Global Perspective on the Impact of the COVID-19 Pandemic on Rheumatology and Health Equity.

Although the public health emergency associated with the COVID-19 pandemic has ended, challenges remain, especially for individuals with rheumatic diseases. We aimed to assess the historical and ongoing effects of COVID-19 on individuals with rheumatic diseases and rheumatology practices globally, with specific attention to vulnerable communities and lessons learned. We reviewed literature from several countries and regions, including Africa, Australia and New Zealand, China, Europe, Latin America, and the US. In this review, we summarize literature that not only examines the impact of the pandemic on individuals with rheumatic diseases, but also research that reports the lasting changes to rheumatology patient care and practice, and health service use. Across countries, challenges faced by individuals with rheumatic diseases during the pandemic included disruptions in health care and medication supply shortages. These challenges were associated with worse disease and mental health outcomes in some studies, particularly among those who had social vulnerabilities defined by socioeconomic, race, or rurality. Moreover, rheumatology practice was impacted in all regions, with the uptake of telemedicine and changes in health care utilization. While many regions developed rapid guidelines to disseminate scientific information, misinformation and disinformation remained widespread. Finally, vaccine uptake among individuals with rheumatic diseases has been uneven across the world. As the acute phase of the pandemic wanes, ongoing efforts are needed to improve health care access, stabilize rheumatology drug supplies, improve public health communication, and implement evidence-based vaccination practices to reduce COVID-19 morbidity and mortality among individuals with rheumatic diseases.

Annual Direct Cost and Cost-Drivers of Systemic Lupus Erythematosus: A Multi-Center Cross-Sectional Study from CSTAR Registry.

BACKGROUND: To estimate the annual direct costs and cost-drivers associated with systemic lupus erythematosus (SLE) patients in China. METHODS: A multi-center, cross-sectional study was conducted based on the CSTAR registry. The information on demography and expenditures for outpatient and inpatient visits due to SLE were collected using online questionnaires. These patients' medical records were from the database of the Chinese Rheumatology Information System (CRIS). The average direct costs and 95% confidence interval were estimated using the bootstrap method with 1000 bootstrap samples by resampling with replacement. The cost-drivers were identified using multivariate regression models. RESULTS: A total of 1778 SLE patients from 101 hospitals participated in our study, with 92.58% as females, a mean age of 33.8 years old, a median duration of SLE of 4.9 years, 63.8% in an active disease state, 77.3% with two organs or more damaged, and 8.3% using biologics as treatment. The average annual direct cost per patient was estimated at CNY 29,727, which approximates to 86% for direct medical costs. For moderate to severe disease activities, the use of biologics, hospitalization, treatment of moderate or high dose glucocorticoids, and peripheral vascular, cardiovascular, and/or renal system involvements were found to substantially increase the direct costs, while health insurance slightly decreased the direct costs of SLE. CONCLUSIONS: This study provided reliable insight into financial pressures on individual SLE patients in China. The efforts focusing on preventing flare occurrences and limiting disease progression were recommended to further reduce the direct cost of SLE.

Risk assessment in systemic lupus erythematosus-associated pulmonary arterial hypertension: CSTAR-PAH cohort study.

Objective: This study evaluated the prognostic value of the multivariable risk assessment for systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH). Methods: A multicenter prospective cohort of SLE-associated PAH (CSTAR-PAH cohort) diagnosed based on right heart catheterization (RHC) was established. Baseline and follow-up records were collected. Three methods of risk assessment, including (1) the number of low-risk criteria, based on World Health Organization functional class (WHO FC), 6-min walking distance (6MWD), right atrial pressure (RAP), and cardiac index (CI); (2) the three-strata stratification based on the average risk score of four variables (WHO FC, 6MWD, RAP, and CI); and (3) the four-strata stratification based on COMPARE 2.0 model were applied. A risk-assessment method using three noninvasive low-risk criteria was applied at the first follow-up visit. Survival curves between patients with different risk groups were compared by Kaplan-Meier's estimation and log-rank test. Results: Three-hundred and ten patients were enrolled from 14 PAH centers. All methods of stratification at baseline and first follow-up significantly discriminated long-term survival. Survival rates were also significantly different based on the noninvasive risk assessment in first follow-up visit. Survival deteriorated with the escalation of risk from baseline to first follow-up. Patients with baseline serositis had a higher rate of risk improvement in their follow-up. Conclusion: The risk assessment has a significant prognostic value at both the baseline and first follow-up assessment of SLE-associated PAH. A noninvasive risk assessment can also be useful when RHC is not available during follow-up. Baseline serositis may be a predictor of good treatment response in patients with SLE-associated PAH.

Systemic Lupus Erythematosus: Targeted Literature Review of the Epidemiology, Current Treatment, and Disease Burden in the Asia Pacific Region.

OBJECTIVE: To understand the epidemiology, current treatment, and disease burden of systemic lupus erythematosus (SLE) in the Asia Pacific (APAC) region. METHODS: A targeted literature review of published evidence on SLE in the APAC region was conducted, using the Medline database (2008-2018), conference proceedings, and other supplementary sources. RESULTS: The current review identified 70 studies conducted in China (n = 15), Japan (n = 13), Taiwan (n = 12), Korea (n = 9), Australia (n = 7), Hong Kong (n = 6), Singapore (n = 4), and multiple places within the APAC region (n = 4). Incidence rates (per 100,000 persons per year) ranged from 0.9-8.4, while prevalence rates ranged from 3.7-127 (per 100,000 persons); however, recent data were limited. Asian patients with SLE were reported to have higher disease severity, disease activity (higher SLE disease activity index scores), and organ damage accrual, along with increased morbidity, mortality, and susceptibility to renal involvement compared with other ethnicities in the APAC region. The risk of developing SLE is higher in the Asian population. Routinely used SLE therapies included belimumab, hydroxychloroquine, cyclophosphamide, tacrolimus, azathioprine, mycophenolate mofetil, and glucocorticoids; however, prescribing patterns varied across the region. Increased disease activity was associated with high economic burden and poor quality of life for SLE patients in the APAC region. CONCLUSION: SLE remains a disease with a significant unmet medical need for an innovative therapy that is well-tolerated and effective for patients in the APAC region. Further evidence is required to better characterize the disease and fully capture the burden and impact of SLE in the APAC region. This review has highlighted where there is a paucity of data from patients across the APAC region.

Presence of Anti-MDA5 Antibody and Its Value for the Clinical Assessment in Patients With COVID-19: A Retrospective Cohort Study.

Background: Striking similarities have been found between coronavirus disease 2019 (COVID-19) and anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis, implying a shared autoinflammatory aberrance. Herein, we aim to investigate whether the anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Methods and Findings: We retrospectively recruited 274 adult inpatients with COVID-19 in this study, including 48, 164, and 62 cases of deaths, severe, and non-severe patients respectively. The anti-MDA5 Ab was determined by ELISA and verified by Western Blotting, which indicated that the positive rate of anti-MDA5 Ab in COVID-19 patients was 48.2% (132/274). The clinical and laboratory features, as well as outcomes between patients with positive and negative anti-MDA5 Ab were compared and we found that the anti-MDA5 Ab positive patients tended to represent severe disease (88.6% vs 66.9%, P<0.0001). We also demonstrated that the titer of anti-MDA5 Ab was significantly elevated in the non-survivals (5.95 ± 5.16 vs 8.22 ± 6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding severe COVID-19 patients, we found that high titer of anti-MDA5 Ab (≥10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, a dynamic analysis of anti-MDA5 Ab was conducted at different time-points of COVID-19, which revealed that early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Conclusions: Anti-MDA5 Ab was prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes.

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database.

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CONCLUSIONS: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

Successful treatment of refractory thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus with combination of plasma exchange and low-dose rituximab.

OBJECTIVES: Thrombotic thrombocytopenia purpura (TTP) associated with systemic lupus erythematous (SLE) (i.e., SLE-TTP) is a rare life-threatening disease often requiring intensive immunosuppressive agents, in addition to high-dose corticosteroids and plasma exchange (PEX). The optimal therapy of rituximab is unclear, but 375 mg/m2 weekly for 4 weeks is the usual practice, adopted from regimens for non-Hodgkin's lymphoma. We reported two cases of refractory SLE-TTP that showed good efficacy and prognosis with combination of methylprednisolone (MP) pulse, plasma exchange and low-dose rituximab (100 mg weekly for 4 weeks) treatment. METHODS: Clinical data and treatment outcomes were reviewed of two patients diagnosed with refractory SLE-TTP at Peking Union Medical College Hospital between July 2017 and July 2018. RESULTS: Both patients had SLE and presented with microangiopathic anemia and thrombocytopenia. Laboratory assays revealed high anti-nuclear antibody titers, reduced complement 3 and 4 levels, proteinuria, significantly elevated lactate dehydrogenase, schistocytes on peripheral blood smear, low ADAMTS13 activity, and the presence of ADAMTS13 inhibitor. In both patients, platelet counts remained below 50 × 109/L after MP pulse and 6 PEXs, confirming the diagnosis of refractory SLE-TTP. Low-dose rituximab (100 mg weekly for 4 weeks) was administered in both cases, resulting in normalization of platelet counts and significant reductions in B-lymphocyte counts. No TTP relapse or SLE flare occurred during 24 months of follow-up. CONCLUSIONS: Our cases confirmed the efficacy and good follow-up outcomes of low-dose rituximab treatment (100 mg weekly for 4 weeks) for refractory SLE-TTP.

Assessment of lung glucose uptake in patients with systemic lupus erythematosus pulmonary arterial hypertension: a quantitative FDG-PET imaging study.

PURPOSE: Pulmonary arterial hypertension (PAH) is a recognized complication of systemic lupus erythematosus (SLE-PAH) patients and its lung pathology shares similarity to idiopathic PAH (IPAH) with distinctive inflammatory feature. FDG-PET reports glucose metabolism from both hyperproliferative and inflammatory cellular elements of vascular pathology in PAH. We explored the application of FDG-PET in reporting SLE-PAH pulmonary vascular pathology. METHODS: Sixty-minute dynamic FDG-PET imaging was applied in 14 SLE-PAH patients, 20 IPAH patients and 10 healthy volunteers. Patlak analysis was used to quantify lung FDG uptake (influx rate Ki). RESULTS: Mean lung FDG uptake in SLE-PAH (Ki 0.00714 ± 0.000602 mL/g/min) was significantly higher than that of the healthy volunteers (Ki 0.000262 ± 0.000168 mL/g/min) (p < 0.05). SLE-PAH patients with SLE disease activity score SLEDAI ≥ 5 demonstrated significantly increased lung FDG uptake (Ki 0.001075 ± 0.00055 mL/g/min) than those with SLEDAI < 5 (Ki 0.000233 ± 0.00017 mL/g/min) (p = 0.0038) and IPAH (Ki 0.000524 ± 0.000314 mL/g/min) (p = 0.0025). Lung FDG uptake in SLE-PAH correlated with SLEDAI score and plasma complement C3 and C4 levels (Ki vs SLEDAI, r = 0.607, p = 0.021; Ki vs C3, r = - 0.568, p = 0.034; Ki vs C4, r = - 0.661, p = 0.010). There were no significantly correlations between lung FDG uptake and pulmonary vascular haemodynamics and 6 min walking distance in both IPAH and SLE-PAH patients. CONCLUSIONS: Our data indicated that increased lung FDG uptake in SLE-PAH patients correlates with SLE disease activity (SLEDAI) and immune/inflammatory status (C3 and C4). FDG-PET imaging may be developed as a potential intrapulmonary disease activity marker in SLE-PAH patients.

Treatment satisfaction with rheumatoid arthritis in patients with different disease severity and financial burden: A subgroup analysis of a nationwide survey in China.

BACKGROUND: Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patient-assessed) and proportions of treatment cost to household income. METHODS: This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients' treatment satisfaction. RESULTS: When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 13.183, P = 0.004). For biological disease-modifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 8.794, P = 0.032). CONCLUSION: Higher disease severity and higher financial burden were associated with lower patient satisfaction.

Chinese SLE Treatment and Research Group (CSTAR) registry:VIII. Influence of socioeconomic and geographical variables on disease phenotype and activity in Chinese patients with SLE.

AIM: The aim of this study was to estimate the influence of socioeconomic and geographical variables on disease phenotype and activity of systemic lupus erythematosus (SLE) in a Chinese population. METHODS: Data on 904 therapy-naïve SLE patients from the Chinese SLE Treatment and Research Group (CSTAR), which is a nation-wide database of SLE patients, were used to evaluate the influence of socioeconomic status (SES) and geographical regions on disease phenotypes. The influence of regional climate and economic variables (i.e., data from the database of the Chinese Statistical Yearly Annals) on disease activity and nephropathy was further analyzed in a multivariate analysis to identify some of the environmental factors contributing to SLE. RESULTS: Phenotype differences in SLE were found between patients with different SES. In the multivariate regression analysis that considered regional economic and climate factors, after adjusting for age, gender and disease duration, lower educational levels (ß: -0.122, P = 0.001), lower availability of medical technical personnel (MTP) per 1000 people (ß: -0.192, P < 0.001), higher annual duration of sunshine (ß: 0.178, P = 0.010) and residence in southern China (ß: 0.165, P = 0.001) were significantly associated with higher disease activity scores. Living in southern China (odds ratio [OR]: 1.907, P = 0.002) seemed to be a significant risk factor for nephropathy. A high number of MTP per 1000 people (OR: 0.951, P = 0.014) and relatively high temperatures were determined to be protective factors for nephropathy (OR: 0.946, P = 0.011). CONCLUSIONS: The phenotype pattern and disease activity varied between SLE patients by SES and other regional variables, such as educational level, availability of medical technical personnel, annual sunshine duration and regional temperature.

Promoting innovation and access to quality, safe, efficacious, and affordable medicines for children: A China approach on the 69th World Health Assembly.

This study is to provide reference for the proper understanding of the content of "Promoting Innovation and Access to Quality, Safe, Efficacious, and Affordable Medicines for Children" resolution of 69th World Health Assembly (WHA), and facilitate the policy making and implication of the Resolution. Through descriptive analysis, the author introduce the proposal background and approving process of the resolution, and interpret the resolution content. The approval of "Promoting Innovation and Access to Quality, Safe, Efficacious, and Affordable Medicines for Children" at WHA represents China's international discourse right on improving the basic medical service among children, the most vulnerable population; highlights China's responsibility and magnitude of a great nation. It is an effective promotion for China's new medical reform and the implication of the Millennium Development Goals (MDGs), as well as a great contribution to the global health of children from China.

A preliminary study of acoustic radiation force impulse quantification for the assessment of skin in diffuse cutaneous systemic sclerosis.

OBJECTIVE: To investigate skin elasticity using acoustic radiation force impulse (ARFI) quantification in systemic sclerosis (SSc), and compare the modified Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of the skin. METHODS: Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age-matched and sex-matched healthy controls were evaluated. The SWV and thickness of skin were measured at 17 sites corresponding to those assessed in the mRSS in each participant. The SWV measurements of skin were compared between patients with dcSSc and healthy controls. The correlations between the mRSS and the skin SWV and thickness were explored using Spearman's correlation. RESULTS: The SWV values were higher in patients with dcSSc compared with healthy controls at right hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum, and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of uninvolved skin were higher than those of controls (p < 0.001), and the SWV values increased with increasing skin scores except for skin score 3 (p < 0.05). The sum of the SWV values correlated with total clinical skin score (r = 0.841, p < 0.001), and the sum of the skin thickness correlated with total clinical skin score (r = 0.740, p = 0.002). CONCLUSION: ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc. ARFI quantification could identify early skin change that may precede palpable skin involvement, and may be a valuable adjunct to skin evaluation in patients with SSc.

[The value of Doppler echocardiography in assessment of pulmonary capillary wedge pressure in pulmonary hypertension].

OBJECTIVE: To explore the association between Doppler echocardiography parameters and pulmonary capillary wedge pressure (PCWP) obtained by right heart catheterization (RHC) in patients with pulmonary hypertension (PH). METHODS: RHC and a simultaneous echocardiography were performed in 86 PH patients. The correlation between the echocardiographic parameters and PCWP was analyzed. RESULTS: The early diastolic velocity (E) of mitral valve blood flow was significantly correlated with PCWP (r = 0.36, P < 0.01). Tissue Doppler imaging measured the diastolic velocity of mitral annulus on the lateral (E'L) and the septal (E'S) wall. Then the average E'M was calculated. The ratio of E to E'L, E'S and E'M showed a strong correlation with PCWP (r = 0.62, 0.34 and 0.47 respectively, P < 0.01). E/E'L < 6 accurately predicted 100% PCWP ≤ 15 mm Hg (1 mm Hg = 0.133 kPa), and E/E'L > 15 could predict PCWP > 15 mm Hg with specificity of 98.5%. CONCLUSION: There are positive correlation between E/E' and PCWP obtained by RHC in PH patients.