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The Burden of IBD
Charles N. Bernstein, MDUniversity of Manitoba
IBD Clinical and Research Centre
Winnipeg, Manitoba, Canada
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IBD Database Construction
Persons with at least one IBD contact, 1984-1995 (n=10,541)
Exclude if <3 contactsbeginning prior to 1993(n=5,359)
Distribute consent and demographic questionnaire to current residents. (n=4,514)
Optimize “case definitions”versus self-reported diagnosis
Analyze medical contact patternsfor questionnaire respondents.(n=2,725)
“Crohn’s disease”(n=1,230)
“Ulcerative colitis”(n=1,222)
“No IBD”(n=273)
Evaluate “case definitions”versus random charts (n=448)
Apply case definitions toentire health database
60%
Bernstein Am J Epidemiol 1999
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Case Definitions: Crohn’s Disease and UC
• At least 5 separate hospital/physician contacts with a diagnosis between 1984 and 1995.
OR
• If registered with Manitoba Health for <2 years, at least 3 separate hospital/physician contacts with a diagnosis.
• If both CD and UC criteria were met, then the majority diagnosis of the most recent 9 contacts was used.
• Diagnosis date is the first hospital/physician contact (applied only to first contacts beginning in 1988 or later).
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Time Trends
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Crohn’s disease prevalence and incidence, Manitoba,
1990 - 2001, cases/100,000, age standardized to the 1996 Manitoba population
165178
190199 208 217 225
237249 256 262 270
15.2 15.9 14.5 14.6 13.9 12.6 14.9 18.2 16.6 12.6 15.1 13.70
50
100
150
200
250
300
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
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143155 163
173188
199 208 216 223 231 236 241
16.2 13.4 13.6 17.8 18.2 15.2 12.6 14.3 15.3 14.1 13.8 10.50
50
100
150
200
250
300
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
UC prevalence and incidence, Manitoba, 1990 - 2001, cases/100,000
age standardized to the 1996 Manitoba population
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Annual Age-Adjusted Prevalence of CD and UC,
by First Nation (FN) Status, Manitoba.
0
50
100
150
200
250
1987 1988 1989 1990 1991 1992 1993 1994
Pre
vale
nce
per
100
,000
Non-FN CD
Non-FN UC
FN UC
FN CD
176
14
57
209
Blanchard Am J Epidemiol 2001
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M
BM
B
BCAB
SKNS
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Age-specific incidence of Crohn’s Disease: by Province
05
1015202530354045
<10 10-19
20-29
30-39
40-49
50-59
60-69
70-79
80+
Age Group
Inci
den
ce p
er 1
00,0
00
BC
AB
SASK
MB
NS
Bernstein AJGI 2005
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Age-specific incidence of UC: by Province (1998-2000)
0
5
10
15
20
25
30
35
<10 10-19
20-29
30-39
40-49
50-59
60-69
70-79
80+
Age Group
Inci
den
ce p
er 1
00,0
00
BC
AB
SASK
MB
NS
Bernstein AJGI 2005
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Age-specific prevalence of Crohn’s Disease: by Province
(2000)
0
100
200
300
400
500
600
<10 10-19
20-29
30-39
40-49
50-59
60-69
70-79
80+
Age Group
Cas
es p
er 1
00,0
00
BC
AB
SASK
MB
NS
Bernstein AJGI 2005
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Age-specific prevalence of UC: by Province (2000)
050
100150200250300350400450
<10 10-19
20-29
30-39
40-49
50-59
60-69
70-79
80+
Age Group
Cas
es p
er 1
00,0
00 BC
AB
SASK
MB
NS
Bernstein AJGI 2005
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Population = 30,750,087
Prevalence of Crohn’s disease: 85,854
Prevalence of UC: 64,975
Total IBD: 150,829
?2005: 170,000
Projected prevalence of IBD in Canada in 2000
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• MB rates similar to elsewhere in Canada
• Low rates of Crohn’s disease in BC; 22% visible minorities
• High rates of both Crohn’s & UC in Canada;
?North-South gradient
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Place - Geographic Distribution
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Published Estimates of the Incidence of Crohn’s Disease from
Around the World
0
2
4
6
8
10
12
14
16
Nor 83-
86
Swe 78
-87
Den 7
9-87
UK Car
diff 8
1-85
Neth 8
8-92
N Fra
nce 8
8-90 Ger
Ital 7
8-87
Spain 7
9-88
USA, Min
n 84-
93
USA, Bal
t 77-
79
Man
itoba
1988
-96
Inci
den
ce p
er 1
00,0
00
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Published Estimates of the Incidence of Ulcerative Colitis from
Around the WorldIn
cid
ence
per
100
,000
No
r 83
-86
Sw
e 78
-87
Den
79-
87
UK
Car
dif
f 81
-85
Net
h 8
8-92
N F
ran
ce 8
8-90
Ger
Ital
78-
87
Sp
ain
79-
88
US
A,M
inn
84-
93
Man
ito
ba
88-9
6
16
141210
8
6
4
2
0
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CD Incidence, 1990 - 2001Cases/10,000, Smoothed
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An Ecological StudyGreen Am J Epidemiol 2006
Crohn’s disease UC
Females 1.37 (1.24-1.50) 1.11 (1.02-1.2)
Urban 1.29 (1.17-1.41) 1.12 (1.04-1.21)
SESI top1/3 1.77 (1.55-2.02) 1.48 (1.34-1.63)
Non-Aboriginal 6.91 (3.15-15.16) 2.22 (1.71-2.89)
Non-Aboriginal* 5.47 (3.37-8.87) 1.99 (1.55-2.55)
Jewish* 1.52 (1.22-1.89) 1.45 (1.21-1.74)
Non-vis minorities
1.06 (0.92-1.22) 1.23 (1.1-1.39)
Low enteric infect
MS
1.52 (1.31-1.78)
2.90 (2.19-3.85)
1.19 (1.06-1.33)
1.8 (1.49-2.17)
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Extraintestinal burden
to the patient
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There is approximately 1 DVT-PE / 200 patient-
years
Bernstein Thromb Hemostasis 2001
Venous thrombosis in IBD
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Venous thrombosis in IBD
DVT+PE IRR (95% CI)
Crohn’s disease 4.1 (3.21-5.25)
UC 3.04 (2.43-3.8)
All IBD 3.47 (2.94-4.09)
Males 3.11 (2.42-4.00)
Females 3.78 (3.53-4.71)
Bernstein Thromb Hemostasis 2001
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Site-specific cancer IRR comparing cohorts with IBD to Site-specific cancer IRR comparing cohorts with IBD to non-IBD cohorts matched by age, gender and postal non-IBD cohorts matched by age, gender and postal
area of residence, Manitoba, Canada, 1984-1997.area of residence, Manitoba, Canada, 1984-1997.
Crohn’s UC Total IBD
Cancer typeIRR
(95% C.I.)IRR
(95% C.I.)IRR
(95% C.I.)
Lymphoma 2.40(1.17-4.97)
1.03 (0.47-2.24)
1.52 (0.90-2.57)
Hodgkin’s Undefined Undefined Undefined
Leukemia/Other
0.79 (0.24-2.54)
1.02 (0.37-2.86)
0.91(0.42-1.96)
Bernstein Cancer 2001
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Other cancer risk ratesCrohn’s disease UC Total IBD
Cancer type IRR(95% C.I.)
IRR(95% C.I.)
IRR(95% C.I.)
Colon 2.64(1.69-4.12)
2.75(1.91-3.97)
2.71(2.04-3.59)
Rectum 1.08(0.43-2.70)
1.90(1.05-3.43)
1.56(0.95-2.57)
Small Bowel 17.4(4.16-72.9)
Undefined 10.4(3.02-36.1)
Hepatobiliary 5.22(0.96-28.5)
3.96(1.05-3.43)
4.38(1.54-12.4)
Bernstein Cancer 2001
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Colon cancer population under 50 yrs Colon cancer population 50 yrs + older
Rectal cancer population under 50 yrs Rectal cancer population 50 yrs + older
Age-specific rates of selected comorbidity in IBD and non-IBD hospitalized population, 1994/95-2002/03
Rate per 100,000
**
*
0
50
100
150
200
250
300
1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03
IBD Non-IBD
Rate per 100,000
0
100
200
300
400
500
1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03
IBD Non-IBD
Rate per 100,000
******
0
100
200
300
400
500
1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03
IBD Non-IBD
Rate per 100,000
0
50
100
150
200
250
300
1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03
IBD Non-IBD
* The rate is significantly higher in IBD compared to non-IBD cases, p<0.05.
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Pulmonary emboli population under 50 yrs Pulmonary emboli population 50 yrs + older
DVT population under 50 yrs DVT population 50 yrs + older
Rate per 100,000
0
100
200
300
400
1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03
IBD Non-IBD
Rate per 100,000
0
100
200
300
400
1994
/95
1995
/96
1996
/97
1997
/98
1998
/99
1999
/00
2000
/01
2001
/02
2002
/03
IBD Non-IBD
Rate per 100,000
0150300450600750900
1994
/95
1995
/96
1996
/97
1997
/98
1998
/99
1999
/00
2000
/01
2001
/02
2002
/03
IBD Non-IBD
Rate per 100,000
0150300450
600750900
1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03
IBD Non-IBD
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There is approximately 1 fracture/100 patient-
years
Bernstein Ann Intern Med 2000
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Incidence rate ratios of All fractures comparing IBD to matched population-
based non-IBD cohorts
Crohn’sIRR
UCIRR
All IBDIRR
0-39 yrs 1.37 1.38 1.37(1.10-1.69)
40-59 yrs 1.27 1.60 1.44(1.17-1.76)
60+ yrs 1.41 1.41 1.41(1.21-1.64)
Total 1.36(1.17-1.59)
1.45(1.26-1.67)
1.41(1.27-1.56)
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A positive association between chronic inflammatory diseases with either form of IBD could suggest
• common genetic predisposition
• common etiologic triggers,
• or possibly the triggering of one inflammatory condition secondary to Rx of a primary inflammatory condition.
Am J Gastroenterol 2001Gastroenterology 2005
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• Since the specificity of a single contact of any of these conditions is not known we analyzed the data for having
at least 5 health system contacts.
The precedent for this in Manitoba:
• Ulcerative colitis
• Crohn’s disease
• Multiple sclerosis
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Manitoba: 6.2% have a single extraintestinal disease (exclusive of arthritis)(0.3% have >1 extraintestinal disease)
Sweden (UC): 6-12% (CD): <12%(includes abnormal liver tests)
UC Crohn’s
Uveitis 1.6% 1%
PSC 3.7% <10%
Ank Spond 1.6% 2.2%
PG 0.8% 0.6%
E. nodosum 2.6% 1.9%
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Period Prevalence of comorbid diagnoses in UC Disease Controls UC PR (95% CI)
Asthma 4.9% 7.88% 1.66(1.46-1.88)
Bronchitis 0.32% 0.67% 2.10(1.36-3.23)
Arthritis 8.35% 11.77% 1.55(1.39-1.74)
MS 0.29% 0.54% 1.90(1.19-3.03)
Ch Renal Dis 0.16% 0.39% 2.46(1.40-4.35)
Psoriasis 1.04% 1.7% 1.65(1.27-2.15)
Pericarditis 0.07% 0.23% 3.33 (1.57-7.07)
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Period Prevalence of comorbid diagnoses in CD Disease Controls CD PR (95% CI)
Asthma 5.1% 7.09% 1.43(1.26-1.62)
Bronchitis 0.26% 0.48% 1.86(1.15-3.02)
Arthritis 6.32% 7.88% 1.24(1.12-1.39)
Psoriasis 1.07% 1.7% 1.59(1.24-2.05)
Pericarditis 0.06% 0.19% 3.07 (1.39-6.78)
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Sociological burden
*Health Care Utilization
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IBD(n=5756)
Controls(n=66,406)
% Users 91% 77% P<0.05
Mean # Visits 14.4 (0.19) 9.8 (0.05) P<0.05
≤5 25% 41%
6-11 27% 29%
12-23 31% 23% OR=1.50 (1.32 – 1.71)
24+ 17% 7% OR=2.72 (2.24 – 3.30)
OR (95% CI) Visit 3.14 (2.87 – 3.46) P<0.05
OR (95% CI) Surgery
2.82 (2.65 – 3.00) P<0.05
Cross-Sectional StudyIBD vs. Controls: Outpatient Visits
2000-2001
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IBD(n=5756)
Controls (n=66,406)
% Users 16% 7% P<0.05
Mean # Days (se) 10.9 (0.85) 10.5 (0.37) not sig
Mean # Visits (se) 1.53 (0.03) 1.34 (0.01) P<0.05
OR (95% CI) Visit 2.52 (2.32 – 2.72) P<0.05
OR (95% CI) Surgery 1.73 (1.29 – 2.26) P<0.05
Cross-Sectional StudyIBD vs. Controls: Hospitalizations
2000-2001
Longobardi CGH 2006
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Longitudinal Study II15 Year Follow-up 1987 IBD
Incidence Cohort Between 1987 and 2002
43% IBD cases have an IBD-specific overnight hospitalization
47% CD
21% UC
30% IBD cases have an IBD-specific inpatient visit with a digestive disease surgery (excluding diagnostic endoscopy)
41% CD
16% UCLongobardi CGH 2006
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Longitudinal Study II15 Year Follow-up 1987 IBD
Incidence Cohort Readmission Rates Between 1987 and 2002
65% IBD cases admitted for an IBD-specific overnight hospitalization are readmitted
70% CD
53% UC
39% IBD cases admitted for an IBD-specific inpatient visit with a digestive disease surgery (excluding diagnostic endoscopy) are readmitted
39% CD
39% UC
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Longitudinal & cross sectional population-based studies in Manitoba
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5 year cohort studyThe Manitoba IBD Cohort Study
To describe predictors and patterns of outcomes among subjects diagnosed within 7 years
• Psychological
• Disease outcomes (phenotype)
• Genotype
• Health care utilization
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Risk factor study
Population-based case control study
• Crohn’s disease and UC from U of M IBD Research Registry
• Matched healthy controls from MH Registry
• Non-affected sibs
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Environmental Study• Assessing water sources to
high and low incidence areas
• Assessing biofilms, filters, and water for microbes
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Health Sciences: The Organizational Unit of
ApplicationMolecular &SubmolecularParticles
Cells Organs Individuals Families Communities Societies
Epidemiology
Clinical Research
Pathology, Physiology
Cell Biology
Molecular Biology