Geographic variation of inflammatory bowel disease within the United States

Geographic variation of inflammatory bowel disease within the United States

GASTROENTEROLOGY 1991;100:143-149 Geographic Variation of Inflammatory Bowel Disease Within the United States AMNON SONNENBERG, DANIEL J. MCCARTY, a...

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GASTROENTEROLOGY

1991;100:143-149

Geographic Variation of Inflammatory Bowel Disease Within the United States AMNON SONNENBERG, DANIEL J. MCCARTY, and STEVEN J. JACOBSEN Division Veterans

of Gastroenterology, Department of Biostatistics Affairs Medical Center and the Medical College

One approach to learn about possible environmental risks in inflammatory bowel disease relates to studying its geographic pattern of occurrence. The geographic variation of inflammatory bowel disease within the United States was analyzed using the accumulated 17.5 million hospital discharges of all U.S. Medicare beneficiaries during two consecutive years. To validate the geographic pattern shown by the Medicare data, hospitalization was compared with mortality from inflammatory bowel disease among different states. Mortality and hospitalization statistics both suggested that the occurrence of inflammatory bowel disease was determined by environmental factors that had a marked geographic variation within the United States. Both Crohn’s disease and ulcerative colitis appeared to be more frequent in northern parts of the United States than in southern and in urban more than rural parts. These trends were observed for men and women and for blacks and whites alike. Similar geographic patterns of Crohn’s disease and ulcerative colitis suggested the influence of one or more identical risk factors for both diseases.

I

nflammatory bowel diseases (IBD) is characterized by mucosal damage of the small and large intestine triggered in genetically predisposed individuals by one or several environmental agents. Increased consumption of refined carbohydrates (l-5), cigarette consumption (5-9), and contraceptives (8-10)have been claimed to be associated with the occurrence of IBD. These environmental factors, however, seem to play only mediating roles rather than be directly involved in its etiology. The nature of other more crucial environmental influences leading to mucosal inflammation and destruction is yet unknown. One approach to learn about possible environmental risks relates to studying the geographic pattern of IBD occurrence. Multiple studies from different locations

and Epidemiology, Department of of Wisconsin, Milwaukee, Wisconsin

have provided a fairly comprehensive picture of the geographic distribution of IBD outside the United States (11-13). The marked differences between countries of similar culture, standard of living, and ethnically related populations have strengthened the contention of an environmental influence. The characteristic differences between individual countries are present in various parameters of IBD morbidity alike, such as incidence, prevalence, hospital discharges, The frequency of IBD in the and mortality (11-15). United States seems to be within the range of the European countries. Limited information suggests that a geographic variation of IBD occurs also within the United States (16-20). Health care systems, medical training, and principles of diagnosis and therapy are more homogeneous within the United States than among any other set of countries, such as the European countries or Europe and North America. A study of the geographic variation of IBD within the United States is less likely to be confounded by these variations of medical practice and reveal more clearly the influence of exogenous risk factors. In the present study, we accessed the accumulated 17.5 million hospital discharges of Medicare beneficiaries from 2 consecutive years to analyze the geographic distribution of hospital discharges secondary to Crohn’s disease and ulcerative colitis. To validate the geographic pattern shown by the Medicare data, hospitalization was compared with mortality from IBD among different states.

Abbreviations used in this paper: CI, confidence interval; HCFA, Health Care Financing Administration; ICD, International Classification of Diagnoses; IBD, inhmmatory bowel disease; MEDPAR, Medicare Provider Analyses and Review; RR, relative risk; SMR, standardized morbidity ratio. o 1991 by the American Gastroenterological Association 0016-5065/91/$3.00

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Materials

and Methods

Medicare Data Files The Medicare Provider Analyses and Review (MEDPAR) is collected on an annual basis by the Health Care Financing Administration (HCFA). The annual file contains records of 8.8 million hospital discharges among all Medicare beneficiaries. The present analysis was based on the complete files of 1986 and 1987, available as computer tapes at HCFA in Baltimore, Maryland. Access to the HCFA files was granted to the Department of Biostatistics and Epidemiology through dedicated phone lines. Each annual file contained detailed accommodation and departmental charge data, days of care, diagnostic and surgical information, beneficiary and hospital demographics. Up to five medical diagnoses were coded for each case, each diagnosis listed as four-digit code of the ninth revision of the International Classification of Diagnoses (ICD) (21). Individual patients could be identified by personal code numbers. The following information was extracted from the HCFA data files: age, sex, race, U.S. state of residence, principal diagnosis and possibly four secondary diagnoses. The personal identifiers were extracted to exclude repeat admissions of identical patients. The HCFA data served to evaluate the geographic distribution of Crohn’s disease (ICD code 555) and ulcerative colitis (ICD code 556) within the United States. The geographic distributions of achalasia (530.0), gastric ulcer (531), duodenal ulcer (532), constipation (564.0), and gallstones (574) served to validate the uniqueness of the pattern observed in IBD.

Vital Statistics The number of deaths resulting from IBD between 1968 and 1978 was available from Vital Statistics, volume II, part B, published annually by the National Center for Health Statistics (22). Because the present study relied on published data, it was necessary to use vital statistics from a decade before the hospitalization data. In the eighth revision of the ICD, IBD was assigned the code 563. A more detailed breakdown by the individual diseases regional enteritis (563.0) and ulcerative colitis (563.1) was not available. In subsequent publications of the Vital Statistics since 1979, inclusion of IBD into tables showing deaths by individual states has been abandoned altogether. The records contained a breakdown by state, sex, and race, i.e., white and nonwhite. Published in volume II, part A, annually from 1968 to 1978, summary tables for the whole United States also contained mortality from IBD by age, sex, race, and 5-year age groups.

Statistical Analyses To guarantee a large number of cases, the records of hospital discharges during 1986 and 1987 were pooled and analyzed together. The analysis of the Medicare data was confined to patients aged 65 years and older. In addition, subjects of unspecified race (660 subjects) and other races than white or black (90 subjects) were disregarded in the present analysis. All records with IBD appearing either as

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primary or secondary diagnosis were extracted from the complete Medicare population of the 2 consecutive years and aggregated by state of residence, sex, and race. The occurrence of IBD in each state was expressed as a standardized morbidity ratio (SMR), i.e., the ratio of observed over expected number of cases (23). To calculate the expected number of cases, the numbers of all IBD cases in the whole United States was broken down by 5-year age groups and expressed as age-specific rates per 100,000 U.S. population. The age-specific U.S. rates were then multiplied by the corresponding age-specific numbers of residents in each individual state. Thus, for each state, the total expected number is the sum of cases expected in the individual age-groups of its population, if the average U.S. age-specific morbidity rate had been applicable to it. The population of each state by age, sex, and race was obtained from the latest 1980 census of the United States (24). Standard morbidity ratios were calculated for Crohn’s disease and ulcerative colitis alone and for both diseases combined as IBD. Separate SMRs were calculated for white and black men and women, respectively. In a second separate analysis, the entirety of hospital discharges in the Medicare population instead of the U.S. census population was used as external standard to calculate SMR values. To guarantee a large enough number of deaths from IBD in individual states, the data of the 11 consecutive years from 1968 to 1978 were analyzed together. Mortality from IBD in each state was expressed as standardized mortality ratio. The standardized mortality ratio was calculated similarly to the SMR described above, as the ratio of observed over expected number of deaths. The age-specific U.S. death rates were calculated as average values of the total period 1968 to 1978. Calculation of the standardized mortality ratio of IBD between 1968 and 1978 was based on the population of each state by age, sex, and race obtained from the 1970 U.S. census (24). Separate SMRs were calculated for white and nonwhite men and women, respectively. The geographic distributions of men vs. women, Crohn’s disease vs. ulcerative colitis, and hospitalization (Medicare) vs. mortality (Vital Statistics) were compared by leastsquares linear regression analyses (25). Rates in men vs. women and whites vs. blacks were compared by calculating the relative risk (RR) and its 95% confidence interval (CI) (23). Results During 1986 and 1987, over 22,000 Medicare patients aged 65 and older were discharged from U.S. hospitals with the primary or secondary diagnosis of IBD. Hospital discharge rates were similar in men and women (RR, 1.02; CI, 1.01-1.03). They were about twofold higher in whites than blacks (RR, 2.18; 95% CI, 2.18-2.19). Similar relative risks were calculated using all hospital discharges among Medicare beneficiaries as denominator rather than the U.S. census population (Table 1). Among whites, there was a threefold to fourfold variation between states with the lowest and highest rates of IBD (Table 2). In smaller states, calculation of SMR by sex and race was based

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Table 1. Number of Deaths and Hospital Discharges by Race and Sex Whites Men Deaths (1968-1978) IBD Census population (1970) Medicare hospital discharges (1986-1987) Ulcerative colitis Crohn’s disease IBD Hospital discharges of patients > 65 years old Census population > 65 years old (1980) “Nonwhites

in Medicare

comprises

Nonwhites” Women

Men

Women

4503 86,717,987

5934 91,027,628

340 12,194,205

420 13,272,106

4695 3947 8642

6106 6813 12,919

182 108 290

357 252 609

3,331,450

4,330,830

272,770

367,980

9,222,062

13,726,131

846,712

1,240,146

only blacks,

on relatively small numbers (Table 2). Therefore, most subsequent analyses were restricted to the 20 or 30 larger U.S. states; their size was determined by the number of white or black residents aged 65 and older. Hospitalization resulting from IBD seemed to be more common in northern than southern states. In Figure 1, this geographic distribution is exemplified for 30 states with the largest white populations. There were several noteworthy exceptions to this general pattern; Arizona and Florida represented two southern states with exceptionally high rates, whereas several northern states, such as Minnesota, Iowa, and Indiana, showed relatively low rates. Besides southern states, rural states in general appeared to be characterized by low morbidity rates of IBD. A northsouth gradient of IBD morbidity was also observed in blacks (Figure 2). The rates in blacks were significantly correlated with those in whites (Figure 3). Similar geographic patterns were observed in men and women, and, accordingly, significant correlations were also found between the geographic distributions of the two sexes (Figure 4). Ulcerative colitis and Crohn’s disease showed a similar geographic distribution (Figure 5). Significant correlations between the two diseases were also found, if their rates were compared separately in white and black men and women, respectively. Three analyses were carried out to validate the geographic pattern shown by the Medicare data. First, the SMRs using the entirety of hospital admissions as external standard showed an identical geographic pattern and were characterized by the same correlations as the SMRs standardized by the U.S. census population. Second, the geographic distribution of IBD was analyzed by an independent data set, i.e., the Vital Statistics, and compared with the Medicare data. Over 11,000people died of IBD throughout the United States between 1968 and 1978 (Table 1).Sex and race distributions of mortality resembled those

observed with regard to hospitalization. Mortality was similar in men and women (RR, 1.24; CI, 1.22-1.26) but twofold higher in whites than in blacks (RR, 1.97; (Table 1). As found in the hospitalizaCI, 1.96-1.98) tion data, SMR of white men and women showed a similar geographic variation with a correlation of r = 0.62 (n = 30; P < 0.001). Most importantly, mortality and hospitalization were characterized by a similar geographic distribution (Figure 6). The significant correlation between mortality and hospitalization was also found, if male and female SMRs were analyzed separately. As a third means to validate the uniqueness of the geographic distribution of IBD, it was compared with the geographic distribution of other gastrointestinal diseases and all diseases taken together. No significant correlations were found between IBD on one hand and, on the other hand, between achalasia, gastric ulcer, duodenal ulcer, constipation, or gallstones. Discussion As shown by the HCFA data, there is a marked variation in the geographic distribution of hospitalization for IBD among different states. More hospitalizations for IBD occurred in northern than in southern states. The validity of this pattern was supported by three independent findings: (1)similar patterns were shown by two independent data sources, i.e., hospital and mortality statistics; (2) similar patterns were found in men and women as well as in whites and nonwhites: and (3) Crohn’s disease and ulcerative colitis were characterized by a similar geographic variation, not shared by other gastrointestinal diseases. In addition, the present data confirm previous studies which have suggested a low prevalence of IBD in the South and high prevalence in the North or Northeast of the United States (16-20). These studies, however, were based on a much smaller number of

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Table 2. Observed Number and Standardized Ulcerative

Morbidity Ratio of Hospitalization and Mortality by State and Race colitis*

White State Alabama Alaska Arizona Arkansas California Colorado Connecticut Delaware District of Columbia Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota Ohio Oklahoma Oregon Pennsylvania Rhode Island South Carolina South Dakota Tennessee Texas Utah Vermont Virginia Washington West Virginia Wisconsin Wyoming

Rank 22 51 29 33 1 28 25 48 47 7 13 39 41 5 12 27 32 23 19 38 18 11 8 21 31 15 44 35 43 42 9 37 2 10 46 6 26 30 4 40 24 45 17 3 36 49 14 20 34 16 50

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Crohn’s

Black

OBS

SMR

OBS

132 5 136 92 944 97 155 31 14 811 144 5 57 583 225 168 123 128 125 66 147 394 417 145 70 253 49 86 25 67 455 41 1108 140 40 549 130 139 856 57 69 34 185 457 64 27 187 199 105 254 11

85 135 102 74 94 88 94 127 96 110 78 50 131 109 86 91 88 71 91 99 94 118 108 64 77 89 126 89 88 138 122 89 121 62 106 108 81 99 128 97 71 80 89 83 128 98 96 101 98 96 64

28 0 1 6 30 0 2 4 10 27 36 0 0 40 11 1 1 5 19 1 23 2 34 0 12 14 1 1 0 0 24 0 43 27 0 22 7 0 21 0 8 0 12 27 0 0 31 2 1 5 0

OBS, observed number of cases; SMR = 100 x observed/expected “Rank by size of total population according to the 1980 census. “Hospital discharges in 1986-1987. “Deaths. 1968-1978.

disease*

White SMR 110 0 84 53 111 0 76 251 100 114 126 0 0 155 154 154 41 80 74 2680 169 65 175 0 53 127 5108 143 0 0 175 0 111 100 0 110 145 0 92 0 44 0 70 79 0 0 151 175 42 309 0

Vital statistics”

Black

White

OBS

SMR

OBS

SMR

135 7 153 93 924 105 191 27 4 816 143 14 31 556 220 135 123 128 101 98 171 514 417 147 76 306 42 68 24 60 408 38 981 207 22 555 139 123 754 96 86 30 165 467 46 32 189 221 103 255 13

86 187 114 75 93 96 116 111 28 111 77 140 72 104 85 75 90 71 73 149 109 155 109 67 83 109 110 72 83 125 110 82 107 91 60 110 87 89 113 165 87 73 79 85 92 118 97 114 97 99 77

12 0 1 4 10 1 0 1 4 18 20 0 0 25 7 0 2 6 9 0 9 6 20 2 8 10 0 0 0 0 10 0 40 17 0 22 4 0 29 1 4 0 6 24 2 0 18 2 6 0 0

71 0 126 54 55 130 0 94 59 113 104 0 0 144 147 0 124 145 53 0 98 293 154 496 53 137 0 0 0 0 108 0 152 94 0 165 125 0 190 397 33 0 53 106 3048 0 132 260 380 0

number

of cases.

0

OBS

Nonwhite SMR

OBS

SMR

131 7

92

92 84 975 99 167 14 13 476 148 3 29 656 287 150 107 168 101 65 157 357 435 186 67 244 51 110 37 50 440 41 1089 189 28 595 129 124 658 58 84 45 157 507 54 27 211 172 95 250 18

105 83 97 88 100 57 68 113 83 26 74 114 105 84 79 97 76 107 93 105 103 85 82 90 132 119 169 116 115 94 109 90 79 109 89 100 98 103 92 112 82 97 111 104 107 93 93 99 101

20 2 15 11 60 2 5 0 20 31 44 5 0 55 14 2 2 8 37 0 16 3 38 1 23 11 1 5 0 0 29 8 66 30 1 34 9 2 30 1 19 1 17 45 0 0 24 3 2 6 2

67 135 348 86 96 78 97 0 123 100 121 34 0 130 129 164 51 97 109 0 78 47 127 53 87 70 128 354 0 0 126 323 95 86 237 112 97 118 90 109 83 112 83 98 0 0 88 69 70 153 805

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Minnesota Kentucky Arkansas North Carolina Georgia Lousiana Iowa Texas Tennessee Oklahoma Indiana Alabama Kansas California Oregon

6o /

I.0

I

0

r

3070

90

80

??

I

147

I

0.78, ” = 20, p < 0.001

I

I

I

100

110

120

130

Whites Illinois Washington Michigan Arizona Ohio Florida New York New Jersey Pennsylvania Massachusetts

Figure 3. Correlation between the geographic variation of IBD in blacks and whites. Each point represents the SMRs of one state; only the 20 largest states are shown.

I-

I-

150

Standardized Morbidity Ratio Figure 1. Geographic distribution of IBD among whites in the 30 largest states. Striped and stippled hors represent the SMR of southern and northern states. resoectivelv.

South Carolina Mississippi Arkansas Tennessee Lousiana California Texas Alabama NorthCarolina

Florida

cases than the present study, were restricted to few U.S. regions rather than individual states, or reported the occurrence of IBD from only one location. Although the majority of states followed the prevailing north-south gradient, some states obviously did not. Florida and Arizona, for instance, would have been expected to lie below rather than above the average SMR value of 100.The warm climate of some southern states has attracted many retired and elderly people. Rates in these states may not reflect the true risk of residency but may be artificially inflated if elderly people moved in, specifically, after having contracted IBD elsewhere. As shown in Figures 1 and 2, the low rates of several northern states also failed to fit the overall pattern. Additional risk factors, such as living in an urban vs. rural environment, could be superimposed on a north-south gradient and partly counteract its influence. It is interesting to note that other available data on the geographic distribution of IBD point in the same direction. In Europe, the highest incidence rates were

Georgia New York Missouri Pennsylvania rn al

Ohio Maryland

m

E al u

Virginia New Jersey Illinois

120

100 80

Michigan 60

Standardized Morbidity Ratio Figure 2. Geographic distribution of IBD among blacks in the 20 largest states. Striped and stippled barsrepresent the SMR of southern and northern states, respectively.

60

80

100

120

140

160

Males Figure 4. Correlation between the geographic variation of IBD in men and women. Each point represents the SMRs of one state; only the 30 largest states are shown.

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80

--80

80

100

120

140

160

Crohn’s Disease Figure 5. Correlation between the geographic variation of ulcerative colitis and Crohn’s disease. Each point represents the SMRs of one state; only the 30 largest states are shown.

reported from the Scandinavian countries and Great Britain, while relatively low rates were found among the Mediterranean countries. Israel provides a telltale example, in which initially high incidence rates of IBD had been expected based on its predominantly Jewish population; yet low rates in the same range as other Mediterranean countries were eventually found (26,27). It appears as if southern countries provide some protection against contracting IBD or lack one or more essential risk factors. Among the things to consider are climate and other associated environmental influences, such as insulation, humidity, temperature, precipitation, etc. In the present study, mortality and hospitalization data covered the periods 1968 to 1978 and 1986 to 1987, respectively; yet they were significantly correlated despite the 8-21 years between them. The persistence of the geographic pattern in the United States and its consistency with patterns found outside the United States could speak in favor of climatic factors. One might expect that other environmental influences would have been less persistent and more susceptible to changes and assimilation

80

100

120

140

Hospitalization Figure 6. Correlation between the geographic variation of mortality and hospitalization resulting from IBD. Eachpoint represents the SMRs of one state; only the 30 largest states are shown.

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in lifestyles among different regions. Further studies are needed to pursue this hypothesis and test the influence of climatic factors. The uniqueness of the geographic pattern of IBD is suggested by its similar occurrence in various subgroups affected by Crohn’s disease or ulcerative colitis. The pattern is quite different from the geographic variations of other gastrointestinal diseases. It may be speculated that a variation in medical care delivery contributed to the observed pattern. A general tendency to hospitalize all types of patients more readily would inflate the hospital discharge rates of IBD, and states where hospitalization is handled more restrictively would show disproportionately low IBD discharge rates. To rule out such a confounding influence, a second set of SMRs was calculated using, instead of the U.S. population, the entirety of hospital admissions for all ICD codes as external standard. An identical geographic pattern and similar correlations were established with both types of SMRs. However, it is still possible that geographic variations affecting specifically the diagnostic and therapeutic management of IBD have confounded the observed geographic pattern. The occurrence and consistency of the pattern do not allow to unequivocally ascertain its cause(s). Other interpretations than a north-south or urban-rural gradient are conceivable. Because the particular geographic variation described in the present paper remains valid independently of its interpretation, it may actually help to validate or refute other hypotheses regarding the geographic distribution of IBD. The present study used the accumulated data of all Medicare beneficiaries from 2 consecutive years to analyze the geographic distribution of IBD in the United States. The strengths of the data relate to the large number of records that are available to study rare medical conditions. There is a high accuracy in reporting. Up to five medical diagnoses are available for each patient, each diagnosis listed as four-digit code of the ninth ICD. Because of the large number of subjects included in the MEDPAR data file, the statistical power of most associations is strong, and rates can be calculated for individual states. The MEDPAR data file comprises a total enumeration of all Medicare beneficiaries in the United States per year. Hence, the population is not biased by any selection process, such as geographic boundaries, personal choices, and access to or referral of a particular patient population. The discharge diagnoses are established and listed on the discharge summary without any prospective goal, underlying medical hypothesis, or scientific intentions. They represent the diagnosis as recorded by physicians distributed throughout the United States, blinded and oblivious to the further use of these data.

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1991

In summary, mortality and hospitalization statistics both suggest that the occurrence of IBD is determined by environmental factors that show a marked geographic variation within the United States. Both Crohn’s disease and ulcerative colitis seem to be more frequent in the northern than in the southern parts of the United States. A parallel geographic variation of Crohn’s disease and ulcerative colitis indicates the influence of one or more identical risk factors shared by both diseases. References 1. Martini

2.

3. 4.

5.

6.

7.

8.

9.

10.

11. 12. 13.

GA, Brandes JW. Increased consumption of refined carbohydrates in patients with Crohn’s disease. Klin Wochenschr 1976;54:367-371. Thornton JR, Emmett PM, Heaton KW. Diet and Crohn’s disease: characteristics of the preillness habit. Br Med J 1979;2: 762-764. Mayberry JF, Rhodes J, Newcombe RG. Increased sugar consumption in Crohn’s disease. Digestion 1980;20:323-326. Mayberry JF, Rhodes J, Allen R, Newcombe RG, Regan GM, Chamberlain LM, Wragg KG. Diet in Crohn’s disease: two studies of current and previous habits in newly diagnosed patients. Dig Dis Sci 1981;26:444-448. Katschinski B, Logan RFA, Edmond M, Langman MJS. Smoking and sugar intake are separate but interactive risk factors in Crohn’s disease. Gut 1988;29:1202-1206. Tobin MV, Logan RFA, Langman MJS, McConnell RB, Gilmore IT. Cigarette smoking and inflammatory bowel disease. Gastroenterology 1987;93:316-321. Lindberg E, Tysk C, Andersson K, Jarnerot G. Smoking and inflammatory bowel disease. A case control study. Gut 1988;29: 352-357. Vessey M, Jewel1 D, Smith A, Yeates D, McPherson K. Chronic inflammatory bowel disease, cigarette smoking, and use of oral contraceptives: findings in a large cohort study of women of childbearing age. Br Med J 1986;292:1101-1103. Logan RFA, Kay CR. Oral contraception, smoking and inflammatory bowel disease-findings in the Royal College of General Practioners Oral Contraceptive Study. Int J Epidemiol 1989;18:105-107. Lesko SM, Kaufman DW, Rosenberg L, Helmrich SP, Miller DR, Stolley PD, Shapiro S. Evidence for an increased risk of Crohn’s disease in oral contraceptive users. Gastroenterology 1985;89: 1046-1049. Mayberry JF, Rhodes J. Epidemiological aspects of Crohn’s disease: a review of the literature. Gut 1984;25:886-899. Mayberry JF. Some aspects of the epidemiology of ulcerative colitis. Gut 1985;26:968-974. Mayberry JF. Recent epidemiology of ulcerative colitis and Crohn’s disease. Int J Colorect Dis 1989;4:59-66.

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14. Sonnenberg A. Geographic variation in the incidence and mortality from inflammatory bowel disease. Dis Colon Rectum 1986;29:854-861. 15. Sonnenberg A. Hospital discharges for inflammatory bowel disease. Time trends from England and the United States. Dig Dis Sci 1990;35:375-381. 16. Mendeloff AI, Calkins BM. Epidemiology of idiopathic inflammatory bowel disease. In: Kirshner JB, Shorter RG, eds. Inflammatory bowel disease. 3rd ed. Philadelphia: Lea & Febiger, 1988:3-34. 17. Acheson ED, Nefzger MD. Ulcerative colitis in the US army in 1944. Gastroenterology 1963;44:7-19. 18. McMahon JM, Morton B. Ulcerative colitis in a southern general hospital and a southern industrial-rural area. A concept of etiology and an attempt at a geography of the disease. Am J Gastroenterol 1959;31:183-191. 19. Weiner HA, Lewis CM. Some notes on the epidemiology of nonspecific ulcerative colitis. An apparent dence in Jews. Dig Dis Sci 1960;5:406-418.

increase

in inci-

20. Garland CF, Lilienfeld AM, Mendeloff AI, Markowitz JA, Terre11 KB, Garland FC. Incidence rates of ulcerative colitis and Crohn’s disease in fifteen areas of the United States. Gastroenterology 1981;81:1115-1124. 21. World Health Organization. The international classification of diseases. 9th revision. Clinical modification. 2nd ed. DHHS Pub. No. (PHS) 80-1260. Washington, DC: Public Health Service, US Government Printing Office, 1980. 22. National Center for Health Statistics. Vital Statistics of the United States. Volume II, Mortality, part A and B, 1968-1978. Washington, DC: US Department of Health, Education, and Welfare, Public Health Service, US Government Printing Office, 1972-1982. 23. Kahn HA, Sempos CT: Statistical methods in epidemiology. New York: Oxford University Press, 1989. 24. U.S. Bureau of the Census. U.S. Census of Population: 1980. Volume 1, chapter B. General Population Characteristics. Washington, DC: US Government Printing Office, 1982. 25. Zar JH. Biostatistical analysis. 2nd ed. Englewood Cliffs, NJ: Prentice-Hall, 1984:406-439. 26. Gilat T, Ribak J, Benaroya Y, Zemishlany 2. Weissman I. Ulcerative colitis in the Jewish population of Tel-Aviv-Yafo. I. Epidemiology. Gastroenterology 1974;66:335-342. 27. Rozen P, Zonis J, Yekutiel P, Gilat T. Crohn’s disease in the Jewish population of Tel-Aviv-Yafo. Gastroenterology 1979;76: 25-30.

Received November 6,1989. Accepted July 14, 1990. Address reprint requests to: Amnon Sonnenberg, M.D., Gastroenterology Section, 111-C C.J. Zablocki VA Medical Center, 5000 West National Avenue, Milwaukee, Wisconsin 53295. Dr. Sonnenberg was supported by grant So 172/1-l from the Deutsche Forschungsgemeinschaft.