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to investigate the characteristics of patients affecting the duration of positivity test by RT-PCR in the population of Piedmont, a Region of North-West of Italy. DESIGN: observational cohort study.from the administrative database of the regional SARS-CoV-2 surveillance system, a cohort of all patients who tested positive by a RT-PCR assay to SARS-CoV-2 occurring from 22.02.2020 to 30.09.2020 in the Piedmont Region (N. 29,292) was obtained. The cohort has been linked to the hospital discharge database and to the vital statistics database.outcome of the study was the risk of non negativization, estimated by fitting Generalizing Estimating Equation model (GEE), a longitudinal model which consider for each subject several records collected on fixed time intervals 15, 30, 45 or 60+ days from the first positive test. Negativization was defined as the condition in which two consecutive samples taken from the patient at least 24 hours apart were negative for the presence of SARS-CoV-2.the median duration of positive RT-PCR was 27 days. A higher median of days until positive persistence was observed in people over 80 (34 days, IQR 25-49), female (28 days, IQR 18-40), symptomatic patients (28 days, IQR 19-40), hospitalized people (32 days, IQR 21-44), patients with Charlson's index0 (34 days, IQR 23-49), patients host of elderly nursing homes (37 days, IQR 25-51). In the GEE multivariable model, the variables associated to the non negativization at all times intervals were: older age (at 15th day: class 65+, OR 2.56, 95%CI 2.39-2.74), female gender (at 15th day: OR 1.12, 95%CI 1.06-1.18), and to be hospitalized for COVID-19 (at 15th day: OR 1.38, 95%CI 1.29-1.48). The presence of comorbidities and of symptoms were associate with the non negativization at 15th day (respectively, class 4+: OR 1.29, 95%CI 1.08-1.56 and symptoms: OR 1.20, 95%CI 1.13-1.27), but not at 45th day.older age, female gender, presence of comorbidities and severity of disease (proxy hospitalization for COVID-19) were risk factors for non negativization at all times intervals. The presence of symptoms was a risk factors for the non negativization after 2 weeks from the first diagnosis and not at 45th day. Using a longitudinal model for the analysis of the dataset, it is possible to compare the weight of the variables included in the model at different times and correct an overestimation of the attributable risk after the first considered time interval.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy

This is a pre-copyedited, author-produced version of an article accepted for publication in The American Journal of Clinical Nutrition following peer review. The version of record, Zamora-Ros, R., Lujan-Barroso, L., Achaintre, D., Franceschi, S., Kyrø, C., Overvad, K., ... Agudo, A. (2020). Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. American Journal of Clinical Nutrition, 113(1), 162-171, is available online at: https://doi.org/10.1093/ajcn/nqaa277. Background - Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives - The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods - A nested case–control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results - Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions - Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

Measures implemented in many countries to contain the COVID-19 pandemic resulted in a change in lifestyle with unpredictable consequences on physical and mental health. We aimed at identifying the variables associated with psychological distress during the lockdown between April and May 2020 in the Italian academic population. We conducted a multicenter cross-sectional online survey (IO CONTO 2020) within five Italian universities. Among about 240,000 individuals invited to participate through institutional communications, 18 120 filled the questionnaire. Psychological distress was measured by the self-administered Hospital Anxiety and Depression Scale (HADS). The covariates collected included demographic and lifestyle characteristics, trust in government, doctors and scientists. Associations of covariates with influenza-like symptoms or positive COVID-19 test and with psychological distress were assessed by multiple regression models at the local level; a meta-analysis of the results was then performed. Severe levels of anxiety or depression were reported by 20% of the sample and were associated with being a student or having a lower income, irrespective of their health condition and worries about contracting the virus. The probability of being severely anxious or depressed also depended on physical activity: compared to those never exercising, the highest OR being for those who stopped during lockdown (1.53; 95% CI, 1.28 to 1.84) and the lowest for those who continued (0.78; 95% CI, 0.64 to 0.95). Up to 21% of severe cases of anxiety or depression might have been avoided if during lockdown participants had continued to exercise as before. Socioeconomic insecurity contributes to increase mental problems related to the COVID-19 pandemic and to the measures to contain it. Maintaining or introducing an adequate level of physical activity is likely to mitigate such detrimental effects. Promoting safe practice of physical activity should remain a public health priority to reduce health risks during the pandemic.

IntroductionFew epidemiological studies have assessed the risk of parkinsonisms after prolonged use of neuroleptics. We aimed to examine the long-term risk of degenerative parkinsonisms (DP) associated with previous use of neuroleptics.MethodsAll residents in Piedmont, Northern-west Italy, older than 39 years (2,526,319 subjects), were retrospectively followed up from 2013 to 2017. Exposure to neuroleptics was assessed through the regional archive of drug prescriptions. The development of DP was assessed using the regional archives of both drug prescriptions and hospital admissions. We excluded prevalent DP cases at baseline as well as those occurred in the first 18 months (short-term risk). The risk of DP associated with previous use of neuroleptics was examined through Cox regression, using a matched cohort design.ResultsThe risk of DP was compared between 63,356 exposed and 316,779 unexposed subjects. A more than threefold higher risk of DP was observed among subjects exposed to antipsychotics, compared to those unexposed (HR = 3.27, 95% CI 3.00–3.57), and was higher for exposure to atypical than typical antipsychotics. The risk decreased after 2 years from therapy cessation but remained significantly elevated (HR = 2.38, 95% CI 1.76–3.21).ConclusionsThese results indicate a high risk of developing DP long time from the start of use and from the cessation for both typical and atypical neuroleptics, suggesting the need of monitoring treated patients even after long-term use and cessation.

Background Aim of this study was to examine the association between unemployment and mortality, taking into account potential confounders of this association. A secondary objective was to assess whether the association between unemployment and mortality was modified by lack of household economic resources. Methods Prospective cohort composed of a representative sample of Italian subjects 30–55 years who participated in the Italian National Health Survey 1999–2000, followed up for mortality up to 2012 (15 656 men and 11 463 women). Data were analyzed using Cox regression models, stratified by gender and adjusted for health status, behavioral risk factors, socioeconomic position and position in the household. The modifying effect of the lack of economic resources was assessed by testing its interaction with unemployment on mortality. Results Among women, unemployment was not associated with mortality, whereas among men, higher mortality was found from all causes (HR = 1.82), which was not modified by lack of economic resources, and from neoplasms (HR = 1.59), cardiovascular diseases (HR = 2.58) and suicides (HR = 5.01). Conclusions Results for men were robust to the adjustment for main potential confounders, suggesting a causal relationship between unemployment and mortality. The lack of effect modification by economic resources supports the relevance of the loss of non-material benefits of work on mortality.

Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

This study aimed to compare calculated nutrient intakes from two different food composition databases using data from the European prospective investigation into cancer and nutrition (EPIC) cohort. Dietary intake data of the EPIC cohort was recently matched to 150 food components from the U.S. nutrient database (USNDB). Twenty-eight of these nutrients were already included in the EPIC nutrient database (ENDB&mdash, based upon country specific food composition tables), and used for comparison. Paired sample t-tests, Pearson&rsquo, s correlations (r), weighted kappa&rsquo, s (&kappa, ) and Bland-Altman plots were used to compare the dietary intake of 28 nutrients estimated by the USNDB and the ENDB for 476,768 participants. Small but significant differences were shown between the USNDB and the ENDB for energy and macronutrient intakes. Moderate to very strong correlations (r = 0.60&ndash, 1.00) were found for all macro- and micronutrients. A strong agreement (&kappa, &gt, 0.80) was found for energy, water, total fat, carbohydrates, sugar, alcohol, potassium and vitamin C, whereas a weak agreement (&kappa, &lt, 0.60) was found for starch, vitamin D and vitamin E. Dietary intakes estimated via the USNDB compare adequately with those obtained via the ENDB for most macro- and micronutrients, although the agreement was weak for starch, vitamin D and vitamin E. The USNDB will allow exposure assessments for 150 nutrients to investigate associations with disease outcomes within the EPIC cohort.

The article aims to present the most recent evidence on the life-expectancy differentials across socio-economic groups in Italy and discuss their implications in terms of equity and fairness of the pension systems. In fact, Italian pension rules are set according to average life expectancy, ignoring the shorter life expectancy at retirement observed in more disadvantaged socioeconomic groups, as well as in many occupations and economic sectors. This produces unintended consequences in terms of redistribution, which reinforce and exacerbate inequalities present in the labour market. This article will present updated evidence on the evolution of life expectancy inequalities across job titles, sectors and occupational class in Italy to assess whether the social gap, already highlighted by previous scholars, has been widening or narrowing. Only a few studies are available in the literature on this subject, almost exclusively from the US, which suggest that the gap in terms of life expectancy at ages approaching retirement is increasing, mainly driven by a faster improvement in longevity across most advantaged groups. It is crucial to examine the trend in a country like Italy where retirement age has been strongly tightened and linked automatically to average life expectancy in the population. These results may be important in order to inform the public debate about future reforms on retirement rules and in particular for the definition of the so called “arduous and hazardous jobs” (in Italian: lavori gravosi), that could be exempted from the postponement of pension age. In order to estimate life expectancy differentials among different occupations, three of the largest Italian longitudinal studies will be used: the Turin Longitudinal Study (SLT), the Italian Longitudinal Study (SLI) and WHIP-Health Study, all studies where it is possible to conduct mortality follow-up through administrative record linkage with archives of mortality of large cohorts until recent years.

Background: Optimum antenatal and postnatal care services are recognized to be among the most effective interventions to reduce maternal and newborn morbidity and mortality. However; optimum antenatal care (ANC) and postnatal care (PNC) service utilization among young women in Africa is very low, especially in rural zones. Therefore, this study was conducted to determine the magnitude of optimum ANC and PNC services utilization and the factors associated, in the Eastern Zone of Tigray, Northern Ethiopia. Methods: Using a cross-sectional study design, 352 young women aged 15 to 24 were interviewed. Among those, 101 and 100 were eligible and included for studying optimum ANC and PNC service utilization, respectively. Multivariable logistic regression models were performed to identify independent determinants of the two outcome variables (optimum ANC and PNC utilization). Results: Optimum ANC and PNC services utilization was reached in 75% (95%CI: 64.50-84.20) and 16% (95%CI: 9.00-24.00) of the cases, respectively. Being older (20-24 years old vs. 18-19: AOR=9.21; 95% CI: 1.62-52.25) and knowing the availability of adolescent and youth friendly health service (AYFHS) (AOR= 4.01; 95% CI: 1.08-14.89) were significantly associated with optimum ANC service utilization. Furthermore; knowing the availability of AYFHS (AOR=10.81; 95%CI: 1.57-71.18) and having the right to decide about her own health care spending (AOR=6.16; 95%CI: 1.22-31.05) were significantly associated with optimum PNC service utilization. Conclusion: In rural zones in Tigray, PNC services utilization is far away from the optimum, while ANC service utilization is closer, even if a significant number of young women did not receive optimum ANC services. The presence of an AYFHS and its knowledge are shown to be related to an increase of optimal services utilization and hence interventions need to be designed accordingly.

Pro-inflammatory diets are associated with risk of developing colorectal cancer (CRC), however inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute towards a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumours). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More pro- inflammatory diets were related to a higher CRC risk, particularly for colon cancer; Hazar Ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval (CI) 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS were 1.62 (95% CI 1.31- 2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. This study shows that more pro-inflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men. This article is protected by copyright. All rights reserved.

Some aspects of the management of caustic ingestion in children are still debated. We aimed to determine the predictive value of epidemiological and clinical features of caustic ingestion, and to define guidelines adherence. This is a retrospective study on children ≤18 years referred to our Emergency Department over 6 years because of caustic ingestion. Statistical significance at p

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

Background and aims The overall macronutrient composition of diet, rather than just calorie intake, may influence long-term changes of anthropometry. We investigated relationships between dietary macronutrient composition and long-term changes in weight and waist circumference in participants of the EPIC–Italy – the Italian section of the European Prospective Investigation into Cancer and Nutrition – study. Methods and results A total of 32,119 participants provided anthropometric measures at recruitment and 12 years later (mean). Diet at recruitment was assessed using validated semi-quantitative food frequency questionnaires. Weight and waist changes associated with replacing 10% of energy from one macronutrient with 10% of energy from another macronutrient were assessed by multivariable linear regression. Increased energy from total protein at the expense of any other macronutrient was significantly associated with increased weight and waist circumference. Increased starch at the expense of sugar and total protein was associated with significantly decreased weight and waist circumference; when starch replaced total fat, weight significantly decreased. Increased sugar at the expense of starch and total fat was significantly associated with increased weight and waist circumference; but increase at the expense of total protein was significantly associated with decreased weight and waist circumference. Conclusion Our results suggest that increasing protein at the expense of fat or carbohydrates, and reducing starch by increasing other macronutrients, might be associated with increased weight and waist gain.

Endometrial cancer (EC) incidence rates vary ~10‐fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low‐risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow‐up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2) and HT use (to all non‐HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks., What's new? Endometrial cancer rates vary considerably around the world, with incidence rates higher in Europe and North America than in parts of Asia and Africa. Here, the authors investigated how much of the risk disparity arises from modifiable factors, and how much modifying these factors could reduce cancer incidence. The 10% of European women with lowest risk had similar incidence to women in low‐risk countries, they found. Their model predicted that in European women, maintaining BMI below 23 kg/m2 and avoiding postmenopausal hormone use could reduce risk by 30%. Long‐term use of oral contraceptives could reduce risk by 42.5%.

Objective To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design Prospective case-cohort study. Setting Populations from eight European countries. Participants 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure Incident type 2 diabetes. Results In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

This work was supported by the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (WCRF 2014/1180 to Konstantinos K Tsilidis). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF),Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (UK)., Heath, A.K., Muller, D.C., Van Den Brandt, P.A., Papadimitriou, N., Critselis, E., Gunter, M., Vineis, P., Weiderpass, E., Fagherazzi, G., Boeing, H., Ferrari, P., Olsen, A., Tjønneland, A., Arveux, P., Boutron-Ruault, M.-C., Mancini, F.R., Kühn, T., Turzanski-Fortner, R., Schulze, M.B., Karakatsani, A., Thriskos, P., Trichopoulou, A., Masala, G., Contiero, P., Ricceri, F., Panico, S., Bueno-De-Mesquita, B., Bakker, M.F., Van Gils, C.H., Olsen, K.S., Skeie, G., Lasheras, C., Agudo, A., Rodríguez-Barranco, M., Sánchez, M.-J., Amiano, P., Chirlaque, M.-D., Barricarte, A., Drake, I., Ericson, U., Johansson, I., Winkvist, A., Key, T., Freisling, H., His, M., Huybrechts, I., Christakoudi, S., Ellingjord-Dale, M., Riboli, E., Tsilidis, K.K., Tzoulaki, I.

Background Frailty is one of the most critical age-related conditions in older adults. It is often recognized as a syndrome of physiological decline in late life, characterized by a marked vulnerability to adverse health outcomes. A clear operational definition of frailty, however, has not been agreed so far. There is a wide range of studies on the detection of frailty and their association with mortality. Several of these studies have focused on the possible risk factors associated with frailty in the elderly population while predicting who will be at increased risk of frailty is still overlooked in clinical settings. Objective The objective of our study was to develop predictive models for frailty conditions in older people using different machine learning methods based on a database of clinical characteristics and socioeconomic factors. Methods An administrative health database containing 1,095,612 elderly people aged 65 or older with 58 input variables and 6 output variables was used. We first identify and define six problems/outputs as surrogates of frailty. We then resolve the imbalanced nature of the data through resampling process and a comparative study between the different machine learning (ML) algorithms – Artificial neural network (ANN), Genetic programming (GP), Support vector machines (SVM), Random Forest (RF), Logistic regression (LR) and Decision tree (DT) – was carried out. The performance of each model was evaluated using a separate unseen dataset. Results Predicting mortality outcome has shown higher performance with ANN (TPR 0.81, TNR 0.76, accuracy 0.78, F1-score 0.79) and SVM (TPR 0.77, TNR 0.80, accuracy 0.79, F1-score 0.78) than predicting the other outcomes. On average, over the six problems, the DT classifier has shown the lowest accuracy, while other models (GP, LR, RF, ANN, and SVM) performed better. All models have shown lower accuracy in predicting an event of an emergency admission with red code than predicting fracture and disability. In predicting urgent hospitalization, only SVM achieved better performance (TPR 0.75, TNR 0.77, accuracy 0.73, F1-score 0.76) with the 10-fold cross validation compared with other models in all evaluation metrics. Conclusions We developed machine learning models for predicting frailty conditions (mortality, urgent hospitalization, disability, fracture, and emergency admission). The results show that the prediction performance of machine learning models significantly varies from problem to problem in terms of different evaluation metrics. Through further improvement, the model that performs better can be used as a base for developing decision-support tools to improve early identification and prediction of frail older adults.

Frailty appears to be the most problematic expression of elderly people. Frail older adults have a high risk of mortality, hospitalization, disability and other adverse outcomes, resulting in burden to individuals, their families, health care services and society. Early detection and screening would help to deliver preventive interventions and reduce the burden of frailty. For this purpose, several studies have been conducted to detect frailty that demonstrates its association with mortality and other health outcomes. Most of these studies have concentrated on the possible risk factors associated with frailty in the elderly population; however, efforts to identify and predict groups of elderly people who are at increased risk of frailty is still challenging in clinical settings. In this paper, Genetic Programming (GP) is exploited to detect and define frailty based on the whole elderly population of the Piedmont, Italy, using administrative databases of clinical characteristics and socio-economic factors. Specifically, GP is designed to predict frailty according to the expected risk of mortality, urgent hospitalization, disability, fracture, and access to the emergency department. The performance of GP model is evaluated using sensitivity, specificity, and accuracy metrics by dividing each dataset into a training set and test set. We find that GP shows competitive performance in predicting frailty compared to the traditional machine learning models. The study demonstrates that the proposed model might be used to screen future frail older adults using clinical, psychological and socio-economic variables, which are commonly collected in community healthcare institutions.

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case–control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.

Funded by the European Commission Horizon 2020 programme, the Lifepath research consortium aimed to investigate the effects of socioeconomic inequalities on the biology of healthy aging. The main research questions included the impact of inequalities on health, the role of behavioral and other risk factors, the underlying biological mechanisms, the efficacy of selected policies, and the general implications of our findings for theories and policies. The project adopted a life-course and comparative approach, considering lifetime effects from childhood and adulthood, and pooled data on up to 1.7 million participants of longitudinal cohort studies from Europe, USA, and Australia. These data showed that socioeconomic circumstances predicted mortality and functional decline as strongly as established risk factors currently targeted by global prevention programmes. Analyses also looked at socioeconomically patterned biological markers, allostatic load, and DNA methylation using richly phenotyped cohorts, unraveling their association with aging processes across the life-course. Lifepath studies suggest that socioeconomic circumstances are embedded in our biology from the outset—i.e., disadvantage influences biological systems from molecules to organs. Our findings have important implications for policy, suggesting that (a) intervening on unfavorable socioeconomic conditions is complementary and as important as targeting well-known risk factors, such as tobacco and alcohol consumption, low fruit and vegetable intake, obesity and a sedentary lifestyle, and that (b) effects of preventive interventions in early life integrate interventions in adulthood. The report has an executive summary that refers to the different sections of the main paper. This study was supported by the European Commission (Horizon 2020 grant number 633666) and the Swiss State Secretariat for Education, Research and Innovation SERI.

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39–0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46–1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45–1.10 and 0.71, 0.45–1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

International audience; The study aimed to assess the proportion mediated by the duration of exposure to ergonomic factors at work on the relationship between socioeconomic position (SEP) and low walking speed. This cross-sectional study was performed on data collected at baseline on 19,704 men and 20,273 women 45-70 years old, currently or previously employed, enrolled in the Constances cohort. SEP was assigned through current or last occupation, categorized in three classes, based on the European Socioeconomic Classification. Walking speed was assessed through one measurement of normal walking for 3 m and dichotomized at the lowest quintile of the sex- and age- (5-year) specific distribution. Self-reported workplace exposure throughout working life to repetitive work, intense physical work, and lifting/carrying heavy loads was used to assess the duration of exposure to each factor, categorized in four classes. Through Poisson regression models, adjusted for BMI, smoking, alcohol intake, hypertension, physical activity, diabetes, cardiovascular diseases, and a cognitive score, the attenuation in the prevalence ratio (PR) of low walking speed by SEP produced by the inclusion of duration of exposure to each factor was evaluated. The mediating effect of work ergonomic exposures on the relationship between SEP and low walking speed was assessed using the weighted method by Vanderweele. In the fully adjusted model without ergonomic exposures, both men and women in the middle and the lowest SEP had a significantly increased risk of low walking speed compared with those in the highest SEP (men: PR = 1.30 and PR = 1.46, respectively; women: PR = 1.24 and PR = 1.45, respectively). The inclusion in separate regression models of exposure duration to repetitive work, intense physical work, and handling of heavy loads produced modest risk attenuations in both men and women, all smaller or around 10%. Mediation analysis revealed in both sexes significant mediation effects for most ergonomic exposures considered, although also with low mediation effects. Significant differences in walking speed by SEP were observed in this large sample, but the proportion of such differences explained by the duration of exposure to ergonomic factors at work was low using either the risk attenuation or the mediation analysis methods.

Introduction: Beverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another. Objective: The aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study of 8 European countries (n = 27,662, with 12,333 cases of incident T2D, 1992-2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D. Results: Mean +/- SD of estimated consumption of SSB was 55 +/- 105 g/d. Means +/- SDs for the other beverages were as follows: fruit juice, 59 +/- 101 g/d; milk, 209 +/- 203 g/d; coffee, 381 +/- 372 g/d; and tea, 152 +/- 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was -12.0 (95% CI: -20.0, -5.0) per 10,000 person-years among adults consuming SSBs >= 250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or -11.0 (95% CI:-20.0, -2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly. Conclusions: These findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations., The InterAct project was funded by the EU FP6 program (LSHM_CT_2006_037197). InterAct investigators acknowledge funding from the following agencies: Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/1, MC_UU_12015/5); National Institute for Health Research, Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014); the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the State of Brandenburg, Germany; Netherlands Agency grant IGE05012 and an Incentive Grant from the Board of the University Medical Center Utrecht (Netherlands); Dutch Ministry of Public Health, Welfare, and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, and Statistics Netherlands; Swedish Research Council, Novo Nordisk, Swedish Heart Lung Foundation, and Swedish Diabetes Association; Danish Cancer Society; Deutsche Krebshilfe; Associazione Italiana per la Ricerca sul Cancro; Asturias Regional Government; Navarra Regional Government, Health Research Fund of the Spanish Ministry of Health; CIBER Epidemiologia y Salud Publica, Spain; Murcia Regional Government (grant 6236); and AIRE-ONLUS Ragusa, AVIS-Ragusa, and Sicilian Regional Government.

Background Breast cancer (BC) is the malignant tumor with the highest incidence in women in the world with an estimate of about 500,000 new cases per year in Europe. Guidelines for BC treatment include surgery followed by radiotherapy, hormonal therapy or chemotherapy. Several studies showed that BC treatment increases the risk of myocardial infarction (MI) while only few studies investigated the risk of stroke after BC. The aim of the present study was to assess the risk of MI and stroke in BC survivors, taking into account the possible influence of treatments. Methods Women included in the study are part of a longitudinal cohort including all residents in the Piedmont region linked to the 2011 census data and followed-up through administrative data on mortality, hospital admissions, drug prescriptions, and outpatient consultations. Validated algorithms to identify BC incident cases and their therapies as well as to identify MI and stroke were applied. The effect of BC on the risk of MI and stroke was tested using Cox models (adjusted for confounding variables) that allow to account for the competing risks. First, BC patients were compared to healthy women, then BC women that undertwent a specific therapy were compared with both healthy women and other BC patients. Results Women with BC showed an increased risk compared to healthy women for both MI (HR: 1.20; 95% CI: 1.05-1.38) and stroke (HR: 1.58; 95%CI: 1.38-1.82). Chemotherapy almost doubled the risk of MI, while radiotherapy did not seem to have a similar effect, even comparing with other BC patients. The high risk of stroke observed comparing BC (any therapy) with healthy women disappeared when comparing specific therapies among BC patients. Conclusions Chemotherapy increased the risk of MI in BC patients, while recent radiotherapy strategies had less impact, if any. Moreover, the mechanism for which BC patients have an increased risk of stroke seems not to be related to a late effect of therapies. Key messages Breast cancer women are at higher risk of developing cardio and cerebrovascular diseases and this should be taken into account when planning therapies and follow-up surveillance. Despite the increase in quality of the therapeutic approaches for breast cancer patients, chemotherapy increases the risk of myocardial infarction, while radiotherapy dangerousness recently decreased.

Funder: Centre International de Recherche sur le Cancer; doi: http://dx.doi.org/10.13039/100008700, Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS). Results: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS. Conclusions: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.

Purpose:Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5years of follow-up. Methods:A total of 255,170 participants aged 25–70years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. Results:A one-SD increment in CEL intake was associated with 0.111kg (95% CI 0.087–0.135) additional weight gain over 5years. The corresponding additional weight gain for CML and MG-H1 was 0.065kg (0.041–0.089) and 0.034kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. Conclusion:In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5years of follow-up.

Objective There are many different methods for computing the Predisposition Infection Response Organ (PIRO) dysfunction score. We compared three PIRO methods (PIRO1 (Howell), PIRO2 (Rubulotta) and PIRO3 (Rathour)) for the stratification of mortality and high level of care admission in septic patients arriving at the Emergency Department (ED) of an Italian Hospital. Design, setting and participants We prospectively collected clinical data of 470 patients admitted due to infection in the ED to compute PIRO according to three different methods. We tested PIRO variables for the prediction of mortality in the univariate analysis. Calculation and comparison were made of the area under the receiver operating curve (AUC) for the three PIRO methods, SOFA and qSOFA. Results Most of the variables included in PIRO were related to mortality in the univariate analysis. Increased PIRO scores were related to higher mortality. In relation to mortality, PIRO 1 performed better than PIRO2 at 30 d ((AUC 0.77 (0.716–0.824) vs. AUC 0.699 (0.64–0.758) (p = 0.03) and similarly at 60 d (AUC 0.767 (0.715–0.819) vs AUC 0.709 (0.656–0.763)(p = 0.55)); PIRO1 performed similarly to PIRO3 (AUC 0.765 (0.71–0.82) at 30 d, AUC 0.754 (0.701–0.806) at 60 d, p = ns). Both PIRO1 and PIRO3 were as good as SOFA referred to mortality (AUC 0.758 (0.699, 0.816) at 30 d vs. AUC 0.738 (0.681, 0.795) at 60 d; p = ns). For high level of care admission, PIRO proved inferior to SOFA. Conclusions We support the use of PIRO1, which combines ease of use and the best performance referred to mortality over the short term. PIRO2 proved to be less accurate and more complex to use, suffering from missing microbiological data in the ED setting.

BACKGROUND Frailty is one of the most critical age-related conditions in older adults. It is often recognized as a syndrome of physiological decline in late life, characterized by a marked vulnerability to adverse health outcomes. A clear operational definition of frailty, however, has not been agreed so far. There is a wide range of studies on the detection of frailty and their association with mortality. Several of these studies have focused on the possible risk factors associated with frailty in the elderly population while predicting who will be at increased risk of frailty is still overlooked in clinical settings. OBJECTIVE The objective of our study was to develop predictive models for frailty conditions in older people using different machine learning methods based on a database of clinical characteristics and socioeconomic factors. METHODS An administrative health database containing 1,095,612 elderly people aged 65 or older with 58 input variables and 6 output variables was used. We first identify and define six problems/outputs as surrogates of frailty. We then resolve the imbalanced nature of the data through resampling process and a comparative study between the different machine learning (ML) algorithms – Artificial neural network (ANN), Genetic programming (GP), Support vector machines (SVM), Random Forest (RF), Logistic regression (LR) and Decision tree (DT) – was carried out. The performance of each model was evaluated using a separate unseen dataset. RESULTS Predicting mortality outcome has shown higher performance with ANN (TPR 0.81, TNR 0.76, accuracy 0.78, F1-score 0.79) and SVM (TPR 0.77, TNR 0.80, accuracy 0.79, F1-score 0.78) than predicting the other outcomes. On average, over the six problems, the DT classifier has shown the lowest accuracy, while other models (GP, LR, RF, ANN, and SVM) performed better. All models have shown lower accuracy in predicting an event of an emergency admission with red code than predicting fracture and disability. In predicting urgent hospitalization, only SVM achieved better performance (TPR 0.75, TNR 0.77, accuracy 0.73, F1-score 0.76) with the 10-fold cross validation compared with other models in all evaluation metrics. CONCLUSIONS We developed machine learning models for predicting frailty conditions (mortality, urgent hospitalization, disability, fracture, and emergency admission). The results show that the prediction performance of machine learning models significantly varies from problem to problem in terms of different evaluation metrics. Through further improvement, the model that performs better can be used as a base for developing decision-support tools to improve early identification and prediction of frail older adults.

Aim To determine the red flags for serious organic causes of headache in children, to analyze if the management of headache in the Pediatric Emergency Department is appropriate, and whether the follow-up may limit repeated visits to the Emergency Department. Methods All the patients ≤ 18 years referred to our pediatric Emergency Department for non-traumatic headache over 5 years were retrospectively reviewed. The patients followed up by the Pediatric Headache Centre were also screened. Statistical analysis was undertaken using the Chi-squared test or Fisher’s exact test and multivariate analysis; significance at p Results 1833 patients (54.6% males) accessed our Emergency Department 2086 times; 62.1% had primary headache, 30.0% had secondary headache, 7.8% received inconsistent diagnosis. Among those with secondary headache, 24 (1.1% of total visits) were diagnosed with serious disorders. The clinical red flags for “serious headache” were: Cranial nerves palsy, strabismus, and drowsiness. One hundred and eighty four patients (8.8 %) underwent neuroimaging (rate of pathological findings: 7.1 %); 37.2 % of the patients received analgesic therapy. One hundred and fifteen patients (6.2 %) returned within three months; 24 of these were referred to the Headache Centre, with only one accessing the Emergency Department again. Conclusions The vast majority of headaches referred to the Pediatric Emergency Department are benign, and primary forms prevail. “Serious headache” is rare and shows typical clinical features and abnormal neurologic evaluation; specific clinical red flags, along with suggestive personal history, should lead the pediatrician to prescribe only appropriate neuroimaging. Pain relief is still insufficient in the Pediatric Emergency Department despite appropriate guidelines. Last, the collaboration with the Headache Centre is crucial to limit repeated visits.

The association between oral lichen planus (OLP) and hypothyroidism has been debated with conflicting results: some authors detected a statistically significant association between these two, while others did not confirm it. The aim of this study was to evaluate the thyroid status in patients with newly diagnosed OLP to test the null hypothesis that thyroid disease is not associated with an increased incidence of oral lesions, with a prospective case-control approach. A total of 549 patients have been evaluated, of whom 355 were female. Odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Patients suffering from thyroid diseases were associated with an almost 3-fold increased odds of having OLP (OR 2.85, 95% CI: 1.65–4.94), after adjusting this analysis for age, gender, body mass index, smoking status, diabetes, hypertension and hepatitis C infection. It would be appropriate to further investigate the possible concomitance of OLP among patients with thyroid disorder; endocrinologists should be aware of this association, especially because OLP is considered a potentially malignant oral disorder.

Background: Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed due to measurement error in self-reported assessments. The identification of biomarkers of habitual alcohol intake may enhance evidence on the role of alcohol in cancer onset. Methods: Untargeted metabolomics was used to identify metabolites correlated with habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n=454). Significant correlations were replicated in independent datasets of controls from case-control studies nested within EPIC (n=281) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n=438) study. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies. Results: Two metabolites displayed a dose-response association with alcohol intake: 2-hydroxy-3-methylbutyric acid and an unidentified compound (m/z(+):231.0839). A 1-SD increase in log2-transformed levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR=2.14; 95% CI=1.39-3.31) and pancreatic cancer (OR=1.65; 95% CI=1.17-2.32) in EPIC and liver cancer (OR=2.00; 95% CI=1.44-2.77) and liver disease mortality (OR=2.16; 95% CI=1.63-2.86) in ATBC. Conversely, a 1-SD increase in log2-transformed questionnaire-derived alcohol intake was not associated with risk of HCC or pancreatic cancer in EPIC or liver cancer in ATBC but was associated with risk of liver disease mortality (OR=2.19; 95% CI=1.60-2.98) in ATBC. Conclusions: 2-Hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that may advance the study of alcohol and cancer risk in population-based studies. Citation Format: Erikka Loftfield, Magdalena Stepien, Vivian Viallon, Laura Trijsburg, Joseph Rothwell, Nivonirina Robinot, Carine Biessy, Ingvar A. Bergdahl, Stina Bodén, Matthias B. Schulze, Manuela Bergmann, Elisabete Weiderpass, Julie A. Schmidt, Rual Zamora-Ros, Therese H. Nøst, Torkjel M. Sandanger, Emily Sonestedt, Bodil Ohlsson, Verena Katzke, Rudolf Kaaks, Fulvio Ricceri, Anne Tjønneland, Christina C. Dahm, Maria-Jose Sánchez, Antonia Trichopoulou, Rosario Tumino, María-Dolores Chirlaque, Giovanna Masala, Eva Ardanaz, Roel Vermeulen, Paul Brennan, Demetrius Albanes, Stephanie J. Weinstein, Augustin Scalbert, Augustin Scalbert, Neal D. Freedman, Marc J. Gunter, Mazda Jenab, Rashmi Sinha, Pekka Keski-Rahkonen, Pietro Ferrari. Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 747.

Fruit and vegetable (FV 95% CI: 0.68-1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend = 0.06). This study did not find any significant association between FV however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: −69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

In vitro studies have shown several beneficial properties of resveratrol. Epidemiological evidence is still scarce, probably because of the difficulty in estimating resveratrol exposure accurately. The current study aimed to assess the relationships between acute and habitual dietary resveratrol and wine intake and urinary resveratrol excretion in a European population. A stratified random subsample of 475 men and women from four countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study, who had provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day, were included. Acute and habitual dietary data were collected using standardised 24-HDR software and a validated country-specific dietary questionnaire, respectively. Phenol-Explorer was used to estimate the intake of resveratrol and other stilbenes. Urinary resveratrol was analysed using tandem MS. Spearman’s correlation coefficients between estimated dietary intakes of resveratrol and other stilbenes and consumption of wine, their main food source, were very high (r>0·9) when measured using dietary questionnaires and were slightly lower with 24-HDR (r>0·8). Partial Spearman’s correlations between urinary resveratrol excretion and intake of resveratrol, total stilbenes or wine were found to be higher when using the 24-HDR (R2partial approximately 0·6) than when using the dietary questionnaires (R2partial approximately 0·5). Moderate to high correlations between dietary resveratrol, total stilbenes and wine, and urinary resveratrol concentrations were observed. These support the earlier findings that 24-h urinary resveratrol is an effective biomarker of both resveratrol and wine intakes. These correlations also support the validity of the estimation of resveratrol intake using the dietary questionnaire and Phenol-Explorer.

Adherence to the Mediterranean diet (MD) has a preventive effect on colorectal cancer (CRC). Several biological mechanisms have been hypothesized to explain this effect, but the involvement of clinical mediators has not been experimentally proven. We examined the role of abdominal adiposity (i.e., waist-to-hip ratio, WHR) as a potential mediator of the relationship between the MD and CRC in the Italian centres of the European Prospective Investigation into Cancer and Nutrition. We evaluated the effect of the Italian Mediterranean Index (IMI) on WHR and of WHR on CRC risk. We then estimated the natural indirect effect (NIE, mediated by WHR) and the pure direct effect (PDE, unmediated) of IMI on CRC risk using mediation analyses, considering age, sex, education, physical activity, smoking and EPIC centre as confounders. Increased IMI was associated with significantly decreased odds of high WHR (odds ratio [OR] for an IMI of 6-11 vs. 0-1: 0.88, 95% confidence interval [CI]: 0.81-0.97). There was a positive relationship between WHR and CRC (hazard ratio [HR] for high vs. low WHR: 1.34, 95%CI: 1.09-1.66). The total effect of IMI was protective on CRC risk and was mainly explained by the PDE (HR for an IMI of 6-11 vs. 0-1: 0.51, 95%CI: 0.31-0.83), whereas the NIE was 1.00 (95%CI: 0.94-1.10). In this Mediterranean cohort, the protective effect of the MD on the development of CRC was not mediated by abdominal adiposity. Since this is the first study to investigate the mediating effect of abdominal obesity, other studies are needed to replicate this result.

Purpose: To analyze the inter-methods agreement in arteriovenous ratio (AVR) evaluation between spectral-domain optical coherence tomography (SD-OCT) and Dynamic Vessel Analyzer (DVA). Methods: Healthy volunteers underwent DVA and SD-OCT examination. AVR was measured by SD-OCT using the four external lines of the optic nerve head-centered 7-line cube and by DVA using an automated AVR estimation. The mean AVR was calculated, twice, separately by two independent readers for each tool. Results: Twenty-two eyes of 11 healthy subjects (five women and six men, mean age 35) were included. AVR analysis by DVA showed high inter-observer agreement between reader 1 and 2, and high intra-observer agreement for both reader 1 and reader 2. With regard to AVR analysis on SD-OCT, we found high inter-observer agreement between reader 1 and 2, and low intra-observer agreement for reader 2 but high intra-observer agreement for reader 1. Overall, the mean AVR measured on SD-OCT turned out to be significantly higher than mean AVR measured through DVA (reader 1, 0.9023 ± 0.06 vs 0.8036 ± 0.08; p < 0.001, and reader 2, 0.9067 ± 0.06 vs 0.8083 ± 0.05; p= 0.003). Conclusions: No inter-method agreement in AVR could be detected in the present study due to bias in measurements (shift between DVA and SD-OCT). We found significant difference in the two noninvasive methods for AVR measurement, with a tendency for SD-OCT to overestimate retinal vascular caliber in comparison to DVA. This may be useful for achieving greater accuracy in the evaluation of retinal vessel in ocular as well as systemic diseases.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vit ...

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutant ...

AIM: Febrile seizures (FS) involve 2-5% of the paediatric population, among which Complex FS (CFS) account for one third of accesses for FS in Emergency Departments (EDs). The aim of our study was to define the epidemiology, the clinical, diagnostic and therapeutic approach to FS and CFSs in the Italian EDs. METHODS: A multicenter prospective observational study was performed between April 2014 and March 2015. Patients between 1 and 60 months of age, randomly accessing to ED for ongoing FS or reported FS at home were included. Demographic features and diagnostic-therapeutic follow-up were recorded. FS were categorized in simple (30min). RESULTS: The study population consisted of 268 children. Most of the children experienced simple FS (71.65%). Among the 68 (25.37%) patients with complex FS, 11 were 6-12 month-old, accounting for 45.83% of all the infants with FS in the younger age group. No therapy has been administered at home in 76.12% patients; 23.51% of them received endorectal diazepam and only 1 patient received buccal midazolam. At arrival at ED, no therapy was necessary for 70.52% patients; 50.63% received endorectal diazepam and 17.72% an i.v. bolus of midazolam. Blood tests and acid-base balanced were performed respectively in 82.09% of cases. An electroencephalogram at ED was performed in 21.64% of patients. Neuroimagings were done in 3.73% of cases. A neurologic consultation was asked for 36 patients (13.43%). CONCLUSION: this is the first study assessing epidemiologic characteristics of FS in the Italian pediatric population, evidencing a higher prevalence of CFSs in children younger than 12 months of age and opening a new research scenario on the blood brain barrier vulnerability. On a national level, our study showed the need for a diagnostic standardized work-up to improve the cost/benefit ratio on CFS management.

Background Flexible employment is increasing across Europe and recent studies show an association with poor mental health. The goal of the current study is to examine this association in the Italian population to assess the possible mediating role of financial strain. Methods Data were obtained by two Italian cross-sectional studies (PASSI and HIS) aimed at monitoring the general population health status, health behaviours and determinants. Mental health status was assessed using alternatively two validated questionnaires (the PHQ-2 and the MCS-12 score) and Poisson regression models were performed to assess if precarious work was associated with poor mental health. A formal mediation analysis was conducted to evaluate if the association between precarious work and mental health was mediated by financial strain. Results The analyses were performed on 31,948 subjects in PASSI and on 21,894 subjects in HIS. A nearly two-fold risk of depression and poor mental health was found among precarious workers, compared to workers with a permanent contract, which was strongly mediated by financial strain. Conclusions Even with the limitations of a cross-sectional design, this research supports that precarious employment contributes through financial strain to reduce the mental health related quality of life and to increase mental disorders such as symptoms of depression or dysthymia. This suggests that when stability in work cannot be guaranteed, it would be appropriate to intervene on the wages of precarious jobs and to provide social safety nets for ensuring adequate income. Electronic supplementary material The online version of this article (10.1186/s12889-019-7243-x) contains supplementary material, which is available to authorized users.

Background There is no universally-accepted classification of Spitzoid tumors. This makes it difficult to assign a correct diagnosis and select a treatment that minimizes the risk of overestimating, or worse, underestimating, the malignant potential of these tumors. The aim of this study was to describe the clinical-pathological and epidemiological features of Spitzoid tumors, as well as to assess mortality in these patients. Methods This retrospective cohort study looked at data on Spitzoid tumors excised in 1999-2012 at the Dermatologic Clinic of the Turin University Hospital. Spitzoid melanoma specific survival curves were generated with the Kaplan-Meier method and compared using the log-rank test. Results In this time period, 1663 lesion were described at the pathologic report as Spitzoid. 262 (15.75%) were Spitz nevi, 307 (18.46%) Reed nevi, 827 (49.73%), 810 (48.71%) Spitzoid dysplastic nevi, 17(1.02%) atypical Spitzoid tumors, and 267 (16.06%) Spitzoid melanomas. Median follow-up time was 9 years. Out of the entire cohort only 24 patients died from melanoma. All of them received a diagnosis of Spitzoid melanoma. None of the patients with a diagnosis of not melanoma Spitz tumor died for melanoma during the follow-up. Conclusions In the large majority of the cases, Spitz tumor should be considered as benign lesion and excised only if melanoma features are seen. The used clinical pathological classification avoid misdiagnoses, inappropriate treatment and the risk of death for melanoma.

In this study, we aimed to study the correlation between acute and habitual intakes of flavonols, their main food sources and their 24-h urinary concentrations in an European population. A 24-h dietary recall (24-HDR) and 24-h urine samples were collected on the same day from a convenience subsample of 475 men and women from four countries (France, Italy, Greece and Germany) of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A standardized 24-HDR software and a country/centre-specific validated dietary questionnaire (DQ) were used to collect acute and habitual dietary data, respectively. The intake of dietary flavonols was estimated using the Phenol-Explorer database. Urinary flavonols (quercetin, isorhamnetin, and kaempferol) were analysed using tandem mass spectrometry with a previous enzymatic hydrolysis. Weak partial Spearman correlations between both dietary acute and habitual intake and urinary concentrations of quercetin (both Rpartial ~ 0.3) and total flavonols (both Rpartial ~ 0.2) were observed. No significant correlations were found for kaempferol and isorhamentin. Regarding flavonol-rich foods, weak correlations were found between urinary concentrations of quercetin and total flavonols and the acute intake of onions and garlics, fruits, tea, and herbal tea (all Rpartial ~ 0.2). For habitual intake, statistically significant correlations were only found between urinary quercetin concentration and herbal tea (Rpartial = 0.345) and between urinary total flavonol concentration and tea, and herbal tea consumption (Rpartial ~ 0.2). Our results suggest that urinary quercetin level can be used as potential concentration biomarkers of both acute and habitual quercetin intake, while urinary concentrations of flavonols are unlikely to be useful biomarkers of individual flavonol-rich foods.

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by Partial Least Square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct (NDE) and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor positive tumours with respectively TE=1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-SD deviation increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE=1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone, was associated with BC risk (OR=1.25 (1.07,1.47)) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association. This article is protected by copyright. All rights reserved.

The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347-SERPINE1 and cg20674490-RUNX3) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490-RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a ‘meet-in-the-middle’ approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.

BACKGROUND Despite the frequency of oral involvement, there are unexpectedly few studies of either on the oral manifestations of pemphigus or their long-term management, and diagnostic delay in Dentistry is frequent. METHODS We have examined outcome of patients presenting with predominantly oral pemphigus vulgaris (PV). Ninety-eight subjects were followed up for 85.12 months and treated with systemic steroids: 48 of them received adjunctive therapy with azathioprine, 16 with rituximab, 13 with mycophenolate mofetil, three with immunoglobulin and one with dapsone. RESULTS Clinical remission was achieved in 80 patients (84.21%); 39 of them were off therapy and 41 on therapy. Fifteen patients were not in remission, having been under systemic therapy for 72.16 months. Sixty-nine patients developed detectable adverse effects. Two fatal outcomes were recorded. Each additional year of steroid therapy ensured 47% chance of developing 1 or 2 side effects, and 64% chance of developing more than 3 (ORs 1.47, CI 1.162-1.903; ORs 1.64, CI 1.107-2.130, respectively). CONCLUSION In one of the largest available cohort with the longest follow-up ever reported, we observed that the management remains need-based and patient-specific, still relying on systemic corticosteroids.

Objective:To assess the psychological impact of a mass casualty incident (MCI) in a subset of personnel in a level I hospital.Methods:Emergency department staff responded to an MCI in June 2017 in Turin, Italy by an unexpected sudden surge of casualties following a stampede (mass escape). Participants completed the Psychological Simple Triage and Rapid Treatment Responder Self-Triage System (PsySTART-R), which classified the potential risk of psychological distress in “no risk” versus “at risk” categorization and identified a range of impacts aggregated for the population of medical responders. Participants were administered a questionnaire on the perceived effectiveness of management of the MCI. Two months later, the participants were evaluated using the Hospital Anxiety and Depression Scale (HADS), the Kessler Psychological Distress Scale (K6), and the Posttraumatic Stress Disorder Checklist (PCL-5).Results:The majority of the responders were classified as “no risk” by the PsySTART-R; no significant differences on HADS, K6, and PCL-5 were found in the participants grouped by the PsySTART-R categories. The personnel acquainted to work in emergency contexts (emergency department and intensive care unit) scored significantly lower in the HADS than the personnel usually working in other wards. The number of positive PsySTART-R criteria correlated with the HADS depression score.Conclusions:Most of the adverse psychological implications of the MCI were well handled and averted by the responders. A possible explanation could be related to factors such as the clinical condition of the victims (most were not severely injured, no fatalities), the small number of casualties (87) brought to the hospital, the event not being considered life-threatening, and its brief duration, among others. Responders had mainly to cope with a sudden surge in casualties and with organizational issues.