New diagnostic imaging tools for inflammatory bowel disease.
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Colitis, Ulcerative↗
Biomedical subjects
C N Bernstein
Publications and source records attributed to C N Bernstein.
A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn's disease.
AIM: To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease. METHODS: Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo. Corticosteroid therapy was decreased following a predefined schedule. The primary efficacy end-point was the percentage of patients with corticosteroid-sparing [i.e. no disease flare (Crohn's Disease Activity Index score > or =220 points) and no longer requiring corticosteroid therapy] at week 10. The major secondary efficacy end-point was corticosteroid-sparing at week 16. RESULTS: Seventy-one patients received treatment. Corticosteroid-sparing was achieved by 19 of 39 (48.7%) CDP571 patients and 13 of 42 (40.6%) placebo patients (P = 0.452) at week 10, and by 18 of 39 (46.2%) CDP571 patients and seven of 32 (21.9%) placebo patients (P = 0.032) at week 16. CDP571 therapy was well-tolerated and the incidence of serious adverse events was similar to placebo. CONCLUSIONS: The CDP571 was effective for corticosteroid-sparing at week 16 but not week 10, and was well-tolerated in patients with corticosteroid-dependent Crohn's disease.
Adult↗
Review article: Osteoporosis and inflammatory bowel disease.
Studies using dual-energy X-ray absorptiometry have suggested a high prevalence of osteoporosis in inflammatory bowel disease. However, population-based data on fracture incidence suggest only a small increased risk of fracture amongst patients with inflammatory bowel disease compared with the general population. Therefore, it would be helpful to identify patients with inflammatory bowel disease at particularly high risk for fracture so that these risks might be modified or interventions might be undertaken. The data on calcium intake as a predictor of bone mineral density are conflicting. Although there are data suggesting that a one-time survey to determine current calcium intake will not help to predict bone mineral density in inflammatory bowel disease, persistently reduced calcium intake does appear to lead to lower bone mineral density. In the general population, body mass is strongly correlated with bone mineral density, which also appears to be true in Crohn's disease. Hence, subjects with inflammatory bowel disease and considerable weight loss, or who are obviously malnourished, could be considered for bone mineral density testing, and the finding of a low bone mineral density would suggest the need for more aggressive nutritional support. Although vitamin D is undoubtedly important in bone health, vitamin D intake and serum vitamin D levels do not correlate well with bone mineral density. Sex hormone deficiency can also adversely affect bone health, although a well-developed strategy for sex hormone measurements in patients with inflammatory bowel disease remains to be established. Ultimately, the determination of genetic mutations that accurately predict fracture susceptibility may be the best hope for developing a simplified strategy for managing bone health in inflammatory bowel disease. The therapy of osteoporosis in inflammatory bowel disease has been adapted from other osteoporosis settings, such as post-menopausal or corticosteroid-induced osteoporosis. To date, there remains no therapy proven to be efficacious in inflammatory bowel disease-related osteoporosis; however, calcium and vitamin D supplementation and bisphosphonates have their roles.
Adrenal Cortex Hormones↗
Detection of species-specific helicobacter ribosomal DNA in intestinal biopsy samples from a population-based cohort of patients with ulcerative colitis.
The inflammatory bowel diseases are considered an abnormal host immune response to an environmental stimulus. Evidence suggests a role for intestinal bacteria in initiating and/or providing an ongoing stimulus for inflammation in inflammatory bowel disease. Helicobacter pylori is the major cause of active chronic gastritis and peptic ulcers in humans and has been linked to gastric carcinoma and lymphoma. Studies in various animal models, particularly mice, have identified enterohepatic Helicobacter species that are capable of causing hepatitis and enterocolitis. We hypothesize that Helicobacter species may have a role in maintaining inflammation in humans with inflammatory bowel disease. In order to investigate this, biopsy specimens were obtained from patients with and without inflammatory bowel disease. DNA was extracted from the tissues and subjected to PCR with primers designed to detect the ribosomal DNA of members of the Helicobacter species. DNA from six biopsy samples from 60 inflammatory bowel disease patients tested positive. This included 5 of 33 ulcerative colitis patients that were positive compared to 0 of 29 age-matched controls (P < 0.04). Sequencing of the bands produced by PCR amplification revealed >or=99% homology with H. pylori. These results indicate that a member of the Helicobacter species may be involved in some cases of ulcerative colitis.
Base Sequence↗
Therapeutic value of a gastroenterology consultation in irritable bowel syndrome.
BACKGROUND: Functional patients comprise the largest group in gastroenterology practice. Pharmacological therapy of irritable bowel syndrome is disappointing. One treatment strategy for irritable bowel syndrome emphasizes the physician's role; the physician is promoted as the therapeutic modality. AIM: To determine the therapeutic value of the contemporary approach to irritable bowel syndrome by examining health care utilization and patient morbidity. METHODS: We performed an observational study over 4 years using an administrative database and morbidity scales. Health care utilization was assessed for 2 years pre- and post-intervention. Patient morbidity was assessed at baseline and 1 and 2 years post-intervention. The participants included 70 irritable bowel syndrome patients referred by primary physicians. A structured consultation was performed, establishing a positive diagnosis of irritable bowel syndrome and providing disease conceptualization. RESULTS: Health care utilization for gastrointestinal diagnoses increased in the year prior to the intervention and declined immediately after to baseline; psychiatric and other visits remained unchanged for 4 years. Pain was reduced but other morbidity persisted. CONCLUSIONS: A consultation itself is a therapeutic intervention in irritable bowel syndrome with regard to its impact on societal economic burden. It is associated with a durable decrease in illness-specific health care utilization. It may not address all aspects of irritable bowel syndrome; multiple domains of morbidity demonstrated persistent distress.
Adolescent↗
Viral hepatitis in a Canadian First Nations community.
Serological markers for hepatitis A (HAV), B (HBV) and C (HCV) were documented in 315 inhabitants (27%) of a central Manitoba First Nations community. Serologic evidence of HAV infection (anti-HAV positive) was almost universal (92%) by the age of 20 years. HBV infection (antibody to hepatitis B core antigen positive) had occurred in only 2.3% of the study population and no chronic carriers were identified. Serological evidence of HCV infection (anti-HCV positive) was documented in 2.2% of the population but ongoing viremia (HCV-RNA positive by polymerase chain reaction) was absent. The results of this study highlight the importance of universal HAV vaccination; likely reflect the efficacy of existing prenatal screening and immunoprophylaxis programs for HBV; and raise the possibility that First Nations peoples have an enhanced ability to spontaneously clear HCV.
Adult↗
Generational differences in the age at diagnosis with Ibd: genetic anticipation, bias, or temporal effects.
OBJECTIVE: Previous cross-sectional research has demonstrated generational differences in age at diagnosis (AAD) in inflammatory bowel disease (IBD). This observation has at times been ascribed to genetic anticipation, but could also be due to biases related to case ascertainment or follow-up or to temporal changes in IBD epidemiology. We aimed to explore this issue using a population-based database. METHODS: In 1995 we used the comprehensive administrative databases in the province of Manitoba, Canada to establish a population-based IBD Research Registry that includes clinical and demographic information for persons. We contacted those subjects within our Research Registry who reported having any family members with IBD and their family members for verification of diagnosis and AAD. Differences in AAD between familial pairs were calculated. In addition, to assess whether duration of follow-up accounted for generational differences in AAD, we computed the mean AAD for subjects with and without family histories of IBD based on age at the time of interview (i.e., < 45 and > or = 45 yr of age). RESULTS: Of the 2445 persons with IBD in the Research Registry, 548 reported positive family histories, and 315 of these (58%) were reached by telephone. There were 169 Crohn's disease and 146 ulcerative colitis subjects with positive family histories. The mean AADs for the parents, aunts/uncles, and grandparents were significantly greater than the mean AADs for the children, nieces/nephews, and grandchildren, respectively. There was a doubling of the mean AAD when comparing the grandparent/grandchild cases with the parent/child or aunt/uncle-niece/nephew cases. No statistically significant difference in anticipation was observed, whether or not the older generation was male or female or had Crohn's disease or ulcerative colitis. The AAD was substantially greater for those interviewed at > or = 45 yr of age for subjects with and without family histories. However, there was no substantial difference in mean AAD between familial and nonfamilial subjects. CONCLUSION: The present study has demonstrated that there is a tendency for children to be younger than their parents at the time of diagnosis of familial IBD, and that this difference in mean AAD is almost doubled for grandparent/grandchild pairs. However, we conclude that these differences are most likely due to a bias based on length of follow-up or recent multigenerational temporal changes in the risk of IBD, or both.
Adult↗
Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis.
The objectives of this study were to describe variations in the incidence of inflammatory bowel disease (IBD) within the Canadian province of Manitoba and to analyze sociodemographic factors associated with these variations. The authors used the Manitoba Health insurance databases to measure incidence rates of Crohn's disease and ulcerative colitis for each of 52 postal areas in Manitoba, in 1987-1996. The sociodemographic characteristics of the postal areas were based on data from the 1996 Canadian census. The overall incidence rates of Crohn's disease and ulcerative colitis were identical-15.6 per 100,000. Both diseases showed substantial geographic variation, with incidence rates differing significantly from the provincial average in 15 postal areas for Crohn's disease and in 13 postal areas for ulcerative colitis. There was a significant geographic correlation in the incidence of Crohn's disease and ulcerative colitis (r = 0.49, p < 0.001). The incidence of IBD was higher in urban areas (incidence rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.00, 1.45). Aboriginal Canadians had significantly lower rates of both Crohn's disease (IRR = 0.11, 95% CI: 0.05, 0.22) and ulcerative colitis (IRR = 0.57, 95% CI: 0.42, 0.79). A higher incidence of IBD was ecologically associated with a higher average family income, a lower proportion of immigrant and Aboriginal Canadian populations, and a smaller average family size.
Adult↗
Cancer risk in patients with inflammatory bowel disease: a population-based study.
BACKGROUND: The objective of the current study was to determine the incidence of cancer among persons with inflammatory bowel disease (IBD) and to compare these incidence rates with those of the non-IBD population using population-based data from the administrative claims data of Manitoba's universal provincial insurance plan (Manitoba Health). METHODS: IBD patients were matched 1:10 to randomly selected members of the population without IBD based on year, age, gender, and postal area of residence. The incidence of cancer was determined by linking records from the IBD and non-IBD cohorts with the comprehensive Cancer Care Manitoba registry. Incidence rates and rate ratios (IRR) were calculated based on person-years of follow-up (Crohn's disease = 21,340 person-years and ulcerative colitis [UC] = 19,665 person-years) for 1984-1997. RESULTS: There was an increased IRR of colon carcinoma for both Crohn disease patients (2.64; 95% confidence interval [95% CI], 1.69-4.12) and UC patients (2.75; 95% CI, 1.91-3.97). There was an increased IRR of rectal carcinoma only among patients with UC (1.90; 95% CI, 1.05-3.43) and an increased IRR of carcinoma of the small intestine only in Crohn disease patients (17.4; 95% CI, 4.16-72.9). An increased IRR of extraintestinal tumors was observed only for the liver and biliary tract in both Crohn disease patients (5.22; 95% CI, 0.96-28.5) and UC patients (3.96; 95% CI, 1.05-14.9). There was an increased IRR of lymphoma for males with Crohn disease only (3.63; 95% CI, 1.53-8.62), and this finding did not appear to be related to use of immunomodulatory therapy. Compared with controls, Crohn's disease was associated with an increased risk of cancer overall, but UC was not. CONCLUSIONS: There appear to be similar increased risks for developing colon carcinoma and hepatobiliary carcinoma among patients with Crohn disease and UC. There is an increased risk of developing rectal carcinoma in UC patients, an increased risk of developing carcinoma of the small bowel in Crohn disease patients, and an increased risk of developing lymphoma among males with Crohn disease.
Adult↗
Extraintestinal manifestations of inflammatory bowel disease.
Patients with inflammatory bowel disease (IBD) may confront a variety of nonintestinal problems. The first North American population-based data describing the incidence rates of several of these disorders have been reported over the past year. Reports have also documented our expanding knowledge of peristomal pyoderma gangrenosum, and of ulcerative colitis following liver transplantation in patients with primary sclerosing cholangitis. Osteopenia continues to receive considerable attention. Factors such as osteoprotegrin ligand, and its interaction with receptor activator of nuclear factor kappa B, are connected with T-cell activity, inflammation, and osteoclastogenesis. Studies in these and other areas are addressed in this review.
Cholangitis, Sclerosing↗
Does gastroenterology consultation change management of patients receiving hematopoietic stem cell transplantation?
Gastrointestinal complications following hematopoietic stem cell transplantations (HSCTs) are common, but it is unknown how often gastroenterology consultation (GEC) early post BMT leads to specific changes in patient management. We aimed to determine the reason(s) for GEC, the diagnoses found through GEC, whether the advice or intervention led to change(s) in management and if intervention led to any adverse outcome within the first 100 days post HSCT. We undertook a retrospective review of all patients at least 18 years old (n = 197) who underwent HSCT between November 1990 and April 1998. Of these, 79 patients had 92 consultations for a total of 163 separate GE problems within the first 100 days post HSCT. Data were obtained through chart review. It was determined whether the intervention or advice given by the consultant led to actual changes in patient management or outcome. We found that the characteristics more likely to be associated with GEC included female patient vs male (P = 0.03), allogeneic vs autologous transplants (P < 0.001), hematologic vs solid malignancies (P = 0.006), and leukemias vs lymphomas (P = 0.013). Overall, a definitive diagnosis for an identified complaint was made in 71% (range 25-87%). A change in management was effected in 54% of cases (range 0-59%). Endoscopy led to perforation and subsequent death in two patients (1.8%). Gastrointestinal disease was a direct cause of death in 2.5% of all patients. In conclusion, a definite diagnosis was reached in 71% of gastrointestinal problems and management was effected in 54% of cases. Since endoscopy was associated with a mortality of 1.8%, minimizing its use for the cases in which no impact is made, should be considered.
Adult↗
An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial.
BACKGROUND & AIMS: We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. METHODS: One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points. RESULTS: At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. CONCLUSIONS: CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.
Adolescent↗
The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases: distinguishing ulcerative colitis from Crohn's disease.
OBJECTIVES: The distinction between the two major forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn's disease is sometimes difficult and may lead to a diagnosis of indeterminate colitis. We have used 1H magnetic resonance spectroscopy (MRS) combined with multivariate methods of spectral data analysis to differentiate UC from Crohn's disease and to evaluate normal-appearing mucosa in IBD. METHODS: Colon mucosal biopsies (45 UC and 31 Crohn's disease) were submitted to 1H MRS, and multivariate analysis was applied to distinguish the two diseases. A second study was performed to test endoscopically and histologically normal biopsies from IBD patients. A classifier was developed by training on 101 spectra (76 inflamed IBD tissues and 25 normal control tissues). The spectra of 38 biopsies obtained from endoscopically and histologically normal areas of the colons of patients with IBD were put into the validation test set. RESULTS: The classification accuracy between UC and Crohn's disease was 98.6%, with only one case of Crohn's disease and no cases of UC misclassified. The diagnostic spectral regions identified by our algorithm included those for taurine, lysine, and lipid. In the second study, the classification accuracy between normal controls and IBD was 97.9%. Only 47.4% of the endoscopically and histologically normal IBD tissue spectra were classified as true normals; 34.2% showed "abnormal" magnetic resonance spectral profiles, and the remaining 18.4% could not be classified unambiguously. CONCLUSIONS: There is a strong potential for MRS to be used in the accurate diagnosis of indeterminate colitis; it may also be sensitive in detecting preclinical inflammatory changes in the colon.
Adult↗
The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study.
OBJECTIVE: The aim of this study was to determine the prevalence of the major extraintestinal manifestations of inflammatory bowel disease (IBD) and their relation to disease diagnosis and gender. METHODS: We used the population-based University of Manitoba IBD Database, which includes longitudinal files on all subjects of all health system contacts identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We extracted a cohort from our database, which included subjects with a known diagnosis of IBD for at least 10 yr. We then determined how many contacts each subject had for each of the following extraintestinal IBD-associated immune diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the extraintestinal diseases using an administrative definition of having at least five health system contacts for the diagnosis in question. This administrative definition has previously been validated in Crohn's disease and ulcerative colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major extraintestinal diseases studied in this report. Only 0.3% of patients had multiple extraintestinal diseases. Iritis/uveitis was the most common extraintestinal disease of all assessed (2.2% of women and 1.1% of men). Iritis/uveitis was more common among women, particularly those with UC (3.8%). Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing spondylitis was more common among men, and the highest rate was seen among men with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's (1.2%) with no gender predilection. Erythema nodosum was similarly present in Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The associations of immune mediated diseases in extraintestinal sites may help us to further our understanding of IBD pathogenesis, and it may help us in developing a paradigm of disease subsets.
Adult↗
The relationship between inflammatory bowel disease and socioeconomic variables.
OBJECTIVES: Inflammatory bowel diseases (IBD) are chronic diseases associated with considerable morbidity. This morbidity may have an impact on the ability of patients to remain employed, on their marital status, and on their ability to complete a course of higher education. It has long been held that IBD patients are of a higher socioeconomic status and more educated than the general population. Our aim was to determine the relationship between IBD and employment, income, disability, education, and marital status in two population-based data sets based in the province of Manitoba, Canada. METHODS: Two studies are reported here. In study A, we surveyed persons with IBD, using the population-based University of Manitoba IBD Database, created in 1995-1996. We compared these IBD patients to the general population with respect to employment, education, and marital status using data from the 1996 National Population Health Survey. IBD patients were queried as to their socioeconomic status as of the time of diagnosis and also at the time of the survey (1995-1996). In study B, we used a database that linked health care and census variables to determine differences in employment, income, occupation, and marital status among individuals who met the administrative definition of IBD (created in forming the University of Manitoba IBD Database, based on ICD-9-CM codes 555 for Crohn's disease and 556 for ulcerative colitis) compared with the rest of working-age population. RESULTS: In study A we found that, compared with the general population, patients with IBD were more likely to be unemployed. Crohn's disease appeared to affect employment more than ulcerative colitis. IBD patients, however, had a low rate of reporting themselves as disabled (1.3%). Among those married when diagnosed with IBD, approximately 10% of men and up to 20% of women were no longer married 5 yr later. More patients with IBD were married in 1995 compared with the general population; however, more were also divorced. Fewer patients with IBD achieved postsecondary education. In study B, we found that individuals with IBD were twice as likely to be out of the labor force as were controls. Sedentary occupations were twice as likely to be associated with IBD. The income, education level, and marital status of IBD patients were not significantly different from those of controls. CONCLUSIONS: Individuals with IBD at some time in the course of their illness are more likely not to be working than are those in the general population. Based on employment status and job classification, as well as income and education, IBD patients are not of a higher socioeconomic status as previously reported. IBD patients are at least as likely as the general population to be married.
Adolescent↗
Use of pharmaceuticals by inflammatory bowel disease patients: a population-based study.
OBJECTIVES: In 1996 we created the population-based University of Manitoba Inflammatory Bowel Disease (IBD) Database. In 1994, Manitoba Health established the Drug Program Information Network (DPIN), which identified all ambulatory prescription drugs dispensed to each individual resident of the province. All residents have a personal health identification number, and use of this number allowed linkage of the IBD database with the DPIN database. Our aim was to use the linkage of these databases to describe prescription drug use by patients with IBD in Manitoba in 1997. METHODS: We analyzed all prescriptions and costs for fiscal year 1997, and stratified our analysis by age, sex, urban versus nonurban residence, income, and disease (Crohn's disease vs ulcerative colitis). We also extracted all subjects diagnosed with IBD in 1984-1987 and those diagnosed in 1994-97 and compared any differences in prescribing patterns in 1997 for these two cohorts. RESULTS: A total of 87.5% of IBD subjects received prescriptions in 1997. There was a direct, significant relationship between increasing age and number of different prescriptions per IBD drug user and total prescription costs per IBD drug user (in adults only), particularly for alimentary drugs. Female patients used a greater number of different prescriptions, but there was no difference between sexes in costs per user. Only 7.8% of patients used immunomodulatory drugs, but these accounted for the greatest cost ($1404) per user. Patients whose disease was diagnosed in 1994-1997 were significantly more likely to be prescribed oral or rectal 5-aminosalicylic acid and steroids than were those whose disease was diagnosed in 1984-1987. In addition, prescriptions for rectal 5-aminosalicylic acid were significantly increased in those patients whose diagnoses were made later over those whose diagnoses were made earlier. Male patients and Crohn's disease patients were more likely to use oral steroids and immunomodulatory medications. Based on the decade of diagnosis, there was no difference in prescribing patterns for immunomodulatory medications. CONCLUSIONS: The linkage of the University of Manitoba IBD Database and the Manitoba DPIN Database allowed a description of patterns of prescription use in a population-based sample of IBD patients. Among the important findings are the lack of effect of gender and urban residence on prescription use in IBD patients; however the decade of diagnosis did affect prescribing patterns. Furthermore, only 7.8% overall receive immunomodulatory medications, but this was independent of the decade of diagnosis.
Adjuvants, Immunologic↗
Who gets irritable bowel syndrome and does seeing a gastroenterologist affect its course?
A review of studies involving patients with irritable bowel syndrome is presented. This review looks at the impact of gastroenterology consultation on health care utilization patterns and the well-being of the patient when followed up over a two-year period. A structured gastroenterological consultation between the physician and patient may decrease the number of office visits for gastrointestinal-related problems.
Colonic Diseases, Functional↗
Osteonecrosis in a patient with Crohn's disease unrelated to corticosteroid use.
Osteonecrosis is a feared complication of corticosteroid use. However, a direct association between corticosteroid use and osteonecrosis has never been proven. The present report examines the case of a patient with longstanding Crohn's disease who had never been treated with corticosteroids and who developed osteonecrosis of the talus. The association of systemic inflammatory disorders with osteonecrosis and the possible association with vascular thrombosis are discussed.
Acute Disease↗