Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

High levels of women's satisfaction and compliance with transdermal contraception: results from a European multinational, 6-month study.

OBJECTIVE: To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch. METHODS: Women (18-46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 µg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods. RESULTS: Of the 778 participants, 36.8% (n = 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n = 334) and barrier methods (21.5%, n = 106). Of oral contraception users, 63.5% (n = 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8% (n = 260) reporting missed doses. After 3 and 6 cycles, >80% of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated. CONCLUSION: Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential to offer high compliance and efficacy.

[Italian national register of low etiological fraction occupational cancer pursuant to art. 244 of legislative decree n. 81/2008]. / Il registro nazionale dei casi di neoplasia a bassa frazione eziologica con sospetta origine professionale istituito dall'art. 244 del D.Lgs. n. 81/2008.

Legislative decree No. 81/2008 in the article n. 244 states that ISPESL, now INAIL, realizes a register of occupational cancers with low etiological fraction by means of a data collection method based exclusively on voluntary reports by GPs, healthcare and social security agencies (ReNaLOC) and a surveillance cancer monitoring system (OCCAM) based on linkage of routinely available data (cancer registries, hospital discharge records, Italian Social Security archives). ReNaLOC has produced a partial picture of the situation, it includes 1.584 cases as of June 2011. With OCCAM many situations of known risks were identified and others are worthy to be deepen.

[Study of lung cancer risk in the electroplating industry in Lombardy based on the OCCAM method]. / Studio del rischio cancerogeno per il polmone nell'industria galvanica in Lombardia basato sul metodo OCCAM.

BACKGROUND: The OCCAM method consists of case-control studies aimed at estimating occupational risks by cancer site, by area and by economic sector, using available archives to identify cases and controls; for exposure definition each subject is assigned to the category code of the economic sector or company where he/she worked the longest, obtained by automatic link with the Social Security Institute (INPS) files. The reference category (unexposed) consists of service industry workers. The economic sector is given by the ATECO category that INPS assigns to each firm. OBJECTIVES: In the Lombardy Region, lung cancer risk evaluated for the "metal treatment" industry as a whole was 1.32 (90% CI 1.33-3.10, 67 cases) for males and 1.33 (90% CI 0.51-3.59, 10 cases) for females. The aim of the study was to estimate lung cancer risk among metal electroplating workers only. METHODS: The metal electroplating firms were identified according to the detailed description of production, data which was also contained in INPS files, instead of using the "metal treatment" ATECO code. Lung cancer risk was evaluated using 2001-2008 incident cases identified from hospital discharge records of residents in the Lombardy Region. Controls were a sample from National Health Service files. RESULTS: For the group of firms identified as metal electroplating industries the risk was 2.03 (90% CI 1.69-8.32, 18 cases) for males and 3.75 (90% CI 1.38-9.03, 4 cases) for females. CONCLUSIONS: Focusing on the true electroplating firms increased the risk estimates. Even though these risk were due to past exposures, case histories and recent acute effects indicate that, at least in some factories, a carcinogenic hazard still exists.

Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: a nested case-control study.

BACKGROUND AND AIMS: The increase in breast cancer incidence over recent decades has been accompanied by an increase in the frequency of metabolic syndrome. Several studies suggest that breast cancer risk is associated with the components of metabolic syndrome (high serum glucose and triglycerides, low HDL-cholesterol, high blood pressure, and abdominal obesity), but no prospective study has investigated risk in relation to the presence of explicitly defined metabolic syndrome. We investigated associations between metabolic syndrome, its components, and breast cancer risk in a nested case-control study on postmenopausal women of the ORDET cohort. METHODS AND RESULTS: After a median follow-up of 13.5 years, 163 women developed breast cancer; metabolic syndrome was present in 29.8%. Four matched controls per case were selected by incidence density sampling, and rate ratios were estimated by conditional logistic regression. Metabolic syndrome (i.e. presence of three or more metabolic syndrome components) was significantly associated with breast cancer risk (rate ratio 1.58 [95% confidence interval 1.07-2.33]), with a significant risk increase for increasing number of components (P for trend 0.004). Among individual metabolic syndrome components, only low serum HDL-cholesterol and high triglycerides were significantly associated with increased risk. CONCLUSIONS: This prospective study indicates that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women. Although serum HDL-cholesterol and triglycerides had the strongest association with breast cancer, all components may contribute to increased risk by multiple interacting mechanisms. Prevention or reversal of metabolic syndrome by life-style changes may be effective in preventing breast cancer in postmenopausal women.

[Confounding and confusion: recognition of causative relation and identification of victims of occupational carcinogens]. / I confonditori e le confusioni: il riconoscimento del nesso causale e la identificazione delle vittime dei cancerogeni professionali.

The recognition of occupational cancers is often hampered by the confusion between the individual determinants of the disease and the effect at the group exposure. Here we propose an approach based on the evaluation of the attributable risk at group level aimed to quantify the respective role of multiple causes, and the individual rebounds of it.

[In-progress matrix for occupational cancer recognition]. / Matrice "inprogress" per la consultazione dei dati bibliografici relativi alle neoplasie di sospetta origine professionale.

BACKGROUND: In Italy only a small proportion of all cancers is reported to the national labour insurance board and recognized as having an occupational origin. Cancers with a lower etiological fraction such as lung or bladder cancer have a lower rate of recognition than mesotheliomas or sino-nasal tumours either because of a lack of information obtained via specific occupational anamnesis or because knowledge concerning occupational carcinogens is still uncertain. OBJECTIVES: To interpret findings and advance new working hypotheses, within the framework of an occupational monitoring survey project (OCCAM) we performed an extensive bibliographical search in the scientific literature on occupational cancer. METHODS AND RESULTS: We built an on-line "literature matrix" (www.occam.it) containing positive" results from 685 cohort, case-control and cross-sectional epidemiological studies on occupational cancer, from which 1870 citations were obtained describing risk increases by type of cancer and industry. Production cycles or type of industry (iron foundry, leather and shoe manufacturing, etc.) constitute one axis of the matrix and the other consists of type of cancer by site. CONCLUSIONS: This tool is not only useful for interpretation of evidence arising from occupational cancer surveys but was also intended to be a fast and easy-to-use working tool for occupational physicians, general practitioners and many other specialists to investigate and ascertain the possible occupational origin of a cancer case.

[Active search of work related tumours: preliminary findings]. / La ricerca attiva deli tumori di origine professionale: primi risultati.

UNLABELLED: The OCCAM (Occupational Cancer Monitoring) project enabled the active detection of occupational cancer cases in Lombardy Region. METHODS: OCCAM is based on a record linkage with social security files to obtain occupational histories for all subjects having worked in private firms, since 1974. It provides risks by area, site and job. RESULTS: 271 incident cancer cases obtained by hospital discharge record in the period 2001-2002 where investigate to assess eventually their occupational origin. Approximately 38% where considered to be occupational cancers. CONCLUSIONS: OCCAM provides name of the firms and their economic activity completed by information coming from OCCAM risks ascertainment and deeper knowledge on productive cycle retained by local occupational health services. Thus this system can lead to detection of many cancer cases of occupational origin suitable for compensation and determine strategies for the improvement of the work environment.

[The contraceptive method that changed the world]. / La contraccezione ha cambiato il mondo.

During the past century human life expectancy doubled while the birth rate dropped. The widespread use of effective contraceptives has led to a better control of human fertility and changed the structure of modern societies: the elderly now increasingly outnumber the young. Scientifically controlled human reproduction has also resulted in fewer voluntary abortions. The choice of contraceptive strategies differs by geographic area and seems to be linked to such simple mechanisms as the ''door-to-door'' effect. In European countries where the pill is the most widely used contraceptive, interesting variations in the biological profile of oral contraceptive users can be observed; for example, women taking a hormonal contraceptive have only half the risk of developing ovarian cancer. The world is no longer the same since the advent of the pill.

Age, menopausal status and homocysteine levels in women around menopause.

OBJECTIVE: To obtain data on the relation between age, menopause and homocysteine levels in women around menopause, we collected data for a sample of about 500 women attending a menopause clinic in Milan, Italy. STUDY DESIGN: Eligible for the study were all women aged 45-75 years, never HRT users consecutively observed for the first time at the Menopause Center of the 1st Obstetric Gynecological Clinic of the University of Milan. Fasting blood samples for total homocysteine plasma levels were collected during the visit. Of the 490 study subjects, 107 were pre-menopausal and 383 post-menopausal. RESULTS: In the total series, the mean homocysteine level was 8.3 micromol/L (S.D. 3.7, range 3.2-48.8). The values increased from 7.8 micromol/L in women aged <47 years to 9.0 micromol/L in those aged >59. Among pre-menopausal women the mean homocysteine level was 7.7 micromol/L compared to 8.3 micromol/L in post-menopausal women: this difference disappeared on the adjusted values. In post-menopausal women only, no clear relationship emerged between years since menopause and homocysteine levels. CONCLUSION: In our population, age, and not menopausal status, was the main determinant of homocysteine levels in women around menopause.

The EpiLink record linkage software: presentation and results of linkage test on cancer registry files.

OBJECTIVES: Record linkage, the process of bringing together separately compiled but related records from different databases, is essential in many areas of biomedical research. We developed a record linkage program (EpiLink), which employs a simple mathematical approach. We describe the program and present results obtained testing it in a linkage task. METHODS: EpiLink was designed to be flexible with user-friendly settings to tailor linkage and operating parameters to specific linkage tasks, and employ deterministic, probabilistic or sequential deterministic-probabilistic linkage strategies as required. The user can also standardize data format, examine linkage results and accept or discard them. We used EpiLink to link a subset of cases of the Lombardy Cancer Registry (20,724 records) with the Social Security file of the population (1,021,846 records) covered by the registry. The linkage strategy was deterministic, followed by several probabilistic linkage steps. RESULTS: Manual inspection of the results showed that EpiLink achieved 98.8% specificity and 96.5% sensitivity. CONCLUSIONS: EpiLink is a practical and accurate means of linking records from different databases that can be used by non-statisticians and is efficient in terms of human and financial resources.

The lowering of lipoprotein[a] induced by estrogen plus progesterone replacement therapy in postmenopausal women.

OBJECTIVE: To evaluate whether estrogen plus progesterone replacement therapy influences the plasma lipoprotein[a] (Lp[a]) levels in postmenopausal women. DESIGN: Fifty-five women who had been menopausal for at least 1 year were followed up for 12 months. Twenty-four subjects served as the control group and 31 subjects served as the therapy group. The therapy consisted of conjugated estrogen (1.25 mg/d) and medroxyprogesterone acetate (10 mg/d for 10 days a month). Blood samples were obtained before the start of therapy and at 6 months and 12 months after therapy. Nine subjects in the therapy group were followed up for an additional year after the treatment was suspended (washout group). SETTINGS: All subjects were healthy women (mean age, 52 years) who had natural menopause at least 1 year before the beginning of recruitment. None of the women had received exogenous sex steroids or drugs known to influence lipid and lipoprotein metabolism in the previous 12 months. MAIN RESULTS: In the control group, no change was noted in the plasma Lp[a] concentrations during the study. In the treatment group, the mean plasma Lp[a] concentrations decreased 50% after 6 months (P < .01) and remained at this level 12 months after treatment was started. In the washout group, mean plasma Lp[a] levels tended to return to pretherapy values. In addition, estrogen plus progesterone treatment significantly lowered total cholesterol levels by 15% and low-density lipoprotein cholesterol levels by 30%; it increased high-density lipoprotein cholesterol levels by 19%. CONCLUSION: The results suggest that in estrogen plus progesterone-treated postmenopausal women, the lipid profile is improved not only by lowering low-density lipoprotein cholesterol levels and raising high-density lipoprotein levels, but also by lowering plasma Lp[a] concentrations.

Looking to Europe: something's changed in Italy.

The new Italian law regulating the use of assisted reproduction technologies (ARTs) prohibits treatment widely practiced in Europe. The new regulations have already given rise to a humiliating form of "reproductive tourism" of Italian subfertile couples.

[Use of pension records for occupational health surveillance: example of record-linkage with hospital discharge records to study the association between work and the incidence of leukaemias, lung and bladder cancer, and miscarriage]. / Il linkage tra le storie professionali di fonte INPS e i dati dei ricoveri ospedalieri per lo studio delle cause lavorative di alcuni tumori e degli aborti spontanei.

BACKGROUND: Epidemiologic surveillance of occupational health based on routinely collected data allows groups of workers to be studied, whose type of work (e.g. small enterprises, self-employed workers, artisans) makes it difficult to use a traditional cohort study design. OBJECTIVE: To evaluate the validity of a study design based on the record-linkage between hospital discharge records and INPS social security records (National Institute for Social Security), in order to investigate the association between past employment in an economic sector and occurrence of diseases with a low fraction attributable to occupation and a high frequency in the population, where it is too costly to perform retrospective interviews to gather data from each recruited subject. METHODS: A case-control study design was used in which hospital discharge records from 1995 in the Piedmont Region represented the source of subjects enrolled. Four series of cases were identified: males aged 40-75 years, with first hospital admission for leukaemia, lung or bladder cancer; and women aged 18-39 years, admitted for miscarriage. The controls were a random sample of patients admitted in the same year and matched by sex and age. The exposure variable was the prevalent economic sector in the occupational history of the subjects enrolled, as inferred from INPS social security records. RESULTS: No economic sector examined showed a significant excess of incidence of bladder cancer or leukaemia. There was a significant excess of lung cancer in subjects with longest employment in the building industry, in metal working, and in the "foundries, heat pressing, forging, and rolling mills" sector. A significant excess of miscarriages was present only in women working in commerce. DISCUSSION: The results demonstrated overall a low consistency compared with those obtained via other surveillance systems of occupational morbidity and mortality, as well as by means of analytical studies. The results appear more plausible for the sectors characterized by a low number of job tasks, or by a more homogenous exposure to risk factors among workers in different jobs. Among the limitations of this study the lack of a complete occupational history, the absence of information on potential confounders like smoking and alcohol consumption, and the probable non-differential misclassification of the longest held job need to be stressed

[A monitoring system for occupational cancer]. / Un sistema di monitoraggio per i tumori di origine professionale.

INTRODUCTION: The Italian Occupation and Safety Act (d.lgs 626/94) provided for the establishment of a nationwide occupational cancer registry, under the National Institute for Occupational Health and Safety (ISPESL), with the aim of detecting cancer cases of occupational origin and estimating the influence of occupation in cancer causation. METHODS: Information on cancer cases, drawn from six Italian population-based cancer registries (CRs of Friuli Venezia Giulia Region, Genoa Town and Genoa Province, Macerata Town, Umbria Region, Varese Town, Veneto Region), and on a random sample of population controls selected in each CRs area were linked with data on subjects employed in private enterprises that have been available in electronic form since 1974 at the National Institute for Social Security (INPS). In this way, both for cases and controls, the occupational histories of past employment were collected. A population-based case-control study covering the period 1990-1998 was carried out with the aim of estimating occupational cancer risk in the private sector by site and economic category in each area. Since one of the major drawbacks of this approach is the difficulty in distinguishing true occupational hazards from incidental findings derived from multiple comparisons, an extensive research of occupational literature was carried out, independently of the study results, to compare our results with existing knowledge on occupational risks. RESULTS: Pooled analysis of the most recent incidence data based on 36,379 cases and 29,572 controls was performed; 34 "statistically significant" associations were found for 11 economic categories. Using our literature review, 10 associations were supported by more than 5 publishedpapers, 14 by a number of papers between 1 and 5, and 10 associations had not been previously reported. CONCLUSIONS: This system appears suitable for assessing existing occupational cancer risks and can eventually lead to detecting occupational hazards in many areas of Italy. The system can also provide a list of cases suitable for in-depth search for past occupational exposures.

Effect of three serotonin antagonists on plasma prolactin response to suckling in puerperal women.

The effect of the acute administration of three serotonin antagonists on plasma PRL levels and on the PRL response to suckling was investigated in a group of puerperal women. A single oral dose of metergoline or methysergide induced a significant decrease of plasma PRL levels and abolished the PRL response to suckling. Cyproheptadine administration did not modify either the plasma PRL levels or the PRL response to suckling. These results are discussed in light of the known pharmacological properties of the three antiserotonergic drugs.

Functional characterization of hypothalamic hyperprolactinemia.

PRL secretory dynamics were evaluated by several stimulation and suppression tests in nine patients with hyperprolactinemia due to organic hypothalamic disease. Basal PRL levels ranged between 20-63 ng/ml. There was a normal PRL response to TRH in eight cases (i.e. doubling of basal levels), whereas none of the seven tested subjects responded to sulpiride. The same dissociation of responses was not observed in any of the patients who were still hyperprolactinemic after surgery. Concomitant dopamine infusion resulted in sulpiride-induced PRL release in the four subjects so studied. None of 50 other hyperprolactinemic patients (11 with macroprolactinoma, 18 with microprolactinoma, and 21 with idiopathic hyperprolactinemia) showed PRL response to TRH but not to sulpiride. The TRH-induced PRL increase was significantly higher than that induced by sulpiride in hypothalamic hyperprolactinemia and significantly lower in idiopathic disease as well as in healthy controls; no differences were found in prolactinoma patients. The administration of substances resulting in stimulation of pituitary dopamine receptors, such as dopamine and L-dopa, induced a normal PRL suppression in 7 patients with hypothalamic disease so tested, whereas central nervous system-acting dopaminergic drugs, such as carbidopa plus L-dopa and nomifensine, failed to lower PRL levels in most cases (even when normoprolactinemic after surgery). These data suggest that the mild to moderate hyperprolactinemia found in many patients with hypothalamic lesions is due to dopamine deficiency at the pituitary level, that TRH and dopamine receptors at the lactotropes are intact in this condition, and that paired TRH and sulpiride tests may be of some diagnostic utility in hyperprolactinemic patients. They further suggest that subjects with so-called idiopathic hyperprolactinemia do not suffer from the type of hypothalamic derangement exhibited by patients with organic lesions of the hypothalamus.

Failure of dopamine infusion to suppress the plasma prolactin response to sulpiride in normal and hyperprolactinemic subjects.

In eleven normal women dopamine infusion (5 microgram/Kg/min) significantly lowered plasma prolactin levels but failed to suppress the PRL response to sulpiride (10 or 100 mg i.v.), while the same dose of dopamine was effective in abolishing the PRL response to TRH (200 microgram i.v.). In four hyperprolactinemic women showing an impaired PRL response to sulpiride, dopamine infusion was effective both in lowering PRL circulating levels and in restoring an evident response to sulpiride. This finding suggests an impairment of endogenous dopamine activity in hyperprolactinemic amenorrhea.

Prolactin-lowering effect of acute and once weekly repetitive oral administration of cabergoline at two dose levels in hyperprolactinemic patients.

To further evaluate the potency and time course of the PRL-lowering effect of single oral doses of cabergoline, two doses of the drug were given to 51 hyperprolactinemic patients who also received 2.5 mg bromocriptine according to a randomized cross-over design. One group (n = 26) received 0.3 mg, and the other (n = 25) received 0.6 mg. Both cabergoline doses induced a significant fall in serum PRL levels, which lasted, on the average, from 3 h to 5 days after 0.3 mg and from 3 h to 14 days after 0.6 mg; the mean maximum decrease after 0.3 mg was -65 +/-4% (+/- SEM), significantly (P less than 0.05) less than that after bromocriptine (group mean, -73 +/- 4%), and it was -76 +/- 3% after 0.6 mg, not significantly different from that induced by bromocriptine (group mean, -71 +/- 4%). The effect of 0.6 mg cabergoline was significantly greater than that of 0.3 mg (P less than 0.01). In a second study designed to evaluate the possible therapeutic use of the new drug, 0.3 or 0.6 mg cabergoline was administered orally once weekly for 9 weeks to 2 groups of 15 and 16 hyperprolactinemic patients, respectively. Serum PRL levels fell significantly by the first week and reached a plateau after 2 doses in the 0.6 mg cabergoline-treated group and after 5 doses in the 0.3 mg-treated group; the absolute PRL decrease was greater in the former. Ten patients in each group achieved normal serum PRL levels, and a marked decrease (greater than 50% of pretreatment values) occurred in all patients treated with 0.6 mg and in 13 treated with 0.3 mg weekly. Resumption of menses occurred during the treatment period in 15 of the 17 premenopausal women with amenorrhea. Six patients who had poor responses had better responses when given higher drug doses for 4 weeks, and serum PRL levels became normal in the 3 receiving 0.6 mg twice weekly. These data confirm that cabergoline is a long-acting oral dopaminergic drug and suggest that it may be a useful agent for the treatment of patients with hyperprolactinemia.

Failure of nomifensine administration to discriminate between tumorous and nontumorous hyperprolactinemia.

It has recently been claimed that the PRL-lowering response to nomifensine administration (200 mg, orally) reliably discriminates patients with PRL-secreting tumors from those with so-called functional hyperprolactinemia. In the present study, this test was performed in 15 healthy controls, 7 hyperprolactinemic subjects without evidence of pituitary tumor, and 16 patients with prolactinoma. A decrease of serum PRL to below 65% of basal levels, which seemed to be the cut-off point in the previous study, was obtained in 11 subjects of the first group, in 4 subjects of the second group, and in 4 subjects of the third group. The decrease of mean serum PRL concentration after nomifensine was only significant in the first and second groups. Analysis of variance showed a significant difference in the PRL inhibition by nomifensine between the tumor group and the two groups without evidence of pituitary adenoma. Nevertheless, this study shows that the nomifensine test is unable to discriminate in the individual patient the tumorous or nontumorous origin of excessive PRL secretion.