[Second Austrian consensus on the safe use of anti-TNFα-antibodies in patients with inflammatory bowel diseases]. / Zweiter österreichischer Konsensus zur sicheren Anwendung von anti-TNF-α-Antikörpern bei chronisch-entzündlichen Darmerkrankungen.

Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i. e., Clostridium difficile, Tuberculosis, food hygiene), Pneumocystis jiroveci, viral infections (i. e., Hepatitis B, Hepatitis C, HIV, CMV, VZV), vaccination in general and recommendation for vaccines, gastrointestinal aspects (i. e., perianal fistula, abdominal fistula, intestinal strictures, stenosis and bowel obstruction), dermatologic aspects (skin malignancies, eczema-like drug-related skin eruption), infusion reactions and immunogenicity, demyelinating diseases, hepatotoxicity, haematotoxicity, congestive heart failure, risk and history of malignancies, and pregnancy and breast feeding. For practical reasons, the relevant aspects are summarized in a checklist which is divided into two parts: issues to be addressed before therapy and issues to be addressed during therapy.

Depression as an independent risk factor for mortality in critically ill patients.

OBJECTIVE: Mortality on medical intensive care units (ICU) is approximately 25%. It is associated with age, severity of illness, and comorbidities. Preexisting depression is a risk factor for worse outcome in many diseases. The impact of depression on outcome of ICU patients has not been investigated. We assessed a possible association between mortality and preexisting depressive mood at the time of ICU admission. The primary end point was 28-day mortality. METHODS: This single-center cohort study was conducted in a tertiary medical ICU. Two hundred patients were evaluated for preexisting depressive mood at ICU admission, determined by Hospital Anxiety and Depression Scale (HADS) score ≥8 in the depression dimension in patients with appropriate cognitive function. Patients with insufficient cognitive function were assessed using observer rating by next of kin by Hammond scale (cutoff ≥4) and/or a modified version of the Hospital Anxiety and Depression Scale for observer rating (cutoff ≥10). RESULTS: In total, 66 (33%) of 200 patients were classified with preexisting depressive mood. Forty-nine (24.5%) of 200 patients had died by day 28. Of these, 23 (47%) had preexisting depressive mood as compared with 43 of 151 (29%) 28-day survivors (p = .017). Multiple logistic regression analysis revealed that preexisting depressive mood at the time of ICU admission is an independent risk factor for 28-day (odds ratio = 2.2, 95% confidence interval = 1.08-4.5, p = .030) and in-hospital mortality (median time till death = 20.5 [2-186] days, odds ratio = 2.58, 95% confidence interval = 1.31-5.1, p = .006). CONCLUSION: Preexisting depressive mood might be an independent risk factor for 28-day mortality in medical ICU patients. This could have diagnostic and therapeutic implications for critically ill patients.

Prediction of Response to Systemic Corticosteroids in Active UC by Microbial Composition-A Prospective Multicenter Study.

BACKGROUND: Corticosteroids are used for induction of remission in patients with moderately to severely active ulcerative colitis. However, up to one-third of patients fail to this therapy. We investigated if fecal microbial composition or its metabolic capacity are associated with response to systemic corticosteroids. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥4) receiving systemic corticosteroids were eligible. Data were assessed and fecal samples collected before and after 4 weeks of treatment. Patients were divided into responders (decrease of Lichtiger Score ≥50%) and nonresponders. The fecal microbiome was assessed by the 16S rRNA gene marker and analyzed with QIIME 2. Microbial metabolic pathways were predicted using parsimonious flux balance analysis. RESULTS: Among 93 included patients, 69 (74%) patients responded to corticosteroids after 4 weeks. At baseline, responders could not be distinguished from nonresponders by microbial diversity and composition, except for a subgroup of biologic-naïve patients. Within 4 weeks of treatment, responders experienced changes in beta diversity with enrichment of ascribed beneficial taxa, including Blautia, Anaerostipes, and Bifidobacterium, as well as an increase in predicted butyrate synthesis. Nonresponders had only minor longitudinal taxonomic changes with a significant increase of Streptococcus salivarius and a microbial composition shifting away from responders. CONCLUSION: Baseline microbial diversity and composition seem to be of limited use to predict response to systemic corticosteroids in active ulcerative colitis. Response is longitudinally associated with restoration of microbial composition and its metabolic capacity.

Long-term success of GUT-directed group hypnosis for patients with refractory irritable bowel syndrome: a randomized controlled trial.

OBJECTIVES: Gut-directed hypnotherapy (GHT) in individual sessions is highly effective in the treatment of irritable bowel syndrome (IBS). This study aimed to assess the long-term effect of GHT in group sessions for refractory IBS. METHODS: A total of 164 patients with IBS (Rome-III-criteria) were screened, and 100 refractory to usual treatment were randomized 1:1 either to supportive talks with medical treatment (SMT) or to SMT with GHT (10 weekly sessions within 12 weeks). The primary end point was a clinically important improvement on several dimensions of daily life (assessed by IBS impact scale) after treatment and 12-month follow-up. The secondary end point was improvement in general quality of life (QOL; Medical Outcome Study Short-Form-36), psychological status (Hospital Anxiety Depression Scale) and reduction of single IBS symptoms. Analysis was by intention to treat. RESULTS: A total of 90 patients received allocated intervention. After treatment, 28 (60.8%) out of 46 GHT patients and 18 (40.9%) out of 44 SMTs improved (absolute difference 20.0%; 95% confidence interval (CI): 0-40.2%; P=0.046); over 15 months, 54.3% of GHT patients and 25.0% of controls improved (absolute difference 29.4%; 95% CI 10.1-48.6%; P=0.004). GHT with SMT improved physical and psychological well being significantly more than SMT alone (P<0.001). Gender, age, disease duration and IBS type did not have an influence on the long-term success of GHT. CONCLUSIONS: GHT improves IBS-related QOL, is superior to SMT alone, and shows a long-term effect even in refractory IBS.

Factors Associated with Response to Systemic Corticosteroids in Active Ulcerative Colitis: Results from a Prospective, Multicenter Trial.

BACKGROUND: Among patients with ulcerative colitis, 30-50% receive corticosteroids within the first five years after diagnosis. We aimed to reconsider their effectiveness in the context of the biologic era. METHODS: In this prospective, multicenter study, patients with active ulcerative colitis (Lichtiger score ≥ 4) were eligible if initiating systemic corticosteroids. The primary endpoint was clinical response (decrease in the Lichtiger score of ≥50%) at week 4. Secondary endpoints included combined response defined as clinical response and any reduction in elevated biomarkers (CRP and/or calprotectin). Steroid dependence was assessed after three months. RESULTS: A total of 103 patients were included. Clinical response was achieved by 73% of patients, and combined response by 68%. A total of 15% of patients were steroid-dependent. Activity of colitis did not influence short-term response to treatment but increased the risk for steroid dependence. Biologic-naïve patients responded better than biologic-experienced patients. Past smoking history (OR 5.38 [1.71, 20.1], p = 0.003), hemoglobin levels (OR 0.76 [0.57, 0.99] for higher levels, p = 0.045), and biologic experience (OR 3.30 [1.08, 10.6], p = 0.036) were independently associated with nonresponse. CONCLUSION: Disease activity was not associated with short-term response to systemic corticosteroids but was associated with steroid dependence in patients with active ulcerative colitis. Exposure to biologics negatively affects response rates.

Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk of a first venous thromboembolism (VTE), yet their risk of recurrent VTE is unknown. We performed a cohort study to determine the risk for recurrent VTE among patients with IBD compared with subjects without IBD. METHODS: We assessed 2811 patients with IBD for a history of VTE, recruited from outpatient clinics at 14 referral centers (June 2006-December 2008). Patients with VTE before a diagnosis of IBD or those not confirmed to have VTE, cancer, or a VTE other than deep vein thrombosis or pulmonary embolism, were excluded. Recurrence rates were compared with 1255 prospectively followed patients without IBD that had a first unprovoked VTE (not triggered by trauma, surgery, or pregnancy). The primary end point was symptomatic, objectively confirmed, recurrent VTE after discontinuation of anticoagulation therapy after a first VTE. RESULTS: Overall, of 116 IBD patients who had a history of first VTE, 86 were unprovoked. The probability of recurrence 5 years after discontinuation of anticoagulation therapy was higher among patients with IBD than patients without IBD (33.4%; 95% confidence interval [CI]: 21.8-45.0 vs 21.7%; 95% CI: 18.8-24.6; P = .01). After adjustment for potential confounders, IBD was an independent risk factor of recurrence (hazard ratio = 2.5; 95% CI: 1.4-4.2; P = .001). CONCLUSIONS: Patients with IBD are at an increased risk of recurrent VTE compared to patients without IBD.

Accuracy and reliability of a subcutaneous continuous glucose-monitoring system in critically ill patients.

BACKGROUND: Continuous glucose monitoring has been proposed to optimize glucose control in critically ill patients. To achieve strict glucose regulation, accurate and reliable continuous glucose-monitoring systems are essential. OBJECTIVE: Evaluation of a subcutaneous continuous glucose-monitoring system for use in critically ill patients. DESIGN: Pooled-data analysis of two prospective, randomized, controlled trials. SETTING: An eight-bed medical intensive care unit of a university hospital. PATIENTS: A total of 174 critically ill patients on intensive insulin therapy. INTERVENTIONS: Subcutaneous continuous glucose monitoring. MEASUREMENTS: Two thousand forty-five continuous glucose-monitoring system sensor glucose values were compared with arterial reference blood glucose levels, determined by a blood gas analyzer. Continuous glucose monitoring data were recorded continuously for up to 72 hrs by using a subcutaneous continuous glucose-monitoring sensor. The correlation of both methods and differences between continuous glucose-monitoring systems and reference values were calculated, as well as the conformity of continuous glucose-monitoring values with the International Organization for Standardization criteria (<0.83 mmol/L [15 mg/dL] difference for glucose values ≤ 4.12 mmol/L [≤ 75 mg/dL] and <20% difference for glucose values >4.12 mmol/L [>75 mg/dL]). RESULTS: The Pearson correlation coefficient was 0.92, showing strong correlation between the two methods. The intraclass correlation coefficient was 0.92, indicating that 92% of the variability is due to subjects and measurement occasions. Mean difference between continuous glucose-monitoring system and reference values was -0.10 mmol/L (confidence interval: -0.13 to -0.07) (-2 mg/dL [confidence interval: -2 to -1]) (continuous glucose-monitoring system minus reference) and absolute difference 0.44 mmol/L (confidence interval: 0.41-0.47) (8 mg/dL [confidence interval: 7-8]). According to the insulin titration error grid analysis, 99.1% of continuous glucose-monitoring system values were in the acceptable treatment zone. No continuous glucose-monitoring system measurements were found in the life-threatening zone, and 92.9% of the continuous glucose-monitoring system glucose values met the International Organization for Standardization criteria. CONCLUSION: The subcutaneous continuous glucose-monitoring system is reliable for use in critically ill patients and showed glucose values with a strong correlation to arterial reference blood glucose levels, determined by a blood gas analyzer.

Jejunal tube placement in critically ill patients: A prospective, randomized trial comparing the endoscopic technique with the electromagnetically visualized method.

OBJECTIVE: Head-to-head comparison of the success rate of jejunal placement of a new electromagnetically visualized jejunal tube with that of the endoscopic technique in critically ill patients. DESIGN: : Prospective, randomized clinical trial. SETTING: Two intensive care units at a university hospital. PATIENTS: : A total of 66 critically ill patients not tolerating intragastric nutrition. INTERVENTIONS: Patients were randomly assigned (2:1 ratio) to receive an electromagnetically visualized jejunal feeding tube or an endoscopically placed jejunal tube. The success rate of correct jejunal placement after 24 hrs was the main outcome parameter. MEASUREMENTS AND MAIN RESULTS: The correct jejunal tube position was reached in 21 of 22 patients using the endoscopic technique and in 40 of 44 patients using the electromagnetically visualized jejunal tube (95% vs. 91%; relative risk 0.9524, confidence interval 0.804-1.127, p = .571). In the remaining four patients, successful endoscopic jejunal tube placement was performed subsequently. The implantation times, times in the right position, and occurrences of nose bleeding were not different between the two groups. The electromagnetically visualized technique resulted in the correct jejunal position more often at the first attempt. Factors associated with successful placement at the first attempt of the electromagnetically visualized jejunal tube seem to be a higher body mass index and absence of emesis. This trial is registered at ClinicalTrials.gov, number NCT00500851. CONCLUSIONS: In a head-to-head comparison correct jejunal tube placement using the new electromagnetically visualized method was as fast, safe, and successful as the endoscopic method in a comparative intensive care unit patient population.

Predictors of indeterminate IFN-γ release assay in screening for latent TB in inflammatory bowel diseases.

BACKGROUND: IFN-γ release assays (IGRA), widely used for latent tuberculosis screening prior to anti-TNF-α treatment, are limited by indeterminate results in patients under immunomodulatory (IM) therapy. The aim of our observational study was to delineate factors associated with indeterminate IGRA results. METHODS: A total of 190 patients with inflammatory bowel disease were included. IGRA was indeterminate if the result of IFN-γ concentration was < 0·35 IU mL(-1) for tuberculosis-specific antigens and < 0·5 IU mL(-1) for the positive control. Predictors for indeterminate results were delineated from multivariate logistic regression. RESULTS: IFN-γ release assays was indeterminate in 26/190 (13·7%) patients. Indeterminate IGRA were associated with lower serum albumin levels (odds ratio [OR] 0·88, 95% confidence interval [CI] 0·79-0·96), lower absolute lymphocyte count (OR 0·39, 95% CI 0·18-0·75) and double IM therapy (OR 2·98, 95% CI 0·95-8·90). Sub-analysis of IM therapy revealed an association of steroid therapy with indeterminate IGRA (OR 3·19, 95% CI 1·35-7·70). Hypoalbuminaemia increased the risk of indeterminate IGRA by (OR 2·97, 95% CI 1·03-8·61) and lymphopaenia by (OR 3·28, 95% CI 1·41-7·65). After a mean of 18·5 ± 14·4 days, retesting of IGRA in 18 patients with indeterminate results yielded 9 negative vs. 9 indeterminate results. CONCLUSIONS: Our results reveal associations of indeterminate IGRA with low serum albumin levels and absolute lymphocyte count and double IM therapy. IGRA testing appears best to be performed prior to initiation of IM therapy in patients with inflammatory bowel disease.

Passive Smoking Increases the Risk for Intestinal Surgeries in Patients With Crohn's Disease.

BACKGROUND: Despite substantial evidence on the negative effect of active smoking, the impact of passive smoking on the course of Crohn's disease (CD) remains largely unclear. Our aim was to assess passive smoking as a risk factor for intestinal surgeries in CD. METHODS: The study was conducted in a university-based, monocentric cohort of 563 patients with CD. Patients underwent a structured interview on exposure to passive and active smoking. For clinical data, chart review was performed. Response rate was 84%, leaving 471 cases available for analysis. For evaluation of the primary objective, which was the impact of exposure to passive smoking on the risk for intestinal surgery, only never actively smoking patients were included. RESULTS: Of 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking. Exposed patients were more likely to undergo intestinal surgery than nonexposed patients (67% vs 30%; P < 0.001). Multivariate Cox regression analysis revealed that passive smoking was an independent risk factor for intestinal surgeries (hazard ratio, 1.7; 95% CI, 1.04-2.9; P = 0.034) after adjustment for ileal disease at diagnosis (hazard ratio, 2.9; 95% CI, 1.9-4.5; P < 0.001) and stricturing or penetrating behavior at diagnosis (hazard ratio, 1.9; 95% CI, 1.2-3.1; P = 0.01). Passive smoking during childhood was a risk factor for becoming an active smoker in later life (odds ratio, 2.2; 95% CI, 1.5-3.2; P < 0.001). CONCLUSION: Passive smoking increases the risk for intestinal surgeries in patients with CD.

Inflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism.

BACKGROUND: Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. METHODS: This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. RESULTS: We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. CONCLUSION: The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.

Use of complementary and alternative medicine and low quality of life associate with the need for psychological and psychotherapeutic interventions in inflammatory bowel disease.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) suffer from various symptoms, impairing their quality of life and often affecting psychosocial issues. This may lead to the need for additional psychological care. This study investigated patients' subjective need for integrated psychosomatic support and psychotherapy and indicators for it. MATERIALS AND METHODS: This is a cross-sectional multicentre study in Austrian IBD patients who were in routine care at 18 IBD outpatient clinics. Patients filled in an anonymous, validated questionnaire (Assessment of the Demand for Additional Psychological Treatment Questionnaire [ADAPT]) assessing the need for psychological care. The ADAPT gives two separate scores: the need for integrated psychosomatic support and for psychotherapy. In addition, health-related quality of life and the use of complementary and alternative medicine as well as clinical and socio-demographic variables were queried. Multivariable regression analysis was performed to estimate the effect of the previously mentioned variables on the need for additional psychological care. RESULTS: Of 1286 patients, 29.7% expressed a need for additional psychological care, 19.6% expressed a need for integrated psychosomatic support and 20.2% expressed a need for psychotherapy. In the multivariable analysis, the two strongest indicators for the need for both types of psychological care were the use of complementary and alternative medicine (for integrated psychosomatic support: odds ratio = 1.64, 95% confidence interval 1.13-2.39, p = 0.010; for psychotherapy: odds ratio = 1.74, 95% confidence interval 1.20-2.53, p = 0.004), and a low health-related quality of life score (for integrated psychosomatic support: odds ratio = 0.95, 95% confidence interval 0.94-0.96, p < 0.001; for psychotherapy: odds ratio = 0.96, 95% confidence interval 0.94-0.97, p < 0.001). DISCUSSION: About 30% of the Austrian IBD patients expressed a need for integrated psychosomatic support and/or psychotherapy. The most important indicators for this need were the use of complementary and alternative medicine and low quality of life.

The impact of thiopurines on the risk of surgical recurrence in patients with Crohn's disease after first intestinal surgery.

OBJECTIVES: Smoking and a lack of immunosuppressive (IS) therapy are considered risk factors for intestinal surgery in Crohn's disease (CD). Good evidence for the latter is lacking. The objective of this study was to evaluate the impact of thiopurine treatment on surgical recurrence in patients after first intestinal resection for CD and its possible interaction with smoking. METHODS: Data on 326 patients after first intestinal resection were retrieved retrospectively, and subjects were grouped according to their postoperative exposure to thiopurines. Treatment with either azathioprine (AZA) or 6-mercaptopurine (6-MP) was recorded on 161 patients (49%). Smoking status was assessed by directly contacting the patients. RESULTS: Surgical recurrence occurred in 151/326 (46.3%) patients after a median time of 71 (range 3-265) months. Cox regression revealed a significant reduction of re-operation rate in patients treated with AZA/6-MP for > or = 36 months as compared with patients treated for 3-35 months, for less than 3 months, and to those without postoperative treatment with AZA/6-MP (P=0.004). Cox regression analysis revealed treatment with thiopurines for > or = 36 months (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.23-0.76, P=0.004) and smoking (HR 1.6; 95% CI 1.14-2.4, P=0.008) as independent predictors for surgical recurrence. Furthermore, longer duration of disease tended to be protective (HR 0.99; 95% CI 0.99-1.0, P=0.067). CONCLUSIONS: Long-term maintenance treatment with AZA/6-MP reduces the risk of surgical recurrence in patients with CD. We also identified smoking as a risk factor for surgical recurrence.

Mortality, morbidity and special issues of obese ICU patients.

Obesity is on the advance in western industrialised countries and is therefore increasingly relevant also to intensive care medicine. In contrast to the common prejudice that obese patients probably have a higher ICU mortality than lean patients, convincing meta-analyses have revealed that this is not the case. Nevertheless, obese ICU patients are challenging. Especially mechanic ventilation has to be addressed: besides obesity-related anatomical problems that may complicate intubation, obstructive sleep apnoea, obesity hypoventilation syndrome and increased intra-abdominal pressure are of major relevance concerning ventilation, weaning and successful extubation. Also the risk of infections is increased in obese ICU patients, although this does not seem to increase the risk of sepsis. Nevertheless, the interplay of obesity and sepsis is a fascinating field in that adipous tissue is not just a passive reservoir of energy but an active endocrine and immunomodulating organ. However, the way of how adipokines interact with inflammation and coagulation in sepsis has yet to be clarified.

Severity of organ failure is an independent predictor of intracranial hypertension in acute liver failure.

BACKGROUND & AIMS: Ionized ammonia (NH(3)) and partial pressure of the gaseous ammonia (pNH(3)) are associated with hepatic encephalopathy and intracranial hypertension in patients with acute liver failure; NH(3) is also believed to contribute to extrahepatic organ failure. We investigated whether the severity of organ failure was associated with intracranial hypertension and evaluated the correlation between NH(3) and pNH(3) and grade of hepatic encephalopathy. METHODS: In 87 patients with acute liver failure admitted to the intensive care unit, we simultaneously evaluated arterial ammonia, pNH(3), clinical grade of hepatic encephalopathy, the sequential organ failure assessment score (SOFA score), and evidence of intracranial hypertension. RESULTS: In comparing patients with intracranial hypertension (n = 37) with patients without intracranial hypertension (n = 50), the highest NH(3) and pNH(3) levels and SOFA scores before onset of intracranial hypertension were independent predictors of intracranial hypertension (P < .001). Among patients with NH(3) levels less than 146 mumol/L, those with intracranial hypertension had a higher SOFA score than those without intracranial hypertension (median, 10 vs 5.5; P = .004), despite the patients' similar levels of NH(3). NH(3) (r = 0.68, P < .0001) and pNH(3) (r = 0.78, P < .0001) both correlated with grade of hepatic encephalopathy. However, in multiple regression analysis, only pNH(3) (P < .0001) was shown to be a significant independent parameter for predicting grade of hepatic encephalopathy (P = .27). CONCLUSIONS: SOFA score and ammonia levels are independent predictors of intracranial hypertension. In patients with acute liver failure admitted to the intensive care unit, pNH(3) level is a better predictor of clinical grade of hepatic encephalopathy than arterial NH(3) level.

Prevalence and indicators of use of complementary and alternative medicine in Austrian patients with inflammatory bowel disease.

OBJECTIVE: Complementary and alternative medicine (CAM) seems to be frequently used among patients with inflammatory bowel disease (IBD). We aimed to determine the prevalence and indicators of CAM use in Austrian IBD patients. METHODS: In a multicentre cross-sectional study, adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded use of CAM as well as medical and socioeconomic characteristics. Patients were recruited between June 2014 and June 2015. The study outcome was the prevalence of CAM use and its socioeconomic and disease-related associations. RESULTS: A total of 1286 patients (Crohn's disease 830, ulcerative colitis 435, IBD unclassified 21; females 651) with a median age of 40 years (interquartile range 31-52 years) and a median disease duration of 10 years (4-18 years) were analysed. The prevalence of previous and/or current CAM use was 50.7%, with similar results for Crohn's disease and ulcerative colitis. In the multivariable analysis, female gender and a university education were independent socioeconomic indicators of CAM use. IBD-related indicators were longer duration of the disease and previous and/or current treatment with steroids and TNF-α inhibitors. CONCLUSION: CAM use for IBD is frequent in Austrian IBD patients and associated with female gender, higher educational level of university degree, longer duration of the disease, and treatment with steroids and TNF-α inhibitors.

Diagnostic delay in patients with inflammatory bowel disease in Austria.

BACKGROUND: Delayed diagnosis seems to be common in inflammatory bowel diseases (IBD). The study was carried out to investigate the diagnostic delay and associated risk factors in Austrian IBD patients. METHODS: In a multicenter cross-sectional study adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded medical and socioeconomic characteristics. The study outcome was diagnostic delay defined as the period from symptom onset to diagnosis of IBD. RESULTS: A total of 1286 patients (Crohn's disease 830, ulcerative colitis 435, inflammatory bowel disease unclassified 21; females 651) with a median age of 40 years (interquartile range 31-52 years) and a median disease duration of 10 years (4-18 years) were analyzed. The median diagnostic delay was 6 months (2-23 months) in Crohn's disease and 3 months (1-10 months) in ulcerative colitis (p < 0.001). In the multivariable regression analysis Crohn's disease, greater age at diagnosis and a high educational level (compared to middle degree level) were independently associated with longer diagnostic delay. CONCLUSION: The diagnostic delay was longer in Crohn's disease than in ulcerative colitis patients and was associated with greater age at diagnosis and a higher educational level.

NOD2/CARD15 gene variants are linked to failure of antibiotic treatment in perianal fistulating Crohn's disease.

OBJECTIVES: The Crohn's disease (CD) susceptibility gene, nucleotide-binding oligomerizetion domain 2 (NOD2)/caspase recruitment domain 15 (CARD15), is linked to the innate immune response associated with altered epithelial bacterial defense. Its relevance in antibiotic therapy of perianal fistulating CD remains elusive. The aim of the study was to explore systematically the association between NOD2/CARD15 variants and clinical response of perianal fistulas in patients using antibiotic therapy. METHODS: Fifty-two patients (median age 36 yr) with draining perianal fistulas were treated with ciprofloxacin (N = 49) or metronidazole (N = 3) for a median duration of 7 wk. Complete response was defined as the absence of any draining fistula despite gentle finger compression. Genotyping for NOD2/CARD15 variants and human beta (beta)-defensin 2 (HBD-2) copies was performed by 5' nuclease assays (Applied Biosystems, Foster City, CA). The examiners and laboratory investigators were blinded. The Fisher exact test and Wilcoxon signed rank test were used for statistical analysis. RESULTS: Ciprofloxacin was discontinued in one patient due to diarrhea after 2 wk. Complete fistula response was observed in 13 of 39 patients with NOD2/CARD15 wild-type (33.3%) compared with none in patients carrying NOD2/CARD15 variants (0%, P= 0.02). The median number of HBD-2 gene copies between responders and partial/nonresponders was similar. CONCLUSIONS: The study result suggests a substantial contribution of NOD2/CARD15 to the antibiotic treatment outcome of perianal fistulating CD. NOD2/CARD15 variants may predispose to an altered intestinal microflora in perianal fistulas that is less responsive to antibiotic treatment.

Impact of interobserver disagreement on phenotype-genotype associations in Crohn's disease.

BACKGROUND: Nonvalidated definitions of disease-related parameters in inflammatory bowel disease cause variations in diagnosis and disease classification. We determined interobserver agreement on applications of definitions of the Vienna Classification variables and computed the potential influence of misclassification on genotype/phenotype associations. METHODS: Ten records of patients with Crohn's disease (CD) were independently evaluated by 19 observers using a standardized inflammatory bowel disease documentation system, which included the Vienna Classification. Interobserver agreement (IOA) was calculated as a percentage of the observers' agreement with a predetermined reference observer and by Cohen's kappa. Randomized reclassifications were then computed with 10,000 simulation runs using the IOA results and published NOD2/CARD15 gene status. A chi-square independence test was calculated for each simulation run. RESULTS: IOA for location and behavior was 70% (K = 0.57) and 95% (K = 0.91), respectively. IOA for location subgroups ranged from 48% to 88% and for behavior from 91% to 97%. By including the results of histopathology into the evaluation of location, the overall IOA increased significantly, to 80% (P = 0.019). Assuming a true genotype/phenotype association, the proportion of studies with nonsignificant findings (P > 0.05) because of the observed misclassification of location ranged from 13.3% to 63.8% and of behavior from 0.2% to 22.2%, depending on a study sample size of 500 or 150 patients respectively. CONCLUSIONS: We concluded that there is appreciable interobserver disagreement on the location of CD according to the original Vienna Classification that may obscure true genotype/phenotype associations. Definitions of disease parameters have to be validated before being used as the bases for classifications.

Assessment of the need for psychosomatic care in patients with suspected cardiac disease.

OBJECTIVE: The study aimed to assess the subjectively perceived need for additional general disease-oriented and psychotherapeutic care in patients with suspected cardiac disease and to investigate if the request for additional care is consistent with impairment of generic quality of life and the presence of psychosomatic risk factors. MATERIAL AND METHODS: Patients referred for cardiac stress testing because of suspected cardiac disease completed the assessment of the demand for additional psychological treatment (ADAPT) questionnaire, an assessment tool for counselling demand in patients with chronic illness, the SF-36 quality of life and the hospital anxiety and depression scale (HADS) questionnaires. RESULTS: The questionnaires were administered to 233 patients (age: 54.5 ± 13.4, 57.5 % male). Exclusive demand for disease-oriented counselling was indicated by 45.1 %, demand for psychotherapeutic counselling (exclusive or combined with disease-oriented demand) by 33.9 %. Almost all patients with psychotherapeutic demand (96.3 %) expressed also request for disease-oriented counselling. Patients with exclusive demand for disease-oriented counselling showed significantly lower scores in the emotional and physical functioning and role domains of the SF-36 than the norm population. Patients demanding psychotherapeutic counselling reported significantly lower scores in all SF-36 domains than the norm population. Psychotherapeutic demand was strongly associated with positive indicators for mental distress: SF-36 MH (OR: 4.1), SF-36 MCS (OR: 5.9), HADS anxiety (OR: 3.9), and HADS depression (OR: 3.0). CONCLUSIONS: Our study shows that the patients' request for additional care reflects impairment of generic health status and psychological risk load. This indicates that the assessment of subjectively perceived demand allows to screen for patients who are in need of psychosomatic care and motivated to participate in additional counselling and therapy.