The prevalence and incidence of thrombotic primary antiphospholipid syndrome in adults aged 18-49 years: A population-based study in a mountain community in northern Italy.

OBJECTIVE: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years. METHODS: The study was carried out in Valtrompia, a valley in northern Italy, in 2011-2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events. RESULTS: Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4-41.0) and 5.0 (2.6-8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women. CONCLUSIONS: Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18-49 years, but a different type of onset was observed.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

[SARS-CoV-2 epidemic among Italians e resident immigrant population: differential incidence from an interregional multicentre study]. / L'epidemia di SARS-CoV-2 nella popolazione italiana e straniera: differenze di incidenza che emergono da uno studio multicentrico interregionale.

OBJECTIVES: to describe differences in the incidence of SARS-CoV-2 infections between Italians and foreigners residing in seven Italian Regions during the different phases of the pandemic and by gender. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: all confirmed SARS-CoV-2 infections from 02.02. 2020 to 16.07.2021 in the seven Regions under study were included. Italian resident population calculated by the National Institute of Statistics as of 01.01.2020 was used to calculate the rates. The considered period is divided into 5 sub-periods (phases). MAIN OUTCOME MEASURES: number of confirmed SARS-CoV-2 infections in the five phases of the pandemic and crude rates by citizenship (Italian vs foreign). Distribution of infections by age group and by week. Crude and age-adjusted incidence rates ratios (IRR) were calculated, by Region, gender, and phase of the pandemic. RESULTS: an epidemic curve delay was observed in foreigners in the first phase of the epidemic, in particular in the northern Regions, the most affected in that phase. The first phase of the epidemic was characterized by a greater proportion of cases occurred in people aged over 60 years than the other phases, both in Italians and in foreigners. The incidence among foreigners is higher during the summer of 2020 (intermediate period: June-September 2020) and during the last period (May-July 2021) in all Regions. The overall figure shows a lower incidence among foreigners than Italians, except for males in Tuscany. CONCLUSIONS: the lower incidence rates among foreigners should be interpreted with caution as the available data suggest that it is at least partly attributable to less access to diagnostic tests. Regional differences found in the study deserve further research together with the effect of gender and country of origin.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

A community-acquired Legionnaires' disease outbreak caused by Legionella pneumophila serogroup 2: an uncommon event, Italy, August to October 2018.

In September 2018 in Brescia province, northern Italy, an outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 2 (Lp2) occurred. The 33 cases (two fatal) resided in seven municipalities along the Chiese river. All cases were negative by urinary antigen test (UAT) and most were diagnosed by real-time PCR and serology. In only three cases, respiratory sample cultures were positive, and Lp2 was identified and typed as sequence type (ST)1455. In another three cases, nested sequence-based typing was directly applied to respiratory samples, which provided allelic profiles highly similar to ST1455. An environmental investigation was undertaken immediately and water samples were collected from private homes, municipal water systems, cooling towers and the river. Overall, 533 environmental water samples were analysed and 34 were positive for Lp. Of these, only three samples, all collected from the Chiese river, were Lp2 ST1455. If and how the river water could have been aerosolised causing the LD cases remains unexplained. This outbreak, the first to our knowledge caused by Lp2, highlights the limits of UAT for LD diagnosis, underlining the importance of adopting multiple tests to ensure that serogroups other than serogroup 1, as well as other Legionella species, are identified.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Evaluation of a diagnostic therapeutic educational pathway for asthma management in youth.

BACKGROUND: In spite of some evidence for positive effects of patient's education to asthma self-management by randomized clinical trials, there are few studies on the impact of patient' s educational programs in the real world. We aimed to assess the impact of a diagnostic therapeutic educational pathway (DTEP) on asthma control of children and adolescents by comparing frequency of outcomes indicative of asthma control before and after attending the pathway. METHODS: This is a retrospective cohort study including all patients aged 6-11 and 12-17 years who attended the DTEP in 2007-2014. The DTEP includes 3 specialist's evaluations at 8- to 12-week intervals and two follow-up visits. Patients and their parents receive an educational course concerning prevention measures, early recognition of symptoms, and appropriate use of drugs and devices. The rates of hospitalizations, outpatient services, emergency room visits, and drug prescriptions were considered as outcomes and computed as number of events divided by person-time. RESULTS: A total of 806 patients were enrolled. A statistically significant decrease in rates from before to after DTEP was observed for almost all outcomes, in both age groups, with relative risks ranging from 0.12 to 0.60. The rates of drug prescription showed a statistically significant decrease, from before to after DTEP, for each type of medicine for asthma, in both age groups, from percent difference of -66% to -24.3%. CONCLUSIONS: The positive impact of this program on the outcomes indicative of asthma control in both children and adolescents suggests that it may be valuable for asthma management.

Incidence of cardiovascular events in HIV-positive patients compared to general population over the last decade: a population-based study from 2000 to 2012.

Cardiovascular diseases are currently a main cause of death among people living with HIV. This population-based study aimed to investigate the incidence of cardiovascular events (CVEs) in HIV-positive people and factors associated with CVEs. We performed a retrospective cohort study of the HIV-infected patients residing in the Local Health Authority of Brescia, northern Italy, from 2000 to 2012. Incidence of CVEs events in HIV-positive patients was compared with that expected in general population living in the same area, computing standardized incidence ratios (SIRs). CVEs-associated risk factors were assessed using Cox regression analysis and competing risk model of death. About 3766 HIV-infected patients were included in the study. Over the 12-year-period, we recorded 134 CVEs: 83 (61.9%) acute myocardial infarctions (CVE type-1), and 51 (38.1%) strokes (CVE type-2). A twofold increased risk (SIR = 2.02) of CVEs was found in HIV-infected patients compared to the general population. Notably, within male patients: for CVE type-1, SIR = 1.89, for CVE type-2 SIR = 2.25; within female patients: for CVE type-1, SIR = 2.91, for CVE type-2 SIR = 2.07. Age >45 years, male gender, diabetes, and total blood cholesterol >200 mg/dl were significantly associated with CVEs incidence (for all, p < .05). These results were confirmed using the competing risk model. Our cohort study confirmed the higher incidence of CVEs in HIV-positive patients, and put emphasis on the importance of traditional cardiovascular risk factors. Overall CVE risk in HIV-positive patients was twice as high as CVE risk in general population. We found a peculiar gender distribution, with a relative risk for CVE type-1 higher in HIV-positive females, and a higher CVE type-2 risk in male patients. More studies are needed in order to support these findings and to further highlight possible gender differences in the risk of developing CVEs in HIV-positive patients.

The burden of chronic diseases and cost-of-care in subjects with HIV infection in a Health District of Northern Italy over a 12-year period compared to that of the general population.

BACKGROUND: The increase in life expectancy of HIV-infected patients has driven increased costs due to life-long HIV treatment and concurrent age-related comorbidities. This population-based study aimed to investigate the burden of chronic diseases and health costs for HIV+ subjects compared to the general population living in Brescia Local health Agency (LHA) over a 12-year period. METHODS: LHA database recorded diagnoses, deaths, drug prescriptions and health resource utilization for all residents during 2003-2014. We estimated HIV prevalence and incidence, HIV-related mortality as well as prevalence of chronic diseases in HIV+ subjects. Observed/expected ratio of chronic diseases was calculated by indirect standardization with the general population as reference. Direct cost of HIV care and determinants were estimates across the period. RESULTS: HIV prevalence increased from 220 to 307 per 100 000 person-years while incidence decreased from 16.1 to 10.8 per 100 000 person-years from 2003 to 2014. Prevalence of most comorbidities increased over time but it reduced significantly (annual mean change - 0.7 %) when adjusting for age and gender. Observed to expected ratio for each chronic disease in HIV+ subjects decreased over time. Cost of HIV+ cures increased (+25 %) mainly due to cost for drugs (+50 %) but it stabilized in recent years. CD4+ cell count at the time of diagnosis was an important predictor of cost for HIV management. CONCLUSIONS: Expenditures for HIV-infection are driven mainly by drugs cost and they have increased overtime. However, our findings suggest that spending on public health for HIV care can improve prognosis of HIV-infected patients, reduce transmission of HIV infection and reduce the global burden of chronic diseases, leading to a reduction of HIV global cost in the medium-long time.

The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

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.

Polychlorinated biphenyls and non-Hodgkin's lymphoma: a case-control study in Northern Italy.

BACKGROUND: Polychlorinated biphenyls (PCBs) have been hypothesized to increase the risk of non-Hodgkin lymphoma (NHL), although conclusive evidence is still lacking. High levels of PCBs were found in soil in some areas close to a PCB-producing factory in Brescia, North Italy. We conducted a population-based case-control study among residents of the town to investigate the possible association between PCB pollution and NHL in this area. METHODS: We included both incident and deceased NHL cases, and a random sample of the town residents as controls, frequency matched to cases as regards age and gender. Exposure to PCBs was estimated on the basis of the lifetime residential history of cases and controls in four different areas of the town-A, B and C (polluted areas) and D (control area). RESULTS: A total of 495 cases (287 incident cases) and 1467 controls were enrolled. Positive associations were found between NHL and having resided for at least 10 years in the area A, the most polluted area (odds ratio, OR=1.8; p=0.02) and for having resided in any of the polluted areas considered together (A+B+C) (OR=1.4; p=0.08). However, no associations were evident for having resided 20 years or longer in the polluted areas or when analyzing the association with each subject's main residence in his/her lifetime. CONCLUSION: This study provides some evidence for an association between PCB exposure and NHL, though results should be considered with caution in the absence of individual biological measures of exposure.

Maternal characteristics during pregnancy and risk factors for positive HIV RNA at delivery: a single-cohort observational study (Brescia, Northern Italy).

BACKGROUND: Detectable HIV RNA in mothers at delivery is an important risk factor for HIV transmission to newborns. Our hypothesis was that, in migrant women, the risk of detectable HIV RNA at delivery is greater owing to late HIV diagnosis. Therefore, we examined pregnant women by regional provenance and measured variables that could be associated with detectable HIV RNA at delivery. METHODS: A observational retrospective study was conducted from January 1999 to May 2008. Univariate and multivariable regression analyses (generalized linear models) were used, with detectable HIV RNA at delivery as dependent variable. RESULTS: The overall population comprised 154 women (46.8% migrants). Presentation was later in migrant women than Italians, as assessed by CD4-T-cell count at first contact (mean 417/mm³ versus 545/mm³, respectively; p = 0.003). Likewise, HIV diagnosis was made before pregnancy and HAART was already prescribed at the time of pregnancy in more Italians (91% and 75%, respectively) than migrants (61% and 42.8%, respectively). A subgroup of women with available HIV RNA close to term (i.e., ≤30 days before labour) was studied for risk factors of detectable HIV RNA (≥50 copies/ml) at delivery. Among 93 women, 25 (26.9%) had detectable HIV RNA. A trend toward an association between non-Italian nationality and detectable HIV RNA at delivery was demonstrated by univariate analysis (relative risk, RR = 1.86; p = 0.099). However, by multivariable regression analysis, the following factors appeared to be more important: lack of stable (i.e., ≥14 days) antiretroviral therapy at the time of HIV RNA testing (RR = 4.3; p < 0.0001), and higher CD4+ T-cell count at pregnancy (per 50/mm³, RR = 0.94; p = 0.038). CONCLUSIONS: These results reinforce the importance of extensive screening for HIV infection, earlier initiation of antiretroviral therapy and stricter monitoring of pregnant women to reduce the risk of detectable HIV RNA at delivery. Public health interventions should be particularly targeted to migrant women who are frequently unaware of their HIV status at the time of pregnancy.

Is survival for hepatocellular carcinoma increasing? A population-based study on survival of hepatocellular carcinoma patients in the 1990s and 2000s.

BACKGROUND: Improvement of survival rates for hepatocellular carcinoma during the last two decades and related factors are still debated. This study aimed to evaluate the risk of death and the role of prognostic factors in patients with hepatocellular carcinoma diagnosed in 1995-2001 and 2004-2006. METHODS: We performed univariate and multivariable survival analyses of subjects with a first hepatocellular carcinoma diagnosis in 1995-2001 and in 2004-2006, all residing in Brescia province, Italy. Mediation analysis of treatment role in survival was conducted. RESULTS: During follow-up (median 21.1 months) 913 subjects died (95.5%). The 1-, 3- and 5-year survival rates were higher for cases diagnosed in 2004-2006 (64.4%, 35.9% and 24.3%) than in 1995-2001 (60.8%, 34.5% and 20.7%). T stage, metastasis, cirrhosis, Child-Pugh class, portal vein invasion, serum creatinine level, treatment approach and diabetes were survival predictors in both periods. Patients with diagnosis in 2004-2006 had 36% lower risk of death than those with diagnosis in 1995-2001 using adjusted Cox proportional hazard model. The association between diagnosis period and risk of death was mediated by changes in treatment approach. CONCLUSION: We observed a decreased risk of death for first hepatocellular carcinoma diagnosis from 2004-2006 to 1995-2001, which was partially attributable to improvements in treatment approach.

Tuberculosis trend among native and foreign-born people over a 17 year period (2004-2020) in a large province in Northern Italy.

Tuberculosis (TB) incidence should decline by 20% in the Europe in 2015-2020, in line with End-TB milestones. We retrospectively evaluated TB notifications in the province of Brescia from 2004 to 2020. Cases were classified per patient origin and entitlement to Health Assistance for foreign born people: Italians (ITA), Foreigners permanently entitled (PEF) or Temporarily Entitled (TEF) to Health Regional Assistance. Poisson regression analysis was performed to assess associations between incidence and age, sex, continent of origin and year of notification. Overall 2279 TB cases were notified: 1290 (56.6%) in PEF, 700 (30.7%) in ITA and 289 (12.7%) in TEF. Notifications declined from 15.2/100,000 in 2004 to 6.9/100,000 in 2020 (54.6% reduction, temporary increase in 2013-2018 for TEF). Age (Incidence Risk Ratio, IRR, 1.02, 1.019-1.024 95%CI), sex (IRR 1.22, 1.12-1.34 95%CI), and continent of origin were positively associated with notifications (IRR 34.8, 30.8-39.2 95%CI for Asiatic, and IRR 20.6, 18.1-23.4 95%CI for African origin), p < 0.001. Notification decline was sharper in 2020, especially among TEF. End-TB milestone for 2020 was reached, but foreigners continue to represent a high risk group for the disease. Discontinuation of services due to the COVID-19 pandemic was associated with a sharp decrease in TB notification in 2020.

Evaluation of influenza vaccination efficacy in reducing influenza-related complications and excess mortality in Northern Italy (2014-2017).

OBJECTIVE: The main objective of this study was to estimate the efficacy of influenza vaccination in reducing influenza-attributable hospitalization and emergency room (ER) admission for severe complications and influenza-attributable excess mortality in individuals ≥65 years of age. METHODS: We analyzed the ≥65 years-old community (n = 952,822) afferent to the Brescia (Northern Italy) Health Protection Agency, considered an Italian population reference, to evaluate the efficacy of influenza vaccination (seasons 2014-17) in reducing deaths, ER-admissions, and hospitalizations for influenza-related complications in the elderly. RESULTS: A protective effect of influenza vaccination emerged in reducing hospitalization and ER admission for diseases of the respiratory system and for death from all causes in people ≥65 years. The major effect of influenza vaccination was the reduction in risk of death from all causes, increasing with age and comorbidity. CONCLUSION: Influenza vaccination has reduced the number of ER admissions and hospitalizations caused by influenza-related complications and has prevented death among high-risk groups in elderly ≥65 years, resulting in social and public health cost savings. Stronger or new vaccination strategies are needed to improve vaccination rates among the elderly.

Polychlorinated biphenyls and risk of hepatocellular carcinoma in the population living in a highly polluted area in Italy.

Polychlorinated biphenyls (PCBs) are human carcinogens, based on sufficient evidence for melanoma and limited evidence for non-Hodgkin lymphoma and breast cancer. Few data are available for liver cancer, although PCBs cause it in rats and determined liver damage in poisoned people. We investigated the association between PCB serum levels and hepatocellular carcinoma (HCC) with a case-control study in a PCB-polluted area in North Italy. We enrolled prospectively 102 HCC incident cases and 102 age and gender-matched hospital controls. Serum concentrations of 33 PCB congeners were determined by a gas chromatograph coupled to mass spectrometry. Of 102 HCC cases, 62 who had lost < 3 kg of body weight in past 3 years were included in the analysis (67.7% males, mean age 68 years). The odds ratio (OR) for HCC for 3rd compared to 1st tertile of PCB distribution was 1.76 (95% confidence interval 0.62-5.03) for total PCB, adjusting for socio-demographic variables and risk factors for HCC by logistic regression. For most PCB congeners, ORs > 1.5 or 2 were found, although the 95% CIs included the null value for almost all of them. This preliminary study suggests that PCBs might play a role in HCC development.

Neoplastic and inflammatory skin disorders and serum levels of polychlorinated biphenyls in a population living in a highly polluted area.

BACKGROUND: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. OBJECTIVES: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders. MATERIALS & METHODS: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases. RESULTS: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error. CONCLUSION: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

Impact of a diagnostic therapeutic educational pathway program for asthma management in preschool children.

BACKGROUND: Preschool children with clinically-diagnosed asthma have a higher rate of emergency department visits and consume more resources for management than older children. However, no clinical trials have yet been performed measuring the impact of a combined diagnostic, therapeutic and educational pathway regimen for evaluation of wheezing control in children aged less than 6 years. The purpose of the present study was to assess the impact of a pediatric program developed in Italy, the Diagnostic Therapeutic Educational Pathway (DTEP), for asthma management in children less than 6 years old attending an asthma referral center. METHODS: This is a retrospective population-based cohort study performed in children with asthma aged 0-5 years, attending at "Io e l'Asma center", Brescia, Italy between September 2007 and December 2014. The incidence rates (IRs) of hospitalization, emergency room visits, use of outpatient services and drug usage for dyspnea, wheezing, or respiratory symptoms were evaluated for time periods prior to and after DTEP intervention. RESULTS: A total of 741 patients, aged 0-5 years completed the DTEP, including 391 and 350 children aged 0-2 and 3-5 years, respectively. The percentage of children aged 0-2 and 3-5 years showing improved control of wheezing symptoms during the 1st to 3rd visit interval as a result of the DTEP intervention increased from 39.5 to 60.9% and from 25.5 to 75.5%, respectively. During these periods, the IRs showed a significant decrease for all outcomes, from-8.6% to - 80.4%. Although specific IRs for drug prescriptions declined, particularly for LABA plus corticosteroids, antibiotics, and systemic corticosteroids, they increased for SABA, inhaled corticosteroid and leukotriene receptor antagonist usage. CONCLUSIONS: The results suggest that a real-world assessment of the integrated DTEP program for preschool children provides evidence for improved wheezing control and reduction of adverse therapeutic related outcomes.

The early phase of the COVID-19 epidemic in Lombardy, Italy.

BACKGROUND: In the night of February 20, 2020, the first epidemic of the novel coronavirus disease (COVID-19) outside Asia was uncovered by the identification of its first patient in Lombardy region, Italy. In the following weeks, Lombardy experienced a sudden increase in the number of ascertained infections and strict measures were imposed to contain the epidemic spread. METHODS: We analyzed official records of cases occurred in Lombardy to characterize the epidemiology of SARS-CoV-2 during the early phase of the outbreak. A line list of laboratory-confirmed cases was set up and later retrospectively consolidated, using standardized interviews to ascertained cases and their close contacts. We provide estimates of the serial interval, of the basic reproduction number, and of the temporal variation of the net reproduction number of SARS-CoV-2. RESULTS: Epidemiological investigations detected over 500 cases (median age: 69, IQR: 57-78) before the first COVID-19 diagnosed patient (February 20, 2020), and suggested that SARS-CoV-2 was already circulating in at least 222 out of 1506 (14.7%) municipalities with sustained transmission across all the Lombardy provinces. We estimated the mean serial interval to be 6.6 days (95% CrI, 0.7-19). Our estimates of the basic reproduction number range from 2.6 in Pavia (95% CI, 2.1-3.2) to 3.3 in Milan (95% CI, 2.9-3.8). A decreasing trend in the net reproduction number was observed following the detection of the first case. CONCLUSIONS: At the time of first case notification, COVID-19 was already widespread in the entire Lombardy region. This may explain the large number of critical cases experienced by this region in a very short timeframe. The slight decrease of the reproduction number observed in the early days after February 20, 2020 might be due to increased population awareness and early interventions implemented before the regional lockdown imposed on March 8, 2020.