Scoping review on health-related physical fitness in patients with inflammatory bowel disease: Assessment, interventions, and future directions.

BACKGROUND: Reaching the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II (STRIDE-II) therapeutic targets for inflammatory bowel disease (IBD) requires an interdisciplinary approach. Lifestyle interventions focusing on enhancing and preserving health-related physical fitness (HRPF) may aid in improving subjective health, decreasing disability, or even controlling inflammation. However, ambiguity remains about the status and impact of HRPF (i.e. body composition, cardiorespiratory fitness, muscular strength, muscular endurance, and flexibility) in IBD patients, hindering the development of physical activity and physical exercise training guidelines. AIM: To review HRPF components in IBD patients and the impact of physical activity and physical exercise training interventions on HRPF. METHODS: A systematic search in multiple databases was conducted for original studies that included patients with IBD, assessed one or more HRPF components, and/or evaluated physical activity or physical exercise training interventions. RESULTS: Sixty-eight articles were included. No study examined the complete concept of HRPF, and considerable heterogeneity existed in assessment methods, with frequent use of non-validated tests. According to studies that used gold standard tests, cardiorespiratory fitness seemed to be reduced, but findings on muscular strength and endurance were inconsistent. A limited number of studies that evaluated physical activity or physical exercise training interventions reported effects on HRPF, overall showing a positive impact. CONCLUSION: We performed a scoping review using a systematic and iterative approach to identify and synthesize an emerging body of literature on health-related physical fitness in patients with IBD, highlighting several research gaps and opportunities for future research. Findings of this review revealed a gap in the literature regarding the accurate assessment of HRPF in patients with IBD and highlighted important methodological limitations of studies that evaluated physical activity or physical exercise training interventions. This scoping review is a step towards performing studies and systematic reviews in the future, which was not possible at present given the heterogeneity in endpoints and designs of the available studies on this topic. Future well-designed studies are required to determine the optimal training paradigm for improving HRPF in patients with IBD before guidelines can be developed and integrated into the therapeutic strategy.

The Socioeconomic Impact of Irritable Bowel Syndrome: An Analysis of Direct and Indirect Health Care Costs.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with substantial costs to society. Extensive data on direct costs (health care consumption) and indirect costs (health-related productivity loss) are lacking. Hence, we examined the socioeconomic costs of IBS and assessed which patient characteristics are associated with higher costs. METHODS: Cross-sectional data from 3 Rome-defined Dutch IBS patient cohorts (n = 419) were collected. Bootstrapped mean direct and indirect costs were evaluated per patient with IBS using validated questionnaires (ie, medical cost questionnaire and productivity cost questionnaire, respectively). Multivariable regression analyses were performed to identify variables associated with higher costs. RESULTS: Quarterly mean total costs per patient were €2.156 (95% confidence interval (CI), €1793-€2541 [$2444]), consisting of €802 (95% CI, €625-€1010 [$909]) direct costs and €1.354 (95% CI, €1072-€1670 [$1535]) indirect costs. Direct costs consisted primarily of health care professional consultations, with costs related to gastrointestinal clinic visits accounting for 6% and costs related to mental health care visits for 20%. Higher direct costs were significantly associated with older age (P = .007), unemployment (P = .001), IBS subtypes other than constipation (P = .033), lower disease-specific quality of life (P = .027), and more severe depressive symptoms (P = .001). Indirect costs consisted of absenteeism (45%), presenteeism (42%), and productivity loss related to unpaid labor (13%) and were significantly associated with the male sex (P = .014) and more severe depressive symptoms (P = .047). CONCLUSIONS: Productivity loss is the main contributor to the socioeconomic burden of IBS. Direct costs were not predominantly related to gastrointestinal care, but rather to mental health care. Awareness of the nature of costs and contributing patient factors should lead to significant socioeconomic benefits for society.

Development and Validation of a Remote Monitoring Tool for Assessment of Mild, Moderate, and Severe Infections in Inflammatory Bowel Disease.

BACKGROUND: Immunomodulators and biologics are cornerstones in the management of inflammatory bowel disease [IBD], but are associated with increased risk of infections. Post-marketing surveillance registries are pivotal to assess this risk, yet mainly focus on severe infections. Data on the prevalence of mild and moderate infections are scarce. We developed and validated a remote monitoring tool for real-world assessment of infections in IBD patients. METHODS: A 7-item Patient-Reported Infections Questionnaire [PRIQ] covering 15 infection categories was developed with a 3-month recall period. Infection severity was defined as mild [self-limiting or topical treatment], moderate [oral antibiotics, antivirals, or antifungals], or severe [hospitalisation or intravenous treatment]. Comprehensiveness and comprehensibility were ascertained through cognitive interviewing of 36 IBD outpatients. After implementation in the telemedicine platform myIBDcoach, a prospective, multicentre cohort study was performed between June 2020 and June 2021 in 584 patients, to assess diagnostic accuracy. Events were cross-checked with general practitioner and pharmacy data [gold standard]. Agreement was evaluated using linear-weighted kappa with cluster-bootstrapping to account for within-patient level correlation. RESULTS: Patient understanding was good and interviews did not result in reduction of PRIQ items. During validation, 584 IBD patients {57.8% female, mean age 48.6 (standard deviaton [SD]: 14.8), disease duration 12.6 years [SD: 10.9]} completed 1386 periodic assessments, reporting 1626 events. Linear-weighted kappa for agreement between PRIQ and gold standard was 0.92 (95% confidence interval [CI] 0.89-0.94). Sensitivity and specificity for infection [yes/no] were 93.9% [95% CI 91.8-96.0] and 98.5% [95% CI 97.5-99.4], respectively. CONCLUSIONS: The PRIQ is a valid and accurate remote monitoring tool to assess infections in IBD patients, providing means to personalise medicine based on adequate benefit-risk assessments.

A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent, chronic gastrointestinal disorder that imposes a substantial socioeconomic burden. Peppermint oil is a frequently used treatment for IBS, but evidence about cost-effectiveness is lacking. OBJECTIVE: We aimed to assess cost-effectiveness of small-intestinal release peppermint oil versus placebo in IBS patients. METHODS: In a multicenter randomized placebo-controlled trial, cost-effectiveness was evaluated from a societal perspective. The incremental cost-effectiveness ratios (ICERs) were expressed as (1) incremental costs per Quality Adjusted Life Years (QALY), and (2) incremental costs per successfully treated patient, that is per abdominal pain responder (according to FDA definitions), both after an eight-week treatment period with placebo versus peppermint oil. Cost-utility and uncertainty were estimated using non-parametric bootstrapping. Sensitivity analyses were performed. RESULTS: The analysis comprised 126 patients (N = 64 placebo, N = 62 small-intestinal release peppermint oil). Peppermint oil was a dominant treatment compared to placebo in 46% of bootstrap replications. Peppermint oil was also more effective but at higher cost in 31% of replications. The net-benefit acceptability curve showed that peppermint oil has a 56% probability of being cost-effective at a conservative willingness-to-pay threshold of €10.000/QALY. Peppermint oil was also a dominant treatment per additional successfully treated patient according to FDA definitions, that is in 51% of replications. In this case, the acceptability curve showed an 89% probability of being cost-effective. CONCLUSIONS: In patients with IBS, small-intestinal release peppermint oil appears to be a cost-effective treatment although there is uncertainty surrounding the ICER. When using abdominal pain responder as outcome measure for the ICER, peppermint oil has a high probability of being cost-effective. The use of peppermint oil, which is a low-cost treatment, can be justified by the modest QALY gains and slightly higher proportion of abdominal pain responders. More research and long-term data are necessary to confirm the cost-effectiveness of peppermint oil. NCT02716285.

Correction: Smart Data Collection for the Assessment of Treatment Effects in Irritable Bowel Syndrome: Observational Study.

[This corrects the article DOI: 10.2196/19696.].

Smart Data Collection for the Assessment of Treatment Effects in Irritable Bowel Syndrome: Observational Study.

BACKGROUND: End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response. OBJECTIVE: Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients' adherence to diary use and characteristics associated with adherence. METHODS: A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed. RESULTS: Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P<.001). No significant association was found between adherence and gender (P=.84), age (P=.22), or education level (lower education level: P=.58, middle education level: P=.46, versus high education level), while higher anxiety scores were associated with lower adherence (P=.03). Adherence to the online questionnaires was also high (>99%). Missing data due to technical issues were limited. CONCLUSIONS: The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.

Cost-effectiveness of Telemedicine-directed Specialized vs Standard Care for Patients With Inflammatory Bowel Diseases in a Randomized Trial.

BACKGROUND & AIMS: Telemedicine can be used to monitor determinants and outcomes of patients with chronic diseases, possibly increasing the quality and value of care. Telemedicine was found to reduce outpatient visits and hospital admissions for patients with inflammatory bowel diseases (IBD). We performed a full economic evaluation of telemedicine interventions in patients with IBD, comparing the cost-utility of telemedicine vs standard care. METHODS: We performed a randomized trial of 909 patients with IBD at 2 academic and 2 non-academic hospitals in The Netherlands. Patients were randomly assigned to groups that received telemedicine (myIBDcoach; n = 465) or standard outpatient care (n = 444) and followed for 12 months. Costs were measured from a societal perspective. Direct healthcare costs were based on actual resource use. Indirect costs comprised self-reported hours sick leave from work, intervention costs (annual license fee of €40 per patient [$45]), and utility costs (assessed using EQ5D). Cost-utility and uncertainty were estimated using the non-parametric bootstrapping method. RESULTS: Telemedicine resulted in lower mean annual costs of €547/patient [$612] (95% CI, €1029-2143 [$1150-2393]; mean costs of €9481 [$10,587] for standard care and €8924 [$9965] for telemedicine) without changing quality adjusted life years. At the Dutch threshold of €80,000 [$89,335] per quality adjusted life year, the intervention had increased incremental cost-effectiveness over standard care in 83% of replications and an incremental net monetary benefit of €707/patient [$790] (95% CI, €1241-2544 [$1386-2841]). CONCLUSIONS: Telemedicine with myIBDcoach is cost saving and has a high probability of being cost effective for patients with IBD. This self-management tool enables continuous registration of quality indicators and (patient-reported) outcomes and might help reorganize IBD care toward value-based healthcare. ClinicalTrials.gov no: NCT02173002.

Use of Rome criteria for the diagnosis of irritable bowel syndrome in primary care: a survey among European countries.

BACKGROUND AND OBJECTIVES: The majority of patients with irritable bowel syndrome (IBS) are diagnosed and treated in primary care. The aim of this study was to investigate the implementation of the Rome criteria in daily primary care clinical practice and adherence of general practitioners (GPs) to recommended diagnostic approaches for IBS. PATIENTS AND METHODS: A survey consisting of 18 questions was distributed across 11 European countries and was used to assess GPs' diagnostic approach of IBS, the use of Rome criteria in daily practice and GPs' perspective on the aetiology of the disorder. RESULTS: Overall, 185 GPs completed the survey. In daily clinical practice, 32% of GPs reported that they usually make a positive diagnosis on the basis of symptoms only, whereas 36% of GPs reported regular use of the Rome criteria to diagnose IBS. Furthermore, 62% of the responders reported that they applied additional diagnostics, such as blood tests, 31% found it necessary to perform endoscopy to make a positive diagnosis of IBS and 29% referred patients with IBS to a specialist. Psychological factors were the most frequently selected potential aetiological factor of IBS (88% of GPs). Overall, 52% of GPs reported systematically including questions on psychological symptoms in the assessment of history of IBS. CONCLUSION: Only about one-third of GPs regularly used the Rome criteria to diagnose IBS. In daily primary care practice, IBS largely remains a diagnosis of exclusion. This has implications in terms of GPs' specialty training and questions the applicability of IBS guidelines in daily care, which advocate an early, positive, symptom-based diagnosis.

Pancreatitis-associated protein has no additional value as a marker of disease activity in a real-life cohort of IBD patients.

BACKGROUND AND AIM: Monitoring of mucosal inflammation in inflammatory bowel disease (IBD) is of major importance. New noninvasive markers for intestinal inflammation are needed. Previous studies have reported that pancreatitis-associated protein (PAP) correlates with clinical activity in IBD subgroups. Our aim was to investigate the correlation of serum and fecal PAP with clinical and biochemical parameters of disease activity in a real-life IBD cohort. PATIENTS AND METHODS: Two hundred and five consecutive IBD patients were enrolled. Clinical disease activity was scored by the Harvey-Bradshaw Index or the Simple Clinical Colitis Activity Index; also, C-reactive protein (CRP), erythrocyte sedimentation rate, and fecal calprotectin were determined. As surrogate for endoscopy, a combination score of clinical indices with CRP or calprotectin was used to define active disease. Fecal and serum PAP were measured by ELISA. RESULTS: The median serum and fecal PAP did not differ in Crohn's disease (CD) or ulcerative colitis (UC) patients with active compared with inactive disease according to clinical activity indices. Defining active disease by a combination score of Harvey-Bradshaw Index of more than 4 and CRP of more than 5 mg/l or calprotectin more than 250 µg/g, serum PAP (P=0.01), but not fecal PAP (P=0.32), was significantly higher in active than inactive CD patients. Area under the curve of the corresponding receiver operating curve (ROC) was 0.64. No differences were found in serum or fecal PAP levels using the combination score for active disease in UC. CONCLUSION: Serum but not fecal PAP was higher in active compared with nonactive CD and may reflect mucosal inflammation in CD, but not in UC. However, the accuracy of serum PAP for the diagnosis of active disease was poor, and therefore, serum PAP does not seem to have additional value compared with the current noninvasive markers.