High fatigue scores in patients with idiopathic inflammatory myopathies: a multigroup comparative study from the COVAD e-survey

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0–10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1–6). Patients with IIMs had similar fatigue scores (5, IQR 3–7) to non-IIM SAIDs [5 (IQR 2–7)], but higher compared to HCs (2, IQR 1–5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient −0.17; 95%CI −0.21 to −13; P < 0.001) and Caucasians (reference Caucasians; coefficient −0.22; 95%CI −0.30 to −0.14; P < 0.001 for Asians and coefficient −0.08; 95%CI −0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life

Global disparities in the treatment of idiopathic inflammatory myopathies: results from an international online survey study

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 (DM, PM, 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], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. Results: Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (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 biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). 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-centred care and available resources

COVAD survey 2 long-term outcomes: unmet need and protocol

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups

Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks

The role of nucleotides in intracellular energy provision and nucleic acid synthesis has been known for a long time. In the past decade, evidence has been presented that, in addition to these functions, nucleotides are also autocrine and paracrine messenger molecules that initiate and regulate a large number of biological processes. The actions of extracellular nucleotides are mediated by ionotropic P2X and metabotropic P2Y receptors, while hydrolysis by ecto-enzymes modulates the initial signal. An increasing number of studies have been performed to obtain information on the signal transduction pathways activated by nucleotide receptors. The development of specific and stable purinergic receptor agonists and antagonists with therapeutical potential largely contributed to the identification of receptors responsible for nucleotide-activated pathways. This article reviews the signal transduction pathways activated by P2Y receptors, the involved second messenger systems, GTPases and protein kinases, as well as recent findings concerning P2Y receptor signalling in C6 glioma cells. Besides vertical signal transduction, lateral cross-talks with pathways activated by other G protein-coupled receptors and growth factor receptors are discussed

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey

Objectives To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs

Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model

Background:Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. Methods: Five anaesthetised pigs were studied after surfactant depletion via a saline lavage model of R/D. Animals were ventilated with mean FiO2 of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E) and three types of breath hold manoeuvre were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. Results: During tidal ventilation, expiratory lung collapse increased when I:E and#60; 1 (mean (SD) lung collapse = 15.7 (8.7)%, pand#60;0.05), but the amplitude of respiratory PaO2 oscillations (2.2 (0.8) kPa) did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was not clear. Lung collapse increased during breath-hold manoeuvres (pand#60;0.005) at end-expiration and end-inspiration (14% vs. 0.9-2.1%, pand#60;0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (pand#60;0.0001). Conclusions: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of R/D. The results suggest changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury

Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model

Background:Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. Methods: Five anaesthetised pigs were studied after surfactant depletion via a saline lavage model of R/D. Animals were ventilated with mean FiO2 of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E) and three types of breath hold manoeuvre were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. Results: During tidal ventilation, expiratory lung collapse increased when I:E &lt; 1 (mean (SD) lung collapse = 15.7 (8.7)%, p&lt;0.05), but the amplitude of respiratory PaO2 oscillations (2.2 (0.8) kPa) did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was not clear. Lung collapse increased during breath-hold manoeuvres (p&lt;0.005) at end-expiration and end-inspiration (14% vs. 0.9-2.1%, p&lt;0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (p&lt;0.0001). Conclusions: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of R/D. The results suggest changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury

Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model

Background: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. Methods: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O-2 (FiO(2)) of 0.7 and a tidal volume of 10 ml kg(-1) Protocolised changes in pressure-and volume-controlled modes, inspiratory: expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. Results: During tidal ventilation, the expiratory lung collapse increased when I: E &lt;1 [mean (standard deviation) lung collapse = .7 (8.7)%; P&lt;0.05], but the amplitude of respiratory PaO2 oscillations [ 2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P&lt;0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P&lt;0.0001). Conclusions: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury