Glucocorticoid‐enhanced extinction‐based exposure therapy in irritable bowel syndrome – a proof of concept study

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Full text

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Örebro  University  

School  of  Medical  Science   Degree  project,  30  ECTS   2016-­‐01-­‐07          

 

 

Glucocorticoid-­‐enhanced  extinction-­‐based  

exposure  therapy  in  irritable  bowel  syndrome  

–  a  proof  of  concept  study    

Version  1                  

Author:  Malin  Hoglert,  bachelor  of  medicine,  Örebro  University,  

malin.hoglert@gmail.com  

Supervisor:  Michiel  van  Nieuwenhoven,  MD,  PhD,  Associate  Professor,    

Dept.  of  Gastroenterology,  Örebro  University  Hospital,    

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ABSTRACT

Introduction

IBS is associated with a decreased serotonergic activity in amygdala, which increases activity in the emotional arousal network, resulting in an increased perception of visceral pain. This pattern is also seen in phobic disorders, resulting in enhanced fear response. Recent studies demonstrated that a combination of exposure therapy and acute cortisone administration is highly effective in the treatment of acrophobia. We hypothesize that IBS-patients demonstrate a phobic response following visceral stimulation, and that visceral stimulation with a rectal balloon (barostat) combined with i.v. cortisol administration will lead to a decreased visceral pain perception and improvement of abdominal symptoms.

Aim

To establish whether Glucocorticoid-enhanced Extinction-based Exposure Therapy (GEET) is able to improve visceral hypersensitivity, abdominal complaints and anxiety in IBS patients.

Methods

A pilot study based on a semi-blinded placebo-controlled parallel design. Six IBS-patients were randomized into two groups receiving GEET or placebo. GEET was applied 3 times within 1 week and consisted of a 30 min barostat protocol combined with 40 mg cortisol i.v. Visceral perception data, and symptom- and psychometric questionnaires, were evaluated at baseline, 1 week and 5-6 weeks after treatment.

Results

In treatment-group median pressure at baseline was: key4 24mmHg, key5 40mmhg. At first follow up: key4 24mmHg, key5 32mmHg. In placebo-group: key4 12mmHg, key5 24mmHg at baseline. At first follow up: key4 16mmHg, key5 20mmHg. Treatment-group median value for IBS-SSS was 100,7 at baseline and 71,2 at first follow up, IBS-QoL 30,1 and 52,2, VSI 65 and 61 respectively. In placebo-group the median value for IBS-SSS was 48,2 and 34,7, IBS-QoL 82,4 and 93,4, VSI 52 and 17 respectively.

Conclusions

Until now we have included 6 patients, this number does not allow non-parametric statistics. Descriptive statistics show no differences in visceral sensitivity, GI-symptoms and anxiety between placebo and treatment group. Further inclusion of subjects is needed for a final conclusion.

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ABBREVIATIONS

IBS Irritable Bowel Syndrome

GEET Glucocorticoid-enhanced Extinction-based Exposure Therapy

GI Gastrointestinal

SOP Standard Operation Procedure

IBS-SSS IBS Symptom Severity Scale

GSRS-IBS Gastrointestinal Symptom Rating Scale IBS

SF-NDI NEPEAN Dyspepsia Index

IBS-QoL IBS Quality of Life

VSI Visceral Sensitivity Index

GAD-7 Generalized Anxiety Disorder 7

HADS Hospital Anxiety and Depression Scale

PHQ Patient Health Questionnaire

B Baseline

F1 First follow up

F2 Second follow up

T Treatment-patient

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TABLE of CONTENTS

  ABSTRACT  ...  1   ABBREVIATIONS  ...  2   TABLE of CONTENTS  ...  3   INTRODUCTION  ...  4   Aim  ...  5   Research  Questions  ...  5  

MATERIAL and METHODS  ...  6  

Study Design  ...  6   Material  ...  6   Barostat  ...  7   Method  ...  7   Data  ...  8   Ethics  ...  9   Study finance  ...  9   RESULTS  ...  9   Barostat  ...  9   Questionnaires  ...  11   DISCUSSION  ...  13   Conclusion  ...  15   Acknowledgements  ...  15   REFERENCES  ...  16  

Appendix A: ROME III  ...  18  

Appendix B: SOP Rectal Barostat  ...  21  

Appendix C: Questionnaires of GI-symptoms  ...  26  

IBS-SSS  ...  26  

GSRS-IBS  ...  27  

SF-NDI  ...  29  

PHQ-15  ...  33  

Appendix  D:  Questionnaires  of  anxiety  ...  34  

IBS-­‐Quality  of  Life  ...  34  

Visceral Sensitivity Index  ...  36  

GAD-7  ...  37  

PHQ-9  ...  38  

Hospital Acquired Depression Scale (HADS)  ...  39  

Appendix E: Produktresumé Solu-Cortef  ...  40  

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INTRODUCTION

IBS is a functional bowel disorder characterized by pain or discomfort with changes in stool pattern [1]. The pathophysiology of IBS is multifactorial and not completely understood, increased visceral perception (hypersensitivity) and disturbed

bidirectional brain-gut signalling are considered key factors [2,3]. The disturbed brain-gut signalling is might be associated with serotonergic dysregulation [4], which is also associated with a high prevalence of mood/anxiety disorders in IBS patients [5].

Experimental lowering of serotonergic activity in healthy controls, by means of a nutritional intervention called Acute Trypthophan Depletion, results in a loss of negative feedback inhibition of the amygdala, which leads to increased activity in the emotional arousal network [6]. The alteration in the activity of the emotional arousal circuits in healthy controls leads to increased visceral pain perception when exposed to a rectal stimulus [7]. IBS patients show similar pattern in the emotional arousal network when exposed to a rectal stimulus, which may provide an explanation for the visceral hypersensitivity in IBS-patients [6,7].

The amygdala plays an important part in consolidation of memory, activation of amygdala, and its efferent projections, enforces the storage of information [8]. Stress hormones and stress-activated neurotransmitters affect the activity of the amygdala and enhance the consolidation of memory in situations which are emotionally arousing [8]. Glucocorticoids are one of these stress hormones which improve memory and learning [8,9], but they can also facilitate extinction processes and inhibit retrieval of fear memories [10,11]. When people are exposed to chronic stress, or intensely emotional events, memory consolidation via the amygdala can produce traumatic memories and induce an enhanced fear response, thus leading to anxiety disorders like phobia or affective disorders [8].

In anxiety disorders conditioning and associative learning leads to formation of a fear memory [12-14]. Individuals with a phobic disorder demonstrate, when exposed to their phobic stimuli, a major fear response, due to retrieval of the stimulus-associated fear memory [15]. During a phobic response to a stimulus the activity in the

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amygdala increases and the activity in the emotional arousal network increases as well [16-18]. This pattern of increased activation in the emotional arousal network with a central role for the amygdala is similar to the pattern showed in IBS patients during a rectal stimulus [6,7,16-18].

Phobic disorders are often treated with exposure-based behavioural therapy, which is thought to eradicate the exaggerated fear response when exposed to stimulus [14]. Recently, de Quervain et al. demonstrated that a combination of exposure therapy and acute corticosteroid administration is highly effective in the treatment of acrophobia [14]. Other studies exploring cortisol-augmented cognitive behavioural therapy in phobic disorders have also shown beneficial result [11,19,20].

We hypothesize that visceral sensations should be considered as phobic stimuli in IBS patients, resulting in increased activity within the emotional arousal network, leading to central pain amplification. Hence, we hypothesize that Glucocorticoid-enhanced Extinction-based Exposure Therapy (GEET) results in a decreased visceral pain perception and improvement of abdominal complaints. This approach is completely new; no other studies have been carried out with respect to this topic.

The treatment offered to IBS patients is very limited. Lifestyle-alterations and diets can be difficult to maintain. Selective smooth muscle relaxants andprobiotic administration have limited effects [21,22],and antidepressants have side effects [23,24].Hence the findings of a new alternative and effective IBS-treatment would be significant for the healthcare and IBS patients.

Aim  

 

The aim of this study is to establish whether GEET is able to improve (i.e. decrease) visceral hypersensitivity, abdominal complaints and anxiety in IBS patients.

Research  Questions  

 

• Is GEET able to improve (i.e. decrease) visceral perception in IBS patients? • Does GEET affect (i.e. decrease) abdominal symptoms and parameters of

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MATERIAL and METHODS

Study Design

 

This is a proof-of-concept pilot study; the design is a semi-blind placebo-controlled parallel design. The data described in this paper are part of a larger study; in which 24 IBS-patients are to be included.So far 6 subjects have been randomized into two groups receiving GEET or placebo. Randomization was conducted using 6 envelopes, 3 envelopes contained the word treatment and 3 envelopes contained the word control. For each subject an envelope was drawn at random. The subjects were not told if the were to receive treatment or placebo, hence the study was semi-blinded.

Material

 

Recruitment of subjects was performed at the gastroenterology outpatient clinic at Örebro University Hospital during Sept-November 2015. The inclusion criteria were: 1. Subjects fulfil Rome III diagnostic criteria for IBS (see appendix A) and

pain/discomfort frequency is at least 2 days a week in the last 12 weeks. 2. Visual Analogue Scale score of subject’s global assessment of abdominal pain and

discomfort equals ≥ 35mm at the randomisation visit.3. Males or females aged 18-65 years. 4. Signed informed consent. Exclusion criteria were: 1. Concurrent or recent treatment with drugs affecting intestinal function or mood, e.g. antidepressants. 2. Concurrent or recent (< 2 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St John’s Worth and probiotics). 3. Diagnosis of major psychiatric or somatic disease other than part of IBS. 4.

Pregnancy or breastfeeding. 5. Abuse of alcohol or drugs. 6. A recent history of systemic or oral steroid therapy.

8 patients met the criteria and were asked to participate, 6 patients chose to

participate. The 2 patients who chose not to participate did so because of lack of time for participation. The study group consisted of 1 male and 5 female, age ranging from 22 to 55, median age 28. Placebo-group consisted of 3 females, median age 24. Treatment-group consisted of 1 male and 2 female, median age 34. One treatment-patient chose to end the study before second follow up because of lack of treatment

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for IBS-symptoms. One patient in each group did not go through second follow up before the study ended. Therefore two patients from the treatment-group and one patient from placebo-group did not participate in second follow up.

Barostat

 

The barostat is a device that allows examinations of pressure-volume relations and visceral sensitivity in a hollow organ, such as the bowel or stomach. It can also be used as a tool to apply visceral stimuli to the rectum. It comprises of a computer-controlled pump, which is connected via a catheter to a polyethylene rectal probe.

In this study, visceral sensitivity measurements as well as treatment, by means of repeated rectal stimuli, were conducted using a barostat (Dual Drive Barostat Distender II Series, G&J Electronics Inc., Toronto, Ontario, Canada). Protocol Plus Deluxe Software (G&J Electronics Inc.) was used.One hour before every barostat procedure, a 750ml water enema was administrated for bowel preparation.

Method

 

The baseline barostat protocol was conducted according to SOP Rectal Barostat, see appendix B. Visceral sensations are scored on a scale; 1 first sensation, 2 first desire to defecate, 3 urgency, 4 discomfort, 5 maximal tolerable pressure/pain. The baseline examination also included several symptom questionnaires (appendix C); Visceral Sensitivity Index (VSI), IBS Symptom Severity Scale (IBS-SSS), Gastrointestinal Symptom Rating Scale IBS (GSRS-IBS), Nepean Dyspepsia Index (SF-NDI), Patient Health Questionnaire 15 (PHQ-15). And psychometric questionnaires (appendix D); IBS Quality of Life (IBS-QoL), Generalized Anxiety Disorder 7 (GAD-7), Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire 9 (PHQ-9).

One week later patients received treatment with GEET or placebo 3 times within a week (Mon-Wed-Fri). GEET comprised a combination of a 40 mg hydrocortisone (Solu-Cortef, Pfizer, see appendix E) i.v. a one hour before barostat exposure, and a 30 min barostat protocol based on the baseline measurements. Treatment protocol

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  starts at 4mmHg, increase in steps of 4 mmHg for 15 seconds each, until the pressure reaches 85% of the maximal tolerable pressure of baseline, thereafter the pressure alternates between the pressure corresponding key 2 (first desire to defecate) and 85% of the corresponding pressure of key 5 (maximal tolerable pressure) measured at baseline, for 20 seconds in each step for a total of 30 minutes. The control group received 1 ml 0.9% NaCl solution i.v. one hour before barostat exposure, combined with rectal placement of the barostat probe, which was not inflated, i.e a “sham-procedure”.

The SOP Rectal Barostat was conducted again 1 week and 5-6 weeks after treatment for evaluation of visceral perception. During these examinations, the patients filled in the same symptom- and psychometric questionnaires as previous. For flow-chart of the process, see appendix F.

Data

 

Primary outcome parameter comprises evaluation of visceral sensitivity, measured with the barostat method. Secondary outcome parameters comprise evaluation of abdominal complaints and parameters ofanxiety and stress, using questionnaires. Data presented are from SOP Rectal Barostat and questionnaires at baseline (B), 1 week after treatment (F1) and 6-7 weeks after treatment (F2).

Visceral perception data and questionnaires are presented as individually results. Baseline and first follow up data are also presented as median for each group.For visceral perception and questionnaires the between subjects factor is treatment (two levels: GEET, placebo), and the within subjects factor were time (baseline, after 3 weeks and after 9 weeks) for questionnaires and time and pressure for visceral perception.

Descriptive statistics were used for analysis of the barostat data and questionnaires, as the patient number does not allow non-parametric comparisons. Data are presented in charts and tables. After completion of the whole study, the data will be statistically analysed using the non-parametric Wilcoxon signed-rank test for within subject factors, and Mann-Whitney U-test for between subject factors.

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Ethics

 

The study was approved by the Ethical Committee in Uppsala, EPN 2013/292. Patients signed an informed consent after been given oral and written information. The barostat method is a widely used technique and well established, it does not cause severe pain or discomfort for the patients.Intravenous administration of

hydrocortisone or placebo was not considered harmful for the patients. Performance of the study was justifiable as treatment for IBS is limited and often ineffective. Subjects received reimbursement for participation.

Study finance

 

The study was conducted with contribution from Nyckelfonden Foundation for Medical Research at Örebro University Hospital.

RESULTS

 

Barostat

 

For individual results se table 1.

In treatment-group median pressure at baseline was: key1 12mmHg, key2 16mmHg, key3 24mmHg, key4 24mmHg, key5 40mmhg. Ranging from 4mmHg to 40mmHg. At first follow up: key1 12mmHg, key2 20mmHg, key3 24mmHg, key4 24mmHg, key5 32mmHg. Ranging from 4mmHg to 52mmHg.

In placebo-group median pressure at baseline was: key1 8mmHg, key2 8mmHg, key3 16mmHg, key4 12mmHg, key5 24mmHg. Pressure ranging between 4mmHg and 24mmHg. At first follow up: key1 8mmHg, key2 12mmHg, key3 20mmHg, key4 16mmHg, key5 20mmHg. Ranging from 4mmHg to 32mmHg.

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  Table 1. Individual Barostat Data.

Baseline First Follow Up Second Follow Up

Patient Key1 Key2 Key3 Key4 Key5 Key1 Key2 Key3 Key4 Key5 Key1 Key2 Key3 Key4 Key5

T1 4 12 16 16 40 4 4 12 8 32 4 12 12 16 24 T2 12 18 24 24 28 12 20 24 24 28 8 12 16 16 20 T3 16 16 24 28 40 20 20 28 36 52 P1 4 8 12 8 24 4 8 12 12 20 P2 8 8 20 16 24 12 16 20 16 20 8 12 16 16 20 P3 8 12 16 12 20 8 12 24 24 32

Table 1. Barostat data in unit mmHg. T and P stand for Treatment-patient and Placebo-patient respectively. Individual data from barostat examinations at baseline, first follow up and second follow up.

Chart 1. Barostat Data in Treatment Group

Chart 1. Barostat data, treatment group. T stands for Treatment-patient. Shows the corresponding pressure for the sensation: 1 First sensation, 2 First desire to defecate, 3 Urgency, 4 Discomfort, 5 Pain. At baseline, first and second follow up.

0 10 20 30 40 50 60

Key1 Key2 Key3 Key4 Key5 Key1 Key2 Key3 Key4 Key5 Key1 Key2 Key3 Key4 Key5

Patient T1 Patient T2 Patient T3

Treatment

Pressure mmHg

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Chart 2. Barostat Data in Placebo Group

Chart 2. Barostat data, placebo group. P stands for Placebo-patient. Shows the corresponding pressure for the sensations: 1 First sensation, 2 First desire to defecate, 3 Urgency, 4 Discomfort, 5 Pain. At baseline, first and second follow up.

 

Questionnaires

 

Patients  filled  in  several  GI-­‐symptomatic  questionnaires,  for  individual  results  se   table  2,  and  questionnaires  of  anxiety  and  GI-­‐specific  anxiety,  for  individual   results  se  table  3.    

 

In  treatment  group  median  value  for  IBS-­‐SSS  was  100,7  at  baseline  and  71,2  at   first  follow  up.    GSRS  scoring  was  51  and  33  respectively.  SF-­‐NDI  was  125  and  71   respectively.  PHQ-­‐15  was  16  and  8  respectively.  

In  placebo  group  the  median  value  for  IBS-­‐SSS  was  48,2  at  baseline  and  34,7  at   first  follow  up.  GSRS  scoring  was  41  and  33  respectively.  SF-­‐NDI  was  88  and  40   respectively.  PHQ-­‐15  was  8  and  5  respectively.  

 

In treatment group median value for IBS-QoL was 30,1 at baseline and 52,2 at first follow up. VSI scoring was 65 and 61 respectively. GAD-7 was 14 and 14

respectively. HADS anxiety score was 16 and 12 respectively; HADS depression score was 12 and 8 respectively. PHQ-9 was 12 and 6 respectively.

0 5 10 15 20 25 30 35

Key1 Key2 Key3 Key4 Key5 Key1 Key2 Key3 Key4 Key5 Key1 Key2 Key3 Key4 Key5

Patient P1 Patient P2 Patient P3

Placebo

Pressure mmHg

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  In placebo group median value for IBS-QoL was 82,4 at baseline and 93,4 at first

follow up. VSI scoring was 52 and 17 respectively. GAD-7 was 3 and 0 respectively. HADS anxiety score was 3 and 5 respectively; HADS depression score was 0 and 1 respectively. PHQ-9 was 4 and 3 respectively.

Table  2.  Individual  Results  in  GI-­‐symptomatic  Questionnaires.  

Patient IBS-SSS B IBS-SSS F1 IBS-SSS F2 GSRS B GSRS F1 GSRS F2 SF-NDI B SF-NDI F1 SF-NDI F2 PHQ-15 B PHQ-15 F1 PHQ-15 F2 T1 100,7 80,1 91,3 51 60 59 154 138 143 21 18 21 T2 110,7 71,2 133,2 56 33 61 125 71 105 16 7 14 T3 50,1 36,1 - 39 32 - 46 53 - 10 8 - P1 101,6 78,9 - 50 45 - 135 111 - 21 22 - P2 48,2 29,9 40,2 39 27 37 88 40 40 6 5 4 P3 37,4 34,7 - 41 33 - 35 34 - 8 5 -

Table  2.  Results  for  GI-symptomatic questionnaires. T and P stand for Treatment-patient and Placebo-patient respectively. Baseline (B), first follow up (F1) and second follow up (F2). IBS-SSS score ranging between 0-140, GSRS score ranging between 0-91, SF-NDI score ranging between 0-245. A higher score represents more severe GI-symptoms. PHQ-15 ranging between 0-30, a higher score indicates more severe somatic symptoms.

 

 

Table 3. Individual Results in Anxiety and GI-Specific Anxiety Questionnaires.

Patient IBS-QoL B IBS-QoL F1 IBS-QoL F2 VS I B VSI F1 VSI F2 GAD-7 B GAD-7 F1 GAD-7 F2 HADS B HADS F1 HAD S F2 PHQ-9 B PHQ-9 F1 PHQ-9 F2 T1 30,1 27,2 45,6 65 66 63 16 14 10 A18 D13 A12 D12 A13 D8 22 22 15

T2 13,2 52,2 27,9 73 61 65 14 15 10 A16 D12 A14 D8 A13 D8 12 6 8 T3 75 79,4 - 26 27 - 3 6 - A9 D3 A5 D1 - 5 4 - P1 58,8 58,8 - 52 56 - 11 15 - A11 D5 A16 D7 - 14 23 - P2 86 94,9 96,3 53 17 17 3 0 2 A3 D0 A5 D0 A3 D0 1 0 0 P3 82,4 93,4 - 19 6 - 0 0 - A1 D0 A0 D1 - 4 3 -

Table 3. Results for anxiety and GI-specific anxiety questionnaires. T and P stand for Treatment-patient and Placebo-patient respectively. Baseline (B), first follow up (F1) and second follow up (F2). GI-specific questionnaires: IBS-QoL ranging between 0-100, a higher score indicates higher life quality, VSI ranging between 0-75, a higher score indicates more severe GI-specific anxiety. Questionnaires of anxiety and depression: GAD-7 ranging between 0-21, HADS ranging between 0-21 in both anxiety (A) and depression (D) scores, PHQ-9 ranging between 0-27, a higher score indicates poorer mental health.

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DISCUSSION

 

Median values in both groups show similar trends. Median value in the placebo-group shows improvement in discomfort but worsening in pain from baseline to first follow up. There is an improvement in GI-symptoms and an improvement in anxiety; only HADS showed a small worsening. In treatment-group median values reports no difference in discomfort and a worsening in pain from baseline till first follow up, but there is an improvement in both GI-symptoms and anxiety. However the low number of patients, with only 3 patients in each group, does not allow preliminary

conclusions.

In treatment-group patient 1 (T1) showed worsening in visceral sensitivity at each follow up, but reported fewer GI-symptoms at first, at second follow up the symptoms had increased but were still lower or the same as in baseline. The questionnaires of anxiety and GI-specific anxiety showed no clear trend. Patient T2 showed no

difference in visceral sensitivity at first but reported an improvement in GI-symptoms and mental health. This patient reported a worsening in visceral sensitivity and GI-symptoms till the second follow up, with mixed result in the psychometric data. Patient T3 showed improvement in discomfort and pain at first follow up, but did not demonstrate a big improvement in GI-symptoms or in the psychometric data.

The results in the placebo-group were very similar; Patient 1 (P1) had an improvement in discomfort but worsening in pain, and reported a worsening in psychometric data, but a small decrease in GI-symptoms. Patient P2 showed no difference in discomfort and a worsening in pain, but reported fewer GI-symptoms and improvement in the psychometric data. Patient P3 showed improvement in visceral sensitivity, but no direct or little improvement in GI-symptoms and in the psychometric data.

Until now, the results do not show differences in descriptive data between groups, and the low number of patients does not allow non-parametric statistics.

The limitations of this study are dominated by the low number of patients included. This is a mechanistic pilot study and no other study has been made on the subject. Because of lack of data, it is not possible to perform an exact and formal sample size

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  calculation. Based on earlier IBS-barostat studies, a power calculation has been

performed and it was estimated that a minimum of 24 patients have to be included. Hence, 6 patients are not sufficient for an accurate conclusion.

As the study takes 9 weeks for each patient, including several hospital visits,

completion of the whole study is time-consuming, and was also limited by the amount of barostat-equipment and personnel operating it. The duration and amount of time for each examination may be a reason for patients not to participate or to withdraw from the study. Two of the 8 patients asked to participate chose not to because of lack of time, and two patients, one treatment and one placebo, did not go through the second follow before the study ended.

The study is semi blinded. Patients were told that they would receive treatment or placebo; that they would receive NaCl or Solu-Cortef, and either an inflation or a flat barostat protocol, but not in which combination. One weakness in this is that the treatment protocol compared to the “sham-procedure” differs a lot in sensation, and patients could figure out and it could affect the results.

A well-known problem is that IBS-patients often show fluctuating symptoms, some periods worse than others. Fluctuation in anxiety and mood can also influence the results. In some of the patients in this study there occurred troublesome life events during the study period, which could influence GI- and anxiety-symptoms.

The study is a mechanistic pilot study and there is yet no other data on the magnitude and variation of GEET on visceral perception using the barostat protocol. It can, however, not be excluded that another design would be more effective and show different results.

However, this study explores a new territory and lays a good foundation for further research. Inclusion of more patients, and further exploration of variation in treatment, could answer if GEET is a possible treatment for IBS. A continuation could also investigate if there is a difference in treatment result between sexes. Or if any

personality type benefits more from treatment than others, considering the great result in studies of GEET in treating anxiety disorders like acrophobia.

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Conclusion    

Until now we have included 6 patients, this number does not allow non-parametric statistics. Descriptive statistics do not show differences in visceral sensitivity, GI-symptoms and anxiety between placebo and treatment group. Further inclusion of subjects is needed for a final conclusion.

Acknowledgements

I would like to give a special thanks to my supervisor Michiel van Nieuwenhoven for introducing me to this interesting project, for the help with forming this study, and for all the guidance in with the result and paper. I would also like to give my warmest thanks to the Endoscopy Unit at Örebro University Hospital for all the help with the Barostat, and for making room to perform the examinations. My final thanks goes to all the personnel at the gastroenterology outpatient clinic at Örebro University Hospital for the helping hand and warm welcome.

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23. Cascade E, Kalali AH, Kennedy SH. Real-World Data on SSRI Antidepressant Side Effects. Psychiatry (Edgmont) 2009 Feb;6(2):16-18.

24. Kelly K, Posternak M, Alpert JE. Toward achieving optimal response:

understanding and managing antidepressant side effects. Dialogues Clin Neurosci 2008;10(4):409-418.

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Appendix A: ROME III

   

FRÅGOR OM BESVÄR  

RELATERADE TILL  

MAGEN/BUKEN  

 

 

ROME III  

                         

ROME III – Svensk vers 1.0: Magnus Simrén och Anna Rydén, Sahlgrenska Universitetssjukhus, Göteborg   Originalvers: D A Drossman, E Corazziari, M Delvaux, R C Spiller, N J Talley, W G Thompson, W E Whitehead.  

   

 

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1. Under de 3 senaste månaderna, hur ofta har Du haft obehag eller ont i magen/buken?  

 

0=avsluta  

2. För kvinnor: Kände Du det här obehaget eller smärtan i samband med menstruationen men inte annars?  

   

3. Har Du känt det här obehaget eller smärtan 6 månader eller längre?  

   

 

4. Hur ofta blev obehaget/smärtan bättre eller upphörde helt när Du tömt tarmen?  

 

 

5. När den här obehaget/smärtan började, fick Du då tömma tarmen oftare?  

 

 

6. När den här obehaget/smärtan började, fick Du då tömma tarmen mer sällan?  

 

 

 

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TACK FÖR DIN MEDVERKAN!  

7. När den här obehaget/smärtan började, var Din avföring lösare än vanligt?  

   

8. När den här obehaget/smärtan började, hur ofta var Din avföring hårdare än vanligt?  

   

9. Under de 3 senaste månaderna, hur ofta har Din avföring varit hård eller klumpig?  

   

10. Under de 3 senaste månaderna, hur ofta har Din avföring varit lös, grötig eller vattning?  

 

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Appendix B: SOP Rectal Barostat

 

SOP:  Rectal  barostat  

 

After  an  overnight  fast,  the  subjects  present  to  the  laboratory  at  7.30  a.m.  They  receive   a  cleansing  tap  water  enema  (750mL)  and  after  bowel  emptying,  they  are  placed  in  a   left  lateral  decubitus  position  in  a  hospital  bed  tilted  by  15°.  Put  a  pillow  between  legs   and  offer  several  pillows  to  go  under  the  head  to  make  patients  more  comfortable.    A   rectal  barostat  catheter  with  a  polyethylene  bag  attached  will  be  inserted  into  the   rectum  so  that  the  middle  of  the  bag  is  located  approximately  10  cm  from  the  anal   verge,  and  the  barostat  catheter  will  be  taped  to  the  buttocks.  The  catheter  is  to  be   inserted  following  lubrication  of  the  catheter  and  barostat  bag  with  KY  jelly  (or  similar   non-­‐anesthetic  lubricant).  Digital  examination  may  be  performed  for  catheter  

insertion,  but  is  not  strictly  required.  No  endoscopic  insertion  aids  are  to  be  used  for   catheter  placement.  The  barostat  bag  is  then  unfolded  by  transiently  inflating  it  with75   mL  of  air  and  subsequently  deflating  it  completely  but  leaving  it  in  situ.  Flow  rate  for   barostat  inflations  32  ml/s.  

After  a  20–30  min  recovery  period,  the  catheter  is  connected  to  a  barostat  and  the   pressure  in  the  bag  increased  from  4  mmHg  in  steps  of  1  mmHg  for  1  min  per  step  until   respiratory  excursions  are  observed.  The  baseline  operating  pressure  (BOP)  is  defined   as  2  mmHg  above  the  minimal  distension  pressure  at  which  respiratory  excursions  are   clearly  recorded  from  the  barostat  tracing.  If  respiratory  variations  are  not  seen  by  18   mmHg,  BOP  is  set  at  12  mmHg.  Next,  an  initial  “conditioning“  distension  of  the  rectum   will  be  performed  in  which  the  pressure  is  increased  from  0  mmHg  to  20  mmHg  in   steps  of  4  mmHg  for  15  sec  per  step.  Subsequently,  the  bag  is  deflated  to  0  mmHg  but   left  in  situ,  and  the  patients  are  allowed  to  rest  for  10  min  before  proceeding  to  the   ascending  method  of  limits  (AML)  protocol.  

 

Ascending  Method  of  Limits  (AML)  protocol  

Sensory  pressure  thresholds  and  colorectal  compliance  will  be  measured  by  ramp   inflation,  starting  at  0  mmHg  and  increasing  in  steps  of  4  mmHg  for  1  min  per  step  to  a   maximum  of  60  mmHg.  Thresholds  for  first  sensation,  first  desire  to  defecate,  urgency,   discomfort  and  pain  will  be  indicated  by  the  patients  by  pressing  a  button  at  the   distension  pressure  at  which  sensations  are  perceived.  Ramp  inflation  is  terminated  as   soon  as  the  patients  report  the  first  sensation  of  pain.  Following  this  procedure,  the  bag   is  deflated  to  BOP  and  left  in  situ,  and  the  patients  are  allowed  to  rest  for  10  min,  then   the  random  phasic  distensions  (RPD)  protocol  will  be  conducted.  

 

Random  Order  Phasic  Distensions  (RPD)  protocol  

Phasic  distensions  of  12,  24,  36  and  48  mmHg  above  BOP  will  be  each  applied  once  in  a   random  order.  The  maximum  pressure  to  be  used  for  RPD  is  limited  by  the  pain  

threshold  from  the  previous  AML,  so  that  only  the  next  higher  pressure  should  be   applied  for  RPD  (e.g.  if  pressure  threshold  in  AML  is  30  mmHg  above  BOP,  use  12,  24   and  36  mmHg  above  BOP,but  not  48  mmHg  above  BOP).  Each  distension  will  be   maintained  for  60  sec  with  an  interstimulus  interval  of  2  min  during  which  the  bag  is   deflated  to  BOP.  The  subjects  will  rate  the  intensity  of  four  different  sensations  during   the  last  30  sec  of  each  distension  (gas,  urgency,  discomfort  and  pain).  

         

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  Outcome  variables:  

• The  sensory  thresholds  for  first  sensation,  first  desire  to  defecate,  urgency,   discomfort  and  pain  during  AML;  i.e.,  the  barostat  pressures  [mmHg]  at  which   the  patients  press  the  button  to  signal  perception  of  the  corresponding  

sensation,  and  the  corresponding  balloon  volumes  (ml).  

• The  aggregate  sensation  intensity  scores  for  gas,  urgency,  discomfort  and  pain  in   response  to  the  four  random  phasic  distensions  during  RPD  (12,  24,  36  and  48   mmHg  above  baseline  operating  pressure  (BOP));  i.e.,  the  visual  analogue  scale   (VAS)  scores  [mm]  marked  by  the  patients  at  each  distension.  

• Colorectal  compliance,  summarized  as  the  distension  pressure  Pr1/2  [mmHg]  at   half  of  the  maximum  observed  volume  of  the  barostat  bag  during  AML.  A  

pressure-­‐volume  curve  will  also  be  created  during  the  AML  distension  (balloon   volume  during  the  last  10  sec  of  each  pressure  step).  

 

Definition  of  sensations  to  be  recorded  during  AML  and  RPD    

Patients  will  be  given  instructions  separately  before  AML  and  RPD.  During  the  AML   there  should  be  no  interaction  between  operator  and  patient,  i.e.  just  let  the  patient   select  the  AML  sensation  via  the  keypad  as  indicated  in  the  script.  

NOTE:  For  AML,  sensations  are  to  be  reported  if  they  occur  immediately  after  balloon   inflation.  The  5  sensation  pressure  thresholds  do  not  have  to  occur  according  to  their   numerical  order.  If  any  sensation  buttons  are  not  hit  during  AML,  report  sensation  as   greater  than  60  mmHg.  

For  RPD,  a  prompt  should  be  given  approximately  30  seconds  into  the  distension   indicating  that  the  subject  should  now  complete  the  4  VAS  supplied  by  the  operator  for   each  distension.  

If  on  the  pain  VAS  the  subject  scores  greater  than  80mm,  the  distension  is  to  be   immediately  aborted  and  no  higher  pressures  are  to  be  applied.  

NOTE:  Due  to  the  AML-­‐based  cap  to  applied  pressures,  patients  may  not  receive  all  4   distension  pressures.  Please  briefly  instruct  patients  prior  to  each  RPD  session  how   many  distensions  to  expect  (may  vary).  Distensions  are  to  be  numbered  consecutively,   even  if  you  skip  distension(s)  from  the  applicable  randomization  scheme  (i.e.  if  you  use   3  distensions,  you  will  have  distensions  #1,  2  and  3;  if  you  use  2  distensions,  you  will   have  distensions  #1  and  2  only.  Please  cross  out  any  omitted  distensions  on  the   randomization  list  to  be  part  of  the  source  documents).  

   

Definition  of  volumes  for  compliance  calculations  to  be  recorded  during  AML   Volumes  recorded  for  compliance  should  reflect  average  volume  during  the  2nd  30  sec   period  of  each  AML  step  reached  during  the  procedure.  

NOTE:  This  applies  only  for  non-­‐painful  balloon  distensions.  For  the  last  (painful)   pressure  exerted  during  AML,  the  following  rules  apply:  

a.  If  pressure  applied  for  >  30  sec,  average  last  30  sec;   b.  If  pressure  ≤  30  sec,  average  last  15  sec;  

c.  If  pressure  <  15  sec,  average  last  5  sec  if/where  the  volume  has  stabilized  (<10%   volume  change)  

d.  If  none  of  the  above  applies,  skip  value  and  make  a  note    

   

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Suggested  patient  script    

On  arrival  outline  the  procedure  to  the  patient  

•  Today  we  will  ask  you  some  questions  about  your  IBS  and  your  bowel  habits.   •  We  will  then  give  you  a  saline  enema  to  clean  out  the  lower  part  of  your  bowel.   •  One  hour  after  this  we  will  put  the  barostat  catheter  in  place.  

•  You  will  be  asked  to  lie  on  your  left  hand  side  with  your  legs  bent.  After  a  brief  rectal   examination  the  catheter  will  be  eased  gently  into  place.  

•  The  catheter  consists  of  a  thin  flexible  tube  with  a  polythene  bag  attached  at  the  end.   The  bag  will  be  inflated  slowly  with  a  little  air  and  then  deflated  to  ensure  that  it  is   lying  correctly.  

•  After  about  20  minutes  we  will  start  the  barostat  procedure.  First  of  all  only  small   amounts  of  air  will  be  put  into  the  bag  till  we  have  established  the  baseline.  Then  a   “conditioning”  step  will  follow,  when  the  pressure  in  the  bag  will  increase  stepwise  for   15  seconds  per  step.  

•  The  bag  is  then  deflated  and  there  is  a  10  minute  rest  period.    

 

Ascending  Method  of  Limits    

General  guidance  

•  During  the  next  part  of  the  test  I  will  not  be  able  to  talk  to  you  but  I  will  give  you  full   instructions  beforehand.  

•  Increasing  amounts  of  air  will  be  put  into  the  bag  and  you  will  be  given  a  keypad  to   register  the  sensations  that  you  feel.  The  air  will  then  be  removed  and  you  will  have  a   10  minute  rest.  

 

Instructions  given  before  AML  

•  This  part  of  the  study  must  be  done  with  a  minimum  of  interaction  between  you  and   me,  so  I  will  not  be  able  to  speak  to  you  unless  there  is  a  problem.  

•  The  bag  will  now  be  inflated  with  increasing  amounts  of  air  for  1  minute  before  going   on  to  the  next  inflation.  Here  is  a  keypad  with  labelled  buttons.  

•  We  ask  that  you  press  these  buttons  when  you  first  feel  a  particular  sensation.   o  First  Sensation  –  press  the  first  time  you  feel  something  different.  

o  First  Desire  to  Defecate  (pass  a  bowel  movement)  -­‐  press  the  first  time  you   feel  this  desire.  

o  Urgency  –  press  when  you  feel  that  you  would  have  to  stop  what  you  are  doing   to  have  a  bowel  movement  immediately.  

o  Discomfort  –  press  if  you  feel  discomfort.   o  Pain  –  press  if  you  feel  pain.  

•  As  soon  as  you  press  the  pain  button  the  inflations  will  stop  and  the  bag  will  be   deflated.  

•  You  may  not  feel  all  of  these  sensations  and  you  won’t  necessarily  feel  them  in  the   order  of  the  buttons.  You  will  be  given  a  card  with  the  explanation  for  each  button  on  to   remind  you  of  the  sensations  that  we  are  asking  about.  

•  It  is  important  for  you  to  know  that  although  during  this  procedure/test  you  will  feel   that  you  need  to  have  a  bowel  movement,  you  will  not,  as  it  is  only  the  inflation  of  the   bag  that  makes  you  feel  the  sensation.  

       

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Random  Phasic  Distension  (RPD)    

General  guidance  

•  During  this  final  part,  the  bag  will  be  inflated  to  four  different  pressures  in  a  random   order  with  a  short  rest  between  each  inflation.  

•  You  will  be  given  a  score  sheet  to  record  your  rating  of  what  you  feel.   •  The  tube  will  then  be  removed  and  you  will  be  finished  for  this  visit.    

Instructions  given  before  RPD  

•  During  this  section  the  bag  will  be  inflated  to  four  different  levels  in  a  random  order.   •  30  seconds  after  the  bag  has  been  inflated  I  will  hand  you  a  sheet  of  paper.  

•  On  the  sheet  there  will  be  4  lines:  one  for  gas,  one  for  urgency,  one  for  discomfort  and   one  for  pain.  

•  We  want  you  to  mark  on  each  line  your  sensation  score  for  each  of  the  different   sensations,  with  no  sensation  on  the  left,  going  up  to  unbearable  on  the  right.  

•  For  instance  if  it  felt  like  you  had  a  lot  of  gas  that  needed  to  be  passed  you  would  put  a   vertical  mark  on  the  line  far  over  towards  the  right  hand  side,  corresponding  to  the   level  of  gas  you  felt.  

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Appendix C: Questionnaires of GI-symptoms

IBS-SSS

 

   IBS symptom Severity Scale

Namn _________________________________________________ Datum ______________ Endast för

Ålder _________ Kön (ringa in): M F Annat __________________________

summa:

Det här formuläret är utformat för att mäta och utvärdera graden av din IBS. Det är rimligt att dina symptom varierar över tid, besvara därför frågorna utifrån hur du för tillfället känner dig (dvs. under de senaste 10 dagarna ungefär). All information behandlas strikt konfidentiellt.

1. a) Lider du för tillfället av magsmärtor? b) Om ja, hur kraftiga är dina magsmärtor?

0 % 100 %

Ingen smärta Inte så kraftig Ganska kraftig Kraftig Mycket kraftig

c) Vänligen fyll i antalet dagar som du har smärta under en 10-dagars period. Om du till exempel skriver 4 betyder det att du har smärta under 4 av 10 dagar. Om du har smärta varje dag så skriver du 10.

X 10 Antalet dagar med smärta:

2. a) Är du för tillfället uppblåst i magen?

(till exempel uppsvälld, svullen eller spänd i magen.

För kvinnor- ignorera eventuell uppblåsthet under menstruationen)

b) Om ja, hur allvarlig är uppblåstheten/spändheten i magen?

0 % 100 %

Ingen uppblåsthet Inte så kraftig Ganska kraftig Kraftig Mycket kraftig

3. Hur nöjd är du med dina avföringsmönster?

0 % 100 %

Mycket nöjd Ganska nöjd Missnöjd Mycket missnöjd

4. Vänligen indikera på linjen nedan med ett kryss hur mycket IBS generellt sett påverkar eller stör ditt liv.

0 % 100 %

Inte alls Inte mycket Ganska mycket Helt och hållet

Ja Nej

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GSRS-IBS                

THE GASTROINTESTINAL SYMPTOM RATING SCALE (GSRS)

Undersökningen innehåller frågor om hur Du mår och hur Du har haft det DEN SENASTE VECKAN. Markera med ett kryss X det alternativ som bäst passar in på Dig och Din situation.

Inga besvär alls Obetyd-liga besvär Milda besvär Måttliga besvär Ganska svåra besvär Svåra besvär Mycket svåra besvär

1. Har du under den senaste veckan besvärats av ont i magen?

2. Har du under den senaste veckan besvärats av smärta eller obehag i magen som blir bättre när du tömmer tarmen?

3. Har du under den senaste veckan besvärats av en känsla av uppkördhet i magen? 4. Har du under den senaste veckan besvärats

av att du släpper ut gaser?

5. Har du under den senaste veckan besvärats av förstoppning? (problem med att tömma tarmen.)

6. Har du under den senaste veckan besvärats av många tarmtömningar per dag?

7. Har du under den senaste veckan besvärats av lös avföring?

8. Har du under den senaste veckan besvärats av hård avföring?

9. Har du under den senaste veckan besvärats av trängande avföringsbehov? (bråttom till toaletten.)

10. Har du under den senaste veckan besvärats av en känsla av att du inte riktigt kan tömma tarmen?

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11. Har du under den senaste veckan besvärats av att du känt dig mätt innan du har ätit färdigt? (blir fort mätt.)

12. Har du under den senaste veckan besvärats av att du känt dig mätt länge efter att du ätit (färdigt)?

13. Har du under den senaste veckan besvärats av att magen svullnar så att det syns?

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SF-NDI

 

NEPEAN DYSPEPSI FRÅGEFORMULÄR

- KORTVERSION

SF-NDI

®

Tack för att du hjälper oss med den här undersökningen. Det här frågeformuläret innehåller detaljerade frågor om dina magbesvär och hur de påverkar dig och ditt liv.

En del av frågorna är ganska personliga, men informationen som du lämnar kommer att behandlas med sekretess och känslighet.

                                       

SF-NDI© Nicholas J Talley, 1998

Detta är den ÖVRE DELEN AV BUKEN (magen)  

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Nepean dyspepsi frågeformulär - kortversion (SF-NDI)©

 

Var vänlig SKRIV SIFFROR i tabellen nedan för att ange hur ofta du har haft magbesvär under de senaste 14 DAGARNA och hur intensiva och besvärande de har varit. Illustrationen på framsidan visar den ”ÖVRE DELEN AV BUKEN” – var vänlig titta på illustrationen när du svarar på frågor om besvär i den ”ÖVRE DELEN AV BUKEN”.  

Under de senaste 14 dagarna, hade du något av

följande MAGBESVÄR?

Hur MÅNGA DAGAR hade du

det? 0  =  Inga  alls   1  =  En  till  fyra  dagar   2  =  Fem  till  åtta  dagar   3  =  Nio  till  tolv  dagar   4  =  Varje  dag/nästan  

varje  dag  

Om du upplevde detta symptom, hur INTENSIVT var

det vanligtvis? 0  =  Inte  alls   1  =  Väldig  svagt   2  =  Svagt   3  =  Måttligt   4  =  Kraftigt   5  =  Väldigt  kraftigt   Om du upplevde detta symptom, hur BESVÄRANDE var det? 0  =  Inte  alls   1  =  Lite  grann   2  =  Måttligt   3  =  Mycket   4  =  Extremt  mycket  

Smärta  eller  värk  i  den  övre  delen  av  

buken  (magen)        

Obehag  i  den  övre  delen  av  buken  

(magen)        

Brännande  känsla  i  den  övre  delen  av  

buken  (magen)        

Brännande  känsla  i  bröstet  (halsbränna)         Kramper  i  den  övre  delen  av  buken  

(magen)        

Smärta  eller  värk  i  bröstet,  ovanför  

magen        

Oförmåga  att  avsluta  en  vanlig  måltid         Bitter/sur  vätska  som  kommer  upp  i  din  

mun  eller  hals        

Tidig  mättnadskänsla  vid  måltid  eller  

långsam  matsmältning        

Tryck  i  den  övre  delen  av  buken  (magen)        

Känsla  av  uppsvälldhet  i  magen        

Illamående        

Rapningar        

Kräkningar        

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Spänningar    

1. Har ditt ALLMÄNNA KÄNSLOMÄSSIGA VÄLBEFINNANDE blivit stört av dina

magbesvär under de senaste 14 dagarna?   1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket  

2. Har du varit LÄTTRETLIG, SPÄND eller FRUSTRERAD under de senaste 14 dagarna på grund av dina magbesvär?

  1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket    

Störning  av  dagliga  aktiviteter  

3. Har din FÖRMÅGA att engagera dig i saker som du vanligtvis gör som

FRITIDSAKTIVITET (som rekreation, uteliv, hobbies, sport mm) blivit störd av dina magbesvär under de senaste 14 dagarna?

  1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket

4. Har din GLÄDJE av det du vanligtvis gör som FRITIDSAKTIVITET (som rekreation, uteliv, hobbies, sport mm) blivit störd av dina magbesvär under de senaste 14 dagarna?   1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket

6 Ej tillämpligt (Jag har inte kunnat göra någon av dessa saker under de senaste 14 dagarna, på grund av mina magbesvär)

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Att  äta/dricka  

5. Har din FÖRMÅGA att ÄTA eller DRICKA (inklusive när, vad och hur mycket) blivit störd av dina magbesvär under de senaste 14 dagarna?

  1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket

6. Har din GLÄDJE av att ÄTA och/eller DRICKA störts av dina magbesvär under de senaste 14 dagarna? (Inkludera din aptit och hur du mår efter mat eller dryck).   1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket    

Kunskap  om/kontroll  över  magbesvären  

   

7. Under de senaste 14 dagarna, har du UNDRAT om du ALLTID kommer att ha de här magbesvären?   1 Nästan aldrig 2 Ibland 3 Ofta 4 Väldigt ofta 5 Ständigt  

8. Under de senaste 14 dagarna, har du UNDRAT om dina magbesvär kan bero på en mycket ALLVARLIG sjukdom (såsom cancer eller hjärtproblem)?   1 Nästan aldrig 2 Ibland 3 Ofta 4 Väldigt ofta 5 Ständigt

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Arbete/hushållsarbete/studier  

   

9. Har din FÖRMÅGA att ARBETA, STUDERA eller göra HUSHÅLLSARBETE

störts av dina magbesvär under de senaste 14 dagarna?   1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket

6 Ej tillämpligt (Jag har inte arbetat, studerat eller gjort

hushållsarbete under de senaste 14 dagarna, på grund av mina magbesvär)

   

10. Har din GLÄDJE av att ARBETA, STUDERA eller göra HUSHÅLLSARBETE

störts av dina magbesvär under de senaste 14 dagarna?   1 Inte alls 2 Lite grann 3 Måttligt 4 Mycket 5 Extremt mycket

6 Ej tillämpligt (Jag har inte arbetat, studerat eller gjort

hushållsarbete under de senaste 14 dagarna, på grund av mina magbesvär)

   

Poängräkning:  Summera  poängen  för  vart  och  ett  av  de  fem  områdena  (varje  område  kan  få  2-­‐10   poäng).  

 

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PHQ-15

 

 

 

FYSISKA SYMTOM

(PHQ-15)

Hur mycket har du besvärats av något av följande symptom under de senaste fyra veckorna?

Inte alls

(0) Något (1) Mycket (2)

a. Ont i magen b. Ryggsmärta

c. Smärta i armar, ben eller leder (knän, höfter o.s.v.) d. Kramp eller andra problem vid menstruation

ENDAST KVINNOR

e. Huvudvärk

f. Smärta i bröstkorgen g. Yrsel

h. Svimningsanfall

i. Känning av hjärtklappning eller att hjärtat slår häftigt j. Andfåddhet

k. Smärta eller problem vid samlag l. Förstoppning, lös avföring eller diarré m. Illamående, gas- eller matsmältningsbesvär n. Trötthetskänsla eller brist på energi

o. Svårt att sova

(For office coding: Total Score T_____ = _____ + _____ )

Utvecklat av Dr. Robert L. Spitzer, Janet B.W. Williams, Kurt Kroenke och kolleger, med ett utbildningsbidrag från Pfizer Inc. Ingen behörighet att reproducera, översätta, visa eller distribuera.

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Appendix  D:  Questionnaires  of  anxiety  

 

IBS-­‐Quality  of  Life  

 

Om  hur  du  känner  dig  

Tänk på ditt liv under den senaste månaden (senaste 30 dagarna), och titta på påståendena nedan. Varje påstående har fem olika svar. För varje påstående, ringa in det svar som bäst beskriver dina känslor.

Inte alls

Lite Måttligt Mycket Väldigt mycket

1 2 3 4 5

1. Jag känner mig hjälplös på grund av mina tarmproblem.

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2. Jag är generad över lukten orsakad av mina tarmproblem.

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3. Jag är besvärad av hur mycket tid som jag spenderar på toaletten.

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4. Jag känner mig sårbar för andra sjukdomar på grund av mina tarmproblem.

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5. Jag känner mig tjock/uppsvälld på grund av mina tarmproblem.

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6. Jag känner att jag håller på att tappa kontrollen över mitt liv på grund av mina tarmproblem.

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7. Jag känner att mitt liv känns mindre njutbart på grund av mina tarmproblem.

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8. Jag känner mig obehaglig till mods när jag talar om mina tarmproblem.

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9. Jag känner mig nedstämd på grund av mina tarmproblem.

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10. Jag känner mig isolerad från andra på grund av mina tarmproblem.

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11. Jag måste se upp med den mängd mat jag äter på grund av mina tarmproblem.

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12. Sexuella aktiviteter/intimitet är besvärligt för mig på grund av mina tarmproblem. (Om ej tillämplig,

markera in "INTE ALLS").

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13. Jag känner mig arg för att jag har tarmproblem.

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1. Jag känner att jag irriterar andra på grund av mina tarmproblem.

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2. Jag oroar mig för att mina tarmproblem skall förvärras.

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3. Jag känner mig lättretlig på grund av mina tarmproblem.

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Inte

alls

Lite Måttligt Mycket Väldigt mycket 1 2 3 4 5

4. Jag oroar mig för att folk tycker att jag överdriver mina tarmproblem.

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5. Jag känner att jag får mindre gjort på grund av mina tarmproblem.

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6. Jag måste undvika stressande situationer på grund av mina tarmproblem.

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7. Mina tarmproblem minskar sexlusten.

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8. Mina tarmproblem begränsar vad jag kan ha på mig.

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9. Jag måste undvika fysiskt ansträngande aktiviteter på grund av mina tarmproblem.

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10. Jag måste se upp med vilken sorts mat som jag äter på grund av mina tarmproblem.

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11. På grund av mina tarmproblem har jag svårt för att vara bland folk jag inte känner väl.

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12. Jag känner mig slö på grund av mina tarmproblem.

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13. Jag känner mig inte riktigt fräsch på grund av mina tarmproblem.

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14. Långa resor är svåra för mig på grund av mina tarmproblem.

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15. Jag känner mig frustrerad över att jag inte kan äta när jag vill på grund av mina tarmproblem.

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16. Det är viktigt att vara nära en toalett på grund av mina tarmproblem.

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17. Mitt liv kretsar kring mina tarmproblem.

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18. Jag oroar mig över att förlora kontrollen över mina tarmtömningar.

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19. Jag är rädd för att jag inte skall kunna ha en tarmtömning.

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20. Mina tarmproblem påverkar mina närmaste relationer.

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21. Jag tycker att ingen förstår mina tarmproblem.

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Figur

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Referenser

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