Philippe Lambert

Effect of a collaborative approach on the quality of prescribing for geriatric inpatients: a randomized, controlled trial.

OBJECTIVES: To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management (GEM) care on the appropriateness of prescribing.

Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis : results of a pilot study

Objective:In experimental animals, recent results suggest that the addition of inulin-type fructans such as oligofructose (OFS) in the diet decreases triacylglycerol accumulation in the liver tissue. Therefore, we have investigated the effect of daily ingestion of OFS in seven patients with nonalcoholic steatohepatitis (NASH), confirmed by liver biopsies.Design:They received 16 g/day OFS or maltodextrine (placebo) for 8 weeks in a randomized double-blind crossover design. Energy intake, body composition, liver steatosis and blood parameters were analysed after 4 and 8 weeks of dietary supplementation.Results:Compared to placebo, OFS decreased significantly serum aminotransferases, aspartate aminotransferase after 8 weeks, and insulin level after 4 weeks, but this could not be related to significant effect on plasma lipids.Conclusion:This pilot study supports the putative interest of OFS in the management of liver diseases associated with abnormal lipid accumulation in humans.

On the appropriateness of marginal models for repeated measurements in clinical trials

Although models developed directly to describe marginal distributions have become widespread in the analysis of repeated measurements, some of their disadvantages are not well enough known. These include producing profile curves that correspond to no possible individual, possibly showing that a treatment is superior on average when it is poorer for each individual subject, implicitly generating complex and implausible physiological explanations, including underdispersion in subgroups, and sometimes corresponding to no possible probabilistic data generating mechanism. We conclude that such marginal models may sometimes be appropriate for descriptive observational studies, such as sample surveys in epidemiology, but should only be used with great care in causal experimental settings, such as clinical trials.

Effect of Conventional Controlled-Rate Freezing and Vitrification on Morphology and Metabolism of Bovine Blastocysts Produced In Vitro

Abstract This study compares the effects of conventional controlled-rate freezing and vitrification on the morphology and metabolism of in vitro-produced bovine blastocysts. Day 7 expanded blastocysts cultured in synthetic oviduct fluid with 5% fetal calf serum were frozen in 1.36 M glycerol, 0.25 M sucrose or vitrified in 25% glycerol, 25% ethylene glycol. Cell alterations and in vitro development were evaluated immediately after thawing or after 72 h. The effect of cryopreservation on inner cell mass and trophectoderm (TE) cell number as well as glucose, pyruvate, and oxygen uptakes, and lactate release by blastocysts were evaluated. Immediately after thawing, blastocysts showed equivalent cell membrane permeabilization after both cryopreservation procedures, while alterations in nuclear staining were more frequent in vitrified embryos. After culture, similar survival and hatching rates were observed. Both procedures decreased cell number immediately after thawing and after 72 h. However, the number of TE cells was lower in frozen embryos than in vitrified ones. In relation to this, frozen blastocysts showed a decrease in glucose, pyruvate, and oxygen uptake, although those parameters were not altered in vitrified embryos. An increased glycolytic activity was also observed in frozen embryos, indicating a stress response to this procedure.

Generalized Pareto Fit to the Society of Actuaries’ Large Claims Database

Abstract This paper discusses a statistical modeling strategy based on extreme value theory to describe the behavior of an insurance portfolio, with particular emphasis on large claims. The strategy is illustrated using the 1991–92 group medical claims database maintained by the Society of Actuaries. Using extreme value theory, the modeling strategy focuses on the “excesses over threshold” approach to fit generalized Pareto distributions. The proposed strategy is compared to standard parametric modeling based on gamma, lognormal, and log-gamma distributions. Extreme value theory outperforms classical parametric fits and allows the actuary to easily estimate high quantiles and the probable maximum loss from the data.

Robust specification of the roughness penalty prior distribution in spatially adaptive Bayesian P-splines models

The potential important role of the prior distribution of the roughness penalty parameter in the resulting smoothness of Bayesian P-splines models is considered. The recommended specification for that distribution yields models that can lack flexibility in specific circumstances. In such instances, these are shown to correspond to a frequentist P-splines model with a predefined and severe roughness penalty parameter, an obviously undesirable feature. It is shown that the specification of a hyperprior distribution for one parameter of that prior distribution provides the desired flexibility. Alternatively, a mixture prior can also be used. An extension of these two models by enabling adaptive penalties is provided. The posterior of all the proposed models can be quickly explored using the convenient Gibbs sampler.

Set up of a serum-free culture system for bovine embryos: embryo development and quality before and after transient transfer.

It is well known that serum in culture medium negatively affects blastocyst quality. The objective of this work was to develop and test a serum-free culture medium which could improve embryo quality, measured by the resistance to freezing, lipid and glutathione content of the resulting blastocysts, as well as the ability of the blastocysts to elongate after transient transfer to recipient cows. In a first experiment we showed that adding a mixture of insulin, transferrin and selenium to serum-free Synthetic Oviduct Fluid medium (SOF-ITS) improved embryo development and quality. In the second experiment, the addition of BSA to SOF-ITS further improved blastocyst development. Moreover, a reduction in lipid content of morulae was observed in SOF-ITS-BSA by comparison with morulae cultured with serum (SOF-FCS). The resistance to freezing measured by hatching rates 24h post-thawing was also improved for blastocysts with a diameter between 160 and 180 microm cultured in SOF-ITS-BSA by comparison to those produced with serum. In order to evaluate the redox potential of the embryos, reduced glutathione content (GSH) was evaluated both before and after cryopreservation. A significant decrease in glutathione was observed after freezing, whatever the culture medium, but no difference was observed between culture conditions. Transient transfers were performed and elongated D-13 embryos were recovered. Elongation was more pronounced and the embryonic disk more often visible in embryos cultured in SOF-ITS-BSA than in embryos cultured with FCS. In conclusion, the serum-free system we developed to produce in vitro bovine embryos meets the developmental and qualitative requirements for a large-scale use.

Efficacy of pre-ascent climbing route visual inspection in indoor sport climbing

Pre‐ascent climbing route visual inspection (route preview) has been suggested as a key climbing performance parameter although its role has never been verified experimentally. We examined the efficacy of this perceptual‐cognitive skill on indoor sport climbing performance. Twenty‐nine male climbers, divided into intermediate, advanced and expert climbing level groups, climbed two indoor sport routes matching their climbing level and, where applicable, routes below their climbing level. At each level, one route was climbed with a preview, where participants benefited from a 3‐min pre‐ascent climbing route visual inspection. Performance was assessed in terms of output (route completion) and form (number and duration of moves and stops). Route preview did not influence the output performance. Climbers using visual inspection were no more likely to finish the ascent than those without the option of using visual inspection. Conversely, route preview did influence form performance; climbers made fewer, and shorter stops during their ascent following a preview of the route. Form performances differences remained when baseline ability levels were taken into account, although for shorter duration of stops only with expert climbers benefiting most from route preview. The ability to visually inspect a climb before its ascent may represent an essential component of performance optimization.

Analysing financial returns by using regression models based on non-symmetric stable distributions

The daily evolution of the price of Abbey National shares over a 10-week period is analysed by using regression models based on possibly non-symmetric stable distributions. These distributions, which are only known through their characteristic function, can be used in practice for interactive modelling of heavy-tailed processes. A regression model for the location parameter is proposed and shown to induce a similar model for the mode. Finally, regression models for the other three parameters of the stable distribution are introduced. The model found to fit best allows the skewness of the distribution, rather than the location or scale parameters, to vary over time. The most likely share return is thus changing over time although the region where most returns are observed is stationary.

A Bayesian Design Space for Analytical Methods Based on Multivariate Models and Predictions

The International Conference for Harmonization (ICH) has released regulatory guidelines for pharmaceutical development. In the document ICH Q8, the design space of a process is presented as the set of factor settings providing satisfactory results. However, ICH Q8 does not propose any practical methodology to define, derive, and compute design space. In parallel, in the last decades, it has been observed that the diversity and the quality of analytical methods have evolved exponentially, allowing substantial gains in selectivity and sensitivity. However, there is still a lack of a rationale toward the development of robust separation methods in a systematic way. Applying ICH Q8 to analytical methods provides a methodology for predicting a region of the space of factors in which results will be reliable. Combining design of experiments and Bayesian standard multivariate regression, an identified form of the predictive distribution of a new response vector has been identified and used, under noninformative as well as informative prior distributions of the parameters. From the responses and their predictive distribution, various critical quality attributes can be easily derived. This Bayesian framework was then extended to the multicriteria setting to estimate the predictive probability that several critical quality attributes will be jointly achieved in the future use of an analytical method. An example based on a high-performance liquid chromatography (HPLC) method is given. For this example, a constrained sampling scheme was applied to ensure the modeled responses have desirable properties.