Letters to the Editors In the present study, the number of patients with ‘good’ and ‘very good’ satisfactory relief of symptoms in the treatment period with enriched artichokes was 12 out of 20. The number was 16 if ‘moderate’ relief of symptoms was also included. The overall treatment-phase preference was assessed by patients at the end of the study by responding to the following question ‘Which treatment period (period 1, period 2, or no preference) did you prefer in the management of your constipation concerning the stool consistency and/or frequency?’ (Treatment 1 was better than treatment 2; treatment 2 was better than treatment 1; treatment 1 was equal to treatment 2). Finally, a modified intention-to-treat (ITT) analysis instead of a true ITT was used. Recently, the ‘modified ITT’ analysis has become popular as an alternative to a ‘strict ITT’ analysis. This design allows some exclusions from the ITT population, if these exclusions can be justified as unlikely to bias the results. In this framework, the
Letter: inflammatory bowel disease, complementary and alternative medicine, and genetics A. M. Bianco, J. Vuch, M. Girardelli, V. Zanin, A. Marcuzzi & S. Crovella Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, University of Trieste, Trieste, Italy. E-mail: [email protected] doi:10.1111/j.1365-2036.2012.05065.x
SIRS, In their article, Weizman et al. described the use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD).1 CAM is usually employed when conventional medicine is not able to improve patients’ clinical phenotype. Physicians should be able to explain the rationale for the use of CAM to patients and how it can be tailored to their needs. An important distinction should exist between CAM, that is safe and scientifically proven to provide a therapeutic benefit, and CAM with inconsistent or controversial clinical results. For example, probiotic supplementation maintains or improves health,2 and the intake of fish oil reduces heart disease.3 It must be taken into account that CAM should be proven to be more effective than a placebo.4 All this considered we would like to discuss the following issues. IBD is a complex disease, where genetics 1110
authors defined their analysis as a ‘modified ITT’ one, since the group of five patients who were excluded from the study never started the treatment. Therefore, their exclusion neither affected the results of the study nor introduced a potential bias in their interpretation.
ACKNOWLEDGEMENTS Declaration of personal interests: None. Declaration of funding interests: The study was funded in part by Copaim (Albinia, GR, Italy), grant no. 271, May 28, 2009. REFERENCES 1. Patel VM, Donnellan CF. Letter: the efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation. Aliment Pharmacol Ther 2012; 35: 1109. 2. Riezzo G, Orlando A, D’Attoma B, et al. Randomised clinical trial: efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation – a doubleblind, controlled, crossover study. Aliment Pharmacol Ther 2012; 35: 441–50.
play an important role, when considering IBD patients with a family history. It is crucial to obtain, in addition to patient’s genetic common background, information concerning the eventual use of CAM to evaluate potential side effects and adverse reactions; therefore medical geneticists should be familiar with alternative therapies to best serve their patients.5 The identification of Mendelian forms among early-onset IBD patients could provide useful hints for genetic counselling, aimed at assessing the risk of surgical intervention, and treatment that can be conventional or related to CAM. In the study of Weizman et al.,1 we cannot exclude patients’ emotional component and psychological approach. For this reason, we think that not including children in such a study represents a limit to understanding the real effectiveness of CAM. In conclusion, we would like to open a discussion aimed to better disclose the effectiveness of CAM in IBD, including early-onset patients, to evaluate their potential role in improving patient’s life quality.
ACKNOWLEDGEMENTS Declaration of personal interests: This study was supported by a grant from the Institute of Child HealthIRCCS Burlo Garofolo, Trieste, Italy (RC 42/2011). All authors read and approved the final manuscript. The manuscript was not previously published or under consideration for publication elsewhere. Crovella S. is recipient of a fellowship grant from European Project Aliment Pharmacol Ther 2012; 35: 1109-1111 ª 2012 Blackwell Publishing Ltd
Letters to the Editors “Talents for an International House” within the framework of the 7th Research & Development Framework Programme PEOPLE – Marie Curie Actions – COFUND (Co-Funding of Regional, National and International Programmes). Declaration of funding interests: None.
REFERENCES 1. Weizman AV, Ahn E, Thanabalan R, et al. Characterisation of complementary and alternative medicine use and its impact on medication adherence in inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35: 342–9.
Letter: endoscopic monitoring and treatment step-up in post-operative Crohn’s disease T. Yamamoto Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan. E-mail: [email protected] doi:10.1111/j.1365-2036.2012.05064.x
SIRS, I read with interest the “Review article: the natural history of post-operative Crohn’s disease (CD) recurrence” by Buisson et al.1 The authors found that smoking was the most significant risk factor for post-operative CD recurrence. Prior intestinal resection, penetrating behaviour, perianal disease and extensive bowel disease were also risk factors for post-operative recurrence. Although these clinical parameters can be identified at the time of operation, it is not easy to make a precise assessment of risk for future recurrence in an individual patient. Furthermore, there have been few studies showing that in patients with these parameters, the risk of post-operative recurrence could be significantly reduced with medical treatment.2 The authors found that 48–93% of patients developed endoscopic lesions in the neo-terminal ileum within 1 year after surgery, whereas 20–37% had clinical recurrence.1 These results suggest that early endoscopic lesions are observed before clinical signs, and symptoms develop after surgery for CD. We conducted a prospective cohort study to investigate impacts of endoscopic findings in the neo-terminal ileum on subsequent clinical recurrence following ileocolonic resection for CD.3 There was a significant positive correlation between the endoscopic severity at 6 months after surgery and the clinical recurAliment Pharmacol Ther 2012; 35: 1109-1111 ª 2012 Blackwell Publishing Ltd
2. Bron PA, van Baarlen P, Kleerebezem M. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol 2012; 10: 66–78. 3. Kromhout D, Menotti A, Kesteloot H, et al. Prevention of coronary heart disease by diet and lifestyle: evidence from prospective cross-cultural, cohort, and intervention studies. Circulation 2002; 105: 893–8. 4. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. 5. Buehler BA. Complementary and alternative medicine (CAM) in genetics. Am J Med Genet A 2007; 143A: 2889–92.
rence rate during the following 1 year. Thus, the severity of endoscopic inflammation in the early post-operative period should be a reliable predictive parameter for future clinical recurrence. Recently, the effects of infliximab on early endoscopic lesions after resection for CD were investigated. Two prospective studies found that infliximab therapy significantly improved endoscopic inflammation and reduced the risk of subsequent clinical recurrence.4, 5 Further studies are necessary to establish criteria for recurrence risk assessment and prophylactic treatment strategy in the management of post-operative CD. However, endoscopic monitoring and treatment step-up should be important therapeutic strategies for prevention of post-operative recurrence in patients with CD.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Buisson A, Chevaux JB, Allen PB, Bommelaer G, Peyrin-Biroulet L. Review article: the natural history of post-operative Crohn’s disease recurrence. Aliment Pharmacol Ther 2012; 35: 625–33. 2. D’Haens GR, Vermeire S, Van Assche G, et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn’s disease: a controlled randomized trial. Gastroenterology 2008; 135: 1123–9. 3. Yamamoto T, Umegae S, Matsumoto K, Saniabadi AR. The relationship between endoscopic findings at the proximal site of anastomosis and subsequent clinical relapse following ileal/ ileocolonic resection for Crohn’s disease: a prospective endoscopic cohort study. Gut 2009; 58(Suppl. 2): A175. 4. Yamamoto T, Umegae S, Matsumoto K. Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn’s disease: a prospective pilot study. Inflamm Bowel Dis 2009; 15: 1460–6. 5. Sorrentino D, Terrosu G, Paviotti A, et al. Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn’s disease: partial benefit by infliximab – a pilot study. Dig Dis Sci 2012 [Epub ahead of print].
1111
Letter: inflammatory bowel disease, complementary and alternative medicine, and genetics A. M. Bianco, J. Vuch, M. Girardelli, V. Zanin, A. Marcuzzi & S. Crovella Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, University of Trieste, Trieste, Italy. E-mail: [email protected] doi:10.1111/j.1365-2036.2012.05065.x
SIRS, In their article, Weizman et al. described the use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD).1 CAM is usually employed when conventional medicine is not able to improve patients’ clinical phenotype. Physicians should be able to explain the rationale for the use of CAM to patients and how it can be tailored to their needs. An important distinction should exist between CAM, that is safe and scientifically proven to provide a therapeutic benefit, and CAM with inconsistent or controversial clinical results. For example, probiotic supplementation maintains or improves health,2 and the intake of fish oil reduces heart disease.3 It must be taken into account that CAM should be proven to be more effective than a placebo.4 All this considered we would like to discuss the following issues. IBD is a complex disease, where genetics 1110
authors defined their analysis as a ‘modified ITT’ one, since the group of five patients who were excluded from the study never started the treatment. Therefore, their exclusion neither affected the results of the study nor introduced a potential bias in their interpretation.
ACKNOWLEDGEMENTS Declaration of personal interests: None. Declaration of funding interests: The study was funded in part by Copaim (Albinia, GR, Italy), grant no. 271, May 28, 2009. REFERENCES 1. Patel VM, Donnellan CF. Letter: the efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation. Aliment Pharmacol Ther 2012; 35: 1109. 2. Riezzo G, Orlando A, D’Attoma B, et al. Randomised clinical trial: efficacy of Lactobacillus paracasei-enriched artichokes in the treatment of patients with functional constipation – a doubleblind, controlled, crossover study. Aliment Pharmacol Ther 2012; 35: 441–50.
play an important role, when considering IBD patients with a family history. It is crucial to obtain, in addition to patient’s genetic common background, information concerning the eventual use of CAM to evaluate potential side effects and adverse reactions; therefore medical geneticists should be familiar with alternative therapies to best serve their patients.5 The identification of Mendelian forms among early-onset IBD patients could provide useful hints for genetic counselling, aimed at assessing the risk of surgical intervention, and treatment that can be conventional or related to CAM. In the study of Weizman et al.,1 we cannot exclude patients’ emotional component and psychological approach. For this reason, we think that not including children in such a study represents a limit to understanding the real effectiveness of CAM. In conclusion, we would like to open a discussion aimed to better disclose the effectiveness of CAM in IBD, including early-onset patients, to evaluate their potential role in improving patient’s life quality.
ACKNOWLEDGEMENTS Declaration of personal interests: This study was supported by a grant from the Institute of Child HealthIRCCS Burlo Garofolo, Trieste, Italy (RC 42/2011). All authors read and approved the final manuscript. The manuscript was not previously published or under consideration for publication elsewhere. Crovella S. is recipient of a fellowship grant from European Project Aliment Pharmacol Ther 2012; 35: 1109-1111 ª 2012 Blackwell Publishing Ltd
Letters to the Editors “Talents for an International House” within the framework of the 7th Research & Development Framework Programme PEOPLE – Marie Curie Actions – COFUND (Co-Funding of Regional, National and International Programmes). Declaration of funding interests: None.
REFERENCES 1. Weizman AV, Ahn E, Thanabalan R, et al. Characterisation of complementary and alternative medicine use and its impact on medication adherence in inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35: 342–9.
Letter: endoscopic monitoring and treatment step-up in post-operative Crohn’s disease T. Yamamoto Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan. E-mail: [email protected] doi:10.1111/j.1365-2036.2012.05064.x
SIRS, I read with interest the “Review article: the natural history of post-operative Crohn’s disease (CD) recurrence” by Buisson et al.1 The authors found that smoking was the most significant risk factor for post-operative CD recurrence. Prior intestinal resection, penetrating behaviour, perianal disease and extensive bowel disease were also risk factors for post-operative recurrence. Although these clinical parameters can be identified at the time of operation, it is not easy to make a precise assessment of risk for future recurrence in an individual patient. Furthermore, there have been few studies showing that in patients with these parameters, the risk of post-operative recurrence could be significantly reduced with medical treatment.2 The authors found that 48–93% of patients developed endoscopic lesions in the neo-terminal ileum within 1 year after surgery, whereas 20–37% had clinical recurrence.1 These results suggest that early endoscopic lesions are observed before clinical signs, and symptoms develop after surgery for CD. We conducted a prospective cohort study to investigate impacts of endoscopic findings in the neo-terminal ileum on subsequent clinical recurrence following ileocolonic resection for CD.3 There was a significant positive correlation between the endoscopic severity at 6 months after surgery and the clinical recurAliment Pharmacol Ther 2012; 35: 1109-1111 ª 2012 Blackwell Publishing Ltd
2. Bron PA, van Baarlen P, Kleerebezem M. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol 2012; 10: 66–78. 3. Kromhout D, Menotti A, Kesteloot H, et al. Prevention of coronary heart disease by diet and lifestyle: evidence from prospective cross-cultural, cohort, and intervention studies. Circulation 2002; 105: 893–8. 4. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. 5. Buehler BA. Complementary and alternative medicine (CAM) in genetics. Am J Med Genet A 2007; 143A: 2889–92.
rence rate during the following 1 year. Thus, the severity of endoscopic inflammation in the early post-operative period should be a reliable predictive parameter for future clinical recurrence. Recently, the effects of infliximab on early endoscopic lesions after resection for CD were investigated. Two prospective studies found that infliximab therapy significantly improved endoscopic inflammation and reduced the risk of subsequent clinical recurrence.4, 5 Further studies are necessary to establish criteria for recurrence risk assessment and prophylactic treatment strategy in the management of post-operative CD. However, endoscopic monitoring and treatment step-up should be important therapeutic strategies for prevention of post-operative recurrence in patients with CD.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Buisson A, Chevaux JB, Allen PB, Bommelaer G, Peyrin-Biroulet L. Review article: the natural history of post-operative Crohn’s disease recurrence. Aliment Pharmacol Ther 2012; 35: 625–33. 2. D’Haens GR, Vermeire S, Van Assche G, et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn’s disease: a controlled randomized trial. Gastroenterology 2008; 135: 1123–9. 3. Yamamoto T, Umegae S, Matsumoto K, Saniabadi AR. The relationship between endoscopic findings at the proximal site of anastomosis and subsequent clinical relapse following ileal/ ileocolonic resection for Crohn’s disease: a prospective endoscopic cohort study. Gut 2009; 58(Suppl. 2): A175. 4. Yamamoto T, Umegae S, Matsumoto K. Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn’s disease: a prospective pilot study. Inflamm Bowel Dis 2009; 15: 1460–6. 5. Sorrentino D, Terrosu G, Paviotti A, et al. Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn’s disease: partial benefit by infliximab – a pilot study. Dig Dis Sci 2012 [Epub ahead of print].
1111
