Search

This study determined the issues and challenges encountered by the parents who facilitated learning at home. This research was a Qualitative-Phenomenological study that utilized the Narrative Form using the responses of the parent-participants in the Key Informant Interview conducted by the researcher. Creswell Method applied in qualitative analysis of these reactions to explore the lived experience of parents who served as Learning Facilitators in Modular Distance Learning. From the responses of the participants in the Key Informant Interview conducted, the researcher was able to extract the following themes that describe their overall ability in painting the portrait of their children: FB: Keeping You Informed, Education Must Continue, Education Cannot Wait, MDL Finds a Way, Painting a Portrait as Consecrated Responsibility, Race Against Time, and Time Works Wonders. The researcher was able to draw out issues with implications of the findings on the lived experiences of the parents in painting the portrait of their children as not just a simple task. Their ability to paint the picture and helping their children with their studies were perceived as challenging but added colors in making their future even more meaningful. Keywords: Paint a Portrait, Modular Distance Learning, Learning Facilitator

Objective To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Summary background data Uncertainty regarding the postoperative risks of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Methods As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results A total of 1,581 patients were included; more than half of them were males (n= 822, 52.0%) and older than 50 years (n=835, 52.8%). Most procedures (n=1,261, 79.8%) were emergent, and laparotomies (n= 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (OR 2.46, 95% CI [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.

Enhanced Recovery After Surgery (ERAS) is a paradigm shift in perioperative care and incorporates patient-centered, evidence-based, and multidisciplinary team-developed pathways for a surgical specialty. ERAS pathways aim to reduce the patient's surgical stress response, optimize their physiologic function, facilitate recovery, and reduce the length of stay. The bariatric program at our institution was previously managed by many surgeons with anecdotal preferences, resulting in increased costs, lengths of stay, and opioid prescribing.To describe a standardized ERAS pathway for patients undergoing a laparoscopic sleeve gastrectomy procedure in order to enhance perioperative care and reduce opioid usage.ERAS bariatric program in New Jersey.The ERAS bariatric program at our institution was implemented in January 2018. All patients who underwent sleeve gastrectomy from January 2016 to November 2017 (preimplementation) as well as from February 2018 to October 2020 (postimplementation) were included in this retrospective study, with those undergoing procedures in December 2017 and January 2018 excluded due to the transition to the ERAS protocol. Differences in lengths of stay, direct costs, and 30-day readmission rates were compared between the pre- and postimplementation periods. The primary goal of our ERAS pathway was to optimize patient care with reduced opioid usage, and the secondary goal was to reduce the costs for care.A total of 1988 patients who underwent sleeve gastrectomy were identified, with 789 patients in the preimplementation group and 1199 patients in the postimplementation group. In a multivariate analysis, the mean length of a hospital stay in the postimplementation period was 18% lower (95% confidence interval [CI], 14-22) than that of the preimplementation period (P.001), while the average opioid morphine milligram equivalents administered in the postoperative period was 61% (95% CI, 57%-65%) less than that of the preimplementation period (P.001). Average direct costs decreased by $155 (95% CI, -$358 to $48) per case in the postimplementation period (P = .133), and there was no significant difference in the 30-day readmission rate between the pre- and postimplementation periods (3.8% versus 3.0%, respectively; odds ratio, .81; 95% CI, .49-1.35; P = .413).In this study, patient outcomes after ERAS pathway implementation were significantly better than in historical cases. Implementing the bariatric ERAS program for laparoscopic sleeve gastrectomy at our institution has led to rapid postoperative recovery of patients, shorter lengths of stay, reduced opioid usage, and decreased costs per case, thereby increasing the overall cost savings to the hospital. ERAS pathways in bariatric surgery represent an opportunity to enhance patient care while decreasing overall costs. We propose that cost-effective, tailor-made ERAS pathways for sleeve gastrectomy should be implemented in all designated centers of excellence, as they can have a great economic impact on the healthcare system.

International audience; Background Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.Objective To develop a pretest score for HIT.Design Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839).Setting Thirty-one tertiary hospitals in France, Switzerland, and Belgium.Patients Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts.Measurements Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results.Results Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); >= 40% decrease in platelet count over

Polyhydramnios is a common feature diagnosed by ultrasound in the second half of pregnancy. Biochemical analysis of amniotic fluid can be useful when suspecting Bartter syndrome or digestive atresia but in most of cases, no etiology of polyhydramnios is found because of the complex regulation of amniotic fluid. Aquaporins (AQP) are transmembrane channel proteins contributing to water transfers. Some of them are expressed in fetal membranes and placenta. Their expression has been shown to be disrupted in some pathological conditions such as maternal diabetes, often associated with polyhydramnios. AQP-1, 3 and 8 levels in amniotic fluid were retrospectively measured in patients suffering from polyhydramnios (n=21) from 23 weeks of gestation (WG). They were compared to the levels observed in control subjects (n=96) and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels were physiologically fluctuating, AQP-1 levels always being the lowest and AQP-3 the highest, with a significant decrease at the end of pregnancy. AQPs/AFP ratios increased about 8 folds during pregnancy, their kinetic profiles reflecting physiological dynamic evolution of amniotic fluid volume. In polyhydramnios, AQP-3 level tended to be decreased whereas AQP-8 level was decreased from mid-gestation whatever the etiology of polyhydramnios. No significant relationship was found between AQPs levels and either the fetal prematurity degree or macrosomia. No specific pattern was observed in idiopathic polyhydramnios, limiting the interest of AQPs dosage in amniotic fluid in the management of those complicated pregnancies.

Introduction The TROPHIES observational study enrolled patients with type 2 diabetes mellitus (T2DM) initiating their first injectable treatment with the glucagon-like peptide 1 receptor agonists (GLP-1 RAs) dulaglutide or liraglutide. This manuscript focuses on the study design, baseline characteristics of the enrolled population, and factors associated with GLP-1 RA choice. Methods TROPHIES is a prospective, observational, 24-month study conducted in France, Germany, and Italy. Inclusion criteria include adult patients with T2DM, naïve to injectable antihyperglycemic treatments, initiating dulaglutide or liraglutide per routine clinical practice. The primary outcome is the duration of treatment on dulaglutide or liraglutide without a significant treatment change. Results The analysis included 2181 patients (dulaglutide, 1130; liraglutide, 1051) (cutoff date May 15, 2019). The population was 56% male with mean [standard deviation (SD)] patient characteristics at baseline as follows: age, 59.2 (11.0) years; body mass index (BMI), 33.9 (6.6) kg/m2; T2DM duration, 8.5 (6.9) years; and glycated hemoglobin (HbA1c), 8.2 (1.3)%. Between-cohort demographic and clinical characteristics were balanced. The mean (SD) HbA1c and BMI values for French, German, and Italian patients were, respectively, 8.6 (1.4)%, 8.2 (1.4)%, 8.0 (0.8)%; 33.3 (6.1) kg/m2, 36.0 (7.2) kg/m2, and 32.6 (5.9) kg/m2. Conclusion This study analysis at baseline provides an opportunity to evaluate between-country differences in baseline HbA1c, weight, macrovascular complications, and factors driving GLP-1 RA selection for patients with T2DM in daily practice. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01076-0., Plain Language Summary Dulaglutide and liraglutide are medications that can help people with type 2 diabetes mellitus (T2DM) to control their blood sugar levels. These medications may also reduce body weight and reduce the risk of major cardiovascular disease. Given these treatment effects, it is essential to know how they are used in everyday clinical practice. Therefore, a study is being performed in three countries (France, Germany, and Italy) in people with T2DM who had a first-ever injectable therapy for T2DM with dulaglutide or liraglutide. Here, we present the study design, the patient characteristics at the start of treatment, and the factors driving the choice of one or the other medication. We analyzed data from 2181 people with T2DM. On average, it was shown that they were middle-aged and obese. On average, these people were diagnosed with T2DM 8.5 years before the start of dulaglutide or liraglutide and had high blood sugar levels when these medications were started. The patient characteristics were slightly different between the three countries. Country-specific factors driving the choice of either medication were also identified. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01076-0.

In Senegal, reducing neonatal mortality remains a challenge. The management of neonatal infections remains problematic and presents a strong clinical focus. Indeed, like all developing countries, the difficulty of acquiring state-of-the-art infrastructure and the financial cost impact on the routine use of biomarkers. It is in this context that we conducted this study to identify the best biological strategy for making a reliable diagnosis. Ninety-nine newborns were recruited at the pediatric service of the Diamniadio Children's Hospital (Senegal). CRP was assayed by latex immuno-agglutination method, IL-6 and IL-8 using Luminex® technology, PCT by chemiluminescence, orosomucoid by immunoturbidimetry and SAA by ELISA technique. 20 newborns had probable infection and six established infection. Deaths and complications were significantly greater in these groups. With an optimal decision threshold of 16.3 mg/L, CRP performed better (compared to the other tested blood biomarkers) with AUC, sensitivity and specificity of 94%, 88% and 99%, respectively. With the performance obtained from CRP in the diagnosis of neonatal bacterial infections, the installation of panels with other biomarkers with advanced and expensive technology is not necessary. Thus, optimal care and within a reasonable timeframe can be done in our health facilities, with this accessible marker that is CRP.

Background Mild traumatic brain injury (mTBI) is one of the most common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnosis tool to identify intracranial complications in adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging. Method We realised a bibliographic state of art providing a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management. Results The S100B protein is the only biomarker that can be used today in the clinical routine for management of mTBI with appropriate evidence-based medicine. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management with considered, consensual and pragmatic use. In this state of art, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A state of art on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP) is also conducted. Some of these other biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP + H-FABP ± S100B ± IL10) can improve the specificity of S100B. Conclusion Using a bibliographic state of art, we highlighted the added values of the blood biomarkers for the clinical management of mTBI.

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.

Introduction Fibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date. Objective The aim of this study was to address the experience of FEP management in children. Study design A retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed. Results A total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1–48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1–10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1–34) months. Discussion The main limitation of our study is the retrospective design, although it is the largest one for this pathology. Conclusion This series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences. Level of Evidence Level V.

Using robotic devices might improve recovery post-stroke, but the optimal way to apply robotic assistance has yet to be determined. The current study aimed to investigate whether training under the robotic active-assisted mode improves bimanual motor skill learning (biMSkL) more than training under the active mode in stroke patients. Twenty-six healthy individuals (HI) and 23 chronic hemiparetic stroke patients with a detectable lesion on MRI or CT scan, who demonstrated motor deficits in the upper limb, were randomly allocated to two parallel groups. The protocol included a two-day training on a new bimanual cooperative task, LIFT-THE-TRAY, under either the active or active-assisted modes (where assistance decreased in a pre-determined stepwise fashion) with the bimanual version of the REAplan® robotic device. The hypothesis was that the active-assisted mode would result in greater biMSkL than the active mode. The biMSkL was quantified by a speed-accuracy trade-off (SAT) before (T1) and immediately after (T2) training on days 1 and 2 (T3 and T4). The change in SAT after 2 days of training (T4/T1) indicated that both HI and stroke patients learned and retained the bimanual cooperative task. After 2 days of training, the active-assisted mode did not improve biMSkL more than the active mode (T4/T1) in HI nor stroke patients. Whereas HI generalized the learned bimanual skill to different execution speeds in both the active and active-assisted subgroups, the stroke patients generalized the learned skill only in the active subgroup. Taken together, the active-assisted mode, applied in a pre-determined stepwise decreasing fashion, did not improve biMSkL more than the active mode in HI and stroke subjects. Stroke subjects might benefit more from robotic assistance when applied "as-needed." This study was approved by the local ethical committee (Comité d'éthique médicale, CHU UCL Namur, Mont-Godinne, Yvoir, Belgium; Internal number: 54/2010, EudraCT number: NUB B039201317382) on July 14, 2016 and was registered with ClinicalTrials.gov (Identifier: NCT03974750) on June 5, 2019.

Morphological analysis of text is one of the most important stages of natural language processing (NLP). Traditional and well-studied problems of morphological analysis include normalization (lemmatization) of a given word form, recognition of its morphological characteristics and their morphological disambiguation. The morphological analysis also involves the problem of morpheme segmentation of words (i.e., segmentation of words into constituent morphs and their classification), which is actual in some NLP applications. In recent years, several machine learning models have been developed, which increase the accuracy of traditional morphological analysis and morpheme segmentation, but performance of such models is insufficient for many applied problems. For morpheme segmentation, high-precision models have been built only for lemmas (normalized word forms). This paper describes two new high-accuracy neural network models that implement morphemic segmentation of Russian word forms with sufficiently high performance. The first model is based on convolutional neural networks and shows the state-of-the-art quality of morphemic segmentation for Russian word forms. The second model, besides morpheme segmentation of a word form, preliminarily refines its morphological characteristics, thereby performing their disambiguation. The performance of this joined morphological model is the best among the considered morpheme segmentation models, with comparable accuracy of segmentation.

In order to propose a course of action to be taken in the face of any hyperhomocysteinemia, we have reported for the first time in a French journal the recommendations made within the framework of the European E-HOD project for the diagnosis and treatment of remethylation disorders. The remethylation route ensures homocysteine-methionine conversion. It is linked to the folate cycle and the intracellular metabolism of cobalamins. Remethylation disorders can be classified into three groups: 1) isolated disorders (cblD-HC, cblE, cblG) corresponding to an isolated deficit in the production of methylcobalamin, cofactor of methionine synthase; 2) combined disorders (cblC, cblD-MMA/HC, cblF, cblJ) corresponding to an alteration of the transport and intracellular metabolism of cobalamins, which causes a defect in the synthesis of the two functional forms of cobalamin: methylcobalamin and adenosylcobalamin, a cofactor for methyl malonylCoA mutase; 3) MTHFR deficit, an abnormality of the folate cycle. The biological anomalies observed are hyperhomocysteinemia and hypomethioninaemia associated in the case of disorders combined with increased urinary excretion of methylmalonic acid. The clinical presentation is however heterogeneous according to the remethylation disorder but also for the same pathology according to the age. Given the large number of pathologies grouped together in remethylation disorders, this point is illustrated by only two clinical cases concerning the same deficit (deficit in MTHFR) but with different discovery circumstances: a neonatal form and a late form.

European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine’s (EFLM) proposed Common Training Framework for non-medical Specialists in Laboratory Medicine is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive’s enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM’s position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission.

Introduction In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance. Electronic supplementary material The online version of this article (10.1007/s40744-020-00250-3) contains supplementary material, which is available to authorized users.

This transcendental phenomenological study focused on analyzing and scrutinizing the lived experiences of school principals in the City Schools Division of Cabuyao. This study is geared towards achieving the central question of determining the journey of school principals in coping with the demands and challenges they encountered for school development. The researchers deemed that conduct of Key Informant Interview was suitable for attaining the problem’s statement. Since the research problem of this inquiry focused on describing and understanding the lived experience of public school principals, which is a phenomenon in academia, the researchers used phenomenological research design. The study reflected the challenges and demands encountered by the school heads as well as the strategies and techniques they utilized to surpass them all. This study also provided an illumination that the school heads need to extend the horizon and tried their best to attain the acme of school success.

Background Health economic evaluations require cost data as key inputs. Many countries do not have standardized reference costs so costs used often vary between studies, thereby reducing transparency and transferability. The present review provided a comprehensive overview of cost sources and suggested unit costs for France, Germany and Italy, to support health economic evaluations in these countries, particularly in the field of diabetes. Methods A literature review was conducted across multiple databases to identify published unit costs and cost data sources for resource items commonly used in health economic evaluations of antidiabetic therapies. The quality of unit cost reporting was assessed with regard to comprehensiveness of cost reporting and referencing as well as accessibility of cost sources from published cost-effectiveness analyses (CEA) of antidiabetic medications. Results An overview of cost sources, including tariff and fee schedules as well as published estimates, was developed for France, Germany and Italy, covering primary and specialist outpatient care, emergency care, hospital treatment, pharmacy costs and lost productivity. Based on these sources, unit cost datasets were suggested for each country. The assessment of unit cost reporting showed that only 60% and 40% of CEAs reported unit costs and referenced them for all pharmacy items, respectively. Less than 20% of CEAs obtained all pharmacy costs from publicly available sources. Conclusions This review provides a comprehensive account of available costs and cost sources in France, Germany and Italy to support health economists and increase transparency in health economic evaluations in diabetes.

Introduction Although patient-reported outcome (PRO) measures provide important information beyond clinical data, studies that assess the PROs of type 2 diabetes mellitus (T2DM) patients initiating injectable glucose-lowering medications in routine clinical practice are limited. We describe the perspectives of patients based on a diversified panel of generic and disease-specific PRO measures at the time of enrollment (baseline) in the TROPHIES study. Methods TROPHIES is a 24-month prospective observational study performed in France, Germany, and Italy in patients with T2DM who initiated their first injectable glucose-lowering medication with once-weekly dulaglutide or once-daily liraglutide. To better understand the perspectives of these patients regarding their overall health, treatment satisfaction, and quality of life and work, the patients’ responses to the following questionnaires were collected at baseline before they initiated treatment with dulaglutide or liraglutide: EQ-5D-5L (scale: 0–1), EQ-VAS (visual analog scale: 0–100), Impact of Weight on Self-Perceptions Questionnaire (IW-SP; scale: 0–100), Diabetes Treatment Satisfaction Questionnaire Status (DTSQs; scale: 0–36), and Diabetes Productivity Measure (DPM; scale: 0–100). Analyses were descriptive in nature, with higher scores reflecting better outcomes. Results Data from patients at the time of enrollment were analyzed. At baseline, patients initiating dulaglutide (N = 1130) or liraglutide (N = 1051) rated their quality of life in terms of mean EQ-5D-5L index as 0.84 and 0.83, and in terms of mean EQ-VAS as 67.5 and 67.5, respectively. The mean baseline scores in patients initiating dulaglutide or liraglutide were 59.8 and 61.3 for IW-SP, 24.6 and 25.8 for DTSQs, 78.6 and 79.5 for DPM Life Productivity, and 87.5 and 86.8 for DPM Work Productivity, respectively. Conclusion The information from this varied panel of PRO instruments collected at baseline complements clinical outcomes data. Electronic supplementary material The online version of this article (10.1007/s13300-020-00908-9) contains supplementary material, which is available to authorized users.

ObjectivesSPIRIT head-to-head (H2H) is a 52-week (Wk) trial comparing ixekizumab (IXE) with adalimumab (ADA) for simultaneous American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 responses in 566 patients (distributed evenly across both groups) with psoriatic arthritis (PsA). IXE was superior to ADA for this primary end point at Wk24. We aimed to determine the final efficacy and safety results through Wk52 including a prespecified subgroup analysis of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) use.MethodsSPIRIT-H2H is a Wk52 multicentre, open-label, blinded-assessor study comparing IXE and ADA in bionaïve patients with PsA. Patients were randomised 1:1 to IXE or ADA with stratification by concomitant csDMARD use and presence of moderate-to-severe plaque psoriasis. Prespecified end points at Wk24 and Wk52 included musculoskeletal, psoriasis, quality-of life outcomes, subgroup analyses and safety.ResultsA significantly higher proportion of patients treated with IXE versus ADA simultaneously achieved ACR50 and PASI100 (39% vs 26%, pConclusionsIXE provided significantly greater simultaneous joint and skin improvement than ADA through Wk52 in bionaïve patients with PsA. IXE showed better efficacy on psoriasis and performed at least as well as ADA on musculoskeletal manifestations. IXE efficacy was consistent irrespective of concomitant csDMARD use.Trial registration numberNCT03151551.

Background Interleukin-17A (IL-17A) antagonists are a recent innovation for treating psoriatic arthritis (PsA). There are currently no cost-effectiveness analyses (CEAs) comparing the IL-17A antagonists ixekizumab and secukinumab in PsA from a UK perspective. Objective We conducted a CEA from the UK National Health Service perspective to compare ixekizumab versus secukinumab in patients with PsA and concomitant moderate-to-severe plaque psoriasis. Methods A Markov model was developed based on the widely accepted York model. In biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, ixekizumab → ustekinumab → best supportive care (BSC) was compared with secukinumab → ustekinumab → BSC. For bDMARD-experienced patients, ixekizumab → BSC was compared with secukinumab → BSC. At the end of the bDMARD trial period, Psoriatic Arthritis Response Criteria (PsARC) responders continued to receive the bDMARD in the continuous treatment period. PsARC nonresponders and patients who ceased continuous treatment transitioned to the trial period of the next treatment. Results Ixekizumab was less costly and provided more quality-adjusted life-years (QALYs) than secukinumab in bDMARD-naïve and -experienced patients based on list prices, although cost savings and QALY gains were small to modest. In bDMARD-naïve patients, total costs were £155,455 compared with £155,530 for secukinumab (year 2017 values). Total QALYs were 8.127 versus 7.989. In bDMARD-experienced patients, the corresponding values were £140,051 versus £140,264 for total costs and 3.996 versus 3.875 for total QALYs. Conclusion Ixekizumab provided more QALYs at a marginally lower cost than secukinumab, and the results were most sensitive to changes in drug costs. Other factors, such as patient preferences for the number of injections and confidential price discounts, may be important considerations in clinical decision-making. Electronic supplementary material The online version of this article (10.1007/s41669-020-00202-1) contains supplementary material, which is available to authorized users.

INTRODUCTION: Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity. METHODS: SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity. RESULTS: A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups. CONCLUSIONS: Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis. ispartof: RHEUMATOLOGY AND THERAPY vol:9 issue:1 pages:109-125 ispartof: location:England status: published

Background Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24-26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics. Objective To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24-26. Methods A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24-26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F). Results The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1-58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0-61.0; 79%), adalimumab (28.3%; 24.4-32.4; 62%), guselkumab (27.7%; 21.1-35.1; 58%), ustekinumab (20.8%; 10.2-35.2; 37%), and infliximab (0.8%; 0.0-8.9; 17%). Conclusion In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24-26. Findings should be interpreted carefully because of inherent study limitations.

International audience; Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.

Introduction Improvements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA). Objective These post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study. Methods Patients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes. Results Patients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points. Conclusion High levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity. Trial registration NCT03151551 Key Points• Treatment goals for patients with psoriatic arthritis emphasise the importance of improving both musculoskeletal and non-musculoskeletal manifestations of the disease.• A combined endpoint considering both these manifestations, achievement of at least 50% improvement in American College of Rheumatology criteria and 100% improvement in Psoriasis Area Severity Index, was linked with achievement of a number of other endpoints relevant to psoriatic arthritis, including health-related quality of life that are important to patients with psoriatic arthritis.• Patients meeting the combined endpoint were more likely to achieve a disease state of remission, which is the stated aim of treatment for psoriasis.

International audience; PurposeTo conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject.MethodThe PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium).ResultsWe included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55–1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41–1.78) and malondialdehyde (1.78, 0.83–2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (−0.63, −0.89 to −0.36), with a significant decrease in total antioxidant capacity/status (−1.65, −2.88 to −0.43), aldehyde/NADPH dehydrogenase (−0.77, −1.38 to −0.17), lactoferrin/transferrin/albumin (−1.92, −2.96 to −0.89) and selenium/zinc (−1.42, −2.23 to −0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium.ConclusionOxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.

The SARS-CoV-2 virus is responsible for an epidemic disease called COVID-19, which was initially evidenced in Wuhan, China, and spread very rapidly in China and around the world. In France, the first isolated case seems now to be reported in December 2019, stage 3 of the COVID-19 epidemic was triggered on March 14(th), the start of the planned containment exit from May 11(th). Healthcare services have faced a large influx of patients who may be beyond their capacity to receive and care, particularly in the Large-East and Ile-de-France regions. Some patients show an evolution of the disease never observed before with other coronaviruses and develop in a few days a very important inflammatory reaction, which can lead to death of patients. A working group of the French Society of Clinical Biology (SFBC) was set up with the objective of providing updated information on the current status of the biological prescriptions (focusing on biochemistry ones) and their evolution during the epidemic, and of analyzing the biological parameters associated with comorbidities and patient evolution in order to link biological results with medical events. The expanded working group covers all sectors of medical biology in France and extends to the French-speaking world: hospital sectors (CHU and CH, Army Training Hospitals) and the private sector opening a field of view on the biological situation in establishments for dependent elderly, social establishments and clinical medical institutions. The purpose of this article is the presentation of this working group and its immediate and future actions., Le virus SARS-CoV-2 est responsable d’une maladie épidémique dénommée COVID-19 initialement mise en évidence à Wuhan (Chine) et qui s’est propagée très rapidement en Chine puis dans le monde entier. En France, le premier cas isolé semble être signalé dès la fin du mois de décembre2019, le stade 3 de l’épidémie a été déclenché le 14 mars 2020 et la sortie progressive du confinement est prévue à partir du 11 mai 2020. Les services de soins ont fait face à un afflux massif de patients pouvant déborder leurs capacités d’accueil et de prise en charge, notamment dans les régions Grand-Est et Ile-de-France. Certains patients présentent une évolution de la maladie encore jamais observée avec les coronavirus et développent en quelques jours une réaction inflammatoire très importante, pouvant mener au décès. Un groupe de travail de la Société française de biologie clinique (SFBC) s’est constitué, ayant pour objectif de faire le point sur les prescriptions biologiques et leur évolution au cours de l’épidémie, d’analyser les paramètres biologiques, avec un focus biochimique, associés aux comorbidités et à l’évolution du patient, dans le but de relier les résultats biologiques avec des évènements du parcours de soins du patient. Ce groupe de travail recouvre tous les secteurs publics (CHU, CH, Hôpitaux d’instruction des armées) et privés de la biologie médicale en France métropolitaine et ultra-marine ; il s’étend également à la francophonie. Il permet une vision large sur la situation biologique en milieu hospitalier, établissements d’hébergements de personnes âgées dépendantes (Ehpad), établissements médicaux sociaux (EMS) et en cliniques. Le but de cet article est la présentation de ce groupe de travail et ses actions immédiates et à venir.

This special issue introduces the 2017 Social Networks and Social Resources module of the International Social Survey Program (ISSP). This module has been newly developed based on specific, up-to-date theoretical and methodological foundations. Within certain limits the designers of this module aimed at allowing comparisons with the previously fielded ISSP modules on Social Networks from 1986 and 2001. The module encompasses measures on social capital and social resources, assessed by both a position generator and questions on social resources coming from network members or formal organizations. They are complemented by other important social network dimensions capturing network structure and opportunities to access and mobilize social relationships. A strength of the new module is to assess multiple dimensions of social networks and social resources, which are crucial either for instrumental or expressive outcomes also introduced in the survey. The special issue includes first an introduction presenting the motivations behind the 2017 new module on Social Networks and Social Resources, the underlying model of the final questionnaire, a description focusing on the core of the social networks and resources measurement with some descriptive results on social capital, network support and sociability, and open the discussion toward some research questions it allows to examine in a comparative perspective., NA

BACKGROUND AND OBJECTIVES Respiratory diseases are common in children with esophageal atresia (EA), leading to increased morbidity and mortality in the first year. The primary study objective was to identify the factors associated with readmissions for respiratory causes in the first year in EA children. METHODS A population-based study. We included all children born between 2008 and 2016 with available data and analyzed factors at birth and 1 year follow-up. Factors with a P value RESULTS Among 1460 patients born with EA, 97 (7%) were deceased before the age of 1 year, and follow-up data were available for 1287 patients, who constituted our study population. EAs were Ladd classification type III or IV in 89%, preterm birth was observed in 38%, and associated malformations were observed in 52%. Collectively, 61% were readmitted after initial discharge in the first year, 31% for a respiratory cause. Among these, respiratory infections occurred in 64%, and 35% received a respiratory treatment. In logistic regression models, factors associated with readmission for a respiratory cause were recurrence of tracheoesophageal fistula, aortopexy, antireflux surgery, and tube feeding; factors associated with respiratory treatment were male sex and laryngeal cleft. CONCLUSIONS Respiratory morbidity in the first year after EA repair is frequent, accounting for >50% of readmissions. Identifying high risk groups of EA patients (ie, those with chronic aspiration, anomalies of the respiratory tract, and need for tube feeding) may guide follow-up strategies.

We consider a small-scale overground compressed-air energy storage (CAES) system intended for use in micro-grid power networks. This work goes beyond previous efforts in the literature by developing and showing results from a first-of-a-kind small-scale (20 kWh) near-isothermal CAES system employing a novel, reversible liquid-piston gas compressor and expander (LPGC/E). Additionally, we extend our study to assessments, for the first time, of the economic and environmental characteristics of these small-scale overground CAES systems through a combination of experimental, thermodynamic, technoeconomic and environmental analyses. Five system configurations are considered: (1) CAESbase, which is the base-case system; (2) CAESplate, in which parallel plates are inserted into the LPGC/E as a heat exchanger for achieving near-isothermal compression and expansion; (3) CAESPCM, in which a phase change material (PCM) is employed to store thermal energy from the compressed air during charging that is later recovered during discharge; (4) CAESPCM&plate, which is a combination of the CAESplate and CAESPCM arrangements; and (5) CAESheater, in which a heater is utilised instead of the PCM to preheat the compressed air during discharge. Data for the validation of a computational design tool based on which the assessments were performed were obtained from a prototype of the CAESbase system. Results show that the CAESPCM&plate system exhibits the highest roundtrip efficiency of 63% and the shortest payback period of 7 years; the latter with the inclusion of governmental incentives and an electricity smart export guarantee (SEG) support rate of 5.5 p/kWh (6.8 ¢/kWh). The CAESPCM&plate system is found to be cost-effective even without incentives, with a payback period of 10 years. This system is also associated with 71 tonnes of fuel consumption savings and reduced CO2 emissions amounting to 51 tonnes over a lifetime of 20 years.

Preterm prelabor ruptures of fetal membranes (pPROM) are a pregnancy complication responsible for 30% of all preterm births. This pathology currently appears more as a consequence of early and uncontrolled process runaway activation, which is usually implicated in the physiologic rupture at term: inflammation. This phenomenon can be septic but also sterile. In this latter case, the inflammation depends on some specific molecules called “alarmins” or “damage-associated molecular patterns” (DAMPs) that are recognized by pattern recognition receptors (PRRs), leading to a microbial-free inflammatory response. Recent data clarify how this activation works and which receptor translates this inflammatory signaling into fetal membranes (FM) to manage a successful rupture after 37 weeks of gestation. In this context, this review focused on two PRRs: the receptor for advanced glycation end-products (RAGE) and the NLRP7 inflammasome.

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC, (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization, and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

BackgroundNeurological complications are common in the premature and full-term neonates admitted to the intensive care unit, but the diagnosis of these complications is often difficult to make. S100B protein, measured in cord blood, may represent a valuable tool to better identify patients at risk of brain injury.MethodsAs a first step, we established S100B cord blood serum reference intervals from 183 preterm and 200 full-term neonates. We then measured cord blood serum S100B to identify neurological complications in 272 neonates hospitalized at the neonatal intensive care unit (NICU). Diagnosis of brain injury relied on imaging examination.ResultsThe 95th percentiles of S100B concentration in cord blood were established as 1.21 μg/L for the 383 neonates, 0.96 μg/L for full-term neonates and 1.36 μg/L for premature neonates. Among the 272 neonates hospitalized at the NICU, 11 presented neurological complications. Using 1.27 μg/L as the optimal sensitivity/specificity threshold, S100B differentiate neonates with and without neurological complications with a sensitivity of 45.5% (95% confidence intervals [CI]: 16.7–76.6) and a specificity of 88.9% (95% CI: 84.4–92.4) (p = 0.006). In combination with arterial pH (ConclusionsCord blood S100B protein, in combination with arterial cord blood pH, has the potential to help clinicians to detect at birth neurological complications in neonates hospitalized in an NCIU.

With an increase in flow of the processed and stored information in insurance organizations in Kazakhstan, associated with the building of customers’ base, mergers and acquisitions processes and implementation of the new insurance products; the relevance of the problem of preliminary information processing for its structuring, allocation of distinctive attributed, generalization and sorting grows. Without appropriate scientific and methodological approach, data processing and analysis will be more difficult for insurance organizations and, may require the utilization of significant informational-computing and financial resources. In the present article as a modern scientific-research approach to the solution of this problem, it is suggested to apply a procedure of the cluster analysis by k-means algorithm, which makes it possible to simplify the processing and further analysis of data set by arranging data in relatively homogeneous groups. Particularly, the present article describes a process of the cluster analysis application by the k-means algorithm to the data on losses by a class of Compulsory insurance of civil-legal liability of the vehicles’ owners. The purpose of the present article is to split the losses by this class of insurance into homogeneous qualitative groups (clusters) based on frequency and severity of losses and, to interpret acquired clusters. Results of the k-means algorithm confirm that each acquired cluster has statistically significant data with similar impact upon losses’ process, which may be employed in the future for evaluation of losses of the insurance organization. Methodological approaches and results obtained in this article will, first of all, be interesting to the professional participants of insurance market of the Republic of Kazakhstan to conduct better underwriting research on the formation of the efficient structure of the insurance portfolio of Compulsory insurance of civil-legal liability of the vehicles’ owners in accordance with tariff rates.

BACKGROUND: The specific impact of neuropathic pain and recommended neuropathic pain treatments on the hormonal and immune status of patients has been so far poorly explored. This study aimed at studying, in real life, the hypothalamic-pituitary-adrenal axis and the cytokine profile of patients with neuropathic pain. It also explored their links with cognition, emotion, quality of life, and drug treatment. METHODS: This prospective study (clinicaltrials.gov NCT01543425) included 60 patients with neuropathic pain and 60 age- and gender-matched healthy volunteers after obtaining signatures of informed consent. A number of parameters were measured: adrenocorticotropic hormone, cortisol, cortisol awakening response, dehydroepiandrosterone sulphate, sex hormone binding globulin, testosterone, 17-β-estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, cytokines, brain-derived neurotrophic factor, and vitamin D. Psychological parameters were assessed by questionnaires. RESULTS: Patients with neuropathic pain had lower levels of adrenocorticotropic hormone (P = 0.009) and dehydroepiandrosterone sulphate (P < 0.001) than controls, and the cortisol awakening response was impaired. Patients were more depressed and anxious (P < 0.001) and had a diminished quality of life (P < 0.001), which was influenced by cytokines (P = 0.0067) and testosterone (P = 0.028). Antidepressants and antiepileptics appeared to interfere with testosterone and cognitivo-emotional domains. CONCLUSION: An impairment of the hormonal status and of the immune system was observed in patients. It identified testosterone as a potential pivotal mediator between antidepressants/antiepileptics and quality of life. Further studies must address the exact impact of different types of drugs on central effects, of gender differences, and of the immune system of neuropathic pain.

The plasma soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury with prognostic value when measured at baseline in acute respiratory distress syndrome (ARDS). However, whether changes in plasma sRAGE could inform prognosis in ARDS remains unknown. In this secondary analysis of the Lung Imaging for Ventilator Setting in ARDS (LIVE) multicenter randomized controlled trial, which evaluated a personalized ventilation strategy tailored to lung morphology, plasma sRAGE was measured upon study entry (baseline) and on days one, two, three, four and six. The association between changes in plasma sRAGE over time and 90-day survival was evaluated. Higher baseline plasma sRAGE (HR per-one log increment, 1.53, 95% CI, 1.16–2.03, p = 0.003) and an increase in sRAGE over time (HR for each one-log increment in plasma sRAGE per time unit, 1.01, 95% CI, 1.01–1.02, p &lt, 10−3) were both associated with increased 90-day mortality. Each 100-unit increase in the plasma sRAGE level per unit of time increased the risk of death at day 90 by 1% in joint modeling. Plasma sRAGE increased over time when a strategy of maximal alveolar recruitment was applied in patients with focal ARDS. Current findings suggest that the rate of change in plasma sRAGE over time is associated with 90-day survival and could be helpful as a surrogate outcome in ARDS.

International audience; PurposeTo conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in dry eye disease (DED) compared with healthy subject.MethodThe PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 10 January 2021 for studies reporting oxidative and antioxidative stress markers in DED and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, conjunctival cells or biopsies), Sjögren’s syndrome (SS) (patients with or without SS) and by geographical zones (Asia or Europe).ResultsWe included nine articles, for a total of 333 patients (628 eye samples) with DED and 165 healthy controls (451 eye samples). There is an overall increase in oxidative stress markers in DED compared with healthy controls (standard mean deviation = 2.39, 95% confidence interval 1.85–2.94), with a significant increase in lipid peroxide (1.90, 0.69–3.11), myeloperoxidase (2.17, 1.06–3.28), nitric oxide synthase 3 (2.52, 0.95–4.08), xanthine oxidase/oxidoreductase (2.41, 1.40–5.43), 4-hydroxy-2-nonenal (4HNE) (4.75, 1.67–7.84), malondialdehyde (3.00, 2.55–3.45) and reactive oxygen species (1.31, 0.94–1.68). Oxidative stress markers were higher in tears, conjunctival cells and conjunctival biopsies of DED than controls. Even if small number of studies were included for antioxidants, catalase seemed to be decreased in DED compared with healthy controls (−2.17, −3.00 to −1.34), with an increase of antioxidants in tears of DED patients without SS (1.13, 0.76–1.49).ConclusionOxidative stress markers, and probably antioxidants, were dysregulated in DED, establishing a local oxidative environment in tears, conjunctival cells and tissues.

The Philippines is one of the countries in the world who suffers in different disasters, particularly natural disasters. Every year, there are more than twenty incidents recorded in the country related to different disasters which involve numerous lives of its citizens. It is found that most Filipinos have lack of knowledge in terms of disaster preparation specially, teenagers. This paper intended to develop a mobile-based game that aims to spread awareness on what to do during disasters. Upon development, forty-five (45) respondents were chosen to test the reliability of the application which composed of elementary students, household owners, police officers, fire fighters and IT experts. Further, ISO 25010 was adapted and modified in assessing the project. The results showed that the application is strongly acceptable and gives appropriate output in terms of disaster preparation garnering a total mean of 3.83

Improvements in both musculoskeletal and non-musculoskeletal manifestations are important treatment goals in psoriatic arthritis (PsA).These post hoc analyses determined whether additional benefits related to various PsA domains are observed in patients simultaneously achieving 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100), the primary endpoint of the SPIRIT-H2H study.Patients with active PsA and psoriasis in SPIRIT-H2H (N = 566) were categorised into two sets of four response groups irrespective of treatment allocation (approved dosages of ixekizumab or adalimumab): patients who simultaneously achieved ACR50 and PASI100 response, achieved ACR50 response only, achieved PASI100 response only, or did not achieve ACR50 or PASI100 response after 24 and 52 weeks of treatment. Patients achieving simultaneous ACR50 and PASI100 response were compared with the other patient response groups at the corresponding time point for efficacy and health-related quality of life (HRQoL) outcomes.Patients simultaneously achieving ACR50 and PASI100 responses at week 24 or 52 showed higher rates of ACR70 response, minimal disease activity, Disease Activity in Psoriatic Arthritis ≤ 4, resolution of enthesitis and dactylitis, and HRQoL improvement at weeks 24 and 52, respectively, than the other corresponding response groups at both time points.High levels of disease control, such as those obtained with simultaneous achievement of ACR50 and PASI100 response, were linked to better outcomes across a wide range of endpoints that are important for patients with PsA. Patients meeting this combined endpoint showed more comprehensive and thus greater control of disease activity. Trial registration NCT03151551 Key Points • Treatment goals for patients with psoriatic arthritis emphasise the importance of improving both musculoskeletal and non-musculoskeletal manifestations of the disease. • A combined endpoint considering both these manifestations, achievement of at least 50% improvement in American College of Rheumatology criteria and 100% improvement in Psoriasis Area Severity Index, was linked with achievement of a number of other endpoints relevant to psoriatic arthritis, including health-related quality of life that are important to patients with psoriatic arthritis. • Patients meeting the combined endpoint were more likely to achieve a disease state of remission, which is the stated aim of treatment for psoriasis.

Background Myocarditis is a known cause of sudden cardiac death of the athlete. The impact of direct chest trauma in at-risk sports or activities in patients with a history of myocarditis has never been demonstrated or studied. We report herein two cases of life-threatening ventricular arrhythmia secondary to non-penetrating blunt chest trauma while playing contact sports. Case summary The first patient, a 26-year-old man described a brief loss of consciousness after having received blunt impact to the chest (typical intensity) while playing a rugby match. The loss of consciousness was total and proceeded by rapid and regular palpitations. He had a history of viral myocarditis 10 years prior with a fibrotic sequalae in the inferolateral wall on cardiac magnetic resonance imaging (left ventricular ejection fraction 71%). Right apical ventricular pacing induced a sustained monomorphic ventricular tachycardia reproducing the patient’s symptoms. A subcutaneous implantable cardioverter-defibrillator was implanted. The second patient is a 22-year-old professional rugby player with no known notable history. During a match, a direct blow to the chest wall was followed by a cardiac arrest. A ventricular fibrillation was cardioverted to pulseless electrical activity. Patient died despite cardiopulmonary resuscitation. An autopsy identified a myocardial sequela of fibrosis with no acute inflammatory remodelling compatible with a previous myocarditis. Discussion Myocarditis may increase the risk of life-threatening ventricular arrhythmias caused by blunt impact to the chest, particularly in contact sports. Screening and prevention measures should be considered to reduce this risk.

Background We previously assessed the inclusion of S100B blood determination into clinical decision rules for mild traumatic brain injury (mTBI) management in the Emergency Department (ED) of Clermont-Ferrand Hospital. At the 0.10 µg/L threshold, S100B reduced the use of cranial computed tomography (CCT) scan in adults by at least 30% with a ~100% sensitivity. Older patients had higher serum S100B values, resulting in lower specificity (18.7%) and decreased CCT reduction. We conducted this study to confirm the age effect on S100B concentrations, and to propose new decisional thresholds for older patients. Methods A total of 1172 mTBI patients aged 65 and over were included. They were divided into 3 age groups: 65–79, 80–89, and ≥ 90 years old. S100B’s performance to identify intracranial lesions (sensitivity [SE] and specificity [SP]) was assessed using the routine 0.10 µg/L threshold and also other more efficient thresholds established for each age group. Results S100B concentration medians were 0.18, 0.26, and 0.32 µg/L for the 65–79, 80–89, and ≥ 90 years old age groups, respectively (p < .001). The most efficient thresholds were 0.11 µg/L for the 65–79 age group and 0.15 µg/L for the other groups. At these new thresholds, SP was respectively 28.4%, 34.3%, and 20.5% for each age group versus 24.9%, 18.2%, and 10.5% at the 0.10 µg/L threshold. Conclusions Adjustment of the S100B threshold is necessary in older patients’ management. An increased threshold of 0.15 µg/L is particularly interesting for patients ≥ 80 years old, allowing a significant increase of CCT scan reduction (29.3%).

Background Sports concussion is a major problem that affects thousands of people every year. Concussion-related neurometabolic changes are thought to underlie neurophysiological alterations and post-concussion symptoms, such as headaches and sensitivity to light and noise, disabilities of concentration and tiredness. The injury triggers a complex neurometabolic cascade involving multiple mechanisms. There are pharmaceutical treatments that target one mechanism, but specific nutrients have been found to impact several pathways, thus offering a broader approach. This has prompted intensive research into the use of nutrient supplements as a concussion prevention and treatment strategy. Method We realised a bibliographic state of art providing a contemporary clinical and preclinical studies dealing with nutritional factors in sport-related concussion. Results Numerous supplements, including n-3 polyunsaturated fatty acids, sulfur amino acids, antioxidants and minerals, have shown promising results as aids to concussion recovery or prevention in animal studies, most of which use a fluid percussion technique to cause brain injury, and in a few human studies of severe or moderate traumatic brain injury. Current ongoing human trials can hopefully provide us with more information, in particular, on new options, i.e. probiotics, lactate or amino acids, for the use of nutritional supplements for concussed athletes. Conclusion Nutritional supplementation has emerged as a potential strategy to prevent and/or reduce the deleterious effects of sports-related concussion and subconcussive impacts.

International audience; Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in highfat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg.m(-2)] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5g.day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

Exploring coagulation in newborns and children is a challenge due to the low levels of both procoagulant factors and inhibitors. Conventional coagulation tests might be inadequate to explore all of these changes. The aim of the study is to evaluate the thrombin generation assay, a global test to explore coagulation, in a pediatric population (n=586) compared to an adult population (n=166). The thrombin generation assays were performed using Calibrated Automated Thrombography with two different tissue factor concentrations (1 and 5 pM), with and without thrombomodulin (TM). In the absence of TM, the endogenous thrombin potential (ETP) is significantly lower in the pediatric population, reflecting the decrease in procoagulant factors. In the presence of TM, ETP values in pediatric subjects are within the reference range of adult values. The thrombin generation assay demonstrates that coagulation balance is maintained in the pediatric population.