Multicentric French study on adult intracranial ependymomas: prognostic factors analysis and therapeutic considerations from a cohort of 152 patients.

Ependymomas account for 2% of all intracranial tumours in adults. Considerable controversy continues to exist with regard to their prognostic factors and therapeutic management due to the rarity and the heterogeneity of series reported so far. The authors report a retrospective study of a homogenous population of 152 adult patients harbouring intracranial ependymomas from 24 French Neurosurgical Centres between 1990 and 2004. All clinico-radiological and follow-up data were analysed and a central pathologic review was performed by two confirmed neuropathologists. The 5- and 10-year overall survival rates were 84.8 and 76.5%, respectively; the 5- and 10-year progression-free survival rates were 63.5 and 52.8%, respectively. On multivariate analysis, overall survival rates were associated with histological grade (P < 0.001), extent of surgery (P = 0.006), patient age (P = 0.004) and patient Karnofski performance status (P = 0.03). The multivariate analysis also revealed that the risk of recurrence was associated with high histological grade (P < 0.001), incomplete resection (P < 0.001) and Karnofski performance status < or = 80 (P = 0.04). The impact of radiotherapy was found to be beneficial for incompletely resected low-grade ependymomas and to a lesser extent for completely removed high-grade tumours. In association with Karnofski performance status and extent of surgery, histological grade is a major prognostic factor in adult intracranial ependymomas. The application of a simple and reproducible grading scheme using objective anaplastic criteria seems useful practically and clinically applicable. The role of adjuvant radiotherapy for patients with incompletely resected low-grade ependymomas seems to be beneficial but remains to be addressed for high-grade tumours.

Skin protection by sunscreens is improved by explicit labeling and providing free sunscreen.

Whatever the improvement in the protection spectrum of sunscreens (SCs), actual skin protection mainly depends on the way they are used, especially on the quantity applied. This prospective randomized study assessed how much sun protection factor (SPF) labeling, which is hardly understandable by a layman, and high cost account for misuse of SCs. In three beach resorts in France, 364 individuals were blindly randomized during their holidays to three arms (1) free SCs intervention (FS) = four types of SCs with their usual SPF label (60B-A, 20B-A, 12B-A, 6B-3A) at free disposal; (2) same free SCs with an explicit labeling (FNL), including sunburn protection, likely protection against long-term effects of UV, and possibility to get a tan; and (3) no intervention (NI). As compared to FS, FNL increased the quantity of SCs applied, mainly in the minority of people who were not "tan-seekers", reduced sunburns particularly in sun-sensitive individuals (25.6 vs 58.3%, P=0.005), and induced a shift in the level of SCs chosen. Free delivery SCs were associated with a more systematic application of SCs in case of exposure, and a decreased sunburn occurrence, without increase of exposure. These results suggest that a labeling more explicit for the public would result in a better protection in SC users and that cost could be a limiting factor to use SC as often as necessary.

Sevoflurane alters right ventricular performance but not pulmonary vascular resistance in acutely instrumented anesthetized pigs.

OBJECTIVE: Although the effects of halogenated agents on both normal and diseased left ventricles have been widely studied, the influence of these anesthetic agents on right ventricular (RV) performance remains less well characterized. This study was undertaken to examine the effects of 2 different concentrations of sevoflurane on RV function, and coronary and pulmonary hemodynamics in acutely instrumented anesthetized pigs. DESIGN: Prospective experimental study. SETTING: Laboratory of experimental research in a university teaching hospital. SUBJECTS: Anesthetized pigs. INTERVENTIONS: Regional RV function in 10 pigs was determined from pressure segment length loop analysis, global RV function from stroke work versus end-diastolic pressure relation, right coronary blood flow, and pulmonary vascular resistance (PVR), without and then with 2.6% (minimum alveolar concentration [MAC]) and 3.9 % (1.5 MAC) end-tidal sevoflurane concentrations. MAIN RESULTS: Sevoflurane preserved inflow systolic shortening and RV regional external work, but significantly depressed outflow systolic shortening (p < 0.05). Global RV stroke work was depressed to 72% +/- 12% and 61% +/- 10% of baseline value, respectively, with 1 and 1.5 MAC of sevoflurane (p < 0.05), but without alteration of PVR. Right coronary blood flow decreased dose dependently. CONCLUSIONS: Sevoflurane causes significant depression of global RV function associated with a qualitatively different effect on inflow and outflow tracts, without any modification of PVR.

Comparison of ethanol concentrations in right cardiac blood, left cardiac blood and peripheral blood in a series of 30 cases.

The aim of this study was to compare ethanol concentrations in right cardiac blood, left cardiac blood and peripheral blood. Samples were taken from a series of 30 medicolegal autopsies. Ethanol was measured by headspace GC-FID. In each case, the degree of putrefaction, chest or abdominal injury, and/or regurgitation of gastric contents into the airways were noted. Our results show that there exists in certain cases a marked increase in ethanol concentration in left cardiac blood compared with right cardiac blood and peripheral blood. In these cases, we observed (i) a high concentration of ethanol in the gastric contents and (ii) regurgitation of gastric contents into the airways. The authors discuss the post-mortem redistribution mechanisms which could explain these results and stress the value of sampling right cardiac blood at autopsy.

Superiority of a cognitive education with photographs over ABCD criteria in the education of the general population to the early detection of melanoma: a randomized study.

Most education campaigns for melanoma (MM) detection in the general population have used the "ABCD" algorithm, although recognition of objects in the real life is based on a holistic image recognition rather than on analytic criteria. The objective was to compare analytic (ABCD) and cognitive (photographs) strategies for teaching self-recognition of MM. A prospective 4-arm stratified randomized trial in 255 individuals compared 3 realistic educative interventions by leaflets: 1) ABCD algorithm ("ABCD"), 2) a set of photographs chosen to stimulate recognition of MM among benign pigmented lesions ("Cog"), 3) photographs + explanations ("Cog-Ex" arm) and 4) no intervention ("NI"). A 40-slides test was performed before intervention (T0), 1 week after (T1) and after induction of anxiety (T2). In the "ABCD" arm, sensitivity slightly improved (80 to 83.8%, p = 0.04), but specificity dropped from 65.1 to 56.3% (p < 0.001), with no benefit in accuracy as compared to "NI". In "Cog" arm, there was no change in sensitivity, but a strong increase in specificity (65.9 to 81.1%, p < 0.001) and accuracy (42.1 to 53.1%, p < 0.001). "Cog-ex" resulted in similar although lower benefit. Under stress (T2), there was a dramatic loss of specificity and accuracy in "ABCD" arm (65.1 to 44.1%, p < 0.001 and 40.8% to 35.8%, p < or = 0.001) without higher gain in sensitivity, while sensitivity and accuracy increased (p < 0.005) after "Cog" leaflet, without decreasing specificity. Finally, the "ABCD" message alone does not seem efficacious and is even worse in the context of anxiety, whereas a quick look at a few photographs is sufficient to improve the ability of the laymen to recognize a MM just by optimizing their spontaneous image recognition capacities. Education by photographs is a realistic strategy which should replace or complete "ABCD" message in the campaigns for self-detection of MM.

Analysis of time-dependent covariates in a regressive relative survival model.

Relative survival is a method for assessing prognostic factors for disease-specific mortality. However, most relative survival models assume that the effect of covariate on disease-specific mortality is fixed-in-time, which may not hold in some studies and requires adapted modelling. We propose an extension of the Esteve et al. regressive relative survival model that uses the counting process approach to accommodate time-dependent effect of a predictor's on disease-specific mortality. This approach had shown its robustness, and the properties of the counting process give a simple and attractive computational solution to model time-dependent covariates. Our approach is illustrated with the data from the Stanford Heart Transplant Study and with data from a hospital-based study on invasive breast cancer. Advantages of modelling time-dependent covariates in relative survival analysis are discussed.

Refinement of an automatic method for indexing medical literature--a preliminary study.

OBJECTIVES: to rank according to their significance MeSH terms automatically extracted from Internet sites in the framework of a French project, VUMeF, a contribution to the NLM' UMLS project. MATERIAL AND METHODS: scores are affected to key-words of a given document on the basis of the Semantic Network of the UMLS and frequencies of co-occurring major terms in the Medline literature. If N is the number of major terms of a document, and n is the number of major terms retrieved in the N first terms ranked in descending order according to their scores, the measure of the achievement of the method is n/N. RESULTS: a set of 1444 randomized documents have been extracted from Medline. For each document we computed the retrieved major terms among the first N terms with two methods: a statistical method using only frequencies given by co-occurrences, and our method that uses furthermore the UMLS semantic network. In 34% of cases corresponding to documents indexed by about 16 key-words, about 3 major terms among them, our method produces a better precision (7%) than the statistical method. DISCUSSION: the rough calculation of the proportion of retrieved major terms should be enhanced by the use of a probability law allowing to enlarge the list of terms to select taking into account both the number of major terms and the total number of key-words used to index each document.

Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study.

BACKGROUND: The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. METHODS AND RESULTS: In a multicenter prospective European study, including 384 consecutive patients (aged 57+/-17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). CONCLUSIONS: In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.

RSURV: a function to perform relative survival analysis with S-PLUS or R.

Relative survival is a method used to estimate net survival using the expected mortality in the general population. This method is frequently used in cancer registries, more particularly with the Esteve et al. regressive proportional hazards model. Recently, extensions of this model have been developed to account for time-dependent covariate and for time-dependent hazards using B-spline functions. We propose a function, RSurv, to take into account these extensions. Written in the R/S language this function has the same structure of the standard Cox function coxph of R and S-PLUS software with the goal to homogenise survival functions and to take advantages of the power of R and S-PLUS software. We also propose a function, plot.RSurv, for plotting relative survival curves and time-dependent hazards ratio. The usage of these functions is exemplified by a study of a breast cancer hospital-based data set.

A platform to develop and to improve effectiveness of online computable guidelines.

The quality criteria of guidelines are identified. Taking these criteria into account we have built a platform to improve computable guideline effectiveness and facilitate their production. Our implementation is based on the GLIF Model (GuideLine Interchange Format). We have designed software components to edit, test, index, perform and present guidelines in a user-friendly Web architecture. These components are based on XML specifications in order to preserve their shareability and their re-usability. Several guidelines have been developed using our approach. We discuss the advantages of such an implementation and future evolutions so as to improve guideline integration within the clinician's workflow.

Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases.

OBJECTIVE: Pilocytic astrocytomas (PA) are Grade I brain tumors characterized by an excellent prognosis. In some cases, however, the patient has a bad outcome. The aim of our study was to search for the clinicopathological factors underlying the prognosis for patients with this disease. METHODS: We reviewed the clinical, neuroradiological, and histopathological features of 80 PAs (33 cerebellar, 18 optochiasmatic, 16 brainstem, 7 spinal cord, 3 thalamic, 2 optic nerve, and 1 hemispheric) in pediatric patients. RESULTS: Pathological examination revealed 58 classic PAs and 20 pilomyxoid astrocytomas, which are a histological variant of PAs. Two cases remained unclassified. The mean overall follow-up period was 58 months, the 5-year progression-free survival rate was 75%, and the 5-year survival rates were 100 and 92% after total and partial removal. Univariate statistical analysis revealed that partial resection, optochiasmatic PA localization, and pilomyxoid variant were associated with a worse prognosis, but the latter two parameters were too closely related to the extent of resection to be independent prognostic factors in multivariate analysis. Among the patients who underwent partial surgical removal, only invasion of the surrounding structures was related to prognosis. CONCLUSION: PAs are benign tumors, but some clinicopathological factors, such as partial resection, optochiasmatic location, invasion of surrounding structures, and the pilomyxoid variant, have a worse prognosis.

A relative survival regression model using B-spline functions to model non-proportional hazards.

Relative survival, a method for assessing prognostic factors for disease-specific mortality in unselected populations, is frequently used in population-based studies. However, most relative survival models assume that the effects of covariates on disease-specific mortality conform with the proportional hazards hypothesis, which may not hold in some long-term studies. To accommodate variation over time of a predictor's effect on disease-specific mortality, we developed a new relative survival regression model using B-splines to model the hazard ratio as a flexible function of time, without having to specify a particular functional form. Our method also allows for testing the hypotheses of hazards proportionality and no association on disease-specific hazard. Accuracy of estimation and inference were evaluated in simulations. The method is illustrated by an analysis of a population-based study of colon cancer.

Neural cell adhesion molecule expression in renal cell carcinomas: relation to metastatic behavior.

Neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily, is expressed by a subgroup of renal cell carcinomas (RCCs) and by a limited number of adult organs, including the central nervous system (CNS) and adrenal gland. Because the major function of NCAM is homophilic adhesion between homotypic and heterotypic cells, we hypothesized that NCAM-expressing RCCs should preferentially metastasize to the CNS and adrenal gland. We did a retrospective immunohistochemical analysis of NCAM expression both in 338 primary renal tumors, including 249 conventional RCCs and 31 metastases of conventional RCCs. In primary renal tumors, NCAM was expressed by only 38 (15.2%) conventional RCCs and by no other histological subtypes of renal tumor. This expression correlated with a higher risk of adrenal and CNS metastases (P <0.001). NCAM expression also correlated with tumor size (P <0.001), renal vein involvement (P = 0.02), perirenal invasion (P = 0.02), and Fuhrman grading (P < 0.001). Finally, patients with NCAM-expressing RCCs had a lower survival rate (P = 0.006), especially in the first 2 years after surgery. NCAM expression is of interest both for evaluating the prognosis of patients with conventional RCCs and for determining a subgroup of patients at high risk for adrenal and CNS metastases.

Polysialylated neural cell adhesion molecules expressed in human pituitary tumors and related to extrasellar invasion.

OBJECT: Pituitary adenomas are usually benign tumors; however, some behave aggressively and metastasize. Until now, no specific marker of aggressive behavior or malignancy has been found. The polysialylated neural cell adhesion molecule (NCAM), which is highly expressed in embryonic tissues such as the brain and pituitary, is detected in some and neuroendocrine tumors. Because polysialylation has been implicated in the regulation of cell growth and migration, polysialylated NCAM expression has been considered as a prognostic marker in such tumors. METHODS: In the present study, the authors analyzed polysialylated NCAM expression in 82 pituitary tumors from humans: 49 secreting adenomas, 32 nonfunctioning adenomas, and one growth hormone and prolactin-secreting carcinoma associated with acromegaly and spinal and liver metastases. Based on immunohistochemical analyses, the tumors were classified as somatotropic (22 tumors), prolactinoma (14 tumors), corticotropic (17 tumors), and gonadotropic or so-called null cell adenomas (28 tumors). Assessment of polysialylated NCAM was performed using three different methods (immunohistochemical analysis, Western blot analysis, and enzyme-linked immunosorbent assay) with a specific mouse monoclonal immunoglobulin M (Men B) that recognizes polysialic acid on NCAM. Tumoral NCAM expression was also evaluated with the aid of immunohistochemical analysis. Using this method, NCAM and polysialylated NCAM were studied in six healthy pituitaries. In addition, correlations were investigated using three statistical methods (chi-square test, nonparametric Mann-Whitney U-test, and principal component analysis) to compare tumoral polysialylated NCAM expression and seven parameters (tumor size and type, intrasphenoidal or cavernous sinus invasion, Ki-67 index, mitoses, and patient age and sex). Neural cell adhesion molecules were expressed in the healthy anterior pituitary and in all tumors. In contrast, polysialylated NCAM was not found in the healthy pituitary gland, but was expressed in 46.3% of typical pituitary tumors and 85% of the tumors selected as highly aggressive, including one carcinoma and three tumors with histological characteristics that raised suspicion of malignancy. There was no significant correlation between polysialylated NCAM expression and tumor size, tumor type, Ki-67 index, mitoses, or patient age and sex. In contrast, the expression of polysialylated NCAM, which was sensitive to endoneuraminidase-N treatment, was strongly correlated with tumor invasion (p < 0.0001). CONCLUSIONS: In pituitary tumors in humans, expression of polysialylated NCAM is strongly related to tumor invasion and confirms the clinical diagnosis of aggressiveness.

Experimenting with new paradigms for medical education and the emergence of a distance learning degree using the internet: teaching evidence-based medicine.

This paper is focused on designing and developing a teaching environment associated with an introductory course in evidence-based medicine designed for undergraduates. Attempting to break away from the traditional educational model based on acquisition of factual knowledge, we developed a software tool centred on content management, student assessment and feedback. We ran this course on an educational website, using chat rooms and electronic mail for trainer-trainee communication over one academic year. The website served as a repository for knowledge and information and presented freestanding web-based interactive study modules and a non-interactive degree course. Trainers and trainees responded favourably to the computer applications and the Internet. This project demonstrated the feasibility of computer-aided learning and the advantages of distance teaching over the Internet.