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Keywords:

  • gut-directed hypnotherapy;
  • irritable bowel syndrome;
  • patient satisfaction

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

Background  Gut-directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms.

Methods  We evaluated 83 patients with IBS treated with gut-directed hypnotherapy (1 h week−1, 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment.

Key Results  After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non-responder group.

Conclusions & Inferences  Patient satisfaction with gut-directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option.


Abbreviations:
CSFBD

cognitive scale for functional bowel disorders

HAD

Hospital Anxiety and Depression Scale

IBS

irritable bowel syndrome

QOL

quality of life

SOC

sense of coherence

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders, with a pooled prevalence of 11.2% in available studies.1 IBS is diagnosed based on the Rome III diagnostic criteria,2 which include abdominal pain or discomfort combined with diarrhea and/or constipation. The condition is modestly more common among women than men.3 Patients with more severe, intrusive symptoms are often refractory to current conventional pharmacological treatment options,4 which is associated with substantial reduction in quality of life (QOL)5 and psychological distress.6 The socioeconomic impact of IBS is considerable and patients with IBS consume significant health care recourses.7,8 Several studies of psychological treatments for IBS have been conducted, including cognitive behavior therapy,9,10 gut-directed hypnotherapy,11,12 brief psychodynamic psychotherapy,13 relaxation therapy,14 and stress management.15 Although these treatments generally show beneficial effects,16,17 they have not been widely disseminated in clinical care for IBS.18

Gut-directed hypnotherapy is considered to be an effective treatment for IBS.19 However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. Instead, other factors, not necessarily captured with standard primary endpoints, i.e., improvement in GI symptom severity, may be of importance for patient satisfaction. This observation is strengthened by the fact that in previous trials as many as 74% of the patients, who in terms of effect on IBS symptoms were considered as non-responders, still judged treatment with hypnotherapy to be meaningful.20 In this study, we therefore aimed to assess patient satisfaction with gut-directed hypnotherapy and to evaluate factors of importance for this, as part of a previously published randomized controlled clinical trial.21

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

Recruitment and procedure

Patients who had received gut-directed hypnotherapy because of IBS refractory to standard management were included. The study was performed at Sahlgrenska University Hospital, Gothenburg, Sweden. Patients referred for IBS symptoms refractory to standard dietary and pharmacological therapies were recruited consecutively to a randomized controlled trial, comparing gut-directed hypnotherapy with supportive therapy as control group.21 All patients had undergone appropriate diagnostic tests to rule out any organic GI disorders or other severe co-existing diseases before inclusion in the study and met Rome II criteria22 for IBS. Results from the randomized controlled clinical trial period of this study have been presented in detail previously, as well as 1-year data from the active treatment group.20,21 For the purpose of this study, we also included the patients in the control group, who received supportive therapy during the randomized controlled treatment phase, and who were crossed over to receive hypnotherapy after 6 months. All subjects provided written informed consent before inclusion. The study was approved by the ethics committee of the University of Gothenburg.

At baseline, i.e., before the treatment period, and at the end of the treatment period (i.e., at 12 weeks), patients completed questionnaires to assess IBS symptom severity, QOL, cognitive function, sense of coherence (SOC), depression, and anxiety. Immediately after the treatment period, patients also scored their satisfaction with the gut-directed hypnotherapy.

Gut-directed hypnotherapy

The intervention method used in these studies was based on the gut-directed hypnotherapy protocol, developed by the Manchester group,23 and described in detail in our previous publication.21 Briefly, it is based on muscular and mental relaxation, and general hypnotic suggestions are used to either focus on the symptoms or to distract from them. All patients that participated in the study were treated individually in twelve weekly sessions, each session lasting 60 min. Three experienced, specially trained clinical psychologists conducted the treatment, which took place in their private practices outside the hospital. Patients were told to practice their hypnotic skills at home regularly between sessions. No audiotapes were used.

Questionnaires

GI symptom questionnaire  This questionnaire evaluates the perceived severity of symptoms related to IBS and was created specifically for this study.21,24 It uses a 7-graded Likert scale ranging from no symptoms (=1) to very severe symptoms (=7). The symptoms included are bloating, gas, pain, loose stools, urgency, hard stools, and incomplete evacuation. Scores of the individual symptoms are summarized into a total symptom severity score ranging from 7 to 49 and two different domains: sensory symptoms score (pain, bloating, gas) and bowel habit score (loose stools, urgency, hard stools, and incomplete evacuation). An IBS symptom responder was defined as a subject who reported reduction of the total symptom severity score ≥25% at the end of the treatment period, i.e., at 12 weeks. This responder definition was also used in the randomized controlled trial.21

IBS-QOL  This validated disease specific HRQOL instrument includes 30 items measuring nine dimensions of health: emotional functioning, mental health, sleep, energy, physical functioning, diet, social role, physical role, and sexual relations.25 Raw scores are transformed into a scale of 0–100, with 100 representing the highest possible QOL.

The Hospital Anxiety and Depression Scale (HAD)  This scale was developed for non-psychiatric medical patients to detect anxiety and depression.26 It consists of 14 items, with seven items relating to anxiety and seven items relating to depression. Each item is scored on a 4-graded Likert scale, giving a range from 0 to 21 on the anxiety and depression subscales with higher scores indicating more severe symptoms.

Cognitive scale for functional bowel disorders (CSFBD)  The CSFBD is a scale designed to access cognitions in patients with functional bowel disorders.27 It includes statements derived from typical thoughts of IBS patients, subdivided into themes relating to bowel function and personal characteristics relevant to IBS. The patients are asked to rate to which extent each statement applies to them, using a 7-point scale, ranging from Strongly Disagree (scoring 1) to Neither Agree/Disagree (scoring 4) to Strongly Agree (scoring 7). The final version of the scale consists of 25 items, but an additional six items were used in this study, as was the case in a previous study assessing cognitive change in patients with IBS who underwent gut-directed hypnotherapy.28 Scores for 11 individual themes can be calculated, but in this study we only used a total score (range 31–217), with higher scores indicating more negative IBS-related cognitions.

SOC Scale  Sense of coherence reflects the ability a person has to cope with difficult situations in life.29 The SOC includes 29 items measuring three aspects of this ability; manageability, comprehensibility, and meaningfulness. The scale uses a 7-point response format, where 1 represents the weakest and 7 represents the strongest SOC, A high score indicates successful coping abilities and increased likelihood of having a good health and QOL.

Patient Satisfaction Scale  This scale was developed specifically for this study and was used to evaluate the degree of satisfaction with the intervention. The patients were asked to score their satisfaction with the gut-directed hypnotherapy immediately after the end of the 12-weeks treatment period on a Likert scale, ranging from 1 (specified as ‘not at all satisfied’) to 5 (‘very satisfied’), with the scale steps 2, 3, and 4 not specified. Moreover, the patients were also asked if they would start with gut-directed hypnotherapy again if they had had the knowledge and experience about this intervention that they possess after the treatment period.

Data analysis and statistics

Patient data and results from questionnaires were entered into a database by persons otherwise not involved in the conduct of the studies. The statistical significance of pre to posttreatment changes (GI symptom severity, QOL, cognitive function, SOC, anxiety, and depression) was assessed using Wilcoxon signed-rank tests. Results from the patient satisfaction scale are presented as the proportion of individuals with the different scores (1–5) and the bivariate correlations with age, GI symptom severity, QOL, cognitive function, SOC, anxiety, and depression were assessed with the Spearman Rank Correlation Test. Moreover, the associations between patient satisfaction and gender, IBS subtype according to the Rome II criteria,22 and IBS symptom response status (‘responder’ or ‘non-responder’), were explored with chi-square test. Thereafter, in an attempt to find factors independently associated with patient satisfaction, factors bivariately associated with patient satisfaction at P < 0.05 were entered into a multiple linear regression analysis. Before entering variables into the linear regression analysis, multicollinearity was excluded by testing correlations between the independent variables and highly intercorrelated independent variables were removed (≥0.7), and collinearity diagnostics were performed to rule out low tolerance values (≤0.1). All variables included in the regression analysis are displayed in a table, i.e., the full model is shown. The scores from the questionnaires and demographics are reported as mean ± standard deviation, unless otherwise stated. Statistical significance was accepted at the 5% level.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

Subjects

We included 83 patients [mean age 42 (21–68) years; 65 females] who received gut-directed hypnotherapy because of IBS refractory to standard management. Forty-five of these received hypnotherapy in the active treatment arm in our previously published randomized controlled trial, whereas 38 patients served as control subjects in this trial and received hypnotherapy after 6 months.21 Of the 90 patients that were randomized, three patients in the control group withdrew from the study and four patients (all initially in the control group) did not return any questionnaires after their hypnotherapy treatment and were therefore not included in the analyses of this study. Based on the Rome II criteria,22 13 patients were classified as constipation predominant IBS, 28 as diarrhea predominant IBS, and 42 patients had alternating bowel habit. All patients included in this study had suffered from IBS for at least 5 years.

Effects of gut-directed hypnotherapy

To evaluate the effect of gut-directed hypnotherapy, we compared the scores from the questionnaires after the treatment period, i.e., at 12 weeks, with the scores at baseline, i.e., before the treatment. As can be seen in Table 1, there was a significant reduction in overall IBS symptom severity, and this was true for both sensory symptoms and bowel habit. Moreover, some of the QOL dimensions (mental health, energy, and social role) improved significantly after the treatment, which was also true for cognitive function and anxiety. However, depression and SOC remained unaltered.

Table 1.   Comparisons of gastrointestinal symptom severity, quality of life, cognitive function, sense of coherence, anxiety, and depression before (baseline) versus after gut-directed hypnotherapy (12 weeks)
Questionnaire item/domainBaseline12 weeks P-value
  1. IBS, irritable bowel syndrome; IBS-QOL, IBS-quality of life; CSFBD, cognitive scale for functional bowel disorders; SOC, Sense of Coherence; HAD, Hospital Anxiety and Depression Scale. Bold indicates when P < 0.05.

Total IBS symptoms27.5 ± 7.224.6 ± 7,8 0.005
IBS – sensory symptoms13.7 ± 3.512.2 ± 4.3 0.012
IBS – bowel habits13.5 ± 4.312.3 ± 4.7 0.03
IBS-QOL – emotional functioning48.5 ± 20.950.7 ± 21.60.219
IBS-QOL – mental health66.9 ± 19.571.4 ± 19.5 0.02
IBS-QOL – sleep63.7 ± 24.166.7 ± 24.60.135
IBS-QOL – energy44.2 ± 25.651.5 ± 25.2 0.008
IBS-QOL – physical functioning72.7 ± 24.674.7 ± 22.30.225
IBS-QOL – diet58.6 ± 17.559.1 ± 17.50.605
IBS-QOL – social role53.3 ± 24.061.3 ± 22.3 <0.0001
IBS-QOL – physical role46.7 ± 29.851.6 ± 31.00.173
IBS-QOL – sexual relations55.1 ± 24.060.9 ± 24.20.091
CSFBD – total143.8 ± 37.4133.2 ± 36.9 <0.0001
SOC – comprehensibility4.2 ± 1.04.1 ± 0.90.294
SOC – manageability4.8 ± 1.04.8 ± 0.90.415
SOC – meaningfulness5.1 ± 1.05.0 ± 1.00.292
HAD anxiety9.3 ± 3.88.5 ± 3.4 0.002
HAD depression6.1 ± 3.36.0 ± 3.70.881

Patient satisfaction

Directly after the treatment, 82 of the 83 patients completed the patient satisfaction scale. Thirty patients (36.5%) were very satisfied (score 5) with the treatment at the end of the course of gut-directed hypnotherapy and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Only four patients (4.8%) reported that they were not at all satisfied with the treatment (Fig. 1). Sixty-four patients (77%) also reported that they would start treatment with gut-directed hypnotherapy again if they had had the knowledge and experience about this intervention that they possessed after the treatment period.

image

Figure 1.  Results from the patient satisfaction scale after gut-directed hypnotherapy: ‘are you satisfied with the gut-directed hypnotherapy?’

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Factors associated with patient satisfaction

Baseline characteristics (age, gender, IBS subtype) or scores on the questionnaires before treatment were not significantly correlated with the patient satisfaction after the gut-directed hypnotherapy and were not used in further analyses (data not shown). However, after the treatment period, the scores on the patient satisfaction scale were bivariately associated with GI symptom severity (r = −0.24; P < 0.05), and some of the IBS-QOL domains (sleep: r = 0.23; P < 0.05; physical function: r = 0.28; P < 0.05; physical role: r = 0.22; P < 0.05; and sexual relations: r = 0.40; P < 0.001). No significant correlations were seen between patient satisfaction and SOC, cognitive function, anxiety, or depression (data not shown). Factors bivariately associated with patient satisfaction at P < 0.05 were entered into a multiple linear regression analysis with the patient satisfaction scale as the dependent variable. Preliminary analyses were conducted to ensure no violation of the assumptions of normality, linearity, multicollinearity, and homoscedasticity. The model explained 22.4% of the variance in the dependent variable (R2 = 0.224; F = 3.12; P = 0.015). As can be seen in Table 2, only IBS-QOL sexual relations made a unique statistically significant contribution to the equation.

Table 2.   Multiple linear regression analysis predicting patient satisfaction (R2 = 0.22)
Model β 95% CI for β P-value
  1. GI, gastrointestinal; IBS-QOL, irritable bowel syndrome-quality of life. Bold indicates P < 0.05.

Constant   0.02
Total GI symptoms−0.084−0.056 to 0.0310.57
IBS-QOL sleep0.035−0.014 to 0.0170.84
IBS-QOL physical functioning0.21−0.005 to 0.0270.17
IBS-QOL physical role−0.113−0.017 to 0.0080.50
IBS-QOL sexual relations0.360.003–0.032 0.018

To further exemplify the association between the degree of patient satisfaction and change in symptoms and QOL, we compared baseline and posthypnotherapy scores for GI symptom severity and the IBS-QOL domain which was found to be independently associated with patient satisfaction, sexual function, within each of the scale steps on the patient satisfaction scale. As can be seen in Fig. 2, only patients who were very satisfied with the treatment (score = 5) reported a significant improvement in GI symptom severity (P = 0.008) and IBS-QOL sexual relations (P = 0.004). However, some of the comparisons are hampered by small number of patients in the groups (see Fig. 1 for details).

image

Figure 2.  Comparison between baseline (black bars) and posthypnotherapy scores (white bars) for GI symptom severity (A) and the irritable bowel syndrome-quality of life domain which was found to be independently associated with patient satisfaction, sexual function (B), within each of the scale steps on the patient satisfaction scale. **P < 0.01.

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Using 25% reduction of the total IBS symptom severity (GI symptom questionnaire) to define an ‘IBS symptom responder’ (n = 21), 52% of the ‘IBS symptom responders’ and 31% of the ‘IBS symptom non-responders’ were very satisfied (=score 5; total n = 30) with gut-directed hypnotherapy (P = 0.07) (Fig. 3). If patients scoring 4 or 5 on the patient satisfaction scale were considered to be satisfied with the treatment (n = 57), 71% of the ‘IBS symptom responders’ and 68% of the ‘IBS symptom non-responders’ were satisfied with the treatment (= 0.75).

image

Figure 3.  Irritable bowel syndrome symptom response vs patient satisfaction (= 0.07). For details, please see text.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

In this study, we have demonstrated that a large proportion of patients with IBS refractory to standard medical management respond favorably to gut-directed hypnotherapy and express that they are satisfied with the treatment. Patient satisfaction after gut-directed hypnotherapy is associated with improvement of GI symptoms and QOL, but other factors are also of importance, as a substantial proportion of the patients in this study reported that they were satisfied with this treatment option despite no/minor improvement of GI symptoms.

It has been established that gut-directed hypnotherapy is an effective treatment for patients with refractory IBS.12,19,21 Our clinical experience is that patients in many cases are satisfied with the intervention even if there is no or minor reduction of GI symptom severity. In our recently published long-term follow-up of 208 Swedish patients previously treated with gut-directed hypnotherapy, 74% of the non-responders in terms of effect on IBS symptoms found the intervention being ‘worthwhile’,20 which is in line with the results from another follow-up study of hypnotherapy in IBS.30 These observations prompted us to perform the analyses presented in this study, to better understand factors of importance for patient satisfaction after gut-directed hypnotherapy in IBS patients.

In this study, we confirmed the positive results with gut-directed hypnotherapy obtained in previous studies.12,24,31–33 Moreover, we also demonstrated that, in line with our clinical observations and previous follow-up studies,20,30 a large proportion of patients with IBS are satisfied with this treatment alternative, even though a substantial proportion of the patients who were satisfied did not meet standard primary endpoints, i.e., reduction of GI symptom severity. Based on this, choosing GI symptom severity as the only outcome parameter when treating patients with hypnotherapy, as well as other psychological and educational interventions, may not be the optimal outcome measure. Combining GI symptom assessment with measures of psychological well-being and general treatment satisfaction may provide more robust information. However, to validate this assumption follow-up studies are needed, where the association between different endpoints and the long-term outcome in terms of well-being, health care consumption, and work productivity are evaluated.

Factors of importance for patient satisfaction in general are incompletely understood, and studies measuring predictors of patient satisfaction have explained only a small proportion of the variance in satisfaction, often <20%,34 indirectly indicating that patient satisfaction is relatively complex. In a recent study by Dorn et al.,35 satisfaction with IBS care was conceptualized as a multidimensional construct related to patient characteristics, illness characteristics, the health care setting, and the health care encounter. This model was confirmed in the process of developing a questionnaire to assess IBS satisfaction with care, where different factors seemed to be of importance for satisfaction, and GI symptoms and IBS-related QOL were only modestly associated with satisfaction.35 This is in line with our results where 22% of the variance in patient satisfaction was explained by our model incorporating IBS symptoms and QOL, but where only the IBS-QOL domain sexual relations symptoms made a unique statistically significant contribution to the model. Other factors of potential importance for patient satisfaction not measured in our study may be GI-specific anxiety, factors related to the health care setting, prior health care experiences, expectations, interaction with the therapist, and social factors.34–37

Although the severity of IBS symptoms after treatment with gut-directed hypnotherapy was associated with patient satisfaction, 31% of the IBS symptom non-responders (<25% reduction of IBS symptom severity) were ‘very satisfied’ while 48% of the IBS symptom responders were less satisfied with the intervention. Moreover, if being satisfied with gut-directed hypnotherapy was defined as score 4 or 5 on the patient satisfaction scale, the agreement with being a responder based on GI symptom improvement was even poorer. This further implicates that factors other than GI symptom improvement are of importance for patient satisfaction. Effects on QOL could be expected to drive some of the response in terms of satisfaction, but although there was a positive effect on QOL after the treatment and bivariate associations between patient satisfaction and some QOL domains, only the QOL domain sexual relations was found to be independently associated with the degree of satisfaction, which is interesting given the high degree of sexual dysfunction reported in IBS.38 In a clinical setting IBS patients often reports that previous contacts with health care providers has been inadequate in terms of ‘being taken seriously’39 and therefore there are probably other factors involved that contribute to treatment satisfaction, e.g., the attention the patient receives when participating in this type of treatment. It could also be speculated that the high-grade of satisfaction reflects that gut-directed hypnotherapy affects the ability to cope with symptoms, even if the severity of the IBS symptoms are unchanged. In this study, we could not detect a significant association between SOC among the patients and the degree of satisfaction with gut-directed hypnotherapy. However, a measure more focused on coping strategies rather than on SOC could potentially have captured this, but was unfortunately not included in this trial.40,41

Another positive finding in this study was the fact that only 15% of the patients scored 1 or 2 on the satisfaction scale, indicating that very few patients were dissatisfied with gut-directed hypnotherapy. Even though we are not aware of similar formal measurements regarding patient satisfaction with available pharmacological treatment options in IBS, our clinical experience and some study results indicate that a larger proportion of IBS patients are dissatisfied with the use of available pharmacological agents compared with the patients who were dissatisfied with gut-directed hypnotherapy.42,43

A weakness in this study is that we used a non-validated single-item question when assessing the degree of satisfaction after treatment with hypnotherapy. The use of a single question may be unreliable, given the fact that patient satisfaction is a multidimensional construct.35 However, as our evaluation of patient satisfaction was part of a clinical trial with several other assessments as well, we considered the use of a single-item assessment to be a valid compromise to have reliable results without too many questions for the patients. Moreover, at the time of our study, no condition-specific multidimensional satisfaction scale for IBS existed. In future studies focusing on patient satisfaction in IBS care, it would be of interest to use the recently developed multidimensional IBS Satisfaction with care scale.35 However, the validity of our results is supported by similar results in long-term follow-up studies.18,25

We conclude that the gut-directed hypnotherapy in refractory IBS is an effective treatment with a high grade of subjectively reported patient satisfaction, even among patients who are considered as non-responders in terms of effect on IBS symptoms. Patient satisfaction was associated with GI symptom severity and QOL, but the only factor independently associated with patient satisfaction was the IBS-QOL domain sexual relations. A high grade of individual satisfaction is probably by itself an important goal when treating this often very bothersome, but benign condition. Factors associated with patient satisfaction besides improvement in IBS symptoms and QOL remains to be established and further research to better understand these processes is needed.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

We express our gratitude to the three private practice psychologists, who provided the hypnotherapy – Susanna Carolusson, Berndt Westman, and Anne Holmgren.

Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

This study was supported by Västra Götaland. Region (Dagmar funds), the Swedish Research Council (Grants 13409, 21691 and 21692), the Marianne and Marcus Wallenberg Foundation, University of Gothenburg, Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, and the Faculty of Medicine, University of Gothenburg.

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

Magnus Simrén has received unrestricted research grants from Danone and AstraZeneca, and served as a Consultant/Advisory Board member for Danone, Novartis, and Shire/Movetis. Guarantor of the article: Magnus Simrén, MD, PhD.

Author Contribution

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References

PL, MS and PI were involved in manuscript writing, study design, and data analysis; BL contributed to manuscript writing and data analysis; EB and HA were involved in study design and performance of the study. All authors have approved and critically reviewed the manuscript.

References

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  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Funding
  9. Disclosure
  10. Author Contribution
  11. References
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