Development and investigation of a non-invasive disease severity index for inflammatory bowel disease.

INTRODUCTION: The disease severity index (DSI) encapsulates the inflammatory bowel disease (IBD) burden but requires endoscopic investigations. This study developed a non-invasive DSI using faecal calprotectin (DSI-fCal) and faecal myeloperoxidase (DSI-fMPO) instead of colonoscopy. METHODS: Adults with IBD were recruited prospectively. Baseline biomarker concentrations were used to develop DSI-fCal and DSI-fMPO, and these were correlated with the original DSI, IBD-symptoms, endoscopic activity, and quality-of-life (QoL). Area under the receiver-operating-characteristics curves (AUROC) assessed DSI-fCal/DSI-fMPO as predictors of clinical and biochemical remission at six months (symptom remission and fCal <150 µg/g, respectively), and a complicated IBD-course at 24 months (disease relapse needing escalation of biologicals/immunomodulators/recurrent corticosteroids, IBD-hospitalisations/surgeries). Multivariable logistic regression assessed the utility of DSI-fCal/DSI-fMPO in predicting a complicated IBD-course at 24 months. RESULTS: In total, 171 patients were included (Crohn's disease=99, female=90, median age=46y (IQR 36-59)). DSI-fCal and DSI-fMPO correlated with the original DSI (r>0.9, p<0.001), endoscopic indices (r=0.45-0.49, p<0.001), IBD-symptoms (r=0.53-0.58, p<0.001) and QoL (r=-0.57-0.58, p<0.001). Baseline DSI-fCal (AUROC=0.79, 95% CI 0.65-0.92) and DSI-fMPO (AUROC=0.80, 95% CI 0.67-0.93) were associated with 6-month clinical and biochemical remission. DSI-fCal (AUROC=0.83, 95% CI 0.77-0.89) and DSI-fMPO (AUROC=0.80, 95% CI 0.73-0.87) performed similarly in predicting a complicated IBD-course to the original DSI (pdifference>0.05). The non-invasive DSI was independently associated with a complicated IBD-course on multivariable analyses (DSI-fCal28, aOR=6.04, 95% CI 2.42-15.08; DSI-fMPO25, aOR=7.84, 95% CI 2.96-20.73). CONCLUSIONS: The DSI-fCal and DSI-fMPO perform similarly in prognosticating the longitudinal disease course as the original DSI, whilst avoiding a need for an endoscopic assessment.

The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.

This study shows that the disease severity index (DSI) for inflammatory bowel disease (IBD) is a valid and reliable instrument encapsulating the disease phenotype, disease activity, and impact of the disease on the patient; and it accurately predicts for incident disease complications.

The Impact of Disease Activity on Sexual and Erectile Dysfunction in Patients With Inflammatory Bowel Disease.

BACKGROUND: Increased disease activity may be a risk factor for sexual dysfunction (SD) in patients with inflammatory bowel disease (IBD). This study investigated associations between objective measures of disease activity and sexual function. METHODS: Adults with IBD undergoing ileocolonoscopy were prospectively recruited. Demographic, sexual function (Female Sexual Function Index and International Index of Erectile Function), disease activity (endoscopic, biomarker, and symptoms), psychological symptoms, and quality-of-life data were collected. Rates of SD and erectile dysfunction (ED) were compared between patients with active and inactive inflammation and symptoms using the Fisher's exact test. Logistic regression examined associations between SD and ED, and disease characteristics and psychological symptoms. RESULTS: A total of 159 participants were included, 97 had Crohn's disease and 85 were women. SD was reported in 36 of 59 and 13 of 59 sexually active women and men, respectively and ED in 22 of 59 sexually active men. Rates of SD and ED were similar between individuals with active and inactive IBD based on endoscopic indices (P > .05) and biomarkers (P > .05). Women with active IBD symptoms experienced significantly higher rates of SD (P < .05), but men did not (P > .05). Multivariable logistic regression identified that symptoms of severe depression (odds ratio, 5.77; 95% confidence interval, 1.59-20.94) were associated with SD in women, and severe anxiety (odds ratio, 15.62; 95% confidence interval, 1.74-140.23) was associated with ED in men. CONCLUSIONS: Objective measures of disease activity are not associated with SD or ED in patients with IBD. Clinicians should consider concomitant psychological symptoms contributing to the sexual health of patients with IBD.

Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD], consisting of Crohn's disease [CD] and ulcerative colitis [UC], is a relapsing-remitting illness. Treat-to-target IBD management strategies require monitoring of gastrointestinal inflammation. This study aimed to investigate faecal myeloperoxidase [fMPO], a neutrophil granule enzyme, as a biomarker of IBD activity. METHODS: Prospectively recruited participants with IBD, undergoing ileocolonoscopy for disease assessment, provided biological samples and completed symptom questionnaires prior to endoscopy. fMPO, C-reactive protein [CRP], and faecal calprotectin [fCal] were compared with validated endoscopic indices [simple endoscopic score for CD and UC endoscopic index of severity]. Receiver operating characteristic [ROC] curves assessed the performance of fMPO, CRP, and fCal in predicting endoscopic disease activity. Baseline biomarkers were used to predict a composite endpoint of complicated disease at 12 months [need for escalation of biologic/immunomodulator due to relapse, steroid use, IBD-related hospitalisation, and surgery]. RESULTS: A total of 172 participants were recruited [91 female, 100 with CD]. fMPO was significantly correlated with endoscopic activity in both CD [r = 0.53, p < 0.01] and UC [r = 0.63, p < 0.01], and with fCal in all patients with IBD [r = 0.82, p < 0.01]. fMPO was effective in predicting moderate-to-severely active CD [AUROC 0.86, p < 0.01] and UC [AUROC 0.92, p < 0.01]. Individuals with a baseline fMPO > 26 µg/g were significantly more likely to reach the composite outcome at 12 months (hazard ratio [HR] 3.71, 95% confidence interval [CI] 2.07-6.64, p < 0.01). CONCLUSIONS: Faecal myeloperoxidase is an accurate biomarker of endoscopic activity in IBD and predicted a more complicated IBD course during follow-up.

The disease severity index for inflammatory bowel disease is associated with psychological symptoms and quality of life, and predicts a more complicated disease course.

BACKGROUND: The Disease Severity Index (DSI) is a novel tool to predict disease severity in inflammatory bowel disease (IBD). However, its ability to predict disease complications and the presence of psychosocial comorbidity is unclear. AIMS: To assess prospectively associations between the DSI and psychological symptoms, quality-of-life (QoL) and disease outcomes in an IBD cohort. METHODS: Patients with IBD undergoing ileocolonoscopy were followed prospectively for 12 months. DSI, psychological symptoms (perceived stress (PSS-10), depression (PHQ-9), anxiety (GAD-7)) and QoL (IBDQ-32) scores were assessed at baseline. Logistic regression identified variables predicting a complicated IBD course at 12 months (composite outcome of need for escalation of biological/immunomodulator for disease relapse, recurrent corticosteroid use, IBD-related hospitalisation and surgery). Receiver operating characteristics (ROC) analysis identified optimal DSI thresholds predicting a complicated disease course and multivariable logistic regression assessed the risk of reaching this outcome. RESULTS: One hundred and seventy-two patients were recruited (100 Crohn's disease, 91 female). Median DSI was 21 (IQR 11-32) and 97 patients had endoscopically active disease at baseline. The DSI was significantly higher in patients with symptoms of moderate-severe stress (PSS-10 > 14, p < 0.01), depression (PHQ-9 ≥ 10, p < 0.01), anxiety (GAD-7 ≥ 10, p < 0.05) and impaired quality-of-life (IBDQ-32 < 168, p < 0.01). Only the baseline DSI (OR 1.05, p < 0.01) and endoscopically active disease (OR 6.12, p < 0.01) were associated with a complicated IBD course. A DSI > 23 was strongly predictive of a complicated IBD course (OR 8.31, p < 0.001). CONCLUSIONS: The DSI is associated with psychological distress, impaired QoL and predicts a more complicated disease course in patients with IBD.

The impact of disease activity on psychological symptoms and quality of life in patients with inflammatory bowel disease-results from the Stress, Anxiety and Depression with Disease Activity (SADD) Study.

BACKGROUND: Disease activity may be a risk factor for psychological illness in patients with inflammatory bowel disease (IBD). AIM: To correlate objective measures of disease activity with psychological symptoms. METHODS: Adult patients with IBD undergoing ileocolonoscopy were prospectively recruited. Demographic, psychological symptoms (depression, anxiety, stress), disease activity (symptoms, biomarkers, endoscopy), and quality of life (QoL) data were collected. One-way ANOVA and multivariable analyses examined the associations between disease activity and symptoms of psychological illness, and identified other predictors of mental illness and reduced QoL. RESULTS: A total of 172 patients were included, 107 with Crohn's disease (CD) and 65 with ulcerative colitis (UC). There was no significant association between objective disease activity (endoscopic scores, faecal calprotectin or C-reactive protein) and depression, anxiety or stress scores (P > 0.05 for all comparisons). Gastrointestinal symptoms were significantly associated with symptoms of depression, anxiety and stress in patients with CD and UC (P < 0.05). On multivariable analysis, only gastrointestinal symptoms were associated with severe symptoms of depression (OR 20.78 [6.71-92.37], P < 0.001) and anxiety (OR 4.26 [1.70-12.25], P = 0.004). Anti-TNF and corticosteroid use, the presence of severe depressive, moderate-severe stress and gastrointestinal symptoms, and endoscopically active IBD were associated with a reduced QoL (P < 0.05). Longer duration of IBD predicted an improved QoL (P < 0.05). CONCLUSIONS: Objective measures of disease activity are not associated with symptoms of psychological illness in patients with IBD. Clinicians should consider underlying mental illness in patients with IBD with active gastrointestinal symptoms.

The IBD-Cope: A New Instrument for Measuring Coping in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has a major impact on psychological well-being. How an individual copes with IBD determines quality of life. We aimed to develop a brief, IBD-specific questionnaire to assess coping strategies (IBD-Cope) and to determine its test-retest reliability and validity. METHODS: Twenty IBD coping strategies were initially deemed to have face validity. Participants were recruited from an existing study, specialist outpatient clinics and via email. Distribution analyses were performed before test-retest reliability was determined. Exploratory factor analyses (EFAs) were then performed before cross-sectional validity was tested. RESULTS: The majority of participants in the study samples were female and most had Crohn's disease. All participants were aged between 18 and 65 years. EFA on the initial validation sample produced two components explaining 42% of the variance, and broadly reflected 'good' and 'bad' coping. EFA on the repeat validation sample showed three questions consistently clustering into either good or bad coping strategies. Good and bad coping strategies defined using the IBD-Cope were positively associated with adaptive (r = 0.57, p < 0.01) and maladaptive (r = 0.55, p < 0.01) coping on the Brief Coping Operations Preference Enquiry (Brief COPE), respectively. CONCLUSIONS: The IBD-Cope is a concise IBD-specific coping strategy questionnaire with demonstrated reliability and validity. The IBD-Cope subscales are moderately correlated with adaptive and maladaptive subscales of the Brief COPE. Prospective studies are required to determine whether the 6 questions represented in the IBD-Cope accurately identify IBD patients who may benefit from interventions to improve coping strategies.

What is the lower limit for postprandial venous plasma glucose in healthy young adults?

BACKGROUND: There is general agreement that the lower limit for postprandial venous plasma glucose is the same or higher than for a fasted sample. The finding of a postprandial fall in glucose would therefore have implications for assignment of the lower limit of the normal glucose range. METHODS: An antecubital venous sample was collected before and one hour after breakfast. Plasma was separated immediately after collection and glucose measured using the hexokinase method. Participants with dysglycaemia were excluded from subsequent analysis. RESULTS: Glucose range (mmol/L) for the 96 participants was 4.4-6.0 fasting and 2.7-7.2 postprandially. There was no relationship between postprandial glucose and either gender or carbohydrate intake. About 24% of postprandial concentrations were <3.9 mmol/L. CONCLUSIONS: If laboratories choose to define a random venous plasma glucose reference range, the lower limit should be below 3.9 mmol/L.

Impact of prandial status on the comparison of capillary glucose meter and venous plasma glucose measurements in healthy volunteers.

BACKGROUND: There is a negative glucose gradient between the capillary and venous systems, produced by glucose uptake into peripheral tissues. This gradient is augmented by oral glucose ingestion in healthy volunteers; thus prandial status may impact on capillary glucose meter performance. Our primary aim was to investigate whether the (capillary-venous plasma) glucose difference changed in relation to prandial status, in healthy volunteers. METHODS: Glucose was measured fasting and also one hour after an ad libitum breakfast, in 103 healthy volunteers. Duplicate capillary (finger stick) measurements were undertaken at both time points, using both the FreeStyle Lite and AccuChek Performa meters. Simultaneous venous (antecubital fossa) samples were centrifuged immediately after collection and plasma glucose was measured using the laboratory hexokinase method. Results were compared by Bland-Altman difference analysis. RESULTS: The mean (95% CI) pre- and postprandial (capillary-plasma) glucose differences (mmol/L) were calculated for each meter. For the Freestyle Lite, the preprandial difference was -0.51 (-0.58 to -0.45) and postprandial difference was 0.81 (0.69-0.94). Corresponding differences for the Performa were -0.13 (-0.20 to -0.06) and 1.19 (1.07-1.31), respectively. T-test comparison of participants' paired pre- and postprandial (capillary-plasma) glucose differences confirmed a significant meal-related change in glucose estimation for both meters (P < 0.0001). Also, both meters read highest at lower glucose concentrations. CONCLUSIONS: In healthy volunteers, both glucose meters showed a systematic positive bias one hour after breakfast. The significance of this finding in diabetes remains to be determined.