Shmuel Odes

Budesonide versus prednisone in the treatment of active Crohn's disease

BACKGROUND & AIMS Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohns disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon. METHODS Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded. RESULTS One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohns Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks. CONCLUSIONS BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions.

Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study

OBJECTIVE:The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study.METHODS:Patients with established IBD aged 18–70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject.RESULTS:A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohns disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS).The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85–1.99) versus clinic controls, and 0.96 (0.63–1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p < 0.005). The proportions of ex-smokers were higher in UC patients 29.7%versus 25.9%, and 19.5% in their respective controls (p < 0.001vs community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p < 0.05). Patients with UC were more likely to be light smokers(1–10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11–20 cigarettes/day) in comparison to their controls.CONCLUSIONS:The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.

Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease.

OBJECTIVE:Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohns disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls.METHODS:Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed.RESULTS:Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls.CONCLUSIONS:Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

The Month of Birth is Linked to the Risk of Crohn's Disease in the Israeli Population

OBJECTIVE:The main objective is to study whether the month of birth is associated with the development of Crohns disease (CD) in the Israeli Jewish population.BACKGROUND:It was suggested that perinatal exposure to infectious agents may have a role in the pathogenesis of CD. Due to the seasonal nature of some infections, a linkage between birth dates and a risk to develop CD would support such a hypothesis. Previous studies that addressed this question were conducted in Europe and differed in their findings.METHODS:Birth dates of 844 Jewish ulcerative colitis (UC) and CD patients from three medical centers representing the north, central, and the south of Israel were compared with the monthly rates of birth during the same period of time. The standard incidence ratio was used to define the risk to develop either disease according to the month of birth. The Score method was used for the evaluation of seasonality trends.RESULTS:Birth during the winter period in Israel was associated with increased risk to develop CD, whereas birth during the spring was associated with a reduced risk. The Score method for seasonality showed a significant peak during winter time in these patients (z = 2.02, P = 0.021). No such seasonal variation was noted for UC patients.CONCLUSIONS:A seasonal pattern was observed in the risk to develop CD but not UC. The findings may support the involvement of environmental factors in the pathogenesis of CD.

Effect of threatening life experiences and adverse family relations in ulcerative colitis: analysis using structural equation modeling and comparison with Crohn's disease.

Background and aims We published that threatening life experiences and adverse family relations impact Crohn’s disease (CD) adversely. In this study, we examine the influence of these stressors in ulcerative colitis (UC). Patients and methods Patients completed demography, economic status (ES), the Patient-Simple Clinical Colitis Activity Index (P-SCCAI), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Short-Form Health Survey (SF-36), the Brief Symptom Inventory (BSI), the Family Assessment Device (FAD), and the List of Threatening Life Experiences (LTE). Analysis included multiple linear and quantile regressions and structural equation modeling, comparing CD. Results UC patients (N=148, age 47.55±16.04 years, 50.6% women) had scores [median (interquartile range)] as follows: SCAAI, 2 (0.3–4.8); FAD, 1.8 (1.3–2.2); LTE, 1.0 (0–2.0); SF-36 Physical Health, 49.4 (36.8–55.1); SF-36 Mental Health, 45 (33.6–54.5); Brief Symptom Inventory-Global Severity Index (GSI), 0.5 (0.2–1.0). SIBDQ was 49.76±14.91. There were significant positive associations for LTE and SCAAI (25, 50, 75% quantiles), FAD and SF-36 Mental Health, FAD and LTE with GSI (50, 75, 90% quantiles), and ES with SF-36 and SIBDQ. The negative associations were as follows: LTE with SF-36 Physical/Mental Health, SIBDQ with FAD and LTE, ES with GSI (all quantiles), and P-SCCAI (75, 90% quantiles). In structural equation modeling analysis, LTE impacted ES negatively and ES impacted GSI negatively; LTE impacted GSI positively and GSI impacted P-SCCAI positively. In a split model, ES had a greater effect on GSI in UC than CD, whereas other path magnitudes were similar. Conclusion Threatening life experiences, adverse family relations, and poor ES make UC patients less healthy both physically and mentally. The impact of ES is worse in UC than CD.

Development and validation of novel algorithms to identify patients with inflammatory bowel diseases in Israel: an epi-IIRN group study

Background Before embarking on administrative research, validated case ascertainment algorithms must be developed. We aimed at developing algorithms for identifying inflammatory bowel disease (IBD) patients, date of disease onset, and IBD type (Crohn’s disease [CD] vs ulcerative colitis [UC]) in the databases of the four Israeli Health Maintenance Organizations (HMOs) covering 98% of the population. Methods Algorithms were developed on 5,131 IBD patients and 2,072 controls, following independent chart review (60% CD and 39% UC). We reviewed 942 different combinations of clinical parameters aided by mathematical modeling. The algorithms were validated on an independent cohort of 160,000 random subjects. Results The combination of the following variables achieved the highest diagnostic accuracy: IBD-related codes, alone if more than five to six codes or combined with purchases of IBD-related medications (at least three purchases or ≥3 months from the first to last purchase) (sensitivity 89%, specificity 99%, positive predictive value [PPV] 92%, negative predictive value [NPV] 99%). A look-back period of 2–5 years (depending on the HMO) without IBD-related codes or medications best determined the date of diagnosis (sensitivity 83%, specificity 68%, PPV 82%, NPV 70%). IBD type was determined by the majority of CD/UC codes of the three recent contacts or the most recent when less than three contacts were recorded (sensitivity 92%, specificity 97%, PPV 97%, NPV 92%). Applying these algorithms, a total of 38,291 IBD patients were residing in Israel, corresponding to a prevalence rate of 459/100,000 (0.46%). Conclusion The application of the validated algorithms to Israel’s administrative databases will now create a large and accurate ongoing population-based cohort of IBD patients for future administrative studies.

Corrigendum: methotrexate in chronic active Crohn's disease: a double-blind, randomized, israeli multicenter trial.

Corrigendum: Methotrexate in Chronic Active Crohns Disease: A Double-Blind, Randomized, Israeli Multicenter Trial

Passive smoking in patients with inflammatory bowel disease — an Israeli multicenter case control study

Background The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. Aim To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. Methods Patients with established IBD, aged 18‐70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. Results Five hundred and thirty‐four patients (273 ulcerative colitis (UC) and 261 Crohns disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty‐one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 ± 8.40 vs 9.36 ± 9.46, n = 229, P < 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used ‘never‐smoked’ CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 ± 7.60 vs 8.04 ± 8.72, P < 0.05). Conclusion There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls. Eur J Gastroenterol Hepatol 12:975‐979