Carles Forné

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.

Empathy and burnout of emergency professionals of a health region: A cross-sectional study

Abstract The objective of this study is to assess the association between levels of empathy and burnout of emergency professionals in all the assistance levels. A cross-sectional observational study was conducted in the health region of Lleida and the Pyrenees with 100 professionals from the field of Urgency. Participation reached 40.8%. Empathy and burnout were measured using the Spanish versions of the Jefferson Scale of Physician Empathy (JSPE) and Maslach Burnout Inventory (MBI) respectively. The total MBI score and its 3 dimensions (emotional exhaustion, depersonalization, and personal accomplishment) were analyzed. The JSPE and MBI scores were categorized into tertiles that were identified as “low,” “moderate,” and “high” levels. The median (interquartile range) was 112 (102–123) and 37 (27–53.5) for the JSPE and MBI scores respectively. Professionals with high burnout (MBI≥47) showed the lowest levels of empathy, that is, JSPE score of 105 (98–114); those with moderate burnout (31⩽MBI < 47) had a JSPE score of 114 (104.5–120.5); and those with low burnout (MBI < 31) had a JSPE score of 120.5 (105.8–127.2). In addition, the highest levels of empathy were associated with the lowest levels of burnout, especially in depersonalization, and to a lesser extent in personal accomplishment. There were no differences in empathy and burnout for any of the other study variables. Our findings suggest that the empathy of emergency professionals is associated with burnout. Hence, reducing professional burnout could help keep emergency professionals’ empathy levels high, which in turn would ensure a better quality of care. Nevertheless, it would be necessary to carry out prospective studies to describe the profiles of burnout and empathy as well as their association and evolution.

Bayesian joint ordinal and survival modeling for breast cancer risk assessment

We propose a joint model to analyze the structure and intensity of the association between longitudinal measurements of an ordinal marker and time to a relevant event. The longitudinal process is defined in terms of a proportional‐odds cumulative logit model. Time‐to‐event is modeled through a left‐truncated proportional‐hazards model, which incorporates information of the longitudinal marker as well as baseline covariates. Both longitudinal and survival processes are connected by means of a common vector of random effects. General inferences are discussed under the Bayesian approach and include the posterior distribution of the probabilities associated to each longitudinal category and the assessment of the impact of the baseline covariates and the longitudinal marker on the hazard function. The flexibility provided by the joint model makes possible to dynamically estimate individual event‐free probabilities and predict future longitudinal marker values. The model is applied to the assessment of breast cancer risk in women attending a population‐based screening program. The longitudinal ordinal marker is mammographic breast density measured with the Breast Imaging Reporting and Data System (BI‐RADS) scale in biennial screening exams.

Quality Reporting of Multivariable Regression Models in Observational Studies: Review of a Representative Sample of Articles Published in Biomedical Journals

Abstract Controlling for confounders is a crucial step in analytical observational studies, and multivariable models are widely used as statistical adjustment techniques. However, the validation of the assumptions of the multivariable regression models (MRMs) should be made clear in scientific reporting. The objective of this study is to review the quality of statistical reporting of the most commonly used MRMs (logistic, linear, and Cox regression) that were applied in analytical observational studies published between 2003 and 2014 by journals indexed in MEDLINE. Review of a representative sample of articles indexed in MEDLINE (n = 428) with observational design and use of MRMs (logistic, linear, and Cox regression). We assessed the quality of reporting about: model assumptions and goodness-of-fit, interactions, sensitivity analysis, crude and adjusted effect estimate, and specification of more than 1 adjusted model. The tests of underlying assumptions or goodness-of-fit of the MRMs used were described in 26.2% (95% CI: 22.0–30.3) of the articles and 18.5% (95% CI: 14.8–22.1) reported the interaction analysis. Reporting of all items assessed was higher in articles published in journals with a higher impact factor. A low percentage of articles indexed in MEDLINE that used multivariable techniques provided information demonstrating rigorous application of the model selected as an adjustment method. Given the importance of these methods to the final results and conclusions of observational studies, greater rigor is required in reporting the use of MRMs in the scientific literature.

Características y pronóstico de pacientes ingresados en un servicio de urgencias hospitalario por traumatismo craneoencefálico y con tratamiento anticoagulante o antiagregante

BACKGROUND AND OBJECTIVE To determine mortality and complications of patients with traumatic brain injury (TBI) with antiplatelet or anticoagulant treatment in a hospital emergency department. MATERIALS AND METHODS Study of hospital cohorts of the 243 patients who attended with pure TBI to the emergency service of the Arnau de Vilanova University Hospital in Lleida between June 1, 2015 and June 1, 2016. Sociodemographic, clinical and other variables related to clinical management were collected. Presence of complications and in-hospital mortality were registered at 24hours, at 48hours and one week after TBI. RESULTS Overall, 50.2% of patients were men, with median age of 80.8years, and without CT-scan findings at admission in 62.3% of cases. A total of 14 patients died (5.8%). Overall mortality was associated with comorbidity, with knowledge loss and with fluctuation of the Glasgow comma scale in the acute process. Patients treated with anticoagulants (39.5%) or antiplatelet agents (33.3%) were older, with higher degree of dependency and more comorbidity, but did not present more complications. Without reaching statistical significance, higher mortality was observed during the first week in anticoagulated patients (7.3% vs 4.8%, P=.585) or with antiplatelet treatment (8.6% vs 4.3%, P=.241) with respect to those not treated. CONCLUSIONS No worse results have been observed in number of complications in patients with TBI treated with anticoagulant or antiplatelet treatment, so clinical management seems appropriate. The higher mortality could be explained by the greater complexity of these patients. It would be necessary to carry out more studies, preferably prospective with follow-up after discharge, in order to establish causal mechanisms between clinical management and mortality or associated complications to TBI.

Confidence interval reporting for measures of association in multivariable regression models in observational studies

BACKGROUND/OBJECTIVES To assess the adherence to reporting confidence intervals (CI) for measures of association in multivariable regression models (MRM) in articles with observational design indexed in MEDLINE. MATERIAL AND METHODS A literature search was conducted using the MEDLINE bibliographic database to obtain a representative sample of studies with observational design and applying MRM (logistic, linear, and Cox regression) (n=428). Proportions and 95% CI of articles reporting CI for measures of association in MRM were calculated. Percentage ratios (PRs) were also calculated to describe the change in CI reporting before and after the publication of the STROBE statement. RESULTS 188 of the 236 abstracts with measures of association (79.7%; 95% CI 74.5, 84.8) and 360 of the 428 main texts (84.1%; 80.6, 87.6) were provided with CI. A non-significant increase of 1% in the abstract, PR=1.01 (0.77, 1.29), and 7% in the main text, PR=1.07 (0.87, 1.28), occurred in the CI reporting after the publication of the STROBE guideline. CONCLUSIONS The STROBE guideline recommendation on reporting CI should be more thoroughly followed.

An Ordinal Joint Model for Breast Cancer

We propose a Bayesian joint model to analyze the association between longitudinal measurements of an ordinal marker and time to a relevant event. The longitudinal process is defined in terms of a proportional-odds cumulative logit model and the time-to-event process through a left-truncated Cox proportional hazards model with information of the longitudinal marker and baseline covariates. Both longitudinal and survival processes are connected by a common vector of random effects.

How to Optimize Population Screening Programs for Breast Cancer Using Mathematical Models

Despite the widespread use of mammography, there is an intense debate in the scientific community about the benefits and harms of screening for BC (Autier et al. (2011); Duffy et al. (2010); Jorgensen & Gotzsche (2009); Tabar et al. (2003)). The guidelines of the US Prevention Services Task Force in 2009 recommending biennial screening starting at age 50 (USPSTF (2009)) originated dissension within the scientific community and BC interest groups. At present, the screening recommendations reflect this dissent (ACOG (2011); Schousboe et al. (2011)).