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See detailRandom forest estimation of genomic breeding values for disease susceptibility over different disease incidences and genomic architectures in simulated cow calibration groups
Naderi Darbaghshahi, Saeid ULiege; Yin, T.; König, S.

in Journal of Dairy Science (2016), 99(9), 7261-7273

A simulation study was conducted to investigate the performance of random forest (RF) and genomic BLUP (GBLUP) for genomic predictions of binary disease traits based on cow calibration groups. Training ... [more ▼]

A simulation study was conducted to investigate the performance of random forest (RF) and genomic BLUP (GBLUP) for genomic predictions of binary disease traits based on cow calibration groups. Training and testing sets were modified in different scenarios according to disease incidence, the quantitative-genetic background of the trait (h2 = 0.30 and h2 = 0.10), and the genomic architecture [725 quantitative trait loci (QTL) and 290 QTL, populations with high and low levels of linkage disequilibrium (LD)]. For all scenarios, 10,005 SNP (depicting a low-density 10K SNP chip) and 50,025 SNP (depicting a 50K SNP chip) were evenly spaced along 29 chromosomes. Training and testing sets included 20,000 cows (4,000 sick, 16,000 healthy, disease incidence 20%) from the last 2 generations. Initially, 4,000 sick cows were assigned to the testing set, and the remaining 16,000 healthy cows represented the training set. In the ongoing allocation schemes, the number of sick cows in the training set increased stepwise by moving 10% of the sick animals from the testing set to the training set, and vice versa. The size of the training and testing sets was kept constant. Evaluation criteria for both GBLUP and RF were the correlations between genomic breeding values and true breeding values (prediction accuracy), and the area under the receiving operating characteristic urve (AUROC). Prediction accuracy and AUROC increased for both methods and all scenarios as increasing percentages of sick cows were allocated to the training set. Highest prediction accuracies were observed for disease incidences in training sets that reflected the population disease incidence of 0.20. For this allocation scheme, the largest prediction accuracies of 0.53 for RF and of 0.51 for GBLUP, and the largest AUROC of 0.66 for RF and of 0.64 for GBLUP, were achieved using 50,025 SNP, a heritability of 0.30, and 725 QTL. Heritability decreases from 0.30 to 0.10 and QTL reduction from 725 to 290 were associated with decreasing prediction accuracy and decreasing AUROC for all scenarios. This decrease was more pronounced for RF. Also, the increase of LD had stronger effect on RF results than on GBLUP results. The highest prediction accuracy from the low LD scenario was 0.30 from RF and 0.36 from GBLUP, and increased to 0.39 for both methods in the high LD population. Random forest successfully identified important SNP in close map distance to QTLexplaining a high proportion of the phenotypic trait variations. [less ▲]

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See detailInfliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection.
Regueiro, Miguel; Feagan, Brian G.; Zou, Bin et al

in Gastroenterology (2016), 150(7), 1568-78

BACKGROUND & AIMS: Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability ... [more ▼]

BACKGROUND & AIMS: Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. METHODS: We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a >/=70-point increase from baseline, and endoscopic recurrence (Rutgeerts score >/=i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. RESULTS: A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P = .097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P < .001). Additionally, a significantly smaller proportion of patients in the infliximab group had endoscopic recurrence based only on Rutgeerts scores >/=i2 (22.4% vs 51.3%; ARR with infliximab, 28.9%; 95% confidence interval: 18.4% to 39.4%; P < .001). Patients previously treated with anti-tumor necrosis factor agents or those with more than 1 resection were at greater risk for clinical recurrence. The safety profile of infliximab was similar to that from previous reports. CONCLUSIONS: Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection. However, infliximab does reduce endoscopic recurrence. ClinicalTrials.gov ID NCT01190839. [less ▲]

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See detailPaediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.
De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise et al

in Journal of Pediatric Gastroenterology and Nutrition (2016), 63(2), 253-8

OBJECTIVE: The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited ... [more ▼]

OBJECTIVE: The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. METHODS: Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. RESULTS: At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. CONCLUSIONS: Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36. [less ▲]

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See detailCosts of Crohn's Disease According to Severity States in France: A Prospective Observational Study and Statistical Modeling over 10 Years.
Boschetti, Gilles; Nancey, Stephane; Daniel, Fady et al

in Inflammatory Bowel Diseases (2016), 22(12), 2924-2932

BACKGROUND: To describe the medico-economic characteristics of Crohn's disease (CD), we implemented a multicenter study in France. METHODS: From 2004 to 2006, disease severity states, direct (hospital and ... [more ▼]

BACKGROUND: To describe the medico-economic characteristics of Crohn's disease (CD), we implemented a multicenter study in France. METHODS: From 2004 to 2006, disease severity states, direct (hospital and extra hospital) and indirect costs were prospectively collected over 1 year in patients with CD naive from anti-tumor necrosis factor alpha (infliximab) at inclusion. Economic valorization was performed from the French Social Insurance perspective, and a statistical modeling over 10 years was performed. RESULTS: In 341 patients, the mean total costs of management were &OV0556;6024 per year (&OV0556;4675 for direct costs). As compared to patients in remission, costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery (SURG). The most important expense items were medical and surgical hospitalizations (56% of total costs), including cost of infliximab (36% of hospitalization costs, i.e., 20% of total costs), indirect costs (22%), and drugs (11%). The statistical modeling over 10 years showed that most of the clinical course was spent in drug-responsive state (54%) with 26% of costs or in remission (32%) with 11% of costs; time spent in a SURG state was small (3.2%) but generated 48% of total costs. CONCLUSIONS: Before the introduction of self-injectable anti-tumor necrosis factor alpha, the most important expenses were supported by hospitalizations, explaining why the most costly states were for patients requiring SURG or dependent on inhospital administrated drugs. Projected data show that most time is spent in a stabilized state with appropriate treatments or in remission, and that costs associated with SURG are high. [less ▲]

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See detailRecommandations du groupe EUROVISCO pour le retraitement par acide hyaluronique des patients préalablement traités par viscosupplémentation pour une gonarthrose
Chevalier, X.; Bard, H.; Migliore, A. et al

in Revue du Rhumatisme (Edition Francaise) (2016), 83

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See detailCorrigendum to '2014 OARSI Guidelines for the Non-Surgical Management of Knee Osteoarthritis' [Osteoarthritis and Cartilage 22(2014) 363-388]
McAlindon, T. E.; Bannuru, R. R.; Sullivan, M. C. et al

in Osteoarthritis and Cartilage (2015), 23(6), 1026-1034

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See detailPerception gaps between patients with ulcerative colitis and healthcare professionals: An online survey
Schreiber, S.; Panés, J.; Louis, Edouard ULiege et al

in South African Gastroenterology Review (2015), 13(1), 7-15

Background: The purpose of this study was to examine the differing perspectives and perceptual gaps relating to ulcerative colitis (UC) symptoms and their management between patients and healthcare ... [more ▼]

Background: The purpose of this study was to examine the differing perspectives and perceptual gaps relating to ulcerative colitis (UC) symptoms and their management between patients and healthcare professionals (HCPs). Methods: Structured, cross-sectional, Web-based questionnaires designed to assess a variety of disease indices were completed by adult patients with UC and HCPs involved in the care of patients with UC from Canada, France, Germany, Ireland, Spain, and the United Kingdom. Results: Surveys were completed by 775 patients, 475 physicians, and 50 nurses. Patient self-reported classification of disease severity revealed generally greater severity (mild, 32%; moderate, 53%) compared with physician and nurse estimates of UC severity among their caseloads (mild, 52% and 49%; moderate, 34% and 37%, respectively). Patients reported that an average of 5.5 (standard deviation, 11.0) flares (self-defined) occurred over the past year, compared with 3.4 and 3.8 flares per year estimated by physicians and nurses. Perceived flare triggers differed between patients (stress ranked first) and HCPs (natural disease course ranked first). Fifty-five percent of patients stated that UC symptoms over the past year had affected their quality of life, while physicians and nurses estimated that 35% to 37% of patients would have a reduced quality of life over the same period. Patients ranked urgency and pain as the most bothersome symptoms, while physicians and nurses ranked urgency and stool frequency highest. About half of patients (47%) defined remission as experiencing no symptoms; by comparison, 62% to 63% of HCPs defined remission as requiring the complete absence of symptoms. HCPs (doctors/nurses in general practice and/or hospital) were regarded by patients as their main source of UC information by 72%; however, 59% reported not arranging regular visits to see their HCPs. Conclusions: This large survey identified important differences between patients' and HCPs' perceptions of the impact of UC symptoms on patients' lives. Notably, HCPs may underestimate the effect of specific UC symptoms on patients and may fail to recognize issues that are important to patients. © 2015, In House Publications. All rights reserved. [less ▲]

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See detailLes pratiques professionnelles et l’évaluation de la compréhension en lecture
Schillings, Patricia ULiege; Géron, Stéphanie ULiege

Learning material (2015)

Des enseignants, étudiants du Master en Sciences de l'éducation, décrivent la manière dont leur pratique professionnelle en lien avec l’évaluation de la compréhension en lecture a évolué suite à l’analyse ... [more ▼]

Des enseignants, étudiants du Master en Sciences de l'éducation, décrivent la manière dont leur pratique professionnelle en lien avec l’évaluation de la compréhension en lecture a évolué suite à l’analyse des résultats et des outils d’évaluation relatifs à l’étude PIRLS 2011. [less ▲]

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See detailComplications de la rectocolite hémorragique et impact des traitements actuels sur l'histoire naturelle de ces complications
REENAERS, Catherine ULiege; Louis, Edouard ULiege

in Hépato-Gastro (2015), 22

Ulcerative colitis is a chronic disease progressing to many complications. Impaired quality of life, both physically, professionally and emotionally, is present in the majority of cases. It is linked ... [more ▼]

Ulcerative colitis is a chronic disease progressing to many complications. Impaired quality of life, both physically, professionally and emotionally, is present in the majority of cases. It is linked either to the inflammatory activity of the disease or to the alteration of colonic function due to tissue damage or to the consequences of coloproctectomy. Hospitalization rates are three times higher than the general population and motivated by extensive complications of the disease or investigations and treatments. The long-term consequences of histological inflammation are associated with a twofold risk of colorectal cancer. The surgery rate is 4.9%, 11.6%, 15.6% at 1, 5 and 10 years. The need for surgery is increased in the first years of the diagnosis in case of extensive colitis and if the disease was discovered at a young age. A reduction of inflammatory activity of UC by current treatments, including anti-TNF, leads to improved quality of life and a reduction in hospitalization rates. A reduction in the incidence of colorectal cancer in 5ASA has been demonstrated and, more recently, by purines through their anti-inflammatory activity. We do not currently have data on the effect of anti-TNF. The impact of treatment on surgery rates is controversial from one study to another and must be confirmed. [less ▲]

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See detailThe scientific and regulatory rationale for indication extrapolation: A case study based on the infliximab biosimilar CT-P13
Reinisch, W.; Louis, Edouard ULiege; Danese, S.

in Expert Review of Gastroenterology and Hepatology (2015), 9

Extrapolation of clinical data from other indications is an important concept in the development of biosimilars. This process depends on strict comparability exercises to establish similarity to the ... [more ▼]

Extrapolation of clinical data from other indications is an important concept in the development of biosimilars. This process depends on strict comparability exercises to establish similarity to the reference medicinal product. However, the extrapolation paradigm has prompted a fierce scientific debate. CT-P13 (Remsima®, Inflectra®), an infliximab biosimilar, is a TNF antagonist used to treat immune-mediated inflammatory diseases. On the basis of totality of similarity data, the EMA approved CT-P13 for all indications held by its reference medicinal product (Remicade®) including inflammatory bowel disease. This article reviews the mechanisms of action of TNF antagonists in immune-mediated inflammatory diseases and illustrates the comparable profiles of CT-P13 and reference medicinal product on which the extrapolation of indications including inflammatory bowel disease is based. © 2015 © Informa UK, Ltd. [less ▲]

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See detailWhen and how to stop anti-TNF treatment in inflammatory bowel disease: Predictors of relapse after stopping treatment
Louis, Edouard ULiege

in Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease (2015)

The global benefit-risk ratio of long-term anti-TNF treatment appears favorable. Nevertheless, reasons exist for contemplating treatment cessation, including patient preference, associated side effects ... [more ▼]

The global benefit-risk ratio of long-term anti-TNF treatment appears favorable. Nevertheless, reasons exist for contemplating treatment cessation, including patient preference, associated side effects, the development of infection in high-risk patients, pregnancy and cost. Several prospective studies have shown very consistent relapse rates of around 50% at 1 year. Globally, patients with a low risk of relapse are those with steroid-free, clinical, endoscopic and biological remission of Crohn's disease, while no clear predictor has been identified in ulcerative colitis. These studies as well as larger retrospective studies have also shown excellent responses and remission rates and very good tolerabilities of retreatment with the same anti-TNF agents, particularly when patients are concomitantly treated with an immunosuppressant. © 2015 by S. Karger AG. All rights reserved. [less ▲]

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See detailApplication of random forest methodology for genomic selection of disease traits in dairy cattle
Naderi Darbaghshahi, Saeid ULiege; Yin, T.; König, S.

in DGfZ‐Jahrestagung und DGfZ/GfT‐Gemeinschaftstagung (2014, September 17)

The objective of the present study was the application of RF to binary disease traits recorded in a cow calibration group. Major tasks addressed the impact of the cow calibration group size, the frequency ... [more ▼]

The objective of the present study was the application of RF to binary disease traits recorded in a cow calibration group. Major tasks addressed the impact of the cow calibration group size, the frequency of diseased cows in the reference population, and the genomic architecture on accuracies of GEBV. Results from RF applications were compared with GBLUP methodology. [less ▲]

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