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Calcium Pyrophosphate Crystal Formation and Deposition: Where Do we Stand and What Does the Future hold? 焦磷酸钙晶体的形成与沉积:我们的现状和未来如何?
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-01 DOI: 10.1007/s11926-024-01161-w
Silvia Sirotti, Anna Scanu, Tristan Pascart, Tom Niessink, Paola Maroni, Giovanni Lombardi, Georgios Filippou

Purpose of the review: Although calcium pyrophosphate deposition (CPPD) has been known since the 1960s, our understanding of its pathogenesis remains rudimentary. This review aims to illustrate the known mechanisms underlying calcium pyrophosphate (CPP) crystal formation and deposition and explore future directions in research. By examining various perspectives, from basic research to clinical and imaging assessments, as well as new emerging methodologies, we can establish a starting point for a deeper understanding of CPPD pathogenesis.

Recent findings: Recent years have seen significant advances in CPPD research, particularly in the clinical field with the development of the 2023 ACR/EULAR classification criteria for CPPD disease, and in imaging with the introduction of the OMERACT ultrasonographic definitions and scoring system. However, progress in basic research has been slower. New laboratory approaches, such as Raman spectroscopy and omics sciences, offer promising insights that may help piece together the puzzle of CPPD. CPPD is a common yet understudied condition. As the population ages and CPPD becomes more prevalent, there is an urgent need to better understand the disease and the mechanisms involved in crystal formation and deposition, in order to improve diagnosis and therapeutic approaches.

综述的目的:尽管焦磷酸钙沉积(CPPD)早在 20 世纪 60 年代就已为人所知,但我们对其发病机理的了解仍很有限。本综述旨在说明焦磷酸钙(CPP)晶体形成和沉积的已知机制,并探讨未来的研究方向。通过从基础研究、临床和成像评估以及新出现的方法等不同角度进行研究,我们可以为深入了解焦磷酸钙的发病机制建立一个起点:近年来,CPPD 研究取得了重大进展,尤其是在临床领域,制定了 2023 年 ACR/EULAR CPPD 疾病分类标准;在影像学领域,引入了 OMERACT 超声波定义和评分系统。然而,基础研究方面的进展却较为缓慢。新的实验室方法,如拉曼光谱学和构象科学,提供了有希望的见解,可能有助于拼凑 CPPD 的拼图。CPPD是一种常见的疾病,但研究不足。随着人口老龄化和 CPPD 的流行,迫切需要更好地了解这种疾病以及晶体形成和沉积的相关机制,以改进诊断和治疗方法。
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引用次数: 0
Air Pollution and Rheumatoid Arthritis Risk and Progression: Implications for the Mucosal Origins Hypothesis and Climate Change for RA Pathogenesis. 空气污染与类风湿关节炎的风险和进展:粘膜起源假说和气候变化对类风湿关节炎发病机制的影响》。
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-02 DOI: 10.1007/s11926-024-01160-x
Katarina J Bade, Kevin T Mueller, Jeffrey A Sparks

Purpose of review: The goal of this review paper is to summarize the main research and findings regarding air pollution and its association with the risk and progression of rheumatoid arthritis (RA).

Recent findings: The most studied components of air pollution included particulate matter of ≤ 2.5 microns in diameter (PM2.5), PM10, carbon monoxide (CO), nitrogen dioxide (NO2), nitric oxide (NOx), sulfur dioxide (SO2), and ozone (O3). In addition, specific occupations and occupational inhalants have been investigated for RA risk. Several studies showed that increased exposure to air pollutants increased the risk of developing RA, particularly seropositive RA. There was evidence of gene-inhalant interactions for seropositive RA risk. Fewer studies have been conducted on RA disease activity and bone erosions. Some studies suggest that patients with RA-associated interstitial lung disease may have worse outcomes if exposed to air pollution. We summarized associations between air pollution and increased RA risk, including RA-associated interstitial lung disease. Relatively few studies investigated air pollution and RA disease activity or other outcomes. These results suggest an important role of air pollution for seropositive RA development and suggest that climate change could be a driver in increasing RA incidence as air pollution increases.

综述的目的:本综述旨在总结有关空气污染及其与类风湿性关节炎(RA)风险和病情发展相关性的主要研究和发现:研究最多的空气污染成分包括直径≤2.5微米的颗粒物(PM2.5)、PM10、一氧化碳(CO)、二氧化氮(NO2)、一氧化氮(NOx)、二氧化硫(SO2)和臭氧(O3)。此外,还对特定职业和职业吸入物的 RA 风险进行了调查。一些研究表明,接触空气污染物增加了罹患 RA 的风险,尤其是血清阳性 RA。有证据表明,血清阳性 RA 风险与基因-吸入剂相互作用有关。关于 RA 疾病活动性和骨侵蚀的研究较少。一些研究表明,与 RA 相关的间质性肺部疾病患者如果暴露于空气污染中,其预后可能会更差。我们总结了空气污染与 RA 风险增加(包括 RA 相关间质性肺病)之间的关系。调查空气污染和 RA 疾病活动性或其他结果的研究相对较少。这些结果表明,空气污染对血清阳性 RA 的发展起着重要作用,并表明随着空气污染的加剧,气候变化可能成为增加 RA 发病率的驱动因素。
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引用次数: 0
Updates in diagnosis and treatment of pediatric antiphospholipid syndrome. 诊断和治疗小儿抗磷脂综合征的最新进展。
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-10-01 Epub Date: 2024-07-24 DOI: 10.1007/s11926-024-01156-7
Lucia M Campos, Paula S Marra, Clara R Doria, Sebastian D Cordoba, Clovis A Silva

Purpose of review: This review offers an overview of the most important recent articles on pediatric APS.

Recent findings: Non-thrombotic extra criteria manifestations were prevalent in pediatric APS. Pregnancy morbidity has been described as the first manifestation of APS at youth age, impairing gestational outcomes. The 2023 APS criteria were developed for adult APS patients, and there is still a lack of pediatric-specific APS criteria. Catastrophic APS was more commonly reported as the initial manifestation of pediatric APS than in adults. Regarding treatment, direct oral anticoagulants have been recently approval for pediatric patients with venous thrombosis. New approaches have been proposed for severe cases, for arterial thrombosis, and rituximab for refractory cases. Recurrences typically occurred early and were associated with older age at diagnosis. Current studies highlighted the multifaceted nature of pediatric APS. Further large prospective multicenter studies evaluating new medications capable of reducing recurrence risk and improving prognosis in this population will be required.

综述目的:本综述概述了近期有关小儿 APS 的最重要文章:非血栓性标准外表现在小儿APS中十分普遍。妊娠期发病被描述为青少年 APS 的首发表现,会损害妊娠结局。2023 年 APS 标准是针对成人 APS 患者制定的,目前仍缺乏针对儿科的 APS 标准。与成人相比,灾难性 APS 更常被报告为儿科 APS 的初始表现。在治疗方面,直接口服抗凝剂最近已被批准用于静脉血栓形成的儿科患者。针对严重病例、动脉血栓形成和难治性病例的利妥昔单抗,也提出了新的治疗方法。复发通常发生在早期,与诊断时年龄较大有关。目前的研究强调了儿科 APS 的多面性。需要进一步开展大型前瞻性多中心研究,评估能够降低复发风险和改善该人群预后的新药。
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引用次数: 0
Gaining Insight into Updated MR Imaging for Quantitative Assessment of Cartilage Injury in Knee Osteoarthritis. 深入了解用于定量评估膝关节骨关节炎软骨损伤的最新磁共振成像技术。
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-05-29 DOI: 10.1007/s11926-024-01152-x
Peng Luo, Li Lu, Run Xu, Lei Jiang, Guanwu Li

Purpose of the review: Knee Osteoarthritis (KOA) entails progressive cartilage degradation, reviewed via MRI for morphology, biochemical composition, and microtissue alterations, discussing clinical advantages, limitations, and research applicability.

Recent findings: Compositional MRI, like T2/T2* mapping, T1rho mapping, gagCEST, dGEMRIC, sodium imaging, diffusion-weighted imaging, and diffusion-tensor imaging, provide insights into cartilage injury in KOA. These methods quantitatively measure collagen, glycosaminoglycans, and water content, revealing important information about biochemical compositional and microstructural alterations. Innovative techniques like hybrid multi-dimensional MRI and diffusion-relaxation correlation spectrum imaging show potential in depicting initial cartilage changes at a sub-voxel level. Integration of automated image analysis tools addressed limitations in manual cartilage segmentation, ensuring robust and reproducible assessments of KOA cartilage. Compositional MRI techniques reveal microstructural changes in cartilage. Multi-dimensional MR imaging assesses biochemical alterations in KOA-afflicted cartilage, aiding early degeneration identification. Integrating artificial intelligence enhances cartilage analysis, optimal diagnostic accuracy for early KOA detection and monitoring.

综述目的:膝骨关节炎(KOA)导致软骨逐渐退化,通过磁共振成像检查形态学、生化成分和微组织改变,讨论临床优势、局限性和研究适用性:最近的发现:成分磁共振成像,如 T2/T2* 映像、T1rho 映像、gagCEST、dGEMRIC、钠成像、扩散加权成像和扩散张量成像,为 KOA 中的软骨损伤提供了洞察力。这些方法可定量测量胶原蛋白、糖胺聚糖和水的含量,揭示生化成分和微结构改变的重要信息。混合多维核磁共振成像和弥散-松弛相关频谱成像等创新技术显示了在亚体素水平描述软骨初始变化的潜力。自动图像分析工具的整合解决了人工软骨分割的局限性,确保了对KOA软骨进行稳健且可重复的评估。合成磁共振成像技术揭示了软骨的微观结构变化。多维核磁共振成像可评估受 KOA 影响的软骨的生化变化,有助于早期识别退化。人工智能的整合增强了软骨分析,为早期 KOA 检测和监测提供了最佳诊断准确性。
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引用次数: 0
Classification Criteria for ANCA Associated Vasculitis - Ready for Prime Time? ANCA 相关性血管炎的分类标准--准备好了吗?
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-24 DOI: 10.1007/s11926-024-01154-9
Jens Rathmann, Aladdin J Mohammad

Purpose of review: This review aims to summarize the evolution and recent developments in the classification of ANCA associated vasculitis (AAV) and to summarize evaluations of the 2022 ACR/EULAR classification criteria of AAV in several cohorts.

Recent findings: The classification of AAV has been a field of controversy for some time. The parallel existence of classification criteria and disease definitions produced some overlap in classification, leading to challenges when comparing different cohorts. The 2022 ACR/EULAR classification criteria derived from the largest study ever conducted in vasculitis account for significant changes in vasculitis classification with the integration of ANCA and modern imaging. These criteria show good performance compared to previous ones but also raise questions as ANCA serotypes have substantial impact on classification. In addition, there are some discrepancies with earlier agreed histopathological features of AAV disease phenotypes. During the last 35 years, several sets of classification criteria have evolved to facilitate epidemiologic studies and clinical trials in AAV. While some of these criteria have been in use for many years, they were criticized due to either not using ANCA or not integrating surrogate markers for vasculitis but also due to overlapping when used in parallel. The long-awaited new ACR/EULAR criteria for AAV were published in 2022 and are the result of a large international study, introducing for the first time ANCA and modern imaging in the classification of AAV. Though the criteria show good performance, they bring several other challenges with practical application.

综述目的:本综述旨在总结 ANCA 相关性血管炎(AAV)分类的演变和最新进展,并总结 2022 年 ACR/EULAR AAV 分类标准在多个队列中的评估情况:一段时间以来,AAV 的分类一直存在争议。分类标准和疾病定义的并行存在造成了分类上的一些重叠,导致在比较不同队列时面临挑战。2022 年 ACR/EULAR 分类标准源于有史以来最大规模的脉管炎研究,考虑到了 ANCA 和现代影像学在脉管炎分类中的重大变化。与以前的标准相比,这些标准表现良好,但也提出了一些问题,因为 ANCA 血清型对分类有很大影响。此外,AAV 疾病表型的组织病理学特征与之前达成的共识也存在一些差异。在过去的 35 年中,已经形成了几套分类标准,以促进 AAV 的流行病学研究和临床试验。虽然其中一些标准已使用多年,但由于未使用 ANCA 或未整合血管炎的替代标记物,以及在并行使用时出现重叠,这些标准饱受诟病。人们期待已久的 ACR/EULAR AAV 新标准于 2022 年发布,它是一项大型国际研究的成果,首次在 AAV 分类中引入了 ANCA 和现代成像技术。虽然该标准显示出良好的性能,但在实际应用中也带来了其他一些挑战。
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引用次数: 0
Male Fertility in Spondyloarthritis: from Clinical Issues to Cytokines Milieu. A Narrative Review. 脊柱关节炎的男性生育能力:从临床问题到细胞因子环境。叙述性综述。
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-20 DOI: 10.1007/s11926-024-01153-w
Silvia Scriffignano, Fabio Massimo Perrotta, Ennio Lubrano

Purposeof review: Male fertility is an emergent issue that should be considered in clinical practice, when dealing with chronic inflammatory diseases in young men. As it is known, the chronic inflammation is the main pathophysiologic mechanism in some rheumatological conditions such as spondyloarthritis (SpA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Therefore, it is paramount to be aware if these diseases could impair male fertility, both due to the inflammation or to the treatments needed: we reviewed the literature on the most relevant and recent evidence on male fertility in patients affected by SpA, AS and PsA.

Recent findings: Rheumatological inflammatory diseases (included SpA, AS and PsA) could impair the family planning in man life, especially when diagnosed at young age. Moreover, focusing on sperm quality, it seems that a link between sperm quality impairment and a higher disease activity exist. Focusing on therapies, Tumor Necrosis Factor inhibitors showed a safety profile on human male fertility in clinical studies. Recently, a prospective study and two double-blind placebo-controlled trials assessed the impact of methotrexate and Filgotinib on semen parameters, respectively, showing a safety profile of these drugs on human semen quality. However, there are no clinical data on the impact of Interleukin (IL)17 inhibitors(i), IL12-23i and IL23i. Concerning male fertility in SpA, AS and PsA, an unmet clinical need is still present and new studies are needed to understand the association between these diseases and male fertility, and the implication of the therapies used for these diseases. This narrative review provides an overview of the available data on male fertility in patients affected by SpA, AS and PsA.

综述目的:在临床实践中,当处理年轻男性的慢性炎症性疾病时,男性生育力是一个需要考虑的新问题。众所周知,慢性炎症是脊柱关节炎(SpA)、强直性脊柱炎(AS)和银屑病关节炎(PsA)等风湿病的主要病理生理机制。因此,最重要的是要了解这些疾病是否会因炎症或所需治疗而损害男性生育能力:我们回顾了与 SpA、AS 和 PsA 患者的男性生育能力最相关的最新证据文献:风湿性炎症疾病(包括SpA、AS和PsA)会影响男性的计划生育,尤其是在年轻时确诊的患者。此外,就精子质量而言,精子质量受损与疾病活动性增高之间似乎存在联系。在治疗方面,肿瘤坏死因子抑制剂在临床研究中显示出对男性生育能力的安全性。最近,一项前瞻性研究和两项双盲安慰剂对照试验分别评估了甲氨蝶呤和菲戈替尼对精液参数的影响,结果显示这些药物对人类精液质量具有安全性。然而,目前还没有关于白细胞介素(IL)17抑制剂(i)、IL12-23i和IL23i影响的临床数据。关于SpA、AS和PsA患者的男性生育力,目前仍有临床需求未得到满足,需要进行新的研究以了解这些疾病与男性生育力之间的关联,以及用于这些疾病的疗法的影响。本综述概述了有关SpA、AS和PsA患者男性生育力的现有数据。
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引用次数: 0
Telemedicine for the Care of Patients with Idiopathic Inflammatory Myopathies: Experience, Insights and Future Directions from the International Myositis Assessment and Clinical Studies Telemedicine Scientific Interest Group. 远程医疗用于特发性炎症性肌病患者的护理:国际肌炎评估和临床研究远程医疗科学兴趣小组的经验、见解和未来方向。
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-08-31 DOI: 10.1007/s11926-024-01163-8
Jessica Day, Hani Kushlaf, Stacey Tarvin, Lorenzo Cavagna, Veronica Codullo, Samuel Katsuyuki Shinjo, Xia Lyu, Johannes Knitza, Raouf Hajji, Peter R Blier, Chih Wei Tseng, Simone Appenzeller, Lisa G Rider, Lisa Christopher-Stine, Latika Gupta
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引用次数: 0
How to Distinguish Non-Inflammatory from Inflammatory Pain in RA? 如何区分 RA 中的非炎症性疼痛和炎症性疼痛?
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-08-09 DOI: 10.1007/s11926-024-01159-4
Sharmila Khot, George Tackley, Ernest Choy

Purpose of the review: Managing non-inflammatory pain in rheumatoid arthritis (RA) can be a huge burden for the rheumatologist. Pain that persists despite optimal RA treatment is extremely challenging for patient and physician alike. Here, we outline the latest research relevant to distinguishing non-inflammatory from inflammatory RA pain and review the current understanding of its neurobiology and management.

Recent findings: Nociplastic pain is a recently introduced term by the international pain community. Its definition encompasses the non-inflammatory pain of RA and describes pain that is not driven by inflamed joints or compromised nerves, but that is instead driven by a functional reorganisation of the central nervous system (CNS). Insights from all areas of nociplastic pain research, including fibromyalgia, support a personalised pain management approach for non-inflammatory pain of RA, with evidence-based guidelines favouring use of non-pharmacological interventions. Future developments include novel CNS targeting pharmacotherapeutic approaches to treat nociplastic pain.

综述的目的:治疗类风湿性关节炎(RA)的非炎症性疼痛对风湿病医生来说是一项巨大的负担。对患者和医生而言,在接受最佳 RA 治疗后仍持续存在的疼痛极具挑战性。在此,我们概述了与区分非炎症性和炎症性 RA 疼痛相关的最新研究,并回顾了目前对其神经生物学和管理的理解:非炎症性疼痛是国际疼痛学界最近引入的一个术语。其定义涵盖了 RA 的非炎症性疼痛,描述的疼痛不是由发炎的关节或受损的神经引起的,而是由中枢神经系统(CNS)的功能重组引起的。包括纤维肌痛在内的所有非痉挛性疼痛研究领域的观点都支持针对RA非炎症性疼痛采取个性化的疼痛管理方法,循证指南倾向于使用非药物干预措施。未来的发展包括治疗非运动性疼痛的新型中枢神经系统靶向药物治疗方法。
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引用次数: 0
The Elusive Truth of Cannabinoids for Rheumatic Pain. 大麻素治疗风湿痛的神秘真相
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-08-09 DOI: 10.1007/s11926-024-01162-9
Hance Clarke, Sarah Miles, Miki Peer, Mary-Ann Fitzcharles

Purpose of review: Medical cannabis (MC) has entered mainstream medicine by a unique route. Regulatory acceptance as a medical product in many jurisdictions has bypassed the traditional evidence-based pathway required for therapies. Easier access to MC, especially related to recreational legalization of cannabis, has led to widespread use by patients for symptom relief of a variety of medical conditions and often without medical oversight. Musculoskeletal pain remains the most common reason for MC use. This review examines real-world issues pertaining to MC and offers some guidance for clinical care of patients with rheumatic diseases being treated with MC.

Recent findings: Controlled clinical studies of cannabis products in patients with rheumatic diseases have been small and tested a range of compounds, routes of administration, and clinical populations, limiting our ability to generate conclusions on MC's effectiveness in this population. Observational cohort studies and surveys suggest that use of MC and related products in patients with rheumatic diseases improves pain and associated symptoms but is commonly accompanied by mild to moderate side effects. Conflicting evidence contributes to practitioner and patient uncertainty regarding the use of MC for rheumatic disease-related pain. Despite promising preclinical and observational evidence that MC and cannabis-derived compounds are useful in the management of rheumatic disease-related pain, there remains limited high-quality clinical evidence to substantiate these findings. There are a significant number of clinical trials on this topic currently planned or underway, however, suggesting the next decade may yield more clarity. Nevertheless, given that many people with rheumatic diseases are using cannabis products, healthcare professionals must remain apprised of the evidence pertaining to cannabinoids, communicate such evidence to patients in a meaningful way that is free from personal bias and stigma, and maintain strong collaborative clinical care pertaining to MC.

审查目的:医用大麻(MC)以独特的方式进入主流医学。许多司法管辖区对医用产品的监管认可绕过了传统疗法所需的循证途径。由于更容易获得 MC,特别是与大麻娱乐合法化有关,导致患者广泛使用 MC 来缓解各种病症的症状,而且往往不受医疗监督。肌肉骨骼疼痛仍然是使用 MC 的最常见原因。本综述探讨了与 MC 有关的现实问题,并为使用 MC 治疗风湿病患者的临床护理提供了一些指导:对风湿病患者进行的大麻产品对照临床研究规模较小,并且测试了一系列化合物、给药途径和临床人群,这限制了我们就 MC 在这一人群中的有效性得出结论的能力。观察性队列研究和调查表明,风湿病患者使用大麻和相关产品可以改善疼痛和相关症状,但通常会伴有轻度至中度的副作用。相互矛盾的证据导致从业人员和患者对使用 MC 治疗风湿病相关疼痛存在不确定性。尽管有临床前和观察证据表明 MC 和大麻衍生化合物有助于治疗风湿病相关疼痛,但证实这些发现的高质量临床证据仍然有限。不过,目前有大量有关这一主题的临床试验正在计划或进行中,这表明未来十年可能会有更多明确的结果。尽管如此,鉴于许多风湿病患者都在使用大麻产品,医护人员必须随时了解与大麻素有关的证据,以有意义的方式向患者传达这些证据,避免个人偏见和污名化,并保持与 MC 有关的强有力的临床合作护理。
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引用次数: 0
Digital Health and Self-Management in Idiopathic Inflammatory Myopathies: A Missed Opportunity? 特发性炎症性肌病的数字健康与自我管理:错失良机?
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-08-08 DOI: 10.1007/s11926-024-01157-6
Simone Battista, Benedetto Giardulli, Cristiana Sieiro Santos, Or Aharonov, Darshan Puttaswamy, Anne -Marie Russell, Latika Gupta

Purpose of review: This paper explored the potential of digital health in idiopathic inflammatory myopathies (IIMs), with a focus on self-management. Digital self-management technology includes tailored treatment plans, symptom tracking, educational resources, enhanced communication, and support for long-term planning.

Recent findings: After arguing the importance of digital health in IIMs management, from diagnosis until treatment, our literature review revealed a notable gap in research focusing on the efficacy of digital self-management interventions for individuals with IIMs, with no randomised controlled trials or observational studies addressing this topic. Our review further highlighted the significant unmet need for research in self-management interventions for individuals with IIMs. The absence of studies underscores the necessity for collaborative efforts to address this gap and develop personalised, effective strategies for managing IIMs using digital technology. Individuals with IIMs deserve tailored self-management approaches akin to those available for other rheumatic and musculoskeletal diseases.

综述目的:本文探讨了数字医疗在特发性炎症性肌病(IIMs)中的潜力,重点关注自我管理。数字自我管理技术包括量身定制的治疗计划、症状跟踪、教育资源、增强沟通以及对长期规划的支持:在论证了数字健康在 IIMs 管理(从诊断到治疗)中的重要性之后,我们的文献综述发现,在针对 IIMs 患者的数字自我管理干预措施的有效性研究方面存在明显差距,没有随机对照试验或观察性研究涉及这一主题。我们的综述进一步强调了针对 IIMs 患者的自我管理干预研究的巨大需求尚未得到满足。这些研究的缺失突出表明,有必要共同努力弥补这一空白,并利用数字技术开发个性化的、有效的 IIMs 管理策略。IIMs患者应该获得与其他风湿病和肌肉骨骼疾病患者类似的量身定制的自我管理方法。
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引用次数: 0
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