Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

First nationwide survey on cardiovascular risk factors in Grand-Duchy of Luxembourg (ORISCAV-LUX)

BACKGROUND: The ORISCAV-LUX study is the first baseline survey of an on-going cardiovascular health monitoring programme in Grand-Duchy of Luxembourg. The main objectives of the present manuscript were 1) to describe the study design and conduct, and 2) to present the salient outcomes of the study, in particular the prevalence of the potentially modifiable and treatable cardiovascular disease risk factors in the adult population residing in Luxembourg. METHOD: ORISCAV-LUX is a cross-sectional study based on a random sample of 4496 subjects, stratified by gender, age categories and district, drawn from the national insurance registry of 18-69 years aged Luxembourg residents, assuming a response rate of 30% and a proportion of 5% of institutionalized subjects in each stratum. The cardiovascular health status was assessed by means of a self-administered questionnaire, clinical and anthropometric measures, as well as by blood, urine and hair examinations. The potentially modifiable and treatable risk factors studied included smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity. Both univariate and multivariate statistical analyses used weighted methods to account for the stratified sampling scheme. RESULTS: A total of 1432 subjects took part in the survey, yielding a participation rate of 32.2%. This figure is higher than the minimal sample size of 1285 subjects as estimated by power calculation. The most predominant cardiovascular risk factors were dyslipidemia (69.9%), hypertension (34.5%), smoking (22.3%), and obesity (20.9%), while diabetes amounted 4.4%. All prevalence rates increased with age (except smoking) with marked gender differences (except diabetes). There was a significant difference in the prevalence of hypertension and of lipid disorders by geographic region of birth. The proportion of subjects cumulating two or more cardiovascular risk factors increased remarkably with age and was more predominant in men than in women (P<0.0001). Only 14.7% of men and 23.1% of women were free of any cardiovascular risk factor. High prevalence of non-treated CVRF, notably for hypertension and dyslipidemia, were observed in the study population. CONCLUSION: The population-based ORISCAV-LUX survey revealed a high prevalence of potentially modifiable and treatable cardiovascular risk factors among apparently healthy subjects; significant gender and age-specific differences were seen not only for single but also for combined risk factors. From a public health perspective, these preliminary findings stress the urgent need for early routine health examinations, preventive interventions and lifestyle behavioural changes, even in young asymptomatic adults, to decrease cardiovascular morbidity and mortality in Luxembourg

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Planning in multi-agent partially observable domains using sparse sampling

A large number of sequential decision-making problems in uncertain environments can be modeled as Markov Decision Processes (MDPs). In such settings, an agent can observe at each time step the state of the environment and then executes an action, causing a stochastic transition to a new state of the environment and receiving a reward accordingly. In a finite-horizon MDP, the goal of planning is to maximize the expected total payoff over the given horizon. MDPs can be solved using a number of different algorithms whose complexity is generally some low-order polynomial in the number of states and decision-making horizon. Interactive computer games constitute a great platform of development for AI research in learning and planning. Akin to the real-world problems they simulate, they introduce an additional level of complexity. As a matter of fact, in such settings the agent's sensors provide only partial information about the state of the environment, called an observation. These problems can be modeled as partially observable MDPs (POMDPs). At any point in time, the sequence of observations made by the agent so far determines a probability distribution over states, called a belief state. It has been shown that solving a POMDP can be reduced to solving the corresponding MDP on the set of belief states. This planning problem, however, becomes rapidly intractable in large state spaces with a substential number of observations. In this thesis, we adapt the work of Kearns, Mansour and Ng on sparse sampling algorithms to factored POMDP representations of multi-agent partially observable domains. Applying this algorithm to two domains based on popular video games, we show empirically how a randomly sampled look-ahead tree covering only a small fraction of the full look-ahead tree is sufficient to compute near-optimal policies in these settings. We compare the performance of this approach to the classical methods and conclude that sparse sampling dramatically reduces the running time of the planning algorithm and scales well with the number of enemy agents.Keywords: Running time, Sampling, POMDP, Artificial intelligence, Computer games, Multi-agent, Bomberman, Partially observable, Sparse sampling, Planning, Belief stat

Dispatcher-assisted telephone cardiopulmonary resuscitation using a French-language compression-only protocol in volunteers with or without prior life support training: A randomized trial.

OBJECTIVES: Due to the recent interest in hands-only protocols for dispatcher-assisted cardiopulmonary resuscitation (CPR) and the lack of any validated algorithms in French, our primary objective was to evaluate a new French-language protocol in terms of its efficacy to help previously untrained volunteers in performing basic life support efforts of appropriate quality, and secondarily to investigate its potential utility in subjects with previous training. METHODS: Untrained volunteers were recruited among adults in a public movie centre and previously trained volunteers among undergraduate nursing students. Participants were randomly assigned to 'phone CPR' versus 'no phone CPR' by drawing sets of envelopes. Primary outcome measures were the results of the Cardiff evaluation test; the secondary measures were global scoring of a complete 5min period of CPR, in a manikin model of cardiac arrest. RESULTS: Out of 146 volunteers assessed for eligibility, 36 previously untrained candidates declined participation. 110 participants, distributed into four groups, completed the study: the previously untrained non-guided group (group A, n=30), the previously untrained guided group (group B, n=30), the previously trained non-guided group (group C, n=25) and the previously trained guided group (group D, n=25). Results of the Cardiff test and global evaluation of CPR performance revealed a significant improvement in group B as compared with group A, approaching the level of the group C. Previously trained guided bystanders had the best CPR scores, notably because of an improvement in the quality of airway management. CONCLUSION: When used by dispatchers, this new French-language algorithm offers the opportunity to help previously untrained bystanders initiate CPR. The same protocol may serve to guide volunteers with prior basic life support training to reach their best CPR performance

Predictive ability of 35 frailty scores for cardiovascular events in the general population

Introduction: Frailty is a state of vulnerability in elderly people linked to higher mortality risk. Cardiovascular disease (CVD) is highly prevalent in aged populations and associated with frailty. Thus, frailty state could predict higher risk of CVD. Many frailty scores (FS) have been developed, but none of them is considered the gold standard. We aimed to compare predictive and discriminative ability of an extensive list of FS with regard to incidence of CVD in a sample of the general elderly population in England. We assessed the hypothesis that some FS will have better predictive ability than others, depending on their characteristics. Methods: We performed a prospective analysis of the association between 35 FS in participants free of CVD at baseline wave 2 of the English Longitudinal Study of Ageing (2004-2005), and incident CVD assessed until February 2012. The sample consisted of 4,177 participants (43.0 % men). Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated for each FS using Cox proportional hazards model, adjusted for demographic, lifestyle and comorbidity variables. FS were analyzed on a continuous scale and using original cutoffs. The added predictive ability of FS beyond a basic model consisting of sex and age was studied using Harrel's C statistic (the higher the better). Results: The median follow-up was 5.8 years, the incidence rate of CVD events was 301.2/10,000 person-years and CVD represented 28% of the total cause of death. The mean age was 70.5 (SD: +/-7.8) years. In fully-adjusted models with demographics, lifestyles and comorbidity, HRs ranged from: 1.0 (0.7; 1.6) to 12.7 (5.5; 29.3). Using cutoffs, HRs ranged from 0.7 (0.2; 1.9) to 1.8 (1.3; 2.5). Adjusted for sex and age, delta Harrel's C statistic ranged from-0.8 (-3.4; 1.8) to 3.0 (-0.4; 6.4). The best CVD predictive ability was found for the Frailty Index with 70 variables and the Comprehensive Geriatric Assessment screening FS for continuous and cutoff analyses respectively. In conclusion, there is high variability in the association between different published FS and incident CVD. FS have better predictive ability used as continuous variable. Although most of the analyzed FS have good predictive ability with regard to incident CVD, they do not significantly improve on the discriminative capacity of a basic model. Our results will help to guide clinicians, researchers and public health practitioners in choosing the most informative frailty assessment tool

Correction to: A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol (BMC Pulmonary Medicine, (2020), 20, 1, (317), 10.1186/s12890-020-01361-x)

Following publication of the original article [1], it was brought to the authors’ attention that sentences in the method section were not appropriate, due to an omission in the update of a prior version. Namely, the following sentences have been deleted in the corrected version. © 2021, The Author(s)

Joint data analysis in nutritional epidemiology: identification of observational studies and minimal requirements

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well asminimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration. Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, t he minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition