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The aim of this study was to describe the clinical use of bevacizumab in Lombardy (9.5 million inhabitants), Italy, during 2006 -2007 in patients with metastatic colorectal cancer (mCRC) to evaluate compliance with the Italian Medicine Agency (AIFA) indications, the incidence of adverse events, and the survival rate. We performed computerized record linkage among three different Lombardy health care databases: File F registry, Regional discharge database, and Registry Office records. Patients were classified into approved and off-label uses according to the AIFA indications. Treatment with bevacizumab was administered to 780 patients, of whom 81.7% (n 637) had mCRC. Among these, 37.8% (n 241) of patients received the drug in observance of AIFA indications. Overall, ∼10% of patients had serious treatment-related toxicities (fistula, 3.5%; venous thromboembolism, 2.8%; hemorrhage, 1.9%; intestinal perforation and arterial thromboembolism, <1%). The 1-year survival rate was 74.3% and the 2-year survival rate was 39.2%. The median survival time was 20.5 months, and there were no meaningful differences between gender and age groups. There was a gap between the bevacizumab approved indication and clinical practice pattern: overall, less than one half of the patients received bevacizumab in observance with the regulatory indication. The main reason for nonadherence to the indication was use as a second-line or advanced line of therapy. The incidence of serious adverse events and the survival rates of mCRC patients were similar to those reported in clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: To verify in vivo whether lung cinescintigraphy confirms the effect of asbestos on the patency of the smallest airways and on the efficiency of mucociliary clearance in asbestos cement workers.Methods: 39 male subjects were examined: 30 asbestos cement workers and nine workers never exposed to occupational respiratory irritants. All subjects had a chest radiograph (International Labour Organisation (ILO) 1980); standard questionnaire on chronic bronchitis; spirometry; arterial blood gas analysis; carbon monoxide transfer factor (TLcosb); pulmonary O2 and CO2 ductances (DuO2, DuCO2); electrocardiogram; and lung cinescintigraphy after radioaerosol inhalation for the measurement of mucociliary clearance time in vivo in the smallest ciliated airways and for the assessment of radioaerosol deposition in alveoli (alveolar deposition index).Results: Apart from nine non-exposed subjects, the 30 asbestos cement workers were so classified on the basis of chest radiography: nine of them as healthy exposed, 10 with pleural plaques, and 11 with asbestosis. The four groups had similar ages, work seniority, and smoking habits. Exercise dyspnoea was significantly more frequent in asbestos cement workers. Lung function variables of workers with effects related to asbestos were significantly lower than the other two groups. The PaO2, TLcOsb and DuO2 mean values were significantly lower in exposed workers than non-exposed. The mean PacO2 value was significantly higher in the asbestosis group than in the other three groups. Workers with effects related to asbestos showed a significantly lower alveolar deposition index and a significantly higher mucociliary clearance time than the other two groups. Subjects with asbestosis showed similar differences from those with pleural plaques.Conclusions: Lung cinescintigraphy confirms in vivo the effects of asbestos on bronchiolar and alveolar patency and on efficiency of mucociliary clearance in the smallest ciliated airways. Finally, lung cinescintigraphic variables are able to discriminate workers with asbestosis from those with pleural plaques. [ABSTRACT FROM AUTHOR]

Polymorphic metabolic genes that confer enhanced genetic susceptibility to the carcinogenic effects of certain environmental carcinogens act according to a type 2 interaction between genetic and environmental risk factors. This type of interaction, for which the gene his no effect on disease outcome by itself but only modifies the risk associated with exposure, must be treated differently from other types of gene--environment interaction. We present a method to analyze different dose effects often seen in studies involving these genes. We definea low exposure--gene effect, when a greater degree of gene environment interaction appears at lower doses of exposure (the interaction follows an inverse dose function), and a converse high exposure--gene effect, when the interaction increases as a function of dose. Using a standard logistic regression model, we define a new term, alpha, thatcan be determined as a function of exposure dose in order to analyzeepidemiological studies for the type of exposure--gene effect. Thesemodels are illustrated by the use of hypothetical case-control data as well as examples from the literature. [ABSTRACT FROM AUTHOR]

The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.

Introduction: In a previous paper on acceleration of failure time we highlighted the difficulties of the application to the case of mesothelioma of the methodology proposed by Berry. In this contribution we elaborate further on the concept of anticipation/acceleration, taking into account the content of the III Italian Consensus Document., Methods: We analyzed the ways in which the concept of anticipation/acceleration has been proposed and interpreted in the III Consensus Document., Results: We show that the concept of anticipation of the III Consensus Document has to do with incidence (frequency) in a population (and not with acceleration of the pathological process in an individual case), and is a measure which is alternative to other measures of frequency effects. In addition, we show that the same epidemiological result is compatible with causal models where no cases, all the cases, or some of the cases are anticipated., Discussion: This paper suggests that the concept of anticipation measurable through epidemiologic data has to do exclusively with the anticipation of a frequency indicator (more occurrencies and anticipated occurrencies are indistinguishable and alternative concepts) but not with the acceleration of the biological process in individual cases. In causal terms, without a biological support it is not possible to infer from the epidemiologic results if a causal model is in action with no, all, or some of cases anticipated.

Objective: To assess the risk of maternal, fetal, and neonatal outcomes associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during pregnancy., Design: Historical cohort study., Setting: Singleton pregnancies of the resident population of the Lombardy region of Italy., Participants: All deliveries between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic vaccine, pregnancy, and birth outcomes were retrieved from regional databases. Vaccinated and non-vaccinated women were compared in a propensity score matched analysis to estimate risks of adverse outcomes., Main Outcome Measures: Main maternal outcomes included type of delivery, admission to intensive care unit, eclampsia, and gestational diabetes; fetal and neonatal outcomes included perinatal deaths, small for gestational age births, and congenital malformations., Results: Among the 86,171 eligible pregnancies, 6246 women were vaccinated (3615 (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No difference was observed in terms of spontaneous deliveries (adjusted odds ratio 1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated and non-vaccinated women. A slight increase in congenital malformations, although not statistically significant, was present in the exposed cohort (1.14, 0.99 to 1.31)., Conclusions: Our findings add relevant information about the safety of the MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly explain the increased risk of some maternal outcomes. Meta-analysis of published studies should be conducted to further clarify the risk of infrequent outcomes, such as specific congenital malformations., (© Trotta et al 2014.)

Objectives: to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases., Design: retrospective cohort study., Setting and Participants: all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included., Main Outcome Measures: through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was performed. Estimates were adjusted using multilevel regression models., Results: 12,988 incident cases, without metastatic diseases and other cancers, were included in the cohort: 62% were localized to the breast, 33% to the axillary lymph-nodes, 3% metastatic ab initio, and 2% with unknown stage. Deviations from the expected value of different magnitude depending on the type of indicator were observed: the most important differences were detected for the follow-up indicators. There was, in fact, an excess of several procedures in the first year of follow-up: 75% of the cases performed a dosage of a tumor marker, 67% an ecography or a CT scan or an MR, and 37% a bone scan. On the other hand, the access to neoadjuvant and adjuvant treatments in older women was far below the expected values., Conclusions: the study presents data derived from a large cohort of population cases; the set of indicators was validated by a board of oncologists. The use of indicators calculated by linking the cancer registries (that provide staging) and administrative databases allows the assessment of compliance to the guidelines for diagnosis and treatment of tumours. This experience shows that it is possible to develop a methodology, shared with clinicians, to define indicators that measure the distance between guidelines and current clinical practice in order to decrease variability, to limit inappropriateness, and to reduce unnecessary diagnostic tests for patients (and, consequently, hospitals organizational overload). In order to be sustainable and equitable, a health care system must be able to ensure implementation of protocols/procedures based exclusively on the best available scientific evidences.