I/ARB. The relative re-AMI incidence rate ratios (IRRs) of ACE-I/ARB exposure were estimated by conditional Poisson regression. During drug-covered periods, the risk of AMI recurrence was ∼20% lower, i.e. the IRR (rate of recurrent AMI in exposed versus unexposed periods) was 0.79 (95% CI 0.66–0.96, P = 0.001). The benefit of ACE-I/ARB was confirmed also by sensitivity analyses considering only first recurrences, excluding cases with AMI within previous 3 years, or with long, not AMI, hospital re-admission. Conclusions Poor adherence to ACE-I/ARB prescription medication was associated with a 20% increased risk of recurrent AMI. This was consistent with previous research, but the SCSS study design, even if not randomized, eased previous concerns about healthy-adherer bias.

Colorectal cancer (CRC) occurs rarely in young individuals (45 yr) and represents one of the criteria for suspecting hereditary cancer families. In this study we evaluated clinical features and molecular pathways (chromosomal instability [CIN] and microsatellite instability [MSI]) in early-onset CRC of 71 patients.Detailed family and personal history were obtained for each patient. Expression of APC, beta-catenin, p53, MLH1, MSH2, and MSH6 genes was evaluated by immunohistochemistry. MSI analysis was performed and constitutional main mutations of the mismatch repair (MMR) genes were searched by gene sequencing.Fourteen (19.7%) out of the 71 cases showed both MSI and altered expression of MMR proteins. In the 57 MSI-negative (MSI-) lesions altered expression of APC, beta-catenin, and p53 genes were found more frequently than in MSI-positive(MSI+) tumors. Seven (50%) out of the 14 patients with MSI+ tumors presented clinical features of Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) and in all but one, constitutional mutations in MLH1 or MSH2 genes could be detected. The same mutations were also found in other family members.Our study demonstrates the involvement of CIN in a majority of early-onset colorectal tumors. Furthermore, we identified Lynch syndromes in seven cases (50%) of early-onset colorectal carcinomas with impairment of the MMR system. These results suggest that patients with early-onset CRC should be screened for hereditary cancer syndrome through clinical and molecular characterizations.

Background Beta‐blockers ( BB ) are recommended in secondary prevention of acute myocardial infarction ( AMI ), but adherence to prescription medication is a recognized problem. Most literature on the consequences of poor adherence to prescribed BB is limited by the possibility of “healthy adherer bias” and better‐designed studies have been advocated. Methods and Results We investigated the association between adherence to BB prescription and risk of subsequent AMI s using the self‐controlled case series design, which allows improved control of interpersonal confounding, being based on intrapersonal comparisons. From all the 30 089 patients hospitalized for AMI in the years 2009–2011 in an Italian region we selected those that suffered subsequent AMI s at days 31 to 365 from discharge (1328), and then the 1207 that had at least one BB prescription collected at any of the regional pharmacies. Using information on prescriptions, each individual's observation time was then divided into periods exposed or unexposed to BB and the relative AMI incidence rate ratios ( IRR ) of BB exposure were estimated by conditional P oisson regression. The IRR (rate of recurrent AMI in exposed versus unexposed periods) was 0.79 (95% CI 0.69 to 0.90, P =0.001). Various sensitivity analyses confirmed the robustness to possible failure of assumptions, ie, considering only first recurrences ( IRR 0.76, 95% CI 0.66 to 0.88, P IRR 0.76, 95% CI 0.65 to 0.89, P IRR 0.60, 95% CI 0.43 to 0.83, P =0.002). Conclusions Adherence to recommended BB therapy was associated with a 20% reduction of recurrent AMI s, consistently with previous research, but with decreased concerns about healthy‐adherer bias.

We sought to evaluate the rates, time course, and causes of death in the long-term follow-up of unselected patients with acute coronary syndromes (ACS). We enrolled 2046 consecutive patients hospitalized from January 2004 to December 2005 with an audited final diagnosis of ACS. The primary study end point was 5-year all-cause mortality. In our series, 896 patients had ST-segment elevation (STE) and 1,150 non-ST-segment elevation (NSTE). Mean age of the study population was 71.6 years. Primary percutaneous coronary intervention was performed in 86% of STE-ACS, and 70% of NSTE-ACS was managed invasively. The 5-year all-cause mortality was 36.4% for STE-ACS and 42.0% for NSTE-ACS, with patients with STE-ACS showing a trend boarding statistical significance toward a lower risk of mortality (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.76 to 1.02, p = 0.08). Landmark analysis demonstrated that patients with STE-ACS had a higher risk of 30-day mortality (STE-ACS vs NSTE-ACS HR = 1.53, 95% CI 1.16 to 2.06, p = 0.003) whereas the risk of NSTE-ACS increased markedly after 1 year (STE-ACS vs NSTE-ACS HR = 0.67, 95% CI 0.53 to 0.84, p = 0.001). The contribution of noncardiovascular (CV) causes to overall mortality increased from 3% at 30 days to 34% at 5 years, with cancer and infections being the most common causes of non-CV death both in STE-ACS and NSTE-ACS. In conclusion, long-term mortality after ACS is still too high both for STE-ACS and NSTE-ACS. Although patients with STE-ACS have a higher mortality during the first year, the mortality of patients with NSTE-ACS increases later, when non-CV co-morbidities gain greater importance.

Background The so-called off hour effect—that is, increased mortality for patients admitted outside normal working hours—has never been demonstrated in trauma care. However, most of the studies excluded transferred cases. Because these patients are a special challenge for trauma systems, we hypothesised that their processes of care could be more sensitive to the off hour effect. Methods The study design was retrospective, cohort and population based. We compared the mortality of all patients by daytime and night-time admittance to hospitals in an Italian region, with 4.5 million inhabitants, following a major injury in 2011. Logistic regression was used, adjusted for demographics and severity of injury (TMPM-ICD9), and stratified by transfer status. Results 1940 major trauma cases were included; 105 were acutely transferred. Night-time admission had a significant pejorative effect on mortality in the adjusted analysis (OR=1.49; 95% CI 1.05 to 2.11). This effect was most evident in transferred cases (OR=3.71; 95% CI 1.11 to 12.43). Conclusions The night-time effect in trauma care was demonstrated for the first time and was maximal in transferred cases. This may explain why it was not found in previous studies where these patients were mostly excluded. Also, the use of population based data—whereby patients not accessing trauma centre care and presumably receiving poorer care were included—may have contributed to the findings.