强直性脊柱炎诊疗现状的临床研究
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摘要
研究背景
强直性脊柱炎是一种慢性进展的炎性疾病,往往会造成患者肢体功能、劳动能力及生活质量等诸多方面的重大损害。有文献报道认为,大多数强直性脊柱炎患者在症状出现的第一个10年之内,就会丧失脊柱的绝大部分运动能力。伴随着治疗手段的巨大进步,尤其是肿瘤坏死因子抑制剂的出现,强直性脊柱炎目前治疗的主要目的不再是单纯地缓解症状,而是对疾病进展过程的有效干预。临床证据提示,只有在未发生重大结构破坏或局限于轻度异常的情况下,强直性脊柱炎的治疗才有可能取得最佳效果。因此,建立在强直性脊柱炎早期诊断基础上的早期干预,是强直性脊柱炎治疗的关键。然而不幸的是,大量文献报道显示从最初症状出现到疾病的最终明确诊断,强直性脊柱炎往往要持续进展长达5到10年之久。临床实践中强直性脊柱炎早期诊断的失败主要由以下几个原因引起：(1)炎性背痛出现的滞后；(2)尽管骶髂关节炎的影像学异常出现较晚,仍然被改良的纽约版诊断标准列为强直性脊柱炎诊断的必要条件；(3)强直性脊柱炎的诊断缺少特异性的临床或者实验室指标。除此之外,有些报道认为HLA-B27阴性,家族史阴性以及发病年龄较早也是强直性脊柱炎诊断延迟的危险因素。然而,误诊也可能是另外一个危险因素,因为误诊更有可能直接掩盖强直性脊柱炎的正确诊断并导致强直性脊柱炎患者的错误治疗。最近一篇文献报道提示,早期误诊为腰椎间盘突出症就是阻碍强直性脊柱炎早期确诊的危险因素。另外一篇文献报道认为,类风湿疾病及脊柱结核也是造成强直性脊柱炎确诊延迟的危险因素。目前,针对强直性脊柱炎误诊及其影响的研究较少。国际脊柱关节炎协会(The Assessment in SpondyloArthritis international Society; ASAS)在2009年制定了鉴别中心型与周围型脊柱炎的标准。在临床实践中,这些标准也经常被用于脊柱炎的诊断及鉴别诊断。尽管强直性脊柱炎是脊柱炎的原型,上述标准在强直性脊柱炎早期诊断及鉴别诊断方面的作用目前仍不清楚。
目前强直性脊柱炎的药物治疗不仅可以显著控制症状,还有可能缓解甚至阻止强直性脊柱炎的进展。近年来,对治疗强直性脊柱炎的传统药物如非甾体抗炎药(nonsteroidal anti-inflammatory drugs, NSAIDs),改善病情抗风湿药(disease-modifying antirheumatic drugs, DMARDs)和糖皮质激素的认识发生了较大的变化。NSAIDs作为治疗强直性脊柱炎的一线药物,过去主要用来缓解强直性脊柱炎的症状,然而近年的几项研究显示NSAIDs可能在延缓强直性脊柱炎疾病进展方面也发挥一定作用。尽管DMARDs治疗类风湿关节的效果十分可靠,柳氮磺吡啶(Salazosulfapyridine, SASP)是目前国际脊柱关节炎协会唯一推荐治疗强直性脊柱炎的DMARDs类药物,且仅限于治疗强直性脊柱炎的外周症状。糖皮质激素是有效控制自身免疫炎症的传统药物,目前仅被推荐应用于强直性脊柱炎患者的局部封闭治疗。肿瘤坏死因子(Tumor Necrosis Factor, TNF)抑制剂的出现被认为对强直性脊柱炎的治疗具有划时代的意义。由于多种原因,并不是所有符合使用指征的患者都接受了TNF抑制剂的治疗。为了给临床医生提供指导并规范强直性脊柱炎的治疗,国际脊柱关节炎协会分别制定了一般性的强直性脊柱炎诊疗指南以及专门的TNF抑制剂使用指南。然而,强直性脊柱炎药物治疗的实际情况与上述指南的符合程度目前并不清楚。
尽管强直性脊柱炎的药物治疗已经取得了巨大进展,国际脊柱关节炎协会和欧洲抗风湿病联盟合作制定的强直性诊疗指南依然强调康复锻炼是强直性脊柱炎整体治疗策略中必不可少的组成部分。目前大量的文献报道提示,康复锻炼在缓解强直性脊柱炎患者躯体症状,改善强直性脊柱炎患者躯体功能,心理社会状态及生活质量方面都具有明确的效果。另外,强直性脊柱炎药物治疗联合康复锻炼有可能降低药物的使用量,从而减少药物不良反应。大量研究认为强直性脊柱炎患者的居家锻炼,医生指导下的锻炼以及团体锻炼都有明确的治疗效果。尽管目前研究者们对以何种频率进行何种类型的锻炼方式效果最佳,尚未达成一致意见,“持之以恒”被认为是强直性脊柱炎患者获得最佳锻炼效果的最重要因素。到目前为止,大部分报道主要关注强直性脊柱炎患者在遵循临床医师指导的情况下,进行某种特定锻炼而取得的效果。至于强直性脊柱炎患者在日常生活中进行康复锻炼的实际情况,目前报道的较少。
有报道认为强直性脊柱炎症状出现的年龄越小,累及髋关节的可能性越大。另外,男性,中心型以及起止点炎也被认为是强直性脊柱炎累及髋关节并需要进行髋关节置换术的危险因素。大约有25%到50%的强直性脊柱炎患者出现髋关节受累现象。其中,47%到90%的患者为双侧髋关节都受累及。强直性脊柱炎髋关节的累及往往会造成严重的畸形并有可能影响脊柱的活动能力。脊柱和髋关节僵直的同时出现可导致强直性脊柱炎患者的严重残疾。另外,髋关节受累不仅影响患者躯体状态,也会对患者的就业能力,社会心理状态及整体生活质量都产生重大影响。全髋关节置换术可以有效缓解疼痛并改善功能。直到现在,全髋关节置换术一直被认为是治疗强直性脊柱炎髋关节受累的标准术式。然而,由于脊柱的强直以及其它重要系统比如呼吸系统及心血管系统的受累,对强直性脊柱炎患者实施全髋关节置换术仍然颇具挑战性。之前的研究主要关注全髋关节置换术在改善强直性脊柱炎患者髋关节功能方面的作用,至于全髋关节置换术对强直性脊柱炎疾病活动度,强直性脊柱炎患者日常生活能力,就业及婚姻状况等方面的影响则关注较少,需要进一步探索。
尽管强直性脊柱炎的药物治疗和康复锻炼治疗方面均已取得巨大进展,目前仍然存在一些无论是药物治疗还是康复锻炼治疗治疗都不能有效解决的问题：首先,强直性脊柱炎患者对医嘱的长期依从性不足是一个很普遍的现象。依从性不足往往会严重影响强直性脊柱炎的治疗效果。导致强直性脊柱炎患者依从性差的原因很多,比如患者对强直性脊柱炎及其治疗知识的缺乏等；其次,患者工作及日常生活过程中的一些不良行为有可能进一步恶化强直性脊柱炎的病情；再次,在强直性脊柱炎患者的心理社会状态方面可能有一个恶性循环的存在,即强直性脊柱炎可能会导致患者心理社会状态的异常,而这些异常可能又会影响强直性脊柱炎的疾病进展。上述问题的解决都需要患者教育的有效干预。患者教育早已经被广泛应用在其它一些慢性疾病的治疗过程中,如糖尿病、哮喘及类风湿性关节炎等。尽管ASAS/EULAR指南把患者教育列为强直性脊柱炎非药物治疗的基石,针对强直性脊柱炎患者教育的研究却非常少见。近年来,慢性病的患者教育不再拘泥于面对面或者印刷材料等传统模式,而是呈现出多样化的发展趋势。尤其值得关注的是,计算机及网络在患者教育方面正发挥越来越大的作用。强直性脊柱炎患者大多较为年轻,对这类现代化的交流工具或许更容易接受。然而,这些新兴的患者教育方式对强直性脊柱炎患者的具体效果尚不清楚,需要进一步探讨。
强直性脊柱炎主要在青年时期发病,但是也可以在儿童时期就发病。如果在16岁或16以前发病,属于幼年型强直性脊柱炎,如果是在16岁以后发病,则为成年型强直性脊柱炎。尽管幼年型强直性脊柱炎有一些类似于成年型强直性脊柱炎的特点,比如骶髂关节炎在影像学上的异常表现,幼年型强直性脊柱炎可能也具有一些区别于成年型强直性脊柱炎的临床特点。多数研究认为幼年型强直性脊柱炎比成年型强直性脊柱炎的诊断延迟时间更长,也有些研究在这一方面并没有给出明确的定论。幼年型强直性脊柱炎可能更容易累及外周关节,特别是累及髋关节。尽管髋关节的累及往往意味着患者具有更差的肢体功能,幼年型强直性脊柱炎患者与成年型强直性脊柱炎患者的功能对比结果却不尽一致。目前多数研究认为幼年型强直性脊柱炎患者比成年型强直性脊柱炎患者的功能状态更差,也有些研究并未发现二者在功能状态方面的差别,另外还有一些研究甚至认为幼年型强直性脊柱炎患者遭受的功能损害要比成年型强直性脊柱炎患者更轻。总之,在此之前的研究主要关注幼年型强直性脊柱炎与成年型强直性脊柱炎在临床特点方面的差异。目前,针对幼年型强直性脊柱炎与成年型强直性脊柱炎对患者生活质量相关因素,比如受教育水平,就业情况及婚姻情况等方面影响的差别却非常少见。
目的
(1)探索强直性脊柱炎的误诊情况及其不良影响。
(2)探索强直性脊柱炎药物治疗现状,并分析其与强直性脊柱炎ASAS治疗指南的差别。
(3)探索强直性脊柱炎患者在日常生活中进行康复锻炼的情况,并分析强直性脊柱炎患者对康复锻炼的认识情况。
(4)探索全髋关节置换术对强直性脊柱炎患者在疾病活动度,肢体功能,日常生活能力,就业及婚姻状况方面的影响。另外,鉴于强直性脊柱炎患者全髋关节置换术后是否发生异位骨化的风险更高一直存在争论。本研究中,我们将对强直性脊柱炎,先天性髋臼发育不良继发骨关节炎及股骨头坏死在行全髋关节置换术后异位骨化发生率的情况进行比较。
(5)探索现有文献中关于强直性脊柱炎“患者教育”的研究情况,并探讨“患者教育”的前提,障碍,形式,内容以及“患者教育”效果的评价方式。
(6)差别的探索是制定特异性治疗措施的前提。本研究还比较了幼年型强直性脊柱炎与成年型强直性脊柱炎在临床疾病特点以及对患者生活质量影响方面的差别。
材料与方法
(1)研究对象
第一部分研究共纳入139名强直性脊柱炎患者,第二部分第一章共纳入126名强直性脊柱炎患者,第二部分第二章共纳入140名强直性脊柱炎患者,第二部分第三章共收集在我院进行全髋关节置换术的强直性脊柱炎患者42例,第三部分研究共纳入139名强直性脊柱炎患者。所有纳入本研究的患者都至少满18周岁,而且满足改良的纽约版强直性脊柱炎诊断标准。
(2)研究方法
Ⅰ通过问卷调查获取研究对象的人口基线信息,包括年龄,性别,婚姻(已婚、未婚、离异)及工作情况(在职、失业、从未就业)等。
Ⅱ通过问卷调查获取研究对象一些与疾病特点相关的信息,包括家族史,HLA-B27状态,初始症状(中心型或外周型),强直性脊柱炎症状出现的年龄(幼年型或成年型),强直性脊柱炎确诊的年龄,确诊前有无误诊,误诊为何种疾病,是哪些专业医生做出的误诊。
Ⅲ通过Bath强直性脊柱炎疾病活动指数(BASDAI)评估强直性脊柱炎疾病活动情况。
Ⅳ通过Bath强直性脊柱炎疾病功能指数(BASFI)评估强直性脊柱炎患者肢体功能情况。
Ⅴ通过强直性脊柱炎患者生活质量问卷ASQoL,评估强直性脊柱炎患者生活质量情况。
Ⅵ通过健康益处及障碍量表(EBBS)评估强直性脊柱炎患者对康复锻炼益处及障碍的认知情况。
Ⅶ疾病持续时间通过强直性脊柱炎症状首次出现的年龄到患者当前年龄来界定；确诊延迟通过强直性脊柱炎症状首次出现年龄到最终确诊年龄来界定。
Ⅷ通过问卷调查获取本研究之前的12个月里,强直性脊柱炎患者非生物制剂药物的治疗情况,主要包括：药物类型,更换药物的原因以及停药的原因等。
Ⅸ通过问卷调查获取强直性脊柱炎患者整个病程中TNF抑制剂的使用情况,主要包括：患者所知的TNF抑制剂的类型；不使用TNF抑制剂的原因；曾经使用过的TNF抑制剂的类型以及选择该类型的原因；使用TNF抑制剂的疗程；更换TNF抑制剂的原因；停用TNF抑制剂的原因。
X将调查所得有关强直性脊柱炎药物治疗相关数据与2010版的强直性脊柱炎治疗指南以及2010版的TNF抑制剂使用指南进行对比,以分析现实情况与指南的差别。
Ⅺ通过问卷调查获得有关强直性脊柱炎患者有关康复锻炼的信息,包括医生推荐的锻炼方式,患者日常生活中实际进行的锻炼方式以及康复锻炼的频率(次数/每周)。
Ⅻ通过对因髋关节累及而进行全髋关节置换的强直性脊柱炎患者进行随访,评估全髋关节置换对强直性脊柱炎患者疾病活动度,肢体功能,日常生活能力,就业及婚姻状况方面的影响情况,并分析强直性脊柱炎患者行全髋关节置换术后异位骨化的发生情况。
ⅩⅢ我们于2013年5月利用主题词'ankylosing spondylitis" AND "patient education","ankylosing spondylitis " AND "physiotherapy","ankylosing spondylitis " AND " pharmacotherapy ","ankylosing spondylitis "AND "Nonsteroidal Anti-inflammatory Drug"以及“rheumatoid arthritis" AND "patient education"对PubMed分别进行了检索,语言限制为“英语”。对有关强直性脊柱炎“患者教育”的26篇文献进行了包括样本量,观察时间,患者教育具体形式以及评价指标等方面进行了分析。另外,我们还通过谷歌学术搜索,评估了患者版强直性脊柱炎ASAS诊疗指南的应用情况。
(3)统计学方法
采用SPSS16.0统计分析软件进行分析。第一部分研究中,利用卡方检验分析了有无误诊经历的强直性脊柱炎患者在就业及婚姻方面的差别。利用t-检验分析两组强直性脊柱炎患者在BASDAI, BASFI及确诊延迟方面的差别；第二部分研究中,利用t-检验分析每周坚持至少3次锻炼的强直性脊柱炎患者与锻炼频率少于3次的强直性脊柱炎患者在BASDAI, BASFI及TBPS等方面的差别。利用卡方检验分析强直性脊柱炎患者手术前后就业情况,婚姻情况以及与先天性髋臼发育不良继发骨性关节炎及股骨头坏死患者相比,全髋关节置换术后异位骨化发生的情况。利用配对样本t-检验分析强直性脊柱炎患者术前术后BASDAI, BASFI及IADL等连续性指标的差别,对术前术后患者就业情况与结婚情况进行McNemar检验；第三部分研究中,利用卡方检验来比较幼年型和成年型强直性脊柱炎患者在家族史,HLA-B27状态,性别及初始症状等方面的差异,两组患者的受教育水平,就业情况以及婚姻情况也是利用卡方检验进行比较。利用t检验来分析幼年型和成年型强直性脊柱炎在年龄,诊断延迟,BASDAI, BASFI及ASQoL等方面的差别。P<0.05被认为差异有统计学意义。
结果
共有97名(69.8%)患者曾经历过强直性脊柱炎的误诊,在所有错误诊断中“风湿性关节炎”的频率最高(18.7%),其次是“腰椎间盘突出症”(11.5%)。有误诊和无误诊患者的强直性脊柱炎确诊延迟时间分别为4.0±2.5和2.6±1.9年(t=3.609；P<0.001)。两组患者在BASDAI(t=0.661; P=0.510), BASFI(t=0.832; P=0.407),就业情况(x2=1.298；P=0.255)及婚姻情况方面(χ2=3.609；P=0.323)的差别无统计学意义
32.5%和7.1%的患者分别服用过柳氮磺吡啶和甲氨蝶呤。10.3%和6.3%的患者分别服用过沙利度胺和来氟米特。1.6%的患者口服过糖皮质激素。50.8%的患者曾经服用中草药治疗强直性脊柱炎。46.0%患者的Bath强直性脊柱炎疾病活动指数(BASDAI)≥4,但是只有3.2%的患者正在接受肿瘤坏死因子抑制剂治疗。
31.4%的患者从未得到医生有关康复锻炼方面的建议。20.7%的患者曾经得到过建议,但是医生并未给出具体的锻炼方式。游泳是医生推荐频率最高的锻炼方式(23.6%),而强直性脊柱炎患者自己最经常进行的锻炼方式则是室内伸展运动(12.1%)以及户外散步(5.9%)。只有27.9%的患者每周进行康复锻炼至少3次。“提高身体健康状态”是强直性脊柱炎患者最认可的锻炼益处(53.0%)。“占用时间太长”是阻碍强直性脊柱炎患者进行康复锻炼的主要因素(50.7%)。每周坚持至少3次锻炼的患者与锻炼频率少于3次的患者相比,每周坚持至少3次锻炼的强直性脊柱炎患者与锻炼频率少于3次的强直性脊柱炎患者相比,BASFI的差异有统计学意义(t=2.805；P=0.006),而在BASDAI(t=0.060; P=0.952)及TBPS(t=1.210;P=0.904)方面无统计学意义。
强直性脊柱炎患者行全髋关节置换术后疾病活动情况有所好转(t=2.229；P=0.031),肢体功能改善显著(t=6.674；P<0.001)。全髋关节置换术显著提高了强直性脊柱炎的日常生活自理能力(t=18.504；P<0.001)。强直性脊柱炎患者行全髋关节置换术后,就业率显著升高(χ2=8.640；P=0.003),但是结婚机会的改善并不显著(χ2=2.005；P=0.157)。强直性脊柱炎行髋关节置换术后异位骨化的发生率(37.9%),高于因先天性髋臼发育不良继发骨性关节炎行全髋关节置换术的患者(23.6%),低于因股骨头坏死行全髋关节置换的患者异位骨化的发生率(45.7%)。行全髋关节置换术后,强直性脊柱炎对患者生活影响的总体评价由术前的平均98.0%,下降到术后的平均53.3%,下降幅度不到50%。
利用主题词'ankylosing spondylitis" AND "patient education",我们仅在pubmed检索到26篇英文文献。与此同时,当利用主题词’'ankylosing spondylitis "AND "physiotherapy"或主题词’'ankylosing spondylitis " AND " pharmacotherapy”进行检索时,分别可以检索到多达191和289篇文献。曾有报道认为类风湿关节炎的发病率与强直性脊柱炎类似,当我们利用主题词‘'rheumatoid arthritis" AND "patient education"进行检索时,可以获得多达374篇文献。在利用主题词"ankylosing spondylitis" AND "patient education"获得的26篇文献中,只有8篇文献真正在强直性脊柱炎的治疗过程中对患者实施了“患者教育”。在这8篇文献中,只有1篇文献纳入了200例患者,其余7篇的样本量都在100例以内。所有研究的持续时间都不超过半年。这8篇文献主要是评估患者教育与物理治疗相结合的效果。患者教育与药物治疗或手术治疗相结合的效果没有得到评估。多数研究将肢体功能及症状缓解作为患者教育效果的评价指标,至于患者教育对强直性脊柱炎患者心理及生活质量的影响则需要进一步探索。面对面形式的患者教育方式最常被采用,影像或印刷品教育形式只是偶有报道。没有关于电脑及网络用于强直性脊柱炎患者教育的报道。多数强直性脊柱炎患者只是接受了团体教育,对患者进行个体化教育需要引起进一步的重视。只有1篇文献将强直性脊柱炎患者的家属也列入教育范围。谷歌学术搜索上只能检索到11篇引用“患者版强直性脊柱炎ASAS诊疗指南”的英文文献,但是这11篇文献并未真正将该指南应用于患者教育,只是引用该指南来支持自己的观点。
139名强直性脊柱炎患者中,50人(36.0%)为幼年型强直性脊柱炎患者,89人(64.0%)为成年型强直性脊柱炎患者。相对于成年型强直性脊柱炎,幼年型强直性脊柱炎初发症状多发生在外周关节(χ2=29.433；P<0.001)。幼年型强直性脊柱炎患者往往比成年型强直性脊柱炎患者遭遇更为长久的确诊延迟(t=2.791；P=0.006),拥有更差的功能状态(t=2.591；P=0.011)以及更差的生活质量(t=3.495；P=0.001)。幼年型强直性脊柱炎患者获得大学及以上教育的机会也更少(χ2=4.342；P=0.037),已婚的比例要显著低于成年型强直性脊柱炎患者(χ2=6.208；P=0.013)。另外,幼年型强直性脊柱炎患者的就业率也低于成年型强直性脊柱炎患者,尽管两组患者就业率的差别尚未达到有统计学意义的水平(χ2=1.835；P=0.176),幼年型强直性脊柱炎患者中却有更多的患者自成年后就从未参加过任何工作(χ2=5.590；P=0.015)。
结论
(1)本研究发现大多数强直性脊柱炎患者曾经历过强直性脊柱炎的误诊。误诊可以显著延长强直性脊柱炎的最终确诊时间。强直性脊柱炎误诊对疾病活动度,肢体功能,就业及婚姻方面的影响无统计学意义。
(2)作为治疗强直性脊柱炎的一线药物,非甾体类抗炎药的使用率偏低,柳氮磺吡啶和甲氨蝶呤则被过度应用于强直性脊柱炎。尽管没有被纳入治疗指南,沙利度胺,来氟米特和中草药被广泛应用于强直性脊柱炎的治疗。TNF抑制剂的实际需求远没有得到满足。
(3)绝大多数强直性脊柱炎患者都没有得到关于康复锻炼的科学指导。绝大多数患者没有坚持足够的康复锻炼。强直性脊柱炎患者坚持每周至少3次的功能锻炼拥有更佳的肢体功能状态。
(4)强直性脊柱炎患者行全髋关节置换后疾病活动情况有所好转,可显著改善肢体功能及日常生活自理能力。强直性脊柱炎患者行全髋关节置换术后,就业率显著升高,但是结婚机会的改善并不显著。强直性脊柱炎行髋关节置换术后异位骨化的发生率低于股骨头坏死患者术后异位骨化的发生率,同时高于先天性髋臼发育不良继发骨性关节炎患者异位骨化的发生率。
(5)本研究发现强直性脊柱炎的“患者教育”未得到足够重视。鉴于现有文献中关于强直性脊柱炎“患者教育”的证据严重不足,在对强直性脊柱炎患者进行患者教育的时候,可以考虑借鉴其它慢性疾病患者教育的经验,比如类风湿性关节炎等。
(6)本研究发现幼年型强直性脊柱炎的早期诊断比成年型强直性脊柱炎的早期诊断更具挑战性。幼年型强直性脊柱炎或许需要专门的诊断标准。幼年型强直性脊柱炎患者的肢体功能状态更差,这提示幼年型强直性脊柱炎患者或许需要更为激进的治疗策略。需要制定相关干预措施来帮助患者对抗强直性脊柱炎对其生活质量的影响,尤其是那些幼年型强直性脊柱炎患者。
Background
Ankylosing spondylitis (AS) is a chronic inflammatory disease, often results in significant impairment on physical function, working ability and quality of life. The majority of AS patients may lose most of their spinal mobility within the first10years of onset. With the tremendous development of treatment strategies, in particular, the advent of TNF-inhibitors, the primary aim of AS management has varied from symptom relief to the modification of disease progression. The current evidence implies that only when the structural damage has not happened or just appeared in quite mild extent, could the management modalities achieve the optimal effect. Therefore, early interventions on the basis of early correct diagnosis are essential in the treatment of AS. Unfortunately, it has been frequently reported that AS disease often keeps progressing for as long as5to10years from the onset of symptoms till to the correct diagnosis at last. Early diagnosis of AS is often missed in clinical practice mainly due to several disease characteristics which include:(1) the late onset of inflammatory back pain (IBP);(2) the late onset of radiographic sacroiliitis which is mandatory in the modified New York criteria;(3) the lack of pathognomonic clinical and laboratory tests. In addition, other factors, such as negative HLA-B27, negative family history and early age of onset were also regarded as risk factors of diagnosis delay in some reports. However, misdiagnosis may be anther risk factor which may directly mask the correct diagnosis of AS and lead to mistreatment for AS patients. In a recent study, the initial diagnosis of LDH was reported as an obvious hindering factor for early correct diagnosis of AS. In another study, rheumatoid arthritis and tuberculosis of spine were also regarded as risk factors of diagnosis delay. At present, studies focusing on the misdiagnoses and the related impacts in AS remain limited. The Assessment of SpondyloArthritis International Society (ASAS) group has developed criteria to classify patients with axial or peripheral SpA in2009. In clinical practice, these criteria have been applied in diagnosis as well as differential diagnosis of SpA. Although AS is the prototypical form of axial SpA, the effect of these criteria on diagnosis and differential diagnosis of AS is not clear.
At present, pharmacotherapy has obvious ability to relieve symptoms and the potential ability to slow down or even to prevent AS progression. With the development of evidence, concepts about conventional drugs such as NSAIDs, disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids have been substantially changed in the past decade. NSAIDs have long been regarded as the first-line drug in AS pharmacotherapy and have been often prescribed with the primary aim for symptomatic improvements. Recently, however, the concept toward NSAIDs probably needs to be improved. Several studies indicate that NSAIDs may also play a valuable role in reducing or even reverting the disease progression. Despite the definite efficacy of DMARDs in rheumatoid arthritis (RA), sulfasalazine is at present the only one recommended drug of limited effect for AS patients with peripheral arthritis. Glucocorticoids are traditional drugs in effective control of autoimmune diseases. The available evidence, however, is mainly limited in local injections for AS management. The advent of TNF-inhibitors is thought to have revolutionised the management of AS. Nevertheless, not all of the AS patient meet the criteria to use TNF-inhibitors. In the meanwhile, due to various reasons, such as the high cost and the fear of side effects, not all of the AS patients that meet the criteria for biologic therapy have actually used TNF-inhibitors. Certain time is required for understanding and acceptance of the new changes. In order to provide guidance for clinicians and to standardize the procedure for monitoring and treating patients with AS, evidence based management recommendations was developed under the collaboration of the Assessment in SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism(EULAR) in2005which had been updated once in2010. Consensus statement on the use of TNF-inhibitors was published by ASAS as early as in2003and was updated twice in2006and2010respectively. However, if these recommendations were implemented well enough in clinical practice is not clear.
Despite substantial progress in pharmacotherapy, the recommendations developed under the collaboration of the Assessment in SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism(EULAR) have consistently stressed that exercise is the indispensable component in comprehensive AS management. Substantial evidence in current literature has confirmed the effect of exercise in relieving physical symptom and improving physical function, psychological status and quality of life for AS patients. In addition, the combination of exercise and pharmacotherapy may decrease drug consumption and thus reduce related adverse effects. Home-based exercise, supervised exercise, group exercise and spa-based exercise are all frequently reported with certain benefit. Although there has been no consensus on which specific type of exercise with what frequency is optimal, adherence is thought to be the most important factor for AS patients to benefit from exercise. So far, most reports mainly focused on the effect of certain exercise for AS patients who had followed the clinicians'prescription. Studies investigating the real status of exercise in AS patients'daily life remain scarce.
It is deemed that the younger the age at the onset, the greater is the likelihood of hip involvement. Male, axial disease, and enthesitis are also regarded as risk factors of hip involvement and the need for THA in AS. Hip involvement occurs in25%to50%of patients with AS, and47%to90%of patients who have such involvement have it bilaterally. Hip joint involvement in AS often results in severe deformities and may also harm other activities related to spinal mobility. The combination of the stiff spine and hip can cause severe disability in the patients. In addition, hip involvement can not only affect the patients in physical status but also in employability, psychosocial status and comprehensive quality of life. Till now, THA is still the standard operation for pain relief and function improvement to treat patients with AS. However, THA for AS patients with stiff spine and involvement in other systems such as the pulmonary and cardiovascular systems is still a challenging procedure. More attention should be paid on certain AS-specific problems regarding effect of THA on patients'"disease activity","physical function","ability for daily life","employability", and "marriage".
Despite substantial progress in pharmacotherapy and physical therapy in AS management, certain problems still exist which could not be effectively resolved by neither pharmacotherapy nor physical therapy at present. The optimal therapeutic effects are often missed due to the insufficiency of patients'long-term compliance with the prescriptions. Actually, this phenomenon of poor compliance with the doctors'prescriptions may be quite common among AS patients. There are a variety of reasons to explain it, for example the lack of knowledge about AS disease and its' treatment. Besides, certain inappropriate behaviors in the patients'daily life or work may further aggravate the disease condition. A potential vicious circle may exist in aspect of psychological status of AS patients. The disease may lead to certain psychological abnormalities and these abnormalities may in turn affect the development of AS. Solutions to these problems mentioned above necessitate effective patient education which has been widely applied in other chronic diseases, such as diabetes, asthma and rheumatoid arthritis (RA). Although it has been stressed as the cornerstone in the non-pharmacotherapy for AS in ASAS/EULAR recommendations, studies concentrating on AS patient education remain quite scanty in current literature. In recent years, types of patient education for chronic diseases have been no longer limited in face-to-face or written educational forms but have taken on a tendency of diversification. In particular, computer and internet have been frequently reported to play an increasing important role in patient education and AS patients seem to be of high access to these modern communication means due to their relatively young age. The specific effects of these educational types, however, remain indefinite in AS patients and need to be explored.
AS occurs predominantly in early adulthood, but can also occur in childhood. When AS occurs≤16years of age, it is termed JoAS, and when it occurs after the age of16, it is termed AoAS. Although JoAS shares certain similar features with AoAS, for example the presence of radiographic sacroiliitis, it may also have some specific clinical characteristics that distinguish it from AoAS. Most of the studies reflected that JoAS often had significant longer diagnosis delay compared with AoAS whereas some other studies had not included the comparison in this aspect. JoAS has been reported with higher frequency of peripheral joints involvement, especially the involvement of the hip joint. Although hip joint involvement has been thought to be associated with worse functional outcome for AS patients, discrepancies, however, exist in the comparison of functional status between JoAS and AoAS. The majority of the present studies reported that JoAS had worse functional outcome than AoAS while some other studies failed to detect the differences between JoAS and AoAS. Moreover, there were also sparse reports that even reflected that JoAS might suffer from less functional impairment than AoAS. Radiographical differences between JoAS and AoAS have also been assessed in several studies and JoAS was reported to have less severe axial involvement radiographically compared with AoAS. Overall, most of the studies so far have mainly focused on the differences in aspect of clinical features between JoAS and AoAS. Studies centering on the potential differences between JoAS and AoAS in certain important aspects of quality of life, such as educational level, status of employment and status of marriage, remain scarce.
Objectives
(1) To assess the current status and related impacts of alternative diagnoses before the final correct diagnosis of AS.
(2) To examine the status of pharmacotherapy for AS in comparison with current recommendations.
(3) To assess the current status of exercise in AS patients'daily life and to analyze the patients'perception to exercise.
(4) To explore effect of THA on patients'"disease activity","physical function","ability for daily life","employability", and "marriage".In addition, we will also compare of rate of HO between patients with AS,DDH and AFN.
(5) To explore the current status of patient education for AS reported in the literature. In addition, the barriers to patient education, prerequisites for patient education, practical educational forms, contents of patient education as well as the educational efficiency assessment will be also explored.
(6) Detection of differences is the precondition for the development of specific interventions. So, in this study, we also tried to compare the differences in clinical features as well as several essential factors related with quality of life between JoAS and AoAS.
Patients and Methods
(1) Patients
All of the included patients were at least18years old and should have a confirmed diagnosis of AS according to modified New York classification criteria.
(2) Methods
I Questionnaire was used which contains a number of demographic variables, such as age, sex, status of marriage (married, unmarried or divorced) and status of employment (employed, unemployed or never got employed).
II Disease characteristics of the study participants were examined by a questionnaire which includes:family history, HLA-B27status, initial symptoms (peripheral or axial), age at onset of AS symptom (juvenile onset or adult onset), age at correct diagnosis of AS, alternative diagnoses before final AS diagnosis and in particular, the specialties of the clinicians who made the alternative diagnoses.
Ⅲ Disease activity measured by BASDAI
Ⅳ Functional status measured by BASFI.
Ⅴ Disease-related quality of life was measured with ASQoL
Ⅵ EBBS was applied to examine AS patients'perception towards benefits of exercise and barriers to exercise.
Ⅶ Disease duration was then defined as the interval between the age at onset of AS symptom and the current age. Diagnosis delay was defined as the gap between the age at onset of AS symptom and the age of correct AS diagnosis.
Ⅷ Questionnaire was designed to assess the whole experience of non-biologic pharmacotherapy during12months prior to this study and included:①type of drugs,②reasons for switching drugs, and③reasons for ceasing drugs.
IX Questionnaire was designed to assess the whole experience of biologic pharmacotherapy not during the previous12months but during the whole course of the disease and included:①types of TNF-inhibitors they know about,②reasons for not using TNF-inhibitors,③types of TNF-inhibitors they have ever used,④reasons for their choice of the type of TNF-inhibitors,⑤duration of TNF-inhibitors treatment,⑥reasons for switching TNF-inhibitors, and⑦reasons for ceasing TNF-inhibitors.
X We took the2010version ASAS/EULAR recommendations for AS management and2010version of ASAS recommendations for application of TNF-inhibitors as the standard to compare the discrepancies.
XI Questionnaire was designed on the basis of exercise interventions in the literature to assess the experience of exercise during the whole course of the AS disease and included:①types of exercise recommended by clinicians,②types of exercise actually performed in daily life,③the frequency of participation (times per week).
M To get information related to effect of THA on patients'"disease activity","physical function","ability for daily life","employability","marriage" and rate of HO by performing follow-up for AS patients with THA.
XIII In May2013, we searched PubMed using the MESH terms "ankylosing spondylitis" AND "patient education", ankylosing spondylitis "AND "physiotherapy","nkylosing spondylitis " AND " pharmacotherapy ", ankylosing spondylitis "AND "Nonsteroidal Anti-inflammatory Drug" as well as the MESH "rheumatoid arthritis" AND "patient education". The language was limited with "English". We then analyze the26articles related patient education in AS treatment in aspects of" Sample of study "," Duration of study ","Forms of education" and "Variables of assessment". We also examine the status of the citation of patient version recommendations by searching Google Scholar.
Result
Misdiagnoses were reported by69.8%of the patients. The most common alternative diagnoses were "Arthritis associated with rheumatic fever"(AARF)(18.7%) and "Lumbar disc herniation"(LDH)(11.5%). Misdiagnoses resulted in significant diagnosis delay (P<0.001). No statistical differences were detected in BASDAI (t=0.661; P=0.510), BASFI (t=0.832; P=0.407), status of employment (χ2=1.298; P=0.255) and marriage (χ2=3.609; P=0.323) between patients with or without alternative diagnoses.
53.2%had taken nonsteroidal anti-inflammatory drugs (NSAIDs).32.5%and7.1%had taken salazopyrine and methotrexate respectively. Thalidomide and leflunomide were respectively used by10.3%and6.3%. Oral glucocorticoids was reported by1.6%. Tramadol was reported by5.6%.50.8%had ever taken Chinese herbal medicine (CHM) for AS.3.2%of the patients were taking TNF-inhibitors regularly while46.0%had a BASDAI≥4.
31.4%had not got exercise recommendations.20.7%had got recommendations but without specific exercise type. Swimming was most commonly recommended by clinicians (23.6%) while the most common exercise actually performed by AS patients were home stretching (12.1%) and walking (5.9%). Only27.9%insisted on exercise at least3times per week."Higher levels of physical fitness"(53.0%) was most frequently reported benefit while the most frequently reported barrier to exercise was "it took me too much time"(50.7%). Statistical difference existed in BASFI between patients insisting on exercise at least3times each week and patients with less frequency (t=2.805; P=0.006). No statistical differences were detected in BASDAI and TBPS between the two groups.
After THA, AS patients'disease activity got relived in certain extent(t=2.229; P=0.031); their physical function (t=6.674; P<0.001) and ability for daily life (t=18.504; P<0.001)was significantly restored. AS patients'rate of employment was obviously upleveled (x2=8.640; P=0.003). However, their chance of getting married was not improved (x2=2.005;P=0.157). Rate of HO after THA among AS patients (37.9%) was higher than that among patients with DDH (23.6%) but lower than that among patients with ADH (45.7%). After THA, effect of disease on AS patients'life decreased from98.0%to53.3%. The decrease is less than50%.
In May2013, we only got26articles published in English language when we searched PubMed using the MESH terms "ankylosing spondylitis" AND "patient education". In the meanwhile, as many as191and289articles were retrieved relatively when we limited the MESH terms as "ankylosing spondylitis " AND "physiotherapy" as well as "ankylosing spondylitis " AND " pharmacotherapy ". Actually, if we use certain specific name of drug as MESH terms, much more reports would be retrieved. For example, as many as327articles could be retrieved when we used the MESH terms "ankylosing spondylitis "AND "Nonsteroidal Anti-inflammatory Drug". The prevalence of RA was reported to be close to the prevalence of AS. Surprisingly, up to374reports could be retrieved when the MESH terms "rheumatoid arthritis" AND "patient education" were used.
Among the26articles retrieved with the MESH terms "ankylosing spondylitis" AND "patient education", only8reports have practically applied certain patient education process in AS treatment. Of the8reports, only one report has included200patients while none of the other7studies have included more than100AS patients. None of the8reports persisted more than6months. The majority of the8reports aimed at evaluating the effect of combining patient education with physiotherapy. Effect of combining patient education with pharmacotherapy or surgery has not been explored. Most of the studies focused on assessing physical variables (function or symptom) while psychological variables and status of quality of life need further concern. Face to face education was the most often used form while the other types such as video and booklet were only applied sparsely. No computer and internet assisted educational form for AS was reported in these8studies. AS patients were often educated in group meeting while their individual needs might require more attention. Only one study has included family member (patients' spouses) in the education.
For the purpose of strengthening patients'knowledge and participation in the management of AS, the Assessment of SpondyloArthritis International Society (ASAS) and the European League Against Rheumatism (EULAR) had converted their recommendations for AS management into a patient-understandable version and published the patient version recommendations in the year of2008. Till now, nearly5years have passed, the patient version recommendations have been merely cited by18reports as reflected in the Google Scholar. These18reports included11English papers and7papers written in other languages. Of the11English papers, no one focused on assessing the practical implementation of the patient version recommendations in AS patient education but just cited it to support their own individual viewpoints.
There were50patients with JoAS (36.0%) and89with AoAS (64.0%). The JoAS group showed more onset with peripheral joints involvement(χ2=29.433; P<0.001), significant diagnosis delay(t=2.791; P=0.006), worse functional status(t=2.591; P=0.011)and poorer status of quality of life(t=3.495; P=0.001). Patients with JoAS also showed significant lower rate in college education(χ2=4.342; P=0.037) and marriage(x2=6.208; P=0.013). The rate of employment in JoAS group was lower than that in AoAS group. Although the difference in employment had not reached statistical level, the JoAS group included more patients who had never got employed since they reached the age of adult (χ2=5.590; P=0.015).
Conclusions
(1) This study reflected that the majority of AS patients have the experience of alternative diagnoses and alternative diagnoses could lead to significant diagnosis delay of AS. The impacts of alternative diagnoses on disease activity, physical function, status of employment and marriage are insignificant.
(2) As the first-line drug for AS treatment, NSAIDs might be not fully used while sulfasalazine and methotrexate were overused in AS. Although not included in recommendations, certain drugs such as thalidomide, leflunomide and CHM were taken frequently by AS patients. There is a substantial unmet need for TNF-inhibitors.
(3) Significantly high percentage of AS patients had not got appropriate exercise recommendations and most of the patients failed to insist on exercise sufficiently. AS patients insisting on exercise at least3times each week have better functional status than patients with less frequency of exercise.
(4) After THA, AS patients'disease activity got relived in certain extent.Their physical function and ability for daily life was significantly restored. AS patients' rate of employment was obviously upleveled. However, their chance of getting married was not improved. Rate of HO after THA among AS patients was higher than that among patients with DDH but lower than that among patients with ADH. After THA, effect of disease on AS patients'life decreased from98.0%to53.3%. The decrease is less than50%.
(5) Our results reflected the actual insufficiency of patient education for AS and more concern in this aspect is required definitely. Due to the extreme lack of AS-specific evidence in patient education, experience from other chronic disease such as rheumatoid arthritis may need to be consulted, when we plan to design educational programme for AS patients.
(6) The data reflected that early diagnosis of JoAS is an even more severe challenge compared with AoAS and specific diagnosing criteria for JoAS is warranted. Patients with JoAS showed worse functional status than patients with AoAS and more aggressive treatment may be needed for JoAS. Certain interventions to counteract the disease impact on life for AS patients are required, especially for patients with JoAS.
强直性脊柱炎是一种慢性进展的炎性疾病,往往会造成患者肢体功能、劳动能力及生活质量等诸多方面的重大损害。有文献报道认为,大多数强直性脊柱炎患者在症状出现的第一个10年之内,就会丧失脊柱的绝大部分运动能力。伴随着治疗手段的巨大进步,尤其是肿瘤坏死因子抑制剂的出现,强直性脊柱炎目前治疗的主要目的不再是单纯地缓解症状,而是对疾病进展过程的有效干预。临床证据提示,只有在未发生重大结构破坏或局限于轻度异常的情况下,强直性脊柱炎的治疗才有可能取得最佳效果。因此,建立在强直性脊柱炎早期诊断基础上的早期干预,是强直性脊柱炎治疗的关键。然而不幸的是,大量文献报道显示从最初症状出现到疾病的最终明确诊断,强直性脊柱炎往往要持续进展长达5到10年之久。临床实践中强直性脊柱炎早期诊断的失败主要由以下几个原因引起：(1)炎性背痛出现的滞后；(2)尽管骶髂关节炎的影像学异常出现较晚,仍然被改良的纽约版诊断标准列为强直性脊柱炎诊断的必要条件；(3)强直性脊柱炎的诊断缺少特异性的临床或者实验室指标。除此之外,有些报道认为HLA-B27阴性,家族史阴性以及发病年龄较早也是强直性脊柱炎诊断延迟的危险因素。然而,误诊也可能是另外一个危险因素,因为误诊更有可能直接掩盖强直性脊柱炎的正确诊断并导致强直性脊柱炎患者的错误治疗。最近一篇文献报道提示,早期误诊为腰椎间盘突出症就是阻碍强直性脊柱炎早期确诊的危险因素。另外一篇文献报道认为,类风湿疾病及脊柱结核也是造成强直性脊柱炎确诊延迟的危险因素。目前,针对强直性脊柱炎误诊及其影响的研究较少。国际脊柱关节炎协会(The Assessment in SpondyloArthritis international Society; ASAS)在2009年制定了鉴别中心型与周围型脊柱炎的标准。在临床实践中,这些标准也经常被用于脊柱炎的诊断及鉴别诊断。尽管强直性脊柱炎是脊柱炎的原型,上述标准在强直性脊柱炎早期诊断及鉴别诊断方面的作用目前仍不清楚。
目前强直性脊柱炎的药物治疗不仅可以显著控制症状,还有可能缓解甚至阻止强直性脊柱炎的进展。近年来,对治疗强直性脊柱炎的传统药物如非甾体抗炎药(nonsteroidal anti-inflammatory drugs, NSAIDs),改善病情抗风湿药(disease-modifying antirheumatic drugs, DMARDs)和糖皮质激素的认识发生了较大的变化。NSAIDs作为治疗强直性脊柱炎的一线药物,过去主要用来缓解强直性脊柱炎的症状,然而近年的几项研究显示NSAIDs可能在延缓强直性脊柱炎疾病进展方面也发挥一定作用。尽管DMARDs治疗类风湿关节的效果十分可靠,柳氮磺吡啶(Salazosulfapyridine, SASP)是目前国际脊柱关节炎协会唯一推荐治疗强直性脊柱炎的DMARDs类药物,且仅限于治疗强直性脊柱炎的外周症状。糖皮质激素是有效控制自身免疫炎症的传统药物,目前仅被推荐应用于强直性脊柱炎患者的局部封闭治疗。肿瘤坏死因子(Tumor Necrosis Factor, TNF)抑制剂的出现被认为对强直性脊柱炎的治疗具有划时代的意义。由于多种原因,并不是所有符合使用指征的患者都接受了TNF抑制剂的治疗。为了给临床医生提供指导并规范强直性脊柱炎的治疗,国际脊柱关节炎协会分别制定了一般性的强直性脊柱炎诊疗指南以及专门的TNF抑制剂使用指南。然而,强直性脊柱炎药物治疗的实际情况与上述指南的符合程度目前并不清楚。
尽管强直性脊柱炎的药物治疗已经取得了巨大进展,国际脊柱关节炎协会和欧洲抗风湿病联盟合作制定的强直性诊疗指南依然强调康复锻炼是强直性脊柱炎整体治疗策略中必不可少的组成部分。目前大量的文献报道提示,康复锻炼在缓解强直性脊柱炎患者躯体症状,改善强直性脊柱炎患者躯体功能,心理社会状态及生活质量方面都具有明确的效果。另外,强直性脊柱炎药物治疗联合康复锻炼有可能降低药物的使用量,从而减少药物不良反应。大量研究认为强直性脊柱炎患者的居家锻炼,医生指导下的锻炼以及团体锻炼都有明确的治疗效果。尽管目前研究者们对以何种频率进行何种类型的锻炼方式效果最佳,尚未达成一致意见,“持之以恒”被认为是强直性脊柱炎患者获得最佳锻炼效果的最重要因素。到目前为止,大部分报道主要关注强直性脊柱炎患者在遵循临床医师指导的情况下,进行某种特定锻炼而取得的效果。至于强直性脊柱炎患者在日常生活中进行康复锻炼的实际情况,目前报道的较少。
有报道认为强直性脊柱炎症状出现的年龄越小,累及髋关节的可能性越大。另外,男性,中心型以及起止点炎也被认为是强直性脊柱炎累及髋关节并需要进行髋关节置换术的危险因素。大约有25%到50%的强直性脊柱炎患者出现髋关节受累现象。其中,47%到90%的患者为双侧髋关节都受累及。强直性脊柱炎髋关节的累及往往会造成严重的畸形并有可能影响脊柱的活动能力。脊柱和髋关节僵直的同时出现可导致强直性脊柱炎患者的严重残疾。另外,髋关节受累不仅影响患者躯体状态,也会对患者的就业能力,社会心理状态及整体生活质量都产生重大影响。全髋关节置换术可以有效缓解疼痛并改善功能。直到现在,全髋关节置换术一直被认为是治疗强直性脊柱炎髋关节受累的标准术式。然而,由于脊柱的强直以及其它重要系统比如呼吸系统及心血管系统的受累,对强直性脊柱炎患者实施全髋关节置换术仍然颇具挑战性。之前的研究主要关注全髋关节置换术在改善强直性脊柱炎患者髋关节功能方面的作用,至于全髋关节置换术对强直性脊柱炎疾病活动度,强直性脊柱炎患者日常生活能力,就业及婚姻状况等方面的影响则关注较少,需要进一步探索。
尽管强直性脊柱炎的药物治疗和康复锻炼治疗方面均已取得巨大进展,目前仍然存在一些无论是药物治疗还是康复锻炼治疗治疗都不能有效解决的问题：首先,强直性脊柱炎患者对医嘱的长期依从性不足是一个很普遍的现象。依从性不足往往会严重影响强直性脊柱炎的治疗效果。导致强直性脊柱炎患者依从性差的原因很多,比如患者对强直性脊柱炎及其治疗知识的缺乏等；其次,患者工作及日常生活过程中的一些不良行为有可能进一步恶化强直性脊柱炎的病情；再次,在强直性脊柱炎患者的心理社会状态方面可能有一个恶性循环的存在,即强直性脊柱炎可能会导致患者心理社会状态的异常,而这些异常可能又会影响强直性脊柱炎的疾病进展。上述问题的解决都需要患者教育的有效干预。患者教育早已经被广泛应用在其它一些慢性疾病的治疗过程中,如糖尿病、哮喘及类风湿性关节炎等。尽管ASAS/EULAR指南把患者教育列为强直性脊柱炎非药物治疗的基石,针对强直性脊柱炎患者教育的研究却非常少见。近年来,慢性病的患者教育不再拘泥于面对面或者印刷材料等传统模式,而是呈现出多样化的发展趋势。尤其值得关注的是,计算机及网络在患者教育方面正发挥越来越大的作用。强直性脊柱炎患者大多较为年轻,对这类现代化的交流工具或许更容易接受。然而,这些新兴的患者教育方式对强直性脊柱炎患者的具体效果尚不清楚,需要进一步探讨。
强直性脊柱炎主要在青年时期发病,但是也可以在儿童时期就发病。如果在16岁或16以前发病,属于幼年型强直性脊柱炎,如果是在16岁以后发病,则为成年型强直性脊柱炎。尽管幼年型强直性脊柱炎有一些类似于成年型强直性脊柱炎的特点,比如骶髂关节炎在影像学上的异常表现,幼年型强直性脊柱炎可能也具有一些区别于成年型强直性脊柱炎的临床特点。多数研究认为幼年型强直性脊柱炎比成年型强直性脊柱炎的诊断延迟时间更长,也有些研究在这一方面并没有给出明确的定论。幼年型强直性脊柱炎可能更容易累及外周关节,特别是累及髋关节。尽管髋关节的累及往往意味着患者具有更差的肢体功能,幼年型强直性脊柱炎患者与成年型强直性脊柱炎患者的功能对比结果却不尽一致。目前多数研究认为幼年型强直性脊柱炎患者比成年型强直性脊柱炎患者的功能状态更差,也有些研究并未发现二者在功能状态方面的差别,另外还有一些研究甚至认为幼年型强直性脊柱炎患者遭受的功能损害要比成年型强直性脊柱炎患者更轻。总之,在此之前的研究主要关注幼年型强直性脊柱炎与成年型强直性脊柱炎在临床特点方面的差异。目前,针对幼年型强直性脊柱炎与成年型强直性脊柱炎对患者生活质量相关因素,比如受教育水平,就业情况及婚姻情况等方面影响的差别却非常少见。
目的
(1)探索强直性脊柱炎的误诊情况及其不良影响。
(2)探索强直性脊柱炎药物治疗现状,并分析其与强直性脊柱炎ASAS治疗指南的差别。
(3)探索强直性脊柱炎患者在日常生活中进行康复锻炼的情况,并分析强直性脊柱炎患者对康复锻炼的认识情况。
(4)探索全髋关节置换术对强直性脊柱炎患者在疾病活动度,肢体功能,日常生活能力,就业及婚姻状况方面的影响。另外,鉴于强直性脊柱炎患者全髋关节置换术后是否发生异位骨化的风险更高一直存在争论。本研究中,我们将对强直性脊柱炎,先天性髋臼发育不良继发骨关节炎及股骨头坏死在行全髋关节置换术后异位骨化发生率的情况进行比较。
(5)探索现有文献中关于强直性脊柱炎“患者教育”的研究情况,并探讨“患者教育”的前提,障碍,形式,内容以及“患者教育”效果的评价方式。
(6)差别的探索是制定特异性治疗措施的前提。本研究还比较了幼年型强直性脊柱炎与成年型强直性脊柱炎在临床疾病特点以及对患者生活质量影响方面的差别。
材料与方法
(1)研究对象
第一部分研究共纳入139名强直性脊柱炎患者,第二部分第一章共纳入126名强直性脊柱炎患者,第二部分第二章共纳入140名强直性脊柱炎患者,第二部分第三章共收集在我院进行全髋关节置换术的强直性脊柱炎患者42例,第三部分研究共纳入139名强直性脊柱炎患者。所有纳入本研究的患者都至少满18周岁,而且满足改良的纽约版强直性脊柱炎诊断标准。
(2)研究方法
Ⅰ通过问卷调查获取研究对象的人口基线信息,包括年龄,性别,婚姻(已婚、未婚、离异)及工作情况(在职、失业、从未就业)等。
Ⅱ通过问卷调查获取研究对象一些与疾病特点相关的信息,包括家族史,HLA-B27状态,初始症状(中心型或外周型),强直性脊柱炎症状出现的年龄(幼年型或成年型),强直性脊柱炎确诊的年龄,确诊前有无误诊,误诊为何种疾病,是哪些专业医生做出的误诊。
Ⅲ通过Bath强直性脊柱炎疾病活动指数(BASDAI)评估强直性脊柱炎疾病活动情况。
Ⅳ通过Bath强直性脊柱炎疾病功能指数(BASFI)评估强直性脊柱炎患者肢体功能情况。
Ⅴ通过强直性脊柱炎患者生活质量问卷ASQoL,评估强直性脊柱炎患者生活质量情况。
Ⅵ通过健康益处及障碍量表(EBBS)评估强直性脊柱炎患者对康复锻炼益处及障碍的认知情况。
Ⅶ疾病持续时间通过强直性脊柱炎症状首次出现的年龄到患者当前年龄来界定；确诊延迟通过强直性脊柱炎症状首次出现年龄到最终确诊年龄来界定。
Ⅷ通过问卷调查获取本研究之前的12个月里,强直性脊柱炎患者非生物制剂药物的治疗情况,主要包括：药物类型,更换药物的原因以及停药的原因等。
Ⅸ通过问卷调查获取强直性脊柱炎患者整个病程中TNF抑制剂的使用情况,主要包括：患者所知的TNF抑制剂的类型；不使用TNF抑制剂的原因；曾经使用过的TNF抑制剂的类型以及选择该类型的原因；使用TNF抑制剂的疗程；更换TNF抑制剂的原因；停用TNF抑制剂的原因。
X将调查所得有关强直性脊柱炎药物治疗相关数据与2010版的强直性脊柱炎治疗指南以及2010版的TNF抑制剂使用指南进行对比,以分析现实情况与指南的差别。
Ⅺ通过问卷调查获得有关强直性脊柱炎患者有关康复锻炼的信息,包括医生推荐的锻炼方式,患者日常生活中实际进行的锻炼方式以及康复锻炼的频率(次数/每周)。
Ⅻ通过对因髋关节累及而进行全髋关节置换的强直性脊柱炎患者进行随访,评估全髋关节置换对强直性脊柱炎患者疾病活动度,肢体功能,日常生活能力,就业及婚姻状况方面的影响情况,并分析强直性脊柱炎患者行全髋关节置换术后异位骨化的发生情况。
ⅩⅢ我们于2013年5月利用主题词'ankylosing spondylitis" AND "patient education","ankylosing spondylitis " AND "physiotherapy","ankylosing spondylitis " AND " pharmacotherapy ","ankylosing spondylitis "AND "Nonsteroidal Anti-inflammatory Drug"以及“rheumatoid arthritis" AND "patient education"对PubMed分别进行了检索,语言限制为“英语”。对有关强直性脊柱炎“患者教育”的26篇文献进行了包括样本量,观察时间,患者教育具体形式以及评价指标等方面进行了分析。另外,我们还通过谷歌学术搜索,评估了患者版强直性脊柱炎ASAS诊疗指南的应用情况。
(3)统计学方法
采用SPSS16.0统计分析软件进行分析。第一部分研究中,利用卡方检验分析了有无误诊经历的强直性脊柱炎患者在就业及婚姻方面的差别。利用t-检验分析两组强直性脊柱炎患者在BASDAI, BASFI及确诊延迟方面的差别；第二部分研究中,利用t-检验分析每周坚持至少3次锻炼的强直性脊柱炎患者与锻炼频率少于3次的强直性脊柱炎患者在BASDAI, BASFI及TBPS等方面的差别。利用卡方检验分析强直性脊柱炎患者手术前后就业情况,婚姻情况以及与先天性髋臼发育不良继发骨性关节炎及股骨头坏死患者相比,全髋关节置换术后异位骨化发生的情况。利用配对样本t-检验分析强直性脊柱炎患者术前术后BASDAI, BASFI及IADL等连续性指标的差别,对术前术后患者就业情况与结婚情况进行McNemar检验；第三部分研究中,利用卡方检验来比较幼年型和成年型强直性脊柱炎患者在家族史,HLA-B27状态,性别及初始症状等方面的差异,两组患者的受教育水平,就业情况以及婚姻情况也是利用卡方检验进行比较。利用t检验来分析幼年型和成年型强直性脊柱炎在年龄,诊断延迟,BASDAI, BASFI及ASQoL等方面的差别。P<0.05被认为差异有统计学意义。
结果
共有97名(69.8%)患者曾经历过强直性脊柱炎的误诊,在所有错误诊断中“风湿性关节炎”的频率最高(18.7%),其次是“腰椎间盘突出症”(11.5%)。有误诊和无误诊患者的强直性脊柱炎确诊延迟时间分别为4.0±2.5和2.6±1.9年(t=3.609；P<0.001)。两组患者在BASDAI(t=0.661; P=0.510), BASFI(t=0.832; P=0.407),就业情况(x2=1.298；P=0.255)及婚姻情况方面(χ2=3.609；P=0.323)的差别无统计学意义
32.5%和7.1%的患者分别服用过柳氮磺吡啶和甲氨蝶呤。10.3%和6.3%的患者分别服用过沙利度胺和来氟米特。1.6%的患者口服过糖皮质激素。50.8%的患者曾经服用中草药治疗强直性脊柱炎。46.0%患者的Bath强直性脊柱炎疾病活动指数(BASDAI)≥4,但是只有3.2%的患者正在接受肿瘤坏死因子抑制剂治疗。
31.4%的患者从未得到医生有关康复锻炼方面的建议。20.7%的患者曾经得到过建议,但是医生并未给出具体的锻炼方式。游泳是医生推荐频率最高的锻炼方式(23.6%),而强直性脊柱炎患者自己最经常进行的锻炼方式则是室内伸展运动(12.1%)以及户外散步(5.9%)。只有27.9%的患者每周进行康复锻炼至少3次。“提高身体健康状态”是强直性脊柱炎患者最认可的锻炼益处(53.0%)。“占用时间太长”是阻碍强直性脊柱炎患者进行康复锻炼的主要因素(50.7%)。每周坚持至少3次锻炼的患者与锻炼频率少于3次的患者相比,每周坚持至少3次锻炼的强直性脊柱炎患者与锻炼频率少于3次的强直性脊柱炎患者相比,BASFI的差异有统计学意义(t=2.805；P=0.006),而在BASDAI(t=0.060; P=0.952)及TBPS(t=1.210;P=0.904)方面无统计学意义。
强直性脊柱炎患者行全髋关节置换术后疾病活动情况有所好转(t=2.229；P=0.031),肢体功能改善显著(t=6.674；P<0.001)。全髋关节置换术显著提高了强直性脊柱炎的日常生活自理能力(t=18.504；P<0.001)。强直性脊柱炎患者行全髋关节置换术后,就业率显著升高(χ2=8.640；P=0.003),但是结婚机会的改善并不显著(χ2=2.005；P=0.157)。强直性脊柱炎行髋关节置换术后异位骨化的发生率(37.9%),高于因先天性髋臼发育不良继发骨性关节炎行全髋关节置换术的患者(23.6%),低于因股骨头坏死行全髋关节置换的患者异位骨化的发生率(45.7%)。行全髋关节置换术后,强直性脊柱炎对患者生活影响的总体评价由术前的平均98.0%,下降到术后的平均53.3%,下降幅度不到50%。
利用主题词'ankylosing spondylitis" AND "patient education",我们仅在pubmed检索到26篇英文文献。与此同时,当利用主题词’'ankylosing spondylitis "AND "physiotherapy"或主题词’'ankylosing spondylitis " AND " pharmacotherapy”进行检索时,分别可以检索到多达191和289篇文献。曾有报道认为类风湿关节炎的发病率与强直性脊柱炎类似,当我们利用主题词‘'rheumatoid arthritis" AND "patient education"进行检索时,可以获得多达374篇文献。在利用主题词"ankylosing spondylitis" AND "patient education"获得的26篇文献中,只有8篇文献真正在强直性脊柱炎的治疗过程中对患者实施了“患者教育”。在这8篇文献中,只有1篇文献纳入了200例患者,其余7篇的样本量都在100例以内。所有研究的持续时间都不超过半年。这8篇文献主要是评估患者教育与物理治疗相结合的效果。患者教育与药物治疗或手术治疗相结合的效果没有得到评估。多数研究将肢体功能及症状缓解作为患者教育效果的评价指标,至于患者教育对强直性脊柱炎患者心理及生活质量的影响则需要进一步探索。面对面形式的患者教育方式最常被采用,影像或印刷品教育形式只是偶有报道。没有关于电脑及网络用于强直性脊柱炎患者教育的报道。多数强直性脊柱炎患者只是接受了团体教育,对患者进行个体化教育需要引起进一步的重视。只有1篇文献将强直性脊柱炎患者的家属也列入教育范围。谷歌学术搜索上只能检索到11篇引用“患者版强直性脊柱炎ASAS诊疗指南”的英文文献,但是这11篇文献并未真正将该指南应用于患者教育,只是引用该指南来支持自己的观点。
139名强直性脊柱炎患者中,50人(36.0%)为幼年型强直性脊柱炎患者,89人(64.0%)为成年型强直性脊柱炎患者。相对于成年型强直性脊柱炎,幼年型强直性脊柱炎初发症状多发生在外周关节(χ2=29.433；P<0.001)。幼年型强直性脊柱炎患者往往比成年型强直性脊柱炎患者遭遇更为长久的确诊延迟(t=2.791；P=0.006),拥有更差的功能状态(t=2.591；P=0.011)以及更差的生活质量(t=3.495；P=0.001)。幼年型强直性脊柱炎患者获得大学及以上教育的机会也更少(χ2=4.342；P=0.037),已婚的比例要显著低于成年型强直性脊柱炎患者(χ2=6.208；P=0.013)。另外,幼年型强直性脊柱炎患者的就业率也低于成年型强直性脊柱炎患者,尽管两组患者就业率的差别尚未达到有统计学意义的水平(χ2=1.835；P=0.176),幼年型强直性脊柱炎患者中却有更多的患者自成年后就从未参加过任何工作(χ2=5.590；P=0.015)。
结论
(1)本研究发现大多数强直性脊柱炎患者曾经历过强直性脊柱炎的误诊。误诊可以显著延长强直性脊柱炎的最终确诊时间。强直性脊柱炎误诊对疾病活动度,肢体功能,就业及婚姻方面的影响无统计学意义。
(2)作为治疗强直性脊柱炎的一线药物,非甾体类抗炎药的使用率偏低,柳氮磺吡啶和甲氨蝶呤则被过度应用于强直性脊柱炎。尽管没有被纳入治疗指南,沙利度胺,来氟米特和中草药被广泛应用于强直性脊柱炎的治疗。TNF抑制剂的实际需求远没有得到满足。
(3)绝大多数强直性脊柱炎患者都没有得到关于康复锻炼的科学指导。绝大多数患者没有坚持足够的康复锻炼。强直性脊柱炎患者坚持每周至少3次的功能锻炼拥有更佳的肢体功能状态。
(4)强直性脊柱炎患者行全髋关节置换后疾病活动情况有所好转,可显著改善肢体功能及日常生活自理能力。强直性脊柱炎患者行全髋关节置换术后,就业率显著升高,但是结婚机会的改善并不显著。强直性脊柱炎行髋关节置换术后异位骨化的发生率低于股骨头坏死患者术后异位骨化的发生率,同时高于先天性髋臼发育不良继发骨性关节炎患者异位骨化的发生率。
(5)本研究发现强直性脊柱炎的“患者教育”未得到足够重视。鉴于现有文献中关于强直性脊柱炎“患者教育”的证据严重不足,在对强直性脊柱炎患者进行患者教育的时候,可以考虑借鉴其它慢性疾病患者教育的经验,比如类风湿性关节炎等。
(6)本研究发现幼年型强直性脊柱炎的早期诊断比成年型强直性脊柱炎的早期诊断更具挑战性。幼年型强直性脊柱炎或许需要专门的诊断标准。幼年型强直性脊柱炎患者的肢体功能状态更差,这提示幼年型强直性脊柱炎患者或许需要更为激进的治疗策略。需要制定相关干预措施来帮助患者对抗强直性脊柱炎对其生活质量的影响,尤其是那些幼年型强直性脊柱炎患者。
Background
Ankylosing spondylitis (AS) is a chronic inflammatory disease, often results in significant impairment on physical function, working ability and quality of life. The majority of AS patients may lose most of their spinal mobility within the first10years of onset. With the tremendous development of treatment strategies, in particular, the advent of TNF-inhibitors, the primary aim of AS management has varied from symptom relief to the modification of disease progression. The current evidence implies that only when the structural damage has not happened or just appeared in quite mild extent, could the management modalities achieve the optimal effect. Therefore, early interventions on the basis of early correct diagnosis are essential in the treatment of AS. Unfortunately, it has been frequently reported that AS disease often keeps progressing for as long as5to10years from the onset of symptoms till to the correct diagnosis at last. Early diagnosis of AS is often missed in clinical practice mainly due to several disease characteristics which include:(1) the late onset of inflammatory back pain (IBP);(2) the late onset of radiographic sacroiliitis which is mandatory in the modified New York criteria;(3) the lack of pathognomonic clinical and laboratory tests. In addition, other factors, such as negative HLA-B27, negative family history and early age of onset were also regarded as risk factors of diagnosis delay in some reports. However, misdiagnosis may be anther risk factor which may directly mask the correct diagnosis of AS and lead to mistreatment for AS patients. In a recent study, the initial diagnosis of LDH was reported as an obvious hindering factor for early correct diagnosis of AS. In another study, rheumatoid arthritis and tuberculosis of spine were also regarded as risk factors of diagnosis delay. At present, studies focusing on the misdiagnoses and the related impacts in AS remain limited. The Assessment of SpondyloArthritis International Society (ASAS) group has developed criteria to classify patients with axial or peripheral SpA in2009. In clinical practice, these criteria have been applied in diagnosis as well as differential diagnosis of SpA. Although AS is the prototypical form of axial SpA, the effect of these criteria on diagnosis and differential diagnosis of AS is not clear.
At present, pharmacotherapy has obvious ability to relieve symptoms and the potential ability to slow down or even to prevent AS progression. With the development of evidence, concepts about conventional drugs such as NSAIDs, disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids have been substantially changed in the past decade. NSAIDs have long been regarded as the first-line drug in AS pharmacotherapy and have been often prescribed with the primary aim for symptomatic improvements. Recently, however, the concept toward NSAIDs probably needs to be improved. Several studies indicate that NSAIDs may also play a valuable role in reducing or even reverting the disease progression. Despite the definite efficacy of DMARDs in rheumatoid arthritis (RA), sulfasalazine is at present the only one recommended drug of limited effect for AS patients with peripheral arthritis. Glucocorticoids are traditional drugs in effective control of autoimmune diseases. The available evidence, however, is mainly limited in local injections for AS management. The advent of TNF-inhibitors is thought to have revolutionised the management of AS. Nevertheless, not all of the AS patient meet the criteria to use TNF-inhibitors. In the meanwhile, due to various reasons, such as the high cost and the fear of side effects, not all of the AS patients that meet the criteria for biologic therapy have actually used TNF-inhibitors. Certain time is required for understanding and acceptance of the new changes. In order to provide guidance for clinicians and to standardize the procedure for monitoring and treating patients with AS, evidence based management recommendations was developed under the collaboration of the Assessment in SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism(EULAR) in2005which had been updated once in2010. Consensus statement on the use of TNF-inhibitors was published by ASAS as early as in2003and was updated twice in2006and2010respectively. However, if these recommendations were implemented well enough in clinical practice is not clear.
Despite substantial progress in pharmacotherapy, the recommendations developed under the collaboration of the Assessment in SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism(EULAR) have consistently stressed that exercise is the indispensable component in comprehensive AS management. Substantial evidence in current literature has confirmed the effect of exercise in relieving physical symptom and improving physical function, psychological status and quality of life for AS patients. In addition, the combination of exercise and pharmacotherapy may decrease drug consumption and thus reduce related adverse effects. Home-based exercise, supervised exercise, group exercise and spa-based exercise are all frequently reported with certain benefit. Although there has been no consensus on which specific type of exercise with what frequency is optimal, adherence is thought to be the most important factor for AS patients to benefit from exercise. So far, most reports mainly focused on the effect of certain exercise for AS patients who had followed the clinicians'prescription. Studies investigating the real status of exercise in AS patients'daily life remain scarce.
It is deemed that the younger the age at the onset, the greater is the likelihood of hip involvement. Male, axial disease, and enthesitis are also regarded as risk factors of hip involvement and the need for THA in AS. Hip involvement occurs in25%to50%of patients with AS, and47%to90%of patients who have such involvement have it bilaterally. Hip joint involvement in AS often results in severe deformities and may also harm other activities related to spinal mobility. The combination of the stiff spine and hip can cause severe disability in the patients. In addition, hip involvement can not only affect the patients in physical status but also in employability, psychosocial status and comprehensive quality of life. Till now, THA is still the standard operation for pain relief and function improvement to treat patients with AS. However, THA for AS patients with stiff spine and involvement in other systems such as the pulmonary and cardiovascular systems is still a challenging procedure. More attention should be paid on certain AS-specific problems regarding effect of THA on patients'"disease activity","physical function","ability for daily life","employability", and "marriage".
Despite substantial progress in pharmacotherapy and physical therapy in AS management, certain problems still exist which could not be effectively resolved by neither pharmacotherapy nor physical therapy at present. The optimal therapeutic effects are often missed due to the insufficiency of patients'long-term compliance with the prescriptions. Actually, this phenomenon of poor compliance with the doctors'prescriptions may be quite common among AS patients. There are a variety of reasons to explain it, for example the lack of knowledge about AS disease and its' treatment. Besides, certain inappropriate behaviors in the patients'daily life or work may further aggravate the disease condition. A potential vicious circle may exist in aspect of psychological status of AS patients. The disease may lead to certain psychological abnormalities and these abnormalities may in turn affect the development of AS. Solutions to these problems mentioned above necessitate effective patient education which has been widely applied in other chronic diseases, such as diabetes, asthma and rheumatoid arthritis (RA). Although it has been stressed as the cornerstone in the non-pharmacotherapy for AS in ASAS/EULAR recommendations, studies concentrating on AS patient education remain quite scanty in current literature. In recent years, types of patient education for chronic diseases have been no longer limited in face-to-face or written educational forms but have taken on a tendency of diversification. In particular, computer and internet have been frequently reported to play an increasing important role in patient education and AS patients seem to be of high access to these modern communication means due to their relatively young age. The specific effects of these educational types, however, remain indefinite in AS patients and need to be explored.
AS occurs predominantly in early adulthood, but can also occur in childhood. When AS occurs≤16years of age, it is termed JoAS, and when it occurs after the age of16, it is termed AoAS. Although JoAS shares certain similar features with AoAS, for example the presence of radiographic sacroiliitis, it may also have some specific clinical characteristics that distinguish it from AoAS. Most of the studies reflected that JoAS often had significant longer diagnosis delay compared with AoAS whereas some other studies had not included the comparison in this aspect. JoAS has been reported with higher frequency of peripheral joints involvement, especially the involvement of the hip joint. Although hip joint involvement has been thought to be associated with worse functional outcome for AS patients, discrepancies, however, exist in the comparison of functional status between JoAS and AoAS. The majority of the present studies reported that JoAS had worse functional outcome than AoAS while some other studies failed to detect the differences between JoAS and AoAS. Moreover, there were also sparse reports that even reflected that JoAS might suffer from less functional impairment than AoAS. Radiographical differences between JoAS and AoAS have also been assessed in several studies and JoAS was reported to have less severe axial involvement radiographically compared with AoAS. Overall, most of the studies so far have mainly focused on the differences in aspect of clinical features between JoAS and AoAS. Studies centering on the potential differences between JoAS and AoAS in certain important aspects of quality of life, such as educational level, status of employment and status of marriage, remain scarce.
Objectives
(1) To assess the current status and related impacts of alternative diagnoses before the final correct diagnosis of AS.
(2) To examine the status of pharmacotherapy for AS in comparison with current recommendations.
(3) To assess the current status of exercise in AS patients'daily life and to analyze the patients'perception to exercise.
(4) To explore effect of THA on patients'"disease activity","physical function","ability for daily life","employability", and "marriage".In addition, we will also compare of rate of HO between patients with AS,DDH and AFN.
(5) To explore the current status of patient education for AS reported in the literature. In addition, the barriers to patient education, prerequisites for patient education, practical educational forms, contents of patient education as well as the educational efficiency assessment will be also explored.
(6) Detection of differences is the precondition for the development of specific interventions. So, in this study, we also tried to compare the differences in clinical features as well as several essential factors related with quality of life between JoAS and AoAS.
Patients and Methods
(1) Patients
All of the included patients were at least18years old and should have a confirmed diagnosis of AS according to modified New York classification criteria.
(2) Methods
I Questionnaire was used which contains a number of demographic variables, such as age, sex, status of marriage (married, unmarried or divorced) and status of employment (employed, unemployed or never got employed).
II Disease characteristics of the study participants were examined by a questionnaire which includes:family history, HLA-B27status, initial symptoms (peripheral or axial), age at onset of AS symptom (juvenile onset or adult onset), age at correct diagnosis of AS, alternative diagnoses before final AS diagnosis and in particular, the specialties of the clinicians who made the alternative diagnoses.
Ⅲ Disease activity measured by BASDAI
Ⅳ Functional status measured by BASFI.
Ⅴ Disease-related quality of life was measured with ASQoL
Ⅵ EBBS was applied to examine AS patients'perception towards benefits of exercise and barriers to exercise.
Ⅶ Disease duration was then defined as the interval between the age at onset of AS symptom and the current age. Diagnosis delay was defined as the gap between the age at onset of AS symptom and the age of correct AS diagnosis.
Ⅷ Questionnaire was designed to assess the whole experience of non-biologic pharmacotherapy during12months prior to this study and included:①type of drugs,②reasons for switching drugs, and③reasons for ceasing drugs.
IX Questionnaire was designed to assess the whole experience of biologic pharmacotherapy not during the previous12months but during the whole course of the disease and included:①types of TNF-inhibitors they know about,②reasons for not using TNF-inhibitors,③types of TNF-inhibitors they have ever used,④reasons for their choice of the type of TNF-inhibitors,⑤duration of TNF-inhibitors treatment,⑥reasons for switching TNF-inhibitors, and⑦reasons for ceasing TNF-inhibitors.
X We took the2010version ASAS/EULAR recommendations for AS management and2010version of ASAS recommendations for application of TNF-inhibitors as the standard to compare the discrepancies.
XI Questionnaire was designed on the basis of exercise interventions in the literature to assess the experience of exercise during the whole course of the AS disease and included:①types of exercise recommended by clinicians,②types of exercise actually performed in daily life,③the frequency of participation (times per week).
M To get information related to effect of THA on patients'"disease activity","physical function","ability for daily life","employability","marriage" and rate of HO by performing follow-up for AS patients with THA.
XIII In May2013, we searched PubMed using the MESH terms "ankylosing spondylitis" AND "patient education", ankylosing spondylitis "AND "physiotherapy","nkylosing spondylitis " AND " pharmacotherapy ", ankylosing spondylitis "AND "Nonsteroidal Anti-inflammatory Drug" as well as the MESH "rheumatoid arthritis" AND "patient education". The language was limited with "English". We then analyze the26articles related patient education in AS treatment in aspects of" Sample of study "," Duration of study ","Forms of education" and "Variables of assessment". We also examine the status of the citation of patient version recommendations by searching Google Scholar.
Result
Misdiagnoses were reported by69.8%of the patients. The most common alternative diagnoses were "Arthritis associated with rheumatic fever"(AARF)(18.7%) and "Lumbar disc herniation"(LDH)(11.5%). Misdiagnoses resulted in significant diagnosis delay (P<0.001). No statistical differences were detected in BASDAI (t=0.661; P=0.510), BASFI (t=0.832; P=0.407), status of employment (χ2=1.298; P=0.255) and marriage (χ2=3.609; P=0.323) between patients with or without alternative diagnoses.
53.2%had taken nonsteroidal anti-inflammatory drugs (NSAIDs).32.5%and7.1%had taken salazopyrine and methotrexate respectively. Thalidomide and leflunomide were respectively used by10.3%and6.3%. Oral glucocorticoids was reported by1.6%. Tramadol was reported by5.6%.50.8%had ever taken Chinese herbal medicine (CHM) for AS.3.2%of the patients were taking TNF-inhibitors regularly while46.0%had a BASDAI≥4.
31.4%had not got exercise recommendations.20.7%had got recommendations but without specific exercise type. Swimming was most commonly recommended by clinicians (23.6%) while the most common exercise actually performed by AS patients were home stretching (12.1%) and walking (5.9%). Only27.9%insisted on exercise at least3times per week."Higher levels of physical fitness"(53.0%) was most frequently reported benefit while the most frequently reported barrier to exercise was "it took me too much time"(50.7%). Statistical difference existed in BASFI between patients insisting on exercise at least3times each week and patients with less frequency (t=2.805; P=0.006). No statistical differences were detected in BASDAI and TBPS between the two groups.
After THA, AS patients'disease activity got relived in certain extent(t=2.229; P=0.031); their physical function (t=6.674; P<0.001) and ability for daily life (t=18.504; P<0.001)was significantly restored. AS patients'rate of employment was obviously upleveled (x2=8.640; P=0.003). However, their chance of getting married was not improved (x2=2.005;P=0.157). Rate of HO after THA among AS patients (37.9%) was higher than that among patients with DDH (23.6%) but lower than that among patients with ADH (45.7%). After THA, effect of disease on AS patients'life decreased from98.0%to53.3%. The decrease is less than50%.
In May2013, we only got26articles published in English language when we searched PubMed using the MESH terms "ankylosing spondylitis" AND "patient education". In the meanwhile, as many as191and289articles were retrieved relatively when we limited the MESH terms as "ankylosing spondylitis " AND "physiotherapy" as well as "ankylosing spondylitis " AND " pharmacotherapy ". Actually, if we use certain specific name of drug as MESH terms, much more reports would be retrieved. For example, as many as327articles could be retrieved when we used the MESH terms "ankylosing spondylitis "AND "Nonsteroidal Anti-inflammatory Drug". The prevalence of RA was reported to be close to the prevalence of AS. Surprisingly, up to374reports could be retrieved when the MESH terms "rheumatoid arthritis" AND "patient education" were used.
Among the26articles retrieved with the MESH terms "ankylosing spondylitis" AND "patient education", only8reports have practically applied certain patient education process in AS treatment. Of the8reports, only one report has included200patients while none of the other7studies have included more than100AS patients. None of the8reports persisted more than6months. The majority of the8reports aimed at evaluating the effect of combining patient education with physiotherapy. Effect of combining patient education with pharmacotherapy or surgery has not been explored. Most of the studies focused on assessing physical variables (function or symptom) while psychological variables and status of quality of life need further concern. Face to face education was the most often used form while the other types such as video and booklet were only applied sparsely. No computer and internet assisted educational form for AS was reported in these8studies. AS patients were often educated in group meeting while their individual needs might require more attention. Only one study has included family member (patients' spouses) in the education.
For the purpose of strengthening patients'knowledge and participation in the management of AS, the Assessment of SpondyloArthritis International Society (ASAS) and the European League Against Rheumatism (EULAR) had converted their recommendations for AS management into a patient-understandable version and published the patient version recommendations in the year of2008. Till now, nearly5years have passed, the patient version recommendations have been merely cited by18reports as reflected in the Google Scholar. These18reports included11English papers and7papers written in other languages. Of the11English papers, no one focused on assessing the practical implementation of the patient version recommendations in AS patient education but just cited it to support their own individual viewpoints.
There were50patients with JoAS (36.0%) and89with AoAS (64.0%). The JoAS group showed more onset with peripheral joints involvement(χ2=29.433; P<0.001), significant diagnosis delay(t=2.791; P=0.006), worse functional status(t=2.591; P=0.011)and poorer status of quality of life(t=3.495; P=0.001). Patients with JoAS also showed significant lower rate in college education(χ2=4.342; P=0.037) and marriage(x2=6.208; P=0.013). The rate of employment in JoAS group was lower than that in AoAS group. Although the difference in employment had not reached statistical level, the JoAS group included more patients who had never got employed since they reached the age of adult (χ2=5.590; P=0.015).
Conclusions
(1) This study reflected that the majority of AS patients have the experience of alternative diagnoses and alternative diagnoses could lead to significant diagnosis delay of AS. The impacts of alternative diagnoses on disease activity, physical function, status of employment and marriage are insignificant.
(2) As the first-line drug for AS treatment, NSAIDs might be not fully used while sulfasalazine and methotrexate were overused in AS. Although not included in recommendations, certain drugs such as thalidomide, leflunomide and CHM were taken frequently by AS patients. There is a substantial unmet need for TNF-inhibitors.
(3) Significantly high percentage of AS patients had not got appropriate exercise recommendations and most of the patients failed to insist on exercise sufficiently. AS patients insisting on exercise at least3times each week have better functional status than patients with less frequency of exercise.
(4) After THA, AS patients'disease activity got relived in certain extent.Their physical function and ability for daily life was significantly restored. AS patients' rate of employment was obviously upleveled. However, their chance of getting married was not improved. Rate of HO after THA among AS patients was higher than that among patients with DDH but lower than that among patients with ADH. After THA, effect of disease on AS patients'life decreased from98.0%to53.3%. The decrease is less than50%.
(5) Our results reflected the actual insufficiency of patient education for AS and more concern in this aspect is required definitely. Due to the extreme lack of AS-specific evidence in patient education, experience from other chronic disease such as rheumatoid arthritis may need to be consulted, when we plan to design educational programme for AS patients.
(6) The data reflected that early diagnosis of JoAS is an even more severe challenge compared with AoAS and specific diagnosing criteria for JoAS is warranted. Patients with JoAS showed worse functional status than patients with AoAS and more aggressive treatment may be needed for JoAS. Certain interventions to counteract the disease impact on life for AS patients are required, especially for patients with JoAS.
引文
[1]Meyer K, Niedermann K, Tschopp A, et al. Is the work ability index useful to evaluate absence days in ankylosing spondylitis patients? A cross-sectional study[J]. BMJ Open,2013,3(3).
[2]Carette S, Graham D, Little H, et al. The natural disease course of ankylosing spondylitis[J]. Arthritis Rheum,1983,26(2):186-190.
[3]Shaikh S A. Ankylosing spondylitis:recent breakthroughs in diagnosis and treatment[J]. J Can Chiropr Assoc,2007,51(4):249-260.
[4]Glintborg B, Ostergaard M, Krogh N S, et al. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor:results from 8 years'surveillance in the Danish nationwide DANBIO registry[J]. Ann Rheum Dis,2010,69(11):2002-2008.
[5]Arends S, Brouwer E, van der Veer E, et al. Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis:a prospective longitudinal observational cohort study[J]. Arthritis Res Ther,2011,13(3):R94.
[6]Dincer U, Cakar E, Kiralp M Z, et al. Diagnosis delay in patients with ankylosing spondylitis:possible reasons and proposals for new diagnostic criteria[J]. Clin Rheumatol,2008,27(4):457-462.
[7]Reed M D, Dharmage S, Boers A, et al. Ankylosing spondylitis:an Australian experience[J]. Intern Med J,2008,38(5):321-327.
[8]Rudwaleit M, Khan M A, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis:do we need new criteria?[J]. Arthritis Rheum,2005,52(4):1000-1008.
[9]van der Linden S, Valkenburg H A, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria[J]. Arthritis Rheum,1984,27(4):361-368.
[10]Zochling J, Braun J. Assessments in ankylosing spondylitis[J]. Best Pract Res Clin Rheumatol,2007,21(4):699-712.
[11]Underwood M R, Dawes P. Inflammatory back pain in primary care[J]. Br J Rheumatol,1995,34(11):1074-1077.
[12]Mansour M, Cheema G S, Naguwa S M, et al. Ankylosing spondylitis:a contemporary perspective on diagnosis and treatment[J]. Semin Arthritis Rheum,2007,36(4):210-223.
[13]Feldtkeller E, Khan M A, van der Heijde D, et al. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis[J]. Rheumatol Int,2003,23(2):61-66.
[14]Aggarwal R, Malaviya A N. Diagnosis delay in patients with ankylosing spondylitis:factors and outcomes--an Indian perspective [J]. Clin Rheumatol,2009,28(3):327-331.
[15]Stone M, Warren R W, Bruckel J, et al. Juvenile-onset ankylosing spondylitis is associated with worse functional outcomes than adult-onset ankylosing spondylitis[J]. Arthritis Rheum,2005,53(3):445-451.
[16]Gerdan V, Akar S, Solmaz D, et al. Initial diagnosis of lumbar disc herniation is associated with a delay in diagnosis of ankylosing spondylitis[J]. J Rheumatol,2012,39(10):1996-1999.
[17]Lin Z, Xu H, Gu J, et al. Investigation and analysis on the delayed diagnosis in patients with ankylosing spondylitis in a Chinese population[J]. Clin Exp Rheumatol,2008,26(6):1163.
[18]Rudwaleit M, Landewe R, van der Heijde D, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I):classification of paper patients by expert opinion including uncertainty appraisal[J]. Ann Rheum Dis,2009,68(6):770-776.
[19]Rudwaleit M, van der Heijde D, Landewe R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II):validation and final selection[J]. Ann Rheum Dis,2009,68(6):777-783.
[20]van den Berg R, van der Heijde D M. How should we diagnose spondyloarthritis according to the ASAS classification criteria:a guide for practicing physicians[J]. Pol Arch Med Wewn,2010,120(11):452-457.
[21]Garrett S, Jenkinson T, Kennedy L G, et al. A new approach to defining disease status in ankylosing spondylitis:the Bath Ankylosing Spondylitis Disease Activity Index[J]. J Rheumatol,1994,21(12):2286-2291.
[22]Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis:the development of the Bath Ankylosing Spondylitis Functional Index[J]. J Rheumatol,1994,21(12):2281-2285.
[23]Ibn Y Y, Amine B, Laatiris A, et al. Relationship between diagnosis delay and disease features in Moroccan patients with ankylosing spondylitis [J]. Rheumatol Int,2012,32(2):357-360.
[24]Feldtkeller E, Bruckel J, Khan M A. Scientific contributions of ankylosing spondylitis patient advocacy groups[J]. Curr Opin Rheumatol,2000,12(4):239-247.
[25]Zhang S, Li Y, Deng X, et al. Similarities and differences between spondyloarthritis in Asia and other parts of the world[J]. Curr Opin Rheumatol,2011,23(4):334-338.
[26]Barkham N, Kong K O, Tennant A, et al. The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing spondylitis[J]. Rheumatology (Oxford),2005,44(10):1277-1281.
[27]Arturi P, Schneeberger E E, Sommerfleck F, et al. Adherence to treatment in patients with ankylosing spondylitis[J]. Clin Rheumatol,2013.
[28]Poddubnyy D, Rudwaleit M, Haibel H, et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis:results from the German Spondyloarthritis Inception Cohort[J]. Ann Rheum Dis,2012,71(10):1616-1622.
[29]Kroon F, Landewe R, Dougados M, et al. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis[J]. Ann Rheum Dis,2012,71(10):1623-1629.
[30]Braun J, van den Berg R, Baraliakos X, et al.2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis[J]. Ann Rheum Dis,2011,70(6):896-904.
[31]van der Heijde D, Sieper J, Maksymowych W P, et al.2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis[J]. Ann Rheum Dis,2011,70(6):905-908.
[32]Zochling J, Bohl-Buhler M H, Baraliakos X, et al. Nonsteroidal anti-inflammatory drug use in ankylosing spondylitis--a population-based survey[J]. Clin Rheumatol,2006,25(6):794-800.
[33]Baser O, Burkan A, Baser E, et al. Health care costs associated with ankylosing spondylitis in Turkey:an analysis from nationwide real-world data[J]. Int J Rheumatol,2013,2013:139608.
[34]Sundstrom B, Wallberg-Jonsson S, Johansson G. Diet, disease activity, and gastrointestinal symptoms in patients with ankylosing spondylitis[J]. Clin Rheumatol,2011,30(1):71-76.
[35]Gallinaro A L, Ventura C, Sampaio B P, et al. Spondyloarthritis:analysis of a Brazilian series compared with a large Ibero-American registry (RESPONDIA group)[J]. Rev Bras Reumatol,2010,50(5):581-589.
[36]Breban M, Gombert B, Amor B, et al. Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis[J]. Arthritis Rheum,1999,42(3):580-581.
[37]Wei J C, Chan T W, Lin H S, et al. Thalidomide for severe refractory ankylosing spondylitis:a 6-month open-label trial[J]. J Rheumatol,2003,30(12):2627-2631.
[38]Deng X, Zhang J, Zhang J, et al. Thalidomide reduces recurrence of ankylosing spondylitis in patients following discontinuation of etanercept[J]. Rheumatol Int,2012.
[39]Huang F, Gu J, Zhao W, et al. One-year open-label trial of thalidomide in ankylosing spondylitis[J]. Arthritis Rheum,2002,47(3):249-254.
[40]Haibel H, Rudwaleit M, Braun J, et al. Six months open label trial of leflunomide in active ankylosing spondylitis[J]. Ann Rheum Dis,2005,64(1):124-126.
[41]van Denderen J C, van der Paardt M, Nurmohamed M T, et al. Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis [J]. Ann Rheum Dis,2005,64(12):1761-1764.
[42]Winthrop K L, Baddley J W, Chen L, et al. Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster[J]. JAMA,2013,309(9):887-895.
[43]Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis [J]. Ann Rheum Dis,2006,65(4):442-452.
[44]Karapolat H, Akkoc Y, Sari I, et al. Comparison of group-based exercise versus home-based exercise in patients with ankylosing spondylitis:effects on Bath Ankylosing Spondylitis Indices, quality of life and depression[J]. Clin Rheumatol,2008,27(6):695-700.
[45]Durmus D, Alayli G, Cil E, et al. Effects of a home-based exercise program on quality of life, fatigue, and depression in patients with ankylosing spondylitis[J]. Rheumatol Int,2009,29(6):673-677.
[46]Gyurcsik Z N, Andras A, Bodnar N, et al. Improvement in pain intensity, spine stiffness, and mobility during a controlled individualized physiotherapy program in ankylosing spondylitis[J]. Rheumatol Int,2012,32(12):3931-3936.
[47]Yigit S, Sahin Z, Demir S E, et al. Home-based exercise therapy in ankylosing spondylitis:short-term prospective study in patients receiving tumor necrosis factor alpha inhibitors[J]. Rheumatol Int,2013,33(1):71-77.
[48]Tishler M, Brostovski Y, Yaron M. Effect of spa therapy in Tiberias on patients with ankylosing spondylitis [J]. Clin Rheumatol,1995,14(1):21-25.
[49]Santos H, Brophy S, Calin A. Exercise in ankylosing spondylitis:how much is optimum?[J]. J Rheumatol,1998,25(11):2156-2160.
[50]Aytekin E, Caglar N S, Ozgonenel L, et al. Home-based exercise therapy in patients with ankylosing spondylitis:effects on pain, mobility, disease activity, quality of life, and respiratory functions[J]. Clin Rheumatol,2012,31(1):91-97.
[51]Sechrist K R, Walker S N, Pender N J. Development and psychometric evaluation of the exercise benefits/barriers scale[J]. Res Nurs Health,1987,10(6):357-365.
[52]Sundstrom B, Ekergard H, Sundelin G. Exercise habits among patients with ankylosing spondylitis. A questionnaire based survey in the County of Vasterbotten, Sweden[J]. Scand J Rheumatol,2002,31(3):163-167.
[53]Dagfinrud H, Halvorsen S, Vollestad N K, et al. Exercise programs in trials for patients with ankylosing spondylitis:do they really have the potential for effectiveness?[J]. Arthritis Care Res (Hoboken),2011,63(4):597-603.
[54]Dubey S G, Leeder J, Gaffney K. Physical therapy in anti-TNF treated patients with ankylosing spondylitis[J]. Rheumatology (Oxford),2008,47(7):1100-1101.
[55]Falkenbach A. Disability motivates patients with ankylosing spondylitis for more frequent physical exercise[J]. Arch Phys Med Rehabil,2003,84(3):382-383.
[56]Passalent L A, Soever L J, O'Shea F D, et al. Exercise in ankylosing spondylitis:discrepancies between recommendations and reality [J]. J Rheumatol,2010,37(4):835-841.
[57]Cooksey R, Brophy S, Husain M J, et al. The information needs of people living with ankylosing spondylitis:a questionnaire survey [J]. BMC Musculoskelet Disord,2012,13:243.
[58]Lim H J, Moon Y I, Lee M S. Effects of home-based daily exercise therapy on joint mobility, daily activity, pain, and depression in patients with ankylosing spondylitis[J]. Rheumatol Int,2005,25(3):225-229.
[59]Karapolat H, Eyigor S, Zoghi M, et al. Are swimming or aerobic exercise better than conventional exercise in ankylosing spondylitis patients? A randomized controlled study[J]. Eur J Phys Rehabil Med,2009,45(4):449-457.
[60]van Tubergen A, Landewe R, van der Heijde D, et al. Combined spa-exercise therapy is effective in patients with ankylosing spondylitis:a randomized controlled trial[J]. Arthritis Rheum,2001,45(5):430-438.
[61]Van Tubergen A, Boonen A, Landewe R, et al. Cost effectiveness of combined spa-exercise therapy in ankylosing spondylitis:a randomized controlled trial[J]. Arthritis Rheum,2002,47(5):459-467.
[62]van Tubergen A, Hidding A. Spa and exercise treatment in ankylosing spondylitis:fact or fancy?[J]. Best Pract Res Clin Rheumatol,2002,16(4):653-666.
[63]Ciprian L, Lo N A, Rizzo M, et al. The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors[J]. Rheumatol Int,2013,33(1):241-245.
[64]Gensler L S, Ward M M, Reveille J D, et al. Clinical, radiographic and functional differences between juvenile-onset and adult-onset ankylosing spondylitis:results from the PSOAS cohort[J]. Ann Rheum Dis,2008,67(2):233-237.
[65]Ibn Y Y, Amine B, Laatiris A, et al. Gender and disease features in Moroccan patients with ankylosing spondylitis[J]. Clin Rheumatol,2012,31(2):293-297.
[66]Hamdi W, Alaya Z, Ghannouchi M M, et al. Associated risk factors with worse functional prognosis and hip replacement surgery in ankylosing spondylitis[J]. Joint Bone Spine,2012,79(1):94-96.
[67]Kobelt G, Andlin-Sobocki P, Maksymowych W P. Costs and quality of life of patients with ankylosing spondylitis in Canada[J]. J Rheumatol,2006, 33(2):289-295.
[68]Backhaus M, Citak M, Kalicke T, et al. [Spine fractures in patients with ankylosing spondylitis:an analysis of 129 fractures after surgical treatment][J]. Orthopade,2011,40(10):917-920,922-924.
[69]Wulf H. Epidural anaesthesia and spinal haematoma[J]. Can J Anaesth,1996,43(12):1260-1271.
[70]Batra Y K, Sharma A, Rajeev S. Total spinal anaesthesia following epidural test dose in an ankylosing spondylitic patient with anticipated difficult airway undergoing total hip replacement[J]. Eur J Anaesthesiol,2006,23(10):897-898.
[71]Bhan S, Eachempati K K, Malhotra R. Primary cementless total hip arthroplasty for bony ankylosis in patients with ankylosing spondylitis[J]. J Arthroplasty,2008,23(6):859-866.
[72]Bangjian H, Peijian T, Ju L. Bilateral synchronous total hip arthroplasty for ankylosed hips[J]. Int Orthop,2012,36(4):697-701.
[73]Tang W M, Chiu K Y. Primary total hip arthroplasty in patients with ankylosing spondylitis[J]. J Arthroplasty,2000,15(1):52-58.
[74]Williams E, Taylor A R, Arden G P, et al. Arthroplasty of the hip in ankylosing spondylitis[J]. J Bone Joint Surg Br,1977,59-B(4):393-397.
[75]Baldursson H, Brattstrom H, Olsson T. Total hip replacement in ankylosing spondylitis[J]. Acta Orthop Scand,1977,48(5):499-507.
[76]Finsterbush A, Amir D, Vatashki E, et al. Joint surgery in severe ankylosing spondylitis[J]. Acta Orthop Scand,1988,59(5):491-496.
[77]Sweeney S, Gupta R, Taylor G, et al. Total hip arthroplasty in ankylosing spondylitis:outcome in 340 patients[J]. J Rheumatol,2001,28(8):1862-1866.
[78]Calin A, Elswood J. The outcome of 138 total hip replacements and 12 revisions in ankylosing spondylitis:high success rate after a mean followup of 7.5 years[J]. J Rheumatol,1989,16(7):955-958.
[79]Delee J, Ferrari A, Charnley J. Ectopic bone formation following low friction arthroplasty of the hip[J]. Clin Orthop Relat Res,1976(121):53-59.
[80]Bisla R S, Ranawat C S, Inglis A E. Total hip replacement in patients with ankylosing spondylitis with involvement of the hip[J]. J Bone Joint Surg Am,1976,58(2):233-238.
[81]Wilde A H, Collins H R, Mackenzie A H. Reankylosis of the hip joint in ankylosing spondylitis after total hip replacement[J]. Arthritis Rheum, 1972,15(5):493-496.
[82]Joshi A B, Markovic L, Hardinge K, et al. Total hip arthroplasty in ankylosing spondylitis:an analysis of 181 hips[J]. J Arthroplasty,2002,17(4):427-433.
[83]Sochart D H, Porter M L. Long-term results of total hip replacement in young patients who had ankylosing spondylitis. Eighteen to thirty-year results with survivorship analysis[J]. J Bone Joint Surg Am,1997,79(8):1181-1189.
[84]Brinker M R, Rosenberg A G, Kull L, et al. Primary noncemented total hip arthroplasty in patients with ankylosing spondylitis. Clinical and radiographic results at an average follow-up period of 6 years[J]. J Arthroplasty, 1996,11(7):802-812.
[85]Tani Y, Nishioka J, Inoue K, et al. Relation between ectopic ossification after total hip arthroplasty and activity of general inflammation in patients with ankylosing spondylitis[J]. Ann Rheum Dis,1998,57(10):634.
[86]Chorus A M, Miedema H S, Boonen A, et al. Quality of life and work in patients with rheumatoid arthritis and ankylosing spondylitis of working age[J]. Ann Rheum Dis,2003,62(12):1178-1184.
[87]Jang J H, Green C E, Assassi S, et al. The contribution of disease activity on functional limitations over time through psychological mediators:a 12-month longitudinal study in patients with ankylosing spondylitis [J]. Rheumatology (Oxford),2011,50(11):2087-2092.
[88]Jarvis J, Skinner T C, Carey M E, et al. How can structured self-management patient education improve outcomes in people with type 2 diabetes?[J]. Diabetes Obes Metab,2010,12(1):12-19.
[89]Smith S, Mitchell C, Bowler S. Patient-centered education:applying learner-centered concepts to asthma education[J]. J Asthma,2007, 44(10):799-804.
[90]John H, Carroll D, Kitas G D. Cardiovascular education for people with rheumatoid arthritis:what can existing patient education programmes teach us?[J]. Rheumatology (Oxford),2011,50(10):1751-1759.
[91]Friedman A J, Cosby R, Boyko S, et al. Effective teaching strategies and methods of delivery for patient education:a systematic review and practice guideline recommendations [J]. J Cancer Educ,2011,26(1):12-21.
[92]Gordon M M, Capell H A, Madhok R. The use of the Internet as a resource for health information among patients attending a rheumatology clinic[J]. Rheumatology (Oxford),2002,41 (12):1402-1405.
[93]Kiltz U, van der Heijde D, Mielants H, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis:the patient version[J]. Ann Rheum Dis,2009,68(9):1381-1386.
[94]Sudre A, Figuereido I T, Lukas C, et al. On the impact of a dedicated educational program for ankylosing spondylitis:effect on patient satisfaction, disease knowledge and spinal mobility, a pilot study [J]. Joint Bone Spine,2012,79(1):99-100.
[95]Barlow J H, Barefoot J. Group education for people with arthritis[J]. Patient Educ Couns,1996,27(3):257-267.
[96]Sweeney S, Taylor G, Calin A. The effect of a home based exercise intervention package on outcome in ankylosing spondylitis:a randomized controlled trial[J]. J Rheumatol,2002,29(4):763-766.
[97]Silva E M, Andrade S C, Vilar M J. Evaluation of the effects of Global Postural Reeducation in patients with ankylosing spondylitis [J]. Rheumatol Int,2012,32(7):2155-2163.
[98]Masiero S, Bonaldo L, Pigatto M, et al. Rehabilitation treatment in patients with ankylosing spondylitis stabilized with tumor necrosis factor inhibitor therapy:a randomized controlled trial[J]. J Rheumatol,2011,38(7):1335-1342.
[99]Kraag G, Stokes B, Groh J, et al. The effects of comprehensive home physiotherapy and supervision on patients with ankylosing spondylitis--a randomized controlled trial[J]. J Rheumatol,1990,17(2):228-233.
[100]Gross M, Brandt K D. Educational support groups of patients with ankylosing spondylitis:a preliminary report[J]. Patient Couns Health Educ,1981, 3(1):6-12.
[101]Kjeken I, Dagfinrud H, Mowinckel P, et al. Rheumatology care:Involvement in medical decisions, received information, satisfaction with care, and unmet health care needs in patients with rheumatoid arthritis and ankylosing spondylitis[J]. Arthritis Rheum,2006,55(3):394-401.
[102]Coulter A, Entwistle V, Gilbert D. Sharing decisions with patients:is the information good enough?[J]. BMJ,1999,318(7179):318-322.
[103]Giraldo G. Scoring Points for Holistic Medicine:Anisio Leon, MD, MS and Pedro Carmona, BS, Natural & Traditional Medicine Unit, Sports Medicine Institute, Havana[J]. MEDICC Rev,2009,11(2):12-14.
[104]Nour K, Laforest S, Gauvin L, et al. Behavior change following a self-management intervention for housebound older adults with arthritis:an experimental study[J]. Int J Behav Nutr Phys Act,2006,3:12.
[105]Freda M C. Issues in patient education[J]. J Midwifery Womens Health,2004,49(3):203-209.
[106]Chang M, Kelly A E. Patient education:addressing cultural diversity and health literacy issues[J]. Urol Nurs,2007,27(5):411-417,418.
[107]Taal E, Seydel E R, Rasker J J, et al. Psychosocial aspects of rheumatic diseases:introduction[J]. Patient Educ Couns,1993,20(2-3):55-61.
[108]Nghiem F T, Donohue J P. Rehabilitation in ankylosing spondylitis[J]. Curr Opin Rheumatol,2008,20(2):203-207.
[109]Hoving C, Visser A, Mullen P D, et al. A history of patient education by health professionals in Europe and North America:from authority to shared decision making education[J]. Patient Educ Couns,2010,78(3):275-281.
[110]Makelainen P, Vehvilainen-Julkunen K, Pietila A M. Rheumatoid arthritis patients'education-contents and methods[J]. J Clin Nurs,2007,16(11C):258-267.
[111]Hill J. An overview of education for patients with rheumatic diseases [J]. Nurs Times,2003,99(19):26-27.
[112]Demir S E, Rezvani A, Ok S. Assessment of sexual functions in female patients with ankylosing spondylitis compared with healthy controls [J]. Rheumatol Int,2013,33(1):57-63.
[113]Rostom S, Mengat M, Mawani N, et al. Sexual activity in Moroccan men with ankylosing spondylitis[J]. Rheumatol Int,2012.
[114]Schrieber L, Colley M. Patient education[J]. Best Pract Res Clin Rheumatol,2004,18(4):465-476.
[115]Zhang X, Chen L W, Mueller K, et al. Tracking the effectiveness of health care reform in China:a case study of community health centers in a district of Beijing[J]. Health Policy,2011,100(2-3):181-188.
[116]Johnson A, Sandford J. Written and verbal information versus verbal information only for patients being discharged from acute hospital settings to home:systematic review[J]. Health Educ Res,2005,20(4):423-429.
[117]Fox M P. A systematic review of the literature reporting on studies that examined the impact of interactive, computer-based patient education programs[J]. Patient Educ Couns,2009,77(1):6-13.
[118]Singleton E M, Hutson S E. Anterior uveitis, inflammatory bowel disease, and ankylosing spondylitis in a HLA-B27-positive woman[J]. South Med J,2006,99(5):531-533.
[119]Sowden E, Hassan W, Gooden A, et al. Limited end-user knowledge of methotrexate despite patient education:an assessment of rheumatologic preventive practice and effectiveness[J]. J Clin Rheumatol,2012, 18(3):130-133.
[120]Ward M M, Reveille J D, Learch T J, et al. Impact of ankylosing spondylitis on work and family life:comparisons with the US population[J]. Arthritis Rheum,2008,59(4):497-503.
[121]Montacer K M, Mehdi G M, Hamdi W, et al. Impact of the ankylosing spondylitis on the professional activity [J]. Joint Bone Spine,2009, 76(4):378-382.
[122]Anderson A S, Klemm P. The Internet:friend or foe when providing patient education?[J]. Clin J Oncol Nurs,2008,12(1):55-63.
[123]Mccormick M C, Stemmler M M, Athreya B H. The impact of childhood rheumatic diseases on the family [J]. Arthritis Rheum,1986,29(7):872-879.
[124]Niedermann K, Fransen J, Knols R, et al. Gap between short-and long-term effects of patient education in rheumatoid arthritis patients:a systematic review[J]. Arthritis Rheum,2004,51(3):388-398.
[125]Bukulmez H, Colbert R A. Juvenile spondyloarthropathies and related arthritis[J]. Curr Opin Rheumatol,2002,14(5):531-535.
[126]O'Shea F D, Boyle E, Riarh R, et al. Comparison of clinical and radiographic severity of juvenile-onset versus adult-onset ankylosing spondylitis[J]. Ann Rheum Dis,2009,68(9):1407-1412.
[127]Marks S H, Barnett M, Calin A. A case-control study of juvenile-and adult-onset ankylosing spondylitis [J]. J Rheumatol,1982,9(5):739-741.
[128]Ozgocmen S, Ardicoglu O, Kamanli A, et al. Pattern of disease onset, diagnostic delay, and clinical features in juvenile onset and adult onset ankylosing spondylitis[J]. J Rheumatol,2009,36(12):2830-2833.
[129]Baek H J, Shin K C, Lee Y J, et al. Juvenile onset ankylosing spondylitis (JAS) has less severe spinal disease course than adult onset ankylosing spondylitis (AAS):clinical comparison between JAS and AAS in Korea[J]. J Rheumatol,2002,29(8):1780-1785.
[130]Baraliakos X, Braun J. Hip involvement in ankylosing spondylitis:what is the verdict?[J]. Rheumatology (Oxford),2010,49(1):3-4.
[131]Garcia-Morteo O, Maldonado-Cocco J A, Suarez-Almazor M E, et al. Ankylosing spondylitis of juvenile onset:comparison with adult onset disease[J]. Scand J Rheumatol,1983,12(3):246-248.
[132]Kim T J, Kim T H. Clinical spectrum of ankylosing spondylitis in Korea[J]. Joint Bone Spine,2010,77(3):235-240.
[133]Calin A, Elswood J. The natural history of juvenile-onset ankylosing spondylitis:a 24-year retrospective case-control study [J]. Br J Rheumatol,1988,27(2):91-93.
[134]Doward L C, Spoorenberg A, Cook S A, et al. Development of the ASQoL:a quality of life instrument specific to ankylosing spondylitis[J]. Ann Rheum Dis,2003,62(1):20-26.
[135]Riley M J, Ansell B M, Bywaters E G. Radiological manifestations of ankylosing spondylitis according to age at onset[J]. Ann Rheum Dis,1971,30(2):138-148.
[136]Aggarwal A, Hissaria P, Misra R. Juvenile ankylosing spondylitis-is it the same disease as adult ankylosing spondylitis?[J]. Rheumatol Int,2005, 25(2):94-96.
[137]Bodur H, Ataman S, Rezvani A, et al. Quality of life and related variables in patients with ankylosing spondylitis[J]. Qual Life Res,2011,20(4):543-549.
[138]Boonen A, Braun J, van der Horst B I, et al. ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS):how to classify the impact of AS on functioning and health[J]. Ann Rheum Dis,2010,69(1):102-107.
[139]Boonen A, Mau W. The economic burden of disease:comparison between rheumatoid arthritis and ankylosing spondylitis [J]. Clin Exp Rheumatol, 2009,27(4 Suppl 55):S112-S117.
[140]Roussou E, Kennedy L G, Garrett S, et al. Socioeconomic status in ankylosing spondylitis:relationship between occupation and disease activity[J]. J Rheumatol,1997,24(5):908-911.
[1]Cooksey R, Brophy S, Husain MJ, Irvine E, Davies H, Siebert S (2012) The information needs of people living with ankylosing spondylitis:a questionnaire survey. BMC Musculoskelet Disord 13:243
[2]Gensler LS, Ward MM, Reveille JD, Learch TJ, Weisman MH, Davis JJ (2008) Clinical, radiographic and functional differences between juvenile-onset and adult-onset ankylosing spondylitis:results from the PSOAS cohort. Ann Rheum Dis 67:233-7
[3]Ibn YY, Amine B, Laatiris A, Hajjaj-Hassouni N (2012) Gender and disease features in Moroccan patients with ankylosing spondylitis. Clin Rheumatol 31: 293-7
[4]Hamdi W, Alaya Z, Ghannouchi MM, Haouel M, Kchir MM (2012) Associated risk factors with worse functional prognosis and hip replacement surgery in ankylosing spondylitis. Joint Bone Spine 79:94-6
[5]Kobelt G, Andlin-Sobocki P, Maksymowych WP (2006) Costs and quality of life of patients with ankylosing spondylitis in Canada. J Rheumatol 33:289-95
[6]Kjeken I, Bo I, Ronningen A, Spada C, Mowinckel P, Hagen KB, Dagfinrud H (2013) A three-week multidisciplinary in-patient rehabilitation programme had positive long-term effects in patients with ankylosing spondylitis:Randomized controlled trial. J Rehabil Med 45:260-7
[7]Ince G, Sarpel T, Durgun B, Erdogan S (2006) Effects of a multimodal exercise program for people with ankylosing spondylitis. Phys Ther 86:924-35
[8]Heikkila S, Viitanen JV, Kautiainen H, Kauppi M (2000) Sensitivity to change of mobility tests; effect of short term intensive physiotherapy and exercise on spinal, hip, and shoulder measurements in spondyloarthropathy. J Rheumatol 27: 1251-6
[9]Yigit S, Sahin Z, Demir SE, Aytac DH (2013) Home-based exercise therapy in ankylosing spondylitis:short-term prospective study in patients receiving tumor necrosis factor alpha inhibitors. Rheumatol Int 33:71-7
[10]Passalent LA (2011) Physiotherapy for ankylosing spondylitis:evidence and application. Curr Opin Rheumatol 23:142-7
[11]Ozgocmen S, Akgul O, Altay Z, Altindag O, Baysal O, Calis M, Capkin E, Cevik R, Durmus B, Gur A, Kamanli A, Karkucak M, Madenci E, Melikoglu MA, Nas K, Senel K, Ugur M (2012) Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis. Int J Rheum Dis 15:229-38
[12]Braun J, van der Horst-Bruinsma IE, Huang F, Burgos-Vargas R, Vlahos B, Koenig AS, Freundlich B (2011) Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis:a randomized, double-blind trial. Arthritis Rheum 63:1543-51
[13]Chen J, Veras MM, Liu C, Lin J (2013) Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev 2:CD004524
[14]Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, Zeidler H, Dougados M (2005) Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis:a randomized clinical trial. Arthritis Rheum 52:1756-65
[15]Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker-Hermann E, Zeidler H, Braun J, Sieper J (2012) Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis:results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis 71: 1616-22
[16]Kroon F, Landewe R, Dougados M, van der Heijde D (2012) Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann Rheum Dis 71:1623-9
[17]Conaghan PG (2012) A turbulent decade for NSAIDs:update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int 32:1491-502
[18]Wang D, Ma L, Wu D (2011) Efficacy of etanercept in ankylosing spondylitis hip lesions. Joint Bone Spine 78:531-2
[19]Lian F, Yang X, Liang L, Xu H, Zhan Z, Qiu Q, Ye Y (2012) Treatment efficacy of etanercept and MTX combination therapy for ankylosing spondylitis hip joint lesion in Chinese population. Rheumatol Int 32:1663-7
[20]van der Heijde D, Landewe R, Einstein S, Ory P, Vosse D, Ni L, Lin SL, Tsuji W, Davis JJ (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58:1324-31
[21]van der Heijde D, Landewe R, Baraliakos X, Houben H, van Tubergen A, Williamson P, Xu W, Baker D, Goldstein N, Braun J (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 58:3063-70
[22]van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R (2009) Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 11:R127
[23]Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JJ, Dijkmans B, Dougados M, Geher P, Inman RD, Khan MA, Kvien TK, Leirisalo-Repo M, Olivieri I, Pavelka K, Sieper J, Stucki G, Sturrock RD, van der Linden S, Wendling D, Bohm H, van Royen BJ, Braun J (2006) ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 65:442-52
[24]Backhaus M, Citak M, Kalicke T, Sobottke R, Russe O, Meindl R, Muhr G, Frangen TM (2011) [Spine fractures in patients with ankylosing spondylitis:an analysis of 129 fractures after surgical treatment]. Orthopade 40:917-20,922-4
[25]Wulf H (1996) Epidural anaesthesia and spinal haematoma. Can J Anaesth 43: 1260-71
[26]Batra YK, Sharma A, Rajeev S (2006) Total spinal anaesthesia following epidural test dose in an ankylosing spondylitic patient with anticipated difficult airway undergoing total hip replacement. Eur J Anaesthesiol 23:897-8
[27]Bhan S, Eachempati KK, Malhotra R (2008) Primary cementless total hip arthroplasty for bony ankylosis in patients with ankylosing spondylitis. J Arthroplasty 23:859-66
[28]Bangjian H, Peijian T, Ju L (2012) Bilateral synchronous total hip arthroplasty for ankylosed hips. Int Orthop 36:697-701
[29]Tang WM, Chiu KY (2000) Primary total hip arthroplasty in patients with ankylosing spondylitis. J Arthroplasty 15:52-8
[30]Williams E, Taylor AR, Arden GP, Edwards DH (1977) Arthroplasty of the hip in ankylosing spondylitis. J Bone Joint Surg Br 59-B:393-7
[31]Baldursson H, Brattstrom H, Olsson T (1977) Total hip replacement in ankylosing spondylitis. Acta Orthop Scand 48:499-507
[32]Finsterbush A, Amir D, Vatashki E, Husseini N (1988) Joint surgery in severe ankylosing spondylitis. Acta Orthop Scand 59:491-6
[33]Sweeney S, Gupta R, Taylor G, Calin A (2001) Total hip arthroplasty in ankylosing spondylitis:outcome in 340 patients. J Rheumatol 28:1862-6
[34]Calin A, Elswood J (1989) The outcome of 138 total hip replacements and 12 revisions in ankylosing spondylitis:high success rate after a mean followup of 7.5 years. J Rheumatol 16:955-8
[35]Bisla RS, Ranawat CS, Inglis AE (1976) Total hip replacement in patients with ankylosing spondylitis with involvement of the hip. J Bone Joint Surg Am 58: 233-8
[36]Joshi AB, Markovic L, Hardinge K, Murphy JC (2002) Total hip arthroplasty in ankylosing spondylitis:an analysis of 181 hips. J Arthroplasty 17:427-33
[37]Sandri A, Regis D, Marino MA, Perandini S, Bonetti I, Toso M (2012) Deep external pudendal artery injury after percutaneous adductor tenotomy during THA in ankylosing spondylitis. Orthopedics 35:e566-9
[38]Brinker MR, Rosenberg AG, Kull L, Cox DD (1996) Primary noncemented total hip arthroplasty in patients with ankylosing spondylitis. Clinical and radiographic results at an average follow-up period of 6 years. J Arthroplasty 11:802-12
[39]Sochart DH, Porter ML (1997) Long-term results of total hip replacement in young patients who had ankylosing spondylitis. Eighteen to thirty-year results with survivorship analysis. J Bone Joint Surg Am 79:1181-9
[40]DeLee J, Ferrari A, Charnley J (1976) Ectopic bone formation following low friction arthroplasty of the hip. Clin Orthop Relat Res:53-9
[41]Wilde AH, Collins HR, Mackenzie AH (1972) Reankylosis of the hip joint in ankylosing spondylitis after total hip replacement. Arthritis Rheum 15:493-6
[42]Tani Y, Nishioka J, Inoue K, Hukuda S, Tsujimoto M (1998) Relation between ectopic ossification after total hip arthroplasty and activity of general inflammation in patients with ankylosing spondylitis. Ann Rheum Dis 57:634
[43]Kubiak EN, Moskovich R, Errico TJ, Di Cesare PE (2005) Orthopaedic management of ankylosing spondylitis. J Am Acad Orthop Surg 13:267-78
[44]Shih LY, Chen TH, Lo WH, Yang DJ (1995) Total hip arthroplasty in patients with ankylosing spondylitis:longterm followup. J Rheumatol 22:1704-9
[45]Busti AJ, Hooper JS, Amaya CJ, Kazi S (2005) Effects of perioperative antiinflammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy25:1566-91
[46]Radzikowska B (2000) Rheumatological considerations in the qualification of rheumatoid patients for surgical treatment and principles for pre-and post-operative management. Ortop Traumatol Rehabil 2:83-6
[47]Goh L, Jewell T, Laversuch C, Samanta A (2012) Should anti-TNF therapy be discontinued in rheumatoid arthritis patients undergoing elective orthopaedic surgery? A systematic review of the evidence. Rheumatol Int 32:5-13
[48]Kawakami K, Ikari K, Kawamura K, Tsukahara S, Iwamoto T, Yano K, Sakuma Y, Tokita A, Momohara S (2010) Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers:perioperative interruption of tumour necrosis factor-alpha blockers decreases complications? Rheumatology (Oxford) 49:341-7
[49]Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, Paulus HE, Mudano A, Pisu M, Elkins-Melton M, Outman R, Allison JJ, Suarez AM, Bridges SJ, Chatham WW, Hochberg M, MacLean C, Mikuls T, Moreland LW, O'Dell J, Turkiewicz AM, Furst DE (2008) American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 59:762-84
[50]Ledingham J, Deighton C (2005) Update on the British Society for Rheumatology guidelines for prescribing TNFalpha blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology (Oxford) 44:157-63
[2]Carette S, Graham D, Little H, et al. The natural disease course of ankylosing spondylitis[J]. Arthritis Rheum,1983,26(2):186-190.
[3]Shaikh S A. Ankylosing spondylitis:recent breakthroughs in diagnosis and treatment[J]. J Can Chiropr Assoc,2007,51(4):249-260.
[4]Glintborg B, Ostergaard M, Krogh N S, et al. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor:results from 8 years'surveillance in the Danish nationwide DANBIO registry[J]. Ann Rheum Dis,2010,69(11):2002-2008.
[5]Arends S, Brouwer E, van der Veer E, et al. Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis:a prospective longitudinal observational cohort study[J]. Arthritis Res Ther,2011,13(3):R94.
[6]Dincer U, Cakar E, Kiralp M Z, et al. Diagnosis delay in patients with ankylosing spondylitis:possible reasons and proposals for new diagnostic criteria[J]. Clin Rheumatol,2008,27(4):457-462.
[7]Reed M D, Dharmage S, Boers A, et al. Ankylosing spondylitis:an Australian experience[J]. Intern Med J,2008,38(5):321-327.
[8]Rudwaleit M, Khan M A, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis:do we need new criteria?[J]. Arthritis Rheum,2005,52(4):1000-1008.
[9]van der Linden S, Valkenburg H A, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria[J]. Arthritis Rheum,1984,27(4):361-368.
[10]Zochling J, Braun J. Assessments in ankylosing spondylitis[J]. Best Pract Res Clin Rheumatol,2007,21(4):699-712.
[11]Underwood M R, Dawes P. Inflammatory back pain in primary care[J]. Br J Rheumatol,1995,34(11):1074-1077.
[12]Mansour M, Cheema G S, Naguwa S M, et al. Ankylosing spondylitis:a contemporary perspective on diagnosis and treatment[J]. Semin Arthritis Rheum,2007,36(4):210-223.
[13]Feldtkeller E, Khan M A, van der Heijde D, et al. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis[J]. Rheumatol Int,2003,23(2):61-66.
[14]Aggarwal R, Malaviya A N. Diagnosis delay in patients with ankylosing spondylitis:factors and outcomes--an Indian perspective [J]. Clin Rheumatol,2009,28(3):327-331.
[15]Stone M, Warren R W, Bruckel J, et al. Juvenile-onset ankylosing spondylitis is associated with worse functional outcomes than adult-onset ankylosing spondylitis[J]. Arthritis Rheum,2005,53(3):445-451.
[16]Gerdan V, Akar S, Solmaz D, et al. Initial diagnosis of lumbar disc herniation is associated with a delay in diagnosis of ankylosing spondylitis[J]. J Rheumatol,2012,39(10):1996-1999.
[17]Lin Z, Xu H, Gu J, et al. Investigation and analysis on the delayed diagnosis in patients with ankylosing spondylitis in a Chinese population[J]. Clin Exp Rheumatol,2008,26(6):1163.
[18]Rudwaleit M, Landewe R, van der Heijde D, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I):classification of paper patients by expert opinion including uncertainty appraisal[J]. Ann Rheum Dis,2009,68(6):770-776.
[19]Rudwaleit M, van der Heijde D, Landewe R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II):validation and final selection[J]. Ann Rheum Dis,2009,68(6):777-783.
[20]van den Berg R, van der Heijde D M. How should we diagnose spondyloarthritis according to the ASAS classification criteria:a guide for practicing physicians[J]. Pol Arch Med Wewn,2010,120(11):452-457.
[21]Garrett S, Jenkinson T, Kennedy L G, et al. A new approach to defining disease status in ankylosing spondylitis:the Bath Ankylosing Spondylitis Disease Activity Index[J]. J Rheumatol,1994,21(12):2286-2291.
[22]Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis:the development of the Bath Ankylosing Spondylitis Functional Index[J]. J Rheumatol,1994,21(12):2281-2285.
[23]Ibn Y Y, Amine B, Laatiris A, et al. Relationship between diagnosis delay and disease features in Moroccan patients with ankylosing spondylitis [J]. Rheumatol Int,2012,32(2):357-360.
[24]Feldtkeller E, Bruckel J, Khan M A. Scientific contributions of ankylosing spondylitis patient advocacy groups[J]. Curr Opin Rheumatol,2000,12(4):239-247.
[25]Zhang S, Li Y, Deng X, et al. Similarities and differences between spondyloarthritis in Asia and other parts of the world[J]. Curr Opin Rheumatol,2011,23(4):334-338.
[26]Barkham N, Kong K O, Tennant A, et al. The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing spondylitis[J]. Rheumatology (Oxford),2005,44(10):1277-1281.
[27]Arturi P, Schneeberger E E, Sommerfleck F, et al. Adherence to treatment in patients with ankylosing spondylitis[J]. Clin Rheumatol,2013.
[28]Poddubnyy D, Rudwaleit M, Haibel H, et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis:results from the German Spondyloarthritis Inception Cohort[J]. Ann Rheum Dis,2012,71(10):1616-1622.
[29]Kroon F, Landewe R, Dougados M, et al. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis[J]. Ann Rheum Dis,2012,71(10):1623-1629.
[30]Braun J, van den Berg R, Baraliakos X, et al.2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis[J]. Ann Rheum Dis,2011,70(6):896-904.
[31]van der Heijde D, Sieper J, Maksymowych W P, et al.2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis[J]. Ann Rheum Dis,2011,70(6):905-908.
[32]Zochling J, Bohl-Buhler M H, Baraliakos X, et al. Nonsteroidal anti-inflammatory drug use in ankylosing spondylitis--a population-based survey[J]. Clin Rheumatol,2006,25(6):794-800.
[33]Baser O, Burkan A, Baser E, et al. Health care costs associated with ankylosing spondylitis in Turkey:an analysis from nationwide real-world data[J]. Int J Rheumatol,2013,2013:139608.
[34]Sundstrom B, Wallberg-Jonsson S, Johansson G. Diet, disease activity, and gastrointestinal symptoms in patients with ankylosing spondylitis[J]. Clin Rheumatol,2011,30(1):71-76.
[35]Gallinaro A L, Ventura C, Sampaio B P, et al. Spondyloarthritis:analysis of a Brazilian series compared with a large Ibero-American registry (RESPONDIA group)[J]. Rev Bras Reumatol,2010,50(5):581-589.
[36]Breban M, Gombert B, Amor B, et al. Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis[J]. Arthritis Rheum,1999,42(3):580-581.
[37]Wei J C, Chan T W, Lin H S, et al. Thalidomide for severe refractory ankylosing spondylitis:a 6-month open-label trial[J]. J Rheumatol,2003,30(12):2627-2631.
[38]Deng X, Zhang J, Zhang J, et al. Thalidomide reduces recurrence of ankylosing spondylitis in patients following discontinuation of etanercept[J]. Rheumatol Int,2012.
[39]Huang F, Gu J, Zhao W, et al. One-year open-label trial of thalidomide in ankylosing spondylitis[J]. Arthritis Rheum,2002,47(3):249-254.
[40]Haibel H, Rudwaleit M, Braun J, et al. Six months open label trial of leflunomide in active ankylosing spondylitis[J]. Ann Rheum Dis,2005,64(1):124-126.
[41]van Denderen J C, van der Paardt M, Nurmohamed M T, et al. Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis [J]. Ann Rheum Dis,2005,64(12):1761-1764.
[42]Winthrop K L, Baddley J W, Chen L, et al. Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster[J]. JAMA,2013,309(9):887-895.
[43]Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis [J]. Ann Rheum Dis,2006,65(4):442-452.
[44]Karapolat H, Akkoc Y, Sari I, et al. Comparison of group-based exercise versus home-based exercise in patients with ankylosing spondylitis:effects on Bath Ankylosing Spondylitis Indices, quality of life and depression[J]. Clin Rheumatol,2008,27(6):695-700.
[45]Durmus D, Alayli G, Cil E, et al. Effects of a home-based exercise program on quality of life, fatigue, and depression in patients with ankylosing spondylitis[J]. Rheumatol Int,2009,29(6):673-677.
[46]Gyurcsik Z N, Andras A, Bodnar N, et al. Improvement in pain intensity, spine stiffness, and mobility during a controlled individualized physiotherapy program in ankylosing spondylitis[J]. Rheumatol Int,2012,32(12):3931-3936.
[47]Yigit S, Sahin Z, Demir S E, et al. Home-based exercise therapy in ankylosing spondylitis:short-term prospective study in patients receiving tumor necrosis factor alpha inhibitors[J]. Rheumatol Int,2013,33(1):71-77.
[48]Tishler M, Brostovski Y, Yaron M. Effect of spa therapy in Tiberias on patients with ankylosing spondylitis [J]. Clin Rheumatol,1995,14(1):21-25.
[49]Santos H, Brophy S, Calin A. Exercise in ankylosing spondylitis:how much is optimum?[J]. J Rheumatol,1998,25(11):2156-2160.
[50]Aytekin E, Caglar N S, Ozgonenel L, et al. Home-based exercise therapy in patients with ankylosing spondylitis:effects on pain, mobility, disease activity, quality of life, and respiratory functions[J]. Clin Rheumatol,2012,31(1):91-97.
[51]Sechrist K R, Walker S N, Pender N J. Development and psychometric evaluation of the exercise benefits/barriers scale[J]. Res Nurs Health,1987,10(6):357-365.
[52]Sundstrom B, Ekergard H, Sundelin G. Exercise habits among patients with ankylosing spondylitis. A questionnaire based survey in the County of Vasterbotten, Sweden[J]. Scand J Rheumatol,2002,31(3):163-167.
[53]Dagfinrud H, Halvorsen S, Vollestad N K, et al. Exercise programs in trials for patients with ankylosing spondylitis:do they really have the potential for effectiveness?[J]. Arthritis Care Res (Hoboken),2011,63(4):597-603.
[54]Dubey S G, Leeder J, Gaffney K. Physical therapy in anti-TNF treated patients with ankylosing spondylitis[J]. Rheumatology (Oxford),2008,47(7):1100-1101.
[55]Falkenbach A. Disability motivates patients with ankylosing spondylitis for more frequent physical exercise[J]. Arch Phys Med Rehabil,2003,84(3):382-383.
[56]Passalent L A, Soever L J, O'Shea F D, et al. Exercise in ankylosing spondylitis:discrepancies between recommendations and reality [J]. J Rheumatol,2010,37(4):835-841.
[57]Cooksey R, Brophy S, Husain M J, et al. The information needs of people living with ankylosing spondylitis:a questionnaire survey [J]. BMC Musculoskelet Disord,2012,13:243.
[58]Lim H J, Moon Y I, Lee M S. Effects of home-based daily exercise therapy on joint mobility, daily activity, pain, and depression in patients with ankylosing spondylitis[J]. Rheumatol Int,2005,25(3):225-229.
[59]Karapolat H, Eyigor S, Zoghi M, et al. Are swimming or aerobic exercise better than conventional exercise in ankylosing spondylitis patients? A randomized controlled study[J]. Eur J Phys Rehabil Med,2009,45(4):449-457.
[60]van Tubergen A, Landewe R, van der Heijde D, et al. Combined spa-exercise therapy is effective in patients with ankylosing spondylitis:a randomized controlled trial[J]. Arthritis Rheum,2001,45(5):430-438.
[61]Van Tubergen A, Boonen A, Landewe R, et al. Cost effectiveness of combined spa-exercise therapy in ankylosing spondylitis:a randomized controlled trial[J]. Arthritis Rheum,2002,47(5):459-467.
[62]van Tubergen A, Hidding A. Spa and exercise treatment in ankylosing spondylitis:fact or fancy?[J]. Best Pract Res Clin Rheumatol,2002,16(4):653-666.
[63]Ciprian L, Lo N A, Rizzo M, et al. The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors[J]. Rheumatol Int,2013,33(1):241-245.
[64]Gensler L S, Ward M M, Reveille J D, et al. Clinical, radiographic and functional differences between juvenile-onset and adult-onset ankylosing spondylitis:results from the PSOAS cohort[J]. Ann Rheum Dis,2008,67(2):233-237.
[65]Ibn Y Y, Amine B, Laatiris A, et al. Gender and disease features in Moroccan patients with ankylosing spondylitis[J]. Clin Rheumatol,2012,31(2):293-297.
[66]Hamdi W, Alaya Z, Ghannouchi M M, et al. Associated risk factors with worse functional prognosis and hip replacement surgery in ankylosing spondylitis[J]. Joint Bone Spine,2012,79(1):94-96.
[67]Kobelt G, Andlin-Sobocki P, Maksymowych W P. Costs and quality of life of patients with ankylosing spondylitis in Canada[J]. J Rheumatol,2006, 33(2):289-295.
[68]Backhaus M, Citak M, Kalicke T, et al. [Spine fractures in patients with ankylosing spondylitis:an analysis of 129 fractures after surgical treatment][J]. Orthopade,2011,40(10):917-920,922-924.
[69]Wulf H. Epidural anaesthesia and spinal haematoma[J]. Can J Anaesth,1996,43(12):1260-1271.
[70]Batra Y K, Sharma A, Rajeev S. Total spinal anaesthesia following epidural test dose in an ankylosing spondylitic patient with anticipated difficult airway undergoing total hip replacement[J]. Eur J Anaesthesiol,2006,23(10):897-898.
[71]Bhan S, Eachempati K K, Malhotra R. Primary cementless total hip arthroplasty for bony ankylosis in patients with ankylosing spondylitis[J]. J Arthroplasty,2008,23(6):859-866.
[72]Bangjian H, Peijian T, Ju L. Bilateral synchronous total hip arthroplasty for ankylosed hips[J]. Int Orthop,2012,36(4):697-701.
[73]Tang W M, Chiu K Y. Primary total hip arthroplasty in patients with ankylosing spondylitis[J]. J Arthroplasty,2000,15(1):52-58.
[74]Williams E, Taylor A R, Arden G P, et al. Arthroplasty of the hip in ankylosing spondylitis[J]. J Bone Joint Surg Br,1977,59-B(4):393-397.
[75]Baldursson H, Brattstrom H, Olsson T. Total hip replacement in ankylosing spondylitis[J]. Acta Orthop Scand,1977,48(5):499-507.
[76]Finsterbush A, Amir D, Vatashki E, et al. Joint surgery in severe ankylosing spondylitis[J]. Acta Orthop Scand,1988,59(5):491-496.
[77]Sweeney S, Gupta R, Taylor G, et al. Total hip arthroplasty in ankylosing spondylitis:outcome in 340 patients[J]. J Rheumatol,2001,28(8):1862-1866.
[78]Calin A, Elswood J. The outcome of 138 total hip replacements and 12 revisions in ankylosing spondylitis:high success rate after a mean followup of 7.5 years[J]. J Rheumatol,1989,16(7):955-958.
[79]Delee J, Ferrari A, Charnley J. Ectopic bone formation following low friction arthroplasty of the hip[J]. Clin Orthop Relat Res,1976(121):53-59.
[80]Bisla R S, Ranawat C S, Inglis A E. Total hip replacement in patients with ankylosing spondylitis with involvement of the hip[J]. J Bone Joint Surg Am,1976,58(2):233-238.
[81]Wilde A H, Collins H R, Mackenzie A H. Reankylosis of the hip joint in ankylosing spondylitis after total hip replacement[J]. Arthritis Rheum, 1972,15(5):493-496.
[82]Joshi A B, Markovic L, Hardinge K, et al. Total hip arthroplasty in ankylosing spondylitis:an analysis of 181 hips[J]. J Arthroplasty,2002,17(4):427-433.
[83]Sochart D H, Porter M L. Long-term results of total hip replacement in young patients who had ankylosing spondylitis. Eighteen to thirty-year results with survivorship analysis[J]. J Bone Joint Surg Am,1997,79(8):1181-1189.
[84]Brinker M R, Rosenberg A G, Kull L, et al. Primary noncemented total hip arthroplasty in patients with ankylosing spondylitis. Clinical and radiographic results at an average follow-up period of 6 years[J]. J Arthroplasty, 1996,11(7):802-812.
[85]Tani Y, Nishioka J, Inoue K, et al. Relation between ectopic ossification after total hip arthroplasty and activity of general inflammation in patients with ankylosing spondylitis[J]. Ann Rheum Dis,1998,57(10):634.
[86]Chorus A M, Miedema H S, Boonen A, et al. Quality of life and work in patients with rheumatoid arthritis and ankylosing spondylitis of working age[J]. Ann Rheum Dis,2003,62(12):1178-1184.
[87]Jang J H, Green C E, Assassi S, et al. The contribution of disease activity on functional limitations over time through psychological mediators:a 12-month longitudinal study in patients with ankylosing spondylitis [J]. Rheumatology (Oxford),2011,50(11):2087-2092.
[88]Jarvis J, Skinner T C, Carey M E, et al. How can structured self-management patient education improve outcomes in people with type 2 diabetes?[J]. Diabetes Obes Metab,2010,12(1):12-19.
[89]Smith S, Mitchell C, Bowler S. Patient-centered education:applying learner-centered concepts to asthma education[J]. J Asthma,2007, 44(10):799-804.
[90]John H, Carroll D, Kitas G D. Cardiovascular education for people with rheumatoid arthritis:what can existing patient education programmes teach us?[J]. Rheumatology (Oxford),2011,50(10):1751-1759.
[91]Friedman A J, Cosby R, Boyko S, et al. Effective teaching strategies and methods of delivery for patient education:a systematic review and practice guideline recommendations [J]. J Cancer Educ,2011,26(1):12-21.
[92]Gordon M M, Capell H A, Madhok R. The use of the Internet as a resource for health information among patients attending a rheumatology clinic[J]. Rheumatology (Oxford),2002,41 (12):1402-1405.
[93]Kiltz U, van der Heijde D, Mielants H, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis:the patient version[J]. Ann Rheum Dis,2009,68(9):1381-1386.
[94]Sudre A, Figuereido I T, Lukas C, et al. On the impact of a dedicated educational program for ankylosing spondylitis:effect on patient satisfaction, disease knowledge and spinal mobility, a pilot study [J]. Joint Bone Spine,2012,79(1):99-100.
[95]Barlow J H, Barefoot J. Group education for people with arthritis[J]. Patient Educ Couns,1996,27(3):257-267.
[96]Sweeney S, Taylor G, Calin A. The effect of a home based exercise intervention package on outcome in ankylosing spondylitis:a randomized controlled trial[J]. J Rheumatol,2002,29(4):763-766.
[97]Silva E M, Andrade S C, Vilar M J. Evaluation of the effects of Global Postural Reeducation in patients with ankylosing spondylitis [J]. Rheumatol Int,2012,32(7):2155-2163.
[98]Masiero S, Bonaldo L, Pigatto M, et al. Rehabilitation treatment in patients with ankylosing spondylitis stabilized with tumor necrosis factor inhibitor therapy:a randomized controlled trial[J]. J Rheumatol,2011,38(7):1335-1342.
[99]Kraag G, Stokes B, Groh J, et al. The effects of comprehensive home physiotherapy and supervision on patients with ankylosing spondylitis--a randomized controlled trial[J]. J Rheumatol,1990,17(2):228-233.
[100]Gross M, Brandt K D. Educational support groups of patients with ankylosing spondylitis:a preliminary report[J]. Patient Couns Health Educ,1981, 3(1):6-12.
[101]Kjeken I, Dagfinrud H, Mowinckel P, et al. Rheumatology care:Involvement in medical decisions, received information, satisfaction with care, and unmet health care needs in patients with rheumatoid arthritis and ankylosing spondylitis[J]. Arthritis Rheum,2006,55(3):394-401.
[102]Coulter A, Entwistle V, Gilbert D. Sharing decisions with patients:is the information good enough?[J]. BMJ,1999,318(7179):318-322.
[103]Giraldo G. Scoring Points for Holistic Medicine:Anisio Leon, MD, MS and Pedro Carmona, BS, Natural & Traditional Medicine Unit, Sports Medicine Institute, Havana[J]. MEDICC Rev,2009,11(2):12-14.
[104]Nour K, Laforest S, Gauvin L, et al. Behavior change following a self-management intervention for housebound older adults with arthritis:an experimental study[J]. Int J Behav Nutr Phys Act,2006,3:12.
[105]Freda M C. Issues in patient education[J]. J Midwifery Womens Health,2004,49(3):203-209.
[106]Chang M, Kelly A E. Patient education:addressing cultural diversity and health literacy issues[J]. Urol Nurs,2007,27(5):411-417,418.
[107]Taal E, Seydel E R, Rasker J J, et al. Psychosocial aspects of rheumatic diseases:introduction[J]. Patient Educ Couns,1993,20(2-3):55-61.
[108]Nghiem F T, Donohue J P. Rehabilitation in ankylosing spondylitis[J]. Curr Opin Rheumatol,2008,20(2):203-207.
[109]Hoving C, Visser A, Mullen P D, et al. A history of patient education by health professionals in Europe and North America:from authority to shared decision making education[J]. Patient Educ Couns,2010,78(3):275-281.
[110]Makelainen P, Vehvilainen-Julkunen K, Pietila A M. Rheumatoid arthritis patients'education-contents and methods[J]. J Clin Nurs,2007,16(11C):258-267.
[111]Hill J. An overview of education for patients with rheumatic diseases [J]. Nurs Times,2003,99(19):26-27.
[112]Demir S E, Rezvani A, Ok S. Assessment of sexual functions in female patients with ankylosing spondylitis compared with healthy controls [J]. Rheumatol Int,2013,33(1):57-63.
[113]Rostom S, Mengat M, Mawani N, et al. Sexual activity in Moroccan men with ankylosing spondylitis[J]. Rheumatol Int,2012.
[114]Schrieber L, Colley M. Patient education[J]. Best Pract Res Clin Rheumatol,2004,18(4):465-476.
[115]Zhang X, Chen L W, Mueller K, et al. Tracking the effectiveness of health care reform in China:a case study of community health centers in a district of Beijing[J]. Health Policy,2011,100(2-3):181-188.
[116]Johnson A, Sandford J. Written and verbal information versus verbal information only for patients being discharged from acute hospital settings to home:systematic review[J]. Health Educ Res,2005,20(4):423-429.
[117]Fox M P. A systematic review of the literature reporting on studies that examined the impact of interactive, computer-based patient education programs[J]. Patient Educ Couns,2009,77(1):6-13.
[118]Singleton E M, Hutson S E. Anterior uveitis, inflammatory bowel disease, and ankylosing spondylitis in a HLA-B27-positive woman[J]. South Med J,2006,99(5):531-533.
[119]Sowden E, Hassan W, Gooden A, et al. Limited end-user knowledge of methotrexate despite patient education:an assessment of rheumatologic preventive practice and effectiveness[J]. J Clin Rheumatol,2012, 18(3):130-133.
[120]Ward M M, Reveille J D, Learch T J, et al. Impact of ankylosing spondylitis on work and family life:comparisons with the US population[J]. Arthritis Rheum,2008,59(4):497-503.
[121]Montacer K M, Mehdi G M, Hamdi W, et al. Impact of the ankylosing spondylitis on the professional activity [J]. Joint Bone Spine,2009, 76(4):378-382.
[122]Anderson A S, Klemm P. The Internet:friend or foe when providing patient education?[J]. Clin J Oncol Nurs,2008,12(1):55-63.
[123]Mccormick M C, Stemmler M M, Athreya B H. The impact of childhood rheumatic diseases on the family [J]. Arthritis Rheum,1986,29(7):872-879.
[124]Niedermann K, Fransen J, Knols R, et al. Gap between short-and long-term effects of patient education in rheumatoid arthritis patients:a systematic review[J]. Arthritis Rheum,2004,51(3):388-398.
[125]Bukulmez H, Colbert R A. Juvenile spondyloarthropathies and related arthritis[J]. Curr Opin Rheumatol,2002,14(5):531-535.
[126]O'Shea F D, Boyle E, Riarh R, et al. Comparison of clinical and radiographic severity of juvenile-onset versus adult-onset ankylosing spondylitis[J]. Ann Rheum Dis,2009,68(9):1407-1412.
[127]Marks S H, Barnett M, Calin A. A case-control study of juvenile-and adult-onset ankylosing spondylitis [J]. J Rheumatol,1982,9(5):739-741.
[128]Ozgocmen S, Ardicoglu O, Kamanli A, et al. Pattern of disease onset, diagnostic delay, and clinical features in juvenile onset and adult onset ankylosing spondylitis[J]. J Rheumatol,2009,36(12):2830-2833.
[129]Baek H J, Shin K C, Lee Y J, et al. Juvenile onset ankylosing spondylitis (JAS) has less severe spinal disease course than adult onset ankylosing spondylitis (AAS):clinical comparison between JAS and AAS in Korea[J]. J Rheumatol,2002,29(8):1780-1785.
[130]Baraliakos X, Braun J. Hip involvement in ankylosing spondylitis:what is the verdict?[J]. Rheumatology (Oxford),2010,49(1):3-4.
[131]Garcia-Morteo O, Maldonado-Cocco J A, Suarez-Almazor M E, et al. Ankylosing spondylitis of juvenile onset:comparison with adult onset disease[J]. Scand J Rheumatol,1983,12(3):246-248.
[132]Kim T J, Kim T H. Clinical spectrum of ankylosing spondylitis in Korea[J]. Joint Bone Spine,2010,77(3):235-240.
[133]Calin A, Elswood J. The natural history of juvenile-onset ankylosing spondylitis:a 24-year retrospective case-control study [J]. Br J Rheumatol,1988,27(2):91-93.
[134]Doward L C, Spoorenberg A, Cook S A, et al. Development of the ASQoL:a quality of life instrument specific to ankylosing spondylitis[J]. Ann Rheum Dis,2003,62(1):20-26.
[135]Riley M J, Ansell B M, Bywaters E G. Radiological manifestations of ankylosing spondylitis according to age at onset[J]. Ann Rheum Dis,1971,30(2):138-148.
[136]Aggarwal A, Hissaria P, Misra R. Juvenile ankylosing spondylitis-is it the same disease as adult ankylosing spondylitis?[J]. Rheumatol Int,2005, 25(2):94-96.
[137]Bodur H, Ataman S, Rezvani A, et al. Quality of life and related variables in patients with ankylosing spondylitis[J]. Qual Life Res,2011,20(4):543-549.
[138]Boonen A, Braun J, van der Horst B I, et al. ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS):how to classify the impact of AS on functioning and health[J]. Ann Rheum Dis,2010,69(1):102-107.
[139]Boonen A, Mau W. The economic burden of disease:comparison between rheumatoid arthritis and ankylosing spondylitis [J]. Clin Exp Rheumatol, 2009,27(4 Suppl 55):S112-S117.
[140]Roussou E, Kennedy L G, Garrett S, et al. Socioeconomic status in ankylosing spondylitis:relationship between occupation and disease activity[J]. J Rheumatol,1997,24(5):908-911.
[1]Cooksey R, Brophy S, Husain MJ, Irvine E, Davies H, Siebert S (2012) The information needs of people living with ankylosing spondylitis:a questionnaire survey. BMC Musculoskelet Disord 13:243
[2]Gensler LS, Ward MM, Reveille JD, Learch TJ, Weisman MH, Davis JJ (2008) Clinical, radiographic and functional differences between juvenile-onset and adult-onset ankylosing spondylitis:results from the PSOAS cohort. Ann Rheum Dis 67:233-7
[3]Ibn YY, Amine B, Laatiris A, Hajjaj-Hassouni N (2012) Gender and disease features in Moroccan patients with ankylosing spondylitis. Clin Rheumatol 31: 293-7
[4]Hamdi W, Alaya Z, Ghannouchi MM, Haouel M, Kchir MM (2012) Associated risk factors with worse functional prognosis and hip replacement surgery in ankylosing spondylitis. Joint Bone Spine 79:94-6
[5]Kobelt G, Andlin-Sobocki P, Maksymowych WP (2006) Costs and quality of life of patients with ankylosing spondylitis in Canada. J Rheumatol 33:289-95
[6]Kjeken I, Bo I, Ronningen A, Spada C, Mowinckel P, Hagen KB, Dagfinrud H (2013) A three-week multidisciplinary in-patient rehabilitation programme had positive long-term effects in patients with ankylosing spondylitis:Randomized controlled trial. J Rehabil Med 45:260-7
[7]Ince G, Sarpel T, Durgun B, Erdogan S (2006) Effects of a multimodal exercise program for people with ankylosing spondylitis. Phys Ther 86:924-35
[8]Heikkila S, Viitanen JV, Kautiainen H, Kauppi M (2000) Sensitivity to change of mobility tests; effect of short term intensive physiotherapy and exercise on spinal, hip, and shoulder measurements in spondyloarthropathy. J Rheumatol 27: 1251-6
[9]Yigit S, Sahin Z, Demir SE, Aytac DH (2013) Home-based exercise therapy in ankylosing spondylitis:short-term prospective study in patients receiving tumor necrosis factor alpha inhibitors. Rheumatol Int 33:71-7
[10]Passalent LA (2011) Physiotherapy for ankylosing spondylitis:evidence and application. Curr Opin Rheumatol 23:142-7
[11]Ozgocmen S, Akgul O, Altay Z, Altindag O, Baysal O, Calis M, Capkin E, Cevik R, Durmus B, Gur A, Kamanli A, Karkucak M, Madenci E, Melikoglu MA, Nas K, Senel K, Ugur M (2012) Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis. Int J Rheum Dis 15:229-38
[12]Braun J, van der Horst-Bruinsma IE, Huang F, Burgos-Vargas R, Vlahos B, Koenig AS, Freundlich B (2011) Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis:a randomized, double-blind trial. Arthritis Rheum 63:1543-51
[13]Chen J, Veras MM, Liu C, Lin J (2013) Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev 2:CD004524
[14]Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, Zeidler H, Dougados M (2005) Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis:a randomized clinical trial. Arthritis Rheum 52:1756-65
[15]Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker-Hermann E, Zeidler H, Braun J, Sieper J (2012) Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis:results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis 71: 1616-22
[16]Kroon F, Landewe R, Dougados M, van der Heijde D (2012) Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann Rheum Dis 71:1623-9
[17]Conaghan PG (2012) A turbulent decade for NSAIDs:update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int 32:1491-502
[18]Wang D, Ma L, Wu D (2011) Efficacy of etanercept in ankylosing spondylitis hip lesions. Joint Bone Spine 78:531-2
[19]Lian F, Yang X, Liang L, Xu H, Zhan Z, Qiu Q, Ye Y (2012) Treatment efficacy of etanercept and MTX combination therapy for ankylosing spondylitis hip joint lesion in Chinese population. Rheumatol Int 32:1663-7
[20]van der Heijde D, Landewe R, Einstein S, Ory P, Vosse D, Ni L, Lin SL, Tsuji W, Davis JJ (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58:1324-31
[21]van der Heijde D, Landewe R, Baraliakos X, Houben H, van Tubergen A, Williamson P, Xu W, Baker D, Goldstein N, Braun J (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 58:3063-70
[22]van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, Ballal S, Gibson E, Wong R (2009) Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 11:R127
[23]Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JJ, Dijkmans B, Dougados M, Geher P, Inman RD, Khan MA, Kvien TK, Leirisalo-Repo M, Olivieri I, Pavelka K, Sieper J, Stucki G, Sturrock RD, van der Linden S, Wendling D, Bohm H, van Royen BJ, Braun J (2006) ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 65:442-52
[24]Backhaus M, Citak M, Kalicke T, Sobottke R, Russe O, Meindl R, Muhr G, Frangen TM (2011) [Spine fractures in patients with ankylosing spondylitis:an analysis of 129 fractures after surgical treatment]. Orthopade 40:917-20,922-4
[25]Wulf H (1996) Epidural anaesthesia and spinal haematoma. Can J Anaesth 43: 1260-71
[26]Batra YK, Sharma A, Rajeev S (2006) Total spinal anaesthesia following epidural test dose in an ankylosing spondylitic patient with anticipated difficult airway undergoing total hip replacement. Eur J Anaesthesiol 23:897-8
[27]Bhan S, Eachempati KK, Malhotra R (2008) Primary cementless total hip arthroplasty for bony ankylosis in patients with ankylosing spondylitis. J Arthroplasty 23:859-66
[28]Bangjian H, Peijian T, Ju L (2012) Bilateral synchronous total hip arthroplasty for ankylosed hips. Int Orthop 36:697-701
[29]Tang WM, Chiu KY (2000) Primary total hip arthroplasty in patients with ankylosing spondylitis. J Arthroplasty 15:52-8
[30]Williams E, Taylor AR, Arden GP, Edwards DH (1977) Arthroplasty of the hip in ankylosing spondylitis. J Bone Joint Surg Br 59-B:393-7
[31]Baldursson H, Brattstrom H, Olsson T (1977) Total hip replacement in ankylosing spondylitis. Acta Orthop Scand 48:499-507
[32]Finsterbush A, Amir D, Vatashki E, Husseini N (1988) Joint surgery in severe ankylosing spondylitis. Acta Orthop Scand 59:491-6
[33]Sweeney S, Gupta R, Taylor G, Calin A (2001) Total hip arthroplasty in ankylosing spondylitis:outcome in 340 patients. J Rheumatol 28:1862-6
[34]Calin A, Elswood J (1989) The outcome of 138 total hip replacements and 12 revisions in ankylosing spondylitis:high success rate after a mean followup of 7.5 years. J Rheumatol 16:955-8
[35]Bisla RS, Ranawat CS, Inglis AE (1976) Total hip replacement in patients with ankylosing spondylitis with involvement of the hip. J Bone Joint Surg Am 58: 233-8
[36]Joshi AB, Markovic L, Hardinge K, Murphy JC (2002) Total hip arthroplasty in ankylosing spondylitis:an analysis of 181 hips. J Arthroplasty 17:427-33
[37]Sandri A, Regis D, Marino MA, Perandini S, Bonetti I, Toso M (2012) Deep external pudendal artery injury after percutaneous adductor tenotomy during THA in ankylosing spondylitis. Orthopedics 35:e566-9
[38]Brinker MR, Rosenberg AG, Kull L, Cox DD (1996) Primary noncemented total hip arthroplasty in patients with ankylosing spondylitis. Clinical and radiographic results at an average follow-up period of 6 years. J Arthroplasty 11:802-12
[39]Sochart DH, Porter ML (1997) Long-term results of total hip replacement in young patients who had ankylosing spondylitis. Eighteen to thirty-year results with survivorship analysis. J Bone Joint Surg Am 79:1181-9
[40]DeLee J, Ferrari A, Charnley J (1976) Ectopic bone formation following low friction arthroplasty of the hip. Clin Orthop Relat Res:53-9
[41]Wilde AH, Collins HR, Mackenzie AH (1972) Reankylosis of the hip joint in ankylosing spondylitis after total hip replacement. Arthritis Rheum 15:493-6
[42]Tani Y, Nishioka J, Inoue K, Hukuda S, Tsujimoto M (1998) Relation between ectopic ossification after total hip arthroplasty and activity of general inflammation in patients with ankylosing spondylitis. Ann Rheum Dis 57:634
[43]Kubiak EN, Moskovich R, Errico TJ, Di Cesare PE (2005) Orthopaedic management of ankylosing spondylitis. J Am Acad Orthop Surg 13:267-78
[44]Shih LY, Chen TH, Lo WH, Yang DJ (1995) Total hip arthroplasty in patients with ankylosing spondylitis:longterm followup. J Rheumatol 22:1704-9
[45]Busti AJ, Hooper JS, Amaya CJ, Kazi S (2005) Effects of perioperative antiinflammatory and immunomodulating therapy on surgical wound healing. Pharmacotherapy25:1566-91
[46]Radzikowska B (2000) Rheumatological considerations in the qualification of rheumatoid patients for surgical treatment and principles for pre-and post-operative management. Ortop Traumatol Rehabil 2:83-6
[47]Goh L, Jewell T, Laversuch C, Samanta A (2012) Should anti-TNF therapy be discontinued in rheumatoid arthritis patients undergoing elective orthopaedic surgery? A systematic review of the evidence. Rheumatol Int 32:5-13
[48]Kawakami K, Ikari K, Kawamura K, Tsukahara S, Iwamoto T, Yano K, Sakuma Y, Tokita A, Momohara S (2010) Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers:perioperative interruption of tumour necrosis factor-alpha blockers decreases complications? Rheumatology (Oxford) 49:341-7
[49]Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, Paulus HE, Mudano A, Pisu M, Elkins-Melton M, Outman R, Allison JJ, Suarez AM, Bridges SJ, Chatham WW, Hochberg M, MacLean C, Mikuls T, Moreland LW, O'Dell J, Turkiewicz AM, Furst DE (2008) American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 59:762-84
[50]Ledingham J, Deighton C (2005) Update on the British Society for Rheumatology guidelines for prescribing TNFalpha blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology (Oxford) 44:157-63