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Summary Background Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country. Methods Estimates for Italy were extracted from GBD 2017. Data on Italy are presented for 1990 and 2017, on prevalence, causes of death, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth and at age 65 years, healthy life expectancy, and Healthcare Access and Quality (HAQ) Index. We compared the estimates for Italy with those of 15 other western European countries. Findings The quality of the universal health system and healthy behaviours contribute to favourable overall health, even in comparison with other western European countries. In 2017, life expectancy and HAQ Index score in Italy were among the highest globally, with life expectancy at birth reaching 85·3 years for females and 80·8 for males in 2017, ranking Italy eighth globally for females and sixth for males, and an HAQ Index score of 94·9 in 2016 compared with 81·54 in 1990, keeping Italy ranked as ninth globally. Between 1990 and 2017 age-standardised death rates for cardiovascular diseases decreased by 53·7% (95% uncertainty interval −56·1 to −51·4), for neoplasms decreased by 28·2% (−32·3 to −24·6), and for transport injuries decreased by 62·1% (−64·6 to −59·2). However, population ageing is causing an increase in the burden of specific diseases, such as Alzheimer's disease and other dementias (DALYs increased by 77·9% [68·4 to 87·2]) and pancreatic (DALYs increased by 39·7% [28·4 to 51·7]) and uterine cancers (DALYs increased by 164·7% [129·7 to 202·5]). Behavioural risk factors, which are potentially modifiable, still have a strong effect, particularly on cardiovascular diseases and neoplasms. For instance, in 2017, 44 400 (41 200 to 47 800) cancer deaths were attributed to smoking, 12 000 (9600 to 14 800) to alcohol use, and 9500 (5400 to 14 200) to high body-mass index, while 47 000 (31 100 to 65 700) deaths due to cardiovascular diseases could be attributed to high LDL cholesterol, 28 700 (19 700 to 38 500) to diets low in whole grains, and 15 900 (8500 to 24 900) to low physical activity. Interpretation Italy provides an interesting example of the results that can be achieved by a mix of relatively healthy lifestyles and a universal health system. Two main issues require attention, population ageing and gradual decrease of public health financing, which both pose several challenges to the future of Italy's health status. Our findings should be useful to Italy's policy makers and health system experts elsewhere. Funding Bill & Melinda Gates Foundation.

Introduction: Second-hand smoke exposure in the home is a serious cause of ill-health for children. Behaviour change interventions have been developed to encourage parents to keep homes smoke-free. This study evaluates a novel air quality feedback intervention using remote air quality monitoring with SMS and email messaging to promote smoke-free homes among families from deprived areas. Methods: This paper presents a pre-post study of this intervention. Using internet connected monitors developed with the Dylos DC1700, daily SMS and weekly email feedback provided for 16 days to participants recruited in four European countries. Participants were recruited based on their stage of change, in order to target those most able to achieve smoke-free homes. The primary outcome measure was median change in mean fine particulate matter (PM2.5) concentration between baseline and follow-up periods, while secondary outcome measures included change in time over the World Health Organisation (WHO) guideline limit for PM2.5 exposure over 24 h (25 mu g/m(3)) in those periods and the number of homes where PM2.5 concentrations reduced. Telephone interviews were conducted with participants in Scotland post-intervention to explore intervention experience and perceived effectiveness. Results: Of 86 homes that completed the intervention study, 57 (66%) experienced pre-post reductions in measured PM2.5. The median reduction experienced was 4.1 mu g/m(3) (a reduction of 19% from baseline, p = 0.008). Eight homes where concentrations were higher than the WHO guideline limit at baseline fell below that level at follow-up. In follow-up interviews, participants expressed positive views on the usefulness of air quality feedback. Discussion: Household air quality monitoring with SMS and email feedback can lead to behaviour change and consequent reductions in SHS in homes, but within the context of our study few homes became totally smoke-free.

Our aim was to provide a systematic review of studies on the burden of disease due to second-hand smoke (SHS) exposure, reviewing methods, exposure assessment, diseases causally linked to SHS, health outcomes, and estimates available to date. A literature review of studies on the burden of disease from SHS exposure, available in PubMed and SCOPUS, published 2007-2018 in English language, was carried out following the PRISMA recommendations. Overall, 588 studies were first identified, and 94 were eligible. Seventy-two studies were included in the systematic review. Most of them were based on the comparative risk assessment approach, assessing SHS exposure using mainly surveys on exposure at home/workplaces. Diseases more frequently studied were: lung cancer, ischemic heart disease, stroke, chronic obstructive pulmonary disease, asthma and breast cancer in adults; lower respiratory tract infection, otitis media, asthma, sudden infant death syndrome and low birth weight in children. The SHS exposure assessment and the reported population attributable fractions (PAF) were largely heterogeneous. As an example, the PAF from lung cancer varied between 0.6% and 20.5%. Moreover, PAF were estimated applying relative risks and SHS exposures with no consistent definitions or with different age classes. The research gap on the SHS exposure burden is shrinking. However, estimates are not yet available for a number of countries, particularly the Middle Eastern and African countries, and not all diseases with the strongest evidence of causation, such as sudden infant death syndrome, have been explored. Moreover, in some cases the applied methodology revealed relatively low quality of data.

Background: Large-scale international collaboration is essential to decipher relevant information in the context of omics-scale interrogations in cancer research. This is even more important for rare and fatal diseases like pancreas cancer (PC). Methods: The COST Action BM1204 is a unique platform to facilitate the collaboration of a broad range of European and international PC multidisciplinary research groups in order to: (1) integrate knowledge and experience in a multidisciplinary way ‘from cell to society', (2) promote the application of uniform study tools and protocols, (3) foster their optimal use by early-stage researchers, (4) enhance the mobility and training of researchers, and (5) disseminate the results produced to the broader society. Results: This Action will develop novel interdisciplinary tools for collaborative research to improve our understanding of PC and its prevention, diagnosis and treatment. It also aims to answer questions related to the etiology, early detection, evidence-based and personalized treatment, and health management for PC. Furthermore, the Action will contribute to new insights into PC personalized medicine and beyond as well as to the understanding of complex and rare diseases taking PC as a best practice example. The Action aims at attracting young scholars across a range of disciplines in collaboration with more experienced researchers and enhancing active European participation in the international scenario of PC research. Conclusion: The ultimate aim is to foster PC research in Europe and to coordinate this effort with other international initiatives to reduce disease mortality.

Aims and background. Data on kidney cancer incidence and prevalence are not available on a national and regional level. We provided estimates of the number of incident and prevalent cases of kidney and renal cell cancer in Italy overall and in various regions in 2002 and gave projections for the years 2007 and 2012. Methods. We derived annual numbers of incident cases combining mortality data provided by the World Health Organization and information on relative Survival from kidney cancer and we subsequently derived 5-year prevalence by combining incidence with information on survival. We provided different projection estimates for the years 2007 and 2012 for incidence and prevalence, on the basis of various hypothetical scenarios, i.e., stable rates over time or steady falls by 1% per year. Results. In 2002, there were about 8000 incident cases and 26,800 prevalent cases of kidney cancer in Italy. Of these, approximately 6800 and 22,750 were incident and prevalent cases of renal cell cancer, respectively. The most reliable estimate of incident kidney cancer cases in Italy over the period 2007-2012 is likely to range between 7000 and 9000. Of these, between 6000 and 8000 are renal cell cancer cases. The best estimate of prevalence of kidney cancer is between 20,000 and 34,000 cases and that of renal cell cancer between 17,000 and 29,000 cases. Conclusions. Incidence and prevalence of renal cell cancer are likely to remain approximately stable between 2002 and 2007. Increased diagnostic attention due to widespread use of echography and other diagnostic techniques may, however, lead to earlier detection of kidney neoplasms and consequently to an apparent increase in the incidence of renal cell cancer.

European epidemiological studies on ambient air pollution and cancer published before December 2006 are reviewed, with focus on five analytic studies providing data on the association between various measures of particulate matter (PM) and lung cancer. A case-control study of 755 men who died from lung cancer in Trieste, Italy, reported that, compared with less than 0.18 g/m/day of deposition of particulate, the relative risk (RR) was 1.1 [95% confidence interval (CI): 0.8-1.5] for 0.18-0.30 and 1.4 (95% CI: 1.1-1.8) for more than 0.30 g/m/day. In the Netherlands Cohort Study on Diet and Cancer with 60 deaths from lung cancer, the RR was 1.06 (95% CI: 0.43-2.63) for an increase of 10 µg/m in black smoke. In the French Pollution Atmospherique et Affections Respiratoires Chroniques study cohort based on 178 deaths from lung cancer, the RR associated with an increase in exposure to 10 µg/m of total suspended particulate was 0.97 (95% CI: 0.94-1.01). A nested case-control study within the European Prospective Investigation on Cancer and Nutrition included 113 nonsmokers or exsmokers diagnosed with lung cancer and 312 controls. The RRs were 0.91 (95% CI: 0.70-1.18) for an increase in PM with diameter =10 µm (PM10) of 10 µg/m, and 0.98 (95% CI: 0.66-1.45) for exposure over 27 µg/m compared with less than 27 µg/m. In a Norwegian record linkage study, based on 1453 lung cancer deaths, no significant excess risk was found for men, and a modest association was observed for women. European studies of PM exposure and lung cancer do not show a clear association, but uncertainties remain for the measurement of exposure and latency. © 2008 Lippincott Williams & Wilkins, Inc.

The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41-0.75), and vitamin C (OR = 0.72, 95% CI = 0.54-0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59-1.08) for retinol, 0.82 (95% CI = 0.61-1.10) for a-carotene, 0.90 (95% CI = 0.68-1.20) for beta-carotene, 0.94 (95% CI = 0.73-1.21) for beta-criptoxanthin, 0.85 (95% CI = 0.63-1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57-1.01) for vitamin D, 0.75 (95% CI = 0.55-1.01) for thiamine, 0.88 (95% CI = 0.66-1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64-1.13), 0.85 (95% CI = 0.64-1.12) for folate and 0.80 (95% CI = 0.60-1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC. (c) 2006 Wiley-Liss, Inc.

Mortality from oral cancer has been rising in the young in several areas of the world until the early 1990s. We analysed data from two case-control studies from Italy and Switzerland including 137 cases of oral and pharyngeal cancer below age 46 and 298 hospital controls. The multivariate odds ratios (OR) were 20.7 for heavy smokers and 4.9 for heavy drinkers. The combination of high tobacco and alcohol consumption led to an OR of over 48. Body mass index (OR=0.28, for the highest tertile), high consumption of coffee (OR=0.25), fresh vegetables (011=039), fruit (OR=0.73) and beta-carotene (OR=0.48) were inversely related to risk. Tobacco accounted for 77% of all cancer cases in this population, alcohol for 52%, low vegetable consumption for 52%, and the combination of the three factors for 85%. (C) 2003 Elsevier Ltd. All rights reserved.

Objectives. To examine the association between alcohol and the risk of prostate cancer/benign prostatic hyperplasia (BPH) in a population with a wide range of alcohol consumption, using a hospital-based, case-control study. Data from several epidemiologic studies have allowed us to exclude a strong association between alcohol drinking and prostate cancer risk. However, limited information is available for BPH. Also, it is unclear whether various types of alcoholic beverages may have a different impact on risk. Methods. We conducted this hospital-based case-control study in Italy between 1991 and 2002. A total of 2663 men younger than 75 years had incident, histologically confirmed prostate carcinoma (1294 cases) or symptomatic obstructive BPH (1369 cases) (maximal flow rate less than 15 mL/s) refractory to medical treatment. A total of 1451 patients younger than 75 years were used as controls. Odds ratios and corresponding 95% confidence intervals were estimated using unconditional multiple logistic regression models including terms for age, center, education, body mass index, physical activity, and family history of prostate cancer. Results. Alcohol consumption showed no consistent association with prostate cancer risk, but a statistically significant inverse trend in risk for BPH. Compared with abstainers, the odds ratio was 0.88 for fewer than three drinks, 0.71 for three to four drinks, 0.79 for five to six drinks, and 0.65 for seven or more drinks per day. The patterns of risk were similar with reference to different alcoholic beverages. The inverse relation between elevated alcohol consumption and BPH was apparently stronger in subjects with a lower body mass index. Conclusions. Alcohol drinking is unrelated to prostate cancer risk. The inverse relationship with BPH may be related to the hormonal correlates (ie, lower androgen levels) of heavy alcohol drinkers. UROLOGY (C) 2004 Elsevier Inc.

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. Methods: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for greater than or equal to25 cigarettes/day) and for duration of smoking (OR = 37.2 for greater than or equal to40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for greater than or equal to56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Objective: To investigate the relation between various micronutrients and laryngeal cancer risk. Methods: A case-control study was conducted in Italy and Switzerland between 1992 and 2000. Cases were 527 patients with incident cancer of larynx, admitted to the major teaching and general hospitals of the study areas. Controls were 1297 subjects admitted for acute, non-neoplastic diseases to the same network of hospitals. Dietary habits were assessed using a validated food-frequency questionnaire. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed using multiple logistic regression. Results: Significant inverse relations emerged between laryngeal cancer risk and intake of vitamin C (OR = 0.2, for the highest versus the lowest intake quintile; 95% CI: 0.2-0.4), beta-carotene (OR = 0.2; 95% CI: 0.2-0.4), alpha-carotene (OR = 0.3; 95% CI: 0.2-0.5), lutein/zeaxanthin (OR = 0.4; 95% CI: 0.3 - 0.6), vitamin E (OR = 0.4; 95% CI: 0.3 0.6), beta-criptoxanthin (OR = 0.4; 95% CI: 0.2-0.5), folic acid (OR = 0.4; 95% CI: 0.2 - 0.6), thiamin (OR = 0.4; 95% CI: 0.3 - 0.6), glutathione (OR = 0.5; 95% CI: 0.4-0.8), reduced glutathione (OR = 0.6; 95% CI: 0.4-0.8), vitamin B6 (OR = 0.6; 95% CI: 0.4 - 0.9) and potassium(OR = 0.6; 95% CI: 0.4-0.9). Direct associations were found with zinc (OR = 1.5; 95% CI: 1.0 - 2.2) and vitamin D (OR = 1.8; 95% CI: 1.2-2.6). Combining low intakes of vitamin C, carotene, vitamin E, and folate with heavy smoking and drinking led to ORs between 80 and 170. Conclusions: This study provides further support that, independently from smoking and alcohol consumption, the intake of several micronutrients, including selected antioxidants, is inversely related to laryngeal cancer risk. RI Parpinel, Maria/B-1605-2012

Objective: This study investigates the potential role of olive oil and other added fats used for seasoning or cooking on ovarian carcinogenesis. Methods: We analyzed data from a multicentre case-control study conducted between 1992 and 1999 in Italy, including a total of 1031 incident with a first diagnosis, histologically confirmed epithelial ovarian cancer cases and 2411 hospital controls with acute, non-malignant and non-gynecological conditions. The subjects' usual diet was investigated through a validated food-frequency questionnaire, including specific questions aimed at assessing added fat intake patterns. Results: After allowance for study centre, year at interview, age, education, parity, oral contraceptive use, and total energy intake, a reduced risk of ovarian cancer was observed for high intake of olive oil (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.50-0.93 for the highest quintile of intake, compared to the lowest one) and for a group of specific seed oils (i.e. sunflower, maize, peanut, and soya) (OR = 0.59, 95% CI 0.46-0.76). No significant associations were observed for mixed seed oils, butter, and margarine. Conclusions: The present study suggests a favorable effect of olive oil and other vegetable oils on ovarian cancer in this Italian population.

Objective: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. Methods: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. Results: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromso, and Vaud. Conversely, the ORs for the studies in Los Angeles, Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR=0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR=0.65, 95% CI 0.48-0.88). Conclusion: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.

The relation between selected micronutrients and oral and pharyngeal cancer risk was investigated using data from a case-control study conducted between January 1992 and November 1997 in Italy and Switzerland. Cases were 754 incident, histologically confirmed oral cancers (344 of the oral cavity and 410 of the pharynx) admitted to the major teaching and general hospitals in the study areas. Controls were 1,775 subjects with no history of cancer admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were computed after allowance for age, sex, center, education, occupation, body mass index, smoking and drinking habits and non-alcohol energy intake. Micronutrients were analyzed both as continuous variables and in quintiles. in the former case, the unit was set to 1 SD of the distribution of controls. ORs for the continuous analysis were 0.95 for retinol, 0.61 for carotene, 0.91 for lycopene, 0.83 for vitamin D, 0.74 for vitamin E, 0.63 for vitamin C, 0.82 for thiamine, 0.87 for riboflavin, 0.59 for vitamin B-6, 0.61 for folic acid, 0.62 for niacin, 0.91 for calcium, 0.88 for phosphorus, 0.65 for potassium, 0.82 for iron, 0.67 for non-alcohol iron and 0.89 for zinc; the 95% confidence interval excluded one for carotene, vitamin C and E, thiamine, vitamin B-6, folic acid, niacin, potassium and iron. ORs were similar for the 2 sexes and in strata of age. When the combined intake of vitamins C and E and carotene was considered, the protective effect of each nutrient was more marked or restricted to subjects with low intake of the other 2. The association with vitamin C and carotene was independent of smoking and drinking habits, while that with vitamin E was less evident in those heavily exposed to alcohol or tobacco. In general, the more a micronutrient was correlated to total vegetable and fruit intake, the stronger was its protective effect against oral cancer. int. J. Cancer 86:122-127, 2000. (C) 2000 Wiley-Liss, Inc. RI Parpinel, Maria/B-1605-2012

We have investigated the relation between alcohol, tobacco and dietary habits and risk of adenocarcinoma of the small intestine using data from 2 hospital-based case control studies on intestinal cancers conducted in 6 Italian centres between 1985 and 1996. Cases were 23 patients below age 75 years with adenocarcinoma of the small intestine. Controls were 230 patients admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract diseases, matched to cases on sex, age, study and centre. Odds ratios (ORs) were estimated using conditional logistic regression. Alcohol and tobacco consumption did not increase the risk of adenocarcinoma of the small intestine. The risk appeared to be directly related to intake of bread, pasta or rice (OR = 3.8), sugar (OR = 2.9) and red meat (OR = 4.6), and inversely to coffee (OR = 0.4), fish (OR = 0.3), vegetables (OR = 0.3) and fruit (OR 0.6). Our results suggest that dietary correlates of adenocarcinoma of the small intestine are similar to those of colon cancer and at least of the same magnitude. While the present data are inconsistent with a major effect of tobacco or alcohol, a moderate association between these factors and small bowel cancer may have been obscured by the play of chance. (C) 1999 Wiley-Liss, Inc.

In order to evaluate the short-term effects (3 weeks) on selected coronary heart disease (CHD) risk factors, 90 obese in-patients (body mass index, BMI, > or = 35 kg/m2 received a same low-calorie diet (1200-1800 kcal/day), nutritional education and psychological counselling, and were randomly assigned to either a non-specific, high-volume, low-intensity exercise training program (NET), or to an individualised, low-volume and high-intensity exercise training program (IET), for 5 days/week for 3 weeks. NET and IET programs lead to a significant reduction in blood glucose (6.2 and 7.7% respectively), total cholesterol (17.3%, 12.3%), HDL-cholesterol (13.7%, 15.2%), systolic (8.9%, 5.3%) and diastolic resting blood pressure (10.6%, 3.3%). Total CHD scores were also significantly improved (38.1%, 33.1%). The changes occurred with a relatively moderate decrease in body weight (4.2%, 4.4%) and with still elevated BMI values (41.6 kg/m2). Although IET, compared to NET program, induced smaller reductions of blood pressure, it requires 30% daily training period and may possibly enhance long-term patient compliance.

Laryngeal cancer is the neoplasm with the largest male to female sex ratio in most populations. Thus, inadequate data are available on women. We analyzed several risk factors in the combined dataset from two case-control studies conducted between 1986 and 2000 in northern Italy and Switzerland. Cases were 68 women under age 79 years, with incident, histologically confirmed cancer of the larynx. Controls were 340 women, admitted to the same network of hospitals as cases, for acute, nonmalignant conditions, unrelated to tobacco and alcohol consumption. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated by logistic regression models, conditioned by age, study center and year of interview, and including terms for education, body mass index, tobacco, alcohol drinking, and nonalcohol energy intake. Laryngeal cancer was strongly associated with cigarette smoking (OR 435.7, 95% CI: 38.2-4964.4 for smokers of greater than or equal to25 cigarettes/day) and alcohol drinking (OR = 4.3, 95% CI: 0.8-24.1 for greater than or equal to5 drinks/day). An inverse relation was found for vegetables (OR = 0.3, 95% CI: 0.1-0.9 for the highest level of consumption), fruit (OR = 0.5, 95% CI: 0.2-1.3), and olive oil (OR = 0.3, 95% CI: 0.1-0.9). Reproductive and hormonal factors were not consistently associated to laryngeal cancer risk. This investigation, based on a uniquely large number of laryngeal cancers in women, provides definite evidence that cigarette smoking is the prominent risk factor for laryngeal cancer in women, accounting for 78% of cases in this population. Alcohol and selected dietary aspects account for similar to30% of cases, whereas menstrual and hormonal factors do not appear to have a consistent role in laryngeal carcinogenesis.

The hypothesis that the Mediterranean diet has a beneficial role on the risk of cancers of the upper aerodigestive tract has been evaluated using data from three case-control studies conducted in Italy between 1992 and 2000. The first study included 598 cases with incident, histologically confirmed cancers of the oral cavity and pharynx and 1491 hospital controls admitted to the same network of hospitals as cases for acute, nonneoplastic diseases. The second one included 304 subjects with squamous cell carcinoma of the esophagus and 743 controls. The third one included 460 laryngeal cancer cases and 1088 controls. A score summarizing eight of the major characteristics of the Mediterranean diet was used. Odds ratios and corresponding 95% confidence intervals (CIs) for increasing levels of this score were estimated using unconditional regression models, adjusted for age, sex, study center, years of education, tobacco consumption, body mass index, and total energy intake. For all cancers considered, a reduced risk was found for increasing levels of the Mediterranean score: the odds ratios for subjects with six or more Mediterranean characteristics, compared with those with less than three characteristics, were 0.40 (95% CI, 0.26-0.62) for oral and pharyngeal, 0.26 (95% CI, 0.13-0.51) for esophageal, and 0.23 (95% CI, 0.13-0.40) for laryngeal cancer. All of the estimates were consistent in strata of the major identified risk factors for these neoplasms. This study provides evidence that an a priori defined nutritional pattern, which includes several aspects of the Mediterranean diet, favorably affects the risk of cancers of the upper aerodigestive tract.

Alcohol and tobacco, alone or in combination, are associated with an increased risk of various cancers, including those of the upper aero-digestive tract and liver. Both alcohol and tobacco use can increase the risk of cancer of the oral cavity and throat (pharynx, and their combined use has a multiplicative effect on risk. Moreover, those regions of the mouth and pharynx that are more directly exposed to alcohol or tobacco are more likely to be affected by cancer than other regions. A similar effect was found with respect to cancer of the voice box (larynx). For squamous cell carcinoma of the esophagus, alcohol and tobacco also appear to increase risk synergistically. With liver cancer, in contrast, alcohol consumption and tobaacco use appear to be independent risk factors.

The relation between selected aspects of diet and the risk of oral and pharyngeal cancer was considered in a few cohort studies and approximately 30 case-control studies. These studies reported consistent inverse associations with fruit and vegetable consumption. beta-carotene, vitamin C and selected flavonoids were also inversely related to risk, although it remains difficult to disentangle their potential effect from that of fruit and vegetables. Whole-grain cereals, but not refined grain ones, were also favorably related to the risk of oral and pharyngeal cancer. The results were not consistent for other foods, including meat, fish, eggs, milk and dairy products, but it is now possible to exclude a strong relation with oral and pharyngeal cancer risk. Data are also reassuring for coffee and tea, while hot maté drinking has been related to increased risk in studies from Argentina and Brazil. There is no consistent association with total fat intake, but monounsaturated fats (and olive oil) have resulted inversely related to risk. In developed countries, selected aspects of diet may account for 20% to 25% of oral and pharyngeal cancers. This proportion is likely greater in selected developing countries.

The COVID-19 pandemic and the adoption of restrictive measurements to control the SARS-CoV-2 spread disrupted general population lifestyles including dietary behaviours. However, there is poor knowledge on potential socioeconomic and gender disparities in dietary changes. We conducted a telephone-based survey during fall 2020 on a sample of 4,400 participants representative of the population aged 65-99 years living in Lombardy, Italy. Changes in a Mediterranean lifestyle were assessed retrospectively by asking participants to report modifications in the consumption of nine food groups and five diet-related behaviours (e.g., consumption of organic and local foods) compared to the previous year (2019). We then computed a Mediterranean COVID-19 Pandemic Score (MedCovid-19 Score), reflecting changes during pandemic, ranging from -14 to 14, with increasing values indicating improvements in line with a Mediterranean lifestyle. Overall, 18.3% of the study participants worsened their Mediterranean lifestyle (MedCovid-19 Score

Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [–5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [–5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. Funding: Bill & Melinda Gates Foundation.

Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta-analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case–control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non-drinkers was 0.54 (95% confidence interval [CI] 0.38-0.76) for case–control studies and 0.64 (95% CI 0.56-0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49-0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57-0.85), and that for high drinkers was 0.45 (95% CI 0.38-0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72-0.83) from case–control studies, 0.75 (95% CI 0.65-0.85) from cohort studies, and 0.77 (95% CI 0.72-0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. Conclusion: The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion. (HEPATOLOGY 2007.)

After a steady increase since the 1950s, laryngeal cancer mortality had tended to level off since the early 1980s in men from most European countries. To update trends in laryngeal cancer mortality in Europe, age-standardized (world standard) mortality rates per 100,000 were derived from the WHO mortality database for 33 European countries over the period 1980-2001. Jointpoint analysis was used to identify significant changes in mortality rates. In the European Union (EU) as a whole, male mortality declined by 0.8% per year between 1980 and 1989, by 2.8% between 1989 and 1995, by 5.3% between 1995 and 1998, and by 1.5% thereafter ( I rates were 5.1/100,000 in 1980-1981 and 3.3/100,000 in 2000-2001). This mainly reflects a decrease in rates in men from western and southern European countries, which had exceedingly high rates in the past. Male laryngeal mortality rose up to the early 1990s, and leveled off thereafter in several countries from central and eastern Europe. In 20002001 there was still a 10-15-fold variation in male laryngeal mortality between the highest rates in Croatia (7.9/100,000) and Hungary (7.7/100,000) and the lowest ones in Sweden (0.5/100,000) and Finland (0.8/100,000). Laryngeal cancer mortality was comparatively low in women from most European countries, with stable rates around 0.3/100,000 in the EU as a whole over the last 2 decades. Laryngeal cancer trends should be interpreted in terms of patterns and changes in exposure to alcohol and tobacco. Despite recent declines, the persistence of a wide variability in male laryngeal cancer mortality indicates that there is still ample scope for prevention of laryngeal cancer in Europe. (c) 2006 Wiley-Liss, Inc.

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975-2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000-2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000-2004. In France and Italy - which had the highest rates in the past - male rates have steadily declined during the last two decades (annual percent change, APC 5 24.8% in 1998-2004 in France and 22.6% in 1986-2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC 5 6.9% in 1975-1993 and 1.4% in 1993-2004) and Slovakia (16.9/100,000; APC 5 0.14% in 1992-2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.3/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC 5 4.7% in 1975-2004) and Denmark (1.6/100,000; APC 5 1.3% in 1975-2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe.

A varied diet may have a favorable role against digestive tract cancers. We analyzed the relationship between diet diversity (i.e. measured by the number of different foods consumed at least once per week) and the risk of esophageal cancer. We considered data from a case-control study conducted between 1992 and 1997 in northern Italy on 304 squamous cell esophageal cancer cases below age 78 years and 743 controls admitted to hospital for acute, normeoplastic conditions, unrelated to tobacco or alcohol consumption. There was a significant inverse association for total diet diversity: the multivariate odds ratio (OR), adjusted for age, sex, area of residence, education, tobacco smoking, alcohol drinking and non-alcohol energy intake was 0.42 (95% confidence interval, CI: 0.25-0.71) for subjects in the highest versus those in the lowest quartile of diversity. Inverse relations were also found for diversity within vegetables (OR = 0.34, 95% CI: 0.21-0.55) and fruits (OR = 0.51, 95% CI: 0.33-0.80). No significant association was found for meat and cereal diversity. These results add epidemiological support to the dietary guidelines recommending a more varied diet, particularly in fruit and vegetables, for esophageal cancer prevention. (C) 2008 Wiley-Liss, Inc.

The intake of flavonoids has been inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. We used data from a case-control study conducted in Italy between 1992 and 2005 to examine the relationship between flavonoid intake and oral and pharyngeal cancer risk. The study included 805 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,081 hospital controls admitted for acute, nonneoplastic conditions. We have applied data on food and beverage content of six major classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. The odds ratios (OR) were calculated using multiple logistic regression models, conditioned on study center, sex, and age. After adjustment for education, tobacco, alcohol, body mass index, and non–alcohol energy intake, ORs for the highest versus the lowest quintile of intake were 0.51 [95% confidence intervals (95% CI), 0.37-0.71] for flavanones, 0.62 (CI, 0.43-0.89) for flavonols, and 0.56 (95% CI, 0.40-0.78) for total flavonoids. No significant association emerged for isoflavones (OR, 0.90), anthocyanidins (OR, 0.86), flavan-3-ols (OR, 0.84), and flavones (OR, 0.75). The ORs were consistent across strata of age, sex, education, body mass index, tobacco, and alcohol. After allowance for vegetable and fruit consumption, the inverse relations with total flavonoids and flavanones remained significant, whereas that with flavonols became nonsignificant. None of the associations were significant after further allowance for vitamin C, probably on account of the high collinearity between these compounds. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1621–5)

Background: Flavonoids may play an important role in explaining the protective effect of vegetables and fruit against cancer. Patients and methods: To investigate the relation between flavonoids and laryngeal cancer risk, we have applied data on the composition of foods and beverages in terms of six principal classes of flavonoids to a case-control study of laryngeal cancer conducted from 1992 to 2000 in Italy. Cases were 460 subjects with incident, histologically confirmed laryngeal cancer; controls were 1088 patients admitted for acute, non-neoplastic diseases. Odds ratios (OR) were estimated through multiple logistic regression models, including terms for sociodemographic and lifestyle factors, tobacco smoking, alcohol consumption and energy intake. Results: Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only for flavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake. Conclusion: This study provides support for a beneficial effect of selected flavonoids on laryngeal cancer risk. RI Parpinel, Maria/B-1605-2012

Background A role for diet in laryngeal carcinogenesis has been suggested, but only a few studies have examined the potential relationship with a wide variety of macronutrients. Patients and methods A case–control study was conducted between 1992 and 2000 in Italy and Switzerland, including 527 incident cases of laryngeal cancer, and 1297 controls hospitalized for acute, non-neoplastic conditions. The subjects’ usual diet was investigated through a validated food frequency questionnaire, including 78 foods and beverages. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. Results Cases reported higher energy intake than controls. The continuous OR for 100 kcal/day was 1.16 (95% CI 1.12–1.21) for alcohol energy, and 1.02 (95% CI 1.01–1.04) for non-alcohol energy. A significantly increased risk of laryngeal cancer was observed for animal protein (continuous OR = 1.21, 95% CI 1.03–1.41), polyunsaturated fats other than linoleic and linolenic fatty acids (OR = 1.43, 95% CI 1.19–1.70), and cholesterol intake (OR = 1.43, 95% CI 1.19–1.71). Laryngeal cancer risk was slightly reduced with increasing vegetable protein (OR = 0.75, 95% CI 0.62–0.91), sugar (OR = 0.84, 95% CI 0.71–1.00) and monounsaturated fatty acid intake (OR = 0.83, 95% CI 0.70–0.99). Conclusions Laryngeal cancer cases have a higher energy intake than control subjects, and report a higher intake of animal protein and cholesterol.

The role of aspirin on the risk of cancers of the upper aerodigestive tract was investigated in the combined data of three Italian case-control studies, including 965 cases and 1779 hospital controls. The odds ratio was 0,33 for users of greater than or equal to5 years, and 0.51 for greater than or equal to5 years since first use. (C) 2003 Cancer Research UK.

Introduction: Smell and taste loss are characteristic symptoms of SARS-CoV-2 infection. The aim of this study is to investigate the prevalence and risk factors associated with olfactory and gustatory dysfunctions in coronavirus disease (COVID-19) patients. Methods: We conducted an observational, retrospective study on 376 patients with documented SARS-CoV-2 infection admitted to the San Gerardo Hospital in Monza, Italy, from March to July 2020. All patients answered a phone questionnaire providing information on age, sex, smoking status, and clinical characteristics. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated through logistic regression models including relevant covariates. Results: The prevalence of olfactory and gustatory dysfunctions in COVID-19 patients was 33.5 and 35.6%, respectively. Olfactory dysfunctions were significantly directly associated with current smoking and history of allergy, the multivariable ORs being 6.53 (95% CI 1.16–36.86) for current smokers versus never smokers, and 1.89 (95% CI 1.05–3.39) for those with an allergy compared to those without any allergy. Respiratory allergy in particular was significantly associated with olfactory dysfunctions (multivariable OR 2.30, 95% CI 1.02–5.17). Significant inverse associations were observed for patients aged 60 years or more (multivariable OR 0.33, 95% CI 0.19–0.57) and hospitalization (multivariable OR 0.22, 95% CI 0.06–0.89). Considering gustatory dysfunctions, after allowance of other variables a significant direct association was found for respiratory allergies (OR 2.24, 95% CI 1.03–4.86), and an inverse association was found only for hospitalization (OR 0.21, 95% CI 0.06–0.76). Conclusion: Our study indicates that current smoking and history of allergy (particularly respiratory) significantly increase the risk for smell loss in COVID-19 patients; the latter is also significantly associated to taste loss. Hospitalization has an inverse association with the risk of olfactory and gustatory dysfunctions, suggesting that these may be symptoms characteristics of less severe SARS-CoV-2 infection.

To provide an up-to-date overview of recent trends in mortality from oral and pharyngeal cancer, we analyzed death certification data for 61 countries worldwide provided by the World Health Organization in 2010–2015, and, for selected most populous countries, over the period 1970–2016. For 12 largest countries, we analyzed incidence derived from Cancer Incidence in Five Continents in 1960–2012 for all oral and pharyngeal cancers and by subsites. In 2015, male age-standardized (world population) death rates per 100,000 were 5.03 in the European Union (EU), 8.33 in the Russian Federation, 2.53 in the United States (USA), and 3.04 in Japan; corresponding rates in women were 1.23, 1.23, 0.82, and 0.76. Male mortality decreased over the last decades in several European countries, with earlier and sharper declines in southern Europe; conversely, mortality was still increasing in a few eastern European countries and the United Kingdom. Mortality in men also decreased in Argentina, Australia, and Hong Kong, while it leveled off over more recent calendar years in Brazil, Japan, Mexico, the Republic of Korea, as well as in Australia and the USA. Female mortality slightly rose in various European countries. Overall incidence trends in the largest countries were broadly consistent with mortality ones, but oropharyngeal cancer incidence rose in many countries. Changes in tobacco and alcohol exposure in men over the last decades likely explain the favorable trends in oral and pharyngeal cancer mortality and incidence observed in selected countries worldwide, while increased human papillomavirus infection is likely responsible for the rise in oropharyngeal cancer incidence.

Purpose We aim to provide the most accurate and updated quantification of the effect of cigarette smoking on kidney cancer risk focusing on dose-response relationships. Methods We conducted a meta-analysis, using an innovative approach combining an umbrella review and a traditional literature search. Results Fifty-six original studies were included, providing pooled relative risks (RR) of kidney cancer of 1.39 (95% confidence interval, CI: 1.28–1.51) for current and 1.20 (95% CI: 1.14–1.27) for former compared with never smokers. Kidney cancer risk increased non-linearly with smoking intensity, the RR compared with never smokers being 1.18 (95% CI: 1.11–1.26) for five and 1.72 (95% CI: 1.52–1.95) for 30 cigarettes/day, and increased linearly with smoking duration, the RR being 1.70 (95% CI: 1.10–2.64) after 25 years. The risk linearly decreased with time-since-quitting. Conclusions Even smoking few cigarettes per day significantly increases kidney cancer risk. Quitting smoking reduces the risk, the earlier the better.

Background: Pancreatic cancer is one of the leading causes of cancer mortality. Diet may be associated with pancreatic cancer, but it is unknown whether specific dietary components contribute to its risk. The potential differential role of dietary antioxidants warrants further investigation. Methods: We analysed data from a case-control study of 326 pancreatic cancer cases and 652 controls conducted between 1991 and 2008 in Northern Italy. Subjects' usual diet was assessed through a validated and reproducible food frequency questionnaire. Using this information and an Italian food composition database, we calculated three indices of dietary total antioxidant capacity (TAC): Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric-reducing antioxidant power (FRAP). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer using multiple logistic regression models conditioned on study centre, sex and age, and adjusted for major known pancreatic cancer risk factors. Results: Significant inverse associations were found for the highest tertile of TAC compared with the lowest tertile for both TEAC and FRAP. The ORs were 0.61 (95% CI 0.39-0.94, P-value for trend 0.03) and 0.63 (95% CI 0.41-0.99, P-value for trend 0.05), respectively. Total radical-trapping antioxidant parameter was inversely, but not significantly, associated with pancreatic cancer risk, with an OR of 0.78 (95% CI 0.49-1.24, P-value for trend 0.27). Conclusions: Diet high in TAC, as measured by TEAC and FRAP, is inversely associated with pancreatic cancer risk. © 2016 Cancer Research UK.

Background: Pancreatic cancer is a leading cause of cancer death. A role of dietary factors in pancreatic carcinogenesis has been suggested. The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published 8 recommendations for cancer prevention. We evaluated the effect of adherence to the WCRF/AICR recommendations on pancreatic cancer risk. Methods: We operationalized 7 of the 8 WCRF/AICR recommendations to generate a WCRF/AICR score. We examined the association of WCRF/AICR score with pancreatic cancer in data from an Italian case-control study of 326 incident cases and 652 controls. Results: Adherence to WCRF/AICR recommendations was associated with a significantly decreased risk of pancreatic cancer. Using a WCRF/AICR score

Aim Cigarette smoking is an established risk factor for pancreatic cancer but an updated quantification of the association is lacking. Our aim is to provide the most accurate and updated estimate of the dose–response relationships between cigarette smoking and pancreatic cancer risk. Methods Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of epidemiological studies published on the issue up to April 2017. Random effects models were used to provide pooled estimates for the cigarette smoking status; dose–risk relationships were evaluated using one-stage random effects models with restricted cubic splines. Results Seventy-eight studies were included, providing a pooled relative risk (RR) of pancreatic cancer of 1.8 (95% confidence interval, CI: 1.7–1.9) for the current and 1.2 (95% CI: 1.1–1.2) for the former vs. never smokers. A sharp increase in pancreatic cancer risk was found already with a low number of cigarettes and up to 30 cigarettes/day (RR 2.2, 95% CI: 1.9–2.4). Similarly, the risk of pancreatic cancer steady increased after a few years of smoking up to 30 years (RR 1.8, 95% CI: 1.6–2.0). The risk rapidly decreased with increasing time since quitting and was 0.6 (95% CI: 0.5–0.7, for the former vs. current smokers) after 20 years of quitting. Conclusions The present meta-analysis indicates that pancreatic cancer risk sharply increases with a low number of cigarettes or after a few years of smoking and that it rapidly decreases a few years after cessation, although it takes almost 20 years to reach that of never smokers.

Background and aims There are concerns that incretin-based antidiabetic drugs – including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists – increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting. Methods and results Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry. The multivariate odds ratios (ORs) of HF in relation to current use of incretin-based drugs as compared to current use of two or more oral antidiabetics was 1.06 (95% confidence interval, CI, 0.83–1.35), with no evidence of a trend in risk with increasing duration of use. The corresponding ORs were 1.10 (95% CI 0.85–1.41) for DPP-4 inhibitors and 0.84 (95% CI 0.48–1.47) for GLP-1 receptor agonists. Estimates were consistent in various sensitivity analyses. Conclusions This study indicates that incretin-based drugs are not associated with an increased risk of hospitalization for HF, thus providing further reassurance on the cardiovascular safety of these antidiabetic drugs in the clinical practice.