Stone JK, Shafer LA, Graff LA, Witges K, Lix L, Sexton KA, Haviva C, Targownik LE, Bernstein CN. The association of efficacy, optimism, uncertainty and health anxiety with inflammatory bowel disease activity. Journal of Psychosomatic Research 2022; Mar; 154: 110719.

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Positive and negative psychological attributes have been shown to influence disease outcomes in many chronic health conditions. We aimed to evaluate the association between self-efficacy, optimism, health anxiety and intolerance of uncertainty and disease activity in IBD. Adults with confirmed and recently active IBD enrolled in a prospective cohort study. Demographics, disease information, validated measures of psychological functioning related to general self-efficacy, optimism, health anxiety and intolerance of uncertainty were collected at baseline, week 26 and week 52. Clinical disease activity was assessed using the Inflammatory Bowel Disease Symptom Inventory (IBDSI), self-reported flares, and intestinal inflammation using fecal calprotectin (FCAL), collected at baseline, weeks 26 and 52. Generalized estimating equations were used to test the association between psychological functioning and disease activity. Results: 154 participants mean age was 43.4 years (SD 12.5), 69.5% were women and 64.1% had Crohn’s disease. Adjusting for demographic variables, higher self-efficacy was associated with a 20% lower likelihood of flare by self-report (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.71,0.91) and 11% by IBDSI (OR 0.89, 95%CI 0.80,0.99), while higher health anxiety was associated with a slightly greater likelihood of flare by self-report (OR 1.07, 95% CI 1.01,1.18) and higher symptomatic disease activity (IBDSI; OR 1.14, 95% CI 1.05,1.24). The psychological attributes were not significantly associated with active disease as measured by inflammation (FCAL).  Conclusion: General self-efficacy and health anxiety are relevant in understanding patient experience with disease activity, and may be appropriate targets for psychological intervention in the care of individuals with IBD. 

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Kulyk A, Shafer LA, Graff LA, Stone J, Witges K, Targownik LE, Bernstein CN. Urgency for bowel movements is a highly discriminatory symptom for active disease in persons with IBD (the Manitoba Living with IBD study). Alimentary Pharmacology & Therapeutics 2022; 56:1570-80.

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We aimed to assess the prevalence of symptoms, and examine which symptoms are most associated with disease activity as measured by a symptom index or an objective measure of inflammation. The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly Inflammatory Bowel Disease Symptom Inventory (IBDSI) surveys. Relative risks (RR), positive and negative predictive values (PPV, NPV) were reported for each symptom to predict active disease, independently defined as: (1) active IBDSI, (2) self-reported flare, and (3) elevated fecal calprotectin (FCAL, greater than 250ug/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn’s disease, CD ulcerative colitis, UC). Results: 69.2% of participants were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, respectively, across all 3 disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). Absence of fatigue had a high NPV for active IBDSI in both CD and UC. Urgency had a strong NPV and PPV across all three disease measures in both CD and UC and females and males. Number of loose/liquid bowel movements predicted elevated FCAL in UC males and females. In CD, excessive bowel gas and urgency predicted increased FCAL in males. No symptom significantly predicted FCAL in females with CD. Conclusions: Fatigue was the most prevalent symptom irrespective of disease activity measure. Individual symptoms have different impacts on whether IBDSI (subjective measure) or FCAL (objective measure) is increased in IBD. 

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Vagianos K, Shafer LA, Graff LA, Witges K, Targownik LE, Bernstein CN. Self-reported flares among people living with IBD are associated with stress and worry but not associated with recent diet changes: The Manitoba Living with IBD Study. Journal of Parenteral and Enteral Nutrition 2022; 46: 1686-1698.

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In this matched case-control longitudinal study among people living with IBD, we investigated beliefs about what triggers a flare.  Adults with confirmed IBD and active disease within 2 years were enrolled in the Manitoba Living with IBD Study and followed biweekly with online surveys for 1 year. The 7-point IBD Symptom Change Indicator was used for participant identification of a flare. Flare cases were matched to non-flare controls by sex and disease type. Members of each matched pair completed supplemental information on diet changes and psychological functioning in the previous two weeks, and provided stool samples to assess fecal calprotectin (FCAL). Results: Of 128 enrolled participants, 95 matched flare/non-flare pairs were created. Those reporting a flare were more likely to have elevated FCAL (51% vs 34% among non-flares, p=0.043). Although 61% of study participants believed at baseline that a food may trigger flares, and 25% of those in a flare believed that a food may have triggered their current flare, there was no difference in consumption of assessed foods between flares and non-flares in the previous two weeks. Flares were more likely to be having difficulties in emotional state than controls (40% vs 18%, p=0.001) and more likely to be stressed or worried (64% vs 33%, p=0.001). Conclusion: While a majority of individuals with IBD believe that specificfoods trigger their disease flares, this was not supported by the current findings. Recent psychological functioning was associated with self-reported IBD flare.

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Witges K, Sexton K, Graff LA, Targownik LE, Lix LM, Haviva C, Stone J, Shafer LA, Vagianos K, Bernstein CN. What is a flare? The Manitoba Living with IBD study. Inflammatory Bowel Diseases 2022; 28: 862-869.

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Flare is a poorly defined term used by patients and clinicians to indicate IBD status. This study aimed to evaluate the validity of a single item 7-point flare indicator, relative to other measures of disease flare. The longitudinal Manitoba Living with IBD Study followed persons with IBD for one year; they completed biweekly online surveys and provided 3 stool samples. Disease flare on a single item flare indicator with seven possible responses developed for the study was defined by report of symptoms as ‘moderately’ or ‘much’ worse. The flare indicator was evaluated against five measures of disease activity:  fecal calprotectin score (FCAL), a 2-point disease status indicator, a 4-point flare certainty indicator, the IBD Symptom Index short form (SIBDSI), and the short form IBD Questionnaire (SIBDQ). Participants in a flare, based on the 7-point measure, were matched to a non-flaring participant, and a stool sample was collected. Results: Of the 155 IBD participants, almost half (n=74) experienced a flare.  Of those who flared, 97.0% endorsed active IBD on the 2-point indicator (controls 42.5%; p<0.001); 91.9% endorsed active IBD on the 4-point certainty indicator (controls 32.9%; p<0.001); 90.5% endorsed active disease on the SIBDSI (controls 34.2%; p<0.001); and 48.5% had an elevated FCAL (controls 34.3%; p < 0.05). The mean SIBDQ was lower for the flare group compared to controls [43.9(SD 11.1) vs 58.3(SD 8.5) p<0.001], indicating worse disease. Conclusions: The 7-point flare indicator robustly identified symptomatic flares. This patient self-report indicator reflected meaningful changes in more complex clinical indices, and had only weak concordance with the presence of inflammation.

 

Stone JA, Shafer LA, Graff LA, Witges K, Lix L. Sexton KA, Haviva C, Targownik LE, Bernstein CN. The association of efficacy, optimism, uncertainty and health anxiety with inflammatory bowel disease activity. Journal of Psychosomatic Research 2022; in press.

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Positive and negative psychological attributes have been shown to influence disease outcomes in many chronic health conditions. We aimed to evaluate the association between self-efficacy, optimism, health anxiety and intolerance of uncertainty and disease activity in IBD.  Adults with confirmed and recently active IBD enrolled in a prospective cohort study. Demographics, disease information, validated measures of psychological functioning related to general self-efficacy, optimism, health anxiety and intolerance of uncertainty were collected at baseline, week 26 and week 52. Clinical disease activity was assessed using the Inflammatory Bowel Disease Symptom Inventory (IBDSI), self-reported flares, and intestinal inflammation using fecal calprotectin (FCAL), collected at baseline, weeks 26 and 52. Generalized estimating equations were used to test the association between psychological functioning and disease activity. There were 154 participants of whom 64.1% had Crohn's disease. Adjusting for demographic variables, higher self-efficacy was associated with lower likelihood of flare by self-report (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.71, 0.91) and IBDSI (OR 0.89, 95% CI 0.80, 0.99), while higher health anxiety was associated with greater likelihood of flare by self-report (OR 1.07, 95% CI 1.01, 1.18) and higher symptomatic disease activity (IBDSI; OR 1.14, 95% CI 1.05, 1.24). The psychological attributes were not significantly associated with active disease as measured by inflammation (FCAL).

We concluded that general self-efficacy and health anxiety are relevant in understanding patient experience with disease activity, and may be appropriate targets for psychological intervention in the care of individuals with IBD.

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Dolovich C, Shafer LA, Vagianos K, Witges K, Targownik LE, Bernstein CN. The complex relationship between diet, symptoms and intestinal inflammation in persons with IBD: The Manitoba Living with IBD Study. Journal of Parenteral and Enteral Nutrition 2021; in press.

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We aimed to examine whether an association exists between diet quality, based on the Prospective Urban and Rural Epidemiologic Study (PURE) Healthy Diet Score, and active IBD. Participants were drawn from the Manitoba Living with IBD Study cohort. The Harvard Food Frequency Questionnaire was used to calculate the Healthy Diet Score at two time points; baseline and 1-year follow-up. Using generalized estimating equations logistic regression, we assessed the association between the Healthy Diet Score and: 1. the IBD Symptom Inventory (IBDSI), 2. intestinal inflammation, measured by fecal calprotectin, and 3. self-reported IBD flares. There were 294 completed Food Frequency Questionnaires among 153 people. Of these, 100% had completed data about an IBD flare, 98% had fecal calprotectin measurements and 96% had completed IBDSI scores. On a Healthy Diet Score scoring method of 0-8, the odds of fecal calprotectin >250 were lower for participants with a Healthy Diet Score of 4 versus 0-3 [adjusted OR 0.38, 95% CI, 0.19-0.77]. When applying a second Healthy Diet Score scoring method (8-40), the odds of having an IBD flare were 3.6 times greater for participants with a Healthy Diet Score between 21 and 24 compared to a Healthy Diet Score ≤20, [adjusted OR 3.63, 95% CI, 1.03-12.78].

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We found that active inflammation was less likely among those with a moderate Healthy Diet Score, while symptomatic IBD flares were more likely. People may choose to consume a moderate amount of healthy foods such as fruits and vegetables, even if known that those foods may cause a symptomatic flare.

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Witges K, Sexton K, Graff LA, Targownik LE, Lix LM, Haviva C, Stone J, Shafer LA, Vagianos K, Bernstein CN. What is a flare? The Manitoba Living with IBD study. Inflammatory Bowel Diseases 2021; in press.

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Flare is a poorly defined term used by patients and clinicians to indicate IBD status. This study aimed to evaluate the validity of a single-item 7-point flare indicator relative to other measures of disease flare. The longitudinal Manitoba Living with IBD Study followed persons with IBD for 1 year; they completed biweekly online surveys and provided 3 stool samples. Disease flare on a single-item flare indicator with 7 possible responses developed for the study was defined by report of symptoms as "moderately" or "much" worse. The flare indicator was evaluated against 5 measures of disease activity: fecal calprotectin score, a 2-point disease status indicator, a 4-point flare certainty indicator, the IBD Symptom Index short form (SIBDSI), and the short form IBD Questionnaire (SIBDQ). Participants in a flare, based on the 7-point measure, were matched to a nonflaring participant, and a stool sample was collected. Of the 155 IBD participants, almost half (n = 74) experienced a flare. Of those who flared, 97.0% endorsed active IBD on the 2-point indicator (controls 42.5%; P < .001); 91.9% endorsed active IBD on the 4-point certainty indicator (controls 32.9%; P < .001); 90.5% endorsed active disease on the SIBDSI (controls 34.2%; P < .001); and 48.5% had an elevated fecal calprotectin (controls 34.3%; P < .05). The mean SIBDQ was lower for the flare group compared with controls (43.9 [SD 11.1] vs 58.3 [SD 8.5]; P < .001), indicating worse disease.

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We concluded that the 7-point flare indicator robustly identified symptomatic flares. This patient self-report indicator reflected meaningful changes in more complex clinical indices and had only weak concordance with the presence of inflammation.

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Vagianos K, Shafer LA, Witges K, Targownik LE, Haviva C, Graff LA, Lix LM, Sexton KA, Sargent M, Bernstein CN.  Association between Change in Inflammatory Aspects of Diet and Change in IBD-related Inflammation and Symptoms over 1 Year: The Manitoba Living with IBD Study. Inflammatory Bowel Diseases 2021; 27: 190-202.

 

We aimed to investigate: (1) the stability of inflammatory aspects of diet over one year among persons with Inflammatory Bowel Disease (IBD) and (2) the impact of change in diet on changes in inflammation and IBD symptoms over one year. Participants were recruited into the Manitoba Living with IBD Study and completed the Harvard Food Frequency Questionnaire (FFQ). The Dietary Inflammatory Index (DII) and the Empirical Dietary Inflammatory Index (EDII) were used to calculate the inflammatory potential of the diet. Inflammation was measured by fecal calprotectin (> 250 ug/g). Symptoms were measured by the IBD Symptom Inventory (IBDSI). All measures were obtained at baseline and one year. DII and EDII scores > 0 and < 0 reflect pro- and anti-inflammatory diet, respectively. Variance components analyses were used to describe diet stability. Associations between changes in diet and changes in active inflammation and symptoms were assessed using ordinal logistic regression and multilevel linear regression modelling. 135 participants (66% Crohn’s disease) were included. Approximately one-third of the variance in EDII (36%) and DII (33%) scores was explained by changes in diet over time. Each unit increase in the change in EDII (baseline to follow-up) was associated with a greater odds of fecal calprotectin indicating active inflammation (>250 ug/g; OR=3.1, 95% C.I. 1.02-9.93, p=0.04) and with a rise in IBDSI of 6.7 (95% C.I. 1.0-12.4, p=0.022) (theoretical IBDSI range: 0-81). There was no association between changes in DII and changes in fecal calprotectin or IBDSI.

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We concluded that the EDII, but not the DII, may have utility to identify the inflammatory potential of diet. This inflammatory potential can contribute to inflammation and/or disease symptoms in persons with IBD.

 

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Stone J, Shafer LA, Graff LA, Lix L, Witges K, Targownik LE, Haviva C, Sexton K, Bernstein CN. Utility of the MARS-5 in assessing medication adherence in IBD. Inflammatory Bowel Diseases 2021; 27: 317-324.

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We aimed to validate the Medication Adherence Report Scale-5 (MARS-5) as a tool for assessing medication adherence in inflammatory bowel disease (IBD), and determine predictors of medication adherence.  One-hundred and twelve (n=112) adults with confirmed IBD, participating in the longitudinal Manitoba Living with IBD Study were eligible. Demographics, IBD type, surgeries, disease activity (using Inflammatory Bowel Disease Symptom Inventory and fecal calprotectin levels), perceived stress and medication use were collected biweekly through online surveys. MARS-5 scores were obtained at baseline and at 1 year. Correlation between medication monitoring data and MARS-5 scores was performed and the optimal MAR-5 cut-off point for adherence assessment determined. Predictors of medication adherence were assessed at both ≥90% and ≥80%.  Participants were predominantly female (71.4%); mean age was 42.9 years (SD 12.8), and the majority (67.9%) had Crohn’s disease.  Almost half (46.4%) were taking more than one IBD medication, with thiopurines (41.9%) and biologics (36.6%) the most common. Only 17.9% (n=20) were non-adherent at <90% level; of those, 90% (n=18) were using oral medications.  The MARS-5 was significantly associated with adherence based on medication monitoring data at baseline (r=0.48) and week 52 (r=0.57). Sensitivity and specificity for adherence ≥80% and ≥90% was maximized at MARS-5 scores of  greater than 22 and greater than 23, respectively. Having Crohn’s disease (Odds ratio 4.62; 95% CI 1.36-15.7) was the only significant predictor of adherence.

 

We concluded that MARS-5 is a useful measure to evaluate adherence in an IBD population. In this highly adherent sample, disease type (Crohn’s disease) was the only predictor of medication adherence.

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Witges K, Targownik LE, Haviva C, Walker JR, Graff LA, Sexton K, Lix L, Sargent M, Vagianos K, Bernstein CN. Living With Inflammatory Bowel disease: Protocol for a longitudinal study of factors associated with symptom exacerbations. Journal of Medical Internet Research Research Protocols 2018 (Nov 12); 7(11):e11317.

 

There has been limited longitudinal research that has comprehensively evaluated possible factors in the exacerbation of inflammatory bowel disease  symptoms with or without associated inflammation. Evolving Web-based technologies facilitate frequent monitoring of patients' experiences and allow a fine-grained assessment of disease course. We aimed to prospectively identify factors associated with symptom exacerbation and inflammation in IBD including psychological functioning, diet, health behaviors, and medication adherence. Between June 2015 and May 2017, we enrolled adults with IBD, recruited from multiple sources, who had been symptomatically active at least once within the prior 2 years. They completed a Web-based survey every 2 weeks for 1 year and submitted a stool sample at baseline, 26 weeks, and 52 weeks. Any participant reporting a symptom exacerbation was matched to a control within the cohort, based on disease type, sex, age, and time of enrollment; both were sent a supplemental survey and stool collection kit. Biweekly surveys included validated measures of the disease course, psychological functioning, health comorbidities, and medication use. Intestinal inflammation was identified through fecal calprotectin (positive level >250 μg/g stool). There were 155 participants enrolled with confirmed IBD, 66.5% (103/155) with Crohn’s disease and 33.5% (52/155) with ulcerative colitis, of whom 98.7% (153/155) completed the study. Over the 1-year period, 47.7% (74/155) participants experienced a symptom exacerbation. The results of analyses on risk factors for symptom exacerbations are pending. We recruited and retained a longitudinal IBD cohort that will allow the determination of risk factors for symptom exacerbation with and without inflammation. This will increase understanding of symptom exacerbations among persons with IBD.

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