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Charles N Bernstein

Publications and source records attributed to Charles N Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed2006

Natural history and management of flat and polypoid dysplasia in inflammatory bowel disease.

Dysplasia can be a marker that cancer is already present or is coming in the near future. Hence, Physicians should not be cavalier in approach to finding it or in approach after it is found, whether it is in flat mucosa or raised mucosa. Low-grade dysplasia should garner similar respect to high-grade dysplasia, if for no other reason than the difficulty that expert pathologists have with distinguishing low-grade dysplasia from high-grade dysplasia. There is no sure way to reduce the likelihood that dysplasia will arise in UC. Some investigators have promoted the use of 5-ASA. This topic is covered in greater detail elsewhere in this issue (see article by Rubin and Kavitt elsewhere in this issue); however, there is no definitive evidence that 5-ASA can reduce cancer incidence.

Colitis, Ulcerative↗
PubMed2006

Hospitalization, surgery, and readmission rates of IBD in Canada: a population-based study.

BACKGROUND: We aimed to define the rates of hospitalization and readmission for inflammatory bowel disease in Canada. METHODS: The data source was Statistics Canada Person Oriented Information Database (1994-2001). The number of stays for a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) by ICD-9-CM code 555 or 556 was extracted (and assessed when CD or UC was the first diagnosis or was 1 of 16 diagnoses on the patient discharge abstract). Age-, gender-, and disease-specific rates of hospitalization, length of stay, readmission, and surgery were assessed. RESULTS: The age-adjusted hospitalization rate for CD declined over 1994-2001 from 29.2 to 26.9/100,000 but was stable for UC at 12.6-13.3 per 100,000. In the 7 yr, 39.4% of CD patients (21.3-24.0%/yr) and 33.7% of UC patients (18.5-20.3%/yr) got readmitted at least once. The average length of stay declined from 10.3 (1994-1995) to 9.1 days (2000-2001) (p = 0.029) in CD and in UC declined from 12.2 to 10.1 days (p = 0.054). Of all hospitalizations, major surgery occurred in 48% of CD (44.8-49.8% per yr) and 55% of UC (51.5-59.0% per yr). CONCLUSIONS: Rates of hospitalization declined slightly for CD over the 7 yr but still remained twice as great as the rates for UC. Approximately 20% of CD and UC subjects got readmitted per year and over 7 yr approximately 35% got readmitted. Major surgery was a more common reason for hospitalization in UC than in CD.

Adolescent↗
PubMed2006

A population-based case control study of potential risk factors for IBD.

BACKGROUND: We aimed to pursue potential etiological clues to Crohn's disease (CD) and ulcerative colitis (UC) through a population-based case control survey study. METHODS: Cases with CD (n = 364) and UC (n = 217), ages 18-50 yr were drawn from the population-based University of Manitoba IBD Research Registry. Potential control subjects were drawn from the population-based Manitoba Health Registry by age, gender, and geographic residence matching to the cases (n = 433). Subjects were administered a multiitem questionnaire. RESULTS: By univariate analysis, some of the variables predictive of CD included lower likelihood of living on a farm, of having drunk unpasteurized milk or having eaten pork, and UC patients were less likely to have drunk unpasteurized milk and to have eaten pork. On multivariate analysis, variables significantly associated with CD were being Jewish (OR = 4.32, 95% CI 1.10-16.9), having a first degree relative with IBD (OR = 3.07, 95% CI 1.73-5.46), ever having smoked (OR = 1.54, 95% CI, 1.06-2.25), living longer with a smoker (OR = 1.03, 95% CI, 1.01-1.04). Being a first generation Canadian (OR = 0.33, 95% CI, 0.17-0.62), having pet cats before age 5 (OR = 0.66, 95% CI, 0.46-0.96) and having larger families (OR = 0.87, 95% CI, 0.79-0.96) were protective against CD. For UC being Jewish (OR = 7.46, 95% CI, 2.33-23.89), having a relative with IBD (OR = 2.23, 95% CI, 1.27-3.9), and ever smoking (OR = 1.62, 95% CI, 1.14-2.32) were predictive. CONCLUSION: This study reinforced the increased risk associated with family history, being Jewish, and smoking history, however, a number of significant associations with CD and UC on univariate and multivariate analysis may support the "hygiene hypothesis" and warrant further exploration in prospective studies.

Adolescent↗
PubMed2006

On studying the connection between stress and IBD.

A number of investigators over the years have attempted to determine if a relationship exists between flares of inflammatory bowel disease (IBD) and stress. There are many complexities to addressing this issue, including determining the appropriate tools to measure stress, determining the appropriate measures of quantifying a disease flare and also determining the point at which the timing of the stress could be seen to be reasonably related to the onset of the flare. While advances have been made in understanding physiological responses to acute stress, it is unclear whether it is acute, chronic, or recurrent stress that might most impact on a chronic inflammatory disease. In the case of IBD, the disease itself poses a stress to the individual further clouding the issue.

Humans↗
PubMed2006

The epidemiology of inflammatory bowel disease in Canada: a population-based study.

BACKGROUND: Previously, we have demonstrated a high incidence and prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in the Canadian province of Manitoba. However, the epidemiology of inflammatory bowel disease (IBD) in other regions of Canada has not been defined. The aim of this study was to estimate the incidence and prevalence of CD and UC in diverse regions of Canada and the overall burden of IBD in Canada. METHODS: We applied a common case identification algorithm, previously validated in Manitoba to the provincial health databases in British Columbia (BC), Alberta (AB), Saskatchewan (SK), Manitoba (MB), and Nova Scotia (NS) to determine the age-adjusted incidence rates per 100,000 person-years for 1998-2000 and prevalence per 100,000 for mid 2000 and to estimate the IBD burden in Canada. Poisson regression was used to assess differences in incidence rates and prevalence by gender, age, and province. RESULTS: The incidence rate for CD ranged from 8.8 (BC) to 20.2 (NS), and for UC ranged from 9.9 (BC) to 19.5 (NS). The prevalence of CD was approximately 15- to 20-fold higher than the incidence rate, ranging from 161 (BC) to 319 (NS). This was similar for the prevalence of UC, which ranged from 162 (BC) to 249 (MB). Adjusting for age and province, the female:male ratio for incidence ratio was 1.31 (p < 0.0001) for CD and 1.02 (n.s.) for UC and was mostly stable across the five provinces. CONCLUSIONS: Approximately 0.5% of the Canadian population has IBD. Canada has the highest incidence and prevalence of CD yet reported.

Adolescent↗
PubMed2005

Diversity of the human intestinal microbial flora.

The human endogenous intestinal microflora is an essential "organ" in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.

Adult↗
PubMed2005

Defining the predictors of the placebo response in irritable bowel syndrome.

BACKGROUND AND AIMS: We sought to determine the components of irritable bowel syndrome (IBS) clinical trials that correlate with higher levels of placebo response. METHODS: We performed a systematic review of placebo-controlled trials in patients with IBS to assess which variables correlate with a higher placebo response. Placebo responses for global symptom improvement and for decreased abdominal pain were assessed. Univariate and multiple linear regression analyses were conducted. RESULTS: Higher rates of global improvement correlated with frequency of administration of study intervention ( r = .31, P = .03), duration of the study ( r = .28, P = .04), and overall treatment effect of the active agent being studied ( r = .33, P = .02). Higher rates of decreased abdominal pain correlated with the frequency of intervention ( r = .39, P = .02) and overall treatment effect ( r = .40, P = .01), whereas lower placebo response rates correlated with year of the study ( r = -.36, P = .03), median age ( r = -.38, P = .04), and duration of study run-in period ( r = -.33, P = .04). On multivariate analysis, global improvement in the placebo group was associated significantly with intervention frequency ( P = .0079), overall treatment response ( P = .0031), and parallel study design ( P = .0044). Decreased abdominal pain was associated significantly with frequency of intervention ( P = .0061) and overall treatment response ( P = .0128). CONCLUSIONS: In IBS studies, higher placebo response rates correlated with frequency of the intervention and with overall treatment effect of the active agent being studied. In designing IBS trials, it may be possible to minimize placebo response by less frequent dosing. In treating patients with IBS, it may be possible to harness the placebo response and maximize therapeutic response rates by more frequent dosing.

Clinical Trials as Topic↗
PubMed2005

Therapy insight: Osteoporosis in inflammatory bowel disease--advances and retreats.

There is a discrepancy between the high rates of reduced bone mineral density (BMD) reported in patients with inflammatory bowel disease (IBD) and the relatively low fracture rates observed in population-based studies. When fractures occur, they are most common among the elderly IBD population. It has become clear that BMD is but one of several important factors to be considered when assessing fracture risk. Ideally, BMD should be assessed selectively, as opposed to assessing this measure in all IBD patients simply because they carry an IBD diagnosis. Preventing bone loss should begin with an attempt to limit corticosteroid-induced bone loss. This can be done by using the minimum effective prednisolone dose, substituting budesonide when appropriate, administering other steroid-sparing immunomodulators, or by prescribing additional agents that enhance bone health. The administration of calcium and vitamin D appears to maintain or enhance bone mass. Bisphosphonates are of unclear additional benefit to the majority of patients who are at low fracture risk. Although more data are required to understand the best strategy to prevent fractures, a greater appreciation of the role of selective BMD testing and the utility of simple therapeutic strategies (such as calcium and vitamin D supplements) is emerging.

Bone Density↗
PubMed2005

The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study.

BACKGROUND & AIMS: We aimed to discern the relative risk for several chronic inflammatory conditions in patients with ulcerative colitis (UC) and Crohn's disease. METHODS: We used the population-based University of Manitoba IBD Database that includes longitudinal files on all patients from all health system contacts identified by International Classification of Diseases, 9th revision, Clinical Modification codes for visit diagnosis. From the provincial database we extracted a control cohort matching the IBD patients 10:1 by age, sex, and geography. We considered a potential comorbid disease to be present if the patient had 5 or more health system contacts for that diagnosis. The comorbid disease period prevalence was analyzed separately for patients with UC and Crohn's disease and a prevalence ratio was calculated comparing the IBD populations with the matched cohort. RESULTS: There were 8072 cases of IBD from 1984 to 2003, including UC (n = 3879) and Crohn's disease (n = 4193). There was a mean of approximately 16 person-years of coverage for both patients and control patients. Both UC and Crohn's disease patients had a significantly greater likelihood of having arthritis, asthma, bronchitis, psoriasis, and pericarditis than population controls. An increased risk for chronic renal disease and multiple sclerosis was noted in UC but not Crohn's disease patients. The most common nonintestinal comorbidities identified were arthritis and asthma. CONCLUSIONS: The finding of asthma as the most common comorbidity increased in Crohn's disease patients compared with the general population is novel. These may be diseases with common causes or complications of one disease that lead to the presentation with another. Studies such as this should encourage further research into the common triggers in the organ systems that lead to autoimmune diseases.

Asthma↗
PubMed2005

A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease.

BACKGROUND & AIMS: To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab' fragment of anti-tumor necrosis factor, CDP870) in Crohn's disease. METHODS: In a placebo-controlled, phase II study, 292 patients with moderate to severe Crohn's disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn's Disease Activity Index decrease of > or = 100 points or remission [Crohn's Disease Activity Index < or = 150 points]) in the intent-to-treat population. RESULTS: All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1%; certolizumab 100 mg, 29.7% [P = .033]; 200 mg, 30.6% [P = .026]; 400 mg, 33.3% [P = .010]). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8%; placebo, 30.1%; P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4%; placebo, 35.6%; P = .278). Patients with baseline C-reactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical response: certolizumab 400 mg, 53.1%; placebo, 17.9%; P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups. CONCLUSIONS: Certolizumab 400 mg may be effective and is well tolerated in patients with active Crohn's disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.

Adult↗
PubMed2005

Serum osteoprotegerin is increased in Crohn's disease: a population-based case control study.

BACKGROUND: There is a potential interface between osteoporosis and the chronic inflammation of inflammatory bowel disease (IBD), and the osteoprotegerin (OPG)/receptor for activated nuclear factor-kappaB (RANK)/RANK ligand (RANKL) signaling pathway may be an important mediator, although data are limited. METHODS: We conducted a population-based case-control seroassay study to look for alterations in serum OPG and soluble RANKL (sRANKL). The study population included IBD patients who were 18 to 50 years old with Crohn's disease (CD; n = 287) or ulcerative colitis (UC; n = 166), age-matched healthy controls (n = 368), and nonaffected siblings of IBD patients (n = 146). Serum OPG and sRANKL were measured by enzyme-linked immunoassay. Sex-specific reference ranges were derived from the healthy controls. RESULTS: Analysis of variance (ANOVA) confirmed significant group differences in women for mean serum OPG (P = 0.018). CD women had higher values of OPG than UC women (P = 0.028) or healthy controls (P = 0.045), whereas the other groups were similar. OPG levels were above the reference range in 13/173 (8%) of CD women, exceeding the expected proportion (P = 0.032). In contrast, no differences in OPG were seen in men between controls, CD, or UC. Estrogen use in women (P = 0.000002) and corticosteroid use in men (P = 0.026) were associated with higher OPG levels. In multivariate analysis, CD diagnosis (P = 0.031) and estrogen use (P = 0.000002) were independently associated with higher OPG levels. No group differences were seen in mean serum sRANKL measurements. CONCLUSIONS: An OPG:sRANKL imbalance with OPG exceeding sRANKL should inhibit osteoclastogenesis and promote bone formation. CD is associated with increased fracture risk, and possibly, the paradoxically higher OPG is a counterregulatory response to factors such as inflammatory cytokines, promoting high bone turnover. Alternatively, elevated OPG in CD may reflect T-cell activation.

Adult↗
PubMed2005

A prospective comparison study of MRI versus small bowel follow-through in recurrent Crohn's disease.

BACKGROUND: We aimed to determine the utility of magnetic resonance imaging (MRI) compared with small bowel follow-through (SBFT) in the assessment of known Crohn's disease. METHODS: Subjects, over age 18 yr who were to undergo SBFT investigations to assess for complications or extent of Crohn's disease were eligible. SBFT was performed by a single radiologist (IB), and within 4 wk MRI was performed by a single radiologist (HG) who was blinded to the SBFT results. For MRI, oral contrast was 2% barium sulfate (1,350 mL). After unenhanced T1 weighted images and single shot fast spin echo T2 imaging, intravenous (IV) glucagon and gadolinium were given. Fast multiplanar spoiled-gradient recalled T1 coronal sequences were obtained followed by abdominal and pelvic axial images. MRI and SBFT were compared for extent of disease, presence of complications, and for identification of extraintestinal disease. RESULTS: Paired studies were undertaken within a mean of 22 days in 30 subjects. Ten studies were normal by both modalities and 8 studies showed similar extent of Crohn's disease. SBFT revealed additional information in 4, including a stricture in 1 and ileosigmoid fistulas in 2. MRI provided enhanced information in 8, including identifying active inflammation in strictured areas based on wall enhancement patterns, vasa recta changes, and lymphadenopathy. CONCLUSIONS: On the basis of cost and accessibility, SBFT may still be a first line procedure of choice in some centers without MRI, but MRI's advantages of no radiation and the potential to identify active inflammation in strictured areas, extraintestinal, and colorectal disease make it an attractive alternative.

Barium Sulfate↗
PubMed2005

The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease.

BACKGROUND AND AIMS: Emerging data indicate that alterations in cytokine synthesis may play a role in inflammatory bowel disease (IBD) pathogenesis. The differential production of cytokines has been linked to single nucleotide polymorphisms in gene promoter regions, signal sequences, and gene introns. The aim of this study was to assess the relationship between polymorphisms involving five cytokine genes (TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma), and IBD susceptibility and disease phenotype. METHODS: Cytokine genotyping was performed utilizing polymerase chain reaction. The specific gene polymorphisms that were probed for included: -1082(G/A), -819(T/C), and -592(A/C) in the IL-10 promoter, -308(G/A) in the TNF-alpha promoter, codon 10 (T/C), and codon 25 (G/C) of the TGF-beta signal sequence, +874(T/A) of intron 1 of IFN-gamma, and -174(C/G) in the IL-6 promoter. RESULTS: A total of 193 IBD patients (138 Crohn's disease (CD) and 55 ulcerative colitis (UC)) and 92 controls were evaluated. No association between IBD, UC, or CD susceptibility and the cytokine gene polymorphisms were found. Patients with ileocolonic CD were more likely to possess the IL-6 -174 GG genotype compared to those with nonileocolonic disease (p= 0.006). Patients with ileal CD were more likely to possess the IL-6 -174 GC genotype compared to those with nonileal disease (p= 0.0004). An increased number of CD patients with isolated colonic disease possessed the IL-6 -174 CC genotype compared to those with nonisolated colonic disease (p= 0.032). CONCLUSION: The cytokine gene polymorphisms studied here do not appear to influence IBD susceptibility. There does, however, appear to be an influence on disease phenotype, particularly on CD site.

Adult↗
PubMed2005

The anti-Saccharomyces cerevisiae antibody assay in a province-wide practice: accurate in identifying cases of Crohn's disease and predicting inflammatory disease.

OBJECTIVE: To determine the utility of the anti-Saccharomyces cerevisiae antibody (ASCA) ELISA test developed in Manitoba in 2001 in a population-wide sample referred from physicians across Manitoba in their investigation of patients with gastrointestinal symptoms. METHODS: Patients whose serum was referred for ASCA testing in 2001 and 2002 were eligible for the present study. ELISA was performed by a technologist, blind to patient diagnoses. A single investigator contacted physicians to facilitate chart review. Data collected included demographics, final diagnoses and tests used to substantiate the final diagnosis. RESULTS: Of 482 subjects identified, 410 charts were available for review and 29 of those were unavailable for follow-up or had incomplete charts. The present study population included Crohn's disease (CD, n=114), ulcerative colitis (n=74), indeterminate colitis (n=31), celiac disease (n=9), irritable bowel syndrome (n=75), other diagnoses (n=33) and no disease (n=45). ASCA had a sensitivity of 37% (95% CI 27.8 to 46.8) and specificity of 97% (95% CI 93.8 to 98.6) for diagnosing CD and an odds ratio for a diagnosis of CD of 18.4 (95% CI 8.2 to 41.3). The 47 ASCA-positive patients included the following diagnoses: CD=39, ulcerative colitis=3, indeterminate colitis=1, celiac disease=3 and no disease=1. The likelihood of having an inflammatory disease if ASCA is positive was nearly 40-fold. CONCLUSION: A positive ASCA test using this assay nearly clinches a diagnosis of some form of inflammatory intestinal disease, which is highly likely to be CD. In symptomatic patients, a positive ASCA test should encourage the clinician to pursue further investigations.

Adolescent↗
PubMed2005

Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology.

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Biomarkers↗
PubMed2004

Infliximab maintenance therapy for fistulizing Crohn's disease.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Adult↗