Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Dissemination of periodic mammography and patterns of use, by birth cohort, in Catalonia (Spain)

<p>Abstract</p> <p>Background</p> <p>In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. In this work we have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006.</p> <p>Methods</p> <p>Cross-sectional data from three Catalan Health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year.</p> <p>Results</p> <p>For women born from 1938 to 1952, mammography clearly had a period effect, meaning that they started to have periodic mammograms at the same calendar years but at different ages. The age at which approximately 50% of the women were receiving periodic mammograms went from 57.8 years of age for women born in 1938–1942 to 37.3 years of age for women born in 1963–1967. Women in all age groups experienced an increase in periodic mammography use over time, although women in the 50–69 age group have experienced the highest increase. Currently, the target population of the Catalan Breast Cancer Screening Program, 50–69 years of age, is the group that self-reports the highest utilization of periodic mammograms, followed by the 40–49 age group. A higher proportion of women of all age groups have annual mammograms rather than biennial or irregular ones.</p> <p>Conclusion</p> <p>Mammography in Catalonia became more widely implemented during the 1990s. We estimated when cohorts initiated periodic mammograms and how frequently women are receiving them. These two pieces of information will be entered into a cost-effectiveness model of early detection in Catalonia.</p

Determinants of non attendance to mammography program in a region with high voluntary health insurance coverage

<p>Abstract</p> <p>Background</p> <p>High participation rates are needed to ensure that breast cancer screening programs effectively reduce mortality. We identified the determinants of non-participation in a public breast cancer screening program.</p> <p>Methods</p> <p>In this case-control study, 274 women aged 50 to 64 years included in a population-based mammography screening program were personally interviewed. Socio-demographic characteristics, health beliefs, health service utilization, insurance coverage, prior mammography and other preventive activities were examined.</p> <p>Results</p> <p>Of the 192 cases and 194 controls contacted, 101 and 173, respectively, were subsequently interviewed. Factors related to non-participation in the breast cancer screening program included higher education (odds ratio [OR] = 5.28; 95% confidence interval [CI95%] = 1.57–17.68), annual dental checks-ups (OR = 1.81; CI95%1.08–3.03), prior mammography at a private health center (OR = 7.27; CI95% 3.97–13.32), gynecologist recommendation of mammography (OR = 2.2; CI95%1.3–3.8), number of visits to a gynecologist (median visits by cases = 1.2, versus controls = 0.92, P = 0.001), and supplemental private insurance (OR = 5.62; CI95% = 3.28–9.6). Among women who had not received a prior mammogram or who had done so at a public center, perceived barriers were the main factors related to non-participation. Among women who had previously received mammograms at a private center, supplemental private health insurance also influenced non-participation. Benign breast symptoms increased the likelihood of participation.</p> <p>Conclusion</p> <p>Our data indicate that factors related to the type of insurance coverage (such as prior mammography at a private health center and supplemental private insurance) influenced non-participation in the screening program.</p

Colorectal cancer health services research study protocol: the CCR-CARESS observational prospective cohort project

BACKGROUND: Colorectal cancers are one of the most common forms of malignancy worldwide. But two significant areas of research less studied deserve attention: health services use and development of patient stratification risk tools for these patients. METHODS:DESIGN: a prospective multicenter cohort study with a follow up period of up to 5 years after surgical intervention. Participant centers: 22 hospitals representing six autonomous communities of Spain. Participants/Study population: Patients diagnosed with colorectal cancer that have undergone surgical intervention and have consented to participate in the study between June 2010 and December 2012. Variables collected include pre-intervention background, sociodemographic parameters, hospital admission records, biological and clinical parameters, treatment information, and outcomes up to 5 years after surgical intervention. Patients completed the following questionnaires prior to surgery and in the follow up period: EuroQol-5D, EORTC QLQ-C30 (The European Organization for Research and Treatment of Cancer quality of life questionnaire) and QLQ-CR29 (module for colorectal cancer), the Duke Functional Social Support Questionnaire, the Hospital Anxiety and Depression Scale, and the Barthel Index. The main endpoints of the study are mortality, tumor recurrence, major complications, readmissions, and changes in health-related quality of life at 30 days and at 1, 2, 3 and 5 years after surgical intervention. STATISTICAL ANALYSIS: In relation to the different endpoints, predictive models will be used by means of multivariate logistic models, Cox or linear mixed-effects regression models. Simulation models for the prediction of discrete events in the long term will also be used, and an economic evaluation of different treatment strategies will be performed through the use of generalized linear models. DISCUSSION: The identification of potential risk factors for adverse events may help clinicians in the clinical decision making process. Also, the follow up by 5 years of this large cohort of patients may provide useful information to answer different health services research questions

Condutas na prevenção secundária do câncer de mama e fatores associados Breast cancer's secondary prevention and associated factors

OBJETIVO: Avaliar a prevalência de condutas na prevenção secundária do câncer de mama e fatores associados. MÉTODOS: Foi realizado estudo transversal de base populacional na cidade de Pelotas, RS, em 2002, com amostra de 879 mulheres de 40 a 69 anos. Foram coletadas informações sobre variáveis demográficas, socioeconômicas, comportamentais, biológicas e referentes ao manejo médico. A análise estatística das variáveis foi realizada utilizando o método de regressão de Poisson. RESULTADOS: A prevalência do "hábito de realizar o auto-exame" encontrada foi de 83,5% (IC 95%: 80,9-85,9), sendo que, dessas mulheres, 80,4% (IC 95%: 77,3-83,2) o realizavam ao menos uma vez ao mês. A prevalência de "exame clínico de mamas" foi de 83,3% (IC 95%: 80,6-85,7). "Mamografia alguma vez na vida" mostrou prevalência de 70% (IC 95%: 66,8-73,0), sendo que 83,7% (IC 95%: 80,5-86,6) realizaram a última mamografia há dois anos ou menos. Das entrevistadas, 62% (IC 95%: 58,7-65,2) consultaram ginecologista ao menos uma vez no último ano. Os fatores associados a maiores prevalências das condutas na prevenção secundária do câncer de mama foram: pertencer às classes sociais mais altas; ter a maior combinação de fatores de risco para neoplasia mamária; ter história familiar de câncer de mama; fazer uso de terapia de reposição hormonal e ter sido submetida à biópsia por patologia mamária. CONCLUSÕES: As medidas preventivas para o câncer de mama vêm sendo bastante utilizadas quantitativamente; entretanto, os dados apontam para limitações em relação à sua adequação. O nível socioeconômico parece ser o principal determinante do acesso à consulta ginecológica e, conseqüentemente, às demais condutas na prevenção secundária do câncer de mama.<br>OBJECTIVE: To evaluate the prevalence of secondary prevention of breast cancer and associated factors. METHODS: A population-based cross-sectional study was conducted in the city of Pelotas, southeastern Brazil, in 2002. The study sample comprised 879 women aged 40 to 69 years. Information was collected on demographic, social, economic, behavioral, biological and care management variables. Statistical analysis based on Poisson regression model was carried out. RESULTS: The prevalence of breast self-examination (BSE) was 83.5% (95% CI: 80.9-85.9). Of them, 80.4% (95% CI: 77.3-83.2) carried out BSE at least once a month. The prevalence of clinical breast examination was 83.3% (95% CI: 80.6-85.7). Mammography was occasionally performed in 70% (95% CI: 66.8-73.0) of the sample. Of these women, 83.7% (95% CI: 80.5-86.6) underwent mammography at least once in the last two years. Sixty-two percent (95% CI: 58.7-65.2) of the women interviewed attended a gynecological visit at least once in the last year. The factors mainly associated to the high prevalence of secondary prevention of breast cancer were: higher social status; greater association of risk factors for breast cancer; family history of breast cancer; hormone replacement therapy and previous breast biopsy or surgery. CONCLUSIONS: Preventive measures for breast cancer have been widely taken in the study sample; however, data points out to some limitations related to efficacy. Social and economic status seems to be a major determinant to gynecological care access and, consequently, access to secondary prevention of breast cancer