L’imputation multiple des données manquantes aléatoirement : concepts généraux et présentation d’une méthode Monte-Carlo

BackgroundStatistical analysis of a data set with missing data is a frequent problem to deal with in epidemiology. Methods are available to manage incomplete observations, avoiding biased estimates and improving their precision, compared to more traditional methods, such as the analysis of the sub-sample of complete observations.MethodsOne of these approaches is multiple imputation, which consists in imputing successively several values for each missing data item. Several completed data sets having the same distribution characteristics as the observed data (variability and correlations) are thus generated. Standard analyses are done separately on each completed dataset then combined to obtain a global result. In this paper, we discuss the various assumptions made on the origin of missing data (at random or not), and we present in a pragmatic way the process of multiple imputation. A recent method, Multiple Imputation by Chained Equations (MICE), based on a Monte-Carlo Markov Chain algorithm under missing at random data (MAR) hypothesis, is described. An illustrative example of the MICE method is detailed for the analysis of the relation between a dichotomous variable and two covariates presenting MAR data with no particular structure, through multivariate logistic regression.ResultsCompared with the original dataset without missing data, the results show a substantial improvement of the regression coefficient estimates with the MICE method, relatively to those obtained on the dataset with complete observations.ConclusionThis method does not require any direct assumption on joint distribution of the variables and it is presently implemented in standard statistical software (Splus, Stata). It can be used for multiple imputation of missing data of several variables with no particular structure.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

In vitro cytotoxicity of a remineralizing resin-based calcium phosphate cement.

Recently, a resin-based calcium phosphate cement (RCPC) has been reported as a remineralizing pulp-capping or lining cement. RCPC consists mainly of tetracalcium and dicalcium phosphates, ethoxylated bisphenol A dimethacrylate and pyromellitic glycerol dimethacrylate monomers and photo- and chemical initiators. OBJECTIVES: Here, the cytotoxic effects of RCPC were evaluated. The hypothesis was that RCPC induced only minor cytotoxic response in immortalized murine odontoblast and pulp cells, comparable to that produced by similar dimethacrylates due to unpolymerized dimethacrylate monomer present after curing. METHODS: Cytotoxicity was determined following the changes in cell succinate dehydrogenase activity after 24 h exposure to the cement components and after a 24 h recovery period. A fourfold range of concentrations was tested of the monomers, the eluate of cured RCPC leached in Dulbecco's modified Eagle's medium, and crushed cured cement in dimethyl sulfoxide. RESULTS: The monomers themselves had cytotoxicities similar to those reported for other dimethacrylates, although they are significantly less toxic than Bis-GMA. Differential cell sensitivity was demonstrated, with the pulp cells having greater sensitivity to the unpolymerized monomer than the odontoblast-like cells. The leached components have cytotoxicity similar to that of the free monomers. The crushed material demonstrated no apparent cytotoxicity at the dilutions tested. SIGNIFICANCE: These data demonstrate that RCPC has an in vitro cytotoxicity that is comparable to other materials containing dimethacrylate monomers and suggest that the material may be suitable for use in dental restorations. The data also indicate that the pulp cells appear more sensitive to dimethacrylates than the odontoblasts.     

Advancement Flaps: A Basic Theme with Many Variations

Background. The advancement flap involves the linear advancement of tissue in one direction. Despite its straightforwardness and simple concept, it can be used to close a variety of defects, ranging from small defects on the scalp or extremities to large, complicated defects involving cosmetic units on the face.
Objectives. To provide a basic and useful review for the indications, advantages, disadvantages, and techniques for the use of advancement flaps in the reconstruction of defects in dermatologic surgery.
Materials and Methods. We performed a literature search for articles discussing advancement flaps and compiled a brief review of our findings.
Results. The movement of the advancement flap must be balanced by the blood supply of the flap. The excision of Burow's triangles along various aspects of the advancement flap can increase movement and improve cosmesis of the flap. The types of advancement flaps discussed include the single advancement flap, double advancement flap, A-T flap (O-T flap), Burow's triangle flap (Burow's wedge flap), crescenteric advancement flap, island pedicle flap (V-Y flap), helical rim advancement flap, and facelift flap.
Conclusion. Advancement flaps are versatile and useful basic flaps for repairing defects.     

Association of psychological and physiological measures of stress in health‐care professionals during an 8‐week mindfulness meditation program: mindfulness in practice

Work stress, burnout, and diminished empathy are prevalent issues for health‐care professionals. Mindfulness meditation (MM) is one commonly used strategy to manage stress. Measuring salivary cortisol allows for the assessment of serum cortisol level, a known stress level indicator. This study evaluated the association of subject‐reported stress symptoms and salivary cortisol in health‐care professionals, in an 8‐week MM program, with data collected prospectively at baseline and 8 weeks after program completion. Questionnaires [Profile of Mood States—Short Form (POMS‐SF), Maslach Burnout Inventory (MBI), and Interpersonal Reactivity Index (IRI)] measured mood, burnout and empathy. A paired t‐test between groups for pre/post‐salivary cortisol yielded no significant change. The POMS‐SF was most sensitive to change (mean increase 12.4; p = 0.020). Emotional exhaustion, measured in the MBI, was also affected by MM (mean decrease 4.54; p = 0.001). Changes in empathy may not have been captured due to either absence of effect of MM on empathy, subject number or scale sensitivity. Baseline and 8‐week correlations between salivary cortisol and survey results, and correlations between changes in these measures, were weak and not statistically significant. Nevertheless, psychometric results present a strong case for additional clinical trials of MM to reduce stress for health‐care professionals. Copyright © 2005 John Wiley & Sons, Ltd.     

An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

The surgical risk of colectomy in patients with cirrhosis

The records of 54 patients with documented cirrhosis who underwent colectomy between January 1970 and January 1984 were studied to assess the operative risk and to determine the preoperative predictive risk factors. In-hospital mortality was 24 percent (13 patients), and postoperative complications occurred in 48 percent (26 patients). The risk of surgical intervention was significantly increased if encephalopathy, ascites, anemia, or hypoalbuminemia was present before operation. A simple operative risk index involving the presence of encephalopathy and ascites and the levels of hemoglobin and albumin is proposed to help distinguish a low-risk subgroup in whom postoperative mortality was 12.8 percent from a high-risk subgroup in whom postoperative mortality was 53.3 percent.