A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

The association of socioeconomic disadvantage with postoperative complications after major elective cardiovascular surgery.

BACKGROUND: Understanding the mechanism by which both patient- and hospital level factors act in generating disparities has important implications for clinicians and policy-makers. OBJECTIVE: To measure the association between socioeconomic position (SEP) and postoperative complications after major elective cardiovascular procedures. DESIGN: Multicity hospital-based study. SUBJECTS: Using Hospital Discharge Registries (ICD-9-CM codes), 19 310 patients were identified undergoing five cardiovascular operations (coronary artery bypass grafting (CABG), valve replacement, carotid endarterectomy, major vascular bypass, repair of unruptured abdominal aorta aneurysm (AAA repair)) in four Italian cities, 1997-2000. MEASURES: For each patient, a five-level median income index by census block of residence was calculated. In-hospital 30-day mortality, cardiovascular complications (CCs) and non-cardiovascular complications (NCCs) were the outcomes. Odds ratios (ORs) were estimated with multilevel logistic regression adjusting for city of residence, gender, age and comorbidities taking into account hospital and individual dependencies. MAIN RESULTS: In-hospital 30-day mortality varied by type of surgery (CABG 3.7%, valve replacement 5.7%, carotid endarterectomy 0.9%, major vascular bypass 8.8%, AAA repair 4.0%). Disadvantaged people were more likely to die after CABG (lowest vs highest income OR 1.93, p trend 0.023). For other surgeries, the relationship between SEP and mortality was less clear. For cardiac surgery, SEP differences in mortality were higher for publicly funded patients in low-volume hospitals (lowest vs highest income OR 3.90, p trend 0.039) than for privately funded patients (OR 1.46, p trend 0.444); however, the difference in the SEP gradients was not statistically significant. CONCLUSIONS: Disadvantaged people seem particularly vulnerable to mortality after cardiovascular surgery. Efforts are needed to identify structural factors that may enlarge SEP disparities within hospitals.

Time To Pregnancy and occupational lead exposure.

BACKGROUND: Lead exposure is known to be harmful to the male reproductive system, including impairment of fertility. However, it is unclear whether currently existing low levels of exposure have this effect. AIMS: To study retrospectively current workers in lead using industries (battery manufacture, smelting, etc), and in non-lead using control industries, in four European countries, with Time To Pregnancy as the outcome variable, as part of the EU funded Asclepios Project. METHODS: Exposure assessment was mainly by blood lead values, which were available from the late 1970s, supplemented by imputed values where necessary. Three exposure models were studied: (1) short term (recent) exposure; (2) total duration of work in a lead using industry; and (3) cumulative exposure. A Cox proportional hazards model with discrete ties was used for the statistical analysis, with covariates for both partners. RESULTS: A total of 1104 subjects took part, of whom 638 were occupationally exposed to lead at the relevant time. Blood lead levels were mainly less than 50 microg/dl. No consistent association of Time To Pregnancy with lead exposure was found in any of the exposure models, although reduced fertility was observed in one category each in models (2) and (3). CONCLUSIONS: This basically negative result is unlikely to be due to the misclassification of key variables, to insufficient statistical power, or to bias, for example, response bias. If any impairment of male reproductive function exists at the levels of occupational lead exposure now current, it does not appear to reduce biological fertility.

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Body mass index and delayed conception: a European Multicenter Study on Infertility and Subfecundity.

Obesity has become a health problem in affluent societies, but few studies have investigated its effect on subfertility. Previous studies were based on select groups of women, focused mainly on ovulatory dysfunctions, and yielded controversial results. The authors evaluated the effect of body mass index on delayed conception by using a European population-based survey of pregnant women from five countries. Delayed conception was defined as a time to pregnancy that exceeded 9.5 months of unprotected intercourse. During 1992, 4,035 pregnant women from well-defined geographic areas were recruited consecutively at antenatal clinics or hospitals after at least 20 weeks of gestation. For women smokers, after adjustment for sociodemographic, biologic, and lifestyle-related factors, there was a strong association between obesity (body mass index of > or =30 kg/m2) and delayed conception (odds ratio = 11.54, 95% confidence interval: 3.68, 36.15) and also an increased risk for women whose body mass index was <20 kg/m2 (odds ratio = 1.70; 95% confidence interval: 1.01, 2.83). The same analysis conducted for women nonsmokers showed no association. The authors concluded that for women who achieve a clinically detectable pregnancy, those who are underweight or obese require a longer time to conceive only if they also smoke.

Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children. SIDRIA Collaborative Group, Italy (Italian Studies on Respiratory Disorders in Children and the Environment).

BACKGROUND: A beneficial effect of fresh fruit consumption on lung function has been observed in several studies. The epidemiological evidence of the effect on respiratory symptoms and asthma is limited. The consumption of fruit rich in vitamin C was examined in relation to wheezing and other respiratory symptoms in cross sectional and follow up studies of Italian children. METHODS: Standardised respiratory questionnaires were filled in by parents of 18 737 children aged 6-7 years living in eight areas of Northern and Central Italy. The winter intake of citrus fruit and kiwi fruit by the children was categorised as less than once per week, 1-2 per week, 3-4 per week, and 5-7 per week. A subset of 4104 children from two areas was reinvestigated after one year using a second parental questionnaire to record the occurrence of wheezing symptoms over the intervening period. RESULTS: In the cross sectional analysis, after controlling for several confounders (sex, study area, paternal education, household density, maternal smoking, paternal smoking, dampness or mould in the child's bedroom, parental asthma), intake of citrus fruit or kiwi fruit was a highly significant protective factor for wheeze in the last 12 months (odds ratio (OR) = 0.66, 95% confidence intervals (CI) 0.55 to 0.78, for those eating fruit 5-7 times per week compared with less than once per week), shortness of breath with wheeze (OR = 0.68, 95% CI 0.56 to 0.84), severe wheeze (OR = 0.59, 95% CI 0.40 to 0.85), nocturnal cough (OR = 0.73, 95% CI 0.65 to 0.83), chronic cough (OR = 0.75, 95% CI 0.65 to 0.88), and non-coryzal rhinitis (OR = 0.72, 95% CI 0.63 to 0.83). In the follow up study fruit intake recorded at baseline was a strong and independent predictor of all symptoms investigated except non-coryzal rhinitis. In most cases the protective effect was evident even among children whose intake of fruit was only 1-2 times per week and no clear dose-response relationship was found. The effect was stronger (although not significantly so (p = 0.13)) in subjects with a history of asthma; those eating fresh fruit at least once a week experienced a lower one year occurrence of wheeze (29. 3%) than those eating fruit less than once per week (47.1%) (OR = 0. 46, 95% CI 0.27 to 0.81). CONCLUSIONS: Although the effect of other dietary components cannot be excluded, it is concluded that the consumption of fruit rich in vitamin C, even at a low level of intake, may reduce wheezing symptoms in childhood, especially among already susceptible individuals.

Differences in parental- and self-report of asthma, rhinitis and eczema among Italian adolescents. SIDRIA collaborative group. Studi Italiani sui Disordini Respiratori dell' Infanzia e l'Ambiente.

Epidemiological and clinical information on respiratory and allergic disorders in adolescents has been collected from the adolescents themselves or from their parents, but little is known about the differences between these two sources of information. This study compared the responses to 10 identically worded questions from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire on asthma, rhinitis and eczema between written self- and parent-completed questionnaires in a large sample of 21,068 adolescent Italians aged 13-14 yrs. The effects of sex, latitude of residence, urbanization, socioeconomic status, previous diagnosis of asthma, family history of allergic diseases and adolescent's smoking habits on the prevalence estimates obtained with the two questionnaires were analysed using multiple logistic regression. Prevalence of self-reported symptoms was significantly higher in self-reported for all questions except for lifetime eczema, which was higher in parental report. Agreement between the two sources of information was poor, although it was slightly better for questions relative to clinical diagnosis of asthma, hay fever or eczema than for related symptoms, and for respiratory with respect to cutaneous disorders. When compared with self-reported, parent-reported was consistently higher in males and was more affected by socioeconomic level and by a diagnosis of asthma or family history of allergic diseases, whereas self-reported was more sensitive to the effect of the adolescent's smoking habits. It is concluded that, in adolescents, parent- and self-reported respiratory and allergic symptoms differ significantly and are differently affected by several constitutional and environmental factors. Obtaining direct information from adolescents may be essential for a correct evaluation of respiratory symptoms.

Repeating episodes of low fecundability. A multicentre European study. The European Study Group on Infertility and Subfecundity.

Many reproductive failures tend to repeat themselves within the same couple. Whether fecundability (the probability of conceiving in a given number of menstrual cycles) follows the same pattern is studied using data from the European Studies on Infertility and Subfecundity (ESIS): 6630 women were interviewed on 'time to pregnancy' (TTP) and other aspects of their pregnancy history. Surveys were conducted between 1991 and 1994 in seven regions from five European countries. Furthermore, the pattern of fecundability in this population was compared with results from computer simulations based upon a population with fixed fecundability parameters. Results from ESIS speak in favour of the stability of fecundability in the relatively short reproductive life of a couple. However, a substantial proportion of couples with up to two events of subfecundability (TTP >9.5 months) became pregnant shortly after trying again. This finding calls for reservation in starting expensive and/ or unpleasant diagnostic procedures at an early stage when a couple tries to become pregnant again.

Caffeine intake and delayed conception: a European multicenter study on infertility and subfecundity. European Study Group on Infertility Subfecundity.

The effects of caffeine consumption on delayed conception were evaluated in a European multicenter study on risk factors of infertility. Information was collected retrospectively on time of unprotected intercourse for the first pregnancy and the most recent waiting time episode in a randomly selected sample of 3,187 women aged 25-44 years from five European countries (Denmark, Germany, Italy, Poland, and Spain) between August 1991 and February 1993. The consumption of caffeinated beverages at the beginning of the waiting time was used to estimate daily caffeine intake, which was categorized as 0-100, 101-300, 301-500, and > or = 501 mg. Risk of subfecundity (> or = 9.5 months) and the fecundability ratio, respectively, were assessed by logistic regression and Cox proportional hazard analyses, adjusting for age, parity, smoking, alcohol consumption, frequency of intercourse, educational level, working status, use of oral contraceptives, and country. A significantly increased odds ratio (OR) of 1.45 (95% confidence interval (CI) 1.03-2.04) for subfecundity in the first pregnancy was observed for women drinking more than 500 mg of caffeine per day, the effect being relatively stronger in smokers (OR = 1.56, 95% CI 0.92-2.63) than in nonsmokers (OR = 1.38, 95% CI 0.85-2.23). Women in the highest level of consumption had an increase in the time leading to the first pregnancy of 11% (hazard ratio = 0.90, 95% CI 0.78-1.03). These associations were observed consistently in all countries as well as for the most recent waiting time episode. The authors conclude that high levels of caffeine intake may delay conception among fertile women.

Cancer mortality in ethylene oxide workers.

A cohort of 1971 chemical workers licensed to handle ethylene oxide was followed up retrospectively from 1940 to 1984 and the vital status of each subject was ascertained. No quantitative information on exposure was available and therefore cohort members were considered as presumably exposed to ethylene oxide. The cohort comprised 637 subjects allowed to handle only ethylene oxide and 1334 subjects who obtained a licence valid for ethylene oxide as well as other toxic gases. Potential confounding arising from the exposure to these other chemical agents was taken into consideration. Causes of death were found from death certificates and comparisons of mortality were made with the general population of the region where cohort members were resident. Seventy six deaths were reported whereas 98.8 were expected; the difference was statistically significant. The number of malignancies for any site exceeded the expected number (standardised mortality ratio (SMR) = 130; 43 observed deaths; 95% confidence interval (95% CI) 94-175) and approached statistical significance. For all considered cancer sites the SMRs were higher than 100 but the excess was only significant (p < 0.05, two sided test) for lymphosarcoma and reticulosarcoma (International Classification of Diseases--9th revision (ICD-9) = 200; SMR = 682; four observed deaths; 95% CI 186-1745). The excess of cases for all cancers of haematopoietic tissue (ICD-9 = 200-208) also approached statistical significance (SMR = 250; six observed deaths; 95% CI 91-544). Focusing the analysis on the subcohort of the ethylene oxide only licensed workers, who are likely to have experienced a more severe exposure to this gas, it became evident that all but one of the observed cases of haematopoietic tissue cancers in the cohort were confined to this subgroup, enhancing the relevant SMR to 700 (95% CI 237-1637) and the SMR of lymphosarcoma and reticulosarcoma to 1693 (95% CI 349-4953).

Ethiopian National Hepatitis B Study.

A nationwide seroepidemiological study of hepatitis B markers prevalence was conducted in Ethiopia on 5,270 young males from all regions of the country. Overall prevalence rates were 10.8% for HBsAg and 73.3% for "at least one marker positive"; a remarkable geographical and ethnic variability of marker prevalence was observed, reflecting the wide differences existing in Ethiopia in sociocultural environment and activities such as tribal practices and traditional surgery. Sexual practices and medical exposure also play some role as determinants of hepatitis B marker prevalence in Ethiopia. General preventive measures, with particular reference to health education, by affecting incriminating habits and practices could have some impact on infection rates in Ethiopia, in the absence of a vaccination strategy presently unrealistic in this region of the world.