[Deprivation indices in small-area studies of environment and health in Italy]. / L'indice di deprivazione negli studi di piccola area su ambiente e salute.

The use of deprivation indices in small-area studies of environment and health is described, with particular reference to the Italian context. Deprivation indices can represent a proxy for individual deprivation and/or contextual deprivation. In Italy, deprivation indices have been constructed using Census variables. They are applied at census tract level in studies with a local basis; in national based studies, they can be used at municipality level. In SENTIERI Project (Mortality study of residents in Italian polluted sites) an ad hoc deprivation index at municipal level was used (DI SENTIERI). Its strength and weaknesses are discussed. In addition, suggestions about the use of socioeconomic indices in small area studies of environment and health are given. For a description of SENTIERI, refer to the 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI Project.

[The contribution of cancer registries in environmental health studies]. / Il contributo dei Registri tumori negli studi su ambiente e salute.

Cancer incidence is an outcome of interest in studies assessing the health impact of polluted sites, for which an example is represented by SENTIERI Project. Incidence data are characterized by better diagnostic quality and are not influenced by survival factors, furthermore they allow the investigation of high-survival neoplasms (i.e. childhood cancer) and rare malignancies. Furthermore, the study of incidence is more informative than mortality for non-lethal tumours, therefore it represents an advancement in respect to the study of mortality completed in SENTIERI Project. In the last decade in Italy some environmental epidemiology studies used cancer register data, for example the Biancavilla (Sicily) investigation on fluoro-edenite related mesothelioma and the study in an area of Naples Province where hazardous waste was extensively dumped. In this frame, ISS planned some collaborative studies with Siracusa, Mantua and Ferrara cancer Registries, where three major polluted sites are located. Following these pilot studies an ISS-AIRTUM (Italian Association of Cancer Registries) collaborative study has been planned. For a description of SENTIERI, refer to the 2010 supplement of Epidemiology & Prevention, devoted to the Project.

[Global burden of mortality in Italian polluted sites]. / Valutazioni globali del carico di mortalità nei siti di interesse nazionale per le bonifiche.

SENTIERI Project has assessed the overall mortality profile in all the IPSs combined, and performed IPS-specific analyses. The epidemiological evidence of the causal association between cause of death and exposure was classified into one of these three categories: Sufficient (S), Limited (L) and Inadequate (I). The procedures and results of the evidence evaluation have been presented in a 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI. Mortality for causes of death with a priori Sufficient or Limited evidence of association with the environmental exposure exceeds the expected figures, with a SMR of 115.8 for men (90%CI 114.4-117.2; 2 439 extra deaths) and 114.4 for women (90% CI 112.4-116.5; 1 069 extra deaths). These excesses are also observed when analysis is extended to all the causes of death (i.e. with no restriction to the ones with a priori Sufficient or Limited evidence): for a total of 403 692 deaths (men and women combined), an excess of 9 969 deaths is observed, with an average of around 1 200 extra deaths per year. Most of these excesses are observed in IPSs located in Southern and Central Italy. The distribution of the causes of deaths shows that the excesses are not evenly distributed: cancer mortality accounts for 30%of all deaths, but is 43.2%of the excess deaths (4 309 cases of 9 969). Conversely, the percentage of excesses in non cancer causes, 19%, is lower than their share of total mortality (42%). Consistently with previous studies, the results suggest that the health status of populations living in the IPSs is worse than what regional averages show. Compared to previous studies, the analysis of the causes selected in SENTIERI, on the basis of a priori Sufficient or Limited evidence of association with the environmental exposures, provides additional information on their role, though some limitations, due to methodology and data used, should be considered.

[Mortality results in SENTIERI Project]. / Risultati dell'analisi della mortalità nel Progetto SENTIERI.

SENTIERI Project (Mortality study of residents in Italian polluted sites) studies mortality of residents in 44 sites of national interest for environmental remediation (Italian polluted sites, IPS). The epidemiological evidence of the causal association between causes of death and exposures was a priori classified into one of these three categories: Sufficient (S), Limited (L) and Inadequate (I). In these sites various environmental exposures are present. Asbestos (or asbestiform fibres as in Biancavilla) has been the motivation for defining six sites as IPSs (Balangero, Emarese, Casale Monferrato, Broni, Bari-Fibronit, Biancavilla). In five of these, increases in malignant neoplasm or pleura mortality are detected; in four of them, results are consistent in both genders. In six other sites (Pitelli, Massa Carrara, Aree del Litorale Vesuviano, Tito, "Aree industriali della Val Basento", Priolo), where other sources of environmental pollution in addition to asbestos are reported, mortality from malignant neoplasm of pleura is increased in both genders in Pitelli, Massa Carrara, Priolo, "Litorale vesuviano". In the time span 1995-2002, a total of 416 extra cases of malignant neoplasm of pleura are detected in the twelve asbestos-polluted sites. Asbestos and pleural neoplasm represent an unique case. Unlike mesothelioma, most causes of death analyzed in SENTIERI have multifactorial etiology; furthermore, in most IPSs multiple sources of different pollutants are present, sometimes concurrently with air pollution from urban areas: in these cases, drawing conclusions on the association between environmental exposures and specific health outcomes might be complicated. Notwithstanding these difficulties, in a number of cases an etiological role could be attributed to some environmental exposures. The attribution could be possible on the basis of increases observed in both genders and in different age classes, and the exclusion of a major role of occupational exposures was thus allowed. For example, a role of emissions from refineries and petrochemical plants was hypothesized for the observed increases in mortality from lung cancer and respiratory diseases in Gela and Porto Torres; a role of emissions from metal industries was suggested to explain increased mortality from respiratory diseases in Taranto and in Sulcis-Iglesiente-Guspinese. An etiological role of air pollution in the raise in congenital anomalies and perinatal disorders was suggested in Falconara Marittima, Massa-Carrara, Milazzo and Porto Torres. A causal role of heavy metals, PAH's and halogenated compounds was suspected for mortality from renal failure in Massa Carrara, Piombino, Orbetello, "Basso bacino del fiume Chienti" and Sulcis-Iglesiente-Guspinese. In Trento-Nord, Grado and Marano, and "Basso bacino del fiume Chienti" increases in neurological diseases, for which an etiological role of lead, mercury and organohalogenated solvents is possible, were reported. The increase for non-Hodgkin lymphomas in Brescia was associated with the widespread PCB pollution. Mortality for causes of death with a priori Sufficient or Limited evidence of association with the environmental exposure exceeds the expected figures, with a SMR of 115.8% for men (90% IC 114.4-117.2; 2 439 extra deaths) and 114.4% for women (90% CI 112.4-116.5; 1 069 extra deaths). These excesses are also observed when analysis is extended to all the causes of death (i.e. with no restriction to the ones with a priori Sufficient or Limited evidence): for a total of 403 692 deaths (both men and women), an excess of 9 969 deaths is observed, with an average of about 1 200 extra deaths per year. Most of these excesses are observed in IPSs located in Southern and Central Italy. The procedures and results of the evidence evaluation are presented in a 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI.

[Scientific collaboration between Istituto Superiore di Sanità and Italian Association of Cancer Registries for the study of cancer incidence in Italian polluted sites]. / Collaborazione scientifica ISS-AIRTUM per lo studio dell'incidenza dei tumori nei siti di interesse nazionale per le bonifiche.

The collaborative study between Istituto superiore di sanità and Associazione italiana registri tumori (ISS-AIRTUM) aims at investigating cancer incidence in polluted sites for adults and for children (0-14 years) and adolescents (15-19 years) to comment the study results in the light of a set of a priori hypotheses. On the whole, 141 out of 298 municipalities included in SENTIERI Project are served by a Cancer Register participating to the AIRTUM network. For a description of SENTIERI, refer to the 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI Project. The time window of the study is the period 1996-2005. The number of expected cases in each polluted site will be estimated by applying incidence rates of the national pool of cancer registries and of the pool of the geographic macroarea in which each site is located: Northern, Central, Southern Italy and Islands. Cancer incidence in children and adolescents is one of the main priorities of international public health institutions, because of the need to protect childhood health from involuntary exposure to environmental risk factors. Standardized incidence ratios (SIRs) will be computed using expected figures derived from the national pool of cancer registries.

Impaired decision-making in opiate-dependent subjects: effect of pharmacological therapies.

Cognitive dysfunction is a major feature of drug addiction. In the present paper, we compared the decision-making ability using the Iowa gambling task of methadone- and buprenorphine-maintained individuals to non opiate-dependent drug-free controls. Buprenorphine-maintained individuals performed better than methadone-maintained individuals, and not differently than non opiate-dependent controls. In addition, methadone-maintained individuals had more perseverative errors on the Wisconsin card sorting task (WCST) as compared with non opiate-dependent drug-free controls whereas buprenorphine-maintained individuals had intermediate scores. Scores on Weschler adult intelligence scale (WAIS-R) were similar for methadone- and buprenorphine-maintained individuals whereas drug-free controls had significantly higher scores. In addition, both opiate-dependent groups performed more poorly than drug-free controls on the Benton visual retention test (BVRT). The results suggest that buprenorphine in contrast to methadone improves decision-making, and thus may be more effective in rehabilitation programs of opiate-dependent subjects and this improvement may be related to its distinct pharmacological action as a k antagonist.

Retrospective mortality cohort study of Italian workers compensated for silicosis.

OBJECTIVES: To estimate cause specific mortality in a large cohort of Italian workers compensated for silicosis. METHODS: The cohort included 14 929 subjects (14,098 men and 831 women) compensated for silicosis between 1946 and 1979, alive on 1 January 1980, and resident in Tuscany (a region of central Italy with 3,547,000 inhabitants). Mortality follow up ranged from 1980 to 1999. Vital status and the causes of death were determined by linkage with the regional mortality registry and with the national mortality database. The cohort mortality rates were compared to the rates of the local reference population. SMRs and their 95% confidence intervals were computed assuming a Poisson distribution of the observed deaths. Specific SMR analyses were performed according to the level of disability, the year of compensation assignment, and the job type. RESULTS: A significant excess mortality was observed in male silicotics for cancer of the lung, trachea, and bronchus and cancer of the liver, respiratory diseases (silicosis, asbestosis, antracosilicosis, and other pneumoconiosis), and for tubercolosis. Statistically significant mortality excess was observed in female silicotics for respiratory diseases (specifically silicosis and other pneumoconiosis) and tuberculosis. Analyses for period of compensation assignment showed a twofold increased SMR for biliary tract cancer among female workers and for liver cancer among male workers compensated before 1970. CONCLUSIONS: The excess mortality from respiratory tract cancers and respiratory tract diseases detected in Italian compensated silicotics are in agreement with previous epidemiological studies. Although the twofold increased risk for liver cancer among males is suggestive of a possible association with silica dust exposure, the finding needs to be confirmed.

[Epidemiological survey on smoking habit among young students in Sardinia. A cross sectional study]. / Il fumo fra i giovani: indagine trasversale nelle scuole medie superiori della Sardegna.

The study reports the prevalence of cigarette smoking among 11401 high school Sardinian students. The prevalence of smokers (40.2%) significantly differs between gender (41.1% males and 38.4% females). Males have an early initiation of smoking with an evident addictive effect by age. 54.3% are daily smokers and 21.4% smoke 15 or more cigarettes per day. More than 50% smoke to look grown-up and to be accepted by the group. Besides age (OR=1.10; 95%CI: 1.06-1.15), other factors are associated with smoke: low education level of father (OR=1.08; 95%CI: 1.02-1.15), no maternal support (OR = 1.73; 95%CI: 1.17-2.54), to have at least one smoker cohabitant (OR=1.66; 95%CI: 1.54-1.80) and alcohol drinking (OR=3.46; 95%CI: 3.04-3.93). The smokers' knowledge on smoke topics significantly differ from non smokers. Our results suggest the need of community preventive interventions, diversified for specific target populations, to modify the students' behaviours so that they respect their own health and that of their fellow citizens.

Gamma-hydroxybutyric acid for treatment of opiate withdrawal syndrome.

In a double-blind placebo-controlled trial, gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) suppressed most of the withdrawal symptomatology in 14 heroin addicts and 13 methadone-maintained subjects. The GHB effect was prompt (within 15 minutes) and persisted for between 2 and 3 hours. Subsequently, the same patients received GHB in an open study every 2 to 4 hours for the first 2 days and 4 to 6 hours for the following 6 days: most abstinence signs and symptoms remained suppressed and patients reported felling well. Urine analysis failed to detect any presence of opiate metabolites. No withdrawal symptomatology recurred after 8 days of treatment when GHB was suspended, and patients were challenged with an intravenous injection of 0.4 mg naloxone. The results indicate that GHB may be useful in the management of opiate withdrawal.

A cohort study on vinyl chloride manufacturers in Italy: study design and preliminary results.

A cohort mortality study of 5000 vinyl chloride manufacturers is ongoing in 9 Italian plants. They represent the entire workforce of those ever employed in the production of the monomer and its polymerization. The objectives of the study are to investigate the mortality of the exposed population and to clear up the carcinogenic spectrum of vinyl chloride. This article gives the results for 3 out of 9 plants, Rosignano, Ferrara and Ravenna, which represent about 25% of the total cohort. The expected deaths have been calculated using the mortality rates of the Italian population. For the deceased persons information from the death certificates were used in the analysis of mortality; additional clinical and pathological data were collected (best pathological evidence, b.p.e.). In Ferrara a statistically significant excess for all malignant tumors and lung cancer was detected. In Rosignano and Ravenna the number of observed deaths were small and therefore no comments can be made on cancer mortality. The cohort study is ongoing in the 6 remaining cohorts and the future analysis will consider duration and level of exposure and latency.

Nitrate and nitrite exposure in Italian populations with different gastric cancer rates.

Exposure to nitrate and nitrite from dietary sources was estimated by questionnaire and measurement of salivary levels of the ions in residents of four regions of Italy with longstanding, contrasting, gastric cancer mortality rates. Whether using salivary levels or dietary questionnaire estimations no association was found between nitrate and nitrite exposure and gastric cancer mortality rates. For salivary nitrate and nitrite, the intra-provincial variation was greater than any inter-province difference. However, for dietary nitrate and nitrite intakes, there were significant differences between the regional groups (but not related to gastric cancer risk). Despite the limitations of the methods used, there was a weak positive association between salivary concentrations of nitrate and questionnaire assessment. Dietary factors are likely to play key roles at different stages of the gastric carcinogenic process. Nitrate may play a part but is unlikely to be a rate-limiting factor in all individuals or populations.

Prohibition of take-home dosages: negative consequences on methadone maintenance treatment.

Patients on methadone maintenance were forewarned that a law prohibiting take-home dosages was to be enforced within 6 months. At the end of the 6-month period preceding the enforcement of the law the effect of the anticipated suppression of the take-home privilege was studied on a cohort of 211 methadone-maintained patients on take-home dosages. The outcome of the treatment of these patients was compared to that of a control group of 220 patients at the end of a 6-month period prior to the announcement of the new law. The outcome of the study suggests that the restrictive regulation is counterproductive for retaining patients in treatment.

Buprenorphine: a controlled clinical trial in the treatment of opioid dependence.

Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence.

Cancer mortality of art glass workers in Tuscany, Italy.

OBJECTIVES: This study considers the cause-specific mortality from cancer among art glass workers employed in 17 industrial facilities in Tuscany, Italy. METHODS: A cohort of 3390 workers, 3180 men and 210 women, employed at least 1 year, was taken from company payrolls. It was followed between the year each factory started operation, mostly the mid-1950s, and 31 December 1993. The cause-specific expected mortality from cancer was computed for men relative to Tuscany rates, specified for gender, 5-year age groups, and calendar year. Separate analyses were carried out for the job title of maker and former and for batch mixers. RESULTS: For 3180 men, the observed mortality was above the expected for larynx [standardized mortality ratio (SMR) 166, 90% confidence interval (90% CI) 90-282], lung (SMR 123, 90% CI 100-151), stomach (SMR 105, 90% CI76-142), and brain (SMR 150, 90%CI 71-282) cancer. Increases for these causes were also found for the makers and formers. Mortality from larynx and lung cancer increased with latency, and significantly increased SMR values were observed for > or =21 years since first exposure. The increasing pattern was also present after adjustment for smoking. CONCLUSIONS: The results showed consistently increased mortality from larynx and lung cancer in the overall cohort and among makers and formers. Stomach and brain cancer was also increased in the overall cohort and among the makers and formers.

Bladder cancer: a selected review of the epidemiological literature.

The present contribution reviews the epidemiological literature on the risk factors for bladder cancer in humans, pointing to the new leads from the available knowledge and to suggestions on prevention and research needs. Smoking accounts for about 50% of bladder cancer cases in western countries, occupational exposures are second in importance in bladder cancer development. Exposure to aromatic amines in dyestuff manufacture, in the rubber and textile industry, occupations entailing exposure to paints and solvents, leather dust, inks, some metals, PAH, combustion products and diesel exhausts have been identified as risk factors from epidemiological studies. Other investigations have detected increased risk for bladder cancer in association with dietary factors, specifically fats and cholesterol, and with contamination of drinking water by chlorination by-products.

[The epidemiologist in the court: requirements, professional standards, and deontologic considerations]. / L'epidemiologo in tribunale: requisiti, standard professionali e considerazioni deontologiche.

This paper examines two issues associated with the activity of epidemiologists who act as expert witness in courts: professional standards and deontologic codes. These issues are to be viewed in the light of the various roles the epidemiologist is called to play in court, as consultant for the prosecutor, the defendant and the plaintiffs. The criteria adopted in court should not differ from the ones usually followed in good epidemiologic practice. Potential conflict of interest that may occur when the personal interest of a researcher leads to introduce bias in his/her/witnes is another relevant issue. Another relevant point is how an epidemiologist deals with his/her colleagues in the courts: diversity in opinions and rigorous critics are acceptable but they must be adequately documented.

[Causality in epidemiology: populations, individuals, and alternative explanations]. / Causalità in epidemiologia: popolazioni, individui e spiegazioni alternative.

The purpose of the present paper is to review issues concerning causal reasoning in epidemiology, with special emphasis on the relationship between observation at the individual and population level. The sequence of the three sections of the paper, causality in epidemiology, individual and population, alternative explanations, reflects the need to deal with issues of research methodology mainly derived from discussions in the frame of risk assessment, decision making, regulation and legal setting. In discussing the aforementioned topics, special attention is given to the attribution of causality to a single exposure in the presence of a plurality of potential causes. As a case study, data concerning the occurrence of hepatic and pulmonary tumors among subjects exposed to vinyl chloride are considered making reference to hearings on this topic which took place in Court.

[An epidemiological study of workers exposed to vinyl chloride in the plants of Ferrara, Rosignano and Ravenna]. / Indagine epidemiologica sui lavoratori esposti a cloruro di vinile negli stabilimenti di Ferrara, Rosignano e Ravenna.

The aim of the present study is to investigate cause-specific mortality among male workers employed in vinyl chloride manufacture and polymerization in three Italian plants located in Ferrara, Rosignano and Ravenna. The cohorts include all workers hired between start of operation and, respectively 1985, 1978 and 1985, amounting to 418, 206 and 635 subjects followed up for mortality until 1996 (Ferrara and Rosignano) and 1997 (Ravenna). Cause specific SMRs (Standardized mortality ratios) were computed. Expected figures were obtained from mortality rates for the population resident in the region where the plant was located, for each SMR value a 90% confidence interval (CI) was calculated on the assumption of a Poisson distribution. The study detected an increased mortality for primary liver cancer in all three plants; SMR values were 444 in Ferrara (4 Obs. 90% CI 160-1069), 200 in Rosignano (1 Obs. 90% CI 10-869) and 375 in Ravenna (3 Obs. 90% CI 110-1038). In the pooled cohort liver cancer SMR was equal to 364 (8 Obs. 90% CI 108-390). In one plant, Ferrara, observed mortality was above the expected for lung cancer, SMR = 146 (14 Obs. 90% CI 89-229) and for larynx cancer, SMR = 500 (4 Obs. 90% CI 174-1167). One death from pleural cancer was observed in Rosignano (SMR = 1000 90% CI 47-4331). A non significant increase was detected for liver cirrhosis, in Ferrara (SMR 108, 6 Obs. 90% CI 73-332) and Rosignano (SMR 129, 3 Obs. 90% CI 35-332). The study results are confirming the carcinogenic action of vinyl chloride on the liver, they are pointing to its possible role in lung cancer development, as already shown for workers employed in Porto Marghera; an increased risk for larynx cancer is also shown.