CROHNS-00954; No of Pages 6 Journal of Crohn's and Colitis (2014) xx, xxx–xxx
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Diagnostic delay in a French cohort of Crohn's disease patients Stéphane Nahon a,⁎, Pierre Lahmek b , Bruno Lesgourgues a , Cécile Poupardin a , Stanislas Chaussade c , Laurent Peyrin-Biroulet d , Vered Abitbol c a
Division of Gastroenterology and Hepatology, GHI Le Raincy-Montfermeil, Montfermeil, France Hopital Emile Roux, Limeil-Brevannes, France c Division of Gastroenterology and Hepatology, Hopital Cochin, Paris, France d Division of Gastroenterology and Hepatology, Inserm U954, University of Nancy, Nancy, France b
Received 17 November 2013; received in revised form 25 January 2014; accepted 27 January 2014 KEYWORDS Crohn's disease; Diagnostic delay; Socioeconomic deprivation
Abstract Diagnostic delay is frequent in Crohn's disease (CD) and may partly depend on socioeconomic status. The aim of this study was to determine the diagnostic delay and to identify associated risk factors, including socioeconomic deprivation in a French cohort of CD patients. Methods: Medical and socioeconomic characteristics of all consecutive CD patients followed in 2 referral centers between September 2002 and July 2012 were prospectively recorded using an electronic database. Diagnostic delay was defined as the time period (months) from the first symptom onset to CD diagnosis. A long diagnostic delay was defined by the upper quartile of this time period. Univariate and multivariate analyses were performed to identify the baseline characteristics of patients associated with a long diagnostic delay. Results: Three hundred and sixty-four patients with CD (mean age = 29.2 ± 12.6 years, 40.8% men) were analyzed. Median diagnostic delay was 5 months, and a long diagnostic delay was more than 12 months. Fifty-six patients (15.3%) had perianal lesions, and 28 patients (8.6%) had complicated disease at diagnosis. None of the following factors were associated with a long diagnostic delay: age, gender, CD location and behavior, marital and educational, language understanding, geographic origin and socioeconomic deprivation score measured by the EPICES score. Conclusion: In this French referral center-based cohort of CD patients, the median diagnostic delay was 5 months. None of the baseline characteristics of the CD, including socioeconomic deprivation, influenced diagnostic delay in this cohort. © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
⁎ Corresponding author at: Service d'hépatogastroentérologie, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, 10 avenue du Général Leclerc, 93370 Montfermeil, France. Tel.: +33 1 41 70 81 21; fax: +33 1 41 70 81 94. E-mail addresses: [email protected], [email protected] (S. Nahon). 1873-9946/$ - see front matter © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.crohns.2014.01.023 Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
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1. Introduction Crohn's disease (CD) is a chronic and disabling condition leading to irreversible bowel damage over time. Due to unspecific symptoms and limited test accuracies, a diagnostic delay is frequent in CD. In the Swiss inflammatory bowel disease (IBD) cohort, the median diagnostic delay was 9 months.1 Whether this result can be extrapolated to other countries such as France is unknown as this may depend on the health care system. Factors associated with diagnostic delay in CD are poorly known. In the Swiss IBD cohort, age b 40 years and ileal location were associated with diagnostic delay.1 A recent European study showed that the rates of death and poorer self-assessments of health were substantially higher in groups of lower socioeconomic status.2,3 The impact of socioeconomic deprivation on diagnostic delay is unknown in inflammatory bowel disease (IBD).4 The concept of early treatment to avoid later complications and the need for surgery in CD, aligned to rheumatoid arthritis treatments, is gaining momentum.5–7 The identification of factors associated with diagnostic delay may allow earlier therapeutic intervention that could changed the course of CD as demonstrated by mucosal healing rates in the SONIC trial.8 The aim of this study was therefore to determine the diagnostic delay and to identify associated risk factors in French patients with IBD.
gangrenosum), disease location and phenotype according to Montreal classification, anoperineal lesions. Socioeconomic deprivation was assessed using the “Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé” (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score computed on the basis of individual conditions of deprivation.6,9,10 The questions of the EPICES score are listed in Appendix A. The EPICES score was used as a quantitative or as a dichotomous variable with the EPICES median considered as the cutoff value to divide the population into two subgroups: the less deprived with a score of 30.17 and the more deprived with a score of N 30.17. The questionnaire was administered since 2006 to all new diagnosis of CD. For patients diagnosed before 2006, the questionnaire was administered retrospectively. We also collected birth country (France, Europe, North Africa and others) as well as language understanding (poor versus good, according to the quality of the rephrasing by the patient) assessed by gastroenterologists (SN, VA).
2.3. Statistical analysis
Diagnostic delay was defined as the time period (months) from the first symptom onset to establishment of CD diagnosis by the gastroenterologist. All consecutive patients diagnosed in our hospitals were asked about their symptom onset, and their diagnostic delay was recorded at diagnosis. In patients with CD diagnosis made elsewhere, diagnostic delay was calculated on the base of patient's interview and the medical chart. Similarly to Vavricka et al.,1 we defined “a long diagnostic delay” as the upper quartile of this time period.
Analyses were conducted with long diagnosis delay as the primary dependent variable. Variables were coded both categorically (sex, CD location, anoperineal lesion, etc.) and continuously (age, diagnostic delay, EPICES score, etc). Data were expressed as mean ± standard deviation or as median and range. Univariate and multivariate analysis were performed to compare the baseline characteristics of the group of patients with long diagnosis delay to the others for the following data: age, gender, age at diagnosis, family history of IBD, extraintestinal manifestations, past history of appendectomy, most relevant symptom, complications at diagnosis (occlusion, abscess, peritonitis), CD location and CD phenotype, marital status, education, language understanding, birth country, geographic origin and EPICES score (a score N 30.17 defined deprivation). The disease was classified as of a disabling and/or severe disease when at least two of the following disabling predictors defined by Beaugerie et al.11 were observed at diagnosis: age below 40 years, active perianal disease and need for oral steroids. For these analyses, we used Student's t test and ANOVA for continuous data and the chi-square test or Fisher's exact test for categorical data. Significant variables resulting from univariate analyses (P ≤ 0.20) were processed in a stepwise multivariate model. Individual odds ratio (OR) and their 95% confidence intervals (CI) were computed for each variable. A two-tailed P value b 0.05 was considered statistically significant. Statistical analysis was performed by SPSS software (version 18.0).
2.2. Data collected
3. Results
The following sociodemographic and characteristics of CD data were collected: age, gender, marital, education and employment status, family history of IBD, symptoms at diagnosis (and the most relevant of them), extraintestinal manifestation (peripheral arthritis, ankylosing spondylitis, aphthous stomatitis, uveitis, erythema nodosa, pyoderma
3.1. Patient's characteristics at diagnosis
2. Patients and methods All consecutive CD patients followed in two referral centers [Groupe Hospitalier Le Raincy-Montfermeil (suburbs of Paris) and Hopital Cochin (Paris)] were invited to participate in a prospective cohort after they gave informed consent. Clinical and socioeconomic characteristics of all consecutive CD patients between September 2002 and November 2012 were prospectively recorded using an electronic database (FileMaker Pro V 9.0).
2.1. Definition of diagnostic delay
During the study period, the cohort comprised 390 patients with Crohn's disease. A total of 364 patients with CD (40.8% men) were analyzed. Two hundred and forty-three patients (67%) had their CD diagnosis made in one of the two referral
Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
Diagnostic delay in a French cohort of Crohn's disease patients centers (Montfermeil or Cochin Hospital). The mean age at diagnosis was 29.6 ± 13.1 years. Sociodemographic and clinical characteristics of the population at diagnosis according to diagnostic delay are presented in Table 1. CD location and phenotype are presented in Table 2. Most of the patients had ileal location [L1, n = 132 (41.4%)], followed by ileocolonic (L3, n = 107 33.5%) and colonic (L2, n = 80, 25.1%) location. One hundred and seventy-five patients (56.3%) had non-stricturing and non-penetrating behavior (B1), 92 (29.6%) had stricturing behavior (B2), and 44 (14.1%) had penetrating behavior (B3) at diagnosis. Fifty-six patients (15.3%) had perianal lesions at diagnostic, and 28 patients (7.7%) had complications revealing CD (occlusion n = 22, intra-abdominal abscess n = 5, peritonitis n = 1).
3.2. Socioeconomic status Sixty-two percent of the patients were active workers. Fifty-seven percent had high school graduation or higher. Sixty-six percent were married or in a couple. Twenty-nine percent of the patients were deprived (EPICES score N 30.17). The EPICES score was not statistically different between the two-referral centers (31% vs. 25%, respectively; OR = 1.39, CI = 95% 0.84–2.30, p b 0.2). Twenty-two patients had poor language understanding.
3.3. Diagnostic delay The median diagnostic delay was 5 months.2–12 Early diagnosis (first quartile) corresponded to a period below 2 months from first symptoms to CD diagnosis. Late diagnosis (third quartile) was more than 12 months after the onset of symptoms.
3.4. Factors associated with a long diagnostic delay None of the following factors were associated with a long diagnostic delay: age at diagnosis, gender, family history of IBD, CD location and behavior, past history of appendectomy, extra-intestinal manifestations, year of diagnosis, marital status, education, language understanding, birth Table 1
3 country, geographic origin and socioeconomic deprivation (EPICES) score (Tables 1–3).
4. Discussion Identifying predictors of diagnostic delay is an important issue when managing chronic disabling and progressive conditions such as rheumatoid arthritis and CD. In fact, as recently observed in the Swiss IBD cohort,12 a diagnostic delay might be associated with worse long-term outcomes (disability and bowel damage). Accordingly, an early introduction of disease-modifying anti-IBD drugs (DMAIDs)13 should be considered in some CD patients with severe disease and/or poor prognostic factors according to ECCO consensus.14 In this context, evaluating diagnostic delay and its associated factors in CD may have direct implications for our clinical practice; recently, in the Swiss IBD cohort, the median time to diagnosis of CD was 9 months, and 75% of CD patients were diagnosed within 24 months.1 Burisch et al.15 reported a median time to diagnosis of 4.6 months in the ECCO-Epicom cohort (prospective European cohort of patients with IBD). As the diagnostic delay may be influenced by the health care system, whether these data from Switzerland can be extrapolated to other countries is unknown. This study shows a suitable delay between diagnosis and first symptoms in patients with CD followed in two referral centers in France. The diagnosis was made with a median time to diagnosis of 5 months and during the first year for 75% of the patients. This is in accordance with the French population-based cohort EPIMAD, which records all incident cases of IBD since 1988 in northern France.16 In this cohort, the median interval between first symptoms and diagnosis was 3 months for the entire period, with a significant decrease in the proportion of intervals longer than 9 months, from 28% in 1988–1990 to 22% in 2006–2007 (p b 0.0001).16 Seventy-five percent of the patients were diagnosed within 8 months between first symptoms to diagnosis.1 In both the EPIMAD and the Swiss IBD cohorts, there was a significant difference between CD and UC regarding diagnostic delay.1,16 In the EPIMAD cohort, the median time to
Sociodemographic and clinical characteristics of the population at diagnosis according to diagnostic delay.
Number of patients (data available) Sex ratio M/F (n = 364) Age (mean ± SD) A1 b 17 years A2 (17–39 years) A3 (N 40 years) Family history of IBD (344) Active smoking (358) Extraintestinal manifestations (341) Past history of appendectomy (346) Predominant symptom Diarrhea Abdominal pain Rectal bleeding
Total sample
Delay b 12 months
Delay N 12 months
364 149/215 40 267 57 82 110 22 104
275 114/161 29.7 ± 13.9 34 (12.3%) 197 (71.7%) 44 (16%) 66 (24%) 83 (30%) 18 (5.6%) 72 (26.2%)
89 35/54 29.96 ± 10.6 6 (6.7%) 70 (78.6%) 13 (14.6%) 16 (17.9%) 27 (30.3%) 4 (4.5%) 32 (35.9%)
169 69 40
127 (46.2%) 57 (20.7%) 30 (10.9%)
42 (47.2%) 12 (13.5%) 10 (11.2%)
OR
CI 95%
p
1.09
0.67–1.78
0.5 Reference 0.83 0.7 0.99 1.49 1.44
0.2–1.23 – 0.42–1.63 0.37–1.28 0.59–1.67 0.49–4.52 0.87–2.4
0.72 0.87 0.12 – 0.59 0.24 0.97 0.48 0.16
0.76 1.57 0.88
0.43–1.37 0.78–3.16 0.4–1.92
0.36 0.20 0.74
Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
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S. Nahon et al. Table 2
Characteristics of the disease at diagnosis according to diagnostic delay.
Number of patients (data available) CD location L1 L2 L3 L4 Anoperineal location Phenotype B1 B2 B3 B2 + B3 Disabling disease a a
Total sample
Delay b 12 months
Delay N 12 months
364 319 132 80 107 37 56 311 175 92 44 136 201
275
89
98 (35.6%) 63 (22.9%) 82 (29.8%) 26 (9.4%) 34 (12.4%) 138 (50.2%) 67 (24.4%) 30 (10.9%) 97 (35.3%) 153 (66.5%)
CI 95%
p
34 (38.2%) 17 (19.1%) 25 (28%) 11 (12.3%) 22 (24.7%)
Reference 0.78 0.18 – 0.49
– 0.4–1.51 0.49–1.59 – 0.27–0.89
– 0.45 0.67 – 0.01
37 (41.5%) 25 (28.1%) 14 (15.7%) 39 (43.8%) 48 (58.5%)
Reference 1.39 1.74 1.5 1.41
– 0.78–2.5 0.84–3.61 0.89–2.52 0.84–2.36
– 0.27 0.13 0.12 0.19
Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosnes J. Predictors of Crohn's disease. Gastroenterology 2006; 130: 650–6.
diagnosis was 3 months for CD patients and 2 months for UC patients, while in the Swiss IBD cohort, the median time to diagnosis was 9 months for CD and 4 months for UC (p b 0.001). Such discrepancy between CD and UC is likely explained by the fact that rectal bleeding in UC patients causes them to consult their general practitioner or gastroenterologist earlier, whereas symptoms are often unspecific in CD. In our study enrolling only CD patients, rectal bleeding was not associated with an earlier diagnosis compared with other symptoms such as diarrhea or abdominal pain. Interestingly, we did not find any difference between patients with long diagnostic delay (more than 12 months) and those with a shorter delay for the following parameters: CD location, CD behavior, complications (occlusion or abdominal abscesses) and the severity of the disease. In
Table 3
the study by Vavricka et al.,1 ileal location was associated with a longer time to diagnosis. The authors explained this finding by the fact that ileal location is more frequently revealed by abdominal pain without diarrhea, which can be confused with irritable bowel syndrome.1 We found a high rate (43.7%) of patients with stricturing or penetrating behavior at diagnosis when compared to previous reports.17,18 This may explain why ileal location, which is known to be the main site for disease complications, was not associated with diagnostic delay in our study. Indeed, strictures and fistulas/abscesses are more often symptomatic and more specific than uncomplicated CD. In addition, we did not observe that CD patients with extraintestinal manifestation had an earlier diagnosis, as observed in the Swiss cohort.1,19 Other physicians such as rheumatologists may be not well informed about the
Socioeconomic status according to diagnostic delay.
Number of patients Deprivation (EPICES score a N 30.17) Education status High school graduation or higher Marital status Married or in a couple Single Separated or divorced Employment status Working Unemployed or disabled Student Retired Language understanding (poor) Birth country France Europe North Africa Other a
OR
Total sample
Delay b 12 months
Delay N 12 months
OR
CI 95%
p
364 340
275 255 71 (27.8%) 224 124 (55.4%)
89 85 27 (31.7%) 76 47 (61.8%)
0.83
0.49–1.41
0.49
0.77
0.45–1.3
0.32
160 69 17
57 19 4
Reference 0.77 0.66
0.43–1.4 0.21–2.05
0.39 0.46
143 (59.3%) 44 (18.2%) 36 (14.9%) 18 (7.4%) 12 (6.1%)
59 (71.1%) 12 (14.4) 6 (7.2%) 6 (7.2%) 3 (5.2%)
Reference 0.66 0.4 0.81 0.84
0.33–1.34 0.16–1.01 0.31–2.14 0.23–3.08
0.25 0.05 0.66 0.79
168 (66.9%) 13 (5.2%) 61 (24.3%) 9 (3.6%)
51 (60.7%) 2 (2.4%) 28 (33.3%) 3 (3.6%)
Reference 0.51 1.51 1.1
0.11–2.32 0.88–2.61 0.29–4.21
0.51 0.13 0.89
300 326
324
255 335
Score of deprivation.
Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
Diagnostic delay in a French cohort of Crohn's disease patients possibility of having IBD in patients with digestive symptoms in France. This will require further investigation. Studies have long shown inequalities in access to, and utilization of, healthcare services among patients of minority race and reduced socioeconomic status.2–4 A recent European study showed that the rates of death and poorer self-assessments of health were substantially higher in groups of lower socioeconomic status.2–4 Because IBD care often entails frequent visits to gastroenterologists, endoscopic examinations and disease surveillance, equal access to, and utilization of, necessary services is of vital importance.4 Socioeconomic deprivation, which is associated with less frequent and later care, can result in belated diagnosis and treatment in chronic disease and also in IBD.4,20 Only one study focused on the impact of socioeconomic deprivation on delay in diagnosis in IBD patients.21 In this small pediatric study, underinsured subjects had a nearly 4-fold longer delay in diagnosis of IBD than insured subjects.21 This is the first study evaluating the impact of socioeconomic deprivation on diagnostic delay using a validated score of deprivation, namely, the EPICES score.10,11 In our work, socioeconomic deprivation evaluated by the EPICES score was not associated with diagnostic delay in CD. We could also show that socioeconomic deprivation does not impact neither diagnostic delay neither severity of CD in this cohort of French CD patients.10,22 French healthcare is based on a compromise between egalitarianism and free market. All citizens are said to be equal, yet choice and competition are fiercely protected. Access to Health care is available to everyone without waiting lists. The French patient pays their doctor's fee and then claim back 75%–80%. As payment may deter the poorest people from seeking care, about 6 million people are exempt in France. Thus, patients with low socioeconomic status have easy access to health care and treatment. The main strength of this work is the assessment of the socioeconomic deprivation by a validated questionnaire (EPICES score),9,10 as it is a major determinant of diagnostic delay. A limitation of this study is that in patients with a long history of symptoms before diagnosis or with CD diagnosis made outside our hospitals, a recall bias of symptom onset is possible. It is noteworthy that patients enrolled in this study were recruited from 2 different centers. The first hospital is located in the suburbs of Paris (Montfermeil Hospital) and attracts a population of patients expected to be disadvantaged, while the second hospital located in Paris (Cochin Hospital) attracts a population of less disadvantaged patients. However, the EPICES score was not statistically different between the two-referral centers. In conclusion, in this French cohort of CD patients, diagnostic delay was relatively short, being 5 months. None of the baseline characteristics, including socioeconomic deprivation influenced diagnostic delay in our cohort.
Conflict of interest All authors have no conflicts of interest or financial ties relevant to the manuscript to disclose. Specific author contributions: (1) study concept and design, (2) acquisition of data, (3) analysis and interpretation
5 of data, (4) drafting of the manuscript, (5) critical revision of the manuscript for important intellectual content, (6) statistical analysis, (7) technical or material support and (8) study supervision. Stéphane Nahon: 1, 2, 3, 4 and 8; Pierre Lahmek: 3 and 6; Bruno Lesgourgues: 5 and 7; Cécile Poupardin: 2; Stanislas Chaussade: 4; Laurent Peyrin-Biroulet: 5; Vered Abitbol: 1, 2, 3, 5 and 8.
Appendix A. Questions of the EPICES score and their coefficient. Questions
Coefficient
1. Do you sometimes meet a social worker (welfare worker. educator)? 2. Do you have a complementary health insurance (mutual insurance)? 3. Do you live as a couple? 4. Are you a homeowner or will you be one in the near future? 5. Are there periods in the month when you have real financial difficulties to face your needs (food, rent, electricity)? 6. Have you done any sport activities in the last 12 months? 7. Have you gone to any shows (cinema, theatre) over the last 12 months? 8. Have you gone on holiday over the last 12 months? 9. Have you seen any family member over the last six months (other than your parents or children)? 10. If you have difficulties (financial, family or health), is there anyone around you who could take you in for a few days? 11. If you have difficulties (financial, family or health), is there anyone around you who could help you financially (material aid such as money lending)? Intercept
10.06 − 11.83 − 8.28 − 8.28 14.80
− 6.51 − 7.10 − 7.10 − 9.47
− 9.47
− 7.10
75.14
EPICES: Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé. Score calculation: each question coefficient is added to intercept whenever the answer is “yes.” A score equal to 0 corresponds to non-deprivation; a score equal to 100 corresponds to maximum deprivation. Questions were translated from French to English.
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Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
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Diagnostic delay in a French cohort of Crohn's disease patients Stéphane Nahon a,⁎, Pierre Lahmek b , Bruno Lesgourgues a , Cécile Poupardin a , Stanislas Chaussade c , Laurent Peyrin-Biroulet d , Vered Abitbol c a
Division of Gastroenterology and Hepatology, GHI Le Raincy-Montfermeil, Montfermeil, France Hopital Emile Roux, Limeil-Brevannes, France c Division of Gastroenterology and Hepatology, Hopital Cochin, Paris, France d Division of Gastroenterology and Hepatology, Inserm U954, University of Nancy, Nancy, France b
Received 17 November 2013; received in revised form 25 January 2014; accepted 27 January 2014 KEYWORDS Crohn's disease; Diagnostic delay; Socioeconomic deprivation
Abstract Diagnostic delay is frequent in Crohn's disease (CD) and may partly depend on socioeconomic status. The aim of this study was to determine the diagnostic delay and to identify associated risk factors, including socioeconomic deprivation in a French cohort of CD patients. Methods: Medical and socioeconomic characteristics of all consecutive CD patients followed in 2 referral centers between September 2002 and July 2012 were prospectively recorded using an electronic database. Diagnostic delay was defined as the time period (months) from the first symptom onset to CD diagnosis. A long diagnostic delay was defined by the upper quartile of this time period. Univariate and multivariate analyses were performed to identify the baseline characteristics of patients associated with a long diagnostic delay. Results: Three hundred and sixty-four patients with CD (mean age = 29.2 ± 12.6 years, 40.8% men) were analyzed. Median diagnostic delay was 5 months, and a long diagnostic delay was more than 12 months. Fifty-six patients (15.3%) had perianal lesions, and 28 patients (8.6%) had complicated disease at diagnosis. None of the following factors were associated with a long diagnostic delay: age, gender, CD location and behavior, marital and educational, language understanding, geographic origin and socioeconomic deprivation score measured by the EPICES score. Conclusion: In this French referral center-based cohort of CD patients, the median diagnostic delay was 5 months. None of the baseline characteristics of the CD, including socioeconomic deprivation, influenced diagnostic delay in this cohort. © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
⁎ Corresponding author at: Service d'hépatogastroentérologie, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, 10 avenue du Général Leclerc, 93370 Montfermeil, France. Tel.: +33 1 41 70 81 21; fax: +33 1 41 70 81 94. E-mail addresses: [email protected], [email protected] (S. Nahon). 1873-9946/$ - see front matter © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.crohns.2014.01.023 Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
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S. Nahon et al.
1. Introduction Crohn's disease (CD) is a chronic and disabling condition leading to irreversible bowel damage over time. Due to unspecific symptoms and limited test accuracies, a diagnostic delay is frequent in CD. In the Swiss inflammatory bowel disease (IBD) cohort, the median diagnostic delay was 9 months.1 Whether this result can be extrapolated to other countries such as France is unknown as this may depend on the health care system. Factors associated with diagnostic delay in CD are poorly known. In the Swiss IBD cohort, age b 40 years and ileal location were associated with diagnostic delay.1 A recent European study showed that the rates of death and poorer self-assessments of health were substantially higher in groups of lower socioeconomic status.2,3 The impact of socioeconomic deprivation on diagnostic delay is unknown in inflammatory bowel disease (IBD).4 The concept of early treatment to avoid later complications and the need for surgery in CD, aligned to rheumatoid arthritis treatments, is gaining momentum.5–7 The identification of factors associated with diagnostic delay may allow earlier therapeutic intervention that could changed the course of CD as demonstrated by mucosal healing rates in the SONIC trial.8 The aim of this study was therefore to determine the diagnostic delay and to identify associated risk factors in French patients with IBD.
gangrenosum), disease location and phenotype according to Montreal classification, anoperineal lesions. Socioeconomic deprivation was assessed using the “Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé” (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score computed on the basis of individual conditions of deprivation.6,9,10 The questions of the EPICES score are listed in Appendix A. The EPICES score was used as a quantitative or as a dichotomous variable with the EPICES median considered as the cutoff value to divide the population into two subgroups: the less deprived with a score of 30.17 and the more deprived with a score of N 30.17. The questionnaire was administered since 2006 to all new diagnosis of CD. For patients diagnosed before 2006, the questionnaire was administered retrospectively. We also collected birth country (France, Europe, North Africa and others) as well as language understanding (poor versus good, according to the quality of the rephrasing by the patient) assessed by gastroenterologists (SN, VA).
2.3. Statistical analysis
Diagnostic delay was defined as the time period (months) from the first symptom onset to establishment of CD diagnosis by the gastroenterologist. All consecutive patients diagnosed in our hospitals were asked about their symptom onset, and their diagnostic delay was recorded at diagnosis. In patients with CD diagnosis made elsewhere, diagnostic delay was calculated on the base of patient's interview and the medical chart. Similarly to Vavricka et al.,1 we defined “a long diagnostic delay” as the upper quartile of this time period.
Analyses were conducted with long diagnosis delay as the primary dependent variable. Variables were coded both categorically (sex, CD location, anoperineal lesion, etc.) and continuously (age, diagnostic delay, EPICES score, etc). Data were expressed as mean ± standard deviation or as median and range. Univariate and multivariate analysis were performed to compare the baseline characteristics of the group of patients with long diagnosis delay to the others for the following data: age, gender, age at diagnosis, family history of IBD, extraintestinal manifestations, past history of appendectomy, most relevant symptom, complications at diagnosis (occlusion, abscess, peritonitis), CD location and CD phenotype, marital status, education, language understanding, birth country, geographic origin and EPICES score (a score N 30.17 defined deprivation). The disease was classified as of a disabling and/or severe disease when at least two of the following disabling predictors defined by Beaugerie et al.11 were observed at diagnosis: age below 40 years, active perianal disease and need for oral steroids. For these analyses, we used Student's t test and ANOVA for continuous data and the chi-square test or Fisher's exact test for categorical data. Significant variables resulting from univariate analyses (P ≤ 0.20) were processed in a stepwise multivariate model. Individual odds ratio (OR) and their 95% confidence intervals (CI) were computed for each variable. A two-tailed P value b 0.05 was considered statistically significant. Statistical analysis was performed by SPSS software (version 18.0).
2.2. Data collected
3. Results
The following sociodemographic and characteristics of CD data were collected: age, gender, marital, education and employment status, family history of IBD, symptoms at diagnosis (and the most relevant of them), extraintestinal manifestation (peripheral arthritis, ankylosing spondylitis, aphthous stomatitis, uveitis, erythema nodosa, pyoderma
3.1. Patient's characteristics at diagnosis
2. Patients and methods All consecutive CD patients followed in two referral centers [Groupe Hospitalier Le Raincy-Montfermeil (suburbs of Paris) and Hopital Cochin (Paris)] were invited to participate in a prospective cohort after they gave informed consent. Clinical and socioeconomic characteristics of all consecutive CD patients between September 2002 and November 2012 were prospectively recorded using an electronic database (FileMaker Pro V 9.0).
2.1. Definition of diagnostic delay
During the study period, the cohort comprised 390 patients with Crohn's disease. A total of 364 patients with CD (40.8% men) were analyzed. Two hundred and forty-three patients (67%) had their CD diagnosis made in one of the two referral
Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
Diagnostic delay in a French cohort of Crohn's disease patients centers (Montfermeil or Cochin Hospital). The mean age at diagnosis was 29.6 ± 13.1 years. Sociodemographic and clinical characteristics of the population at diagnosis according to diagnostic delay are presented in Table 1. CD location and phenotype are presented in Table 2. Most of the patients had ileal location [L1, n = 132 (41.4%)], followed by ileocolonic (L3, n = 107 33.5%) and colonic (L2, n = 80, 25.1%) location. One hundred and seventy-five patients (56.3%) had non-stricturing and non-penetrating behavior (B1), 92 (29.6%) had stricturing behavior (B2), and 44 (14.1%) had penetrating behavior (B3) at diagnosis. Fifty-six patients (15.3%) had perianal lesions at diagnostic, and 28 patients (7.7%) had complications revealing CD (occlusion n = 22, intra-abdominal abscess n = 5, peritonitis n = 1).
3.2. Socioeconomic status Sixty-two percent of the patients were active workers. Fifty-seven percent had high school graduation or higher. Sixty-six percent were married or in a couple. Twenty-nine percent of the patients were deprived (EPICES score N 30.17). The EPICES score was not statistically different between the two-referral centers (31% vs. 25%, respectively; OR = 1.39, CI = 95% 0.84–2.30, p b 0.2). Twenty-two patients had poor language understanding.
3.3. Diagnostic delay The median diagnostic delay was 5 months.2–12 Early diagnosis (first quartile) corresponded to a period below 2 months from first symptoms to CD diagnosis. Late diagnosis (third quartile) was more than 12 months after the onset of symptoms.
3.4. Factors associated with a long diagnostic delay None of the following factors were associated with a long diagnostic delay: age at diagnosis, gender, family history of IBD, CD location and behavior, past history of appendectomy, extra-intestinal manifestations, year of diagnosis, marital status, education, language understanding, birth Table 1
3 country, geographic origin and socioeconomic deprivation (EPICES) score (Tables 1–3).
4. Discussion Identifying predictors of diagnostic delay is an important issue when managing chronic disabling and progressive conditions such as rheumatoid arthritis and CD. In fact, as recently observed in the Swiss IBD cohort,12 a diagnostic delay might be associated with worse long-term outcomes (disability and bowel damage). Accordingly, an early introduction of disease-modifying anti-IBD drugs (DMAIDs)13 should be considered in some CD patients with severe disease and/or poor prognostic factors according to ECCO consensus.14 In this context, evaluating diagnostic delay and its associated factors in CD may have direct implications for our clinical practice; recently, in the Swiss IBD cohort, the median time to diagnosis of CD was 9 months, and 75% of CD patients were diagnosed within 24 months.1 Burisch et al.15 reported a median time to diagnosis of 4.6 months in the ECCO-Epicom cohort (prospective European cohort of patients with IBD). As the diagnostic delay may be influenced by the health care system, whether these data from Switzerland can be extrapolated to other countries is unknown. This study shows a suitable delay between diagnosis and first symptoms in patients with CD followed in two referral centers in France. The diagnosis was made with a median time to diagnosis of 5 months and during the first year for 75% of the patients. This is in accordance with the French population-based cohort EPIMAD, which records all incident cases of IBD since 1988 in northern France.16 In this cohort, the median interval between first symptoms and diagnosis was 3 months for the entire period, with a significant decrease in the proportion of intervals longer than 9 months, from 28% in 1988–1990 to 22% in 2006–2007 (p b 0.0001).16 Seventy-five percent of the patients were diagnosed within 8 months between first symptoms to diagnosis.1 In both the EPIMAD and the Swiss IBD cohorts, there was a significant difference between CD and UC regarding diagnostic delay.1,16 In the EPIMAD cohort, the median time to
Sociodemographic and clinical characteristics of the population at diagnosis according to diagnostic delay.
Number of patients (data available) Sex ratio M/F (n = 364) Age (mean ± SD) A1 b 17 years A2 (17–39 years) A3 (N 40 years) Family history of IBD (344) Active smoking (358) Extraintestinal manifestations (341) Past history of appendectomy (346) Predominant symptom Diarrhea Abdominal pain Rectal bleeding
Total sample
Delay b 12 months
Delay N 12 months
364 149/215 40 267 57 82 110 22 104
275 114/161 29.7 ± 13.9 34 (12.3%) 197 (71.7%) 44 (16%) 66 (24%) 83 (30%) 18 (5.6%) 72 (26.2%)
89 35/54 29.96 ± 10.6 6 (6.7%) 70 (78.6%) 13 (14.6%) 16 (17.9%) 27 (30.3%) 4 (4.5%) 32 (35.9%)
169 69 40
127 (46.2%) 57 (20.7%) 30 (10.9%)
42 (47.2%) 12 (13.5%) 10 (11.2%)
OR
CI 95%
p
1.09
0.67–1.78
0.5 Reference 0.83 0.7 0.99 1.49 1.44
0.2–1.23 – 0.42–1.63 0.37–1.28 0.59–1.67 0.49–4.52 0.87–2.4
0.72 0.87 0.12 – 0.59 0.24 0.97 0.48 0.16
0.76 1.57 0.88
0.43–1.37 0.78–3.16 0.4–1.92
0.36 0.20 0.74
Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
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S. Nahon et al. Table 2
Characteristics of the disease at diagnosis according to diagnostic delay.
Number of patients (data available) CD location L1 L2 L3 L4 Anoperineal location Phenotype B1 B2 B3 B2 + B3 Disabling disease a a
Total sample
Delay b 12 months
Delay N 12 months
364 319 132 80 107 37 56 311 175 92 44 136 201
275
89
98 (35.6%) 63 (22.9%) 82 (29.8%) 26 (9.4%) 34 (12.4%) 138 (50.2%) 67 (24.4%) 30 (10.9%) 97 (35.3%) 153 (66.5%)
CI 95%
p
34 (38.2%) 17 (19.1%) 25 (28%) 11 (12.3%) 22 (24.7%)
Reference 0.78 0.18 – 0.49
– 0.4–1.51 0.49–1.59 – 0.27–0.89
– 0.45 0.67 – 0.01
37 (41.5%) 25 (28.1%) 14 (15.7%) 39 (43.8%) 48 (58.5%)
Reference 1.39 1.74 1.5 1.41
– 0.78–2.5 0.84–3.61 0.89–2.52 0.84–2.36
– 0.27 0.13 0.12 0.19
Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosnes J. Predictors of Crohn's disease. Gastroenterology 2006; 130: 650–6.
diagnosis was 3 months for CD patients and 2 months for UC patients, while in the Swiss IBD cohort, the median time to diagnosis was 9 months for CD and 4 months for UC (p b 0.001). Such discrepancy between CD and UC is likely explained by the fact that rectal bleeding in UC patients causes them to consult their general practitioner or gastroenterologist earlier, whereas symptoms are often unspecific in CD. In our study enrolling only CD patients, rectal bleeding was not associated with an earlier diagnosis compared with other symptoms such as diarrhea or abdominal pain. Interestingly, we did not find any difference between patients with long diagnostic delay (more than 12 months) and those with a shorter delay for the following parameters: CD location, CD behavior, complications (occlusion or abdominal abscesses) and the severity of the disease. In
Table 3
the study by Vavricka et al.,1 ileal location was associated with a longer time to diagnosis. The authors explained this finding by the fact that ileal location is more frequently revealed by abdominal pain without diarrhea, which can be confused with irritable bowel syndrome.1 We found a high rate (43.7%) of patients with stricturing or penetrating behavior at diagnosis when compared to previous reports.17,18 This may explain why ileal location, which is known to be the main site for disease complications, was not associated with diagnostic delay in our study. Indeed, strictures and fistulas/abscesses are more often symptomatic and more specific than uncomplicated CD. In addition, we did not observe that CD patients with extraintestinal manifestation had an earlier diagnosis, as observed in the Swiss cohort.1,19 Other physicians such as rheumatologists may be not well informed about the
Socioeconomic status according to diagnostic delay.
Number of patients Deprivation (EPICES score a N 30.17) Education status High school graduation or higher Marital status Married or in a couple Single Separated or divorced Employment status Working Unemployed or disabled Student Retired Language understanding (poor) Birth country France Europe North Africa Other a
OR
Total sample
Delay b 12 months
Delay N 12 months
OR
CI 95%
p
364 340
275 255 71 (27.8%) 224 124 (55.4%)
89 85 27 (31.7%) 76 47 (61.8%)
0.83
0.49–1.41
0.49
0.77
0.45–1.3
0.32
160 69 17
57 19 4
Reference 0.77 0.66
0.43–1.4 0.21–2.05
0.39 0.46
143 (59.3%) 44 (18.2%) 36 (14.9%) 18 (7.4%) 12 (6.1%)
59 (71.1%) 12 (14.4) 6 (7.2%) 6 (7.2%) 3 (5.2%)
Reference 0.66 0.4 0.81 0.84
0.33–1.34 0.16–1.01 0.31–2.14 0.23–3.08
0.25 0.05 0.66 0.79
168 (66.9%) 13 (5.2%) 61 (24.3%) 9 (3.6%)
51 (60.7%) 2 (2.4%) 28 (33.3%) 3 (3.6%)
Reference 0.51 1.51 1.1
0.11–2.32 0.88–2.61 0.29–4.21
0.51 0.13 0.89
300 326
324
255 335
Score of deprivation.
Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
Diagnostic delay in a French cohort of Crohn's disease patients possibility of having IBD in patients with digestive symptoms in France. This will require further investigation. Studies have long shown inequalities in access to, and utilization of, healthcare services among patients of minority race and reduced socioeconomic status.2–4 A recent European study showed that the rates of death and poorer self-assessments of health were substantially higher in groups of lower socioeconomic status.2–4 Because IBD care often entails frequent visits to gastroenterologists, endoscopic examinations and disease surveillance, equal access to, and utilization of, necessary services is of vital importance.4 Socioeconomic deprivation, which is associated with less frequent and later care, can result in belated diagnosis and treatment in chronic disease and also in IBD.4,20 Only one study focused on the impact of socioeconomic deprivation on delay in diagnosis in IBD patients.21 In this small pediatric study, underinsured subjects had a nearly 4-fold longer delay in diagnosis of IBD than insured subjects.21 This is the first study evaluating the impact of socioeconomic deprivation on diagnostic delay using a validated score of deprivation, namely, the EPICES score.10,11 In our work, socioeconomic deprivation evaluated by the EPICES score was not associated with diagnostic delay in CD. We could also show that socioeconomic deprivation does not impact neither diagnostic delay neither severity of CD in this cohort of French CD patients.10,22 French healthcare is based on a compromise between egalitarianism and free market. All citizens are said to be equal, yet choice and competition are fiercely protected. Access to Health care is available to everyone without waiting lists. The French patient pays their doctor's fee and then claim back 75%–80%. As payment may deter the poorest people from seeking care, about 6 million people are exempt in France. Thus, patients with low socioeconomic status have easy access to health care and treatment. The main strength of this work is the assessment of the socioeconomic deprivation by a validated questionnaire (EPICES score),9,10 as it is a major determinant of diagnostic delay. A limitation of this study is that in patients with a long history of symptoms before diagnosis or with CD diagnosis made outside our hospitals, a recall bias of symptom onset is possible. It is noteworthy that patients enrolled in this study were recruited from 2 different centers. The first hospital is located in the suburbs of Paris (Montfermeil Hospital) and attracts a population of patients expected to be disadvantaged, while the second hospital located in Paris (Cochin Hospital) attracts a population of less disadvantaged patients. However, the EPICES score was not statistically different between the two-referral centers. In conclusion, in this French cohort of CD patients, diagnostic delay was relatively short, being 5 months. None of the baseline characteristics, including socioeconomic deprivation influenced diagnostic delay in our cohort.
Conflict of interest All authors have no conflicts of interest or financial ties relevant to the manuscript to disclose. Specific author contributions: (1) study concept and design, (2) acquisition of data, (3) analysis and interpretation
5 of data, (4) drafting of the manuscript, (5) critical revision of the manuscript for important intellectual content, (6) statistical analysis, (7) technical or material support and (8) study supervision. Stéphane Nahon: 1, 2, 3, 4 and 8; Pierre Lahmek: 3 and 6; Bruno Lesgourgues: 5 and 7; Cécile Poupardin: 2; Stanislas Chaussade: 4; Laurent Peyrin-Biroulet: 5; Vered Abitbol: 1, 2, 3, 5 and 8.
Appendix A. Questions of the EPICES score and their coefficient. Questions
Coefficient
1. Do you sometimes meet a social worker (welfare worker. educator)? 2. Do you have a complementary health insurance (mutual insurance)? 3. Do you live as a couple? 4. Are you a homeowner or will you be one in the near future? 5. Are there periods in the month when you have real financial difficulties to face your needs (food, rent, electricity)? 6. Have you done any sport activities in the last 12 months? 7. Have you gone to any shows (cinema, theatre) over the last 12 months? 8. Have you gone on holiday over the last 12 months? 9. Have you seen any family member over the last six months (other than your parents or children)? 10. If you have difficulties (financial, family or health), is there anyone around you who could take you in for a few days? 11. If you have difficulties (financial, family or health), is there anyone around you who could help you financially (material aid such as money lending)? Intercept
10.06 − 11.83 − 8.28 − 8.28 14.80
− 6.51 − 7.10 − 7.10 − 9.47
− 9.47
− 7.10
75.14
EPICES: Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé. Score calculation: each question coefficient is added to intercept whenever the answer is “yes.” A score equal to 0 corresponds to non-deprivation; a score equal to 100 corresponds to maximum deprivation. Questions were translated from French to English.
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Please cite this article as: Nahon S, et al, Diagnostic delay in a French cohort of Crohn's disease patients, J Crohns Colitis (2014), http:// dx.doi.org/10.1016/j.crohns.2014.01.023
