Emergency department utilisation for inflammatory bowel disease in the United States from 2006 to 2014.

BACKGROUND: Despite advances in treatment, patients with inflammatory bowel disease (IBD) frequently require emergency department (ED) visits and hospitalisations. AIMS: To analyse trends in ED visits and subsequent hospitalisations for IBD in the United States (US). METHODS: Data were analysed from the Nationwide Emergency Department Sample (NEDS) years 2006-2014. The NEDS is the largest all-payer ED database in the US, weighted to represent 135 million visits/year. IBD was identified using ICD-9 codes for Crohn's disease (CD) or ulcerative colitis (UC). Surgeries were identified using procedure codes. RESULTS: The frequency of IBD-ED visits increased 51.8%, from 90 846 visits in 2006 to 137 946 in 2014, which was statistically significant in linear regression. For comparison, all-case ED use between 2006 and 2014 increased 14.8%. In-patient hospitalisations from the ED decreased 12.1% for IBD (from 64.7% rate of hospitalisation from the ED in 2006 to 52.6% in 2014), with a UC:CD ratio of 1.2:1 in 2006 and 1.3:1 in 2014. Chi-square analysis revealed that this was a significant decrease. Surgery rates also showed a statistically significant decrease. The mean ED charge per patient rose 102.5% and the aggregate national cost of IBD-ED visits increased 207.5%. CD accounted for over twice as many visits as UC in both years. UC, age, male gender, highest income quartile, private insurance, Medicaid/Medicare, and tobacco use were associated with in-patient admissions. CONCLUSIONS: The number of ED visits due to IBD and associated charges have continued to rise, while the rates of in-patient hospitalisations referred from the ED and surgeries have decreased.

Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis.

BACKGROUND: Endoscopic and histologic healing are emerging as new therapeutic goals in ulcerative colitis (UC), as these endpoints are associated with less relapse, hospitalization and colectomy. AIM: To investigate the association of serum infliximab trough concentrations during maintenance therapy with endoscopic or histologic healing in UC. METHODS: In this multi-center retrospective cohort study, we included consecutive patients with moderate-to-severe UC on infliximab maintenance therapy who had an endoscopic evaluation and underwent therapeutic drug monitoring within three months of the colonoscopy, between February 2008 and March 2016. Per event analysis was performed. Endoscopic healing was defined as Mayo endoscopic sub-score of ≤1. Histologic healing was defined as no or only focal mild active inflammation. RESULTS: Seventy colonoscopies from 56 patients were evaluated. Infliximab trough concentrations (median [interquartile range]) were significantly higher in patients with endoscopic (11.3 [7.6-14.5] vs 6.3 [0-9.8] µg/mL, P < .001) or histologic (11.1 [6.7-14.5] vs 6.7 [0-9.9] µg/mL, P = .002) healing, respectively, compared to patients without healing. Receiver-operating characteristic analyses identified infliximab trough concentration thresholds of 7.5 (area under the curve [AUC]: 0.758) and 10.5 (AUC: 0.721) µg/mL to be associated with endoscopic and histologic healing, respectively. Multiple logistic regression analysis identified infliximab trough concentration ≥7.5 (P = .013; odds ratio [OR]: 4.3; 95% confidence intervals [CI]: 1.4-13.3) and ≥10.5 µg/mL (P = .013; OR: 3.8; 95% CI: 1.3-11) as independent factors associated with endoscopic and histologic healing, respectively. CONCLUSIONS: This study demonstrated that infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in patients with UC.

A rare case series of concomitant inflammatory bowel disease, sporadic adenomas, and serrated polyposis syndrome.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas further increasing their risk of colorectal cancer. Current knowledge of IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe four patients with both IBD and SPS. METHODS: Four patients with inflammatory bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical Center meeting the World Health Organization (WHO) criteria for SPS were identified. RESULTS: Four patients with long standing IBD involving the colon were identified. All of these patients' IBD were in clinical remission. Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each patient was also found to have multiple sessile serrated adenomas and hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had colonoscopy with chromoendoscopy which improved polyp detection. Discussions were held with each patient regarding the potentially increased risk of colorectal cancer with the combination of IBD and SPS. Patients were advised that colectomy would be the safest method to reduce the risk of cancer. None of the patients opted for colectomy and instead planned on a repeat colonoscopy with chromoendoscopy at 3-12 month intervals. CONCLUSION: Serrated polyposis syndrome develops in patients with IBD. It is unclear how high the risk of colon cancer is in patients who have both IBD and SPS and what the recommendations should be regarding the frequency of surveillance or surgery. Further studies are necessary to identify the optimal management of these patients.

The use of pharmacological prophylaxis against venous thromboembolism in hospitalised patients with severe active ulcerative colitis.

BACKGROUND: Hospitalised patients with inflammatory bowel disease are 1.5- to 3.5-fold more likely to develop venous thromboembolism compared to controls. Clinical guidelines recommend pharmacological prophylaxis. AIM: To determine the rate of pharmacological venous thromboembolism prophylaxis prescription and administration in a cohort of hospitalised patients with severe active ulcerative colitis and to assess predictors of failure to order pharmacological prophylaxis at 24 h. METHODS: This is a retrospective review of hospitalised patients with severe active ulcerative colitis, identified by ICD-9-CM discharge code 556.x, admitted to a single tertiary care hospital from 1 January 2005 to 31 August 2012. Adequate thromboembolism prophylaxis was defined as an order for low-dose unfractionated heparin two to three times daily, low-molecular weight heparin 40 mg daily or fondaparinux 2.5 mg daily ordered and administered for >80% of the admission. Patient related factors associated with failure to order prophylaxis at 24 h were accessed as secondary outcomes. RESULTS: Three hundred and thirty-six patients were hospitalised with severe active ulcerative colitis. Hospitalists had prescribed appropriate pharmacological prophylaxis by 48 h in only 37% of cases. Of these, nurses administered all prescribed doses in 18% of cases. Only 7% of patients (22/304, 95% CI: 5-11%) received adequate pharmacological prophylaxis for >80% of their hospitalisation. Hematochezia (P = 0.002), elevated platelets (P = 0.008), male gender coupled with younger age (P = 0.005) and admission on a biologic (P = 0.03) were associated with failure to order prophylaxis. CONCLUSION: Hospitalised patients admitted with severe active ulcerative colitis are not receiving appropriate pharmacological venous thromboembolism prophylaxis.

Systematic review: the quality of the scientific evidence and conflicts of interest in international inflammatory bowel disease practice guidelines.

BACKGROUND: Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes. AIM: We examined inflammatory bowel disease guidelines (IBD) for quality of evidence, methods of grading evidence and conflicts of interest (COI). METHODS: All 182 guidelines published by the American College of Gastroenterology, American Gastroenterological Association, British Society of Gastroenterology, Canadian Association of Gastroenterology, Crohn's and Colitis Foundation of America and European Crohn's and Colitis Organisation as of 27 September 2012 were reviewed. Nineteen IBD guidelines were found. RESULTS: Eighty-nine per cent (n = 17/19) of the guidelines graded the levels of evidence using seven different systems. Of the 1070 recommendations reviewed, 23% (n = 249) cited level A evidence; 28% (n = 302) level B; 36% (n = 383) level C and 13% (n = 136) level D. The mean age of the guidelines was 4.2 years. In addition, 61% (n = 11/19) of the guidelines failed to comment on COI. All eight articles commenting on COI had conflicts with 81% (n = 92/113) of authors reported an average 11.7 COI. Lastly, there were variations in the recommendations between societies. CONCLUSIONS: Nearly half the IBD guideline recommendations are based on expert opinion or no evidence. Majority of the guidelines fail to disclose any COI, and when commenting, all have numerous COI. Furthermore, the guidelines are not updated frequently and there is a lack of consensus between societal guidelines. This study highlights the critical need to centralize and redesign the guidelines development process.

The Crohn's disease activity index (CDAI) is similarly elevated in patients with Crohn's disease and in patients with irritable bowel syndrome.

BACKGROUND: While the Crohn's disease activity index (CDAI) is the gold standard for defining clinical endpoints in Crohn's disease (Crohn's) clinical trials, its ability to distinguish symptoms due to inflammation from those that are non-inflammatory has been questioned. AIM: To compare CDAI scores in patients with Crohn's and those with Irritable Bowel Syndrome (IBS). METHODS: This was a prospective, cross-sectional cohort study of 91 patients with either Crohn's (n = 44) or IBS (n = 47). Total CDAI and individual component scores were recorded and comparisons were made between Crohn's and IBS patients. RESULTS: Mean CDAI scores were higher in the IBS patients (183 vs. 157, P = 0.1). Sixty-two per cent (n = 29) of IBS patients had CDAI scores greater than 150. Mean CDAI haematocrit score (35.9 vs. 23.0, P = 0.02) and CRP level (6.8 vs. 2.0, P = 0.002) were higher in the Crohn's group. Analysis of CDAI sub-scores demonstrated that IBS patients had significantly higher pain (mean 1.7 vs. 0.8, P = 0.0007) and well-being scores (mean 1.2 vs. 0.8, P = 0.04) relative to patients with Crohn's. Specifically evaluating patients with CDAI greater than 150 (n = 51), IBS patients had higher pain sub-scores (mean 2.4 vs. 1.4, P = 0.002), whereas patients with Crohn's had higher CRP (mean 8.4 vs. 1.8, P = 0.001). CONCLUSIONS: Our study demonstrates that the CDAI does not discriminate patients with symptoms due to active Crohn's from patients with IBS. Patients with IBS can have CDAI scores in the clinically meaningful range. Objective measures, such as CDAI haematocrit score and CRP, are more specific markers of inflammation.

Setting priorities for comparative effectiveness research in inflammatory bowel disease: results of an international provider survey, expert RAND panel, and patient focus groups.

BACKGROUND: Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). METHODS: Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. RESULTS: Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. CONCLUSIONS: We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies.

Outcomes after escalation of infliximab therapy in ambulatory patients with moderately active ulcerative colitis.

BACKGROUND: Infliximab (IFX) therapy escalation during maintenance treatment occurs frequently in clinical practice in patients with ulcerative colitis (UC). Outcomes for these patients have not been described. AIM: To describe the prevalence of, and outcomes after, IFX escalation during maintenance therapy in patients with moderate-severe UC. METHODS: Retrospective observational study of clinical outcomes in ambulatory patients with moderate-severe UC treated with maintenance IFX. RESULTS: Fifty-six ambulatory patients received IFX for moderate-severe UC; fifty (89%) responded and proceeded to maintenance therapy. Mean duration of maintenance therapy was 14 months, with mean follow-up of 38 months. Twenty-seven patients (54%) required IFX therapy escalation after a mean of six maintenance infusions. Clinical remission was noted in 36% of the entire cohort (18/50) at 12 months; 19% in the escalation group and 56% in the non-escalation group. Patients who required IFX escalation were less likely to be in clinical remission at 12 months (OR 0.2, 95% CI 0.1-0.6, P = 0.01) when compared with those who did not. During the follow-up period, 27% of patients required a colectomy, and the mean time to colectomy was 17 months. Patients in the escalation group required a colectomy in 33% of cases, compared with 21% of non-escalation patients. CONCLUSIONS: A significant proportion of ambulatory patients with UC treated with maintenance infliximab required therapy escalation over time. This was associated with lower remission, and higher colectomy, rates.

Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature.

BACKGROUND Anti-tumour necrosis factor (TNF) antibodies are used to treat both psoriasis and inflammatory bowel disease. The seemingly paradoxical occurrence of psoriasis in patients treated with anti-TNF antibodies is increasingly recognised, but the distinct features associated with inflammatory bowel disease have been incompletely characterised. AIM To identify inflammatory bowel disease patients who developed psoriasis while receiving an anti-TNF antibody at two academic medical centres between 2000 and 2009 and review all published cases of this phenomenon in inflammatory bowel disease. METHODS We identified retrospectively all cases of anti-TNF-induced psoriasis in inflammatory bowel disease patients attending two North American healthcare centres. We analysed these cases alongside the published reports of anti-TNF-induced psoriasis. RESULTS We identified 30 subjects who developed a psoriatic rash while receiving anti-TNF therapy for inflammatory bowel disease. Forty-seven per cent (14/30) responded to topical therapy and 23% (7/30) ultimately discontinued the anti-TNF. The new data were combined with those from 120 published cases of anti-TNF-induced psoriasis in inflammatory bowel disease. Anti-TNF-induced psoriasis in inflammatory bowel disease was more common in women (70%). The most common distributions were palmoplantar (43%) and scalp (42%). Complete follow-up in 148 cases showed that 41% responded to topical therapy but 43% required definitive withdrawal of anti-TNF therapy due to the rash. A second anti-TNF was tried in 27 cases with recurrence or persistence of the rash in 14 (52%). CONCLUSIONS In this analysis, psoriasiform lesions related to anti-TNF therapy in inflammatory bowel disease occurred most commonly in women. Approximately 41% of those who developed psoriasis while on anti-TNFs responded to topical therapy and were able to continue the drug, while 52% of those treated with an alternate anti-TNF had recurrence of the rash.

Meta-analysis: targeting the intestinal microbiota in prophylaxis for post-operative Crohn's disease.

BACKGROUND: Enteric bacteria play an important early role in the pathogenesis of Crohn's disease. AIM: To perform a meta-analysis of trials testing antibiotics or probiotics for prevention of post-operative recurrence of Crohn's disease. METHODS: Review of all randomized controlled trials comparing antibiotics or probiotics with placebo in prevention of endoscopic or clinical recurrence of Crohn's disease after surgical resection. Fixed-effect meta-analysis was performed with dichotomous data summarized using relative risk with 95% confidence intervals, where appropriate. RESULTS: Seven studies were identified as suitable for inclusion (two comparing antibiotics with placebo, five comparing probiotics with placebo). The use of nitroimidazole antibiotics (metronidazole, ornidazole) reduced the risk of clinical (RR 0.23; 95% CI 0.09-0.57, NNT = 4) and endoscopic (RR 0.44; 95% CI 0.26-0.74, NNT = 4) recurrence relative to placebo. However, these agents were associated with higher risk of adverse events (RR 2.39, 95% CI 1.5-3.7) and patient withdrawal. Probiotic administration was not associated with any significant difference in risk of recurrence compared with placebo. CONCLUSIONS: Nitroimidazole antibiotics are effective in the prevention of post-operative Crohn's disease recurrence, but their side-effects limit acceptability. Probiotics have failed to show efficacy for post-operative prophylaxis, but may merit further study.

The impact of infliximab infusion reactions on long-term outcomes in patients with Crohn's disease.

BACKGROUND: Little is known about long-term outcomes in patients who experience infusion reactions while receiving infliximab. AIM: To investigate long-term outcomes in patients who experience infusion reactions while receiving infliximab. METHODS: Retrospective electronic chart review of long-term clinical outcomes. RESULTS: Clinical data on 287 patients who received infliximab infusions for Crohn's disease were reviewed, of whom 51 developed at least one infusion reaction (18%). Ileo-colonic disease (OR 2.2, 95% CI 1.1-4.4) and episodic infliximab (OR 2.4, 95% CI 1.2-4.7) were associated with a higher risk of infusion reactions in univariate analysis, but concomitant azathioprine/mercaptopurine therapy at the initiation of infliximab was associated with a reduced risk (OR 0.4, 95% CI 0.2-0.8). Only the effect of concomitant immunomodulators persisted on multivariate analysis. Patients who experienced infusion reactions were less likely to be in remission at 1 year (OR 0.6, 95% CI 0.3-1.2), 2 years (OR 0.4, 95% CI 0.2-0.8, P = 0.01), or 5 years (OR 0.4, 95% CI 0.1-1.3) and more likely to require surgery (OR 2.2, 95% CI 1.1-4.1, P = 0.01) than those who did not experience such reactions. CONCLUSIONS: Patients who experienced infusion reactions to infliximab had a high rate of discontinuation of therapy in this cohort. Concomitant immunomodulators and maintenance therapy reduced the risk of infusion reactions.