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The Seveso accident in 1976 caused a large, populated area north of Milan, Italy, to be contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study, the authors followed up the exposed population for chronic effects; this paper reports the results of the mortality follow-up extension for 1997–2001. The study cohort includes 278,108 subjects resident at the time of the accident or immigrating/born in the 10 years thereafter in three contaminated zones with decreasing TCDD soil levels (zone A, very high; zone B, high; zone R, low) and in a reference territory comprising surrounding, noncontaminated municipalities. Vital status and cause-of-death ascertainment were 99% complete. Adjusted rate ratios and 95% confidence intervals were calculated by using Poisson regression. Results confirmed previous findings of excesses of lymphatic and hematopoietic tissue neoplasms in zones A (six deaths; rate ratio = 2.23, 95% confidence interval: 1.00, 4.97) and B (28 deaths; rate ratio = 1.59, 95% confidence interval: 1.09, 2.33). These zones also showed increased mortality from circulatory diseases in the first years after the accident, from chronic obstructive pulmonary disease, and from diabetes mellitus among females. A toxic and carcinogenic risk to humans after high TCDD exposure is supported by the results of this study. [ABSTRACT FROM AUTHOR]

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use. [ABSTRACT FROM AUTHOR]

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Health Study. TCDD concentrations were measured in 1976 (n = 981) and 1996 (n = 260), and levels of total thyroxine, free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were measured in 1996 (n = 909) and 2008 (n = 724). We used conditional multiple linear regression and marginal structural models with inverse-probability-of-treatment weights to evaluate associations and causal effects. TCDD concentration in 1976 was inversely associated with total thyroxine level in 1996 but not in 2008. Associations were stronger among women who had been exposed before menarche. Among these women, associations between total thyroxine and concurrent 1996 TCDD were slightly weaker than those with 1976 TCDD. A model including both 1976 and 1996 measurements strengthened the relationship between 1976 TCDD and total thyroxine but drove the association with 1996 TCDD to the null. TCDD exposure was not associated with levels of other thyroid hormones. TCDD exposure, particularly exposure before menarche, may have enduring impacts on women's total thyroxine levels. Initial exposure appears to be more influential than remaining body burden. [ABSTRACT FROM PUBLISHER]

MF59-adjuvanted trivalent influenza vaccine (Novartis Vaccines and Diagnostics, Siena, Italy) has been shown to be more effective than nonadjuvanted vaccine in the elderly population. Here we present results from a large-scale, observational, noninterventional, prospective postlicensure study that evaluated the safety of MF59-adjuvanted vaccine in elderly subjects aged 65 years or more. The study was performed in 5 northern Italian health districts during the 2006–2007, 2007–2008, and 2008–2009 influenza seasons. The choice of vaccine—either adjuvanted vaccine or a nonadjuvanted influenza vaccine—was determined by individual providers on the basis of local influenza vaccination policy. Hospitalizations for potential adverse events of special interest (AESIs) were identified from hospital databases and then reviewed against recognized case definitions to identify confirmed cases of AESI. Cumulative incidences were calculated for AESIs in predefined biologically plausible time windows, as well as in a 6-month window following vaccination. During the 3-year study period, 170,988 vaccine doses were administered to a total of 107,661 persons. Despite the large study size, cases of AESI resulting in hospitalization were rare, and risks of AESI were similar in both the MF59-adjuvanted and nonadjuvanted vaccination groups. In conclusion, similar safety profiles were observed for both nonadjuvanted and MF59-adjuvanted seasonal influenza vaccines in elderly recipients. [ABSTRACT FROM PUBLISHER]

Adverse health effects of particulate matter 10) and high temperatures are well known, but the extent of their interaction on mortality is less clear. This paper describes effect modification of temperature in the PM10–mortality association and tests the hypothesis that higher PM10 effects in summer are due to enhanced exposure to particles. All deaths of residents of nine Italian cities between 1997 and 2004 were selected. The case-crossover approach was adopted to estimate the effect of PM10 on mortality by season and temperature level. Three strata of temperature corresponding to low, medium, and high “ventilation” were identified, and the interaction between PM10 and temperature within each stratum was examined. Season and temperature levels strongly modified the PM10–mortality association: for a 10-μg/m3 variation in PM10, a 2.54% increase in risk of death in summer (95% confidence interval: 1.31, 3.78) compared with 0.20% (95% confidence interval: −0.08, 0.49) in winter. Analysis of the interaction between PM10 and temperature within temperature strata resulted in positive but, in most cases, nonstatistically significant coefficients. The authors found much higher PM10 effects on mortality during warmer days. The hypothesis that such an effect is attributable to enhanced exposure to particles in summer could not be rejected. [ABSTRACT FROM AUTHOR]

In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (β = −0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13–0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age. [ABSTRACT FROM AUTHOR]

This population-based study was conducted in Veneto and Trentino (northwestern Italy, population 5 million). In this area, neonatal screening for cystic fibrosis started in 1973 and has been virtually universal since the early 1980s. During this study, the estimated incidence of cystic fibrosis in this region was 1/2,650 livebirths per year. The authors analyzed data on 593 patients born in 1938–2000 and living in the region who were followed by a single referral center. Median time from birth to confirmation of diagnosis after screening was 32 days (range, 0–1,531). For patients whose disease was recognized after symptoms occurred, median age at diagnosis was always less than 1 year. Median survival age was 37.7 years. Long-term survival (to age 20–30 years) was not significantly influenced by mode of diagnosis (screened or unscreened), sex, or age at diagnosis for unscreened patients (<1, 1–5, >5 years). Current survival analysis of three consecutive decades showed that improving survival tended to vanish in the last years of the study. The authors concluded that a regional neonatal screening program allows very early recognition of cystic fibrosis. They could not conclude that neonatal screening improves long-term survival if compared with diagnosis by symptoms in early infancy. [ABSTRACT FROM PUBLISHER]

The authors evaluated objective measurements of constitutive skin color and ultraviolet light sensitivity in relation to risk of cutaneous malignant melanoma (CMM). Incident CMM cases (n = 183) were diagnosed between December 1994 and January 1999 at the Maurizio Bufalini Hospital in Cesena, Italy. Controls (n = 179) were mostly spouses/partners of cases and were frequency-matched by age and sex. In addition to interviews, constitutive skin color and skin ultraviolet light sensitivity were assessed by colorimetry and minimal erythema dose (MED), respectively. Odds ratios were estimated using unconditional logistic regression. The odds of CMM increased by a factor of 1.20 (95 percent confidence interval: 1.12, 1.30) for each unit of skin brightness and by a factor of 1.24 (95 percent confidence interval: 1.07, 1.43) per 10 mJ/cm2 of MED. These associations were largely independent of phenotypic or sun-related characteristics and were modified by sun exposure. Increased risk of CMM was observed only among subjects with the highest levels of sun exposure. Epidemiologic studies of CMM may benefit from the inclusion of colorimetric and MED measurements along with traditional risk factors to obtain more accurate, quantitative, and objective information. [ABSTRACT FROM PUBLISHER]

Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects. [ABSTRACT FROM PUBLISHER]

To determine whether initial CD4 cell counts after human immunodeficiency virus (HIV) seroconversion have decreased over calendar time among participants in the Italian Seroconversion Study, HIV seroconverters who between 1985 and 1992 had a documented negative serology followed by a positive serology within 12 months and a first CD4 cell measurement within 24 months of seroconversion (defined as midpoint of negative and positive HIV tests) were cross-tabulated by year of seroconversion. Linear regression methods were used to examine temporal trends in initial CD4 level after adjustment for age, lag time of seroconversion, lag time of CD4 cell measurement, risk group, and clinical center. Between 1985 and 1992, the overall median initial CD4 cell level after seroconversion was 660 μl with a median lag time of 212 days and 137 days for seroconversion and first CD4 cell measurement, respectively. In univariate and multivariate models, the CD4 cell count increases of 4.3 and 4.2 cells μl/year, respectively, were not statistically significant. These data do not identify a trend of lower CD4 counts following HIV seroconversion in Italy and suggest indirectly that HIV has probably not become more virulent between 1985 and 1992. [ABSTRACT FROM AUTHOR]

The authors reflect on how the Sesevo, Italy findings influenced conclusions on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a human carcinogen. They mention that the Working Group from the International Agency for Research on Cancer (IARC) decided to classify TCDD as a group 1 human carcinogen based on a clause on the evaluation criteria. They argue that a liberal interpretation should be considered since the mechanisms causing human cancer have not yet fully understood.