Competing risks methods

Competing risks data usually arises in studies in which the failure of an individual may be classified into one of k (k > 1) mutually exclusive causes of failure. When competing risks are present, classical survival analysis techniques may not be appropriate to use. The main goal of this paper is to review the specific methods to deal with competing risks. To this aim, we first focus on how to specify a competing risks model, which is the structure of observed data in this framework, and how components of the model are estimated from a given random sample. In addition, we discuss how to correctly interpret probabilities in the presence of competing risks, and regression models are considered in detail. To conclude, we illustrate the problem with data from a bladder cancer study

MB-MDR: Model-Based Multifactor Dimensionality Reduction for detecting interactions in high-dimensional genomic data

L’anàlisi de l’efecte dels gens i els factors ambientals en el desenvolupament de malalties complexes és un gran repte estadístic i computacional. Entre les diverses metodologies de mineria de dades que s’han proposat per a l’anàlisi d’interaccions una de les més populars és el mètode Multifactor Dimensionality Reduction, MDR, (Ritchie i al. 2001). L’estratègia d’aquest mètode és reduir la dimensió multifactorial a u mitjançant l’agrupació dels diferents genotips en dos grups de risc: alt i baix. Tot i la seva utilitat demostrada, el mètode MDR té alguns inconvenients entre els quals l’agrupació excessiva de genotips pot fer que algunes interaccions importants no siguin detectades i que no permet ajustar per efectes principals ni per variables confusores. En aquest article il•lustrem les limitacions de l’estratègia MDR i d’altres aproximacions no paramètriques i demostrem la conveniència d’utilitzar metodologies parametriques per analitzar interaccions en estudis cas-control on es requereix l’ajust per variables confusores i per efectes principals. Proposem una nova metodologia, una versió paramètrica del mètode MDR, que anomenem Model-Based Multifactor Dimensionality Reduction (MB-MDR). La metodologia proposada té com a objectiu la identificació de genotips específics que estiguin associats a la malaltia i permet ajustar per efectes marginals i variables confusores. La nova metodologia s’il•lustra amb dades de l’Estudi Espanyol de Cancer de Bufeta

Cyclooxygenase-2 Expression in Bladder Cancer and Patient Prognosis: Results from a Large Clinical Cohort and Meta-Analysis

Aberrant overexpression of cyclooxygenase-2 (COX2) is observed in urothelial carcinoma of the bladder (UCB). Studies evaluating COX2 as a prognostic marker in UCB report contradictory results. We determined the prognostic potential of COX2 expression in UCB and quantitatively summarize the results with those of the literature through a meta-analysis. Newly diagnosed UCB patients recruited between 1998–2001 in 18 Spanish hospitals were prospectively included in the study and followed-up (median, 70.7 months). Diagnostic slides were reviewed and uniformly classified by expert pathologists. Clinical data was retrieved from hospital charts. Tissue microarrays containing non-muscle invasive (n = 557) and muscle invasive (n = 216) tumours were analyzed by immunohistochemistry using quantitative image analysis. Expression was evaluated in Cox regression models to assess the risk of recurrence, progression and disease-specific mortality. Meta-hazard ratios were estimated using our results and those from 11 additional evaluable studies. COX2 expression was observed in 38% (211/557) of non-muscle invasive and 63% (137/216) of muscle invasive tumors. Expression was associated with advanced pathological stage and grade (p<0.0001). In the univariable analyses, COX2 expression - as a categorical variable - was not associated with any of the outcomes analyzed. As a continuous variable, a weak association with recurrence in non-muscle invasive tumors was observed (p-value = 0.048). In the multivariable analyses, COX2 expression did not independently predict any of the considered outcomes. The meta-analysis confirmed these results. We did not find evidence that COX2 expression is an independent prognostic marker of recurrence, progression or survival in patients with UCB.The work was partially supported by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain (G03/174, 00/0745, PI051436, PI061614 and G03/174); Red Temática de Investigación Cooperativa en Cáncer- RD06/0020-RTICC; Consolider ONCOBIO; EU-FP6-STREP-37739-DRoP-ToP; EU-FP7-HEALTH-F2-2008-201663-UROMOL; EU-FP7-HEALTH-F2-2008-201333-DECanBio; USA-NIH-RO1-CA089715; and a PhD fellowship awarded to MJC from the ‘‘la Caixa’’ foundation, Spain, and a postdoctoral fellowship awarded to AFSA from the Fundación Científica de la AEC

Emergency admission for cancer: a matter of survival?

The objective of this study was to compare the pre-hospital health care process, clinical characteristics at admission and survival of patients with a digestive tract cancer first admitted to hospital either electively or via the emergency department. The study involved cross-sectional analysis of information elicited through personal interview and prospective follow-up. The setting was a 450-bed public teaching hospital primarily serving a low-income area of Barcelona, Catalonia, Spain. Two hundred and forty-eight symptomatic patients were studied, who had cancer of the oesophagus (n = 31), stomach (n = 70), colon (n = 82) and rectum (n = 65). The main outcome measures were stage, type and intention of treatment and time elapsed from admission to surgery; the relative risk of death was calculated using Cox's regression. There were 161 (65%) patients admitted via the emergency department and 87 (35%) electively. The type of physician seen at the first pre-hospital visit had more often been a general practitioner in the emergency than in the elective group (89% vs 75%, P < 0.01). Emergency patients had seen a lower number of physicians from symptom onset until admission, but two-thirds had made repeated visits to a primary care physician. Emergency patients were less likely to have a localized tumour and a diagnosis of cancer at admission, and surgery as the initial treatment. Median survival was 30 months for elective patients and 8 months for emergency patients (P < 0.001), and the relative risk of death (RR) was 1.83 (95% confidence interval, CI, 1.32-2.54). After adjustment for strong prognostic factors, emergency patients continued to experience a significant excess risk (RR = 1.58; CI 1.10-2.27). In conclusion, in digestive tract cancers, admission to hospital via the emergency department is a clinically important marker of a poorer prognosis. Emergency departments can only partly counterbalance deficiencies in the effectiveness of and integration among the different levels of the health system

In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations

8 pages, 4 pages.-- PMID: 19797353 [PubMed].-- Printed version published Nov 2009.While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103). OCs were measured by high-resolution gas chromatography with electron capture detection. Cases whose tumours harboured a KRAS mutation had higher concentrations of p,p′-dichlorodiphenyltrichloroethane (DDT), p,p′-dichlorodiphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs) 138, 153 and 180 than cases with wild-type KRAS, but differences were statistically significant only for p,p′-DDT and PCBs 138 and 153. The association between coffee intake and KRAS mutations remained significant (P-trend < 0.015) when most OCs where accounted for. When p,p′-DDT, PCB 153, coffee and alcohol intake were included in the same model, all were associated with KRAS (P = 0.042, 0.007, 0.016 and 0.025, respectively). p,p′-DDT, p,p′-DDE and PCB 138 were significantly associated with the two most prevalent KRAS mutations (Val and Asp). OCs and coffee may have independent roles in the aetiopathogenesis of PDA through modulation of KRAS activation, acquisition or persistence, plausibly through non-genotoxic or epigenetic mechanisms. Given that KRAS mutations are the most frequent abnormality of oncogenes in human cancers, and the lifelong accumulation of OCs in humans, refutation or replication of the findings is required before any implications are assessed.Government of Catalonia (2009 SGR 1350); ‘Red temática de investigación cooperativa de centros en Cáncer’ (C03/10); ‘Red temática de investigación cooperativa de centros en Epidemiología y salud pública’ (C03/09); CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Government of Spain.Peer reviewe

Perception of the inltlation and evolutlon of symptomatology in hospitalized patients with cancer of the digestive tract

El estudio de las características del intervalo entre el primer síntoma y el diagnóstico del cáncer viene condicionado por la forma en que el paciente percibe y refiere la aparición de los signos y síntomas iniciales. El propósito de este estudio fue analizar los factores que influyen en dicha percepción. Para ello se entrevistaron 68 pacientes con neoplasia máligna del tubo digestivo, sintomáticos, ingresados en el Hospital del Mar de Barcelona, mediante un cuestionario estandarizado. El tiempo de aparición de toda la sintomatología fue de una semana en el 38 % de los pacientes, igual o inferior a un mes en el 53 %, e igual o inferior a 3 meses en el 75 %. Un 76 % de los enfermos acudieron al médico por el primer síntoma. Los síntomas que con mayor frecuencia motivaron la primera visita al médico por el proceso neoplásico fueron los hemorrágicos y los de aparición brusca o violenta; los síntomas menos asociados a la primera visita fueron el dolor abdominal y la anorexia. Sólo 5 enfermos manifestaron haber asociado el síntoma inicial a una enfermedad nueva y grave, el 61 % manifestaron no haber atribuido ninguna importancia al primer síntoma, un 15 % lo asociaron a otra enfermedad anterior, y un 17 % a una enfermedad nueva pero de carácter leve. Las mujeres refirieron 4 síntomas de mediana frente a 2 en los hombres (p<0,04). Mientras que el número de síntomas fue discretamente superior entre los pacientes no fumadores y en los afectos de un cáncer de estómago, no guardó relación con el nivel de estudios ni con el grado de diseminación de la neoplasia. Los primeros síntomas producidos por una enfermedad cancerosa no suelen relacionarse con una situación grave por el paciente, lo cual retrasa el diagnóstico. Es importante prestar atención a la percepción de los síntomas por los pacientes, así como a su forma de comunicarlos

Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.

The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis

Concordancia entre la información facilitada por el paciente y un familiar sobre antecedentes, patológicos, consumo de tabaco, de alcohol, de café, y dieta en el cáncer de páncreas exocrino y del sistema biliar extrahepático

ResumenObjetivoNingún estudio sobre mutaciones en el oncogén K-ras y los cánceres de páncreas exocrino y del sistema biliar ha analizado la fiabilidad de la información clínica y epidemiológica utilizada. En el contexto de un estudio prospectivo multicéntrico sobre dichas neoplasias se ha analizado la concordancia entre la información facilitada por el paciente y la facilitada por un familiar respecto a diversos factores asociados a aquéllas.MétodosSe cumplimentaron un total de 110 pares de entrevistas y el acuerdo se midió mediante los índices kappa simple (k) y ponderado (kp), el porcentaje de acuerdo simple, y los porcentajes de acuerdo para los valores positivos y negativos.ResultadosLa concordancia para los distintos antecedentes patológicos fue excelente (k entre 0,89 y 0,76), al igual que para el consumo habitual de tabaco (k=0,98). El acuerdo fue entre moderado y alto para el consumo habitual de café (k=0,68) y las frecuencias de consumo de grupos de alimentos (kp entre 0,66 y 0,38). Los familiares refirieron sistemáticamente un mayor consumo de bebidas alcohólicas que los pacientes (k entre 0,71 y 0,32).ConclusiónEn general, los familiares pueden tomarse como fuente de información alternativa en caso de incapacidad de los pacientes, aunque deben considerarse con cautela los datos referentes al consumo de alcohol.SummaryObjectiveNo study on mutations in the K-ras oncogene and cancer of the exocrine pancreas or cancer of the biliary system has analyzed the reliability of clinical and epidemiological information.MethodsAgreement between patient and surrogate on factors potentially related to both tumours was evaluated within a multicentre prospective study. Interviews were personally adminstered to both patient and surrogate (N=110 pairs). Agreement was examined viathe simple kappa index (k), the weighted kappa index (kw), the percentage of simple agreement, and the percentages of positive and negative agreement.ResultsAgreement for medical history was excellent (k between 0.89 and 0.76), as it was for tobacco consumption (k=0.98). Agreement was moderate for coffee consumption (k=0.68), frequencies of food groups (kw from 0.66 to 0.38), and consumption of alcoholic drinks (k from 0.66 to 0.32). Surrogates indicated a higher consumption of alcohol than patients.ConclusionSurrogates can be an alternative source of information when patients cannot be interviewed, but information on alcohol consumption should be treated with caution