Gastroenterology

Can adjuncts to bowel preparation for colonoscopy improve patient experience and result in superior bowel cleanliness? A systematic review and meta-analysis (2020)

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Type of publication:
Systematic Review

Author(s):
Kamran, Umair; *Abbasi, Abdullah; Tahir, Imran; Hodson, James; Siau, Keith

Citation:
United European gastroenterology journal; Aug 2020 [epub ahead of print]

Abstract:
BACKGROUND Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness).METHODS A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I2-statistics.RESULTS Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p = 0.007), but no difference in nausea (p = 0.10) or abdominal pain (p = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate.CONCLUSION In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.

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Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn's Disease (2021)

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Type of publication:
Randomised controlled trial

Author(s):
Rhodes J.M.; Subramanian S.; Martin K.; Probert C.; Flanagan P.K.; Horgan G.W.; Mansfield J.; Parkes M.; Hart A.; Dallal H.; Iqbal T.; *Butterworth J.; Culshaw K.

Citation:
Digestive Diseases and Sciences; Aug 2021; vol. 66 (no. 8); p. 2700-2711

Abstract:
Background: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain. Aim(s): To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. Method(s): Adults with moderately active disease (CDAI > 220-450 plus C reactive protein >= 5 mg/l and/or fecal calprotectin > 250 mug/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI <= 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy. Result(s): Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location. Conclusion(s): Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.

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Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial (2020)

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Type of publication:
Randomised controlled trial

Author(s):
The HALT-IT Trial Collaborators (including *John Jones and *Charlotte Owen)

Citation:
Lancet, 2020; Vol. 395: pp. 1927–36

Abstract:
Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.
Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.
Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and
placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.

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Duplication of the Gallbladder and its Surgical Challenges (2019)

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Type of publication:
Conference abstract

Author(s):
*Tamvakeras P.; *Riera M.

Citation:
British Journal of Surgery; Sep 2019; vol. 106, S6; p. 28

Abstract:
Aims: Duplication of the gallbladder is a rare congenital anomaly. However, awareness of this anatomical variation is crucial when treating gallstone disease. We present the case of a patient with two gallbladders, incidentally found during laparoscopic cholecystectomy. We review the literature and discuss the associated surgical challenges.
Methods: Case presentation and literature review of the classification, clinical presentation, radiological diagnosis and management of gallbladder duplication.
Results: A 37 year old healthy man presented with a two year history of post prandial right upper quadrant abdominal pain. Routine blood investigations were normal and ultrasonography (US) demonstrated gallstones with normal biliary ducts. During laparoscopy he was found to have gallbladder duplication with a Y-shaped type cystic duct, this consisted of two ducts joining together to form a main cystic duct which drained into an otherwise normal common bile duct. No cholangiogram was performed. After meticulous dissection and demonstration of the anatomy, the cholecystectomy was performed. The patient recovered uneventfully and was discharged the next day. Histology showed gallstones and chronic inflammation in both
gallbladders.
Conclusions: A duplicate gallbladder is a rare congenital variation. Preoperative diagnosis can be challenging. Understanding its classification based on the relational anatomy to the biliary tree is essential to avoid biliary injuries. Imaging modalities such as US and computed tomography (CT) may not be sensitive enough. MRCP may demonstrate the biliary tree more clearly. Laparoscopic cholecystectomy can be safely performed, in the presence of symptomatic gallstone disease.

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Practice pattern variability in the management of acute severe colitis: A UK provider survey (2019)

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Type of publication:
Journal article

Author(s):
Sebastian S.; Lisle J.; Subramanian S.; Dhar A.; Shenoy A.; Limdi J.; *Butterworth J.; Allen P.B.; Samuel S.; Moran G.; Shenderey R.; Parkes G.; Raine T.; Lobo A.J.; Kennedy N.A.

Citation:
Frontline Gastroenterology; Jul 2020; vol. 11 (no. 4); p. 272-279

Abstract:
Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy. Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted. The survey evaluated provider characteristics and general practice in the setting of ASUC, followed by a vignette with linked questions.
Result(s): The response rate of the survey was 31% (209/682 IBD section members). 134 (78%) reported they would use standard infliximab dose (5 mg/kg) while 37 (22%) favoured a higher front-loading dose of 10 mg/kg citing low albumin, high C-reactive protein as their reason for their preference. IBD specialists chose the higher front-loading dose more often compared with other gastroenterologists (p=0.01) In the specific case vignette, accelerated induction (AI) was favoured by 51% of the respondents while 25% used the standard induction regime and 19% favoured colectomy. IBD specialists more often favoured AI compared with other gastroenterologists (p=0.03) with the main reason being presence of predictors of low infliximab levels (74%). The reasons cited for favouring standard induction (n=57) included lack of evidence for AI (18), their usual practice (11), unlicensed regime (7), and safety concerns (4).
Conclusion(s): There are significant variations in practice in the use of infliximab rescue therapies with an urgent need for development of care pathways to standardise practice.

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Infliximab induction regimes in steroid refractory acute severe colitis: A multi-centre retrospective cohort study with propensity score analysis (2019)

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Type of publication:
Conference abstract

Author(s):
Sebastian S.; Myers S.; Syed N.; Argyriou K.; Samuel S.; Moran G.; Martin G.; Allen P.B.; *Los L.; *Butterworth J.; Fiske J.; Limdy J.; Ranjan R.; Dhar A.; Cooper B.; Shenoy A.H.; Patel N.; Subramanian S.; Goodoory V.; Shaikh F.; Shenderey R.; Ching H.L.; Lobo A.; Jayasooriya N.; Parkes G.; Brooks J.; Raine T.

Citation:
Journal of Crohn's and Colitis; Mar 2019; vol. 13

Abstract:
Background: While infliximab is used as rescue therapy for steroid refractory acute severe colitis (ASUC),
between 30 and 40% of patients do not respond and undergo colectomy. Accelerated induction regimes of
infliximab have been proposed to improve response rates. We aimed to evaluate colectomy rates in steroid
refractory ASUC patients receiving standard induction (SI) vs. accelerated induction (AI) of infliximab.
Method(s): Data collected on hospitalised patients receiving rescue therapy for steroid refractory ASUC. The choice of rescue therapy was at the discretion of the treating clinician. Accelerated induction (AI) was defined as receiving second dose of infliximab within 8 days of first rescue therapy or receiving front loading dose of 10 mg/kg. Our primary outcome was the short-term (in-patient, 30 days and 90 days) colectomy rate. Secondary outcomes were 12-month colectomy rates, length of hospital stay (LOS), and complication rates. We used a propensity score analysis with optimal calliper matching using a priori defined high-risk covariates at the start of rescue therapy (albumin, CRP, CRP-albumin ratio, haemoglobin nadir and pancolitis) to reduce potential provider selection bias.
Result(s): A total of 131 patients receiving infliximab rescue therapy were included, of whom 102 patients
received SI and 29 received AI. There was no difference in age, duration of diagnosis, age at rescue therapy,
Montreal class or use of steroids, 5ASAs or thiopurines prior to index admission. In the unmatched overall
cohort, there was no difference in colectomy during index admission (13% vs. 20%, p = 0.26), 30-day colectomy (18% vs. 20%, p = 0.45), 90-day colectomy (20% vs. 24%, p = 0.38) or 6 month colectomy (25% vs. 27%, p = 0.49). The LOS was shorter in the SI group (14.87 +/- 8.1 days vs. 19.31 +/- 5.8 days, p = 0.007). In patients who underwent colectomy, there were no differences in complications or serious infection rates. In the propensity score-matched cohort of 52 patients, there was no difference in overall colectomy rates between SI and AI groups (57% vs. 31%, p = 0.09), but the index admission colectomy (53% vs. 23%, p = 0.045) and 30-day colectomy (57% vs. 27%, p = 0.048) rates were higher in those receiving SI. There was no significant difference in LOS between SI and AI groups (23.6 +/- 4.3 vs. 18.2 +/- 7.1 days, p = 0.09) or in overall complication and infection rates but there was a mortality in AI group.
Conclusion(s): In this retrospective cohort study, there was no difference in overall colectomy rates in ASUC patients receiving different induction dosing regimens of infliximab. However, using propensity score matching, the short-term colectomy rates appear to be better in those receiving accelerated induction regime. A prospective study to confirm findings is planned.

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A randomised, multi-centre, double-blind, placebo-controlled study of a targeted release oral cyclosporine formulation in the treatment of mild-to-moderate ulcerative colitis: Efficacy results (2019)

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Type of publication:
Conference abstract

Author(s):
Bloom S.; Iqbal T.; Nwokolo C.; *Smith M.; O'Donoghue D.; Hall J.; Dzyngel B.

Citation:
Journal of Crohn's and Colitis; Mar 2019; vol. 13

Abstract:
Background: Cyclosporine (CsA) is an effective treatment for patients with acute severe ulcerative colitis (UC), and studies have shown that it has an impact on disease activity comparable to the anti-TNF agent,
infliximab.1,2 Concerns regarding systemic toxicities have limited its role to short-term induction therapy and as a bridge to other therapies. ST-0529 is a novel low dose, controlled release formulation of CsA. A Phase 1 dose-ranging study demonstrated that tissue concentrations improved when it is given twice daily (BID).3
Methods: A total of 118 subjects with mild (baseline DAI < 6) or moderate (baseline DAI >= 6) UC were
randomised 1:1 to receive 75 mg ST-0529 once daily or placebo (53 and 65 patients, respectively) for 4 weeks in a multi-centre, randomised, double-blind, placebo-controlled, Phase IIa study. Patients using UC medications (eg low-dose steroids, 5-aminosalicylates, and immunomodulatory agents) on screening could continue them if agreed to maintain a stable dosing regimen during the study. The primary objective was to evaluate the efficacy of ST-0529 in inducing clinical remission (DAI score <=2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary objectives included clinical response, mucosal and histological healing, safety, and tolerability.
Result(s): A numerical although not statistically significant advantage of ST-0529 over placebo was found for rates of clinical remission (ST-0529: 13.2%; placebo: 6.3%, p = 0.2211) and clinical response (ST-0529: 30.2%; placebo: 18.8%, p = 0.1923). There were no differences between the treatment groups for mucosal and histological healing. ST-0529 was safe and well-tolerated. A post hoc subgroup analysis was performed to evaluate effects by disease severity. Clinical remission and clinical response rates in subjects with moderate (baseline DAI >=6) and mild (baseline DAI <6) disease (ITT, N = 118)
Conclusion(s): In this pilot study, ST-0529 given once daily, was safe, well tolerated, and showed a numerically higher, but not statistically significant difference in remission rate in patients with mild-to-moderate UC compared with placebo after 4 weeks of treatment. In the post hoc analysis, differences in the clinical response between treatment subgroups achieved statistical significance in some subgroups, the largest clinical response rate in moderate UC patients taking 5-aminosalicylates and/or steroids. These preliminary data, added to the data from a Phase 1 study, support further development of ST-0529 as a treatment for the induction and maintenance of remission in UC patients with moderate to severe disease. (Table Presented).

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Coeliac disease (2019)

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Type of publication:
Journal article

Author(s):
*Butterworth J.; *Los L.

Citation:
Medicine (United Kingdom); 2019; vol. 47, no. 5, p. 314-319

Abstract:
Coeliac disease (CD) is a common, chronic, immune-mediated small bowel enteropathy resulting from gluten exposure in genetically susceptible individuals. Considerable clinical and immunopathological heterogeneity is seen in newly diagnosed patients, and the diagnosis is not always straightforward even for experienced physicians. Population screening using tissue transglutaminase 2 has revealed a higher prevalence of seropositivity than previously appreciated. There is a wide differential diagnosis for mucosal villous atrophy, crypt hyperplasia and increased intraepithelial lymphocyte concentrations. Life-long adherence to a gluten-free diet is currently the only recommended treatment for CD, although many newer approaches are being explored. CD is rightly described as a multisystem disorder and is associated with other gastrointestinal and non-gastrointestinal related disorders, numerous complications and possibly reduced survival. The landscape has recently expanded with the identification that some patients with symptoms suggestive of CD but without the mucosal changes seem to respond to a gluten-free diet. This group of patients are currently labelled as having non-coeliac gluten sensitivity. Controversy exists over whether this is a separate disease entity. This review briefly discusses the important clinical, immunological and therapeutic aspects of CD.

Screening for colorectal cancer in defunctioned colons (2018)

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Type of publication:
Journal article

Author(s):
*Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

Citation:
Journal of medical screening; Dec 2018; vol. 25 (no. 4); p. 178-182

Abstract:
OBJECTIVES Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons.METHODS An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. RESULTS Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area.CONCLUSIONS Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

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Perplexing presentations in paediatric gastroenterology (2018)

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Type of publication:
Journal article

Author(s):
Pigott, Anna Jane; Saran, Shashwat; *Monaghan, Sean

Citation:
Paediatrics & Child Health; Nov 2018; vol. 28 (no. 11); p. 515-519

Abstract:
Abstract The nature of gastroenterological conditions often lead the clinician to rely on the history offered by the parents or carers to make a diagnosis and create a management plan. It is no coincidence that some of the most frequent presentations of fabricated or induced illness (FII) are with apparent gastroenterological complaints. This review details elements in the presenting history of vomiting, constipation, diarrhoea, blood in stool, faltering growth and abdominal pain that potentially make FII a more likely diagnosis, and proposes a management approach to a suspected presentation of FII.