Montserrat Rué

ETV6 mutations in early immature human T cell leukemias

A substantial proportion of adult T-ALL samples display gene expression and mutation characteristics of both T cell and acute myeloid leukemias; mutations in ETV6 are found exclusively within this new molecular subgroup of adult T-ALL patients.

Emergency hospital services utilization in Lleida (Spain): A cross-sectional study of immigrant and Spanish-born populations.

BackgroundThe use of emergency hospital services (EHS) has increased steadily in Spain in the last decade while the number of immigrants has increased dramatically. Studies show that immigrants use EHS differently than native-born individuals, and this work investigates demographics, diagnoses and utilization rates of EHS in Lleida (Spain).MethodsCross-sectional study of all the 96,916 EHS visits by patients 15 to 64 years old, attended during the years 2004 and 2005 in a public teaching hospital. Demographic data, diagnoses of the EHS visits, frequency of hospital admissions, mortality and diagnoses at hospital discharge were obtained. Utilization rates were estimated by group of origin. Poisson regression was used to estimate the rate ratios of being visited in the EHS with respect to the Spanish-born population.ResultsImmigrants from low-income countries use EHS services more than the Spanish-born population. Differences in utilization patterns are particularly marked for Maghrebi men and women and sub-Saharan women. Immigrant males are at lower risk of being admitted to the hospital, as compared with Spanish-born males. On the other hand, immigrant women are at higher risk of being admitted. After excluding the visits with gynecologic and obstetric diagnoses, women from sub-Saharan Africa and the Maghreb are still at a higher risk of being admitted than their Spanish-born counterparts.ConclusionIn Lleida (Spain), immigrants use more EHS than the Spanish born population. Future research should indicate whether the same pattern is found in other areas of Spain and whether EHS use is attributable to health needs, barriers to access to the primary care services or similarities in the way immigrants access health care in their countries of origin.

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

Adult T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor associated with poor outcome. In this study, we analyzed the prognostic relevance of genetic alterations, immunophenotypic markers, and microarray gene expression signatures in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial. An early immature gene expression signature, the absence of bi-allelic TCRG deletion, CD13 surface expression, heterozygous deletions of the short arm of chromosome 17, and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series. In contrast, expression of CD8 or CD62L, homozygous deletion of CDKN2A/CDKN2B, NOTCH1 and/or FBXW7 mutations, and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival. Importantly, the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical and mature T-ALLs. Conversely, mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs. This trial was registered at www.clinicaltrials.gov as #NCT00002514.

Cost-effectiveness and harm-benefit analyses of risk-based screening strategies for breast cancer

The one-size-fits-all paradigm in organized screening of breast cancer is shifting towards a personalized approach. The present study has two objectives: 1) To perform an economic evaluation and to assess the harm-benefit ratios of screening strategies that vary in their intensity and interval ages based on breast cancer risk; and 2) To estimate the gain in terms of cost and harm reductions using risk-based screening with respect to the usual practice. We used a probabilistic model and input data from Spanish population registries and screening programs, as well as from clinical studies, to estimate the benefit, harm, and costs over time of 2,624 screening strategies, uniform or risk-based. We defined four risk groups, low, moderate-low, moderate-high and high, based on breast density, family history of breast cancer and personal history of breast biopsy. The risk-based strategies were obtained combining the exam periodicity (annual, biennial, triennial and quinquennial), the starting ages (40, 45 and 50 years) and the ending ages (69 and 74 years) in the four risk groups. Incremental cost-effectiveness and harm-benefit ratios were used to select the optimal strategies. Compared to risk-based strategies, the uniform ones result in a much lower benefit for a specific cost. Reductions close to 10% in costs and higher than 20% in false-positive results and overdiagnosed cases were obtained for risk-based strategies. Optimal screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group. Risk-based strategies can reduce harm and costs. It is necessary to develop accurate measures of individual risk and to work on how to implement risk-based screening strategies.

Breast cancer incidence and overdiagnosis in Catalonia (Spain).

IntroductionEarly detection of breast cancer (BC) with mammography may cause overdiagnosis and overtreatment, detecting tumors which would remain undiagnosed during a lifetime. The aims of this study were: first, to model invasive BC incidence trends in Catalonia (Spain) taking into account reproductive and screening data; and second, to quantify the extent of BC overdiagnosis.MethodsWe modeled the incidence of invasive BC using a Poisson regression model. Explanatory variables were: age at diagnosis and cohort characteristics (completed fertility rate, percentage of women that use mammography at age 50, and year of birth). This model also was used to estimate the background incidence in the absence of screening. We used a probabilistic model to estimate the expected BC incidence if women in the population used mammography as reported in health surveys. The difference between the observed and expected cumulative incidences provided an estimate of overdiagnosis.ResultsIncidence of invasive BC increased, especially in cohorts born from 1940 to 1955. The biggest increase was observed in these cohorts between the ages of 50 to 65 years, where the final BC incidence rates more than doubled the initial ones. Dissemination of mammography was significantly associated with BC incidence and overdiagnosis. Our estimates of overdiagnosis ranged from 0.4% to 46.6%, for women born around 1935 and 1950, respectively.ConclusionsOur results support the existence of overdiagnosis in Catalonia attributed to mammography usage, and the limited malignant potential of some tumors may play an important role. Women should be better informed about this risk. Research should be oriented towards personalized screening and risk assessment tools.

Daily assessment of severity of illness and mortality prediction for individual patients.

ObjectiveTo refine the prognosis of critically ill patients using a statistical model that incorporates the daily probabilities of hospital mortality during the first week of stay in the intensive care unit (ICU). DesignProspective inception cohort. SettingFifteen adult medical and surgical ICUs in Spain. PatientsA total of 1,441 patients aged ≥18 yrs who were consecutively admitted from April 1, 1995, through July 31, 1995. InterventionsProspective data collection during the stay of the patient in the ICU. Data collected included vital status at hospital discharge as well as all variables necessary for computing the Mortality Probability Models II system at admission and during the first 7 days of stay in the ICU. Measurements and Main Results Four logistic regression models were obtained. These models contained survival status at hospital discharge as a dependent variable and the following explanatory variables: (model 1) only the probability of dying at admission; (model 2) only the probability of dying during the current day; (model 3) the probability of dying at admission and during the current day; and (model 4) the probabilities of dying at admission and during the previous and current days.Models were evaluated using the Hosmer-Lemeshow statistic and the area under the receiver operating characteristic curve. For survivor and nonsurvivor patients, mortality probabilities obtained using the aforementioned models were compared using linear regression and the paired Student’s t-test.Although severity at admission was a statistically significant variable, models 2 and 3 produced almost the same probabilities of hospital mortality, as shown with the linear regression and paired Student’s t-test results. ConclusionsTo have an accurate measurement of the prognosis, it is necessary to update the severity measure. The best estimate of hospital mortality was the probability of death on the current day. Severity at admission and at previous days did not improve the assessment of prognosis.

Cost-effectiveness of early detection of breast cancer in Catalonia (Spain)

BackgroundBreast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care.MethodsWe used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios.ResultsStrategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY.ConclusionsA reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area.

Differences in pharmaceutical consumption and expenses between immigrant and Spanish-born populations in Lleida, (Spain): A 6-months prospective observational study

BackgroundThere are few studies comparing pharmaceutical costs and the use of medications between immigrants and the autochthonous population in Spain. The objective of this study is to evaluate whether there are differences in pharmaceutical consumption and expenses between immigrant and Spanish-born populations.MethodsProspective observational study in 1,630 immigrants and 4,154 Spanish-born individuals visited by fifteen primary care physicians at five public Primary Care Clinics (PCC) during 2005 in the city of Lleida, Catalonia (Spain). Data on pharmaceutical consumption and expenses was obtained from a comprehensive computerized data-collection system. Multinomial regression models were used to estimate relative risks and confidence intervals of pharmaceutical expenditure, adjusting for age and sex.ResultsThe percentage of individuals that purchased medications during a six-month period was 53.7% in the immigrant group and 79.2% in the autochthonous group. Pharmaceutical expenses and consumption were lower in immigrants than in autochthonous patients in all age groups and both genders. The relative risks of being in the highest quartile of expenditure, for Spanish-born versus immigrants, were 6.9, 95% CI = (4.2, 11.5) in men and 5.3, 95% CI = (3.5, 8.0) in women, with the reference category being not having any pharmaceutical expenditure.ConclusionPharmaceutical expenses are much lower for immigrants with respect to autochthonous patients, both in the percentage of prescriptions filled at pharmacies and the number of containers of medication obtained, as well as the prices of the medications used. Future studies should explore which factors explain the observed differences in pharmaceutical expenses and if these disparities produce health inequalities.

A predictive index for the diagnosis of cirrhosis in hepatitis C based on clinical, laboratory, and ultrasound findings.

Objective To develop and validate a non-invasive index to predict the presence of cirrhosis in patients with chronic hepatitis C on the basis of clinical, laboratory, and ultrasound findings. Materials and methods Data from the complete history and physical examination, serologic studies, liver ultrasound, and liver biopsy of patients with chronic hepatitis C were analyzed using multivariate regression to develop a cirrhosis predictive index. This index was then applied prospectively to another group of patients with chronic hepatitis C to determine its accuracy. Results Three hundred and thirty-two patients were included (mean age, 48.5±18.7 years; male–female ratio, 1.27). Sixty-seven patients (20%) had cirrhosis at histology. Logistic regression identified seven variables that predicted cirrhosis: age ≥60 years, platelet count ≤100 (×109/L), AST/ALT ≥1, prothrombin time (Ratio) ≥1.1, caudate hypertrophy, right lobe atrophy and splenomegaly. Patients scoring ≥22 in total had a statistically significant probability of cirrhosis (sensitivity, 80%; specificity, 96%; and diagnostic accuracy, 94%). Conclusion Cirrhosis can be predicted in patients with chronic hepatitis C by the evaluation of seven clinical, laboratory, and sonographic variables. The index will be useful for the management and follow-up of hepatitis C patients drastically reducing the indications for biopsy in this context.

Performance of the Mortality Probability Models in assessing severity of illness during the first week in the intensive care unit.

ObjectiveTo extend the Mortality Probability Models (MPM) II severity system to time periods between 4 and 7 days after admission to the intensive care unit (ICU). DesignProspective inception cohort. SettingFifteen adult medical and surgical ICUs in Spain. PatientsA total of 1,441 patients aged ≥18 yrs consecutively admitted from April 1, 1995 through July 31, 1995. InterventionsProspective data collection during the stay of the patient in the ICU. Data collected included demographic information, length-of-stay and vital status at both ICU and hospital discharge, as well as all variables necessary for computing the MPM II system at admission and during the first 7 days of stay in the ICU Measurements and Main ResultsCalibration and discrimination of the four existing MPM II models (MPM0, MPM24, MPM48, and MPM72) were assessed in the study database. The MPM II system overestimated the mortality of patients with probabilities of death ≥0.4. The MPM24 model was customized. Models for time periods between 48 hrs and 7 days (MPM48 to MPMd7) were obtained using the same strategy that was used to develop the original MPM48 and the MPM72 models. The variable coefficients of the MPM24 model were kept fixed and the constant terms of the MPM48 to MPMd7 models were estimated by logistic regression.The constant term stabilized after the fourth day of admission and it was similar to the constant term of the MPM72 model. The customized MPM72 performed very well for days 4 to 7 after admission to the ICU. ConclusionsIf the patient’s condition stays the same day after day, the probability of dying in the hospital increases until 72 hrs, and then stabilizes. A severity measure that performs well at 72 hrs can be a useful tool for measuring severity at later time periods.