Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Health-Related Quality of Life in Chinese Patients with Mild and Moderately Active Ulcerative Colitis

  • Kai Zheng,

    Affiliation Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

  • Shengsheng Zhang,

    Affiliation Department of Gastroenterology, Beijing Hospital of Chinese Medicine, Beijing, China

  • Chuijie Wang,

    Affiliation Department of Gastroenterology, Affiliated Hospital of Liaoning University of Chinese Medicine, Shenyang, Liaoning, China

  • Wenxia Zhao,

    Affiliation Department of Gastroenterology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China

  • Hong Shen

    jiangsutcm@163.com

    Affiliation Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

Health-Related Quality of Life in Chinese Patients with Mild and Moderately Active Ulcerative Colitis

  • Kai Zheng, 
  • Shengsheng Zhang, 
  • Chuijie Wang, 
  • Wenxia Zhao, 
  • Hong Shen
PLOS
x

Abstract

Background

Ulcerative colitis (UC) impairs the health-related quality of life (HRQOL). The difference in HRQOL between patients with mild and moderately active UC is not well-defined. Few studies have been conducted to explore the factors that influence HRQOL in Chinese patients. Our study aims were to (1) compare HRQOL of mildly active UC patients with moderate patients; (2) explore the factors that influence HRQOL in Chinese patients with UC; and (3) analyze demographic and disease characteristics of UC in China.

Methods

A total of 110 mild and 114 moderate patients with UC were enrolled. The demographic and disease characteristics were recorded. HRQOL was measured by the Chinese version of the inflammatory bowel disease questionnaire (IBDQ) between mild and moderate patients, male and female patients, and different disease distributions. Stepwise regression analysis was used to assess factors influencing the IBDQ score.

Results

Patients with moderate UC had significantly lower IBDQ total scores compared to patients with mild UC (P=0.001). The IBDQ total score had a negative correlation with the Mayo score (r=–0.263, P<0.001). Stepwise regression analysis showed that the disease activity index and gender had an influence on the IBDQ total score (P<0.05). The female patients had a lower score than the male patients (P<0.05), especially in the emotional function domain (P=0.002). Different disease distributions were not statistically significant in the IBDQ total score (P=0.183).

Conclusions

UC has a negative influence on HRQOL. HRQOL in patients with moderate UC was lower than HRQOL in patients with mild UC, as measured by the IBDQ. UC disease activity has a negative correlation with HRQOL. Gender and the disease activity index are important factors involved in the impairment of HRQOL in Chinese patients with UC. Chinese females may benefit from increased psychological care as part of UC therapy.

Introduction

Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is an idiopathic, chronic inflammatory disorder of the colonic mucosa. The main symptoms of UC include diarrhea, rectal bleeding, and abdominal pain. Systemic features, such as fever, fatigue, and weight loss are more common if all or most of the colon is involved in patients with UC. Most commonly, UC follows a chronic intermittent course with periods of remission interspersed with relapse lasting weeks to months. Patients with UC have been reported to experience an exacerbation of symptoms prior to remission [1,2]. The disease profoundly impacts patients’ quality of life [3,4].

The concept of health-related quality of life (HRQOL) encompasses a more complete evaluation of the effects of the disease, incorporating physical, emotional, and social aspects of health perception and health functioning [4]. Measurement of HRQOL is becoming more prominent in studies of patients with IBD and evaluation of disease [5,6]. Instruments that measure the HRQOL can be divided into generic instruments or disease-specific questionnaires. One such disease-specific instrument, the inflammatory bowel disease questionnaire (IBDQ), as developed by Guyatt and Irvine [7,8], has been shown to be valuable in assessing patients with IBD [911] and has widely been used in assessing the therapeutic efficacy in clinical trials [5,6,12,13].

The HRQOL correlates with disease activity in patients with UC [1416]. IBDQ scores are significantly different between patients with active disease and patients in remission [9,17], as well as patients with mild and moderate-severe disease [11,18]; however, no studies have been conducted involving the HRQOL in patients with mild and moderate UC.

Some factors have a significant effect on the HRQOL in patients with UC. Disease characteristics, such as disease and endoscopic activity indices, correlate with the HRQOL, but disease distribution, duration of disease, and hospital admission, as well as demographic parameters, such as educational status, economic status, and marital status, do not significantly affect the IBDQ total scores [15,19]; factors, including gender and age, are controversial. Some studies support the effect of gender and age related to the HRQOL [20,21], while others do not [15,19]. In China, a study explored factors affecting 92 patients with UC and Crohn disease in one province [22], but no large-sample study involving the factors which influence the HRQOL in patients with UC in different regions of China has been conducted.

The aims of our study were to (1) compare HRQOL of mildly active UC patients with moderate patients; (2) explore the factors that influence the HRQOL in Chinese patients with UC; and (3) analyze demographic and disease characteristics of UC in China.

Methods

Study population

Patients with mild and moderately active UC were recruited from outpatients and inpatients at the Affiliated Hospital of Nanjing University of Chinese Medicine, Beijing Hospital of Chinese Medicine, Affiliated Hospital of Liaoning University of Chinese Medicine, and the First Affiliated Hospital of Henan University of Chinese Medicine in this cross-sectional study. The inclusion criteria were as follows: participants were between 18 and 65 years of age and had a confirmed diagnosis of mild or moderate UC. Before enrollment, all of the patients underwent a colonoscopy examination within 1 month. The diagnosis of UC was made according to the UC practice guidelines in adults (update) [1]. The Mayo score was used to assess disease activity (Table 1) [23]; specifically, mild UC was defined as a Mayo score of 3–5 points, moderate UC was defined as a Mayo score of 6–10 points, and remission was defined as a Mayo score ≤ 2 [2,24]. The exclusion criteria were the inability to comprehend or complete the IBDQ or the presence of co-existing diseases, including congestive heart failure, a history of a cerebrovascular accident, renal insufficiency, cirrhosis, peptic ulcers, diabetes mellitus, malignancies, and psychiatric disorders impacting HRQOL.

Two hundred forty-five Chinese patients with confirmed mild or moderate UC were enrolled. Twenty-one patients were excluded because of co-existing diseases which may impact the HRQOL. Finally, 110 mild and 114 moderate patients with UC were included.

The demographic parameters recorded were ID number, gender, and age. The disease characteristics included disease distribution, endoscopic grade, Mayo score, extra-intestinal manifestations, duration of disease, hospital admission, laboratory testing results, and medications.

Instruments

The IBDQ is a disease-specific questionnaire which contains 32 items categorized under four domains: bowel symptoms (10 questions); systemic symptoms (5 questions); emotional function (12 questions); and social function (5 questions). Responses are scored on a 7-point Likert scale in which 7 corresponds to the highest level of function. The final score ranges from 32 to 224; the higher the score, the better the HRQOL.

We obtained the questionnaire license agreement: use of the IBDQ, authored by Dr. Jan Irvine, was made under license from McMaster University, Hamilton, Canada. Dr. Jan Irvine authorised the Chinese version of the IBDQ, which is a translation from the original English version. Patients were requested to complete the Chinese IBDQ to reflect the HRQOL of the previous 2 weeks.

Statistics

Statistical analysis was performed with SPSS (version 17.0 for Windows, SPSS Inc., Chicago, IL, USA). Frequency, median, and mean ± standard deviation (SD) were used for descriptive statistics. Student’s t-test and analysis of variance were used for continuous variables with a normal distribution. The Mann–Whitney U-test and Kruskal–Wallis test were used for continuous variables with abnormal distribution. A chi-square test was used for categorical variables. Linear regression was used to assess the association and Spearman correlation coefficients were used to assess the correlation between the IBDQ score and Mayo score. Stepwise regression analysis was used to assess factors influencing the IBDQ score. The IBDQ total scores were used as dependent variables, and gender, age, hospital admission, Mayo score, extra-intestinal manifestations, disease duration, endoscopic grade, and disease distribution were used as explanatory variables. The choice of explanatory variables was based on literature reviews [15,16,20,2527] and clinical experience. Three explanatory variables (disease duration, endoscopic grade, and disease distribution) were categorical variables with three levels. These variables were transformed appropriately to three sets of dummy variables. For all analyses, a P value <0.05 was considered statistically significant.

Ethics

The study was approved by the Institutional Review Board of Human Research of the Affiliated Hospital of Nanjing University of Chinese Medicine. The patients gave their informed consent before enrollment. Participants provided their written informed consent to participate in this study.

Results

Patient characteristics

The demographic and disease characteristics of all 110 mild and 114 moderately active patients are listed in Table 2. There were no significant differences in age, gender, extra-intestinal manifestations, disease duration, and hospital admission between the patients with mild and moderate UC. The disease distribution and endoscopic grade were statistically significant between the mild and moderate patients (P<0.05); specifically, 45.5% and 14.5% of the patients with mild UC had proctitis and extensive colitis compared to 34.2% and 28.1% in the patients with moderate UC, respectively. Moderate and severe findings were noted on endoscopy in 57.9% and 34.2% of patients with moderate UC compared to 28.2% and 29.1% in patients with mild UC, respectively.

The patients’ ages were non-normally distributed (Table 2), and ranged from 19 to 65 years. The median age of patients was 38 years. The frequency of 28–30 years was higher than the other ages. There were more males than females included in UC patients (58% vs. 42%). Only 1.3% of patients had extra-intestinal manifestations, including axial arthropathy and erythema nodosum. Of the patients, 90.6% were outpatients. The leukocyte counts and CRP levels in patients with mild UC were significantly lower than the leukocyte counts and CRP levels in the patients with moderate UC (P<0.05; Table 2); however, there was no significant difference between the two groups with respect to the hemoglobin levels. The patients’ medications are listed in Table 2.

HRQOL of mild and moderately active UC

The mean ± SD IBDQ total scores of patients with mild and moderate UC were 156.20±24.99 and 143.94±28.10, respectively (Table 3); the patients with moderate UC had a significantly lower total score compared with the patients with mild UC (P = 0.001). The moderate patients’ mean or median of four domains was also significantly lower than the patients with mild UC (P<0.05), especially with respect to the bowel symptoms domain (P = 0.001).

thumbnail
Table 3. IBDQ total and domain score in patients with mild and moderate UC.

https://doi.org/10.1371/journal.pone.0124211.t003

Correlation between HRQOL and disease activity

The mean IBDQ total score of patients with mild and moderately active UC was 149.76±27.58. The Spearman correlation coefficients between the IBDQ domain score and disease activity index are shown in Table 4. The Mayo score includes stool frequency, rectal bleeding, findings on endoscopy, and the physician’s global assessment. Bowel symptoms are one component of the Mayo score. The correlation with Mayo scores appeared to be weaker with respect to systemic symptoms, emotional function, and social function domain scores than the bowel symptoms; social function had the weakest correlation (r2 = –0.026; P<0.05). A negative correlation existed between the IBDQ total and Mayo scores (r2 = –0.069, P<0.001), Although the correlation was weak because many factors, such as disease activity index, gender, education level, employment status, a family history of IBD, smoking status, and previous surgical resection, may influence HRQOL. S1 Fig represents the relationship between the IBDQ total and Mayo scores by linear regression (y = –4.144x+175.585, P<0.001).

thumbnail
Table 4. Correlation between IBDQ total and domain scores and Mayo score.

https://doi.org/10.1371/journal.pone.0124211.t004

Factors influence the HRQOL

Linear regression analysis showed that higher disease activity index and female gender were associated with a lower total IBDQ score (both P<0.05), even after adjustment for age, disease distribution, endoscopic grade, extra-intestinal manifestations, disease duration, and hospital admission (Table 5).

HRQOL of male and female patients

Altogether, 130 male and 94 female patients with UC were enrolled. The mean ± SD IBDQ total score of female patients was 142.91±29.45, which was significantly lower than male patients (158.37±24.32, P<0.01). The mean or median of bowel symptoms, systemic symptoms, emotional function, and social function was lower in female patients than male patients (Table 6). Four domains between male and female patients were statistically significant (P<0.05), especially the emotional function domain (P = 0.002).

HRQOL of different disease distribution

Eighty-nine, 87, and 48 patients with UC had proctitis, left-sided colitis, and extensive colitis, respectively. The median IBDQ total scores for patients with proctitis, left-sided colitis, and extensive colitis were 152.00, 154.00, and 160.50, respectively (Table 7). The differences in disease distribution were not statistically significant with respect to the IBDQ total score (P = 0.183) and four domains (P>0.05).

thumbnail
Table 7. IBDQ total and domain score in different disease distributions.

https://doi.org/10.1371/journal.pone.0124211.t007

HRQOL of corticosteroids

Thirty-six and 27 patients with moderate UC received 5-aminosalicylates and 5-aminosalicylates and corticosteroids, respectively. Patients receiving 5-aminosalicylates and corticosteroids had lower IBDQ scores than patients only receiving 5-aminosalicylates (Table 8). The mean of the total score, bowel symptoms, systemic symptoms, and emotional function symptoms was significantly lower in patients taking 5-aminosalicylates and corticosteroids (P<0.05). The difference in social function was not statistically significant (P>0.05).

thumbnail
Table 8. IBDQ total and domain score in patients with moderate UC and different medications.

https://doi.org/10.1371/journal.pone.0124211.t008

Discussion

The incidence of UC in China is less than Europe and North America, but is increasing rapidly [28]. An increasing number of Chinese patients with UC have a low HRQOL [22]. Zhou [22] studied 92 patients with UC and Crohn’s disease in Zhejiang, China. HRQOL was impaired in patients with UC and Crohn’s disease. Only the disease activity index and employment status affected HRQOL in the Zhou study [22]. Gender had no impact on the HRQOL. We described the demographic and disease characteristics and HRQOL features of patients with UC in China. We analyzed 224 patients with UC in 4 provinces of China and showed that gender and the disease activity index are important factors involved in impairment of the HRQOL. Of note, the female patients had a lower HRQOL. Gender appeared to be most strongly related to IBDQ total scores in the current study and other studies [20,25]; however, the influence of gender on HRQOL remains controversial and gender has not been reported to be a significant predictor of HRQOL in some studies [14,29]. In the current study, female patients had lower IBDQ total scores than males, especially with respect to emotional function compared to other domains. Chinese female patients with UC had more emotional problems compared to male patients [30]. This may be due to the traditional Oriental introversion of Chinese females that makes the results different from other studies in other countries. Psychological disorders in patients with IBD contribute to a poor HRQOL. Treatment of psychological disorders in patients with IBD disease has the potential to improve the HRQOL [26], thus implying that Chinese females need more psychological care in conjunction with UC therapy.

Patients with severe UC require hospitalization. Severe UC seriously affects the HRQOL with respect to bowel symptoms, systemic symptoms, emotional function, and social function domains. Nevertheless, patients with mild and moderate UC are mostly outpatients. The mean values of the IBDQ total score in patients with mild and moderate UC were <170 in the current study, while patients in remission have a score ≥170 [5,8]. The HRQOL in patients with mild and moderate UC was affected. The mean or median values of the IBDQ total score and four domain scores in patients with moderate UC were also lower than the HRQOL in patients with mild UC, especially with respect to the bowel symptoms domain. Thus, there was a difference in HRQOL between patients with mild and moderate UC. Our study showed the HRQOL to have a negative correlation with Mayo scores. Patients receiving corticosteroids and 5-aminosalicylates had an impaired HRQOL compared to patients who only received 5-aminosalicylates in the current study. Patients receiving corticosteroids had a worse HRQOL, which may be due to complications and adverse reactions to corticosteroids [31].

The age of patients with active UC in our study did not have a normal distribution. We suggest the chief reason for the non-normal distribution was due to age of UC onset. UC has a bimodal pattern of incidence, with the focal onset peak between ages 20 and 30 years, especially in the 30 years, and a second smaller peak between ages 60 and 70 years [32]. The peak of age distribution in our study was at 28–30 years; however, we did not identify the second smaller peak in Chinese patients. The second reason for the non-normal distribution was we did not include patients <18 years of age in our study. In most studies involving UC, there is a slight male predominance [32]. Zhou [22] analyzed 52 patients with UC in Zhejiang province, China; the male-to-female ratio was 1.26. Jiang [28] analyzed 10,218 patients with UC in China; the male-to-female ratio was 1.09. We analyzed 224 patients with UC in four provinces of China; there still tended to be a slight male predominance, with a male-to-female ratio of 1.38. Of the patients in the current study, 1.3% had extra-intestinal manifestations, which is less than the report (6.1%) by Jiang [28] in China. Age, extra-intestinal manifestations, and hospital admission did not correlate with the HRQOL in our study.

Leukocyte counts and CRP levels in patients with mild UC were lower than the leukocyte counts and CRP levels in patients with moderate UC, implying that disease progressed with inflammatory infiltration. The disease distribution and endoscopic grades between patients with mild and moderate UC were significantly different in the current study, implying that the disease progressed with an expanded disease distribution and more severe endoscopic manifestations. The disease activity correlated with disease distribution and endoscopic grade; however, disease distribution and endoscopic grade did not the predictors of HRQOL in our study. HRQOL included bowel symptoms, systemic symptoms, emotional function, and social function. Disease distribution and endoscopic grade were connected with bowel symptoms, but not decisive factors regarding emotional and social functions. Thus, the correlations were weaker between HRQOL, and disease distribution and endoscopic grade. Based on stepwise regression analysis after controlling for disease activity, disease distribution and endoscopic grade appeared to be disease activity-related, and therefore there was a diminishing correlation with the HRQOL. Different disease distributions were not statistically significant with respect to the IBDQ score. The disease activity index (Mayo score) had a negative correlation with the HRQOL in the current study, which is in agreement with previous reports [15,16].

There were several limitations to our study. We did not recruit patients in remission to compare with patients who had mild UC. Education level, employment status, a family history of IBD, smoking status, and previous surgical resection are some factors that we could further explore with respect to HRQOL in patients with UC. The relationship between fecal calprotectin levels and disease activity index will be determined in corollary studies.

Conclusion

The HRQOL in patients with moderately active UC was less than the HRQOL in patients with mild UC. The HRQOL has a negative correlation with UC disease activity. IBDQ is a valid and reliable assessment tool that reflects the HRQOL of patients with UC. Factors, such as gender and the disease activity index (Mayo score), correlate with the HRQOL in China, but age, disease distribution, endoscopic grade, extra-intestinal manifestations, disease duration, and hospital admission have no correlations. Chinese females may benefit from additional psychological care in UC therapy.

Supporting Information

S1 Dataset. Research data.

The research data used in this study.

https://doi.org/10.1371/journal.pone.0124211.s001

(XLS)

S1 Fig. Relationship between IBDQ total and Mayo scores.

The disease activity index (Mayo score) had a negative correlation with the HRQOL.

https://doi.org/10.1371/journal.pone.0124211.s002

(TIFF)

Acknowledgments

We thank Dr. Jan Irvine for allowing us to use the Chinese Inflammatory Bowel Disease Questionnaire. We also thank Drs. Jie Han, Yufeng Li, Peiyi Zhu, Tao Zhou, Chao Cui and Jia Jia who gave their time and effort to help this study. We also thank International Science Editing for editing the manuscript.

Author Contributions

Conceived and designed the experiments: HS KZ SZ CW WZ. Performed the experiments: KZ SZ CW WZ HS. Analyzed the data: KZ HS. Wrote the paper: KZ.

References

  1. 1. Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of G (2004) Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. The American journal of gastroenterology 99: 1371–1385. pmid:15233681
  2. 2. Chinese Cooperative Group For The Study On IBD, Chinese Society Of G, Ouyang Q, Hu PJ, Qian JM, Zheng JJ, et al. (2008) Consensus on the management of inflammatory bowel disease in China in 2007. Journal of digestive diseases 9: 52–62. pmid:18251795
  3. 3. Hjortswang H, Strom M, Almer S (1998) Health-related quality of life in Swedish patients with ulcerative colitis. The American journal of gastroenterology 93: 2203–2211. pmid:9820397
  4. 4. Irvine EJ (1997) Quality of life issues in patients with inflammatory bowel disease. The American journal of gastroenterology 92: 18S–24S. pmid:9395348
  5. 5. Feagan BG, Reinisch W, Rutgeerts P, Sandborn WJ, Yan S, Eisenberg D, et al. (2007) The effects of infliximab therapy on health-related quality of life in ulcerative colitis patients. The American journal of gastroenterology 102: 794–802. pmid:17324131
  6. 6. Suzuki Y, Motoya S, Takazoe M, Kosaka T, Date M, Nii M, et al. (2013) Efficacy and tolerability of oral budesonide in Japanese patients with active Crohn's disease: a multicentre, double-blind, randomized, parallel-group Phase II study. Journal of Crohn's & colitis 7: 239–247.
  7. 7. Guyatt G, Mitchell A, Irvine EJ, Singer J, Williams N, Goodacre R, et al. (1989) A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology 96: 804–810. pmid:2644154
  8. 8. Irvine EJ, Feagan B, Rochon J, Archambault A, Fedorak RN, Groll A, et al. (1994) Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group. Gastroenterology 106: 287–296. pmid:8299896
  9. 9. Cheung WY, Garratt AM, Russell IT, Williams JG (2000) The UK IBDQ-a British version of the inflammatory bowel disease questionnaire. development and validation. Journal of clinical epidemiology 53: 297–306. pmid:10760641
  10. 10. Ciccocioppo R, Klersy C, Russo ML, Valli M, Boccaccio V, Imbesi V, et al. (2011) Validation of the Italian translation of the Inflammatory Bowel Disease Questionnaire. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 43: 535–541.
  11. 11. Bernklev T, Moum B, Moum T, Inflammatory Bowel South-Eastern Norway Group of G (2002) Quality of life in patients with inflammatory bowel disease: translation, data quality, scaling assumptions, validity, reliability and sensitivity to change of the Norwegian version of IBDQ. Scandinavian journal of gastroenterology 37: 1164–1174. pmid:12408521
  12. 12. Malik BA, Gibbons K, Spady D, Lees G, Otley A, Huynh HQ (2013) Health-related quality of life in pediatric ulcerative colitis patients on conventional medical treatment compared to those after restorative proctocolectomy. International journal of colorectal disease 28: 325–333. pmid:22914964
  13. 13. Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. (2013) Subcutaneous Golimumab Induces Clinical Response and Remission in Patients With Moderate-to-Severe Ulcerative Colitis. Gastroenterology
  14. 14. Casellas F, Alcala MJ, Prieto L, Miro JR, Malagelada JR (2004) Assessment of the influence of disease activity on the quality of life of patients with inflammatory bowel disease using a short questionnaire. The American journal of gastroenterology 99: 457–461. pmid:15056085
  15. 15. Zahn A, Hinz U, Karner M, Ehehalt R, Stremmel W (2006) Health-related quality of life correlates with clinical and endoscopic activity indexes but not with demographic features in patients with ulcerative colitis. Inflammatory bowel diseases 12: 1058–1067. pmid:17075347
  16. 16. Haapamaki J, Roine RP, Sintonen H, Kolho KL (2011) Health-related quality of life in paediatric patients with inflammatory bowel disease related to disease activity. Journal of paediatrics and child health 47: 832–837. pmid:21435075
  17. 17. Hjortswang H, Jarnerot G, Curman B, Sandberg-Gertzen H, Tysk C, Blomberg B, et al. (2001) Validation of the inflammatory bowel disease questionnaire in Swedish patients with ulcerative colitis. Scandinavian journal of gastroenterology 36: 77–85. pmid:11218243
  18. 18. Lopez-Vivancos J, Casellas F, Badia X, Vilaseca J, Malagelada JR (1999) Validation of the spanish version of the inflammatory bowel disease questionnaire on ulcerative colitis and Crohn's disease. Digestion 60: 274–280. pmid:10343142
  19. 19. Kim WH, Cho YS, Yoo HM, Park IS, Park EC, Lim JG (1999) Quality of life in Korean patients with inflammatory bowel diseases: ulcerative colitis, Crohn's disease and intestinal Behcet's disease. International journal of colorectal disease 14: 52–57. pmid:10207731
  20. 20. Haapamaki J, Turunen U, Roine RP, Farkkila MA, Arkkila PE (2009) Impact of demographic factors, medication and symptoms on disease-specific quality of life in inflammatory bowel disease. Quality of life research: an international journal of quality of life aspects of treatment, care and rehabilitation 18: 961–969. pmid:19629750
  21. 21. Bernklev T, Jahnsen J, Aadland E, Sauar J, Schulz T, Lygren I, et al. (2004) Health-related quality of life in patients with inflammatory bowel disease five years after the initial diagnosis. Scandinavian journal of gastroenterology 39: 365–373. pmid:15125469
  22. 22. Zhou Y, Ren W, Irvine EJ, Yang D (2010) Assessing health-related quality of life in patients with inflammatory bowel disease in Zhejiang, China. Journal of clinical nursing 19: 79–88. pmid:20500246
  23. 23. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. The New England journal of medicine 353: 2462–2476. pmid:16339095
  24. 24. Ouyang Q, Tandon R, Goh KL, Pan GZ, Fock KM, Fiocchi C, et al. (2006) Management consensus of inflammatory bowel disease for the Asia-Pacific region. Journal of gastroenterology and hepatology 21: 1772–1782. pmid:17074013
  25. 25. Casellas F, Lopez-Vivancos J, Casado A, Malagelada JR (2002) Factors affecting health related quality of life of patients with inflammatory bowel disease. Quality of life research: an international journal of quality of life aspects of treatment, care and rehabilitation 11: 775–781. pmid:12482161
  26. 26. Guthrie E, Jackson J, Shaffer J, Thompson D, Tomenson B, Creed F (2002) Psychological disorder and severity of inflammatory bowel disease predict health-related quality of life in ulcerative colitis and Crohn's disease. The American journal of gastroenterology 97: 1994–1999. pmid:12190166
  27. 27. Hjortswang H, Jarnerot G, Curman B, Sandberg-Gertzen H, Tysk C, Blomberg B, et al. (2003) The influence of demographic and disease-related factors on health-related quality of life in patients with ulcerative colitis. European journal of gastroenterology & hepatology 15: 1011–1020. pmid:19308310
  28. 28. Jiang XL, Cui HF (2002) An analysis of 10218 ulcerative colitis cases in China. World journal of gastroenterology: WJG 8: 158–161. pmid:11833094
  29. 29. Casellas F, Lopez-Vivancos J, Badia X, Vilaseca J, Malagelada JR (2001) Influence of inflammatory bowel disease on different dimensions of quality of life. European journal of gastroenterology & hepatology 13: 567–572. pmid:19308310
  30. 30. Li XJ, He YL, Ma H, Liu ZN, Jia FJ, Zhang L, et al. (2012) Prevalence of depressive and anxiety disorders in Chinese gastroenterological outpatients. World journal of gastroenterology: WJG 18: 2561–2568. pmid:22654455
  31. 31. Kuriyama M, Kato J, Kuwaki K, Morimoto N, Nawa T, Fujimoto T, et al. (2008) Clinical factors that impair health-related quality of life in ulcerative colitis patients vary with the disease duration. European journal of gastroenterology & hepatology 20: 634–641. pmid:19308310
  32. 32. Loftus EV Jr., Sandborn WJ (2002) Epidemiology of inflammatory bowel disease. Gastroenterology clinics of North America 31: 1–20. pmid:12122726