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Séverine Vermeire,1 François D’heygere,2 Antoine Nakad,3 Denis Franchimont,4 Fernand Fontaine,5 Edouard Louis,6 Philippe Van Hootegem,7 Olivier Dewit,8 Guy Lambrecht,9 Beatrijs Strubbe,10 Filip Baert11 1Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 2Department of Gastroenterology, AZ Groeninge, Kortrijk, Belgium; 3Department of Gastroenterology, CHWAPI, Tournai, Belgium; 4Department of Gastroenterology, Erasme Hospital, Brussels, Belgium; 5Department of Gastroenterology, CHC St Joseph, Liège, Belgium; 6Department of Gastroenterology, University Hospital CHU Sart Tilman, Liège, Belgium; 7Department of Gastroenterology, AZ St Lucas, Brugge, Belgium; 8Department of Gastroenterology, UCL St Luc, Brussels, Belgium; 9Department of Gastroenterology, AZ Damiaan, Oostende, Belgium; 10Department of Gastroenterology, OLV Hospital, Aalst, Belgium; 11Department of Gastroenterology, AZ Delta, Roeselare-Menen, Belgium Purpose: Simponi® (golimumab, MSD) is a fully human monoclonal antibody against tumor necrosis factor alpha administered subcutaneously using an autoinjector or a prefilled syringe. This study examined preference for administration of golimumab by autoinjector or prefilled syringe in patients with moderate-to-severe ulcerative colitis (UC). Patients and methods: This was a multicenter, open-label, randomized crossover trial (EudraCT no 2014-000656-29). Patients with moderate-to-severe UC were randomized 1:1 to receive 2 subcutaneous injections of 50 mg golimumab with the autoinjector followed by 2 injections of 50 mg with the prefilled syringe or the same 4 injections administered in the opposite order. Patients assessed preference, ease of use, and discomfort immediately after the injections and 2 weeks later. Results: Ninety-one patients were included (median age=42.7 years [range, 19.7–93.7]; 58% male). The autoinjector was preferred by 76.9% of patients immediately after injections and by 71.4% 2 weeks later. The autoinjector was more often considered extremely easy or easy to use (94.5%) than the prefilled syringe (73.6%). Moderate discomfort or worse was reported by more patients when using the prefilled syringe (20.9%) than when using the autoinjector (5.5%), and severe discomfort or discomfort preventing injection of future doses was reported by 8.8% for the prefilled syringe but not at all when using the autoinjector. A favorable or extremely favorable overall impression was reported by 89.0% for the autoinjector and 72.5% for the prefilled syringe. Conclusion: Most patients with moderate-to-severe UC preferred to self-administer golimumab with the autoinjector over a prefilled syringe. Keywords: autoinjector, adherence, anti-TNF, subcutaneous injection, treatment, self-injection

Background and Aims Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect. Methods We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation. Results Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8–11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43–0.94], p  = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1–2.5], p  = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0–39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5–94.9] in the early switch group and 59.3% [95% CI 48.9–71.9] in the other group [ p  < 0.01]. Conclusions Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse. [ABSTRACT FROM AUTHOR]

Aims: To assess the acceptability and feasibility of whole body air displacement plethysmography in children and to determine its precision and agreement with hydrodensitometry, an appropriate reference method.Methods: Age specific two component model equations were used to predict fat mass from body density in 22 children aged 8-12 years and in 10 adults for comparison of methods. Precision for each method was established from duplicate measurements.Results: Plethysmography was accepted more readily than hydrodensitometry (100% v 69% provided duplicate measurements). Precision for fat mass in children was 0.38 kg by plethysmography and 0.68 kg by hydrodensitometry, and results were similar in adults. The mean (SD) fat mass in children was 6.9 kg (4.0) and 6.7 kg (4. 2) by plethysmography and hydrodensitometry, respectively, but 95% limits of agreement between methods were large (-4.1 kg to 3.5 kg fat).Conclusion: Plethysmography was more readily accepted and had better precision than hydrodensitometry. It also provided similar body composition results for the group but not for all individual children. [ABSTRACT FROM AUTHOR]

Background Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis ( UC); however, multi-dosing regimens are inconvenient. Aim To compare the efficacy and safety of once- ( OD) vs. twice- ( BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study. Methods Eligible patients ( n = 206) were randomised to 8 weeks of mesalazine (4 g/day), either OD with two sachets of 2 g mesalazine granules in the morning ( n = 102) or BD with one 2 g sachet in the morning and one in the evening ( n = 104). Patients also received 4 weeks of mesalazine enema 1 g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index ( UC- DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8 weeks. Patients recorded stool frequency and rectal bleeding in a daily diary. Results The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8 weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval −3.4, 24.1; P = 0.14). Improvement of UC- DAI score (92% vs. 79%; P = 0.01) and mucosal healing (87.5% vs. 71.1%; P = 0.007) were significantly better, time to remission significantly shorter (26 vs. 28 days; P = 0.04) and safety similar with OD vs. BD dosing. Conclusions When combined with mesalazine enema, prolonged-release mesalazine once-daily 4 g is as effective and well tolerated as 2 g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789). [ABSTRACT FROM AUTHOR]

OBJECTIVES:Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX.METHODS:This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed.RESULTS:A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (±s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (±s.e.) was 61.3±5.3% at 3 months and 41.3±5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy.CONCLUSIONS:In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually. [ABSTRACT FROM AUTHOR]

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Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK3 receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK3 receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14–17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants. [ABSTRACT FROM AUTHOR]

Background SPD476 (MMX™ mesalazine), is a novel, once daily, high-strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System™ (MMX) technology to delay and extend delivery of the active drug throughout the colon. Aim To assess the safety and efficacy of MMX mesalazine in patients with mild-to-moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202). Methods Thirty-eight patients with mild-to-moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis-disease activity index (UC-DAI) ≤1, a score of 0 for rectal bleeding and stool frequency, and ≥1-point reduction in sigmoidoscopy score from baseline was the primary end point. Results Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC-DAI and component scores from baseline, compared with the 1.2 g/day group. Conclusion MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild-to-moderately active ulcerative colitis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the potential of segmental bioelectrical impedance analysis (BIA) for assessing regional composition and muscle mass in children. DESIGN: Strengths of relationships were determined between (a) BIA indices of trunk, limbs or limb segments and (b) segment fat or fat-free mass (FFM) assessed using dual-energy X-ray absorptiometry (DXA); the extent of agreement was established between two independent models, based on DXA and BIA, of limb muscle and adipose tissue (AT) mass. SUBJECTS: Eighteen boys and 19 girls aged 8-12 y. MEASUREMENTS: BIA and anthropometry of trunk, whole limbs, limb segments and defined sections were used to calculate segmental impedance indices and specific resistivities; segment fat and FFM were obtained using DXA; muscle and AT masses of limbs, segments and sections were estimated using DXA and BIA models, and by anthropometry. RESULTS: Segmental BIA indices were significantly related to composition of the segments assessed using DXA; although substantial bias was observed, there was fairly good agreement (low 9.5% limits of agreement) between the BIA and DXA models of muscle mass and estimates from each were similarly categorised in tertiles, as were estimates of AT. CONCLUSION: Segmental BIA appears to have potential for assessing in children the composition of body segments, as obtained using DXA, and the masses of muscle and AT in whole limbs, limb segments and defined sections. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the potential of segmental bioelectrical impedance analysis (BIA) for estimating whole-body composition in children. DESIGN: Strengths of relationships were determined between indices of impedance or specific resistivities of body segments and reference four-component model (4-CM) assessments of body composition. SUBJECTS: Eighteen boys and 19 girls aged 8-12y. MEASUREMENTS: Whole-body and segment BIA and anthropometry were used to calculate impedance indices of the whole body and segments and specific resistivities of segments; total body water (TBW), fat-free mass (FFM) and body fat were assessed using the 4-CM. RESULTS: Segmental BIA indices were significantly related to body composition, provided that appropriate comparisons were undertaken for each index: impedance adjusted for unit segment length was better related to TBW and FFM, whereas segment specific resistivity was better related to body fat. Differences between body composition estimates obtained with the 4-CM and predicted using BIA were partly dependent on limb-to-trunk ratios of BIA indices. CONCLUSION: Segmental BIA has potential for providing additional alternative approaches to the assessment of whole-body composition in children: (a) FFM and TBW were best related to impedance adjusted for segment length; (b) body fat was best related to segment specific resistivity; and (c) the relative influences of different segment BIA indices may be utilisable for generating more valid whole-body composition estimates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Body composition in children is generally measured by 2-component (2C) models, which are subject to error arising from variation in fat-free mass (FFM) composition. The 4-component (4C) model, which divides body weight into fat, water, mineral, and protein, can overcome these limitations. OBJECTIVE: The aims of our study were to 1) describe 4C model data for children aged 8-12 y; 2) evaluate interindividual variability in the hydration, bone mineral content, and density of FFM; 3) evaluate the success with which 2C models and bedside techniques measure body composition in this age group with use of the 4C model as a reference. DESIGN: Dual-energy X-ray absorptiometry, underwater weighing, deuterium dilution, bioelectrical impedance analysis, and anthropometry were used to determine body composition in 30 children. The contribution of methodologic error to the observed variability in the hydration and density of FFM was evaluated by using propagation of error. RESULTS: Mean (+/-SD) FFM density and hydration were 1.0864+/-0.0074 kg/L and 75.3+/-2.2%, respectively, and were significantly different from adult values (P < 0.02). Relative to the 4C model, deuterium dilution and dual-energy X-ray absorptiometry showed no mean bias for fatness, whereas underwater weighing underestimated fatness (P < 0.025). Fatness determined by using skinfold-thickness and bioelectrical impedance analysis measurements along with published equations showed poor agreement with 4C model data. CONCLUSIONS: Biological variability and methodologic error contribute equally to the variability of FFM composition. Our findings have major implications for bedside prediction methods used for children, traditionally developed in relation to underwater weighing. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished children without diarrhoea were giardia positive. Twenty-three children with chronic diarrhoea were reinvestigated after treatment with metronidazole; giardia was found in 11 of them. These results show that giardia is highly prevalent in children with chronic diarrhoea and malnutrition and that the infection does not respond to standard therapeutic measures. [ABSTRACT FROM AUTHOR]