Summary
Background Functional gut symptoms are induced by inclusion and reduced by dietary restriction of poorly absorbed short‐chain carbohydrates (FODMAPs), but the mechanisms of action remain ...untested.
Aims To determine the effect of dietary FODMAPs on the content of water and fermentable substrates of ileal effluent.
Methods Twelve ileostomates without evidence of small intestinal disease undertook two 4‐day dietary periods, comprising diets differing only in FODMAP content in a randomized, cross‐over, single‐blinded intervention study. Daytime (14 h) ileal effluent was collected on day four of each diet. Patients rated effluent volume and consistency on a 10‐cm visual analogue scale. The FODMAP content of the diet and effluent was measured.
Results Ingested FODMAPs of 32% (range 6–73%) was recovered in the high FODMAP diet effluent. Effluent collection weight increased by a mean of 22% (95% CI, 5–39), water content by 20% (2–38%) and dry weight by 24% (4–43%) with the high compared to low FODMAP diet arm. Output increased by 95 (28–161) mL. Volunteers perceived effluent consistency was thicker (95% CI, 0.6–1.9) with the low FODMAP diet than with the high FODMAP diet (3.5–6.1; P = 0.006).
Conclusions These data support the hypothetical mechanism; FODMAPs increase delivery of water and fermentable substrates to the proximal colon.
Summary
Background Corticosteroids are a well‐established treatment for active Crohn’s disease and have been widely used for decades. It has become apparent, however, that a proportion of patients ...either fails to respond to corticosteroids or is unable to withdraw from them without relapsing. Furthermore, their use is associated with a range of side effects, such that long‐term treatment carries unacceptable risk.
Aim To review the evidence regarding the appropriate use of corticosteroids in Crohn’s disease, along with their side effects, safety and alternatives.
Methods To collect relevant articles, a PubMed search was performed from 1966 to November 2006 using the terms ‘steroid’, ‘corticosteroid’, ‘glucocorticoid’, ‘prednisolone’, ‘prednisone’, ‘methylprednislone’, ‘hydrocortisone’, ‘dexamethasone’ and ‘budesonide’ in combination with ‘Crohn(s) disease’. Relevant articles were reviewed, as were their reference lists to identify further articles.
Results When used correctly, corticosteroids are a highly effective, well tolerated, cheap and generally safe treatment for active Crohn’ disease. Nevertheless, approximately 50% of recipients will either fail to respond (steroid‐resistant) or will be steroid dependent at 1 year. Newer alternatives to corticosteroids are not, however, without risk themselves and, moreover, are not necessarily available universally.
Conclusions Steroids are used widely to treat Crohn’s disease, a situation that is unlikely to change in the near future. Accordingly, efforts should be made to ensure that they are used correctly and that their side effects are minimized. Reference is made to recently published guidelines and a simplified ‘users guide’ is presented.
Background: Emerging evidence indicates that the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may result in symptoms in some patients with ...irritable bowel syndrome (IBS). The present study aimed to determine whether a low FODMAP diet is effective for symptom control in patients with IBS and to compare its effects with those of standard dietary advice based on the UK National Institute for Health and Clinical Excellence (NICE) guidelines.
Methods: Consecutive patients with IBS who attended a follow‐up dietetic outpatient visit for dietary management of their symptoms were included. Questionnaires were completed for patients who received standard (n = 39) or low FODMAP dietary advice (n = 43). Data were recorded on symptom change and comparisons were made between groups.
Results: In total, more patients in the low FODMAP group reported satisfaction with their symptom response (76%) compared to the standard group (54%, P = 0.038). Composite symptom score data showed better overall symptom response in the low FODMAP group (86%) compared to the standard group (49%, P < 0.001). Significantly more patients in the low FODMAP group compared to the standard group reported improvements in bloating (low FODMAP 82% versus standard 49%, P = 0.002), abdominal pain (low FODMAP 85% versus standard 61%, P = 0.023) and flatulence (low FODMAP 87% versus standard 50%, P = 0.001).
Conclusions: A low FODMAP diet appears to be more effective than standard dietary advice for symptom control in IBS.
COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of ...disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.
Background
The low‐FODMAP diet is a frequently used treatment for irritable bowel syndrome (IBS). Most research has focused on short‐term FODMAP restriction; however, guidelines recommend that ...high‐FODMAP foods are reintroduced to individual tolerance. This study aimed to assess the long‐term effectiveness of the low‐FODMAP diet following FODMAP reintroduction in IBS patients.
Methods
Patients with IBS were prospectively recruited to a questionnaire study following completion of dietitian‐led low‐FODMAP education. At baseline and following FODMAP restriction (short term) only, gastrointestinal symptoms were measured as part of routine clinical care. Following FODMAP reintroduction, (long term), symptoms, dietary intake, acceptability, food‐related quality of life (QOL), and healthcare utilization were assessed. Data were reported for patients who continued long‐term FODMAP restriction (adapted FODMAP) and/or returned to a habitual diet (habitual).
Key Results
Of 103 patients, satisfactory relief of symptoms was reported in 12% at baseline, 61% at short‐term follow‐up, and 57% at long‐term follow‐up. At long‐term follow‐up, 84 (82%) patients continued an ‘adapted FODMAP’ diet (total FODMAP intake mean 20.6, SD 14.9 g/d) compared with 19 (18%) of patients following a ‘habitual’ diet (29.4, SD 22.9 g/d, P=.039). Nutritional adequacy was not compromised for either group. The ‘adapted FODMAP’ group reported the diet cost significantly more than the ‘habitual’ group (P<.001) and affected social eating (P<.01) but there was no effect on food‐related QOL. Healthcare utilization was similar between both groups.
Conclusion and Inferences
Low‐FODMAP education is effective for long‐term IBS management, enables a nutritionally adequate diet, and is broadly acceptable to patients.
This study assessed the long‐term impact of the low‐FODMAP diet on clinical response, dietary intake, patient acceptability, food‐related QOL, and healthcare use. Over half of patients report long‐term symptom relief, the diet is nutritionally adequate, and acceptable to patients. The findings support using the low‐FODMAP diet for long‐term IBS management. Baseline; Short‐term follow‐up; Long‐term follow‐up.
Summary
Background Fructose malabsorption, lactose malabsorption and an early rise in breath hydrogen after lactulose (ERBHAL) may play roles in induction of symptoms in gastrointestinal conditions.
...Aim To compare prevalence and interactions of fructose malabsorption, lactose malabsorption and ERBHAL among healthy subjects and those with chronic intestinal disorders using consistent breath hydrogen testing methodologies.
Methods Consecutive series of Caucasian patients with Crohn’s disease (n = 91), ulcerative colitis (56), functional gastrointestinal disorders (FGID) (201), coeliac disease (136) and 71 healthy volunteers underwent breath hydrogen testing using lactulose, fructose and lactose.
Results Early rise in breath hydrogen after lactulose occurred more commonly in healthy controls (39%) than in Crohn’s disease (20%) and untreated coeliac disease (14%; P < 0.008), but not FGID (27%), ulcerative colitis (26%) or treated coeliac disease (29%). Fructose malabsorption was more frequent in Crohn’s disease (61%) than other groups (33–44%, P < 0.05). Lactose malabsorption was most common in Crohn’s disease (42%) and ulcerative colitis (40%) and uncommon (10%) in 79 patients with newly diagnosed coeliac disease. In Crohn’s disease, concurrent Fructose malabsorption and lactose malabsorption was most common (29%), and the association of fructose malabsorption with ERBHAL seen overall (62%) was not observed (36%, P < 0.0001).
Conclusions Carbohydrate malabsorption and ERBHAL are normal physiological phenomena. The abnormal patterns observed in Crohn’s disease may have pathogenic importance.
Up to 1/5 of patients with wildtype thiopurine-S-methyltransferase (TPMT) activity prescribed azathioprine (AZA) or mercaptopurine (MP) demonstrate a skewed drug metabolism in which MP is ...preferentially methylated to yield methylmercaptopurine (MeMP). This is known as thiopurine hypermethylation and is associated with drug toxicity and treatment non-response. Co-prescription of allopurinol with low dose AZA/MP (25–33%) circumvents this phenotype and leads to a dramatic reduction in methylated metabolites; however, the biochemical mechanism remains unclear. Using intact and lysate red cell models we propose a novel pathway of allopurinol mediated TPMT inhibition, through the production of thioxanthine (TX, 2-hydroxymercaptopurine). In red blood cells pre-incubated with 250μM MP for 2h prior to the addition of 250μM TX or an equivalent volume of Earle's balanced salt solution, there was a significant reduction in the concentration of MeMP detected at 4h and 6h in cells exposed to TX (4h, 1.68, p=0.0005, t-test). TX acts as a direct TPMT inhibitor with an apparent Ki of 0.329mM. In addition we have confirmed that the mechanism is relevant to in vivo metabolism by demonstrating raised urinary TX levels in patients receiving combination therapy. We conclude that the formation of TX in patients receiving combination therapy with AZA/MP and allopurinol, likely explains the significant reduction of methylated metabolites due to direct TPMT inhibition.
BACKGROUND: Restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is an effective dietary treatment for irritable bowel syndrome (IBS). Patient dietary ...education is essential but labour intensive. Group FODMAP education may alleviate this somewhat but has not previously been investigated. The present study aimed to investigate the clinical effectiveness of low FODMAP group education in patients with IBS and to explore the cost of a group pathway. METHODS: Patients with IBS (n = 364) were assessed for their suitability to attend dietitian‐led group education or traditional one‐to‐one education in a novel group pathway. Clinical effectiveness (global symptom question, symptom prevalence, stool output) were compared at baseline and follow‐up using the chi‐squared test. The costs of the novel group pathway were assessed using a decision model. RESULTS: The global symptom question indicated more patients were satisfied with their symptoms following dietary advice, in both group education baseline 48/263 (18%) versus follow‐up 142/263 (54%), P < 0.001 and one‐to‐one education baseline 5/101 (5%) versus follow‐up 61/101 (60%), P < 0.001, with no difference between group and one‐to‐one education at follow‐up (P = 0.271). Overall, there was a significant decrease in symptom severity from baseline to follow‐up (P < 0.001 for both groups) but no difference in symptom response between group and one‐to‐one education. The cost for the group education pathway for all 364 patients was £31 713.36. CONCLUSIONS: The present study shows that dietitian‐led FODMAP group education is clinically effective and the costs associated with a FODMAP group pathway are worthy of further consideration for routine clinical care.
Summary
Background
Medication non‐adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome.
Aims
To assess ...whether non‐adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co‐morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8‐item Adherence Scale (MMAS‐8) to detect non‐adherence.
Methods
Seventy young adults 51% (36) male and 74 62% (46) male adults were included. Psychological co‐morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self‐reported adherence using the MMAS‐8.
Results
Twelve percent (18/144) of the patients were non‐adherent. Multivariate analysis OR, (95% CI), P value confirmed that being young adult 6.1 (1.7–22.5), 0.001, of lower socio‐economic status 1.1 (1.0–1.1), <0.01 and reporting higher HADS‐D scores 1.2 (1.0–1.4), 0.01 were associated with non‐adherence. Receiver operator curve analysis of MMAS‐8 scores gave an area under the curve (95% CI) of 0.85 (0.77–0.92), (P < 0.0001): using a cut‐off of <6, the MMAS‐8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non‐adherence. Non‐adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up.
Conclusions
Non‐adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio‐economic status and depression. The high negative predictive value of MMAS‐8 scores <6 suggests that it could be a useful screen for thiopurine non‐adherence.
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