Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Immune system. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

AMPK inhibition in health and disease.

Abstract: All living organisms depend on dynamic mechanisms that repeatedly reassess the status of amassed energy, in order to adapt energy supply to demand. The AMP-activated protein kinase (AMPK) alphabetagamma heterotrimer has emerged as an important integrator of signals managing energy balance. Control of AMPK activity involves allosteric AMP and ATP regulation, auto-inhibitory features and phosphorylation of its catalytic (alpha) and regulatory (beta and gamma) subunits. AMPK has a prominent role not only as a peripheral sensor but also in the central nervous system as a multifunctional metabolic regulator. AMPK represents an ideal second messenger for reporting cellular energy state. For this reason, activated AMPK acts as a protective response to energy stress in numerous systems. However, AMPK inhibition also actively participates in the control of whole body energy homeostasis. In this review, we discuss recent findings that support the role and function of AMPK inhibition under physiological and pathological states.

Influence of trial sample size on treatment effect estimates: meta-epidemiological study

Abstract: Objective To assess the influence of trial sample size on treatment effect estimates within meta-analyses. Design Meta-epidemiological study. Data sources 93 meta-analyses (735 randomised controlled trials) assessing therapeutic interventions with binary outcomes, published in the 10 leading journals of each medical subject category of the Journal Citation Reports or in the Cochrane Database of Systematic Reviews . Data extraction Sample size, outcome data, and risk of bias extracted from each trial. Data synthesis Trials within each meta-analysis were sorted by their sample size: using quarters within each meta-analysis (from quarter 1 with 25% of the smallest trials, to quarter 4 with 25% of the largest trials), and using size groups across meta-analyses (ranging from Results Treatment effect estimates were significantly larger in smaller trials, regardless of sample size. Compared with quarter 4 (which included the largest trials), treatment effects were, on average, 32% larger in trials in quarter 1 (which included the smallest trials; ratio of odds ratios 0.68, 95% confidence interval 0.57 to 0.82), 17% larger in trials in quarter 2 (0.83, 0.75 to 0.91), and 12% larger in trials in quarter 3 (0.88, 0.82 to 0.95). Similar results were obtained when comparing treatment effect estimates between different size groups. Compared with trials of 1000 patients or more, treatment effects were, on average, 48% larger in trials with fewer than 50 patients (0.52, 0.41 to 0.66) and 10% larger in trials with 500-999 patients (0.90, 0.82 to 1.00). Conclusions Treatment effect estimates differed within meta-analyses solely based on trial sample size, with stronger effect estimates seen in small to moderately sized trials than in the largest trials.

Days out of role due to common physical and mental conditions: results from the WHO World Mental Health surveys

Abstract: Days out of role because of health problems are a major source of lost human capital. We examined the relative importance of commonly occurring physical and mental disorders in accounting for days out of role in 24 countries that participated in the World Health Organization (WHO) World Mental Health (WMH) surveys. Face-to-face interviews were carried out with 62 971 respondents (72.0% pooled response rate). Presence of ten chronic physical disorders and nine mental disorders was assessed for each respondent along with information about the number of days in the past month each respondent reported being totally unable to work or carry out their other normal daily activities because of problems with either physical or mental health. Multiple regression analysis was used to estimate associations of specific conditions and comorbidities with days out of role, controlling by basic socio-demographics (age, gender, employment status and country). Overall, 12.8% of respondents had some day totally out of role, with a median of 51.1 a year. The strongest individual-level effects (days out of role per year) were associated with neurological disorders (17.4), bipolar disorder (17.3) and post-traumatic stress disorder (15.2). The strongest population-level effect was associated with pain conditions, which accounted for 21.5% of all days out of role (population attributable risk proportion). The 19 conditions accounted for 62.2% of all days out of role. Common health conditions, including mental disorders, make up a large proportion of the number of days out of role across a wide range of countries and should be addressed to substantially increase overall productivity.

Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis

Abstract: Objectives To assess the efficacy and safety of synthetic disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA)—a first step in a European League Against Rheumatism (EULAR) initiative to produce recommendations for the management of RA. Methods A systematic review of the literature using PubMed, Embase and the Cochrane library was performed up to January 2009. All randomised controlled trials (RCTs) reporting the efficacy of synthetic DMARDs (vs placebo or other synthetic DMARDs) on signs and symptoms, disability and/or radiographic structural damage in patients with RA were selected. Studies of biological agents or glucocorticoids were excluded. A pooled effect size (ES) was calculated by meta-analysis. Safety and the occurrence of infections and neoplasia was also assessed. Results 97 RCTs (14 159 patients) were analysed for efficacy. The pooled analysis indicated that methotrexate (MTX) was more efficacious in reducing signs and symptoms, disability and radiographic structural damage than other synthetic DMARDs pooled: ES for swollen joint count (SJC) versus pooled DMARDs=1.42 (95% CI 0.65 to 2.18). Leflunomide appeared to be as effective as MTX. Sulfasalazine and injectable gold were efficacious in reducing signs and symptoms and structural damage. Ciclosporin, minocycline, tacrolimus and hydroxychloroquine showed some efficacy in reducing SJC. Auranofin and D-penicillamine showed no significant superiority over placebo. The risks of cancer and of infection were increased with cyclophosphamide and azathioprine. Conclusions MTX was well-tolerated and effective in reducing signs and symptoms, disability and structural damage. A comparison with other synthetic DMARDs was in favour of MTX, though at the tested doses MTX and leflunomide were equally effective.