Audrey D Nguyen, Zsuzsanna H McMahan, Elizabeth R Volkmann
Purpose: The primary aim is to identify the micronutrient deficiencies commonly reported in SSc. The exploratory aim is to evaluate associations between micronutrient deficiencies and SSc clinical manifestations.
Patient and methods: We conducted a scoping review of all published reports on SSc and nutrition in PubMed from its inception to August 2020. Clinical trials, observational studies, meta-analyses, and case series (with ≥20 cases) containing data on nutritional deficiency and SSc were included. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for reporting our findings. Two reviewers (ADN and ERV) studied the titles and abstracts of all search results with pre-specified inclusion and exclusion criteria.
Results: Among 790 retrieved publications, 35 full-length articles and 3 abstracts met the inclusion/exclusion criteria. Included studies took place across multiple geographic locations and included patients with both diffuse and limited cutaneous SSc. Vitamin D deficiency was the most commonly reported deficiency described in SSc, followed by vitamin B12, vitamin B9, selenium, zinc, and iron. In addition, some small studies found deficiencies in vitamins B1, B6, C, E, and A. While some studies reported associations between specific micronutrient deficiencies and SSc disease features (eg, interstitial lung disease was commonly associated with vitamin D deficiency and elevated homocysteine [Hcy]), the evidence to support these associations was not robust.
Conclusion: Micronutrient deficiencies are common in SSc and are associated with specific SSc features. Routine screening for micronutrient deficiencies may lead to early detection of malnutrition. Future studies are needed to understand how interventions to replete micronutrient deficiencies affect patient outcomes in SSc.
{"title":"Micronutrient Deficiencies in Systemic Sclerosis: A Scoping Review.","authors":"Audrey D Nguyen, Zsuzsanna H McMahan, Elizabeth R Volkmann","doi":"10.2147/OARRR.S354736","DOIUrl":"https://doi.org/10.2147/OARRR.S354736","url":null,"abstract":"<p><strong>Purpose: </strong>The primary aim is to identify the micronutrient deficiencies commonly reported in SSc. The exploratory aim is to evaluate associations between micronutrient deficiencies and SSc clinical manifestations.</p><p><strong>Patient and methods: </strong>We conducted a scoping review of all published reports on SSc and nutrition in PubMed from its inception to August 2020. Clinical trials, observational studies, meta-analyses, and case series (with ≥20 cases) containing data on nutritional deficiency and SSc were included. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for reporting our findings. Two reviewers (ADN and ERV) studied the titles and abstracts of all search results with pre-specified inclusion and exclusion criteria.</p><p><strong>Results: </strong>Among 790 retrieved publications, 35 full-length articles and 3 abstracts met the inclusion/exclusion criteria. Included studies took place across multiple geographic locations and included patients with both diffuse and limited cutaneous SSc. Vitamin D deficiency was the most commonly reported deficiency described in SSc, followed by vitamin B12, vitamin B9, selenium, zinc, and iron. In addition, some small studies found deficiencies in vitamins B1, B6, C, E, and A. While some studies reported associations between specific micronutrient deficiencies and SSc disease features (eg, interstitial lung disease was commonly associated with vitamin D deficiency and elevated homocysteine [Hcy]), the evidence to support these associations was not robust.</p><p><strong>Conclusion: </strong>Micronutrient deficiencies are common in SSc and are associated with specific SSc features. Routine screening for micronutrient deficiencies may lead to early detection of malnutrition. Future studies are needed to understand how interventions to replete micronutrient deficiencies affect patient outcomes in SSc.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"14 ","pages":"309-327"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/05/oarrr-14-309.PMC9769137.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ben Ochola, Joaniter Nankabirwa, William Buwembo, Mark Kaddumukasa, Harriet Mayanja-Kizza
Background: Rheumatoid arthritis (RA) is a chronic, debilitating disease that leads to joint destruction and disability if left untreated. Few studies on RA have been conducted in Uganda, and there is limited information on disease severity and associated factors. This study sought to characterize the clinical presentation and to determine disease severity and the factors associated with disease severity among participants with RA in Uganda.
Methods: Between August 2018 and February 2019, patients presenting to the rheumatology outpatient clinic in Mulago National Referral Hospital were enrolled into the study using a cross-sectional design. Participants' demographics and clinical characteristics were collected using a study questionnaire, and laboratory results were extracted from their charts. The patients' functionality was assessed using the Modified Health Assessment Questionnaire and their disease severity was assessed using the RA Disease Activity Score based on 28-joint count (DAS28).
Results: A total of 170 participants were enrolled, of whom 81.2% were female. Nearly two-thirds (111/170) were classified as having severe disease. Having a functional status score of >0.5 (adjusted odds ratio 1.7, 95% confidence interval 1.4-2.2, p<0.001) was significantly associated with severe disease.
Conclusion: In this population, the majority of the patients seen at the rheumatology outpatient clinic had severe disease, suggesting that patients may be presenting late, with limited early detection of the disease. Impaired functional status was associated with increased disease severity and may be used by clinicians to highlight disease severity when it is not possible to assess the RA DAS28.
{"title":"The Clinical Presentation and Factors Associated with Disease Severity of Rheumatoid Arthritis in Uganda: A Cross-Sectional Study.","authors":"Ben Ochola, Joaniter Nankabirwa, William Buwembo, Mark Kaddumukasa, Harriet Mayanja-Kizza","doi":"10.2147/OARRR.S361454","DOIUrl":"https://doi.org/10.2147/OARRR.S361454","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic, debilitating disease that leads to joint destruction and disability if left untreated. Few studies on RA have been conducted in Uganda, and there is limited information on disease severity and associated factors. This study sought to characterize the clinical presentation and to determine disease severity and the factors associated with disease severity among participants with RA in Uganda.</p><p><strong>Methods: </strong>Between August 2018 and February 2019, patients presenting to the rheumatology outpatient clinic in Mulago National Referral Hospital were enrolled into the study using a cross-sectional design. Participants' demographics and clinical characteristics were collected using a study questionnaire, and laboratory results were extracted from their charts. The patients' functionality was assessed using the Modified Health Assessment Questionnaire and their disease severity was assessed using the RA Disease Activity Score based on 28-joint count (DAS28).</p><p><strong>Results: </strong>A total of 170 participants were enrolled, of whom 81.2% were female. Nearly two-thirds (111/170) were classified as having severe disease. Having a functional status score of >0.5 (adjusted odds ratio 1.7, 95% confidence interval 1.4-2.2, <i>p</i><0.001) was significantly associated with severe disease.</p><p><strong>Conclusion: </strong>In this population, the majority of the patients seen at the rheumatology outpatient clinic had severe disease, suggesting that patients may be presenting late, with limited early detection of the disease. Impaired functional status was associated with increased disease severity and may be used by clinicians to highlight disease severity when it is not possible to assess the RA DAS28.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"14 ","pages":"75-86"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/a2/oarrr-14-75.PMC9078424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9131614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-09eCollection Date: 2021-01-01DOI: 10.2147/OARRR.S335206
Sulafah Abdelgalil Ali Ahmed, Mohammed Elmujtba Adam Essa, Amar F Ahmed, Elnour Mohammed Elagib, Noha Ibrahim Ahmed Eltahir, Huyam Awadallah, Abubakr Hassan, Amna Sirag Mohammed Khair, Mustafa Abdalla Bakhit Ebad
Background: Mixed connective tissue disease (MCTD) is a rare autoimmune disease, characterized by the production of specific autoantibody anti-RNP, which presents with varied overlapping symptoms of different connective tissue disorders. The aim of this study is to identify the frequency and patterns of MCTD.
Methods: This is a descriptive cross-sectional hospital-based study conducted at the rheumatology clinic at Omdurman Military Hospital between February 2019 and July 2019. The study included 30 patients and data were collected using a designated questionnaire.
Results: The study showed that the majority of patients (96.7%) were females and only 3.3% was male. About 30% of the patients aged between 30 and 39 years were the most affected. As a first diagnosis, 10% of the patients had a MCTD fulfilling the Alarcon-Segovia criteria. The remaining 90% of the patients were diagnosed with other diseases before evolving into MCTD. The most common clinical presentation was arthralgia in 100% of the patients, 90% were symmetrically followed by myositis in 70% of the patients, arthritis in 63.3% of the patients, puffy fingers in 63.3% of the patients, and hand swelling in 60% as major musculoskeletal symptoms. Regarding the initial results in immunological profile, the most common positive autoantibodies among the patients were anti-RNP titer in 96.7% of the patients, ANA in 90%, anti-Sm in 50%, RF in 50%, anti-Ds DNA in 46.7%, and anti-Ro in 43.3%.
Conclusion: This study showed that MCTD is more common in females, only 10% of patients presented with a fulfilling criteria of the disease at diagnosis, and the rest of the patients presented with other rheumatologic diseases before evolving into MCTD.
{"title":"Incidence and Clinical Pattern of Mixed Connective Tissue Disease in Sudanese Patients at Omdurman Military Hospital: Hospital-Based Study.","authors":"Sulafah Abdelgalil Ali Ahmed, Mohammed Elmujtba Adam Essa, Amar F Ahmed, Elnour Mohammed Elagib, Noha Ibrahim Ahmed Eltahir, Huyam Awadallah, Abubakr Hassan, Amna Sirag Mohammed Khair, Mustafa Abdalla Bakhit Ebad","doi":"10.2147/OARRR.S335206","DOIUrl":"https://doi.org/10.2147/OARRR.S335206","url":null,"abstract":"<p><strong>Background: </strong>Mixed connective tissue disease (MCTD) is a rare autoimmune disease, characterized by the production of specific autoantibody anti-RNP, which presents with varied overlapping symptoms of different connective tissue disorders. The aim of this study is to identify the frequency and patterns of MCTD.</p><p><strong>Methods: </strong>This is a descriptive cross-sectional hospital-based study conducted at the rheumatology clinic at Omdurman Military Hospital between February 2019 and July 2019. The study included 30 patients and data were collected using a designated questionnaire.</p><p><strong>Results: </strong>The study showed that the majority of patients (96.7%) were females and only 3.3% was male. About 30% of the patients aged between 30 and 39 years were the most affected. As a first diagnosis, 10% of the patients had a MCTD fulfilling the Alarcon-Segovia criteria. The remaining 90% of the patients were diagnosed with other diseases before evolving into MCTD. The most common clinical presentation was arthralgia in 100% of the patients, 90% were symmetrically followed by myositis in 70% of the patients, arthritis in 63.3% of the patients, puffy fingers in 63.3% of the patients, and hand swelling in 60% as major musculoskeletal symptoms. Regarding the initial results in immunological profile, the most common positive autoantibodies among the patients were anti-RNP titer in 96.7% of the patients, ANA in 90%, anti-Sm in 50%, RF in 50%, anti-Ds DNA in 46.7%, and anti-Ro in 43.3%.</p><p><strong>Conclusion: </strong>This study showed that MCTD is more common in females, only 10% of patients presented with a fulfilling criteria of the disease at diagnosis, and the rest of the patients presented with other rheumatologic diseases before evolving into MCTD.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"333-341"},"PeriodicalIF":2.1,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/17/oarrr-13-333.PMC8668256.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39845178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. I. Sarbu, N. Sârbu, Doriana Cristea Ene, Daniela Corche, R. Baz, D. Negru, A. Nechita, S. Fotea, Lucreţia Anghel, A. Tatu
Abstract Psoriatic arthritis is a chronic inflammatory condition that can lead to severe functional impairment and irreversible damage. The diagnosis can be difficult in early cases where the clinical exam is often scarce. The lack of a serological biomarker can lead to a considerable delay in diagnosis. In this review, we discuss the existent imaging methods that have improved the diagnosis of psoriatic arthritis (PsA). The degree and type of musculoskeletal involvement cannot be assessed by only one imaging method. We think that a combination of methods is the best approach to evaluate both structural damage and inflammatory lesions and that ultrasound (US) could be the best tool to screen a patient when considering the diagnosis of PsA. US is an accessible, non-ionizing technique that offers information regarding active inflammation in joints, entheses, and soft tissues.
{"title":"New Perspectives on Diagnosing Psoriatic Arthritis by Imaging Techniques","authors":"M. I. Sarbu, N. Sârbu, Doriana Cristea Ene, Daniela Corche, R. Baz, D. Negru, A. Nechita, S. Fotea, Lucreţia Anghel, A. Tatu","doi":"10.2147/OARRR.S331859","DOIUrl":"https://doi.org/10.2147/OARRR.S331859","url":null,"abstract":"Abstract Psoriatic arthritis is a chronic inflammatory condition that can lead to severe functional impairment and irreversible damage. The diagnosis can be difficult in early cases where the clinical exam is often scarce. The lack of a serological biomarker can lead to a considerable delay in diagnosis. In this review, we discuss the existent imaging methods that have improved the diagnosis of psoriatic arthritis (PsA). The degree and type of musculoskeletal involvement cannot be assessed by only one imaging method. We think that a combination of methods is the best approach to evaluate both structural damage and inflammatory lesions and that ultrasound (US) could be the best tool to screen a patient when considering the diagnosis of PsA. US is an accessible, non-ionizing technique that offers information regarding active inflammation in joints, entheses, and soft tissues.","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 1","pages":"343 - 352"},"PeriodicalIF":2.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48797270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-30eCollection Date: 2021-01-01DOI: 10.2147/OARRR.S339134
Ahmed Seri, Hala Kamal Ali Mohamed, Mohammed Elmujtba Adam Essa, Elnour Mohammed Elagib, Noha Ibrahim Ahmed Eltahirm, Salma Mohammed Alfatih Mansour, Abdelkareem A Ahmed
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovial membrane. RA is classified as seropositive or seronegative, according to the absence or presence of primarily IgM RF, RF, and/or ACPA. The aim of this study is to identify the relationship between the serotype of rheumatoid arthritis and the level of ESR.
Methods and materials: This is a descriptive, cross-sectional study done in Omdurman military hospital, Khartoum, Sudan. Conducted with 60 patients with RA, data were collected through a designated questionnaire which included demographic, age, gender, duration of the disease, laboratory finding. All the patients in the study were treated with conventional DMARDs and diagnosed according to the 2010 ACR/EULAR criteria; their disease activity status was assessed by DAS28/ESR. Data were analyzed using SPSS version 23.
Results: The study found that 91.7% of the patients were females, patients of age group between 36 and 50 years had the highest percentage at 38.3% followed by those between 51 and 70 years and the least age group between 20 and 35 years, 36.7% and 15%, respectively. Of all the patients 61.7% were found to be SPRA, while the remaining 38.3% were seronegative (SNRA). Altogether 55% of the patients had moderate disease activity, followed by 16.7% who had a remission, 15% had high disease activity and the remaining 13.3% had low disease activity. The metacarpophalangeal (MCP) joint was found to be the only joint that was significantly associated with DAS28 and its involvement was greater among seropositive patients. The most affected joints were found to be shoulders, knees, wrist, MCP, PIP and elbow, in that order.
Conclusion: Females, middle-age group and shoulder joint were the most affected. Most RA was found to be SPRA, and the seropositive group was found to be more associated with high disease activity, while the seronegative group was associated with remission and low disease activity.
类风湿关节炎(RA)是一种以滑膜炎症为特征的慢性自身免疫性疾病。根据主要IgM、RF、RF和/或ACPA是否存在,RA分为血清阳性或血清阴性。本研究的目的是确定类风湿关节炎血清型与ESR水平之间的关系。方法和材料:这是在苏丹喀土穆的恩图曼军事医院进行的一项描述性横断面研究。对60名RA患者进行研究,通过指定的问卷收集数据,包括人口统计、年龄、性别、疾病持续时间、实验室结果。研究中所有患者均接受常规dmard治疗,并根据2010年ACR/EULAR标准进行诊断;采用DAS28/ESR评估其疾病活动状态。数据分析采用SPSS version 23。结果:研究发现,女性占91.7%,36 ~ 50岁患者比例最高,为38.3%,51 ~ 70岁患者比例次之,20 ~ 35岁患者比例最低,分别为36.7%和15%。SPRA阳性率为61.7%,SNRA阳性率为38.3%。总共55%的患者有中度疾病活动性,其次是16.7%的患者有缓解,15%的患者有高疾病活动性,其余13.3%的患者有低疾病活动性。发现掌指关节(MCP)是唯一与DAS28显著相关的关节,其累及程度在血清阳性患者中更大。受影响最大的关节依次是肩膀、膝盖、手腕、MCP、PIP和肘关节。结论:以女性、中年人和肩关节为主。大多数RA被发现为SPRA,血清阳性组与高疾病活动性相关,而血清阴性组与缓解和低疾病活动性相关。
{"title":"Analysis of Serum Immune Markers in Seropositive and Seronegative Rheumatoid Arthritis Among Sudanese Patients and the Relation Between the Serotype and Joint Involvement: A Cohort Study.","authors":"Ahmed Seri, Hala Kamal Ali Mohamed, Mohammed Elmujtba Adam Essa, Elnour Mohammed Elagib, Noha Ibrahim Ahmed Eltahirm, Salma Mohammed Alfatih Mansour, Abdelkareem A Ahmed","doi":"10.2147/OARRR.S339134","DOIUrl":"https://doi.org/10.2147/OARRR.S339134","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovial membrane. RA is classified as seropositive or seronegative, according to the absence or presence of primarily IgM RF, RF, and/or ACPA. The aim of this study is to identify the relationship between the serotype of rheumatoid arthritis and the level of ESR.</p><p><strong>Methods and materials: </strong>This is a descriptive, cross-sectional study done in Omdurman military hospital, Khartoum, Sudan. Conducted with 60 patients with RA, data were collected through a designated questionnaire which included demographic, age, gender, duration of the disease, laboratory finding. All the patients in the study were treated with conventional DMARDs and diagnosed according to the 2010 ACR/EULAR criteria; their disease activity status was assessed by DAS28/ESR. Data were analyzed using SPSS version 23.</p><p><strong>Results: </strong>The study found that 91.7% of the patients were females, patients of age group between 36 and 50 years had the highest percentage at 38.3% followed by those between 51 and 70 years and the least age group between 20 and 35 years, 36.7% and 15%, respectively. Of all the patients 61.7% were found to be SPRA, while the remaining 38.3% were seronegative (SNRA). Altogether 55% of the patients had moderate disease activity, followed by 16.7% who had a remission, 15% had high disease activity and the remaining 13.3% had low disease activity. The metacarpophalangeal (MCP) joint was found to be the only joint that was significantly associated with DAS28 and its involvement was greater among seropositive patients. The most affected joints were found to be shoulders, knees, wrist, MCP, PIP and elbow, in that order.</p><p><strong>Conclusion: </strong>Females, middle-age group and shoulder joint were the most affected. Most RA was found to be SPRA, and the seropositive group was found to be more associated with high disease activity, while the seronegative group was associated with remission and low disease activity.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"325-332"},"PeriodicalIF":2.1,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/13/oarrr-13-325.PMC8643210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39578635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-15eCollection Date: 2021-01-01DOI: 10.2147/OARRR.S329766
Kyle Hayes, Mary P Panaccio, Parul Houston, John Niewoehner, Mohammed Fahim, George J Wan, Bhavna Dhillon
Purpose: Repository corticotropin injection (RCI; Acthar® Gel) is a naturally sourced mixture of adrenocorticotropic hormone analogs and other pituitary peptides that exerts anti-inflammatory and immunomodulatory properties via melanocortin receptors. RCI is approved as a short-term adjunctive therapy for rheumatoid arthritis (RA) and is typically used in patients with refractory RA. The objective of this study was to describe real-world outcomes of RA patients treated with RCI by retrospective analysis of an electronic medical records (EMR) database.
Patients and methods: EMR data were obtained from the United Rheumatology-Normal Integrated Community Evidence (UR-NICETM) data repository for patients who used RCI for the treatment of RA. Demographics, comorbidities, disease history, medications, and laboratory evaluations 365 days prior to and 365 days after initiation of RCI were examined.
Results: The patient cohort was predominantly White females with a mean age of 60 years and high RA activity prior to RCI therapy. Clinical measures of disease severity indicated that patients had high RA activity before starting RCI therapy. Clinical Disease Activity Index (CDAI) scores were significantly reduced 365 days post-initiation of RCI. Swollen and tender joint counts and patient-reported outcomes, including Routine Assessment of Patient Index Data 3 (RAPID3), Physician Global Assessment, and patient assessment of pain severity were also significantly lower. The number of patients taking conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), biologic (b) DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDS), and opioids decreased, as did the number of drugs tried within each class for csDMARDs, bDMARDs, NSAIDs, and glucocorticoids.
Conclusions: These findings suggest that RCI significantly improves clinical outcomes of RA and decreases the need for concomitant medications for up to 1 year following initiation of therapy. The study provides valuable insights into the use of RCI and management of these difficult-to-treat RA patients during routine clinical practice.
目的蓄积性促肾上腺皮质激素注射液(RCI;Acthar® Gel)是一种天然来源的促肾上腺皮质激素类似物和其他垂体肽混合物,可通过黑色素皮质素受体发挥抗炎和免疫调节作用。RCI 已被批准作为类风湿性关节炎(RA)的短期辅助疗法,通常用于难治性 RA 患者。本研究的目的是通过对电子病历(EMR)数据库进行回顾性分析,描述接受 RCI 治疗的 RA 患者的实际疗效:患者和方法:从联合风湿病学-正常综合社区证据(UR-NICETM)数据存储库中获取了使用RCI治疗RA患者的EMR数据。研究人员对患者的人口统计学特征、合并症、疾病史、用药情况以及开始使用 RCI 之前 365 天和之后 365 天的实验室评估进行了研究:患者主要为白人女性,平均年龄为 60 岁,接受 RCI 治疗前的 RA 活动度较高。疾病严重程度的临床测量结果表明,患者在开始接受 RCI 治疗前具有较高的 RA 活动度。临床疾病活动指数(CDAI)评分在开始 RCI 治疗后的 365 天内显著降低。关节肿胀和触痛次数以及患者报告的结果(包括患者指数数据常规评估 3 (RAPID3)、医生总体评估和患者疼痛严重程度评估)也明显降低。服用传统合成(cs)改良抗风湿药(DMARDs)、生物(b)DMARDs、非甾体抗炎药(NSAIDS)和阿片类药物的患者人数减少,csDMARDs、bDMARDs、NSAIDs和糖皮质激素每类药物的尝试次数也减少:这些研究结果表明,RCI 能显著改善 RA 的临床疗效,并能在开始治疗后的一年内减少对伴随药物的需求。这项研究为在常规临床实践中使用RCI和管理这些难以治疗的RA患者提供了宝贵的见解。
{"title":"Real-World Treatment Patterns and Outcomes from an Electronic Medical Records Database for Patients with Rheumatoid Arthritis Treated with Repository Corticotropin Injection.","authors":"Kyle Hayes, Mary P Panaccio, Parul Houston, John Niewoehner, Mohammed Fahim, George J Wan, Bhavna Dhillon","doi":"10.2147/OARRR.S329766","DOIUrl":"10.2147/OARRR.S329766","url":null,"abstract":"<p><strong>Purpose: </strong>Repository corticotropin injection (RCI; Acthar<sup>®</sup> Gel) is a naturally sourced mixture of adrenocorticotropic hormone analogs and other pituitary peptides that exerts anti-inflammatory and immunomodulatory properties via melanocortin receptors. RCI is approved as a short-term adjunctive therapy for rheumatoid arthritis (RA) and is typically used in patients with refractory RA. The objective of this study was to describe real-world outcomes of RA patients treated with RCI by retrospective analysis of an electronic medical records (EMR) database.</p><p><strong>Patients and methods: </strong>EMR data were obtained from the United Rheumatology-Normal Integrated Community Evidence (UR-NICE<sup>TM</sup>) data repository for patients who used RCI for the treatment of RA. Demographics, comorbidities, disease history, medications, and laboratory evaluations 365 days prior to and 365 days after initiation of RCI were examined.</p><p><strong>Results: </strong>The patient cohort was predominantly White females with a mean age of 60 years and high RA activity prior to RCI therapy. Clinical measures of disease severity indicated that patients had high RA activity before starting RCI therapy. Clinical Disease Activity Index (CDAI) scores were significantly reduced 365 days post-initiation of RCI. Swollen and tender joint counts and patient-reported outcomes, including Routine Assessment of Patient Index Data 3 (RAPID3), Physician Global Assessment, and patient assessment of pain severity were also significantly lower. The number of patients taking conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), biologic (b) DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDS), and opioids decreased, as did the number of drugs tried within each class for csDMARDs, bDMARDs, NSAIDs, and glucocorticoids.</p><p><strong>Conclusions: </strong>These findings suggest that RCI significantly improves clinical outcomes of RA and decreases the need for concomitant medications for up to 1 year following initiation of therapy. The study provides valuable insights into the use of RCI and management of these difficult-to-treat RA patients during routine clinical practice.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"315-323"},"PeriodicalIF":2.1,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/72/oarrr-13-315.PMC8526946.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39564092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To detect the prevalence of hyperuricemia in Egyptian rheumatoid arthritis (RA) patients as well as to assess its association with the severity of joint inflammation and disease-modifying antirheumatic drugs (DMARDs) in those patients.
Methods: A total of 150 RA patients were recruited; all patients were subjected to (1) clinical and functional assessment by disease activity score in 28 joints (DAS28) and modified health assessment questionnaire (MHAQ). (2) Laboratory investigations: serum uric acid (SUA) level, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), tumor necrosis factor α (TNF-α), interleukin 1 (IL1), and interleukin 6 (IL6) levels. (3) Radiological evaluation: (A) plain X-ray of both hands and feet; (B) musculoskeletal ultrasound (MSUS) of both wrists, hands, shoulder, ankle, and knee joints.
Results: SUA was significantly correlated with disease activity by DAS28. Acute-phase reactants and inflammatory markers (IL1β, IL6, and TNF-α) were also significantly elevated in RA patients with low and high hyperuricemia compared to those with normal SUA. A total of 90% of RA patients with low hyperuricemia had synovial proliferation with power Doppler (1+ and 2+), and 30 patients had mild effusion (1+), while nearly all patients with high hyperuricemia had hypoechoic synovial proliferation (2+ and 3+), and 20 patients had moderate effusion. However, 70% RA patients with normal serum uric acid showed mild synovitis and effusion (1+). No significant association was found between the administered DMARDs and levels of SUA as well as inflammatory markers; however, high-dose steroid treatment was associated with high SUA level.
Conclusion: Elevation of serum uric acid levels in Egyptian RA patients was prevalent and might be an inflammatory marker for severity of joint inflammation. Moreover, higher doses of steroids could be considered a cause of hyperuricemia.
{"title":"Hyperuricemia Among Egyptian Rheumatoid Arthritis Patients. Is It an Association or an Inflammatory Marker? A Cross-Sectional Observational Study.","authors":"Doaa Nada, Rasha Gaber, Al Shymaa Mahmoud, Radwa Elkhouly, Doaa Alashkar","doi":"10.2147/OARRR.S331488","DOIUrl":"10.2147/OARRR.S331488","url":null,"abstract":"<p><strong>Objective: </strong>To detect the prevalence of hyperuricemia in Egyptian rheumatoid arthritis (RA) patients as well as to assess its association with the severity of joint inflammation and disease-modifying antirheumatic drugs (DMARDs) in those patients.</p><p><strong>Methods: </strong>A total of 150 RA patients were recruited; all patients were subjected to (1) clinical and functional assessment by disease activity score in 28 joints (DAS28) and modified health assessment questionnaire (MHAQ). (2) Laboratory investigations: serum uric acid (SUA) level, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), tumor necrosis factor α (TNF-α), interleukin 1 (IL1), and interleukin 6 (IL6) levels. (3) Radiological evaluation: (A) plain X-ray of both hands and feet; (B) musculoskeletal ultrasound (MSUS) of both wrists, hands, shoulder, ankle, and knee joints.</p><p><strong>Results: </strong>SUA was significantly correlated with disease activity by DAS28. Acute-phase reactants and inflammatory markers (IL1β, IL6, and TNF-α) were also significantly elevated in RA patients with low and high hyperuricemia compared to those with normal SUA. A total of 90% of RA patients with low hyperuricemia had synovial proliferation with power Doppler (1+ and 2+), and 30 patients had mild effusion (1+), while nearly all patients with high hyperuricemia had hypoechoic synovial proliferation (2+ and 3+), and 20 patients had moderate effusion. However, 70% RA patients with normal serum uric acid showed mild synovitis and effusion (1+). No significant association was found between the administered DMARDs and levels of SUA as well as inflammatory markers; however, high-dose steroid treatment was associated with high SUA level.</p><p><strong>Conclusion: </strong>Elevation of serum uric acid levels in Egyptian RA patients was prevalent and might be an inflammatory marker for severity of joint inflammation. Moreover, higher doses of steroids could be considered a cause of hyperuricemia.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"305-314"},"PeriodicalIF":2.1,"publicationDate":"2021-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/e7/oarrr-13-305.PMC8502065.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39540233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-28eCollection Date: 2021-01-01DOI: 10.2147/OARRR.S328211
Yoshio Ozaki, Shosaku Nomura
The treatment of connective tissue disease (CTD) and CTD-related intractable diseases (CTD-IDs) currently depends on the use of steroid therapy. Approximately 20 years have passed since the approval of infliximab for rheumatoid arthritis in 2003. Since then, several biological therapeutics have been marketed and adapted for many CTDs and CTD-IDs other than rheumatoid arthritis. Although conventional treatment for patients with these diseases is rarely used because of their poor prognosis, these cases may benefit from biological therapeutics. However, choosing biological therapeutics is difficult because they have different target molecules compared with conventional therapeutics. In this review, we address the current situation of biological therapeutics for CTD-IDs including Behcet's disease, psoriatic arthritis, ankylosing spondylitis, anti-neutrophil cytoplasmic antibody-related arthritis, and adult Still's disease, as well as the choice of biological therapeutics in clinical practice.
{"title":"Treatment of Connective Tissue Disease-Related Intractable Disease with Biological Therapeutics.","authors":"Yoshio Ozaki, Shosaku Nomura","doi":"10.2147/OARRR.S328211","DOIUrl":"https://doi.org/10.2147/OARRR.S328211","url":null,"abstract":"<p><p>The treatment of connective tissue disease (CTD) and CTD-related intractable diseases (CTD-IDs) currently depends on the use of steroid therapy. Approximately 20 years have passed since the approval of infliximab for rheumatoid arthritis in 2003. Since then, several biological therapeutics have been marketed and adapted for many CTDs and CTD-IDs other than rheumatoid arthritis. Although conventional treatment for patients with these diseases is rarely used because of their poor prognosis, these cases may benefit from biological therapeutics. However, choosing biological therapeutics is difficult because they have different target molecules compared with conventional therapeutics. In this review, we address the current situation of biological therapeutics for CTD-IDs including Behcet's disease, psoriatic arthritis, ankylosing spondylitis, anti-neutrophil cytoplasmic antibody-related arthritis, and adult Still's disease, as well as the choice of biological therapeutics in clinical practice.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"293-303"},"PeriodicalIF":2.1,"publicationDate":"2021-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/05/oarrr-13-293.PMC8487282.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39489856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-18eCollection Date: 2021-01-01DOI: 10.2147/OARRR.S331562
Georgia Carney, Andrew Harrison, Jane Fitzpatrick
Purpose: To determine the duration of symptom relief following repeated administration of hyaluronic acid injections for osteoarthritis.
Patients and methods: This was a 6-year observational study with 623 consecutive patients who had received hyaluronic acid injections. The primary outcome measure was the mean time between injections measured in days. Classical one-sample 2-sided t-tests, one-way analysis of variances and post-hoc analyses were performed to determine if there were statistically significant differences between age, gender, radiographic severity and the type of joints injected. All patients were invited to complete an online post-treatment experience and satisfaction survey.
Results: The analysis included 727 joints (mean Kellgren-Lawrence grade, 2.9 ± 0.8 (range 2-4)) in 623 patients (297 (47.7%) male; mean age at first injection, 57.8 ± 12.7 years (range 21.2-92.1)). Patients ranged from having 1-8 injections per joint. The mean time between injections in days was 466.8 ± 321.7 (2nd injection, 157 joints), 400.5 ± 164.7 (3rd injection, 58 joints), 378.2 ± 223.1 (4th injection, 27 joints), 405.3 ± 216.3 (5th injection, 7 joints), 268.4 ± 104.4 (6th injection, 5 joints), 289.8 ± 99.4 (7th injection, 4 joints), and 272.5 ± 33.2 (8th injection, 2 joints). Patients with grades 2 and 3 compared to grade 4 osteoarthritis experienced a longer time between injections (F (2, 154) = 3.53, p = 0.0316). No statistically significant differences were observed between age, gender, or joint groups. The survey included 233 participants (109 (46.8% male)). A total of 144 respondents (64.9%) recommended hyaluronic acid injections for osteoarthritis.
Conclusion: Pain relief from hyaluronic acid injections was sustained for on average 466.8 days post initial treatment. Patients who received subsequent 3rd, 4th, and 5th injections also experienced extended duration of benefit. Patients with grades 2 or 3 osteoarthritis are more likely to experience a longer duration of relief.
目的:确定反复注射透明质酸治疗骨关节炎后症状缓解的持续时间。患者和方法:这是一项为期6年的观察性研究,共有623名连续接受透明质酸注射的患者。主要结局指标是注射间隔的平均时间(以天为单位)。进行经典的单样本双侧t检验、单因素方差分析和事后分析,以确定年龄、性别、放射学严重性和注射关节类型之间是否存在统计学上的显著差异。所有患者被邀请完成在线治疗后体验和满意度调查。结果:623例患者共纳入727个关节(平均Kellgren-Lawrence评分2.9±0.8(范围2-4)),其中男性297例(47.7%);平均首次注射年龄57.8±12.7岁(范围21.2 ~ 92.1)。患者每个关节注射1-8次不等。平均注射间隔时间为466.8±321.7(第2次注射,157个关节)、4000.5±164.7(第3次注射,58个关节)、378.2±223.1(第4次注射,27个关节)、405.3±216.3(第5次注射,7个关节)、268.4±104.4(第6次注射,5个关节)、289.8±99.4(第7次注射,4个关节)、272.5±33.2(第8次注射,2个关节)。与4级骨关节炎患者相比,2级和3级骨关节炎患者的注射间隔时间更长(F (2,154) = 3.53, p = 0.0316)。在年龄、性别或关节组之间没有统计学上的显著差异。调查对象共有233人,其中109人(46.8%为男性)。共有144名受访者(64.9%)推荐注射透明质酸治疗骨关节炎。结论:透明质酸注射后疼痛缓解持续时间平均为466.8天。随后接受第3次、第4次和第5次注射的患者也经历了延长的获益时间。2级或3级骨关节炎患者更有可能经历更长的缓解时间。
{"title":"Long-Term Outcome Measures of Repeated Non-Animal Stabilized Hyaluronic Acid (Durolane) Injections in Osteoarthritis: A 6-Year Cohort Study with 623 Consecutive Patients.","authors":"Georgia Carney, Andrew Harrison, Jane Fitzpatrick","doi":"10.2147/OARRR.S331562","DOIUrl":"https://doi.org/10.2147/OARRR.S331562","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the duration of symptom relief following repeated administration of hyaluronic acid injections for osteoarthritis.</p><p><strong>Patients and methods: </strong>This was a 6-year observational study with 623 consecutive patients who had received hyaluronic acid injections. The primary outcome measure was the mean time between injections measured in days. Classical one-sample 2-sided <i>t</i>-tests, one-way analysis of variances and post-hoc analyses were performed to determine if there were statistically significant differences between age, gender, radiographic severity and the type of joints injected. All patients were invited to complete an online post-treatment experience and satisfaction survey.</p><p><strong>Results: </strong>The analysis included 727 joints (mean Kellgren-Lawrence grade, 2.9 ± 0.8 (range 2-4)) in 623 patients (297 (47.7%) male; mean age at first injection, 57.8 ± 12.7 years (range 21.2-92.1)). Patients ranged from having 1-8 injections per joint. The mean time between injections in days was 466.8 ± 321.7 (2nd injection, 157 joints), 400.5 ± 164.7 (3rd injection, 58 joints), 378.2 ± 223.1 (4th injection, 27 joints), 405.3 ± 216.3 (5th injection, 7 joints), 268.4 ± 104.4 (6th injection, 5 joints), 289.8 ± 99.4 (7th injection, 4 joints), and 272.5 ± 33.2 (8th injection, 2 joints). Patients with grades 2 and 3 compared to grade 4 osteoarthritis experienced a longer time between injections (F (2, 154) = 3.53, p = 0.0316). No statistically significant differences were observed between age, gender, or joint groups. The survey included 233 participants (109 (46.8% male)). A total of 144 respondents (64.9%) recommended hyaluronic acid injections for osteoarthritis.</p><p><strong>Conclusion: </strong>Pain relief from hyaluronic acid injections was sustained for on average 466.8 days post initial treatment. Patients who received subsequent 3rd, 4th, and 5th injections also experienced extended duration of benefit. Patients with grades 2 or 3 osteoarthritis are more likely to experience a longer duration of relief.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"285-292"},"PeriodicalIF":2.1,"publicationDate":"2021-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/a2/oarrr-13-285.PMC8457651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39451336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-14eCollection Date: 2021-01-01DOI: 10.2147/OARRR.S329178
Alan Morrison, Melissa E Stauffer, Anna S Kaufman
Introduction: Patients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug's therapeutic effect remains unclear.
Methods: After weekly oral dosing of methotrexate (MTX) for rheumatoid arthritis, its polyglutamate derivatives (MTXglu) accumulate in red blood cells, where they are markers for the drug's therapeutic effectiveness. We used Medication Event Monitoring System data and pharmacokinetic modeling to analyze whether missing MTX doses causes the MTXglu level in red blood cells to fall below the range associated with the drug's clinical effect.
Results: For patients initiating oral MTX, the threshold for clinical effectiveness and the steady state level were reached in medians of 6 weeks and 22 weeks, respectively. For patients at steady state who discontinued MTX, the MTXglu level fell below the therapeutic threshold after a median of 3 weeks. After initiating MTX, single missed doses did not cause a loss of therapeutic effect in the median patient if they occurred after 10 weeks, while runs of ≥3 consecutive missed doses did cause the MTXglu level to fall below the therapeutic threshold.
Conclusion: While there is considerable variation between patients, pharmacokinetic modeling indicates that instances of isolated single missed doses of MTX typically will not cause polyglutamated methotrexate levels in red blood cells to fall below the range associated with the therapeutic effect. Runs of ≥3 consecutive missed doses, however, are typically expected to result in a loss of the therapeutic effect.
{"title":"Effect of Missed Doses on the Therapeutic Effect of Methotrexate for Rheumatoid Arthritis: A Pharmacokinetic Modeling Study.","authors":"Alan Morrison, Melissa E Stauffer, Anna S Kaufman","doi":"10.2147/OARRR.S329178","DOIUrl":"https://doi.org/10.2147/OARRR.S329178","url":null,"abstract":"<p><strong>Introduction: </strong>Patients rarely, if ever, take their medications exactly as prescribed. The extent to which missed doses interfere with a drug's therapeutic effect remains unclear.</p><p><strong>Methods: </strong>After weekly oral dosing of methotrexate (MTX) for rheumatoid arthritis, its polyglutamate derivatives (MTXglu) accumulate in red blood cells, where they are markers for the drug's therapeutic effectiveness. We used Medication Event Monitoring System data and pharmacokinetic modeling to analyze whether missing MTX doses causes the MTXglu level in red blood cells to fall below the range associated with the drug's clinical effect.</p><p><strong>Results: </strong>For patients initiating oral MTX, the threshold for clinical effectiveness and the steady state level were reached in medians of 6 weeks and 22 weeks, respectively. For patients at steady state who discontinued MTX, the MTXglu level fell below the therapeutic threshold after a median of 3 weeks. After initiating MTX, single missed doses did not cause a loss of therapeutic effect in the median patient if they occurred after 10 weeks, while runs of ≥3 consecutive missed doses did cause the MTXglu level to fall below the therapeutic threshold.</p><p><strong>Conclusion: </strong>While there is considerable variation between patients, pharmacokinetic modeling indicates that instances of isolated single missed doses of MTX typically will not cause polyglutamated methotrexate levels in red blood cells to fall below the range associated with the therapeutic effect. Runs of ≥3 consecutive missed doses, however, are typically expected to result in a loss of the therapeutic effect.</p>","PeriodicalId":45545,"journal":{"name":"Open Access Rheumatology-Research and Reviews","volume":"13 ","pages":"267-274"},"PeriodicalIF":2.1,"publicationDate":"2021-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/07/oarrr-13-267.PMC8450605.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39442589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}