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Background : The Safety and Immunogenicity of COVID-19 Vaccines in Systemic Autoimmune-Mediated Inflammatory Diseases (SUCCEED) study was created to better understand COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Knowing the frequency of COVID-19 breakthrough infections is important, particularly in IMID. Our objective was to assess these events in IMID. Methods : We prospectively studied IMID participants who had received ≥three COVID-19 vaccine doses. Individuals provided saliva samples monthly (September 2022 to August 2023). These were evaluated by polymerase chain reaction (PCR) for SARS-CoV-2. We also assessed antibodies against SARS-CoV-2 (anti-spike, SmT1, receptor binding domain, RBD, and nucleocapsid, NP) based on dried blood spots. Multivariable general estimating equation regression produced odd ratios (OR) for PCR SARS-CoV-2 positivity, related to demographics, immunosuppressives, and antibody levels. Results : Diagnoses included rheumatoid arthritis RA ( N = 161, 44% of the total), systemic lupus, psoriatic arthritis, spondylarthritis, vasculitis, systemic sclerosis, and inflammatory bowel disease. Of the 366 participants, most were taking immunosuppressive medication. Of 1266 saliva samples, 56 (5.1%) were positive for SARS-CoV-2 on PCR. Higher anti-SmT1 antibodies were inversely associated with SARS-CoV-2 detection on PCR (adjusted OR 0.66, 95% confidence interval 0.45-0.97). Antibodies to SmT1, RBD, and NP were correlated and thus could not be included in a single model, but when anti-RBD was used in place of anti-SmT1, the results were similar. No other factor (including prior COVID-19 infection) was clearly associated with SARS-CoV-2 detection. Conclusions : This is the first study of SARS-CoV-2 in a large prospective cohort of triple (or more) vaccinated individuals with IMIDs. Anti-SmT1 antibodies appeared to be protective against later SARS-CoV-2 positivity, although recent past infection was not clearly related. This suggests the importance of maintaining robust vaccine-induced immunity through vaccination in IMID.

We were tasked by Canada's COVID-19 Immunity Task Force to describe severe adverse events (SAEs) associated with emergency department (ED) visits and/or hospitalizations in individuals with immune-mediated inflammatory diseases (IMIDs). At eight Canadian centres, data were collected from adults with rheumatoid arthritis (RA), axial spondyloarthritis (AxS), systemic lupus (SLE), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). We administered questionnaires, analyzing SAEs experienced within 31 days following SARS-CoV-2 vaccination. About two-thirds (63%) of 1556 participants were female; the mean age was 52.5 years. The BNT162b2 (Pfizer) vaccine was the most common, with mRNA-1273 (Moderna) being second. A total of 49% of participants had IBD, 27.4% had RA, 14.3% had PsA, 5.3% had SpA, and 4% had SLE. Twelve (0.77% of 1556 participants) SAEs leading to an ED visit or hospitalization were self-reported, occurring in 11 participants. SAEs included six (0.39% of 1556 participants) ED visits (including one due to Bell's Palsy 31 days after first vaccination) and six (0.39% of 1556 participants) hospitalizations (including one due to Guillain-Barré syndrome 15 days after the first vaccination). Two SAEs included pericarditis, one involved SLE (considered a serious disease flare), and one involved RA. Thus, in the 31 days after SARS-CoV-2 vaccination in our IMID sample, very few serious adverse events occurred. As SARS-CoV2 continues to be a common cause of death, our findings may help optimize vaccination acceptance.

Objective: In the face of the ongoing circulation of SARS-CoV-2, the durability of neutralization post-COVID-19 vaccination in immune-mediated inflammatory disease (IMID) is a key issue, as are the effects of medications., Methods: Adults (n = 112) with inflammatory bowel disease, psoriasis/psoriatic arthritis, rheumatoid arthritis, spondylarthritis, and systemic lupus were recruited from participating Canadian medical centers from 2021 to 2023. We focused on log-transformed neutralization (lentivirus methods) as a continuous outcome, with separate models for wild-type and Omicron strains BA.1 and BA.5., Results: Compared with 30 to 120 days postvaccination, subsequent periods were associated with greater neutralization in unadjusted models for wild-type, BA.1, and BA.5 strains and against the BA.1 strain in adjusted models. Rituximab was associated with lower neutralization for the BA.1 strain in adjusted models, with a similar trend for BA.5. In methotrexate users, there were trends for less neutralization of BA.1 and BA.5 in all unadjusted models, whereas in adjusted models, there was significantly lower neutralization only for the wild type. Three or more doses and Omicron-specific vaccines were both independently associated with better neutralization ability for all three strains. A COVID-19 infection within six months before sampling was associated with higher neutralization of wild type and BA.1 in adjusted analyses. Anti-tumor necrosis factor agents were associated with lower neutralization ability for BA.5 in adjusted analyses., Conclusion: Neutralization responses in immunosuppressed individuals with IMID were durable over time and were augmented by more than three doses and Omicron-specific vaccines. Less neutralization was seen with certain medications. Our work clarifies the joint effects of vaccine history, infection, and medications on COVID-19 immunity., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors., Methods: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG., Results: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days., Conclusion: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs)., Methods: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression., Results: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81)., Conclusion: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs., Competing Interests: Competing interests: MP reports grants from AbbVie—SELECT-GCA Participating Center and AstraZeneca—MANDARA Participating Center; and consulting fees from Novartis, outside the submitted work. ES is a board member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. SES reports research funding related to clinical trials from AstraZeneca (MANDARA) and is supported by the Vasculitis Clinical Research Consortium and Vasculitis Foundation, outside the submitted work. CH is a stockholder for Aurinia Pharmaceuticals; an Advisory Board member for Aurinia Pharmaceuticals, AstraZeneca Pharmaceuticals and UCB Pharmaceuticals; and reports consulting fees from AstraZeneca, UCB, Antidote and Aurinia Pharmaceuticals, outside the submitted work. MJL reports grants from American College of Rheumatology, during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gilead, Johnson & Johnson, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi and Union Chimique Belge, outside the submitted work. SB reports non-branded consulting fees from AbbVie, Amgen, Horizon Pharma, Novartis and Pfizer outside the submitted work, and is a Pfizer employee as of September 2021. RG reports speaker honoraria from AbbVie New Zealand, Cornerstones and Janssen New Zealand; speaker honoraria and non-financial support Pfizer Australia; non-financial support from Janssen Australia and personal fees from Novartis (all <$A10 000) outside the submitted work. PMM reports consulting fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and Union Chimique Belge; and grants and consulting fees from Orphazyme, outside the submitted work. PCR reports personal fees from AbbVie, Gilead, Eli Lilly and Roche; grants and personal fees from Novartis, Union Chimique Belge, Janssen and Pfizer and non-financial support from Bristol Myers Squibb, outside the submitted work. ZSW reports grants from NIH, Bristol Myers Squibb and Principia/Sanofi; and personal fees from Viela Bio and MedPace, outside the submitted work. JY reports grants from NIH/NIAMS K24 during the conduct of the study and outside the submitted work, reports research grants from Gilead, BMS Foundation and AstraZeneca; consulting fees from Pfizer, AstraZeneca and Aurinia. MG-M reports consulting fees for BMS, BI, JNJ and Aurinia (all <$A10 000), outside the submitted work. RH reports grants from AbbVie, Amgen, Boehringer Ingleheim, Johnson & Johnson, Eli Lilly, Novartis, Pfizer and Union Chimique Belge, all paid to Spondylitis Association of America, and consultant fees from GlaxoSmithKline and Novartis, outside the submitted work. RH also owns stocks (<20 shares and representing <4% of personal investments) in AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Merck, Novartis, Pfizer, Teva and Union Chimique Belge. DA-R is a scientific advisor for and reports personal fees from GlaxoSmithKilne Mexico unrelated to this work. RC reports speaker fees from Janssen, Roche, Sanofi and AbbVie, outside the submitted work. AD-G reports grants from the Centers for Disease Control and Prevention, Rheumatology Research Foundation and Mayo Clinic, outside the submitted work. JAS has received consultant fees from Schipher, Crealta/Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS has received institutional research support from Zimmer Biomet Holdings. JAS received food and beverage payments from Intuitive Surgical/Philips Electronics North America. JAS owns stock options in TPT Global Tech, Vaxart Pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals Holding and Charlotte’s Web Holdings. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker’s bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organisation that develops outcome measures in rheumatology and receives arms-length funding from eight companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Board (FAB). JAS is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. MFU-G reports research grants from Pfizer and Janssen, unrelated to this work. JSH reports grants from and Rheumatology Research Alliance; consulting fees from Novartis, Pfizer and Biogen; and is a member of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). JFS received research grant funding from the National Institutes of Health unrelated to this work (NIAMS R01 AR077103 and NIAID R01 AI154533). JSp is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR077607, P30 AR070253 and P30 AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, the Llura Gund Award for Rheumatoid Arthritis Research and Care and Bristol Myers Squibb; and personal fees for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum and Pfizer, unrelated to this work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We assessed central and peripheral visual field processing in children with epilepsy who were exposed to vigabatrin during infancy., Methods: Steady-state visual evoked potentials and pattern electroretinograms to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) were recorded from Oz and at the eye in seven school-age children (10.1 ± 3.5 years) exposed to vigabatrin early in life, compared with children early exposed to other antiepileptic drugs (n = 9) and healthy children (n = 8). The stimulation was made of two concentric circles (0 to 5 and 30 to 60 degrees of angle) and presented at four contrast levels (96%, 64%, 32%, and 16%)., Results: Ocular responses were similar in all groups for central but not for the peripheral stimulations, which were significantly lower in the vigabatrin-exposed group at high contrast level. This peripheral retinal response was negatively correlated to vigabatrin exposure duration. Cortical responses to central stimulations, including contrast response functions in the children with epilepsy in both groups, were lower than those in normally developing children., Conclusions: Alteration of ocular processing was found only in the vigabatrin-exposed children. Central cortical processing, however, was impaired in both epileptic groups, with more pronounced effects in vigabatrin-exposed children. Our study suggests that asymptomatic long-term visual toxicity may still be present at school age, even several years after discontinuation of drug therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to develop a fast and efficient electrophysiological protocol to examine the visual field's integrity, which would be useful in pediatric testing., Methods: Steady-state visual-evoked potentials (ssVEPs) to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) recorded at Oz were collected from 22 participants from 5 to 34 years old and from 5 visually impaired adolescents (12-16 years old). Responses from additional leads (POz, O1, O2), and the impact of gaze deviation on the signals, were also investigated in a subgroup of participants., Results: Steady-state visual-evoked potentials responses were similar at all electrode sites, although the signal from the central stimulation was significantly higher at Oz and was highly sensitive in detecting gaze deviation. No effect of age or sex was found, indicating similar ssVEP responses between adults and healthy children. Visual acuity was related to the central signal when comparing healthy participants with four central visual impaired adolescents. Clinical validation of our electrophysiological protocol was also achieved in a 15-year-old adolescent with a severe peripheral visual deficit, as assessed with Goldmann perimetry., Conclusions: A single electrode over Oz is sufficient to gather both central and peripheral visual signals and also to control for gaze deviation. Our method presents several advantages in evaluating visual fields integrity, as it is fast, reliable, and efficient, and applicable in children as young as 5 years old. However, a larger sample of healthy children should be tested to establish clinical norms.

Background: Precise knowledge of variability in colonic anatomy is of great importance for numerical modeling studies of the abdomen. This knowledge would allow the creation of personalized models for the gastrointestinal tract used for surgical simulations or in studies of virtual trauma., Materials and Methods: To determine the colonic configuration in the general population and define its variability by gender, age, and corpulence, the layout of the colon was determined via the following reference points: ileocecal junction, left and right colonic flexures, and colosigmoid junction (CSJ). Three-dimensional coordinates for each point were recorded on scanned sections of 100 healthy adults to examine the colonic layout under physiological conditions. Coordinates were repositioned in a new anatomical reference for comparison. The average points' coordinates, standard deviations, and distances between them were compared for each group., Results: The right colonic flexure was the most variable point. The CSJ was the least variable. Gender affected mainly the height of the colonic flexures and the length of its segments. Age affected the length of the transverse mesocolon root. Corpulence affected both the position of the ileocecal and CSJs and the length of the right colon. Differences in size and perivisceral fat distribution between groups explained these differences. Three-dimensional anatomical models of the colon were defined for each group by statistical equations., Conclusion: These equations, combined with data concerning the actual lengths of the colonic segments, enable reconstruction of different anatomical models of the colon that are representative according to gender, age, and corpulence., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The distribution of stresses in the scoliotic spine is still not well known despite its biomechanical importance in the pathomechanisms and treatment of scoliosis. Gravitational forces are one of the sources of these stresses. Existing finite element models (FEMs), when considering gravity, applied these forces on a geometry acquired from radiographs while the patient was already subjected to gravity, which resulted in a deformed spine different from the actual one. A new method to include gravitational forces on a scoliotic trunk FEM and compute the stresses in the spine was consequently developed. The 3D geometry of three scoliotic patients was acquired using a multi-view X-ray 3D reconstruction technique and surface topography. The FEM of the patients' trunk was created using this geometry. A simulation process was developed to apply the gravitational forces at the centers of gravity of each vertebra level. First the "zero-gravity" geometry was determined by applying adequate upwards forces on the initial geometry. The stresses were reset to zero and then the gravity forces were applied to compute the geometry of the spine subjected to gravity. An optimization process was necessary to find the appropriate zero-gravity and gravity geometries. The design variables were the forces applied on the model to find the zero-gravity geometry. After optimization the difference between the vertebral positions acquired from radiographs and the vertebral positions simulated with the model was inferior to 3 mm. The forces and compressive stresses in the scoliotic spine were then computed. There was an asymmetrical load in the coronal plane, particularly, at the apices of the scoliotic curves. Difference of mean compressive stresses between concavity and convexity of the scoliotic curves ranged between 0.1 and 0.2 MPa. In conclusion, a realistic way of integrating gravity in a scoliotic trunk FEM was developed and stresses due to gravity were explicitly computed. This is a valuable improvement for further biomechanical modeling studies of scoliosis.

Endoscopic vertebral body stapling is an innovative technique intended to treat adolescent idiopathic scoliosis, but the optimal instrumentation design is not yet established. The objective was to simulate the immediate correction obtained from two stapling configurations. A parametric finite element model of a typical right thoracic scoliotic spine (Cobb 21 degrees ) was developed using geometrical and mechanical data from the literature. Staple insertion and closing were modeled. The intra-operative lateral decubitus and standing positions were taken into account. Two implant configurations, varying the number of staples per vertebra, were simulated. The major correction (9 degrees ) came by simulating the intra-operative posture. The immediate Cobb angle correction due to the staples alone was less then 1 degrees for both configurations. However, the staples helped maintain the correction obtained by the intra-operative posture when the post-operative standing position was simulated. Next steps are to validate the model using surgical cases, implement growth modulation modeling, improve lateral decubitus modeling, and analyze different vertebral stapling strategies for different scoliotic curves.

Recent research examining infants' understanding of intentional action claims to be studying the early origins or precursors of children's later theories of mind If these infant understandings are continuous with later preschool achievements, there should be empirical connections between the two. We provide initial evidence that infants' social attention predicts later social cognition. Specifically, 14-month-olds' habituation to human intentional action significantly predicts later preschool mentalistic construal of persons, as measured on a Theory of Mind Scale.