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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.109 no.3 Madrid mar. 2017

http://dx.doi.org/10.17235/reed.2017.4621/2016 

ORIGINAL PAPERS

 

The concerns of Spanish patients with inflammatory bowel disease as measured by the RFIPC questionnaire

Las preocupaciones de los pacientes españoles con enfermedad inflamatoria intestinal medidas con el cuestionario RFIPC

 

 

E. del Berroa-de-la-Rosa, Natalia Mora-Cuadrado and Luis Fernández-Salazar

Department of Digestive Diseases. Hospital Clínico Universitario de Valladolid. Valladolid, Spain

Correspondence

 

 


ABSTRACT

Background and objectives: Concerns impact the quality of life for patients with inflammatory bowel disease (IBD). We attempted to identify the concerns of IBD patients in our practice, and to assess the applicability of the Rating Form of IBD Patients Concerns (RFIPC) questionnaire to Spanish patients.
Patients and methods: One hundred and thirty-one patients seen in our practice filled out the Spanish version of RFIPC. The questionnaire's reliability, validity, and discriminating power were analyzed.
Results: The total score was 46.93, with a standard deviation (SD) of 21.475. Primary concerns included: "having an ostomy bag", "effects of medication", "developing cancer", "energy level", and "uncertain nature of disease". Female patients scored higher on total RFIPC and on most items. Cronbach's alpha was 0.924. A good correlation was seen between two consecutive answers for 37 patients; the Spearman's coefficient was 0.842 (p < 0.001), and the intraclass correlation coefficient (ICC) was 0.775 (p < 0.001). Correlation was also found between RFIPC and both the IBDQ-32 emotional domain (0.413, p < 0.001) and anxiety scale (0.543, p < 0.001).
Conclusions: The RFIPC questionnaire may be administered to Spanish patients.

Key words: Concerns. Crohn's disease. Ulcerative colitis. Quality of life.


RESUMEN

Antecedentes y objetivos: las preocupaciones influyen en la calidad de vida de los pacientes con enfermedad inflamatoria intestinal (EII). Pretendemos identificar las preocupaciones de los pacientes con EII que atendemos en nuestra consulta y comprobar si el Rating Form of IBD Patients Concerns (RFIPC) es un cuestionario aplicable a los pacientes españoles.
Pacientes y métodos: ciento treinta y un pacientes atendidos en la consulta contestaron la versión española del RFIPC. Se ha estudiado la fiabilidad, validez y capacidad discriminadora del cuestionario.
Resultados: la puntuación total fue 46,93 con desviación estándar (DS) de 21,475. Las preocupaciones principales fueron: "que me coloquen una bolsa", "reacciones a medicamentos", "padecer cáncer", "vitalidad" y "situación incierta de la enfermedad". Los pacientes de sexo femenino puntuaron más alto en el RFIPC y en la mayoría de los ítems. El valor alfa de Cronbach fue 0,924. Se comprobó una buena correlación entre dos respuestas consecutivas de 37 pacientes, Spearman 0,842 (p < 0,001) y coeficiente de correlación intraclase (CCI) 0,775 (p < 0,001). También hubo correlación entre el RFIPC y el dominio emocional del Inflammatoy Bowel Disease Questionnarie (IBDQ) 32 0,413 (p < 0,001) y la escala de ansiedad 0,543 (p < 0,001).
Conclusiones: el cuestionario RFIPC puede aplicarse a los pacientes españoles.

Palabras clave: Preocupaciones. Enfermedad de Crohn. Colitis ulcerosa. Calidad de vida.


 

Introduction

Health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD) has become an endpoint for recent clinical trials (1,2) given its obvious significance. A wider HRQoL concept has been suggested from various interrelated dimensions, biological or physiological data, symptoms, performance status, perceived health status, and patient concerns (3,4). Correlation among these dimensions is poor or non-existent, hence they provide more encompassing information on patient experience. The RFIPC questionnaire (5,6) has been available for nearly 30 years now, and has identified the major concerns of IBD patients in different countries (5-14), and found a North-South severity gradient within them (15). We found no Spanish papers where this questionnaire was used, and thought it might be applicable in our country as well. With the present study we set out to validate and check the applicability of the RFIPC questionnaire in Spanish patients.

 

Material and methods

Study design

This was a cross-sectional study of 180 patients consecutively seen from November 2014 to April 2016 at the outpatient gastroenterology clinic, Hospital Clínico Universitario, Valladolid, Spain, who were invited to take part. This clinic covers most patients with IBD in the hospital's health area, but it is not a monographic unit.

To be included, patients had to be of advanced age and suffer from ulcerative colitis (UC) or Crohn's disease (CD). Exclusion criteria included: patients living in a different town or city, hence needing to travel to our hospital to participate in the study, difficulties in interpreting the questionnaire or in understanding the study's goals, and inappropriate doctor-patient relationship.

Patients who agreed to participate were scheduled for an interview. Interviews lasted for about 20 minutes. Patients were briefed on the study's objectives, and then given questionnaires once their consent was obtained. The study was approved by the Ethics Committee of the Hospital Clínico Universitario de Valladolid, with the code: PI 15-324.

Questionnaires

Patients received the IBDQ-32 quality-of-life questionnaire, HAD anxiety and depression scales, and the RFIPC questionnaire.

The RFIPC questionnaire assesses the extent of patient concern on various aspects (16). It consists of 25 items under the following heading: "because of your condition, how concerned are you with...?" Patients respond using a visual analogue scale ranging from 0 to 100 (0 meaning "not at all" and 100 meaning "a great deal") (5). A score is obtained for each item, and a mean total score is then estimated. This questionnaire has been translated into Spanish by and remains the intellectual property of the Fundación Roma (17), which granted user rights to LFS for research purposes. Validated Spanish versions of IBDQ-32 (18) and HAD scales (19) were used.

In addition to this initial interview, 50 patients were asked to fill out the RFIPC questionnaire on a second occasion. A self-addressed pre-stamped envelope with a RFIPC copy was handed to 39 patients, who were instructed to fill out the questionnaire after four weeks and then return it by mail provided their clinical status had not changed, and the questionnaire was again administered to 11 patients with improved clinical status after treatment with biologics or surgery.

Patient demographic and clinical characteristics were obtained from hospital records. The applicability of the RFIPC questionnaire in our setting was assessed as follows: a) an analysis of reliability took into account the percentage of patients who completed the questionnaire, floor and ceiling effects, internal consistency, and reproducibility; b) validity was established by assessing correlation between RFIPC responses and IBDQ-32 scores (total and for the bowel, systemic, emotional, and social domains) as well as HAD scales; and c) discriminating power to detect clinical changes was assessed by comparing the differences seen in initial and second RFIPC scores between patients with unchanged and improved clinical status.

Statistics

Normality of quantitative variables was assessed based on descriptive statistics (minimum and maximum values according to standard deviation, asymmetry and kurtosis), Kolmogorov-Smirnov and Saphiro-Wilks tests, and histogram representations. In the case of normality, continuous variables were expressed as mean and standard deviation (SD), and compared using the Student's t-test. For non-normal distributions, variables were expressed as median and interquartile range (IQR), and compared using non-parametric Mann-Whitney U tests. IBDQ-32 total and domain scores, and HAD scale scores were presented as median and IQR values, and compared using non-parametric tests. Repeated measures were compared using paired-variables t-tests for normally distributed differences, or using Wilcoxon's test for non-normally distributed variables. Qualitative variables were compared using the Chi-squared test. Correlation was assessed with the Spearman's rho test. Questionnaire response consistency was estimated using the intraclass correlation coefficient (ICC) for absolute agreement. RFIPC internal consistency was measured with Cronbach's alpha coefficient.

Statistical significance was considered as p < 0.05. The statistical analysis was performed using the IBM SPSS Statistics 20 package.

 

Results

Patient characteristics

Of all the 131 patients who consented to take part in the research, 127 completed the questionnaire. The IBDQ-32 instrument was appropriately completed by 120 patients. HAD scales were handed out to 57 patients. All 57 responded appropriately. Among the 39 patients with no clinical changes who were instructed to complete and return a second RFIPC questionnaire, two only filled it out partially; hence we only have 37 second questionnaires completed by patients with no clinical changes. All 11 patients with significant clinical improvement completed the questionnaire appropriately.

Patients were around 52 years of age, and had suffered from IBD for around ten years. Overall, their clinical status was good at the time of being interviewed. Over one third were receiving immunosuppressants (IMs), and 15% were on biologics. The demographic and clinical characteristics of all 131 patients are listed in table I.

 

 

Total RFIPC score was 46.93 (CI 43.29-50.57), and the SD was 21.47. Concerns with higher scores included: "having an ostomy bag" 80 (50), "effects of medication" 80 (60), "developing cancer" 70 (60), "energy level" 70 (60), and "uncertain nature of disease" 70 (60). Women scored higher than men in total RFIPC, with a mean difference of 13.5 (CI 6.3-20.7, p < 0.001), and in 18 out of 25 items. Table II summarizes the results obtained for total RFIPC and for each item both in all patients and by gender.

 

 

No statistically significant differences in total score or item scores were seen between UC and CD patients. Patients with CD scored higher on "pain or suffering", 60 (50) vs 50 (50), and "effects of medication", 80 (58) vs 70 (60), with p values of 0.089 and 0.097, respectively.

The study of RFIPC applicability to Spanish patients

RFIPC reliability was confirmed in the study patients. The questionnaire was viable and was thoroughly completed by 100% of study subjects. The questionnaire's internal validity was assessed giving consideration to the "floor" and "ceiling" effects. No patient provided a maximum 100-point score or a minimum 0-point score. The item where fewer patients scored highest was "attractiveness", and the item where more patients scored highest was "having an ostomy bag". The frequencies were 1.5% and 31.2%, respectively. "Being a burden or depending on others" was the item least scored as zero, and "ability to have children" was the item most commonly scored as zero. The frequencies were 5.3% and 63.3%, respectively. Internal consistency was assessed using Cronbach's alpha for all patients who completed the initial questionnaire, which was 0.924.

Correlation and consistency between two consecutive measurements were also analyzed for each item and total score in 37 patients with no clinical changes, a repeat questionnaire being completed at least four weeks after the initial interview. Spearman's correlation coefficient analysis was 0.842 (p < 0.001), and the intraclass correlation coefficient was 0.775 (p < 0.001). The mean difference between both scores was 0.200 (95% CI -4.290-4.690), with a SD of 14.770. A comparison of both scores using a t-test for related samples reflects a p value of 0.929. For the various items, the Spearman's correlation coefficient ranged from 0.507 for energy level to 0.808 for financial difficulties, and the intraclass agreement coefficient ranged from 0.500 for ability to have children to 0.825 for financial difficulties. For all 25 items correlation and intraclass agreement had a p value < 0.001.

Validity was confirmed by measuring the correlation between the RFIPC and IBDQ-32 scores (-0.328, p = 0.001), and between RFIPC and IBDQ-32 bowel (-0.228, p = 0.018), systemic (-0.277, p = 0.003), emotional (-0.413, p < 0.001), and social (-0.285, p = 0.002) domains, and between the RFIPC and HAD anxiety (0.543, p < 0.001) and depression (0.293, p = 0.033) scales.

Discriminating power to detect changes as related to clinical changes was confirmed by comparing differences in two consecutive measurements between two patient groups. In the first group, including 37 patients with no clinically significant changes, the scores hardly varied, with a difference (RFIPC pre-RFIPC post) of 0.4 (14.6). In the second group, including 11 patients with improved clinical status because of treatment with biologics or surgery, the scores were slightly reduced (-6.0, 13.2). A comparison of these differences almost reached statistical significance (Mann Whitney U test, p = 0.054).

 

Discussion

The concerns of IBD patients cared for in our institution are similar to those of patients in other countries. In the pioneering studies by Drossmann, and in the subsequent studies carried out in countries such as Germany, Austria, Canada, France, Norway, and Sweden with the RFIPC, primary patient concerns also include having surgery (mainly because of ostomy bags), uncertain nature of disease, energy level, and effects of medication. Their order varies in the different studies, and surgery is not always present among those receiving higher scores. Other highly scored items in other studies include developing cancer, loss of bowel control, passing the disease onto others (which is a barely present concern according to our results and, on the contrary, among those most highly scored in a Norwegian study [9]) and being a burden (or depending) on others (5-14).

As in other studies (6,7,10,11,14,20), items of least concern for patients seen in our clinic include the ability to have children (likely related to patient age), passing the disease onto others, being treated as different and attractiveness.

Aspects missed in the RFIPC questionnaire, at least given the present situation in our country, include unemployment and absenteeism (21), which in our setting are likely not equivalent to financial difficulties.

We found a clear relationship between female gender and higher scores in the RFIPC tool, both total and in many items. Our results are consistent with those obtained by other authors (6,11,14,22). As early as in 2002, a Spanish paper showed that women with IBD had a poorer quality of life (23). Other authors have also confirmed that women have a poorer quality of life as well as higher anxiety and depression rates (24). Also women with rheumatic conditions or psoriasis score higher than men in subjective indices in spite of similar therapies (25). However, a study in nearly one thousand patients was recently reported, which demonstrates poorer IBD control and IBD management in female patients (26).

According to our results, only pain or suffering and effects of medication receive higher scores among CD patients as compared to UC patients, albeit without statistical significance. Abdominal pain is more common in CD, which may explain this difference that others have identified as well (8).

The RFIPC questionnaire has been used and validated in a number of countries. While already translated into our language, no Spanish studies have reported on its use. To ascertain its applicability we followed the guidelines of other questionnaire-validating studies (9,13,27,28). The vast majority of patients who agreed to participate responded to all questions, and the internal consistency of their answers was found to be excellent, similar or superior to other studies (9,13), with acceptable "ceiling" and "floor" effects. Questionnaire reproducibility was confirmed with a good correlation and intraclass agreement values, with a mean difference in total score between administrations of 0.2.

There is no "gold standard" available for comparison with the RFIPC questionnaire in order to demonstrate its validity. Different studies have confirmed a correlation between overall RFIPC score and the scores of functional, psychological, or mental domains of quality-of-life questionnaires such as SF36 or IBDQ (9,13), with perceived overall health status (5), psychological wellbeing (13,29) and with physical, mental, or social activities (3,5,6,30). RFIPC scores have also been correlated with indices to measure the need for psychological care or to classify coping styles (11,16). A good correlation has also been found between total RFIPC and the question "how concerned are you with your bowel disease?" (4,13,31). This simplification may be more practical in daily clinical practice.

The correlation ascertained, particularly with the IBDQ-32 emotional domain and the HAD scale, provides validity to the RFIPC questionnaire. In fact, the IBDQ-32 instrument includes questions that also address concerns related to having surgery, loss of bowel control, developing cancer, or the uncertain nature of the disease.

As other authors (13), we found RFIPC poorly sensitive to clinical change. The difference in score seen in clinically improved patients versus patients with no clinical change is small, only 6 points. This renders the RFIPC score complementary to clinical manifestations.

RFIPC scores are higher for Northern European versus Southern European patients, and a gradient in this respect has been reported (15). Differences in educational level, financial status, and culture have been suggested to account for this gradient. However, some of these papers were published over ten years ago (9,11,15), and since then additional factors may have played a role, including the use of biologics, occupational changes in the setting of the current financial crisis, social changes, etc. However, a French study comparing patient concerns between 2001 and 2011 barely managed to identify any changes in RFIPC scores (10,32).

We acknowledge the limitations of our study. While the clinical characteristics of our patients are those to be expected from a series followed at an outpatient clinic especially devoted to IBD, their mean age of around 50 years may render concerns relevant to younger patients less salient, particularly concerns involving emotional issues, intimacy, wish to have children, etc. Furthermore, only 57 patients completed the anxiety and depression scale. We introduced this scale late during the study after becoming aware of the significance that psychological aspects have among patient concerns. We believe that correlation between RFIPC and the HAD instrument would have been even more obvious were the latter used from the start.

To conclude, we may apply the Spanish RFIPC questionnaire for the identification and assessment of Spanish patient concerns.

 

References

1. Guyatt G, Mitchell A, Irvine EJ, et al. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterol 1989;96(3):804-10. DOI: 10.1016/0016-5085(89)90905-0.         [ Links ]

2. Vogelaar L, Spijker AV, Van der Woude CJ. The impact of biologics on health-related quality of life in patients with inflammatory bowel disease. Clin Exp Gastroenterol 2009;2:101-9. DOI: 10.2147/CEG.S4512.         [ Links ]

3. Hjortswang H, Almer S, Strom M. The network: A strategy to describe the relationship between quality of life and disease activity. The case of inflammatory bowel disease. Eur J Gastroenterol Hepatol 1999;11(10):1099-104. DOI: 10.1097/00042737-199910000-00005.         [ Links ]

4. Hjortswang H, Jarnerot G, Curman B, et al. The Short Health Scale: A valid measure of subjective health in ulcerative colitis. Scand J Gastroenterol 2006;41(10):1196-203. DOI: 10.1080/00365520600610618.         [ Links ]

5. Drossman DA, Patrick DL, Mitchell CM, et al. Health-related quality of life in inflammatory bowel disease. Functional status and patient worries and concerns. Dig Dis Sci 1989;34(9):1379-86. DOI: 10.1007/BF01538073.         [ Links ]

6. Drossman DA, Leserman J, Li ZM, et al. The rating form of IBD patient concerns: A new measure of health status. Psychosom Med 1991;53(6):701-12. DOI: 10.1097/00006842-199111000-00010.         [ Links ]

7. Moser G, Tillinger W, Sachs G, et al. Disease-related worries and concerns: A study on out-patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 1995;7(9):853-8.         [ Links ]

8. Colombel JF, Yazdanpanah Y, Laurent F, et al. Quality of life in chronic inflammatory bowel diseases. Validation of a questionnaire and first French data. Gastroenterol Clin Biol 1996;20(12):1071-7.         [ Links ]

9. Jelsness-Jorgensen LP, Moum B, Bernklev T. Worries and concerns among inflammatory bowel disease patients followed prospectively over one year. Gastroenterol Res Pract 2011;2011:492034.         [ Links ]

10. Lesage AC, Hagege H, Tucat G, et al. Results of a national survey on quality of life in inflammatory bowel diseases. Clin Res Hepatol Gastroenterol 2011;35(2):117-24. DOI: 10.1016/j.gcb.2009.08.015.         [ Links ]

11. Mussell M, Bocker U, Nagel N, et al. Predictors of disease-related concerns and other aspects of health-related quality of life in outpatients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2004;16(12):1273-80. DOI: 10.1097/00042737-200412000-00007.         [ Links ]

12. Hjortswang H, Strom M, Almer S. Health-related quality of life in Swedish patients with ulcerative colitis. Am J Gastroenterolo 1998;93(11):2203-11. DOI: 10.1111/j.1572-0241.1998.00537.x.         [ Links ]

13. Stjernman H, Tysk C, Almer S, et al. Worries and concerns in a large unselected cohort of patients with Crohn's disease. Scand J Gastroenterol 2010;45(6):696-706. DOI: 10.3109/00365521003734141.         [ Links ]

14. Maunder R, Toner B, De Rooy E, et al. Influence of sex and disease on illness-related concerns in inflammatory bowel disease. Can J Gastroenterol 1999;13(9):728-32. DOI: 10.1155/1999/701645.         [ Links ]

15. Levenstein S, Li Z, Almer S, et al. Cross-cultural variation in disease-related concerns among patients with inflammatory bowel disease. Am J Gastroenterol 2001;96(6):1822-30. DOI: 10.1111/j.1572-0241.2001.03878.x.         [ Links ]

16. Miehsler W, Weichselberger M, Offerlbauer-Ernst A, et al. Assessing the demand for psychological care in chronic diseases: Development and validation of a questionnaire based on the example of inflammatory bowel disease. Inflamm Bowel Dis 2004;10(5):637-45. DOI: 10.1097/00054725-200409000-00021.         [ Links ]

17. Fundación Roma. http://theromefoundation.org.         [ Links ]

18. Masachs M, Casellas F, Malagelada JR. Spanish translation, adaptation, and validation of the 32-item questionnaire on quality of life for inflammatory bowel disease (IBDQ-32). Rev Esp Enferm Dig 2007;99(9):511-9. DOI: 10.4321/S1130-01082007000900006.         [ Links ]

19. Herrero MJ, Blanch J, Peri JM, et al. A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population. Gen Hosp Psychiatry 2003;25(4):277-83. DOI: 10.1016/S0163-8343(03)00043-4.         [ Links ]

20. De Rooy EC, Toner BB, Maunder RG, et al. Concerns of patients with inflammatory bowel disease: Results from a clinical population. Am J Gastroenterol 2001;96(6):1816-21. DOI: 10.1111/j.1572-0241.2001.03877.x.         [ Links ]

21. Restall GJ, Simms AM, Walker JR, et al. Understanding work experiences of people with inflammatory bowel disease. Inflamm Bowel Dis 2016;22(7):1688-97. DOI: 10.1097/MIB.0000000000000826.         [ Links ]

22. Keeton RL, Mikocka-Walus A, Andrews JM. Concerns and worries in people living with inflammatory bowel disease (IBD): A mixed methods study. J Psychosom Res 2015;78(6):573-8. DOI: 10.1016/j.jpsychores.2014.12.004.         [ Links ]

23. Casellas F, López-Vivancos J, Casado A, et al. Factors affecting health related quality of life of patients with inflammatory bowel disease. Qual Life Res 2002;11(8):775-81.         [ Links ]

24. Hauser G, Tkalcic M, Stimac D, et al. Gender related differences in quality of life and affective status in patients with inflammatory bowel disease. Coll Antropol 2011;35(Suppl 2):203-7.         [ Links ]

25. Lesuis N, Befrits R, Nyberg F, et al. Gender and the treatment of immune-mediated chronic inflammatory diseases - Rheumatoid arthritis, inflammatory bowel disease and psoriasis: An observational study. BMC Med 2012;10:82. DOI: 10.1186/1741-7015-10-82.         [ Links ]

26. Blumenstein I, Herrmann E, Filmann N, et al. Female patients suffering from inflammatory bowel diseases are treated less frequently with immunosuppressive medication and have a higher disease activity: A subgroup analysis of a large multi-centre, prospective, internet-based study. J Crohn's Col 2011;5(3):203-10. DOI: 10.1016/j.crohns.2010.12.012.         [ Links ]

27. Casellas F, Rodrigo L, Molina-Infante J, et al. Transcultural adaptation and validation of the Celiac Disease Quality of Life (CD-QOL) Survey, a specific questionnaire to measure quality of life in patients with celiac disease. Rev Esp Enferm Dig 2013;105(10):585-93. DOI: 10.4321/S1130-01082013001000003.         [ Links ]

28. Lucendo AJ, Sánchez-Cazalilla M, Molina-Infante J, et al. Transcultural adaptation and validation of the "Adult Eosinophilic Esophagitis Quality of Life Questionnaire" into Spanish. Rev Esp Enferm Dig 2014;106(6):386-94.         [ Links ]

29. Bergquist U, Babic A. Aspects of certainty in patient classification using a health-related quality-of-life instrument in inflammatory bowel disease. Proc AMIA Symp 1999:202-6.         [ Links ]

30. Hjortswang H, Strom M, Almeida RT, et al. Evaluation of the RFIPC, a disease-specific health-related quality of life questionnaire, in Swedish patients with ulcerative colitis. Scand J Gastroenterol 1997;32(12):1235-40. DOI: 10.3109/00365529709028153.         [ Links ]

31. Stjernman H, Granno C, Jarnerot G, et al. Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease. Inflamm Bowel Dis 2008;14(1):47-52. DOI: 10.1002/ibd.20255.         [ Links ]

32. Blondel-Kucharski F, Chircop C, Marquis P, et al. Health-related quality of life in Crohn's disease: A prospective longitudinal study in 231 patients. Am J Gastroenterol 2001;96(10):2915-20. DOI: 10.1111/j.1572-0241.2001.04681.x.         [ Links ]

 

 

Correspondence:
Luis Fernández-Salazar.
Department of Digestive Diseases.
Hospital Clínico Universitario de Valladolid.
Av. Ramón y Cajal, 3.
47003 Valladolid, Spain
e-mail: luisfernsal@gmail.com

Received: 20-09-2016
Accepted: 13-11-2016