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1.
J Pediatr Gastroenterol Nutr ; 78(6): 1261-1272, 2024 Jun.
Article En | MEDLINE | ID: mdl-38651614

OBJECTIVES: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery. METHODS: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals. Patient characteristics were compared by surgical outcome multivariable Cox regression. RESULTS: Fifty-six patients (61% boys) aged 12.2 ± 2.7 years at diagnosis of CD were included. Median duration of CD before diagnosis of stricture was 11.7 months (interquartile range [IQR]: 25-75: 1.2-29.9). Nineteen (34%) patients had stricturing phenotype (B2) at baseline. Treatments received  before stricture diagnosis included MODULEN-IBD (n = 31), corticosteroids (n = 35), antibiotics (n = 10), anti-TNF (n = 27), immunosuppressants (n = 28). Thirty-six patients (64%) required surgery, within 4.8 months (IQR: 25-75: 1.8-17.3) after stricture diagnosis. Parameters associated with surgical resection were antibiotic exposure before stricture diagnosis (adjusted odds ratio [aOR]: 15.62 [3.35-72.73], p = 0.0005), Crohn's disease obstructive symptoms score (CDOS) > 4 (aOR: 3.04 [1.15-8.03], p = 0.02) and dilation proximal to stricture >28 mm (aOR: 3.62 [1.17-11.20], p = 0.03). CONCLUSION: In this study, antibiotic treatment before stricture diagnosis, intensity of obstructive symptoms, and diameter of dilation proximal to small bowel stricture on MRE were associated with risk for surgical resection.


Crohn Disease , Intestine, Small , Humans , Crohn Disease/surgery , Crohn Disease/complications , Male , Retrospective Studies , Female , Risk Factors , Child , Intestine, Small/surgery , Intestine, Small/pathology , Adolescent , Constriction, Pathologic/etiology , France , Magnetic Resonance Imaging , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery
2.
Eur J Pediatr ; 182(5): 2005-2012, 2023 May.
Article En | MEDLINE | ID: mdl-36872380

The purpose of this study is to assess quality of life (QoL) after laparoscopic anti-reflux surgery (LARS) in children with gastroesophageal reflux disease (GERD) and to evaluate GERD symptoms and their impact on daily life and school. From June 2016 to June 2019, all children with GERD from 2 to 16 years of age, without neurologic impairment or malformation-related reflux, were prospectively included in a monocentric study. Patients (or their parents according to the age of the child) answered the Pediatric Questionnaire on Gastroesophageal Symptoms and QoL (PGSQ) before surgery and 3 and 12 months after surgery. Variables were compared by paired, bilateral Student t-test. Twenty-eight children (16 boys) were included. The median age at surgery was 77 months (IQR: 59.2-137) with median weight of 22 kg (IQR: 19.8-42.3). All had a laparoscopic Toupet fundoplication. Median duration of follow-up was 14.7 months (IQR: 12.3-22.5). One patient (4%) had a recurrence of GERD symptoms without abnormalities on follow-up examinations. Preoperative total PGSQ score was 1.42 (± 0.7) and decreased significantly 3 months (0.56 ± 0.6; p < 0.001) and 12 months after surgery (0.34 ± 0.4; p < 0.001). PGSQ subscale analysis revealed a significant decrease at 3 and 12 months for GERD symptoms (p < 0.001), impact on daily life (p < 0.001), and impact on school (p = 0.03). CONCLUSION: There was a significant improvement in symptoms and their frequency after LARS in children, as well as an improvement of QoL, in the short and medium term. The impact of GERD should be taken into consideration in the treatment decision, given that surgery clearly improves the QoL. WHAT IS KNOWN: • Laparoscopic anti-reflux surgery (LARS) is an established and effective treatment option in pediatric patients with severe GERD refractory to medical treatment. • Effect of LARS on the quality of life (QoL) has been mainly investigated in the adult population but there is very little data on the effect of LARS on the QoL in pediatric patients. WHAT IS NEW: • Our prospective study was the first to analyze the effect of LARS on QoL in pediatric patients without neurologic impairment using validated questionnaires at two postoperative time points with a significant improvement in postoperative QoL at 3 and 12 months. • Our study emphasizes the importance of evaluating QoL and impact of GERD on all the aspects of daily life and of taking these into consideration in the treatment decision.


Gastroesophageal Reflux , Laparoscopy , Nervous System Diseases , Male , Adult , Humans , Child , Child, Preschool , Infant , Quality of Life , Prospective Studies , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/surgery , Treatment Outcome , Nervous System Diseases/surgery
3.
J Crohns Colitis ; 17(4): 524-534, 2023 Apr 19.
Article En | MEDLINE | ID: mdl-36316987

BACKGROUND AND AIMS: Paediatric-onset IBD [pIBD] is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer. METHODS: All patients diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] before the age of 17 years between 1988 and 2011 in the EPIMAD registry were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence [SIR] and mortality ratios [SMR] were estimated compared to the general population. Cox regression was used to compare the effect of exposures on cancer and mortality among IBD patients. RESULTS: We included 1344 patients [52% males, 75% CD], totalling 12 957 patient-years for cancer incidence and 18 817 patient-years for mortality. There were 14 cases of cancer [median age 27.8 years] and 15 deaths [median age 28.8 years]. The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIR = 2.7 (95% confidence interval [CI]: 1.5-4.8), SMR = 1.7 [95% CI: 1.0-2.8]. Colorectal cancer had the highest SIR and SMR: SIR = 41.2 [95% CI: 17.2-99.0], SMR = 70.4 [95% CI 22.7-218.2]. Cancer was associated with (hazard ratio [HR], 95% CI): active smoking at diagnosis [5.5, 1.8-16.5], p = 0.002; any exposure to anti-tumour necrosis factor [6.1, 1.7-22.3], p = 0.0065; and exposure to combination therapy [7.4, 1.8-29.7], p = 0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 [95% CI: 1.7-13.8], p = 0.003). CONCLUSIONS: In this large population-based cohort, patients with pIBD had an increased risk of both cancer [2.7-fold] and mortality [1.7-fold], particularly for colorectal cancer.


Colitis, Ulcerative , Colorectal Neoplasms , Crohn Disease , Inflammatory Bowel Diseases , Male , Child , Humans , Adult , Adolescent , Female , Retrospective Studies , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/epidemiology , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Incidence , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology
4.
Pancreas ; 51(2): 128-134, 2022 02 01.
Article En | MEDLINE | ID: mdl-35404887

OBJECTIVES: The identification of patients at risk of developing a severe form of acute pancreatitis is a major issue. The goal of this study was to identify parameters at admission associated with severe pancreatitis to develop a predictive severity score. METHODS: We conducted a retrospective study at Caen University Hospital between January 2014 and December 2017, including 504 patients hospitalized for acute pancreatitis, of whom 74 had a severe form. We developed a predictive score named Admission Severe Acute Pancreatitis (ASAP) score based on parameters associated with a severe form in multivariate analysis. We validated our score in an independent validation cohort of 80 patients. RESULTS: Hypothermia, low oxygen saturation or albumin levels, and high creatinine levels were significantly associated with severe pancreatitis. The ASAP score showed notable predictive accuracy (area under receiver operating characteristic, 0.82), which was significantly higher than Sequential Organ Failure Assessment, persistent Systemic Inflammatory Response Syndrome, and Balthazar. Using the -2.1742 threshold, the ASAP score had a sensitivity and specificity of 74% and a negative predictive value of 95%. These predictive performances for ASAP score were confirmed in the validation cohort. CONCLUSIONS: The ASAP score demonstrates remarkable predictive accuracy in distinguishing severe forms of acute pancreatitis.


Pancreatitis , Acute Disease , Humans , Pancreatitis/complications , Pancreatitis/diagnosis , Predictive Value of Tests , Prognosis , ROC Curve , Retrospective Studies , Severity of Illness Index
5.
Arch Dis Child ; 107(1): 52-58, 2022 01.
Article En | MEDLINE | ID: mdl-33863700

INTRODUCTION: With advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD. METHODS: The Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children's Hospital Feeding Scale. RESULTS: Of the 248 eligible children, 145 children, with a median age of 2.3 years (Q1-Q3 1.8-2.9, min-max 1.1-4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication. CONCLUSION: PFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth.


Esophageal Atresia/epidemiology , Feeding and Eating Disorders/epidemiology , Anastomosis, Surgical/methods , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Enteral Nutrition/methods , Esophageal Atresia/therapy , Feeding and Eating Disorders/therapy , Female , France/epidemiology , Humans , Infant , Male , Postoperative Complications/epidemiology , Prevalence
6.
PLoS One ; 16(11): e0259135, 2021.
Article En | MEDLINE | ID: mdl-34735489

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor ß2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1ß, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.


Colitis/diagnostic imaging , Magnetic Resonance Imaging/methods , Trinitrobenzenesulfonic Acid/adverse effects , Animals , Colitis/chemically induced , Cyclooxygenase 2/metabolism , Disease Models, Animal , Interleukin-1beta/metabolism , Male , Mice , Nitric Oxide Synthase Type II/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism
7.
J Pediatr Gastroenterol Nutr ; 73(3): 333-337, 2021 09 01.
Article En | MEDLINE | ID: mdl-34117192

OBJECTIVES: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat. METHODS: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU. RESULTS: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1-23] months, and first symptoms occurred 39 [22-106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19-67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). CONCLUSIONS: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.


Crohn Disease , Digestive System Surgical Procedures , Hirschsprung Disease , Anastomosis, Surgical , Child , Crohn Disease/complications , Crohn Disease/diagnosis , Crohn Disease/therapy , Female , Humans , Infant , Infant, Newborn , Male , Ulcer/diagnosis , Ulcer/etiology , Young Adult
8.
Dig Liver Dis ; 53(10): 1268-1275, 2021 Oct.
Article En | MEDLINE | ID: mdl-34187767

BACKGROUND: Chronic abdominal pain occurs frequently in pediatric patients with inflammatory bowel disease (IBD) in remission. AIMS: To assess the prevalence and factors associated with Functional Abdominal Pain Disorders among IBD children in remission (IBD-FAPD). METHODS: Patients with IBD for > 1 year, in clinical remission for ≥ 3 months were recruited from a National IBD network. IBD-FAPDs were assessed using the Rome III questionnaire criteria. Patient- or parent- reported outcomes were assessed. RESULTS: Among 102 included patients, 57 (56%) were boys, mean age (DS) was 15.0 (± 2.0) years and 75 (74%) had Crohn's disease. Twenty-two patients (22%) had at least one Functional Gastrointestinal Disorder among which 17 had at least one IBD-FAPD. Past severity of disease or treatments received and level of remission were not significantly associated with IBD-FAPD. Patients with IBD-FAPD reported more fatigue (peds-FACIT-F: 35.9 ± 9.8 vs. 43.0 ± 6.9, p = 0.01) and a lower HR-QoL (IMPACT III: 76.5 ± 9.6 vs. 81.6 ± 9.2, p = 0.04) than patients without FAPD, and their parents had higher levels of State and Trait anxiety than the other parents. CONCLUSIONS: Prevalence of IBD-FAPD was 17%. IBD-FAPD was not associated with past severity of disease, but with fatigue and lower HR-QoL.


Abdominal Pain/etiology , Inflammatory Bowel Diseases/complications , Quality of Life , Abdominal Pain/psychology , Adolescent , Case-Control Studies , Cross-Sectional Studies , Fatigue/etiology , Fatigue/psychology , Female , Humans , Inflammatory Bowel Diseases/psychology , Male , Parents/psychology , Patient Reported Outcome Measures , Remission Induction , Severity of Illness Index
9.
BMC Gastroenterol ; 20(1): 416, 2020 Dec 10.
Article En | MEDLINE | ID: mdl-33302890

BACKGROUND: Pediatric Crohn's disease is characterized by a higher incidence of complicated phenotypes. Murine models help to better understand the dynamic process of intestinal fibrosis and test therapeutic interventions. Pre-pubertal models are lacking. We aimed to adapt a model of chronic colitis to pre-pubertal rats and test if a polymeric diet rich in TGF-ß2 could reduce TNBS-induced intestinal inflammation and fibrosis. METHODS: Colitis was induced in 20 five-week-old Sprague-Dawley male rats by weekly rectal injections of increasing doses of TNBS (90 mg/kg, 140 mg/kg and 180 mg/kg) for 3 weeks, while 10 controls received phosphate-buffered saline. Rats were anesthetized using ketamine and chlorpromazine. After first administration of TNBS, 10 rats were fed exclusively MODULEN IBD® powder, while remaining rats were fed breeding chow. Colitis was assessed one week after last dose of TNBS by histopathology and magnetic resonance colonography (MRC). RESULTS: Histological inflammation and fibrosis scores were higher in TNBS group than controls (p < 0.05 for both). MRC showed increased colon wall thickness in TNBS group compared to controls (p < 0.01), and increased prevalence of strictures and target sign (p < 0.05). Colon expression of COL1A1, CTGF, α-SMA and COX-2 did not differ between TNBS rats and controls. TNBS colitis was not associated with growth failure. Treatment with MODULEN IBD® was associated with growth failure, increased colon weight/length ratio (p < 0.01), but did not affect histological scores or MRI characteristics. Colon expression of α-SMA was significantly lower in the MODULEN group versus controls (p = 0.005). CONCLUSION: Features of chronic colitis were confirmed in this model, based on MRC and histopathology. Treatment with MODULEN did not reverse inflammation or fibrosis.


Colitis , Transforming Growth Factor beta2 , Animals , Colitis/chemically induced , Colitis/drug therapy , Colon , Diet , Disease Models, Animal , Inflammation , Male , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Trinitrobenzenes , Trinitrobenzenesulfonic Acid
10.
Inflamm Bowel Dis ; 26(10): 1572-1578, 2020 09 18.
Article En | MEDLINE | ID: mdl-32407484

BACKGROUND: Diagnostic markers for distinguishing between Crohn disease (CD) and ulcerative colitis (UC) remain elusive. We studied whether methylation marks across the promoters of the transforming growth factor beta 1 (TGFß1) and interleukin-6 genes have diagnostic utility. METHODS: A case-control study was carried out. Cases were treatment-naïve, diagnosed before age 20, and recruited from 3 pediatric gastroenterology clinics across Canada. Control patients did not have inflammatory bowel disease and were recruited from orthopedic clinics within the same hospitals as the gastroenterology clinics. Patient DNA from peripheral blood was processed to identify methylation sites (CpG) across the promoter regions of the TGFß1 and interleukin-6 genes. After initial nonparametric univariate analyses, multivariate logistic regression models were fit. Models with the best fit (Akaike information criteria) and strongest discriminatory capabilities (area under the curve [AUC]) were identified, and P values were adjusted for multiple comparisons using the false discovery rate method. RESULTS: A total of 67 CD, 31 UC, and 43 control patients were included. The age distribution of the 3 groups was similar. Most CD patients had ileocolonic disease (44.8%) and inflammatory disease (88.1%). Most UC patients had extensive (71%) and moderate disease (51.6%). Logistic regression analysis revealed the following: 14 TGFß1 CpG sites discriminated between CD and control patients (AUC = 0.94), 9 TGFß1 CpG sites discriminated between UC and control patients (AUC = 0.99), 3 TGFß1 CpG sites discriminated between CD and UC (AUC = 0.81), and 6 TGFß1 CpG sites distinguished colonic CD from UC (AUC = 0.91). CONCLUSIONS: We found that CpG methylation in the promoter of the TGFß1 gene has high discriminative power for identifying CD and UC and could serve as an important diagnostic marker.


Colitis, Ulcerative/diagnosis , CpG Islands/genetics , Crohn Disease/diagnosis , Interleukin-6/blood , Transforming Growth Factor beta/blood , Adolescent , Area Under Curve , Biomarkers/blood , Canada , Case-Control Studies , Child , Colitis, Ulcerative/genetics , Crohn Disease/genetics , Diagnosis, Differential , Female , Humans , Interleukin-6/genetics , Logistic Models , Male , Methylation , Transforming Growth Factor beta/genetics , Young Adult
11.
J Pediatr ; 211: 120-125.e1, 2019 08.
Article En | MEDLINE | ID: mdl-31072651

OBJECTIVE: To identify predictors of and factors associated with the performance of antireflux surgery during the first year of life in children born with esophageal atresia. STUDY DESIGN: All patients were included in a French registry for esophageal atresia. All 38 multidisciplinary French centers completed questionnaires about perinatal characteristics and one-year outcome for children born with esophageal atresia. RESULTS: Of 835 infants with esophageal atresia born in France from 2010 to 2014, 682 patients, excluding those with long-gap esophageal atresia, were included. Three patients had type I, 669 had type III, and 10 had type IV esophageal atresia. Fifty-three children (7.8%) received fundoplication during the first year of life. The median age at the time of the end-to-end esophageal anastomosis was 1.1 day (range 0-15). Multivariate analysis identified three perioperative factors that predicted the need for early antireflux surgery: anastomotic tension (P = .004), associated malformations (P = .019), and low birth weight (P = .018). Six other factors, measured during the first year of life, were associated with the need for antireflux surgery: gastroesophageal reflux (P < .001), anastomotic stricture (P < .001), gastrostomy (P < .001), acute life-threatening event (P = .002), respiratory complications (P = .045), and poor nutritional status (P < .001). CONCLUSIONS: Gastroesophageal reflux disease, low birth weight, poor nutrition, and surgical anastomosis difficulties predicted the performance of antireflux surgery in the first year of life in infants with esophageal atresia.


Esophageal Atresia/surgery , Fundoplication , Anastomosis, Surgical/adverse effects , Constriction, Pathologic , Esophageal Atresia/classification , Female , France , Gastroesophageal Reflux/surgery , Gastrostomy , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Male , Multivariate Analysis , Nutritional Status , Registries
12.
Surg Endosc ; 32(10): 4191-4199, 2018 10.
Article En | MEDLINE | ID: mdl-29602990

BACKGROUND: Laparoscopic fundoplication in children under 5 kg is still debated. Our objective was to evaluate the safety and efficacy of laparoscopic fundoplication (LF) in children under 5 kg. METHODS: We reviewed the cases of 96 children treated by laparoscopic fundoplication between 2005 and 2014. Thirty-five patients had a weight of 5 kg or less at the time of LF (Low Weight Group) and 61 patients had a weight between 5.1 and 10 kg (High Weight Group). The pre-operative, peri-operative, post-operative data regarding surgery and anesthesia were compared between groups. RESULTS: Mean weight was 3.9 ± 0.8 kg in the LWG and 7.8 ± 1.5 kg in the HWG. Children in the LWG were more prone to pre-operative respiratory management (40% mechanical ventilation and 42.9% oxygen therapy). The operating times (82 ± 28 min for LWG and 85 ± 31 min for HWG) and respiratory parameters during the procedure (PCO2) were comparable between groups. Post-operative complications were 1 gastric perforation with peritonitis and 1 small bowel obstruction in the LWG, 2 cases of gastric perforation with peritonitis in the HWG. Mean follow-up was 67 ± 44 months. Significant recurrence of GERD requiring a redo fundoplication was noted in 3 patients in the LWG and 1 patient in the HWG. CONCLUSION: Laparoscopic fundoplication is a safe procedure in infants ≤ 5 kg without increase of post-operative complications, recurrence, or mean operative time.


Body Weight , Fundoplication/methods , Gastroesophageal Reflux/surgery , Laparoscopy , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Patient Safety , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Recurrence , Retrospective Studies , Treatment Outcome
14.
Inflamm Bowel Dis ; 23(2): 298-303, 2017 02.
Article En | MEDLINE | ID: mdl-28107279

BACKGROUND: Methotrexate (MTX) intolerance is defined as gastrointestinal and behavioral symptoms occurring before or after MTX administration that may lead to treatment discontinuation. The aim of this study was to determine prevalence of MTX intolerance in pediatric inflammatory bowel disease (IBD) using the Methotrexate Intolerance Severity Score developed in rheumatology and to identify risk factors for MTX intolerance. METHODS: Patients with pediatric IBD followed in the IBD clinic of Sainte Justine Hospital who had received MTX for IBD between 2004 and 2016 and were still actively on MTX were invited to fill out the Methotrexate Intolerance Severity Score questionnaire. A cutoff score of ≥6 points was used to define MTX intolerance, with at least one point for anticipatory, associative or behavioral items. RESULTS: Among 102 pediatric patients with IBD, 32 (31%) patients reported symptoms of MTX intolerance. Using a multivariable logistic regression model, factors that were associated with having symptoms of MTX intolerance were female sex (odds ratio 4.31 [95% confidence interval, 1.37-13.60], P = 0.01), receiving a dose of MTX higher than 20 mg/wk at the time of the questionnaire (odds ratio 4.06 [95% confidence interval, 1.30-12.70], P = 0.02), and having active disease according to Physician's Global Assessment (odds ratio 3.44 [95% confidence interval, 1.15-10.26], P = 0.03). Prophylactic prescription of antiemetics and folic acid did not prevent symptoms of MTX intolerance. CONCLUSIONS: Symptoms of MTX intolerance are frequent in pediatric IBD. The Methotrexate Intolerance Severity Score questionnaire could help better recognition of these symptoms. Identification of risk factors could have important implications for the success of treatment.


Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Methotrexate/adverse effects , Adolescent , Child , Female , Humans , Logistic Models , Male , Multivariate Analysis , Retrospective Studies , Risk Factors , Severity of Illness Index , Surveys and Questionnaires , Treatment Outcome
16.
J Crohns Colitis ; 10(7): 795-804, 2016 Jul.
Article En | MEDLINE | ID: mdl-26822611

BACKGROUND AND AIMS: Loss of response to infliximab resulting in discontinuation of therapy is a frequent problem encountered in paediatric Crohn's disease. Although identifying patients at risk of failure could have important implications for follow-up, literature in this area remains sparse. Our primary aim was to identify predictors of loss of response to infliximab among patients who were responders to induction. The secondary aim was to identify predictors of non-response to induction. METHODS: A retrospective cohort of patients with paediatric Crohn's disease treated with infliximab between 2000 and 2013 was followed until loss of response to infliximab or transfer to adult care. Predictors of response to induction therapy were studied by multivariate logistic regression. Time to treatment failure was analysed with a multivariate Cox model. RESULTS: Two-hundred and forty-eight patients were eligible for the study. Of these, 196 (79%) were responders to induction (57% clinical remission and 22% clinical response) and 52 (21%) were non-responders. Steroid resistance was the only variable independently associated with primary non-response (odds ratio [OR] 4.57, 95% confidence interval [CI] 1.67-12.50, p = 0.002). Thirty-one of the 196 responders discontinued infliximab due to loss of response after a mean of 1.6±1.3 years of treatment. Predictors of loss of response were level of response to induction (clinical response vs clinical remission, hazard ratio [HR] 3.74, 95% CI 1.80-7.80, p = 0.0004) and isolated colonic disease (HR 2.72, 95% CI 1.30-5.71, p = 0.008). CONCLUSIONS: Patients who fail to achieve clinical remission after induction and/or who have isolated colonic disease are at increased risk of loss of response to infliximab.


Crohn Disease/drug therapy , Drug Resistance , Drug Tolerance , Gastrointestinal Agents/therapeutic use , Induction Chemotherapy , Infliximab/therapeutic use , Maintenance Chemotherapy , Adolescent , Child , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Logistic Models , Male , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Treatment Failure
18.
J Pediatr Surg ; 47(12): e5-7, 2012 Dec.
Article En | MEDLINE | ID: mdl-23217918

We report the case of a girl who had tetralogy of fallot (TOF) repaired at birth without any associated diaphragmatic hernia. At the age of 2½ years, she experienced an upper gastrointestinal occlusion. At laparoscopy an organoaxial gastric volvulus was observed related to a peritoneal adhesion secondary to pericardial drainage that had been performed at the time of the TOF repair. After reduction of the volvulus, a phrenofundopexy was done. Postoperatively, the child has remained asymptomatic with a follow-up of 24 months. There are few cases of pericardial drainage complications documented in the literature but none in the pediatric population. Based on this observation, we advise that during pericardial drainage tube placement, the peritoneal cavity be carefully avoided to prevent formation of intra-peritoneal adhesions and the risk of gastric volvulus.


Drainage/adverse effects , Pericardial Effusion/surgery , Stomach Volvulus/etiology , Acute Disease , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Child, Preschool , Drainage/methods , Female , Follow-Up Studies , Humans , Laparoscopy/methods , Pericardial Effusion/diagnostic imaging , Risk Assessment , Stomach Volvulus/diagnostic imaging , Stomach Volvulus/surgery , Tetralogy of Fallot/surgery , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
19.
Dig Liver Dis ; 43(9): 714-20, 2011 Sep.
Article En | MEDLINE | ID: mdl-21530429

BACKGROUND: Survival from colorectal cancer is poorer in patients of lower socioeconomic level, or living far from the cancer reference centre. AIMS: To evaluate the impact of material deprivation and geographical remoteness on the uptake of colonoscopy after a positive screening faecal occult blood test. METHODS: Data from two large French average-risk population-based trials comparing two faecal occult blood tests were used. Compliance with colonoscopy after a positive faecal occult blood test was analysed using a logistic model and a Cox model considering time between faecal occult blood test and colonoscopy. Covariates studied were sex, age, distance to nearest gastroenterologist, distance to regional capital, and Townsend's deprivation score. RESULTS: Amongst 4320 eligible subjects, 4131 were included. The rate of colonoscopy was 83.8%, within a median time of 66.0 days after faecal occult blood test. Distance to regional capital (p-trend=0.02) and study centre (p<0.0001) were independently associated with colonoscopy uptake. Time from positive faecal occult blood test to colonoscopy, was associated only with distance to the regional capital (p<0.0001, multivariate model stratified on study centre). CONCLUSION: Geographical remoteness but not material deprivation was responsible for lower uptake of colonoscopy. Healthcare decision-makers should focus on geographical remoteness to promote equal access to diagnostic procedures in faecal occult blood test colorectal cancer screening programmes.


Colonoscopy/statistics & numerical data , Colorectal Neoplasms/diagnosis , Health Services Accessibility , Occult Blood , Patient Compliance/statistics & numerical data , Aged , Female , France , Humans , Logistic Models , Male , Middle Aged , Proportional Hazards Models , Socioeconomic Factors , Time Factors
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