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Rapid Responses: Rapid Responses published:
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Topical treatments for osteoarthritis include nettle sting
- Adrian R White, Colin Randall, Charlotte Paterson, Geoffrey Harding, Richard Haigh (21 January 2008)
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choice of treatmment in OA of the knee
- colin bradshaw (23 January 2008)
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Patients in research like choice
- Hasnain M Dalal, Jennifer Wingham,Royal Cornwall Hospital,Truro;Philip Evans, Rod Taylor & John Campbell, Peninsula College of Medicine and Denistry, Exeter (23 January 2008)
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Patients prefer rubs rather than pills
- Martin Duerden (26 January 2008)
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Topical NSAIDs have unknown effectiveness
- Peter C Gøtzsche (2 February 2008)
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Adrian R White, Clinical Research Fellow N32 ITTC, Tamar Science Park, Plymouth PL6 8BX, Colin Randall, Charlotte Paterson, Geoffrey Harding, Richard Haigh
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Underwood and colleagues have demonstrated that oral and topical NSAIDs had an equivalent effect for knee pain and that patients demonstrated a strong preference for topical treatment, especially when the pain is localized and transient or when they had concerns about combining medication or previous intolerance of oral treatment.1;2 The accompanying editorial encourages further research into the wide variety of topical treatments that are available to patients,3 a research priority that has already been recommended by the European League against Rheumatism.4 One such treatment which is currently being evaluated is the use of the common and readily available stinging nettle, Urtica dioica, applied to relieve musculo-skeletal pain in the upper and lower limbs. One week of a daily application of the nettle sting to the painful joint, either by brushing a stem of leaves over it or by pressing a leaf on the area, is one folk remedy which we have shown to be acceptable to patients and general practitioners, more effective than a placebo in the treatment of base-of-thumb pain,5 and sometimes able to provide sustained pain relief.6 A recent mixed-method randomized pilot study in people with OA of knee confirmed that the treatment was acceptable and feasible and that a full-scale trial is indicated.7 We are particularly interested in the self -help aspect of this intervention, and are currently working with users of nettle sting to develop ‘Guidelines for Use’. These may be used within a clinical trial and by others interested in this topical treatment. They are available from the authors. 1. Underwood M, Ashby D, Cross P, Hennessy E, Letley L, Martin J et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. BMJ 2007;336:138-42. 2. Carnes D, Anwer Y, Underwood M, Harding G, Parsons S, on behalf of the TOIB study team. Influences on older people's decision making regarding choice of topical or oral NSAIDs for knee pain: qualitative study. BMJ 2007;336:142-5. 3. Dieppe P. Osteoarthritis of the knee in primary care. Topical NSAIDS are as effective as oral NSAIDs, and patients prefer them. BMJ 2007; 336:105-6. 4. Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Annals of Rheumatic Diseases 2003;62:1145-55. 5. Randall C, Randall H, Dobbs F, Hutton C, Sanders H. Randomized controlled trial of nettle sting for treatment of base-of-thumb pain. Journal of the Royal Society of Medicine 2000;93:305-9. 6. Randall C, Meetham K, Randall H, Dobbs F. Nettle sting of Urtica dioica for joint pain - an exploratory study of this complementary therapy. Complement Ther Med 1999;7:126-31. 7. Randall C, Dickens A, White A, Sanders H, Fox M, Campbell J. Nettle sting for chronic knee pain: a randomised controlled pilot study. Complement Ther Med 2007;in press. doi. 10.1016/j.ctim.2007.01.012 Competing interests: None declared |
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colin bradshaw, GP Marsden Road Health Centre, South Shields NE34 6RE
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In Dieppe's editorial commentary of the paper by Underwood and colleagues, he states that "participants with more constant or severe pain and other painful sites .......opted for the topical gel. These choices seem reasonable" I don't know if there has been a printing error here but the comment as it stands doesn't seem reasonable to me. Patients with multiple painful sites would have to rub NSAIDs in various areas whilst a single pill would treat all there ills. Nor does statement accurately represent the comments of Underwood et al who say "those with more severe or widespread pain chose oral rather than topical treatment. If I'd skipped the research paper, as I frequently do when pressed for time, and merely read the editorial, I may have felt very differently about how to treat more widespread osteoarthritis. Dieppe P, Osteoarthritis of the knee in primary care, BMJ 2008:336: 105-6 Underwood M, Ashby D, Cross P et al. Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study. BMJ 2008: 336:138-42 Competing interests: None declared |
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Hasnain M Dalal, General Practitioner Truro TR1 2LZ, Jennifer Wingham,Royal Cornwall Hospital,Truro;Philip Evans, Rod Taylor & John Campbell, Peninsula College of Medicine and Denistry, Exeter
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Dieppe’s editorial highlights a new study of osteoarthritis of the knee that used a patient preference design and reported that more people chose to be in the preference study [1]. In a cardiac rehabilitation trial of post-MI patients that included patient preference arms we also found that the majority of participants (55%) did not wish to be randomised and wanted to choose their intervention [2;3]. A recent systematic review of patient preference trials concluded that although patient preference can affect the numbers of patients recruited to the randomised arms of the trial,the effect is small and does not affect the external validity of the study. Moreover, patient preferences do not affect clinical outcomes and thus do not compromise the internal validity of RCTs [4]. Given that recruitment to RCTs is difficult with less than 50% of eligible patients consenting to randomisation [5], sponsors of research and journal editors should be encouraging the conduct and publication of trials that include a patient preference design. Reference List (1) Dieppe P. Osteoarthritis of the knee in primary care. BMJ 2008; 336(7636):105-106. (2) Dalal HM, Evans PH, Campbell JL, Taylor RS, Watt A, Read KL et al. Home-based versus hospital-based rehabilitation after myocardial infarction: A randomized trial with preference arms--Cornwall Heart Attack Rehabilitation Management Study (CHARMS). Int J Cardiol 2007; 119(2):202- 211. (3) Wingham J, Dalal HM, Sweeney KG, Evans PH. Listening to patients: choice in cardiac rehabilitation. Eur J Cardiovasc Nurs 2006; 5(4):289-294. (4) Bower P, King M, Nazareth I, Lampe F, Sibbald B. Patient preferences in randomised controlled trials: conceptual framework and implications for research. Soc Sci Med 2005; 61(3):685-695. (5) Olschewski M, Schumacher M, Davis KB. Analysis of randomized and nonrandomized patients in clinical trials using the comprehensive cohort follow-up study design. Control Clin Trials 1992; 13(3):226-239. Competing interests: None declared |
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Martin Duerden, General Practitioner Meddygfa Gyffin, Conwy, North Wales, LL32 8LT
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Dieppe suggests we should use topical non-steroidal anti-inflammatory drugs (NSAIDs) rather than oral NSAIDs because patients prefer them.[1] As he mentions, the crucial information is to what extent they work better than placebo. Over the years there has been scepticism (he uses the term cynicism) over whether studies that show they work better than placebo are correct.[2][3][4] The problem is that most trials are of poor quality, most being short (many 4 weeks or less), and many unblinded. There is also the taint of publication bias: how many negative studies have never been published? If you put such poor and incomplete data into a meta-analysis, you get dodgy conclusions out. Alongside these methodological concerns it is difficult to envisage how topical NSAIDs work. Why should the NSAID permeate through skin and subcutaneous tissue and localise to the joint? If they work by systemic effects, why should the low concentration of the drug achieved through skin absorption be effective? Many people buy rubs and rubefacients for themselves and their pets. As patient preference is for rubbing rather than pills why do these rubs need to contain NSAID? I think there is an important education message here and I do not agree with Dieppe that we should prescribe topical NSAIDs because we are unable to prescribe topical placebo. For example, my strong preference for my painful knee is a hot water bottle. If I take care to avoid burns this is very cheap and has little potential for adverse effects. If I also favour the idea of adding ibuprofen to the hot water, this does not mean I should be encouraged to do it. [1] Dieppe P. Osteoarthritis of the knee in primary care. BMJ 2008;336:105-106. [2] Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ. Quantitative systematic review of topically applied non-steroidal anti- inflammatory drugs. BMJ 1998;316:333-8. [3] Duerden M, Barton S, Johnstone E, et al. Topical NSAIDs are better than placebo? BMJ 1998 317: 280. [4] Lin, J, Zhang, W, Jones, A, Doherty, M. Efficacy of topical non- steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta -analysis of randomised controlled trials. BMJ 2004; 329: 324-26. Competing interests: None declared |
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Peter C Gøtzsche, Director Nordic Cochrane Centre, Rigshospitalet, Dept. 3343, DK-2100 Copenhagen Ø, Denmark
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Paul Dieppe claimed in an editorial about osteoarthritis that topical NSAIDs are as effective as oral NSAIDs (1). But he seems to disagree with himself, as he also says that it is sad that we no longer can prescribe "placebos even if, like topical NSAIDs for osteoarthritis, they are safe and useful". There is no convincing evidence that these drugs work. Dippe refers to a NICE report, but that report has serious limitations. It describes two meta-analyses and notes that the authors assessed the trials for quality but the 424-page NICE report says nothing about that quality. This is curious, as the authors of one the meta-analyses reported that the trials were of poor quality and that the effect decreased significantly and substantially with increasing sample size of the trials (2). Dieppe also quotes a systematic review of topical NSAIDs in people with musculoskeletal pain. The authors reported that small trials exaggerated the effects. When some of the same authors updated this review in people with acute musculoskeletal pain, the effect again decreased significantly and substantially with increasing sample size of the trials (3). However, they paid no attention to this problem as their results build on all the trials, although I pointed out that this was a major compulsory revision they needed to do when I peer reviewed their manuscript (4). There was also enormous statistical heterogeneity in their trials, but again, the authors refused to pay any attention to this fundamental problem. Their reply to the peer review comments (4) are interesting as it demonstrates that their review is of very poor quality and that its authors did not take account of the most basic methodological evidence that exists for performing systematic reviews, even though this was pointed out to them. I have described these issues in my chapter on NSAIDs in Clinical Evidence (5). There are other problems with the trials, e.g. the effect on pain compared with placebo was significant at 2 weeks but not at 4 weeks (2), and the analysis at 2 weeks was statistically heterogeneous (P < 0.001). It is difficult to interpret such results, and I have concluded, in accordance with the evidence categories used by Clinical Evidence, that topical NSAIDs have unknown effectiveness (5). 1. Dieppe P.Osteoarthritis of the knee in primary care: Topical NSAIDs are as effective as oral NSAIDs, and patients prefer them. BMJ 2008;336:105-6. 2. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non- steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta -analysis of randomised controlled trials. BMJ 2004;329:324–326. 3. Mason L, Moore RA, Edwards JE, Derry S, McQuay HJ. Topical NSAIDs for acute pain: a meta-analysis. Topical NSAIDs for acute pain: a meta- analysis. BMC Fam Pract 2004;5:10. 4. Prepublication history for: Mason L, Moore RA, Edwards JE, et al. Topical NSAIDs for acute pain: a meta-analysis. BMC Fam Pract 2004;5:10. Available online at: http://www.biomedcentral.com/1471-2296/5/10/prepub (accessed 2 Feb 2008). 5. Gøtzsche PC. NSAIDs. http://clinicalevidence.bmj.com/ceweb/conditions/msd/1108/1108.jsp. Web publication date: 01 Jun 2007 (accessed 2 Feb 2008). Competing interests: None declared |
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