Assessment of hesitancy to COVID-19 vaccine in patients with rheumatic arthritis.

OBJECTIVE: The COVID-19 pandemic caused by SARS-CoV-2 in 2019 has greatly impacted global health, leading to high morbidity and mortality rates. Rheumatoid arthritis (RA) patients have faced numerous challenges during the pandemic, including concerns about infection, limited medical resources, and shortages of medication. While vaccination is a crucial strategy against COVID-19, the reasons behind vaccine hesitancy (VH) among people with RA remain largely unexplored. SUBJECTS AND METHODS: We conducted a cross-sectional, single-arm study in China from July 18 to August 18, 2021. Using a self-administered questionnaire and a convenient sampling method, we investigated vaccine attitudes and VH among RA patients. The questionnaire developed by the investigators was validated by two public health experts and one senior rheumatologist. It covered sociodemographics, disease-related variables, vaccination attitudes, and willingness, etc. We employed Chi-squared and regression analyses to identify factors associated with VH toward COVID-19 vaccination. RESULTS: A total of 184 RA patients were enrolled in the survey, with 113 (61.41%) expressing unwillingness to be vaccinated. The Chi-squared test revealed significant differences in employment status and related systemic damage (p < 0.05). Among the unvaccinated RA patients, 71.68% believed COVID-19 vaccination might impact their disease. Binary and multicollinearity logistic regression analyses showed that the acute stage of RA (p < 0.001, OR = -3.165, 95% CI: 0.035 - 0.164) and fear of disease development caused by drug discontinuation during vaccination (p < 0.001, OR = -3.591, 95% CI: 0.005 - 0.157) were the restricting factors influencing the COVID-19 vaccine inoculation rate in RA patients. CONCLUSIONS: The COVID-19 vaccination rate among RA patients in China is low due to limited knowledge, misconceptions, and insufficient promotion. Boosting confidence and understanding of the vaccine's effectiveness and safety is crucial to improve vaccination success.

Assessment of Myocardial Mechanics in Acute Rheumatic Fever Using Speckle-Tracking Echocardiography.

BACKGROUND: This study aims to evaluate the role of speckle-tracking echocardiography to identify myocardial deformation in acute rheumatic fever. METHODS: Twenty-seven patients and 27 healthy children were prospectively evaluated. The patient group was divided into 2 subgroups based on echocardiographic findings, with or without carditis. The left ventricular global longitudinal strain and strain rate, left ventricular global circumferential strain and strain rate, and right ventricular global lon-gitudinal strain and strain rate were assessed by speckle-tracking echocardiography. RESULTS: In the acute phase of the disease, all values except the right ventricular global longitudinal strain were found to be significantly below the control group in the patient cohort. No significant difference was found between the patients grouped as carditis and non-carditis in the acute period. Comparison of the acute period with the post-treatment period revealed a significant increase in all strain values of the patients with carditis and significant increases observed in all values except left ventricular global longitudinal strain rate, left ventricular global circumferential strain rate, and right ventricular global longitudinal strain rate values in patients without carditis. Apart from the right ventricular global longitudinal strain rate, which was significantly lower in the non-carditis group compared to the control group, there was no significant difference in strain values between the patient and control groups following treatment. CONCLUSION: In the present study, we found that all patients, including patients in whom no valvular involvement was detected by echocardiography in the acute phase of acute rheumatic fever, had a lower right and left ventricular strain and strain rate measurements and that these findings improved after treatment, suggesting that strain echocardiography may be a helpful diagnostic method, especially in patients without valvular involvement.

A pilot study to develop assessment tools for Group A Streptococcus surveillance studies.

Introduction: Group A Streptococcus (GAS) causes pharyngitis (sore throat) and impetigo (skin sores) GAS pharyngitis triggers rheumatic fever (RF) with epidemiological evidence supporting that GAS impetigo may also trigger RF in Australian Aboriginal children. Understanding the concurrent burden of these superficial GAS infections is critical to RF prevention. This pilot study aimed to trial tools for concurrent surveillance of sore throats and skins sore for contemporary studies of RF pathogenesis including development of a sore throat checklist for Aboriginal families and pharynx photography. Methods: Yarning circle conversations and semi-structured interviews were performed with Aboriginal caregivers and used to develop the language and composition of a sore throat checklist. The sore throat story checklist was combined with established methods of GAS pharyngitis and impetigo surveillance (examination, bacteriological culture, rapid antigen detection and serological tests) and new technologies (photography) and used for a pilot cross-sectional surveillance study of Aboriginal children attending their health clinic for a routine appointment. Feasibility, acceptability, and study costs were compiled. Results: Ten Aboriginal caregivers participated in the sore-throat yarning circles; a checklist was derived from predominant symptoms and their common descriptors. Over two days, 21 Aboriginal children were approached for the pilot surveillance study, of whom 17 were recruited; median age was 9 years [IQR 5.5-13.5], 65% were female. One child declined throat swabbing and three declined finger pricks; all other surveillance elements were completed by each child indicating high acceptability of surveillance assessments. Mean time for screening assessment was 19 minutes per child. Transport of clinical specimens enabled gold standard microbiological and serological testing for GAS. Retrospective examination of sore throat photography concorded with assessments performed on the day. Conclusion: Yarning circle conversations were effective in deriving culturally appropriate sore throat questionnaires for GAS pharyngitis surveillance. New and established tools were feasible, practical and acceptable to participants and enable surveillance to determine the burden of superficial GAS infections in communities at high risk of RF. Surveillance of GAS pharyngitis and impetgio in remote Australia informs primary RF prevention with potential global translation.

Evaluating efficiency and equity of prevention and control strategies for rheumatic fever and rheumatic heart disease in India: an extended cost-effectiveness analysis.

BACKGROUND: There is a dearth of evidence on the cost-effectiveness of a combination of population-based primary, secondary, and tertiary prevention and control strategies for rheumatic fever and rheumatic heart disease. The present analysis evaluated the cost-effectiveness and distributional effect of primary, secondary, and tertiary interventions and their combinations for the prevention and control of rheumatic fever and rheumatic heart disease in India. METHODS: A Markov model was constructed to estimate the lifetime costs and consequences among a hypothetical cohort of 5-year-old healthy children. Both health system costs and out-of-pocket expenditure (OOPE) were included. OOPE and health-related quality-of-life were assessed by interviewing 702 patients enrolled in a population-based rheumatic fever and rheumatic heart disease registry in India. Health consequences were measured in terms of life-years and quality-adjusted life-years (QALY) gained. Furthermore, an extended cost-effectiveness analysis was undertaken to assess the costs and outcomes across different wealth quartiles. All future costs and consequences were discounted at an annual rate of 3%. FINDINGS: A combination of secondary and tertiary prevention strategies, which had an incremental cost of ₹23 051 (US$30) per QALY gained, was the most cost-effective strategy for the prevention and control of rheumatic fever and rheumatic heart disease in India. The number of rheumatic heart disease cases prevented among the population belonging to the poorest quartile (four cases per 1000) was four times higher than the richest quartile (one per 1000). Similarly, the reduction in OOPE after the intervention was higher among the poorest income group (29·8%) than among the richest income group (27·0%). INTERPRETATION: The combined secondary and tertiary prevention and control strategy is the most cost-effective option for the management of rheumatic fever and rheumatic heart disease in India, and the benefits of public spending are likely to be accrued much more by those in the lowest income groups. The quantification of non-health gains provides strong evidence for informing policy decisions by efficient resource allocation on rheumatic fever and rheumatic heart disease prevention and control in India. FUNDING: Department of Health Research, Ministry of Health and Family Welfare, New Delhi.

Assessment of serum galectin-3 levels in acute rheumatic fever.

BACKGROUND: Galectin-3 is a biomarker which takes a role in both acute and chronic inflammation as well as fibrosis and oxidative stress. Increased levels of it are associated with cardiovascular diseases. This study was performed to investigate the levels of galectin-3 in acute rheumatic fever (ARF). METHODS: 30 patients with ARF and 26 healthy children were included. Galectin-3 levels of the patients were compared with the controls, as well as within the patients before and after the treatment. RESULTS: The patients had significantly lower galectin-3 levels on admission than the control (p=0.02), but its levels were not significantly different between these groups at the end of treatment (p=0.714). The mean galectin-3 levels of the patients were increased after the treatment (p < 0.001). Severity of carditis and galectin-3 levels were negatively correlated (r=-539, p=0.02). CONCLUSIONS: Children with ARF have significantly reduced levels of galectin-3 and there is a negative correlation between the severity of the carditis and galectin-3 levels. Studies with larger sample sizes may give more accurate data about the role of galectin-3 in ARF.

Burden of Group A Streptococcal Pharyngitis, Rheumatic Fever, and Rheumatic Heart Disease in India: A Systematic Review and Meta-Analysis.

OBJECTIVE: To estimate the burden of group A streptococcal pharyngitis (GAS) pharyngitis, rheumatic fever (RF), and rheumatic heart disease (RHD) in India using existing data sources, as well as to recognize the most serious gaps in GAS disease burden data. METHODS: Four electronic databases-PubMed, Scopus, Embase, and Web of Science were searched using a comprehensive search strategy. Data were identified primarily from observational studies including school surveys, community-based and hospital-based studies. The standard methodological procedures as per Cochrane guidelines were used. Eligible studies were pooled for estimating prevalence, incidence, and case fatality rate using R software version 3.3.3. The protocol was registered with PROSPERO; registration number CRD42018075742. RESULTS: The pooled prevalence of GAS pharyngitis among asymptomatic children and pharyngitis cases aged 5 to 15 y was estimated as 2.79 percent [95% Confidence interval (CI): 1.58-4.89] and 13 percent (95% CI: 3.18-41.97), respectively. The prevalence rate of rheumatic fever was found to be 0.04% (95% CI: 0.01-0.17). The pooled prevalence rate of RHD among children aged 5-15 y using clinical auscultation and echocardiography was estimated as 0.36 percent (95% CI: 0.02-7.52) and 0.28 percent (95% CI: 0.08-1.03), respectively. CONCLUSION: The study emphasizes the importance of developing a population-based surveillance framework to track patterns, management strategies, and outcomes in order to develop informed recommendations for launching contextual measures to regulate RF and RHD.

Early diagnosis of acute rheumatic fever and rheumatic heart disease as part of a secondary prevention strategy: Narrative review.

Acute rheumatic fever (ARF) and its sequela rheumatic heart disease (RHD) remain significant causes of morbidity and mortality. In New Zealand, ARF almost exclusively affects Indigenous Maori and Pacific children. This narrative review aims to present secondary interventions to improve early and accurate diagnosis of ARF and RHD, in order to minimise disease progression in New Zealand. Medline, EMBASE and Scopus databases were searched as well as other electronic publications. Included were 56 publications from 1980 onwards. Diagnosing ARF and RHD as early as possible is central to reducing disease progression. Recent identification of specific ARF biomarkers offer the opportunity to aid initial diagnosis and portable echocardiography has the potential to detect undiagnosed RHD in high-risk areas. However, further research into the benefits and risks to children with subclinical RHD is necessary, as well as an economic evaluation.

Pediatric rheumatic carditis in Italy and Rwanda: The same disease, different socio-economic settings.

BACKGROUND: Acute Rheumatic Fever and Rheumatic Heart Disease are the leading cause of acquired heart disease in Low-Income Countries, and a common cause in High-Income Countries. We compared rheumatic carditis, its echocardiographic presentation at diagnosis and its progression in Italy and Rwanda. METHODS: Retrospective study including all consecutive patients diagnosed with rheumatic carditis in an Italian (IT) and two Rwandan Hospitals (RW). Echocardiography was performed at diagnosis and three follow-up visits. Baseline characteristics, history of primary and secondary prophylaxis and cardiovascular complications data were collected. RESULTS: Seventy-nine and 135 patients were enrolled in IT and RW, respectively. Mitral regurgitation was the most common lesion (IT: 70%, RW: 96%) in both cohorts; mixed valve lesions and severe lesions were more prevalent in RW. Age at diagnosis (IT: 8.4 ± 2.9 yrs.; RW: 11.1 ± 2.7 yrs.; P < 0.001), adherence to secondary prophylaxis (IT: 99%; RW: 48%; P < 0.001) and history of primary prophylaxis (IT: 65%; RW: 6%; P < 0.001) were different. During the follow-up, native valve lesions completely resolved in 38% of IT and in 2% of RW patients (P < 0.001). By contrast, cardiac surgery was performed in 31% of RW and 5% of IT patients (P < 0.001). Cardiovascular complications and death were only observed in RW. CONCLUSIONS: The more severe cardiac involvement, the higher rate of valve surgery, CV complications and deaths in RW, could be due to delayed diagnosis and treatment, scarce adherence to secondary prophylaxis and differences in social determinants of health.

Rheumatic heart disease in Indigenous young peoples.

Indigenous children and young peoples live with an inequitable burden of acute rheumatic fever and rheumatic heart disease. In this Review, we focus on the epidemiological burden and lived experience of these conditions for Indigenous young peoples in Australia, New Zealand, and Canada. We outline the direct and indirect drivers of rheumatic heart disease risk and their mitigation. Specifically, we identify the opportunities and limitations of predominantly biomedical approaches to the primary, secondary, and tertiary prevention of disease among Indigenous peoples. We explain why these biomedical approaches must be coupled with decolonising approaches to address the underlying cause of disease. Initiatives underway to reduce acute rheumatic fever and rheumatic heart disease in Australia, New Zealand, and Canada are reviewed to identify how an Indigenous rights-based approach could contribute to elimination of rheumatic heart disease and global disease control goals.

Rising Ethnic Inequalities in Acute Rheumatic Fever and Rheumatic Heart Disease, New Zealand, 2000-2018.

We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000-2018 and RHD mortality rates during 2000-2016. We found elevated rates of initial ARF hospitalizations for persons of Maori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0-14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9-27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Maori (aRR 3.2, 95% CI 2.9-3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2-5.1) groups and RHD deaths among these groups (Maori aRR 12.3, 95% CI 10.3-14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1-13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.

Pacific Fono: a community-based initiative to improve rheumatic fever service delivery for Pacific Peoples in South Auckland.

BACKGROUND AND CONTEXT Rheumatic fever inequitably affects Maori and Pacific children in New Zealand. School-based throat swabbing services, such as the South Auckland Mana Kidz programme, are a key element of rheumatic fever prevention interventions. ASSESSMENT OF THE PROBLEM Counties Manukau has the highest national rates of rheumatic fever (4.7 per 100,000 for first recorded rates). Given these disparities, Mana Kidz undertook an exploratory, community-based initiative to improve its service delivery for Pacific Peoples. RESULTS Mana Kidz held a Pacific Leaders' Fono (meeting) to discuss initiatives to improve rheumatic fever outcomes in South Auckland focused around challenges and solutions for addressing rheumatic fever, effective engagement strategies and leadership qualities needed to drive initiatives. Oral and written responses from 66 attendees were collected and thematically analysed. Four key themes were identified around challenges and solutions for rheumatic fever: social determinants of health; cultural responsiveness; health system challenges; and education, promotion and literacy. Three effective engagement strategies were identified: by Pacific for Pacific; developing a rheumatic fever campaign; improving health services. Three key leadership attributes were identified: culturally responsive leaders; having specific expertise and skills; youth-driven leadership. STRATEGIES FOR IMPROVEMENT Mana Kidz has now created Pacific leadership roles in rheumatic fever governance groups, promotes Pacific workforce development and endorses Pacific-led initiatives and partnerships. LESSONS Recognising the value of critical reflection and the importance of good governance and collaborative, right-based partnerships in health services.

Computer- and Telephone-Delivered Interventions on Patient Outcomes and Resource Utilization in Patients With Orthopaedic Conditions: A Systematic Review and Narrative Synthesis.

BACKGROUND: As the number of patients with orthopaedic conditions has risen continuously, hospital-based healthcare resources have become limited. Delivery of additional services is needed to adapt to this trend. PURPOSE: The purpose of this study was to describe the current literature of computer- and telephone-delivered interventions on patient outcomes and resource utilization in patients with orthopaedic conditions. METHODS: The systematic review was conducted in January 2019. The standardized checklist for randomized controlled trials was used to assess the quality of the relevant studies. A meta-analysis was not possible due to heterogeneity in the included studies, and a narrative synthesis was conducted to draw informative conclusions relevant to current research, policy, and practice. RESULTS: A total of 1,173 articles were retrieved. Six randomized controlled trials met the inclusion criteria, providing evidence from 434 individuals across four countries. Two studies reported findings of computer-delivered interventions and four reported findings of telephone-delivered interventions. The patients who received both computer- and telephone-delivered interventions showed improvements in patient outcomes that were similar or better to those of patients receiving conventional care. This was without any increase in adverse events or costs. CONCLUSION: Computer- and telephone-delivered interventions are promising and safe alternatives to conventional care. This review, however, identifies a gap in evidence of high-quality studies exploring the effects of computer- and telephone-delivered interventions on patient outcomes and resource utilization. In future, these interventions should be evaluated from the perspective of intervention content, self-management, and patient empowerment. In addition, they should consider the whole care journey and the development of the newest technological innovations. Additionally, future surgery studies should take into account the personalized needs of special, high-risk patient groups and focus on patient-centric care to reduce postdischarge health problems and resource utilization in this population.

Contemporary Incidence and Prevalence of Rheumatic Fever and Rheumatic Heart Disease in Australia Using Linked Data: The Case for Policy Change.

Background In 2018, the World Health Organization prioritized control of acute rheumatic fever (ARF) and rheumatic heart disease (RHD), including disease surveillance. We developed strategies for estimating contemporary ARF/RHD incidence and prevalence in Australia (2015-2017) by age group, sex, and region for Indigenous and non-Indigenous Australians based on innovative, direct methods. Methods and Results This population-based study used linked administrative data from 5 Australian jurisdictions. A cohort of ARF (age <45 years) and RHD cases (<55 years) were sourced from jurisdictional ARF/RHD registers, surgical registries, and inpatient data. We developed robust methods for epidemiologic case ascertainment for ARF/RHD. We calculated age-specific and age-standardized incidence and prevalence. Age-standardized rate and prevalence ratios compared disease burden between demographic subgroups. Of 1425 ARF episodes, 72.1% were first-ever, 88.8% in Indigenous people and 78.6% were aged <25 years. The age-standardized ARF first-ever rates were 71.9 and 0.60/100 000 for Indigenous and non-Indigenous populations, respectively (age-standardized rate ratio=124.1; 95% CI, 105.2-146.3). The 2017 Global Burden of Disease RHD prevalent counts for Australia (<55 years) underestimate the burden (1518 versus 6156 Australia-wide extrapolated from our study). The Indigenous age-standardized RHD prevalence (666.3/100 000) was 61.4 times higher (95% CI, 59.3-63.5) than non-Indigenous (10.9/100 000). Female RHD prevalence was double that in males. Regions in northern Australia had the highest rates. Conclusions This study provides the most accurate estimates to date of Australian ARF and RHD rates. The high Indigenous burden necessitates urgent government action. Findings suggest RHD may be underestimated in many high-resource settings. The linked data methods outlined here have potential for global applicability.

Correlação entre dois testes e a pontuação do Child Health Assessment Questionnaire em crianças com cardiopatia reumática / Correlation between two tests and Children Health Assessment Questionnaire in child with rheumatic cardiopathy

As crianças que evoluem para cardiopatia reumática passam a conviver com limitações, tornam-se comumente restritas no desempenho de atividade do cotidiano. OBJETIVO: Verificar a existência de correlação entre o desempenho no teste de caminhada de seis minutos (TC6M) e do degrau de três minutos (TD3) e a pontuação do child health assessment questionnaire (CHAQ) em criança com febre reumática. MÉTODOS: Estudo seccional sem grupo de comparação, descritivo e exploratório, realizado com 15 crianças. Foram avaliadas através dos testes submáximos, o TC6M e o TD3 e a avaliação da capacidade física sob a percepção do cuidador foi realizada por meio da aplicação do CHAQ. RESULTADOS: A média de idade 13,7 anos, desvio padrão 1,9 anos. A maioria dos acompanhantes eram mães, 66,7%, e uma parcela considerável dos cuidadores apresentou baixo nível socioeconômico e de escolaridade. O valor obtido na distância percorrida através do TC6M demonstrou um baixo desempenho, mediana (intervalo interquartil) 420 (101) metros que também foi observado no teste do degrau de três minutos, mediana (intervalo interquartil) 68 (6,5) degraus. Em relação ao questionário CHAQ foi observado ausência de comprometimento da capacidade física diante da percepção dos responsáveis com escore final do questionário de 0,1. A correlação entre o questionário e o teste de caminhada de seis minutos (correlação de Sperman = - 0,21) e, entre o questionário e o teste do degrau de três minutos, (correlação de Sperman = - 0,39). CONCLUSÃO: Não foi encontrada correlação dos testes submáximos, em relação à capacidade física obtida através da percepção dos responsáveis avaliada através do questionário. Esse resultado chama a atenção para a importância do fisioterapeuta inserir na sua prática clínica, nesse perfil de pacientes os testes submáximos.

Children who develop rheumatic heart disease live with limitations, they become commonly restricted in the performance of everyday activities. OBJECTIVE: To verify the correlation between performance between two submaximal exercise tests and the questionnaire score in children with chronic rheumatic disease. METHODS: A cross-sectional, descriptive and exploratory study with 15 children. They were evaluated through the submaximal tests, the 6MWT and TD3 and the physical capacity assessment under the caregiver's perception was performed through the application of the questionnaire of CHAQ. RESULTS: Mean age 13.7 years, standard deviation 1.9 years. Most of the companions were mothers, 66.7%, and a considerable portion of the caregivers had low socioeconomic and educational levels. The value obtained in the distance covered by the 6MWT demonstrated a low performance, median (interquartile range) 420 (101) meters, which was also observed in the three-minute step test, median (interquartile range) 68 (6.5) steps. Regarding the CHAQ questionnaire, there was an absence of impairment of physical capacity in view of the perception of those responsible with a final score of 0.1. The correlation between the questionnaire and the six-minute walk test (Sperman correlation = -0.21) and between the questionnaire and the three-minute step test (Sperman's correlation = -0.39). CONCLUSION: No correlation was found between submaximal tests, in relation to the physical capacity obtained through the perception of those responsible, assessed through the questionnaire. This result draws attention to the importance of the physiotherapist inserting submaximal tests in his clinical practice.

Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment.

PURPOSE: Dapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance. METHODS: DH-TENV formulations were prepared using an injection- sonication method and optimized using a 33 Box-Behnken-design with Design Expert® software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RA-specific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-Β ligand (RANKL) were also assessed. RESULTS: The optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE- % and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42- and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid. CONCLUSION: The results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.