CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites.

BACKGROUND: Endogenous sex hormones are well-established risk factors for breast cancer; the contribution of specific oestrogen metabolites (EMs) and/or ratios of specific EMs is less clear. We have previously identified a CYP3A7*1C allele that is associated with lower urinary oestrone (E1) levels in premenopausal women. The purpose of this analysis was to determine whether this allele was associated with specific pathway EMs. METHODS: We measured successfully 12 EMs in mid-follicular phase urine samples from 30 CYP3A7*1C carriers and 30 non-carriers using HPLC-MS/MS. RESULTS: In addition to having lower urinary E1 levels, CYP3A7*1C carriers had significantly lower levels of four of the 2-hydroxylation pathway EMs that we measured (2-hydroxyestrone, P=1.1 × 10-12; 2-hydroxyestradiol, P=2.7 × 10-7; 2-methoxyestrone, P=1.9 × 10-12; and 2-methoxyestradiol, P=0.0009). By contrast, 16α-hydroxylation pathway EMs were slightly higher in carriers and significantly so for 17-epiestriol (P=0.002). CONCLUSIONS: The CYP3A7*1C allele is associated with a lower urinary E1 levels, a more pronounced reduction in 2-hydroxylation pathway EMs and a lower ratio of 2-hydroxylation:16α-hydroxylation EMs in premenopausal women. To further characterise the association between parent oestrogens, EMs and subsequent risk of breast cancer, characterisation of additional genetic variants that influence oestrogen metabolism and large prospective studies of a broad spectrum of EMs will be required.

Impact of type of full-field digital image on mammographic density assessment and breast cancer risk estimation: a case-control study.

BACKGROUND: Full-field digital mammography, which is gradually being introduced in most clinical and screening settings, produces two types of images: raw and processed. However, the extent to which mammographic density measurements, and their ability to predict breast cancer risk, vary according to type of image is not fully known. METHODS: We compared the performance of the semi-automated Cumulus method on digital raw, "analogue-like" raw and processed images, and the performance of a recently developed method - Laboratory for Breast Radiodensity Assessment (LIBRA) - on digital raw and processed images, in a case-control study (414 patients (cases) and 684 controls) by evaluating the extent to which their measurements were associated with breast cancer risk factors, and by comparing their ability to predict breast cancer risk. RESULTS: Valid Cumulus and LIBRA measurements were obtained from all available images, but the resulting distributions differed according to the method and type of image used. Both Cumulus and LIBRA percent density were inversely associated with age, body mass index (BMI), parity and postmenopausal status, regardless of type of image used. Cumulus percent density was strongly associated with breast cancer risk, but with the magnitude of the association slightly stronger for processed (risk increase per one SD increase in percent density (95 % CI): 1.55 (1.29, 1.85)) and "analogue-like" raw (1.52 (1.28, 1.80)) than for raw (1.35 (1.14, 1.60)) images. LIBRA percent density produced weaker associations with risk, albeit stronger for processed (1.32 (1.08, 1.61)) than raw images (1.17 (0.99, 1.37)). The percent density values yielded by the various density assessment/type of image combinations had similar ability to discriminate between patients and controls (area under the receiving operating curve values for percent density, age, BMI, parity and menopausal status combined ranged from 0.61 and 0.64). CONCLUSIONS: The findings showed that Cumulus can be used to measure density on all types of digital images. They also indicate that LIBRA may provide a valid fully automated alternative to the more labour-intensive Cumulus. However, the same digital image type and assessment method should be used when examining mammographic density across populations, or longitudinal changes in density within a single population.

Assessing within-woman changes in mammographic density: a comparison of fully versus semi-automated area-based approaches.

BACKGROUND: Mammographic density (MD) varies throughout a woman's life. We compared the performance of a fully automated (ImageJ-based) method to the observer-dependent Cumulus approach in the assessment of within-woman changes in MD over time. METHODS: MD was assessed in annual pre-diagnostic films (from age 40 to early 50s) from 313 breast cancer cases and 452 matched controls using Cumulus (left medio-lateral oblique (MLO) readings) and the ImageJ-based method (mean left-right MLO readings). Linear mixed models were used to compare within-woman changes in MD among controls. Associations between individual-specific MD trajectories and breast cancer were examined using conditional logistic regression. RESULTS: The age-related trajectories predicted by Cumulus and the ImageJ-based method were similar for all MD measures, except that the ImageJ-based method yielded slightly higher (by 2.54%, 95% CI 2.07%, 3.00%) estimates for percent MD. For both methods, the yearly rate of change in percent MD was twice faster after menopause than before, and higher BMI was associated with lower mean percent MD, but not associated with rate of change. Both methods yielded similar associations of individual-specific MD trajectories with breast cancer risk. CONCLUSIONS: The ImageJ-based method is a valid fully automated alternative to Cumulus for measuring within-woman changes in MD in digitized films. The Age Trial is registered as an International Standard Randomized Controlled Trial, number ISRCTN24647151.

European enhanced surveillance of invasive pneumococcal disease in 2010: data from 26 European countries in the post-heptavalent conjugate vaccine era.

Streptococcus pneumoniae is a leading cause of severe infectious diseases worldwide. This paper presents the results from the first European invasive pneumococcal disease (IPD) enhanced surveillance where additional and valuable data were reported and analysed. Following its authorisation in Europe in 2001 for use in children aged between two months and five years, the heptavalent pneumococcal conjugate vaccine (PCV7) was progressively introduced in the European Union (EU)/European Economic Area (EEA) countries, albeit with different schemes and policies. In mid-2010 European countries started to switch to a higher valency vaccine (PCV10/PCV13), still without a significant impact by the time of this surveillance. Therefore, this surveillance provides an overview of baseline data from the transition period between the introduction of PCV7 and the implementation of PCV10/PCV13. In 2010, 26 EU/EEA countries reported 21 565 cases of IPD to The European Surveillance System (TESSy) applying the EU 2008 case definition. Serotype was determined in 9946/21565 (46.1%) cases. The most common serotypes were 19A, 1, 7F, 3, 14, 22F, 8, 4, 12F and 19F, accounting for 5949/9946 (59.8%) of the serotyped isolates. Data on antimicrobial susceptibility testing (AST) in the form of minimum inhibitory concentrations (MIC) were submitted for penicillin 5384/21565 (25.0%), erythromycin 4031/21565 (18.7%) and cefotaxime 5252/21565 (24.4%). Non-susceptibility to erythromycin was highest at 17.6% followed by penicillin at 8.9%. PCV7 serotype coverage among children <5 years in Europe, was 19.2%; for the same age group, the serotype coverage for PCV10 and PCV13 were 46.1% and 73.1%, respectively. In the era of pneumococcal conjugate vaccines, the monitoring of changing trends in antimicrobial resistance and serotype distribution are essential in assessing the impact of vaccines and antibiotic use control programmes across European countries.

Hospitalisation for rotavirus gastroenteritis in the paediatric population in the Veneto Region, Italy.

BACKGROUND: This study evaluates the epidemiological impact of RVGE hospitalisation in the Veneto Region during the period spanning from 2000-2007 along with the associated costs. The analysis was conducted in an area where rotavirus vaccination is not included into immunization programmes and is an attempt to assess the potential benefits of such introduction. METHODS: To update the estimates of acute RVGE hospitalisation rates in children ≤5 years in the Veneto Region, we conducted an 8 year retrospective observational population-based analysis (2000-2007). RESULTS: Over the study period, a total of 4,119 admissions for RVGE were reported, with a mean hospital stay of 3.5 days. The population-based hospitalisation RVGE incidence rate was 195.8 per 100,000 children aged ≤5 years (lower than other European countries). CONCLUSIONS: RVGE is an important cause of paediatric hospitalisation in the Veneto Region. The data reaffirm the substantial burden of rotavirus hospitalisations in children and the potential health benefits of the vaccination as well as the possibility of adding rotavirus vaccination to the current schedule.

Immunogenicity of three different influenza vaccines against homologous and heterologous strains in nursing home elderly residents.

We studied whether MF59-adjuvanted influenza vaccine improves immunity against drifted influenza strains in institutionalised elderly with underling chronic health conditions. Sera from a randomized study, comparing MF59-adjuvanted (Sub/MF59, n = 72), virosomal (SVV, n = 39), and split (n = 88) vaccines, were retested using a hemagglutination inhibition (HI) assay against homologous (Northern Hemisphere [NH] 1998/99) and drifted (NH 2006/07) strains. Corrected postvaccination HI antibody titres were significantly higher with Sub/MF59 than SVV for all strains; GMTs against homologous A/H3N2 and B and both drifted A strains were significantly higher for Sub/MF59 than split. Seroprotection rates and mean-fold titer increases were generally higher with Sub/MF59 for all A influenza strains. MF59-adjuvanted influenza vaccine induced greater and broader immune responses in elderly people with chronic conditions, than conventional virosomal and split vaccines, particularly for A/H1 and A/H3 strains, potentially giving clinical benefit in seasons where antigenic mismatch occurs.

Varicella: epidemiological aspects and vaccination coverage in the Veneto Region.

BACKGROUND: With the control of many infections through national vaccination programmes, varicella is currently the most widespread preventable childhood disease in industrialized nations. In 2005 varicella vaccination was added to the Veneto Region routine immunization schedule for all children at 14 months of age and 12 year-old susceptible adolescents through an active and a free of charge offer. To evaluate parameters at the start of the programme, we conducted a study to describe the epidemiology of varicella infection and coverage rates for varicella vaccine in the Veneto Region (North-East Italy). METHODS: We examined incidence rates and median age of case patients in the Veneto Region for 2000-2007 period using two data sources: the mandatory notification of infections diseases and the Italian Paediatric Sentinel Surveillance System of Vaccine Preventable Diseases. Corrected coverage rates were calculated from data supplied by the Public Health and Screening Section of the Regional Department for Prevention. RESULTS: In the Veneto Region from 2000 to 2007, a total of 99,351 varicella cases were reported through mandatory notifications, mostly in children under 15 years of age. The overall standardised annual incidence ranged from 2.0 to 3.3 per 1,000 population, with fluctuations from year to year. The analysis by geographic area showed a similar monthly incidence rate in Italy and in the Veneto Region. The vaccination average adherence rate was 8.2% in 2004 cohort, 63.5% in 2005 cohort and 86.5% in 2006 cohort. Corrected coverage rates were 8.1% in 2004 cohort, 59.9% in 2005 cohort and 70.0% in 2006 cohort, respectively. CONCLUSION: Data from passive and active surveillance systems confirm that varicella is a common disease which each year affects a large proportion of the population, mainly children. Uptake of the varicella vaccination programme was strikingly good with average coverage rates of about 70% after only 3 years. Sustained implementation of existing vaccine policies is needed to warrant any significant reduction of varicella incidence in the Veneto Region. Continued surveillance will be important to monitor the impact of the recently introduced mass vaccination policy.