Evaluación de la efectividad vacunal de la vacuna conjugada contra el meningococo C en España

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Faculta de Medicina, Departamento de Medicina Preventiva y Salud Pública y Micorobiología. Fecha de lectura: 11-12-201

Enfermedad meningocócica en España. Análisis de la temporada 2009-2010

La enfermedad meningocócica es de declaración obligatoria en España. Los casos se notifican de manera individualizada con periodicidad semanal y con una serie de datos epidemiológicos a través de la Red Nacional de Vigilancia Epidemiológica (RENAVE). Se presenta el análisis de los resultados de la vigilancia epidemiológica de enfermedad meningocócica para la temporada 2009-2010 en España

Hypochlorous acid in a double formulation (liquid plus gel) is a key prognostic factor for healing and absence of infection in chronic ulcers. A nonrandomized concurrent treatment study

Background and aims: Diverse protocols prevent infection and/or improve ulcer epithelialization. The existing protocols tend to antagonize the risk factors that promote the chronicity of this type of wound. Hypochlorous acid (HOCl) is used to treat ulcers and wounds because of its antiseptic and noncytotoxic properties. Its liquid form is effective but has little residual effect, while in gel it has more residual power. Methods: An experimental nonrandomized study has been carried out treating 346 chronic ulcers of various etiologies in 220 patients. Ulcer outcomes were originally classified as: "complete healing," "incomplete healing without infection," and "incomplete healing with infection." Various antiseptic solutions were used as ulcers cleaning solutions: liquid HOCl, gel HOCl, polymeric biguanide, or chlorhexidine. Only one was applied to the lesion as monotherapy. But, in other cases, we used a combined HOCl (liquid then gel: bitherapy). Bivariate (Chi-square and variance tests) and multivariate studies (logistic regression) evaluated associations of ulcer characteristics and mono or bitherapy outcomes. Results: Four factors reduce the probability of complete ulcer healing: patient age (odds ratio [OR]: 0.97); weeks of ulcer evolution (OR: 0.99); poor granulation on admission (OR: 0.35); and need for antibiotic therapy (OR: 0.41). One factor favored healing: combined HOCl therapy with liquid plus gel (OR: 4.8). Infections were associated with longer times of evolution (OR: 1.002) and bad odor of the ulcer on admission (OR: 14), but bitreatment with HOCl reduced the risk of infection (OR: 0.3). Conclusion: A double HOCl formulation (liquid plus gel) reduces the probability of poor healing and infection, in chronic ulcers of various etiologies.S

Epidemiology of childhood tuberculosis in Spain: 2005-2009

BACKGROUND: European recent data about paediatric tuberculosis point out the importance of evaluate the trends of the disease to study the recent transmission, as well as the necessity of improving the microbiological diagnosis in paediatric cases. The aim of this paper is to study the epidemiology and trend evolution of paediatric tuberculosis in Spain during the period 2005-2009 and to establish the epidemiological differences between adult and paediatric tuberculosis. METHODS: Data reported to the National Surveillance Net (Red Nacional de Vigilancia Epidemiológica) in Spain was checked. Lineal regression was developed to establish the trend of the disease in all, adult and paediatric cases. Bivariate and multivariate logistic regression was used to compare paediatric and adult cases reported in 2009 and estimate the influence of different factors in the development of the disease. RESULTS: A total 39775, 2690 paediatrics (6.76%) cases of tuberculosis were reported during 2005-2009 period. Paediatric tuberculosis rates showed a slight increasing tendency (y=0.15x+7.8), while adult rates decrease during the period (y=-0.28x+20.2). In 2009, rates were 8.1 and 18.3 cases/100,000 inhab. for children and adults respectively. Paediatric cases presented higher proportion of pulmonary locations (84% vs. 76% in adults) and lower percentages of cases confirmed by culture (51% vs. 82% in adults) and of cases in non-Spanish population (25% vs. 34%). CONCLUSIONS: Paediatric tuberculosis rates showed a slight increasing tendency, while global and adult rates decrease slightly during the period. Tuberculosis disease shows different epidemiology in children and adults, what it is important to take into account to design public heh interventions

Vigilancia epidemiológica de la hepatitis B en España. Años 1997 a 2008

Se ha realizado un estudio epidemiológico descriptivo de la incidencia y mortalidad por hepatitis B en España con datos desde 1997 a 2008. Se han utilizado como fuentes de información el Sistema de Enfermedades de Declaración Obligatoria y el Sistema de Información Microbiológica, ambos integrados en la Red Nacional de Vigilancia Epidemiológica (RENAVE) junto con otras fuentes complementarias como son el Conjunto Mínimo Básico de Datos (Morbilidad Hospitalaria) y la Estadística de Causa de Muerte

Evaluation of mammographic density patterns: reproducibility and concordance among scales

<p>Abstract</p> <p>Background</p> <p>Increased mammographic breast density is a moderate risk factor for breast cancer. Different scales have been proposed for classifying mammographic density. This study sought to assess intra-rater agreement for the most widely used scales (Wolfe, Tabár, BI-RADS and Boyd) and compare them in terms of classifying mammograms as high- or low-density.</p> <p>Methods</p> <p>The study covered 3572 mammograms drawn from women included in the DDM-Spain study, carried-out in seven Spanish Autonomous Regions. Each mammogram was read by an expert radiologist and classified using the Wolfe, Tabár, BI-RADS and Boyd scales. In addition, 375 mammograms randomly selected were read a second time to estimate intra-rater agreement for each scale using the kappa statistic. Owing to the ordinal nature of the scales, weighted kappa was computed. The entire set of mammograms (3572) was used to calculate agreement among the different scales in classifying high/low-density patterns, with the kappa statistic being computed on a pair-wise basis. High density was defined as follows: percentage of dense tissue greater than 50% for the Boyd, "heterogeneously dense and extremely dense" categories for the BI-RADS, categories P2 and DY for the Wolfe, and categories IV and V for the Tabár scales.</p> <p>Results</p> <p>There was good agreement between the first and second reading, with weighted kappa values of 0.84 for Wolfe, 0.71 for Tabár, 0.90 for BI-RADS, and 0.92 for Boyd scale. Furthermore, there was substantial agreement among the different scales in classifying high- versus low-density patterns. Agreement was almost perfect between the quantitative scales, Boyd and BI-RADS, and good for those based on the observed pattern, i.e., Tabár and Wolfe (kappa 0.81). Agreement was lower when comparing a pattern-based (Wolfe or Tabár) versus a quantitative-based (BI-RADS or Boyd) scale. Moreover, the Wolfe and Tabár scales classified more mammograms in the high-risk group, 46.61 and 37.32% respectively, while this percentage was lower for the quantitative scales (21.89% for BI-RADS and 21.86% for Boyd).</p> <p>Conclusions</p> <p>Visual scales of mammographic density show a high reproducibility when appropriate training is provided. Their ability to distinguish between high and low risk render them useful for routine use by breast cancer screening programs. Quantitative-based scales are more specific than pattern-based scales in classifying populations in the high-risk group.</p

Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction

The task of breast density quantification is becoming increasingly relevant due to its association with breast cancer risk. In this work, a semi-automated and a fully automated tools to assess breast density from full-field digitized mammograms are presented. The first tool is based on a supervised interactive thresholding procedure for segmenting dense from fatty tissue and is used with a twofold goal: for assessing mammographic density(MD) in a more objective and accurate way than via visual-based methods and for labeling the mammograms that are later employed to train the fully automated tool. Although most automated methods rely on supervised approaches based on a global labeling of the mammogram, the proposed method relies on pixel-level labeling, allowing better tissue classification and density measurement on a continuous scale. The fully automated method presented combines a classification scheme based on local features and thresholding operations that improve the performance of the classifier. A dataset of 655 mammograms was used to test the concordance of both approaches in measuring MD. Three expert radiologists measured MD in each of the mammograms using the semi-automated tool (DM-Scan). It was then measured by the fully automated system and the correlation between both methods was computed. The relation between MD and breast cancer was then analyzed using a case-control dataset consisting of 230 mammograms. The Intraclass Correlation Coefficient (ICC) was used to compute reliability among raters and between techniques. The results obtained showed an average ICC = 0.922 among raters when using the semi-automated tool, whilst the average correlation between the semi-automated and automated measures was ICC = 0.838. In the case-control study, the results obtained showed Odds Ratios (OR) of 1.38 and 1.50 per 10% increase in MD when using the semi-automated and fully automated approaches respectively. It can therefore be concluded that the automated and semi-automated MD assessments present a good correlation. Both the methods also found an association between MD and breast cancer risk, which warrants the proposed tools for breast cancer risk prediction and clinical decision making. A full version of the DM-Scan is freely available. (C) 2014 Elsevier Ireland Ltd. All rights reserved.This work was supported by research grants from Gent per Gent Fund (EDEMAC Project); Spain's Health Research Fund (Fondo de Investigacion Santiaria) (PI060386 & FIS PS09/00790); Spanish MICINN grants TIN2009-14205-C04-02 and Consolider-Ingenio 2010: MIPRCV (CSD2007-00018); Spanish Federation of Breast Cancer Patients (Federacion Espanola de Cancer de Mama) (FECMA 485 EPY 1170-10). The English revision of this paper was funded by the Universitat Politecnica de Valencia, Spain.Llobet Azpitarte, R.; Pollán, M.; Antón Guirao, J.; Miranda-García, J.; Casals El Busto, M.; Martinez Gomez, I.; Ruiz Perales, F.... (2014). Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction. Computer Methods and Programs in Biomedicine. 116(2):105-115. https://doi.org/10.1016/j.cmpb.2014.01.021S105115116

An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain

Background: The aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk. Methods: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic. Results: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories. Conclusions: These models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.This study was funded by grant PS09/01340 and The Spanish Network on Chronic Diseases REDISSEC (RD12/0001/0007) from the Health Research Fund (Fondo de Investigación Sanitaria) of the Spanish Ministry of Health

Validation of DM-Scan, a computer-assisted tool to assess mammographic density in full-field digital mammograms

We developed a semi-automated tool to assess mammographic density (MD), a phenotype risk marker for breast cancer (BC), in full-field digital images and evaluated its performance testing its reproducibility, comparing our MD estimates with those obtained by visual inspection and using Cumulus, verifying their association with factors that influence MD, and studying the association between MD measures and subsequent BC risk. Three radiologists assessed MD using DM-Scan, the new tool, on 655 processed images (craniocaudal view) obtained in two screening centers. Reproducibility was explored computing pair-wise concordance correlation coefficients (CCC). The agreement between DM-Scan estimates and visual assessment (semi- uantitative scale, 6 categories) was quantified computing weighted kappa statistics (quadratic weights). DM-Scan and Cumulus readings were compared using CCC. Variation of DM-Scan measures by age, body mass index (BMI) and other MD modifiers was tested in regression mixed models with mammographic device as a random-effect term. The association between DM-Scan measures and subsequent BC was estimated in a case control study. All BC cases in screening attendants (2007 2010) at a center with full-field digital mammography were matched by age and screening year with healthy controls (127 pairs). DM-Scan was used to blindly assess MD in available mammograms (112 cases/119 controls). Unconditional logistic models were fitted, including age, menopausal status and BMI as confounders. DM-Scan estimates were very reliable (pairwise CCC: 0.921, 0.928 and 0.916). They showed a reasonable agreement with visual MD assessment (weighted kappa ranging 0.79-0.81). DM-Scan and Cumulus measures were highly concordant (CCC ranging 0.80-0.84), but ours tended to be higher (4%-5% on average). As expected, DM-Scan estimates varied with age, BMI, parity and family history of BC. Finally, DM-Scan measures were significantly associated with BC (p-trend=0.005). Taking MD=29%=3.10 (95% CI=1.35-7.14). Our results confirm that DM-Scan is a reliable tool to assess MD in full-field digital mammograms.This work was supported by research grants from Spain's Health Research Fund (Fondo de INvestigacion Santiaria) (PI060386 & PI09/1230); Gent per Gent Fund (EDEMAC Project) and the Spanish Federation of Breast Cancer Patients (Federacion Espanola de Cancer de Mama) (FECMA 485 EPY 1170-10).Pollán, M.; Llobet Azpitarte, R.; Miranda García, J.; Antón Guirao, J.; Casals El Busto, M.; Martinez Gomez, I.; Palop Jonquères, C.... (2013). Validation of DM-Scan, a computer-assisted tool to assess mammographic density in full-field digital mammograms. 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Obstetric history and mammographic density: a population-based cross-sectional study in Spain (DDM-Spain)

High mammographic density (MD) is used as a phenotype risk marker for developing breast cancer. During pregnancy and lactation the breast attains full development, with a cellular-proliferation followed by a lobular-differentiation stage. This study investigates the influence of obstetric factors on MD among pre- and post-menopausal women. We enrolled 3,574 women aged 45–68 years who were participating in breast cancer screening programmes in seven screening centers. To measure MD, blind anonymous readings were taken by an experienced radiologist, using craniocaudal mammography and Boyd’s semiquantitative scale. Demographic and reproductive data were directly surveyed by purpose-trained staff at the date of screening. The association between MD and obstetric variables was quantified by ordinal logistic regression, with screening centre introduced as a random effect term. We adjusted for age, number of children and body mass index, and stratified by menopausal status. Parity was inversely associated with density, the probability of having high MD decreased by 16% for each new birth (P value < 0.001). Among parous women, a positive association was detected with duration of lactation [>9 months: odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.02–1.72] and weight of first child (>3,500 g: OR = 1.32; 95% CI = 1.12–1.54). Age at first birth showed a different effect in pre- and post-menopausal women (P value for interaction = 0.030). No association was found among pre-menopausal women. However, in post-menopausal women the probability of having high MD increased in women who had their first child after the age of 30 (OR = 1.53; 95% CI = 1.17–2.00). A higher risk associated with birth of twins was also mainly observed in post-menopausal women (OR = 2.02; 95% CI = 1.18–3.46). Our study shows a greater prevalence of high MD in mothers of advanced age at first birth, those who had twins, those who have breastfed for longer periods, and mothers whose first child had an elevated birth weight. These results suggest the influence of hormones and growth factors over the proliferative activity of the mammary gland