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Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country

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.

In many hypertensive patients, treatment is not upgraded despite lack of blood pressure control because of therapeutic inertia. Information is limited, however, on the extent of this phenomenon in real-life medicine. We studied 125 635 patients (age 40-85 years) from the Lombardy region (Italy) who started antihypertensive treatment with 1 drug (n=100 982) or a 2-drug fixed-dose or free combination (n=24 653). A log-binomial regression model was used to estimate the prevalence ratio of combination therapy in relation to the initial treatment strategy. In the initial monotherapy group, patients under drug combinations were 22%, 27%, 32%, and 36% at 6 months, 1, 2, and 3 years later. In the initial combination treatment group, the corresponding percentages were 85%, 82%, 79%, and 78%. This translated into a markedly greater covariate-adjusted propensity of being under a multidrug prescription throughout the follow-up: 3.92 (95% CI, 3.84-4.00) after 6 months and 3.18 (3.12-3.25), 2.56 (2.51-2.60), and 2.23 (2.19-2.27) after 1, 2 and 3 years of treatment. In a propensity score analysis, initial 2-drug combination treatment was also associated with significant reductions in the risk of death (−20%, 11% to 28%) and hospitalization for cardiovascular events (−16%, 10% to 21%) compared with initial monotherapy. Thus, in real life, a large number of patients prescribed initial monotherapy fails to move to combination treatment, as recommended by guidelines. This implies that therapeutic inertia frequently prevents proper treatment uptitration, thereby playing a major role in the low rate of hypertension control that exists worldwide.

Aims: Guidelines support use of drug combinations in most hypertensive patients, and recently treatment initiation with two drugs has been also recommended. However, limited evidence is available on whether this leads to greater cardiovascular (CV) protection compared to initial monotherapy. Methods and results: Using the healthcare utilization database of the Lombardy Region (Italy), the 44 534 residents of the region (age 40-80 years) who in 2010 started treatment with one antihypertensive drug (n = 37 078) or a two-drug fixed-dose combination (FDC, n = 7456) were followed for 1 year after treatment initiation to compare the risk of hospitalization for CV disease associated with the two treatment strategies. To limit the confounding associated with non-randomized between-group comparisons, data were also analysed by: (i) matching the two groups by the high-dimensional propensity score (HDPS) and (ii) comparing, in patients experiencing one or more CV events (n = 2212), the CV event incidence during subperiods in which patients were prescribed mono- or FDC therapy (self-controlled case series design). Compared to initial monotherapy, patients on initial FDC therapy showed a reduced 1 year risk of hospitalization for any CV event (-21%, P < 0.01). This was the case also when groups were compared according to the HDPS analysis (-15%, P < 0.05). Finally, in patients experiencing CV events, the event incidence was much less when, during the 1 year follow-up, they were under FDC therapy than under monotherapy (-56%, P < 0.01). The reduced risk of hospitalization was always significant for ischaemic heart disease and new onset atrial fibrillation, and included hospitalization for cerebrovascular disease and heart failure when monotherapy and FDC therapy were compared within patients. Conclusion: In a real-life setting, a comparison of the incidence of early CV events during antihypertensive monotherapy and FDC shows that the latter strategy leads to a more effective CV p

Introduction: Nimesulide is the most prescribed non-steroidal anti-inflammatory drug in Italy, and it is currently marketed in about 50 countries worldwide. The association between the use of nimesulide in early pregnancy and the risk of birth defects was investigated in a large cohort of pregnant women from Italy. Methods: Data were from the healthcare utilization databases of the Italian region of Lombardy. The cohort of 353,081 newborns occurring in Lombardy during the period 2005–2010 was investigated. Exposure to nimesulide during the first trimester of pregnancy, and congenital malformations detected at presentation and within 90 days after birth (outcome), were investigated. Exposure–outcome association was measured by the ratio between the prevalence of congenital malformations among users and non-users of nimesulide. Propensity score stratification was used to control for potential confounders, including maternal medical comorbidities, concomitant medications and sociodemographic characteristics. Results: The 627 (0.18%) women who filled prescriptions for nimesulide in the first trimester of pregnancy had a 2.6-fold risk of having children with congenital urinary tract anomalies compared to those who did not (adjusted prevalence ratio 2.6; 95% CI 1.2–5.7). Weaker and non-significant evidence for congenital malformations as a whole was found (adjusted prevalence ratio 1.2, 95% CI 0.9–1.6). Conclusion: Our study suggests that the use of nimesulide in early pregnancy may result in a greater risk of having births with congenital urinary tract anomalies. Funding: This study was funded by grants from the Italian Ministry of the Education, University and Research (’Fondo d’Ateneo per la Ricerca’ portion, year 2015)

OBJECTIVE: Combining multiple healthcare databases allows comparing the effects of a wide variety of healthcare services. There is a growing interest in methods for combining the results from multiple databases. We attempted to learn lessons about the performance of one-stage and two-stage approaches from the re-analysis of data drawn from two studies of pharmacoepidemiology based on multiple databases. STUDY DESIGN AND SETTING: Two nested case-control studies were carried out for estimating the tricyclic antidepressants-arrhythmia and etoricoxib-heart failure associations, respectively from the Italian I-GrADE and the European SOS programs. The associations of interest were modelled by conditional logistic regression for matched case-control sets, fitting fixed-effect and random-effect models with both one-stage and two-stage approaches. RESULTS: One-stage and two-stage approaches gave very similar results, showing uncertainty of tricyclic antidepressants-arrhythmia association (random-effect odds ratios, 95% confidence interval, 1.26, 0.71-2.24, and 1.30, 0.66-2.55, respectively) and statistical evidence for etoricoxib-heart failure association (fixed-effect odds ratios, 95% confidence interval, 1.53, 1.41-1.66, and 1.54, 1.42-1.66, respectively). CONCLUSION: Our study offers further evidence that two-stage approach generates estimates very similar as those from one-stage approach, even in the case of between databases exposure heterogeneity and when several covariates must to be concurrently considered. As current rules limit the free movement of electronic health data, our findings open the door of treating data within the country where they are generated, and then to apply conventional techniques for summarizing estimates, that is the two-stage approach for meta-analysis using individual participant data

Background It becomes more and more clear that people with the same cancer can have different forms of the disease, so responses to treatment and their toxicity can vary. Beside the widely accepted and old fashioned clinical guidelines, personalized medicine needs the DSS (Decision Support System) to be implemented in order to offer a valuable assistance in clinical decision making and in daily practice. DSS are represented by softwares, apps, nomograms all based on the creation of predictive models (PM) that require standardization of data collection. Ontology represents a fundamental tool to establish a common language without knowing, beforehand, which one of the described features could be the most relevant for a specific hypothesis. Through the creation of a ontology for a specific technique [Stereotactic Radiotherapy (SRT)], this multicentric study aims at collecting standardized data in order to build up a predictive model. We started focusing on brain metastases SRT. Material and Methods The first two centres involved selected personnel in order to create a multidisciplinary team made of physicians, physicist, nurses and therapists. They meet twice a month. The first step of the project was to identify variables, validate them and built up the ontology. The second step was to implement a system that defines variables characteristics and the relationships among them. The semantic web technology was put into practice and the team is now collecting data on a dedicated software called BOA (Beyond Ontology Awareness) with its own WEB platform. The future development is to involve other RT centres to combine multiple datasets. Results The drafted ontology is made up of more than 130 variables related with brain SRT, including both general “brain” nomenclature and SRT specific features. All the features were collected and organized in three levels (‘registry’, ‘procedural’ and ‘research’ level) that classify all the information in order to easily diversify queries.

Background: Several gray areas and controversies exist concerning the management of pulmonary ground-glass opacities (GGOs), and there is a lack of consensus among clinicians on this topic. One of the main aims of the Italian Society of Thoracic Surgery is to promote education and research, so we decided to perform a survey on this topic to estimate current trends in practice in a large sample of thoracic surgeons. Methods: A total of 160 thoracic surgeons responded, namely, completed our questionnaire (response rate, 53%; 160 of 302). The survey was composed of 36 questions divided into six subsections: (1) demographic characteristics of the respondents; (2) terminology and taxonomy; (3) radiologic and radiometabolic evaluation; (4) diagnostic approach and indications for surgery; (5) surgical management; and (6) radiologic surveillance. Results: We observed some divergence of opinion regarding the definition of mixed GGOs, the role of 18F fluorodeoxyglucose positron emission tomography and computed tomography scans, indications for nonsurgical biopsy, intraoperative techniques for localizing GGOs, indications for surgery, extension of lung resection and lymph node dissection according to the radiologic scenario, use of intraoperative frozen section analysis, and radiologic surveillance of pure GGOs. Conclusions: This topic warrants more investigation in the future. An upcoming consensus conference of Italian Society of Thoracic Surgery experts (also open to experts in other specialties) could provide updated indications for GGO management based on the literature, expert opinions, and the results of the present survey.

OBJECTIVES: Lung transplantation (LTx) is the only effective treatment for end-stage lung disease. In rapidly deteriorating patients awaiting transplant, supportive strategies for lung function allow only a short period of support and lung transplantation remains the definitive therapy. An urgent transplant programme may reduce the waiting time, allowing lung transplantation in these patients.METHODS: Since November 2010 a nation-wide urgent lung transplant programme has been established in Italy and patients on the waiting list dependent on mechanical ventilation and/or extracorporeal lung support (ECLS) can be transplanted on an emergency basis with the first available graft in the country. Results of the first 14 months of this programme are analysed here.RESULTS: From November 2010 to December 2011, 28 patients (14 males, mean age 33.6 ± 14.4 years) were considered for urgent LTx. Rapidly deteriorating lung function was supported with mechanical ventilation alone in 4 patients (14.3%), ECLS in 13 patients (46.4%) and mechanical ventilation plus ECLS in the remaining 11 patients (39.3%). Three patients (10.7%) were excluded because of worsening conditions, 3 patients (10.7%) while on the urgent listed and 22 patients (78.6%) underwent transplantation after 9.8 ± 6.2 days of being on the urgent list. The 30-day mortality rate after LTx was 18%, and the 1-year survival rate was 71.4%.CONCLUSIONS: The urgent lung transplant programme allowed transplantation in a significant percentage of prioritized patients with acceptable 30-day and 1-year mortality rates. An accurate selection of recipients may further improve the clinical impact of this programme, reducing the ethical concerns about transplantation in high-risk patients.

Background: Joinpoint regression analysis is usually applied to study varying trends over time in order to identify the time point(s) in which the trend significantly changes. We illustrate three epidemiological investigations in which this methodology was applied with time-on-study as time-scale. Methods: Data were retrieved from the healthcare utilization databases of Lombardy Region (Italy). We investigated the trend of the: (1) mortality rate among centenarians hospitalized for hip fracture (2004-2011); (2) proportion of persistent patients after the initial prescription of antihypertensive drugs during the first year of treatment according to gender (2005); (3) prescription rate of statins in the year before and after the hospital admission among patients hospitalized for a transient ischemic attack (2008-2009). Results: The following results were obtained: (1) a joinpoint was identified in the fourth month, showing an increased risk of death during the three months after hip fracture hospitalization; (2) the proportion of patients still under antihypertensive treatment falls until the fifth month, remaining stable afterwards; there was evidence that the prevalence of patients who discontinued the treatment was significantly higher among women than men; (3) during the year after the transient ischemic attack episode, monthly rate of available statins was double than the previous year with a significant decrease in the first four months. Conclusions: The joinpoint regression analysis can be a useful tool in epidemiologic framework when a temporal trend is the objective of the investigation since it allows to make inference by means of a quantitative method rather than a qualitative evaluation.

Objective To develop and validate a novel comorbidity score (multisource comorbidity score (MCS)) predictive of mortality, hospital admissions and healthcare costs using multiple source information from the administrative Italian National Health System (NHS) databases. Methods An index of 34 variables (measured from inpatient diagnoses and outpatient drug prescriptions within 2 years before baseline) independently predicting 1-year mortality in a sample of 500 000 individuals aged 50 years or older randomly selected from the NHS beneficiaries of the Italian region of Lombardy (training set) was developed. The corresponding weights were assigned from the regression coefficients of a Weibull survival model. MCS performance was evaluated by using an internal (ie, another sample of 500 000 NHS beneficiaries from Lombardy) and three external (each consisting of 500 000 NHS beneficiaries from Emilia-Romagna, Lazio and Sicily) validation sets. Discriminant power and net reclassification improvement were used to compare MCS performance with that of other comorbidity scores. MCS ability to predict secondary health outcomes (ie, hospital admissions and costs) was also investigated. results Primary and secondary outcomes progressively increased with increasing MCS value. MCS improved the net 1-year mortality reclassification from 27% (with respect to the Chronic Disease Score) to 69% (with respect to the Elixhauser Index). MCS discrimination performance was similar in the four regions of Italy we tested, the area under the receiver operating characteristic curves (95% CI) being 0.78 (0.77 to 0.79) in Lombardy, 0.78 (0.77 to 0.79) in Emilia-Romagna, 0.77 (0.76 to 0.78) in Lazio and 0.78 (0.77 to 0.79) in Sicily. conclusion MCS seems better than conventional scores for predicting health outcomes, at least in the general population from Italy. This May offer an improved tool for risk adjustment, policy planning and identifying patients in need of a focused treatment approach in t

Background: Understanding the gap between evidence-based recommendations and real-world management is important to inform priority setting and health service planning. Methods: The 7,776 residents in the Italian Lombardy Region who were newly hospitalized for transient ischemic attack (TIA) during 2008-2009 entered into the cohort and were followed until 2012. Exposure to medical care including selected drugs, diagnostic procedures and laboratory tests was recorded. A composite outcome was employed taking into account all-cause death and hospitalization for stroke and acute myocardial infarction. A multivariable proportional hazards model was fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association. Results: During the first year after discharge, 8.6, 49.7 and 48.5% of patients did not use any drugs, diagnostic procedures and laboratory tests respectively. Patients exposed to medical care had 59% reduced risk (95% CI, 50 to 66%) with respect to those who did not use any of these services. Conclusions: Although the Italian National Health System supplies universal coverage for healthcare, several TIA patients receive suboptimal care. Systematic improvements are necessary in order to improve patient outcomes.

Real-world evidence can provide answers on healthcare utilization and appropriateness, post-marketing drugs safety and comparative effectiveness, and cost-effectiveness profiles of healthcare pathways. Healthcare utilization databases, possibly integrated with drug and disease registries, electronic medical records, survey and cohort data (i.e. real-world data), allow to trace healthcare ‘footprints’ left from beneficiaries of National Health Service. Beaver is a research platform available on demand to Italian regions which we developed for computing indicators of healthcare utilization and clinical outcomes, as well as for generating evidence on effectiveness and cost-effectiveness profile. Two distinct solutions may be adopted. One, the so-called Beaver Light front-end allows to automatically compute health indicators of adherence to official guidelines. Two, the so-called Beaver Full front-end involves an eight-step procedure entirely driven by the study protocol. In order to fulfil the directives recently issued by the European Parliament and Council and the Italian Authority for the protection of individual data, the platform resides in each region’s infrastructure, so limiting the free movement of electronic health data. Indeed, regional authorities should be responsible for data safety and for allowing data accessibility. The use of standardized and validated algorithms enables to obtain regional estimates that, being obtained by employing regional platforms containing data extracted with standardized procedure, may be compared and possibly summarized by using common meta-analytic techniques. In conclusion, the Beaver regional platform is a promising tool which may contribute to stimulate healthcare research in Italy.