1. TREATMENT AND REHABILITATION OF RHEUMATIC DISEASES IN BALKAN SPAS; THE EVIDENCE Müfit Zeki Karagülle TURKSPA

2. A vivid custom; still popular and “widely” used have been considered mainstream at least in part, reimbursed by health insurance systems Balkan Spas for health

3. frequently indicated for the patients with chronic disorders, in particular of the musculoskeletal system – one of the oldest forms of therapy for patients with arthritis – to soothe the pain, – improve joint motion – and as a consequence to relieve people' suffering – and make them feel well Therapy and Rehabilitation of Rheumatism in Balkan Spas

5. Comprehensive medical practice for a diversity of health conditions including rheumatic and musculoskeletal diseases; – Prevention – Treatment – Rehabilitation Based on balneo- hydro- peloido- and climatotherapy and “healing environment” Institutions/facilities thermal cure centers thermal hotels special spa clinics, hospitals, sanatoriums Medicine at Balkan Spas/Health Resorts

6. Core and combined spa treatments the use of water – Balneotherapy thermal / mineral waters – Hydrotherapy Plain water the use of medicinal muds (peliods) – Mud therapy the use of climate and environment – Climatoherapy – Thalassotherapy – Forest therapy the use of other factors the use of other therapeutics – Exercise therapy – Massage therapy – Diet (nutrition) therapy) – Health education – Authentic therapies Hamam Sauna Herbs Nutrition

7. Evidence Based Medicine

8. Research Design for Evidence *Research that is descriptive, anecdotal or authoritative; ** Research without intervention, with results that may be used in future studies; *** Research not involving a control group or randomization but with an evaluation; **** Research involving a systematic study with control groups but without randomisation; ***** Research involving a systematic study with a randomized control group.

9. Meta- analyzes

10. Categories of evidence Ann Rheum Dis 2003;62;1145-1155 adapted from the classification of the United States Agency for Health Care Policy and Research. Category Evidence from: 1A Meta-analysis of RCTs 1B At least one Randomised Control Trial - RCT 2A At least one controlled study without randomisation 2B At least one quasi-experimental study 3 Descriptive studies, such as comparative, correlation or case-control studies 4 Expert committee reports or opinions and/or clinical experience of respected authors

11. In the year 2004 there was 1B and 2A level of evidence for efficacy and effectiveness of spa therapy on the main rheumatic diseases Osteoarthritis - 2A Rheumatoid arthritis - 1B Fibromyalgia - 1B Ankylosing spondylitis - 1B Low back pain - 1B

12. Now, a decade later since our article for Turkey was published, we aimed to review and evaluate the current evidence on the treatment and rehabilitation of rheumatic musculoskeletal diseases (RMSD) in Balkan spas A comprehensive search of databases to identify the meta- analysiz and randomized controlled trials on the effectiveness of balneotherapy and spa therapy in Balkans for patients with RMSD were published in peer reviewed journals in English during last decade.

13. Fibromyalgia syndrome Meta-Analysis, 1A

14. Pamukkale (Ardıç et al) Afyon (Evcik et al) Bursa (Yurtkuran et al) Balçova (Dönmez et al) Tuzla-Istanbul (Özkurt et al)

15. Systematic reviews and RCTs; Rheumatoid Arthritis

16. Systematic reviews Rheumatoid Arthritis

17. Systematic reviews and RCTs; Rheumatoid Arthritis

19. RCTs; Rheumatoid Arthritis Terme Ilidza, Sarajevo, Bosnia and Herzegovina University Clinical Center and a nearby spa (rehabilitation hospital) BANJSKO-REHABILITACIJSKI CENTER BANJA TERME ILIDŽA

20. RCTs; Rheumatoid Arthritis Bursa, Turkey

21. Osteoarthritis, Controlled studies Serbia and Turkey Obadasi E, Karagülle MZ, Karagülle Z, Turan M, Karagülle O. Comparison of two spa therapy regimens in patients with knee OA, an exploratory study. Phys Med Rehab Kuror 2002; 12: 337-41. Bostan B, Sen U, Günes T et al. Comparison of intra-articular hyaluronic acid injections and mud-pack therapy in the treatment of knee osteoarthritis. Acta Orthop Traumatol Turc 2010;44:427. Odabası E, Turan M, Erdem H, Pay S, Gülec¸ M, Karagülle MZ. The effect of Mud pack treatment in knee osteoarthritis. Turk J Rheumatol 2009;24:72–76. Cutovic M, Jovic S, Konstantinovic L, Lazovic M, Jovanovic T, Vesovic V. The effects of balneotherapy on knee osteoarthritis. Med Pregl 2006;59 Suppl 1: 47-50. Jokic A, Sremcevic N, Karagülle Z, Pekmezovic T, Davidovic V. Oxidative stress, hemoglobin content, superoxide dismutase and catalase activity influenced by sulphur baths and mud packs in patients with osteoarthritis. Vojnosanit Pregl 2010;67:5738.

22. Osteoarthritis, RCTs Karagülle M, Karagülle MZ, Karagülle O, Dönmez A, Turan M. A 10-day course of SPA therapy is beneficial for people with severe knee OA. A 24-week randomized, controlled pilot study. Clin Rheumatol 2007; 12: 2063-71. Evcik D, Kavuncu V, Yeter A, Yigit Ilktur. The efficacity of balneotherapy and mud pack therapy in patients with knee OA. Joint Bone Spine 2007; 74(1):60-5. Yurkturan M, Yurkturan M, Alp A, Nasicilar A, Bingol U, Altan L, Sarpdere G. Balneotherapy and tap water in the treatment of knee OA. Rheumatol int 2006; 27: 19-27. Alaçatı, Çeşme, Izmir

23. Ankylosing Spondylitis Case control studies ; Turkey

24. Ankylosing Spondylitis RCTs; Turkey

25. Ankylosing Spondylitis; RCT, Turkey and Mentenegro

26. Low Back Pain, Meta-Analysis Pittler MH, Karagülle MZ, Karagülle M, Ernst E. Spa therapy and balneotherapy for treating low back pain: meta-analysis of randomized trials. Rheumatology (Oxford). 2006;45:880-4. © The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org significant intergroup differences in favor of balneotherapy compared with control groups (weighted mean difference 18.8 mm, 95% CI 10.3–27.3, n = 138) Yurtkuran M, Kahraman Z, Sivrioğlu K, Afşin Y, Doğan M, Balneotherapy in Low Back Pain. Eur J Phys Med Rehabil 1997; 7: 120-123

27. Low Back Pain, New RCTs, Turkey Demirel R, Ucok K, Kavuncu V, Gecici O, Evcik D, Dundar U, Solak O, Mollaoglu H. Effects of balneotherapy with exercise in patients with low back pain. J Back Musculoskelet Rehabil. 2008;21: 263-72 Dogan M, Sahin O, Elden H, Hayta E, Kaptanoglu E. Additional therapeutic effect of balneotherapy in low back pain. South Med J. 2011;104:574-8. Kesiktaş N, Karakaş S, Gün K, Gün N, Murat S, Uludağ M. Balneotherapy for chronic low back pain: a randomized, controlled study. Rheumatol Int. 2012;32:3193-9. Onat SS, Taşoğlu O, Güneri FD, Özişler Z, Safer VB, Özgirgin N. The effectiveness of balneotherapy in chronic low back pain. Clin Rheumatol. 2014 Oct;33(10):1509-15. doi: 10.1007/s10067-014-2545-y. Epub 2014 Mar 6.

28. Mud in Balkans

29. Mud therapy; Meta-Analysis

30. Forest plot of the mean differences in visual analogue pain scores with 95% confidence intervals (CI) in the mud therapy group versus control group, and the overall total, in six studies included in a meta-analysis conducted to examine the effect of mud therapy on pain relief in patients with knee osteoarthritis. Liu H et al. Journal of International Medical Research 2013;41:1418-1425 Copyright © by a Creative Commons Attribution License, unless otherwise noted.

31. Forest plot of the mean differences in the Western Ontario and McMaster Universities Osteoarthritis Index pain scores with 95% confidence intervals (CI) in the mud therapy group versus control group, and the overall total, in four studies included in a meta-analysis conducted to examine the effect of mud therapy on pain relief in patients with knee osteoarthritis. Liu H et al. Journal of International Medical Research 2013;41:1418-1425 Copyright © by a Creative Commons Attribution License, unless otherwise noted.

32. Message for the audiance The available high level evidence suggests that balneotherapy and spa therapy in Balkan Spas is effective in the treatment and rehabilitation of major rheumatic musculoskeletal diseases; Osteoarthritis Fibromyalgia Ankylosing Spondylitis Rheumatoid arthritis Chronic low back pain

33. There is encouraging and compelling evidence -level 1A and 1B - for spa and balneotherapy in Balkan spas for treatment and rehabilitation of rheumatic musculoskeletal diseases

34. Future; Balkan Trials ! More high-quality, randomized, controlled trials need to be conducted in Balkans to confirm this conclusion.