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Summary: Background: The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown. Aims: To evaluate the operating properties of instruments used to assess BP quality in patients with CD. Methods: We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100‐mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES‐CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within‐patient correlation between instruments and the visual analogue scale using mixed‐effect models. The correlation between BP quality and SES‐SD scores was assessed using Spearman's rho. Results: Inter‐ and intra‐rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter‐rater reliability ICC ≥0.41). The visual analogue scale had substantial inter‐ and almost perfect (ICC ≥0.81) intra‐rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated. Conclusion: Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD. [ABSTRACT FROM AUTHOR]

Summary: Background: Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. Aims: To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. Methods: We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. Results: For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid‐dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti‐tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild‐to‐moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. Conclusion: Methotrexate is effective at inducing and maintaining remission in steroid‐refractory Crohn's disease and can reduce anti‐TNF‐induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first‐line conventional option for the treatment of mild‐to‐moderate Crohn's disease. [ABSTRACT FROM AUTHOR]

Summary: Background: Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross‐sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri‐enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. Aims: To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. Methods: We searched four databases up to 6 January 2024. Two‐stage screening was done in duplicate. We assessed risk of bias using QUADAS‐2. Results: There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. Conclusions: This systematic review is the first step for a structured program to develop a stricture IUS index for CD. [ABSTRACT FROM AUTHOR]

Summary: Background: Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. Aim: To assess the efficacy of medical treatments for UP. Methods: We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. Results: We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First‐line therapies included topical 5‐aminosalicylic acid (5‐ASA), conventional corticosteroids, budesonide, and oral 5‐ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5‐ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94–3.82) and maintenance of remission (RR 2.09, 95% CI 1.26–3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62–4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44–3.81). Combination therapy with topical 5‐ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2–18.49) and maintenance of remission (RR 2.08, 95% CI 1.31–3.32). Conclusions: Topical 5‐ASA and corticosteroids are effective for active UP. Topical 5‐ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under‐represented population. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis. Methods: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis. Results: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88–2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51–2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty‐five percent (34/40) of De Simone Formulation participants maintained remission at 9–12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86–88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty‐one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27–8.08, moderate certainty evidence). Prophylaxis: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02–2.21, moderate certainty evidence). Conclusions: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain. [ABSTRACT FROM AUTHOR]

Summary: Background: Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials. Aims: The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC. Methods: EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo‐controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random‐effects models. Stratified analyses based on disease‐ and trial‐level characteristics, leave‐one‐out meta‐analysis, and cumulative meta‐analysis were performed. Results: Twelve RCTs enrolling a total of 391 patients (placebo n = 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%–38.4%), I2 = 60.8%, p < 0.01, and 19.9% (95% CI: 5.3%–39.0%), I2 = 66.4%, p = 0.01 (tests for heterogeneity), respectively. Clinical response to placebo was numerically higher in patients with lymphocytic compared to collagenous colitis (39.9% vs. 19.8%, p = 0.08). Heterogeneity in clinical response to placebo was significantly reduced when the Miehlke 2014 RCT was excluded in the leave‐one‐out meta‐analysis or when a more stringent secondary definition of response based on the Hjortswang criteria was applied. Conclusions: Approximately one‐quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo. [ABSTRACT FROM AUTHOR]

Summary: Background: There are no data to assess the value associated with a treat‐to‐target (T2T) strategy based on tight control of mild–moderate ulcerative colitis (UC). Aim: To assess the cost‐effectiveness of a T2T approach based on the normalisation of clinical signs and faecal calprotectin (FC) Methods: A decision analytical Markov model was developed to compare T2T algorithm combining clinical symptoms and FC levels to define treatment response and the possible switch to the next treatment line (T2T‐FC), and the reference strategy based only on symptoms. The model included five treatment lines and was conducted from the Italian national health service (NHS) perspective using a 3‐year time horizon. The model calculated the incremental cost‐effectiveness ratio as € per relapse avoided. Deterministic and probabilistic sensitivity analyses were conducted. Results: The cost‐effectiveness analysis produced an increased time spent by a patient in clinical remission and FC ≤ 100 level (+0.177 years; about 2 months) and a decreasing number of relapses (−0.1937; −20.9%) per patient using a T2T‐FC approach compared to only symptoms. Furthermore, the T2T‐FC was associated with higher cost (+€1795). The ICER estimated was €9263 per relapse avoided. These results were confirmed by sensitivity analyses. Conclusions: T2T‐FC approach resulted in a higher benefit for mild–moderate UC patients in terms of time in remission and incidence of relapse but was associated with higher costs. Clinical trials and real‐world clinical studies are needed to provide additional data on the cost–benefit of this approach. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Aliu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17988 and https://doi.org/10.1111/apt.18031. [ABSTRACT FROM AUTHOR]

Summary: Background: It is unclear whether improvement in patient‐reported outcomes (PROs) relative to baseline symptom burden in Crohn's disease (CD) is associated with subsequent endoscopic remission. Aim: To evaluate the relationship between dominant PRO resolution post‐induction and achievement of clinical and endoscopic remission. Methods: This post‐hoc analysis of clinical trial data from 251 participants evaluated the relationship between the resolution of the dominant PRO (most severely elevated baseline PRO) or clinical response (CDAI ≥100 reduction) after induction therapy with biologics (post‐induction) and 1‐year clinical remission (CDAI <150) and/or endoscopic remission (SES‐CD <3). Multivariate logistic regression models evaluated the relationship between post‐induction‐dominant PRO resolution and 1‐year outcomes adjusted for confounders. Results: Participants with dominant PRO resolution post‐induction had higher odds of combined endoscopic and clinical remission compared to those without resolution (aOR: 1.94 [95% CI: 1.01–3.74], P = 0.047). Combining dominant PRO resolution with post‐induction endoscopic response (SES‐CD ≥50% reduction) was associated with higher odds of 1‐year endoscopic and clinical remission (aOR: 6.89 [95% CI: 1.65–28.72], P = 0.008). Clinical and PRO2 response (≥30% decrease in stool frequency and/or ≥30% decrease in abdominal pain score and both not worse than baseline) at post‐induction did not predict these outcomes. No significant differences were observed with 1‐year endoscopic remission for post‐induction‐dominant PRO resolution, clinical or PRO2 response. Conclusions: Post‐induction resolution of dominant PRO, but not clinical or PRO2 response, was strongly associated with 1‐year endoscopic and clinical remission. Resolution of dominant baseline PRO after induction therapy may be informative for 1‐year outcomes. Further validation is required. [ABSTRACT FROM AUTHOR]

Summary: Background: Accurate estimates for the risk of COVID‐19 in IBD, and an understanding of the impact of COVID‐19 on IBD course and the risk of incident post‐infectious IBD are needed. Aims: To estimate the risk of COVID‐19 in IBD and study its impact on IBD course and the risk of incident post‐infectious IBD. Methods: A retrospective propensity score matched cohort study utilising multi‐institutional research network TriNetX. COVID‐19 patients with and without IBD were identified to quantify the risk of COVID‐19 in patients with IBD, COVID‐19 outcomes in patients with IBD and the impact of COVID‐19 on IBD disease course. The risk of incident post‐infectious IBD in COVID‐19 patients was compared to the population not infected with COVID‐19 during a similar time period. Results: Incidence rate ratio for COVID‐19 was lower in IBD patients compared to the non‐IBD population (0.79, 95% CI: 0.72‐0.86). COVID‐19‐infected patients with IBD were at increased risk for requiring hospitalisation compared to non‐IBD population (RR: 1.17, 95% CI: 1.02‐1.34) with no differences in need for mechanical ventilation or mortality. Patients with IBD on steroids were at an increased risk for critical care need (RR: 2.22, 95% CI: 1.29‐3.82). Up to 7% of patients with IBD infected with COVID‐19 suffered an IBD flare 3‐months post‐infection. Risk for incident IBD post‐COVID was lower than that seen in the non‐COVID population (RR: 0.64, 95% CI: 0.54‐0.65). Conclusion: We observed no increase in risk for COVID‐19 amongst patients with IBD or risk for de novo IBD after COVID‐19 infection. We confirmed prior observations regarding the impact of steroid use on COVID‐19 severity in patients with IBD. [ABSTRACT FROM AUTHOR]

Summary: Background: Although there is interest in developing pharmacotherapies for the treatment of immune checkpoint inhibitor‐associated enterocolitis (ICIC), there is currently no consensus on how to optimally measure disease activity in this condition. Aims: To identify all scoring indices used for the measurement of disease activity in ICIC, assess their operating properties, and explore their potential utility as outcome measures. Methods: We searched MEDLINE, EMBASE and the Cochrane Library from inception to November 2020 to identify studies that evaluated disease activity and severity in patients with ICI‐associated enterocolitis. These scoring tools could be designed specifically for ICIC or adapted from other diseases, and assessed clinical, endoscopic, or histologic disease activity. Results: Sixty‐four studies were included. The Common Terminology Criteria for Adverse Events is commonly used to describe symptoms, although has only been partially validated and was not designed as a disease activity index. Endoscopic and histologic indices used in inflammatory bowel disease have been adopted for ICIC including the Mayo Endoscopic Subscore, Ulcerative Colitis Endoscopic Index of Severity, Simple Endoscopic Score for Crohn's Disease, Nancy Histological Index, Robarts Histopathological Index, and Geboes Score, among others. None of these indices has been validated for use in ICIC, and all lacked content validity and responsiveness. Conclusions: There are no validated clinical, endoscopic, or histologic outcomes to assess disease activity in ICIC. Development and validation of reliable and responsive outcome measures that can be used to measure disease activity will be paramount for both clinical practice and for the development of treatments. [ABSTRACT FROM AUTHOR]

Summary: Background: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn's disease (CD). However, there is no widely accepted luminal disease activity index. Aims: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials. Methods: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1‐9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting. Results: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions. Conclusions: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed. [ABSTRACT FROM AUTHOR]

Summary: Background: The optimal ulcerative colitis biopsy protocol is unclear. Aim: To evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitis Methods: Biopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4‐biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item‐level ratings from four biopsies, was compared to 1‐, 2‐ and 3‐biopsy estimates. Agreement was determined using bivariate errors‐in‐variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed. Results: Forty‐six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2‐biopsy (tolerance interval: −7.66, 4.79) and 3‐biopsy (tolerance interval: −4.86, 3.46) RHI scores demonstrated acceptable agreement with 4‐biopsy scores. One‐biopsy scores demonstrated unacceptable agreement (tolerance interval: −13.99, 7.78). Mean RHI scores using the 2‐, 3‐ and 4‐biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1‐biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2‐, 3‐ and 4‐biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1). Conclusions: A minimum of two — conservatively, three — biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice. [ABSTRACT FROM AUTHOR]

Summary: Background: Clinical remission is the recommended treatment target in ulcerative colitis. The predictors and outcomes of achieving histologic remission within a treat‐to‐target paradigm are not well established. Aim: To evaluate the predictors and outcomes of achieving histologic remission in patients with ulcerative colitis treated‐to‐target of endoscopic healing (modified Mayo endoscopy score 0 or 1). Methods: We conducted a retrospective cohort study in adults with active ulcerative colitis (modified Mayo endoscopy score 2 or 3), whose treatment was iteratively optimised to achieve endoscopic healing. We identified predictors of achieving histologic remission, and outcomes (risk of symptomatic relapse, and ulcerative colitis‐related hospitalisation and/or surgery) of achieving histologic remission vs persistent histologic activity, using Cox proportional hazard analysis. Results: Of the 411 patients with clinically active ulcerative colitis, 270 achieved endoscopic healing. Of the 270 patients, 55% simultaneously achieved histologic remission. Depth of endoscopic healing at final endoscopic assessment was the only independent determinant of histologic remission (modified Mayo endoscopy score 0 vs 1: odds ratio, 0.31 [95% confidence intervals, 0.18‐0.52]). Over 28 months, achieving histologic remission was associated with a lower risk of clinical relapse (1‐year cumulative risk: 18.7% vs 29.5%; adjusted hazard ratio, 0.56 [0.37‐0.85]), and lower risk of hospitalisation (hazard ratio, 0.44 [0.20‐0.94]). The incremental benefit of achieving histologic remission was observed only in patients achieving Mayo endoscopy score 1, but not Mayo endoscopy score 0. Conclusions: In patients with active ulcerative colitis treated‐to‐target of endoscopic healing, 55% simultaneously achieved histologic remission. Histologic remission, particularly in patients achieving modified Mayo endoscopy score 1, was associated with favourable outcomes. Treating to a target of histologic remission over endoscopic healing requires prospective evaluation. [ABSTRACT FROM AUTHOR]

Summary: Background: Whilst continuation of 5‐aminosalicylates (5‐ASA) after escalation to biologic therapy is considered ineffective in patients with ulcerative colitis (UC), their role in patients escalated to anti‐metabolites is unclear. Aim: To compared patterns and outcomes of continuing vs stopping 5‐ASA in patients with UC who escalated to anti‐metabolite monotherapy, using a de‐identified administrative claims database. Methods: We identified patients with UC who were new users of anti‐metabolite monotherapy who were receiving 5‐ASA, and were followed for at least 12 months after starting anti‐metabolite therapy. We evaluated patterns of 5‐ASA use (stopped 5‐ASA, short‐term 5‐ASA use for <6 months after starting anti‐metabolites, persistent 5‐ASA use for >6 months after starting anti‐metabolites). We compared outcomes (risk of UC‐related hospitalisation and/or surgery, need for corticosteroids, treatment escalation to biologic therapy) by pattern of 5‐ASA use, using Cox proportional hazard analysis adjusting for age, sex, race, comorbidity burden, and hospitalisation or emergency department visit, abdominal surgery and corticosteroid use in the previous 12 months (as measures of disease severity), with a 12‐month immortal time period. Results: Of 4068 patients with UC who were new‐users of anti‐metabolite monotherapy, 578 (14.2%), 782 (19.2%) and 2708 (66.6%) stopped 5‐ASA, used 5‐ASA transiently or persistently, respectively. Compared to patients who stopped 5‐ASA after starting anti‐metabolites, persistent 5‐ASA use was associated with a higher risk of UC‐related hospitalisation (HR, 1.40 [1.07‐1.83]) and corticosteroid use (HR, 1.48 [1.28‐1.70]), without an increase in risk of UC‐related surgery (HR, 1.32 [0.86‐2.00]) or treatment escalation (HR, 0.80 [0.53‐1.20]). Sensitivity analyses using a 3 months window after initiation of anti‐metabolites to classify patients as continuing vs stopping 5‐ASA showed similar results. Residual confounding by disease severity could not be excluded. Conclusion: 5‐ASA are usually continued long‐term even after escalating to anti‐metabolite therapy in patients with UC without clinical benefit. [ABSTRACT FROM AUTHOR]

Summary: Background: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). Aim: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. Methods: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. Results: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%‐41.3%) and 18.5% (95% CI: 8.3%‐36.2%), respectively over a median follow‐up of 23 months (range 5.5‐105.8), and 21.8 months (range 5‐47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%‐77.3%) over a median follow‐up of 21.8 months (range 5‐47). Conclusions: There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: Patient‐reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies. Aims: To develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research). Methods: Concept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi‐structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status. Results: In all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31‐item Symptoms and Impacts Questionnaire for CD (SIQ‐CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29‐item Symptoms and Impacts Questionnaire for UC (SIQ‐UC) was developed. Both instruments include four symptom and six impact domains. Conclusions: We developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing. [ABSTRACT FROM AUTHOR]

Summary: Background: A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease. Aim: To assess the utility of this CDST for predicting exposure‐efficacy and disease outcomes. Methods: Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST‐defined response groups (low, intermediate and high). Results: A linear relationship existed between CDST‐defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST‐defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high‐probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high‐intermediate and low‐probability groups within GETAID were no longer significant when including low‐probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low‐ to intermediate‐probability vs high‐probability patients (adjusted HR 2.06, 95% CI 1.33‐3.21). Conclusions: We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure‐efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment targets for ulcerative colitis are evolving towards achievement of endoscopic improvement and remission in addition to symptom resolution. It remains to be accurately quantified what proportion of patients with symptom resolution have residual endoscopic activity that might warrant treatment modification. Aim: To quantify the prevalence of endoscopic improvement and remission amongst ulcerative colitis patients with various permutations of patient‐reported outcomes. Methods: Individual participant data from active intervention and placebo arms of clinical trials of infliximab, golimumab, vedolizumab and tofacitinib were pooled to estimate the prevalence of endoscopic improvement (Mayo endoscopic sub‐score [MES] 0 or 1) and remission (MES 0) scores with various permutations of the rectal bleeding sub‐score (RBS) and stool frequency sub‐score (SFS) of the Mayo score, following induction (6‐8 weeks) and maintenance (30‐54 weeks) therapy. Subgroup analyses were performed by year of publication and centrally read endoscopy scoring. Results: Data from 2586 trial participants were analysed. Using locally scored endoscopy, the prevalence of endoscopic improvement and remission was highest among participants with a RBS 0 + SFS 0 post‐induction (MES 0/1:81%, [95% CI 78‐84]; MES 0:29% [26‐33]) and during maintenance (MES 0/1:91% [87‐93]; MES 0:57% [52‐62]). Prevalence estimates were lower for more recently performed trials (P <.01). In comparison to locally scored endoscopy, when using central endoscopy scoring, the prevalence of endoscopic improvement and remission was lower post‐induction (MES 0/1 57% [50‐64], P <.001; MES 0 15% [11‐21], P =.09) and during maintenance (MES 0/1 74% [67‐81], P =.001; MES 0 31% [24‐38], P =.001) for participants achieving a RBS 0 + SFS 0. Conclusions: Approximately 8 of 10 patients with normalisation of rectal bleeding and stool frequency have improvement in endoscopic disease activity, whereas approximately only half of these patients have endoscopic remission. [ABSTRACT FROM AUTHOR]

Summary: Background: Lifetime risk of surgery in patients with Crohn's disease remains high. Aim: To assess population‐level markers of Crohn's disease (CD) in the era of biological therapy. Methods: Population‐based cohort study using administrative data from Ontario, Canada including 45 235 prevalent patients in the Ontario Crohn's and Colitis Cohort (OCCC) from 1 April 2003 to 31 March 2014. Results: CD‐related hospitalisations declined 32.4% from 2003 to 2014 from 154/1000 (95% confidence interval (CI) [150, 159]) patients to 104/1000 (95% CI [101, 107]) (P < .001). There was a 39.6% decline in in‐patient surgeries from 53/1000 (95% CI [50, 55]) to 32/1000 (95% CI [30, 34]) from 2003 to 2014 (P < .001). In‐patient surgeries were mostly bowel resections. Out‐patient surgeries increased from 8/1000 (95% CI [7, 9]) patients to 12/1000 (95% CI [10, 13]) (P < .001). Out‐patient surgeries were largely related to fistulas and perianal disease and for stricture dilations/stricturoplasty. CD‐related emergency department (ED) visits declined 28.4% from 141/1000 (95% CI [137, 146]) cases to 101/1000 (95% CI [99, 104]) from 2003 to 2014 (P < .001). Over the same time, patients receiving government drug benefits received infliximab or adalimumab at a combined rate of 2.2% in 2003 which increased to 18.8% of eligible patients by 2014. Conclusions: Rates of hospitalisations, ED visits and in‐patient surgeries markedly declined in Ontario over the study period, while rates of biologic medication use increased markedly for those receiving public drug benefits. [ABSTRACT FROM AUTHOR]

Summary: Background: There is conflicting evidence about nephrotoxicity risk associated with 5‐aminosalicylates for treatment of IBD. Aims: To determine population‐based temporal trends for 5‐aminosalicylates and estimated risk of nephrotoxicity associated with 5‐aminosalicylate use for ulcerative colitis (UC) and Crohn's disease (CD). Methods: Retrospective cohort and nested case‐control study, using the Health Improvement Network primary care database linked to hospital discharge coding for patients in England, 1996‐2017. Nephrotoxicity risk analysis was a first recorded renal impairment diagnosis adjusted for key variables and was assessed between 2008 and 2017. Results: A total of 35 601 patients with prevalent UC or CD were included. The proportion of patients prescribed 5‐aminosalicylates fell from 83% in 1996‐1999 to 71% in 2012‐2015 for UC patients and 64% to 45% for CD patients. Thirty per cent of patients had prolonged 5‐aminosalicylate use. Between 2008 and 2017, the incident rate of nephrotoxicity was similar and stable for UC (12.6/1000 person‐years) and CD (10.9/1000 person‐years) patients. Multivariate analysis showed no evidence for association between current prescription of 5‐aminosalicylate and nephrotoxicity in UC or CD patients, comparing ≤ 30 days prescription prior to index vs 31‐≤180 days. However, active disease, disease duration, concomitant cardiovascular disease or diabetes and nephrotoxic drug use were independently associated with development of nephrotoxicity in UC and CD. Conclusions: Despite the paucity of evidence for their benefit, 5‐aminosalicylates were prescribed to approximately half of CD patients (30% prolonged therapy). Nephrotoxicity was rare in this patient cohort, and was not associated with 5‐aminosalicylate use, but rather with disease status, comorbidity and use of nephrotoxic drugs. [ABSTRACT FROM AUTHOR]

Summary: Background: Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. Aims: To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods: PubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo‐controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open‐label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random‐effects model. Results: A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n = 844), tofacitinib (n = 1882), filgotinib (n = 130), peficitinib (n = 176), upadacitinib (n = 387) or TD‐1473 (n = 31). JAK inhibitor treatment was associated with induction of clinical remission in CD (RR, relative risk 1.38 [95% confidence interval CI 1.04‐1.83], P = 0.025, I2 = 14%) and UC (RR 3.07 [95% CI 2.03‐4.63], P < 0.001, I2 = 0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe = 0/1) (RR 2.43 [95% CI 1.64‐3.59], P < 0.001, I2 = 27%) and mucosal healing (MCSe = 0) (RR 5.50 [95% CI 2.46‐12.32], P < 0.001, I2 = 0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1.40 [95% CI 1.18‐1.67], P < 0.001, I2 = 0%), particularly for herpes zoster. Conclusions: JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications. [ABSTRACT FROM AUTHOR]

Summary: Background: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. Aim: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. Methods: Fifty‐one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins‐6, ‐8 and ‐23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase‐positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. Results: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase‐positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. Conclusions: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures. [ABSTRACT FROM AUTHOR]

Summary: Background: Physicians may be reluctant to prescribe combined immunosuppression in older patients with Crohn's disease due to perceived risk of treatment‐related complications. Aim: To evaluate the impact of age on risk of Crohn's disease‐related complications in patients treated with early combined immunosuppression vs conventional management in a post hoc analysis of the randomised evaluation of an algorithm for Crohn's treatment (REACT), a cluster‐randomised trial. Methods: We compared efficacy (time to major adverse outcome of Crohn's disease‐related surgery, hospitalisation or serious complications; corticosteroid‐free clinical remission) and safety outcomes at 24 months, between patients aged <60 vs ≥60 years randomised to early combined immunosuppression or conventional management, using Cox proportional hazard analysis or modified Poisson model. In the early combined immunosuppression arm, patients with failure to achieve clinical remission within 4‐12 weeks of corticosteroids were treated with a combination of tumour necrosis factor‐α antagonist plus anti‐metabolite and sequentially escalated in a stepwise algorithm. Results: Of 1981 patients, 311 were ≥60 years (15.7%; 173 randomised to early combined immunosuppression and 138 to conventional management). Over 24 months, 10% of older patients developed Crohn's disease‐related complications (early combined immunosuppression vs conventional management: 6.4% vs 14.5%) and 14 patients died (3.5% vs 5.8%). There was no difference between younger and older patients in risk of achieving corticosteroid‐free clinical remission (<60 years, early combined immunosuppression (72.6%) vs conventional management (64.4%): relative risk [RR], 1.06 [95% CI, 0.98‐1.15] vs ≥60 years, early combined immunosuppression (74.8%) vs conventional management (63.0%): RR, 1.09 [0.90‐1.33], P‐interaction = 0.78) or time to major adverse outcome (<60 years: hazard ratio [HR], 0.71 [0.53‐0.96] vs ≥60 years: HR, 0.69 [0.31‐1.51], P‐interaction = 0.92) with early combined immunosuppression vs conventional management. Conclusions: We observed no difference in efficacy and safety of early combined immunosuppression compared to conventional management in older and younger patients. Early combined immunosuppression may be considered as a treatment option in selected older patients with Crohn's disease with suboptimal disease control. Clinical Trial Identifier: NCT01030809. [ABSTRACT FROM AUTHOR]

Summary: Background: Restrictive red blood cell (RBC) transfusion reduces mortality and rebleeding after upper gastrointestinal bleeding (UGIB). However, there is no evidence to guide transfusion strategies in lower gastrointestinal bleeding (LGIB). Aim: To assess the association between RBC transfusion strategies and outcomes in patients with LGIB Methods: This was a post hoc analysis of the UK National Comparative Audit of LGIB and the Use of Blood. The relationships between liberal RBC transfusion and clinical outcomes of rebleeding, mortality and a composite outcome for safe discharge were examined. Transfusion strategy was dichotomised and defined as "liberal" when transfusion was administered for haemoglobin (Hb) ≥80 g/L (or ≥90 g/L in patients with acute coronary syndrome) or major haemorrhage, and "restrictive" otherwise. Multivariable logistic regression models were used to assess the independent association between liberal RBC transfusion and outcomes. Results: Of 2528 consecutive patients enrolled from 143 hospitals in the original study, 666 (26.3%) received RBC transfusion (mean age 73.3 ± 16 years, 49% female, initial mean haemoglobin 90 ± 24 g/L, 2.3% had haemodynamic instability). The rebleeding rate in transfused patients was 42.3%. After adjusting for potential confounders, there was no difference between liberal and restrictive RBC transfusion strategies for the odds of rebleeding (OR 0.89, 95% CI 0.6‐1.22), in‐hospital mortality (OR 0.54, 95% CI 0.3‐1.1) or of achieving the composite outcome (OR 0.72, 95% CI 0.5‐1.1). Conclusion: Although these results could be due to residual confounding, they provide an important foundation for the design of randomised trials to evaluate transfusion strategies for LGIB. [ABSTRACT FROM AUTHOR]

Summary: Background: Outcomes after Nonvariceal upper gastrointestinal bleeding (NVUGIB) have historically focused on ulcer‐related causes. Little is known regarding non‐ulcer bleeding, the most common cause of NVUGIB. Aim: To compare outcomes between ulcer‐ and non‐ulcer‐related NVUGIB and explore whether these could be explained by differences in baseline characteristics, bleeding severity or processes of care. Methods: Analysis of 4474 patients with NVUGIB from 212 United Kingdom hospitals as part of a nationwide audit. Logistic regression models were used to adjust for baseline characteristics, bleeding severity and processes of care. Results: 1682 patients had ulcer‐related and 2792 patients had non‐ulcer‐related bleeding. Those with ulcer‐related bleeding were older (median age 73 vs 69, P < 0.001), less likely to have been taking a PPI (18% vs 32%, P < 0.001), more likely to have been taking aspirin (40% vs 27%, P < 0.001) and present with shock (43% vs 32%, P < 0.001). Furthermore, those with ulcer‐related bleeding were more likely to receive blood transfusion (66% vs 39%, P < 0.001), PPI infusion (27% vs 5%, P < 0.001) and endoscopic therapy (37% vs 8%, P < 0.001). Overall, ulcer‐related bleeding had higher odds of in‐hospital mortality (OR: 1.54; 95% CI: 1.21‐1.96, P < 0.0001), rebleeding (OR: 2.08; 95% CI: 1.73‐2.51, P < 0.0001) and need for surgical/radiologic intervention (OR: 2.64; 95% CI: 1.85‐3.77, P < 0.0001). The associations disappeared after adjustment for bleeding severity, whereas adjustment for patient characteristics or process of care factors had no impact. Conclusion: Patients with ulcer‐related NVUGIB bleeding have worse outcomes than those with non‐ulcer‐related NVUGIB bleeding, which is due to more severe bleeding. [ABSTRACT FROM AUTHOR]

Summary: Background: Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. Aims: To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. Methods: MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo‐controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random‐effects model. Meta‐regression was performed to assess trial‐level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. Results: Thirty‐two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co‐prescribed aminosalicylates was 80.7% (95% CI 75.5%‐85.1%), with considerable observed heterogeneity (I2 = 95%). In univariable meta‐regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. Conclusions: Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Zymogen granule glycoprotein 2 (GP2) is a major autoantigen of Crohn's disease‐specific pancreatic autoantibodies. Aim: To test a link between loss of tolerance to isoforms of GP2 and pouch disorders in a cross‐sectional study in ulcerative colitis patients with ileal pouch‐anal anastomosis (IPAA). Methods: Serum samples of 117 consecutive ulcerative colitis patients after IPAA were tested for presence of Anti‐GP2 isoforms 1 (GP21) & 4 (GP24) IgG and IgA as well as anti‐Saccaromyces cervisiae (ASCA) IgG and IgA antibodies in a blinded fashion via enzyme‐linked immunosorbent assay. Pouch disorders were diagnosed based on clinical, endoscopic, histological and radiographic criteria. Crohn's disease of the pouch was defined as involvement of the small bowel mucosa proximal to the ileal pouch with Crohn's disease, development of perianal complications or pouch fistula more than 3 months after ileostomy closure. Results: Positivity and level of Anti‐GP21 IgG (AUC 0.77; P < 0.001 & P = 0.02, respectively), Anti‐GP24 IgG (AUC 0.74; P < 0.001 & P = 0.025, respectively) and Anti‐GP24 IgA (AUC 0.77; P < 0.001 to P = 0.018, respectively) were specifically associated with Crohn's disease of the pouch. Anti‐GP2 was not associated with endoscopic or histological pouch disease activity index. Neither positivity nor levels of ASCA IgG (AUC 0.63; P = 0.12 & P = 0.35, respectively) or ASCA IgA (AUC 0.67; P = 0.38 & P = 0.53) were associated with pouch phenotypes. Conclusions: The novel anti‐GP21 and GP24 antibodies are associated with Crohn's disease of the pouch in ulcerative colitis patients after IPAA. Serological anti‐GP2 antibodies could aid in diagnosis of Crohn's disease of the pouch. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Cushing et al and Cushing and Ananthakrishnan papers. To view these articles, visit https://doi.org/10.1111/apt.15568 and https://doi.org/10.1111/apt.15621. [ABSTRACT FROM AUTHOR]

In cluster randomised cross-over (CRXO) trials, clusters receive multiple treatments in a randomised sequence over time. In such trials, there is usual correlation between patients in the same cluster. In addition, within a cluster, patients in the same period may be more similar to each other than to patients in other periods. We demonstrate that it is necessary to account for these correlations in the analysis to obtain correct Type I error rates. We then use simulation to compare different methods of analysing a binary outcome from a two-period CRXO design. Our simulations demonstrated that hierarchical models without random effects for period-within-cluster, which do not account for any extra within-period correlation, performed poorly with greatly inflated Type I errors in many scenarios. In scenarios where extra within-period correlation was present, a hierarchical model with random effects for cluster and period-within-cluster only had correct Type I errors when there were large numbers of clusters; with small numbers of clusters, the error rate was inflated. We also found that generalised estimating equations did not give correct error rates in any scenarios considered. An unweighted cluster-level summary regression performed best overall, maintaining an error rate close to 5% for all scenarios, although it lost power when extra within-period correlation was present, especially for small numbers of clusters. Results from our simulation study show that it is important to model both levels of clustering in CRXO trials, and that any extra within-period correlation should be accounted for. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Wong et al papers. To view these articles, visit https://doi.org/10.1111/apt.16805 and https://doi.org/10.1111/apt.16843 [ABSTRACT FROM AUTHOR]

Background & Aims Cirrhosis is a complex acquired disorder of coagulation and frequent indication for transfusion of blood components. We characterised blood component use in patients with cirrhosis and compared this to transfusion guidelines. Methods All National Health Service trusts with representation on the British Society of Gastroenterology membership list were invited to take part. Data were collected prospectively on consecutive, unselected, hospitalised admissions with cirrhosis over 28 days. Detailed information was recorded for patients receiving blood components including indication (for bleeding or prophylaxis), type of component, laboratory indices triggering transfusion, complications, thromboembolic events and clinical outcome to day 28. Results Data on 1313 consecutive patients with cirrhosis were collected from 85 hospitals. A total of 391/1313 (30%) were transfused a blood component; in 238/391 (61%), this was for treatment of bleeding and in 153/391 (39%) for prophylaxis of bleeding. In 48/185 (26%) cases with bleeding, the haemoglobin threshold was >80 g/L prior to red blood cell transfusion. In the prophylaxis group, 238/391 (61%) received transfusion in response to an abnormal haematological value in the absence of any planned procedure. In patients transfused for procedural prophylaxis, 10/34 (29%) received fresh frozen plasma at an International Normalised Ratio lower than the threshold where a benefit would be anticipated. An in-patient thromboembolic event was recorded in 3% (35/1313) and 10% (138/1313) died by day 28. Conclusions One-third of hospitalised patients with cirrhosis were transfused. Strategies for Patient Blood Management should include ensuring transfusion practice is consistent with guidelines and greater emphasis on alternatives to transfusion. [ABSTRACT FROM AUTHOR]

The article discusses the importance of standardizing bowel preparation scales for patients with Crohn's disease. The study examined the reliability and validity of four bowel preparation instruments and found that all of them were effective in assessing bowel preparation quality. The study also highlighted the negative correlation between bowel preparation quality and disease activity in the colon. The authors recommend using the Boston Bowel Preparation Scale as the preferred assessment tool for patients with Crohn's disease. [Extracted from the article]

LINKED CONTENT This article is linked to Sedano et al and Laube & Selinger papers. To view these articles, visit https://doi.org/10.1111/apt.16328 and https://doi.org/10.1111/apt.16341 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Goodsall et al and Abushamma & Deepak papers. To view these articles, visit https://doi.org/10.1111/apt.16288 and https://doi.org/10.1111/apt.16308 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Jangi et al and Maeda et al papers. To view these articles, visit https://doi.org/10.1111/apt.16026 and https://doi.org/10.1111/apt.16302 [ABSTRACT FROM AUTHOR]

BACKGROUND: Coagulopathy after major hemorrhage has been found to be an independent risk factor for mortality after traumatic bleeding. It is unclear whether similar associations are present in other causes of major hemorrhage. We describe the prevalence, use of plasma, and outcomes of patients with coagulopathy after acute nonvariceal upper gastrointestinal bleeding (NVUGIB). STUDY DESIGN AND METHODS: This study was a multicenter UK national audit. Data were collected prospectively on consecutive admissions with upper gastrointestinal bleeding over a 2-month period to 212 UK hospitals. Coagulopathy was defined as an international normalized ratio (INR) of at least 1.5. Logistic regression was used to examine the relationship between coagulopathy and patient-related outcome measures of mortality, rebleeding, and need for surgery and/or radiologic intervention. RESULTS: A total of 4478 patients were included in the study. Coagulopathy was present in 16.4% (444/2709) of patients in whom an INR was recorded. Patients with coagulopathy were more likely to present with hemodynamic shock (45% vs. 36%), have a higher clinical Rockall score (4 vs. 2), receive red blood cell transfusion (79% vs. 48%) and have high-risk stigmata of hemorrhage at endoscopy (34% vs. 25%). After adjustment for confounders the presence of a coagulopathy was associated with a fivefold increased in the odds of mortality (odds ratio, 5.63; 95% confidence interval, 3.09-10.27; p < 0.001). Only 35% of patients with coagulopathy received fresh-frozen plasma transfusion. CONCLUSIONS: Coagulopathy was prevalent in 16% of patients after NVUGIB and independently associated with more than a fivefold increase in the odds of in-hospital mortality. Wide variation in plasma use exists indicates clinical uncertainty regarding optimal practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute upper gastrointestinal bleeding (AUGIB) accounts for 14% of all red blood cell (RBC) transfusions in the United Kingdom, despite little evidence to guide optimal blood transfusion strategies and few data on the variation in practice. We aimed to survey UK clinicians about their RBC transfusion practice in AUGIB. STUDY DESIGN AND METHODS: A survey describing six clinical vignettes of AUGIB was sent to practicing gastroenterologists, acute care physicians, and upper gastrointestinal surgeons. Respondents were asked to select a hemoglobin (Hb) trigger at which they would ordinarily transfuse RBCs. RESULTS: The response rate was 48% (815/1709). Transfusion triggers differed significantly between all six cases (p < 0.001). There was significant variation in the selected Hb trigger between different clinical specialties for five of the six scenarios. Surgeons were more likely to select a lower Hb transfusion trigger than physicians across all six scenarios (p < 0.005), as were clinicians who had graduated more recently (p < 0.05 for Scenarios 1-3). The responses suggested the belief that restrictive use of RBCs is appropriate, which is in part discordant with actual observed practice. Only 70% of respondents reported familiarity with national guidelines for AUGIB. CONCLUSIONS: There is significant variation in the reported approach to transfusion practice among clinicians caring for patients with AUGIB, with both patient- and clinician-related factors accounting for these differences. Further studies are needed to evaluate the safety and efficacy of differing blood transfusion strategies in patients presenting with AUGIB. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Pai et al and Rowe papers. To view these articles, visit https://doi.org/10.1111/apt.15503 and https://doi.org/10.1111/apt.15537. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al papers. To view these articles, visit https://doi.org/10.1111/apt.15184 and https://doi.org/10.1111/apt.15392. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Novak et al and Bryant and Costello papers. To view these articles, visit https://doi.org/10.1111/apt.15250 and https://doi.org/10.1111/apt.15284. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Morar et al and Kamm papers. To view these articles visit https://doi.org/10.1111/apt.13388 and https://doi.org/10.1111/apt.14987. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Almradi et al paper. To view this article, visit https://doi.org/10.1111/apt.16248 [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Singh et al and Paul and Robin papers. To view these articles, visit https://doi.org/10.1111/apt.15214 and https://doi.org/10.1111/apt.15312. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Singh et al and Murray papers. To view these articles, visit https://doi.org/10.1111/apt.15214 and https://doi.org/10.1111/apt.15259. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Kherad et al and Taha papers. To view these articles, visit https://doi.org/10.1111/apt.15158 and https://doi.org/10.1111/apt.15172. [ABSTRACT FROM AUTHOR]

Background: Pouchitis is a condition with large unmet medical needs and no approved therapies. Lack of validated instruments to measure disease activity and treatment response is a major barrier to drug development., Aim: To conduct a modified RAND/University of California Los Angeles appropriateness process to produce a standardised assessment of pouchitis disease activity in clinical trials., Methods: A list of 164 items generated upon a systematic review and expert opinion were rated based on a 9-point scale (appropriate, uncertain and inappropriate), by a panel including 16 gastroenterologists, surgeons and histopathologists., Results: Items rated as appropriate to evaluate in pouchitis clinical trials were: (a) clinical: stool frequency and faecal urgency; (b) endoscopic: primary assessment in the pouch body according to the percentage of affected area (<50%, 50%-75% and >75%), evaluation of the presence of ulcers/erosions according to size (erosions <5 mm, ulcers ≥5 mm to 2 cm and large ulcers >2 cm) and ulcerated area (<10%, 10%-30% and >30%); (c) histologic: two biopsies from each segment, from the ulcer's edge when present, or endoscopically normal areas, assessment of lamina propria chronic inflammation, epithelial and lamina propria neutrophils, epithelial damage, erosions and ulcers; and (d) clinical trial inclusion/outcome criteria: minimum histologic disease activity for inclusion, a primary endpoint based on stool frequency and assessment of clinical, endoscopic and histologic response and remission. The overall majority of items surveyed (100/164) were rated 'uncertain'., Conclusion: We conducted a RAND/UCLA appropriateness process to help inform measurement of pouchitis disease activity within clinical trials and foster the development of novel therapies., (© 2021 John Wiley & Sons Ltd.)

Background: Targeting histological remission or response in Crohn's disease (CD) is not recommended in clinical practice guidelines or as an outcome in clinical trials due to uncertainties regarding index validity and prognostic relevance., Aims: To conduct a modified RAND/University of California Los Angeles appropriateness process with the goal of producing a framework to standardise histological assessment of CD activity in clinical trials., Methods: A total of 115 statements generated from literature review and expert opinion were rated on a scale of 1-9 by a panel of 11 histopathologists and 6 gastroenterologists. Statements were classified as inappropriate, uncertain or appropriate based upon the median panel rating and degree of disagreement., Results: The panellists considered it important to measure histological activity in clinical trials to determine efficacy and that absence of neutrophilic inflammation is an appropriate histological target. They were uncertain whether the Global Histological Activity Score was an appropriate instrument for measuring histological activity. The Geboes Score and Robarts Histopathology Index were considered appropriate. Two biopsies from five segments should be biopsied, and the colon and the ileum should be analysed separately for all indices. Endoscopic mucosal appearance should guide biopsy procurement site with biopsies taken from the ulcer edge, or the most macroscopically inflamed area in the absence of ulcers., Conclusion: We evaluated the appropriateness of items for assessing histological disease activity in CD clinical trials. These items will be used to develop a novel histological index., (© 2020 John Wiley & Sons Ltd.)

Background: There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease (NAFLD) are operationalised., Aim: To develop a consensus-based framework for standardising histologic assessment of liver biopsies in clinical trials of NAFLD., Methods: An expert panel of 14 liver pathologists and three hepatologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 130 items derived from literature review and expert opinion were rated by each panel member on a 1-9 scale. Disagreement was defined as ≥5 ratings in the lowest (1-3) and highest (7-9) categories. Items were classified as inappropriate (median 1-3.5 without disagreement), uncertain (median 3.5-6.5 or any median with disagreement) or appropriate (median 6.5-9 without disagreement). Survey results were discussed as a group before voting., Results: Current measures of disease activity and fibrosis may not fully capture important features of non-alcoholic steatohepatitis (NASH). Alternative methods to evaluate ballooning degeneration are needed. Panellists were uncertain whether portal inflammation, degree of steatosis and Mallory-Denk bodies are important measures of disease activity. Furthermore, it was felt that current staging systems do not capture the full spectrum of fibrosis in NASH. A consensus definition and sub-stages for bridging fibrosis are needed. The severity of perisinusoidal fibrosis should be captured at all stages. Lastly, a method to evaluate features of fibrosis regression should be developed., Conclusion: The operating properties of the modifications proposed should be evaluated prospectively to determine reliability and responsiveness., (© 2019 John Wiley & Sons Ltd.)