https://orcid.org/0009-0006-5705-8096
Figures
Abstract
Background
Inflammatory bowel diseases (IBD) pose a considerable burden on patients and society. Rehabilitation programs are increasingly being considered as a complementary treatment. However, empirical evidence on the effectiveness of this approach is still sparse. We therefore investigated changes in patient-reported outcomes and an objective biomarker throughout a three-week inpatient gastrointestinal rehabilitation.
Methods
We conducted a longitudinal prospective observational study with a pretest-posttest design. Patients completed questionnaires on their subjective health-related quality of life (HRQoL), psychological distress, disease-specific burden, and work ability. Stool samples were collected to determine fecal calprotectin levels. Mean level changes were analyzed by means of t tests for repeated measurements, while differential changes between Crohn’s disease and ulcerative colitis patients were compared using analysis of variance.
Results
Subjective disease burden and psychological distress decreased over the course of rehabilitation, whereas HRQoL and work ability increased. Fecal calprotectin levels slightly rose and were not meaningfully related to changes in subjective perception of illness.
Conclusions
We present evidence on rehabilitation as an important treatment in people with IBD in terms of subjective disease burden and various indicators of personal well-being. Furthermore, we advise against the use of fecal calprotectin as a marker for monitoring disease activity in short-term rehabilitation settings.
Citation: Kuzdas-Sallaberger M, Steininger B, Stöhr D, Mustak-Blagusz M, Mauel C (2025) Changes in patient-reported outcomes (PROs) and fecal calprotectin levels in patients with inflammatory bowel disease following a three-week gastrointestinal inpatient rehabilitation. PLoS One 20(8): e0330922. https://doi.org/10.1371/journal.pone.0330922
Editor: Sophia Eugenia Martínez-Vázquez, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, MEXICO
Received: April 28, 2025; Accepted: August 7, 2025; Published: August 29, 2025
Copyright: © 2025 Kuzdas-Sallaberger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: 'The data of this study contains confidential patient information and thus cannot be disseminated. Ethical restrictions have been imposed by the data protection officials of the Pensionsversicherung, who may be contacted for data access. Inquiries should be directed to: Datenschutzbeauftragter, Friedrich-Hillegeist-Straße 1, 1020 Wien; dsb@pv.at.
Funding: The author(s) received no specific funding for this work.
Competing interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: All authors of this study are currently employed by the Pensionsversicherung, Austria.
Introduction
Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory conditions. The most common forms of IBD are Crohn’s disease (CD) and ulcerative colitis (UC), which are characterised by alternating phases of remission and relapse [1,2]. Much of the aetiology of these diseases remains unclear, but appears to be multifactorial and influenced by the individual’s immune system, genetic predisposition, and environmental factors [1,3]. The patient’s prognosis is unstable, with frequent changes between high disease activity and relative health [4]. The most common symptoms include diarrhoea, abdominal pain, frequent bowel movements, rapid fatigue, or weakness [5,6]. These symptoms are often accompanied by psychosocial problems that affect patients’ quality of life (QoL) and severely restrict their ability to participate in social and occupational activities [6].
In Europe, about 0.3% of the population is affected by IBD, which may appear somewhat low, yet is of considerable rehabilitative and socio-medical importance, as it poses a considerable burden on patients (i.e., a “disease burden”), as well as on healthcare systems and society at large (i.e., a “economic burden”) [7]. Although the conditions are chronic, no definitive cure is currently available and medications only target symptom relief, patients often seek supportive, complementary therapies. Therefore, rehabilitation programs for patients with IBD are increasingly being considered [1,6]. This approach seems promising, as non-pharmacological therapies (i.e., diet, exercise, and psychological treatments) have a positive impact on QoL, inflammation, and mental health in patients with IBD, especially when embedded in a holistic program, as opposed to single interventions [8].
Rehabilitation measures based on the bio-psychosocial model of the International Classification of Functioning, Disability and Health (ICF) take a holistic approach to support the restoration of patients’ participation in social and occupational activities. Rehabilitation programs for individuals with IBD that combine physical therapy, structured exercise therapy, nutritional counselling, and mental health support could optimize medical outcomes, patients’ psychophysical functioning, work capacity, and health-related quality of life (HRQoL) [9]. Indeed, inpatient rehabilitation for patients with IBD has been shown to have positive effects on social participation, disease activity, HRQoL, and self-management, compared to standard care [10]. Further evidence on rehabilitation in patients with IBD and its effectiveness is still sparse [9].
In Austria, individuals have the opportunity of applying for rehabilitation following medical treatment with the aim of either maintaining the success of the treatment or alleviating the consequences of the disease. Typically, the duration of these rehabilitation programs is three weeks, and they are conducted in either inpatient or outpatient rehabilitation centres. Individuals diagnosed with IBD, due to the chronic nature of the condition, are eligible to make regular applications for rehabilitation procedures.
Given the comprehensive scope of rehabilitation measures, it is essential to assess various outcomes throughout a rehabilitation program. Biomarkers, such as fecal calprotectin, are used to measure changes in disease progression objectively. Fecal calprotectin appears to be a suitable biomarker for monitoring inflammation in IBD patients [11]. It is a calcium-binding protein, primarily derived from neutrophils, plays a regulatory role in inflammatory processes, and has shown to be stable and resistant to bacterial degradation in feces [11]. Therefore, fecal calprotectin may potentially be a useful marker for tracking changes in disease activity during short-term settings, like rehabilitation, as well.
In addition to biomarkers, patient-reported outcomes (PROs) provide valuable insights into patients’ HRQoL, ability to work, and disease burden, providing a complementary subjective perspective. These aspects elude objective measurement, and it is, therefore, important to consider them in order to gain a comprehensive understanding of the patients’ progress [12].
Given the lack of evidence on the effectiveness of rehabilitative measures in reducing disease activity and burden, we aimed to assess changes in an objective biomarker (fecal calprotectin) and selected PROs over the course of a three-week inpatient gastrointestinal rehabilitation. We expected a reduction in calprotectin levels, subjective disease burden, and psychological distress over the course of treatment, as well as an increase in HRQoL and subjective work ability.
Materials and methods
Study design
The present study was conducted as a longitudinal prospective observational study with two measurement points. Prior to the collection of any data, we conducted an a-priori power analysis to derive an estimate of the required sample size. Taking into account a drop-out rate of 5% and an expected medium-sized effect, it was planned to include 200 patients (100 patients per IBD-type, i.e., CD and UC).
Patients with IBD who were admitted to the Austrian rehabilitation center in Bad Aussee for a three-week gastrointestinal rehabilitation were approached by a clinician and asked to participate in the study. Patients were given information about the study and following a consultation with a physician agreed to participate by signing a consent form. Participation was voluntary and could be withdrawn at any time during the study. All individuals aged 18 years or older with a diagnosis of either K50 (CD) or K51 (UC) according to the International Classification of Diseases (ICD) were considered eligible for inclusion. Premature termination of the rehabilitation stay resulted in exclusion from the study. Patient recruitment and data collection was conducted between August 2022 and July 2023.
Intervention
Patients underwent a three-week inpatient gastrointestinal multidisciplinary rehabilitation program at the rehabilitation center in Bad Aussee (Austria). This multidisciplinary program is a coordinated pool of treatments and therapeutic interventions to provide the best possible physical, mental and social condition for alleviating the disease burdens in patients with IBD. The goal of the rehabilitation program may be individual for each patient, but can be generalized as maintaining or regaining optimal functioning in his or her community through their own efforts and slowing or reversing disease progression through improved health behaviors. The fundamentals of the rehabilitation program entailed interdisciplinary and problem-orientated care within the framework of the bio-psychosocial model of the International Classification of Functioning, Disability and Health (ICF). Accordingly, multidisciplinary rehabilitation is a complex and comprehensive intervention, which includes exercise training, physical therapy, patient education, psychosocial management and behavioral modification programs to improve physical, psychosocial and emotional health [13]. In Austria, a specific amount of „therapy minutes“is allocated for each rehabilitation patient, with the objective of customizing an individualized program. Patients diagnosed with IBD have 2400 minutes of therapy and treatment at their disposal. The number and type of different therapy sessions are contingent upon the degree of each patient’s impairment, as determined by the ICF framework [14]. The 2400 minutes of therapy were distributed among active therapy, passive treatments and educational measures (detailed description in Table 1). Treatment and therapeutic interventions encompass both group-based sessions, such as group exercise training, and individualized therapies, including, e.g., one-on-one physical therapy.
Outcome measures
Fecal calprotectin.
Stool samples were collected from patients at the time of admission and at the time of discharge. Patients were provided with illustrated instructions to ensure that stool samples were collected correctly. Each test tube was filled on average with 5 g of stool and sent to the in-house laboratory on the same day. Calprotectin remains stable in stool at room temperature for three days and in the refrigerator for up to seven days. In the laboratory, samples were stored at 5°C in a refrigerator and analyzed within one to a maximum of two days. For each patient, one to two stool samples (upon admission and discharge) were tested using an EU-Fast Reader (Eurospital, Italy).
Firstly, 56 mg of stool were mixed with 2.8 ml of buffer (salinity and pH-controlled solution) in a high-speed homogenizer. The homogenate was then centrifuged at 3,000 revolutions per minute for 10 minutes using a Rotina 35 centrifuge (Hettich Zentrifugen, Germany), before the supernatant was collected. Lastly, calprotectin levels were measured using an immunoassay. The lower limit of detection of the analytical method was 50.00 μg/g, and all observations with a value below this threshold were fixed at 50.00 μg/g.
EuroQol 5 dimensions 5 level version (EQ-5D-5L).
The EuroQol 5 Dimensions 5 Level Version (EQ-5D-5L) is a self-report questionnaire designed to assess subjective HRQoL. This is subdivided into five dimensions using the questionnaire, each of which is covered by a single item: (1) mobility, (2) self-care, (3) usual activities, (4) pain/discomfort, and (5) anxiety/depression. These items are rated on a five-point scale, ranging from 1 (no problems) to 5 (extreme problems). Respondents’ answers to each item can then be used to construct a health profile. Calculating a score from this health profile is also possible based on country-specific weighting factors. As no value set exists for the Austrian population, we opted to use the German value set to calculate the EQ-5D-5L score, which ranges from −0.661 (extreme problems in all dimensions) to 1 (no problems in any dimension) [15]. In addition to the aforementioned items, the EQ-5D-5L includes a visual analog scale (VAS) on which respondents are asked to assess their subjective health state on a scale from 0 (“worst health you can imagine”) to 100 (“best health you can imagine”).
Work ability index (WAI).
The Work Ability Index (WAI) is a self-report questionnaire that provides a subjective assessment of work ability. The questionnaire can be divided into seven dimensions:
(1) current work ability compared to the best work ability ever achieved, (2) current work ability in relation to the physical and mental demands of the job, (3) current number of medically diagnosed diseases, (4) extent of work limitations due to illnesses/injuries, (5) sick leave days during the last 12 months, (6) self-assessment of work ability in the next 2 years, and (7) mental resources and well-being. The WAI score can range from 7 to 49 points, with higher values indicating higher work ability [16].
Patient health questionnaire-4 (PHQ-4).
The Patient Health Questionnaire 4 (PHQ-4) is an ultra-brief screening tool designed to assess psychological distress related to anxiety and depression [17]. The questionnaire comprises a total of four items that are self-reported on a four-point scale ranging from 0 (not at all) to 3 (nearly every day). Scores are calculated by summing the individual responses. The total score can range from 0 to 12, with higher values indicating greater psychological distress [18].
IBD disk.
The IBD Disk is a 10-item self-report tool used to assess patients’ disease burden related to abdominal pain, bowel control, interpersonal interactions, education and work, sleep, energy, emotions, body image, sexual function, and joint pain [19]. Each item is answered on an 11-point scale, ranging from 0 (absolutely disagree) to 10 (absolutely agree). The score is calculated by summing the individual items, the result ranging from 0 to 100. Higher values indicate greater subjective disease burden.
Statistical analyses
All statistical analyses were performed in SAS Viya V.03.05 (SAS Institute Inc.). Prior to conducting the analyses, a thorough examination was performed to determine whether all focal study variables met the requirement of normality and identify any potential outliers.
Immediate changes (admission vs. discharge) in fecal calprotectin levels, HRQoL, subjective work ability, mental impairment, and disease-specific burden in both CD and UC patients were examined separately using welch t-tests for paired samples, and Cohen’s d as the measure of effect size. The extent of differences in the immediate changes in the aforementioned parameters following rehabilitation were statistically compared between the two types of inflammatory bowel disease (CD vs. UC) using analysis of variance and by comparing the magnitude of raw and standardized mean changes. In this case, the bias-adjusted Hedges’ g was used as an indicator of effect size strength, as the group sizes were not identical.
We based our interpretation of findings predominantly on the strength of effect sizes and their precision rather than nominal null-hypothesis significance testing, as is strongly recommended in the current literature [20]. Nevertheless, results of null-hypothesis significance tests are reported throughout. In the case of multiple comparisons, Bonferroni-Holm adjusted p-values are reported. In terms of interpreting effect meaningfulness, we used the well-established classification of Cohen [21], with absolute values exceeding d and g = 0.20, 0.50, and 0.80, and r = 0.10, 0.30, and 0.50 indicating small, medium, and large effects, respectively.
In the case of missing data in individual outcomes, affected cases were excluded for these specific outcomes. The fact that premature termination of rehabilitation led to exclusion from the study meant that missing data relating to entire measurement points did not have to be addressed.
Ethical considerations
This study was approved by the ethics committee of the Medical University of Graz (1198–2022). The participation in the study requires a signed consent form and could be terminated at any time. Refusal to participate or premature withdrawal had no adverse effects on the medical care provided to the patients.
Results
Patient characteristics
In all, 226 patients were recruited at the beginning of their gastrointestinal rehabilitation. A total of 13 patients prematurely terminated their rehabilitation program, resulting in a total sample of 213 patients eligible for inclusion in the study. Table 2 shows demographic and clinical characteristics of the study population at baseline (i.e., at the time of admission).
Overall changes in fecal calprotectin and patient-reported outcome measures
Mean changes in focal study variables (admission vs. discharge) are reported in Table 3. The data were found to be approximately normal distributed. In order to verify the robustness of the analytical process, all analyzed parameters were also subjected to non-parametric testing (e.g., Wilcoxon signed-ranks test, etc.). The findings from the non-parametric tests exhibited congruence with those derived from the parametric tests (see S1 Table in the supporting information), thereby substantiating the validity of the latter. Consequently, the more powerful parametric tests were used for the final analysis.
Fecal calprotectin levels increased over the course of the rehabilitation stay, but not statistically significant. IBD-related disease burden only decreased by a small effect but only in UC (t (92) = −3.58, Padj =.008, d = − 0.32 [−0.50, −0.14]). In both groups psychological distress decreased by small effects between the time of admission and discharge, as indicated by lower PHQ-4 values, at the end of treatment. In the total sample, the most meaningful changes regarding IBD-related disease burden were observed in the energy (t(206) = −9.68, Padj < .001, d = −0.72 [−0.88, −0.56]), emotions (t(206) = −4.99, Padj < .001, d = −0.38 [−0.53, −0.22]), and joint pain subscales (t(206) = −2.76, Padj = .05, d = −0.17 [−0.30, −0.05]). In CD patients, non-trivial changes were related to the energy (t(113) = −7.08, Padj < .001, d = −0.70 [−0.91, −0.49]), emotions (t(113) = −3.27, Padj = .013, d = −0.32 [−0.52, −0.13]), and joint pain subscales (t(113) = −2.34, Padj = .17, d = −0.20 [−0.37, −0.03]). Somewhat deviating from this pattern, in UC patients, the biggest changes were observed in the energy (t(93) = −6.57, Padj = < .001, d = −0.74 [−0.98, −0.49]), emotions (t(93) = −3.79, Padj = .003, d = −0.44 [−0.68, −0.20]), and sexual functions subscales (t(93) = −3.17, Padj = .016, d = −0.27 [−0.44, −0.10]).
Subjective HRQoL increased during the rehabilitation stay, as indicated by increasing EQ-5D-5L scores, although the change was more pronounced in CD than in UC. Patients’ ratings of their subjective health state, as indicated by the VAS, increased by a medium-sized effect over the course of treatment in both groups. Subjective work ability increased during patients’ rehabilitation, albeit by small and trivial effects for CD and UC, respectively.
Differential changes in outcome measures between groups
Differential changes in outcome measures between groups over the course of rehabilitation are reported in Table 4. Differences in focal outcomes between groups were predominantly trivial, as reflected in their standardized mean differences (g range = 0.06 to 0.19), with the exception of a small difference in EQ-5D-5L scores. However, confidence intervals were broad throughout, indicating low precision, and none of the comparisons reached nominal statistical significance, as indicated by non-significant interaction terms (i.e., interaction of group and time) in the analysis of variance models. The change over time is similar in both groups.
Relationship between fecal calprotectin and patient-reported outcome measures
Calprotectin levels were not meaningfully related to any patient-reported outcome measures at the time of admission (r range −.03 to.02), with the exception of a small correlation with WAI scores (r = −.12, 95% CI [−.26,.03], P = .119). Calprotectin levels at discharge exhibited small negative correlations with the total PHQ (r = −.16, 95% CI [−.29, −.03], P = .019) and IBD-Disc scores (r = −.12, 95% CI [−.26,.02], P = .082), i.e., while calprotectin levels increased, psychological distress and patients’ disease burden decreased. All other associations were of trivial size (r = −.01 to.04 for EQ-5D-5L and WAI scores, respectively).
Discussion
Here, we present compelling new evidence about the role of rehabilitation measures in alleviating subjective disease burden and psychological distress, as well as in improving subjective HRQoL and work ability in patients with IBD. Furthermore, we demonstrate and discuss that fecal calprotectin, as an objective biological parameter, does not appear to be suitable as a monitoring parameter for assessing therapeutic success in this rehabilitation setting, and it does not meaningfully reflect subjective well-being.
Over the course of rehabilitation, the subjective overall disease burden, as measured by the IBD Disk score, decreased by a small effect for CD and UC patients alike. The biggest improvement was seen in energy levels, i.e., patients reported meaningfully reduced tiredness and felt more refreshed during the day at the time of discharge than at the time of admission. Previously, the introduction of regular physical activity has been associated with improvements in physical fatigue in CD patients [23]. Furthermore, psychological treatments have shown to be promising in reducing fatigue in patients with IBD [24]. Since these specific single interventions showed some promise in targeting IBD-related fatigue, it seems plausible that a multifaceted approach may have synergetic and beneficial effects. Our results – based on a multidisciplinary rehabilitation treatment – are in line with this assumption, and may position rehabilitation measures as an effective form of complementary treatment for subjective disease burden in IBD.
Patients also reported reduced symptoms of anxiety and depression, corresponding to lower PHQ-4 and Emotion-scores in the IBD Disk. Recent evidence suggests that behavioral therapies are not only beneficial in the treatment of depression and anxiety, but may also be effective in reducing IBD-related symptoms [25]. Furthermore, previous research suggested a meaningful reduction in PHQ-4 scores following inpatient medical rehabilitation in a German IBD sample [10]. Our results are consistent with these findings, yielding comparable effect size estimates for the reduction in depressive and anxiety symptoms over the course of treatment.
Subjective HRQoL improved significantly and meaningfully over the course of treatment, with small to medium-sized effects found in the EQ-5D-5L scores and the VAS, respectively. Comparing our results with a study on the role of medical rehabilitation in IBD patients from Germany [10], we found that while in both samples, treatment was followed by increased HRQoL (based on the VAS), the improvement in our sample even exceeded that of the comparative study. It should be noted, however, that the patients’ responses differed substantially between both measures. While subjective HRQoL, as measured by the EQ-5D-5L score, improved by a small effect (excerpting UC patients, where the change was trivial in size), it increased by a medium-sized effect in the VAS. This suggests that respondents’ global view of their health state was more affected by the rehabilitation program than the changes felt in specific domains of HRQoL.
Patients showed limited work capacity at the beginning of rehabilitation. Throughout treatment, an increase in subjective work ability was observed, albeit only to a small degree. It should be noted, however, that between measurements, patients were on sick leave due to the rehabilitation treatment and, therefore, may not have been able to gauge their own work ability in a sufficiently meaningful way. Accordingly, future research should employ follow-up measurements to allow patients to return to work and subsequently assess their work capacity more accurately.
Contrary to our expectations, fecal calprotectin increased slightly over the course of rehabilitation, in both UC and CD patients, but mean values remained relatively low throughout, being indicative of mild disease activity [26]. However, possible explanations for this noteworthy finding are manifold. First, the interval between our two measurement points (i.e., three weeks of inpatient rehabilitation) could have been too short to adequately show the possible effects of the intervention in fecal calprotectin levels, as opposed to the subjectively assessed PROs. With most drug therapies, the first signs of decreased fecal calprotectin levels appeared after eight weeks and later [27]. It could be possible that multimodal interventions – like rehabilitation – also have a delayed efficacy in affecting biological markers. Second, fecal calprotectin is characterized by substantial intra-individual variability [28,29]. Due to this variability, resampling of stool samples could be used to detect these intra-individual patterns. However, this approach seems unfeasible because of the relatively short period of inpatient care in most rehabilitation settings provided in Austria. Third, fecal calprotectin levels can be affected by a multitude of factors, such as non-steroidal anti-inflammatory drug intake [29], comorbidities (e.g., gastroenteritis, gastrointestinal malignancies, reflux disease, cystic fibrosis, and diverticulitis) [30], age [31] and dietary exposure [32].
We also assessed if – and to what extent – objective indicators of intestinal inflammation (i.e., fecal calprotectin) correspond to various subjective outcomes relating to HRQoL, psychological distress, subjective disease burden, and work ability in patients with IBD. Contrary to our expectations, we found that these aspects were virtually unrelated. Even more surprising, in cases of associations, these were counterintuitive. For example, upon discharge, we found that higher inflammatory activity was linked to reduced psychological distress. Similarly, increased calprotectin levels were associated with reduced subjective disease burden, as indicated by lower IBD Disk values. While these relationships could indeed be Type-I errors, they should be subject to further investigation to disentangle a potential area of future research from mere statistical artefacts. The lack of substantial correlations between subjective and objective markers of rehabilitation success and the various factors that – independently from rehabilitative measures – influence calprotectin levels, caution against using fecal calprotectin as such. This suggests that fecal calprotectin is not a suitable biomarker for monitoring disease activity in a short-term rehabilitation setting.
Limitations
However, this study also has some limitations. Firstly, while the sample size was adequate in terms of overall mean changes in the total sample and subgroup analyses (according to the a-priori power analyses) it appeared to be insufficient for the analyses of interaction terms in the analysis of variance models. This resulted in a lack of power, as indicated by small effects that failed to achieve nominal statistical significance. Furthermore, lack of study power often leads to the possibility of effect size estimates being inflated [33]. Consequently, our findings regarding the analyses of variance models should be interpreted with caution. Therefore, high-powered future research is needed to obtain robust estimates of the differential changes in focal study parameters between CD and UC patients.
Second, the outcomes observed here were limited to immediate changes over the course of a three-week inpatient rehabilitation program. Although these results appear promising in the short term, research on longer-term effects is needed to gain deeper insight into the role of rehabilitation in improving patients’ subjective disease burden, psychological distress, HRQoL, and work ability over a longer period.
Third, as our study was not based on a randomized intervention-control design, the observed changes over the course of rehabilitation cannot be causally attributed to the investigated intervention. These changes may be the result of natural recovery processes or other influencing factors, such as being in a structured environment away from home and personal routines. Furthermore, we did not explicitly account for further potential confounding factors such as between-subjects variation in diet, medications, exercise, and psychological interventions. Therefore, further research is needed to address the complexity of a multimodal and multidisciplinary rehabilitation for IBD-patients.
Conclusions
Here, we provide empirical evidence suggesting that multidisciplinary medical rehabilitation is an important treatment in patients with Crohn’s disease and ulcerative colitis. During the three-week inpatient gastrointestinal rehabilitation, the subjective disease burden and psychological distress meaningfully decreased, while HRQoL and work ability improved. Additionally, although it may be valuable in long-term monitoring of intestinal inflammation, we advise caution against the use of fecal calprotectin as an indicator of rehabilitation success in short-term settings.
Supporting information
S1 Table. Results of the non-parametric analysis (Wilcoxon sign-ranked test).
Abbreviations: N, sample size; IQR, Interquartile range; P, P-value; Padj, Bonferroni-Holm corrected P-values.
https://doi.org/10.1371/journal.pone.0330922.s001
(DOC)
Acknowledgments
The authors thank Drita Bytyqi and Diana Feßl from the Pensionsversicherung, who helped with data management.
References
- 1. Eckert KG, Abbasi-Neureither I, Köppel M, Huber G. Structured physical activity interventions as a complementary therapy for patients with inflammatory bowel disease - a scoping review and practical implications. BMC Gastroenterol. 2019;19(1):115. pmid:31266461
- 2. Raman M, Rajagopalan V, Kaur S, Reimer RA, Ma C, Ghosh S, et al. Physical Activity in Patients With Inflammatory Bowel Disease: A Narrative Review. Inflamm Bowel Dis. 2022;28(7):1100–11. pmid:34605548
- 3. Saez A, Herrero-Fernandez B, Gomez-Bris R, Sánchez-Martinez H, Gonzalez-Granado JM. Pathophysiology of Inflammatory Bowel Disease: Innate Immune System. Int J Mol Sci. 2023;24(2):1526. pmid:36675038
- 4. Langbrandtner J, Steimann G, Reichel C, Bokemeyer B, Hüppe A. Inflammatory Bowel Disease - Challenges in the Workplace and Support for Coping with Disease. Rehabilitation (Stuttg). 2022;61(2):97–106. pmid:34544161
- 5. Streibelt M, Hüppe A, Langbrandtner J, Steimann G, Zollmann P. Work Participation after Multimodal Rehabilitation due to Diseases of the Digestive System. Representative Analyses using Routine Data of the German Pension Insurance. Rehabilitation (Stuttg). 2023;62(3):165–73. pmid:36288747
- 6. Elia J, Kane S. Adult Inflammatory Bowel Disease, Physical Rehabilitation, and Structured Exercise. Inflamm Bowel Dis. 2018;24(12):2543–9. pmid:29850914
- 7. Walter E, Hausberger S-C, Groß E, Siebert U. Health-related quality of life, work productivity and costs related to patients with inflammatory bowel disease in Austria. J Med Econ. 2020;23(10):1061–71. pmid:32713223
- 8. Duff W, Haskey N, Potter G, Alcorn J, Hunter P, Fowler S. Non-pharmacological therapies for inflammatory bowel disease: Recommendations for self-care and physician guidance. World J Gastroenterol. 2018;24(28):3055–70. pmid:30065553
- 9. Abegunde AT, Goyes D, Farooq U, Luke AH, Huggins E, Cooper RS, et al. The impact of physical exercise on health-related quality of life in inflammatory bowel disease. Cochrane Database of Systematic Reviews. 2023;2023(8).
- 10. Hüppe A, Langbrandtner J, Lill C, Raspe H. The Effectiveness of Actively Induced Medical Rehabilitation in Chronic Inflammatory Bowel Disease. Dtsch Arztebl Int. 2020;117(6):89–96. pmid:32102728
- 11. Chang M-H, Chou J-W, Chen S-M, Tsai M-C, Sun Y-S, Lin C-C, et al. Faecal calprotectin as a novel biomarker for differentiating between inflammatory bowel disease and irritable bowel syndrome. Mol Med Rep. 2014;10(1):522–6. pmid:24788223
- 12. Calvert M, Kyte D, Price G, Valderas JM, Hjollund NH. Maximising the impact of patient reported outcome assessment for patients and society. BMJ. 2019;364.
- 13.
Pensionsvericherungsanstalt. Medizinisches Leistungsprofil für die stationäre Rehabilitation (MLP STAT). 1 ed. Pensionsversicherungsanstalt. 2025.
- 14.
World Health O. International classification of functioning, disability and health: ICF. Geneva: World Health Organization. 2001.
- 15. Ludwig K, Graf von der Schulenburg J-M, Greiner W. German Value Set for the EQ-5D-5L. Pharmacoeconomics. 2018;36(6):663–74. pmid:29460066
- 16.
Hasselhorn HM, Freude G. Der Work Ability Index - ein Leitfaden. Wirtschaftsverlag NW. 2007.
- 17. Kroenke K, Spitzer RL, Williams JBW, Löwe B. An ultra-brief screening scale for anxiety and depression: the PHQ-4. Psychosomatics. 2009;50(6):613–21. pmid:19996233
- 18. Löwe B, Wahl I, Rose M, Spitzer C, Glaesmer H, Wingenfeld K, et al. A 4-item measure of depression and anxiety: validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J Affect Disord. 2010;122(1–2):86–95. pmid:19616305
- 19. Ghosh S, Louis E, Beaugerie L, Bossuyt P, Bouguen G, Bourreille A, et al. Development of the IBD Disk: A Visual Self-administered Tool for Assessing Disability in Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2017;23(3):333–40. pmid:28146002
- 20. Cumming G. The New Statistics: Why and How. Psychological Science. 2014;25(1):7–29.
- 21.
Cohen J. Statistical power analysis for the behavioral sciences. 2 ed. Hillsdale, NJ: Erlbaum. 1988.
- 22.
Gaetano J. Holm-Bonferroni sequential correction: An Excel calculator. 2018.
- 23. van Langenberg DR, Gibson PR. Factors associated with physical and cognitive fatigue in patients with Crohn’s disease: a cross-sectional and longitudinal study. Inflammatory Bowel Diseases. 2014;20(1):115–25.
- 24. Emerson C, Barhoun P, Olive L, Fuller-Tyszkiewicz M, Gibson PR, Skvarc D, et al. A systematic review of psychological treatments to manage fatigue in patients with inflammatory bowel disease. J Psychosom Res. 2021;147:110524. pmid:34034138
- 25. Bisgaard TH, Allin KH, Keefer L, Ananthakrishnan AN, Jess T. Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment. Nat Rev Gastroenterol Hepatol. 2022;19(11):717–26. pmid:35732730
- 26. Li J, Xu M, Qian W, Ling F, Chen Y, Li S, et al. Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn’s disease. Front Physiol. 2023;14:1186665. pmid:37324392
- 27. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570–83. pmid:33359090
- 28. Cremer A, Ku J, Amininejad L, Bouvry M-R, Brohet F, Liefferinckx C, et al. Variability of Faecal Calprotectin in Inflammatory Bowel Disease Patients: An Observational Case-control Study. J Crohns Colitis. 2019;13(11):1372–9. pmid:30944925
- 29. Ikhtaire S, Shajib MS, Reinisch W, Khan WI. Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. J Gastroenterol. 2016;51(5):434–46. pmid:26897740
- 30. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341:c3369. pmid:20634346
- 31. Mendall MA, Chan D, Patel R, Kumar D. Faecal calprotectin: factors affecting levels and its potential role as a surrogate marker for risk of development of Crohn’s Disease. BMC Gastroenterol. 2016;16(1):126. pmid:27717310
- 32. Gubatan J, Kulkarni CV, Talamantes SM, Temby M, Fardeen T, Sinha SR. Dietary exposures and interventions in inflammatory bowel disease: current evidence and emerging concepts. Nutrients. 2023;15(3):579.
- 33. Ioannidis JPA. Why most discovered true associations are inflated. Epidemiology. 2008;19(5):640–8.