Pediatric inflammatory bowel disease: Fecal calprotectin response to Anti-tumor necrosis factor alpha.

BACKGROUND: Fecal calprotectin (FC) is a marker of mucosal inflammation in inflammatory bowel disease (IBD). We aimed to assess the effect of anti-tumor necrosis factor alpha (TNFα) therapy on FC levels in children with IBD. METHODS: The medical records of pediatric patients treated with anti-TNFα agents (2015-2020) were reviewed retrospectively. 63 patients had FC levels measured prior to anti TNFα induction with sequential measurements during follow-up. The main outcome measures were time to FC response according to cutoffs of 250, 150, 100 and 50 µgr/gr. RESULTS: Mean age was 13.6 ± 3 years [females 28 (44.4%), Crohn's 55 (87%)]. Outcomes of < 250, < 150, < 100 and < 50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%), respectively. The median time for achieving these cutoffs was 4.8 (1.8-15.6), 7.9 (2.6-16.4), 10.0 (3.5-20.5) and 18.5 (7.0-64.7) months, respectively. Shorter time from diagnosis to treatment was associated with achievement of FC < 50 µgr/gr (p = 0.03). There was no association between age, disease type, anti-TNFα type, inflammatory markers, disease activity indices at baseline and induction anti-TNFα trough concentration and FC response. CONCLUSIONS: FC response was achieved by the majority of patients treated with anti-TNFα within a short period of time. FC normalization in responders required almost one year. IMPACT: Fecal calprotectin response was achieved by the majority of pediatric patients within a relatively short period of time after anti-TNFα induction and maintenance therapy. Fecal calprotectin normalization required an average period of approximately one year in responders. The faster response of fecal calprotectin is associated with shorter time from diagnosis to anti-TNFα treatment. Inflammatory bowel disease treating physicians should be aware of the relatively prolonged time to fecal calprotectin normalization and to allow enough time for anti-TNFα therapy to express its full potential prior to significant interventions.

High anti-TNFα Concentrations Are Not Associated With More Adverse Events in Pediatric Inflammatory Bowel Disease.

ABSTRACT: Anti-tumor necrosis factor alpha (anti-TNFα) therapy is commonly used to treat refractory pediatric inflammatory bowel disease (IBD) and carry risks for adverse events. We aimed to assess the relationship between anti-TNFα trough concentrations and adverse events rate among pediatric patients with IBD. The medical records of pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 and had sequential monitoring of trough concentration (TC) were reviewed retrospectively for the presence of adverse events. The study cohort included 135 eligible patients (59 [43.7%] girls, mean age at diagnosis 12.9 [±3] years, 111 [82.2%] Crohn disease) who had 1589 measurements of TCs (1037 [63%] infliximab). During a median follow-up period of 1.7 years (IQR 1.1-2.7), we recorded 156 adverse events in 50 patients (37%). Higher TCs were not associated with higher rate of anti-TNFα-related adverse events whereas these events (excluding increase in liver transaminases) were associated with younger age.

Paediatric Colonoscopy Direct Observation of Procedural Skills: Evidence of Validity and Competency Development.

INTRODUCTION: The paediatric series of direct observation of procedural skills (DOPS) were introduced into the UK national endoscopy training curriculum in 2016, but lack validity evidence. We aimed to present validity evidence for paediatric colonoscopy DOPS and study competency development in a national trainee cohort. METHODS: This prospective UK-wide study analysed formative paediatric colonoscopy DOPS which were submitted to the e-Portfolio between 2016 and 2018. Item, domain, and average DOPS scores were correlated with the overall DOPS rating to evidence internal structure validity. Overall DOPS ratings were compared over lifetime procedure count to demonstrate learning curves (discriminant validity). Consequential validity was founded on receiver operating characteristic curve analyses. RESULTS: A total of 203 DOPS assessments were completed for 29 trainees from 11 UK training centres. Internal structure validity was provided through item-total correlation analyses. DOPS scores positively correlated with trainee seniority (P < 0.001) and lifetime procedure count (P < 0.001). Competency acquisition followed the order of: "preprocedure," "postprocedure," "endoscopic nontechnical skills," "management," "procedure" domains, followed by overall DOPS competency, which was achieved in 81% of the cohort after 125 to 149 procedures. Mean DOPS scores could be used to predict overall procedure competence (area under receiver operating characteristic curve 0.969, P < 0.001), with a mean score of 3.9 demonstrating optimal sensitivity (93.5%) and specificity (87.6%). CONCLUSIONS: This study provides validity evidence supporting the use of paediatric colonoscopy DOPS as an in-training competence assessment tool. DOPS may also be used to measure competency development and benchmark performance during training, which may be of value to trainees, trainers, and training programmes.

Validity Evidence for Direct Observation of Procedural Skills in Paediatric Gastroscopy.

OBJECTIVES: Direct observation of procedural skills (DOPS) are competence-assessment tools in endoscopy. Formative paediatric gastroscopy DOPS were implemented into the UK curriculum in 2016 but lack validity evidence; we aimed to assess validity evidence using a recognised contemporary validity framework. METHODS: We performed a prospective UK-wide analysis of formative paediatric gastroscopy DOPS submitted to the e-Portfolio over 1 year. Internal structure validity was assessed using interitem correlations between DOPS items, average domain, and skillset scores and with the overall competency rating. Overall competence scores and mean DOPS scores were compared by trainee seniority and procedure count (discriminative validity). Receiver operating characteristic curve analysis was performed to explore if DOPS scores could be used to delineate procedural competency (consequential validity). RESULTS: A total of 157 DOPS assessments were completed by 20 trainers for 17 trainees. Strengths of correlations varied between DOPS components, with overall competency correlating most with technical-predominant items, domains and skillsets. Both the overall assessor's rating and mean DOPS scores increased with trainee seniority (P < 0.001) and lifetime procedure count (P < 0.001). Overall competency could be delineated using mean DOPS scores (area under receiver operating characteristic curve 0.95, P < 0.001), with a threshold of 3.9 providing optimal sensitivity (94.4%) and specificity (89.7%). CONCLUSIONS: Competencies in paediatric gastroscopy, as assessed using DOPS, vary in their correlation with overall competence and increase with trainee experience. Formative DOPS thresholds could be used to indicate readiness for summative assessment. Our study therefore provides evidence of internal structure, discriminative, and consequential validity in support of formative paediatric gastroscopy DOPS.

Effects of testosterone replacement in middle-aged men with dysthymia: a randomized, placebo-controlled clinical trial.

Mid-life onset male dysthymic disorder (DD) seems to be a distinct clinical condition with limited therapeutic options. Testosterone replacement is mood-enhancing and has been proposed as an antidepressant therapy, though this strategy has received limited systematic study. We therefore conducted a six-week double-blind placebo-controlled clinical trial in 23 men with DD and with low or low-normal testosterone (T) level (i.e, screening total serum testosterone <350 ng/dL). Enrolled men were randomized to receive intramuscular injections of 200 mg of testosterone cypionate or placebo every 10 days. The primary outcome measures were the Clinical Global Impression (CGI) improvement score and the 21-item Hamilton Depression Rating Scale (HDRS) score.Twenty-three patients were randomized. The mean (SD) age of the enrolled patients was 50.6 (7.0) years and that of total testosterone level was 339 (93) ng/dL. The median duration of the current dysthymic episode was 3.6 (2.3) years, and the mean (SD) HDRS was 14.0 (2.9). After the intervention, the mean HDRS score decreased significantly more in the testosterone group (7.46 [4.56]) than in the placebo group (1.8 [4.13], t21 = -3.07, P = 0.006). Remission, defined as a CGI improvement score of 1 or 2 and a final HDRS score lower than 8, was achieved by 7 (53.8%) of 13 in the testosterone group and 1 (10%) of 10 in the placebo group (P = 0.03). Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia.

Dietary regulation of gene expression.

PURPOSE OF REVIEW: The intestine has traditionally been assumed to process food by digestion and absorption. The possibility that the intestine or other genes in the body respond to diet has only slowly been appreciated. RECENT FINDINGS: This review examines recent evidence that nutrients act on genes in the intestine and in distant sites such as the brain, liver, and skeletal muscle. The article reviews how nutrients affect genes involved in cancer in the intestine; it also studies dietary effects on inflammatory pathways and changes in the brain. Studies in the liver have given insights as to how amino acids may regulate gene promoter activity. Finally, target of rapamycin, an epigenetic regulator, links nutrition to histone acetylation, a key event in gene expression. SUMMARY: The evidence that nutrients regulate gene expression continues to increase.