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Abstract Background Work productivity (WP) loss includes absence from work (absenteeism) and productivity loss while working (presenteeism), which leads to high indirect costs in inflammatory bowel disease (IBD). Prior health economic analyses predominantly focused on absenteeism. Here we focus on presenteeism and assess predictors of WP loss, fatigue, and reduced health-related quality of life (HRQL). Methods Employed IBD patients completed the following surveys: Work Productivity and Activity Impairment, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire. Predictors were assessed using uni- and multivariable regression analyses. Annual costs were calculated using percentages of WP loss, hourly wages, and contract hours. Results Out of 1590 invited patients, 768 (48%) responded and 510 (32%) were included. Absenteeism, presenteeism, and overall WP loss were reported by 94 (18%), 257 (50%), and 269 (53%) patients, respectively, resulting in mean (SD) annual costs of €1738 (5505), €5478 (8629), and €6597 (9987), respectively. Disease activity and active perianal disease were predictors of WP loss (odds ratio [OR] = 6.6; 95% confidence interval [CI], 3.6-12.1); OR = 3.7; 95% CI, 1.5-8.7). Disease activity and arthralgia were associated with fatigue (OR = 3.6; 95% CI, 1.9-6.8; OR = 1.8; 95% CI, 1.0-3.3)) and reduced HRQL (OR = 10.3; 95% CI, 5.9-17.9; OR = 2.3; 95 % CI, 1.4-3.8). Fatigue was the main reason for absenteeism (56%) and presenteeism (70%). Fatigue and reduced HRQL led to increased costs compared with absence of fatigue and normal HRQL (mean difference = €6630; 95% CI, €4977–€8283, P < 0.01; mean difference = €9575; 95% CI, €7767–€11,384, P < 0.01). Conclusions Disease activity and disease burden lead to WP loss in approximately half of the employed IBD population, driving indirect costs. Fatigue is the most important reason for WP loss.

Abstract Background Patients with inflammatory bowel disease (IBD) express a need for additional psychotherapy; however, psychological support is not incorporated in the routine care of persons with IBD. This systematic review aims to assess the effect of psychotherapy on quality of life (QoL). Methods A systematic search was conducted on October 7, 2019, using Embase, Medline (Ovid), PubMed, Cochrane, Web of Science, PsycInfo, and Google Scholar to collect all types of clinical trials with psychotherapeutic interventions that measured QoL in patients with IBD aged ≥18 years. Quality of evidence was systematically assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Results Out of 2560 articles, 31 studies (32 articles) were included with a total number of 2397 patients with active and inactive IBD. Of the 31 eligible studies, 11 reported a significant positive effect and 6 had ambiguous results regarding the impact of psychotherapeutic interventions on QoL. Treatment modalities differed in the reported studies and consisted of cognitive-behavioral therapy, psychodynamic therapy, acceptance and commitment therapy, stress management programs, mindfulness, hypnosis, or solution-focused therapy. All 4 studies focusing on patients with active disease reported a positive effect of psychotherapy. Trials applying cognitive-behavioral therapy reported the most consistent positive results. Conclusions Psychotherapeutic interventions can improve QoL in patients with IBD. More high-quality research is needed before psychological therapy may be implemented in daily IBD practice and to evaluate whether early psychological intervention after diagnosis will result in better coping strategies and QoL throughout life.

BackgroundWork-related aspects are important determinants of health for inflammatory bowel disease (IBD) patients.AimsWe aimed to describe quality of working life (QWL) in IBD patients and to assess variables that are associated with QWL.MethodsEmployed IBD patients of two tertiary and two secondary referral hospitals were included. QWL (range 0–100) was measured using the Quality of Working Life Questionnaire (QWLQ). Work productivity (WP), fatigue, and health-related quality of life (HRQL) were assessed using the Work Productivity and Activity Impairment questionnaire, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire, respectively. Active disease was defined as a score > 4 for the patient-reported Harvey–Bradshaw index in Crohn’s disease (CD) or Simple Clinical Colitis Activity Index in ulcerative colitis patients.ResultsIn total, 510 IBD patients were included (59% female, 53% CD, mean age 43 (SD 12) years). The mean QWLQ score was 78 (SD 11). The lowest subscore (54 (SD 26)) was observed for “problems due to the health situation”: 63% reported fatigue-related problems at work, 48% agreed being hampered at work, 46% had limited confidence in their body, and 48% felt insecure about the future due to their health situation. Intermediate/strong associations were found between QWL and fatigue (r = − 0.543, p < 0.001), HRQL (r = 0.527, p < 0.001), WP loss (r = − 0.453, p < 0.001) and disease activity (r = − 0.331, p < 0.001). Independent predictors of impaired QWL in hierarchical regression analyses were fatigue (B = − 0.204, p < 0.001), WP loss (B = − 0.070, p < 0.001), and impaired HRQL (B = 0.248, p = 0.001).ConclusionsIBD-related problems at work negatively influence QWL. Fatigue, reduced HRQL, and WP loss were independent predictors of impaired QWL in IBD.

Sensor drift is a well-known disadvantage of electronic nose (eNose) technology and may affect the accuracy of diagnostic algorithms. Correction for this phenomenon is not routinely performed. The aim of this study was to investigate the influence of eNose sensor drift on the development of a disease-specific algorithm in a real-life cohort of inflammatory bowel disease patients (IBD). In this multi-center cohort, patients undergoing colonoscopy collected a fecal sample prior to bowel lavage. Mucosal disease activity was assessed based on endoscopy. Controls underwent colonoscopy for various reasons and had no endoscopic abnormalities. Fecal eNose profiles were measured using Cyranose 320®. Fecal samples of 63 IBD patients and 63 controls were measured on four subsequent days. Sensor data displayed associations with date of measurement, which was reproducible across all samples irrespective of disease state, disease activity state, disease localization and diet of participants. Based on logistic regression, corrections for sensor drift improved accuracy to differentiate between IBD patients and controls based on the significant differences of six sensors (p = 0.004; p < 0.001; p = 0.001; p = 0.028; p < 0.001 and p = 0.005) with an accuracy of 0.68. In this clinical study, short-term sensor drift affected fecal eNose profiles more profoundly than clinical features. These outcomes emphasize the importance of sensor drift correction to improve reliability and repeatability, both within and across eNose studies.

The gut microbiota and its related metabolites differ between inflammatory bowel disease (IBD) patients and healthy controls. In this study, we compared faecal volatile organic compound (VOC) patterns of paediatric IBD patients and controls with gastrointestinal symptoms (CGIs). Additionally, we aimed to assess if baseline VOC profiles could predict treatment response in paediatric IBD patients. We collected faecal samples from a cohort of de novo therapy-naïve paediatric IBD patients and CGIs. VOCs were analysed using gas chromatography–ion mobility spectrometry (GC-IMS). Response was defined as a combination of clinical response based on disease activity scores, without requiring treatment escalation. We included 109 paediatric IBD patients and 75 CGIs, aged 4 to 17 years. Faecal VOC profiles of paediatric IBD patients were distinguishable from those of CGIs (AUC ± 95% CI, p-values: 0.71 (0.64–0.79), <0.001). This discrimination was observed in both Crohn’s disease (CD) (0.75 (0.67–0.84), <0.001) and ulcerative colitis (UC) (0.67 (0.56–0.78), 0.01) patients. VOC profiles between CD and UC patients were not distinguishable (0.57 (0.45–0.69), 0.87). Baseline VOC profiles of responders did not differ from non-responders (0.70 (0.58–0.83), 0.1). In conclusion, faecal VOC profiles of paediatric IBD patients differ significantly from those of CGIs.

(1) Background: Colorectal cancer is the second commonest cause of cancer deaths worldwide; recently, volatile organic compounds (VOCs) have been proposed as potential biomarkers of this disease. In this paper, we aim to identify and review the available literature on the influence of mechanical bowel preparation on VOC production and measurement. (2) Methods: A systematic search for studies was carried out for articles relevant to mechanical bowel preparation and its effects on volatile organic compounds. A total of 4 of 1349 papers initially derived from the search were selected. (3) Results: Two studies with a total of 134 patients found no difference in measured breath VOC profiles after bowel preparation; one other study found an increase in breath acetone in 61 patients after bowel preparation, but no other compounds were affected. Finally, the last study showed the alteration of urinary VOC profiles. (4) Conclusions: There is limited data on the effect of bowel preparation on VOC production in the body. As further studies of VOCs are conducted in patients with symptoms of gastrointestinal disease, the quantification of the effect of bowel preparation on their abundance is required.

INTRODUCTION:Colonoscopy surveillance for Lynch syndrome is burdensome and postcolonoscopy colorectal cancers (CRCs) still occur. The noninvasive fecal immunochemical test (FIT) might guide optimal colonoscopy intervals.METHODS:Prospective, multicenter observational study in which individuals with Lynch syndrome performed a quantitative FIT before high-quality surveillance colonoscopy. Diagnostic performance of FIT at various thresholds ≤20 μg Hb/g feces was assessed for relevant neoplasia, including advanced neoplasia (CRC, advanced adenomas [AAs] and advanced serrated lesions [ASLs]) and non-advanced adenomas (NAAs).RESULTS:Of the 217 included individuals (59% female, median age 51 years), 4 had CRC, 5 AA, 4 ASL, and 57 NAA as most relevant neoplasia. The lowest FIT positivity threshold (2.5 μg Hb/g feces, 14% positivity rate) maximized detection: 4/4 CRCs, 4/5 AA, 1/4 ASL, and 9/57 NAA were detected, resulting in a sensitivity and negative predictive value of, respectively, 89% and 99% for CRC plus AA, 69% and 97% for advanced neoplasia, and 26% and 72% for all relevant neoplasia (91% specificity for all groups). At equal sensitivity and negative predictive value, specificity for advanced neoplasia optimized to 94% at threshold 4.1 μg/g. Per 100 FITs at threshold 4.1 μg/g, 11 individuals would test positive and thus proceed to colonoscopy, 2 individuals with advanced neoplasia would be missed and 3 individuals would need colonoscopy to detect 1 advanced neoplasia.DISCUSSION:FIT at thresholds ≤4.1 μg Hb/g feces may be a promising strategy to postpone colonoscopy in approximately 9 of 10 individuals with Lynch syndrome. Large validation studies that also provide gene variant-specific outcomes should be prioritized.

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer. However, histologically, it is challenging to distinguish between IBD-associated dysplasia from sporadic adenomas. We have molecularly characterized these precursor lesions and show that IBD-associated dysplasia lesions are genomically much more unstable.AbstractBackgroundPatients with longstanding inflammatory bowel disease (IBD; ie, ulcerative colitis and Crohn’s disease) have an increased risk of colorectal cancer (CRC). Due to ongoing inflammation, IBD-associated dysplastic lesions can develop. These lesions have an increased risk to progress to cancer compared with sporadic adenomas, which are also found in these patients. Differentiating between these 2 types of dysplasia remains challenging, both clinically and histologically, while treatment strategies may differ. Therefore, the aim of this study was to investigate molecular alterations associated with colorectal dysplasia to cancer progression in IBD and evaluate to what extent these alterations differ from sporadic adenomas.MethodsDNA copy number aberrations and mutation analyses of 48 genes were performed by next-generation sequencing in 43 IBD-associated dysplastic lesions, 30 of which were dysplastic and 13 of which were cancers. Results were compared with existing DNA copy number and mutation data from 118 sporadic adenomas and 24 sporadic cancers.ResultsInflammatory bowel disease–associated dysplastic lesions harbor patterns of DNA copy number aberrations comparable to carcinomas, which are rare in sporadic adenomas. TP53 mutation was the most frequent mutation observed in IBD-associated dysplastic lesions and in cancers. FBXW7 was mutated significantly more often in IBD-associated dysplastic lesions than in sporadic adenomas.ConclusionsInflammatory bowel disease–associated dysplastic lesions show more DNA copy number aberrations than sporadic adenomas. TP53 and FBXW7 mutations appear to be involved in the development of IBD-associated dysplastic lesions and cancer. These findings indicate that IBD-associated dysplastic lesions are more genomically unstable, possibly reflecting a faster progression toward cancer.

Abstract Background and Aims Therapeutic drug monitoring (TDM) of methotrexate (MTX) is challenging due to its pharmacokinetics and short plasma half-life. Intracellular MTX–polyglutamates (PG1–5), which accumulate over time, have not been assessed in pediatric inflammatory bowel disease (IBD). This study aimed to evaluate erythrocyte MTX-PG as a potential TDM tool in pediatric IBD. Methods In this cross-sectional study, MTX-PG concentrations were measured in erythrocytes of children with IBD on stable low-dose MTX for at least 12 weeks using stable-isotope dilution liquid chromatography–tandem mass spectrometry. The influence of administration route, MTX dosage, and anthropometrics on MTX-PG concentrations was examined. Results Seventy-eight patients were included, showing MTX-PG3 as the predominant subspecies (median 27.0 nmol/L) with a median MTX-PGtotal of 74.8 nmol/L. A higher MTX dose correlated significantly with elevated levels of MTX-PG3, MTX-PG4, MTX-PG5, and MTX-PGtotal (P < .01). Adjusted for body surface area, MTX dose remained significantly associated with higher MTX-PG concentrations (P < .01). However, comparison by administration route was limited due to a few patients on subcutaneous MTX (n = 4). Conclusions We observed high interindividual variability in the reached erythrocyte MTX-PG concentrations. Body surface adjusted or unadjusted MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in children with IBD. This is a prerequisite for TDM and provides a strong basis for further research into the relation between TDM of MTX, efficacy, and toxicity. Lay Summary This study investigated erythrocyte methotrexate–polyglutamate (MTX-PG) levels in pediatric inflammatory bowel disease patients, finding that higher MTX doses correlate with increased long-chain MTX-PG concentrations. Results showed substantial interindividual variability, supporting further research on MTX-PG’s potential as a therapeutic drug monitoring tool.