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Background and Study Aims: Bowel-cleansing studies are frequently underpowered, poorly designed, and with subjective assessments. Consensus on tolerability of the bowel-cleansing agents is thus lacking. This study developed and validated a bowel-preparation tolerability questionnaire and used it to assess the tolerability of three bowel-cleansing agents, sodium phosphate (NaP), polyethylene glycol (PEG), and sodium picosulphate (Pico), in a prospective randomized single-blinded trial of ambulatory patients. Patients and Methods: The bowel-preparation tolerability questionnaire was validated in 125 consecutive patients and then bowel-preparation agent tolerability was assessed in 634 patients in a prospective randomized single-blinded trial. Results: The questionnaire's internal consistency was satisfactory with good to excellent 'test-retest' reliability for aggregate tolerability and visual analogue scores. Validity assessment confirmed it as reliable and accurate. Of 634 patients, 97.8 % took >75 % of the allocated preparation and 98.9 % completed the questionnaire. Overall, Pico was better tolerated than PEG ( p < 0.001) and NaP ( p < 0.001). NaP was better tolerated than PEG ( p < 0.001). Regardless of the bowel-preparation agent used, males tolerated them better than females ( p = 0.009) as did patients having their procedure in the AM. Older patients, however, tolerated all preparations better than younger patients ( p = 0.006). Conclusions: This study used the first validated bowel-preparation tolerability questionnaire and identified that age, sex, and procedure time all impacted tolerability. Overall, Pico was best tolerated, but PEG's tolerability in patients ≥60 years was equal to that of Pico and NaP, suggesting that PEG can be recommended for older patients to avoid the electrolyte disturbances associated with the osmotic preparations. [ABSTRACT FROM AUTHOR]

Background and study aims: Bowel-cleansing studies are frequently underpowered, poorly designed, and use subjective bowel cleansing assessments. Consensus on efficacy, tolerability, and preparation-induced mucosal abnormalities is lacking. This study aimed to clarify the differences in efficacy and preparation-induced mucosal inflammation of sodium phosphate (NaP), colon- LYTLEY (PEG), and Picoprep (Pico). Patients and methods: This was a prospective randomized single-blinded trial of ambulatory patients to assess the efficacy of bowel preparation and preparation-induced mucosal inflammation. Proceduralists who were blinded to the preparation taken, assessed both bowel cleansing by using the Ottawa bowel preparation assessment tool and preparation-induced mucosal inflammation. Results: Of the 634 patients, 98% ingested more than 75% of the bowel preparation and data were complete for colonic preparation scoring in 99%. The preparation used, time of procedure, and patient sex all independently impacted on bowel cleansing. NaP was less efficacious than PEG (P < 0.001) and Pico (P < 0.001) for morning procedures whereas all bowel preparations were equally efficacious for afternoon procedures. Preparation-induced mucosal inflammation was 10-fold greater with NaP (P = 0.03) and Pico (P = 0.03) compared with PEG. Conclusions: This is the largest published prospective randomized blinded study on this topic and the first to evaluate the three major classes of preparation with a validated tool. The bowel preparation used, time of procedure, and patient sex all independently impacted on bowel cleansing. NaP gave the worst preparation for morning procedures whereas all preparations were equally effective for afternoon procedures. NaP and Pico induced mucosal inflammation 10-fold more frequently than PEG, a finding that requires further investigation. [ABSTRACT FROM AUTHOR]

Background Treatment options for fistulizing Crohn's disease (CD) are limited. Aim To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. Methods Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ⩾100-point decrease from baseline in the Crohn's Disease Activity Index. Nonresponders (50 / 108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. Results The majority of patients (55 / 58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol-defined fistula closure (⩾50% closure at two consecutive post-baseline visits ⩾3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. Conclusion Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo. [ABSTRACT FROM AUTHOR]

Background Resistant ulcerative proctitis can be extremely difficult to manage. Oral tacrolimus can be effective, but may have numerous adverse effects. Topically administered tacrolimus, however, may also be effective in proctitis. Aim To undertake a pilot study to assess a potential role for topical tacrolimus in the management of resistant ulcerative proctitis. Methods Patients with resistant ulcerative proctitis were assessed prospectively by the colitis activity index (CAI) and Modified Mayo score. Topical rectal tacrolimus ointment was commenced at 0.3 mg/mL 3 mL b.d. and increased depending on clinical response. CAI and modified Mayo scores were assessed at 0 and 8 weeks, as were steroid usage and adverse effects. Results Eight patients (five male/three female) with inflammation to a maximum of 30 cm from the anus were included. All patients had failed disease control with 5-aminosalicylic acids, steroids, immunosuppressants and infliximab therapy. The mean initial CAI was 12.1 (range 9–16) and the mean modified Mayo score was 8.0 (range 6–9). After 8 weeks, six of eight patients achieved remission with steroids reduced or ceased in five of six. There were no significant adverse effects. Conclusions This prospective pilot study demonstrated that topical rectal tacrolimus ointment can be effective in ulcerative proctitis. The preparation was well tolerated with no significant adverse effects. Further controlled studies are required. [ABSTRACT FROM AUTHOR]

In this article, the author reflects on the importance of validating genetic profiles in inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC). Topics discussed include diagnosis of inflammatory disorders with the help of serological testing with antineutrophil cytoplasmic antibody (ANCA), incorporation of genes to differentiate between controls CD and UC patients and information on how to distinguishing between UC and CD.

Background Current models of care for ulcerative colitis ( UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. Aims This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. Methods Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. Results Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. Conclusion Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non-specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed. [ABSTRACT FROM AUTHOR]

Background Acute severe ulcerative colitis ( ASUC) is a potentially life-threatening complication of ulcerative colitis. Aim To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. Methods Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. Results Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. Conclusion These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments. [ABSTRACT FROM AUTHOR]

Background Many patients with active Crohn's disease do not adequately respond to therapies, highlighting the need for new treatments. Aims To conduct a randomised, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of vercirnon, an oral inhibitor of CC chemokine receptor-9, for the treatment of patients with moderately-to-severely active Crohn's disease. Methods Patients with a Crohn's Disease Activity Index ( CDAI) of 220-450, plus evidence of active disease (endoscopically confirmed or elevation of both C-reactive protein and faecal calprotectin), who had failed corticosteroid or immunosuppressant therapy were enrolled. Patients were equally randomised to receive placebo, vercirnon 500 mg once daily or vercirnon 500 mg twice daily. The primary endpoint was clinical response, defined as a 100-point decrease in CDAI from baseline to week 12. Results Six hundred and eight patients were randomised. Patient characteristics and baseline demographics were similar among the groups. The proportions of patients achieving a clinical response were 25.1%, 27.6% and 27.2% for placebo, once daily and twice daily respectively; treatment differences were not significant (2.5%; 95% confidence interval, CI −6.1% to 11.0%, P = 0.546 for once daily vs. placebo, and 2.1%; 95% CI −6.5% to 10.7%, P = 0.648 for twice daily vs. placebo). Adverse events were reported in 69.8%, 73.3% and 78.1% with serious adverse events in 8.9%, 5.9%, and 6.0% of patients in the placebo, once-daily and twice-daily groups, respectively. Conclusions We did not demonstrate efficacy of vercirnon as an induction therapy in patients with moderately-to-severely active Crohn's disease; its effect in maintenance therapy was not addressed. [ABSTRACT FROM AUTHOR]

Background Crohn's disease recurs in the majority of patients after intestinal resection. Aim To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. Methods As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. Results A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). Conclusions In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence. [ABSTRACT FROM AUTHOR]

Background 'Dose tailoring' of anti-tumour necrosis factor alpha ( TNF-α) therapy in Crohn disease ( CD), by dose escalation, or shortening of dosing intervals, has been suggested to regain clinical response following a flare in a proportion of patients. However, reported outcome data are sparse and none exists from Australia. Method In an observational multicentre, retrospective study, the impact of anti- TNF-α dose tailoring on corticosteroid use, the need for surgery and physician perception of clinical efficacy was examined in a real-world setting at six Australian adult teaching hospitals. Demographics, disease characteristics, medications, indication for and duration of dose tailoring were documented. Results Fifty-five CD patients were identified as requiring dose tailoring and secondary loss of response was the indication in 96%. Either adalimumab (64%) or infliximab (36%) was dose escalated for a median of 5 months (range 1-47), with a median of 20 months follow up (range 3-65). At 3 months, dose tailoring reduced the mean number of days on high-dose corticosteroids (45 vs 23, P = 0.01). Most (78%) patients remained resection free, and 73% of physicians reported good clinical efficacy of dose tailoring. Of those who de-escalated therapy due to induction of remission, long-term (>12 months) follow up and complete data on steroid use were available in 15/28, with 12/15 (80%) remaining steroid free at 1 year. Conclusion Short-term dose tailoring regains disease response in the majority of patients with CD. Of these, most will remain free of corticosteroids at 1 year after de-escalating therapy. [ABSTRACT FROM AUTHOR]