Work productivity loss is determined by fatigue and reduced quality of life in employed inflammatory bowel disease patients: a prospective multicentre cohort study.

OBJECTIVE: Inflammatory bowel disease (IBD) patients experience problems at work resulting in work productivity loss driving indirect healthcare costs. We aimed to find determinants for work productivity loss in employed IBD patients while correcting for disease severity according to prior and active maintenance treatment. METHODS: In this longitudinal multicentre cohort study, 510 employed IBD patients completed online questionnaires during 18 months follow-up. Work productivity, fatigue and health-related quality of life (HRQL) were measured using the Work Productivity and Activity Impairment questionnaire, the Multidimensional Fatigue Inventory (score 20-100) and Short-Inflammatory Bowel Disease Questionnaire (score 10-70). Linear mixed model analyses including random, repeated and fixed effects were performed. RESULTS: Fatigue (ß 0.22; 95% CI, 0.12-0.32) and reduced HRQL (ß -1.15; 95% CI, -1.35 to -0.95) were the strongest determinants for work productivity loss in employed IBD patients. Clinical disease activity (ß 9.50, 95% CI 6.48-12.51) and corticosteroid use (ß 10.09, 95% CI 5.25-15.84) were associated with work productivity loss in the total IBD group and ulcerative colitis subgroup, but not in Crohn's disease patients. History of IBD-related surgery (ß 9.41; 95% CI, 2.62-16.20) and vedolizumab use (ß 12.74; 95% CI, 3.63-21.86) were significantly associated with work productivity loss in the ulcerative colitis subgroup. CONCLUSIONS: Fatigue and reduced HRQL were the strongest determinants for work productivity loss in employed IBD patients while correcting for disease severity and activity. These results underline the importance of monitoring fatigue and HRQL in routine care to reduce work productivity loss and indirect costs.

High Disease Burden Drives Indirect Costs in Employed Inflammatory Bowel Disease Patients: The WORK-IBD Study.

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.

Impaired Quality of Working Life in Inflammatory Bowel Disease Patients.

BACKGROUND: Work-related aspects are important determinants of health for inflammatory bowel disease (IBD) patients. AIMS: We aimed to describe quality of working life (QWL) in IBD patients and to assess variables that are associated with QWL. METHODS: Employed 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. RESULTS: In 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). CONCLUSIONS: IBD-related problems at work negatively influence QWL. Fatigue, reduced HRQL, and WP loss were independent predictors of impaired QWL in IBD.

The vanishing duodenal polyp: mesenteric invagination presenting as duodenal pseudopolyp.

Duodenal polypoid masses are an uncommon finding mainly diagnosed incidentally at endoscopy or surgery. We report a 39-year-old female patient with symptoms of intermittent stabbing pain in the upper right abdominal quadrant and an iron deficiency anaemia, without complaints of weight loss, haematemesis or melaena. A duodenal polyp and acute duodenitis have been described during endoscopic examinations and CT and ultrasound. Surgical excision of the polyp was advised. Intraoperatively, an elongated duodenum was remarkable; however, at duodenotomy, no polyp was found, nor during intraoperative endoscopy. Looking back at the endoscopy and imaging results, it was noted that the polyp varied in size and location. It was therefore concluded that we dealt with the pseudopolyp phenomenon, caused by invagination of the duodenal wall and its mesentery into the duodenum, presenting as a lipomatous pseudopolyp. Telescopic invagination of the duodenal wall was facilitated by the elongated hypermobile duodenum.

Hepatocyte nuclear factor-1alpha is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo.

Hepatocyte nuclear factor-1alpha (HNF-1alpha) is a modified homeodomain-containing transcription factor that has been implicated in the regulation of intestinal genes. To define the importance and underlying mechanism of HNF-1alpha for the regulation of intestinal gene expression in vivo, we analyzed the expression of the intestinal differentiation markers and putative HNF-1alpha targets lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) in hnf1alpha null mice. We found that in adult jejunum, LPH mRNA in hnf1alpha(-/-) mice was reduced 95% compared with wild-type controls (P < 0.01, n = 4), whereas SI mRNA was virtually identical to that in wild-type mice. Furthermore, SI mRNA abundance was unchanged in the absence of HNF-1alpha along the length of the adult mouse small intestine as well as in newborn jejunum. We found that HNF-1alpha occupies the promoters of both the LPH and SI genes in vivo. However, in contrast to liver and pancreas, where HNF-1alpha regulates target genes by recruitment of histone acetyl transferase activity to the promoter, the histone acetylation state of the LPH and SI promoters was not affected by the presence or absence of HNF-1alpha. Finally, we showed that a subset of hypothesized intestinal target genes is regulated by HNF-1alpha in vivo and that this regulation occurs in a defined tissue-specific and developmental context. These data indicate that HNF-1alpha is an activator of a subset of intestinal genes and induces these genes through an alternative mechanism in which it is dispensable for chromatin remodeling.