The need for interdisciplinary quality of life studies for patients with Crohn’s Disease – a systematic review

Crohn’s disease is a chronic, lifelong condition with increasing rates of morbidity. It can have a significant impact on one’s physical, emotional, economic and social functioning. Both medical as well as social fields of studies have adapted the construct of Quality of Life to assess the well being of patients. The purpose of this paper is to investigate the nature of scientist’s research concerning Quality of Life in Crohn’s disease patients from an interdisciplinary, medical and psychological perspective exceeding beyond a single definition or a paradigm. EBSCOhost Research Databases platform was used to conduct the preliminary search. Then, a further qualitative analysis of texts was conducted. The results showed a declining interest in Quality of Life of Crohn’s disease patients in the studied 10-year scope on average by 11.49% from year to year. Also, an un-derrepresentation of studies of the nature of psychological variables in relation to studies of the medical description was found. An information gap in scientific cognition related to the interdisciplinary approach regarding the studied topic was recognized. There is a necessity to broaden the horizons of the conducted research to include further issues at several levels of inference. This approach would be needed not only in the dimen-sion of scientific considerations, but also or above all in the practical dimension.


INTRODUCTION
Crohn's disease (CD) among Ulcerative Colitis (CU) is classified as a type of chronic Inflammatory Bowel Disease (IBD).Both CU and CD are lifelong, incurable conditions.The etiology of these disorders is yet uncertain but is believed to be multifactorial, whereby genetically susceptible subjects develop the disease that may be triggered by environmental factors and perpetuated by an abnormal host immune response [1].Both CD and CU are chronic diseases, which characterize by alternating periods of remissions and relapses [1].The most common symptoms are rectal bleeding, abdominal pain and diarrhea [1].
Over the past decades, there has been a significant increase in the incidence of Crohn's.In the United Kingdom for instance, morbidity has risen from 220 to 400 cases of illness per 100 thousand people just between the years 2000 and 2018 [2].These results are in line with a recent Canadian study which findings estimate a 35% increase in CD incidence over the next decade [3].Crohn's disease is geographically conditioned with highest morbidity rates in North America and Europe.Also, rapid increases are being noted in developing nations adopting a Westernized lifestyle whereas incidence of CD were seldom.In the literature on the sub-Archives of Psychiatry and Psychotherapy, 2023; 3: 42-62 ject, the increasing incidence of CD is yet unexplained.There are no studies confirming the cause of rising morbidity.It seems rational to look for dependencies in the popularization of access to health care, the development of medical diagnostics, and the constant improvement of doctors' competences through education.
Few factors are recognised yet to have an impact on the course of IBD.Some of them are: cigarette smoking (increased severity of symptoms in Crohn disease, decreased in ulcerative colitis) [4], higher socioeconomic class [5], use of nonsteroidal anti-inflammatory drugs [6].So far, however, these environmental factors are suggested to play only a mediating role, rather than being directly involved in the disease course and its etiology [1].
Living with an incurable, chronic disease is challenging and can have an influence on one's Quality of Life (QoL).In the context of health and disease, QoL is commonly referred to as health-related quality of life (HRQoL) to differentiate it from other aspects of quality of life.It has become apparent that HRQoL is an important outcome variable on its own independent of medical treatment results.Furthermore, HRQoL outcomes can guide decisions on alternative treatments or efficacy of interventions at a patient group level [7].
HRQoL is a comprehensive and complex concept for which no universally accepted definition is available [8].However, two aspects of HRQoL are key in most interpretations.Firstly, it is a multidimensional concept that can be recognised as a latent construct which describes the physical and social role functioning, as well as psychological aspects of well-being [9], [10], [11].Secondly, in contrast to QoL, which is by very nature subjective [12], HRQoL can include both objective and subjective perspectives in each of these domains [13].The objective assessment focuses on what the individual can do, and it is important in determining the degree of health.While the subjective assessment includes the meaning to the individual; essentially it involves the translation or appraisal of the more objective measurement of health status into the experience of QoL.Differences in appraisal account for the fact that individuals with the same objective health status can report very different subjective QoL.[14,15].
Another important topic concerning patients with CD is the psychological distress which can be a common and significant factor that influences one's QoL.
Symptoms of psychological distress such as heightened levels of anxiety or depression are well recognized to co-occur with chronic diseases.Empirical studies have shown that: anxiety or depression as well as anxiety and depression are reported jointly by up to 61.7% of CD patients [16], people with CD have an increased frequency of anxiety and depressive disorders in every period of their lives, compared to control groups [17,18] and the level of mental health is further reduced by the activity of Crohn's disease symptoms [19,20].Increased levels of perceived distress, as well as physical complaints, reduce the quality of life of people with Crohn's disease.It has been proven that, apart from disease activity and the intensity of its somatic symptoms, psychological symptoms also have a negative impact on the quality of life of people with CD [21].It therefore seems necessary to measure and consider the aforementioned variables in the context of estimating CD patients.
Crohn's disease can also impact one's social and economic context.Patients with severe chronic diseases such as CD are undoubtedly a significant challenge for the health systems of many countries, and the costs of treating these patients are not only the costs incurred by the payer, which is the National Health Fund, but also other components, affecting the total social and economic cost [22,23].
On a personal level an average patient with CD spent about PLN 1,000 (225 USD) in 2018 per month on treatment.On a collective level according to data from the Polish National Health Fund Crohn's disease-related hospitalizations have tripled in recent years [24].The consequences of the disease lead to a reduction in professional activity, which translates into the state of the economy and indirectly the state finances.Reducing the effectiveness of the patient's work due to his absence from work or reduced productivity translates into the GDP indicator.
These values unequivocally indicate that raising QoL of CD patients and preventing the progression of the disease could cause significant savings on the part of the patient, but even greater extent reduces the indirect costs affecting economy and society [25].
When treating patients, the effectiveness of the therapy is important, but also awareness of the potential side effects should be considered.Modern clinical observations lead to the conclusion that the average drug works adequately on patients in 40-60%, and the next 15% experience side effects.Therefore, an important part of medical therapy is considering the individual patient's characteristics, including environment and genetic makeup [26,27].The process of optimizing, individualizing therapy and adapting the drug to the needs of a particular patient is defined as personalized medicine.In Crohn's disease this customized approach could prove extremely useful due to the variety of symptoms experienced in this type of illness (intestinal, skin, eye, joint, mental disorders) and diverse medical specialty drugs involved in their treatment.This strategy could be deemed functional however applying a focus on multidimensional characteristics of QoL in CD and future research is necessary.
In summary, it could be highly beneficial to further investigate and understand the determinants of QoL of CD patients from an interdisciplinary, biopsychosocial perspective exceeding beyond a single definition or a paradigm.
In the medical approach questionnaires and tools such as: IBDQ (Inflammatory Bowel Disease Questionnaire), SIBDQ (Short Inflammatory Bowel Disease Questionnaire), EQoL-5D (Euro QoL 5 Dimension Health Questionnaire), SF-36 (The Short Form Health Survey) CDAI (Cronhn's Disease Activity Index) or HBI (Harvey-Bradshaw Index) are often used to determine HRQoL (alone or combined).All of the above mentioned, however focus mainly on measuring.severity of clinical symptoms and have a limited ability to assess the social and emotional function as well as the appraisal of health in context of subjective QoL of CD patients.
This means that QoL and its relation to health is understood and operationalized in a different way than in psychology, whereas the subject of interest is the functioning of a sick person, their attitudes towards the disease and ways of coping with it.
In psychological terms and behaviors patients can vary in extremely different ways of addressing a health problem, experiencing opinions about their own functioning or subjective health, despite a similar intensity of disease symptoms.For instance, there's evidence that illness perception [41], psychological factors [42], personality traits [43], stress, anxiety and depression [44] as well as coping strategies [45] have a significant impact on HRQoL scores of CD patients.This may mean that there are differences between high-functioning and low-functioning people with CD that cannot be grasped by the traditional clinical paradigm.While HRQoL is a wellrecognised outcome measure of CD activity in the medical domain, its influence on other outcome measures, including exacerbation of CD is yet poorly understood.Furthermore, the association between QoL and subsequent inflammation suggests that QoL measures might be useful in detecting upcoming flares before they become clinically apparent [46].This means that a reduced value of this variable may co-occur or predict early manifestation of exacerbation and be beneficial information in the course of early treatment.
The analysis of this diverse reasoning leads to the search for complex determinants of the QoL of people with CD disease.
However, the paradigm of humanistic medicine emphasizes the importance of interdisciplinary approach in the field of medical practice, literature on the subject reveals a cognitive gap in understanding QoL in CD patients.There is no comprehensive research on this topic in the psychological context, and relatively few works give ambiguous results.Therefore, an analysis has been conducted to determine the nature of investigated variables, QoL measures, quantity and types of publications devoted to the subject of Quality of Life of CD patients.

METHOD
The Prisma technique was adapted in this systematic review.In order to collect data the EB-SCOhost Research Databases platform was used with "Crohn's Disease" and "quality of life" imputed as keywords phrases.(The concept of quality of life concerns so many aspects of human functioning in society that in order to conduct in-depth analysis in this area, it was deemed necessary to clarify the scope, limiting it to issues related to CD disease.On the other hand, the author's intention is to examine the specific determinants of the functioning of individuals with CD, ignoring the issues not directly related to their quality of life, but focusing on aspects such as financing of biological therapies, pharmacology, fibrogenesis or statistical analysis).
The following sub databases were included in the search protocol: OpenDissertations, APA PsycTests, APA PsycInfo, Health Source -Consumer Edition and MEDLINE.
The search criterias included: Both keyword phrases had to occur in the title, the paper had to be a scientifically peer-reviewed text, written in English language and published in the last ten ten years, that is between 01.01.2012 and 31.12.2021.
Because of the author's interest in the adult human population suffering from CD an additional age criterion was added.Accordingly, the 18 years and older age group box was checked as a necessary condition for the data collecting model.
Extensions with the use of equivalent themes and the boolean phrase search model was applied.
In the next step all identified texts were collected into a database.Studies which met the search protocol criteria were included in further analysis.All abstracts and subsequently 72 enclosed articles were screened.
Before the research, the following hypotheses were formulated, which together constitute a logical sequence of assumptions: • H1: Due to the increased incidence of CD in scientific journals, the number of articles devoted to this subject is increasing.• H2: Due to the spreading of the humanistic medicine paradigm, including personalized treatment, the interest of medical scientists in issues related to the quality of life of patients is increasing, and therefore, more and more often, in medical articles, explanatory variables are sought based on psychological sciences.• H3: In the scientific journals, there is an underrepresentation of research in psychological variables in relation to the research of the medical description of CD.

RESULTS
As a result of the preliminary query, 149 hit results were obtained meeting the basic search criteria, i.e. they contained in the title both keyword phrases: Quality of Life and Crohn's Disease.After extracting the database and reading the articles, 72 units of analysis that did not meet the criteria were identified (due to the lack of a keyword in the title), as well as repetitions of articles or their discussions (comments, statements or meta-analysis).Subsequently, 5 articles that did not meet the age criteria of the study population (under 18 years of age) were identified.Finally, 72 subjects were included in the further analysis.
To verify the first of the hypotheses, the distribution of articles in the time series was analyzed.The histogram on chart 1. presented below

Inclusion
Texts included (n = 72) Missing data or multiple hits on the same article (n = 72) Excluded by age criteria (n = 5)

Figure 1. Identification, eligibility and inclusion of search results
clearly shows that, contrary to assumptions, the trend is declining.Moreover, it should be noted that in the initial scope of the research period, 12 units of analysis were registered -the most in the studied temporal range, and in the last one, only 4 -which are the lowest indicator in the 2012-2021 scope.
Analyzing the average pace of changes in publications on the topic of interest to us, it should be noted that in the 10-year period of 2012 -2021, the number of articles decreased on average by 11.49% from year to year.
In the 2012 -2021-year scope, the average number of articles was 7,2 and the distribution in time is clearly asymmetric to the right, which means that there was more interest in publishing on CD topic in the initial 5-year study period than in the second half of it.
The author's deliberation also concerned the publishers taking up the analyzed subject matter.The review presented in this text clearly shows that the dominant title is the Journal of Crohn's & Colitis, which published as many as 18 texts on the quality of life of people with CD.The remaining articles are published within other titles which, although admitting articles on the analyzed subject, do not constitute the main area of a given journal.Digestive Diseases and Sciences and Inflammatory Bowel Diseases deserve special attention.The rest of the articles have been scattered over 36 titles.This distribu-tion indicates the limited concentration of scientists around the Journal of Crohn's & Colitis and deconsolidation in other titles, as well as the dominant importance of medical publications among all subjects related to the QoL of patients with CD.
It should also be noted that articles by psychologists or those undertaking research using the methodology characteristic of psychology are published in Value in Health with two publications and one in each of the following: Psychiatria Danubina, Journal of Crohn's & Colitis, The Scientific World Journal, Journal of the American College of Surgeons, Digestive diseases and sciences, PLoS ONE, Arquivos de gastroenterology.
To conduct a qualitative analysis, it was decided to divide the publications into 4 main groups, differing in the type of measured variables.When measurements of mainly clinical variables such as treatment response, clinical symptoms severity, c-reactive protein levels etc. were used, the article was included in the medical group When psychological variables played a high impact role in the article, the text was qualified to the psychological group Variables classified as psychological were for instance: illness perception, ways of coping, self-perceived health, neuroticism, satisfaction with life and so on.An aspect worth mentioning is the measurement of depression and anxiety, because these variables appeared both in the medical and psychological groups.It was assumed that if the anxiety and depression were used for screening diagnostics, as a small subscale of typically used questionnaires or as a background rather than a figura-tive role or personality trait in the study, then the article was included in the group of medical texts.An intermediate category, i.e. one whose authors used both clinical and psychological variables, were articles from the medical/psychological grou The last category were texts in which topics that were difficult to classify, i.e. those concerning nursing care or osteopathy, were classified as other group.
The tables below present all the analytical units that were left in the database which was the basis for the analysis.

Medical/Psychological articles
In this group of articles (n=11) both medical and psychological variables influencing QoL of CD patients were within the scope of the authors scientific interests.Among features measured in QoL questionnaires, psychological and medical variables were used together, both to a significant extent.An emphasis has been placed on the role of perceived stress, anxiety and depression as well as several coping strategies in context of the ongoing disease in the patient's perspective.Authors also examine the associations between Qol in CD and illness perception, psychological well-being, and the influence of selfepistemic authority in CD (knowledge vs uncertainty).Some studies included variables such as marital relationship quality, religious beliefs and behaviors, spiritual coping and overall quality of happiness.Apart from psychological, medical variables were also included such as: impact of surgery (emergency vs elective, laparoscopic vs open), permanent and temporary ostomy, type of biological therapy, steroid therapy, cytokine and chemokine levels as well as disease activity (BMI, CRP, CDAI, fecal calprotectin).

Psychological articles
Authors of publications in this category (n=9) also undertook the topic of QoL however the main emphasis was concentrated on the impact of psychological variables.Studies included questionnaires to assess personality traits (neuroticism, lie subscale), anxiety, depression, illness perception, self-perceived health, adherence to medical recommendations, coping strategies, satisfaction with life as well as the effectiveness of a mindfulness-based cognitive intervention.One of the studies examined and compared Family Quality of Life (FQoL) with a CD and Schizophrenic members.Some medical variables included in this category group were: endoscopic measures of disease activity, pharmaceutical and surgical therapies, number hospitalizations, BMI.Other articles in this group (n=3) also concerned QoL but referred to further accompanying aspects of CD.Texts concerned topics such as nursing needs of CD patients, life impairment and indirect costs of Crohn's disease as well as the impact of soft tissue osteopathic techniques.Results presented on chart 3 indicate that the frequency of texts in the studied time frame decreases.Regardless of the publication type, the number of publications regarding QoL in CD has a descending character.

DISCUSSION
As a result of the conducted analysis, the outcomes were clearly opposed to the first hypothesis presented in the introduction.It seemed that due to the increased incidence of CD, the number of articles in scientific journals devoted to this subject would also increase.Meanwhile, an exactly opposite tendency is noticeable, indicating a declining interest in QoL of CD patients.It can therefore be presumed that from the clinical point of view, this situation is a consequence of the exhaustion of the topic and the lack of breakthrough medical research on this subject.Due to the spreading of the humanistic medicine paradigm, including personalized treatment, it could be expected that the focus of the research would be shifted from strictly medical issues to aspects of psychological measurements, or that the quality of life study of patients with CD would be expanded to include aspects typical to psychological cognition.
The conducted analysis allowed for accepting hypothesis three, according to which it was assumed that in the scientific journals there is an underrepresentation of studies of the nature of psychological variables in relation to studies of the medical description of CD.
Thus, the number of scientific publishers dealing with the subject of disease clearly shows the dominance of medical journals.Hence, the analysis made it possible to identify an information gap in scientific cognition related to the interdisciplinary approach to the quality of life of people struggling with CD.
Also, it should be emphasized that psychological or psychiatric care would be advised to all, but especially to recently diagnosed CD patients due to high risk of anxiety and depressive symptoms co-occurrence and their negative influence on one's well-being.As the above-mentioned research indicated, psychological distress can be present in any stage of CD and can have a significant and lifelong impact on QoL.Subsequent flair ups can cause physical, economic and social impairment as well as psychological distress.Psychotherapy could prove beneficial by helping in dealing with disease as well as its consequences.Recognizing and training in using proper coping strategies and techniques could also improve the well-being of CD patients.
It seems that there is a necessity to broaden the horizons of the conducted research to include psychological distress, concern of social security of patients and their families, as well as economic issues at several levels of inference.This approach would be needed not only in the dimension of scientific considerations, but also or above all in the practical dimension.Justifications for such postulate can be found in many areas.First, CD implies, in the personal unit dimension, above average costs related to treatment, hygiene and quality of life.Secondly, it is worth focusing on the genetic, geographic and social determinants of the disease that affect the health policy of the state.As a rule, preventive programs and early diagnostics require the payer to commit funds lower than the costs of treating the patient.

CONCLUSION
There is a declining interest in QoL of CD patients despite significantly increasing disease morbidity.Focus of the research applies mainly to medical issues and lacks psychological and studies that comprise combined medical and psychological variables.
From a research perspective, it would be a valuable direction to perform a multidisciplinary analysis undertaking psychological, psychiatric, medical as well as methods and techniques adequate to other domains of science to fully understand QoL of CD patients.
From a practical perspective more attention should be emphasized on psychological and mental health as data strongly indicates that an extensive number of CD patients may be experiencing some forms of psychiatric disorders which may affect their QoL significantly.
In summary, QoL of CD patients consists of many dimensions.Their well-being can vary due to their social, economic, physical and psychological resources and needs.Therefore, it seems that additional research is deemed vital.

Chart 3 .
Frequency of publication types in the study time frame.

Table 1 .
HRQoL questionnaires and other variables measured in articles classified as Medical.

Table 2 .
HRQoL questionnaires and other variables measured in articles classified as Medical / psychological

Table 3 .
HRQoL questionnaires and other variables measured in articles classified as Psychological.

Table 4 .
HRQoL questionnaires and other variables measured in articles classified as Other.