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W1202 Influenza Vaccination Awareness and History in Children with Inflammatory Bowel Disease
W1204
Background: Children with Crohn's disease often have poor growth, and several small studies have suggested that they have increased metabolic needs. Measurement of resting energy expenditure may serve as a proxy for disease activity, and may help guide medical and nutritional interventions in children with active Crohn's disease. Aim: To measure resting energy expenditure using a portable, hand-held device in children with Crohn's disease. Methods: Pediatric patients with active Crohn's were underwent both open circuit indirect calorimetry and portable indirect calorimetry using the MedGem (Microlife USA, Inc.; Dunedin, FL) on the day of study. Open circuit indirect respiratory calorimetry was performed to measure resting oxygen consumption, carbon dioxide production, and resting energy expenditure. Measurements were taken over 30 minutes while the patients were quiet and supine. The MedGem measures VO2 and calculates the resting energy expenditure based on a fixed respiratory quotient. Over 5 minutes in a sitting position, the patient breathes through the MedGem device with a noseclip in place. Resting energy expenditure and VO2 were compared between these methods using a paired t-test. Results: Seven patients (mean age 15.2 ± 2.6 yr) were enrolled. The average BSA was 1.6 ± 0.3 kg/m2. No significant difference was noted in resting energy expenditure and VO2 between the MedGem device and open circuit indirect calorimetry. Conclusion: Open circuit indirect calorimetry and portable indirect calorimetry using the MedGem device provide valuable data about metabolic activity in pediatric patients with Crohn's disease. The portability, ease of use, and short duration of the MedGem device makes it a valuable device for the assessment of energy metabolism in pediatric Crohn's disease patients.
W1202 Influenza Vaccination Awareness and History in Children with Inflammatory Bowel Disease Jennifer deBruyn, Iwona T. Wrobel BACKGROUND: The Public Health Agency of Canada recommends annual influenza vaccination for all individuals with chronic immunosuppression (due to underlying disease and/or therapy) as well as household contacts. OBJECTIVES: To evaluate awareness of influenza vaccine recommendations, and personal and family history of influenza vaccination in children with inflammatory bowel disease (IBD). METHODS: Medical care for all children with IBD in southern Alberta (population 1.5 million) is provided at the only tertiary-care center for this region, the Alberta Children's Hospital (ACH). All children with IBD followed at the ACH were invited to participate in a study on influenza vaccine immunogenicity. All participants completed a parent/self-administered questionnaire on awareness of influenza vaccine recommendations and personal and family history of influenza vaccination. Data on demographics, IBD history, and IBD medications were also collected. RESULTS: Sixtyone children with IBD and their families participated in the influenza vaccine immunogenicity study and completed the questionnaire. Thirty-seven and 31 families were aware of influenza vaccine recommendations in immunosuppressed individuals and household contacts, respectively. Thirty-one subjects with IBD had previous influenza vaccination; however 4 subjects had not received any influenza vaccinations in the last 4 years. IBD subjects who were aware of recommendations were more likely to have previous influenza vaccination (odds ratio [OR] 6.4; 95% confidence interval [CI] 2.0-20.7). The reasons for no previous influenza vaccination in subjects with IBD were: no specific reason (13), “didn't know needed it” (11), needle aversion (4), did not believe vaccine effective (3), afraid of side effects (2), vaccine not available (1), and personal philosophy against vaccine (1). Subjects with disease duration ≥ 1 year were more likely to be aware of recommendations (OR 3.6; 95% CI 1.211.1) and have previous vaccination (OR 5.9; 95% CI 1.6-17.4). No association was found between immunosuppressive medication use and awareness of recommendations or previous vaccination. Families aware of recommendations for household contacts were more likely to have previous influenza vaccinations in siblings (OR 7.9; 95% CI 2.3-27.0) and parents (OR 3.0; 95% CI 0.8-11.3). CONCLUSIONS: Families of children with IBD have suboptimal awareness and uptake of influenza vaccination. Physicians prescribing immunosuppressive medications for IBD need to discuss vaccination for vaccine-preventable diseases, especially influenza, with their patients.
W1205 How Variable Is the Mayo Score Between Observers and Might This Affect Trial Recruitment or Outcome? Alissa J. Walsh, Oliver Brain, Satish Keshav, Otto C. Buchel, Brent Merrin, Michal Rolinski, Sally Thomas, Lydia White, Douglas G. Altman, Simon Travis Background:The Mayo score for ulcerative colitis(UC) activity has 4 components:stool frequency(SF),rectal bleeding(RB),flexible sigmoidoscopy(FS)and physician's global assessment(PGA). How interobserver variation(IOV)affects the Mayo score and its impact on criteria for inclusion or outcome of clinical trials are unknown. Methods:100 patients with UC were seen independently, each on the same day,in random order,by 4 gastroenterologists. Both patient and clinician completed a proforma. A separate clinician performed videorecorded FS on the same day which was later scored by the 4 gastroenterologists. Each component of the score and total score were calculated for each patient. Comparison was made with inclusion criteria for ACT 1&2 trials (Mayo 6-12, endoscopy subscore >2),remission outcome (Mayo <2, no subscore >1). For clinical relevance(CR),scores were categorised as remission(<2),mild(3-5),moderate(6-8),or severe(9-12) activity and an experienced, blinded clinician independently assigned an appropriate clinical category (ACC) to each patient by assessing symptoms, examination, blood results, FS and histology. Quadratic weighted κ statistics assessed agreement within the Mayo score,where disagreements are weighted in relation to their magnitude. Results:Of 100 patients, there was complete agreement between 4 clinicians in total Mayo score in 6/96 (4 had no FS), varying by <2 points in 84/96, which changed clinical category in 23/84. Overall agreement for CR and ACC were good (κ=0.88 and κ=0.81 respectively). Between patients and clinicians there was 70% agreement for SF and RB. Between clinicians there was complete agreement in 65% for SF, 74% for RB, but only 21% for FS and 45% for PGA. Most disagreement was by one category (median 81%, range 74-93). For inclusion criteria, at least 1 clinician would have included 41/96, but all agreed in only 17/41(41%). At least ¾ clinicians would have included 22 and excluded 67, so there was at least 25% disagreement in 26/96(27%) and 50% disagreement in 11/96(11%). 11% had FS score ≥2 but total score ≤5;9.1% had a total score >6 but a FS score <1. For remission,at least 1 clinician scored <2 in 43/96, but all agreed in only 20/ 43 (47%) and ¾ agreed in 35/43 (81%). Agreement was not significantly improved by a total score <1 (at least 1 = 39/96; all agree 20/39; ¾ agree 35/39). Conclusion:There is high variability in Mayo scoring between observers,despite good agreement on clinical category. Complete agreement between observers for recruitment to clinical trials or outcome occurs in <50% and ¾ agreement in about 80% patients. IOV should be considered when calculating the power of clinical trials.
W1203 Title: A Single-Center Experience with Methotrexate After Thiopurine Therapy in Pediatric Crohn Disease Brendan Boyle, Laura Mackner, Christina E. Ross, Soma Kumar, Jonathan Moses, Wallace Crandall BODY: Thiopurines are a common, effective means of maintaining remission in pediatric Crohn disease (CD). For those intolerant or unresponsive to thiopurines, maintenance therapy with methotrexate (MTX) may be considered. However, the use of MTX as maintenance therapy following thiopurine failure in pediatric CD is less established. The purpose of this study was to examine our experience using MTX as maintenance therapy in patients previously treated with thiopurines. METHODS: We identified all patients seen at Nationwide Children's Hospital from 2000-2007 with an ICD code indicative of CD. The chart of each patient was reviewed and patients with a confirmed diagnosis of CD, no current infliximab therapy, a history of thiopurine use prior to MTX, and at least 6 months of follow up after MTX initiation were included. Reason for thiopurine discontinuation, prior and concomitant therapies, physician global assessment (PGA), and screening laboratory studies were obtained at initiation. These outcomes were reevaluated at 6 and 12 months in addition to steroid/ infliximab free remission rate, steroid use, progression to infliximab, reason for MTX discontinuation, and adverse events (AE). RESULTS: Twenty-eight patients (17 male) with a mean age at diagnosis of 12.2 +/- 3.7 years and mean disease duration of 1.8 +/- 2.0 years were identified. Indications for MTX included non-response to 6MP/Aza (11), AE (15), and thiopurine non-adherence (2). At MTX initiation, 3 patients were in steroid free remission and eleven were receiving steroids. At 6 months, 14 of the original 28 patients (50%) were in steroid/infliximab free remission. Of 27 patients with evaluable date, 3 were receiving steroids, and 9 had begun infliximab therapy. Three had discontinued MTX secondary to non-response (2) or AE (1), and 1 did not have evaluable data. At 12 months, 11 of the original 28 patients (39.2%) were in steroid/infliximab free remission. Of the 24 with available data, six required steroids and 8 were treated with infliximab. Two additional patients had discontinued MTX due to non-response (1) or parental choice (1), and 3 had no evaluable data. Laboratory studies revealed three patients with transient leukopenia and 4 with transient transaminase elevation over the 12 month period. CONCLUSION: MTX can be effective as maintenance therapy for pediatric CD patients who were intolerant of, or unresponsive to 6MP/azathioprine, with 50% and 39.2% in steroid/infliximab free remission at 6 and 12 months. Approximately one-third of this cohort required escalation to biologic therapy within the first 12 months following MTX initiation. MTX was well tolerated.
W1206 Split-Dose Administration of 6-Mercaptopurine/Azathioprine: A Effective Novel Strategy for IBD Patients with Preferential 6mmp Metabolism David Q. Shih, Minh Nguyen, Patricio Ibañez, Lola Y. Kwan, Stephan R. Targan, Eric A. Vasiliauskas BACKGROUND and AIM: 6 Mercaptopurine (MP) and azathiopurine (AZA) are efficacious in treating IBD. Studies suggest that 6-thioguanine (6TGN) metabolite levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6MMP) levels are associated with risk of hepatotoxicity and possibly myelotoxicity. A subset of IBD patients exhibit preferential 6MMP production, characterized by disproportionate elevations in 6MMP, which may lead to side-effects of leucopenia, hepatoxicity, and flu-like symptoms. 6MMP overproduction and side-effects resolve with dose reduction but the lower dose often fails to suppress disease activity. We observed that splitting the daily dose of thiopurine (e.g. 50mg BID rather than 100mg once daily) can reduce 6MMP while maintaining 6TGN levels and clinical efficacy. The aim of this study is to review the outcomes of thiopurine split-dosing strategy in patients with preferential 6MMP metabolism. METHODS: A restrospective chart review
A-677
AGA Abstracts
AGA Abstracts
Portable Indirect Calorimetry (MedGem) in Pediatric Crohn's Disease Mark R. Corkins, Steven J. Steiner, Scott Denne
Background: Children with Crohn's disease often have poor growth, and several small studies have suggested that they have increased metabolic needs. Measurement of resting energy expenditure may serve as a proxy for disease activity, and may help guide medical and nutritional interventions in children with active Crohn's disease. Aim: To measure resting energy expenditure using a portable, hand-held device in children with Crohn's disease. Methods: Pediatric patients with active Crohn's were underwent both open circuit indirect calorimetry and portable indirect calorimetry using the MedGem (Microlife USA, Inc.; Dunedin, FL) on the day of study. Open circuit indirect respiratory calorimetry was performed to measure resting oxygen consumption, carbon dioxide production, and resting energy expenditure. Measurements were taken over 30 minutes while the patients were quiet and supine. The MedGem measures VO2 and calculates the resting energy expenditure based on a fixed respiratory quotient. Over 5 minutes in a sitting position, the patient breathes through the MedGem device with a noseclip in place. Resting energy expenditure and VO2 were compared between these methods using a paired t-test. Results: Seven patients (mean age 15.2 ± 2.6 yr) were enrolled. The average BSA was 1.6 ± 0.3 kg/m2. No significant difference was noted in resting energy expenditure and VO2 between the MedGem device and open circuit indirect calorimetry. Conclusion: Open circuit indirect calorimetry and portable indirect calorimetry using the MedGem device provide valuable data about metabolic activity in pediatric patients with Crohn's disease. The portability, ease of use, and short duration of the MedGem device makes it a valuable device for the assessment of energy metabolism in pediatric Crohn's disease patients.
W1202 Influenza Vaccination Awareness and History in Children with Inflammatory Bowel Disease Jennifer deBruyn, Iwona T. Wrobel BACKGROUND: The Public Health Agency of Canada recommends annual influenza vaccination for all individuals with chronic immunosuppression (due to underlying disease and/or therapy) as well as household contacts. OBJECTIVES: To evaluate awareness of influenza vaccine recommendations, and personal and family history of influenza vaccination in children with inflammatory bowel disease (IBD). METHODS: Medical care for all children with IBD in southern Alberta (population 1.5 million) is provided at the only tertiary-care center for this region, the Alberta Children's Hospital (ACH). All children with IBD followed at the ACH were invited to participate in a study on influenza vaccine immunogenicity. All participants completed a parent/self-administered questionnaire on awareness of influenza vaccine recommendations and personal and family history of influenza vaccination. Data on demographics, IBD history, and IBD medications were also collected. RESULTS: Sixtyone children with IBD and their families participated in the influenza vaccine immunogenicity study and completed the questionnaire. Thirty-seven and 31 families were aware of influenza vaccine recommendations in immunosuppressed individuals and household contacts, respectively. Thirty-one subjects with IBD had previous influenza vaccination; however 4 subjects had not received any influenza vaccinations in the last 4 years. IBD subjects who were aware of recommendations were more likely to have previous influenza vaccination (odds ratio [OR] 6.4; 95% confidence interval [CI] 2.0-20.7). The reasons for no previous influenza vaccination in subjects with IBD were: no specific reason (13), “didn't know needed it” (11), needle aversion (4), did not believe vaccine effective (3), afraid of side effects (2), vaccine not available (1), and personal philosophy against vaccine (1). Subjects with disease duration ≥ 1 year were more likely to be aware of recommendations (OR 3.6; 95% CI 1.211.1) and have previous vaccination (OR 5.9; 95% CI 1.6-17.4). No association was found between immunosuppressive medication use and awareness of recommendations or previous vaccination. Families aware of recommendations for household contacts were more likely to have previous influenza vaccinations in siblings (OR 7.9; 95% CI 2.3-27.0) and parents (OR 3.0; 95% CI 0.8-11.3). CONCLUSIONS: Families of children with IBD have suboptimal awareness and uptake of influenza vaccination. Physicians prescribing immunosuppressive medications for IBD need to discuss vaccination for vaccine-preventable diseases, especially influenza, with their patients.
W1205 How Variable Is the Mayo Score Between Observers and Might This Affect Trial Recruitment or Outcome? Alissa J. Walsh, Oliver Brain, Satish Keshav, Otto C. Buchel, Brent Merrin, Michal Rolinski, Sally Thomas, Lydia White, Douglas G. Altman, Simon Travis Background:The Mayo score for ulcerative colitis(UC) activity has 4 components:stool frequency(SF),rectal bleeding(RB),flexible sigmoidoscopy(FS)and physician's global assessment(PGA). How interobserver variation(IOV)affects the Mayo score and its impact on criteria for inclusion or outcome of clinical trials are unknown. Methods:100 patients with UC were seen independently, each on the same day,in random order,by 4 gastroenterologists. Both patient and clinician completed a proforma. A separate clinician performed videorecorded FS on the same day which was later scored by the 4 gastroenterologists. Each component of the score and total score were calculated for each patient. Comparison was made with inclusion criteria for ACT 1&2 trials (Mayo 6-12, endoscopy subscore >2),remission outcome (Mayo <2, no subscore >1). For clinical relevance(CR),scores were categorised as remission(<2),mild(3-5),moderate(6-8),or severe(9-12) activity and an experienced, blinded clinician independently assigned an appropriate clinical category (ACC) to each patient by assessing symptoms, examination, blood results, FS and histology. Quadratic weighted κ statistics assessed agreement within the Mayo score,where disagreements are weighted in relation to their magnitude. Results:Of 100 patients, there was complete agreement between 4 clinicians in total Mayo score in 6/96 (4 had no FS), varying by <2 points in 84/96, which changed clinical category in 23/84. Overall agreement for CR and ACC were good (κ=0.88 and κ=0.81 respectively). Between patients and clinicians there was 70% agreement for SF and RB. Between clinicians there was complete agreement in 65% for SF, 74% for RB, but only 21% for FS and 45% for PGA. Most disagreement was by one category (median 81%, range 74-93). For inclusion criteria, at least 1 clinician would have included 41/96, but all agreed in only 17/41(41%). At least ¾ clinicians would have included 22 and excluded 67, so there was at least 25% disagreement in 26/96(27%) and 50% disagreement in 11/96(11%). 11% had FS score ≥2 but total score ≤5;9.1% had a total score >6 but a FS score <1. For remission,at least 1 clinician scored <2 in 43/96, but all agreed in only 20/ 43 (47%) and ¾ agreed in 35/43 (81%). Agreement was not significantly improved by a total score <1 (at least 1 = 39/96; all agree 20/39; ¾ agree 35/39). Conclusion:There is high variability in Mayo scoring between observers,despite good agreement on clinical category. Complete agreement between observers for recruitment to clinical trials or outcome occurs in <50% and ¾ agreement in about 80% patients. IOV should be considered when calculating the power of clinical trials.
W1203 Title: A Single-Center Experience with Methotrexate After Thiopurine Therapy in Pediatric Crohn Disease Brendan Boyle, Laura Mackner, Christina E. Ross, Soma Kumar, Jonathan Moses, Wallace Crandall BODY: Thiopurines are a common, effective means of maintaining remission in pediatric Crohn disease (CD). For those intolerant or unresponsive to thiopurines, maintenance therapy with methotrexate (MTX) may be considered. However, the use of MTX as maintenance therapy following thiopurine failure in pediatric CD is less established. The purpose of this study was to examine our experience using MTX as maintenance therapy in patients previously treated with thiopurines. METHODS: We identified all patients seen at Nationwide Children's Hospital from 2000-2007 with an ICD code indicative of CD. The chart of each patient was reviewed and patients with a confirmed diagnosis of CD, no current infliximab therapy, a history of thiopurine use prior to MTX, and at least 6 months of follow up after MTX initiation were included. Reason for thiopurine discontinuation, prior and concomitant therapies, physician global assessment (PGA), and screening laboratory studies were obtained at initiation. These outcomes were reevaluated at 6 and 12 months in addition to steroid/ infliximab free remission rate, steroid use, progression to infliximab, reason for MTX discontinuation, and adverse events (AE). RESULTS: Twenty-eight patients (17 male) with a mean age at diagnosis of 12.2 +/- 3.7 years and mean disease duration of 1.8 +/- 2.0 years were identified. Indications for MTX included non-response to 6MP/Aza (11), AE (15), and thiopurine non-adherence (2). At MTX initiation, 3 patients were in steroid free remission and eleven were receiving steroids. At 6 months, 14 of the original 28 patients (50%) were in steroid/infliximab free remission. Of 27 patients with evaluable date, 3 were receiving steroids, and 9 had begun infliximab therapy. Three had discontinued MTX secondary to non-response (2) or AE (1), and 1 did not have evaluable data. At 12 months, 11 of the original 28 patients (39.2%) were in steroid/infliximab free remission. Of the 24 with available data, six required steroids and 8 were treated with infliximab. Two additional patients had discontinued MTX due to non-response (1) or parental choice (1), and 3 had no evaluable data. Laboratory studies revealed three patients with transient leukopenia and 4 with transient transaminase elevation over the 12 month period. CONCLUSION: MTX can be effective as maintenance therapy for pediatric CD patients who were intolerant of, or unresponsive to 6MP/azathioprine, with 50% and 39.2% in steroid/infliximab free remission at 6 and 12 months. Approximately one-third of this cohort required escalation to biologic therapy within the first 12 months following MTX initiation. MTX was well tolerated.
W1206 Split-Dose Administration of 6-Mercaptopurine/Azathioprine: A Effective Novel Strategy for IBD Patients with Preferential 6mmp Metabolism David Q. Shih, Minh Nguyen, Patricio Ibañez, Lola Y. Kwan, Stephan R. Targan, Eric A. Vasiliauskas BACKGROUND and AIM: 6 Mercaptopurine (MP) and azathiopurine (AZA) are efficacious in treating IBD. Studies suggest that 6-thioguanine (6TGN) metabolite levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6MMP) levels are associated with risk of hepatotoxicity and possibly myelotoxicity. A subset of IBD patients exhibit preferential 6MMP production, characterized by disproportionate elevations in 6MMP, which may lead to side-effects of leucopenia, hepatoxicity, and flu-like symptoms. 6MMP overproduction and side-effects resolve with dose reduction but the lower dose often fails to suppress disease activity. We observed that splitting the daily dose of thiopurine (e.g. 50mg BID rather than 100mg once daily) can reduce 6MMP while maintaining 6TGN levels and clinical efficacy. The aim of this study is to review the outcomes of thiopurine split-dosing strategy in patients with preferential 6MMP metabolism. METHODS: A restrospective chart review
A-677
AGA Abstracts
AGA Abstracts
Portable Indirect Calorimetry (MedGem) in Pediatric Crohn's Disease Mark R. Corkins, Steven J. Steiner, Scott Denne