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Meta-Analysis
. 2016 May 18;2016(5):CD000478.
doi: 10.1002/14651858.CD000478.pub4.

Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis

Antje Timmer  1 , Petrease H Patton, Nilesh Chande, John W D McDonald, John K MacDonald
Affiliations
Meta-Analysis

Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis

Antje Timmer et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial.

Objectives: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis.

Search methods: The MEDLINE, EMBASE and Cochrane Library databases were searched from inception to 30 July 2015. Both full randomized controlled trials and associated abstracts were included.

Selection criteria: Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (e.g. mesalazine) were included.

Data collection and analysis: Two authors independently extracted data using standard forms. Disagreements were solved by consensus including a third author. Study quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to maintain clinical or endoscopic remission. Secondary outcomes included adverse events and withdrawal due to adverse events. Analyses were performed separately by type of control (placebo, or active comparator). Pooled risk ratios were calculated based on the fixed-effect model unless heterogeneity was shown. The GRADE approach was used to assess the overall quality of evidence for pooled outcomes.

Main results: Seven studies including 302 patients with ulcerative colitis were included in the review. The risk of bias was high in three of the studies due to lack of blinding. Azathioprine was shown to be significantly superior to placebo for maintenance of remission. Fourty-four per cent (51/115) of azathioprine patients failed to maintain remission compared to 65% (76/117) of placebo patients (4 studies, 232 patients; RR 0.68, 95% CI 0.54 to 0.86). A GRADE analysis rated the overall quality of the evidence for this outcome as low due to risk of bias and imprecision (sparse data). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity and thus were not pooled. Fifty per cent (7/14) of 6-mercaptopurine patients failed to maintain remission compared to 100% (8/8) of mesalazine patients (1 study, 22 patients; RR 0.53, 95% CI 0.31 to 0.90). Fifty-eight per cent (7/12) of azathioprine patients failed to maintain remission compared to 38% (5/13) of sulfasalazine patients (1 study, 25 patients; RR 1.52, 95% CI 0.66 to 3.50). One small study found that 6-mercaptopurine was superior to methotrexate for maintenance of remission. In the study, 50% (7/14) of 6-mercaptopurine patients and 92% (11/12) of methotrexate patients failed to maintain remission (1 study, 26 patients; RR 0.55, 95% CI 0.31 to 0.95). One very small study compared azathioprine with cyclosporin and found that there was no significant difference between patients failing remission on azathioprine (50%, 4/8) or cyclosporin (62.5%, 5/8) (1 study, 16 patients, RR 0.80 95% CI 0.33 to 1.92). When placebo-controlled studies were pooled with aminosalicylate-comparator studies to assess adverse events, there was no statistically significant difference between azathioprine and control in the incidence of adverse events. Nine per cent (11/127) of azathioprine patients experienced at least one adverse event compared to 2% (3/130) of placebo patients (5 studies, 257 patients; RR 2.82, 95% CI 0.99 to 8.01). Patients receiving azathioprine were at significantly increased risk of withdrawing due to adverse events. Eight per cent (8/101) of azathioprine patients withdrew due to adverse events compared to 0% (0/98) of control patients (5 studies, 199 patients; RR 5.43, 95% CI 1.02 to 28.75). Adverse events related to study medication included acute pancreatitis (3 cases, plus 1 case on cyclosporin) and significant bone marrow suppression (5 cases). Deaths, opportunistic infection or neoplasia were not reported.

Authors' conclusions: Azathioprine therapy appears to be more effective than placebo for maintenance of remission in ulcerative colitis. Azathioprine or 6-mercaptopurine may be effective as maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine. This review updates the existing review of azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (September 2012).

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Conflict of interest statement

Antje Timmer received grants (paid to institution) from Sanofi‐Aventis, Bayer, Takeda, Celgene, and Novartis for pharmacoepidemiological studies prior to 2014; and payment for lectures from Abbott, Ferring, The Falk Foundation, and MSD Sharp. All of these activities are outside the submitted work.

Petrease H Patton: None known.

Nilesh Chande has received fees for consultancy from Abbott/AbbVie , Ferring, and Actavis; fees for lectures from Abbott, travel expenses from Merck and has stock/stock options in Pfizer, Glaxo Smith Kline, Proctor and Gamble and Johnson and Johnson. All of these financial activities are outside the submitted work.

John WD McDonald: None known.

John K MacDonald: None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Azathioprine versus placebo, Outcome 1 Failure to maintain remission.
1.2
1.2. Analysis
Comparison 1 Azathioprine versus placebo, Outcome 2 Failure to maintain remission in successfully induced cases only.
1.3
1.3. Analysis
Comparison 1 Azathioprine versus placebo, Outcome 3 Any adverse event.
1.4
1.4. Analysis
Comparison 1 Azathioprine versus placebo, Outcome 4 Withdrawal due to adverse event.
2.1
2.1. Analysis
Comparison 2 Azathioprine or 6‐mercaptopurine versus 5‐ASA or sulfasalzine, Outcome 1 Failure to maintain remission.
2.2
2.2. Analysis
Comparison 2 Azathioprine or 6‐mercaptopurine versus 5‐ASA or sulfasalzine, Outcome 2 Any adverse event.
2.3
2.3. Analysis
Comparison 2 Azathioprine or 6‐mercaptopurine versus 5‐ASA or sulfasalzine, Outcome 3 Withdrawal due to adverse event.
3.1
3.1. Analysis
Comparison 3 6‐Mercaptopurine versus methotrexate, Outcome 1 Failure to maintain remission.
3.2
3.2. Analysis
Comparison 3 6‐Mercaptopurine versus methotrexate, Outcome 2 Withdrawal due to adverse event.
4.1
4.1. Analysis
Comparison 4 Azathioprine versus cyclosporin, Outcome 1 Failure to maintain remission.
4.2
4.2. Analysis
Comparison 4 Azathioprine versus cyclosporin, Outcome 2 Any adverse event.
4.3
4.3. Analysis
Comparison 4 Azathioprine versus cyclosporin, Outcome 3 Withdrawal due to an adverse event.
5.1
5.1. Analysis
Comparison 5 Adverse events ‐ all trials, Outcome 1 Any adverse event.
5.2
5.2. Analysis
Comparison 5 Adverse events ‐ all trials, Outcome 2 Withdrawal due to adverse event.
5.3
5.3. Analysis
Comparison 5 Adverse events ‐ all trials, Outcome 3 Acute pancreatitis.
5.4
5.4. Analysis
Comparison 5 Adverse events ‐ all trials, Outcome 4 Bone marrow suppression.
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References

References to studies included in this review

Hawthorne 1992 {published data only}
    1. Hawthorne AB, Logan RF, Hawkey CJ, Foster PN, Axon AT, Swarbrick ET, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ 1992;305(6844):20‐2. - PMC - PubMed
Jewell 1974 {published data only}
    1. Jewell DP, Truelove SC. Azathioprine in ulcerative colitis. Gut 1972;13(4):323. - PubMed
    1. Jewell DP, Truelove SC. Azathioprine in ulcerative colitis: an interim report on a controlled therapeutic trial. British Medical Journal 1972;1(5802):709‐12. - PMC - PubMed
    1. Jewell DP, Truelove SC. Azathioprine in ulcerative colitis: final report on controlled therapeutic trial. British Medical Journal 1974;4(5945):627‐30. - PMC - PubMed
Mate‐Jimenez 2000 {published data only}
    1. Hermida C, Cantero J, Moreno‐Otero R, Mate‐Jimenez J. Methotrexate and 6‐mercaptopurine in steroid‐dependent inflammatory bowel disease patients: A randomized controlled clinical trial.. Gut 1999;45(Suppl V):A132.
    1. Mate‐Jimenez J, Hermida C, Cantero‐Perona J, Moreno‐Otero R. 6‐mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid‐dependent inflammatory bowel disease. European Journal of Gastroenterology and Hepatology 2000;12(11):1227‐33. - PubMed
Paraskeva 2000 {published data only}
    1. Paraskeva KD, Karagiannis JA. Comparative effectiveness and safety of oral azathioprine and low‐dose oral cyclosporin in maintenance of the response in patients with acute steroid‐resistant ulcerative colitis.. Gut 2000;47(Suppl III A241):P932.
Sood 2000 {published data only}
    1. Sood A, Midha V, Sood N, Kaushal V. Role of azathioprine in severe ulcerative colitis: one‐year, placebo‐controlled, randomized trial. Indian Journal of Gastroenterology 2000;19(1):14‐6. - PubMed
Sood 2002 {published data only}
    1. Sood A, Kaushal V, Midha V, Bhatia KL, Sood N, Malhotra V. The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis. Journal of Gastroenterology 2002;37(4):270‐4. - PubMed
Sood 2003 {published data only}
    1. Sood A, Midha V, Sood N, Avasthi G. Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis. Indian Journal of Gastroenterology 2003;22(3):79‐81. - PubMed

References to studies excluded from this review

Ardizzone 1997 {published data only}
    1. Ardizzone S, Molteni P, Imbesi V, Bollani S, Bianchi Porro G. Azathioprine in steroid‐resistant and steroid‐dependent ulcerative colitis. Journal of Clinical Gastroenterology 1997;25(1):330‐3. - PubMed
Ardizzone 2006 {published data only}
    1. Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5‐aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut 2006;55(1):47‐53. - PMC - PubMed
Cassinotti 2009 {published data only}
    1. Cassinotti A, Actis GC, Duca P, Massari A, Colombo E, Gai E, et al. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal. American Journal of Gastroenterology 2009;104(11):2760‐7. - PubMed
Chebli 2010 {published data only}
    1. Chebli LA, Felga GG, Chaves LD, Pimentel FF, Guerra DM, Gaburri PD, et al. Early onset steroid‐dependent ulcerative colitis is a predictor of azathioprine response: a longitudinal 12‐month follow‐up study. Medical Science Monitor 2010;16(2):PI1‐6. - PubMed
Cuffari 2004 {published data only}
    1. Cuffari C, Dassopoulos T, Turnbough L, Thompson RE, Bayless TM. Thiopurine methyltransferase activity influences clinical response to azathioprine in inflammatory bowel disease. Clinical Gastroenterology and Hepatology 2004;2(5):410‐7. - PubMed
Domenech 2002 {published data only}
    1. Domenech E, Garcia‐Planella E, Bernal I, Rosinach M, Cabre E, Fluvia L, et al. Azathioprine without oral ciclosporin in the long‐term maintenance of remission induced by intravenous ciclosporin in severe, steroid‐refractory ulcerative colitis. Alimentary pharmacology & therapeutics 2002;16(12):2061‐5. - PubMed
Fernandez‐Banares 1996 {published data only}
    1. Fernandez‐Banares F, Bertran X, Esteve‐Comas M, Cabre E, Menacho M, Humbert P, et al. Azathioprine is useful in maintaining long‐term remission induced by intravenous cyclosporine in steroid‐refractory severe ulcerative colitis. The American journal of gastroenterology 1996;91(12):2498‐9. - PubMed
Hibi 2003 {published data only}
    1. Hibi T, Naganuma M, Kitahora T, Kinjyo F, Shimoyama T. Low‐dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. Journal of Gastroenterology 2003;38(8):740‐6. - PubMed
Holtmann 2006 {published data only}
    1. Holtmann MH, Krummenauer F, Claas C, Kremeyer K, Lorenz D, Rainer O, et al. Long‐term effectiveness of azathioprine in IBD beyond 4 years: a European multicenter study in 1176 patients. Digestive Diseases and Sciences 2006;51(9):1516‐24. - PubMed
Kirk 1982 {published data only}
    1. Kirk AP, Lennard‐Jones JE. Controlled trial of azathioprine in chronic ulcerative colitis. British Medical Journal 1982;284(6325):1291‐2. - PMC - PubMed
Mantzaris 2004 {published data only}
    1. Mantzaris GJ, Sfakianakis M, Archavlis E, Petraki K, Christidou A, Karagiannidis A, et al. A prospective randomized observer‐blind 2‐year trial of azathioprine monotherapy versus azathioprine and olsalazine for the maintenance of remission of steroid‐dependent ulcerative colitis. American Journal of Gastroenterology 2004;99(6):1122‐8. - PubMed
Paoluzi 2002 {published data only}
    1. Paoluzi OA, Pica R, Marcheggiano A, Crispino P, Iacopini F, Iannoni C, et al. Azathioprine or methotrexate in the treatment of patients with steroid‐dependent or steroid‐resistant ulcerative colitis: results of an open‐label study on efficacy and tolerability in inducing and maintaining remission. Alimentary pharmacology & therapeutics 2002;16(10):1751‐9. [PUBMED: 12269968] - PubMed
Rosenberg 1975 {published data only}
    1. Rosenberg JL, Wall AJ, Levin B, Binder HJ, Kirsner JB. A controlled trial of azathioprine in the management of chronic ulcerative colitis. Gastroenterology 1975;69(1):96‐9. - PubMed
Sakuraba 2012 {published data only}
    1. Sakuraba A, Sato T, Morohoshi Y, Matsuoka K, Okamoto S, Inoue N, et al. Intermittent granulocyte and monocyte apheresis versus mercaptopurine for maintaining remission of ulcerative colitis: a pilot study. Therapeutic Apheresis and Dialysis 2012;16(3):213‐8. - PubMed

Additional references

Baron 1964
    1. Baron JH, Connell AM, Lennard‐Jones JE. Variation between observers in describing mucosal appearances in proctocolitis. British Medical Journal 1964;1(5375):89‐92. - PMC - PubMed
Bowen 1966
    1. Bowen GE, Irons GV Jr, Rhodes JB, Kirsner JB. Early experiences with azathioprine in ulcerative colitis; a note of caution. JAMA 1966;195(6):460‐4. - PubMed
Bressler 2015
    1. Bressler B, Marshall JK, Bernstein CN, Bitton A, Jones J, Leontiadis GI, Panaccione R, Steinhart AH, Tse F, Feagan B, Toronto Ulcerative Colitis Consensus Group. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology 2015;148(5):1035‐1058. [DOI: 10.1053/j.gastro.2015.03.001; PUBMED: 25747596] - DOI - PubMed
Campieri 2003
    1. Campieri M, Rizzello F, Gionchetti P. Maintenance of remission in ulcerative colitis. In: Satsangi J, Sutherland LR, Colombel JF, Fiocchi C, Lofberg R, Pemberton JH, et al. editor(s). Inflammatory Bowel Diseases. Edinburgh, Oxford: Churchill Livingstone, 2003:419‐30.
Chande 2015
    1. Chande N, Patton PH, Tsoulis DJ, Thomas BS, MacDonald JK. Azathioprine or 6‐mercaptopurine for maintenance of remission in Crohn's disease. Cochrane Database of Systematic Reviews 2015, Issue 10. [DOI: 10.1002/14651858.CD000067.pub3] - DOI - PMC - PubMed
Chouchana 2012
    1. Chouchana L, Narjoz C, Beaune P, Loriot MA, Roblin X. Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2012;35(1):15‐36. [DOI: 10.1111/j.1365-2036.2011.04905.x; PUBMED: 22050052 ] - DOI - PubMed
Colombel 2000
    1. Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, et al. Genotypic analysis of thiopurine S‐methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000;118(6):1025‐30. - PubMed
Dubinsky 2004
    1. Dubinsky MC. Azathioprine, 6‐mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clinical Gastroenterology and Hepatology 2004;2(9):731‐43. - PubMed
Freeman 2012
    1. Freeman HJ. Medical management of ulcerative colitis with a specific focus on 5‐aminosalicylates. Clin Med Insights Gastroenterol 2012;Oct(5):77‐83. [DOI: 10.4137/CGast.S8673; PUBMED: 24833937 ] - DOI - PMC - PubMed
Gearry 2004
    1. Gearry RB, Barclay ML, Burt MJ, Collett JA, Chapman BA. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiology and Drug Safety 2004;13(8):563‐7. - PubMed
Gearry 2005
    1. Gearry RB, Barclay ML. Azathioprine and 6‐mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. Journal of Gastroenterology and Hepatology 2005;20(8):1149‐57. - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924‐6. - PMC - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Altman DG. Measuring inconsistency in meta‐analysis. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hilsden 2003
    1. Hilsden RJ, Verhoef MJ, Best A, Pocobelli G. A national survey on the patterns of treatment of inflammatory bowel disease in Canada. BMC Gastroenterology 2003;3(1):10. - PMC - PubMed
Kotlyar 2015
    1. Kotlyar DS, Lewis JD, Beaugerie L, Tierney A, Brensinger CM, Gisbert JP, Loftus EV Jr, Peyrin‐Biroulet L, Blonski WC, Domselaar M, Chaparro M, Sandilya S, Bewtra M, Beigel F, Biancone L, Lichtenstein GR. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6‐mercaptopurine: a meta‐analysis. Clin Gastroenterol Hepatol 2015;13(5):847‐58. [DOI: 10.1016/j.cgh.2014.05.015; PUBMED: 24879926] - DOI - PubMed
Long 2012
    1. Long MD, Martin CF, Pipkin CA, Herfarth HH, Sandler RS, Kappelman MD. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology 2012;143(2):390‐399. [DOI: 10.1053/j.gastro.2012.05.004; PUBMED: 22584081] - DOI - PMC - PubMed
Marshall 2012
    1. Marshall JK, Thabane M, Steinhart AH, Newman JR, Anand A, Irvine EJ. Rectal 5‐aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2012, Issue 11. [DOI: 10.1002/14651858.CD004118.pub2; PUBMED: 23152224] - DOI - PMC - PubMed
Meuwissen 2000
    1. Meuwissen SG, Ewe K, Gassull MA, Geboes K, Jewell D, Pallone F, et al. IOIBD questionnaire on the clinical use of azathioprine, 6‐mercaptoptopurine, cyclosporin A and methotrexate in the treatment of inflammatory bowel diseases. European Journal of Gastroenterology and Hepatology 2000;12(1):13‐8. - PubMed
Present 1989
    1. Present DH, Meltzer SJ, Krumholz MP, Wolke A, Korelitz BI. 6‐Mercaptopurine in the management of inflammatory bowel disease: short‐ and long‐term toxicity. Annals of Internal Medicine 1989;111(8):641‐9. - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment in controlled trials. JAMA 1995;273:408‐12. - PubMed
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Stack 1999
    1. Stack WA, Williams D, Stevenson M, Logan RF. Immunosuppressive therapy for ulcerative colitis: results of a nation‐wide survey among consultant physician members of the British Society of Gastroenterology. Alimentary Pharmacology and Therapeutics 1999;13(5):569‐75. - PubMed
Su 2004
    1. Su C, Lichtenstein GR. Treatment of inflammatory bowel disease with azathioprine and 6‐mercaptopurine. Gastroenterology Clinics of North America 2004;33(2):209‐34, viii. - PubMed
Wallace 2001
    1. Wallace TM, Veldhuyzen van Zanten SJ. Frequency of use and standards of care for the use of azathioprine and 6‐mercaptopurine in the treatment of inflammatory bowel disease: a systematic review of the literature and a survey of Canadian gastroenterologists. Canadian Journal of Gastroenterology 2001;15(1):21‐8. - PubMed
Wang 2016
    1. Wang Y, Parker CE, Feagan BG, MacDonald JK. Oral 5‐aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/14651858.CD000544.pub4] - DOI - PMC - PubMed
Weinshilboum 1980
    1. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. American Journal of Human Genetics 1980;32(5):651‐62. - PMC - PubMed

References to other published versions of this review

Timmer 2007
    1. Timmer A, McDonald JW, MacDonald JK. Azathioprine and 6‐mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD000478.pub2] - DOI - PubMed
Timmer 2012
    1. Timmer A, McDonald JW, Tsoulis DJ, Macdonald JK. Azathioprine and 6‐mercaptopurine for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD000478.pub3; PUBMED: 22972046] - DOI - PubMed

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