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Background and purpose: The COVID-19 pandemic have led to some psychological disorders and sleep problems that should be taken into account after recovery. After recovering from COVID-19 people are at risk of sleep disorders, depression, and low quality of life and there is paucity of information about this issue. The present study aimed to compare the effectiveness of mindfulness and aerobic exercise on depressive symptoms, perceived stress, and sleep quality in recovered COVID-19 patients. Material(s) and Method(s): An intervention field research was performed in 60 male and female patients (mean age: 39.52+/-5.82) recovered from COVID-19 in Kermanshah, Iran. Participants were randomly divided into four groups (n=15): 1) attending mindfulness-based stress reduction (MBSR) program, 2) aerobic exercise, 3) combination of MBSR and aerobic exercise, and 4) control group. The study was carried out at four stages: pretest, interventions, post-test, and follow-up test. Dependent variables included depressive symptoms, perceived stress, and sleep quality. Bonferroni Post hoc test in 4*3 mixed ANOVA was used for data analysis. Result(s): In this study, depression and perceived stress reduced in all experimental groups compared to the control group (P= 0.001). Also, sleep quality improved in these groups compared to the control group (P= 0.001). Post hoc tests showed the superiority of combination of MBSR and aerobic exercise compared to other interventions. Conclusion(s): According to current study, combination of MBSR and physical activity shows to be more helpful than mindfulness training and physical activity alone in improving psychological problems and sleep quality after recovering from COVID-19.Copyright © 2023, Mazandaran University of Medical Sciences. All rights reserved.
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Problem: Although it is rare for a SARS-CoV-2 infection to transmit vertically to the fetus during pregnancy, there is a significantly increased risk of adverse pregnancy outcomes due to maternalCOVID- 19. However, there is a poor understanding of such risks because mechanistic studies on how SARS-CoV-2 infection disrupts placental homeostasis are significantly lacking. The SARS-CoV-2 proteome includes multiple structural and non-structural proteins, including the non-structural accessory proteinORF3a. The roles of these proteins in mediating placental infection remain undefined. We and others have shown that autophagy activity in placental syncytium is essential for barrier function and integrity. Here, we have used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placenta exposed to SARS-CoV-2. The objective of our study was to investigate potential mechanisms through which SARS-CoV-2 impairs placental homeostasis and causes adverse pregnancy outcomes. We tested the central hypothesis that an essential SARS-CoV-2 non-structural and accessory protein, ORF3a, uniquely (amongst multiple viral proteins tested) with a novel three-dimensional structure andwith no homology to any other proteins is a key modulator of placental trophoblast cell dynamics via autophagy and intracellular trafficking of a tight junction protein (TJP), ZO-1. Method(s): We used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placentas exposed to SARS-CoV- 2. Autophagic flux was measured in placental villous biopsies from SARS-CoV-2-exposed and unexposed pregnant women by quantifying the expression of autophagy markers, LC3 and P62. Trophoblast cells (JEG-3, Forskolin-treated JEG-3, HTR8/SVneo, or primary human trophoblasts (PHTs)) were transfected with expression plasmids encoding SARS-CoV-2 proteins including ORF3a. Using western blotting, multi-label immunofluorescence, and confocal imaging, we analyzed the effect of ORF3a on the autophagy, differentiation, invasion, and intracellular trafficking of ZO-1 in trophoblasts. Using coimmunoprecipitation assays, we tested ORF3a interactions with host proteins. t-tests and one-way analyses of variance (ANOVAs) with post hoc tests were used to assess the data, with significance set at P < .05. Result(s): We discovered :1) increased activation of autophagy, but incomplete processing of autophagosome-lysosomal degradation;2) accumulation of protein aggregates in placentas exposed to SARS-CoV- 2. Mechanistically, we showed that the SARS-CoV-2 ORF3a protein, uniquely 3) blocks the autophagy-lysosomal degradation process;4) inhibits maturation of cytotrophoblasts into syncytiotrophoblasts (STBs);5) reduces production ofHCG-beta, a key pregnancy hormone that is also essential for STB maturation;and 6) inhibits trophoblast invasive capacity. Furthermore, ORF3a harbors an intrinsically disordered C-terminus withPDZ-bindingmotifs.We show for the first time that, 7) ORF3a binds to and co-localizes with the PDZ domain of ZO-1, a junctional protein that is essential for STB maturation and the integrity of the placental barrier. Conclusion(s): Our work outlines a new molecular and cellular mechanism involving the SARS-CoV-2 accessory protein ORF3a that may drive the virus's ability to infect the placenta and damage placental syncytial integrity. This implies that the mechanisms facilitating viral maturation, such as the interaction of ORF3a with host factors, can be investigated for additional functionality and even targeted for developing new intervention strategies for treatment or prevention of SARS-CoV-2 infection at the maternal-fetal interface.
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Introduction: Diabetic peripheral neuropathy (DPN) is the most common neuropathic syndrome seen in patients with diabetes. Roughly 30% of the diabetes patient population1 experience painful DPN symptoms including bilateral stabbing or burning pain in addition to numbness in the feet and lower legs. Traditionally painful DPN symptoms have been treated with conventional medical management (CMM) including glycemic control, general risk factor management, as well as pharmaceutical agents. These treatment approaches are often unsuccessful in the long-term1. Spinal cord stimulation (SCS) has been demonstrated as an effective treatment for painful DPN of the lower extremities with multiple publications dating back to 1996 showing benefits of SCS for pain relief and improved Quality of Life (QoL) in DPN patients (Figure 1)2-18. Method(s): A systematic literature review of the robust body of evidence for SCS in the treatment of painful DPN was conducted. Publications were selected for inclusion by two independent reviewers using defined selection criteria. Additional relevant publications from outside the search dates were included. Result(s): SCS was first documented as an effective treatment for DPN in three single-arm studies published between 1996 and 20122,4,5, one of which was followed-up to thirty-six months18, and another to seven-years3. These studies paved the way for two RCTs published in 20146,7, one of which was followed-up to five-years in two publications8,10, and another7 was followed-up with analyses on QoL9 and an evaluation of the effects of burst SCS17. Two meta-analyses were published in 2020 and 202111,12. A post-hoc analysis of a multi-center single-arm study on high frequency (10kHz) SCS to treat DPN was published in 202013 and followed by an RCT published in 202114 with additional 1-year follow-up15,16. Collectively these studies demonstrate that SCS is an effective therapy for patients with painful DPN by reducing pain and increasing QoL for DPN patients (Figure 1). Conclusion(s): This review of a large body of evidence shows a decades-long history of the effectiveness of SCS for symptom relief in patients suffering from painful DPN. Future research on the effectiveness of new waveforms and novel methods of energy delivery to the spinal cord are needed. The study of outcomes in addition to pain relief is also needed, which may better illustrate the breadth of effects of SCS therapy on the underlying disease factors. Increasing awareness of the current evidence is essential to increasing therapy adoption by expanding payer support and influencing referring health care provider behavior. Disclosure: Eric Grigsby, MD: AE Mann Foundation: Consulting Fee: Self, Bioness Inc.: Consulting Fee: Self, Medallion Therapeutics: Consulting Fee: Self, Medtronic: Consulting Fee: Self, SPR Therapeutics: Consultant: Self, Tenex Health: Consultant: Self, Voyager Therapeutics: Consultant: Self, Xalud: Consulting Fee: Self, AE Mann Foundation: Consulting Fee: Self, Medallion Therapeutics: Consulting Fee: Self, Bioness Inc.: N/A: Self, Medallion Therapeutics: N/A: Self, SPR Therapeutics: N/A: Self, Abbott / St. Jude Medical: N/A: Self, Tenex: N/A: Self, Vertos: N/A: Self, Xalud: N/A: Self, AE Mann Foundation: Consulting Fee: Self, Bioness Inc.: Consulting Fee: Self, Medtronic, Inc.: N/A: Self, Collegium Pharmaceutical, Inc.: Trustee: Self, Flowonix Medical: Served on speakers' bureau: Self, Jazz Pharmaceuticals: Served on speakers' bureau: Self, Jazz Pharmaceuticals: Trustee: Self, Spinal Restoration, Inc.: Trustee: Self, Jazz Pharmaceuticals: N/A: Self, Alfred Mann Foundation: N/A: Self, Boston Scientific: N/A: Self, CNS Therapeutics: N/A: Self, Collegium Pharmaceutical, Inc.: N/A: Self, Flowonix Medical: N/A: Self, Jazz Pharmaceuticals: N/A: Self, Medtronic, Inc.: N/A: Self, Myoscience: N/A: Self, NeurAxon Inc.: N/A: Self, Spinal Restoration, Inc.: N/A: Self, St. Jude Medical, Inc.: N/A: Self, Abbott Laboratories: Consultant: Self, Alfred Mann Foundation: Consulting Fee: Self, Cervel Neurotech, Inc.: Consultant: Self, CNS Therapeutics: Consultant: Self, Covidien: Consultant: Self, Cumberland Pharmaceuticals, Inc.: Consultant: Self, Flowonix Medical: Consultant: Self, Jazz Pharmaceuticals: Consultant: Self, Mainstay Medical: Consultant: Self, Medtronic, Inc.: Consultant: Self, Myoscience: Consultant: Self, NeuroPhage Pharmaceuticals: Consultant: Self, Nevro Corp: Consultant: Self, Palyon: Consultant: Self, Spinal Modulation: Consultant: Self, SPR Therapeutics: Consultant: Self, St. Jude Medical, Inc.: Consultant: Self, Tenex Health, Inc.: Consultant: Self, VertiFlex Inc.: Consultant: Self, Vertos Medical, Inc.: Consultant: Self, Xalud Therapeutics, Inc.: Contracted Research: Self, Medtronic, Inc.: Served on speakers' bureau: Self, Flowonix Medical: Served on advisory board: Self, Medtronic, Inc.: N/A: Self, Jazz Pharmaceuticals: N/A: Self, Medtronic, Inc.: Ownership Interest: Own Stock, Stock Options, Future Stock Options: Self, Nevro Corp: Ownership Interest: Own Stock, Stock Options, Future Stock Options: Self, Rachel Slangen, PhD: None, Lisa Johanek, PhD: Medtronic: Salary/Employee: Self, Maddie LaRue, PHD: Medtronic: Employee:, Cecile de Vos, PhD: None, Melissa Murphy: Medtronic: Consulting Fee:, Relievant: Consulting Fee:Copyright © 2023
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Despite their effectiveness in minimizing the spread of infection, movement restrictions adopted during the Coronavirus disease 2019 (COVID-19) pandemic have not been without their health-related consequences, including decreases in physical activity and increases in sedentary behavior. This study aimed to investigate differences in stress and sense of community among Korean citizens in various age groups according to the degree of their participation in physical activity during the COVID-19 pandemic. We analyzed data collected during the Social Survey of Busan Metropolitan City 2020, the population of which included all household members over the age of 15. Data for a total of 33,082 participants (male = 15,129;female = 17,953) were extracted using a two-stage cluster sampling method. Age, stress level, and sense of community were analyzed using independent t-tests, while the frequency of participation in physical activity was analyzed using a Mann-Whitney U test. Differences in stress level and community consciousness according to the frequency of physical activity were examined via multivariate analysis of variance. Variables exhibiting significant differences were evaluated for differences between groups through Scheffe's post hoc analysis. First, stress levels were higher among female adolescents than male adolescents. Among adults and older adults, men exhibited higher overall stress levels than women, whereas sense of community was stronger in women than men. Second, male adolescents in the regular physical activity participation group showed lower levels in some factors of stress than those in the nonparticipating group. Finally, a higher frequency of participation in physical activity among adults and older adults was associated with lower stress and higher sense of community, regardless of gender. In conclusion, regular participation in physical activity should be considered when designing strategies for managing stress and promoting social relationships at the national and individual levels during COVID-19 and any similar pandemics in the future.Copyright ©2023 The Author(s). Published by MRE Press.
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Background and purpose: The COVID-19 pandemic have led to some psychological disorders and sleep problems that should be taken into account after recovery. After recovering from COVID-19 people are at risk of sleep disorders, depression, and low quality of life and there is paucity of information about this issue. The present study aimed to compare the effectiveness of mindfulness and aerobic exercise on depressive symptoms, perceived stress, and sleep quality in recovered COVID-19 patients. Material(s) and Method(s): An intervention field research was performed in 60 male and female patients (mean age: 39.52+/-5.82) recovered from COVID-19 in Kermanshah, Iran. Participants were randomly divided into four groups (n=15): 1) attending mindfulness-based stress reduction (MBSR) program, 2) aerobic exercise, 3) combination of MBSR and aerobic exercise, and 4) control group. The study was carried out at four stages: pretest, interventions, post-test, and follow-up test. Dependent variables included depressive symptoms, perceived stress, and sleep quality. Bonferroni Post hoc test in 4*3 mixed ANOVA was used for data analysis. Result(s): In this study, depression and perceived stress reduced in all experimental groups compared to the control group (P= 0.001). Also, sleep quality improved in these groups compared to the control group (P= 0.001). Post hoc tests showed the superiority of combination of MBSR and aerobic exercise compared to other interventions. Conclusion(s): According to current study, combination of MBSR and physical activity shows to be more helpful than mindfulness training and physical activity alone in improving psychological problems and sleep quality after recovering from COVID-19.Copyright © 2023, Mazandaran University of Medical Sciences. All rights reserved.
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Background: SARS-CoV-2 Omicron sublineages exhibit evolving escape to in vitro neutralization by monoclonal antibodies (mAbs), with an unclear impact on in vivo treatment response. Our aim is to assess the impact of SARS-Cov-2 variants on the decline of viral load (VL) after treatment with 3 different drugs approved in EU for the early treatment of patients with mild-moderate COVID-19. Method(s): Post-hoc analysis from MONET (EudraCT: 2021-004188-28), phase 4 open-label RCT to assess efficacy of 500 mg intravenous sotrovimab (SOT), 600 mg intramuscular tixagevimab/cilgavimab (TIX/CIL) and oral 5-days course of NMV/r 300/100 mg BID, in non-hospitalized high-risk patients (pts) with early COVID-19. Pts' features were analyzed as binary variables by Chi-squared test. SARS-Cov-2 VL in nasopharyngeal swabs was carried out at randomization (1d) and at day 7 (7d) by cycle threshold value (Ct). Variant sequencing was performed at 1d. Ct variation was assessed by mixed effect log-linear model including random intercept at pts' level, log of Ct as independent variable, time, arm, viral variant as dependent variables, and interaction between time and arm. Multiple comparisons were adjusted by Bonferroni. Result(s): Among the 320 pts included between 4 Mar and 16 Nov, 2022, 108 (33.75%) received NMV/r, 103 (32.19%) TIX/CIL, and 109 (34.06%) SOT. Main characteristics were balanced across arms. Most of the pts were infected either with BA.2 (N=194;60.63%) or BA.4/BA.5 (N=100;31.25%) (Fig1A). VL at 1d was similar across the arms. In contrast, mean 7d VL was significantly lower in pts receiving NMV/r than in those receiving TIX/ CIL or SOT (P< 0.001) No significant VL variation was observed between the mAb arms (Fig1B). The analysis of the impact of viral variants suggests that while VL was significantly affected by variants (P=0.034), the superior effect of NMV/r over mAbs was homogeneous across all variant groups (P=0.290 for interaction) (Fig1C). Conclusion(s): Our study provides for the first time strong in vivo evidence that, when used against Omicron lineages, NMV/r exerts a stronger antiviral effect than mAbs. These results confirm previous in vitro evidence suggesting that mAbs may not retain neutralizing activity against all Omicron sublineages and provide preliminary information on how to use VL variation as a surrogate marker of efficacy. Further studies are needed to investigate whether the superior virologic activity of NMV/r over mAbs is confirmed for newly emerging variants, including BQ.1.1 or XBB.
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Background: Neurocognitive symptoms are common in acute as well as convalescent (post-acute sequelae of COVID-19 [PASC]) COVID-19, but mechanisms of CNS pathogenesis are unclear. The aim of this study was to investigate cerebrospinal fluid (CSF) biomarker evidence of CNS infection, immune activation and neuronal injury in convalescent compared with acute infection. Method(s): We included 68 (35% female) patients >=18 years with CSF sampled during acute (46), 3-6 months after (22) SARS-CoV-2 infection or both (17), and 20 (70% female) healthy controls from longitudinal studies. The 22 patients sampled only at 3-6 months were recruited in a PASC protocol. CSF N-Ag was analyzed using an ultrasensitive antigen capture immunoassay platform (S-PLEX SARS-CoV-2 N Kit, Meso Scale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF beta2-microglobulin (beta2M)], IFN-gamma, IL-6, TNF-alpha neurofilament light (NfL), and total and phosphorylated tau. Log-transformed CSF biomarkers were compared using ANOVA (Tukey post-hoc test). Result(s): Patients sampled during acute infection had moderate (27) or severe (19) COVID-19. In patients sampled at 3-6 months, corresponding initial severity was 10 (mild), 14 (moderate), and 15 (severe). At 3-6 months, 31/39 patients reported neurocognitive symptoms;8/17 patients also sampled during acute infection reported full recovery after 3-6 months. CSF biomarker results are shown in Figure 1. SARS-CoV-2 RNA was universally undetectable. N-Ag was detectable only during acute infection (32/35) but was undetectable in all follow up and control samples. Significantly higher CSF concentrations of beta2M (p< 0.0001), IFN-gamma (p=0.02), IL-6 (p< 0.0001) and NfL (p=0.04) were seen in acute compared to post-infection. Compared to controls, beta2M (p< .0001), IL-6 (p< 0.0001) and NfL (p=0.005) were significantly higher in acute infection. No biomarker differences were seen post-infection compared with controls. No differences were seen in CSF GFAp, t-tau or p-tau. Conclusion(s): We found no evidence of residual infection (RNA, N-Ag), inflammation (beta2M, IL-6, IFN-gamma, TNF-alpha), astrocyte activity (GFAp) or neuronal injury (NfL, tau) 3-6 months after initial COVID-19, while significantly higher concentrations of several markers were found during acute infection, suggesting that PASC may be a consequence of earlier injury rather than active CNS damage. CSF beta2M, IL-6, IFN-gamma and NfL were significantly lower after 3-6 months than during acute COVID-19 and not different from healthy controls. (Figure Presented).
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Background: Within the ACTIV-2/A5401 platform (NCT04518410), the safety and efficacy of tixagevimab/cilgavimab (T/C), an anti-SARS-CoV-2 monoclonal antibody combination, was studied in outpatients with COVID-19. Intravenous (IV) and intramuscular (IM) administration of T/C were assessed. Method(s): Non-hospitalized adults >=18 years enrolled within 10 days of positive SARS-CoV-2 test and symptom onset. Participants at higher risk of disease progression were eligible for IV T/C 300mg (150mg each component) or placebo;all were eligible for IM T/C 600mg (300mg each) administered to the lateral thigh or placebo. Co-primary outcomes were: time to symptom improvement through day 28;nasopharyngeal (NP) SARS-CoV-2 RNA below lower limit of quantification (LLoQ) on days 3, 7 or 14;and treatment emergent Grade >=3 adverse events. Result(s): Between February and May 2021, 223 participants (106 T/C, 117 placebo) initiated study intervention and were included in the IM analysis and 114 participants (58 T/C, 56 placebo) in the IV analysis;the IV study was stopped early for administrative reasons. Both studies enrolled 45% Latinx;the IM and IV populations included 12% and 19% Black participants, 49% and 59% female sex at birth, and median age was 39 and 44 years, respectively, all of which were balanced between active vs placebo for each. Median (IQR) days from symptom onset at enrollment was 6 (4, 7). There were no differences in time to symptom improvement comparing IM T/C to placebo (median 8 (IQR 7, 12) vs 10 (8, 13) days;p=0.35) or IV T/C to placebo (11 (9, 15) vs 10 (7, 15) days;p=0.71). A significantly greater proportion (80%) in the IM T/C arm had NP SARS-CoV-2 RNA below LLoQ at day 7 compared to placebo (65%), but not days 3 or 14, overall p=0.003 across visits. Secondary and post-hoc analyses revealed antiviral effects within the smaller IV study. There was no difference in Grade >=3 AEs with either administration route. Fewer participants were hospitalized who received T/C vs placebo (4 vs 7 in IM group;0 vs 4 in IV group), neither group reaching statistical significance. Conclusion(s): Tixagevimab/cilgavimab administered IM or IV was well-tolerated and demonstrated antiviral activity and a trend towards fewer hospitalizations, but did not change time to symptom improvement in mild-to-moderate COVID-19 compared to placebo. Monoclonal antibodies administered intramuscularly to the thigh may present a valuable alternative for early SARSCoV-2 infection. Virologic Outcomes of Tixagevimab/Cilgavimab treatment 600mg IM (panels A and B) or 300mg IV (panels C and D) versus placebo.
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Objectives: The aim of this study was to explore the association of the plasma levels of coagulation proteins with venous thromboembolic events (VTE) in COVID-19 and identify candidate early markers of VTE. Background(s): Coagulopathy and thromboembolism are known complications of SARS-CoV-2 infection. The mechanisms of COVID-19-associated hematologic complications involve endothelial cell and platelet dysfunction and immunothrombosis and have been intensively studied. Yet, a full understanding of the pathogenesis and factors that lead to COVID-19 associated coagulopathy is lacking. Previous studies investigated only small numbers of coagulation proteins together, and they were limited in their ability to adjust for confounders. Method(s): This study was a post-hoc analysis of a previously published dataset (Filbin et al., 2021). We included in our analysis 305 subjects with confirmed SARS-CoV-2 infection who presented to an urban Emergency Department with acute respiratory distress during the first COVID-19 surge in 2020;13 (4.2%) were subsequently diagnosed with venous thromboembolism during hospitalization. Serial samples were obtained on days 0, 3, and 7 and assays were performed on two highly-multiplexed proteomic platforms, that in combination cover 1472 + 4776 proteins. We included 31 coagulation proteins in our analysis. Result(s): Nine coagulation proteins were differentially expressed in patients with thromboembolic events. In multivariable models, day 0 levels of P-selectin, a cell adhesion molecule on the surface of activated endothelial cells, displayed the strongest association with the diagnosis of VTE, independent of disease severity and other confounders (p=0.0025). P-selectin together with D-dimer upon hospital presentation provided better discriminative ability for VTE diagnosis than D-dimer alone (AUROC = 0.834 vs. 0.783). Conclusion(s): Our results suggest that plasma P-selectin is a potential early biomarker for the risk stratification of VTE in COVID-19 disease. Our findings support the importance of endothelial activation in the mechanistic pathway of venous thromboembolism in COVID-19.Copyright © 2023
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Background. Idiopathic inflammatory myopathies (IIM) are a rare, multisystem, heterogeneous disease, and contribute to a high psychological burden. The patients' perception of physical health, deteriorating independence and social and environmental relationships may not always be a direct function of disease activity. To face with these aspects, several worldwide specialized organization have recommended the use of patient reported outcome measures (PROMs) both in clinical trials and observational studies to highlight patient's perception of the disease. Unfortunately, data on fatigue scores in IIM is limited. We compared fatigue VAS scores in patients with IIM, autoimmune diseases (AIDs) and healthy controls (HCs) and triangulated them with PROMIS physical function in a large international cohort made up of answers from the e-survey regarding the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods. Data of 16327 respondents was extracted from the COVAD database on August 31th 2021. VAS fatigue scores were compared between AID, HC and IIM using univariate followed by multivariate analysis after adjusting for baseline differences. We further performed a propensity score matched analysis on 1827 subjects after adjusting for age, gender and ethnicity. The Kruskal-Wallis test was used for continuous variables and chi-square test for categorical variables, and Bonferroni's correction was applied for the post hoc analyses considering IIMs as a reference group. Results. We analyzed answers from 6988 patients, with a mean age of 43.8 years (SD 16.2). The overall percentage of female was 72% and the population ethnicity was mainly composed of White (55.1%), followed by Asian (24.6%), and Hispanic (13.8%). The overall fatigue VAS was 3.6 mm (SD 2.7). IIMs VAS was 4.8 mm (SD 2.6), AIDs 4.5 mm (SD 2.6), and HC 2.8 mm (SD 2.6) (p<0,001). VAS fatigue scores of IIMs were comparable with AIDs (p 0.084), albeit significantly higher than the HCs (p<0,001). Notably, fatigue VAS was lower in IIMs than AIDs in two distinct subsets: inactive disease as defined by the patient's perception and the excellent general health condition group, where IIMs had worse scores (p<0,05). Interestingly, fatigue VAS was comparable in active disease defined by physician assessment, patient perception, based on general functional status, or when defined by steroid dose being prescribed. Notably, after propensity matched analysis of patients adjusting for gender, age and ethnicity (1.827 answers, i.e. 609 subjects per group, p=1) the differences disappeared and IIMs and AIDs had comparable fatigue levels across all levels of disease activity, although the fatigue discrepancies with HCs were substantially confirmed. After application of a multivariate linear regression analysis we found that lower fatigue VAS scores were related to HC (p<0,001), male gender (p<0,001), Asian and Hispanic ethnicities (p<0,001 and 0,003). Conclusions. Our study confirms that there is a higher prevalence of fatigue in all the AIDs patients, with comparable VAS scores between IIMs and other AIDs. We can also read our data commenting that females and/or Caucasians patients suffer a higher impact of this manifestation of chronic autoimmune diseases upon their lives. This is why these subjects, to our judgement, should be carefully evaluated during outpatients visits and to whom we should spend some extra time to discuss health related issues and how to improve them.
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Prior to the COVID-19 pandemic, social work and social care practitioners had some the worst working conditions of any sector in the UK. During the pandemic, data revealed that social care occupations had higher COVID infection and mortality rates than the general population. The article reports the changing working conditions (measured via the Work-Related Quality of Life scale) and well-being (measured via the Short Warwich–Edinburgh Mental Well-being Scale) of UK social care and social workers across three timepoints between May 2020 and July 2021 through an online cross-sectional survey of working conditions and well-being. Analysis of variance demonstrated that both well-being and working conditions were significantly poorer in July 2021 (phase 3 [ n = 1,606]) than the previous two phases (n = 2,523 and n = 2,424, respectively), suggesting that both working conditions and well-being worsened within the social care and social work workforce across the pandemic. Furthermore, each of career satisfaction, working conditions, control, general well-being and home–work interface predicted poorer well-being at Time 3. Whilst chronically poor working conditions can lead to poorer individual psychological and physiological health outcomes, our findings highlight continually poor conditions in this sector, with potential further impacts on organisations and the service users that social care workers support. It is therefore important that individuals, organisations and government develop mechanisms to support these critical workers during and following the pandemic.
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Background: The efficacy and safety of risankizumab (RZB) in patients with Crohn's disease (CD) has been demonstrated.1,2 We reported that an additional 12 weeks (ie, induction period 2) of RZB therapy could induce clinical response in patients with CD who did not achieve clinical response after an initial 12-week induction period.3 In this post hoc analysis, we report the proportion of patients who achieved clinical response over 24 weeks (initial and delayed responders to RZB induction therapy). Method(s): Data were pooled from the ADVANCE and MOTIVATE phase 3 RZB studies. Patients who had not achieved stool frequency (SF)/abdominal pain score (APS) clinical response (>= 30% decrease in average daily SF and/or >= 30% decrease in average daily APS and both not worse than baseline) after an initial 12-week induction with intravenous (IV) RZB (600 mg or 1200 mg) at weeks 0, 4, and 8 were rerandomized 1:1:1 in induction period 2 to receive IV RZB 1200 mg (at weeks 12, 16, and 20) or subcutaneous (SC) RZB (180 mg or 360 mg at weeks 12 and 20) in a double-dummy-blinded fashion. In this post hoc analysis, efficacy was analysed in patients treated with either 600 mg RZB IV or placebo (PBO) for 12 weeks in the PBO-controlled induction period and patients who did not achieve clinical response with 600 mg RZB IV for 12 weeks and were rerandomized to 360 mg RZB SC every 8 weeks during induction period 2 (currently marketed RZB doses). SF/ APS clinical response was assessed at week 12 for initial responders and at week 24 for delayed responders in induction period 2. Nonresponder imputation with no special data handling for data missing due to COVID-19 was used. No multiplicity adjustment was performed. Result(s): Of the 889 patients randomised to 600 mg IV RZB or PBO in the induction studies, 70.0% (369/527) in the RZB group compared with 45.6% (165/362) in the PBO group achieved SF/APS clinical response at week 12. Of the 47 patients who did not achieve initial clinical response to 600 mg IV RZB and received 360 mg SC in induction period 2, 32 (68.1%) achieved delayed SF/APS clinical response at week 24. The proportion of patients achieving SF/APS clinical response over 24 weeks (either initial or delayed responders) was 89.1% (401/450). The safety profile of RZB in patients with CD has been reported.1,2 Conclusion(s): In patients with moderate-to-severe CD, RZB treatment leads to approximately 9 of 10 patients achieving either initial (600 mg IV) or delayed (600 mg IV followed by 360 mg SC) clinical response over 24 weeks.
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Rationale: Interferon beta (IFN-beta) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-beta-1a nebuliser solution) aims to restore lung IFN-beta levels. Method(s): Adults hospitalised due to COVID-19 requiring low flow oxygen were randomized to receive SNG001 (314) or placebo (309) OD for 14 days, plus standard-of-care. Efficacy was assessed by change in clinical condition using the WHO 9-point Ordinal Scale for Clinical Improvement (OSCI). Primary endpoints: time to discharge (OSCI <=2) and time to recovery (OSCI <=1). Key secondary endpoints: progression to severe disease or death (OSCI >=5), progression to intubation or death (OSCI >=6), and death. Result(s): Most patients were discharged rapidly from hospital and there was no effect of SNG001 on time to discharge or recovery. However, there was an encouraging signal for prevention of progression to severe disease or death (ITT 26% relative risk reduction (RRR);Odds Ratio (95% CI): 0.71 (0.44, 1.15);Per Protocol 36% RRR;OR 0.63 (0.35, 1.13)). Post hoc analyses supported this observation with enhanced effects favouring SNG001 in subgroups at higher risk of progression (>=65 years;>=1 comorbidity;oxygen saturation <=92% and/or respiratory rate >=21 breaths/min on oxygen). Conclusion(s): If the encouraging signal in the relative risk of disease progression or death (~30% reduction) observed in this 300 patient/arm trial were confirmed in a larger trial, SNG001 could become a useful treatment option for hospitalised COVID-19 patients.
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Aim: The aim of this study was to determine severity in patients who have had SARS-CoV2 pneumonia. Method(s): A cohort of 802 patients from our post-COVID multidisciplinary unit treated at least 30 days after being discharged from hospital was analyzed. Patients were divided into three groups: group 1 (admission to the Intensive Care Unit or Intermediate Respiratory Care Unit), group 2 (admission to conventional hospitalization), and group 3 (outpatient management without hospitalization). Symptoms, quality of life, daily physical activity, emotional state, biomarkers of systemic inflammation and KL-6 levels were evaluated. Result(s): A total of 802 patients with a median (interquartile range) age 59 (48-70 years) at diagnosis were reviewed, of whom 439 (54.8%) were women. Dyspnea was reported by 351 (66.%) patients and 142 (36.4%) had a grade more than 2 on the mMRC scale. Likewise, 106 (20.1%) presented dry cough and 233 (44.5%) asthenia. There were significant differences between groups 2 and 3 in: dyspnea (p=0.04), myalgia (p=0.04) and asthenia (p=0.01). Group 1 had a higher score in the TTO and VAS rates of the EuroQuoL scale compared to group 2. Finally, the KL6 levels in groups 1, 2 and 3 were: 381.50 (304 - 511.75) U/ml, 372 (249 - 483) U/ml and 298 (231.5 - 398) U/ml, respectively. Statistically significant differences were observed between the 3 groups (p=0.001) and in the post-hoc analysis, lower levels of KL-6 were observed in group 3 compared to the other two groups. Conclusion(s): There is evidence to affirm that KL6 levels in post-COVID patients are related to the severity of the acute episode.
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Supplemental Digital Content is Available in the Text. Introduction.: Since the lockdown in March 2020, the COVID-19 pandemic has inevitably affected all individuals across the world. The purpose of this study was to determine the perceived impacts of the pandemic on doctor of physical therapy (DPT) students and if there were any statistically significant differences based on minority status, gender, or class standing. Review of Literature.: Literature suggested that DPT students experienced negative impacts of the pandemic on academic success and mental health. However, there is a lack of comprehensive understanding of the perceived physical, mental, financial, and academic impacts of the COVID-19 pandemic by physical therapist students nationally. Subjects.: Convenience sampling was used to recruit all students enrolled in physical therapist programs in the United States. Methods.: The research design was a cross-sectional survey administered electronically using the Alchemer survey platform with 12 Likert scale items compiled in the physical, mental, financial, and academic domains. All items were designed to evaluate the perceived impacts of the pandemic on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree). Results.: A total of 1,230 completed responses were received. The mean responses were 3.45 (SD 1.12), 3.48 (SD 0.92), 2.74 (SD 1.03), and 3.33 (SD 0.93) for the physical, mental, financial, and academic domains, respectively. No significant difference was found based on minority status. A statistically significant difference was found in the mental domain, with female students perceiving a more negative impact by the pandemic. First-year students reported a significantly higher negative impact in the physical domain compared with second-year students. The perceived impact in the academic domain was significantly higher for both first- and second-year students than third-year students. Conclusions.: Developing and promoting access to campus and community resources to address the challenges caused by the COVID-19 pandemic is critical to facilitating student success during and after the pandemic.
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Introduction: The COVID-19 pandemic has influenced the whole world, thus also affecting the high school graduates in Croatia. Aim(s): The purpose of the study was to examine the psychological distress high school graduates experienced during the COVID-19 social distancing measures, more precisely to investigate gender and school type differences and to examine the relationship between psychological distress and self-regulated learning. Method(s): In this cross-sectional study, an online questionnaire was administered to 13,037 high school graduates across Croatia. Result(s): The results show that girls exhibit higher levels of psychological distress compared to the boys, while the art school graduates show the highest distress, followed by gymnasium (i.e., secondary grammar school, prep school) graduates, and lastly vocational school graduates. Furthermore, a moderate negative correlation was found between self-efficacy and psychological distress, and significant, but small correlations were found between regulation of effort, management of work, time and environment, self-handicapping as well as elaboration and psychological distress. These results show that higher levels of self-regulation are connected to lower levels of psychological distress. Conclusion(s): These findings demonstrate that a need exists for greater accessibility of mental health care for adolescents.Copyright © 2022 The Authors. Published by Semmelweis University, Institute of Mental Health, Budapest.
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The proceedings contain 14 papers. The topics discussed include: MOG-positive anti-NMDA receptor encephalitis with no demyelinating lesions: two case reports;safety and tolerability of rozanolixizumab in the randomized phase 3 MycarinG study;Outcomes from RAISE: A randomized, phase 3 trial of zilucoplan in generalized myasthenia gravis;efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized Phase 3 RAISE trial;distinct effects among calcium-binding proteins for microglia to produce chemokines associated with the clinical severity of ALS;astroglial connexin 43 is a novel therapeutic target for a chronic multiple sclerosis model;targeting lymphocytes in SPMS: Th cell populations as a biomarker to predict the efficacy of Siponimod;CSF lysophospholipids as a novel biomarker in relapsing-remitting multiple sclerosis;the immune response to SARS-COV-2 MRNA vaccines in siponimod-treated patients with secondary progressive multiple sclerosis;patient characteristics of siponimod-treated SPMS patients in Japan: interim results from post-marketing surveillance;and efficacy of ravulizumab across sex and age subgroups of patients with generalized myasthenia gravis: a post hoc analysis of the CHAMPION MG study.
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Background: Valuable safeguards against fast‐spreading conjectures about learning in times of fear and uncertainty are evidence‐based approaches to the assessment of the impact of sudden and unforeseen disruptions on learning practices. The present research focused on physics learning in such times because conceptual and computational literacy in physics is critical to the development of a scientifically and technologically literate society. Objectives: The present research aimed (a) to offer an objective assessment of whether performance differences in a physics course of the general education curriculum existed between the face‐to‐face medium (familiar mode of instruction) and the online medium (unfamiliar mode of instruction) for both male and female students, and then (b) to develop a response to the evidence collected to ensure a quality education for all parties involved. The research intended to fill two critical gaps in the extant literature: mixed findings concerning students' performance in the face‐to‐face and online mediums as well as scarce coverage of specific domains of knowledge that are critical to STEM learners. Methods: Students' performance was examined as a function of the type of assessment (formative and summative), instructional mode (online and face‐to‐face), and gender. An understudied student population of STEM students of Middle Eastern descent without prior formal exposure to online instruction was targeted. Results and Conclusions: In both formative and summative assessments, male students performed better online than face‐to‐face, whereas the performance of female students was either higher online or equivalent between instructional mediums. The evidence collected suggested that consideration be given to remedies that foster academic success in the face‐to‐face instructional medium, particularly for male students. Takeaways: An evidence‐based approach to learning dismantled emotion‐driven expectations regarding the impact of the online medium on physics learning, and encouraged new perspectives about instruction. Lay Description: What is already known?: Ongoing debates on the impact of the pandemic on students' learning shape decisions regarding future reliance on the online medium for instruction. What this paper adds: The extant literature is mixed concerning performance in the face‐to‐face and online mediums, including particular domains of knowledge critical to STEM learning.This study focused on physics learning in an understudied population of STEM students who were unaccustomed to online instruction.Performance was higher online than face‐to‐face, but gender differences emerged. Implications for practice: Lessons learned focused on the flexibility of online learning and on the need to develop materials to enhance learning in males enrolled in face‐to‐face or hybrid/blended classes.
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Our research uses the environmental pillar of ESG as a proxy for environmental corporate social responsibility. We examine the performance of environmentally clustered portfolios by using simple quantitative investment strategies with optimum asset rotation. Post-hoc, sample-split analysis with non-parametric tests is performed. The results suggest that both environmental status and dynamic environmental performance are key characteristics of divergent financial behaviors. We show that environmentally low-rated companies present better financial performance, while environmental leaders are less risky and show more resilience. Assets with a dynamic environmental profile outperform on average in terms of returns and risk. Furthermore, supporting evidence of positive spillovers in high-rated environmental clusters is identified after the Paris Agreement. We evaluate the resilience of the environmental clusters during the COVID-19 crisis and the Russia-Ukraine war effect. © 2023 Elsevier B.V.
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Background: No studies have so far explored differences in frailty between groups of individuals who are vaccinated/unvaccinated against COVID-19. Therefore, this study aimed to investigate frailty progression in community-dwelling individuals requiring care/support who were using outpatient rehabilitation services during the start phase of vaccination programs against COVID-19. Method(s): A longitudinal survey using the Frailty Screening Index was administered in April 2020, September 2020, and June 2021 to 74 older adults (43 males, 31 females;age, 78.2 +/- 7.2;mean +/- standard deviation) requiring long-term care/support and using outpatient rehabilitation services. Participants were divided into the vaccinated (those who had received COVID-19 vaccinations;41 participants) and unvaccinated (those who had not been vaccinated;33 participants) groups. The Frailty Screening Index and frailty rating (robust, pre-frailty/frailty) at each of the three periods were analyzed using the Cochran's Q test. The resulting items and ratings with significant differences underwent post-hoc testing with the Bonferroni correction. Result(s): Concerning the frailty rating (robust, pre-frailty/frailty), pre-frailty/frailty increased significantly only in the unvaccinated group. Its post hoc tests showed that pre-frailty/frailty increased significantly from April 2020 to June 2021 and from September 2020 to June 2021. Conclusion(s):We find a difference in frailty progression between groups of vaccinated and unvaccinated community-dwelling older adults requiring care/support who were using outpatient rehabilitation services at the beginning of coronavirus vaccination programs during the COVID-19 pandemic.Copyright © 2023, Taiwan Society of Geriatric Emergency & Critical Care Medicine.