25 results on '"Parkes GC"'
Search Results
2. OC-080 Excess Steroid Use in IBD: Too Much, How Much and Why? Results From A Nationwide Audit
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Raine, T, primary, Bassi, A, additional, Fogden, E, additional, Hayee, B, additional, Limdi, JK, additional, Ludlow, H, additional, McLaughlin, S, additional, Parkes, GC, additional, Patel, P, additional, Smith, MA, additional, and Selinger, C, additional
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- 2016
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3. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease
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Walker, AW, Sanderson, JD, Churcher, C, Parkes, GC, Hudspith, BN, Rayment, N, Brostoff, J, Parkhill, J, Dougan, G, Petrovska, L, Walker, AW, Sanderson, JD, Churcher, C, Parkes, GC, Hudspith, BN, Rayment, N, Brostoff, J, Parkhill, J, Dougan, G, and Petrovska, L
- Abstract
BACKGROUND: The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. RESULTS: Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. CONCLUSIONS: These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity.
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- 2011
4. Treating irritable bowel syndrome with probiotics: the evidence.
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Parkes GC, Sanderson JD, and Whelan K
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- 2010
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5. An overview of probiotics and prebiotics.
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Parkes GC
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PROBIOTICS , *GASTROINTESTINAL system , *IMMUNE system , *DIARRHEA , *IRRITABLE colon , *ATOPIC dermatitis - Abstract
This article reviews the origins and background of probiotics. Evidence for the potential mechanisms of probiotics and prebiotics, and their interactions with the gastrointestinal tract and the immune system are discussed. Evidence is examined for the use of probiotics to treat infantile diarrhoea, irritable bowel syndrome, inflammatory bowel disease and atopic dermatitis. [ABSTRACT FROM AUTHOR]
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- 2007
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6. Nutritional intakes in irritable bowel syndrome.
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McCoubrey H, Parkes GC, Sanderson JD, and Lomer MCE
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- 2008
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7. Differences in the Adverse Event Burden of Corticosteroid Use in Inflammatory Bowel Disease as Reported Between Adverse Event Reporting Systems and a Patient Questionnaire.
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Al Sulais E, Louis E, Bokemeyer B, Gecse KB, Parkes GC, Parkes M, Selinger C, Munsaka M, Liu M, Crooks J, Finney-Hayward T, and Raine T
- Abstract
Background and Aims: Corticosteroids are widely used in managing inflammatory bowel disease [IBD]. While adverse events [AEs] of corticosteroids are well recognised, current understanding of corticosteroid-related AE burden in IBD remains incomplete., Methods: AE reports for prednisone/prednisolone and budesonide were extracted from the Food and Drug Administration Adverse Event Reporting System [FAERS] and VigiBase databases. Total and frequently reported AEs were tabulated, and AEs of special interest were compared with reports for all drugs using proportional reporting ratio criteria. Database reports were compared with AEs reported in a patient survey capturing corticosteroid exposure and AE recall., Results: In FAERS and VigiBase, 344,140 and 42,836 AEs were reported, respectively, in patients with IBD; among these, 10,157 [3.0%] and 11,391 [26.6%], respectively, were related to prednisone/prednisolone or budesonide. AEs associated with corticosteroid use in IBD increased over time. Adrenal insufficiency, Cushingoid complications, osteonecrosis, osteoporosis, diabetes and pancreatitis were disproportionately reported for corticosteroids. Among 9229 patients who responded to the survey, 6434 [69.7%] reported corticosteroid exposure. AEs were more frequently recalled by patients exposed to prednisone [61.9%] vs budesonide [27.4%; p = 0.0001]. The most commonly recalled AEs differed from those reported in the pharmacovigilance databases and included weight gain, sleep problems, mood disturbance and skin changes. Younger patients and those with mental health disorders were more likely to recall suicidal thoughts/attempts., Conclusions: AEs associated with IBD-related corticosteroid use were frequent. Patients reported AEs affecting quality of life, while clinicians disproportionately reported AEs based on objective diagnostic criteria., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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8. PANTS extension study: how best to use anti-TNF drugs in Crohn's disease.
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Parkes GC and Hedin CRH
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- Humans, Adalimumab therapeutic use, Adalimumab adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Gastrointestinal Agents therapeutic use, Gastrointestinal Agents adverse effects, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal adverse effects, Randomized Controlled Trials as Topic, Treatment Outcome, Crohn Disease drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors, Infliximab therapeutic use, Infliximab adverse effects
- Abstract
Competing Interests: GCP declares travel expenses from Celltrion Healthcare. CRHH declares no competing interests.
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- 2024
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9. The Historical Role and Contemporary Use of Corticosteroids in Inflammatory Bowel Disease.
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Dorrington AM, Selinger CP, Parkes GC, Smith M, Pollok RC, and Raine T
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- Humans, Adrenal Cortex Hormones pharmacology, Inflammatory Bowel Diseases drug therapy, Patient Care Management trends
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The use of corticosteroids to treat patients with inflammatory bowel disease [IBD] has been the bedrock of IBD therapeutics since the pioneering work of Truelove and Witts in the UK in the 1950s and subsequent large cohort studies in the USA and Europe. Nevertheless, although effective for induction of remission, these agents do not maintain remission and are associated with a long list of recognised side effects, including a risk of increased mortality. With the arrival of an increasing number of therapies for patients with IBD, the question arises as to whether we are using these agents appropriately in contemporary practice. This review discusses the historical background to steroid usage in IBD, and also provides a brief review of the literature on side effects of corticosteroid treatment as relevant to IBD patients. Data on licensed medications are presented with specific reference to the achievement of corticosteroid-free remission. We review available international data on the incidence of corticosteroid exposure and excess, and discuss some of the observations we and others have made concerning health care and patient-level factors associated with the risk of corticosteroid exposure, including identification of 'at-risk' populations., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2020
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10. β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal Bifidobacteria.
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Wilson B, Rossi M, Kanno T, Parkes GC, Anderson S, Mason AJ, Irving PM, Lomer MC, and Whelan K
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- Adult, Combined Modality Therapy, Diet Therapy methods, Feces chemistry, Female, Fermentation, Humans, In Situ Hybridization, Fluorescence, Irritable Bowel Syndrome metabolism, Irritable Bowel Syndrome microbiology, Irritable Bowel Syndrome physiopathology, Male, Middle Aged, RNA, Ribosomal, 16S, Treatment Outcome, Urine chemistry, Young Adult, Bifidobacterium genetics, Diet, Carbohydrate-Restricted methods, Galactose therapeutic use, Gastrointestinal Microbiome genetics, Irritable Bowel Syndrome therapy, Oligosaccharides therapeutic use, Prebiotics
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Introduction: The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria., Methods: We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed., Results: At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2)., Discussion: The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.
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- 2020
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11. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.
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Kennedy NA, Jones GR, Lamb CA, Appleby R, Arnott I, Beattie RM, Bloom S, Brooks AJ, Cooney R, Dart RJ, Edwards C, Fraser A, Gaya DR, Ghosh S, Greveson K, Hansen R, Hart A, Hawthorne AB, Hayee B, Limdi JK, Murray CD, Parkes GC, Parkes M, Patel K, Pollok RC, Powell N, Probert CS, Raine T, Sebastian S, Selinger C, Smith PJ, Stansfield C, Younge L, Lindsay JO, Irving PM, and Lees CW
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- Antiviral Agents adverse effects, Antiviral Agents therapeutic use, COVID-19, Humans, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Risk Assessment, SARS-CoV-2, United Kingdom, COVID-19 Drug Treatment, Betacoronavirus, Coronavirus Infections complications, Coronavirus Infections drug therapy, Coronavirus Infections therapy, Coronavirus Infections transmission, Inflammatory Bowel Diseases therapy, Pandemics, Pneumonia, Viral complications, Pneumonia, Viral therapy, Pneumonia, Viral transmission
- Abstract
The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials., Competing Interests: Competing interests: For details of conflicts of interest see online supplementary table 1., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2020
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12. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, and Hawthorne AB
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- Adult, Humans, United Kingdom, Consensus, Conservative Treatment standards, Disease Management, Gastroenterology, Inflammatory Bowel Diseases therapy, Practice Guidelines as Topic standards, Societies, Medical
- Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends., Competing Interests: Competing interests: Conflicts of interest for authors and contributors are presented in online supplementary table 2., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2019
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13. Assessment of steroid use as a key performance indicator in inflammatory bowel disease-analysis of data from 2385 UK patients.
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Selinger CP, Parkes GC, Bassi A, Limdi JK, Ludlow H, Patel P, Smith M, Saluke S, Ndlovu Z, George B, Saunders J, Adamson M, Fraser A, Robinson J, Donovan F, Parisi I, Tidbury J, Gray L, Pollok R, Scott G, and Raine T
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- Adrenal Cortex Hormones therapeutic use, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents classification, Anti-Inflammatory Agents therapeutic use, Cohort Studies, Female, Humans, Inflammatory Bowel Diseases diagnosis, Male, Middle Aged, Prognosis, Quality Assurance, Health Care, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha immunology, United Kingdom epidemiology, Young Adult, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases epidemiology, Practice Patterns, Physicians' standards, Practice Patterns, Physicians' statistics & numerical data, Quality Indicators, Health Care, Steroids therapeutic use
- Abstract
Background: Patients with IBD are at risk of excess corticosteroids., Aims: To assess steroid excess in a large IBD cohort and test associations with quality improvement and prescribing., Methods: Steroid exposure was recorded for outpatients attending 19 centres and associated factors analysed. Measures taken to avoid excess were assessed., Results: Of 2385 patients, 28% received steroids in the preceding 12 months. 14.8% had steroid excess or dependency. Steroid use was significantly lower at 'intervention centres' which participated in a quality improvement programme (exposure: 23.8% vs 31.0%, P < .001; excess 11.5% vs 17.1%, P < .001). At intervention centres, steroid use fell from 2015 to 2017 (steroid exposure 30.0%-23.8%, P = .003; steroid excess 13.8%-11.5%, P = .17). Steroid excess was judged avoidable in 50.7%. Factors independently associated with reduced steroid excess in Crohn's disease included maintenance with anti-TNF agents (OR 0.61 [95% CI 0.24-0.95]), treatment in a centre with a multi-disciplinary team (OR 0.54 [95% CI 0.20-0.86]) and treatment at an intervention centre (OR 0.72 [95% CI 0.46-0.97]). Treatment with 5-ASA in CD was associated with higher rates of steroid excess (OR 1.72 [95% CI 1.24-2.09]). In ulcerative colitis (UC), thiopurine monotherapy was associated with steroid excess (OR 1.97 [95% CI 1.19-3.01]) and treatment at an intervention centre with less steroid excess (OR 0.72 [95% CI 0.45-0.95])., Conclusions: This study validates steroid assessment as a meaningful quality measure and provides a benchmark for this performance indicator in a large cohort. A programme of quality improvement was associated with lower steroid use., (© 2019 John Wiley & Sons Ltd.)
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- 2019
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14. Oral Anti-Tumour Necrosis Factor Domain Antibody V565 Provides High Intestinal Concentrations, and Reduces Markers of Inflammation in Ulcerative Colitis Patients.
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Nurbhai S, Roberts KJ, Carlton TM, Maggiore L, Cubitt MF, Ray KP, Reckless J, Mohammed H, Irving P, MacDonald TT, Vossenkämper A, West MR, Parkes GC, and Crowe JS
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- Adult, Aged, Antibodies analysis, Antibodies metabolism, Female, Humans, Intestines chemistry, Male, Middle Aged, Recombinant Proteins therapeutic use, Tumor Necrosis Factor-alpha immunology, Antibodies therapeutic use, Colitis, Ulcerative drug therapy, Immunotherapy methods, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
V565 is an engineered TNFα-neutralising single domain antibody formulated into enteric coated mini-tablets to enable release in the intestine after oral administration as a possible oral treatment for inflammatory bowel disease (IBD). Following oral administration, ileal recovery of V565 was investigated in four patients with terminal ileostomy. Intestinal and systemic pharmacokinetics were measured in six patients with Crohn's disease and evidence of target engagement assessed in five patients with ulcerative colitis. Following oral administration, V565 was detected at micromolar concentrations in ileal fluid from the ileostomy patients and in stools of the Crohn's patients. In four of the five ulcerative colitis patients, biopsies taken after 7d dosing demonstrated V565 in the lamina propria with co-immunostaining on CD3
+ T-lymphocytes and CD14+ macrophages. Phosphorylation of signalling proteins in biopsies taken after 7d oral dosing was decreased by approximately 50%. In conclusion, enteric coating of V565 mini-tablets provided protection in the stomach with gradual release in intestinal regions affected by IBD. Immunostaining revealed V565 tissue penetration and association with inflammatory cells, while decreased phosphoproteins after 7d oral dosing was consistent with V565-TNFα engagement and neutralising activity. Overall these results are encouraging for the clinical utility of V565 in the treatment of IBD.- Published
- 2019
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15. Editorial: avoiding corticosteroids in the treatment of inflammatory bowel disease-Author's reply.
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Selinger CP, Parkes GC, and Raine T
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- Humans, Adrenal Cortex Hormones, Inflammatory Bowel Diseases
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- 2018
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16. A multi-centre audit of excess steroid use in 1176 patients with inflammatory bowel disease.
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Selinger CP, Parkes GC, Bassi A, Fogden E, Hayee B, Limdi JK, Ludlow H, McLaughlin S, Patel P, Smith M, and Raine T
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- Humans, Incidence, Remission Induction, Adrenal Cortex Hormones administration & dosage, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy
- Abstract
Background: Corticosteroids are central to inducing remission in inflammatory bowel disease (IBD) but are ineffective maintenance agents., Aim: To benchmark steroid usage in British outpatients and assess factors associated with excess exposure., Methods: We recorded steroid use in unselected IBD outpatients. Cases meeting criteria for steroid dependency or excess were blind peer reviewed to determine whether steroid prescriptions were avoidable. Associations between steroid use and patient/institutional factors were analysed., Results: Of 1176 patients, 30% received steroids in the prior 12 months. 14.9% had steroid dependency or excess, which was more common in moderate/severe ulcerative colitis (UC) than Crohn's disease (CD) (42.6% vs 28.1%; P = .027). Steroid dependency or excess was deemed avoidable in 49.1%. The annual incidence of inappropriate steroid excess was 7.1%. Mixed-effects logistic regression analysis revealed independent predictors of inappropriate steroid excess. The odds ratio (OR, 95%CI) for moderate/severe compared to mild/quiescent disease activity was 4.59 (1.53-20.64) for UC and 4.60 (2.21-12.00) for CD. In CD, lower rates of inappropriate steroid excess were found in centres with an IBD multi-disciplinary team (OR 0.62 [0.46-0.91]), whilst dedicated IBD clinics protected against inappropriate steroid excess in UC (OR 0.64, 95% CI 0.21-0.94). The total number of GI trainees was associated with rates of inappropriate steroid excess., Conclusions: Steroid dependency or excess occurred in 14.9% of British IBD patients (in 7.1% potentially avoidable). We demonstrated positive effects of service configurations (IBD multi-disciplinary team, dedicated IBD clinics). Routine recording of steroid dependency or excess is feasible and should be considered a quality metric., (© 2017 John Wiley & Sons Ltd.)
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- 2017
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17. Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease.
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Elliott TR, Rayment NB, Hudspith BN, Hands RE, Taylor K, Parkes GC, Prescott NJ, Petrovska L, Hermon-Taylor J, Brostoff J, Boussioutas A, Mathew CG, Bustin SA, and Sanderson JD
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- Adult, Aged, Biomarkers metabolism, Case-Control Studies, Colitis, Ulcerative immunology, Colitis, Ulcerative microbiology, Crohn Disease microbiology, Cytokines metabolism, Escherichia coli isolation & purification, Female, Humans, Intestinal Mucosa microbiology, Macrophages metabolism, Male, Middle Aged, Crohn Disease immunology, Escherichia coli immunology, Intestinal Mucosa immunology, Macrophages microbiology, Phenotype
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Background: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage., Methods: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR., Results: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls., Conclusion: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.
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- 2015
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18. Smoking in inflammatory bowel disease: impact on disease course and insights into the aetiology of its effect.
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Parkes GC, Whelan K, and Lindsay JO
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- Colitis, Ulcerative etiology, Crohn Disease etiology, Disease Progression, Female, Humans, Immunity drug effects, Intestines drug effects, Intestines microbiology, Male, Microbiota drug effects, Sex, Tobacco Smoke Pollution adverse effects, Inflammatory Bowel Diseases etiology, Smoking adverse effects
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The chronic intestinal inflammation that characterises Crohn's disease and ulcerative colitis arises from a complex interplay between host genotype, the immune system, and the intestinal microbiota. In addition, environmental factors such as smoking impact on disease onset and progression. Individuals who smoke are more likely to develop Crohn's disease, and smoking is associated with recurrence after surgery and a poor response to medical therapy. Conversely, smoking appears protective against ulcerative colitis and smokers are less likely to require colectomy. The mechanism by which smoking exerts its impact on disease and the rational for the dichotomous effect in patients with Crohn's disease and ulcerative colitis is not clear. Recent evidence suggests that smoking induces alterations to both the innate and acquired immune system. In addition, smoking is associated with a distinct alteration in the intestinal microbiota both in patients with active Crohn's disease and healthy subjects., (Copyright © 2014. Published by Elsevier B.V.)
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- 2014
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19. Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome.
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Parkes GC, Rayment NB, Hudspith BN, Petrovska L, Lomer MC, Brostoff J, Whelan K, and Sanderson JD
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- Adult, Bacteria genetics, Biopsy, Female, Humans, Intestinal Mucosa pathology, Irritable Bowel Syndrome pathology, Irritable Bowel Syndrome physiopathology, Male, Rectum anatomy & histology, Rectum microbiology, Rectum surgery, Intestinal Mucosa microbiology, Irritable Bowel Syndrome microbiology, Metagenome
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Background: There is increasing evidence to support a role for the gastrointestinal microbiota in the etiology of irritable bowel syndrome (IBS). Given the evidence of an inflammatory component to IBS, the mucosa-associated microbiota potentially play a key role in its pathogenesis. The objectives were to compare the mucosa-associated microbiota between patients with diarrhea predominant IBS (IBS-D), constipation predominant IBS (IBS-C) and controls using fluorescent in situ hybridization and to correlate specific bacteria groups with individual IBS symptoms., Methods: Forty-seven patients with IBS (27 IBS-D and 20 IBS-C) and 26 healthy controls were recruited to the study. Snap-frozen rectal biopsies were taken at colonoscopy and bacterial quantification performed by hybridizing frozen sections with bacterial-group specific oligonucleotide probes., Key Results: Patients with IBS had significantly greater numbers of total mucosa-associated bacteria per mm of rectal epithelium than controls [median 218 (IQR - 209) vs 128 (121) P = 0.007], and this was chiefly comprised of bacteroides IBS [69 (67) vs 14 (41) P = 0.001] and Eubacterium rectale-Clostridium coccoides [52 (58) vs 25 (35) P = 0.03]. Analysis of IBS sub-groups demonstrated that bifidobacteria were lower in the IBS-D group than in the IBS-C group and controls [24 (32) vs 54 (88) vs 32 (35) P = 0.011]. Finally, amongst patients with IBS, the maximum number of stools per day negatively correlated with the number of mucosa-associated bifidobacteria (P < 0.001) and lactobacilli (P = 0.002)., Conclusions & Inferences: The mucosa-associated microbiota in patients with IBS is significantly different from healthy controls with increases in bacteroides and clostridia and a reduction in bifidobacteria in patients with IBS-D., (© 2011 Blackwell Publishing Ltd.)
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- 2012
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20. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease.
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Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, Brostoff J, Parkhill J, Dougan G, and Petrovska L
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- Adult, Aged, Bacterial Load, Biopsy, Case-Control Studies, Enterobacteriaceae classification, Enterobacteriaceae genetics, Female, Humans, Male, Middle Aged, RNA, Bacterial genetics, RNA, Ribosomal, 16S genetics, Young Adult, Colitis, Ulcerative microbiology, Colon microbiology, Crohn Disease microbiology, Gene Library, Intestinal Mucosa microbiology, Metagenome
- Abstract
Background: The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles., Results: Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut., Conclusions: These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity.
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- 2011
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21. The mechanisms and efficacy of probiotics in the prevention of Clostridium difficile-associated diarrhoea.
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Parkes GC, Sanderson JD, and Whelan K
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- Anti-Bacterial Agents therapeutic use, Diarrhea microbiology, Enterocolitis, Pseudomembranous drug therapy, Enterocolitis, Pseudomembranous epidemiology, Humans, Probiotics standards, Clostridioides difficile, Diarrhea prevention & control, Enterocolitis, Pseudomembranous prevention & control, Probiotics therapeutic use
- Abstract
The proportion and severity of Clostridium difficile-associated diarrhoea (CDAD) is increasing in health-care settings. Antibiotics remain the most important risk factor for CDAD, due to their limiting the ability of the gastrointestinal flora to inhibit C difficile colonisation. Probiotics have therefore been investigated for primary and secondary prophylaxis against CDAD, with varying success. This Review looks at the current literature for in-vitro and clinical evidence for probiotic use in the prevention of CDAD. Its aim is to examine the mechanisms through which probiotics interact with C difficile and its toxin, and the association of these mechanisms with the clinical evidence for probiotics in the prevention of this disease. The Review briefly describes the recent epidemiological changes in C difficile disease, and our current understanding of its pathophysiology. It looks at the safety profile of probiotics, highlighting patients groups in which their use is inappropriate, and attempts to synthesise guidance for clinicians interested in using probiotics to prevent CDAD within health-care institutions.
- Published
- 2009
- Full Text
- View/download PDF
22. Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment.
- Author
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Parkes GC, Brostoff J, Whelan K, and Sanderson JD
- Subjects
- Feces microbiology, Humans, Irritable Bowel Syndrome pathology, Probiotics therapeutic use, Intestinal Mucosa microbiology, Irritable Bowel Syndrome microbiology, Irritable Bowel Syndrome therapy
- Abstract
Irritable bowel syndrome (IBS) is a chronic disorder characterized by abdominal pain, change in bowel habit, and bloating. It has traditionally been viewed as a disorder of visceral hypersensitivity heavily influenced by stress, and therefore therapeutic strategies to date have largely reflected this. However, more recently, there is good evidence for a role of the gastrointestinal (GI) microbiota in its pathogenesis. Changes in fecal microbiota, the use of probiotics, the phenomenon of postinfectious IBS, and the recognition of an upregulated host immune system response suggest that an interaction between the host and GI microbiota may be important in the pathogenesis of IBS. This article explores the role of the GI microbiota in IBS and how their modification might lead to therapeutic benefit.
- Published
- 2008
- Full Text
- View/download PDF
23. Review article: lactose intolerance in clinical practice--myths and realities.
- Author
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Lomer MC, Parkes GC, and Sanderson JD
- Subjects
- Adult, Animals, Breath Tests, Child, Dairy Products adverse effects, Female, Genetic Variation, Humans, Infant, Newborn, Intestine, Small metabolism, Intestine, Small microbiology, Irritable Bowel Syndrome etiology, Lactase genetics, Lactase metabolism, Pregnancy, Lactose Intolerance diagnosis, Lactose Intolerance diet therapy, Lactose Intolerance genetics
- Abstract
Background: Approximately 70% of the world population has hypolactasia, which often remains undiagnosed and has the potential to cause some morbidity. However, not everyone has lactose intolerance, as several nutritional and genetic factors influence tolerance., Aims: To review current clinical practice and identify published literature on the management of lactose intolerance., Methods: PubMed was searched using the terms lactose, lactase and diet to find original research and reviews. Relevant articles and clinical experience provided the basis for this review., Results: Lactose is found only in mammalian milk and is hydrolysed by lactase in the small intestine. The lactase gene has recently been identified. 'Wild-type' is characterized by lactase nonpersistence, often leading to lactose intolerance. Two genetic polymorphisms responsible for persistence have been identified, with their distribution concentrated in north Europeans. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhoea. Diagnosis is most commonly by the lactose hydrogen breath test. However, most people with hypolactasia, if given appropriate advice, can tolerate some lactose-containing foods without symptoms., Conclusion: In clinical practice, some people with lactose intolerance can consume milk and dairy foods without developing symptoms, whereas others will need lactose restriction.
- Published
- 2008
- Full Text
- View/download PDF
24. Timing of surgery for inflammatory bowel disease.
- Author
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Sanderson JD and Parkes GC
- Subjects
- Elective Surgical Procedures, Humans, Time Factors, Inflammatory Bowel Diseases surgery
- Published
- 2007
- Full Text
- View/download PDF
25. One man and his scope.
- Author
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Parkes GC and Sanderson JD
- Subjects
- Colonoscopy methods, Humans, Clinical Competence standards, Colonoscopy standards
- Published
- 2006
- Full Text
- View/download PDF
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