Multiparametric prognostic evaluation of biological factors in primary breast cancer.

BACKGROUND: An array of biological features related to tumor cell differentiation status, growth rate, and invasive potential have been identified as potential prognostic factors in breast cancer. We were interested in determining their relative importance in predicting patient survival. PURPOSE: We evaluated the relative weight of the following four biological factors in predicting survival of patients with breast cancer: tumor cell DNA content (determined by flow cytometry), tumor cell proliferation rate (determined by thymidine kinase activity), expression levels of cathepsin D and urokinase plasminogen activator, and several "classical" clinical and histological factors. METHODS: Selected from a prospectively updated database, the study population consisted of 319 primary breast cancer patients who received treatment and follow-up care (median, 6 years) in the Centre René Huguenin. To determine the profile of biological factors for each patient, we used frozen tumor specimens and (except for the flow cytometric DNA content assay) commercially available assay kits. We determined by Cox multivariate analysis the relationships of the biological factors to each other, to classical prognostic factors, and to disease-free and metastasis-free survival. RESULTS: In the overall population, disease-free survival was best predicted by node status (P = .004), clinical tumor size (P = .02), and cathepsin D expression (P = .01), whereas metastasis-free survival was best predicted by node status (P = .0004), clinical tumor size (P = .009), and urokinase plasminogen activator expression (P = .04). In node-negative patients, thymidine kinase activity was the only factor selected for disease-free (P = .04) and metastasis-free (P = .05) survival. In node-positive patients, the number of positive axillary lymph nodes was the only factor selected for disease-free (P = .0008) and metastasis-free (P = .00017) survival. CONCLUSIONS: Our retrospective analysis has identified protease expression and tumor cell proliferation rate as important biological prognostic factors in breast cancer. Prospective clinical trials should be undertaken to confirm these results.     

Duration of antibiotic treatment in intensive care: current data

OBJECTIVE: To review the current data on the duration of an antibiotic treatment. METHODS: Analysis of recent and older articles on criteria of discontinuation of an antibiotic treatment in intensive care patients. SYNTHESIS: In intensive care patients the initiation of an antibiotic therapy is more or less codified, in spite of numerous existing problems. The duration of its maintenance, although based on scientific data depends mainly on a multitude of variables. The first step is to assess the therapeutic efficiency in considering the regression of clinical manifestations, the normalization of the acute phase reactants, the sterility of bacteriological samples and the absence of relapse at therapy discontinuation. An assessment after 48 hours is essential, in order to decide the maintenance or the modification of therapy. Finally the indication of bitherapy is considered. The theoretical duration of antibiotic therapy is determined in taking into account the involved microbial agent(s), the centre of infection, the bacterial inoculum, the patient, the presence of foreign material, and the administered antibiotic.     

Mesh compared with non-mesh methods of open groin hernia repair: systematic review of randomized controlled trials

BACKGROUND: Open tension-free methods of groin hernia repair have been widely adopted despite little rigorous evaluation. METHODS: Information was assimilated from all randomized or quasi-randomized trials comparing open mesh with open non-mesh methods to assess benefits and safety. Electronic databases were searched and members of the EU Hernia Trialists Collaboration consulted to identify trials. Prespecified data items were extracted from reports, and quantitative or, if not possible, qualitative meta-analysis was performed. RESULTS: Fifteen eligible trials, which included 4005 participants, were identified. There were similar numbers of complications in each group, with few data to address short-term pain and length of stay in hospital. Return to usual activities was quicker in the mesh group for seven of ten trials (P not significant). There were fewer reported recurrences in the mesh groups: overall 21 (1.4 per cent) of 1513 versus 72 (4.4 per cent) of 1634 (odds ratio 0.39 (95 per cent confidence interval 0.25-0. 59); P < 0.001). CONCLUSION: Although the rigorous search maximized trial identification, formal meta-analysis was limited by the variation in trial reporting. Within the data available, mesh repair was associated with fewer recurrences.     

Laparoscopic compared with open methods of groin hernia repair: systematic review of randomized controlled trials

BACKGROUND: The place of laparoscopic groin hernia repair remains controversial. Individual randomized controlled trials alone have not provided statistically reliable results when considering recurrence, potentially serious complications and chronic pain. METHODS: A rigorous systematic review was performed of published data from all relevant randomized or quasi-randomized trials. Electronic databases were searched and members of the EU Hernia Trialists Collaboration consulted to identify trials. Prespecified data items were extracted from reports and, where possible, quantitative meta-analysis was performed. RESULTS: Thirty-four published reports of eligible trials were included, involving 6804 participants. Sample sizes ranged from 20 to 1051, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (P < 0.001, Sign test). Operative complications were uncommon for both methods, but visceral and vascular injuries were more frequent in the laparoscopic group (4.7 per 1000 versus 1. 1 per 1000). Postoperative pain was less among laparoscopic groups (P = 0.08). Length of hospital stay did not differ significantly between groups (P = 0.50), but return to usual activity was earlier for laparoscopic groups (P < 0.001). Chronic pain and numbness were reported for only a small minority of trials. Overall, recurrences did not differ between groups, but comparison of laparoscopic with open non-mesh repair favoured laparoscopic methods, significantly so for transabdominal preperitoneal repair (Peto odds ratio 0.56 (95 per cent confidence interval 0.33-0.93); P = 0.026). CONCLUSION: Although the rigorous search maximized trial identification, variation in trial reporting made formal meta-analysis difficult. Laparoscopic repair was associated with less postoperative pain and more rapid return to normal activities, but it takes longer to perform and may increase the risk of rare, but serious, complications.     

Recommendations for ICT use in Alzheimer’s disease assessment: Monaco CTAD expert meeting

Alzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient’s care and support to care providers, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients’ performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer’s disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the conditions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials.