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Letter response
Response to: ‘Paying attention to arbitrary causality and the preciseness of conclusion’ by Lei et al We would like to thank Dr Zeng et al1 for the comments on our paper.2 Please see the point-to-point response as below: 1. As pointed out in the discussion of our paper, cross-sectional and case-control designs are not able to infer a causal relationship.2 The conclusion ‘low grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in osteoarthritis (OA)’ does not necessarily imply a cause-effect relationship. It remains controversial whether inflammation is a cause for disease progression or a result of disease manifestation. Traditionally, OA is perceived as noninflammatory disorder. Our meta-analysis aimed to determine whether low grade systemic inflammation is a common feature in OA and to examine its correlation to OA manifestations. 2. As an indicator of low grade inflammation, high sensitivity C-reactive protein (CRP) has a number of advantageous properties over other biomarkers. First, it has a relatively long half-life of 18 h, compared with other inflammatory markers (18.2 min for TNF-α3 and less than 6 h for interleukin 6 (IL-6)4). Second, the circulating levels of CRP are stable without exhibiting circadian variability and are quite easy to measure. In the context of a chronic condition like OA, it can reflect the severity of the disease. On the contrary, TNF-α and IL-6 are subjected to marked diurnal variation which has been well-documented in previous literature.5 6 Therefore, we believe that high sensitivity CRP is a more reliable indicator for low-grade systemic inflammation. 3. The study from Punzi et al7 reported medians and IQRs, and the data distribution appeared to be skewed, so data were not able to be converted to mean and hence were not included in the meta-analysis. In order to present readers with a complete picture, in the online supplementary table S4 of our paper, we summarised study results that were not included in the meta-analysis.2 4. Cochrane Handbook for Systematic Reviews of Interventions is an excellent reference for systematic review of randomised controlled trials. Cochrane Central is a great resource for randomised controlled trials but not for observational studies. However, our systematic review was set out to compare the CRP levels between patients with OA and the non-OA population; therefore, observational study design is the more appropriate study design to answer the question of interest. The search strategy we used was proven to be effectively
Ann Rheum Dis April 2014 Vol 73 No 4
sensitive as it even identified three clinical trials with an embedded case-control design. In addition, reference mining was performed carefully so that there should be very minimal chance for missing papers. Once again, we thank Dr Lei and his colleagues for their interests in our review and for their valuable comments. Xingzhong Jin,1 Julieta Ruiz Beguerie,2 Weiya Zhang,3 Christopher Leigh Blizzard,1 Petr Otahal,1 Graeme Jones,1 Changhai Ding1,4,5 1
Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia 2 Department of Dermatology, Austral University Hospital, Buenos Aires, Argentina 3 Academic Rheumatology, University of Nottingham, Nottingham, UK 4 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 5 Arthritis Research Institute, 1st Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China Correspondence to Dr Changhai Ding, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania 7000, Australia; [email protected] Competing interests None. Provenance and peer review Commissioned; internally peer reviewed. To cite Jin X, Beguerie JR, Zhang W, et al. Ann Rheum Dis 2014;73:e23. Accepted 7 January 2014 Published Online First 29 January 2014
▸ http://dx.doi.org/10.1136/annrheumdis-2014-205175 Ann Rheum Dis 2014;73:e23. doi:10.1136/annrheumdis-2014-205182
REFERENCES 1 2
3 4
5 6 7
Zeng C, Geo S-G, Lei G-H. Paying attention to arbitrary causality and the preciseness of conclusion. Ann Rheum Dis 2014;73:e22. Jin X, Bequerie JR, Zhang W, et al. Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis 2013. Published Online First. 20 Dec 2013. doi: 10.1136/annrheumdis-2013-204494 Oliver JC, Bland LA, Oettinger CW, et al. Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge. Lymphokine Cytokine Res 1993;12:115–20. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101:1767–72. Straub RH, Cutolo M. Circadian rhythms in rheumatoid arthritis: implications for pathophysiology and therapeutic management. Arthritis Rheum 2007;56:399–408. Meier-Ewert HK, Ridker PM, Rifai N, et al. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 2001;47:426–30. Punzi L, Ramonda R, Oliviero F, et al. Value of C reactive protein in the assessment of erosive osteoarthritis of the hand. Ann Rheum Dis 2005;64:955–7.
e23
Downloaded from ard.bmj.com on September 26, 2014 - Published by group.bmj.com
Response to: 'Paying attention to arbitrary causality and the preciseness of conclusion' by Lei et al Xingzhong Jin, Julieta Ruiz Beguerie, Weiya Zhang, et al. Ann Rheum Dis 2014 73: e23 originally published online January 29, 2014
doi: 10.1136/annrheumdis-2014-205182
Updated information and services can be found at: http://ard.bmj.com/content/73/4/e23.full.html
These include:
References
This article cites 5 articles, 3 of which can be accessed free at: http://ard.bmj.com/content/73/4/e23.full.html#ref-list-1
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Articles on similar topics can be found in the following collections Immunology (including allergy) (4340 articles) Inflammation (964 articles) Epidemiology (1189 articles) Degenerative joint disease (3977 articles) Musculoskeletal syndromes (4252 articles) Osteoarthritis (820 articles)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions
To order reprints go to: http://journals.bmj.com/cgi/reprintform
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Letter response
Response to: ‘Paying attention to arbitrary causality and the preciseness of conclusion’ by Lei et al We would like to thank Dr Zeng et al1 for the comments on our paper.2 Please see the point-to-point response as below: 1. As pointed out in the discussion of our paper, cross-sectional and case-control designs are not able to infer a causal relationship.2 The conclusion ‘low grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in osteoarthritis (OA)’ does not necessarily imply a cause-effect relationship. It remains controversial whether inflammation is a cause for disease progression or a result of disease manifestation. Traditionally, OA is perceived as noninflammatory disorder. Our meta-analysis aimed to determine whether low grade systemic inflammation is a common feature in OA and to examine its correlation to OA manifestations. 2. As an indicator of low grade inflammation, high sensitivity C-reactive protein (CRP) has a number of advantageous properties over other biomarkers. First, it has a relatively long half-life of 18 h, compared with other inflammatory markers (18.2 min for TNF-α3 and less than 6 h for interleukin 6 (IL-6)4). Second, the circulating levels of CRP are stable without exhibiting circadian variability and are quite easy to measure. In the context of a chronic condition like OA, it can reflect the severity of the disease. On the contrary, TNF-α and IL-6 are subjected to marked diurnal variation which has been well-documented in previous literature.5 6 Therefore, we believe that high sensitivity CRP is a more reliable indicator for low-grade systemic inflammation. 3. The study from Punzi et al7 reported medians and IQRs, and the data distribution appeared to be skewed, so data were not able to be converted to mean and hence were not included in the meta-analysis. In order to present readers with a complete picture, in the online supplementary table S4 of our paper, we summarised study results that were not included in the meta-analysis.2 4. Cochrane Handbook for Systematic Reviews of Interventions is an excellent reference for systematic review of randomised controlled trials. Cochrane Central is a great resource for randomised controlled trials but not for observational studies. However, our systematic review was set out to compare the CRP levels between patients with OA and the non-OA population; therefore, observational study design is the more appropriate study design to answer the question of interest. The search strategy we used was proven to be effectively
Ann Rheum Dis April 2014 Vol 73 No 4
sensitive as it even identified three clinical trials with an embedded case-control design. In addition, reference mining was performed carefully so that there should be very minimal chance for missing papers. Once again, we thank Dr Lei and his colleagues for their interests in our review and for their valuable comments. Xingzhong Jin,1 Julieta Ruiz Beguerie,2 Weiya Zhang,3 Christopher Leigh Blizzard,1 Petr Otahal,1 Graeme Jones,1 Changhai Ding1,4,5 1
Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia 2 Department of Dermatology, Austral University Hospital, Buenos Aires, Argentina 3 Academic Rheumatology, University of Nottingham, Nottingham, UK 4 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 5 Arthritis Research Institute, 1st Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China Correspondence to Dr Changhai Ding, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania 7000, Australia; [email protected] Competing interests None. Provenance and peer review Commissioned; internally peer reviewed. To cite Jin X, Beguerie JR, Zhang W, et al. Ann Rheum Dis 2014;73:e23. Accepted 7 January 2014 Published Online First 29 January 2014
▸ http://dx.doi.org/10.1136/annrheumdis-2014-205175 Ann Rheum Dis 2014;73:e23. doi:10.1136/annrheumdis-2014-205182
REFERENCES 1 2
3 4
5 6 7
Zeng C, Geo S-G, Lei G-H. Paying attention to arbitrary causality and the preciseness of conclusion. Ann Rheum Dis 2014;73:e22. Jin X, Bequerie JR, Zhang W, et al. Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis 2013. Published Online First. 20 Dec 2013. doi: 10.1136/annrheumdis-2013-204494 Oliver JC, Bland LA, Oettinger CW, et al. Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge. Lymphokine Cytokine Res 1993;12:115–20. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101:1767–72. Straub RH, Cutolo M. Circadian rhythms in rheumatoid arthritis: implications for pathophysiology and therapeutic management. Arthritis Rheum 2007;56:399–408. Meier-Ewert HK, Ridker PM, Rifai N, et al. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 2001;47:426–30. Punzi L, Ramonda R, Oliviero F, et al. Value of C reactive protein in the assessment of erosive osteoarthritis of the hand. Ann Rheum Dis 2005;64:955–7.
e23
Downloaded from ard.bmj.com on September 26, 2014 - Published by group.bmj.com
Response to: 'Paying attention to arbitrary causality and the preciseness of conclusion' by Lei et al Xingzhong Jin, Julieta Ruiz Beguerie, Weiya Zhang, et al. Ann Rheum Dis 2014 73: e23 originally published online January 29, 2014
doi: 10.1136/annrheumdis-2014-205182
Updated information and services can be found at: http://ard.bmj.com/content/73/4/e23.full.html
These include:
References
This article cites 5 articles, 3 of which can be accessed free at: http://ard.bmj.com/content/73/4/e23.full.html#ref-list-1
Email alerting service
Topic Collections
Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Immunology (including allergy) (4340 articles) Inflammation (964 articles) Epidemiology (1189 articles) Degenerative joint disease (3977 articles) Musculoskeletal syndromes (4252 articles) Osteoarthritis (820 articles)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions
To order reprints go to: http://journals.bmj.com/cgi/reprintform
To subscribe to BMJ go to: http://group.bmj.com/subscribe/
