Clustering of pediatric onset inflammatory bowel disease in Finland: a nationwide register-based study
Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset usi...
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| Veröffentlicht in: | BMC gastroenterology Jg. 22; H. 1; S. 512 - 5 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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BioMed Central
12.12.2022
BioMed Central Ltd Springer Nature B.V BMC |
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| Abstract | Background
The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data.
Methods
We included all PIBD cases diagnosed at ages < 18 years during 1992–2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn’s, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez’s Q with an open-access python program
pyjacqQ
.
Results
The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (
p
= 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (
p
= 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (
p
< 10
− 8
).
Conclusion
Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. |
|---|---|
| AbstractList | Background
The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data.
Methods
We included all PIBD cases diagnosed at ages < 18 years during 1992–2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn’s, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez’s Q with an open-access python program
pyjacqQ
.
Results
The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (
p
= 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (
p
= 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (
p
< 10
− 8
).
Conclusion
Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. Methods We included all PIBD cases diagnosed at ages < 18 years during 1992–2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn’s, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez’s Q with an open-access python program pyjacqQ. Results The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10− 8). Conclusion Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. Methods We included all PIBD cases diagnosed at ages < 18 years during 1992-2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn's, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez's Q with an open-access python program pyjacqQ. Results The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10.sup.- 8). Conclusion Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. Keywords: Cluster analysis, Crohn's disease, Environment, Epidemiology, Ulcerative colitis Abstract Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. Methods We included all PIBD cases diagnosed at ages < 18 years during 1992–2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn’s, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez’s Q with an open-access python program pyjacqQ. Results The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10− 8). Conclusion Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. We included all PIBD cases diagnosed at ages < 18 years during 1992-2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn's, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez's Q with an open-access python program pyjacqQ. The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10.sup.- 8). Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data.BACKGROUNDThe incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data.We included all PIBD cases diagnosed at ages < 18 years during 1992-2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn's, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez's Q with an open-access python program pyjacqQ.METHODSWe included all PIBD cases diagnosed at ages < 18 years during 1992-2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn's, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez's Q with an open-access python program pyjacqQ.The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10- 8).RESULTSThe mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10- 8).Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies.CONCLUSIONOur findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. We included all PIBD cases diagnosed at ages < 18 years during 1992-2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn's, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez's Q with an open-access python program pyjacqQ. The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10 ). Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies. |
| ArticleNumber | 512 |
| Audience | Academic |
| Author | Nikkilä, Atte Kolho, Kaija-Leena Auvinen, Anssi |
| Author_xml | – sequence: 1 givenname: Atte surname: Nikkilä fullname: Nikkilä, Atte organization: Faculty of Medicine and Health Technology, Tampere University – sequence: 2 givenname: Anssi surname: Auvinen fullname: Auvinen, Anssi organization: Faculty of Social Sciences, Tampere University, Department of Pediatrics, Tampere University Hospital – sequence: 3 givenname: Kaija-Leena surname: Kolho fullname: Kolho, Kaija-Leena email: kaija-leena.kolho@helsinki.fi organization: Children’s Hospital, Pediatric Research Center, University of Helsinki and HUS |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36503475$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1093/ecco-jcc/jjw148 10.1016/j.cgh.2007.07.012 10.1007/s10620-019-05648-w 10.3748/wjg.v24.i25.2741 10.1016/j.sste.2012.09.002 10.1146/annurev-med-042320-021020 10.1093/ecco-jcc/jjac138 10.18637/jss.v074.i06 10.1097/MPG.0000000000001050 10.1093/aje/kwr400 10.1016/j.cgh.2015.02.045 10.1111/j.1742-7843.2009.00494.x |
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| Keywords | Cluster analysis Environment Epidemiology Crohn’s disease Ulcerative colitis |
| Language | English |
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| PublicationDate_xml | – month: 12 year: 2022 text: 2022-12-12 day: 12 |
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| PublicationTitle | BMC gastroenterology |
| PublicationTitleAbbrev | BMC Gastroenterol |
| PublicationTitleAlternate | BMC Gastroenterol |
| PublicationYear | 2022 |
| Publisher | BioMed Central BioMed Central Ltd Springer Nature B.V BMC |
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| References | M Zhao (2579_CR8) 2019; 64 Y Shan (2579_CR4) 2022; 73 S Jirjies (2579_CR11) 2016; 74 LJ Virta (2579_CR2) 2017; 11 2579_CR3 L Virta (2579_CR10) 2012; 175 MD Kappelman (2579_CR6) 2007; 5 K Furu (2579_CR9) 2010; 106 CD Sloan (2579_CR12) 2012; 3 P Lehtinen (2579_CR5) 2016; 63 J Sýkora (2579_CR1) 2018; 24 Y Ko (2579_CR7) 2015; 13 |
| References_xml | – volume: 11 start-page: 150 year: 2017 ident: 2579_CR2 publication-title: J Crohns Colitis doi: 10.1093/ecco-jcc/jjw148 – volume: 5 start-page: 1424 year: 2007 ident: 2579_CR6 publication-title: Clin Gastroenterol Hepatol doi: 10.1016/j.cgh.2007.07.012 – volume: 64 start-page: 1759 year: 2019 ident: 2579_CR8 publication-title: Dig Dis Sci doi: 10.1007/s10620-019-05648-w – volume: 24 start-page: 2741 year: 2018 ident: 2579_CR1 publication-title: World J Gastroenterol doi: 10.3748/wjg.v24.i25.2741 – volume: 3 start-page: 297 year: 2012 ident: 2579_CR12 publication-title: Spat Spatiotemporal Epidemiol doi: 10.1016/j.sste.2012.09.002 – volume: 73 start-page: 455 year: 2022 ident: 2579_CR4 publication-title: Ann Rev Med doi: 10.1146/annurev-med-042320-021020 – ident: 2579_CR3 doi: 10.1093/ecco-jcc/jjac138 – volume: 74 start-page: 1 year: 2016 ident: 2579_CR11 publication-title: J Stat Softw doi: 10.18637/jss.v074.i06 – volume: 63 start-page: 65 year: 2016 ident: 2579_CR5 publication-title: J Pediatr Gastroenterol Nutr doi: 10.1097/MPG.0000000000001050 – volume: 175 start-page: 775 year: 2012 ident: 2579_CR10 publication-title: Am J Epidemiol doi: 10.1093/aje/kwr400 – volume: 13 start-page: 1453-63.e1 year: 2015 ident: 2579_CR7 publication-title: Clin Gastroenterol Hepatol doi: 10.1016/j.cgh.2015.02.045 – volume: 106 start-page: 86 year: 2010 ident: 2579_CR9 publication-title: Basic Clin Pharmacol Toxicol doi: 10.1111/j.1742-7843.2009.00494.x |
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The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of... The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental... Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of... Abstract Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement... |
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| SubjectTerms | Adolescent Age Care and treatment Child Children Cluster Analysis Colitis, Ulcerative - diagnosis Colitis, Ulcerative - epidemiology Crohn Disease - diagnosis Crohn Disease - epidemiology Crohn’s disease Development and progression Diagnosis Environment Environmental factors Epidemiology Etiology Gastroenterology Health aspects Hepatology Humans Incidence Infant, Newborn Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - epidemiology Internal Medicine Intestine Medicine Medicine & Public Health Methods Pediatric gastroenterology Pediatrics Regression analysis Reimbursement Sex Ulcerative colitis |
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| Title | Clustering of pediatric onset inflammatory bowel disease in Finland: a nationwide register-based study |
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