Background:
We examined short‐ and long‐term benefits and safety of infliximab (IFX) in a population‐based cohort of Crohn's disease (CD) patients <17 years old at diagnosis.
Methods:
The following ...parameters were assessed: short‐ and long‐term efficacy of IFX, impact of drug efficacy, and mode of administration on rate of resection surgery, growth and nutritional catch‐up, and adverse events (AEs).
Results:
In all, 120 patients (69 female) required IFX with a median duration of 32 months (Q1 = 8–Q3 = 60). Median age at diagnosis was 14.5 years (12–16) and median interval between diagnosis and IFX initiation was 41 months (22–78). Median follow‐up since CD diagnosis was 111 months (75–161). Fifty patients (42%) received episodic and 70 (58%) maintenance therapy. Sixty‐five (54%) patients were in the “IFX efficacy” group: 38 (32%) still receiving IFX at the last visit and 27 (22%) stopping IFX while in remission. The “IFX failure” group included 55 (46%) patients: 17 (14%) who stopped IFX due to AEs and 38 (32%) nonresponders. The risk of surgery was reduced (P = 0.009) in the “IFX efficacy” group and lower (P = 0.03) in patients with scheduled versus episodic therapy. Patients in the “IFX efficacy” group had significant catch‐up growth (P = 0.04), while those in the “IFX failure” group did not. Twenty‐four patients presented AEs leading to cessation of IFX in 17 of them.
Conclusions:
In this population‐based cohort of pediatric‐onset CD, IFX treatment was effective in more than half of patients during a median follow‐up of 32 months. Long‐term IFX responders had a lower rate of surgery and improved catch‐up in growth, especially when receiving scheduled IFX therapy. (Inflamm Bowel Dis 2011;)
Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial.
We explored effects of ...rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action.
Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg−1 · d−1) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment.
rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states.
In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.
Background & Aims: Infectious agents are suspected of being involved in the pathogenesis of Crohn's disease. This study was designed to look for the presence of virulent
Escherichia coli strains ...associated with the ileal mucosa of patients with Crohn's disease.
Methods:
E. coli strains were recovered from resected chronic ileal lesions (n = 20), neoterminal ileum after surgery from patients with (n = 19) and without (n = 11) endoscopic recurrence, and controls (n = 13). Bacterial adhesion was determined in vitro using intestinal cell lines; other associated virulence factors were assessed by DNA hybridization and polymerase chain reaction experiments.
Results: None of the strains harbored any of the virulence factor–encoding genes of
E. coli involved in acute enteric diseases. However, mannose-resistant adhesion to differentiated Caco-2 cells was found for 84.6% and 78.9% of the
E. coli strains isolated from chronic and early recurrent lesions, respectively, compared with 33% of controls (
P < 0.02). In addition, 21.8% of the strains induced a cytolytic effect by synthesis of an α-hemolysin.
Conclusions:
E. coli strains isolated from the ileal mucosa of patients with Crohn's disease adhere to differentiated intestinal cells and may disrupt the intestinal barrier by synthesizing an α-hemolysin.
GASTROENTEROLOGY 1998;115:1405-1413
A third Alzheimer and related diseases plan (AP), including a detailed research part has been implemented from 2008 to 2013. The aim of this study was to assess the AP impact on the original articles ...production concerning Alzheimer and related disease (AD) before (2004-2008) and after its implementation (2009-2013).
Number and impact factor (IF) based ranking of original articles coming from French University Hospitals (CHU) have been assessed using the data provided by the SIGAPS bibliometric software used so far for calculating allocation of the governmental medical research funding (MERRI). Scientific production on AD has been compared to four other control pathologies: 2 neurologic (stroke and Parkinson disease) and 2 non-neurologic (diabetes and AIDS). Publication trends of the 27 CHU and of the 7 Interregional grouping of clinical research and innovation (GIRCI) have been analyzed using specialization indices (SI).
The number of AD articles increased from 1277 to 1972 (+54.4 %) as well as SIGAPS score from 18,038 to 29,309 (+62.5 %). Meanwhile number of articles rated A and B (published in the 25 % best journals of the specialty) increased from 430 to 846 (+114.1 %). The figures for these indicators evolved similarly for AD and stroke while quite differently for the 3 other diseases: plateauing at a high level for Parkinson disease and AIDS and modestly increasing for diabetes. SI was>1 for the 3 neurologic diseases, including AD in North-Western and South-West GIRCI. SI of CHU on AD did not vary before and after AP implementation, 4 CHU having both a production and an SI at a high level: Toulouse, Bordeaux, Montpellier and Lille.
The number and "quality" of original articles on AD production by the CHU increased after the AP starting of AP initiation in 2008. Whether or not this was directly due to the financial support provided by the AP remains to be determined. The scientific production on AD was unequally distributed throughout the country, the CHU being already strongly involved in AD research before the AP reinforced their commitment after. This work illustrates the potential implication of SIGAPS as a strategic tool for research policy.
ABSTRACT
Objective:
To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999.
Methods:
A 12‐year ...prospective population‐based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age).
Results:
From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/105 for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2).
Conclusions:
The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12‐year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (−17%; P < 0.0001).
Stress is often perceived by patients with inflammatory bowel disease (IBD) as the leading cause of their disease. The aim of this study was to assess whether stress, evaluated through life event ...(LE) occurrence, is associated with IBD onset.
Incident cases of IBD, including 167 patients with Crohn's disease (CD) and 74 with ulcerative colitis (UC), were compared with two control groups, one of 69 patients with acute self-limited colitis (ASLC) and another of 255 blood donors (BDs). Stress was assessed using Paykel's self-questionnaire of LEs. Only LEs occurring within 6 months before the onset of symptoms in IBD cases and ASLC controls and before blood donation in BD controls were registered. Anxiety and depression were assessed using Bate's and Beck's questionnaires, respectively.
In univariate analysis, occurrence of LEs was more frequent in the 6-month period prior to diagnosis in CD cases than in UC cases or either control group. After adjustment for depression and anxiety scores as well as other characteristics such as smoking status and sociodemographic features, this association appeared no longer significant. No associations were noted between occurrence of LEs and onset of UC relative to controls.
Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.
Un troisième Plan Alzheimer et maladies apparentées (PA) comprenant un volet Recherche détaillé a été mis en œuvre de 2008 à 2013. Le but de ce travail a été d’évaluer l’impact du PA sur la ...production d’articles originaux concernant la maladie d’Alzheimer et maladies apparentées (MA) avant (2004–2008) et après (2009–2013) sa mise en place.
Le nombre et le classement basé sur le facteur d’impact (FI) des articles originaux produits par les 27 centres hospitalo-universitaires (CHU) de Métropole ont été évalués grâce aux données du Système d’interrogation, de gestion et d’analyse des publications scientifiques (SIGAPS) utilisé pour attribuer une partie des crédits de Missions d’enseignement, de recherche, de référence et d’innovation (MERRI). La production scientifique relative à la MA a été comparée à celle concernant 4 pathologies contrôles, 2 neurologiques (accidents vasculaires cérébraux, et maladie de Parkinson) et 2 autres (diabète et sida). La production a été mesurée par centre hospitalo-universitaire (CHU) et par inter-régions selon 7 Groupements interrégionaux de recherche clinique et d’innovation (GIRCI) en calculant leurs indices de spécialisation (IS).
Le nombre d’articles sur la MA a augmenté de 1277 à 1972 (+54,4 %), le score SIGAPS de 18 038 à 29 309 (+62,5 %) et le nombre d’articles classés A et B (correspondant aux 25 % des meilleures revues de la spécialité) de 430 à 846 (+114,1 %). Ces indicateurs ont augmenté de la même manière pour la MA et les AVC, alors que pour les 3 autres pathologies, l’évolution a été variable : stagnation à un haut niveau pour la maladie de Parkinson et le sida et augmentation pour le diabète (+15,5 %). Les IS étaient>1 pour les 3 pathologies neurologiques dont la MA dans le Nord-Ouest et le Sud-Ouest outre-mer (SOOM). Les IS des CHU sur la MA variaient peu entre les 2 périodes, 4 établissements ayant à la fois une production et un IS élevés : Toulouse, Bordeaux, Montpellier et Lille.
La production et la qualité des articles originaux sur la MA par les CHU ont augmenté après la mise en place du PA en 2008. Déterminer si cette augmentation est en rapport avec l’application du volet recherche du PA reste à confirmer. La production sur la MA était inégalement répartie sur le territoire français et les établissements qui avaient déjà une recherche active avant la mise en place d’un PA renforçaient celle-ci après. Enfin, ce travail illustre l’utilisation stratégique qui peut être faite de SIGAPS au-delà de son utilisation comme outil de financement.
A third Alzheimer and related diseases plan (AP), including a detailed research part has been implemented from 2008 to 2013. The aim of this study was to assess the AP impact on the original articles production concerning Alzheimer and related disease (AD) before (2004–2008) and after its implementation (2009–2013).
Number and impact factor (IF) based ranking of original articles coming from French University Hospitals (CHU) have been assessed using the data provided by the SIGAPS bibliometric software used so far for calculating allocation of the governmental medical research funding (MERRI). Scientific production on AD has been compared to four other control pathologies: 2 neurologic (stroke and Parkinson disease) and 2 non-neurologic (diabetes and AIDS). Publication trends of the 27 CHU and of the 7 Interregional grouping of clinical research and innovation (GIRCI) have been analyzed using specialization indices (SI).
The number of AD articles increased from 1277 to 1972 (+54.4 %) as well as SIGAPS score from 18,038 to 29,309 (+62.5 %). Meanwhile number of articles rated A and B (published in the 25 % best journals of the specialty) increased from 430 to 846 (+114.1 %). The figures for these indicators evolved similarly for AD and stroke while quite differently for the 3 other diseases: plateauing at a high level for Parkinson disease and AIDS and modestly increasing for diabetes. SI was>1 for the 3 neurologic diseases, including AD in North-Western and South-West GIRCI. SI of CHU on AD did not vary before and after AP implementation, 4 CHU having both a production and an SI at a high level: Toulouse, Bordeaux, Montpellier and Lille.
The number and “quality” of original articles on AD production by the CHU increased after the AP starting of AP initiation in 2008. Whether or not this was directly due to the financial support provided by the AP remains to be determined. The scientific production on AD was unequally distributed throughout the country, the CHU being already strongly involved in AD research before the AP reinforced their commitment after. This work illustrates the potential implication of SIGAPS as a strategic tool for research policy.
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