Impact of Rome IV irritable bowel syndrome on work and activities of daily living

Summary Background Few studies have demonstrated the impact of irritable bowel syndrome (IBS) on work and activities of daily living. Methods We collected demographic, gastrointestinal symptom, psychological health and quality of life data from 752 adults with Rome IV‐defined IBS. We used the work productivity and activity impairment questionnaire for irritable bowel syndrome and the work and social adjustment scale to examine the degree of both impairment at work and in activities of daily living, as well as factors associated with these. Results Of 467 individuals who were employed, 133 (28.5%) reported absenteeism, 373 (85.6%) presenteeism and 382 (81.8%) overall work impairment. A mean of 1.97 hours of work per week was lost due to IBS. Extrapolating this across the entire UK, we estimate that between 72 and 188 million hours of work are lost per year due to IBS in individuals of working age. Among all 752 participants, 684 (91.0%) reported any activity impairment with 220 (29.3%) reporting impairment in home management, 423 (56.3%) in social leisure activities, 207 (27.5%) in private leisure activities, and 203 (27.0%) in maintaining close relationships. Severe IBS, higher levels of anxiety, depression, somatization and gastrointestinal symptom‐specific anxiety, and lower levels of IBS‐related quality of life were associated with impairment in both work and activities of daily living. Conclusion Patients with IBS experience a substantial impact on their work and activities of daily living because of their IBS. Future studies should assess the impact of medical interventions on the ability to work and participate in social activities.


| INTRODUC TI ON
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction (DGBI), characterised by recurrent abdominal pain associated with a change in stool form or frequency. It affects between 5% and 10% of people worldwide. 1 Because the pathophysiology of IBS is complex and incompletely understood, there is no identifiable biomarker to help make a diagnosis of IBS. 2 Instead, in the absence of red flags, the diagnosis is reached via symptom-based criteria proposed by the Rome Foundation, with the latest iteration being the Rome IV criteria, 3 and limited investigations. 4,5 Patients with IBS, therefore, form a heterogeneous group of individuals with a similar phenotype of abdominal pain and change in bowel habit but are likely to have different underlying causes for their symptoms. Without an identifiable target for therapy, treatment strategies focus on alleviating predominant symptom(s), and drug efficacy in randomised controlled trials is, therefore, modest. [6][7][8][9][10] For most patients, IBS is chronic, with a relapsing and remitting course. 11 Quality of life of people with IBS is affected to the same degree as those with organic gastrointestinal diseases, such as Crohn's disease. 12 Direct healthcare costs of IBS are substantial, estimated at between £1.3 and £2 billion per year in a recent UK study, 13 but the full economic consequences are likely to be even higher due to the effect of IBS on the ability to work. In qualitative studies examining the impact of IBS on work and activities of daily living patients with IBS state that their symptoms leave them fearful, embarrassed or ashamed. [14][15][16][17] The unpredictability of symptoms leads to loss of freedom or spontaneity. 14 Individuals also report feeling embarrassed using toilets at work or in public, or having to pass flatus, due to their IBS symptoms. 15 Other themes include fear of symptoms of urgency or faecal incontinence and the fact that bowel symptoms make it difficult to have physical relationships. 15 Finally, patients report stigma associated with a "functional" disease and the lack of a structural cause for their symptoms makes it difficult for colleagues, friends or family to understand. 14 To gain control of various work and personal situations, patients often make adjustments some of which, such as activity avoidance, are maladaptive in nature. [15][16][17] Although qualitative studies facilitate understanding of themes underlying impairment at work or in activities of daily living, they lack the ability to determine the proportion of individuals affected by their IBS symptoms and to identify predictors of work and activity impairment.
A previous cross-sectional study in secondary care demonstrated that one-quarter of participants with Rome III IBS reported absenteeism, more than 80% presenteeism and that work impairment was associated with severity of IBS, quality of life and gastrointestinal symptom-specific anxiety. 18 Two previous studies have attempted to quantify the impact of IBS on activities of daily living but they were either small, containing only 42 patients, 19 or recruited individuals with Rome III IBS. 20 The impact of IBS, defined according to the Rome IV criteria, on work and activity impairment among a wider population of individuals with IBS is, therefore, unknown. We examined these issues in a cross-sectional study recruiting a large cohort of people with IBS.

| Participants and setting
We recruited individuals registered with ContactME-IBS, a national UK registry of 4280 members with IBS who are interested in volunteering for research. 21 We have reported data from this cohort previously. 22 Briefly, individuals find out about the registry via numerous sources including their general practitioner (GP), specialist hospital clinics, posters in pharmacies or social media. Individuals enrol by completing a short questionnaire about their bowel symptoms and providing contact details. The registry is run by County Durham and Darlington NHS Foundation Trust. Among all registrants, 2268 (53%) have seen their GP with IBS, and another 1455 (34%) a gastroenterologist. There were no exclusion criteria apart from the inability to understand written English. We contacted all registered individuals, via electronic mailshot, in July 2021, directing them to a website where they could access study information. Those willing to participate completed an online questionnaire, with responses stored in an online database. Nonresponders received a reminder email in August 2021. Participants were given a chance to win one of three gift cards (worth £200, £100 or £50). The University of Leeds research ethics committee approved the study in March 2021 (MREC 20-051).

| Demographic and symptom data
We collected basic demographic data, including age, gender, lifestyle (tobacco and alcohol consumption), ethnicity, marital status, educational level and annual income. We also asked respondents to state whether their IBS symptoms commenced after an acute enteric infection. We defined the presence of IBS according to the Rome IV questionnaire, 23 assigning this to all individuals according to the scoring algorithm proposed for its use. 3 We categorised the IBS subtype according to the criteria recommended in the questionnaire, using the proportion of time stools were abnormal according to the Bristol stool form scale. We asked all participants to select their most troublesome symptom from a list of five possibilities, including abdominal pain, constipation, diarrhoea, bloating/distension or urgency.

| IBS symptom severity and impact
We assessed the severity of symptoms using the IBS severity scoring system (IBS-SSS), 24

| Gastrointestinal symptom-specific anxiety
We used the visceral sensitivity index (VSI), 28 which measures gastrointestinal symptom-specific anxiety. Replies to each of the 15 items are provided on a 6-point scale from "strongly disagree" (score 0) to "strongly agree" (score 5). We divided these data into equally sized tertiles, as there are no validated cut offs to define low, medium or high levels of gastrointestinal symptom-specific anxiety.

| IBS-related quality of life
We used the irritable bowel syndrome quality of life (IBS-QOL), a validated IBS-specific questionnaire, to measure health-related quality of life in individuals with IBS. 29,30 The IBS-QOL consists of 34 items, each ranked on a 5-point Likert scale ranging from 0 to 4, with a total possible score of 0-136 and lower scores indicating better quality of life.
The 34 items are based on the following eight variables: dysphoria, interference with activity, body image, health worry, food avoidance, social reactions, sexual activity and relationships. Score were transformed to a 0-to 100-point scale with zero indicating the worst quality of life and 100 indicating the best quality of life. We divided these data into equally sized tertiles, as there are no validated cut offs to define low, medium or high levels of quality of life.

| Impact of IBS on work and activities of daily living
We used the work productivity and activity impairment questionnaire for irritable bowel syndrome (WPAI:IBS), 31 which is validated to assess the level of work productivity loss in people with IBS who are employed, as well as impairment in activities of daily living. There are four domains: absenteeism (percentage of work hours missed because of IBS); presenteeism (percentage of impairment experienced whilst working because of IBS); overall work impairment (percentage of work productivity loss); and activity impairment (percentage impairment in activities of daily living). We also used the work and social adjustment scale (WSAS), 32 which has been used to measure the impact of IBS on individuals' ability to work, manage at home, engage in social and private leisure activities, and maintain close relationships. [33][34][35][36] The five domains are scored on a 9-point scale from "not at all" (score 0), through "definitely" (score 4), to "very severely" (score 8).

| Statistical analysis
We included only participants who met Rome IV criteria for IBS in the analysis. We dichotomised the presence (≥1%) or absence (0%) of absenteeism, presenteeism, overall work impairment or activity impairment and presence (score ≥4 ["definitely" impacting]) or absence (score <4) of an impact of IBS on home management activities, social leisure activities, private leisure activities or maintaining close relationships. We examined the characteristics of participants in each of these groups. We compared categorical variables using a χ 2 test and continuous data using an independent samples t-test, with statistical significance defined as a p value <0.01. We performed logistic regression, controlling for all baseline demographic data (including annual income), IBS subtype, duration, severity and impact of IBS symptoms, most troublesome symptom, presence of meal-related symptoms, presence of continuous abdominal pain, opiate use, number of IBS-related drugs in the last 12 months, mood and somatic symptom reporting, gastrointestinal symptom-specific anxiety and IBS-related quality of life to examine factors associated with absenteeism, presenteeism, overall work impairment or activity impairment, as well as impairment of home management activities, social leisure activities, private leisure activities or maintaining close relationships. We reported results with odds ratios (ORs) with 95% confidence intervals (CIs).
We used a contemporaneous prevalence of Rome IV IBS in the UK of 4.6%, derived from the Rome Foundation three-nation prevalence study, 37 to extrapolate the total number of hours of work lost because of IBS per person from this study across the entire UK adult working population (aged 18-64), using published census data, [38][39][40] and the assumption that individuals worked an average of 46 weeks per year. In the current study, most participants had consulted with a doctor, which may skew the results. We, therefore, contacted the authors of the three-nation Rome Foundation study to obtain the prevalence of individuals with Rome IV IBS consulting a doctor for IBS in the UK, which was 2.8% (data on file, personal communication: Dr Olafur Palsson, University of North Carolina, Chapel Hill, NC, USA).
We used these data to perform a more conservative sensitivity analysis of the number of hours of work lost because of IBS. We used SPSS for Windows (version 27.0 SPSS, Chicago, IL) to perform all analyses.

| Characteristics of patients with impairment at work and in activities of daily living because of IBS
We examined the characteristics of 133 (28.5%) individuals who reported any absenteeism, 373 (85.6%) any presenteeism, 382 (81.8%) any overall work impairment, and 684 (91.0%) any activity impairment compared with those who did not ( Figure 1). Participants with any absenteeism were significantly less likely to be married (          We recruited individuals who self-identified as having IBS and also met the Rome IV criteria. They are, therefore, likely to represent individuals with IBS in the UK because some had never seen a doctor for their IBS, some had seen a primary care physician, and some had seen a gastroenterologist. Our sample also included participants from different age groups, levels of education and income brackets,

| D ISCUSS I ON
suggesting that individuals at different career stages have been included in our study. We used validated questionnaires, including the WPAI:IBS, which has been validated for its use in patients with IBS, 31 and has been used widely. 18,[41][42][43] We obtained near-complete data for variables of interest because we used mandatory fields in our online questionnaire.
Although we used a national UK registry to obtain a sample of individuals with IBS, we were unable to check participants' medical records to rule out other organic gastrointestinal diseases that present with similar symptoms such as celiac disease or inflammatory bowel disease, 44,45 nor did we ask them if they had these conditions. Instead, we assumed that, as they were registered with an IBS research registry, they genuinely had IBS. Given that IBS is more prevalent than these conditions, UK national guidance recommends these conditions are ruled out prior to a diagnosis of IBS, 46,47 and almost 90% of the ContactME-IBS registrants have seen a GP or a gastroenterologist for IBS, we believe this is a reasonable assumption. All involved individuals were UK residents, 97% were White, 87% were female and most had IBS-D or IBS-M.
The results, therefore, are not applicable to individuals outside the UK or from other ethnic groups and may be less relevant to men and those with IBS-C. Using an online questionnaire meant we were unable to assess the number and characteristics of individuals who accessed the questionnaire but chose not to complete it.
Although the WSAS is a validated questionnaire, has been widely used in studies in IBS, and is sensitive to change in IBS treatment   49 We have demonstrated that a large proportion of individuals with IBS experience impairment in their personal and professional lives because of their disorder. Although this was a cross-sectional study, our use of the WPAI:IBS, which has been validated for use in IBS, allowed us to establish that the impairment to work and activities of daily living seen are likely to be a direct consequence of IBS.
It is, perhaps, not surprising that those with more severe symptoms and lower IBS-related quality of life report the greatest impact on work and activities of daily living. Our findings related to the association of psychological comorbidities with work and activity impairment are interesting. Although these psychological comorbidities may themselves impact on work and activities of daily living, our participants attributed their impairment to IBS symptoms, not to these psychological comorbidities. However, psychological comorbidity is also associated with a worse prognosis in IBS, 50  to be an independent predictor of presenteeism and overall work impairment. This is, perhaps, not surprising given that abdominal pain severity appears to drive healthcare-seeking behaviour. 56,57 Finally, the results of studies such as ours can be used to inform cost-effectiveness analyses, 58,59 to facilitate value-based care in IBS.
In summary, our results show that approximately 10% of individuals are unemployed partly as a result of their condition. Among those who are employed, almost one-in-three individuals with IBS report absenteeism, and over 80% presenteeism and overall work impairment because of their IBS. We estimate that, in the UK, between 72 and 188 million hours of work are lost per year due to the condition. More than 90% of participants reported that IBS symptoms interfered with their activities of daily living, with over 50% reporting interference with social leisure activities and over 25% reporting interference with home management, private leisure ac-

ACK N OWLED G EM ENTS
We are grateful to the patients who gave their time freely to answer our questionnaire. We thank Dr Olafur Palsson for answering our queries about his study. writing -review and editing (equal).

AUTH O R S H I P
Guarantor of the article: Alexander C. Ford.