| 1. |
- Sen, P, et al.
(författare)
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Vaccine hesitancy decreases in rheumatic diseases, long-term concerns remain in myositis: a comparative analysis of the COVAD surveys
- 2023
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3291-3301
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveCOVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys.MethodsThe first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups.ResultsWe analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)].ConclusionVaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.
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| 5. |
- Saunois, Marielle, et al.
(författare)
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The Global Methane Budget 2000–2017
- 2020
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 12:3, s. 1561-1623
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations).For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters.Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.The data presented here can be downloaded from https://doi.org/10.18160/GCP-CH4-2019 (Saunois et al., 2020) and from the Global Carbon Project.
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| 11. |
- Attia, Zachi I., et al.
(författare)
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Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram
- 2021
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Ingår i: Mayo Clinic proceedings. - : ELSEVIER SCIENCE INC. - 0025-6196 .- 1942-5546. ; 96:8, s. 2081-2094
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control. (C) 2021 Mayo Foundation Medical Education and Research
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| 12. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 13. |
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| 18. |
- Naveen, R., et al.
(författare)
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Systemic sclerosis and COVID-19 vaccine safety : short-term insights from the global COVID-19 vaccination in autoimmune disease (COVAD) survey
- 2023
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Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 43:7, s. 1265-1275
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Tidskriftsartikel (refereegranskat)abstract
- The safety profile of COVID-19 vaccines is understudied in patients with systemic sclerosis (SSc). We compared short-term adverse events (AEs) 7 days following vaccination in patients with SSc vs other rheumatic (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). The COVID-19 Vaccination in autoimmune diseases (COVAD) self-reporting e-survey was circulated by a group of > 110 collaborators in 94 countries from March to December 2021. AEs were analyzed between different groups using regression models. Of 10,679 complete respondents [73.8% females, mean age 43 years, 53% Caucasians], 478 had SSc. 83% had completed two vaccine doses, Pfizer-BioNTech (BNT162b2) (51%) was the most common. Minor and major AEs were reported by 81.2% and 3.3% SSc patients, respectively, and did not differ significantly with disease activity or different vaccine types, though with minor symptom differences. Frequencies of AEs were not affected by background immunosuppression, though SSc patients receiving hydroxychloroquine experienced fatigue less commonly (OR 0.4; 95% CI 0.2-0.8). Frequency of AEs and hospitalisations were similar to other AIRDs, nrAIDs, and HC except a higher risk of chills (OR 1.3; 95% CI 1.0-1.7) and fatigue (OR 1.3; 95% CI 1.0-1.6) compared to other AIRDs. COVID-19 vaccines were largely safe and well tolerated in SSc patients in the short term. Background immunosuppression and disease activity did not influence the vaccination-related short-term AEs.
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| 19. |
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| 20. |
- Stavert, Ann R., et al.
(författare)
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Regional trends and drivers of the global methane budget
- 2022
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:1, s. 182-200
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Tidskriftsartikel (refereegranskat)abstract
- The ongoing development of the Global Carbon Project (GCP) global methane (CH4) budget shows a continuation of increasing CH4 emissions and CH4 accumulation in the atmosphere during 2000–2017. Here, we decompose the global budget into 19 regions (18 land and 1 oceanic) and five key source sectors to spatially attribute the observed global trends. A comparison of top-down (TD) (atmospheric and transport model-based) and bottom-up (BU) (inventory- and process model-based) CH4 emission estimates demonstrates robust temporal trends with CH4 emissions increasing in 16 of the 19 regions. Five regions—China, Southeast Asia, USA, South Asia, and Brazil—account for >40% of the global total emissions (their anthropogenic and natural sources together totaling >270 Tg CH4 yr−1 in 2008–2017). Two of these regions, China and South Asia, emit predominantly anthropogenic emissions (>75%) and together emit more than 25% of global anthropogenic emissions. China and the Middle East show the largest increases in total emission rates over the 2000 to 2017 period with regional emissions increasing by >20%. In contrast, Europe and Korea and Japan show a steady decline in CH4 emission rates, with total emissions decreasing by ~10% between 2000 and 2017. Coal mining, waste (predominantly solid waste disposal) and livestock (especially enteric fermentation) are dominant drivers of observed emissions increases while declines appear driven by a combination of waste and fossil emission reductions. As such, together these sectors present the greatest risks of further increasing the atmospheric CH4 burden and the greatest opportunities for greenhouse gas abatement.
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| 21. |
- Wei, Shushu, et al.
(författare)
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Slow conformational dynamics of the human A(2A) adenosine receptor are temporally ordered
- 2022
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Ingår i: Structure. - : Elsevier. - 0969-2126 .- 1878-4186. ; 30:3, s. 329-
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Tidskriftsartikel (refereegranskat)abstract
- A more complete depiction of protein energy landscapes includes the identification of different function related conformational states and the determination of the pathways connecting them. We used total internal reflection fluorescence (TIRF) imaging to investigate the conformational dynamics of the human A(2A) adenosine receptor (A(2A)AR), a class A G protein-coupled receptor (GPCR), at the single-molecule level. Slow, reversible conformational exchange was observed among three different fluorescence emission states populated for agonist-bound A(2A)AR. Transitions among these states predominantly occurred in a specific order, and exchange between inactive and active-like conformations proceeded through an intermediate state. Models derived from molecular dynamics simulations with available A(2A)AR structures rationalized the relative fluorescence emission intensities for the highest and lowest emission states but not the transition state. This suggests that the functionally critical intermediate state required to achieve activation is not currently visualized among available A(2A)AR structures.
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| 22. |
- Bose, Subhash, et al.
(författare)
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ASASSN-18am/SN 2018gk : an overluminous Type IIb supernova from a massive progenitor
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 503:3, s. 3472-3491
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Tidskriftsartikel (refereegranskat)abstract
- ASASSN-18am/SN 2018gk is a newly discovered member of the rare group of luminous, hydrogen-rich supernovae (SNe) with a peak absolute magnitude of M-V approximate to -20 mag that is in between normal core-collapse SNe and superluminous SNe. These SNe show no prominent spectroscopic signatures of ejecta interacting with circumstellar material (CSM), and their powering mechanism is debated. ASASSN-18am declines extremely rapidly for a Type II SN, with a photospheric-phase decline rate of similar to 6.0 mag (100 d)(-1). Owing to the weakening of H I and the appearance of He I in its later phases, ASASSN-18am is spectroscopically a Type IIb SN with a partially stripped envelope. However, its photometric and spectroscopic evolution shows significant differences from typical SNe IIb. Using a radiative diffusion model, we find that the light curve requires a high synthesized Ni-56 mass M-Ni similar to 0.4 M-circle dot and ejecta with high kinetic energy E-kin = (7-10) x 10(51) erg. Introducing a magnetar central engine still requires M-Ni similar to 0.3 M-circle dot and E-kin = 3 x 10(51) erg. The high Ni-56 mass is consistent with strong iron-group nebular lines in its spectra, which are also similar to several SNe Ic-BL with high Ni-56 yields. The earliest spectrum shows 'flash ionization' features, from which we estimate a mass-loss rate of (M) over dot approximate to 2 x 10(-4 )M(circle dot) yr(-1). This wind density is too low to power the luminous light curve by ejecta-CSM interaction. We measure expansion velocities as high as 17 000 km s(-1) for H alpha, which is remarkably high compared to other SNe II. We estimate an oxygen core mass of 1.8-3.4 M-circle dot using the [O I] luminosity measured from a nebular-phase spectrum, implying a progenitor with a zero-age main-sequence mass of 19-26 M-circle dot.
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| 23. |
- Chakraborti, Sayan, et al.
(författare)
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A MISSING-LINK IN THE SUPERNOVA-GRB CONNECTION : THE CASE OF SN 2012ap
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 805:2
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly, usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However, supernovae with heavy ejecta can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for a few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. However, the ejecta from SN 2009bb was baryon loaded and in nearly free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than one-sixth of the fluence from GRB 980425. This shows for the first time that central engines in SNe Ic, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.
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| 24. |
- Chang, Kuang Yu, et al.
(författare)
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Observational constraints reduce model spread but not uncertainty in global wetland methane emission estimates
- 2023
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Ingår i: Global Change Biology. - 1354-1013. ; 29:15, s. 4298-4312
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Tidskriftsartikel (refereegranskat)abstract
- The recent rise in atmospheric methane (CH4) concentrations accelerates climate change and offsets mitigation efforts. Although wetlands are the largest natural CH4 source, estimates of global wetland CH4 emissions vary widely among approaches taken by bottom-up (BU) process-based biogeochemical models and top-down (TD) atmospheric inversion methods. Here, we integrate in situ measurements, multi-model ensembles, and a machine learning upscaling product into the International Land Model Benchmarking system to examine the relationship between wetland CH4 emission estimates and model performance. We find that using better-performing models identified by observational constraints reduces the spread of wetland CH4 emission estimates by 62% and 39% for BU- and TD-based approaches, respectively. However, global BU and TD CH4 emission estimate discrepancies increased by about 15% (from 31 to 36 TgCH4 year−1) when the top 20% models were used, although we consider this result moderately uncertain given the unevenly distributed global observations. Our analyses demonstrate that model performance ranking is subject to benchmark selection due to large inter-site variability, highlighting the importance of expanding coverage of benchmark sites to diverse environmental conditions. We encourage future development of wetland CH4 models to move beyond static benchmarking and focus on evaluating site-specific and ecosystem-specific variabilities inferred from observations.
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| 25. |
- Chatterjee, Tulika, et al.
(författare)
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Type 1 diabetes, COVID-19 vaccines and short-term safety : Subgroup analysis from the global COVAD study
- 2024
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Ingår i: Journal of Diabetes Investigation. - : John Wiley & Sons. - 2040-1116 .- 2040-1124. ; 15:1, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients. MATERIALS AND METHODS: This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out.RESULTS: This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients).CONCLUSIONS: COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients.
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| 26. |
- Correia, Jorge C., et al.
(författare)
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Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:11, s. 2215-2230
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Tidskriftsartikel (refereegranskat)abstract
- Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift toward a slow MN identity. In muscle, NRTN increased capillary density and oxidative capacity and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1a1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.
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| 27. |
- Franzen, Bo, et al.
(författare)
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A fine-needle aspiration-based protein signature discriminates benign from malignant breast lesions
- 2018
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 12:9, s. 1415-1428
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Tidskriftsartikel (refereegranskat)abstract
- There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and to follow-up personalized cancer therapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissues; however, the minute sample amounts require sensitive multiplex molecular analysis to achieve clinical utility. We have applied proximity extension assays (PEA) and NanoString (NS) technology for analyses of proteins and of RNA, respectively, in FNA samples. Using samples from patients with breast cancer (BC, n=25) or benign lesions (n=33), we demonstrate that these FNA-based molecular analyses (a) can offer high sensitivity and reproducibility, (b) may provide correct diagnosis in shorter time and at a lower cost than current practice, (c) correlate with results from routine analysis (i.e., benchmarking against immunohistochemistry tests for ER, PR, HER2, and Ki67), and (d) may also help identify new markers related to immunotherapy. A specific 11-protein signature, including FGF binding protein 1, decorin, and furin, distinguished all cancer patient samples from all benign lesions in our main cohort and in smaller replication cohort. Due to the minimally traumatic sampling and rich molecular information, this combined proteomics and transcriptomic methodology is promising for diagnostics and evaluation of treatment efficacy in BC.
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| 28. |
- Gil-Vila, Albert, et al.
(författare)
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COVID-19 Vaccination In Autoimmune Diseases (COVAD) Study : Vaccine Safety In Idiopathic Inflammatory Myopathies
- 2022
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Ingår i: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 66:4, s. 426-437
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION/AIMS: We studied COVID-19 vaccination-related adverse events (ADEs) 7-days post-vaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).METHODS: 7-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics and multivariable regression were performed.RESULTS: 10,900 respondents [1227 IIMs; 4640 SAIDs; 5033 healthy controls (HCs), median age 42 (IQR 30-55) years, 74% female, 45% Caucasian, 69% completely vaccinated] were analysed. 76.3% IIMs patients reported minor and 4.6% major ADEs. Patients with active IIMs reported more frequent major [OR 2.7 (1.04-7.3)] and minor [OR 1.5 (1.1-2.2)] ADEs than inactive IIMs. Rashes were more frequent in IIMs [OR-2.3(1.2-4.2)] than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs [OR 1.9 (1.1-3.3), OR 2.2 (1.1-4.3)]. Overall, ADEs were less frequent in inclusion body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients DISCUSSION: 7-day post-vaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rashes in IIMs. Patients with DM, active disease may be at higher risk, and IBM patients at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, and specifically in IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines.
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| 29. |
- Gowda, Naveen Kumar Chandappa, et al.
(författare)
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Cytosolic splice isoform of Hsp70 nucleotide exchange factor Fes1 is required for the degradation of misfolded proteins in yeast
- 2016
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 27:8, s. 1210-1219
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Tidskriftsartikel (refereegranskat)abstract
- Cells maintain proteostasis by selectively recognizing and targeting misfolded proteins for degradation. In Saccharomyces cerevisiae, the Hsp70 nucleotide exchange factor Fes1 is essential for the degradation of chaperone-associated misfolded proteins by the ubiquitin-proteasome system. Here we show that the FES1 transcript undergoes unique 3' alternative splicing that results in two equally active isoforms with alternative C-termini, Fes1L and Fes1S. Fes1L is actively targeted to the nucleus and represents the first identified nuclear Hsp70 nucleotide exchange factor. In contrast, Fes1S localizes to the cytosol and is essential to maintain proteostasis. In the absence of Fes1S, the heat-shock response is constitutively induced at normally non-stressful conditions. Moreover, cells display severe growth defects when elevated temperatures, amino acid analogues or the ectopic expression of misfolded proteins, induce protein misfolding. Importantly, misfolded proteins are not targeted for degradation by the ubiquitin-proteasome system. These observations support the notion that cytosolic Fes1S maintains proteostasis by supporting the removal of toxic misfolded proteins by proteasomal degradation. This study provides key findings for the understanding of the organization of protein quality control mechanisms in the cytosol and nucleus.
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| 30. |
- Gowda, Naveen Kumar Chandappa, et al.
(författare)
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Hsp70 nucleotide exchange factor Fes1 is essential for ubiquitin-dependent degradation of misfolded cytosolic proteins
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:15, s. 5975-5980
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Tidskriftsartikel (refereegranskat)abstract
- Protein quality control systems protect cells against the accumulation of toxic misfolded proteins by promoting their selective degradation. Malfunctions of quality control systems are linked to aging and neurodegenerative disease. Folding of polypeptides is facilitated by the association of 70 kDa Heat shock protein (Hsp70) molecular chaperones. If folding cannot be achieved, Hsp70 interacts with ubiquitylation enzymes that promote the proteasomal degradation of the misfolded protein. However, the factors that direct Hsp70 substrates toward the degradation machinery have remained unknown. Here, we identify Fes1, an Hsp70 nucleotide exchange factor of hitherto unclear physiological function, as a cytosolic triaging factor that promotes proteasomal degradation of misfolded proteins. Fes1 selectively interacts with misfolded proteins bound by Hsp70 and triggers their release from the chaperone. In the absence of Fes1, misfolded proteins fail to undergo polyubiquitylation, aggregate, and induce a strong heat shock response. Our findings reveal that Hsp70 direct proteins toward either folding or degradation by using distinct nucleotide exchange factors.
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| 31. |
- Gupta, Latika, et al.
(författare)
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FLARES FOLLOWING COVID-19 VACCINATION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : COMBINED ANALYSIS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDIES
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:Suppl. 2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Aims: Flares following COVID-19 vaccination are an emerging concern among patients with rare rheumatic disease like idiopathic inflammatory myositis (IIMs), whereas data and understanding of this is rather limited. We aimed to study the prevalence, characteristics and determinants of IIM flares following COVID-19 vaccination.Methods: CoVAD (COVID-19 Vaccination In Autoimmune Diseases) surveys are global patient self-reported e-surveys from 109 countries conducted in 2021 and 2022. Flares of IIM were defined by 4 definitions; a. patient self-reported, b. physician and immunosuppression (IS) denoted, c. sign directed (new erythematous rash, or worsening myositis or arthritis), d. MCID worsening of PROMISPF10a score between the patients who had taken both surveys. Descriptive statistics and multivariate regression were used to describe the predictors of flare. Cox-regression analysis was used to differentiate flares by IIM subtypes.Results: Among the 1,278 IIM patients, aged 63 (50-71) years, 276 (21.5%) were dermatomyositis, 237 (18.5%) IBM, 899 (70.3%) were female and most were Caucasian (80.8%). Flares of IIM were seen in 123/1278 (9.6%), 163/1278 (12.7%), 112/1278 (8.7%), and 16/96 (19.6%) by definitions a-d respectively with median time to flare being 71.5 (10.7-235) days. Muscle weakness (69.1%), and fatigue (56.9%) were the most common symptoms of flare. The predictors of self-reported flare were: inactive/disease in remission prior to first dose of vaccine (OR ¼ 4.3, 95%CI¼2.4-7.6), and anxiety disorder (OR ¼ 2.2, 95%CI¼1.1-4.7). Rituximab use (OR ¼ 0.3, 95%CI¼0.1-0.7) and IBM (OR ¼ 0.3, 95%CI¼0.1-0.7) were protective. Physician defined flares were seen more often in females, mixed ethnicity, and those with asthma, ILD, and anxiety disorder (OR ranging 1.6-7.0, all p < 0.05). Notably, overlap myositis (OM) had higher HR for flare compared to polymyositis (HR ¼ 2.3, 95%CI¼1.2-4.4, p ¼ 0.010).Conclusion: Nearly one in ten individuals with IIM develop flares after vaccination, more so among women, those with overlap myositis, and inactive disease prior to vaccination. Formal definition of flares in IIM is needed.
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| 32. |
- Gupta, Latika, et al.
(författare)
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POST COVID-19 SYNDROME IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDY
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:Suppl. 2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Aims: Post COVID-19 syndrome (PCS) is an emerging cause of morbidity and poor quality of life in COVID-19 survivors. We aimed to assess the prevalence, risk factors, outcomes, and association with disease flaresof PCS in patients with autoimmune rheumatic diseases (AIRDs) and non-rheumatic autoimmune diseases (nrAIDs), both vulnerable groups understudied in the current literature using data from the 2nd COVID-19 Vaccination in Autoimmune Diseases (COVAD) global multicentre patient self-reported e-survey.Methods: The survey was circulated from February to July 2022 by the international COVAD Study Group (157 collaborators from 106 countries), and demographics, comorbidities, AIRD/nrAID status, COVID-19 history, vaccination details, and PROMIS physical and mental function were recorded. PCS was defined as symptom resolution time >90 days following acute COVID-19. Predictors of PCS were analysed using regression models for the different groups.Results: 7666 total respondents completed the survey. Of these, 2650 respondents with complete responses had positive COVID-19 infection, and 1677 (45.0% AIRDs, 12.5% nrAIDs, 42.5% HCs) completed the survey >90 days post acute COVID-19. Of these, 136 (8.1%) had PCS. Prevalence of PCS was higher in AIRDs (10.8%) than healthy controls HCs (5.3%) (OR: 2.1; 95%CI: 1.4-3.1, p ¼ 0.002).Across the entire cohort, a higher risk of PCS was seen in women (OR: 2.9; 95%CI: 1.1-7.7, p ¼ 0.037), patients with long duration of AIRDs/nrAIDs (OR 1.01; 95%CI: 1.0-1.02, p ¼ 0.016), those with comorbidities (OR: 2.8; 95%CI: 1.4-5.7, p ¼ 0.005), and patients requiring oxygen supplementation for severe acute COVID-19 (OR: 3.8; 95%CI: 1.1-13.6, p ¼ 0.039).Among patients with AIRDs, comorbidities (OR 2.0; 95%CI: 1.08-3.6, p ¼ 0.026), and advanced treatment (OR: 1.9; 95%CI: 1.08-3.3, p ¼ 0.024), or intensive care (OR: 3.8; 95%CI: 1.01-14.4, p ¼ 0.047) for severe COVID-19 were risk factors for PCS.Notably, patients who developed PCS had poorer PROMIS global physical [15 (12-17) vs 12 (9-15)] and mental health [14 (11-16) vs 11 (8-14)] scores than those without PCS.Conclusion: Individuals with AIRDs have a greater risk of PCS than HCs. Associated comorbid conditions, and advanced treatment or intensive care unit admission for severe COVID-19 confer a higher risk of PCS. It is imperative to identify risk factors for PCS for immediate multidisciplinary management in anticipation of poor physical and mental health.
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| 33. |
- Malik, Yashpal Singh, et al.
(författare)
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Coronavirus Disease Pandemic (COVID-19) : Challenges and a Global Perspective
- 2020
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Ingår i: Pathogens. - : MDPI AG. - 2076-0817. ; 9:7
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Forskningsöversikt (refereegranskat)abstract
- The technology-driven world of the 21st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2 ') within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures.
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| 34. |
- Panchawagh, Suhrud, et al.
(författare)
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COVID-19 breakthrough infections in type 1 diabetes mellitus : a cross-sectional study by the COVID-19 Vaccination in Autoimmune Diseases (COVAD) Group
- 2024
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Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the frequency, profile, and severity of COVID-19 breakthrough infections (BI) in patients with type I diabetes mellitus (T1DM) compared to healthy controls (HC) after vaccination. The second COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) survey is a multinational cross-sectional electronic survey which has collected data on patients suffering from various autoimmune diseases including T1DM. We performed a subgroup analysis on this cohort to investigate COVID-19 BI characteristics in patients with T1DM. Logistic regression with propensity score matching analysis was performed. A total of 9595 individuals were included in the analysis, with 100 patients having T1DM. Among the fully vaccinated cohort, 16 (16%) T1DM patients had one BI and 2 (2%) had two BIs. No morbidities or deaths were reported, except for one patient who required hospitalization with oxygen without admission to intensive care. The frequency, clinical features, and severity of BIs were not significantly different between T1DM patients and HCs after adjustment for confounding factors. Our study did not show any statistically significant differences in the frequency, symptoms, duration, or critical care requirements between T1DM and HCs after COVID-19 vaccination. Further research is needed to identify factors associated with inadequate vaccine response in patients with BIs, especially in patients with autoimmune diseases.
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| 35. |
- R., Naveen, et al.
(författare)
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COVID-19 vaccination in autoimmune diseases (COVAD) Study : vaccine safety and tolerance in rheumatoid arthritis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:7, s. 2366-2376
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in rheumatoid arthritis (RA) patients.METHODS: An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). Descriptive and multivariable regression analyses were performed.RESULTS: Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA who had a mean (standard deviation) age of 50.7 (13.7) years, and 74.2% were women, and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both OR = 0.7; 95%CI = 0.5-0.9), and injection site pain (OR = 0.6; 95%CI = 0.5-0.8) with similar major AE and hospitalization frequencies.CONCLUSION: Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs providing reassurance to the safety of COVID-19 vaccination.
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| 36. |
- R., Naveen, et al.
(författare)
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Safety and tolerance of vaccines against SARS-CoV-2 infection in systemic lupus erythematosus : results from the COVAD study
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:7, s. 2453-2463
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine COVID-19 vaccine-related adverse events (AEs) in the seven-day post-vaccination period in patients with SLE versus autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HC).METHODS: Data were captured through the COVID-19 Vaccination in Autoimmune Diseases (COVAD) questionnaire (March-December 2021). Multivariable regression models accounted for age, gender, ethnicity, vaccine type, and background treatment.RESULTS: Among 9462 complete respondents, 583 (6.2%) were SLE patients (mean age: 40.1 years; 94.5% females; 40.5% Asian; 42.9% Pfizer-recipients). Minor AEs were reported by 83.0% of SLE patients, major by 2.6%, hospitalisation by 0.2%.AE and hospitalisation frequencies were similar between patients with active and inactive SLE. Rashes were more frequent in SLE patients versus HC (OR; 95% CI: 1.2; 1.0-1.5), chills less frequent in SLE versus AIRDs (0.6; 0.4-0.8) and nrAIDs (0.5; 0.3-0.8), and fatigue less frequent in SLE versus nrAIDs (0.6; 0.4-0.9). Pfizer-recipients reported higher overall AE (2.2; 1.1-4.2) and injection site pain (2.9; 1.6-5.0) frequencies than recipients of other vaccines, Oxford/AstraZeneca-recipients more body ache, fever, chills (OR: 2.5-3.0), Moderna-recipients more body ache, fever, chills, rashes (OR: 2.6-4.3). Hospitalisation frequencies were similar across vaccine types. AE frequencies were similar across treatment groups, although chills were less frequent in antimalarial users versus non-users (0.5; 0.3-0.9).CONCLUSION: While COVID-19 vaccination-related AEs were reported by four-fifths of SLE patients, those were mostly minor and comparable to AEs reported by healthy individuals, providing reassurance regarding COVID-19 vaccination safety in SLE.
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| 37. |
- Ravi, Naveen, et al.
(författare)
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Identification of targetable lesions in anaplastic thyroid cancer by genome profiling
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Anaplastic thyroid cancer (ATC) is a rare and extremely malignant tumor with no available cure. The genetic landscape of this malignancy has not yet been fully explored. In this study, we performed whole exome sequencing and the RNA-sequencing of fourteen cases of ATC to delineate copy number changes, fusion gene events, and somatic mutations. A high frequency of genomic amplifications was seen, including 29% of cases having amplification of CCNE1 and 9% of CDK6; these events may be targetable by cyclin dependent kinase (CDK) inhibition. Furthermore, 9% harbored amplification of TWIST1, which is also a potentially targetable lesion. A total of 21 fusion genes in five cases were seen, none of which were recurrent. Frequent mutations included TP53 (55%), the TERT promoter (36%), and ATM (27%). Analyses of mutational signatures showed an involvement of processes that are associated with normal aging, defective DNA mismatch repair, activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity, failure of DNA double-strand break repair, and tobacco exposure. Taken together, our results shed new light on the tumorigenesis of ATC and show that a relatively large proportion (36%) of ATCs harbor genetic events that make them candidates for novel therapeutic approaches. When considering that ATC today has a mortality rate of close to 100%, this is highly relevant from a clinical perspective.
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| 38. |
- Sen, Parikshit, et al.
(författare)
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COVID-19 vaccination-related adverse events among autoimmune disease patients : results from the COVAD study
- 2022
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:1, s. 65-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: COVID-19 vaccines have been proven to be safe in the healthy population. However, gaps remain in the evidence of their safety in patients with systemic autoimmune and inflammatory disorders (SAIDs). COVID-19 vaccination related adverse events (ADEs) in patients with SAIDs and healthy controls (HC) seven days post-vaccination were assessed in the COVAD study, a patient self-reported cross-sectional survey.METHODS: The survey was circulated in early 2021 by > 110 collaborators (94 countries) to collect SAID details, COVID-19 vaccination details, and 7-day vaccine ADEs, irrespective of respondent vaccination status. Analysis was performed based on data distribution and variable type.RESULTS: 10900 respondents [42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 5,867 patients (54%) with SAIDs were compared with 5033 HCs.79% had minor and only 3% had major vaccine ADEs requiring urgent medical attention (but not hospital admission) overall. Headache [SAIDs=26%, HCs=24%; OR = 1.1 (1.03-1.3); p = 0.014], abdominal pain [SAIDs=2.6%, HCs=1.4%; OR = 1.5 (1.1-2.3); p = 0.011], and dizziness [SAIDs=6%, HCs=4%; OR = 1.3 (1.07-1.6); p = 0.011], were slightly more frequent in SAIDs. Overall, major ADEs [SAIDs=4%, HCs=2%; OR = 1.9 (1.6-2.2); p < 0.001] and, specifically, throat closure [SAIDs=0.5%, HCs=0.3%; OR = 5.7 (2.9-11); p = 0.010] were more frequent in SAIDs though absolute risk was small (0-4%). Major ADEs and hospitalizations (less than 2%) were comparable across vaccine types in SAIDs.CONCLUSION: Vaccination against COVID-19 is relatively safe in SAID patients. SAIDs were at a higher risk of major ADEs than HCs, though absolute risk was small. There are small differences in minor ADEs between vaccine types in SAID patients.
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| 39. |
- Shinjo, Samuel Katsuyuki, et al.
(författare)
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Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases : A report from the COVAD study
- 2023
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Ingår i: International journal of rheumatic diseases. - : John Wiley & Sons. - 1756-1841 .- 1756-185X. ; 26:4, s. 727-739
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs).METHODS: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores.RESULTS: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios.CONCLUSION: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.
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| 40. |
- Yoshida, Akira, et al.
(författare)
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Impaired physical function in patients with idiopathic inflammatory myopathies : results from the multicentre COVAD patient-reported e-survey
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:3, s. 1204-1215
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs.METHODS: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease.RESULTS: 1057 IIM patients, 3635 non-IIM AIRD patients, and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs (36.3 [95% confidence interval (CI) 35.5-37.1] vs 41.3 [95%CI 40.2-42.5] vs 46.2 [95%CI 45.8-46.6], P < 0.001), irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis.CONCLUSION: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.
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| 41. |
- Ziade, Nelly, et al.
(författare)
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Global disparities in the treatment of idiopathic inflammatory myopathies : results from an international online survey study
- 2024
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 63:3, s. 657-664
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' Gross National Income (GNI), disease subtypes, and symptoms using patient-reported information.METHODS: A cross-sectional ancillary analysis of the "COVID-19 vaccination in auto-immune disease" (COVAD) e-survey containing demographic characteristics, IIM subtypes (dermatomyositis (DM), polymyositis (PM), inclusion-body myositis (IBM), anti-synthetase syndrome (ASSD), immune-mediated necrotizing myopathy (IMNM), overlap myopathies (OM)), current symptoms (surrogate for organ involvement), and treatments (corticosteroids (CS), immunomodulators (IM), i.e., antimalarials, immunosuppressants (IS), intravenous immunoglobulins (IVIG), biological treatments, and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM, and organ involvement, and associated factors were analyzed using multivariable binary logistic regressions.RESULTS: Of 18,851 respondents from 94 countries, 1,418 with IIM were analyzed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%), and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%), and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biological treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnea). Most inter-regional treatment disparities persisted after multivariable analysis.CONCLUSION: We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centered care and available resources.
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