We aim to provide early evidence of mental distress and its associated predictors among adults one month into the COVID-19 crisis in Brazil.
We conducted an online survey of 638 adults in Brazil on ...March 25–28, 2020, about one month (32 days) cross-sectionally after the first COVID-19 case in South America was confirmed in São Paulo. The 638 adults were in 25 states out of the 26 Brazilian states, with the only exception being Roraima, the least populated state in the Amazon. Of all the participating adults, 24%, 20%, and 18% of them were located in Rio de Janeiro state, Santa Catarina state, and São Paulo state respectively.
In Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less reported higher levels of distress. Each individual's distance from the Brazilian epicenter of São Paulo interacted with age and workplace attendance to predict the level of distress. The “typhoon eye effect” was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey.
Identifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis.
•Early evidence of mental distress of Brazilian adults in COVID-19 crisis.•In March 2020, 52% of the adults in Brazil experienced mild or moderate distress.•In March 2020, 18.8% of the adults in Brazil suffered severe mental distress.•Female, younger, more educated or less exercised individuals had higher distress.•Adults further from the epicenter or attended workplace less often suffered more.
The hypothalamic-pituitary-thyroid (HPT) axis is crucial in regulating thyroid hormone levels that contribute to the development and homeostasis of the human body. Current literature supports the ...presence of a local HPT axis equivalent within keratinocytes of the skin, with thyroid hormones playing a potential role in cancer progression. However, this remains to be seen within oral tissue cells. An electronic search of Scopus and PubMed/Medline databases was conducted to identify all original publications that reported data on the production or effects of HPT axis components in normal or malignant cells of the oral cavity. The search identified 221 studies, of which 14 were eligible. Eight studies were retrospective analyses of clinical samples, one study involved both in vivo and in vitro experiments, and the remaining five studies were conducted in vitro using cell lines. The search identified evidence of effects of HPT components on oral cancer cells. However, there were limited data for the production of HPT axis components by oral tissues. We conclude that a possible role of the local HPT axis equivalent in the oral mucosa may not be established at present. The gaps in knowledge identified in this scoping review, particularly regarding the production of HPT components by oral tissues, warrant further investigation.
Objectives. Identifying patients with RA at high risk of rapid radiographic progression (RRP) is critical for making appropriate treatment decisions. We developed an exploratory prediction model for ...the risk of RRP using an RA study population undergoing either conservative or aggressive disease management. Methods. Using data from the active-controlled study of patients receiving infliximab for the treatment of rheumatoid arthritis of early onset (ASPIRE) early RA study, RRP was defined as a threshold change in modified Sharp/van der Heijde score (SHS) of ⩾5 U/year. Spearman's rank analysis was used to identify baseline risk factors for RRP. Logistic regression was used to calculate the probability of RRP in 1 year. The results were combined into a matrix model that consisted of risk factors and initiated treatment arranged in increasing risk of RRP. Data from the anti-TNF trial in rheumatoid arthritis with concomitant therapy (ATTRACT) established RA study were applied to the model to test its generalizability in another population. Results. The 28 swollen joint count, RF, CRP and ESR are included as trichotomous variables and initiated treatment (monotherapy or combination therapy) as a dichotomous variable. Two models, one incorporating all risk factors except CRP and another incorporating all risk factors except ESR, were developed to adjust for collinearity. These models identify subpopulations of RA patients at higher predicted risk for RRP. Conclusions. These preliminary matrix models predict the risk of RRP using initiated treatment and easily accessible clinical and laboratory variables. Further testing in other populations and with other therapies is needed to obtain a definitive risk model that will guide rheumatologists in making treatment decisions for individual RA patients.
To assess the efficacy and safety of golimumab over 104 weeks in patients with active ankylosing spondylitis.
At baseline, patients with active ankylosing spondylitis (n=356) were randomly assigned ...(1:1.8:1.8) to subcutaneous injections of placebo (group 1), golimumab 50 mg (group 2) or golimumab 100 mg (group 3) every 4 weeks. At week 16, patients in groups 1 and 2 with <20% improvement in total back pain and morning stiffness entered early escape to 50 or 100 mg, respectively. At week 24, patients still receiving placebo crossed over to golimumab 50 mg. Findings through week 24 were previously reported; those through week 104 are presented herein.
At week 104, 38.5%, 60.1% and 71.4% of patients in groups 1, 2 and 3, respectively, had at least 20% improvement in the Assessment in SpondyloArthritis international Society response criteria (ASAS20); 38.5%, 55.8% and 54.3% had an ASAS40 response and 21.8%, 31.9% and 30.7% were in ASAS partial remission. Mean Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index scores were <3 at week 104 for all the treatment regimens. Golimumab safety through week 104 was similar to that through week 24.
Clinical response that was achieved by patients receiving golimumab through 24 weeks was sustained through 52 and 104 weeks. The golimumab safety profile appeared to be consistent with the known safety profile of tumour necrosis factor inhibitors.
Systematic analysis of rich behavioral recordings is being used to uncover how circuits encode complex behaviors. Here, we apply this approach to embryos. What are the first embryonic behaviors and ...how do they evolve as early neurodevelopment ensues? To address these questions, we present a systematic description of behavioral maturation for
Caenorhabditis elegans
embryos. Posture libraries were built using a genetically encoded motion capture suit imaged with light-sheet microscopy and annotated using custom tracking software. Analysis of cell trajectories, postures, and behavioral motifs revealed a stereotyped developmental progression. Early movement is dominated by flipping between dorsal and ventral coiling, which gradually slows into a period of reduced motility. Late-stage embryos exhibit sinusoidal waves of dorsoventral bends, prolonged bouts of directed motion, and a rhythmic pattern of pausing, which we designate slow wave twitch (SWT). Synaptic transmission is required for late-stage motion but not for early flipping nor the intervening inactive phase. A high-throughput behavioral assay and calcium imaging revealed that SWT is elicited by the rhythmic activity of a quiescence-promoting neuron (RIS). Similar periodic quiescent states are seen prenatally in diverse animals and may play an important role in promoting normal developmental outcomes.
Introduction
Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity ...Index BASDAI and Ankylosing Spondylitis Disease Activity Score ASDAS), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2.
Methods
DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week 0, week 4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2 years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 peripheral joint pain), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status.
Results
Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6–1.7 for ASDAS; 49–54% achieved BASDAI 50 and 39% achieved ASDAS major improvement at week 100.
Conclusions
Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis.
Trial Registration
Clinicaltrials.gov NCT03158285.
To evaluate the safety and efficacy of intravenous golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) aged < 65 years and those ≥ 65 years who were enrolled in the ...GO-FURTHER study.
In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, patients with active RA were randomized to intravenous (IV) golimumab 2 mg/kg + MTX or placebo + MTX at weeks 0 and 4, then every 8 weeks thereafter (with crossover to golimumab at week 16 early escape or week 24 per-protocol). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology (ACR) 20/50/70 response criteria. Efficacy and adverse events (AEs) were monitored through 2 years. Efficacy and AEs were summarized for patients aged < 65 years or ≥ 65 years; AEs were also summarized for patients < or ≥ 70 years and patients < or ≥ 75 years.
In GO-FURTHER, 592 patients were randomized to receive placebo (n = 197) or golimumab (n = 395), 515 were aged < 65 years and 77 were ≥ 65 years. At week 24, ACR20 response rates were greater for golimumab + MTX patients compared with placebo + MTX for patients < 65 years (61.6% vs 31.3%, p < 0.001) and those ≥ 65 years (69.5% vs 33.3%; p < 0.01). Infections were the most common AE through week 112 (51.6% in patients < 65 years; 55.3% in patients ≥ 65 years); upper respiratory infections were the most common infection in patients < 65 years (13.2%) and those ≥ 65 years (11.8%). Serious AEs occurred in 17.7% in patients < 65 years and 25.0% of patients ≥ 65 years and included malignancies, pneumonia, fractures, acute pancreatitis, cellulitis, and bacterial arthritis.
In GO-FURTHER, ACR response rates were similar between patients < 65 years and patients ≥ 65 years within each treatment group. AEs in elderly patients were similar to the known safety profile of IV golimumab. Immunosenescence is known to increase the risk of infections in the elderly. Elderly patients had a numerically higher incidence of serious infections. Six malignancies occurred in golimumab-treated patients, all in patients < 65 years.
clinicaltrials.gov: NCT00973479 . Registered September 9, 2009.
Abstract
Background
Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have ...not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read.
Methods
The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (
N
= 405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein CRP ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0–10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada SPARCC score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire – Disability Index (HAQ-DI), Investigator’s Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints.
Discussion
This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA.
Trial registration
This trial was registered at ClinicalTrials.gov,
NCT04929210
, on 18 June 2021.
Protocol version: Version 1.0 dated 14 April 2021.
Objective. To evaluate the association between inflammatory markers and relapse in GCA patients longitudinally assessed in a clinical trial of infliximab and glucocorticosteroids.
Methods. Forty-four ...newly diagnosed GCA patients in glucocorticosteroid-induced remission were randomized to receive infliximab 5 mg/kg or placebo plus daily glucocorticosteroids, tapered using a standardized schedule. Sera were analysed for inflammatory markers at multiple, pre-defined time points. Temporal artery biopsies were performed in four patients before and after treatment to analyse changes in inflammatory and vascular remodelling marker expression.
Results. Thirteen of 44 patients relapsed. Similar proportions of relapsed patients were present in both treatment arms. ESR, CRP, intercellular adhesion molecule (ICAM)-1, TNF-α, and IL-12p40 were significantly elevated near relapse. In post-treatment biopsies, mRNA expression of pro-inflammatory cytokines decreased, while vascular remodelling factors increased relative to baseline biopsies. Tissue IL-12p40 and IFN-γ mRNA remained elevated in relapsing vs remitting patients.
Conclusion. Despite prior findings of high concentrations of TNF-α in temporal artery biopsies of GCA patients, infliximab plus glucocorticosteroids did not result in improved clinical outcomes. Increased measures of this biomarker did not provide useful insight into the relative importance of TNF-α in the pathogenesis of GCA. Gene expression analysis in paired temporal artery biopsies pre- and post-treatment revealed decreased inflammatory activity and active vascular remodelling following treatment. In relapsing patients, increased expression of IFN-γ and IL-12p40 in post-treatment biopsies suggests a role in sustaining disease and setting the stage for relapse during treatment withdrawal.
Trial registration. ClinicalTrials.gov; http://www.clinicaltrials.gov; NCT00076726.
ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and ...DISCOVER-2 trials defined by baseline patient characteristics.MethodsAdults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.ResultsBaseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.ConclusionsGuselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.Trial registration numbersNCT03162796, NCT03158285.
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