Prevalence and Outcomes of No Treatment Versus 5-ASA in Ulcerative Colitis: A Nationwide Analysis From the epi-IIRN.

BACKGROUND: Data regarding patients with ulcerative colitis (UC) not receiving maintenance treatment are scarce. In this nationwide study, we aimed to explore the frequency and long-term outcomes of untreated patients with UC vs treated patients. METHODS: We retrieved data from Israel's Health Maintenance Organizations, covering 98% of the population. No maintenance treatment (NMT) was defined as lack of treatment during the period from 3 to 6 months from diagnosis, allowing at most 3 months for induction treatment. RESULTS: A total of 15 111 patients have been diagnosed with UC since 2005, of whom 4410 (29%) have had NMT, with 36 794 person-years of follow-up. NMT was more likely in adults (31%) and in elderly-onset UC (29%) than in pediatric-onset UC (20%; P < .001) and decreased from 38% in 2005 to 18% in 2019 (P < .001). The probability of remaining without treatment was 78%, 49%, and 37% after 1, 3, and 5 years from diagnosis, respectively. In propensity score-matched analysis of 1080 pairs of treated (93% with 5-aminosalicylic acid) and untreated patients, outcomes were comparable for time to biologics (P = .6), surgery (P = .8), steroid dependency (P = .09), and hospitalizations (P = .2). Multivariable modeling indicated that failing NMT was less likely in adults or elderly-onset patients who received at most rectal therapy or antibiotics as induction therapy. CONCLUSIONS: Nowadays, 18% of patients with UC do not receive maintenance therapy, of whom half remain without treatment after 3 years. Matched pairs of patients on NMT and 5-aminosalicylic acid, representing the mildest patients of the latter, had similar outcomes. Prospective studies are needed to further explore the role of NMT in UC.

The rate of no maintenance treatment (NMT) decreased in the last years, but in a propensity score­matched analysis, 5-aminosalicylic acid monotherapy did not demonstrate any therapeutic advantage over NMT. NMT seems to be a viable option in a subset of patients with mild ulcerative colitis.

Randomised clinical trial: Psychological intervention improves work productivity and daily activity by reducing abdominal pain and fatigue in Crohn's disease.

BACKGROUND: Chronic abdominal pain and fatigue are characteristics of Crohn's disease (CD) and contribute to functional impairments. AIMS: To examine whether CD-tailored cognitive-behavioural and mindfulness intervention (COBMINDEX) is effective in reducing abdominal pain and fatigue in patients with CD and whether changes in abdominal pain and fatigue mediate any beneficial effects of COBMINDEX on impairments in work productivity and daily activities. METHODS: This is a secondary analysis of a parallel-group multicentre randomised controlled trial. Patients with mild-to-moderate CD (n = 142) were randomised into either intervention group receiving COBMINDEX, or control group receiving treatment-as-usual for 3 months followed by COBMINDEX. Complete data were collected from 120 patients (34.0 ± 10.7 years, 62.5% female, intervention = 60, control = 60). Analysis of covariance assessed group differences in 3-month follow-up scores, controlling for baseline scores. Multiple parallel mediation analysis assessed the proposed mechanisms for the entire sample. RESULTS: The intervention group demonstrated significantly lower levels of abdominal pain (F = 17.46, p < 0.001, η2 p  = 0.13), fatigue (F = 7.26, p = 0.008, η2 p  = 0.06) and impairments at work (F = 4.82, p = 0.032, η2 p  = 0.07) and daily activities (F = 6.26, p = 0.014, η2 p  = 0.05), compared with treatment-as-usual. Moreover, changes in abdominal pain and fatigue significantly mediated the beneficial effects of COBMINDEX on patients' work productivity (b = -9.90, SE = 2.86, 95% CI: -16.11 to -4.94) and daily activities (b = -9.65, SE = 1.91, 95% CI: -13.77 to 6.35), independent of changes in disease activity. CONCLUSIONS: COBMINDEX is effective at reducing abdominal pain and fatigue in patients with CD, which in turn leads to improvement in functioning. Clinicians should incorporate screening for severe abdominal pain and fatigue and consider offering cognitive-behavioural and mindfulness training. CLINICALTRIALS: gov, Number: NCT05085925. Ministry of Health in Israel (https://my.health.gov.il/CliniTrials/Pages/MOH_2020-02-24_008721.aspx).

Inflammatory bowel disease among first generation immigrants in Israel: A nationwide epi-Israeli Inflammatory Bowel Disease Research Nucleus study.

BACKGROUND: Israel has a high rate of Jewish immigration and a high prevalence of inflammatory bowel disease (IBD). AIM: To compare IBD prevalence in first-generation immigrants vs Israel-born Jews. METHODS: Patients with a diagnosis of IBD as of June 2020 were included from the validated epi-IIRN (Israeli IBD Research Nucleus) cohort that includes 98% of the Israeli population. We stratified the immigration cohort by IBD risk according to country of origin, time period of immigration, and age group as of June 2020. RESULTS: A total of 33544 patients were ascertained, of whom 18524 (55%) had Crohn's disease (CD) and 15020 (45%) had ulcerative colitis (UC); 28394 (85%) were Israel-born and 5150 (15%) were immigrants. UC was more prevalent in immigrants (2717; 53%) than in non-immigrants (12303, 43%, P < 0.001), especially in the < 1990 immigration period. After adjusting for age, longer duration in Israel was associated with a higher point prevalence rate in June 2020 (high-risk origin: Immigration < 1990: 645.9/100000, ≥ 1990: 613.2/100000, P = 0.043; intermediate/low-risk origin: < 1990: 540.5/100000, ≥ 1990: 192.0/100000, P < 0.001). The prevalence was higher in patients immigrating from countries with high risk for IBD (561.4/100000) than those originating from intermediate-/low-risk countries (514.3/100000; P < 0.001); non-immigrant prevalence was 528.9/100000. CONCLUSION: Lending support to the environmental effect on IBD etiology, we found that among immigrants to Israel, the prevalence of IBD increased with longer time since immigration, and was related to the risk of IBD in the country of origin. The UC rate was higher than that of CD only in those immigrating in earlier time periods.

Brain-immune axis regulation is responsive to cognitive behavioral therapy and mindfulness intervention: Observations from a randomized controlled trial in patients with Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the hypothalamus-pituitary-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) impacts their inflammatory process. METHODS: Circulating inflammatory markers and a wide range of psychological parameters related to stress and well-being were measured in CD patients before and after COBMINDEX. Inflammatory markers in CD patients were also compared to age- and sex-matched healthy controls (HCs). RESULTS: CD patients exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by interconnected inflammatory modules represented by IL-6, TNFα, IL-17, MCP-1 and IL-18. Notably, higher IL-18 levels correlated with higher score of stress and a lower score of wellbeing in CD patients. COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 and IFNα and negatively with those of MCP-1. Furthermore, inflammatory markers of CD patients at baseline predicted COBMINDEX efficacy, as higher levels of distinct cytokines and cortisol at baseline, correlated negatively with changes in disease activity (by Harvey-Bradshaw Index) and psychological distress (global severity index measure) following COBMINDEX. CONCLUSION: CD patients have a characteristic immunological profile that correlates with psychological stress, and disease severity. We suggest that COBMINDEX induces stress resilience in CD patients, which impacts their well-being, and their disease-associated inflammatory process.

Randomized Controlled Trial of Cognitive-Behavioral and Mindfulness-Based Stress Reduction on the Quality of Life of Patients With Crohn Disease.

BACKGROUND: Patients with Crohn disease have debilitating psychological symptoms, mental fatigue, and poor quality of life. Psychological intervention may improve these symptoms. METHODS: We performed a randomized parallel-group physician-blinded trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) on quality of life and psychological symptoms in adults with mild-moderate Crohn disease. COBMINDEX was taught by social workers in one-on-one video conferences over 3 months; quotidian home practice was mandated. RESULTS: Fifty-five COBMINDEX and 61 waitlist control patients completed the study; mean age was 33 years and 65% of participants were women. At 3 months, COBMINDEX patients had significantly reduced disease activity (per Harvey-Bradshaw Index score, C-reactive protein level, and calprotectin level), increased quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] score increased from baseline 41 to 50; P < 0.001), decreased psychological symptoms (Global Severity Index [GSI], 0.98-0.70; P < 0.001), reduced fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue, 26-33; P < 0.001), and increased mindfulness disposition (Freiburg Mindfulness Inventory, 33-38; P < 0.001). Waitlist patients had a significant but small change in Harvey-Bradshaw Index, SIBDQ, and GSI scores, without improvement in fatigue or mindfulness. There were significant correlations (0.02 > P < 0.002) in COBMINDEX patients between baseline SIBDQ, GSI, Freiburg Mindfulness Inventory, and Functional Assessment of Chronic Illness Therapy-Fatigue scores with a relative change (baseline to 3 months) of the SIBDQ score, but none among waitlist patients. Predictors of relative change of the SIBDQ score in COBMINDEX patients included the GSI score (90% quantile; coefficient 0.52; P < 0.001), somatization (90%; 0.20; P = 0.001), depression (75%; 0.16; P = 0.03), and phobic anxiety (75%; 0.31; P = 0.008). CONCLUSIONS: COBMINDEX was effective in increasing patients' quality of life and reducing psychological symptoms and fatigue. Patients with severe baseline psychological symptoms benefited the most from COBMINDEX.

Normative data for the Brief Symptom Inventory for patients with Crohn's disease.

OBJECTIVE: The Brief Symptom Inventory (BSI) is a self-report measure of psychological symptoms in clinical and non-clinical populations. However, norms for BSI are lacking for patients with chronic illness, such as Crohn's disease (CD). This study aimed to provide BSI clinical norms using a cohort of CD patients. DESIGN: Adult Israeli CD patients (n = 430) completed questionnaires regarding clinical, demographic and psychological aspects of disease, including BSI. Their BSI data were compared with published norms from adult Israeli population and British psychiatric outpatients. RESULTS: CD patients in active disease state had higher levels of mental health symptoms than those in remission. Interestingly, levels of symptomatology did not differ with respect to disease duration. No significant sex differences in BSI dimensions were found, with the exception of somatization. Being younger than 60 years and having lower economic status were associated with more severe psychological symptoms. Psychological symptom levels in CD patients were high in comparison to the Israeli general population, but low compared to British psychiatric outpatients. CONCLUSION: Results confirm the link between CD and elevated psychological symptoms. The findings highlight the need to use appropriate BSI norms when assessing clinically significant levels of psychological symptoms in non-psychiatric patients with chronic illness.

Epidemiology of Inflammatory Bowel Diseases in Israel: A Nationwide Epi-Israeli IBD Research Nucleus Study.

BACKGROUND: There are currently no nationwide data on the epidemiology of inflammatory bowel diseases (IBD) in Israel. We aimed to determine the population-based epidemiological trends of IBD in the diverse Israeli population. METHODS: Health-administrative data were retrieved from all 4 Israeli health maintenance organizations, insuring 98% of the population, using validated identification algorithms. National trends were determined using Joinpoint regression analysis calculating annual percent change and average annual percent change (AAPC). RESULTS: By 2019, there were 46,074 patients with IBD in Israel, corresponding to a national prevalence of 519/100,000 (0.52%), of whom 54.1% had Crohn disease (CD) and 45.9% had ulcerative colitis (UC). The number of Jewish patients doubled from 18,701 in 2005 (354/100,000) to 38,950 (589/100,000) in 2018 (AAPC, +4.0%; P < 0.05), and the number of Arab patients increased 3-fold from 1096 (102.1/100,000) to 3534 (240.7/100,000; AAPC, +6.8%; P < 0.05) during the same years. However, the increase rate has gradually decelerated over time (annual percent change during 2005-2008, 2009-2014, and 2005-2018 was +6.7%, +4.2%, and +2.3%, respectively; P < 0.05). Pediatric prevalence increased from 37.4 to 52.2/100,000, with CD predominating in both Jews and Arabs. The incidence of CD remained stable (from 15.9/100,000 to 14.9/100,000) and the incidence of UC decreased (15.4/100,000 to 10.5/100,000 (AAPC, -3.2%; P < 0.001)). In contrast, pediatric incidence of CD increased from 7.3/100,000 to 8.3/100,000 (AAPC, +1.9%; P < 0.05) and that of UC increased from 2.6 to 4.4/100,000 (AAPC, +5.8%; P < 0.05). CONCLUSIONS: The IBD prevalence rate in Israel is still increasing but gradually decelerating, probably due to the decreasing overall IBD incidence. Nonetheless, incidence rate in children is still increasing. Ongoing narrowing in the rates between Jews and Arabs over time may indicate shared environmental factors.

Differential relationships of somatization, depression, and anxiety to severity of Crohn's disease.

Patients with Crohn's disease, an inflammatory bowel disease, struggle with chronic somatic symptoms that could bring about emotional distress. This study assessed the relative role of somatization, and depressive and anxiety symptoms in disease activity among 619 Crohn's patients (18-79 years; 58.3% women). Structural equation modeling revealed that somatization was the only unique predictor of disease activity beyond depression and anxiety. In addition, the effect of somatization on disease activity was stronger in men compared to women. Findings suggest that somatization represents a distinct domain of psychological distress that may play a role in the health of patients with Crohn's disease.

Assessment of small bowel mucosal healing by video capsule endoscopy for the prediction of short-term and long-term risk of Crohn's disease flare: a prospective cohort study.

BACKGROUND: The optimal monitoring strategy for predicting disease course in Crohn's disease remains undefined. We aimed to evaluate the accuracy, safety, and tolerability of an intensive monitoring strategy designed to predict the future course of Crohn's disease in patients with quiescent disease. METHODS: In a prospective observational cohort study, we recruited patients older than 18 years with quiescent (for 3-24 months) Crohn's disease involving the small bowel with confirmed small bowel patency from three tertiary medical centres in Israel. Enrolled patients underwent baseline magnetic resonance enterography (MRE) and patency capsule, clinical or biomarker assessment every 3 months, and video capsule endoscopy (VCE) at baseline and every 6 months for 2 years or until a clinical flare (the primary outcome, defined as an increase in the Crohn's disease activity index score by 70 points or more) or disease worsening necessitating treatment intensification. We assessed the ability of the different Crohn's disease monitoring methods used to predict the occurrence of a flare during the 24-month follow-up period. FINDINGS: Of 90 screened patients, 29 were excluded (17 because of non-patent small bowel). Of the 61 patients enrolled between July 3, 2013, and Feb 1, 2015, 17 (28%) had a flare during the 24-month follow-up. No clinicodemographic parameter predicted future flare. A baseline VCE Lewis score of 350 or more identified patients with future flare (area under the curve [AUC] 0·79, 95% CI 0·66-0·88; p<0·0001; hazard ratio 10·7, 3·8-30·3). C-reactive protein at baseline had an AUC of 0·73 (0·6-0·84; p=0·0013) for predicting flare. The AUC of baseline faecal calprotectin for the prediction of flare occurring within 2 years was 0·62 (0·49-0·74; p=0·17), but progressively improved for shorter timespans and reached an AUC of 0·81 (0·76-0·85) for the prediction of flare occurring within 3 months. Of four MRE-based indices, only MRE global score correlated with 2-year flare risk (AUC 0·71, 0·58-0·82; p=0·024). During follow-up, a Lewis score increase of 383 points or more from baseline predicted imminent disease exacerbation within 6 months (AUC 0·79, 0·65-0·89; p=0·011). The safety and tolerability of the 231 VCEs ingested was excellent, with none being retained. INTERPRETATION: In patients with quiescent Crohn's disease involving the small bowel, faecal calprotectin predicts short-term flare risk, whereas VCE predicts both short-term and long-term risk of disease exacerbation. If corroborated by additional studies, protocols incorporating VCE could expand the scope of available methods for monitoring disease activity and predicting outcomes in small bowel Crohn's disease. FUNDING: The Leona M & Harry B Helmsley Charitable Trust.

Effect of Social Support on Psychological Distress and Disease Activity in Inflammatory Bowel Disease Patients.

Background: Psychological distress increases morbidity in ulcerative colitis (UC) and Crohn's disease (CD). We examined whether social support is associated with distress and disease activity. Methods: There were 110 UC and 147 CD patients who completed sociodemography, economic status, disease activity (UC: Patient Simple Clinical Colitis Activity Index (P-SCCAI), CD: Patient Harvey-Bradshaw Index . (P-HBI), Multidimensional Scale of Perceived Social Support (MSPSS), Brief Symptom Inventory with Global Severity Index (GSI) of psychological distress, and 2 health-related quality-of-life scales (SF-36 Physical Health and Mental Health, and Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Analysis included multiple linear regressions and structural equation modeling. Results: Disease activity was mild: UC: P-SCCAI 2.9 ± 3.5, CD: P-HBI 4.7 ± 4.7. Physical Health was better in UC 46.6 ± 11.4 versus CD 43.7 ± 10.9 (P < .02). GSI was lower in UC 0.6 ± 0.7 than CD 0.8 ± 0.7 (P = .002). MSPSS total score was equal in UC (5.9 ± 1.2) and CD (5.9 ± 1.1). MSPSS total correlated with P-SCCAI (correlation coefficient ‒0.240), GSI in UC (‒0.470), and GSI in CD (‒0.333). Economic status correlated with GSI in UC (‒0.408) and CD (‒0.356). MSPSS predicted GSI, Mental Health, and SIBDQ in UC and CD, and predicted P-SCCAI but not P-HBI; economic status predicted all the foregoing. Path analysis depicted GSI as mediating the effects of MSPSS and economic status on disease activity in both UC and CD. MSPSS (UC: ß â€’0.34, CD: ß â€’0.37) and economic status (UC: ß â€’0.38, CD: ß â€’0.22) reduced GSI, which then increased the disease activity (UC: ß 0.56, CD: ß 0.42). Conclusions: Social support and economic status are linked to UC and CD patients' well-being. Interventions addressing these issues should be part of management.

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.

Differing Relationship of Psycho-Social Variables with Active Ulcerative Colitis or Crohn's Disease.

PURPOSE: How psycho-social variables affect the degree of disease activity in patients with ulcerative colitis (UC) or Crohn's disease (CD) is incompletely understood. Therefore, we measured and compared the impact of psycho-social variables on the active disease state in UC and CD. METHOD: One hundred and twenty-two UC and 305 CD patients with active disease completed questionnaires detailing their psychological symptoms, threatening experiences, disease-coping strategies, satisfaction with life, quality of life, and demographics. RESULTS: UC and CD patients were aged (mean, SD) 38.6 ± 14.0 and 45.2 ± 15.1 years, respectively. The psychological symptom index (median, IQR) was greater in UC 1.24 (0.8) than CD 0.9 (0.8), p < 0.001. UC used more emotion-focused strategies, 24.5 (5.7) than CD, 23.0 (5.7), p < 0.03; problem-focused strategies, 16.4 (4.5) vs. 15.4 (4.2), p < 0.04; and dysfunctional strategies, 23.7 (5.7) vs. 22.0 (5.0), p < 0.01. UC activity correlated with gender, age, economic status, psychological symptoms, threatening experiences, all coping strategies, satisfaction with life, and quality of life (p < 0.02-0.001). CD activity correlated with economic status, psychological symptoms, threatening experiences, dysfunctional strategies, satisfaction with life, and quality of life (p < 0.05-0.001). UC activity was predicted by psychological symptoms (9.1% variance), economic status (6.9%), problem-focused strategies (4.2%), and threatening experiences (1.3%); CD activity by threatening experiences (5% variance) and psychological symptoms (4%). In path analysis, psychological symptoms and problem-focused strategies mediated the effects of economic status, age, and threatening experiences on UC activity. In CD, the dominant pathway was threatening experiences impacting on psychological symptoms. CONCLUSION: The impact of psycho-social variables on the active disease state differs between UC and CD, thus indicating a need for specifically tailored psychotherapies.

Daily hassles score associates with the somatic and psychological health of patients with Crohn's disease.

OBJECTIVE: To examine the associations of daily hassles with the somatic and psychological health of Crohn's disease (CD) patients. METHOD: A cross-sectional study of 400 self-selected adult CD patients was performed with completion of demographic, medical, and psychosocial questionnaires: economic status; Patient Harvey-Bradshaw Index of disease activity; Daily Hassles Scale (DHS); Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and Short-Form Health Survey (SF-36 Physical and Mental Health) quality of life measures; Brief Symptom Inventory of psychological stress with summary Global Severity Index (GSI); Family Assessment Device; and List of Threatening Life Experiences. Analyses included correlations, regressions, and Sobel test statistic. RESULTS: The patients were aged 38.7 ± 14.1 years, 61% female and 67% working. The Patient Harvey-Bradshaw Index was 5.52 ± 4.87. The DHS was 88.0 ± 23.2, similar in men and women, higher in smokers, and increased with greater disease activity (p < .001). The most commonly reported hassles were time, social, and work. DHS had significant negative correlations with age, disease duration, and economic status and positive correlations with GSI, SF-36, and SIBDQ. An increased Daily Hassles score was associated with reduced SIBDQ (p < .001) and SF-36 Mental Health (p < .001) and increased GSI (p < .001) and Patient Harvey-Bradshaw Index (p < .001). This effect of DHS on Patient Harvey-Bradshaw Index was mediated by GSI (Sobel t = 6.09, p < 0.001). CONCLUSION: Daily hassles in CD patients are shown for the first time to be associated with increased psychological stress and disease activity and reduced quality of life and lower economic status. This has psychotherapeutic implications.

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.

Simple pain measures reveal psycho-social pathology in patients with Crohn's disease.

AIM: To determine whether pain has psycho-social associations in adult Crohn's disease (CD) patients. METHODS: Patients completed demographics, disease status, Patient Harvey-Bradshaw Index (P-HBI), Short Form Health Survey (SF-36), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and five socio-psychological questionnaires: Brief Symptom Inventory, Brief COPE Inventory, Family Assessment Device, Satisfaction with Life Scale, and Work Productivity and Activity Impairment Questionnaire. Pain sub-scales in P-HBI, SF-36 and SIBDQ measures were recoded into 4 identical scores for univariate and multinomial logistic regression analysis of associations with psycho-social variables. RESULTS: The cohort comprised 594 patients, mean age 38.6 ± 14.8 years, women 52.5%, P-HBI 5.76 ± 5.15. P-HBI, SF-36 and SIBDQ broadly agreed in their assessment of pain intensity. More severe pain was significantly associated with female gender, low socio-economic status, unemployment, Israeli birth and smoking. Higher pain scores correlated positively with psychological stress, dysfunctional coping strategies, poor family relationships, absenteeism, presenteeism, productivity loss and activity impairment and all WPAI sub-scores. Patients exhibiting greater satisfaction with life had less pain. The regression showed increasing odds ratios for psychological stress (lowest 2.26, highest 12.17) and female gender (highest 3.19) with increasing pain. Internet-recruited patients were sicker and differed from hardcopy questionnaire patients in their associations with pain. CONCLUSION: Pain measures in P-HBI, SF-36 and SIBDQ correlate with psycho-social pathology in CD. Physicians should be aware also of these relationships in approaching CD patients with pain.

Effect of psychosocial stressors on patients with Crohn's disease: threatening life experiences and family relations.

BACKGROUND AND AIMS: Threatening life experiences and adverse family relations are major psychosocial stressors affecting mental and physical health in chronic illnesses, but their influence in Crohn's disease (CD) is unclear. We assessed whether these stressors would predict the psychological and medical condition of CD patients. METHODS: Consecutive adult CD patients completed a series of instruments including demography, Patient Harvey-Bradshaw Index (P-HBI), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), short-form survey instrument (SF-36), brief symptom inventory (BSI), family assessment device (FAD), and list of threatening life experiences (LTE). Associations of FAD and LTE with P-HBI, SIBDQ, SF-36, and BSI were examined by multiple linear and quantile regression analyses. RESULTS: The cohort included 391 patients, mean age 38.38±13.95 years, 59.6% women, with intermediate economic status. The median scores were as follows: P-HBI 4 (2-8), FAD 1.67 (1.3-2.1), LTE 1 (0-3), SF-36 physical health 43.75 (33.7-51.0), SF-36 mental health 42.99 (34.1-51.9), and BSI-Global Severity Index 0.81 (0.4-1.4). The SIBDQ was 47.27±13.9. LTE was associated with increased P-HBI in all quantiles and FAD in the 50% quantile. FAD and LTE were associated with reduced SIBDQ (P<0.001). Higher LTE was associated with lower SF-36 physical and mental health (P<0.001); FAD was associated with reduced mental health (P<0.001). FAD and LTE were associated positively with GSI in all quantiles; age was associated negatively. CONCLUSION: CD patients with more threatening life experiences and adverse family relations were less healthy both physically and mentally. Physicians offering patients sociopsychological therapy should relate to threatening life experiences and family relations.

Health-Related Utility Weights in a Cohort of Real-World Crohn's Disease Patients.

BACKGROUND AND AIMS: Estimating health-related utility weights in Crohn's Disease [CD] patients is crucial for assessing the cost-effectiveness of new pharmaceutical interventions. Values used in most analyses are based on secondary data and vary substantially among studies. We estimated utility weights in a consecutive sample of real-world CD patients. METHODS: Patients enrolled in an ongoing socioeconomic study of CD in the Israeli adult patient population completed a self-administered Short Form 36 health survey [SF-36] and Short Inflammatory Bowel Disease [SIBDQ] questionnaires and were assessed for their current clinical status, including the Harvey-Bradshaw Index [HBI] of disease severity. For each patient enrolled we calculated a utility weight using the SF-6D scoring system. RESULTS: The cohort comprised 425 patients [40% male] with mean age of 39.1 [± 14.0] years. The average HBI was 6.1 [± 5.4]; 198 [47%] patients were in remission state [HBI < 5], 99 [23%] had mild disease [HBI 5-7], 102 [25%] moderate [HBI 8-16], and 26 [6%] severe disease [HBI > 16]. Mean utility weights were: 0.667 in all patients, 0.744 in patients with disease remission, 0.638 in mild disease, 0.587 in moderate disease, and 0.505 in severe disease. The significant predictors of utility weights in a multivariable regression analysis were the HBI [ß = -0.494; p < 0.001], economic status [ß = 0.198; p < 0.001], time since diagnosis [ß = 0.106; p < 0.001], male [compared with female] gender [ß = 0.099; p = 0.009], hospital admission in the past year for any cause [ß = -0.086; p = 0.027], and treatment with steroids [ß = -0.100; p = 0.012] where ß denotes the standardised regression coefficients; model adjusted R(2) = 0.428. CONCLUSIONS: Utility weights for patients in the remission and mild disease states were generally lower as compared with values used in published cost-effectiveness analyses. These values should be considered when assessing the value for money of future interventions for CD.

Inflammatory bowel disease: an emergent disease among Ethiopian Jews migrating to Israel.

BACKGROUND: The development and characteristics of inflammatory bowel disease (IBD) in Ethiopian Jewish immigrants to Israel were investigated. METHODS: A case-control study was conducted in 7 tertiary care hospitals in Israel. Patients of Ethiopian origin with IBD >6 months were included. Time of disease onset after immigration and age at diagnosis were recorded. Randomly chosen patients with IBD of Ashkenazi Jewish origin served as controls. Demographics and clinical parameters were compared between the 2 cohorts. RESULTS: Thirty-two Ethiopian patients with IBD were compared with 33 Ashkenazi Jewish patients with IBD. Crohn's disease (CD) was more prevalent than ulcerative colitis (UC) in the Ethiopian group compared with the Ashkenazi group (94% versus 73%, P = 0.02). No Ethiopian-origin patient had a positive family history of IBD compared with 42% of Ashkenazi-origin patients (P < 0.001). Arthritis was more common in Ashkenazi than in Ethiopian patients (27% versus 3%, P < 0.01). One Ashkenazi patient with CD had upper gastrointestinal involvement compared with 7 (23%) in the Ethiopian group (P < 0.02). All other clinical measures were similar between the 2 cohorts. The Ethiopian group lived in Israel with a mean of 13 ± 5 years, and 75% were born in Ethiopia. The shortest time between immigration and developing IBD was 8 years (range, 8-26; median 16 yrs). No Ethiopian patient was diagnosed before immigration. CONCLUSIONS: Ethiopian Jews migrating to Israel are at risk of developing IBD. Larger cohorts are needed to determine the relative importance of environmental and genetic factors that cause IBD in these patients.

A medicoeconomic review of early intervention with biologic agents in the treatment of inflammatory bowel diseases.

The treatment of inflammatory bowel disease with standard therapy fails to control the disease in many patients. Biologic therapy has an increasing role in altering the natural history of Crohn's disease and ulcerative colitis, and is improving patient prognosis. However, indications for treatment and issues with drug costs and value for money remain unclear. Also, when to perform early intervention with biologic agents is at present unclear. We performed an extensive literature search and review to address these issues. The biologics provide better care for many patients. The choice of biologic agent, the indications for its use, the switch between agents, and the considerations of cost are outlined, with a view to guiding the treating physician in managing these cases. Outstanding issues and anticipated future developments are defined.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel.

BACKGROUND: There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. METHODS: Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development. RESULTS: IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. CONCLUSIONS: Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems.