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.

Hospitalizations and emergency department visits trends among elderly individuals in proximity to death: a retrospective population-based study.

Acute healthcare services are extremely important, particularly during the COVID-19 pandemic, as healthcare demand has rapidly intensified, and resources have become insufficient. Studies on specific prepandemic hospitalization and emergency department visit (EDV) trends in proximity to death are limited. We examined time-trend specificities based on sex, age, and cause of death in the last 2 years of life. Datasets containing all hospitalizations and EDVs of elderly residents in Friuli-Venezia Giulia, Italy (N = 411,812), who died between 2002 and 2014 at ≥ 65 years, have been collected. We performed subgroup change-point analysis of monthly trends in the 2 years preceding death according to sex, age at death (65-74, 75-84, 85-94, and ≥ 95 years), and main cause of death (cancer, cardiovascular, or respiratory disease). The proportion of decedents (N = 142,834) accessing acute healthcare services increased exponentially in proximity to death (hospitalizations = 4.7, EDVs = 3.9 months before death). This was inversely related to age, with changes among the youngest and eldest decedents at 6.6 and 3.5 months for hospitalizations and at 4.6 and 3.3 months for EDVs, respectively. Healthcare use among cancer patients intensified earlier in life (hospitalizations = 6.8, EDVs = 5.8 months before death). Decedents from respiratory diseases were most likely to access hospital-based services during the last month of life. No sex-based differences were found. The greater use of acute healthcare services among younger decedents and cancer patients suggests that policies potentiating primary care support targeting these at-risk groups may reduce pressure on hospital-based services.

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

Study on the health status of the population living in Marghera (Venice, Italy) through the use of a longitudinal surveillance system.

The aim of this study is to carry out an investigation to evaluate the industrial area of Porto Marghera (the only Site of National Interest - SNI - for clearance operations in the Veneto region) by means of data from the Venetian Epidemiological Surveillance System (SEIVE - Sistema Epidemiologico Integrato di Venezia). In particular, the aim is to assess the extent at which chronic exposure to industrial pollutants contributes to the genesis of non-communicable diseases such as tumors. We have employed healthcare administrative databases to analyze health conditions of the population residing in the area of Marghera, separately from the rest of the mainland. The results obtained highlight a series of critical problems concerning the population residing in Marghera. These issues, such as an excess in the overall cancer mortality rate, have been observed in both genders, as well as in the lung cancer incidence and mortality rate. In addition, we detected an increase in mortality for respiratory diseases only in the male population.

[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.

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 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.

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.

[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.

Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach.

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

Use of healthcare services at the end of life in decedents compared to their surviving counterparts: A case-control study among adults born before 1946 in Friuli Venezia Giulia.

BACKGROUND: There is a heterogeneous literature on healthcare utilization patterns at the end of life. The objective of this study is to examine the impact of closeness to death on the utilization of acute hospital-based healthcare services and some primary healthcare services and compare differences in gender, age groups and major causes of death disease specific mortality. METHODS: A matched case-control study, nested in a cohort of 411,812 subjects, linked to administrative databases was conducted. All subjects were residents in the Friuli Venezia Giulia Region (Italy), born before 1946, alive in January 2000 and were followed up to December 2014. Overall, 158,571 decedents/cases were matched by gender and year of birth to one control, alive at least one year after their matched case's death (index-date). Hospital admissions, emergency department visits, drug prescriptions, specialist visits and laboratory tests that occurred 365 days before death/index-date, have been evaluated. Odds Ratios (ORs) for healthcare utilization were estimated through conditional regression models, further adjusted for Charlson Comorbidity Index and stratified by gender, age groups and major causes of death. RESULTS: Decedents were significantly more likely of having at least one hospital admission (OR 7.0, 6.9-7.1), emergency department visit (OR 5.2, 5.1-5.3), drug prescription (OR 2.8, 2.7-2.9), specialist visit (OR 1.4, 1.4-1.4) and laboratory test (OR 2.7, 2.6-2.7) than their matched surviving counterparts. The ORs were generally lower in the oldest age group (95+) than in the youngest (55-74). Healthcare utilization did not vary by sex, but was higher in subjects who died of cancer. CONCLUSION: Closeness to death appeared to be strongly associated with healthcare utilization in adult/elderly subjects. The risk seems to be greater among younger age groups than older ones, especially for acute based services. Reducing acute healthcare at the EOL represents an important issue to improve the quality of life in proximity to death.

The Role of Maternal Citizenship on Pediatric Avoidable Hospitalization: A Birth Cohort Study in North-East Italy.

OBJECTIVE: Avoidable hospitalization (AH) has been widely studied as a possible measure of primary health care performance. Since studies evaluating AH in migrant children, particularly in Europe, are lacking, the aim of this study was to investigate the role of maternal citizenship on the risk of AH in children. METHODS: The cohort study included all live newborns recorded in the Medical Birth Register (MBR) of Friuli-Venezia Giulia Region (Italy) in the years 1989-2012, followed from 30 d after their birth up to the 14th year of life. Cox regression models were used to estimate Hazard Ratios (HRs) for any AH and for specific conditions. RESULTS: Among the 213,635 children included in the cohort, authors identified 23,011 AHs in 16,744 children, most of which occurred between 1 and 4 y of age. Children born to mothers from High Migration Pressure Countries had a higher risk of AH for any condition (HR 1.35; 95% CI = 1.27-1.44) than children born to Italian mothers. The risks were higher concerning gastroenteritis (HR 1.74; 1.57-1.94), upper respiratory tract infections (HR 1.58; 1.35-1.84), asthma (HR 1.53; 1.12-2.06) and bacterial pneumonia (HR 1.18; 1.01-1.37). There were no differences in urinary tract infections, short term complications of diabetes and perforated appendix. CONCLUSIONS: Despite the inclusiveness and universality of the Italian healthcare system, children born to immigrant mothers experienced more need of avoidable hospital care than children born to Italian mothers. Access barriers to primary care are plausible causes for the observed disparities.

The effect of job loss on pharmaceutical prescriptions.

We estimate the effect of job loss on the probability that long-tenured workers are prescribed anti-hypertensive and psychotropic drugs. We exploit two administrative data sources from the Veneto region in Italy and estimate an event-study model. Our results indicate that the probability of drug prescription increases among under-40 males but not among older males or female workers. We suggest that the effect on younger male workers is the combined result of their typical role as breadwinners, limited wealth buffers in case of layoff, and unfavourable employment legislative protection.

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.

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.

Lung cancer and socioeconomic status in a pooled analysis of case-control studies.

BACKGROUND: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. METHODS: Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. RESULTS: The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). CONCLUSION: SES remained a risk factor for lung cancer after adjustment for smoking behavior.