Evaluation of the impact of the European Code against Cancer on awareness and attitudes towards cancer prevention at the population and health promoters' levels.

INTRODUCTION: The European Code against Cancer (ECAC) informs the public on steps to take to reduce their cancer risk. Despite over three decades of promotion, no systematic evaluation of its impact has yet been carried out. This study aimed to address the gap in knowledge regarding the impact of the ECAC. METHODS: An online survey targeting adults in the general population was conducted and analysed by age, gender, and country, both descriptive and mutually adjusted in logistic regression analyses. Additionally, semi-structured interviews with health promotion professionals from not-for-profit organisations in Europe were conducted and a qualitative thematic analysis was carried out for each interview. RESULTS: 8171 people from eight European countries responded to the survey. Although 70 % of respondents were aware of cancer prevention guidance, a low percentage of participants had previously heard about the ECAC (2% in UK to 21 % in Hungary and Poland). Females were more likely to make lifestyle changes to reduce their risk of cancer (odds ratio = 1.17; 95 % confidence interval: 1.05-1.29). Twenty-eight online semi-structured interviews with professionals were conducted covering 25 countries. Regional variation in the methods and target groups of the promotion and dissemination of the ECAC was reported. CONCLUSION: Whilst familiarity with the ECAC in the general public is low, professionals frequently use it as a basis for informing population-level actions. Future editions should be accompanied by a systematic evaluation of the ECAC investigating the impact upon society.

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

The lipid theory in the pathogenesis of calcific aortic stenosis.

AIMS: Biologically active phenomena, triggered by atherogenesis and inflammation, lead to aortic valve (AV) calcification. Lipids play an important role in activating the cell signaling leading to AV bone deposition. This review, based on evidence from animal and human studies, mainly focused on the involvement of lipids and atherogenic phenomena in the pathogenesis of calcific aortic stenosis (AS). DATA SYNTHESIS: The role of elevated low density lipoproteins for the risk of both vascular atherosclerosis and AS has been elucidated. Lipid disorders act synergistically with other risk factors to increase prevalence of calcific AS. Atherosclerosis is also involved in the pathogenesis of bone demineralization, a typical hallmark of aging, which is associated with ectopic calcification at vascular and valvular levels. Animal studies have recently contributed to demonstrate that lipids play an important role in AS pathogenesis through the activation of molecular cell signalings, such as Wnt/Lrp5 and RANK/RANKL/Osteprotegerin, which induce the transition of valvular myofibroblasts toward an osteogenic phenotype with consequent valvular bone deposition. Although all these evidence strongly support the lipid theory in AS pathogenesis, lipids lowering therapies failed to demonstrate in controlled trials a significant efficacy to slow AS progression. Encouraging results from animal studies indicate that physical activity may counteract the biological processes inducing AV degeneration. CONCLUSIONS: This review indicates a robust interplay between lipids, inflammation, and calcific AS. This new pathophysiological scenario of such an emerging valvular disease paves the way to the next challenge of cardiovascular research: "prevent and care aortic valve stenosis".

Moderate alcohol consumption predicts long-term mortality in elderly subjects with chronic heart failure.

OBJECTIVE: Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. SETTINGS: community-dwelling from 5 regions of Italy. PARTICIPANTS: A cohort of 1332 subjects aged 65 and older. MEASUREMENT: Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). RESULTS: In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; p<0.01) but it is predictive of mortality in the presence of CHF (HR=1.29; CI 95% 1.05-1.97; p<0.05). CONCLUSIONS: Our data demonstrates that moderate alcohol consumption is associated with an increased long-term mortality risk in the elderly in the presence of CHF.

Matrix metalloproteinases 2 and 9, and extracellular matrix in Kaposi's sarcoma.

Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis and may contribute to the mechanism of KS invasive growth. To date, only a few MMPs have been studied in KS lesions, and exactly which MMPs are involved in KS development and progression remains unanswered. However, MMPs 2 and 9 have been associated with different phases of angiogenesis, but their role in the proteolytic modification of the extracellular matrix has not been investigated. The results of this study confirm that MMPs, specifically MMP-2 and MMP-9, can contribute to angiogenesis by disrupting the vessel basement membrane and other extracellular matrix barriers, and enabling endothelial cells migration through the surrounding tissues.

[Hemostatic effectiveness of TachoSil® patches in radiofrequency assisted minor hepatic resection]. / Efficacia emostatica del TachoSil® nelle resezioni epatiche minori eseguite con device bipolare a radiofrequenza.

AIM: Intra- and postoperative bleeding represents an extremely serious and frequent complication of hepatic surgery. The aim of this study was to evaluate the effectiveness of TachoSil® to improve hemostasis in radiofrequency assisted minor hepatic resection. METHODS: Between July 2008 and June 2010, 31 patients underwent radiofrequency assisted minor hepatic resection. At the end of the liver resection a sponge of TachoSil® was applied on the liver. RESULTS: The mean intraoperative bleeding from the liver was 56.1 mL (range 0-300 mL). No patients received intra- and postoperative blood transfusion. Surgical drains were removed between the first and the sixth-eight postoperative day. CONCLUSION: According to the authors Tacho-sil® is helpful to improve hemostasis and biliary leakage in patients undergoing radiofrequency assisted minor hepatic resection.

Occupation and renal cell cancer in Central and Eastern Europe.

OBJECTIVE: Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer aetiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. METHODS: From 1999 to 2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (ORs) and 95% CI of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. RESULTS: A total of 992 histologically confirmed incident renal cell cancer cases and 1459 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labour and animal husbandry (OR 1.43; 95% CI 1.05 to 1.93), particularly among women employed as general farm workers (OR 2.73; 95% CI 1.05 to 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR 1.89; 95% CI 1.35 to 2.65), and mechanical engineers (OR 1.71; 95% CI 1.03 to 2.84). CONCLUSIONS: Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers.

Bayesian modelling of lung cancer risk and bitumen fume exposure adjusted for unmeasured confounding by smoking.

OBJECTIVES: Residual confounding can be present in epidemiological studies because information on confounding factors was not collected. A Bayesian framework, which has the advantage over frequentist methods that the uncertainty in the association between the confounding factor and exposure and disease can be reflected in the credible intervals of the risk parameter, is proposed to assess the magnitude and direction of this bias. METHODS: To illustrate this method, bias from smoking as an unmeasured confounder in a cohort study of lung cancer risk in the European asphalt industry was assessed. A Poisson disease model was specified to assess lung cancer risk associated with career average, cumulative and lagged bitumen fume exposure. Prior distributions for the exposure strata, as well as for other covariates, were specified as uninformative normal distributions. The priors on smoking habits were specified as Dirichlet distributions based on smoking prevalence estimates available for a sub-cohort and assumptions about precision of these estimates. RESULTS: Median bias in this example was estimated at 13%, and suggested an attenuating effect on the original exposure-disease associations. Nonetheless, the results still implied an increased lung cancer risk, especially for average exposure. CONCLUSIONS: This Bayesian framework provides a method to assess the bias from an unmeasured confounding factor taking into account the uncertainty surrounding the estimate and from random sampling error. Specifically for this example, the bias arising from unmeasured smoking history in this asphalt workers' cohort is unlikely to explain the increased lung cancer risk associated with average bitumen fume exposure found in the original study.

Determination of amprolium in feed by a liquid chromatography-mass spectrometry method.

As a consequence of the finding of veterinarian drugs in food European Community banned several compounds like coccidiostats as amprolium (APL). This antibiotic has been used as a preventive and clinical anticoccidial drug in chicken. The 2005/187/CE, 2005/925/EC Recommendations ban the use of amprolium as additive in chicken feed. For this reason a rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed to detect amprolium in chicken feed following the European community proposed technique (1999/27/EC) for sample preparation. Cause the validation is required for the analytical methods used in feed official control, this method was validated according to 2004/882/EC Regulation.

[Prevention of HCV infection in the hemodialysis setting]. / Prevenzione dell'infezione da HCV in emodialisi.

The discovery of hepatitis C viruses in the 1990s started a new era in hemodialysis. Hepatotropic RNA viruses are able to infect the immune cell populations of the host and show high viral persistence and chronicity rates. Although, like the HIV viruses, they can change inside the host, they are less resistant than hepatitis B viruses both to environmental conditions and common disinfection tools. The clinically subtle course of chronic and acute infections has pivotal importance in the spread of HCV and can explain its prevalence rates of 2-3% in the general population and about 9% in hemodialysis patients. Among the risk factors for transmission, the nosocomial risk is of primary importance in the hemodialysis setting but it is present in every health-care environment. Though low, also the occupational risk is important, particularly for nurses, in whom accidental pricks are responsible for a mean incidence of HCV infection of 1.8%. In the dialysis setting both these risk factors are essentially imputable to sanitary malpractice. In the last 30 years, the most important agencies for the prevention of infection have developed a set of "special" precautions for particular settings such as hemodialysis. In this review we report and recommend these precautions because their regular adoption is fundamental and a sufficient requisite to prevent the spread of hematogenous infections, including HCV.

[Natural history of HCV infection and risk of death in a cohort of patients on long-term hemodialysis]. / Storia naturale dell'infezione da HCV e rischio di morte in una coorte di pazienti in emodialisi da lungo tempo.

BACKGROUND: HCV infection represents the major cause of chronic liver disease in hemodialysis and renal transplant patients. The clinical course of liver disease in hemodialysis patients is generally asymptomatic. Only few studies describe the natural history of HCV infection in haemodialysis patients, showing an association between HCV infections and poor survival. METHODS: A prospective cohort study of our haemodialysis population was conducted to define the natural history of HCV infection and its relation to mortality. 77 patients on haemodialysis were enrolled, 24 (31%) of whom were anti-HCV and 53 (69%) anti-HCV-negative. RESULTS: The HCV-RNA was positive in 18 of the 24 anti-HCV-positive subjects (75%). None of the anti-HCV-negative subjects was HCV-RNA-positive. Eight of the 18 HCV-RNA-positive patients (40%) developed cirrhosis with portal hypertension and ascites within 7 years after the first increase of GPT. Seven of these died, nobody developed hepatocarcinoma (HCC). During 58+/-37-follow-up months mortality rate was higher among anti-HCV-positive patients than among anti-HCV-negative. Besides, the 6 deaths occurred only among anti-HCV-positive and HCV-RNA-positive patients. CONCLUSION: in our haemodialysis patient population the presence of antibodies anti-HCV and HCV-RNA is associated with an increased risk of developing liver cirrhosis and of death, in comparison to anti-HCV-negative patients. Our data show that anti-HCV-positive patients have an accelerated course towards chronic hepatopathy and cirrhosis.

Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet.

Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.

Clinical pathological correlates of renal biopsy in elderly patients.

BACKGROUND: Reports have shown that well-defined histological patterns do not always correspond to equally clear clinical pictures, particularly so in elderly patients. METHODS: With the aim of assessing clinicopathological correlations in the population aged >65 years with that of lower age, we retrospectively analyzed computerized records of renal needle biopsies consecutively performed in the decade 1991-2000 in our unit. RESULTS: Among the 392 eligible subjects, there were 150 patients 65 years of age and more, 76 of whom were over 70. The average serum creatinine was 2.9 mg/dl, with values > 3.5 mg/dl in 25% of cases. The major indication to biopsy was nephrotic syndrome followed by chronic renal failure both in the young adult and the elderly population. The rapidly progressive form led more often to renal biopsy in the elderly patients, and the different prevalence was statistically significant (p < 0.05), as was the higher prevalence of urinary anomalies in the young-adult population. Regarding renal histology, the crescentic necrotizing forms were significantly more frequent in the elderly patients, while IgAN, minimal change disease and SLE predominate in young adults. The most relevant result is the greater prevalence of crescentic necrotizing glomerulonephritis in elderly patients, not only in the cases presenting clinically as rapidly progressive renal failure and acute renal failure, but also in those with the clinical picture of chronic renal failure. CONCLUSIONS: Re-evaluation of our case files verifies the importance of the bioptic approach in selected cases with stages 3-4 chronic kidney damage. This holds true especially for elderly patients.

Lung fibre burden in lung cancer cases employed in the rock and slag wool industry.

OBJECTIVES: To evaluate the relationship between estimated exposure to man-made vitreous fibres (MMVF) and to asbestos fibres and their concentration in the lung tissue of lung cancer cases amongst MMVF production workers. METHODS: Retrospective retrieval of available lung tissue specimens was conducted following a case-control study that assessed estimated occupational exposures of MMVF workers. Fibre recovery and analysis by transmission electron microscopy (TEM) were conducted to determine fibre type, fibre dimension and numbers per gram of dry lung tissue. For cases with detailed exposure data, geometric mean (GM) concentrations were compared across the exposure categories, and regression models were used to investigate the relationship between the lung fibres and the variables of estimated exposure, with and without additional variables that may affect fibre retention. RESULTS: A total of 24 samples from 17 cases of lung cancer were available for analysis: MMVF were detected in all cases. Asbestos fibres were detected in 16. No difference or trend in GM MMVF concentration was observed across the estimated exposure categories. Odds ratio (OR) for MMVF g(-1) dry lung was 0.5 (95% confidence interval: 0.1-2.4) for the second, and 3.5 (0.6-18.9) for the third quartile of index of average exposure to MMVF in industry, compared with the first (lowest exposed) quartile (no cases in the highest quartile). CONCLUSIONS: No observable relationship existed between estimated exposure and directly-measured lung fibres among this sample of cases. Retrospective specimen collection, intra-individual variability in fibre concentration, effect of unknown factors on fibre retention and small sample size militated against this study providing evidence for or against a relationship between estimated exposure and lung fibre concentrations.

Successful treatment with enoximone for severe poisoning with atenolol and verapamil: a case report.

Combined poisoning with calcium channel blockers (CCBs) and beta-blockers is usually associated with severe hypotension and heart failure. Due to the block of the beta receptors, treatment with adrenergic agonists, even at high doses, can be insufficient, and beta-independent inotropes, such as glucagon, may be required. Phosphodiesterase III (PDEIII) inhibitors represent a possible alternative to glucagon in these cases as they have an inotropic effect which is not mediated by a beta receptor.

Risk of fatal industrial accidents and death from other external causes among asphalt workers.

The hypothesis that asphalt workers are at increased risk of mortality from industrial accidents and other external causes was tested. Mortality rates for external and violent causes of death in a cohort of asphalt industry employees from seven European countries and Israel were compared to that of the general population. There was no evidence that mortality from external causes was increased among long term employees in asphalt application and mixing. There was an increased risk for mortality due to external causes among short term workers. However, none of the fatal accidents among short term workers appear to have occurred during employment in the studied asphalt companies. Overall, no evidence was found supporting the hypothesis that asphalt workers are at increased risk of fatal industrial or road accidents. Mortality from other external causes did not increase in this population as a whole, but increased risks among short term workers deserve further attention.