V. Merle

L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: The French controlled, randomized, double-blind, multicenter study*

Objective:Glutamine (Gln)–supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated. Design:Prospective, double-blind, controlled, randomized trial. Setting:ICUs in 16 hospitals in France. Patients:One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11). Interventions:Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids·kg−1·day−1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g·kg−1·day−1; Ala-Gln group, n = 58) or L-alanine + L-proline (control group, n = 56) over at least 5 days. Measurements and Main Results:Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p < .05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p < .05) and incidence of pneumonia (10 vs. 19; p < .05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p < .05) and there were fewer insulin-requiring patients (14 vs. 22; p < .05) in the Ala-Gln group. Conclusions:TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.

The natural history of pediatric ulcerative colitis: a population-based cohort study.

OBJECTIVES:The natural history of ulcerative colitis (UC) has been poorly described in children.METHODS:In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 113 UC patients (age 0–17 years at diagnosis) with a follow-up of at least 2 years. The cumulative risk of colectomy was estimated by the Kaplan–Meier method. Risk factors for disease extension were assessed with logistic regression models, and risk factors for colectomy with Cox hazards proportional models.RESULTS:Median follow-up time was 77 months (46–125). At diagnosis, 28% of patients had proctitis, 35% left-sided colitis, and 37% extensive colitis. Disease course was characterized by disease extension in 49% of patients. A delay in diagnosis of more than 6 months and a family history of inflammatory bowel disease were associated with an increased risk of disease extension, with odds ratios of 5.0 (1.2–21.5) and 11.8 (1.3–111.3), respectively. The cumulative rate of colectomy was 8% at 1 year, 15% at 3 years, and 20% at 5 years. The presence of extra-intestinal manifestations (EIMS) at diagnosis was associated with an increased risk of colectomy (hazard ratio (HR)=3.5 (1.2–10.5)). Among the patients with limited disease at diagnosis, the risk of colectomy was higher in those who experienced disease extension than in those who did not (HR=13.3 1.7–101.7).CONCLUSIONS:Pediatric UC was characterized by widespread localization at diagnosis and a high rate of disease extension. Twenty percent of children had their colon removed after 5 years. The colectomy rate was influenced by disease extension and was associated with the presence of EIMS at diagnosis.

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study

Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. Methods In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohns disease (CD) and 472 ulcerative colitis (UC). Results Median age at diagnosis was similar for CD (70 years (IQR: 65–76)) and UC (69 years (64–74)). Median follow-up was 6 years (2–11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. Conclusions Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

The changing pattern of Crohn’s disease incidence in northern France: a continuing increase in the 10‐ to 19‐year‐old age bracket (1988–2007)

Aliment Pharmacol Ther 2011; 33: 1133–1142

Stressful Life Events as a Risk Factor for Inflammatory Bowel Disease Onset: A Population-Based Case–Control Study

BACKGROUND AND AIMS: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.METHODS:Incident cases of IBD, including 167 patients with Crohns 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 Paykels 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 Bates and Becks questionnaires, respectively.RESULTS: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.CONCLUSIONS:Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.

Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study.

Background: We examined short‐ and long‐term benefits and safety of infliximab (IFX) in a population‐based cohort of Crohns 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;)

Mapping of inflammatory bowel disease in northern France: Spatial variations and relation to affluence

Background:Geographic variations in the incidence of inflammatory bowel disease (IBD) may reflect variations in the distribution of environmental etiologic factors. We assessed spatial variation in the incidence of IBD in northern France and analyzed its association with a deprivation index. Methods:All cases of IBD included in the EPIMAD registry between 1990 and 2003 were extracted. The standardized incidence ratio (SIR) was calculated for each canton in the region. The association between incidence and deprivation was assessed using the Townsend deprivation index. Results:The mean annual incidence rates of Crohns disease (CD) and ulcerative colitis (UC) were 6.2 × 10−5 and 3.8 × 10−5, respectively. The mean cumulative numbers of cases by canton were 18.4 (1–183) for CD and 11.3 (0–148) for UC. For both CD and UC, mapping depicted spatial heterogeneity in the SIR with spatial autocorrelation. A high relative risk (RR) of CD was observed in mainly rural and periurban cantons of the region. For UC, a high RR was found in cantons of the south and the center of Pas‐de‐Calais. No significant correlation was observed between spatial variations in IBD and deprivation. Conclusions:The incidence of IBD is associated with spatial heterogeneity in northern France. The noteworthy predominance of CD in agricultural areas warrants further investigations. (Inflamm Bowel Dis 2009;)

Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study.

Background:To describe long-term postoperative evolution of pediatric-onset Crohns disease (CD) and identify predictors of outcome we studied a population-based cohort (1988–2004) of 404 patients (0–17 years), of which 130 underwent surgery. Methods:Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. Results:In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12–16) were followed for 13 years (9.4–16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. Conclusions:In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery.

Nosocomial Urinary Tract Infections in Urologic Patients: Assessment of a Prospective Surveillance Program Including 10,000 Patients

OBJECTIVE Hospital-acquired urinary tract infections (HUTI) represent a significant impairment in the quality of health care. Incidence in catheterized patients has been estimated at approximately 20%, however few data are available in urologic patients. We report a prospective surveillance program over 6 years in our urologic department and evaluate its evolution. METHODS Population consists of all patients admitted to the urology ward for 48 hours or more over a 6-year period from 1994. Data recorded: age, gender, duration of stay, insertion and removal of catheters, diagnosis of HUTI. ANALYSIS calculation of incidence, and incidence density for HUTI and for catheter-related HUTI, analysis of trends by chi(2) trend test. RESULTS A total of 10,054 consecutive patients were included, 52% were catheterized. The median incidence of catheter-related HUTI in catheterized patients was 13.0%, the incidence density was 25.1 HUTI/1000 patient-days of catheterization. The proportion of HUTI and specific catheter-related HUTI patients decreased, respectively from 8.4% and 14.2% to 6.5% and 12.3% during the study period (p<0.05). CONCLUSION The rate of HUTI was not as high as previously reported, perhaps due to a controlled catheter policy. Surveillance was associated with a significant decrease in infection rates, suggesting a beneficial feedback effect. Evaluation of diagnoses and surgical procedures would ensure an optimal quality control program.

Postoperative management of stage II/III colon cancer: A decision analysis

BACKGROUND & AIMS Two separate decisions must be made for the management of patients with resected stage II/III colon cancer: whether to begin adjuvant chemotherapy and whether patients should be included in a follow-up protocol consisting of regular monitoring of carcinoembryonic antigen level and of colonoscopy and imaging. The standard management for these patients is adjuvant chemotherapy for stage III patients and follow-up for stage II/III patients with resected colon cancer. METHODS Decision analysis was used to compare the effectiveness (5-year survival rate) and cost-effectiveness ratio of 7 strategies of treatment and follow-up. RESULTS The most cost-effective strategies were adjuvant chemotherapy for all patients with stage II/III resected colon cancer, with either no follow-up or follow-up only for patients aged less than 75 years with a seric preoperative carcinoembryonic antigen level of >5 ng/mL (5-year survival, 62.3% or 62.7%; cost per surviving patient,