Inflammatory bowel disease: Incidence, prevalence, and disease characteristics in Barbados, West Indies

ORIGINAL ARTICLE

Inflammatory Bowel Disease: Incidence, Prevalence, and Disease Characteristics in Barbados, West Indies C.N. Edwards, FRCPC, FACP, FACG,* S.G. Griffith, DM, FACG,* A.J. Hennis, PhD, FRCP, FACP,*,† and I.R. Hambleton, BA, MSc, PhD†

Background: The incidence of inflammatory bowel disease (IBD) may be lower among people of African descent than Caucasians. However, incidence studies among the former are uncommon and are often limited by incomplete case ascertainment or uncertainty about the size of the “at-risk” population.

Methods: We report the incidence and prevalence of IBD among people of African ancestry in Barbados from island-wide disease surveillance over a 25-year period beginning January 1980.

Results: The annual incidence of IBD age standardized to the world population was 1.85 per 100,000 person-years (95% confidence interval [CI] 1.53–2.22) for ulcerative colitis (UC) and 0.70 per 100,000 person-years (0.51– 0.95) for Crohn’s disease (CD). These incidence rates increased to 2.09 and 0.76 when standardized to the US population. The UC incidence rate increased from 1.3 in 1980 –1984 to 2.3 in 1995–1999, and decreased to 1.6 in 2000 – 2004. The CD incidence rate followed a similar trend, rising from 0.3 in 1980 –1984 to 1.3 in 1990 –1994 before decreasing to 0.6. IBD prevalence in December 2004 was 44.3 per 100,000 person-years (36.7–53.0) for UC and 16.7 per 100,000 person-years (12.2–22.4) for CD. In the island-nation of Barbados, with a population in 2000 of 270,000, we expect between 4.3 and 6.1 new cases of UC and between 1.5 and 2.6 new cases of CD each year.

Conclusions: The reported rates are generally lower than reported for European and North American Caucasians, and are similar to The French West Indies—the only other IBD disease register in the Caribbean. (Inflamm Bowel Dis 2008;14:1419 –1424) Key Words: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, incidence rate

Received for publication February 14, 2008; Accepted April 1, 2008. From the *Queen Elizabeth Hospital, Martindale’s Road, St Michael, Bridgetown, Barbados, West Indies, †Chronic Disease Research Centre, Tropical Medicine Research Institute, University of the West Indies, Jemmott’s Lane, Barbados, West Indies. Reprints: Dr. Charles Edwards, Queen Elizabeth Hospital, Martindale’s Road, St Michael, Barbados, West Indies (e-mail: cnedwards@ caribsurf.com). Copyright © 2008 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20495 Published online 16 May 2008 in Wiley InterScience (www.interscience. wiley.com).

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I

nflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the intestines with 2 major subtypes, ulcerative colitis (UC) and Crohn’s disease (CD). UC is more common and geographically more widespread than CD, although the latter has seen increasing incidence in Europe in recent decades.1 Disease complications can be triggered by many mechanisms, suggesting a varied etiology. While the disorder has been shown to have underlying genetic, immunologic, bacterial, and environmental components, the relative strength of these elements and the importance of their interplay remains largely unknown.2 Historically, IBD had been assumed to affect Caucasians more than other racial groups. Although IBD is now recognized worldwide, population-based incidence or risk factor studies among non-Caucasian groups remain scarce.3 Additionally, most incidence studies have been conducted in Europe and North America,4 – 6 raising the possibility that race or ethnicity may be partly confounded with environment. There remains a notable lack of basic incidence and prevalence data from Latin America and the Caribbean,7 with just 1 population-based report of IBD incidence among people of African descent.8 In this report we present incidence and prevalence rates of IBD along with selected characteristics from a prospectively identified cohort presenting to the healthcare system in Barbados during the 25-year period between January 1980 and December 2004. At the 2000 household census Barbados had a population of approximately 270,000, and close to 90% of all Barbadians were of African descent.9 The geographic features, comprehensive publicly funded healthcare system, centralized pathology, radiology, and other clinical specialist services on the island, and cooperation of clinical colleagues has allowed the maintenance of a prospective populationbased register of people with IBD.

MATERIALS AND METHODS The Queen Elizabeth Hospital (QEH) is the only public hospital in Barbados. It provides the island’s only anatomical pathology service, as well as specialist gastroenterological services. To ensure completeness of data, all internists, surgeons, radiologists, and pathologists were requested to report or refer all patients with suspected IBD to the 2 gastroenterologists who jointly ran the island’s only gastroenterology

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TABLE 1. Patient Demographics Among 121 Patients with Ulcerative Colitis and 47 Patients with Crohn’s Disease, Identified Between 1980 and 2004 in Barbados Disease

Characteristic Age at diagnosis (in years) 1–44 45–64 65⫹ Year of diagnosis 1980–84 1985–89 1990–94 1995–99 2000–04 Gender Women Men Family history of IBD Smoking at diagnosis

All Number (%) N⫽168

Crohn’s Disease Number (%) N⫽47

Ulcerative Colitis Number (%) N⫽121

121 (72) 39 (23) 8 (5)

35 (74) 10 (21) 2 (4)

86 (71) 29 (24) 6 (5)

19 (11) 29 (17) 48 (29) 38 (23) 34 (20)

4 (9) 7 (15) 18 (38) 9 (19) 9 (19)

15 (12) 22 (18) 30 (25) 29 (24) 25 (21)

101 (60) 67 (40) 9 (5) 5 (3)

26 (55) 21 (45) 6 (13) 2 (4)

75 (62) 46 (38) 3 (2) 3 (2)

P-value 0.91

0.52

0.43

clinic; C.N.E. for the entire study period and S.G.G. after 1998. In 1980, all records at the QEH coded with the diagnosis of colitis, UC, CD, ileitis or chronic diarrhea were retrieved and reviewed. All patients resident in Barbados were then evaluated by C.N.E. Each suspected case of IBD was confirmed by accepted clinical, radiological, and histological criteria. Over time, all patients classified as indeterminate at diagnosis were assigned to an appropriate UC or CD diagnosis using follow-up clinical and investigational data. All patients underwent the relevant air contrast barium studies, flexible sigmoidoscopy, or total colonoscopy with biopsy. Stool samples were also tested for the presence of parasites. Patients newly diagnosed with UC or CD on or after January 1, 1980 were recruited and followed along with the original retrospectively identified group until December 2004. A baseline questionnaire was completed for each study participant, including age and sex of the participant, year of IBD onset, smoking history, whether family member(s) had been diagnosed with IBD (yes/no), details of diagnostic methods, clinical characteristics, and extent of disease at the time of diagnosis. In this report we present data on Barbadians of self-reported African descent.

0.02 0.62

100,000 person-years in Barbados. We defined the prevalence of IBD as the number of cases alive on December 31, 2004 per 100,000 inhabitants. We stratified IBD into UC and CD. For each disease we present the annual incidence of new cases by sex and in 3 age groups (less than 45 years old, 45– 64 years, 65 years and older) between 1980 and 2004. For all calculations we used the most recent census estimates for our population denominator; census data are available for 1980, 1990, and 2000. The incidence of IBD is known to vary with age. To allow comparisons between populations that are independent of age, we calculated age-standardized rates using 1 of 3 standard populations: the 2000 US standard population,10 and the World and European standard million populations.11,12 For crude and age-stratified rates we calculated exact Poisson confidence intervals, and for age-standardized confidence intervals we used a Gamma approximation, which has improved properties when the number of cases is small.13 We tested disease, age, sex, and time differences in incidence rates using incidence rate ratios from log-linear regression models. Finally, we present selected demographics and clinical characteristics of our study population stratified by disease type (UC or CD). We performed all analyses using Stata statistical software (v. 10, StataCorp, College Station, TX).

Statistical Methods We used incidence and prevalence rates as the first step in investigating the epidemiological characteristics of IBD, defining the incidence of IBD as the number of new cases per

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RESULTS Almost three-quarters of patients with UC or CD were diagnosed before 45 years of age (Table 1). A family history

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TABLE 2. Annual Incidence Rates per 100,000 Inhabitants with Ulcerative Colitis and Crohn’s Disease in Barbados, Stratified by Age and Gender No. of Cases

Ulcerative colitis Age groups 1–44 45–64 65⫹ Crude rate Age standardized Age standardized Age standardized Crohn’s disease Age groups 1–44 45–64 65⫹ Crude rate Age standardized Age standardized Age standardized

Age Specific Rate (95% CI)

Women

Men

Women

Men

Women

Men

All

51 20 4 75

35 9 2 46 —

2,345,835 554,085 433,605 3,333,525 —

2,296,150 450,685 292,990 3,039,825 —

—

—

—

2.17 (1.62–2.86) 3.61 (2.20–5.57) 0.92 (0.25–2.36) 2.25 (1.77–2.82) 2.49 (1.95–3.16) 2.47 (1.93–3.14) 2.20 (1.73–2.78)

1.52 (1.06–2.12) 2.00 (0.91–3.79) 0.68 (0.08–2.47) 1.51 (1.11–2.02) 1.63 (1.17–2.27) 1.57 (1.13–2.16) 1.44 (1.05–1.96)

1.85 (1.48–2.29) 2.89 (1.93–4.15) 0.83 (0.30–1.80) 1.90 (1.58–2.27) 2.09 (1.72–2.52) 2.05 (1.69–2.48) 1.85 (1.53–2.22)

17 3 1 21 —

2,345,835 554,085 433,605 3,333,525 —

2,296,150 450,685 292,990 3,039,825 —

—

—

—

0.77 (0.45–1.21) 1.26 (0.51–2.60) 0.23 (0.01–1.28) 0.78 (0.51–1.14) 0.85 (0.55–1.28) 0.85 (0.54–1.28) 0.76 (0.49–1.13)

0.74 (0.43–1.19) 0.67 (0.14–1.95) 0.34 (0.01–1.90) 0.69 (0.43–1.06) 0.66 (0.40–1.11) 0.67 (0.40–1.08) 0.64 (0.39–1.01)

0.75 (0.53–1.05) 1.00 (0.48–1.83) 0.28 (0.03–0.99) 0.74 (0.54–0.98) 0.76 (0.55–1.03) 0.76 (0.55–1.04) 0.70 (0.51–0.95)

rate (US) rate (Europe) rate (world)

18 7 1 26 rate (US) rate (Europe) rate (world)

Person Years

of IBD was reported by 6 or 13% of patients with CD, and this was statistically significantly more than the 3 or 2% reported by patients with UC (Fisher’s exact test, P ⫽ 0.02). Smoking was uncommon in this patient group. We present incidence rates for CD and for UC stratified by age and by sex in Table 2. Annual crude incidence rates were 1.90 per 100,000 (95% confidence interval [CI] 1.58 – 2.27) for UC, and 0.74 per 100,000 (0.54 – 0.98) for CD. Age-standardization to the world population reduced the incidence rates to 1.85 (1.53–2.22) and 0.70 (0.51– 0.95) for UC and CD, respectively. Age-standardization to the European population increased rates to 2.05 (1.69 –2.48) for UC and 0.76 (0.55–1.04) for CD, with the SEER 2000 US standard population raising age-standardized rates a little further. The highest incidence occurred in the 45– 64 age group in both UC and CD. We present rate ratios for IBD incidence in Table 3. There were more than twice as many incident UC cases than CD cases (rate ratio [RR] ⫽ 2.48, 95% CI ⫽ 1.77–3.48, P ⬍ 0.001). Compared to people age 44 and less, the risk of developing IBD was 1.5 times higher in those age 45– 64 (RR ⫽ 1.53, 95% CI ⫽ 1.06 –2.19) and was 2.3 times lower in those age 65 or older (RR ⫽ 0.43, 95% CI ⫽ 0.21– 0.89). There were marginally more incident cases of IBD among women compared to men (RR ⫽ 1.38, 95% 1.01–1.88, P ⫽ 0.04). The UC incidence rate, age-standardized to the world

population, increased from 1.30 (95% CI ⫽ 0.71–2.25) in 1980 –1984 to 2.34 (1.54 –3.43) in 1995–1999, and decreased to 1.58 (1.01–2.44) in 2000 –2004. The CD incidence rate followed a similar trend, rising from 0.28 (0.07– 0.90) in

TABLE 3. Rate Ratios for the Incidence of Ulcerative Colitis and Crohn’s Disease in Barbados Term IBD type Crohn’s disease Ulcerative colitis Sex Male Female Age 0–44 45–64 65⫹ Decade of diagnosis 1980–84 1985–89 1990–94 1995–99 2000–04

Rate Ratio

95% CI

P ⬍0.001

1 2.48

1.77–3.48 0.04

1 1.38

1.01–1.88 0.003

1 1.53 0.43

1.06–2.19 0.21–0.89 0.02

1 1.53 2.36 1.91 1.62

0.86–2.73 1.39–4.02 1.10–3.31 0.92–2.84

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Crohn’s disease Ulcerative colitis

Incidence (per 100,000)

4 3 2.30

2.34

1.92

2

1.58

1.30

1

1.30 0.71

0.64

0.61

0.28

0 1980−4

1990−4

2000−4

Year of diagnosis

FIGURE 1. Secular incidence of ulcerative colitis and Crohn’s disease between 1980 and 2004.

1980 –1984 to 1.30 (0.76 –2.12) in 1990 –1994 before decreasing to 0.61 (0.27–1.26) in 2000 –2004 (Fig. 1). Prevalence rates for UC in 2004 were 55.2 per 100,000 (43.5– 69.0) among women, 32.5 per 100,000 (23.4 – 43.9) among men, and 44.3 per 100,000 (36.7–53.0) overall. Equivalent rates in CD were 17.2 (11.0 –25.6) among women, 16.3 (10.1–24.8) among men, and 16.7 (12.2–22.4) overall. The clinical features of black Barbadian patients with IBD are shown in Table 4. In patients with UC proctitis was diagnosed in 13%, left-sided disease in 53%, and pancolitis in 33% of cases, while sclerosing cholangitis was observed in 10% of patients. In patients with CD, ileitis was diagnosed in 32%, ileo-colitis in 21%, colitis in 45%, and upper gastrointestinal in 2%, while perineal disease was evident in 36% and fistulae in 26% of patients. Ocular complications occurred in 11% and acute arthropathy in 23%.

DISCUSSION We report 25-year results from the longest-running IBD registry in the Caribbean. Annual incidence rates age-standardized to the world population were 1.85 per 100,000 person years for UC and 0.70 per 100,000 person years for CD. Incidence rates of both UC and CD increased markedly in the 1980s and 1990s. The incidence of UC increased from 1.30 in 1980 –1984 to 2.34 in 1995–1999; almost a 2-fold increase in a decade (RR ⫽ 1.89, 95% CI ⫽ 1.02–3.53), before falling to 1.58 in 2000 –2004. The incidence of CD increased from 0.28 in 1980 –1984 to 1.30 in 1990 –1994; a four-fold increase in a decade (RR ⫽ 4.19, 95% CI ⫽ 1.42– 12.38), before falling to 0.61 in 2000 –2004. Prevalence rates in December 2004 were 44.3 per 100,000 people for UC and 16.7 per 100,000 people for CD. Our incidence and prevalence rates provide a comprehensive assessment of the IBD disease burden in Barbados. The centralization of healthcare and the willing cooperation

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of private and public physicians has meant that this IBD registry is likely to have near complete case ascertainment. Moreover, Barbados has a long history of accurate census enumeration, giving good estimates of the underlying study population Although the comparison of incidence rates between populations and geographical regions provides a basic insight into disease variation, the validity of incidence rate comparisons in studies of IBD has important technical limitations. Variation in case ascertainment between studies, accuracy of the population count of a study region, and the availability of diagnostic tests can limit the usefulness of direct incidence rate comparisons. Despite this, a large number of IBD incidence studies are available, and together they paint a broad picture of incidence in many parts of the world. In the many IBD incidence studies from Europe, rates vary from 1.5–20.3 per 100,000 person years for UC and 0.7–9.8 for CD.3 A large prospective study (the EC-IBD study) involving 20 centers in northern and southern Europe

TABLE 4. Clinical Characteristics at Disease Diagnosis Among 121 Patients with Ulcerative Colitis and 47 Patients with Crohn’s Disease, Identified Between 1980 and 2004 in Barbados Disease Characteristic Ocular complications Erythema nodosum Pyoderma gangrenosum Sclerosing cholangitis Perineal disease Arthritis None Acute arthropathy Sacroilitis Ankylosing spondylitis Obstruction Fistula Apthous ulcer Extent of disease (CD) Ileitis Ileocolitis Colitis Upper GI Extent of disease (UC) Proctitis Proctosigmoiditis Left-sided Pancolitis

Crohn’s Disease Number (%)

Ulcerative Colitis Number (%)

5 (11) 3 (7) 3 (7) 0 (—) 16 (36)

3 (2) 2 (2) 3 (3) 12 (10) 4 (3)

35 (74) 11 (23) 1 (2) 0 (—) 14 (31) 12 (26) 8 (18)

106 (88) 11 (9) 1 (1) 3 (2) — — —

15 (32) 10 (21) 21 (45) 1 (2)

— — — —

— — — —

16 (13) 36 (30) 29 (24) 40 (33)

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reported rates of 10.4 (95% CI ⫽ 7.6 –13.1) per 100,000 person years for UC and 5.6 (2.8 – 8.3) per 100,000 person years for CD.14 The EC-IBD study presented rates among people age 15– 64 years age-standardized to the European standard population.12 To allow a direct comparison with these rates we applied the same age restriction and agestandardization. Our rates rose to 2.62 (2.14 –3.20) per 100,000 person years for UC and 0.93 (0.66 –1.30) per 100,000 person years for CD. The EC-IBD registered cases for a 2-year period between 1991 and 1993. When we also restricted our registry cases to a similar time period (1990 – 1994) our rates rose further: 3.41 (2.24 –5.06) per 100,000 person years for UC and 1.84 (1.05–3.10) per 100,000 person years for CD. At all times, and for both UC and CD, our point estimates were less than the lower limits of the EU-IBD confidence intervals. Data from the United States are less comprehensive, with generally smaller regional studies reporting incidence rates from 2.2–14.3 per 100,000 person years for UC and from 3.1–14.6 per 100,000 person years for CD.3 In 1 US incidence study of note, IBD incidence rates have been reported from the Rochester Epidemiology Project. During the period 1984 –1993 rates among residents of Olmsted County, Minnesota, were 8.3 (6.5–10.1) per 100,000 person years for UC and 6.9 (5.3– 8.5) per 100,000 person years for CD. Equivalent rates from this Barbados register (1980 –1989) were 2.45 (1.79 –3.32) for UC and 1.03 (0.64 – 1.63) for CD. Again, Barbados rates were lower than reported from this US study. The question of whether there is an incidence gradient from higher levels in northerly latitudes to lower levels in more southerly latitudes was first examined systematically in Europe, and reported 40% more UC and 80% more CD in northern centers14—smaller than previously thought but still a marked difference. With recent data from Eastern Europe7 and Asia15 suggesting increases in traditional low-incidence areas, this gradient has shown signs of decreasing in size, and has been interpreted as a developed country– developing country disparity.16 The causes of this gradient effect are likely to remain elusive until our understanding of disease etiology improves. Nevertheless, these geographical differences offer a teasing insight that must be explored using further prospective work to separate the continuing genetic and environmental confounding. In the 1970s IBD was considered rare in people of African descent, and the small literature was restricted to simple descriptions of case-series. O’Donoghue and Clarke17 were the first to describe IBD in UK residents of West Indian descent; 3 with CD and 2 with UC. With no IBD reports from the West Indies at the time, the authors suspected an environmental etiology. A subsequent report from Trinidad described a case series of 34 patients with UC and 14 with CD over a 10-year period.18 A further case series of 20 cases subsequently became available from Jamaica.19 A popula-

IBD in Barbados, West Indies

tion-based IBD registry has recently reported IBD incidence in the French West Indies.8 They presented incidence rates age-standardized to the world population of 2.23 per 100,000 for UC and 1.85 per 100,000 for CD during the period 1997–1999 in the combined population of the islands of Martinique and Guadeloupe. The racial and age structure of the overall population is similar to that of Barbados. Recalculating our incidence rates age-standardized to the world population and restricted to the period 1995–1999, we report 2.52 (1.64 –3.77) per 100,000 person years for UC and 0.73 (0.31–1.53) per 100,000 person years for CD. The French West Indian rates suggest a broadly similar burden of disease in these Eastern Caribbean islands, although CD in Barbados may be slightly less common. There is limited evidence that the assumed incidence disparity between races has been decreasing over the past 2 decades, with hospitalizations for complications of IBD now similar in African-Americans and Caucasians.20,21 This evidence remains weak, and a recent clinical review of IBD concluded that it was “difficult to draw any meaningful conclusion about disease incidence, clinical presentation and clinical course among African-Americans based on their representation in clinical studies.”22 The Oxford record linkage study highlighted that admission rates for CD may increase with time while the number of individuals receiving care remains the same.23 The increased familial incidence of IBD is well known,24 and the condition is increasingly seen as a multigenetic disorder.25 Conversely, the relatively low concordance rate among identical twins suggests the importance of environmental influences.26 Work on the genetic determinants of IBD proceeds apace, and to aid future associations with other etiological factors there must be definitive baseline data on the incidence, prevalence, and disease characteristics, stratified by race and location. In this regard, the Caribbean is of particular relevance, as the majority of its inhabitants share a common heredity with other people of African descent living in North America and Europe. We have presented incidence and prevalence data from a 25-year prospective study. This is the longest incidence study of IBD among people of African descent. We presented rates that are generally lower than reports from European and North American Caucasians, and are similar to a single published report from the French West Indies—the only other IBD incidence study in the Caribbean.

ACKNOWLEDGMENTS We thank Dr. Oscar Jordan, the pathologists, radiologists, and surgeons in Barbados for their enthusiastic cooperation with patient identification. Dr. Trevor Seaton of McMaster University gave us important and valued encouragement throughout this long-running project.

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