Socioeconomic status, smoking, and lung cancer: mediation and bias analysis in the SYNERGY study.

BACKGROUND: Increased lung-cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits, and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects (NDE) and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately as well as by multiple quantitative bias analysis, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung-cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung-cancer risk in the multiple bias analysis. Lung-cancer risks remained increased for lower SES groups, with higher risks in men [4th versus 1st (highest) SES quartile: CDE 1.50 (SI 1.32-1.69)] than women [CDE 1.20 (SI 1.01-1.45)]. NDE were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung-cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

Prevalent occupational exposures and risk of lung cancer among women: Results from the application of the Canadian Job-Exposure Matrix (CANJEM) to a combined set of ten case-control studies.

BACKGROUND: Worldwide, lung cancer is the second leading cause of cancer death in women. The present study explored associations between occupational exposures that are prevalent among women, and lung cancer. METHODS: Data from 10 case-control studies of lung cancer from Europe, Canada, and New Zealand conducted between 1988 and 2008 were combined. Lifetime occupational history and information on nonoccupational factors including smoking were available for 3040 incident lung cancer cases and 4187 controls. We linked each reported job to the Canadian Job-Exposure Matrix (CANJEM), which provided estimates of probability, intensity, and frequency of exposure to each selected agent in each job. For this analysis, we selected 15 agents (cleaning agents, biocides, cotton dust, synthetic fibers, formaldehyde, cooking fumes, organic solvents, cellulose, polycyclic aromatic hydrocarbons from petroleum, ammonia, metallic dust, alkanes C18+, iron compounds, isopropanol, and calcium carbonate) that had lifetime exposure prevalence of at least 5% in the combined study population. For each agent, we estimated lung cancer risk in each study center for ever-exposure, by duration of exposure, and by cumulative exposure, using separate logistic regression models adjusted for smoking and other covariates. We then estimated the meta-odds ratios using random-effects meta-analysis. RESULTS AND CONCLUSIONS: None of the agents assessed showed consistent and compelling associations with lung cancer among women. The following agents showed elevated odds ratio in some analyses: metallic dust, iron compounds, isopropanol, and organic solvents. Future research into occupational lung cancer risk factors among women should prioritize these agents.

Occupational exposure to nickel and hexavalent chromium and the risk of lung cancer in a pooled analysis of case-control studies (SYNERGY).

There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Two Relevant Diseases of the Endocrine System: Diabetes Mellitus and Thyroid Disorders.

BACKGROUND: diabetes mellitus (DM) and thyroid disorders (TDs) are two of the most prevalent and relevant endocrine disorders worldwide, and determining their occurrence and their follow-up pathways is essential. In Italy, due to the presence of a universal health care system, administrative data can be effectively used to determine these measurements. DM is an ideal model for surveillance with administrative data, due to its specific pharmacologic treatment, high rate of hospitalization, and specific care units. The identification of TDs, conversely, is more challenging: they are less frequently managed in a hospital setting, and even if the treatment is highly specific, subclinical forms often do not need any pharmacological treatment. OBJECTIVES: to identify and to describe all DM and TD caseidentification algorithms by means of Italian Healthcare Administrative Databases (HADs), through the review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for "primary objectives" (I disease occurrence; II population/cohort selection; III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. Algorithms were divided between those identifying type 2/not specified DM and type 1 DM, and those created to identify hypo- and hyperthyroidism. RESULTS: of the 780 articles identified for DM, 77 were included and a further 14 papers were added by screening the references. For TD, 65 articles were identified through the search string and 5 of them were included. Of the selected articles, 64% and 80% were published after 2014 for DM and TD, respectively, and 33% (for DM) and 20% (for TD) used multicentric national or international data. Forty original algorithms for DM (29 for type 2 DM/not-specified DM, and 11 for type 1 DM) and 9 for TD (6 for hypo- and 3 for hyperthyroidism) were extracted. In 6 algorithms, specific selections were made so as not to include gestational diabetes. With regard to type 2 DM, the most commonly used sources were the drug prescription database (DPD, 27 cases), hospital discharge record database (HDD, 23 cases), and exemption from healthcare co-payment database (ECD, 19 cases). Other sources were the ambulatory care services database (ACD), birth register, and mortality record database (MRD). Among the 11 algorithms to identify type 1 DM, 9 used DPD, 7 ECD, and 6 HDD; in one case ACD codes were added, and all 11 algorithms but one was applied to a population of young people (always <35 years old). With regard to TDs, 2 algorithms from one paper for hypo and hyperthyroidism relied on DPD as the only source, the other 7 original algorithms combined DPD with HDD (5 cases), ECD (3 cases), and ACD (1 case). One paper identified autoimmune/iodine deficiency hypothyroidism by subtracting iatrogenic hypothyroidism cases (identified through records of previous procedures from HDD and ACD) from the whole hypothyroid population (identified through DPD). External validation was performed for two algorithms for DM and none for TD. The first algorithm for DM was obtained through HDD only and its sensitivity ranged from 61% to 70%, the second had a sensitivity of 71%. CONCLUSION: Italian literature on the use of administrative healthcare data for case identification of diabetes is vast; the proposed algorithms are quite similar to one another, and the differences between them are rarely accompanied by clinical justification. On the contrary, the literature concerning thyroid disorders is relatively poor. Further validations of the proposed algorithms, as well as their further implementation, are needed.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Three Relevant Diseases of the Digestive and Genitourinary System: Inflammatory Bowel Diseases, Celiac Disease, and Chronic Kidney Disease.

OBJECTIVES: to identify and describe all Inflammatory Bowel Disease (IBD), Celiac Disease (CD), and Chronic Kidney Disease (CKD) case-identification algorithms by means of Italian Healthcare Administrative Databases (HADs), through a review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers; exclusion criteria were the following: no details of algorithms reported, algorithm not developed in the Italian context, exclusive use of data from the death certificate register, or from general practitioner or pediatrician databases. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for primary objectives (I disease occurrence, II population/cohort selection, III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, followback periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. RESULTS: the search string led to the identification of 98 articles for IBD, 42 articles for CD, and 390 for CKD. By screening the references, one paper for IBD was added. Finally, this led to 5, 9, and 8 pertinent papers respectively for IBD, CD, and CKD. Considering the papers on IBD and CD, specific age selections were applied to focus on children and young adult populations. When a selection on age was applied for CKD, instead, it mostly considered individuals aged more than 18 years. Three algorithms for IBD, 4 for CD, and 5 for CKD were extracted from papers and characterized. Drug prescription databases were used for both IBD and CKD algorithms, whereas the hospital discharge database and co-payment exemption database were used for IBD and CD. Pathology records and specialist visit databases were also used for CD and CKD, respectively. For each disease only one algorithm applied criteria for the exclusion of prevalent cases. External validation was performed only for Crohn's disease among IBDs, in one algorithm. CONCLUSIONS: the results of this review indicate that case identification for IBD and CD from routinely collected data can be considered feasible and can be used to perform different kinds of epidemiological studies. The same is not true for CKD, which requires further efforts, mainly to improve the detection of early stage patients.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Three Relevant Diseases of the Nervous System: Parkinson's Disease, Multiple Sclerosis, and Epilepsy.

BACKGROUND: Parkinson's Disease (PD), Multiple Sclerosis (MS), and Epilepsy are three highly impactful health conditions affecting the nervous system. PD, MS, and epilepsy cases can be identified by means of Healthcare Administrative Databases (HADs) to estimate the occurrence of these diseases, to better monitor the adherence to treatments, and to evaluate patients' outcomes. Nevertheless, the absence of a validated and standardized approach makes it hard to quantify case misclassification. OBJECTIVES: to identify and describe all PD, MS, and epilepsy case-identification algorithms by means of Italian HADs, through the review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for primary objectives (I disease occurrence; II population/cohort selection; III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. RESULTS: the search strategy led to the identification of 70 papers for PD, 154 for MS, and 100 for epilepsy, of which 3 papers for PD, 6 for MS, and 5 for epilepsy were considered pertinent. Most articles were published in the last three years (2014-2017) and focused on a region-wide setting. Out of all pertinent articles, 3 original algorithms for PD, 4 for MS, and 4 for epilepsy were identified. The Drug Prescription Database (DPD) and Hospital Discharge record Database (HDD) were used by almost all PD, MS, and epilepsy case-identification algorithms. The Exemption from healthcare Co-payment Database (ECD) was used by all PD and MS case-identification algorithms, while only 1 epilepsy case-identification algorithm used this source. All epilepsy case-identification algorithms were based on at least a combination of electroencephalogram (EEG) and drug prescriptions. An external validation had been performed by 2 papers for MS, 2 for epilepsy, and only 1 for PD. CONCLUSION: the results of our review highlighted the scarce use of HADs for the identification of cases affected by neurological diseases in Italy. While PD and MS algorithms are not so heterogeneous, epilepsy case-identification algorithms have increased in complexity over time. Further validations are needed to better understand the specific characteristics of these algorithms.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Two Relevant Diseases of the Respiratory System: Asthma and Chronic Obstructive Pulmonary Disease.

OBJECTIVES: to identify and describe all asthma and Chronic Obstructive Pulmonary Disease (COPD) case-identification algorithms by means of Italian Healthcare Administrative Databases (HADs), through the review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers; exclusion criteria were the following: no description of reported algorithms, algorithm developed outside of the Italian context, exclusive use of death certificates, pathology register, general practitioner or pediatrician data. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for primary objectives (I disease occurrence; II population/cohort selection; III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. RESULTS: the search string led to the identification of 98 and 147 papers, respectively for asthma and COPD. By screening the references, 2 papers for asthma and 7 for COPD were added. At the end of the screening process, 14 pertinent papers were identified for asthma and 31 for COPD. Half of these used healthcare data covering a time period between 2008 and 2014. More than 75% considered the age range 6-17 for asthma and >=45 for COPD. About one-third of the articles used algorithms to estimate the occurrence of these diseases. Fourteen algorithms for asthma and 16 for COPD were extracted from the papers and characterized. The Drug Prescription Database (DPD) was used by almost all asthma case-identification algorithms, while only 7 COPD algorithms used this data source. The spectrum of active ingredients was strongly overlapping between the two diseases, with different combinations of drugs and administration routes, as well as specific number of prescriptions, follow-back years, and age ranges. Age class and chronic treatment were the main disease-specific traits that emerged from the algorithms. Three external validation processes have been performed for asthma and three for COPD. High accuracy levels have been found for asthma. COPD sensitivity analyses were unsatisfactory, while a high specificity was found for algorithms based on hospital discharge records. CONCLUSION: elements from the review on the use of healthcare administrative databases represent a useful tool to decide which algorithm to adopt, based on the algorithm's individual requirements, limits, and accuracy, taking into account the specific research objective.

[Effects of high temperature and air pollution on the risk of preterm births. Analysis in six Italian cities, 2001-2010]. / Effetti delle alte temperature e dell'inquinamento atmosferico sul rischio di nascita pretermine. Analisi in sei città italiane, 2001-2010.

OBJECTIVES: to evaluate the association between short term maternal exposure to high temperature and air pollution on preterm births (PBs), which represent the first cause of perinatal mortality and morbidity in developed Countries, and to identify maternal risk factors enhancing individual susceptibility. DESIGN: time series. SETTING E PARTICIPANTS: all singleton live-births occurred in six Italian cities between 1st April and 31st October of each year in the period 2001-2010 were identified through the Certificate of Delivery Care Registry (CedAP). MAIN OUTCOME MEASURES: births occurred between 22nd and 36th week of gestation were defined as preterm births. Daily values were obtained for maximum apparent temperature (MAT), PM10, NO2, and O3. Exposures-preterm births association was estimated using a generalized additive model (GAM) with a Poisson distribution. Exposure and city-specific lag structure were computed using a non-linear distributed lag model (DLNM). RESULTS: 121,797 newborns were enrolled, 6,135 (5.0%) of which were PBs. For MAT, a linear relationship was observed for Turin (Piedmont Region, Northern Italy), Trieste (Friuli Venezia Giulia Region, Northern Italy), Rome (Lazio Region, Central Italy), and Palermo (Sicily Region, Southern Italy), while non-linear relationship was found for Bologna (Emilia-Romagna Region, Northern Italy) and Venice (Veneto Region, Northern Italy). The relative risks (RR) for MAT, computed comparing the 90th vs. the 75th percentile, vary from 1.02 (95%CI 0.95-1.09; lag 0-2) in Palermo to 1.94 (95%CI 1.32-2.85; lag 0-3) in Venice. For pollutants, a significant effect for 10 µg/m3 (IQR) increase of PM10 in Rome (RR: 1.07; 95%CI 1.02-1.12; lag 12-22) and for 16 µg/m3 (IQR) increase of O3 in Palermo (RR: 1.29; 95%CI 1.03-1.62; lag 2-9) was detected. In Rome, a significant effect modification by age and education level of the MAT-PB relationship and by education level and clinical conditions of PM10-PB was found. CONCLUSIONS: results showed a clear positive association between MAT and the risk of NP and a lower and variable effect of pollutants. It is important and necessary to limit the impact of these risk factors on the probability of NP with appropriate prevention programmes.

[Immigrants' health and socioeconomic inequalities of overall population residing in Italy evaluated through the Italian network of Longitudinal Metropolitan Studies]. / Salute degli immigrati e disuguaglianze socioeconomiche nella popolazione residente in Italia valutate attraverso la rete degli Studi Longitudinali Metropolitani.

INTRODUCTION: Describing and monitoring socioeconomic inequalities in health are the prerequisite for planning equity policies. In Italy, some cities have integrated personal information from the municipal registries with Census data and with data from healthcare information systems to set up Longitudinal Metropolitan Studies (LMS). Under the coordination of the Italian National Institute for Health, Migration, and Poverty (NIHMP), six cities in the LMS network have contributed to the present monograph: Turin, Venice, Reggio Emilia, Modena, Bologna, and Rome. MORTALITY RESULTS. Significant socioeconomic differences by level of education were seen in all the participating centres. People who live alone or in single-parent households are more likely to die, as are those living in a substandard dwelling. Immigrants resident in the six cities included in the study showed lower all-cause mortality than Italians (males: MRR 0.83; 95%CI 0.78-0.90 - females: MRR 0.70; 95%CI 0.64-0.77). Sub-Saharan Africans experienced a significant higher mortality than Italians (males: MRR 1.33; 95%CI 1.12-1.59 - females: MMR 1.69; 95%CI 1.31-2.17). Immigrants had a neonatal and post-neonatal mortality risk about 1.5 times higher than Italians (neonatal: OR 1.71; 95%CI 1.22-2.39 - post-neonatal: OR 1.63; 95%CI 1.03-2.57). A difference between Italians and immigrants was also observed for mortality in children aged 1-4 years, though less marked (OR 1.24; 95%CI 0.73-2.11). Excesses concerned particularly immigrants from North Africa and from sub-Saharan Africa as well as those residing in Italy for >5 years. HOSPITALISATION RESULTS. Hospitalisation rates are lower for immigrants than for Italians, except when due to infectious diseases, blood disorders, and, among women, for reasons linked to pregnancy and childbirth. Avoidable hospitalisation rates of adults from low migratory pressure Countries are lower than or equal to those of Italians. On the contrary, adults from low migratory pressure Countries show higher avoidable hospitalisation rates compared to Italians in every cohort, with the exception of Rome (RR 0.81; 95%CI 0.78-0.85), with RR ranging from 1.08 (95%CI 0.96-1.22) in Venice to 1.64 (95%CI 1.47-1.83) in Modena. CONCLUSIONS: Maternal and child health is the most critical area of health for immigrant population. Considering the importance that the issue of health equity has taken on in the political agenda, the data presented in this volume are a great asset, particularly in light of the long recession and the social crisis that have impacted the Country.

A Systematic Review of Case-Identification Algorithms for 18 Conditions Based on Italian Healthcare Administrative Databases: A Study Protocol.

BACKGROUND: there has been a long-standing, consistent use worldwide of Healthcare Administrative Databases (HADs) for epidemiological purposes, especially to identify acute and chronic health conditions. These databases are able to reflect health-related conditions at a population level through disease-specific case-identification algorithms that combine information coded in multiple HADs. In Italy, in the past 10 years, HAD-based case-identification algorithms have experienced a constant increase, with a significant extension of the spectrum of identifiable diseases. Besides estimating incidence and/or prevalence of diseases, these algorithms have been used to enroll cohorts, monitor quality of care, assess the effect of environmental exposure, and identify health outcomes in analytic studies. Despite the rapid increase in the use of case-identification algorithms, information on their accuracy and misclassification rate is currently unavailable for most conditions. OBJECTIVES: to define a protocol to systematically review algorithms used in Italy in the past 10 years for the identification of several chronic and acute diseases, providing an accessible overview to future users in the Italian and international context. METHODS: PubMed will be searched for original research articles, published between 2007 and 2017, in Italian or English. The search string consists of a combination of free text and MeSH terms with a common part on HADs and a disease-specific part. All identified papers will be screened for eligibility by two independent reviewers. All articles that used/defined an algorithm for the identification of each disease of interest using Italian HADs will be included. Algorithms with exclusive use of death certificates, pathology register, general practitioner or pediatrician data will be excluded. Pertinent papers will be classified according to the objective for which the algorithm was used, and only articles that used algorithms with "primary objectives" (I disease occurrence; II population/cohort selection; III outcome identification) will be considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms will be collected. Further information on specific accuracy measures from external validations, sensitivity analyses, and the contribution of each source will be recorded. This protocol will be applied for 16 different systematic reviews concerning eighteen diseases (Hypothyroidism, Hyperthyroidism, Diabetes mellitus, Type 1 diabetes mellitus, Acute myocardial infarction, Ischemic heart disease, Stroke, Hypertension, Heart failure, Congenital heart anomalies, Parkinson's disease, Multiple sclerosis, Epilepsy, Chronic obstructive pulmonary disease, Asthma, Inflammatory bowel disease, Celiac disease, Chronic kidney failure). CONCLUSION: this protocol defines a standardized approach to extensively examine and compare all experiences of case identification algorithms in Italy, on the 18 abovementioned diseases. The methodology proposed may be applied to other systematic reviews concerning diseases not included in this project, as well as other settings, including international ones. Considering the increasing availability of healthcare data, developing standard criteria to describe and update characteristics of published algorithms would be of great use to enhance awareness in the choice of algorithms and provide a greater comparability of results.

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Risk of Fractures in Youths with Celiac Disease-A Population-Based Study.

OBJECTIVE: To assess the risk of any fracture requiring hospital care in a cohort of individuals with celiac disease diagnosed in childhood/adolescence compared with reference individuals matched by age and sex. STUDY DESIGN: Our study cohort consisted of 213 635 people born and residing in Friuli-Venezia Giulia Region, Italy, in 1989-2011. We selected, through pathology reports, hospital discharge records, or co-payment exemptions, 1233 individuals with celiac disease (aged 0-17 years at diagnosis) and compared them with 6167 reference individuals matched by sex and year of birth. Fractures were identified through hospital discharge records. We calculated hazard ratios (HRs) for any fracture after celiac disease diagnosis (or index date for reference individuals) with Cox regression and ORs for any fracture before celiac disease diagnosis with conditional logistic regression. RESULTS: During the follow-up period (maximum 23 years), 22 individuals with celiac disease (9394 person-years) and 128 reference individuals (47 308 person-years) experienced a fracture, giving an overall HR of 0.87 (95% CI 0.55-1.37). The risk was not modified by sex, age at diagnosis, or calendar period of diagnosis. We obtained similar HRs when excluding fractures occurring after the age of 18 years and adjusting for maternal education or vitamin D supplementation. The odds of previous fracture also did not differ between subjects with celiac disease and reference individuals (22 and 96 cases, respectively: OR 1.15; 95% CI 0.72-1.84). CONCLUSIONS: We did not find any evidence of an increased risk of fractures during childhood and youth among patients with celiac disease.

Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium.

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

Avoidable hospitalization among migrants and ethnic minority groups: a systematic review.

Background: The numbers of migrants living in Europe are growing rapidly, and has become essential to assess their access to primary health care (PHC). Avoidable Hospitalization (AH) rates can reflect differences across migrant and ethnic minority groups in the performance of PHC. We aimed to conduct a systematic review of all published studies on AH comparing separately migrants with natives or different racial/ethnic groups, in Europe and elsewhere. Methods: We ran a systematic search for original articles indexed in primary electronic databases on AH among migrants or ethnic minorities. Studies presenting AH rates and/or rate ratios between at least two different ethnic minority groups or between migrants and natives were included. Results: Of the 35 papers considered in the review, 28 (80%) were conducted in the United States, 4 in New Zealand, 2 in Australia, 1 in Singapore, and none in Europe. Most of the studies (91%) used a cross-sectional design. The exposure variable was defined in almost all articles by ethnicity, race, or a combination of the two; country of birth was only used in one Australian study. Most of the studies found significant differences in overall AH rates, with minorities (mainly Black and Hispanics) showing higher rates than non-Hispanic Whites. Conclusions: AH has been used, mostly in the US, to compare different racial/ethnic groups, while it has never been used in Europe to assess migrants' access to PHC. Studies comparing AH rates between migrants and natives in European settings can be helpful in filling this lack of evidence.

[Assessment of an algorithm to identify paediatric-onset celiac disease cases through administrative healthcare databases]. / Valutazione di un algoritmo per l'identificazione dei casi di celiachia a insorgenza pediatrica utilizzando fonti sanitarie correnti.

OBJECTIVES: to assess the role of four administrative healthcare databases (pathology reports, copayment exemptions, hospital discharge records, gluten-free food prescriptions) for the identification of possible paediatric cases of celiac disease. DESIGN: population-based observational study with record linkage of administrative healthcare databases. SETTING AND PARTICIPANT S: children born alive in the Friuli Venezia Giulia Region (Northern Italy) to resident mothers in the years 1989-2012, identified using the regional Medical Birth Register. MAIN OUTCOME MEASURES: we defined possible celiac disease as having at least one of the following, from 2002 onward: 1. a pathology report of intestinal villous atrophy; 2. a copayment exemption for celiac disease; 3. a hospital discharge record with ICD-9-CM code of celiac disease; 4. a gluten-free food prescription. We evaluated the proportion of subjects identified by each archive and by combinations of archives, and examined the temporal relationship of the different sources in cases identified by more than one source. RESULT S: out of 962 possible cases of celiac disease, 660 (68.6%) had a pathology report, 714 (74.2%) a copayment exemption, 667 (69.3%) a hospital discharge record, and 636 (66.1%) a gluten-free food prescription. The four sources coexisted in 42.2% of subjects, whereas 30.2% were identified by two or three sources and 27.6% by a single source (16.9% by pathology reports, 4.2% by hospital discharge records, 3.9% by copayment exemptions, and 2.6% by gluten-free food prescriptions). Excluding pathology reports, 70.6% of cases were identified by at least two sources. A definition based on copayment exemptions and discharge records traced 80.5% of the 962 possible cases of celiac disease; whereas a definition based on copayment exemptions, discharge records, and gluten-free food prescriptions traced 83.1% of those cases. The temporal relationship of the different sources was compatible with the typical diagnostic pathway of subjects with celiac disease. CONCLUSIONS: the four sources were only partially consistent. A relevant proportion of all possible cases of paediatric celiac disease were identified exclusively by pathology reports.

Association Between Short-Term Exposure to PM2.5 and PM10 and Mortality in Susceptible Subgroups: A Multisite Case-Crossover Analysis of Individual Effect Modifiers.

We performed a multisite study to evaluate demographic and clinical conditions as potential modifiers of the particulate matter (PM)-mortality association. We selected 228,619 natural deaths of elderly persons (ages ≥65 years) that occurred in 12 Italian cities during the period 2006-2010. Individual data on causes of death, age, sex, location of death, and preexisting chronic and acute conditions from the previous 5 years' hospitalizations were collected. City-specific conditional logistic regression models were applied within the case-crossover "time-stratified" framework, followed by random-effects meta-analysis. Particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5) and particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10) were positively associated with natural mortality (1.05% and 0.74% increases in mortality risk for increments of 10 µg/m3 and 14.4 µg/m3, respectively), with greater effects being seen among older people, those dying out-of-hospital or during the warm season, and those affected by 2 or more chronic diseases. Limited associations were found among persons with no previous hospital admissions. Diabetes (1.98%, 95% confidence interval (CI): 0.54, 3.44) and cardiac arrhythmia (1.65%, 95% CI: 0.37, 2.95) increased risk of PM2.5-related mortality, while heart conduction disorders increased risk of mortality related to both PM2.5 (4.22%, 95% CI: 0.15, 8.46) and PM10 (4.19%, 95% CI: 0.38, 8.14). Among acute conditions, recent hospital discharge for heart failure modified the PM10-mortality association. The study found increases in natural mortality from PM exposure among people with chronic morbidity; diabetes and cardiac disorders were the main susceptibility factors.

Celiac Disease and Risk of Autoimmune Disorders: A Population-Based Matched Birth Cohort Study.

OBJECTIVES: To estimate the relative risk of developing type 1 diabetes mellitus (T1DM) and autoimmune thyroid disease in children with celiac disease (CD). STUDY DESIGN: A matched cohort design with linkage of administrative data was adopted. A total of 1215 cases of CD and 6075 references matched by sex and year of birth born in Friuli Venezia Giulia Region (Italy) between 1989 and 2011 were included. Cox regression models were used to estimate hazard ratios (HRs) for autoimmune diseases in patients with CD compared with references, stratified by sex and age at diagnosis. RESULTS: Individuals with CD had an increased risk of subsequent hypothyroidism (HR 4.64 [95% CI 2.88-7.46]) and T1DM (HR 2.50 [95% CI 0.94-6.66]), the latter not statistically significant. Risk of hypothyroidism was higher in males (HR 20.00; 95% CI 5.64-70.87) than females (HR 3.21; 95% CI 1.85-5.57) (P value <.01). No differences were observed between males and females risks for diabetes or age at CD diagnosis. The small number of hyperthyroidism cases identified precluded any statistical analysis. CONCLUSIONS: Children and youth with CD are at increased risk of developing autoimmune hypothyroidism and to some extent T1DM. This suggests the need for surveillance of children with CD in order to timely detect the onset of such comorbidities.

Occupational prestige, social mobility and the association with lung cancer in men.

BACKGROUND: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory. METHODS: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results. RESULTS: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories. CONCLUSIONS: Our results indicate that occupational prestige is independently associated with lung cancer among men.

Risks of hospitalization and drug consumption in children and young adults with diagnosed celiac disease and the role of maternal education: a population-based matched birth cohort study.

BACKGROUND: Celiac disease (CD) may affect healthcare use in children and young adults. Socio-economic factors may act as a confounder or effect modifier. We assessed such hypotheses in a population-based birth cohort of young celiac subjects and references matched by maternal education. METHODS: The cohort included all newborns recorded in the Medical Birth Register of Friuli-Venezia Giulia Region (Italy) between 1989 and 2011. CD incident cases were identified through pathology reports, hospital discharges and copayment exemptions and matched with up to five references by sex, year of birth and maternal education. Cox regression models were used to estimate Hazard Ratios (HRs) for major causes of inpatient diagnosis and drug prescription occurring after diagnosis in CD patients compared to references, stratifying by time of first event and maternal education. RESULTS: We identified 1294 CD cases and 5681 references. CD cases had a higher risk of hospital admission for any cause (HR: 2.34; 95 % CI 2.08-2.63) and for all major ICD9-CM categories except obstetric complications, skin and musculoskeletal diseases, and injuries and poisoning. Prescription of all major ATC drug categories, except dermatologicals and genito-urinary medications, was significantly increased in CD subjects. For most outcomes, HRs were highest in the first year after CD diagnosis but remained significant after five or more years. HRs were similar across different categories of maternal education. CONCLUSIONS: Diagnosed CD subjects had a higher risk of hospitalization and medication use compared to the general population, even five or more years after diagnosis, with no effect modification of maternal education.

Antibiotic exposure in the first year of life and later treated asthma, a population based birth cohort study of 143,000 children.

Several epidemiological studies reported an association between antibiotic consumption in the first year of life and later asthma, but results are conflicting and affected by potential biases. We examined this controversial issue in a population-based birth cohort. Using administrative data, we identified 143,163 children born in 1995-2011 in Friuli-Venezia Giulia (Italy) (median follow-up 5.25 years, 927,350 person-years). Antibiotic prescriptions in the first year of life and subsequent treated asthma (defined as ≥2 anti-asthmatic drug prescriptions within a 12-month period) were retrieved from drug prescription records. We estimated incidence rate ratios (IRR) using Poisson regression models, adjusted for perinatal variables and for hospitalizations for infections in the first year of life. We identified 34,957 new-onset asthma cases. Antibiotic consumption in the first year of life increased the risk of new-onset asthma [IRR 1.51, 95% confidence interval (CI) 1.48-1.54] with a dose-response relationship (p-trend <0.001). The risk was highest for asthma identified at 13-35 months of life (IRR 2.07, 95% CI 2.00-2.14), but remained statistically significant for asthma identified at 36-71 months (IRR 1.17, 95% CI 1.14-1.21) and at ≥72 months (IRR 1.15, 95% CI 1.08-1.22). Antibiotics increased the risk of current asthma at ≥6 years (IRR 1.35, 95% CI 1.30-1.41) and at ≥13 years of age (IRR 1.19, 95% CI 1.08-1.33). Antibiotic exposure in infancy is associated with an increased risk of asthma up to adolescence. The association detected at older ages is not explained by reverse causation; however, confounding by respiratory infections not leading to hospital admission cannot be excluded.