浴疗法（水疗疗法）治疗类风湿性关节炎
摘要
研究背景
目前尚无治愈类风湿性关节炎（rheumatoid arthritis, RA）的方法，因此治疗通常侧重于对疼痛、僵硬和活动能力的管理。治疗选择包括药物干预、物理治疗和浴疗法。浴疗法是在天然矿泉水或温泉水中沐浴（例如矿物浴、硫磺浴、死海浴），或者使用泥敷膏，又或者两者兼备。尽管浴疗法很受欢迎，但关于其有效性的科学证据却很少。本系统综述评价浴疗法对RA患者的影响，是对2003年首次发表并于2008年更新的Cochrane综述的再次更新。
研究目的
从疼痛、改善、残疾、关节触痛、关节肿胀和不良事件等方面系统评价浴疗法对RA患者的获益和伤害。
检索策略
我们检索了Cochrane“康复和相关疗法”领域注册库（Cochrane ‘Rehabilitation and Related Therapies' Field Register）（截至2014年12月）、Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials）（2014年第1期）、美国国立医学图书馆（MEDLINE）（1950年至2014年12月）、荷兰医学文摘（EMBASE）（1988年至2014年12月）、保健协会文献索引资料库（Cumulative Index to Nursing and Allied Health Literature, CINAHL）（1982年至2014年12月）、补充医学文献数据库（Allied and Complementary Medicine Database, AMED）（1985年至2014年12月）、美国心理协会文摘索引数据库（PsycINFO）（1806年至2014年12月）和物理治疗证据数据库（Physiotherapy Evidence Database, PEDro）。我们没有语言限制，但是未用英语、荷兰语、丹麦语、瑞典语、挪威语、德语或法语报告的正在等待评价的研究。我们还检索了世界卫生组织（World Health Organization, WHO）国际临床试验注册平台（International Clinical Trials Registry Platform, ICTRP），以获取正在进行的和最近完成的试验。
纳入排除标准
纳入标准为受试者符合1958年美国风湿病协会（American Rheumatism Association, ARA）标准、1988年ARA/美国风湿病学会（American College of Rheumatology, ACR）标准或2010年ACR/欧洲抗风湿病联盟（European League Against Rheumatism, EULAR）标准定义的明确或经典型RA的随机对照试验（randomised controlled trial, RCT），或使用类风湿关节炎的病期分类（Steinbrocker）标准的研究。
浴疗法必须是研究中的干预措施，并且必须与另一种或无干预措施进行对比。
WHO和国际抗风湿病联盟（International League Against Rheumatismm, ILAR）于1992年确定了RA患者临床试验的八个核心终点。我们将疼痛、改善、残疾、关节触痛、关节肿胀和不良事件作为主要结局指标，并排除了仅报告实验室变量作为结局指标的研究。
资料收集与分析
两名综述作者独立筛选试验、提取资料并评价偏倚风险。我们通过协商解决分歧，必要时寻求第三方裁决。
主要结果
本系统综述共纳入九项研究（两项新研究），579名受试者。不幸的是，大多数研究在多数领域存在不明确的偏倚风险。九项研究中有四项因为没有提供资料，对分析没有贡献。
一项涉及45名手部RA受试者的研究对比了泥敷膏与安慰剂。我们发现组间在0至100mm视觉模拟量表（visual analogue scale, VAS）评分的疼痛（均差（mean difference, MD)=0.50，95%置信区间（confidence interval, CI）[‐0.84, 1.84]）、改善（风险比（risk ratio, RR)=0.96，95% CI [0.54, 1.70]）、关节肿胀数量（0至28量表）（MD=0.60, 95% CI [‐0.90, 2.10]）（极低质量证据）方面无统计学重要差异。我们发现关节触痛数量（0至28量表）减少的证据质量极低（MD=‐4.60，95% CI [‐8.72, ‐0.48]；16%绝对差异）。我们没有报告身体残疾，也没有因不良事件或严重不良事件而退出的资料。
涉及194名RA受试者的两项研究评价了二氧化碳浴中加氡的有效性。在三个月的随访中，两组的所有结局无统计学显著差异（低到中等质量证据）。我们发现，在6个月时，增加氡对疼痛频率有一定获益（RR=0.6，95% CI [0.4, 0.9]；降低31%；在四分量表上有一个或多个（类别）的改善；中等质量证据）；在0至100mm的VAS上，疼痛强度降低了9.6%（MD=9.6mm, 95% CI [1.6, 17.6]；中等质量证据）。我们还在一项纳入60名受试者的研究中观察到一些益处，即基于四分量表的一个或多个类别的改善（RR=2.3, 95% CI [1.1, 4.7]；30%绝对差异；低质量证据）。研究作者没有报告身体残疾、关节触痛、关节肿胀、因不良事件或严重不良事件而退出的资料。
一项纳入148名RA受试者的研究对比了浴疗（坐式浸泡）与水疗（水中锻炼）、陆地锻炼或放松疗法。我们发现，在McGill问卷调查中疼痛或身体残疾方面，浴疗法和其他干预措施之间没有统计学上的显著差异（极低质量证据）。未提供关于改善、关节触痛、关节肿胀、因不良事件或严重不良事件而退出的资料。
一项纳入57名RA受试者的研究评价了矿物浴（浴疗法）对比环孢素A的有效性。在8周时，0至100mm的VAS上疼痛强度没有统计学上的显著差异（MD=9.64, 95% CI [‐1.66, 20.94]；低质量证据，10%绝对差异）。在8周时，在五分量表上的整体改善方面，浴疗法有一定获益，达到54%（RR=2.35, 95% CI [1.44, 3.83]）。我们发现关节肿胀的数量在统计学上没有显著差异（低质量证据），但环孢素A在关节触痛数量上有一定获益（MD=8.9, 95% CI [3.8, 14]；极低质量证据）。未报告身体残疾，因不良事件和严重不良事件而退出的资料。
作者结论
总体证据不足以表明浴疗法比不治疗更有效、一种浴疗比另一种浴疗更有效或者一种浴疗比泥敷膏、运动或放松疗法更有效。
PICOs
PICOs
Population
Intervention
Comparison
Outcome
The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.
See more on using PICO in the Cochrane Handbook .
简语概要
浴疗法（水疗疗法）治疗类风湿性关节炎
我们评价了浴疗法（天然矿泉水、气体和泥敷膏或水疗疗法）对类风湿性关节炎患者的获益和伤害的证据。浴疗法是在天然矿泉水或温泉水中沐浴（例如矿物浴、硫磺浴、死海浴），或者使用泥敷膏，又或者两者兼备。通过检索截至2014年12月的所有相关研究，我们找到了九项研究，涉及579名受试者。主要由于受试者人数少及研究设计问题的不足，证据质量极低。
本系统综述表明，对于类风湿性关节炎患者：
• 与安慰剂（假治疗）相比，我们不确定泥敷膏（浴疗法）是否能改善手部类风湿关节炎患者的疼痛、整体健康和关节肿胀。与安慰剂相比，泥敷膏可以轻微缓解关节疼痛，但研究中没有报告有关身体机能和不良事件的信息。
• 与不加氡的二氧化碳浴相比，在二氧化碳浴中添加氡并不能在三个月时降低疼痛强度，但在六个月时可能会改善整体健康和疼痛强度，但这也可能是偶然发生的。研究中未报告有关身体残疾、关节触痛、肿胀以及不良事件的信息。
• 与水疗、运动或放松相比，我们不确定浴疗（坐式浸泡）是否能改善疼痛和提高身体机能。研究中未报告改善、关节触痛、关节肿胀和不良事件。
• 与使用药物（环孢菌素A）相比，我们不确定在矿物浴（浴疗法）是否能改善疼痛和关节肿胀。与环孢素A相比，矿物浴可以改善整体健康状况；与矿物浴相比，环孢素A可以减少关节触痛数量。未报告身体残疾和不良事件。
• 我们没有关于浴疗法的副作用和并发症的准确信息。尤其是罕见的副作用信息。副作用可能包括皮疹、感染和事故，例如在沐浴区附近的潮湿地面上滑倒。唯一报告副作用的研究表明，他们没有发现任何副作用。
什么是类风湿性关节炎，什么是浴疗法？
当您患有类风湿性关节炎（rheumatoid arthritis, RA）时，身体的免疫系统通常会对抗感染导致关节内层发炎，进而会出现关节的疼痛、僵硬和肿胀。手和脚的小关节通常会首先受到影响。目前没有治愈RA的方法，所以治疗的目的是缓解疼痛和僵硬，提高活动能力。
浴疗法（水中沐浴）是一种为减轻疼痛和改善日常功能的疗法，通常在温泉浴或海水浴中心进行。
Authors' conclusions
Summary of findings
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Balneotherapy compared with placebo for participants with rheumatoid arthritis |
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Patient or population:
participants with rheumatoid arthritis
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Outcomes |
Illustrative comparative risks* (95% CI) |
Relative effect
|
Number of participants
|
Quality of the evidence
|
Comments |
|
|
Assumed risk |
Corresponding risk |
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Placebo |
Balneotherapy |
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Pain intensity
|
Mean pain intensity in control groups was
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Mean pain intensity in intervention groups was
|
45
|
⊕⊝⊝⊝
|
MD 0.50 (95% CI ‐0.84 to 1.84) Absolute difference 0.5% (95% CI ‐0.84% to 1.84%) Relative percent change 1% (95% CI ‐2% to 4%) No statistically significant or clinically relevant difference |
|
|
Improvement
measures (> 30% reduction in number of swollen joints, > 30% reduction in number of tender joints,
> 20% improvement in patient VAS for severity of pain and > 20% improvement in physician VAS)
|
522 per 1000 |
501 per 1000
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RR 0.96
|
45
|
⊕⊝⊝⊝
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Absolute difference ‐2% (95% CI ‐31% to 27%) Relative percent change 5% (95% CI ‐42% to 70%) No statistically significant or clinically relevant difference |
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Physical disability Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Tender joints Number of painful joints Scale from 0 to 28 Follow‐up: 3 months |
Mean number of tender joints in control groups was
|
Mean number of tender joints in intervention groups was
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45
|
⊕⊝⊝⊝
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MD ‐4.60 (95% CI ‐8.72 to ‐0.48) Absolute difference ‐16% (95% CI ‐31% to 2%) Relative percent change ‐37% (95% CI ‐70% to ‐4%) NNTB 32 (95% CI 10 to 717) |
|
|
Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 3 months |
Mean number of swollen joints in control groups was
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Mean number of tender joints in intervention groups was
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45
|
⊕⊝⊝⊝
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MD 0.60 (95% CI ‐0.90 to 2.10) Absolute difference 2% (95% CI ‐3% to 8%) Relative percent change 32% (95% CI ‐47% to 110%) No statistically significant or clinically relevant difference |
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Withdrawal due to serious adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
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Adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
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*The basis for the
assumed risk
(e.g. median control group risk across studies) is provided in footnotes. The
corresponding risk
(and its 95% confidence interval) is based on the assumed risk in the comparison group and the
relative effect
of the intervention (and its 95% CI).
|
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GRADE Working Group grades of evidence.
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a
Downgraded because of imprecision.
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Additional radon in carbon dioxide baths compared with carbon dioxide baths only for participants with rheumatoid arthritis |
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Patient or population:
participants with rheumatoid arthritis
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Outcomes |
Illustrative comparative risks* (95% CI) |
Relative effect
|
Number of participants
|
Quality of the evidence
|
Comments |
|
|
Assumed risk |
Corresponding risk |
|||||
|
Carbon dioxide baths only |
Additional radon in carbon dioxide baths |
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|
Pain intensity
|
Mean change in pain intensity in control groups was
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Mean change in pain intensity in intervention groups was
|
194
|
⊕⊕⊕⊝
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MD ‐4.49 (95% CI ‐13.41 to 4.44) Absolute difference 4.5% (95% CI ‐13.4 to 4.4) No statistically significant or clinically relevant difference |
|
|
Pain intensity
|
Mean change in pain intensity in control groups was
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Mean change in pain intensity in intervention groups was
|
194
|
⊕⊕⊕⊝
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MD ‐9.59 (95% CI ‐17.57 to ‐1.6) Absolute difference 9.5% (95% CI ‐17.5 to ‐1.6) Statistically significant but not clinically relevant difference |
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Improvement
|
267 per 1000 |
367 per 1000
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RR 1.38 (0.64 to 2.93) |
60
|
⊕⊕⊝⊝
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Absolute difference 10% (95% CI ‐13% to 33%) Relative percent change 38% (95% CI ‐36% to 22%) No statistically significant or clinically relevant difference |
|
Improvement
|
233 per 1000 |
533 per 1000 |
RR 2.29 (1.1 to 4.74) |
60 (1 study) |
⊕⊕⊝⊝
|
Absolute difference 30% (95% CI 10% to 60%) Relative percent change 129% (95% CI 10% to 474%) Statistically significant and clinical relevant difference |
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Physical disability Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Tender joints Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Swollen joints Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Withdrawal due to serious adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
*The basis for the
assumed risk
(e.g. median control group risk across studies) is provided in footnotes. The
corresponding risk
(and its 95% confidence interval) is based on the assumed risk in the comparison group and the
relative effect
of the intervention (and its 95% CI).
|
||||||
|
GRADE Working Group grades of evidence.
|
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|
a
Downgraded because of imprecision.
|
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Balneotherapy compared with drug treatment for participants with rheumatoid arthritis |
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Patient or population:
participants with rheumatoid arthritis
|
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|
Outcomes |
Illustrative comparative risks* (95% CI) |
Relative effect
|
Number of participants
|
Quality of the evidence
|
Comments |
|
|
Assumed risk |
Corresponding risk |
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|
Drug treatment ‐ Cyclosporin A |
Balneotherapy |
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|
Pain intensity
|
Mean pain intensity in control groups was
|
Mean pain intensity in intervention groups was
|
57
|
⊕⊝⊝⊝
|
MD 9.64 (95% CI ‐1.66 to 20.94) Absolute difference 10% (95% CI ‐2% to 21%) Relative percent change 53% (95% CI ‐9% to 116%) No statistically significant or clinically relevant difference |
|
|
Improvement
|
400 per 1000 |
940 per 1000
|
RR 2.35 (1.44 to 3.83) |
57
|
⊕⊝⊝⊝
|
Absolute difference 54% (95% CI 33% to 75%) Relative percent change 135% (95% CI 44% to 283%) NNTB 2 (95% CI 2 to 3) |
|
Physical disability Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Tender joints Number of tender joints Scale from 0 to 28 Follow‐up: 8 weeks |
Mean number of tender joints in control groups was
|
Mean number of tender joints in intervention groups was
|
57 (1 study) |
⊕⊝⊝⊝
|
MD 8.90 (95% CI 3.83 to 13.97) Absolute difference 31% (95% CI 17% to 50%) Relative percent change 228% (95% CI 98% to 358%) NNTB 22 (95% CI 8 to 96) |
|
|
Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 8 weeks |
Mean number of swollen joints in control groups was
|
Mean number of tender joints in intervention groups was
|
57 (1 study) |
⊕⊝⊝⊝
|
MD 1.50 (95% CI ‐1.25 to 4.25) Absolute difference 5% (95% CI ‐4% to 15%) Relative percent change 79% (95% CI ‐66% to 224%) No statistically significant or clinical relevant difference |
|
|
Withdrawal due to serious adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
*The basis for the
assumed risk
(e.g. median control group risk across studies) is provided in footnotes. The
corresponding risk
(and its 95% confidence interval) is based on the assumed risk in the comparison group and the
relative effect
of the intervention (and its 95% CI).
|
||||||
|
GRADE Working Group grades of evidence.
|
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|
a
Downgraded because of single study.
|
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Background
Description of the condition
Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the peripheral joints. In adults, the incidence of new cases is 50/100 000/y and one‐year prevalence is between 500 and 600/100 000 (0.5% to 1.0%) ( Symmons 1994 ). Common symptoms of RA consist of a combination of pain, fatigue, stiffness, reduced range of motion in the joints and muscle weakness. Inflammation can cause progressive destruction of articular and periarticular structures ( McInnes 2011 ; Symmons 2002 ). RA can affect all joints in the body. The natural course of the disease is a slow but inexorable deterioration in physical condition, leading to difficulty in activities of daily living and poor quality of life. Rheumatoid arthritis is a multi‐system disease that can affect internal organs, causing premature death. With adequate treatment targeted towards strongly reducing or abolishing inflammatory disease, many of these consequences can be prevented.
Description of the intervention
The term 'balneotherapy' comes from the Latin 'balneum' (bath). The term is classically used in (Eastern) European countries when natural mineral or thermal waters are used for bathing, drinking and inhalation. Recently a position paper was published with a proposal for, amongst others, a definition of balneotherapy ( Gutenbrunner 2010 ). One of the core elements of balneotherapy is the use of (natural) mineral waters, gases and peloids (including packs = local application of peloids), often in health resorts (spas). In most European countries, balneotherapy often takes place at centres with thermal baths or seawater baths ( Gutenbrunner 2010 ). In Israel, the main health resort area is located along the western shore of the Dead Sea. The unique environmental conditions in this area are considered beneficial for patients suffering from rheumatic disease ( Sukenik 1994a ).
In Homeric times, baths were applied primarily to cleanse and refresh. At the time of Hippocrates, bathing was regarded as more than a simple hygienic measure. It was considered beneficial in curing most illnesses ( van Tubergen 2001 ). The Romans used water for treatment of orthopaedic conditions, but after the Roman era, spa therapy fell into disuse. In the sixteenth century, baths were rediscovered. Since that time, spa therapy has been practised continuously in the management of musculoskeletal conditions ( Brosseau 2002 ; van Tubergen 2001 ; Verhagen 2007 ).
Balneotherapy is prescribed most often for patients with any form of arthritis, including fibromyalgia. Positive effects have been mentioned in the treatment of psoriasis as well ( Brosseau 2002 ; Buskila 2001 ; Verhagen 2007 ).
Exercise in warm (tap) water is usually called 'hydrotherapy' or 'aquatic therapy'. This Cochrane review focuses on balneotherapy only, which consists of bathing in natural mineral or thermal waters, using mudpacks or doing both.
How the intervention might work
The mechanism by which balneotherapy might work is not clear. Water (thermal water, sea water) is generally used at a temperature of between 34°C and 36°C ( Becker 2009 ; Gutenbrunner 2010 ). Hydrostatic force (Archimedes' principle) brings about relative pain relief by reducing loading ( Becker 2009 ); water reduces gravity in painful and rheumatic joints. The warmth and buoyancy of water may block nociception by acting on thermal receptors and mechanoreceptors ( Bender 2005 ). Warm water may also enhance blood flow, which is thought to help in dissipating algogenic chemicals, and may facilitate muscle relaxation ( Kamioka 2010 ). Apart from these mechanical and thermal mechanisms, one should not undervalue the psychological mechanisms of the spa environment. The related mental relaxation may also play a role in pain relief ( Brosseau 2002 ).
The aim of balneotherapy is to improve the range of joint motion, relieve muscle spasm, maintain or improve functional mobility, soothe pain and, as a consequence, relieve patients' suffering and help them feel well ( Fam 1991 ; Gutenbrunner 2010 ; Jagger 1984 ; Sukenik 1994a ).
Why is it important to do this review?
No cure for RA is known at present, so treatment often focuses on management of symptoms such as pain, stiffness and mobility. Treatment options include pharmacological interventions ( Colebatch 2011 ; Hurkmans 2009 ; Marks 2011 ; Richards 2012a ; Richards 2012b ; Ruiz Garcia 2011 ; Singh 2009 ; Singh 2010a ; Singh 2010b ; Whittle 2011 ), physical therapy ( Brosseau 2003 , Han 2004 ) and balneotherapy ( Verhagen 2008 ). Since our last publication of this Cochrane review ( Verhagen 2008 ), several systematic reviews and meta‐analyses on the effectiveness of balneotherapy have been published ( Falagas 2009 ; Forestier 2008 ; Kamioka 2010 ). These reviews either combine balneotherapy and hydrotherapy ( Forestier 2008 ; Kamioka 2010 ) or combine different diseases ( Falagas 2009 ).
Despite its popularity, reported scientific evidence on the effectiveness or efficacy of balneotherapy is sparse. This review evaluates the benefits and harms of balneotherapy in patients with RA.
Objectives
To perform a systematic review on the benefits and harms of balneotherapy in patients with rheumatoid arthritis in terms of pain, improvement, disability, tender joints, swollen joints and adverse events.
Methods
Criteria for considering studies for this review
Types of studies
Studies were eligible if they were randomised controlled trials (RCTs).
Types of participants
Participants had rheumatoid arthritis (RA), with definitive or classical RA as defined by the American Rheumatism Association (ARA) criteria of 1958 ( Ropes 1958 ), the ARA/American College of Rheumatology (ACR) criteria of 1988 ( Arnett 1988 ) or the ACR/EUropean League Against Rheumatism (EULAR) criteria of 2010 ( Aletaha 2010 ), or by studies using the criteria of Steinbrocker ( Steinbrocker 1949 ).
Types of interventions
Balneotherapy had to be the intervention under study, and had to be compared with another intervention or with no intervention. Balneotherapy is defined as bathing in natural mineral or thermal waters (e.g. mineral baths, sulphur baths, Dead Sea baths), using mudpacks or doing both.
Types of outcome measures
Major outcomes
The World Health Organization (WHO) and the International League Against Rheumatism (ILAR) determined in 1992 a core set of eight endpoints for clinical trials concerning patients with RA ( Boers 1994 ). Major outcomes that we will consider are pain, improvement, disability, tender joints, swollen joints, withdrawals due to adverse events and serious adverse events.
Minor outcomes
Other outcomes that we considered include patient global assessment, physician global assessment, stiffness, range of motion, activities of daily living, quality of life, morning stiffness, walk time, hand grip strength and Ritchie index.
We considered all major outcomes and presented results in the 'Summary of findings' tables.
Search methods for identification of studies
Electronic searches
We searched the Cochrane 'Rehabilitation and Related Therapies' Field Register (to December 2014), the Cochrane Central Register of Controlled Trials (2013, Issue 1), MEDLIINE (1950 to December 2014), EMBASE (1988 to December 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to December 2014), the Allied and Complementary Medicine Database (AMED) (1985 to December 2014), PsycINFO (1806 to December 2014) and the Physiotherapy Evidence Database ( PEDro ) (to December 2014). We applied no language restrictions, but studies not reported in English, Dutch, Danish, Swedish, Norwegian, German or French are awaiting assessment.
We also searched the WHO International Clinical Trials Registry Platform for ongoing and recently completed trials.
In MEDLINE, the subject‐specific strategy was combined with the sensitivity‐ and precision‐maximising version of the Cochrane Highly Sensitive Search Strategy ( Higgins 2011a ) used to identify randomised trials in MEDLINE and modified for use in other databases.
Search strategies performed in MEDLINE, CENTRAL, EMBASE and CINAHL are presented in Appendix 1 .
Searching other resources
We also searched the reference lists of articles and contacted experts in the field.
Data collection and analysis
Selection of studies
Initially, two review authors (SMAB‐Z, JL) independently selected trials by inspecting titles, keywords and abstracts to determine whether studies met the inclusion criteria regarding design, participants and interventions. We retrieved for final assessment full publications of studies of any possible relevance. Next, we used a standardised form to independently perform the final selection of trials to be included in the review. We resolved disagreements by consensus and, if necessary, by third party adjudication (APV).
Data extraction and management
Two review authors (JRC, JL) independently extracted data on trial methods, participants, interventions, types of outcome measures, duration of follow‐up, loss to follow‐up and results using a standardised data extraction form. We resolved disagreements by consensus and, if necessary, by third party adjudication (APV). We contacted trial authors when further information was required to complete the data extraction form.
Assessment of risk of bias in included studies
Two review authors (RAdB, HCWdV) independently assessed risk of bias by using the assessment tool developed by The Cochrane Collaboration ( Higgins 2011a ). This tool involves assessment of randomisation (sequence generation and allocation concealment), blinding (of participants, care providers and outcome assessors), completeness of outcome data, selection of outcomes reported and other sources of bias (baseline comparability, co‐interventions, compliance, timing of outcome measures). All items could be scored as having high, low or unclear risk of bias. We resolved disagreements by consensus; if disagreement persisted, a third review author (APV) made a final decision. We contacted trial authors if further information was required.
Measures of treatment effect
We presented various outcome measures separately. For dichotomous data, we expressed results, if possible, as risk ratios (RRs) with corresponding 95% confidence intervals (CIs). We calculated mean differences (MDs) or, when scales for outcome measures were dissimilar, standardised mean differences (SMDs) with 95% confidence intervals for continuous data ( Lau 1997 ).
Unit of analysis issues
Treatment allocation was done at an individual level in all trials, and no cluster‐randomised or cross‐over trials were found, so the unit of analysis was the individual participant.
Dealing with missing data
When possible, we contacted trial authors to request missing data, and we performed intention‐to‐treat analyses to include all randomly assigned participants. For dichotomous data, we performed a worst‐case scenario when all missing people in the intervention group had a bad outcome, although none of the missing people in the control group had such an outcome. However for continuous data, when dropouts were identified, we used the actual number of participants contributing data at the relevant outcome assessment. Unless missing standard deviations could be derived from confidence intervals or standard errors (from the same study), we did not assume values for the purpose of presenting them in the analyses.
Assessment of heterogeneity
We assessed heterogeneity between pooled trials by using a combination of visual inspection of graphs and consideration of the I 2 statistic ( Higgins 2003 ). Substantial heterogeneity is defined as I 2 greater than 50%.
Assessment of reporting biases
Available data are insufficient for assessment of publication bias via a prepared funnel plot, so publication bias cannot be assessed.
Data synthesis
We used RevMan Analyses (RevMan5) to analyse the data. In the previous review ( Verhagen 2008 ), review authors did not pool data because the included trials were considered clinically heterogeneous in terms of study populations and interventions. Should pooling be possible with new trials included, we will pool results of comparable groups of trials by using a random‐effects model and 95% confidence intervals.
Subgroup analysis and investigation of heterogeneity
Preplanned stratified analyses included:
-
trials comparing balneotherapy versus no treatment or waiting list controls;
-
trials comparing different types of balneotherapy; and
-
trials comparing balneotherapy versus other treatment(s) (e.g. exercise, oral medication).
Sensitivity analysis
A preplanned sensitivity analysis involved the risk of bias items of concealed randomisation and blinding.
'Summary of findings' table
The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of evidence ( Higgins 2011b ). The quality of the evidence was based upon five domains and was downgraded by one level for each of these factors when encountered: (1) limitations in design, (2) indirectness of evidence (i.e. generalisability of findings), (3) unexplained heterogeneity or inconsistency of results (significant statistical heterogeneity (I 2 > 50%) or inconsistent findings among studies, (4) imprecision (total number of participants < 300 for each outcome) and (5) high probability of publication bias. Two review authors (SMSB‐Z,APV) determined these factors. We considered single randomised studies (n < 300 for dichotomous outcomes and n < 400 for continuous outcomes) to be inconsistent and imprecise and to provide “low‐quality evidence”, which could be further downgraded to "very low‐quality evidence" for limitations in design (i.e. high risk of bias), indirectness or other considerations. We applied the following levels of quality of evidence.
-
High quality: Further research is very unlikely to change the level of evidence. Data are sufficient and have narrow confidence intervals. No reporting biases are known or suspected; all domains were fulfilled.
-
Moderate quality: Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate; one of the domains was not fulfilled.
-
Low quality: Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate; two of the domains were not fulfilled.
-
Very low quality: Great uncertainty surrounds the estimate; three of the domains were not fulfilled.
Results
Description of studies
Results of the search
A search conducted for this update resulted in 210 references, from which two review authors (JL, APV) independently selected 16 additional references on the basis of title and abstract. Of these, two studies were found to be eligible on the basis of full paper assessment and were included in this review ( Codish 2005 ; Franke 2007 ); see study flow chart in Figure 1 .
Study flow diagram.
Included studies
Final selection based on consensus resulted in inclusion of nine studies in this review, of which five were of Israeli origin, although they were written in English ( Codish 2005 ; Elkayam 1991 ; Sukenik 1990a ; Sukenik 1990b ; Sukenik 1995 ).
Participants
A total of 579 participants were enrolled, and the number of participants in the intervention groups ranged from eight to 67 (see Characteristics of included studies ). In six of the nine studies, the smallest study arm included fewer than 30 participants, meaning that most studies were underpowered. In seven studies, researchers used ARA criteria when selecting participants, and in two studies, they used the Steinbrocker criteria ( Hall 1996 ; Yurtkuran 1999 ). All studies included participants with RA as defined by ARA or Steinbrocker criteria, although the severity of RA differed slightly between studies. When mentioned, the percentage of males was between 5% and 40%, and mean age ranged from 39 to 62.4 years.
Interventions
Six studies had two treatment arms, and the other three studies had four treatment arms. Only once was a placebo control used in comparison with mudpacks ( Codish 2005 ). In two studies, a no‐treatment control group was used ( Sukenik 1990b ; Sukenik 1995 ). In both studies, participants were aware of the fact that they did not receive baths as treatment. In one other study, the drug treatment group was the control group ( Yurtkuran 1999 ). In all but one study ( Hall 1996 ), the intervention included mineral baths, and in one study, the intervention was given in combination with mudpacks ( Elkayam 1991 ). Two studies evaluated Dead Sea baths ( Sukenik 1990a ; Sukenik 1995 ), and two studies evaluated the added value of radon over carbon dioxide in the bath ( Franke 2000 ; Franke 2007 ).
In all studies, the baths were prepared at between 35°C and 38°C. All participants continued their medication during balneotherapy. One study mentioned standardised exercise therapy ( Hall 1996 ), and in another study, relaxation exercises were allowed ( Yurtkuran 1999 ).
All studies but one were performed at spa resorts; only Codish ( Codish 2005 ) provided mudpacks (and placebo mudpacks) to be used at home.
Outcome measures
All studies used several outcome measures including pain and function. Often a standard set of outcome measures was used, such as duration of morning stiffness, 15‐meter walk time, hand grip strength, Ritchie index, severity of disease as assessed by participant or physician and laboratory variables. In two studies ( Franke 2000 ; Hall 1996 ), investigators used a 'quality of life' instrument (Arthritis Impact Measurement Scales (AIMS) or AIMS2). Three studies ( Codish 2005 ; Franke 2000 ; Yurtkuran 1999 ) reported response to treatment or improvement, but investigators in different studies defined it differently (see Characteristics of included studies ).
The overall follow‐up period was three months; only two studies reported six‐month follow‐up ( Franke 2000 ; Franke 2007 ).
Excluded studies
From the total search, 21 studies are awaiting assessment because of their language of publication (19 first review, two first update); 21 studies were excluded because they appeared not to be RCTs (16 first review, two first update and three second update); 18 were excluded because they did not concern RA (12 first review, two first update and four second update) and eight because of the outcome measures selected (one first review, one first update and six second update).
Risk of bias in included studies
Four studies described their randomisation procedure; three of these studies were considered to use a concealed randomisation procedure ( Franke 2000 ; Franke 2007 ; Hall 1996 ) ( Figure 2 and Figure 3 ).
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Blinding of the observer/outcome assessor is mentioned in all studies, but in several studies, the participant reported the main outcome, and it was unclear whether the participant was blinded, which means that we scored blinding of the outcome assessor as unclear (unclear risk of bias) ( Hall 1996 ; Sukenik 1990b ; Sukenik 1995 ; Yurtkuran 1999 ). Four studies mentioned blinding of the caregiver ( Codish 2005 ; Franke 2000 ; Franke 2007 ; Sukenik 1990a ), but the success of blinding was never evaluated.
Two studies were scored as having low risk of bias on ‘other biases’ because study authors clearly mentioned that groups were comparable at baseline, co‐interventions were comparable and compliance was acceptable ( Franke 2000 ; Franke 2007 ).
Only three studies were considered to have no limitations in design, meaning a low risk of bias in most domains ( Franke 2000 ; Franke 2007 ; Sukenik 1990a ). In terms of the risk of bias assessment, the Kappa between two review authors appeared to be moderate at 0.68.
Effects of interventions
See: Summary of findings for the main comparison Balneotherapy compared with placebo for participants with rheumatoid arthritis ; Summary of findings 2 Additional radon in carbon dioxide baths compared with carbon dioxide baths only for participants with rheumatoid arthritis ; Summary of findings 3 Balneotherapy compared with drug treatment for participants with rheumatoid arthritis
Data presented in the papers, even after communication with the study authors, were too scarce to enable 'between‐group' analysis in almost half the studies. Also the studies used different interventions or comparison treatments and a wide variety of outcome measures; therefore interventions and outcome measures were considered heterogeneous.
One study assessed arms of balneotherapy ( Yurtkuran 1999 ); only one participant complained of headache. In this study, most side effects were found in the control group (Cyclosporin A); between 4% and 16% of participants experienced various side effects such as gastrointestinal disturbance (one participant; 4%) and nephrotoxicity (four participants; 16%) ( Yurtkuran 1999 ).
Trials comparing balneotherapy versus placebo or no treatment/waiting list controls
One study (n = 45) compared mudpacks versus placebo mudpacks for hand RA ( Codish 2005 ).
We found no statistically significant differences between groups in terms of pain intensity (MD 0.50, 95% CI ‐0.84 to 1.84; absolute difference 0.5%), improvement (or ‘response rate’) (RR 0.96, 95% CI 0.54 to 1.70; absolute difference ‐2%) and number of tender joints (MD ‐4.60, 95% CI ‐8.72 to ‐0.48; absolute difference ‐16%) ( Analysis 1.1 ; Analysis 1.2 ; Analysis 1.3 ; summary of findings Table for the main comparison ). Therefore we conclude that very low‐level evidence (single study, downgraded by design) showed unclear benefit of mudpacks over placebo in hand RA in terms of pain, response rate and number of tender joints. Physical disability was not reported. Also no data were presented on improvement, withdrawals due to adverse events or serious adverse events.
Two studies (n = 76) included a control group receiving no treatment ( Sukenik 1990b ; Sukenik 1995 ). Both studies suffer from high risk of bias and low power; short‐term improvement was mentioned in all treatment groups compared with control groups for most outcome measures (see Characteristics of included studies ). No data were provided on pain, improvement, physical disability, number of tender and swollen joints, withdrawals due to adverse events or serious adverse events. The study authors' conclusion of improvement was based on pre/post analysis. Data on harm or side effects were not reported.
Trials comparing different types of balneotherapy
Three studies compared mineral baths versus tapwater baths ( Elkayam 1991 ; Franke 2000 ; Franke 2007 ). We were able to pool the data from two studies (n = 194) evaluating the effectiveness of additional radon in carbon dioxide baths ( Franke 2000 ; Franke 2007 ).
We found no statistically significant differences post treatment and at three months in pain intensity on a VAS, but a statistically significant difference in pain in favour of additional radon at six‐month follow‐up only, with a difference of 9.6 mm on a 100‐mm VAS (95% CI 1.6 to 17.6). Both effect estimates show no clinically relevant differences (> 15%) ( Analysis 2.1 ; summary of findings Table 2 ).
We found no differences post treatment and at three months in terms of improvement in pain frequency on a 4‐point scale (no, sporadic, daily, continuous) or improvement in one or more categories, but a significant difference of only 30% in favour of additional radon at six‐month follow‐up (RR 2.3, 95% CI 1.1 to 4.7) ( Analysis 2.2 ; summary of findings Table 2 ).
For all other outcomes (physical disability, tender joints, swollen joints, withdrawals due to adverse events and serious adverse events), no data were provided.
Therefore we conclude that moderate‐level evidence (downgraded because of imprecision (low power)) shows unclear benefit in terms of pain at end of treatment and at three‐month follow‐up, but benefit of additional radon in carbon dioxide baths for the treatment of participants with RA at six months, although the clinical relevance of this benefit is small. We found low‐level evidence (single study) of unclear benefit for improvement at end of treatment and at three‐month follow‐up, but benefit of additional radon in carbon dioxide baths in the treatment of patients with RA at six months.
Two studies (n = 76) compared Dead Sea salt baths versus normal salt baths ( Sukenik 1990a ) or sulphur baths ( Sukenik 1995 ), and another study (n = 30) compared sulphur baths versus mudpacks ( Sukenik 1990b ). All three studies did not provide sufficient data on pain, improvement, physical disability, number of tender and swollen joints, withdrawal due to adverse events and serious adverse events for the analysis. The authors of original studies mentioned short‐term improvement in all treatment groups on most outcome measurements, but a more profound effect in the groups receiving mineral baths. All studies were of low power, performed a pre/post analysis and presented only point estimates.
Trials comparing balneotherapy versus other treatments (e.g. exercise, oral medication)
In one study (n = 35 in each study arm), 'balneotherapy' (seated immersion) was compared with hydrotherapy (exercise in water), land exercise or relaxation therapy ( Hall 1996 ). Here balneotherapy was performed with tapwater at 36°C ( Analysis 3.1 ).
We found no statistically significant differences in pain (MD 0.05, 95% CI ‐0.32 to 0.42) and physical disability (MD ‐0.70, 95% CI ‐1.50 to 0.10). No data were provided on improvement, tender joints, swollen joints, withdrawal due to adverse events or serious adverse events.
Therefore we conclude that a very low level of evidence (single study and downgraded because of limitations in design (high risk of bias)) shows unclear benefit of tapwater bathing over relaxation, exercise or hydrotherapy.
In another study (n = 57), balneotherapy was compared with drug therapy (Cyclosporin A (CsA) 3.5 mg/kg) ( Yurtkuran 1999 ). We found no statistically significant differences in terms of pain (0 to 100 VAS) (MD 8, 95% CI ‐17.54 to 1.54) or swollen joints (MD 1.50, 95% CI ‐1.25 to 4.25) ( Analysis 3.2 ; summary of findings Table 3 ). We found a statistically significant benefit of mineral baths in terms of overall improvement at eight weeks of 54% (RR 2.35, 95% CI 1.44 to 3.83) ( Analysis 3.3 ) and significant benefit of Cyclosporin A at eight weeks in terms of the number of tender joints (MD 8.9, 95% CI 3.8 to 14) ( Analysis 3.4 ; summary of findings Table 3 ). For all other outcome measures (physical disability, withdrawal due to adverse events and serious adverse events), no data were provided.
Very low‐level evidence (single study and downgraded because of limitations in design (high risk of bias)) suggests some benefit of mineral baths over Cyclosporin A concerning overall improvement, and of Cyclosporin A over mineral baths in terms of the number of swollen joints.
Discussion
Summary of main results
This review evaluated the benefits and harms of balneotherapy in patients with RA. Concerning pain, number of tender joints, ‘response rate’ or improvement, no statistically significant differences were found between mudpacks for the hand and placebo mudpacks (very low level of evidence) or for bathing with tapwater over relaxation, exercise or hydrotherapy (very low level of evidence). Harms were not reported for this comparison.
In terms of pain, some benefit has been associated with additional radon in carbon dioxide baths for the treatment of patients with RA, but the clinical relevance of this benefit is small (moderate level of evidence). Regarding all other outcome measures (improvement, disability, tender joints, swollen joints, withdrawal due to adverse events or serious adverse events), we conclude that the benefit of either form of balneotherapy over another is inconclusive.
For pain, a very low level of evidence of unclear benefit was found. For overall improvement, we found some benefit of balneotherapy over drug treatment (very low level of evidence). In this comparison, withdrawals due to adverse events were not reported.
Overall completeness and applicability of evidence
Rheumatoid arthritis (RA) is a chronic, progressive and disabling disease that has great impact on quality of life. When balneotherapy is evaluated, the outcome measures used and the follow‐up period chosen should be adequate. The main aims of balneotherapy are to maintain or improve functional mobility, soothe pain and let patients feel well. Often a standard set of outcome measures was used. In daily life, patients are trying to deal with pain by using coping strategies. Pain (often assessed by the patient) was reported as an outcome measure in the Methods sections of most studies, but results were seldom reported. A 'quality of life' assessment was reported in only two studies ( Franke 2000 ; Hall 1996 ). This is surprising because one of the aims of balneotherapy, or therapy for patients with chronic disease in general, is to improve health‐related 'quality of life'. The question can be raised whether the outcome measures used in most studies were specific and responsive enough to enable measurement of treatment effect. Also the follow‐up period seems to be rather short. Positive effects of spa therapy have been found in patients with ankylosing spondylitis even after 40 weeks of follow‐up ( van Tubergen 2001 ).
We noted heterogeneity of the intervention 'balneotherapy'. Once balneotherapy consisted of tapwater, once as mineral baths (38°C, daily for 20 minutes) + mudpacks (for 20 minutes), twice as radon/carbon dioxide baths (15 times in four weeks, for 20 minutes), twice as Dead Sea baths (daily for 20 to 30 minutes), twice as sulphur baths (daily for 20 minutes), once as a combination of Dead Sea and sulphur baths, once as a combination of sulphur baths + mudpacks (see table of included studies) and once as only mudpacks. This makes it difficult to determine what the most effective form of balneotherapy is, or even whether an essential element (minerals) in the water is responsible for its effectiveness.
Quality of the evidence
Unfortunately, most studies showed methodological flaws resulting in high risk of bias. Also data presentation was often lacking. When information concerning trial design, especially regarding strategies to avoid bias, is lacking, we could not exclude possible bias in the trial. Therefore, a robust analysis of the effectiveness of balneotherapy cannot be presented.
Potential biases in the review process
Our review might very well suffer from selection bias based on language. We found several studies that were presented in Hebrew, Japanese or one of the Eastern European languages. Often the English abstract was lacking information about the design of the study. These studies are all awaiting assessment.
We used the criteria of the Cochrane Back Review Group (CBRG) for risk of bias assessment ( Furlan 2009 ). This tool is a slightly extended version of the one described in the Cochrane Handbook for Systematic Reviews of Interventions , although with some sub‐items in the different domains, easing the risk of bias assessment. In previous versions of the review, we used the Delphi list, which is comparable with the risk of bias assessment tool of the CBRG ( Verhagen 1998 ). Therefore we observed no major differences concerning risk of bias assessment between the previous version and the current version of the review. Overall this risk of bias assessment tool can be regarded as a reliable and valid instrument ( Furlan 2009 ; Verhagen 2001 ). Nevertheless misclassification is always a possibility.
The 'spa environment' is an important factor in treatment results ( Balint 1993 ; Sukenik 1994a ). Many factors may contribute positively to reported effects ( Fam 1991 ), such as changes in environment, the 'spa scenery', absence of (house)work duties, physical and mental relaxation, the non‐competitive atmosphere with similarly suffering companions, physical therapy and so forth. As such, any benefit of the spa could perhaps be attributed also to the effects of factors unrelated to the "water" therapy per se.
Agreements and disagreements with other studies or reviews
The conclusion of this review that evidence is still insufficient to show the effectiveness of balneotherapy is consistent with the conclusion of other reviews ( Brosseau 2002 ; Kamioka 2010 ; Karagülle 2004 ). Although the selection criteria differ between reviews, all review authors conclude that poor methodological quality and scarce data presentation make it impossible to draw firm conclusions. The more recent studies are of better methodological rigour, but additional studies are needed.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 1 Pain intensity.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 2 Improvement.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 3 Tender joints.
Comparison 1 Balneotherapy versus placebo or no treatment, Outcome 4 Swollen joints.
Comparison 2 Additional radon in carbon dioxide versus carbon dioxide alone, Outcome 1 Pain intensity.
Comparison 2 Additional radon in carbon dioxide versus carbon dioxide alone, Outcome 2 Improvement.
Comparison 3 Balneotherapy versus other treatments, Outcome 1 Versus relaxation.
Comparison 3 Balneotherapy versus other treatments, Outcome 2 Versus drug treatment.
Comparison 3 Balneotherapy versus other treatments, Outcome 3 Versus drug treatment.
Comparison 3 Balneotherapy versus other treatments, Outcome 4 Versus drug treatment.
|
Balneotherapy compared with placebo for participants with rheumatoid arthritis |
||||||
|
Patient or population:
participants with rheumatoid arthritis
|
||||||
|
Outcomes |
Illustrative comparative risks* (95% CI) |
Relative effect
|
Number of participants
|
Quality of the evidence
|
Comments |
|
|
Assumed risk |
Corresponding risk |
|||||
|
Placebo |
Balneotherapy |
|||||
|
Pain intensity
|
Mean pain intensity in control groups was
|
Mean pain intensity in intervention groups was
|
45
|
⊕⊝⊝⊝
|
MD 0.50 (95% CI ‐0.84 to 1.84) Absolute difference 0.5% (95% CI ‐0.84% to 1.84%) Relative percent change 1% (95% CI ‐2% to 4%) No statistically significant or clinically relevant difference |
|
|
Improvement
measures (> 30% reduction in number of swollen joints, > 30% reduction in number of tender joints,
> 20% improvement in patient VAS for severity of pain and > 20% improvement in physician VAS)
|
522 per 1000 |
501 per 1000
|
RR 0.96
|
45
|
⊕⊝⊝⊝
|
Absolute difference ‐2% (95% CI ‐31% to 27%) Relative percent change 5% (95% CI ‐42% to 70%) No statistically significant or clinically relevant difference |
|
Physical disability Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Tender joints Number of painful joints Scale from 0 to 28 Follow‐up: 3 months |
Mean number of tender joints in control groups was
|
Mean number of tender joints in intervention groups was
|
45
|
⊕⊝⊝⊝
|
MD ‐4.60 (95% CI ‐8.72 to ‐0.48) Absolute difference ‐16% (95% CI ‐31% to 2%) Relative percent change ‐37% (95% CI ‐70% to ‐4%) NNTB 32 (95% CI 10 to 717) |
|
|
Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 3 months |
Mean number of swollen joints in control groups was
|
Mean number of tender joints in intervention groups was
|
45
|
⊕⊝⊝⊝
|
MD 0.60 (95% CI ‐0.90 to 2.10) Absolute difference 2% (95% CI ‐3% to 8%) Relative percent change 32% (95% CI ‐47% to 110%) No statistically significant or clinically relevant difference |
|
|
Withdrawal due to serious adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
*The basis for the
assumed risk
(e.g. median control group risk across studies) is provided in footnotes. The
corresponding risk
(and its 95% confidence interval) is based on the assumed risk in the comparison group and the
relative effect
of the intervention (and its 95% CI).
|
||||||
|
GRADE Working Group grades of evidence.
|
||||||
|
a
Downgraded because of imprecision.
|
||||||
|
Additional radon in carbon dioxide baths compared with carbon dioxide baths only for participants with rheumatoid arthritis |
||||||
|
Patient or population:
participants with rheumatoid arthritis
|
||||||
|
Outcomes |
Illustrative comparative risks* (95% CI) |
Relative effect
|
Number of participants
|
Quality of the evidence
|
Comments |
|
|
Assumed risk |
Corresponding risk |
|||||
|
Carbon dioxide baths only |
Additional radon in carbon dioxide baths |
|||||
|
Pain intensity
|
Mean change in pain intensity in control groups was
|
Mean change in pain intensity in intervention groups was
|
194
|
⊕⊕⊕⊝
|
MD ‐4.49 (95% CI ‐13.41 to 4.44) Absolute difference 4.5% (95% CI ‐13.4 to 4.4) No statistically significant or clinically relevant difference |
|
|
Pain intensity
|
Mean change in pain intensity in control groups was
|
Mean change in pain intensity in intervention groups was
|
194
|
⊕⊕⊕⊝
|
MD ‐9.59 (95% CI ‐17.57 to ‐1.6) Absolute difference 9.5% (95% CI ‐17.5 to ‐1.6) Statistically significant but not clinically relevant difference |
|
|
Improvement
|
267 per 1000 |
367 per 1000
|
RR 1.38 (0.64 to 2.93) |
60
|
⊕⊕⊝⊝
|
Absolute difference 10% (95% CI ‐13% to 33%) Relative percent change 38% (95% CI ‐36% to 22%) No statistically significant or clinically relevant difference |
|
Improvement
|
233 per 1000 |
533 per 1000 |
RR 2.29 (1.1 to 4.74) |
60 (1 study) |
⊕⊕⊝⊝
|
Absolute difference 30% (95% CI 10% to 60%) Relative percent change 129% (95% CI 10% to 474%) Statistically significant and clinical relevant difference |
|
Physical disability Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Tender joints Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Swollen joints Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Withdrawal due to serious adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
*The basis for the
assumed risk
(e.g. median control group risk across studies) is provided in footnotes. The
corresponding risk
(and its 95% confidence interval) is based on the assumed risk in the comparison group and the
relative effect
of the intervention (and its 95% CI).
|
||||||
|
GRADE Working Group grades of evidence.
|
||||||
|
a
Downgraded because of imprecision.
|
||||||
|
Balneotherapy compared with drug treatment for participants with rheumatoid arthritis |
||||||
|
Patient or population:
participants with rheumatoid arthritis
|
||||||
|
Outcomes |
Illustrative comparative risks* (95% CI) |
Relative effect
|
Number of participants
|
Quality of the evidence
|
Comments |
|
|
Assumed risk |
Corresponding risk |
|||||
|
Drug treatment ‐ Cyclosporin A |
Balneotherapy |
|||||
|
Pain intensity
|
Mean pain intensity in control groups was
|
Mean pain intensity in intervention groups was
|
57
|
⊕⊝⊝⊝
|
MD 9.64 (95% CI ‐1.66 to 20.94) Absolute difference 10% (95% CI ‐2% to 21%) Relative percent change 53% (95% CI ‐9% to 116%) No statistically significant or clinically relevant difference |
|
|
Improvement
|
400 per 1000 |
940 per 1000
|
RR 2.35 (1.44 to 3.83) |
57
|
⊕⊝⊝⊝
|
Absolute difference 54% (95% CI 33% to 75%) Relative percent change 135% (95% CI 44% to 283%) NNTB 2 (95% CI 2 to 3) |
|
Physical disability Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Tender joints Number of tender joints Scale from 0 to 28 Follow‐up: 8 weeks |
Mean number of tender joints in control groups was
|
Mean number of tender joints in intervention groups was
|
57 (1 study) |
⊕⊝⊝⊝
|
MD 8.90 (95% CI 3.83 to 13.97) Absolute difference 31% (95% CI 17% to 50%) Relative percent change 228% (95% CI 98% to 358%) NNTB 22 (95% CI 8 to 96) |
|
|
Swollen joints Number of swollen joints Scale from 0 to 28 Follow‐up: 8 weeks |
Mean number of swollen joints in control groups was
|
Mean number of tender joints in intervention groups was
|
57 (1 study) |
⊕⊝⊝⊝
|
MD 1.50 (95% CI ‐1.25 to 4.25) Absolute difference 5% (95% CI ‐4% to 15%) Relative percent change 79% (95% CI ‐66% to 224%) No statistically significant or clinical relevant difference |
|
|
Withdrawal due to serious adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
Adverse events Not reported |
See comment |
See comment |
Not estimable |
‐ |
See comment |
Not reported |
|
*The basis for the
assumed risk
(e.g. median control group risk across studies) is provided in footnotes. The
corresponding risk
(and its 95% confidence interval) is based on the assumed risk in the comparison group and the
relative effect
of the intervention (and its 95% CI).
|
||||||
|
GRADE Working Group grades of evidence.
|
||||||
|
a
Downgraded because of single study.
|
||||||
|
Outcome or subgroup title |
No. of studies |
No. of participants |
Statistical method |
Effect size |
|
1 Pain intensity Show forest plot |
1 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
1.1 End of treatment |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
0.20 [‐1.18, 1.58] |
|
1.2 1‐Month follow‐up |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
‐0.40 [‐1.74, 0.94] |
|
1.3 3‐Month follow‐up |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
0.5 [‐0.84, 1.84] |
|
2 Improvement Show forest plot |
1 |
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
|
|
2.1 End of treatment |
1 |
45 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.57, 1.63] |
|
2.2 1‐Month follow‐up |
1 |
45 |
Risk Ratio (M‐H, Random, 95% CI) |
1.05 [0.66, 1.65] |
|
2.3 3‐Month follow‐up |
1 |
45 |
Risk Ratio (M‐H, Random, 95% CI) |
0.96 [0.54, 1.70] |
|
3 Tender joints Show forest plot |
1 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
3.1 End of treatment |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
‐6.0 [‐9.57, ‐2.43] |
|
3.2 1‐Month follow‐up |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
‐5.1 [‐8.58, ‐1.62] |
|
3.3 3‐Month follow‐up |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
‐4.60 [‐8.72, ‐0.48] |
|
4 Swollen joints Show forest plot |
1 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
4.1 End of treatment |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
0.10 [‐1.58, 1.78] |
|
4.2 1‐Month follow‐up |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
0.10 [‐1.45, 1.65] |
|
4.3 3‐Month follow‐up |
1 |
45 |
Mean Difference (IV, Random, 95% CI) |
0.60 [‐0.90, 2.10] |
|
Outcome or subgroup title |
No. of studies |
No. of participants |
Statistical method |
Effect size |
|
1 Pain intensity Show forest plot |
2 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
1.1 Additional radon, post treatment |
2 |
194 |
Mean Difference (IV, Random, 95% CI) |
1.68 [‐4.64, 7.99] |
|
1.2 Additional radon, 3 months |
2 |
194 |
Mean Difference (IV, Random, 95% CI) |
‐4.49 [‐13.41, 4.44] |
|
1.3 Additional radon, 6 months |
2 |
194 |
Mean Difference (IV, Random, 95% CI) |
‐9.59 [‐17.57, ‐1.60] |
|
2 Improvement Show forest plot |
1 |
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
|
|
2.1 Additional radon, post treatment |
1 |
60 |
Risk Ratio (M‐H, Random, 95% CI) |
1.27 [0.69, 2.33] |
|
2.2 Additional radon, 3 months |
1 |
60 |
Risk Ratio (M‐H, Random, 95% CI) |
1.38 [0.64, 2.93] |
|
2.3 Additional radon, 6 months |
1 |
60 |
Risk Ratio (M‐H, Random, 95% CI) |
2.29 [1.10, 4.74] |
|
Outcome or subgroup title |
No. of studies |
No. of participants |
Statistical method |
Effect size |
|
1 Versus relaxation Show forest plot |
1 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
1.1 Pain post treatment |
1 |
70 |
Mean Difference (IV, Random, 95% CI) |
0.30 [‐0.01, 0.61] |
|
1.2 Pain at follow‐up |
1 |
70 |
Mean Difference (IV, Random, 95% CI) |
0.05 [‐0.32, 0.42] |
|
1.3 Physical activity post treatment |
1 |
70 |
Mean Difference (IV, Random, 95% CI) |
‐0.5 [‐1.34, 0.34] |
|
1.4 Physical activity at follow‐up |
1 |
70 |
Mean Difference (IV, Random, 95% CI) |
‐0.70 [‐1.50, 0.10] |
|
2 Versus drug treatment Show forest plot |
1 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
2.1 Pain at 4 weeks |
1 |
57 |
Mean Difference (IV, Random, 95% CI) |
‐8.0 [‐17.54, 1.54] |
|
2.2 Pain intensity at 8 weeks |
1 |
57 |
Mean Difference (IV, Random, 95% CI) |
9.64 [‐1.66, 20.94] |
|
3 Versus drug treatment Show forest plot |
1 |
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
|
|
3.1 Improvement at 8 weeks |
1 |
58 |
Risk Ratio (M‐H, Random, 95% CI) |
2.35 [1.44, 3.83] |
|
4 Versus drug treatment Show forest plot |
1 |
Mean Difference (IV, Random, 95% CI) |
Subtotals only |
|
|
4.1 Tender joints at 8 weeks |
1 |
57 |
Mean Difference (IV, Random, 95% CI) |
8.9 [3.83, 13.97] |
|
4.2 Swollen joints at 8 weeks |
1 |
57 |
Mean Difference (IV, Random, 95% CI) |
1.5 [‐1.25, 4.25] |