Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

[Analysis of predictive factors for non-adherence to organized screening for colorectal and breast cancers in the pre-pandemic period (2018-2019) in Lombardy Region (Northern Italy)]. / Analisi dei fattori predittivi della mancata adesione allo screening organizzato per i tumori del colon retto e della mammella nel periodo pre-pandemico (2018-2019) in Lombardia.

BACKGROUND: according to the International Agency for Cancer Research on Cancer, in 2022, breast cancer is the most common cancer in the Italian population, followed by colorectal cancer. Oncological screenings represent an effective secondary prevention strategy to counteract colorectal and breast cancers, significantly reducing mortality. In Lombardy Region (Northern Italy), screening programmes have been active since 2007, but adherence, especially in specific population subgroups, remains lower than expected. OBJECTIVES: to analyse potential predictors of non-adherence to colorectal and breast cancer screening in the Lombardy Region during the pre-pandemic period of 2018-2019. DESIGN: a retrospective cohort study aimed at investigating the role of sociodemographic variables, health status, and access to the healthcare system on non-adherence to colorectal and breast cancer screening. Statistical analyses were conducted separately by each Agency for Health Protection (ATS). The results of the models were synthesized across the Lombardy region through random-effects meta-analysis. SETTING AND PARTICIPANTS: residents within the territory of each ATS in Lombardy as of 01.01.2018 and aged between 49 and 69 years at the beginning of the follow-up. MAIN OUTCOMES MEASURES: adherence to colorectal and breast cancer screenings. RESULTS: during the study period, across the Lombardy Region, 2,820,138 individuals were eligible to participate in colorectal cancer screening, and 1,357,344 women were eligible to participate in breast cancer screening, with an invitation coverage of 87% and 86%, respectively.For breast cancer screening, older age, cardiopathy, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases (IBD), autoimmune diseases, and presence of a rare disease are associated with a reduced risk of non-adherence. Conversely, foreign citizenship, oncological diagnosis, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, and presence of a neurological diagnosis are associated with significant excess risks of non-participation. For colorectal cancer screening, factors favouring adherence include female gender, older age, cardiopathy, COPD, autoimmune diseases, and having access/utilization of primary care. Non-adherence is associated with foreign citizenship, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, IBD, neurological diseases, residence in assisted living facilities, use of integrated home care, and presence of disability. CONCLUSIONS: this is the first study conducted in the Lombardy Region which explores the theme of equity of access to organized screenings. This analysis highlights how sociodemographic determinants, chronic conditions, and access to the healthcare and social healthcare system constitute significant risk factors for non-adherence to screening programmes. Based on the results of this analysis, communication and/or organizational change interventions will be developed to counteract inequalities in access to effective prevention procedures.

Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

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

[Excess mortality risk in nursing care homes before and during the COVID-19 outbreak in Mantua and Cremona provinces (Lombardy Region, Northern Italy)]. / L'eccesso di rischio di morte nelle residenze sanitarie assistenziali prima e durante l'epidemia di COVID-19 nelle province di Mantova e Cremona.

OBJECTIVES: 1. to evaluate mortality risk excess in the population residing in nursing care homes (NCHs) compared to non-NCHs before the COVID-19 outbreak; 2. to verify if the outbreak modified risk excess; 3. to estimate the COVID-19 impact; 4. to ascertain incidence-mortality relationship. DESIGN: cohort study. SETTING AND POPULATION: Mantua and Cremona provinces (Lombardy Region, Northern Italy) - included in ATS Val Padana - with COVID-19 incidence rate 7.5‰ and 16.9‰, respectively. Inhabitants aged >= 75 years as of 1st January 2018, 2019, and 2020 (three cohorts), stratified in NCH or not. The indicators calculated were: 1. rate ratio (RR) for NCH vs non-NCH, adjusted by gender, age, chronic diseases number, at least 1 hospitalisation, at least 1 Emergency room access in the previous year, for 2018, 2019, and 2020; 2. adjusted RR, 2019 and 2020 vs 2018, both sub-cohorts (i.e., NCH and non-NCH). MAIN OUTCOME MEASURES: first four-month period mortality of the considered years. RESULTS: aproximately 100,000 inhabitants by year, 7% in NCH. In the 2020 first four-month period, 4,343 deaths occurred of which 45% in NCH. RR in NCH population vs non-NCH for the year 2018 was 2.13 (95%CI 1.94-2.34); for the year 2019 was 2.70 (95%CI 2.43-3.00); for the year 2020 was 6.98 (95%CI 6,49-7,50). Adjusted RR for NCH population in 2020 vs 2018 was 2.22 (95%CI 2.05-2.42) in the whole ATS Val Padana; 1.58 (95%CI 1.40-1.77) in Mantua Province; 2.93 (2.62-3.27) in Cremona Province. Adjusted RR in non-NCH population in the year 2020 vs 2018 was 1.59 (95%CI 1.48-1.70) in the whole ATS; 1.34 (95%CI 1.23-1.46) in Mantua Province; 1.89 (95%CI 1.73-2.07) in Cremona Province. CONCLUSIONS: the NCH population experienced an excess risk mortality compared to non-NCH before the COVID-19; this excess increased during the outbreak. In 2020, in NCHs the risk was more than double compared to the 2018 risk, while in non-NCHs it rose approximately by 60%. The gap between NCHs/non-NCHs COVID-19 impact was higher in Cremona than in Mantua.

Diabetes and risk of cancer incidence: results from a population-based cohort study in northern Italy.

BACKGROUND: Aim of this study was to compare cancer incidence in populations with and without diabetes by cancer site. Furthermore, we aimed at comparing excess risk of cancer according to diabetes type, diabetes duration and treatment, the latter as regards Type 2 diabetes. METHODS: By use of the Reggio Emilia diabetes registry we classified the resident population aged 20-84 at December 31st 2009 into two groups: with and without diabetes. By linking with the cancer registry we calculated the 2010-2013 cancer incidence in both groups. The incidence rate ratios (IRR) by cancer site, type of diabetes, diabetes duration, and as concerns Type 2 diabetes, by treatment regimen were computed using Poisson regression model and non-diabetic group as reference. RESULTS: The cohort included 383,799 subjects without diabetes and 23,358 with diabetes. During follow-up, we identified 1464 cancer cases in subjects with diabetes and 9858 in the remaining population. Overall cancer incidence was higher in subjects with diabetes than in those without diabetes (IRR = 1.22, 95%CI 1.15-1.29), with similar results focusing on subjects with at least 2-year diabetes duration. Cancer sites driving overall increased risk were liver, pancreas, Colon rectum, and bladder in both sexes, corpus uteri for females. There was also suggestion of an increased risk for kidney cancer in females and a decreased risk for prostate cancer. Excess risk was found in patients with Type 2 diabetes, more marked among insulin users, especially with combined therapy. We observed an increasing risk for diabetes duration up to 10 years from diagnosis (IRR = 1.44, 95%CI 1.29-1.61) and a subsequent decrease to moderate-higher risk (IRR = 1.15, 95%CI 1.04-1.30). CONCLUSIONS: Our study indicates that the strength of association depends on specific cancer site. Insulin, monotherapy or combined therapy, per se or as an indication of poor blood glucose control, in addition to diabetes duration, may play a role in the association of diabetes and cancer.

Differences in mortality by immigrant status in Italy. Results of the Italian Network of Longitudinal Metropolitan Studies.

Despite a rapid increase in immigration from low-income countries, studies on immigrants' mortality in Italy are scarce. We aimed to describe differences in all and cause-specific mortality among immigrants and Italians residing in Turin and Reggio Emilia (Northern Italy), two cities participating in the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS). We used individual data from the municipal population registers linked to the cause of death registers. All people aged 1-64 years residing between 2001 and 2010 were enrolled (open cohort) and followed up until 2013. The mortality of citizens from high migratory pressure countries (as a whole, and for each macro-area group) was compared with that of Italians; differences were estimated by Poisson regression adjusted by age and calendar year mortality rate ratios (MRRs), and by age-standardized mortality ratios for the analysis of cause-specific mortality. Compared with Italians, immigrants had lower overall mortality (MRR for men: 0.82, 95 % CI: 0.75-0.90; for women: 0.71, 95 % CI: 0.63-0.81). Sub-Saharan Africans experienced a significant higher mortality than Italians (MRR for men 1.29, 95 % CI: 1.03-1.61; for women: 1.70, 95 % CI: 1.22-2.36). Higher mortality for immigrants compared to Italians was observed for infectious diseases, congenital anomalies, some site-specific tumours and homicide mortality. Our study showed heterogeneity in mortality across the macro-areas of origin, and in particular Sub-Saharan Africans seemed to be a vulnerable population. The extension to other cohorts of IN-LiMeS will allow the health status of immigrants and vulnerable groups to be studied and monitored in more depth.

Long-term mortality patterns in a residential cohort exposed to inorganic selenium in drinking water.

Selenium (Se) is a metalloid of considerable nutritional and toxicological importance in humans. To date, limited epidemiologic evidence exists about the health effects of exposure to this trace element in drinking water. We investigated the relationship between Se levels in water and mortality in the municipality of Reggio Emilia, Italy, where high levels of Se were previously observed in drinking water. From 1974 to 1985, 2065 residents consumed drinking water with Se levels close to the European standard of 10µg/l, in its inorganic hexavalent form (selenate). Follow-up was conducted for the years 1986-2012 in Reggio Emilia and a lesser exposed comparison group of around 100,000 municipal residents, with comparable socio-demographic characteristics. Overall mortality from all causes, cardiovascular disease and cancer showed little evidence of differences. However, excess rate ratios were seen for some site specific cancers such as neoplasms of buccal cavity and pharynx, urinary tract, lymphohematopoietic tissue, melanoma, and two neurodegenerative diseases, Parkinson's disease and amyotrophic lateral sclerosis. Excess mortality in the exposed cohort for specific outcomes was concentrated in the first period of follow-up (1986-1997), and waned starting 10 years after the high exposure ended. We also found lower mortality from breast cancer in females during the first period of follow-up. When we extended the analysis to include residents who had been consuming the high-selenium drinking water for a shorter period, mortality rate ratios were also increased, but to a lesser extent. Overall, we found that the mortality patterns related to long-term exposure to inorganic hexavalent selenium through drinking water were elevated for several site-specific cancers and neurodegenerative disease.

Differences in diabetes prevalence and inequalities in disease management and glycaemic control by immigrant status: a population-based study (Italy).

BACKGROUND: The diabetes prevalence increases at an alarming rate around the world and understanding disparities in occurrence, care management, and health outcomes may be a starting point towards achieving more effective strategies to prevent and manage it. The aims of this study are to compare immigrants and Italians in terms of the differences in diabetes prevalence and to evaluate inequalities in disease management and glycaemic control by using information included in Reggio Emilia diabetes register. METHODS: We retrieved from the diabetes register subjects aged 20-74 on December 31(st), 2009. Using citizenship, we created three main groups: Italy, High Developed Countries (HDC), and High Migration Pressure Countries (HMPC). These were split into sub-regions of origin. We calculated age-adjusted prevalence by gender and sub-region. Using logistic regression model, we analyzed the association between area of origin and following indicators: 1) not being in care of diabetes clinics; 2) not having glycated haemoglobin (HbA1c) test in 2010; 3) among those tested, having a HbA1c value > = 9% (75 mmol/mol). RESULTS: We found 15,889 Italian and 1,295 HMPC citizens with diabetes. HMPC citizens had higher age-adjusted prevalence of diabetes than Italians (females 5.0% vs 3.6%; males 6.5% vs 5.5%). The excess was mostly due to a strong excess in immigrants from Southern Asia (females 9.7%, males 10.2%) and Northern Africa (females 9.3%, males 5.9%). HMPC citizens were cared for by diabetes clinics in a similar proportion than Italians (OR: 1.08; 95% CI: 0.93-1.25), but had a greater odds of not being tested for HbA1c (OR: 1.51; 95% CI: 1.34-1.71), as well as of having HbA1c values equal to or over 9% (OR: 2.06; 95% CI: 1.80-3.14). The outcomes were poorer in HMPC females for the first two outcomes, while there was no difference for the HbA1c values (Wald test for heterogeneity p = 0.0850; p = 0.0156; p = 0.6635, respectively). CONCLUSIONS: Our findings highlight the need for gender-oriented actions for prevention and early diagnosis of the diabetes to contrast the higher risk in Northern Africans and Southern Asians. Further studies are required to determine whether the protocols in use are adequate for different immigrant groups.

Effects of immigrant status on Emergency Room (ER) utilisation by children under age one: a population-based study in the province of Reggio Emilia (Italy).

BACKGROUND: The primary aim of this study was to assess the effect of immigrant status on Emergency Room (ER) utilisation by children under age one, considering all, non-urgent, very urgent, and followed by hospitalisation visits. The second aim was to investigate the role played by mother's educational level in the relationship between citizenship and ER utilisation. METHODS: The cohort study included all healthy singleton live births in the years 2008-2009 and residing in the province of Reggio Emilia, followed for the first year of life in order to study their ER visits. The outcomes were the ER utilisation rate for all, non-urgent, very urgent, and followed by hospitalisation visits. The main explanatory variable was mother's citizenship. Other covariates were mother's educational level, maternal age, parity, and child gender. Multivariate analyses (negative binomial regression and zero inflated when appropriate) were performed. Adjusted utilisation Rate Ratios (RR) and their 95% Confidence Intervals (95% CI) were calculated. Trend for age in months by citizenship is depicted. RESULTS: There were 3,191 children (36.4%) with at least one ER visit in the first year of life. Adjusted RR show a significantly greater risk of ER visit for immigrants than for Italians: (RR 1.51; 95% CI 1.39-1.63). Immigrants also had a higher risk of non-urgent visits (RR 1.72; 95% CI 1.48-2.00) and for visits followed by hospitalizations (RR 1.58; 95% CI 1.33-1.89). For very urgent visits, the immigrants had a slightly higher risk compared to Italians (RR 1.25; 95% CI 0.98-1.59).The risk of ER visits is higher in the first two months of life (RR(1st vs 3rd-12th) 2.08; 95% CI 1.93-2.24 and RR(2nd vs 3rd-12th) 1.45; 95% CI 1.33-1.58, respectively). Considering all visits, the ER utilisation rate was inversely related with maternal education only for Italians (low educational level 44.0 and high educational level 73.9 for 100 children; p value for trend test < 0.001). CONCLUSIONS: Our study observed a higher use of ER services by immigrant children and, to a lesser extent, by children of less educated Italian mothers. In immigrants, the excess is mostly due to non-urgent visits and only slightly to high acute conditions.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy.

OBJECTIVE: To assess the effect of insulin on cancer incidence in type 1 (T1DM) and type 2 diabetes (T2DM). METHODS: The cohort included all 401,172 resident population aged 20-84 in December 2009 and still alive on December 2011, classified for DM status. Drug exposure was assessed for 2009-2011 and follow up was conducted from 2012 to 2016 through the cancer registry. Incidence rate ratios (IRRs) were computed for all sites and for the most frequent cancer sites. RESULTS: among residents, 21,190 people had diabetes, 2282 of whom were taking insulin; 1689 cancers occurred, 180 among insulin users. The risk for all site was slightly higher in people with T2DM compared to people without DM (IRR 1.21, 95% CI 1.14-1.27), with no excess for T1DM (IRR 0.73, 95% CI 0.45-1.19). The excess in T2DM remained when comparing with diet-only treatment. In T2DM, excess incidence was observed for liver and pancreas and for NETs: 1.76 (95% CI 1.44-2.17) and 1.37 (95% CI 0.99-1.73), respectively. For bladder, there was an excess both in T1DM (IRR 3.00, 95% CI 1.12, 8.02) and in T2DM (IRR1.27, 95% CI 1.07-1.50). CONCLUSIONS: Insulin was associated with a 20% increase in cancer incidence. The risk was higher for liver, pancreatic, bladder and neuroendocrine tumours.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

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

Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province.

The study aims to describe the distribution of patients with type 2 diabetes (T2D) by care plan and to highlight determinants of underuse and overuse of integrated care (IC). This cross-sectional study included all T2D patients resident in Reggio Emilia on 31/12/2015 based on the population-based diabetes registry. Eligibility for IC requires good glycaemic control, no rapid insulin, no kidney failure and no diabetes complications. We calculated the proportion of IC underuse and overuse and adjusted prevalence estimate using multivariate logistic regression. Determinants were age, sex, citizenship, district of residence and time since diagnosis. Of 29,776 patients, 15,364 (51.6%) were in diabetes clinic plan, 9851 (33.1%) in IC plan and 4561 (15.3%) not in any care plan (i.e., in Other group). There were 10,906 (36.6%) patients eligible for IC, of whom 1000 in Other group. When we adjusted for all covariates and restricted the analysis to patients included in care plans, the proportion of those eligible for IC plan but cared for in diabetes clinic plan (i.e. underuse of IC) was 28% (n = 3028/9906; 95%CI 27-29). Similarly, the proportion of those not eligible for IC but cared for in IC plan (i.e. overuse of IC) was 11% (n = 1720/11,896; 95%CI 10-11).The main determinant of both IC underuse and overuse was the district of residence. Foreign status was associated with underuse (37%; 95%CI 33-43), while old age (≥80 years) with both underuse (36%; 95%CI 0.33-0.38) and overuse (23%; 95%CI 22-25). The criterion for suspension of IC plan most frequently found was renal failure, followed by hospitalization for diabetes-related complications. Patients are more often allocated to more specialized settings than not. Healthcare provider-related factors are the main determinants of inappropriate setting allocation.

Correction: Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province.

[This corrects the article DOI: 10.1371/journal.pone.0219965.].

Effect of different glucose-lowering therapies on cancer incidence in type 2 diabetes: An observational population-based study.

AIM: To assess the effect of metformin on cancer incidence in type 2 diabetes (T2DM), considering possible interactions with other glucose-lowering drugs and diabetes duration. METHODS: Study cohort included diabetes patients aged 20-84 on December 2009, still alive and resident in Reggio Emilia province as of December 2011. Drug exposure was assessed for 2009-2011; subjects taking metformin continuously, with or without other hypoglycaemic drugs, were compared to subjects on diet-only therapy. The cohort was followed up from 2012 to 2014 through the cancer registry. Age- and sex-adjusted incidence rate ratios (IRRs) were computed using Poisson regression models for all sites, lung, breast, liver, colorectal, prostate and pancreatic cancer. RESULTS: The cohort includes 17,026 people with T2DM, 7460 taking metformin. 887 cancers occurred during follow-up, 348 among metformin users. Cancer risk was similar in T2DM patients using metformin and those on diet-only. The risk for prostate (IRR = 0.65; 95%CI:0.36; 1.17), liver (IRR = 0.82; 95%CI:0.36; 1.85) and breast (IRR = 0.77; 95%CI:0.43; 1.40) cancers only was slightly reduced; for lung (IRR = 1.52; 95%CI:0.92; 2.50), pancreas (IRR = 1.51; 95%CI:0.59:3.89) and colon-rectum (IRR = 1.71; 95%CI:0.94; 3.08) the risk was slightly increased. CONCLUSIONS: There is no evidence of antitumor effect of metformin. A possible decrease only for breast, liver and prostate cancer, is compatible with random fluctuations.

Effectiveness of integrated care model for type 2 diabetes: A population-based study in Reggio Emilia (Italy).

AIMS: To compare the effectiveness of integrated care with that of the diabetes clinic care model in terms of mortality and hospitalisation of type 2 diabetes patients with low risk of complications. METHODS: Out of 27234 people with type 2 diabetes residing in the province of Reggio Emilia on 31/12/2011, 3071 were included in this cohort study as eligible for integrated care (i.e., low risk of complications) and cared for with the same care model for at least two years. These patients were followed up from 2012 to 2016, for all-cause and diabetes-related mortality and hospital admissions. We performed a Poisson regression model, using the proportion of eligible patients included in the integrated care model for each general practitioner as an instrumental variable. RESULTS: 1700 patients were cared for by integrated care and 1371 by diabetes clinics. Mortality rate ratios were 0.83 (95%CI 0.60-1.13) and 0.95 (95%CI 0.54-1.70) for all-cause and cardiovascular mortality, respectively, and incidence rate ratios were 0.90 (95%CI 0.76-1.06) and 0.91 (95%CI 0.69-1.20) for all-cause and cardiovascular disease hospitalisation, respectively. CONCLUSION: For low risk patients with type 2 diabetes, the integrated care model involving both general practitioner and diabetes clinic professionals showed similar mortality and hospitalisation as a model with higher use of specialized care in an exclusively diabetes clinic setting.

Cancer incidence following long-term consumption of drinking water with high inorganic selenium content.

Selenium, a trace element to which humans are exposed mainly through diet, has been involved in the etiology of human cancer. We investigated the long-term effects of selenium exposure on cancer incidence using data from a natural experiment in Northern Italy. During the 1970s-1980s, in a part of the Italian municipality of Reggio Emilia, residents were inadvertently exposed to unusually high levels of inorganic hexavalent selenium (selenate) through drinking water. We followed the exposed residents for 28years, generating data on incidence (when available) and mortality rates for selected cancer sites; the remaining municipal residents comprised the unexposed (reference) group. We observed no substantial difference in overall cancer incidence comparing exposed and unexposed cohorts. We detected, however, a higher incidence of cancer at some sites, and for a few of them, namely cancers of the buccal cavity and pharynx, melanoma, urinary tract and lymphoid tissue, the excess incidence was particularly evident in the first period of follow-up but decreased over time. Overall, these results suggest that consumption of water with levels of selenium in its inorganic hexavalent form close to the European standard, 10µg/L, may have unfavourable effects on cancer incidence.

Cohort profile: the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS), a multicentre cohort for socioeconomic inequalities in health monitoring.

PURPOSE: The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. PARTICIPANTS: IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. FINDINGS TO DATE: The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. FUTURE PLANS: We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts.