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Association of historical redlining and present-day racialised economic segregation with health-care utilisation among individuals with rheumatic conditions in Massachusetts and surrounding areas of the USA: a retrospective cohort study 美国马萨诸塞州及周边地区历史上的红线和当今种族经济隔离与风湿病患者使用医疗服务的关系:一项回顾性队列研究。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/S2665-9913(24)00235-2
Sherry Yang BS , Leah Santacroce MS , Jamie E Collins PhD , Candace H Feldman MD ScD
<div><h3>Background</h3><div>Structural racism lies at the root of inequities; however its impact on rheumatology care is understudied. Redlining was a US federal government-sponsored practice that mapped areas with high concentrations of Black and immigrant residents as hazardous for investment. We aimed to investigate the association of historical redlining and present-day racialised economic segregation, on health-care utilisation among individuals with rheumatic conditions in the US state of Massachusetts and surrounding areas.</div></div><div><h3>Methods</h3><div>This retrospective observational cohort study used multihospital data from the Mass General Brigham Research Patient Data Registry to identify individuals aged ≥ 18 years living in Massachusetts and surrounding areas, with two or more International Classification of Diseases codes for a rheumatic condition. Individuals were included if they received care between Jan 1, 2000, and May 1, 2023, at rheumatology practices affiliated with Mass General Brigham (Boston, MA, USA). Addresses were geocoded and overlaid with 1930s Home Owners' Loan Corporation (HOLC) redlining files. The Index of Concentration at the Extremes (ICE) for combined racial and income polarisation was constructed from US Census data. We used multilevel, multinomial logistic regression models to examine the odds of health-care utilisation separately by historical HOLC grade (A [best] to D [hazardous]) and ICE quintile (most deprived [1] to most privileged [5] race and income), adjusting for demographics, insurance, and comorbidities. People with lived experience of a rheumatic condition were not involved in the design or implementation of this study.</div></div><div><h3>Findings</h3><div>The cohort comprised 5597 individuals; 3944 (70·5%) of 5597 patients were female, 1653 (29·5%) were male, 657 (11·7%) were Black, 224 (4·0%) were Hispanic, and the median age was 63 (50–73) years. 1295 (23·1%) of 5597 individuals lived in the most historically redlined areas (HOLC D) and 1780 (31·8%) lived in areas with the most concentrated present-day racialised economic deprivation (ICE quintile 1). Individuals in historically redlined areas (HOLC D) had greater odds of having four or more missed appointments (odds ratio [OR] 1·78 [95% CI 1·21–2·61]; p=0·0033) and of three or more emergency department visits (2·69 [1·48–4·89]; p=0·0011) compared with those in the most desirable neighbourhoods (HOLC A). Individuals in areas with highly concentrated racial and economic deprivation (ICE quintile 1) had greater odds of four or more missed appointments (OR 2·11 [95% CI 1·65–2·71]; p<0·0001) and of three or more emergency department visits (2·97 [2·02–4·35]; p<0·0001) versus those in areas with highly concentrated privilege (ICE quintile 5).</div></div><div><h3>Interpretation</h3><div>Historical redlining could be a structural determinant of inequities in present-day health-care utilisation patterns. Policy interventions that disma
背景:结构性种族主义是不公平的根源,但它对风湿病护理的影响却未得到充分研究。红线是美国联邦政府发起的一种做法,它将黑人和移民居民高度集中的地区划为投资危险区。我们的目的是调查历史上的redlining和当今的种族经济隔离对美国马萨诸塞州及周边地区风湿病患者的医疗保健利用率的影响:这项回顾性观察队列研究利用麻省综合医院布里格姆研究中心病人数据登记处的多医院数据,对居住在马萨诸塞州及周边地区、年龄≥ 18 岁、有两个或两个以上风湿病国际疾病分类代码的人进行识别。在 2000 年 1 月 1 日至 2023 年 5 月 1 日期间,在马萨诸塞州布里格姆综合医院(波士顿,马萨诸塞州,美国)附属风湿病诊所接受过治疗的患者均被纳入其中。地址已进行地理编码,并与 1930 年代房屋所有者贷款公司 (HOLC) 的红线文件进行了叠加。根据美国人口普查数据构建了综合种族和收入两极分化的极端集中指数(ICE)。我们使用多层次、多项式逻辑回归模型,按历史 HOLC 等级(A [最佳] 至 D [危险])和 ICE 五分位数(最贫困 [1] 至最优越 [5] 种族和收入)分别研究了使用医疗服务的几率,并对人口统计学、保险和合并症进行了调整。有风湿病生活经历的人没有参与本研究的设计和实施:组群由 5597 人组成;5597 名患者中有 3944 人(70-5%)为女性,1653 人(29-5%)为男性,657 人(11-7%)为黑人,224 人(4-0%)为西班牙裔,年龄中位数为 63(50-73)岁。5597 人中有 1295 人(23-1%)生活在历史上最贫困的地区(HOLC D),1780 人(31-8%)生活在当今种族经济贫困最集中的地区(ICE 五分法 1)。与居住在最理想社区(HOLC A)的人相比,居住在历史上曾被划为红线的地区(HOLC D)的人有更大的几率错过四次或四次以上的预约(几率比 [OR] 1-78 [95% CI 1-21-2-61]; p=0-0033)和三次或三次以上的急诊就诊(2-69 [1-48-4-89]; p=0-0011)。在种族和经济高度集中的贫困地区(ICE 五分法 1),个人四次或四次以上失约的几率更大(OR 2-11 [95% CI 1-65-2-71];p解释:历史上的 "红线 "可能是当今医疗保健使用模式不平等的结构性决定因素。消除结构性种族主义的政策干预措施可以减少风湿病患者在获得医疗服务方面的不平等:布里斯托尔-迈尔斯-施贵宝基金会。
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引用次数: 0
Blau syndrome presenting as lipoma arborescens 表现为树枝状脂肪瘤的布劳综合征
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/S2665-9913(24)00055-9
Hanlin Yin MD , Wanyi Lin MD , Langxian Zhi MD , Fuli Yin MD , Shaoying Yang MD , Liangjing Lu MD PhD
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引用次数: 0
Heading for remission and its continuation in rheumatoid arthritis. 类风湿性关节炎的缓解及其持续。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-20 DOI: 10.1016/S2665-9913(24)00336-9
Paul Studenic
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引用次数: 0
Allogeneic haematopoietic stem-cell transplantation in systemic juvenile idiopathic arthritis. 异基因造血干细胞移植治疗系统性青少年特发性关节炎。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-20 DOI: 10.1016/S2665-9913(24)00299-6
Pierre Quartier
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引用次数: 0
Sustained DMARD-free remission in subgroups of patients with rheumatoid arthritis: an analysis of two prospective cohorts with early arthritis. 类风湿关节炎亚组患者无 DMARD 持续缓解:对两个前瞻性早期关节炎队列的分析。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-20 DOI: 10.1016/S2665-9913(24)00234-0
Judith W Heutz, Pascal H P de Jong, Marloes Verstappen, Annette H M van der Helm-van Mil, Elise van Mulligen
<p><strong>Background: </strong>About 20% of patients with rheumatoid arthritis on disease-modifying antirheumatic drugs (DMARDs) can reach sustained DMARD-free remission. Nonetheless, the 2022 EULAR recommendations discourage complete cessation of DMARDs due to flare risk. The evidence behind this recommendation is obtained from trial populations using biological DMARDs, representing only a subgroup of the total population of patients with rheumatoid arthritis. We hypothesised that patients requiring biological DMARDs represent a subgroup that is less capable of reaching sustained DMARD-free remission compared with patients not requiring a biological DMARD.</p><p><strong>Methods: </strong>In this study we used data from two prospectively followed up populations of patients with early rheumatoid arthritis, the Leiden Early Arthritis Clinic (EAC) and the treatment in the Rotterdam Early Arthritis Cohort (tREACH), a treat-to-target steered trial in which biological DMARDs were started when patients had inadequate response to triple DMARD-therapy (methotrexate, sulfasalazine, and hydroxychloroquine). Patient partners were involved in the design of both the EAC and tREACH. The primary outcome was sustained DMARD-free remission, which was defined as absence of clinical synovitis after discontinuation of DMARDs for at least 1 year. Patients who did or did not receive biological DMARDs in 5 years (EAC) or 3 years (tREACH) were compared using Kaplan-Meier curves.</p><p><strong>Findings: </strong>627 patients from the EAC were included, of whom 391 (62%) were female and 236 (38%) were male. The mean age was 60 years (SD 14) and 502 (95%) of 529 patients were White. 89 (14%) of 627 patients had ever used a biological DMARD and 538 (86%) had never used a biological DMARD. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 37% of the patients who never used a biological DMARD reached sustained DMARD-free remission at 5 years (hazard ratio [HR] 0·02, 95% CI 0·00-0·10; p<0·0001). From the tREACH population, 425 patients were included in the study. 286 (67%) patients were female, 139 (33%) were male, and the mean age was 54 years (SD 14); ethnicity data not recorded. 154 (36%) of 425 patients had ever used a biological DMARD and 271 (64%) had never used a biological DMARD during follow-up. None of the patients that used a biological DMARD reached sustained DMARD-free remission, whereas 15% of patients who never used a biological DMARD reached sustained DMARD-free remission at 3 years (HR 0·03, 95% CI 0·00-0·21; p<0·0001).</p><p><strong>Interpretation: </strong>For the subgroup of patients with rheumatoid arthritis who require biological DMARDs, sustained DMARD-free remission does not seem attainable. In contrast, in patients with rheumatoid arthritis who do not require biological DMARDs, DMARD-free remission is attainable. These data suggest that the current EULAR recommendation to not stop DMARD use might suffer f
研究背景:大约20%的类风湿关节炎患者使用改善疾病的抗风湿药物(DMARDs)可以达到持续的无dmard缓解。尽管如此,2022年EULAR建议不鼓励完全停止使用dmard,因为有耀斑风险。这一建议背后的证据来自使用生物dmard的试验人群,仅代表类风湿关节炎患者总人群中的一个亚组。我们假设需要生物DMARD的患者代表一个亚组,与不需要生物DMARD的患者相比,他们达到持续无DMARD缓解的能力较差。方法:在这项研究中,我们使用了来自两个前瞻性随访的早期类风湿关节炎患者群体的数据,莱顿早期关节炎诊所(EAC)和鹿特丹早期关节炎队列(tREACH)的治疗,这是一项治疗-靶点导向试验,当患者对三联dmard治疗(甲氨蝶呤,磺胺嘧啶和羟氯喹)反应不足时开始使用生物dmard。患者伴侣参与了EAC和tREACH的设计。主要结局是持续无dmard缓解,定义为停用dmard至少1年后无临床滑膜炎。使用Kaplan-Meier曲线对5年(EAC)或3年(tREACH)接受或未接受生物dmard的患者进行比较。结果:纳入EAC的627例患者,其中391例(62%)为女性,236例(38%)为男性。平均年龄为60岁(SD 14), 529例患者中502例(95%)为白种人,627例患者中89例(14%)曾使用过生物DMARD, 538例(86%)从未使用过生物DMARD。使用生物DMARD的患者均未达到持续无DMARD缓解,而从未使用生物DMARD的患者中有37%在5年时达到持续无DMARD缓解(风险比[HR] 0.02, 95% CI 0.00 - 0.10;结论:对于需要生物dmard的类风湿关节炎患者亚组,持续无dmard缓解似乎无法实现。相比之下,在不需要生物dmard的类风湿性关节炎患者中,可以实现无dmard缓解。这些数据表明,目前EULAR关于不停止使用DMARD的建议可能存在确定偏差。今后关于停用DMARD的建议应加以修订。资助:荷兰关节炎基金会和欧洲研究委员会。
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引用次数: 0
Allogeneic haematopoietic stem-cell transplantation for children with refractory systemic juvenile idiopathic arthritis and associated lung disease: outcomes from an international, retrospective cohort study. 为患有难治性系统性幼年特发性关节炎和相关肺部疾病的儿童进行异体造血干细胞移植:一项国际回顾性队列研究的结果。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-20 DOI: 10.1016/S2665-9913(24)00275-3
Michael G Matt, Daniel Drozdov, Elisabeth Bendstrup, Mia Glerup, Ellen-Margrethe Hauge, Tania Masmas, Elvira Cannizzaro Schneider, Ulrike B Zeilhofer, Rolla F Abu-Arja, Kyla D Driest, Joseph H Oved, Karen Onel, Christen L Ebens, Deepakbabu Chellapandian, Shanmuganathan Chandrakasan, Sampath Prahalad, Johannes Roth, Susan E Prockop, Juliana Silva, Andrew H Schapiro, Christopher Towe, Sharat Chandra, Alexei Grom, Grant S Schulert, Rebecca A Marsh

Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.

Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT. Patients' medical charts were reviewed and their data extracted using a standardised form. The outcomes assessed were allogeneic HSCT outcomes (eg, engraftment and donor chimerism, and transplant-related complications), pulmonary outcomes (eg, oxygen dependence, chest CT findings, and pulmonary function test results), and overall outcomes (eg, death, complete response, or partial response). A complete response was defined as resolution of signs of sJIA without the need for systemic immunomodulatory therapy, in addition to discontinuation of supplemental oxygen.

Findings: Between Jan 18, 2018, and Oct 17, 2022, 13 patients with sJIA-LD, who were refractory to immunosuppressive treatment and who had received an average of six different treatment agents, underwent allogeneic HSCT. Ten (77%) of 13 patients were female and three (23%) were male. The median age at diagnosis of sJIA-LD was 4·8 years (IQR 2·9-14·8) and the median age at transplantation was 9·0 years (5·0-19·0). Pre-HSCT chest CT revealed characteristic sJIA-LD. Five patients required supplemental oxygen before transplantation. Patients received various reduced toxicity or intensity conditioning regimens. Grafts were from 10/10 HLA-matched (n=6) or 9/10 HLA-mismatched (n=5) unrelated donors, a 7/10 related donor (n=1), and a matched sibling (n=1). All patients engrafted. One patient had secondary graft failure and received a second transplant from a different donor. Post-transplantation complications included acute graft-versus-host disease (n=5), bacteraemia (n=8), cytomegalovirus reactivation (n=6), and post-transplantation macrophage activation syndrome (n=3). Four patients died; two from cytomegalovirus pneumonitis, one from intracranial haemorrhage, and one from progressive sJIA-LD. At a median follow-up of 16 months (IQR 6-24), all nine surviving patients had a complete response, with no active features of sJIA, no biological therapy or corticosteroid use, and no supplemental oxygen dependence.

Interpretation: Allogeneic HSCT might be a valuable treatment option for patients with refractory sJIA and sJIA-LD and should be considered for children with worsening oxygen dependence or severe treatment-related morbidity.

Funding: National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR079525).

背景:系统性幼年特发性关节炎相关肺病(sJIA- ld)是难治性系统性幼年特发性关节炎(sJIA)患者的严重并发症。本研究的目的是评估同种异体造血干细胞移植(HSCT)在sJIA-LD患儿队列中的效果。方法:这项国际回顾性队列研究在美国和欧洲的9家医院对接受同种异体造血干细胞移植的sJIA-LD儿童进行了研究。审查了患者的医疗图表,并使用标准化表格提取了他们的数据。评估的结果包括同种异体造血干细胞移植结果(如移植和供体嵌合,以及移植相关并发症)、肺结果(如氧依赖、胸部CT表现和肺功能检查结果)和总体结果(如死亡、完全缓解或部分缓解)。完全缓解被定义为sJIA症状的消退,不需要全身免疫调节治疗,也不需要停止补充氧气。研究结果:在2018年1月18日至2022年10月17日期间,13例sJIA-LD患者接受了同种异体造血干细胞移植,这些患者对免疫抑制治疗难治性,平均接受了6种不同的治疗药物。13例患者中女性10例(77%),男性3例(23%)。sJIA-LD诊断时的中位年龄为4.8岁(IQR为2.9 ~ 14.8),移植时的中位年龄为9.0岁(IQR为5.0 ~ 19.0)。hsct前胸部CT显示特征性sJIA-LD。5例患者在移植前需要补充氧气。患者接受各种降低毒性或强度调节方案。移植物来自10/10 hla匹配(n=6)或9/10 hla不匹配(n=5)无亲缘关系供者,7/10亲缘关系供者(n=1)和匹配的兄弟姐妹(n=1)。所有患者都进行了移植。一名患者继发移植失败,接受了来自不同供者的第二次移植。移植后并发症包括急性移植物抗宿主病(n=5)、菌血症(n=8)、巨细胞病毒再激活(n=6)和移植后巨噬细胞激活综合征(n=3)。4例死亡;2例为巨细胞病毒肺炎,1例为颅内出血,1例为进行性sJIA-LD。在中位随访16个月(IQR 6-24)时,所有9例存活患者均完全缓解,无sJIA活性特征,无生物治疗或皮质类固醇使用,无补充氧依赖。解释:同种异体造血干细胞移植可能是难治性sJIA和sJIA- ld患者的一种有价值的治疗选择,对于氧依赖恶化或严重治疗相关发病率的儿童应考虑。资助:国家关节炎、肌肉骨骼和皮肤疾病研究所(R01-AR079525)。
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引用次数: 0
Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data. 使用秋水仙碱或不使用秋水仙碱进行降尿酸治疗的痛风患者的心血管事件预防:一项回顾性新用户队列研究,使用相关的初级保健、住院和死亡率数据。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-18 DOI: 10.1016/S2665-9913(24)00248-0
Edoardo Cipolletta, Georgina Nakafero, Natalie McCormick, Chio Yokose, Anthony J Avery, Mamas A Mamas, Hyon K Choi, Laila J Tata, Abhishek Abhishek
<p><strong>Background: </strong>Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.</p><p><strong>Methods: </strong>We did a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalisation and mortality records. People with gout initiating urate-lowering therapy for the first time were eligible for inclusion. We compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis. Colchicine prophylaxis (defined as prescription for ≥21 days) prescribed on the same date as urate-lowering therapy was the exposure of interest. A composite of fatal and non-fatal myocardial infarction or stroke within 180 days after urate-lowering therapy initiation regardless of any previous cardiovascular event was the primary outcome. Propensity score overlap weighting was used to balance covariates across study groups. We used Cox regression and performed intention-to-treat and per-protocol analyses, the latter with an inverse probability of censoring weighting. The association was measured using hazard ratio and risk difference with 95% CIs. Members of The UK Gout Society were involved in prioritising the research question.</p><p><strong>Findings: </strong>Of the 111 460 patients eligible for the study, 99 800 patients with gout initiating urate-lowering therapy were included. 25 511 (25·6%) of 99 800 patients were female, 74 289 (74·4%) were male, 84 928 (85·1%) patients were White and the mean age was 62·8 years (SD 15·5). 4063 (4·1%) patients had previous cardiovascular events and 16 028 (16·1%) patients were prescribed colchicine prophylaxis. Patients with colchicine prophylaxis had significantly lower risk of cardiovascular events compared with those without prophylaxis. The weighted rates of cardiovascular events were 28·8 per 1000 person-years (95% CI 25·2 to 33·2) in patients with colchicine prophylaxis and 35·3 per 1000 person-years (33·0 to 37·9) in those without prophylaxis (weighted rate difference -6·5 [95% CI -9·4 to -3·6] per 1000 person-years and weighted hazard ratio 0·82 [0·69-0·94]) in the intention-to-treat analysis. Findings were similar across analytical approaches, stratified analyses, and for secondary outcomes.</p><p><strong>Interpretation: </strong>In patients with gout initiating urate-lowering therapy, the risk of cardiovascular events was reduced in those prescribed colchicine prophylaxis compared with no prophylaxis. These findings provide an additional argument for using colchicine for gout flare prophylaxis.</p><p><strong>Fundin
背景:开始降尿酸治疗可引发痛风发作。痛风发作与心血管事件的风险暂时增加有关。因此,我们的目的是评估与不进行预防相比,使用秋水仙碱(许多国际协会推荐用于预防痛风耀斑的药物)进行降低尿酸盐治疗的痛风患者心血管事件的风险。方法:我们使用临床实践研究数据链Aurum(一个与住院和死亡率记录相关的英国初级保健数据库)的数据进行了一项回顾性新用户队列研究。首次接受降尿酸治疗的痛风患者符合入选条件。我们比较了使用秋水仙碱预防耀斑的患者和未使用任何预防痛风耀斑的患者。与降尿酸治疗同日服用秋水仙碱预防(定义为处方≥21天)是感兴趣的暴露。在开始降尿酸治疗后180天内发生致死性和非致死性心肌梗死或卒中的综合情况,而不管之前是否发生过心血管事件,是主要结局。倾向评分重叠加权用于平衡各研究组间的协变量。我们使用Cox回归并进行意向治疗和协议分析,后者具有反向审查权重的概率。使用风险比和95% ci的风险差异来测量相关性。英国痛风协会的成员参与了研究问题的优先排序。结果:在符合研究条件的11460例患者中,有99800例痛风患者开始接受降尿酸治疗。99 800例患者中女性25 511例(25.6%),男性74 289例(78.4%),白人84 928例(85.1%),平均年龄62.8岁(SD 15.5)。4063例(4.1%)患者既往有心血管事件,16028例(16.1%)患者使用秋水仙碱预防。与未使用秋水仙碱预防的患者相比,使用秋水仙碱预防的患者发生心血管事件的风险显著降低。在意向治疗分析中,秋水仙碱预防组的心血管事件加权率为28.8 / 1000人-年(95% CI 25.2 ~ 33.2),未预防组的心血管事件加权率为35.3 / 1000人-年(33.0 ~ 37.9)(加权率差为- 6.5 [95% CI - 9.4 ~ -3] / 1000人-年,加权风险比为0.82[0.69 ~ 0.94])。分析方法、分层分析和次要结果的结果相似。解释:在开始降尿酸治疗的痛风患者中,秋水仙碱预防与未预防相比,心血管事件的风险降低。这些发现为使用秋水仙碱预防痛风耀斑提供了额外的论据。资助:风湿病学研究基金会。
{"title":"Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data.","authors":"Edoardo Cipolletta, Georgina Nakafero, Natalie McCormick, Chio Yokose, Anthony J Avery, Mamas A Mamas, Hyon K Choi, Laila J Tata, Abhishek Abhishek","doi":"10.1016/S2665-9913(24)00248-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00248-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We did a retrospective new-user cohort study using data from the Clinical Practice Research Datalink Aurum, an English primary-care database linked to hospitalisation and mortality records. People with gout initiating urate-lowering therapy for the first time were eligible for inclusion. We compared people prescribed flare prophylaxis with colchicine with those not prescribed any gout flare prophylaxis. Colchicine prophylaxis (defined as prescription for ≥21 days) prescribed on the same date as urate-lowering therapy was the exposure of interest. A composite of fatal and non-fatal myocardial infarction or stroke within 180 days after urate-lowering therapy initiation regardless of any previous cardiovascular event was the primary outcome. Propensity score overlap weighting was used to balance covariates across study groups. We used Cox regression and performed intention-to-treat and per-protocol analyses, the latter with an inverse probability of censoring weighting. The association was measured using hazard ratio and risk difference with 95% CIs. Members of The UK Gout Society were involved in prioritising the research question.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of the 111 460 patients eligible for the study, 99 800 patients with gout initiating urate-lowering therapy were included. 25 511 (25·6%) of 99 800 patients were female, 74 289 (74·4%) were male, 84 928 (85·1%) patients were White and the mean age was 62·8 years (SD 15·5). 4063 (4·1%) patients had previous cardiovascular events and 16 028 (16·1%) patients were prescribed colchicine prophylaxis. Patients with colchicine prophylaxis had significantly lower risk of cardiovascular events compared with those without prophylaxis. The weighted rates of cardiovascular events were 28·8 per 1000 person-years (95% CI 25·2 to 33·2) in patients with colchicine prophylaxis and 35·3 per 1000 person-years (33·0 to 37·9) in those without prophylaxis (weighted rate difference -6·5 [95% CI -9·4 to -3·6] per 1000 person-years and weighted hazard ratio 0·82 [0·69-0·94]) in the intention-to-treat analysis. Findings were similar across analytical approaches, stratified analyses, and for secondary outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In patients with gout initiating urate-lowering therapy, the risk of cardiovascular events was reduced in those prescribed colchicine prophylaxis compared with no prophylaxis. These findings provide an additional argument for using colchicine for gout flare prophylaxis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Fundin","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beneficial side-effects of colchicine for patients with gout. 秋水仙碱对痛风患者的有益副作用。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-18 DOI: 10.1016/S2665-9913(24)00332-1
Hein Janssens, Matthijs Janssen
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引用次数: 0
Promise and challenges of mesenchymal stromal cell therapy in severe SLE. 间充质间质细胞治疗严重SLE的前景和挑战。
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-17 DOI: 10.1016/S2665-9913(24)00351-5
Ioannis Parodis
{"title":"Promise and challenges of mesenchymal stromal cell therapy in severe SLE.","authors":"Ioannis Parodis","doi":"10.1016/S2665-9913(24)00351-5","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00351-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Allogeneic umbilical cord-derived mesenchymal stromal cells as treatment for systemic lupus erythematosus: a single-centre, open-label, dose-escalation, phase 1 study. 异体脐带间充质间质细胞治疗系统性红斑狼疮:一项单中心、开放标签、剂量递增的1期研究
IF 15 1区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-12-17 DOI: 10.1016/S2665-9913(24)00298-4
Dominique Farge, Lucie Biard, Ben Weil, Virginie Girault, Pauline Lansiaux, Ingrid Munia, Séverine Loisel, Catney Charles, Judikael Saout, Matthieu Resche-Rigon, Anne Sophie Korganow, Clément Beuvon, Grégory Pugnet, Carlotta Cacciatore, Noémie Abisror, Jean Luc Taupin, Audrey Cras, Mark W Lowdell, Karin Tarte
<p><strong>Background: </strong>Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE.</p><p><strong>Methods: </strong>This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 10<sup>6</sup>, 2 × 10<sup>6</sup>, or 4 × 10<sup>6</sup> umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 10<sup>6</sup> cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29.</p><p><strong>Findings: </strong>From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 10<sup>6</sup> dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 10<sup>6</sup> cells per kg (range 2 × 10<sup>6</sup> to 4 × 10<sup>6</sup>). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse.</p><p><strong>Interpretation: </strong>Our results suggest that a single infusion of 2 × 10<sup>6</sup> cells per kg or 4 × 10<sup>6</sup> cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to c
背景:对标准治疗反应不足的系统性红斑狼疮(SLE)患者的治疗需求未得到满足。间充质间质细胞的免疫调节、促血管生成和抗纤维化特性支持其在SLE患者治疗中的应用。我们的目的是评估单次静脉输注同种异体脐带间充质间质细胞治疗严重SLE患者的安全性。方法:这项前瞻性、单中心、开放标签、剂量递增、贝叶斯1期研究在法国巴黎的圣路易斯大学医院完成。符合条件的患者年龄为18-70岁,根据美国风湿病学会标准诊断为SLE,抗核抗体阳性,基线雌激素在红斑狼疮国家评估-SLE疾病活动指数(SELENA-SLEDAI)中的安全性评分为6分或以上,并且患有一线和二线SLE治疗难治性疾病。患者接受单次静脉输注每公斤1 × 106、2 × 106或4 × 106脐带来源的间充质间质细胞(由单个脐带制造),每剂量5例患者,从每公斤2 × 106细胞开始。主要终点是输注脐带源性间充质间质细胞后10天内治疗相关严重不良事件(≥3级)的发生率。有生活经验的人参与了研究设计、患者登记和研究结果的传播。该研究已在ClinicalTrials.gov注册,注册号为NCT03562065,欧盟临床试验注册号为EudraCT2017-001400-29。研究结果:从2019年5月14日至2023年3月6日,29名患者进行了资格筛选,其中8名患者入组研究。纳入8例患者后,研究提前终止,没有患者接受1 × 106剂量的脐带间充质间质细胞治疗。8名参与者中有7名(88%)是顺性女性,1名(13%)是顺性男性。中位年龄为35岁(范围26-57岁),SLE病程中位为12年(5-19年)。所有患者每公斤至少接受2 × 106个细胞(范围为2 × 106至4 × 106)。2例患者在输注后10天内未发生严重不良事件,3例输注相关不良事件(2例1级和1例2级)。随访12·4个月(12-13个月),1例患者复发后无治疗相关严重不良事件发生,3例非治疗相关严重不良事件发生。解释:我们的结果表明,单次输注2 × 106细胞/ kg或4 × 106细胞/ kg的同种异体脐带间充质间质细胞对严重SLE患者是安全的。需要安慰剂对照试验来证实临床疗效和b细胞修饰在临床获益中的作用。资助:雷因基金会、afm - tama - tama联盟、AP-HP临床和创新研究方向和法国ANR eCellFrance。
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Lancet Rheumatology
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