Health-related quality of life (HRQOL) is widely

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006;4: Health-Related Quality of Life in Patients Attending a Gastroenterology Outpatient Clinic: Functional Disorders Versus Organic Diseases MAGNUS SIMRÉN,* JAN SVEDLUND, IRIS POSSERUD,* EINAR S. BJÖRNSSON,* and HASSE ABRAHAMSSON* *Department of Internal Medicine and Section of Psychiatry, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg, Sweden Background & Aims: Several gastrointestinal (GI) disorders have major effects on health-related quality of life (HRQOL), but there are few direct comparisons between functional GI disorders and organic GI diseases. This study aimed to compare HRQOL between these 2 groups and to assess factors of importance for HRQOL. Methods: Three hundred ninety-nine consecutive patients attending a GI outpatient clinic completed HRQOL instruments (Short Form 36 [SF-36] and Psychological General Well-Being index [PGWB]) and the Gastrointestinal Symptom Rating Scale (GSRS). For the analyses we divided the patients into 2 diagnostic groups: functional GI disorders (n 112) and organic GI diseases (n 287). Results: Compared with norm values on SF-36 and PGWB, both patient groups exhibited profound reductions in HRQOL. After correcting for age, gender, and disease duration, patients with a functional GI disorder had significantly lower scores than patients with an organic GI disease on 6 of 8 SF-36 domains and 5 of 6 PGWB domains. Vitality and anxiety on PGWB, abdominal pain and diarrhea on GSRS, age, and gender independently contributed to the physical component score of SF-36 (adjusted R 2 32%). Patients with a functional GI disorder had more severe reflux, abdominal pain, constipation, and indigestion, but the severity of diarrhea did not differ between the groups. HRQOL was reduced with increasing severity of GI symptoms. Conclusion: GI disorders have profound effects on HRQOL, and the impact is greater in patients with functional GI disorders as compared with organic GI diseases. The reduction in HRQOL is associated with the severity of both psychological and GI symptoms. Health-related quality of life (HRQOL) is widely perceived to be a useful concept in clinical research that emphasizes the patient s perspective of the illness. It encompasses several areas, such as physical function, somatic sensation, psychological state, and social interactions, that are affected by the health status of the individual. 1 It has been reported that health care professionals often make poor predictions of the health status perceived by the patients. 2 Therefore, other tools are needed to fully appreciate the health status of patients, and HRQOL assessment has been shown to be of great value. Generic HRQOL instruments, such as the Short- Form 36 (SF-36) 3 and the Psychological General Well- Being (PGWB) index, 4 are advantageous because they allow for comparisons between different kinds of disorders, as well as with the general population. 5,6 Patients attending gastroenterology outpatient clinics often have long-lasting or chronic conditions, such as inflammatory bowel disease or functional gastrointestinal (GI) disorders. It is well-known that patients with chronic conditions often have profound reductions in HRQOL, 7 which is also true for chronic GI disorders. Patients with IBD have convincingly been shown to have reduced HRQOL as compared with healthy control subjects, and this is true for physical, social, and emotional function. 2,8,9 Moreover, of patients with IBD, patients with Crohn s disease in general tend to have greater impairment in HRQOL than those with ulcerative colitis, 2 and patients with active disease have more severe reduction than those in clinical remission. 9 The HRQOL in patients with IBD in long-standing remission is similar to that observed in the general population. 10 Whitehead et al 11 were the first to demonstrate reduced HRQOL by using the SF-36 in patients with irritable bowel syndrome (IBS) as compared with the general population. These results have been confirmed in more recent studies, in which it has been demonstrated that patients with IBS have reductions in HRQOL compara- Abbreviations used in this paper: GI, gastrointestinal; GSRS, Gastrointestinal Symptom Rating Scale; HRQOL, health-related quality of life; IBS, irritable bowel syndrome; PCS, Physical Component Score; PGWB, Psychological General Well-Being; QOL, quality of life; SEM, standard error of the mean; SF-36, Short Form by the American Gastroenterological Association Institute /06/$32.00 PII: /S (05)00981-X

2 188 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 2 ble with patients with medically more severe diseases. 12,13 In addition, patients with other functional GI disorders exhibit reduced HRQOL compared with the general population. 14,15 Direct comparisons of the HRQOL between functional and organic GI disorders in the same clinical setting are scarce. A study in a tertiary care gastroenterology clinic assessed the health status by GI diagnosis and abuse history and found that independent of the abuse history, patients with a functional diagnosis had greater pain severity and psychological distress and poorer daily function. 16 However, a recent Italian study demonstrated comparable HRQOL in IBS and IBD patients attending a GI outpatient clinic. 17 Therefore, although it might be fair to say that patients with either functional or organic GI disorder have reduced HRQOL, it has yet to be determined whether there are any differences between these 2 groups. Therefore, the main aim of the present study was to compare HRQOL in patients with functional GI disorders and organic GI diseases attending our gastroenterology outpatient clinic and to assess to what extent the perceived severity of GI symptoms differed between these groups and influenced the HRQOL. Methods Subjects Six hundred consecutive patients with a chronic ( 3 months duration) GI disorder, attending our university-based gastroenterology outpatient clinic, were invited to participate in the study. Patients attending our outpatient clinic on a regular basis are mainly patients with an organic GI disease, whereas patients with a functional GI disorder are referred to the clinic from general practitioners and referred back to primary care after 1 or 2 visits at our unit. Patients referred from other gastroenterologists are rare in our health care system, but a small minority of such patients was also included in this sample. The patients were informed of the study by one of the nurses, while waiting to see their gastroenterologist at the hospital. Exclusion criteria included age younger than 18 years, comorbid severe cardiovascular, renal, psychiatric, or neurologic disease or active malignancy, hepatic disease as the primary cause for attending the outpatient clinic, and difficulty understanding written Swedish. Of the 600 patients approached, 440 (73%) agreed to participate. Of these, 41 were excluded because of uncertain diagnoses or complicating non-gi disease, leaving 399 patients to be included in the final analyses (67% of those invited to participate). No significant differences regarding age, gender, or disease type were observed between the responders and non-responders (data not shown). Subjects completed 4 self-administered questionnaires (see below) at the hospital, but a small proportion of the subjects completed them at home and returned them by mail. All subjects gave informed consent, and the study was approved by the ethics committee of the University of Göteborg. Questionnaires The following four questionnaires were completed by the subjects. Short Form 36. This generic HRQOL instrument was developed as a comprehensive measure of general health status for use in the Medical Outcomes Study 7 and has been thoroughly tested for validity and reliability. 3,18,19 This questionnaire assesses the extent to which an individual s health limits physical, emotional, and social functioning. It consists of 8 domains: physical functioning (10 items), role limitations caused by physical health problems (4 items), bodily pain (2 items), general health perceptions (5 items), vitality (4 items), social functioning (2 items), role limitations caused by emotional problems (3 items), and mental health (5 items). One item also evaluates the change in the respondent s health during the preceding year. The SF-36 is scored from 0 100, with higher scores indicating better HRQOL. Data can also be provided as physical and mental component scores. 20 There are normative data from the Swedish general population available, as well as thorough assessment of validity and reliability of the Swedish version of SF Psychological general well-being index. The PGWB index was developed as a self-report instrument measuring subjective well-being or distress. 4 Extensive documentation with regard to reliability and validity is available. 4,24 26 Compared with other generic HRQOL instruments, it covers mainly the psychosocial and emotional side of HRQOL. The PGWB includes 22 items that, in addition to combining into an overall global score, are divided into 6 dimensions: anxiety (5 items), depressed mood (3 items), positive well-being (4 items), self-control (3 items), general health (3 items), and vitality (4 items). Total scores range from , with higher scores indicating better psychological well-being. Normative data for the PGWB index are available for the Swedish general population. 27 Gastrointestinal symptom rating scale. The Gastrointestinal Symptom Rating Scale (GSRS), a measure of perceived severity of GI symptoms, was initially developed as an interview-based rating scale for symptoms occurring in patients with IBS and peptic ulcer 28 and later modified into a self-administered questionnaire. The GSRS consists of 15 items, which are grouped into 5 domains: reflux, indigestion, diarrhea, constipation, and abdominal pain. Its validity and reliability are thoroughly documented in several publications. 29,30 The higher the score, the more severe the symptoms. Demographic and disease-related data. A questionnaire evaluating different demographic data, such as marital status, employment, living conditions, educational level, and smoking and drinking habits, was also administered to the patients. Information regarding the diagnosis and disease activity was obtained from the patient s charts. More specifically,

3 February 2006 HRQOL IN GI DISEASES 189 patients were considered to have active IBD when the physician s evaluation, laboratory data (C-reactive protein, erythrocyte sedimentation rate, albumin, and platelets) or the endoscopic picture indicated active inflammation, or when patients were on steroids because of a flare-up of their IBD. On the other hand, patients with IBD were considered to be in remission when no signs of active inflammation could be detected by the treating physician, and the patients had been free of active inflammation for at least 1 month. Information regarding surgery for IBD was also obtained from the patient s charts. Data Analysis Patients were divided into 2 main groups according to the treating physician s diagnosis, which was also confirmed by chart review performed by 2 of the investigators (M.S., I.P.) (100% agreement in the patients included in the analyses): (1) functional GI disorder, which consisted of all patients without signs of organic diseases likely to explain their GI symptoms and, according to the treating physician, fulfilling diagnostic criteria for a functional GI disorder 31 ; and (2) organic GI disorder, which consisted of all patients with chronic, organic GI disorders, such as IBD, microscopic colitis (collagenous colitis, lymphocytic colitis), and celiac disease. HRQOL (SF-36 and PGWB), as well as the perceived severity of GI symptoms (GSRS), were compared between patients with functional and those with organic GI diseases. These comparisons were corrected for group differences regarding demographic factors. Furthermore, the relative contribution of the psychological state, GI symptom severity, and sociodemographic factors to HRQOL was evaluated to develop a model of diminished HRQOL. We also assessed the effect of active versus inactive IBD on HRQOL and GSRS scores, as well as the importance of previous surgery in patients with Crohn s disease. To more thoroughly evaluate the importance of perceived severity of GI symptoms on HRQOL, we divided the whole group of patients into 4 GI symptom severity groups on the basis of the total score on GSRS and compared HRQOL between these 4 groups: (1) mild GI symptom severity (GSRS total score percentile, 0 25); (2) moderate GI symptom severity (GSRS total score percentile, 26 50); (3) severe GI symptom severity (GSRS total score percentile, 51 75); and (4) very severe GI symptom severity (GSRS total score percentile, ). Statistics Initially we used t tests for continuous and 2 tests for categorical comparisons between the diagnostic groups in quality of life, GI symptom severity, and demographic factors. No corrections for multiple comparisons were made at this stage. For clarity, study data were checked against results from the general Swedish population regarding GSRS, PGWB, and SF-36, although no formal statistical comparisons between norm values and the data from our patient group were performed. 27,32 We then performed an analysis of covariance comparing survey results between patients with functional versus organic GI disorders, taking into account demographic factors that differed significantly between the groups. The SF-36 physical component summary (PCS) score was used as the dependent HRQOL variable in a forward stepwise multiple regression model to test the relative contribution of psychological state versus disease status and sociodemographic factors to HRQOL. The variables entered into this regression analysis were sociodemographic characteristics (age, gender, marital status, living alone/not alone, and educational level), disease duration, measures of GI symptom severity (GSRS reflux, abdominal pain, constipation, diarrhea, and indigestion), and psychological assessments (PGWB anxiety, depressed mood, positive wellbeing, self-control, and vitality). These analyses were performed in the whole study sample, as well as in the 2 diagnostic groups separately. To further assess the importance of GI symptom severity, we compared results on the SF-36 and PGWB among the 4 different GI symptom severity groups by using a 1-way analysis of variance with post hoc group differences corrected for multiple comparisons (Bonferroni correction). We also compared patients with IBD in remission versus those with active disease and patients with Crohn s disease who had undergone bowel surgery with those who had not undergone surgery. Unless otherwise stated, significance was accepted at the 5% level (P.05). Results Subject Characteristics There were 399 patients (mean age, 45 years; range, years; 244 women, 154 men) who agreed and were eligible to participate in the study. Of these, 112 had a functional GI disorder (mean age, 41 years; range, years; 85 women, 27 men), and 287 had an organic GI disease (mean age, 46 years; range, years; 159 women, 128 men). The most common diagnoses in the functional GI group were IBS (n 80) and functional dyspepsia (n 21), and 11 patients had other functional GI disorders. In the organic group, the most prevalent diagnoses were ulcerative colitis (n 133), Crohn s disease (n 90), celiac disease (n 23), and microscopic colitis (n 22), and 18 patients had other organic GI diseases. Demographic and disease-related factors are displayed in Table 1. Significant group differences were observed for age, gender, and disease duration. Patients in the functional GI disorder group were younger, more likely female, and had longer disease duration compared with patients with an organic GI disease. Health-Related Quality of Life As can be seen in Figures 1 and 2, patients with both organic and functional GI diseases exhibited clear

4 190 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 2 Table 1. Demographic and Disease-Related Data in the 2 Patient Groups Organic GI disease (n 287) Functional GI disorder (n 112) P value Mean age (SEM) 46 (0.9) y 41 (1.4) y.005 Female/Male 159/127 85/ Disease duration y 18% 7% 1 5 y 20% 24% 5 y 62% 69% Marital status.09 Unmarried 37% 51% Married 47% 37% Divorced 12% 9% Widow/er 4% 3% Living conditions.27 Alone 29% 30% Not alone 71% 70% Educational level Primary school 20% 13%.23 Secondary school 41% 39% Tertiary school 40% 47% (university/college) Employment status.19 Full-time employed 60% 56% Part-time employed 13% 13% Early retirement 7% 15% Long-term sick leave ( 3 mo) 9% 9% Retired 11% 7% Smoking habits.18 Smoker 18% 16% Non-smoker 58% 68% Ex-smoker 24% 16% reductions in HRQOL compared with the general Swedish population, 27,32 except for physical functioning (SF- 36), in which no clear reduction can be seen. When comparing the patient groups without adjusting for differences in demographic variables, patients with functional GI disorders had significant reductions in all domains of SF-36 except for physical functioning (P.38) and role emotional (P.12) (Figure 1), as well as in all domains on PGWB (Figure 2). In the subsequent analysis adjusting for potential confounders (age, gender, and disease duration), significant gender effects were found for all SF-36 domains and for all PGWB domains except for anxiety (Table 2), which was due to reduced scores (lower HRQOL/well-being) in women versus men. A significant age effect was seen for physical functioning, bodily pain, and general health in SF-36, with older patients reporting lower scores (Table 2). Disease duration did not affect the results on the questionnaires. When correcting for these factors, highly significant differences between patients with functional GI disorders and patients with organic GI diseases were still obvious for the majority of the domains on SF-36 Figure 1. Mean scores on the different SF-36 domains in patients with functional GI disorders and organic GI diseases. For comparison, normal values from the Swedish population are displayed, 32 although no formal statistical comparisons between the patients groups and these values were performed. Patients with functional GI disorders had significant reductions in all domains of SF-36 as compared with patients with organic GI diseases, except for physical functioning and role emotional. *P.05, **P.01, ***P.001 functional vs organic group. PF, Physical Functioning; RP, Role Physical; BP, Bodily Pain; GH, General Health; VT, Vitality; SF, Social Functioning; RE, Role Emotional; MH, Mental Health. and PGWB (Table 2), but for physical functioning (P.11) and role emotional (P.07) on SF-36 and vitality on PGWB (P.15), only nonsignificant tendencies toward reduced scores for functional GI disorders were observed. Gastrointestinal Symptoms Patients with functional GI disorders experienced more severe reflux, abdominal pain, constipation, and Figure 2. Mean item scores on the different PGWB domains in patients with functional GI disorders and organic GI diseases. For comparison, normal values from the Swedish population are displayed, 27 although no formal statistical comparisons between the patients groups and these values were performed. Patients with functional GI disorders had significant reductions in all domains as compared with patients with organic GI diseases. *P.05, **P.01, ***P.001 functional vs organic group. Anx, Anxiety; Depr, Depression; Pwb, Psychological Well-Being; Sc, Self control; Gh, General health; Vit, Vitality.

5 February 2006 HRQOL IN GI DISEASES 191 Table 2. Analysis of Covariance Comparing SF-36 and PGWB Results Gender Disease duration Age Functional vs organic F P value F P value F P value F P value SF-36 PF NS NS RP NS 0.22 NS BP NS GH NS VT NS 0.64 NS SF NS 0.41 NS RE NS 2.3 NS 3.3 NS MH NS 0.27 NS PGWB Anx 3.2 NS 0.09 NS 1.6 NS Depr NS 1.0 NS Pwb NS 0.90 NS Sc NS 1.5 NS Gh NS 2.8 NS Vit NS 1.0 NS 2.1 NS PF, Physical Functioning; RP, Role Physical; BP, Bodily Pain; GH, General Health; VT, Vitality; SF, Social Functioning; RE, Role Emotional; MH, Mental Health; Anx, Anxiety; Depr, Depression; Pwb, Psychological Well-Being; Sc, Self control; Gh, General health; Vit, Vitality. indigestion than patients with organic GI diseases as assessed by GSRS. Only for diarrhea was the perceived severity similar in the 2 patient groups (Figure 3). It is also obvious from Figure 3 that the severity of GI symptoms was worse in the patient groups than in the general population. In addition, women experienced more severe abdominal pain, indigestion, and constipation, and older patients reported more severe reflux (Table 3). After correcting for these factors, all group differences in the perceived severity of GI symptoms between patients with functional and organic GI disorders observed in the uncorrected comparisons remained significant (Table 3). Gastrointestinal Symptoms and Health- Related Quality of Life Dividing the patients into 4 groups on the basis of the perceived severity of GI symptoms (GSRS total score) showed that there was an obvious correlation between GI symptom severity and HRQOL, regardless of using the SF-36 (Figure 4) or PGWB (Figure 5). Patients with mild symptom severity did not seem to differ from the general population, but with increasing severity of GI symptoms there was a gradual reduction in HRQOL (P.0001 for all comparisons). For the vast majority of domains, post hoc analyses demonstrated significant differences between the different GI symptom severity groups by using either the PGWB or the SF-36. The mild and moderate groups did not differ significantly for physical functioning and role emotional; the moderate and severe groups did not differ significantly for physical functioning, bodily pain, vitality, social functioning, and mental health; and the severe and very severe groups did not differ significantly for physical functioning, role physical, general health, and role emotional. When performing these analyses separately for those with functional GI disorders versus organic GI diseases, the results were similar (data not shown). Variables Associated With Health-Related Quality of Life The multiple regression analysis with the PCS of SF-36 as the dependent HRQOL variable indicated that Figure 3. Mean item scores on the different domains on GSRS in patients with functional GI disorders and organic GI diseases. For comparison, normal values from the Swedish population are displayed, 27 although no formal statistical comparisons between the patients groups and these values were performed. Patients with functional GI disorders had more severe reflux, abdominal pain, constipation, and indigestion than patients with organic GI diseases as assessed by GSRS, and only for diarrhea was the perceived severity similar in the 2 patient groups. *P.05, **P.01, ***P.001 functional vs organic group.

6 192 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 2 Table 3. Analysis of Covariance Comparing GSRS Results Gender Disease duration Age Functional vs organic F P value F P value F P value F P value GSRS Pain NS 0.7 NS Indigestion NS 0.81 NS Reflux 1.0 NS 1.1 NS Constipation NS 2.9 NS Diarrhea 1.7 NS 0.63 NS 0.29 NS 0.04 NS PGWB vitality and anxiety, severity of abdominal pain and diarrhea (GSRS), together with age and gender, significantly and independently contributed to the variance of HRQOL in the whole study sample. These variables explained 32% of the variance (Table 4). When performing this analysis in patients with organic GI disease only, the same variables, except for gender, were included in the final model, explaining 32% of the variance. In patients with a functional GI disorder, PGWB vitality and anxiety, age, and living alone/not alone significantly and independently contributed to the final model (adjusted R 2 33%). Health-Related Quality of Life in Irritable Bowel Disease IBD patients with active inflammation (n 82) exhibited reduced HRQOL compared with IBD patients in remission (n 132). This was significant across all SF-36 domains (except for physical functioning and role emotional) and all PGWB domains (Table 5). When looking at Crohn s disease and ulcerative colitis separately, these differences were more obvious in patients with ulcerative colitis than in those with Crohn s disease (data not shown). Of interest, none of the SF-36 or PGWB domains differed significantly between patients with functional GI disorders and the IBD patients with active inflammation, whereas highly significant differences (P.001) between IBD patients in remission and patients with functional GI disorders were observed for all domains on PGWB and all domains on SF-36, except for physical functioning and role emotional. There were no differences in any of the domains between patients with Crohn s disease who had undergone surgery as opposed to those who had not (data not shown). Discussion In the present study we have demonstrated profound reductions in HRQOL in patients with chronic GI diseases compared with the general population. This reduction was more pronounced in patients with a functional GI disorder and partly due to gender differences. It was also obvious that HRQOL was closely correlated with the perceived severity of GI symptoms as well as with psychological factors. It has convincingly been shown that HRQOL in people with IBS is worse than in the general population and Figure 4. Mean scores on the different SF-36 domains in patients with different perceived severity of GI symptoms based on the total scores on the GSRS. Patients with mild symptom severity do not seem to differ from the general population, but with increasing severity of GI symptoms, there is a gradual reduction in HRQOL as measured by SF-36 (P.0001 for all comparisons). Figure 5. Mean item scores on the different PGWB domains in patients with different perceived severity of GI symptoms based on the total scores on the GSRS. Patients with mild symptom severity do not seem to differ from the general population, but with increasing severity of GI symptoms, there is a gradual reduction in HRQOL as measured by PGWB (P.0001 for all comparisons).

7 February 2006 HRQOL IN GI DISEASES 193 Table 4. Independent Variables Associated With SF-36 PCS Model Variable included Adjusted R 2, % Regression coefficient Significance in final model (P value) Constant PGWB vitality Age GSRS abdominal pain PGWB anxiety GSRS diarrhea Gender as low as in many other medically more severe disorders, 33,34 but comparisons have primarily been done with non-gi diagnoses, except for gastroesophageal reflux disease. 12,13 A few exceptions exist, in which HRQOL has been compared between patients with different GI diseases. Our results are in concordance with the study performed by Drossman et al 16 in a tertiary care gastroenterology clinic, in which patients with a functional GI diagnosis, as compared with those with an organic GI disease, exhibited greater GI and psychological symptom severity as well as poorer daily function. On the other hand, a recent Italian survey demonstrated similar reductions in SF-36 scores among IBS and IBD patients attending a GI outpatient clinic, which differs from our results. 17 However, in the Italian survey the majority of IBD patients had Crohn s disease, whereas our IBD sample was dominated by patients with ulcerative colitis, a condition with less pronounced effects on Table 5. QOL in Patients With IBD Active (n 82) Versus IBD Remission (n 138) IBD remission (n 138), mean (SD) IBD active (n 82), mean (SD) P value SF-36 PF 85 (19) 84 (18) NS RP 69 (39) 48 (42).001 BP 69 (26) 53 (25).001 GH 59 (25) 45 (24).001 VT 56 (24) 38 (22).001 SF 81 (22) 61 (27).001 RE 72 (38) 64 (55) NS MH 73 (19) 64 (20).007 PGWB Anx 23 (4.7) 21 (4.8).004 Depr 15 (2.6) 14 (3.3).007 Pwb 16 (4.0) 14 (3.4).001 Sc 15 (2.9) 14 (3.0).009 Gh 14 (2.8) 12 (3.4).001 Vit 15 (4.5) 12 (4.3).001 PF, Physical Functioning; RP, Role Physical; BP, Bodily Pain; GH, General Health; VT, Vitality; SF, Social Functioning; RE, Role Emotional; MH, Mental Health; Anx, Anxiety; Depr, Depression; Pwb, Psychological Well-Being; Sc, Self control; Gh, General health; Vit, Vitality. HRQOL. 2 Moreover, a larger proportion in the study by Pace et al 17 had active disease than in our study, and patients with active IBD have reduced quality of life (QOL) relative to those with inactive disease, 9 which was also obvious in our study. Therefore, differences in the composition of the patient population are probable explanations for different results obtained in these studies. A recent survey from the US showed that physicians perceived that patients with organic GI diagnoses had more serious problems, greater disability, and also more reasonable requests than patients with a functional GI disorder. 35 Our study, on the basis of the patients perceptions, showed that patients with functional GI disorders have more reduced HRQOL and perceive their GI symptoms to be worse than patients with an organic GI disease. Taken together, these studies indicate that there is a difference between physician and patient perceptions, and it is quite obvious that the seriousness of the disease from a medical point of view cannot be directly translated into how the disease affects daily life. This message is important for physicians who care for patients with GI disorders to optimize patient management. Female GI patients reported poorer HRQOL and more severe GI symptoms than their male counterparts, which is in line with previous population studies. 27,36 In addition, a previous report from our group demonstrated a gender effect on HRQOL in an IBS sample from primary and secondary care, with female IBS patients reporting reduced HRQOL as compared with men. 37 Of great importance in the present study was the fact that the differences in HRQOL and severity of GI symptoms between patients with functional GI disorders and those with organic GI disease were still significant after correcting for gender. Having a functional GI disorder as opposed to an organic GI disease per se has an impact on the HRQOL, but this is probably at least partly mediated through different psychological states in these patients. A recent study from the United Kingdom in a large group of patients with severe IBS refractory to usual

8 194 SIMRÉN ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 2 treatment and recruited for psychological treatment demonstrated that both abdominal and psychological symptoms were independently associated with HRQOL. 38 In our study this was also true in the whole study sample, as well as in the patients with organic GI disease. However, in patients with a functional GI disorder, GI symptom severity was not included in the final model to predict HRQOL. In this group psychological factors together with sociodemographic characteristics seem to be of greater importance for HRQOL. The difference between these 2 studies might relate to different patient populations included, with severe IBS patients included in the study by Creed et al 38 versus a mixed sample of functional GI disorders not specifically included on the basis of the perceived severity of the symptoms in our study. A major health care goal is to improve the HRQOL in our patients. One cornerstone in achieving this goal is to have effective treatment options to reduce the symptom burden, which is obvious from studies on patients with gastroesophageal reflux disease 39 and IBD. 9 In patients with functional GI disorders, treatment options are in general less effective. Our findings of very poor HRQOL in these patients justify future research for better treatment interventions in IBS, functional dyspepsia, and other functional GI disorders. Underscoring the importance of this concept is that it is almost compulsory today to include an assessment of HRQOL as one of the outcome measures in treatment trials in functional GI disorders. By improving the treatment alternatives for patients with functional GI disorders, profound improvements in HRQOL in these patients can be achieved, possibly also with positive economic implications, such as reductions in work absenteeism, increased productivity, and reduced health care consumption. 34 It was quite obvious in the present study that perceived severity of GI symptoms was related to HRQOL of patients with functional and organic GI disorders. This finding might be helpful for physicians to indirectly assess the patients HRQOL in clinical practice, even though our data do not show a one-to-one relationship between GI symptom severity and HRQOL. Our finding is in line with several previous studies, in which severity of GI symptoms has been found to be the most important factor in affecting health status. 9,37,40,41 This finding can also be used to justify the search for more effective treatment alternatives for both functional and organic GI disorders. However, psychological well-being seems to be of even greater relevance, at least in functional GI disorders, underscoring the importance of treating the psyche as well in these patients. There are, of course, some limitations with our study, which should be addressed. First, our study was performed in a secondary/tertiary care setting; therefore our findings cannot be generalized to patients in primary care or to non-consulting persons with functional GI symptoms in society. For this, specific studies are needed including patients from primary care and non-consulters as well. We have previously shown in an IBS sample that HRQOL is more reduced in patients seen at referral centers versus primary care, 37 which underscores this statement. Second, 33% of our sample did not agree to participate, did not fulfill inclusion criteria, or had exclusion criteria. However, simple comparisons showed that this 33% did not appear to differ significantly from our participants. Moreover, a response rate of 73%, as in our study, is generally regarded to be acceptable. Third, the patient groups were somewhat heterogeneous, with mixed groups of functional and organic GI diagnoses in the 2 main diagnostic groups. However, when discussing GI disorders, this clinical separation between functional and organic disorders is often used by clinicians, and within our 2 diagnostic groups no clear-cut differences between the different diseases of importance for our analyses could be detected. Moreover, we consider the heterogeneity of our patient sample as a strength of our study, because it was our aim to perform a study based on a typical outpatient clinical practice. To conclude, GI disorders have profound effects on HRQOL, and the impact is greater in patients with functional GI disorders as compared with those with organic GI diseases. Reductions in HRQOL are strongly correlated with severity of GI and psychological symptoms. 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Aliment Pharmacol Ther 2004;20: Coffin B, Dapoigny M, Cloarec D, et al. Relationship between severity of symptoms and quality of life in 858 patients with irritable bowel syndrome. Gastroenterol Clin Biol 2004;28: Address requests for reprints to: Magnus Simrén, MD, Section of Gastroenterology and Hepatology, Department of Internal Medicine, S Göteborg, Sweden. magnus.simren@medicine.gu.se; fax: Supported by the Swedish Medical Research Council (grant 13409) and by the Faculty of Medicine, University of Göteborg. The authors would like to express their gratitude to our statistician, Martin Gellerstedt, for invaluable help with the statistical analyses and to our nurses at the outpatient clinic for help with administration of the questionnaires.