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Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal (GI) condition.1 It is a functional disorder characterized by abdominal pain or discomfort associated with defecation or altered bowel habits in the absence of anatomical or biochemical defects.1,2 IBS is one of the disorders of gut-brain interaction (DGBI).3 The global prevalence of DGBI and IBS is estimated at 40% and 4%, respectively, with similar values found in the United States and Romania.4,5 IBS is a chronic and distressing condition with a remitting-relapsing course that can substantially impair quality of life, which generates an important socio-economic burden due to significant healthcare costs.2,6 Although its pathophysiology is not clearly understood,1 it becomes more evident that it is a disorder of the gut-brain axis, with the brain possibly driving many of the various GI and psychological manifestations of the disease. Its pathogenesis may also have nutritional, genetic, infectious, and hormonal components.7 IBS affects women twice as often as men, and women are more likely to report abdominal pain and constipation, while men are more likely to report diarrhea.8,9 Psychological symptoms such as stress, depression, and anxiety are also frequently present in patients with the condition.10 The Rome criteria, which are symptom-based diagnostic criteria, are used to classify and diagnose DGBI.11,12
Alexithymia is a concept that was first introduced 50 years ago and has gained increasing attention from the medical community in the past decades.13,14 Alexithymia is a personality construct characterized by an impaired ability to identify and describe one’s feelings, a poor capacity to distinguish and communicate different feelings, restricted imaginary thinking, and an externally oriented thinking style.15 It is thought to contribute to the development and exacerbation of GI disorders,16,17 including inflammatory bowel disease (IBD) and DGBI such as IBS, and may lead to increased disease severity and poorer outcomes.15-17 Several diagnostic methods have been developed to assess alexithymia. The 20-item Toronto Alexithymia Scale (TAS-20), a self-reported questionnaire assessing the main features of alexithymia, has demonstrated good reliability, validity, and time efficiency, and is now considered the gold standard to assess the personality construct of alexithymia.14,18 It consists of 20 items divided into 3 subscales: (1) 8 items assess the externally oriented thinking, (2) 7 items assess the difficulty identifying feelings, and (3) 5 items assess the difficulty describing feelings. Each item is rated from 1 to 5 on a 5-point Likert scale, 1 meaning strongly disagree and 5 meaning strongly agree.19,20 Total scores range between 20 and 100, with these cutoff values often being used: 51 or less = no alexithymia, 52 to 60 = possible alexithymia, and 61 or more = alexithymia.20
Although several studies have described the presence of alexithymia in patients with GI disorders, current evidence remains inconclusive regarding the strength and direction of the association between IBS and alexithymia and the potential implications in terms of management and outcomes. To our knowledge, no systematic review and meta-analysis has previously been done regarding this particular subject. This, therefore, led us to ask the question: in patients with IBS, is there an increased risk of developing alexithymia compared to healthy subjects or patients with organic GI conditions such as IBD, and does this association impact the treatment and outcomes of IBS patients?
We conducted this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist 2020.21
We carried out a comprehensive search using the electronic databases PubMed, EMBASE, and Scopus to evaluate observational studies assessing the association between IBS and affective symptoms, primarily alexithymia. We used the following terms on PubMed: ([“Affective Symptoms”{Mesh}] OR [“Affective Symptoms”{All Fields}]) AND ([“Irritable Bowel Syndrome”{Mesh}] OR [“Irritable Bowel Syndrome”{All Fields}]); a similar strategy was used on the databases EMBASE and Scopus. We searched for published articles from inception till the third of January 2023. We did not apply any filters or restrictions. We then performed a screening of articles for eligibility. First, we selected articles based on titles and abstracts. Subsequently, the articles matching our eligibility criteria underwent a full-text review. The eligibility of the final studies and data extraction from those studies was realized by 2 authors (A.I. and M.I.) independently while resolving any discrepancies through mutual consensus.
The inclusion criteria of original articles in our systematic review and meta-analysis were as follows: (1) observational studies evaluating the relationship between IBS and alexithymia; (2) evaluation of alexithymia based on the 20-item Toronto Alexithymia Scale (TAS-20) score; (3) human studies only; and (4) studies published in English, German, or Romanian languages.
The exclusion criteria were as follows: editorials, letters to the editor, case reports, conference abstracts, literature and systematic reviews, practice guidelines, commentaries, and abstracts published without an entire article.
We evaluated the risk of bias in individual studies using a standardized quality assessment tool. The Newcastle-Ottawa Scale was used to evaluate the quality of cross-sectional studies. We used this scale to assess the risk of bias as well as the internal validity of the different studies. In the sample representativeness section, we attributed 1 star if the sample was truly or somewhat representative of the average in the target population. In the sample size section, we attributed 1 star if the size of the sample was justified and satisfactory. In the non-respondents’ section, we attributed 1 star if the comparability between respondents and non-respondents characteristics was established, and the response rate was satisfactory. In the ascertainment of the exposure (risk factor) section, we attributed 2 stars if the study used a validated measurement tool, and we attributed 1 star if the study used a non-validated measurement tool, but the tool was available or described. In the comparability section, we attributed 1 star if the study controlled for the most important factor and attributed another star if the study controlled for any additional factor. In the assessment of the outcome section, we attributed 2 stars if the outcome was assessed by independent blink assessment, 2 stars if the outcome was assessed by record linkage, or 1 star if the outcome was assessed by self-report. In the statistical test section, we attributed 1 star if the statistical test used to analyze the data was clearly described and appropriate, and the measurement of the association was presented, including confidence intervals and the probability level (P-value). If in any of these sections, the study did not complete one of the conditions, we left a blank case. The evaluation was performed independently by 2 authors (P.F. and M.I.). A consensus was reached through a discussion between the authors in the case of disagreement.
The primary summary outcome was the mean difference (MD) of TAS-20 scores. The data analysis of the studies included in our meta-analysis was performed using the R with Metafor package (OpenMeta [Analyst]).22,23 Between-study heterogeneity was measured using the χ2-based Q-test and I2. The estimated total effect size was evaluated using the random-effects model and MD. We calculated the mean and standard deviation in studies reporting medians and interquartile ranges, and we combined groups in studies that had multiple subgroups of IBS patients or control subjects without a total group, according to the Cochrane Handbook recommendations. The data from each study was reported as the estimated MD with 95% confidence interval (CI). A P-value below 0.05 was considered statistically significant. The results are reported as TAS-20 scores in IBS patients vs controls, as well as TAS-20 scores in IBS vs IBD patients.
The initial search yielded 176 articles (PubMed = 34 articles, EMBASE = 89, and Scopus = 53), as represented in Figure 1. A total of twelve studies were detected as duplicates and removed. After the removal of duplicates, 164 articles were evaluated for inclusion and exclusion criteria fulfillment by assessing the titles and abstracts. The screening process yielded 11 relevant articles. Of the 11 articles assessed for eligibility, 4 were excluded for the following reason: no TAS-20 scores for the IBS group.24-27 The total number of studies included in the qualitative analysis was 7 articles, 6 of which were included in the quantitative analysis.28-34
A summary of the main study characteristics is shown in Table. This meta-analysis included a total number of 1513 participants. The sex distribution was higher for females (males: 529 [35%] and females:984 [65%]), with a female-to-male ratio of 1.86:1. Of the total population, 654 subjects (43%) were diagnosed with IBS. Three studies were conducted in Europe (Italy n = 2 and Sweden n = 1), 2 in Asia (Japan n = 2), 1 in North America (United States n = 1), and 1 in Oceania (Australia n = 1).
Table. Studies Evaluating Alexithymia in Irritable Bowel Syndrome Patients and Controls
First author/Year/Country Study design | Study characteristics | Main findings | ||||||
---|---|---|---|---|---|---|---|---|
Population | Total subjects | IBS patients | Mean age (yr) | Sex (females) | TAS-20 | |||
Portincasa et al,30/Italy/2003 | Cross-sectional | IBS patients and healthy controls | 200 (IBS: 100; controls: 100) | 100 (50%) | IBS: 48 ± 2; controls: 45 ± 2 | IBS: 73 (73%); controls: 70 (70%) | IBS: 59.1 ± 1.1; controls: 40.5 ± 1.0 | Significantly higher TAS-20 scores in IBS patients than in healthy controls |
Jones et al,29/USA/2006 | Cross-sectional | IBS patients, IBD patients, and healthy controls | 177 (IBS: 74; IBD: 48; controls: 55) | 74 (42%) | IBS: 35 ± 11; IBD: 39 ± 12; controls: 40 ± 13 | IBS: 63 (85%); IBD: 28 (58%); controls: 39 (71%) | IBS: 42 ± 12; IBD: 43 ± 12; controls: 38 ± 9 | Significantly higher TAS-20 scores in IBS and IBD patients compared to healthy controls. No significant difference in scores between both groups |
Endo et al,31/Japan/2011 | Cross-sectional | Junior high school students | 591 | 111 (19%) | 14 years old | Total: 335 (57%); IBS: 69 (62%) | IBS: 56.3 ± 11.1; controls: 50.1 ± 11.3 | Significantly higher TAS-20 scores in students with IBS compared to healthy controls |
Bengtsson et al,28/Sweden/2013 | Cross-sectional | IBS and IBD patients | 155 (IBS: 81; IBD: 74) | 81 (52%) | IBS: 37 ± 12; IBD: 43 ± 17 | IBS: 70 (86%); IBD: 34 (46%) | IBS: 40.06 (32.56-49.56); IBD: 38.56 (30.06-46.06) | No statistically significant differences in TAS-20 scores in IBS and IBD patients with age and gender adjusted |
Phillips et al,32/Australia/2013 | Cross-sectional | IBS patients and healthy controls | 149 (IBS: 82; controls: 67) | 82 (55%) | IBS: 43.8 ± 16.5; controls: 38.8 ± 14.2 | IBS: 64 (78%); controls: 50 (75%) | IBS: 50.8 ± 12.5; controls: 43.4 ± 12.2 | Significantly higher TAS-20 scores in IBS patients compared to healthy controls |
Porcelli et al,33/Italy/2014 | Cross-sectional | Consecutive IBS patients | 177 (Moderate IBS: 87; severe IBS: 90) | 177 (100%) | 34.5 ± 11.7 | 126 (71.2%) | Moderate IBS: 48.79 ± 8.62; severe IBS: 65.33 ± 7.22 | Significantly higher TAS-20 scores in the high severity IBS group compared to the moderate severity IBS group |
Kano et al,34/Japan/2020 | Cross-sectional | IBS patients and healthy controls | 64 (IBS: 29; controls: 35) | 29 (45%) | IBS: 22 ± 2.8; controls: 22.5 ± 2.8 | IBS: 15 (52%); controls: 17 (49%) | IBS: 50.4 ± 10.3; controls: 46.9 ± 10.2 | No statistically significant difference in TAS-20 scores between IBS patients and healthy controls |
IBS, irritable bowel syndrome; TAS-20, 20-item Toronto Alexithymia Scale; IBD, inflammatory bowel disease.
Data are presented as n (%) or mean ± SD.
IBS was assessed using the Rome II criteria in 3 studies,29-31 the Rome III criteria in 2 studies,33,34 and either the Rome II or Rome III criteria in 1 study.28 One study did not mention the criteria used to assess IBS.32
TAS-20 scores were evaluated in 5 studies comparing IBS patients with controls.29-32,34 As shown in Figure 2, the pooled effect of the included studies for the analysis evaluating TAS-20 values in IBS patients vs control subjects was reported as an overall MD of 8.063 (95% CI, 2.554-13.572). Significant heterogeneity was reported with an I2 = 95.88% and a P-value < 0.001.35 Because 5 studies are contributing to this result, heterogeneity should be interpreted cautiously. We performed a leave-one-out sensitivity analysis, and by excluding any study, the results remained statistically significant, with constantly higher TAS-20 scores in patients with IBS compared to healthy individuals.
TAS-20 scores were evaluated in 2 studies comparing IBS patients with IBD patients.28,29 As demonstrated in Figure 3, the pooled studies for the analysis assessing TAS-20 values in IBS patients vs IBD patients showed an overall MD of 0.884 (95% CI, –2.536-4.304). The reported heterogeneity was not significant, with an I2 = 26.89% and a P-value = 0.242. The heterogeneity should be cautiously interpreted since only 2 studies were contributing to this data.
A total of 7 articles were assessed using the Newcastle-Ottawa Scale quality assessment tool for cross-sectional studies,28-34 as shown in Supplementary Table.
One article received an overall rating of 10/10,33 two articles received an overall rating of 9/10,30,34 three articles received an overall rating of 8/10,28,29,31 and one article received an overall rating of 7/10.32 In general, all included studies had a clearly stated research objective or question. In the 7 included studies, the population sample was truly or somewhat representative of the average in the target population, and the size of the population sample was satisfactory and justified. Only 2 studies had well-described, satisfactory, and comparable rates of non-respondents between study groups,29,33 while the other 5 studies had unsatisfactory non-response rates or did not provide a description of the response rates.28,30-32,34 The exposure of study participants was assessed using standardized and validated tools in 6 out of 7 studies,28-31,33,34 and 1 study did not describe the employed measurement tool.32 Five studies controlled for the most important confounding factor and at least 1 additional factor,30-34 one study controlled for an additional confounding factor,28 and 1 study did not control for any factor.29 All included studies assessed the outcome by a validated tool. Six studies employed an appropriate and clearly described statistical test and reported the results adequately, with confidence intervals and a P-value.28-30,32-34 One study used an appropriate statistical test; however, the test was not clearly described.31
It is now well known that IBS has clinical manifestations that are beyond the GI system. In recent years, the psychological manifestations of IBS have been increasingly described, including its association with alexithymia. These new data have seen the emergence of many hypotheses about the mechanisms behind this association, and many concerns related to increased disease severity, worse patient outcomes, and subsequent major health and economic burdens.16 Although several observational studies evaluating the relationship between DGBI and alexithymia existed, the need for a comprehensive review of this subject remained. DGBI are a diverse group of GI disorders that include conditions such as IBS and functional dyspepsia, whose presentation can vary between individuals or within the same individual.14 The primary DGBI evaluated in the gathered studies was IBS, which therefore is the focus of our study. To the best of our knowledge, this is the first systematic review and meta-analysis to evaluate the association between IBS and alexithymia. We included 7 studies in our qualitative synthesis with a total of 1513 individuals with different ethnicities and backgrounds who participated in 7 observational studies that were conducted in Europe, Asia, North America, and Oceania. Furthermore, we included 6 of those studies in our quantitative synthesis. We demonstrated that TAS-20 scores, and thus risk of developing alexithymia, were significantly higher in patients with IBS compared to healthy controls. However, we found no significant difference in TAS-20 scores between IBS and IBD patients.
The association between IBS and alexithymia can be viewed through the lens of DGBI. Individuals with IBS often experience altered gut-brain communication, leading to visceral hypersensitivity and GI symptoms. Alexithymia, characterized by difficulties in recognizing and expressing emotions, may exacerbate these symptoms by hindering the processing of emotional distress, potentially intensifying the physiological response to stressors, and further contributing to the manifestation and persistence of IBS symptoms. This bidirectional relationship underscores the importance of addressing both the GI and emotional aspects in the management of IBS within the context of DGBI.
Our findings demonstrate that IBS is significantly associated with an increased risk for developing alexithymia in comparison to controls. These results are in line with the current literature, which has constantly found high alexithymia levels in patients with IBS.16 Moreover, 1 study showed that as IBS severity increased, alexithymia scores, especially the difficulty describing and identifying feelings, increased as well.33 In addition to showing the association between IBS and alexithymia, these findings suggest the presence of a positive linear relationship between both conditions, with alexithymia as a strong predictor of IBS severity.
In general, it is important to acknowledge that the TAS-20 subscales, particularly “difficulty identifying feelings” have been reported in studies as being associated with various somatic and pain-related disorders, including IBS. On the other hand, “externally oriented thinking” subscale is not often associated with somatic diseases. This suggests that individuals with IBS may experience challenges in expressing their emotions. While our specific analysis did not incorporate these findings due to limited available data, it is essential to recognize the potential impact of these subscales on the emotional and psychological aspects of IBS, which may vary among individuals with the condition. Further research is needed to explore these associations comprehensively and their implications for IBS management.
Several results we reported need further discussion. First of all, the percentage of IBS in our study was 43%, which might be explained by the sampling methodology carried out in the analyzed studies. The final studies were realized in multiple regions of the whole world, with subjects having various origins and backgrounds. IBS has been shown to have a complex and still poorly understood pathophysiology that may involve various mechanisms. However, its prevalence demonstrates considerable variations depending on the country and continent, suggesting that the ethnicity of the patient could play a role in the pathogenesis of the disease, either through genetic factors, environmental factors, or a combination of both.36 Therefore, the variety of races and ethnicities of individuals we included in this systematic review and meta-analysis would provide more reliable and generalizable results.
Secondly, we found almost twice as many women as compared to men, findings similar to the 2:1 female-to-male ratio that was reported in previous studies,8,37 highlighting the fact that the disorder primarily affects women. IBS female patients complain mainly of constipation and abdominal pain, while males most often report diarrhea as the main symptom. Moreover, women tend to report higher levels of anxiety, depressed mood, fatigue, and overall lower quality of life than men.37 These differences in symptoms and presentations emphasize the need for tailored, individualized care with a multidisciplinary approach considering the individual’s sex and its potential health implications when treating patients with IBS.
Thirdly, IBS is a disorder that can be diagnosed using a variety of methods, including a review of the patient’s symptoms, a thorough history, a careful physical examination, an evaluation of the presence of red flags such as anemia and weight loss, and the Rome criteria.38 The Rome criteria, which were first released in 1992, provide a more structured, standardized, and evidence-based way to diagnose IBS, being especially useful for clinical research.11,38,39 We included studies that mostly used the Rome II and/or Rome III criteria for the diagnosis of IBS. A more recent classification, the Rome IV criteria, was released in 2016 and added some changes to the previous Rome III criteria. However, 6 out of 7 included studies were published before 2016, explaining the absence of this more recent diagnostic tool in the design of these studies.11
Previous studies have shown a prevalence of 50% to 90% of psychiatric comorbidities in patients with IBS, including major depressive disorder, anxiety disorders, panic disorders, and schizophrenia.40,41 The presence of psychiatric disturbances was associated with a worse prognosis, more frequent consultations, and greater healthcare costs.41 On the other hand, high rates of alexithymia have been found in patients with major depressive disorder, in which the presence of alexithymia was associated with a more severe clinical picture, higher rates of phobia, and more frequent psychotic symptoms.42 High rates of alexithymia were also described in individuals with anxiety disorders, panic disorders, and posttraumatic stress disorder.43 It is therefore not surprising to observe the recurrent presence of alexithymia in patients with IBS. However, it is still unclear whether alexithymia is directly associated with IBS or whether it is present in those patients because of their psychiatric condition. A mediation analysis would be worth performing to assess whether alexithymia plays a role in the relationship between IBS and other psychological conditions, to better understand their interplay.
One proposed mechanism behind the association between IBS and alexithymia is that the latter possibly increases visceral hypersensitivity, which is one of the main features of IBS.44,45 Alexithymic patients were shown to be especially sensitive to colonic distention, which induced severe pain, stress, and anxiety in these individuals.26 The sensory and affective components of pain may both play a role in the relationship between alexithymia and chronic pain disorders such as IBS.46 Also, patients with alexithymia have difficulties recognizing and describing their feelings and perceptions.47,48 In patients with IBS, this could lead to the underreporting and minimization of their symptoms. The diagnosis of IBS being symptom-based, these behaviors could negatively impact the detection of the condition, leading to underreported disease, treatment delays, and worse outcomes. In the future, interventional studies should be accomplished by treating alexithymia in IBS patients through psychological interventions and then assessing the impact of improved emotional awareness on GI symptoms and quality of life. Nevertheless, the presence of this association highlights the need for a comprehensive approach when treating patients with IBS, involving a multidisciplinary team ideally composed of a general practitioner, a gastroenterologist, and a psychologist or a psychiatrist.
Our findings showed a higher risk of developing alexithymia in patients with IBS compared to controls but showed no significant difference between both IBS and IBD patients. It was previously demonstrated that patients with IBD tend to have greater alexithymia levels than healthy controls.49 Although our review did not demonstrate differences in alexithymia scores between the 2 disorders, previous studies revealed that DGBI and IBD patients were more alexithymic than controls, and DGBI patients showed greater alexithymia scores than IBD patients.50 This discrepancy in results could be due to several factors. First, the study that showed greater alexithymia levels in patients with DGBI may have included more conditions from this group of diseases than just IBS, which may have shown greater alexithymic features than IBS patients alone, and therefore displayed a greater difference in scores in the final results. Secondly, we included only 2 studies comparing IBS and IBD, which may have given insufficient power to detect a significant difference between the 2conditions. Other organic GI diseases, mainly liver diseases such as hepatitis C, liver cirrhosis, and hepatocellular carcinoma, as well as solid organ transplants such as liver and kidney transplantation, have been associated with alexithymia. Previous studies found higher levels of alexithymia in patients with DGBI than in patients with IBD and liver conditions, supporting the fact that alexithymia tends to be more strongly associated with functional disorders than with organic disorders.14 Nevertheless, these GI disorders were highly associated with alexithymia, emphasizing the need for a more psychologically oriented management of patients living with these conditions.
There are limitations to our systematic review and meta-analysis. Firstly, all the studies included in this review had an observational design. Hence, we were not able to confirm or negate causality between the evaluated associations. Secondly, we reported a significant heterogeneity among the studies included in this review. Moreover, 2 studies did not fully adjust their results for confounding factors. Therefore, results should be interpreted carefully due to the potential risk of confounding bias. In addition, we could not detect a significant difference in alexithymia score levels between IBS and IBD patients, possibly due to a too low number of studies. The overall low number of published studies assessing this association deems future research necessary in this field. Furthermore, neuroticism and anxiety are also common features of IBS.51 These 2 factors have the potential to influence the measure of the TAS-20 score and the diagnosis of alexithymia.52,53 Moreover, symptom characteristics and severity, measures in quality of life, or other psychological factors were also not evaluated according to TAS-20 scores in included studies. These are potential issues that were not addressed in the included original studies, and therefore our study did not evaluate them. Future studies should perform a subgroup analysis of study participants to eliminate the potential bias caused by neuroticism, anxiety, depression, and other factors known to influence the assessment of alexithymia. Moreover, we were unable to directly evaluate the prevalence of alexithymia in IBS patients due to the absence of such data in the included studies. Future research should prioritize assessing the prevalence of alexithymia in individuals with IBS, as this would provide valuable insights into the psychological dimensions of the condition and enhance our understanding of its clinical implications. Finally, although DGBI are a vast group of diseases, our study only addressed IBS without referring to other conditions belonging to this group, emphasizing the need for further original studies exploring the link between these functional GI disorders and alexithymia.
In conclusion, while our findings indicate a potential association between IBS and alexithymia, the relationship appears to be modest and warrants further investigation. Additionally, no significant difference in alexithymia scores was observed between patients with IBS and those with IBD. The observed link between IBS and alexithymia suggests that difficulties in identifying and describing feelings may play a role in the experience of GI symptoms, though the strength of this association is limited. This highlights the need for a comprehensive approach and a multidisciplinary team when dealing with IBS patients.
More studies comparing the occurrence of alexithymia in functional disorders such as IBS and organic disorders such as IBD should be realized in the future. Moreover, studies should be conducted to clarify the causal link between these 2 conditions, as well as their association with other psychiatric conditions. Understanding this relationship could bring new horizons in the management of the millions of patients suffering from IBS.
None.
None.
Dan L Dumitrascu had the idea of the manuscript; Abdulrahman Ismaiel and Mohamed Ismaiel independently applied the search strategy and performed the study selection; Paul Foucambert and Mohamed Ismaiel performed risk of bias assessment; Abdulrahman Ismaiel, Paul Foucambert, and Mohamed Ismaiel performed the data extraction; Abdulrahman Ismaiel and Daniel C Leucuta conducted the statistical analysis; Paul Foucambert drafted the manuscript; Abdulrahman Ismaiel, Daniel C Leucuta, Stefan-Lucian Popa, Mohamed Ismaiel, Adriana Baban, and Daniel C Leucut contributed to the writing of the manuscript; and Abdulrahman Ismaiel, Daniel C Leucuta, Adriana Baban, and Dan L Dumitrascu made substantial contributions to the conception and critically revised the manuscript for important intellectual content. All authors revised the final manuscript and approved the final version.
Note: To access the supplementary table mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm23159.
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