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Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.Design Case–control study.Setting Cases from the National Mesothelioma Registry (2000–2018), controls from three previous case–control studies.Methods We selected male PM incident cases diagnosed in 2000–2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002–2004 and 2012–2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.Results The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.Conclusions We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Wireless power transfer (WPT) is now ubiquitous, having penetrated almost every industry within the last 20 years, due to certain desirable attributes explained in this paper. Furthermore, WPT is now in an advanced state whereby it is now technically feasible to apply the methods of WPT to the connector industry and surmount commonplace problems that have plagued the electrical connector industry since the invention of the first electrical connector in 1885. Whereas other common technologies have evolved greatly over the last two centuries with the emergence and development of new primary mechanisms, the primary mechanism used in electrical connectors-the electrical contact-has not changed. The electrical contact is the source of many failure modes, several of which can be eliminated by applying the WPT methodology through a new type of connector called the Non-Metallic Connector (NMC). As a result, connectors can now be made entirely contactless, possessing a hermetically sealed interface that is also shockproof. The NMC concept is applicable to both signal transfer and power transfer. NMCs fall into the categories of both near-zone and far-zone technologies, necessitating thereby the introduction of the $\mu $ WPT in the commonly accepted WPT hierarchy. Appropriate circuit topologies as well as major design challenges are identified for power-transfer NMCs with appropriate methods to overcome those challenges, based on the electrical power handling requirement.

The study describes the 466 cases of malignant mesotheliomas (MM) collected by the National Mesothelioma Register (ReNaM) in Italy in the period 1993-2018 relating to subjects with exclusive asbestos exposure in merchant or military navy. The cases among maritime workers represent 1.8% of the total cases with defined exposure registred in the ReNaM, of which 212 cases (45.4%) among merchant maritime workers and 254 cases (54.5%) among navy. The distribution by site of mesothelioma showed 453 (97.2%) MM cases of the pleura, 11 (2.3%) of the peritoneum and 2 (0.4%) of the tunica vaginalis of the testis. With regard to occupational exposure, it was classified as certain in 318 (68.2%) cases, probable in 69 (14.8%) cases and possible in 79 (16.9%) cases. Among the 23 classified jobs, the highest percentages of certain exposures are among naval engineers, motor mechanics, machine captains and sailors. Machine crew accounted for 49.3% of the cases, deck crew for 27.6%. All cases began exposure on board between 1926 and 1988. Seamen were exposed to asbestos while at sea by virtue of living onboard ships and from continual release of asbestos fibers due to the motion of a vessel. Epidemiological surveillance through the ReNaM has allowed us to verify among cases in the maritime, navy and merchant marine sectors, that in the past, subjects were exposed regardless of the ship's department where have provided service therefore all these cases must be considered as occupational diseases.

Obstetric violence is an issue of global scope and magnitude. Its widespread and continued presence indicates cultural tolerance enabled by policies and procedures that uphold paternalism. Labor and delivery nurses are the health care professionals who spend the most time at the point of care during birth, and their role must be examined. As active bystanders, labor and delivery nurses are uniquely positioned to prevent or perpetuate obstetric violence during labor and birth. Reflection on the nurse role is necessary to provide optimal care, enhance relationships with patients, and continue to evolve as a professional discipline. Perinatal nurses must lead the change to trauma-informed care practices to mitigate obstetric violence and reduce birth trauma., (Copyright © 2023 AWHONN. Published by Elsevier Inc. All rights reserved.)

Background: An increased risk of mesothelioma has been reported in various countries for construction workers. The Italian National Mesothelioma Registry, from 1993 to 2018, reported exposure exclusively in the construction sector in 2310 cases. We describe the characteristics of these cases according to job title., Methods: We converted into 18 groups the original jobs (N=338) as reported by ISTAT codes ('ATECO 91'). The exposure level was attributed at certain, probable and possible in accordance with the qualitative classification of exposure as reported in the Registry guidelines. Descriptive analysis by jobs highlights the total number of subjects for each single job and certain exposure, in descending order, insulator, plumbing, carpenter, mechanic, bricklayer, electrician, machine operator, plasterer, building contractor, painter and labourer., Results: The cases grow for plumbing in the incidence periods 1993-2018, while, as expected, it decreases for insulator. Within each period considered the most numerous cases are always among bricklayers and labourers, these data confirm the prevalence of non-specialised "interchangeable" jobs in Italian construction sector in the past., Conclusions: Despite the 1992 ban, the construction sector still presents an occupational health prevention challenge, circumstances of exposure to asbestos may still occur due to incomplete compliance with prevention and protection measures.

Background: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care., Methods: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs., Results: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males., Conclusions: These results highlight the need to personalize follow-up strategies for AYA cancer survivors., (© 2021 American Cancer Society.)

Objectives: Obesity is associated with sarcopenia in older adults, and weight loss can lead to further muscle mass loss. Oxytocin decreases with age, and animal studies suggest that oxytocin administration has trophic effects on skeletal muscle cells and reduces adiposity. We conducted a clinical trial to examine the safety and preliminary efficacy of intranasal oxytocin for older adults with sarcopenic obesity., Design: A double-blind, placebo-controlled randomized controlled trial of intranasal oxytocin (24 IU 4 times per day) for 8 weeks., Setting and Participants: Twenty-one older (67.5 ± 5.4 years), obese (30-43 kg/m 2 ), sedentary (<2 strenuous exercise per week) adults with slow gait speed (<1 m/s, proxy measure of sarcopenia) were recruited., Measures: Generalized estimating equations were used to evaluate the effect of oxytocin on safety/tolerability of oxytocin administration and whole body muscle and fat mass., Results: At baseline, body mass index (BMI) was 36.8 ± 3.6 kg/m 2 , fat mass 46.09 ± 6.99 kg, lean mass 50.98 ± 11.77 kg, fasting plasma glucose (FPG) 92.0 ± 8.9 mg/dL, hemoglobin A1c (HbA1c) 5.7% ± 0.4%, low density lipoprotein (LDL) 111.3 ± 41.5 mg/dL, high-density lipoprotein (HDL) 47.85 ± 10.96 mg/dL, and triglycerides 140.55 ± 83.50 mg/dL. Oxytocin administration was well tolerated without any significant adverse events. Oxytocin led to a significant increase of 2.25 kg in whole body lean mass compared with placebo (P < .01) with a trend toward decreasing fat mass, and a significantly reduced plasma LDL cholesterol by -19.3 mg/dL (P = .023) compared against placebo. There were no significant changes in BMI, appetite scores, glycemia, plasma HDL, triglycerides, or depressive symptoms., Conclusions and Implications: This proof-of-concept study indicates that oxytocin may be useful for the treatment of sarcopenic obesity in older adults. Oxytocin administration may also provide additional cardiovascular benefits., (Published by Elsevier Inc.)

Objective: To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL -1 (Gla-300) and degludec 100 units ⋅ mL -1 (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D)., Research Design and Methods: Subjects with T1D ( N = 22, 11 men, age 44.3 ± 12.4 years, disease duration 25.5 ± 11.7 years, A1C 7.07 ± 0.63% [53.7 ± 6.9 mmol ⋅ mL -1 ], BMI 22.5 ± 2.7 kg · m -2 ), naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 ± 0.08 units ⋅ kg -1 ) and Deg-100 (0.26 ± 0.06 units ⋅ kg -1 ), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin., Results: At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0-24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR [0-24 h] ) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91-1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and β-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63-0.92)., Conclusions: In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects., (© 2020 by the American Diabetes Association.)

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

Background: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions., Methods: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department., Results: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department., Conclusions: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services., Key Points: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions., What This Study Adds: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures., Objectives: to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer., Design: analysis of data by malignant mesothelioma incident cases surveillance system., Setting and Participants: Italy, network of regional surveillance system, all Italian regions., Main Outcome Measures: a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated., Results: at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818)., Conclusions: the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.

Introduction: A new class of drugs in the treatment of cystic fibrosis (CF) includes two agents: lumacaftor, which corrects CFTR channel protein, and ivacaftor, which increases CFTR channel activity. In our previous study we recruited 50 stable adults with CF and 16 of them showed growth hormone deficit (GHD): 7 patients severe and 9 patients partial GHD., Material and Methods: We decided to re-evaluate ten patients with the GHRH + arginine test of whom only five were treated with lumacaftor/ivacaftor., Results: All CF patients in therapy with lumacaftor/ivacaftor showed a marked improvement in GHD. Two patients moved from a severe GHD to a normal response to the GH/IGF-1 axis test, and three patients who had partial GHD moved to normal response., Conclusion: The pituitary gland may be damaged by CF disease and could benefit of the action of correcting drugs.

Purpose: Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH-IGF1 axis in an adult CF population., Methods: Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m 2 and FEV 1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD., Results: GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency., Conclusions: Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

Background: The aim of this study was to investigate the relationship between dynamic hyperinflation and daily physical activity (DPA) in adults with cystic fibrosis (CF)., Methods: Thirty-four clinically stable CF were studied. All patients undertook incremental cardiopulmonary exercise testing (CPET). CPET-related measurements included: oxygen uptake (V'O 2 ), carbon dioxide production (V'CO 2 ), ventilatory profile, work rate (W), inspiratory capacity (IC), end-expiratory lung volume (EELV). PA was assessed using the accelerometer SenseWear Pro3 Armband., Results: Exercise tolerance was reduced in most of patients and the mean V'O 2,peak value was 75.2% of predicted (28.5 ± 4.8 ml/min/kg). Seventy % of patients responded to CPET with dynamic hyperinflation. Higher incidence of dynamic hyperinflation was found in CF males compared to CF females (p = 0.026). Patients who developed dynamic hyperinflation during CPET had higher vigorous PA (p = 0.01) and more total energy expenditure (p = 0.006) than patients who did not. EELVΔ was related to activities requiring vigorous intensity and total energy expenditure (R = 0.46, p = 0.001; R = 0.57, p <  0.001)., Conclusions: In adults with CF and mild to moderate lung impairment, DPA might not be limited by dynamic hyperinflation.

Introduction: The 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., Methods: Incident 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., Results: In 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., Conclusions: The 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., Competing Interests: Competing interests: The following authors reported that they have served as expert witness for the public prosecutor in court trials on asbestos-related diseases: EM, DM, SS, VG, CM, RC., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure., Methods: The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases., Results: Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100,000) for men and 1.45 for women, respectively. Among the 15,845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12,065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily)., Conclusions: Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM)., Methods: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster., Results: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters., Conclusions: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs.

Introduction: Azilsartan medoxomil is a newly approved angiotensin-receptor blocker for the management of hypertension. It is a prodrug that is quickly hydrolyzed to the active moiety azilsartan, a potent and highly selective angiotensin-receptor blocker with estimated bioavailability of ∼ 60%. This new agent induces a potent and long-lasting antihypertensive effect. The effective therapeutic antihypertensive dosages of azilsartan medoxomil in humans vary from 40 to 80 mg/day., Areas Covered: The authors review the results of clinical trials published in journals indexed in Medline, Scopus and Google Scholar. Primarily the authors discuss articles that analyze the safety and efficacy of azilsartan in lowering blood pressure., Expert Opinion: Clinical trials have demonstrated that azilsartan is superior to other angiotensin-receptor blockers in lowering blood pressure. However, the clinical blood pressure trials of azilsartan published to date have been mainly conducted in patients without serious comorbidities and it is not clear if azilsartan has advantages over other angiotensin-receptor blockers in the treatment of these types of hypertensive patients. In addition, it remains to be determined whether the specific pharmacologic and pharmacokinetic characteristics of azilsartan will have a clinically significant impact on long-term cardiovascular outcomes.

Background: In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) promulgated a cautionary note., Materials and Methods: This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group., Results: Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note., Conclusions: Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

Objective: To show how malignant mesothelioma (MM) surveillance not only identifies settings of exposure representing past industrial history, but it may also detect conditions of current exposure relevant for the prevention, if the wide spectrum of asbestos uses is considered., Design: Active search of MM cases and exposure assessment at individual level through a questionnaire; identification of exposure circumstances relevant for prevention., Setting and Participants: Italy, all the Regions where a Regional Operating Centre (COR) is established to identify all MM cases diagnosed in the population and analyze their occupational, residential, household and environmental histories. Period of diagnosis: 1993-2008., Main Outcome Measures: Descriptive analysis of MM cases and of asbestos exposures., Results: ReNaM includes 15,845 cases of MM diagnosed between 1993 and 2008.The male/female ratio is 2.5. Mean age at diagnosis is 69 years. Pleural MMs represent 93% of all cases. Exposures have been investigated in 12,065 cases (76%). The median latency time is 46 years. In addition to clusters of MM cases in activities well known to entail asbestos use, different current exposure circumstances requiring intervention have been evidenced., Conclusions: On the basis of this experience, epidemiological surveillance of all occupational cancers should be implemented to foster synergies with the compensation system and the Local Health Authorities' occupational safety and health services, as required by the Italian Legislative Decree N. 81/2008.

Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case-list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as "at risk" (asbestos-cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all-too-predictable asbestos effects should be transferred to developing countries where asbestos use is spreading., (Copyright © 2011 UICC.)

Primary empty sella (PES) is a particular anatomical condition characterized by the herniation of liquor within the sella turcica. The pathogenesis of this alteration, frequently observed in general population, is not yet completely understood. Recently reports demonstrated, in these patients, that hormonal pituitary dysfunctions, specially growth hormone (GH)/insulin- like growth factor (IGF-I) axis ones, could be relevant. The aim of this paper is to evaluate GH/IGF-I axis in a group of adult patients affected by PES and to verify its clinical relevance. We studied a population of 28 patients with a diagnosis of PES. In each patient we performed a basal study of thyroid, adrenal and gonadal - pituitary axis and a dynamic evaluation of GH/IGF-I after GH-releasing hormone (GHRH) plus arginine stimulation test. To evaluate the clinical significance of GH/IGF-I axis dysfunction we performed a metabolic and bone status evaluation in every patients. We found the presence of GH deficit in 11 patients (39.2%). The group that displayed a GH/IGF-I axis dysfunction showed an impairment in metabolic profile and bone densitometry. This study confirms the necessity to screen the pituitary function in patients affected by PES and above all GH/IGF-I axis. Moreover the presence of GH deficiency could be clinically significant.

β-Thalassemias are a group of hereditary blood disorders characterized by abnormalities in the synthesis of the β hemoglobin (Hb) chains. This disease causes excessive storage of iron in all organs and endocrine glands. Treatment of β-thalassemia major (β-TM) consists of regular blood transfusions, iron chelation and management of secondary complications of iron overload. Endocrine abnormalities are frequently observed. In the last 25 years, the clinical picture of the disease has changed progressively thanks to improvement of treatments. Today, the majority of thalassemic patients reach adult age. The better prognosis and the longer lifespan of affected patients could be responsible for the susceptibility to other concomitant diseases which can manifest during their life. In this context, the possibility and recent literature reports about some cases of malignancy in thalassemic patients open new scenarios for oncoming years. We describe first reports of endocrine malignancies in thalassemic patients.

Objectives: The epidemiology of extrapleural malignant mesothelioma is rarely discussed and the risk of misdiagnosis and the very low incidence complicate the picture. This study presents data on extrapleural malignant mesothelioma from the Italian National Mesothelioma Register (ReNaM)., Methods: ReNaM works on a regional basis, searching for cases and interviewing subjects to investigate asbestos exposure. Classification and code criteria for certainty of diagnosis and exposure modalities are set by national guidelines. Between 1993 and 2004, 681 cases were collected. Incidence measures and exposure data refer to the ReNaM database. Age-standardised rates were estimated by the direct method using the Italian resident population in 2001. Correlations between the incidence of pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were analysed., Results: Standardised incidence rates (Italy, 2004, per million inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women, respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the pericardial site, varying widely in different parts of the country. Mean age at diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and the men/women ratio was 1.57:1. Median latency was over 40 years for all extrapleural sites combined. The correlation between pleural and peritoneal mesothelioma was 0.71 (Pearson's r coefficient, p<0.001). Modalities of exposure to asbestos fibres were investigated for 392 cases., Conclusions: The rarity of the disease, the low specificity of diagnosis and difficulties in identifying the modalities of asbestos exposure call for caution in discussing aetiological factors other than asbestos.

Background: Dysfunction of GH-IGF-I axis has been described in many patients affected by β-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood., Aim: The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused β-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters., Subjects and Methods: We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study., Results: We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile., Conclusions: This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

This study analyzed the incidence, mortality and survival after cancer of the female breast and reproductive organs in the Umbria region of Italy with the aim of generating hypotheses to explain trends. Mortality data were supplied by ISTAT (1978-1993) and ReNCaM (1994-2005) and incidence (1994-2005) and survival (at 12/31/2007) data by RTUP. Joinpoint regression was applied to evaluate temporal trends of the age-adjusted incidence and mortality rates. Mortality, incidence and relative survival rates were compared with national and international data. The incidence of breast cancer increased up to 2001 and afterwards significantly decreased; mortality rates significantly decreased after 1994. Uterine corpus incidence was practically stable, and decreased over the study period; mortality from all uterine subsites significantly decreased from 1978 onwards. Trends in ovarian cancer incidence and mortality (after 1985) were constant. Trends in occurrence of breast and cervical cancer were linked to population screening of Umbrian women, noting a low compliance by younger females with cervical cancer screening and emphasizing the opportunity of starting breast cancer screening at a younger age. Trends in the incidence of cancer of the uterus and ovary, though unsteady, were probably related to modifications in risk factor exposure. Survival was better for breast and cervical cancers than in the 1978-1982 period and might be due to early diagnosis and progress in therapy.

Objective: To report a rare case of a thyrotropin (TSH)-secreting pituitary adenoma associated with thyroid carcinoma., Methods: We report the clinical history, imaging studies, and laboratory and pathologic data in a male patient affected by TSH-secreting pituitary adenoma and goiter; histologic evaluation revealed thyroid carcinoma., Results: A 50-year-old man complained of years of palpitations, hypertensive crisis, and excessive nervousness that tended to progressively worsen. The basal and dynamic hematologic evaluation showed the presence of high free thyroid hormone levels with inappropriate levels of TSH. The thyroid morphologic study using Doppler ultrasonography showed a gland of increased volume with multiple nodular lesions bilaterally. The nuclear magnetic resonance of the pituitary gland described a microadenoma. A total thyroidectomy was performed followed by neurosurgical treatment of the pituitary lesion. The definitive thyroid histologic examination showed the presence of minimally invasive follicular carcinoma of 17 mm diameter. The patient firmly refused surgical removal of the pituitary adenoma. He was started on replacement therapy with thyroxine. Twelve months later, the hematologic examinations showed normal thyroid hormone levels and a TSH of 6.97 uIU/mL. The pituitary nuclear magnetic resonance showed a stable lesion without difference in size., Conclusion: The clinical association between thyroid carcinoma and TSH-producing adenoma is rare, with the removal of the pituitary lesion being mandatory. Pituitary surgery, in this case, is impossible, showing that TSH-producing microadenoma could seldom have an indolent behavior.

Purpose: Survival of adolescents (15-19 years old) with cancer has shown less favourable improvement in comparison with survival rates for younger children and older adults. This might be partly explained by the relative lack of participation of adolescents in cooperative clinical protocols., Methods: This analysis compares the number of 15- to 19-year-olds treated at the paediatric oncology centres affiliated to the AIEOP (and registered in the 'model 1.01') with the number of incident cases predicted in Italy based on incidence rates from the Italian network of cancer registries (AIRTum)., Results: By 2006, over 22,000 cases had been registered in the model 1.01, and 1743 of these were adolescents. The ratio of observed/expected (O/E) cases of 15- to 19-year-olds was 0.10 (as opposed to 0.77 for the 0-14-year-old children), and this ratio increased from 0.05 to 0.18 over three successive study periods (1989-1994, 1995-2000 and 2001-2006). Sarcomas were the neoplasms with the highest O/E ratios, with 0.28 and 0.43 for osteosarcoma and Ewing sarcoma and 0.33 and 0.39 for rhabdomyosarcoma and other soft-tissue sarcomas, respectively. In the period 1989-2006, 55% of the adolescents registered (versus 69% of the children) were enrolled in formal national trials., Conclusion: Our study confirms a lower referral of 15- to 19-year-old adolescents to paediatric oncology units and their under-representation in clinical trials, but we also observed a progressive improvement in this situation in recent years.