Showing papers by "University of Lorraine published in 2022"

Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis

Abstract: There is a growing armamentarium for the treatment of moderate-to-severe ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics and small molecule drugs for the treatment of patients with moderate-to-severe ulcerative colitis.In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions for articles published between Jan 1, 1990, and July 1, 2021. Major congresses' databases from Jan 1, 2018, to July 3, 2021, were reviewed manually. Phase 3, placebo-controlled or head-to-head randomised controlled trials (RCTs) assessing the efficacy and safety of biologics or small molecule drugs as induction or maintenance therapies for patients with moderate-to-severe ulcerative colitis were included. Phase 2 RCTs were excluded because of their small sample sizes and inclusion of doses not further explored in phase 3 RCTs. Summary data from intention-to-treat analyses were extracted from included reports by JSL and PAO. The primary outcome was the induction of clinical remission. A network meta-analysis was done under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. The surface under the cumulative ranking (SUCRA) was used to rank the included agents for each outcome. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety. Maintenance data on efficacy for treat-straight-through and randomised responder trials are also presented. This study is registered with PROSPERO, CRD42021225329.Our search yielded 5904 results, from which 29 studies (four being head-to-head RCTs) fulfilled our inclusion criteria and were included. Of these, 23 studies assessed induction therapy with either a biologic or small molecule drug, comprising 10 061 patients with ulcerative colitis. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib was significantly superior to all other interventions for the induction of clinical remission (infliximab [OR 2·70, 95% CI 1·18-6·20], adalimumab [4·64, 2·47-8·71], golimumab [3·00, 1·32-6·82], vedolizumab [3·56, 1·84-6·91], ustekinumab [2·92, 1·31-6·51], etrolizumab [4·91, 2·59-9·31], tofacitinib [2·84, 1·28-6·31], filgotinib 100 mg [6·15, 2·98-12·72], filgotinib 200 mg [4·49, 2·18-9·24], and ozanimod (2·70, 1·18-6·20), and ranked highest for the induction of clinical remission (SUCRA 0·996). No differences between active interventions were observed when assessing adverse events and serious adverse events. Vedolizumab ranked lowest for both adverse events (SUCRA 0·184) and serious adverse events (0·139), whereas upadacitinib ranked highest for adverse events (0·843) and ozanimod ranked highest for serious adverse events (0·831).Upadacitinib was the best performing agent for the induction of clinical remission (the primary outcome) but the worst performing agent in terms of adverse events in patients with moderate-to-severe ulcerative colitis. Vedolizumab was the best performing agent for safety outcomes. With the paucity of direct comparisons in the published literature, our results might help clinicians to position drugs in treatment algorithms.None.

Molecular mechanisms governing aquaporin relocalisation

Abstract: The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis.

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation

Abstract: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain.To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO.Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019.Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166).The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO.Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group.In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive.ClinicalTrials.gov Identifier: NCT02754193.

Proposed System Based on a Three-Level Boost Converter to Mitigate Voltage Imbalance in Photovoltaic Power Generation Systems

Abstract: Voltage imbalance poses a challenge to photovoltaic systems. A modular structure based on a three-level boost converter is proposed to address this problem. The three-level boost converter offers advantages, such as a low current ripple and voltage stress, over a classic boost converter. These advantages offset the use of additional elements in the proposed converter circuit. Two capacitors are used to enable the innovative connection between multiple sources and the three-level boost converter. The second capacitor of the first module is shared with the first capacitor of the second module. This structure is used in conjunction with a controller to balance the voltages in the system. The operating modes of the two-module system in a nominal case are introduced. The controller is based on an indirect sliding model, wherein the input current of each energy source and the output voltage balance are considered. The performance of the current and voltage controllers are studied in two scenarios. The first case involves increasing the reference current and the presence of four sliding surfaces related to the current control and voltage balance, whereas the second case involves the presence and absence of two sliding surfaces related to the voltage balance. The dynamic response of this controller is also compared with the Proportional Integral(PI) controller. Large-signal modeling of the two-module system and the accuracy of this model in two cases of radiation change and panel temperature change is investigated. The robustness of the system is investigated using this large-signal model in two cases that involve changing the inductors and capacitors of the system. A topology consisting of two conventional boost converters is chosen to compare energy stored and efficiency with the proposed topology. The capacitance of the system is calculatedfor two topologies. The energy stored in the two systems is compared. The two-module system is simulated using Simulink MATLAB software. The simulation and experimental results validate the proposed system.

Handling the impact of feature uncertainties on SVM: A robust approach based on Sobol sensitivity analysis

Abstract: This paper addresses the problem of classification when target data are subject to feature uncertainties. A robust approach based on Sobol sensitivity analysis is proposed to improve the robustness of support vector machine (SVM) models. SVM is a supervised machine learning method for pattern recognition whose performance depends on the definition of its hyperparameters and the quality of data. The proposed approach analyzes the impact of the uncertainties on the predictive performance of SVM based on Sobol’ sensitivity analysis. Afterwards, a new parameter is introduced to improve the robustness of SVM to the impact of uncertainties. The efficiency of this approach is evaluated by applying it to six real-world datasets. The results are then discussed and analyzed.

High Gain PWM Method and Active Switched Boost Z-Source Inverter With Less Voltage Stress on the Devices

Abstract: This article presents a new circuit topology for high voltage gain active switched boost quasi Z-source inverter (qZSI) and a pulsewidth modulation (PWM) technique. The higher boosting capability with a lower number of elements, the continuous source current, the less voltage stress across the devices, and having the common ground are the main advantages of the proposed structure. The voltage gain of the proposed inverter is twice that of the conventional capacitor-assisted qZSI (sCA-qZSI). Other benefits of the proposed inverter over the sCA-qZSI are the reduction of Z-source passive components and shoot-through current. Compared to the conventional active switched inductor boost qZSI, the proposed inverter has higher output voltage and also lower shoot-through current, while it has fewer components (one fewer inductor, two fewer diodes, but one more capacitor). The boost factor of the proposed inverter is more than twice that of the classic ones. Besides, a high gain PWM technique is proposed, which can be applied to any types of Z-source inverters. Both the simulation and experimental results of the proposed inverter under the proposed PWM technique are examined to validate their operation.

The Impact of Cognitive Biases on Professionals’ Decision-Making: A Review of Four Occupational Areas

Abstract: The author reviewed the research on the impact of cognitive biases on professionals' decision-making in four occupational areas (management, finance, medicine, and law). Two main findings emerged. First, the literature reviewed shows that a dozen of cognitive biases has an impact on professionals' decisions in these four areas, overconfidence being the most recurrent bias. Second, the level of evidence supporting the claim that cognitive biases impact professional decision-making differs across the areas covered. Research in finance relied primarily upon secondary data while research in medicine and law relied mainly upon primary data from vignette studies (both levels of evidence are found in management). Two research gaps are highlighted. The first one is a potential lack of ecological validity of the findings from vignette studies, which are numerous. The second is the neglect of individual differences in cognitive biases, which might lead to the false idea that all professionals are susceptible to biases, to the same extent. To address that issue, we suggest that reliable, specific measures of cognitive biases need to be improved or developed.