Diagnostic Delay in Adult Inflammatory Bowel Disease: A Systematic Review

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Farmer, James A. Prior This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1753316/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The extent of diagnostic delay in inflammatory bowel disease (IBD) is incompletely understood. We aimed to understand the extent of diagnostic delay of IBD in adults and identify associations between patient or healthcare characteristics and length of delay. Methods Articles were sourced from EMBASE, Medline and CINAHL from inception to April 2021. Inclusion criteria were adult cohorts (18 ≥ years old) reporting median time-periods between onset of symptoms for Crohn’s disease (CD), ulcerative colitis (UC) or IBD (i.e., CD and UC together) and a final diagnosis (diagnostic delay). Narrative synthesis was used to examine the extent of diagnostic delay and characteristics associated with delay. Sensitivity analysis was applied by the removal of outliers. Results Thirty-one articles reporting median diagnostic delay for IBD, CD or UC were included. After sensitivity analysis, the majority of IBD studies (7 of 8) reported a median delay of between 2-5.3 months. From the studies examining median delay in UC, three quarters (11 of 16) reported a delay between 2–6 months. In contrast, three quarters of the studies (17 of 23) including CD samples, reported a delay of between 2–12 months. No characteristic had been examined enough to understand their role in diagnostic delay in these populations. Conclusions This systematic review provides robust insight into the extent of diagnostic delay in IBD, particularly in CD, and suggests further intervention is needed to reduce delay. Furthermore, our findings provide a benchmark value range, which such future work can be measured against. Diagnostic Delay Inflammatory Bowel Disease Crohn’s Disease Ulcerative Colitis Figures Figure 1 Introduction Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, the most prevalent examples being Crohn’s disease (CD) and ulcerative colitis (UC)[ 1 ]. Approximately 6.8 million cases of IBD were reported globally in 2017, with nearly a quarter of these cases in North America, resulting in a significant personal and societal burden [ 2 ]. The clinical presentation of IBD is pleomorphic, but can include change in bowel habit, rectal bleeding, fatigue and weight loss [ 3 ]. In addition, approximately 25–40% of individuals with IBD display extra-intestinal manifestations, which include arthritis, axial spondyloarthritis, uveitis, erythema nodosum and primary sclerosing cholangitis [ 4 ]. The range of such presenting symptoms can make it challenging for clinicians to promptly identify patients with IBD, and symptoms can be attributed to other conditions such as irritable bowel syndrome, all of which can lead to diagnostic delay [ 5 ]. Such delays may be further contributed to by factors such as patient demographics, geographical location and the presence of extra-intestinal manifestations [ 6 – 9 ]. For example, in affected countries, symptoms of IBD may be mistaken for abdominal tuberculosis[ 10 ]. In cases of diagnostic delay, adverse impacts on clinical outcomes can occur, including an increased need for subsequent surgical intervention and poor response to medical therapy [ 11 , 12 ]. Recent reports suggest the diagnostic delay of IBD can range anywhere from 5.3 months to 3.6 years [ 7 , 13 ] and that delays in the diagnosis of CD are longer than for UC [ 6 , 12 , 14 ]. This wide variation reported in the differences in the delay experienced by patients, means the true extent of the problem of delay remains unclear. The aim of this systematic review was to provide a clearer benchmark range for the extent of diagnostic delay, as well as providing information on any characteristics that may be associated with delay. Methods Data Sources and Searches: We conducted a systematic review by searching the medical literature databases of Medline, EMBASE and CINAHL from their inception to April 2021, using a combination of free-text and medical subject headings (MeSH) terms, or equivalents from each database ( Supplementary Table 1 ). Search terms were devised for IBD and diagnostic delay using existing systematic reviews that explored other aspects of IBD, and reviews investigating diagnostic delay in other long-term conditions[ 15 – 17 ]. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed during the completion of this systematic review and the protocol was logged with PROSPERO (Registration number: CRD42018108886). Study Selection: The inclusion criteria were developed using the PICOS framework [ 18 ]. The included population were adults aged 18 years or older with a confirmed diagnosis of IBD, CD or UC. Studies with adult populations which included a proportion of participants under 18 years old were retained if the mean age implied the population was largely formed from participants above 18 years old. Studies also had to include the primary outcome of interest, a reported average time-period of diagnostic delay for IBD, CD or UC from symptom onset to final diagnosis. Studies were excluded if their design included case studies or case series with less than ten participants, literature reviews, systematic reviews or conference abstracts. There were no restrictions on time of publication, as databases were searched from inception. Articles in languages other than English were included, individuals who spoke the language were then requested to make initial assessments and then, if necessary, quality appraise and extract pertinent data, with Google Translate also being used if necessary. Once the database searches had been undertaken using the reported criteria, the reference manager software Mendeley was used to remove duplicates (Version 1.16.1, Mendeley Ltd., London, UK). Authors EC and JAP then completed an independent title and abstract review of 50% of the initially identified articles each. Articles that progressed to abstract review underwent a second review, where EC reviewed the abstracts initially reviewed by JAP, and vice versa. These included abstracts then underwent a full text review, with EC independently reviewing all full texts and the remaining three authors (JAP, BS, ADF) reviewing a proportion of full texts each. Throughout the review process, disagreements between reviewers were resolved through discussion and by consulting an arbitrating author (BS). Data Extraction and analysis: Data extraction of included articles was completed by two reviewers (EC, JAP). The primary outcome of interest extracted was the reported average time-period of diagnostic delay of IBD (for articles that did not distinguish between CD and UC), CD or UC, from symptom onset to diagnosis. Average data regarding diagnostic delay was reported as mean or median values, with both being recorded along with their accompanying estimate of accuracy (standard deviation or interquartile range respectively). However, due to the typical non-normality of mean diagnostic delay data, only median values were used in this analysis [ 19 ]. The unit of time that articles used to report diagnostic delay varied from days to years, therefore delay data were converted into months to allow comparability of the data. Additional data extracted included lead author, year of publication, time-period of participant recruitment, gender, country and mean sample age. Finally, information (where reported) on any specific characteristics (e.g., demographics, symptoms) and their association with reported diagnostic delay were identified in the articles and extracted. Regarding this characteristic data, no restriction was placed on the measure of central tendency here, but rather the focus was on whether differences in delay were experienced across comparator samples (i.e., extent of diagnostic delay in males vs females). The data from the included articles were examined using narrative synthesis. In the instance of outlier data, sensitivity analysis was performed, resulting in the exclusion of related studies. Quality Appraisal: A modified Newcastle-Ottawa Score (NOS) was used for quality appraising the included articles, carried out by EC and JAP. The NOS for cohort studies, and an adapted version of the NOS for cross-sectional studies were used [ 20 ]. The ‘Selection of participants’ and ‘Measurement of outcome’ were the two criteria of the NOS used to assess quality of articles. The representativeness of studies was assessed based on the geographical spread of recruitment, as well as variation in population characteristics. Results Search results 10,119 unique articles were identified from the three selected databases and underwent title review. Following the exclusion of 6746 articles based upon title, 3373 articles underwent abstract review. From these, 429 articles were reviewed in full, leaving a final 31 articles that reported median data to be included for narrative synthesis. See PRISMA flowchart, below (Fig. 1 ). Study characteristics Of the 31 articles included in the review, 23 were cohort studies, of which 12 were retrospective [ 6 , 12 – 14 , 21 – 28 ], eight were prospective cohorts [ 9 , 29 – 35 ] and three combined both methods [ 36 – 38 ]. Eight articles used a cross-sectional study design [ 5 , 7 , 8 , 11 , 39 – 42 ]. Nineteen studies were conducted in Europe, seven in Asia, four in North America and one in South America. Twenty articles were based in primary or secondary care, four in tertiary care and five from population registries. Two articles did not report the source from which the sample was drawn. The majority of articles documented the criteria used to diagnose participants, typically using a combination of clinical features, radiologic and histologic findings to diagnose IBD. Formal diagnostic criteria used by articles included Lennard-Jones, ECCO and Copenhagen diagnostic criteria. Nine articles did not outline the use of any diagnostic criteria. The characteristics of each study included in the review have been summarised in Table 1 . Table 1 The characteristics of the studies included in the systematic review (n = 31) Author, Year Country Study Design Recruitment Period Healthcare Setting Condition Diagnostic Criteria for IBD Kyle, 1971 [ 39 ] Scotland Cross-sectional 1955–1969 Not reported CD History and examination findings, radiology/endoscopy Lind,1985 [ 29 ] Norway Prospective cohort 1975–1979 Secondary CD Standardised investigational program (colonoscopy/gastroscopy. biopsy, barium enema) Foxworthy, 1985 [ 30 ] * USA Prospective cohort 1975–1983 Secondary CD Clinical presentation/course, radiologic/histologic/laparotomy appearance Harper, 1986 [ 8 ] * USA Cross-sectional 1983–1984 Secondary CD Typical symptoms/findings, radiologic/endoscopic/operative features Langholz, 1991 [ 31 ] Denmark Prospective cohort 1962–1987 Secondary UC Copenhagen criteria Munkholm, 1992 [ 32 ] Denmark Prospective cohort 1962–1987 Secondary CD Copenhagen criteria Timmer, 1999 [ 33 ] Germany Prospective cohort 1991–1995 Secondary CD Case definition criteria for definite or probable CD Yang, 2000 [ 36 ] South Korea Retrospective & prospective cohort 1986 − 1977 Secondary UC Clinical, sigmoidoscopy, histological/cytological, radiologic/endoscopic features Burgmann, 2006 [ 5 ] Canada Cross-sectional 2004–2005 Manitoba IBD registry CD ICD codes UC ICD codes Albert, 2008 [ 40 ] Germany Cross-sectional 2005–2007 Patient organization CD Not reported Romberg-Camps, 2009 [ 34 ] Netherlands Prospective cohort 1991–2002 Population registry CD Lennard-Jones criteria UC Continuous mucosal inflammation without granuloma, affecting rectum +/ some/ all of the colon in continuity with rectum Guariso, 2010 [ 37 ] Italy Retrospective & prospective cohort 1994–2008 Tertiary IBD Clinical, radiological, endoscopic + histologic findings CD Clinical, radiological, endoscopic + histologic findings UC Clinical, radiological, endoscopic + histologic findings Vavricka, 2012 [ 6 ] Switzerland Retrospective cohort 2006–2009 Population registry CD Not reported UC Not reported Burisch, 2014 [ 9 ] * Europe Prospective cohort Jan 2010-Dec 2010 Secondary CD Copenhagen diagnostic criteria UC Copenhagen diagnostic criteria Pellino, 2015 [ 11 ] Italy Cross-sectional 2000–2009 Secondary CD Accepted ECCO criteria Li, 2015 [ 23 ] China Retrospective cohort 2010–2014 Secondary CD Colonoscopy, enteroscopy, capsule endoscopy, histopathology, haematology Maconi, 2015 [ 22 ] Italy Retrospective cohort 2012–2013 Primary and secondary CD Not reported Basaranoglu, 2015 [ 24 ] Turkey Retrospective cohort 1995–2007 Tertiary CD clinical, radioscopic, endoscopic, histologic findings UC not reported Lin, 2016 [ 25 ] * Taiwan Retrospective cohort 1991–2014 Not reported UC Not reported Lee, 2017 [ 12 ] South Korea Retrospective cohort 2000–2015 Secondary CD Not reported Not reported Cantoro, 2017 [ 21 ] Italy Retrospective cohort 1955–2014 Secondary IBD Not reported Nguyen, 2017 [ 14 ] USA Retrospective cohort 2008–2015 Tertiary CD Not reported UC Not reported Nahon, 2018 [ 38 ] France Retrospective & prospective cohort 2002–2015 Secondary CD Colonoscopy or radiologic examination which strongly suggested IBD UC Irving, 2018 [ 41 ] Finland, Italy, France, Canada, Germany, UK, Spain and Sweden Cross-sectional 2013–2014 General population CD Not reported UC Not reported Szanto, 2018 [ 13 ] Hungary Retrospective cohort 2007–2015 Tertiary CD Lennard-Jones and accepted ECCO criteria UC Lennard-Jones and accepted ECCO criteria Banerjee, 2018 [ 26 ] India Retrospective cohort Not reported Secondary CD Not reported (paediatric CD = Porto criteria) Kang, 2019 [ 27 ] South Korea Retrospective cohort 2006–2016 Secondary UC Clinical, radiological, endoscopic and pathologic findings Novacek, 2019 [ 7 ] Austria Cross-sectional 2014–2015 Secondary CD ECCO criteria UC ECCO criteria Walker, 2020 [ 28 ] UK Retrospective cohort Primary and secondary CD ECCO-ESGAR criteria UC ECCO-ESGAR criteria Gomes, 2021 [ 42 ] Brazil Cross-sectional Not reported Secondary CD Clinical, laboratory, endoscopic and histologic findings UC Clinical, laboratory, endoscopic and histologic findings Chaparro, 2021 [ 35 ] Spain Prospective cohort 2017 Secondary CD ECCO criteria UC ECCO criteria IBD- Inflammatory Bowel Disease; CD- Crohn’s Disease; UC- Ulcerative Colitis; ICD- International Classification of Diseases; ECCO- European Crohn’s and Colitis Organisation. *Studies providing diagnostic delay data for characteristic comparisons only Quality appraisal Of the 23 cohort studies, nine articles were deemed to be ‘truly representative’, 13 ‘somewhat representative’ and one sampled from a ‘selected group of users’. For the eight cross-sectional studies, three articles were ‘truly representative’, three ‘somewhat representative’, one sampled from a ‘selected group of users’ and one ‘did not report the sampling strategy’. Ascertainment of exposure (i.e., diagnosis of IBD) was determined by assessing ‘secure records’ in all cohort studies. For the eight cross-sectional studies, three studies used a ‘validated measurement tool’ to ascertain exposure, in three studies a ‘tool was available and described’ and two studies provided ‘no description’ of how participants with IBD were identified. Assessment of outcome, which in this systematic review was diagnostic delay, was done by ‘record linkage’ in 17 cohort studies and the remaining six by ‘self-report’. Two cross-sectional studies used ‘record linkage’, four used ‘self-reporting’ and two studies provided ‘no description’ for the assessment of outcome. Extent of diagnostic delay There were 11,597 participants providing median data related to IBD, with 4269 participants originating from studies that did not distinguish between CD or UC. 13,998 participants provided data related to CD and 12,895 provided data relating to UC. Median values of diagnostic delay of IBD were provided by nine articles and ranged from 2 to 96 months. Median delay of CD was provided by 24 articles, ranging from 2 to 84 months and 17 articles reported median delays of 2 to 114 months from initial symptoms to final diagnosis of UC (Table 2 ). Table 2 Median diagnostic delay (months) for IBD, CD and UC, ordered from shortest to longest delay Lead author Year Country Sample Size (N) % Male Mean Age (SD)/[range] Diagnostic Delay IQR Range Inflammatory Bowel Disease (IBD) Basaranoglu 2015 Turkey 282 CD- 98 UC- 184 64.2 40.1 (14.7) 2 0–18 Cantoro 2017 Italy 3392 CD- 1537 UC- 1855 53.1 Not reported 3 (0–13) Romberg-Camps 2009 Netherlands 1187 CD- 476 UC- 630 IC- 81 48.9 CD- 34, [5–79] UC- 42, [8–84] IC- 42, [13–77] 3 0-480 Guariso 2010 Italy 179 CD-65 UC-99 IBD-U-15 - 29.1 [ 18 – 40 ] 3 0-135 Chaparro 2021 Spain 3611 52.8 42 † (30–55) 3 1–9 Szanto 2018 Hungary 911 CD- 428 UC- 483 46.3 Not reported 3.6 (0-9.6) Novacek 2019 Austria 1265 CD- 830 UC- 435 49.4 40 (31–52)*, [18–87] 5.3 (2.3–16.4) Gomes 2021 Brazil 658 44.6 44.2 13 5–38 Burgmann 2006 Canada 112 CD- 65 UC- 42 Proctitis- 3 IC-2 42.9 38 (12.9), [16–77] 96 Crohn’s Disease (CD) Basaranoglu 2015 Turkey 98 52.0 37.8 (13.5), [17–79] 2 - [0–18] Guariso 2010 Italy 65 - - 4 - 0–88 Timmer 1999 Germany 132 25 31 (23–47)* 5 - Romberg-Camps 2009 Netherlands 476 39.3 34, [5–79] 5 - [0-360] Chaparro 2021 Spain 1647 50.2 41 † (28–54) 5 - 1–15 Nahon 2018 France 638 5 - - Kyle 1971 Scotland 175 38.3 Not reported 6 - - Lee 2017 South Korea 165 76.4 28.2 (13.8) 6.2 (1.5–21.5) - Novacek 2019 Austria 830 48.1 40 (31–52)* 6.4 (2.3–23.4) - Cantoro 2017 Italy 1537 53.1 Not Reported 7.1 - - Walker 2020 UK 94 - - 7.6 3.1–16.0 0-112 Maconi 2015 Italy 83 41 35.2 (14.5) 8 (3–27) [0-324] Vavricka 2012 Switzerland 932 46.8 41 (15), [16–88] 9 (3–24) - Nguyen 2017 USA 110 41.0 35 (17) 9.5 (3.8–25.6) - Li 2015 China 343 70.0 29.5 (12.0) 10 (2–34) - Pellino 2015 Italy 361 Not reported 32.54 (14.47) 11 - [1-163] Irving 2018 Finland, Italy, France, Canada, Germany, UK, Spain and Sweden 4097 Not reported Not reported 12 - 0-564 Albert 2008 Germany 112 34.8 28 (8.0) F 31 (11.5) M 13 - [0-281] Banerjee 2018 India 720 60.3 32 (18–50)* 18 (6–36) - Gomes 2021 Brazil 303 49.8 32 20 6.5–48 - Lind 1985 Norway 214 56.1 24, [7–63] 22* 24 Szanto 2018 Hungary 428 45.3 26.6 (11.3) 25.2 0-103.2 Munkholm 1992 Denmark 373 42.1 32.5, 8–84 26.4 0-324 Burgmann 2006 Canada 65 33.8 38 (12.9), [16–77] 84 Ulcerative Colitis (UC) Guariso 2010 Italy 99 - - 2 - 0-135 Basaranoglu 2015 Turkey 98 52.0 37.8 (13.5), [17–79] 2 0–15 Cantoro 2017 Italy 1855 53.1 Not Reported 2 Chaparro 2021 Spain 1964 50.1 46 † (34–57) 2 1–5 Kang 2019 South Korea 551 55.7 40.56 (16.11) 2.3 Romberg-Camps 2009 Netherlands 476 39.3 34, 5–79 3 0-480 Nahon 2018 France 272 3 Nguyen 2017 USA 110 41.0 38 (17) 3.1 1.1–9.6 Walker 2020 UK 195 - - 3.3 1.9–7.3 0–65 Novacek 2019 Austria 830 48.1 40 (31–52)* 3.4 1.4–10.3 Vavricka 2012 Switzerland 932 46.8 41 (15), [16–88] 4 1–12 Yang 2000 Korea 94 47.9 35*, [8–68] 6 1-120 Gomes 2021 Brazil 355 38.3 35.3 11 4–29 Irving 2018 Finland, Italy, France, Canada, Germany, UK, Spain and Sweden 3410 Not reported Not reported 12 0-552 Langholz 1991 Denmark 1161 46.7 34, [2–88] 12 0-444 Szanto 2018 Hungary 428 45.3 26.6 (11.3) 30.9 (12.5) 55.2 0-123.6 Burgmann 2006 Canada 65 33.8 38 (12.9), [16–77] 114 IC- Indeterminate Colitis; IBD-U- Unclassified Inflammatory Bowel Disease; SD- Standard Deviation; IQR- Interquartile Range * Median age reported with interquartile range. Studies in italic indicates outliers. † =Median age provided Through the sensitivity analysis one article was excluded due to consistently being an outlier across the three condition groups. Burgmann et al. [ 5 ] reported median delays of approximately 60–75 months longer than the next closest study across the three analyses. After exclusion of this outlier, the median diagnostic delay of IBD across the remaining 8 articles ranged from 2 to 13 months, with three quarters of these reporting a delay of between 2-5.3 months. Of the 23 studies defining samples solely by CD, the overall delay ranged from 2 to 26.4 months, with three quarters of the reported median delays ranging from 2–12 months. Finally, from the16 studies examining UC, median diagnostic delay ranged from 2 to 55.2 months, with two thirds of studies reporting delay between 2 to 6 months. This overall longer median delay observed in patients with CD compared to UC was also observed in the subset of studies where delay had been directly compared between the two conditions within the same populations [ 5 , 7 , 13 , 21 , 24 , 34 ]. Factors associated with diagnostic delay Three studies compared differences in delay related to help-seeking (from symptom onset to primary health care consultation) and that which occurred after the first consultation. Though Vavricka found that delay was significantly greater for CD than UC patients during the help-seeking and first consultation phase, Nguyen only found delay after first consultation to final diagnosis to be significantly greater for CD patients compared to UC patients [ 6 , 14 ]. Walker [ 28 ] reported longer delays across help-seeking, primary care and secondary care in CD over UC (Table 3 ). Table 3 Extent of delay in IBD diagnosis at different stages of the patient journey Median months of delay (IQR) [range] Reason for delay Reason/point of delay Author, year Country CD UC Patient-related delay Non-help-seeking Vavricka, 2012 Switzerland 2 (0–6) 1 (0–4) Nguyen, 2017 USA 1 (0.2–4.9) 0.7 (0.3–3.0) Lee, 2017 South Korea 1.2 (0.5–8.4) 1.9 (0.9–4.9) Walker, 2020 UK 3 (0.9–6.7) 2.1 (0.9–3.9) Healthcare-related delay Delay following first consultation Nguyen, 2017 USA 3.5 (1.2–20.5) 1.1 (0.4–5.4) Vavricka, 2012 Switzerland 4 (0–18) 1 (0–5) Delay from first physician visit to IBD diagnosis Lee, 2017 South Korea 0.7 (0.1–4.6) 0.2 (0.1–0.6) Primary care delay Walker, 2020 UK 0.3 (0.0-1.2) 0.2 (0.0-0.8) Secondary care delay Walker, 2020 UK 1.6 (0.6–3.7) 0.9 (0.5-2.0) Three articles found statistical significance between increasing age and longer diagnostic delay [ 8 , 25 , 30 ]. The study by Foxworthy and Wilson was the only one that reported median values, showing a statistically significant difference in diagnostic delay of CD between patients over 60 (diagnostic delay 16 months) and patients less than 60 years old at diagnosis (diagnostic delay 5 months) [ 30 ]. A prospective cohort study conducted by Burisch et al. grouped data from 14 Western and 8 Eastern European countries to compare differences in diagnostic delay [ 9 ]. For CD, median values of diagnostic delay were 4.6 and 3.4 months, respectively, for Western and Eastern Europe. Diagnostic delay was 2.5 and 2.2 months for UC in Western and Eastern Europe, respectively (Table 4 ). However, these differences were not statistically different. Table 4 Data for additional characteristics of delay Author, Publication Year and Country CD/UC Diagnostic Criteria Comparison Sample Size % Male Mean Age (SEM), range Diagnostic Delay (SD)/range (months) Foxworthy (1985), USA CD Chart review Diagnosis ≥60 years old 10 50% 68 (1.6), 60–78 Median- 16 Diagnosis 64 years old 24 42% 57 (2.5) Mean- 76.8 (18) Diagnosis < 64 years 24 42% 23.3 (2.0) Mean- 28.8 (8.4) Lin (2016), Taiwan UC Not reported Onset ≥60 years old 77 60% 68 (6.0), 60–91 Mean- 26.4 (54), 0- 288 Onset < 60 years old 459 59% 36.8 (11.5), 1–59 Mean- 4.8 (9.6), 0-120 Burisch (2014), Europe CD Copenhagen diagnostic criteria Western Europe 430 51% 38, 16–89 Median- 4.6, 0-372 Eastern Europe 105 60% 32, 15–78 Median- 3.4, 0-240 UC Copenhagen diagnostic criteria Western Europe 668 56% 39, 15–89 Median- 2.5, 0-252 Eastern Europe 145 57% 36, 18–81 Median- 2.2, 0–60 ECCO-ESGAR = European Crohn’s and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR] Discussion This systematic review demonstrates that receiving a prompt diagnosis of IBD remains difficult to achieve, with patients typically experiencing several months of diagnostic delay. In particular, delay is prolonged in patients with CD compared to UC, with the majority of previous studies reporting diagnostic delay less than 12 months for CD, but less than 6 months for UC. However, research examining the specific factors contributing to delay in either condition remains very limited. Ultimately, this data provides a new benchmark against which interventions to reduce delay in patients with IBD can be compared. The skewed nature of diagnostic delay data means that (for the majority) of patients with CD or UC, diagnosis is achieved within a year of symptom onset. However, one in four studies did find that, on average, receiving a final diagnosis of CD could take between 12 to 24 months from the initial onset of symptoms, whereas we identified that three quarter of patients with UC were diagnosed in < 6 months. These findings provide a more accurate understanding of the true extent of diagnostic delay and though not intended to minimise the problem of diagnostic delay in UC, the greatest impact in a reduction in delay for patients with IBD may come from focusing on CD. Our reported findings are based on the studies included in the sensitivity analysis, rather than all identified studies. By removing the study by Burgmann et al , [ 5 ] which reported extremely protracted delays in IBD, CD and UC diagnosis, we have provided a more representative median range for diagnostic delay. Though removal of such outliers is a somewhat arbitrary one, performing this practical sensitivity analysis enabled us to look at the most common length of delay. To support the removal of this studies based on their reported, extreme delay values, we examined the details of the study design but could not identify any clear reason why their data was drastically different to that of the other studies in the systematic review. However, it was of note that this study reported longer diagnostic delay in UC compared to CD, contrary to other included studies. Possible reasons for UC consistently demonstrating shorter diagnostic delays than CD could be because the location of disease is confined to the large bowel and patients experiencing rectal bleeding may be more likely to present to a doctor [ 7 ]. However, CD delays may be longer due to a lack of clinical suspicion and diagnostic testing, associating common CD symptoms like abdominal pain with other conditions such as irritable bowel syndrome and difficulties in identifying disease that is only present in the small bowel [ 12 , 14 , 40 ]. Though overall diagnostic delay in patients with IBD, CD or UC has frequently been reported in the literature, there remains a dearth of data to have examined the role of specific patient or healthcare factors in contributing to delay. Such sub-analysis has proven useful in other systematic reviews into diagnostic delay, as this provides focus on certain characteristics which could prove to be avenues to reduce delay. For example, a previous systematic review on diagnostic delay in giant cell arteritis found delay was greater in those patients who did not experience cranial symptoms compared to those with cranial symptoms [ 16 ]. However, there remains a lack of evidence in such sub-analysis in IBD populations and despite our identification of studies to have considered the role of age at diagnosis and sample country, findings were limited and conflicting. Research exploring the barriers and facilitators to IBD diagnosis is clearly needed. Diagnostic delay has been explored in many other studies for a variety of conditions, including giant cell arteritis, gynaecological cancers and tuberculosis [ 16 , 43 , 44 ]. Exploring the extent of diagnostic delay in medical conditions, where delays are common, is important as it provides a backdrop for future research examining the reasons for prolonged diagnostic delay and potentially inform interventions for reducing delays and improving patient care. As prolonged diagnostic delay of IBD appears to increase the likelihood of complicated disease, reducing delays in IBD diagnosis could improve the clinical outcome of patients with the condition [ 12 , 45 ]. The specific use of the faecal calprotectin test was not discussed in the studies of this systematic review. It detects levels of calprotectin within stool as a consequence of neutrophil aggregation to the gastrointestinal tract due to active inflammation like that found in IBD [ 46 ]. Existing research suggests that this is effective at differentiating between organic and functional origins of bowel disease, thus could reduce delays in IBD diagnosis [ 47 , 48 ]. The focus on median data within the analysis in this systematic review is a key strength as it reduces problems related to overestimation of averages typically related to use of means from skewed data, providing a more robust estimate of diagnostic delay. Furthermore, as well as examining IBD overall, this systematic review examined the most common disease sub-categories of UC and CD, and, finally, we did not restrict study inclusion based on language, leading to additional studies being included in the review. A limitation of this study is the variation between individual study designs, for instance differences in participant age, method of IBD diagnosis and country. However, despite the introduction of such heterogeneity, this data also provides a wider picture of the problem of diagnostic delay in this disease group. In conclusion, this systematic review provides a robust insight into the current extent of diagnostic delay in IBD, indicating that diagnostic delay remains a pertinent issue for patients with IBD, particularly CD, but that the factors which may have a role in delay remain unclear. This systematic review provides a backdrop and benchmark onto which further research can be conducted to reduce the time to IBD diagnosis, particularly exploring knowledge of IBD amongst healthcare professionals and the general population to help reduce overall delay. This future research is particularly important, as reducing diagnostic delay of IBD may improve the clinical course of the disease. Declarations Acknowledgements The authors would like to thank the systematic review team (Dr Nadia Corp and Dr Opeyemi Babatunde) at Keele University School of Medicine for their advice and assistance in the completion of this systematic review. They also wish to thank Dr Kay Polidano who was involved in the translation of selected articles. Conflict of Interest The authors declare no conflict of interest Funding No funding is associated with this publication Author contributions EC: Creation of search strategy, database search, data extraction, article review, narrative synthesis, writing of manuscript JAP: Initial study design, creation of search strategy, data extraction, article review, narrative synthesis, writing of manuscript BS: Initial study design, article review, writing of manuscript ADF: Initial study design, clinical input, article review, writing of manuscript References Rosen, M.J., A. Dhawan, and S.A. Saeed, Inflammatory Bowel Disease in Children and Adolescents . 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Ford, A.C., et al., Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol, 2011. 106 (4): p. 590-9; quiz 600. Methley, A.M., et al., PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews . BMC Health Serv Res, 2014. 14 : p. 579. Sykes, M.P., et al., Delay to diagnosis in axial spondyloarthritis: are we improving in the UK? Rheumatology (Oxford), 2015. 54 (12): p. 2283–4. Herzog, R., et al., Are healthcare workers' intentions to vaccinate related to their knowledge, beliefs and attitudes? A systematic review . BMC Public Health, 2013. 13 : p. 154. Cantoro, L., et al., The Time Course of Diagnostic Delay in Inflammatory Bowel Disease Over the Last Sixty Years: An Italian Multicentre Study . J Crohns Colitis, 2017. 11 (8): p. 975–980. Maconi, G., et al., The impact of symptoms, irritable bowel syndrome pattern and diagnostic investigations on the diagnostic delay of Crohn's disease: A prospective study . Dig Liver Dis, 2015. 47 (8): p. 646–51. Li, Y., et al., Diagnostic delay in Crohn's disease is associated with increased rate of abdominal surgery: A retrospective study in Chinese patients . Dig Liver Dis, 2015. 47 (7): p. 544–8. Basaranoglu, M., et al., Seasonal clustering in inflammatory bowel disease: a single centre experience . Expert Rev Gastroenterol Hepatol, 2015. 9 (6): p. 877–81. Lin, W.C., et al., Elderly Adults with Late-Onset Ulcerative Colitis Tend to Have Atypical, Milder Initial Clinical Presentations but Higher Surgical Rates and Mortality: A Taiwan Society of Inflammatory Bowel Disease Study . J Am Geriatr Soc, 2016. 64 (10): p. e95-e97. Banerjee, R., et al., Risk factors for diagnostic delay in Crohn's disease and their impact on long-term complications: how do they differ in a tuberculosis endemic region? Alimentary Pharmacology and Therapeutics, 2018. 47 (10): p. 1367–1374. Kang, H.S., et al., Two-year delay in ulcerative colitis diagnosis is associated with anti-tumor necrosis factor alpha use . World Journal of Gastroenterology, 2019. 25 (8): p. 989–1001. Walker, G.J., et al., Quality improvement project identifies factors associated with delay in IBD diagnosis . Alimentary Pharmacology and Therapeutics, 2020. 52 (3): p. 471–480. Lind, E., et al., Crohn's disease. Clinical manifestations . Scand J Gastroenterol, 1985. 20 (6): p. 665–70. Foxworthy, D.M. and J.A. Wilson, Crohn's disease in the elderly. Prolonged delay in diagnosis . J Am Geriatr Soc, 1985. 33 (7): p. 492–5. Langholz, E., et al., Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987 . Scand J Gastroenterol, 1991. 26 (12): p. 1247–56. Munkholm, P., et al., Incidence and prevalence of Crohn's disease in the county of Copenhagen, 1962-87: a sixfold increase in incidence . Scand J Gastroenterol, 1992. 27 (7): p. 609–14. Timmer, A., B. Breuer-Katschinski, and H. Goebell, Time trends in the incidence and disease location of Crohn's disease 1980–1995: a prospective analysis in an urban population in Germany . Inflamm Bowel Dis, 1999. 5 (2): p. 79–84. Romberg-Camps, M.J., et al., Inflammatory Bowel Disease in South Limburg (the Netherlands) 1991–2002: Incidence, diagnostic delay, and seasonal variations in onset of symptoms . J Crohns Colitis, 2009. 3 (2): p. 115–24. Chaparro, M., et al., Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study . J Clin Med, 2021. 10 (13). Yang, S.K., et al., Incidence and prevalence of ulcerative colitis in the Songpa-Kangdong District, Seoul, Korea, 1986–1997 . J Gastroenterol Hepatol, 2000. 15 (9): p. 1037–42. Guariso, G., et al., Inflammatory bowel disease developing in paediatric and adult age . J Pediatr Gastroenterol Nutr, 2010. 51 (6): p. 698–707. Nahon, S., et al., Evolution in clinical presentation of inflammatory bowel disease over time at diagnosis: A multicenter cohort study . European Journal of Gastroenterology and Hepatology, 2018. 30 (10): p. 1125–1129. Kyle, J., The early diagnosis of chronic Crohn's disease . Scott Med J, 1971. 16 (3): p. 197–201. Albert, J.G., et al., Course of Crohn's disease prior to establishment of the diagnosis . Z Gastroenterol, 2008. 46 (2): p. 187–92. Irving, P., et al., IBD2020 global forum: results of an international patient survey on quality of care . Intestinal Research, 2018. 16 (4): p. 537–545. Gomes, T.N.F., et al., Clinical and demographic profile of inflammatory bowel disease patients in a reference center of Sao Paulo, Brazil . Clinical and Experimental Gastroenterology, 2021. 14 : p. 91–102. Getnet, F., et al., Delay in diagnosis of pulmonary tuberculosis in low-and middle-income settings: systematic review and meta-analysis . BMC Pulm Med, 2017. 17 (1): p. 202. Williams, P., P. Murchie, and C. Bond, Patient and primary care delays in the diagnostic pathway of gynaecological cancers: a systematic review of influencing factors . Br J Gen Pract, 2019. 69 (679): p. e106-e111. Moon, C.M., et al., Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study . PLoS One, 2015. 10 (12): p. e0144390. Pathirana, W.G.W., et al., Faecal Calprotectin. Clin Biochem Rev, 2018. 39 (3): p. 77–90. Schoepfer, A.M., et al., Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies . Inflamm Bowel Dis, 2008. 14 (1): p. 32–9. Waugh, N., et al., Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation . Health Technol Assess, 2013. 17 (55): p. xv-xix, 1–211. Supplementary Table Supplementary Table 1- Search strategy: Search Strategy 1 Exp inflammatory bowel diseases/ 2 inflammatory bowel disease*.ti,ab,kw. 3 inflammatory bowel disorder*.ti,ab,kw. 4 ibd.ti,ab,kw. 5 crohn*.ti,ab,kw. 6 ulcerative colitis*.ti,ab,kw. 7 inflam* colitis*.ti,ab,kw. 8 colitis*.ti,ab,kw. 9 colitis/ 10 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 11 diagnos* adj3 delay*.ti,ab,kw. 12 diagnos* adj3 lag*.ti,ab,kw. 13 diagnos* adj3 interval*.ti,ab,kw. 14 ((late* or earl*) adj3 diagnos*).ti,ab,kw. 15 ((late* or earl*) adj3 treat*).ti,ab,kw. 16 ((late* or earl*) adj3 consult*).ti,ab,kw. 17 ((late* or earl*) adj3 refer*).ti,ab,kw. 18 ((late* or earl*) adj3 detect*).ti,ab.kw. 19 (health* adj3 seek*).ti,ab,kw. 20 (case* adj3 seek*).ti,ab,kw. 21 (case* adj3 find*).ti,ab,kw. 22 (delay* adj3 consult*).ti,ab,kw. 23 (delay* adj3 detect*).ti,ab,kw. 24 (delay* adj3 interval*).ti,ab,kw. 25 (delay* adj3 refer*).ti,ab,kw. 26 (delay* adj3 treat*).ti,ab,kw. 27 (delay* adj3 seek*).ti,ab,kw. 28 Delayed diagnosis/ 29 Early diagnosis/ 30 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26 OR 27 OR 28 OR 29 31 10 AND 30 Additional Declarations No competing interests reported. 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Farmer","email":"","orcid":"","institution":"Keele University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Adam","middleName":"D.","lastName":"Farmer","suffix":""},{"id":113344554,"identity":"702da051-270a-4bbb-9b52-584a9335dc04","order_by":3,"name":"James A. Prior","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYBACxgYwJcHAwN4GpAtQRAlp4TkGpA2I0IIAEmlEamFuYH7AXLjHQs585rPEBx8MbBj42w+wSc7A6zA2A+YZzySMZW6nHTacYZDGIHEmgU1yA36/GDDzHJBInCGd3ibNY3CYgeEGA5vkA7xa2D9AtEgeb//9x+A/gzxhLTxQWyTYjjEzGBxgMABpweuwZp6CwzMOSBhL8KQlS/YYJPMYnklstsTnfcP29o2PCw7UyUmwHzP88KPCTk7u+OGDN3vwaWlmYDiMLMBDMCLlgZgZr4pRMApGwSgYBQAq+0QiTjRzeAAAAABJRU5ErkJggg==","orcid":"","institution":"Keele University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"James","middleName":"A.","lastName":"Prior","suffix":""}],"badges":[],"createdAt":"2022-06-13 12:14:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1753316/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1753316/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22788445,"identity":"cec589ae-2337-4c01-9750-4f130c4c67f4","added_by":"auto","created_at":"2022-06-17 18:41:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":126748,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA-p flowchart of the screening process used to identify the included articles \u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1753316/v1/df55deeb65b4cf369af574ca.jpg"},{"id":22788474,"identity":"bee4f6c4-5fee-48bf-a6e9-583efdd0ad59","added_by":"auto","created_at":"2022-06-17 18:41:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":753534,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1753316/v1/05cff919-561e-4294-b167-644e0bc0a755.pdf"},{"id":22788473,"identity":"1086c785-3084-44a7-b34f-25a17521a51c","added_by":"auto","created_at":"2022-06-17 18:41:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":753534,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1753316/v1/65513c6c-cebd-4418-8588-da0eb2af32f0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Delay in Adult Inflammatory Bowel Disease: A Systematic Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, the most prevalent examples being Crohn\u0026rsquo;s disease (CD) and ulcerative colitis (UC)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Approximately 6.8\u0026nbsp;million cases of IBD were reported globally in 2017, with nearly a quarter of these cases in North America, resulting in a significant personal and societal burden [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe clinical presentation of IBD is pleomorphic, but can include change in bowel habit, rectal bleeding, fatigue and weight loss [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition, approximately 25\u0026ndash;40% of individuals with IBD display extra-intestinal manifestations, which include arthritis, axial spondyloarthritis, uveitis, erythema nodosum and primary sclerosing cholangitis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The range of such presenting symptoms can make it challenging for clinicians to promptly identify patients with IBD, and symptoms can be attributed to other conditions such as irritable bowel syndrome, all of which can lead to diagnostic delay [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Such delays may be further contributed to by factors such as patient demographics, geographical location and the presence of extra-intestinal manifestations [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. For example, in affected countries, symptoms of IBD may be mistaken for abdominal tuberculosis[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In cases of diagnostic delay, adverse impacts on clinical outcomes can occur, including an increased need for subsequent surgical intervention and poor response to medical therapy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecent reports suggest the diagnostic delay of IBD can range anywhere from 5.3 months to 3.6 years [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and that delays in the diagnosis of CD are longer than for UC [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This wide variation reported in the differences in the delay experienced by patients, means the true extent of the problem of delay remains unclear. The aim of this systematic review was to provide a clearer benchmark range for the extent of diagnostic delay, as well as providing information on any characteristics that may be associated with delay.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Sources and Searches:\u003c/h2\u003e \u003cp\u003eWe conducted a systematic review by searching the medical literature databases of Medline, EMBASE and CINAHL from their inception to April 2021, using a combination of free-text and medical subject headings (MeSH) terms, or equivalents from each database (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). Search terms were devised for IBD and diagnostic delay using existing systematic reviews that explored other aspects of IBD, and reviews investigating diagnostic delay in other long-term conditions[\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed during the completion of this systematic review and the protocol was logged with PROSPERO (Registration number: CRD42018108886).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Selection:\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were developed using the PICOS framework [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The included population were adults aged 18 years or older with a confirmed diagnosis of IBD, CD or UC. Studies with adult populations which included a proportion of participants under 18 years old were retained if the mean age implied the population was largely formed from participants above 18 years old. Studies also had to include the primary outcome of interest, a reported average time-period of diagnostic delay for IBD, CD or UC from symptom onset to final diagnosis.\u003c/p\u003e \u003cp\u003eStudies were excluded if their design included case studies or case series with less than ten participants, literature reviews, systematic reviews or conference abstracts. There were no restrictions on time of publication, as databases were searched from inception. Articles in languages other than English were included, individuals who spoke the language were then requested to make initial assessments and then, if necessary, quality appraise and extract pertinent data, with Google Translate also being used if necessary.\u003c/p\u003e \u003cp\u003eOnce the database searches had been undertaken using the reported criteria, the reference manager software Mendeley was used to remove duplicates (Version 1.16.1, Mendeley Ltd., London, UK). Authors EC and JAP then completed an independent title and abstract review of 50% of the initially identified articles each. Articles that progressed to abstract review underwent a second review, where EC reviewed the abstracts initially reviewed by JAP, and vice versa. These included abstracts then underwent a full text review, with EC independently reviewing all full texts and the remaining three authors (JAP, BS, ADF) reviewing a proportion of full texts each. Throughout the review process, disagreements between reviewers were resolved through discussion and by consulting an arbitrating author (BS).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Extraction and analysis:\u003c/h2\u003e \u003cp\u003eData extraction of included articles was completed by two reviewers (EC, JAP). The primary outcome of interest extracted was the reported average time-period of diagnostic delay of IBD (for articles that did not distinguish between CD and UC), CD or UC, from symptom onset to diagnosis. Average data regarding diagnostic delay was reported as mean or median values, with both being recorded along with their accompanying estimate of accuracy (standard deviation or interquartile range respectively). However, due to the typical non-normality of mean diagnostic delay data, only median values were used in this analysis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The unit of time that articles used to report diagnostic delay varied from days to years, therefore delay data were converted into months to allow comparability of the data.\u003c/p\u003e \u003cp\u003eAdditional data extracted included lead author, year of publication, time-period of participant recruitment, gender, country and mean sample age. Finally, information (where reported) on any specific characteristics (e.g., demographics, symptoms) and their association with reported diagnostic delay were identified in the articles and extracted. Regarding this characteristic data, no restriction was placed on the measure of central tendency here, but rather the focus was on whether differences in delay were experienced across comparator samples (i.e., extent of diagnostic delay in males vs females). The data from the included articles were examined using narrative synthesis. In the instance of outlier data, sensitivity analysis was performed, resulting in the exclusion of related studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eQuality Appraisal:\u003c/h2\u003e \u003cp\u003eA modified Newcastle-Ottawa Score (NOS) was used for quality appraising the included articles, carried out by EC and JAP. The NOS for cohort studies, and an adapted version of the NOS for cross-sectional studies were used [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The \u0026lsquo;Selection of participants\u0026rsquo; and \u0026lsquo;Measurement of outcome\u0026rsquo; were the two criteria of the NOS used to assess quality of articles. The representativeness of studies was assessed based on the geographical spread of recruitment, as well as variation in population characteristics.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003eSearch results\u003c/h2\u003e\n\u003cp\u003e10,119 unique articles were identified from the three selected databases and underwent title review. Following the exclusion of 6746 articles based upon title, 3373 articles underwent abstract review. From these, 429 articles were reviewed in full, leaving a final 31 articles that reported median data to be included for narrative synthesis. See PRISMA flowchart, below (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eStudy characteristics\u003c/h2\u003e\n\u003cp\u003eOf the 31 articles included in the review, 23 were cohort studies, of which 12 were retrospective [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e], eight were prospective cohorts [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e] and three combined both methods [\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]. Eight articles used a cross-sectional study design [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e]. Nineteen studies were conducted in Europe, seven in Asia, four in North America and one in South America. Twenty articles were based in primary or secondary care, four in tertiary care and five from population registries. Two articles did not report the source from which the sample was drawn.\u003c/p\u003e\n\u003cp\u003eThe majority of articles documented the criteria used to diagnose participants, typically using a combination of clinical features, radiologic and histologic findings to diagnose IBD. Formal diagnostic criteria used by articles included Lennard-Jones, ECCO and Copenhagen diagnostic criteria. Nine articles did not outline the use of any diagnostic criteria. The characteristics of each study included in the review have been summarised in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe characteristics of the studies included in the systematic review (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAuthor, Year\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCountry\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eStudy Design\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRecruitment Period\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHealthcare Setting\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCondition\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDiagnostic Criteria for IBD\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eKyle, 1971\u003c/strong\u003e[\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScotland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1955\u0026ndash;1969\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory and examination findings, radiology/endoscopy\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLind,1985\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNorway\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1975\u0026ndash;1979\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStandardised investigational program\u003c/p\u003e\n\u003cp\u003e(colonoscopy/gastroscopy. biopsy, barium enema)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eFoxworthy, 1985\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e] \u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1975\u0026ndash;1983\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical presentation/course, radiologic/histologic/laparotomy appearance\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHarper, 1986\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e] \u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1983\u0026ndash;1984\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTypical symptoms/findings, radiologic/endoscopic/operative features\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLangholz, 1991\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDenmark\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1962\u0026ndash;1987\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCopenhagen criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMunkholm, 1992\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDenmark\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1962\u0026ndash;1987\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCopenhagen criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTimmer, 1999\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGermany\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1991\u0026ndash;1995\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCase definition criteria for definite or probable CD\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eYang, 2000\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective \u0026amp;\u003c/p\u003e\n\u003cp\u003eprospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1986\u0026thinsp;\u0026minus;\u0026thinsp;1977\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, sigmoidoscopy, histological/cytological, radiologic/endoscopic features\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBurgmann, 2006\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCanada\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2004\u0026ndash;2005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eManitoba IBD registry\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICD codes\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICD codes\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAlbert, 2008\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGermany\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2005\u0026ndash;2007\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePatient organization\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRomberg-Camps, 2009\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNetherlands\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1991\u0026ndash;2002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ePopulation registry\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLennard-Jones criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eContinuous mucosal inflammation without granuloma, affecting rectum +/ some/ all of the colon in continuity with rectum\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGuariso, 2010\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eRetrospective \u0026amp;\u003c/p\u003e\n\u003cp\u003eprospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e1994\u0026ndash;2008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eTertiary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIBD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, radiological, endoscopic\u0026thinsp;+\u0026thinsp;histologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, radiological, endoscopic\u0026thinsp;+\u0026thinsp;histologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, radiological, endoscopic\u0026thinsp;+\u0026thinsp;histologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVavricka, 2012\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSwitzerland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2006\u0026ndash;2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ePopulation registry\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBurisch, 2014\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEurope\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eJan 2010-Dec 2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCopenhagen diagnostic criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCopenhagen diagnostic criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePellino, 2015\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2000\u0026ndash;2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAccepted ECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLi, 2015\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChina\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2010\u0026ndash;2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eColonoscopy, enteroscopy, capsule endoscopy, histopathology, haematology\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMaconi, 2015\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2012\u0026ndash;2013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrimary and secondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBasaranoglu, 2015\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTurkey\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1995\u0026ndash;2007\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTertiary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eclinical, radioscopic, endoscopic, histologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLin, 2016\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTaiwan\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1991\u0026ndash;2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLee, 2017\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2000\u0026ndash;2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCantoro, 2017\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1955\u0026ndash;2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIBD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNguyen, 2017\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2008\u0026ndash;2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTertiary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNahon, 2018\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFrance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective \u0026amp;\u003c/p\u003e\n\u003cp\u003eprospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2002\u0026ndash;2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eColonoscopy or radiologic examination which strongly suggested IBD\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eIrving, 2018\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFinland, Italy, France, Canada, Germany, UK, Spain and Sweden\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2013\u0026ndash;2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGeneral population\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSzanto, 2018\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHungary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2007\u0026ndash;2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTertiary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLennard-Jones and accepted ECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLennard-Jones and accepted ECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBanerjee, 2018\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIndia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported (paediatric CD\u0026thinsp;=\u0026thinsp;Porto criteria)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eKang, 2019\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2006\u0026ndash;2016\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, radiological, endoscopic and pathologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNovacek, 2019\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAustria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2014\u0026ndash;2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eWalker, 2020\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRetrospective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ePrimary and secondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECCO-ESGAR criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECCO-ESGAR criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGomes, 2021\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eBrazil\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCross-sectional\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, laboratory, endoscopic and histologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eClinical, laboratory, endoscopic and histologic findings\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eChaparro, 2021\u003c/strong\u003e [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSpain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eProspective cohort\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSecondary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECCO criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003eIBD- Inflammatory Bowel Disease; CD- Crohn\u0026rsquo;s Disease; UC- Ulcerative Colitis; ICD- International Classification of Diseases; ECCO- European Crohn\u0026rsquo;s and Colitis Organisation. *Studies providing diagnostic delay data for characteristic comparisons only\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003eQuality appraisal\u003c/h2\u003e\n\u003cp\u003eOf the 23 cohort studies, nine articles were deemed to be \u0026lsquo;truly representative\u0026rsquo;, 13 \u0026lsquo;somewhat representative\u0026rsquo; and one sampled from a \u0026lsquo;selected group of users\u0026rsquo;. For the eight cross-sectional studies, three articles were \u0026lsquo;truly representative\u0026rsquo;, three \u0026lsquo;somewhat representative\u0026rsquo;, one sampled from a \u0026lsquo;selected group of users\u0026rsquo; and one \u0026lsquo;did not report the sampling strategy\u0026rsquo;. Ascertainment of exposure (i.e., diagnosis of IBD) was determined by assessing \u0026lsquo;secure records\u0026rsquo; in all cohort studies. For the eight cross-sectional studies, three studies used a \u0026lsquo;validated measurement tool\u0026rsquo; to ascertain exposure, in three studies a \u0026lsquo;tool was available and described\u0026rsquo; and two studies provided \u0026lsquo;no description\u0026rsquo; of how participants with IBD were identified. Assessment of outcome, which in this systematic review was diagnostic delay, was done by \u0026lsquo;record linkage\u0026rsquo; in 17 cohort studies and the remaining six by \u0026lsquo;self-report\u0026rsquo;. Two cross-sectional studies used \u0026lsquo;record linkage\u0026rsquo;, four used \u0026lsquo;self-reporting\u0026rsquo; and two studies provided \u0026lsquo;no description\u0026rsquo; for the assessment of outcome.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eExtent of diagnostic delay\u003c/h2\u003e\n\u003cp\u003eThere were 11,597 participants providing median data related to IBD, with 4269 participants originating from studies that did not distinguish between CD or UC. 13,998 participants provided data related to CD and 12,895 provided data relating to UC. Median values of diagnostic delay of IBD were provided by nine articles and ranged from 2 to 96 months. Median delay of CD was provided by 24 articles, ranging from 2 to 84 months and 17 articles reported median delays of 2 to 114 months from initial symptoms to final diagnosis of UC (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMedian diagnostic delay (months) for IBD, CD and UC, ordered from shortest to longest delay\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLead author\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eYear\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCountry\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSample Size (N)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e% Male\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMean Age\u003c/p\u003e\n\u003cp\u003e(SD)/[range]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDiagnostic\u003c/p\u003e\n\u003cp\u003eDelay\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eIQR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eInflammatory Bowel Disease (IBD)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBasaranoglu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTurkey\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e282\u003c/p\u003e\n\u003cp\u003eCD- 98\u003c/p\u003e\n\u003cp\u003eUC- 184\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e64.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.1 (14.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u0026ndash;18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCantoro\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3392\u003c/p\u003e\n\u003cp\u003eCD- 1537\u003c/p\u003e\n\u003cp\u003eUC- 1855\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(0\u0026ndash;13)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRomberg-Camps\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNetherlands\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1187\u003c/p\u003e\n\u003cp\u003eCD- 476\u003c/p\u003e\n\u003cp\u003eUC- 630\u003c/p\u003e\n\u003cp\u003eIC- 81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCD- 34, [5\u0026ndash;79]\u003c/p\u003e\n\u003cp\u003eUC- 42, [8\u0026ndash;84]\u003c/p\u003e\n\u003cp\u003eIC- 42, [13\u0026ndash;77]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-480\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGuariso\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e179\u003c/p\u003e\n\u003cp\u003eCD-65\u003c/p\u003e\n\u003cp\u003eUC-99\u003c/p\u003e\n\u003cp\u003eIBD-U-15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.1 [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-135\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChaparro\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3611\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42\u003csup\u003e\u0026dagger;\u003c/sup\u003e (30\u0026ndash;55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u0026ndash;9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eSzanto\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e2018\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eHungary\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e911\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCD- 428\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eUC- 483\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e46.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eNot reported\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e3.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e(0-9.6)\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNovacek\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAustria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1265\u003c/p\u003e\n\u003cp\u003eCD- 830\u003c/p\u003e\n\u003cp\u003eUC- 435\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (31\u0026ndash;52)*, [18\u0026ndash;87]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(2.3\u0026ndash;16.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGomes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBrazil\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e658\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u0026ndash;38\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eBurgmann\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e2006\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eCanada\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e112\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCD- 65\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eUC- 42\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eProctitis- 3\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIC-2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e42.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e38 (12.9), [16\u0026ndash;77]\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e96\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCrohn\u0026rsquo;s Disease (CD)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBasaranoglu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTurkey\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.8 (13.5), [17\u0026ndash;79]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[0\u0026ndash;18]\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGuariso\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u0026ndash;88\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTimmer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1999\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGermany\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e132\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31 (23\u0026ndash;47)*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRomberg-Camps\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNetherlands\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e476\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34, [5\u0026ndash;79]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[0-360]\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChaparro\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1647\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41\u003csup\u003e\u0026dagger;\u003c/sup\u003e (28\u0026ndash;54)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u0026ndash;15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNahon\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFrance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e638\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKyle\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1971\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScotland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e175\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLee\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e165\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.2 (13.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(1.5\u0026ndash;21.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNovacek\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAustria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e830\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (31\u0026ndash;52)*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(2.3\u0026ndash;23.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCantoro\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1537\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot Reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWalker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.1\u0026ndash;16.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-112\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMaconi\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.2 (14.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(3\u0026ndash;27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[0-324]\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVavricka\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSwitzerland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e932\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41 (15), [16\u0026ndash;88]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(3\u0026ndash;24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNguyen\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e110\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35 (17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(3.8\u0026ndash;25.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLi\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChina\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e343\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.5 (12.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(2\u0026ndash;34)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePellino\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e361\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.54 (14.47)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[1-163]\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIrving\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFinland, Italy, France, Canada, Germany, UK, Spain and Sweden\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4097\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-564\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlbert\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGermany\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e112\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28 (8.0) F\u003c/p\u003e\n\u003cp\u003e31 (11.5) M\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[0-281]\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBanerjee\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIndia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e720\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32 (18\u0026ndash;50)*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(6\u0026ndash;36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGomes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBrazil\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.5\u0026ndash;48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLind\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1985\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNorway\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e214\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24, [7\u0026ndash;63] 22*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSzanto\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHungary\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e428\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.6 (11.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-103.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMunkholm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1992\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDenmark\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e373\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.5, 8\u0026ndash;84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-324\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eBurgmann\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e2006\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eCanada\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e65\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e33.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e38 (12.9), [16\u0026ndash;77]\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e84\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eUlcerative Colitis (UC)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGuariso\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-135\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBasaranoglu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTurkey\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.8 (13.5), [17\u0026ndash;79]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u0026ndash;15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCantoro\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1855\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot Reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChaparro\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1964\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46\u003csup\u003e\u0026dagger;\u003c/sup\u003e (34\u0026ndash;57)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u0026ndash;5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKang\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e551\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.56 (16.11)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRomberg-Camps\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNetherlands\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e476\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34, 5\u0026ndash;79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-480\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNahon\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFrance\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e272\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNguyen\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e110\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38 (17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.1\u0026ndash;9.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWalker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e195\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.9\u0026ndash;7.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u0026ndash;65\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNovacek\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAustria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e830\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (31\u0026ndash;52)*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.4\u0026ndash;10.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVavricka\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSwitzerland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e932\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41 (15), [16\u0026ndash;88]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u0026ndash;12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYang\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKorea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35*, [8\u0026ndash;68]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1-120\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGomes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBrazil\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e355\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u0026ndash;29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIrving\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFinland, Italy, France, Canada, Germany, UK, Spain and Sweden\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3410\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-552\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLangholz\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1991\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDenmark\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1161\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34, [2\u0026ndash;88]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0-444\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eSzanto\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e2018\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eHungary\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e428\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e45.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e26.6 (11.3)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e30.9 (12.5)\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e55.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e0-123.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eBurgmann\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e2006\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eCanada\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e65\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e33.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e38 (12.9), [16\u0026ndash;77]\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e114\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003eIC- Indeterminate Colitis; IBD-U- Unclassified Inflammatory Bowel Disease; SD- Standard Deviation; IQR- Interquartile Range * Median age reported with interquartile range. Studies in italic indicates outliers. \u003csup\u003e\u0026dagger;\u003c/sup\u003e=Median age provided\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThrough the sensitivity analysis one article was excluded due to consistently being an outlier across the three condition groups. Burgmann \u003cem\u003eet al.\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e] reported median delays of approximately 60\u0026ndash;75 months longer than the next closest study across the three analyses. After exclusion of this outlier, the median diagnostic delay of IBD across the remaining 8 articles ranged from 2 to 13 months, with three quarters of these reporting a delay of between 2-5.3 months. Of the 23 studies defining samples solely by CD, the overall delay ranged from 2 to 26.4 months, with three quarters of the reported median delays ranging from 2\u0026ndash;12 months. Finally, from the16 studies examining UC, median diagnostic delay ranged from 2 to 55.2 months, with two thirds of studies reporting delay between 2 to 6 months. This overall longer median delay observed in patients with CD compared to UC was also observed in the subset of studies where delay had been directly compared between the two conditions within the same populations [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eFactors associated with diagnostic delay\u003c/h2\u003e\n\u003cp\u003eThree studies compared differences in delay related to help-seeking (from symptom onset to primary health care consultation) and that which occurred after the first consultation. Though Vavricka found that delay was significantly greater for CD than UC patients during the help-seeking and first consultation phase, Nguyen only found delay after first consultation to final diagnosis to be significantly greater for CD patients compared to UC patients [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Walker [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e] reported longer delays across help-seeking, primary care and secondary care in CD over UC (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eExtent of delay in IBD diagnosis at different stages of the patient journey\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMedian months of delay\u003c/p\u003e\n\u003cp\u003e(IQR) [range]\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eReason for delay\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eReason/point of delay\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor, year\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCD\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eUC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003ePatient-related delay\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eNon-help-seeking\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVavricka, 2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSwitzerland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0\u0026ndash;4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNguyen, 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.2\u0026ndash;4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7 (0.3\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLee, 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2 (0.5\u0026ndash;8.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.9 (0.9\u0026ndash;4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWalker, 2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (0.9\u0026ndash;6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1 (0.9\u0026ndash;3.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eHealthcare-related delay\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDelay following first consultation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNguyen, 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.5 (1.2\u0026ndash;20.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.1 (0.4\u0026ndash;5.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVavricka, 2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSwitzerland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (0\u0026ndash;18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDelay from first physician visit to IBD diagnosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLee, 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7 (0.1\u0026ndash;4.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.2 (0.1\u0026ndash;0.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrimary care delay\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWalker, 2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.3 (0.0-1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.2 (0.0-0.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary care delay\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWalker, 2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.6 (0.6\u0026ndash;3.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9 (0.5-2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eThree articles found statistical significance between increasing age and longer diagnostic delay [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. The study by Foxworthy and Wilson was the only one that reported median values, showing a statistically significant difference in diagnostic delay of CD between patients over 60 (diagnostic delay 16 months) and patients less than 60 years old at diagnosis (diagnostic delay 5 months) [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eA prospective cohort study conducted by Burisch \u003cem\u003eet al.\u003c/em\u003e grouped data from 14 Western and 8 Eastern European countries to compare differences in diagnostic delay [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. For CD, median values of diagnostic delay were 4.6 and 3.4 months, respectively, for Western and Eastern Europe. Diagnostic delay was 2.5 and 2.2 months for UC in Western and Eastern Europe, respectively (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). However, these differences were not statistically different.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eData for additional characteristics of delay\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAuthor, Publication Year and Country\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCD/UC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDiagnostic Criteria\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eComparison\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSample Size\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e% Male\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMean Age (SEM), range\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDiagnostic Delay (SD)/range (months)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFoxworthy (1985), USA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eChart review\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiagnosis \u0026ge;60 years old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68 (1.6), 60\u0026ndash;78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian- 16\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiagnosis\u0026thinsp;\u0026lt;\u0026thinsp;60 years old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (1.6), 20\u0026ndash;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian- 5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHarper (1986), USA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eClinical/radiologic/\u003c/p\u003e\n\u003cp\u003eendoscopic/\u003c/p\u003e\n\u003cp\u003eoperative features\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiagnosis\u0026thinsp;\u0026gt;\u0026thinsp;64 years old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57 (2.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean- 76.8 (18)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiagnosis\u0026thinsp;\u0026lt;\u0026thinsp;64 years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.3 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean- 28.8 (8.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLin (2016), Taiwan\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNot reported\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOnset \u0026ge;60 years old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68 (6.0), 60\u0026ndash;91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean- 26.4 (54), 0- 288\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOnset\u0026thinsp;\u0026lt;\u0026thinsp;60 years old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e459\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.8 (11.5), 1\u0026ndash;59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean- 4.8 (9.6), 0-120\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eBurisch (2014), Europe\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCopenhagen diagnostic criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWestern Europe\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e430\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38, 16\u0026ndash;89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian- 4.6, 0-372\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEastern Europe\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e105\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32, 15\u0026ndash;78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian- 3.4, 0-240\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCopenhagen diagnostic criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWestern Europe\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e668\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39, 15\u0026ndash;89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian- 2.5, 0-252\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEastern Europe\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e145\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36, 18\u0026ndash;81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian- 2.2, 0\u0026ndash;60\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\u003cem\u003eECCO-ESGAR\u0026thinsp;=\u0026thinsp;European Crohn\u0026rsquo;s and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review demonstrates that receiving a prompt diagnosis of IBD remains difficult to achieve, with patients typically experiencing several months of diagnostic delay. In particular, delay is prolonged in patients with CD compared to UC, with the majority of previous studies reporting diagnostic delay less than 12 months for CD, but less than 6 months for UC. However, research examining the specific factors contributing to delay in either condition remains very limited. Ultimately, this data provides a new benchmark against which interventions to reduce delay in patients with IBD can be compared.\u003c/p\u003e \u003cp\u003eThe skewed nature of diagnostic delay data means that (for the majority) of patients with CD or UC, diagnosis is achieved within a year of symptom onset. However, one in four studies did find that, on average, receiving a final diagnosis of CD could take between 12 to 24 months from the initial onset of symptoms, whereas we identified that three quarter of patients with UC were diagnosed in \u0026lt;\u0026thinsp;6 months. These findings provide a more accurate understanding of the true extent of diagnostic delay and though not intended to minimise the problem of diagnostic delay in UC, the greatest impact in a reduction in delay for patients with IBD may come from focusing on CD.\u003c/p\u003e \u003cp\u003eOur reported findings are based on the studies included in the sensitivity analysis, rather than all identified studies. By removing the study by Burgmann \u003cem\u003eet al\u003c/em\u003e, [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] which reported extremely protracted delays in IBD, CD and UC diagnosis, we have provided a more representative median range for diagnostic delay. Though removal of such outliers is a somewhat arbitrary one, performing this practical sensitivity analysis enabled us to look at the most common length of delay. To support the removal of this studies based on their reported, extreme delay values, we examined the details of the study design but could not identify any clear reason why their data was drastically different to that of the other studies in the systematic review. However, it was of note that this study reported longer diagnostic delay in UC compared to CD, contrary to other included studies.\u003c/p\u003e \u003cp\u003ePossible reasons for UC consistently demonstrating shorter diagnostic delays than CD could be because the location of disease is confined to the large bowel and patients experiencing rectal bleeding may be more likely to present to a doctor [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, CD delays may be longer due to a lack of clinical suspicion and diagnostic testing, associating common CD symptoms like abdominal pain with other conditions such as irritable bowel syndrome and difficulties in identifying disease that is only present in the small bowel [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThough overall diagnostic delay in patients with IBD, CD or UC has frequently been reported in the literature, there remains a dearth of data to have examined the role of specific patient or healthcare factors in contributing to delay. Such sub-analysis has proven useful in other systematic reviews into diagnostic delay, as this provides focus on certain characteristics which could prove to be avenues to reduce delay. For example, a previous systematic review on diagnostic delay in giant cell arteritis found delay was greater in those patients who did not experience cranial symptoms compared to those with cranial symptoms [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, there remains a lack of evidence in such sub-analysis in IBD populations and despite our identification of studies to have considered the role of age at diagnosis and sample country, findings were limited and conflicting.\u003c/p\u003e \u003cp\u003eResearch exploring the barriers and facilitators to IBD diagnosis is clearly needed. Diagnostic delay has been explored in many other studies for a variety of conditions, including giant cell arteritis, gynaecological cancers and tuberculosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Exploring the extent of diagnostic delay in medical conditions, where delays are common, is important as it provides a backdrop for future research examining the reasons for prolonged diagnostic delay and potentially inform interventions for reducing delays and improving patient care. As prolonged diagnostic delay of IBD appears to increase the likelihood of complicated disease, reducing delays in IBD diagnosis could improve the clinical outcome of patients with the condition [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The specific use of the faecal calprotectin test was not discussed in the studies of this systematic review. It detects levels of calprotectin within stool as a consequence of neutrophil aggregation to the gastrointestinal tract due to active inflammation like that found in IBD [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Existing research suggests that this is effective at differentiating between organic and functional origins of bowel disease, thus could reduce delays in IBD diagnosis [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe focus on median data within the analysis in this systematic review is a key strength as it reduces problems related to overestimation of averages typically related to use of means from skewed data, providing a more robust estimate of diagnostic delay. Furthermore, as well as examining IBD overall, this systematic review examined the most common disease sub-categories of UC and CD, and, finally, we did not restrict study inclusion based on language, leading to additional studies being included in the review. A limitation of this study is the variation between individual study designs, for instance differences in participant age, method of IBD diagnosis and country. However, despite the introduction of such heterogeneity, this data also provides a wider picture of the problem of diagnostic delay in this disease group.\u003c/p\u003e \u003cp\u003eIn conclusion, this systematic review provides a robust insight into the current extent of diagnostic delay in IBD, indicating that diagnostic delay remains a pertinent issue for patients with IBD, particularly CD, but that the factors which may have a role in delay remain unclear. This systematic review provides a backdrop and benchmark onto which further research can be conducted to reduce the time to IBD diagnosis, particularly exploring knowledge of IBD amongst healthcare professionals and the general population to help reduce overall delay. This future research is particularly important, as reducing diagnostic delay of IBD may improve the clinical course of the disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the systematic review team (Dr Nadia Corp and Dr Opeyemi Babatunde) at Keele University School of Medicine for their advice and assistance in the completion of this systematic review. They also wish to thank Dr Kay Polidano who was involved in the translation of selected articles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding is associated with this publication\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEC: Creation of search strategy, database search, data extraction, article review, narrative synthesis, writing of manuscript\u003c/p\u003e\n\u003cp\u003eJAP: Initial study design, creation of search strategy, data extraction, article review, narrative synthesis, writing of manuscript\u003c/p\u003e\n\u003cp\u003eBS: Initial study design, article review, writing of manuscript\u003c/p\u003e\n\u003cp\u003eADF: Initial study design, clinical input, article review, writing of manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRosen, M.J., A. Dhawan, and S.A. Saeed, \u003cem\u003eInflammatory Bowel Disease in Children and Adolescents\u003c/em\u003e. JAMA Pediatr, 2015. \u003cb\u003e169\u003c/b\u003e(11): p.\u0026nbsp;1053\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollaborators, G.I.B.D., \u003cem\u003eThe global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u0026ndash;2017: a systematic analysis for the Global Burden of Disease Study 2017\u003c/em\u003e. Lancet Gastroenterol Hepatol, 2020. \u003cb\u003e5\u003c/b\u003e(1): p.\u0026nbsp;17\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMowat, C., et al., \u003cem\u003eGuidelines for the management of inflammatory bowel disease in adults\u003c/em\u003e. Gut, 2011. \u003cb\u003e60\u003c/b\u003e(5): p.\u0026nbsp;571\u0026ndash;607.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLevine, J.S. and R. Burakoff, \u003cem\u003eExtraintestinal manifestations of inflammatory bowel disease\u003c/em\u003e. Gastroenterol Hepatol (N Y), 2011. \u003cb\u003e7\u003c/b\u003e(4): p.\u0026nbsp;235\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurgmann, T., et al., \u003cem\u003eThe Manitoba Inflammatory Bowel Disease Cohort Study: prolonged symptoms before diagnosis\u0026ndash;how much is irritable bowel syndrome?\u003c/em\u003e Clin Gastroenterol Hepatol, 2006. \u003cb\u003e4\u003c/b\u003e(5): p.\u0026nbsp;614\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVavricka, S.R., et al., \u003cem\u003eSystematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease\u003c/em\u003e. Inflamm Bowel Dis, 2012. \u003cb\u003e18\u003c/b\u003e(3): p.\u0026nbsp;496\u0026ndash;505.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNovacek, G., et al., \u003cem\u003eDiagnostic delay in patients with inflammatory bowel disease in Austria\u003c/em\u003e. Wiener Klinische Wochenschrift, 2019. \u003cb\u003e131\u003c/b\u003e(5\u0026ndash;6): p.\u0026nbsp;104\u0026ndash;112.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarper, P.C., T.L. McAuliffe, and W.L. Beeken, \u003cem\u003eCrohn's disease in the elderly. A statistical comparison with younger patients matched for sex and duration of disease\u003c/em\u003e. Arch Intern Med, 1986. \u003cb\u003e146\u003c/b\u003e(4): p.\u0026nbsp;753\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurisch, J., \u003cem\u003eCrohn's disease and ulcerative colitis. Occurrence, course and prognosis during the first year of disease in a European population-based inception cohort\u003c/em\u003e. Dan Med J, 2014. \u003cb\u003e61\u003c/b\u003e(1): p.\u0026nbsp;B4778.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDas, K., et al., \u003cem\u003eCrohn's disease in India: a multicenter study from a country where tuberculosis is endemic\u003c/em\u003e. Dig Dis Sci, 2009. \u003cb\u003e54\u003c/b\u003e(5): p.\u0026nbsp;1099\u0026ndash;107.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePellino, G., et al., \u003cem\u003eDelayed diagnosis is influenced by the clinical pattern of Crohn's disease and affects treatment outcomes and quality of life in the long term: a cross-sectional study of 361 patients in Southern Italy\u003c/em\u003e. Eur J Gastroenterol Hepatol, 2015. \u003cb\u003e27\u003c/b\u003e(2): p.\u0026nbsp;175\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, D.W., et al., \u003cem\u003eDiagnostic delay in inflammatory bowel disease increases the risk of intestinal surgery\u003c/em\u003e. World J Gastroenterol, 2017. \u003cb\u003e23\u003c/b\u003e(35): p.\u0026nbsp;6474\u0026ndash;6481.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzanto, K., et al., \u003cem\u003eBiological therapy and surgery rates in inflammatory bowel diseases - Data analysis of almost 1000 patients from a Hungarian tertiary IBD center.\u003c/em\u003e PLoS ONE, 2018. \u003cb\u003e13\u003c/b\u003e (\u003cb\u003e7\u003c/b\u003e) (\u003cb\u003eno pagination\u003c/b\u003e)(e0200824).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen, V.Q., et al., \u003cem\u003eImpact of Diagnostic Delay and Associated Factors on Clinical Outcomes in a U.S. Inflammatory Bowel Disease Cohort\u003c/em\u003e. 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PLoS One, 2015. \u003cb\u003e10\u003c/b\u003e(12): p.\u0026nbsp;e0144390.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePathirana, W.G.W., et al., Faecal Calprotectin. Clin Biochem Rev, 2018. \u003cb\u003e39\u003c/b\u003e(3): p.\u0026nbsp;77\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoepfer, A.M., et al., \u003cem\u003eDiscriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies\u003c/em\u003e. Inflamm Bowel Dis, 2008. \u003cb\u003e14\u003c/b\u003e(1): p.\u0026nbsp;32\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaugh, N., et al., \u003cem\u003eFaecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation\u003c/em\u003e. Health Technol Assess, 2013. \u003cb\u003e17\u003c/b\u003e(55): p.\u0026nbsp;xv-xix, 1\u0026ndash;211.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Supplementary Table","content":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 1- Search strategy:\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eSearch Strategy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003eExp inflammatory bowel diseases/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003einflammatory bowel disease*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003einflammatory bowel disorder*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003eibd.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003ecrohn*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003eulcerative colitis*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003einflam* colitis*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003ecolitis*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003ecolitis/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003ediagnos* adj3 delay*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003ediagnos* adj3 lag*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003ediagnos* adj3 interval*.ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e((late* or earl*) adj3 diagnos*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e((late* or earl*) adj3 treat*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e((late* or earl*) adj3 consult*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e((late* or earl*) adj3 refer*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e((late* or earl*) adj3 detect*).ti,ab.kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(health* adj3 seek*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(case* adj3 seek*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(case* adj3 find*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(delay* adj3 consult*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(delay* adj3 detect*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(delay* adj3 interval*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(delay* adj3 refer*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(delay* adj3 treat*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e(delay* adj3 seek*).ti,ab,kw.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003eDelayed diagnosis/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003eEarly diagnosis/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26 OR 27 OR 28 OR 29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.829493087557603%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"89.17050691244239%\"\u003e\n \u003cp\u003e10 AND 30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Diagnostic Delay, Inflammatory Bowel Disease, Crohn’s Disease, Ulcerative Colitis","lastPublishedDoi":"10.21203/rs.3.rs-1753316/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1753316/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe extent of diagnostic delay in inflammatory bowel disease (IBD) is incompletely understood. We aimed to understand the extent of diagnostic delay of IBD in adults and identify associations between patient or healthcare characteristics and length of delay.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eArticles were sourced from EMBASE, Medline and CINAHL from inception to April 2021. Inclusion criteria were adult cohorts (18\u0026thinsp;\u0026ge;\u0026thinsp;years old) reporting median time-periods between onset of symptoms for Crohn\u0026rsquo;s disease (CD), ulcerative colitis (UC) or IBD (i.e., CD and UC together) and a final diagnosis (diagnostic delay). Narrative synthesis was used to examine the extent of diagnostic delay and characteristics associated with delay. Sensitivity analysis was applied by the removal of outliers.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThirty-one articles reporting median diagnostic delay for IBD, CD or UC were included. After sensitivity analysis, the majority of IBD studies (7 of 8) reported a median delay of between 2-5.3 months. From the studies examining median delay in UC, three quarters (11 of 16) reported a delay between 2\u0026ndash;6 months. In contrast, three quarters of the studies (17 of 23) including CD samples, reported a delay of between 2\u0026ndash;12 months. No characteristic had been examined enough to understand their role in diagnostic delay in these populations.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis systematic review provides robust insight into the extent of diagnostic delay in IBD, particularly in CD, and suggests further intervention is needed to reduce delay. Furthermore, our findings provide a benchmark value range, which such future work can be measured against.\u003c/p\u003e","manuscriptTitle":"Diagnostic Delay in Adult Inflammatory Bowel Disease: A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-17 18:41:01","doi":"10.21203/rs.3.rs-1753316/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ec5e1e3a-c00b-48d7-90f9-8392089670ab","owner":[],"postedDate":"June 17th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-06-17T18:41:02+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-17 18:41:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1753316","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1753316","identity":"rs-1753316","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}