Ulcerative Colitis: Timmer A

Timmer A, Obermeier F. · No affiliation provided · BMJ. · Pubmed #19273505 No free full text.

This publication has no abstract.

Preiss JC, Timmer A, Zeitz M, Hoffmann JC. · Medizinische Klinik I (Gastroenterologie/Infektiologie/Rheumatologie), Charité Campus Benjamin Franklin, Berlin. · Z Gastroenterol. · Pubmed #17924306 No free full text.

Abstract: The German Society for Digestive and Metabolic Diseases (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, DGVS) has already published an impressive number of clinical practice guidelines, with more topics currently being under development. The guideline method within the DGVS as well as between medical professional societies varies greatly. In particular, the levels of evidence as well as the grades of recommendations are often applied very differently. Most guidelines in Germany use the grades of the US Agency for Health Care Policy and Research (AHCPR), which were first published in 1992. Some newer guidelines, e.g., the ulcerative colitis guideline of the DGVS or the guidelines of the German Diabetes Association, try to circumvent problems of this method. They adopted variations of the very simple AHCPR grades. Sometimes these new grading methods have serious shortcomings too. They may not be reproducible, ignore important parts of the consensus process, can only be applied to therapeutic interventions, or they do not adequately distinguish between the strength of a recommendation and the quality of evidence. Meanwhile, an enormous number of different and partially contradictory methodologies for the grading of guideline recommendations are being used. In the GRADE working group several renowned clinical epidemiologists came together to develop a uniform grading systematic that avoids the problems of earlier guideline methods. With GRADE first the quality of evidence is assessed in a systematic manner. The quality of each study plays an important role in this process. Hence randomised trials of poor quality can end up with a lower overall quality rating than well performed observational trials. The strength of recommendation is based on the balance between the expected benefit and harm of the intervention in the respective population for which the recommendations of the guideline are made. The quality of evidence is only one factor contributing to the strength of recommendation. The GRADE method can be more cumbersome in its application compared to older methods. Nevertheless, more and more organisations are adopting GRADE for their guidelines and recommendations. Possibly the DGVS guidelines could benefit from this new system too.

Timmer A, McDonald JW, Macdonald JK. · German Cochrane Center, Stefan Meier Str. 26, Freiburg, Germany, 79104. · Cochrane Database Syst Rev. · Pubmed #17253451 No free full text.

Abstract: BACKGROUND: Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial. OBJECTIVES: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis. SEARCH STRATEGY: The MEDLINE database was used to search literature from 1966 to 2006. A manual search was also performed using references from these articles as well as review articles, proceedings from major gastrointestinal meetings and data available from the Cochrane Collaboration database. Authors of maintenance trials were asked about unpublished studies. SELECTION CRITERIA: Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (mesalamine) were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two raters using standard forms. Disagreements were solved by informal consent, including a third rater. Jadad scores were applied to assess study quality. Analyses were performed separately by type of control (placebo, or active comparator). Pooled odds ratios were calculated based on the fixed effects model unless heterogeneity was shown. MAIN RESULTS: Six studies were identified including 286 patients with ulcerative colitis. The study quality was mostly poor. Azathioprine was shown to be superior for the maintenance of remission as compared to placebo based on four trials (failure to maintain remission: OR 0.41; 95% CI 0.24 to 0.70). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity. Both studies using active comparators were open label. Adverse effects occurred in 11 of 127 patients receiving azathioprine, including acute pancreatitis (3 cases) and significant bone marrow suppression (5 cases). AUTHORS' CONCLUSIONS: Azathioprine may be an effective maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine.

Timmer A. · Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany. · Dig Dis. · Pubmed #14571108 No free full text.

Abstract: Environmental factors play an important role in the disease manifestation, course and prognosis of inflammatory bowel disease. Observations on temporal trends and geographical distribution point at risk factors associated with a Western lifestyle. A large number of studies have been performed on various factors such as diet, smoking, and several infectious agents. Childhood exposures modifying immune responses in later life form a particularly interesting field. However, so far, only smoking in Crohn's disease, and smoking cessation in ulcerative colitis can be considered established as risk factors for the manifestation of the disease. Smoking is also associated with a poor prognosis in Crohn's disease. A strong negative association of appendectomy with ulcerative colitis has been very consistent across many studies; however, the implications of this finding are still obscure.

Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC. · Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. · BMC Gastroenterol. · Pubmed #15113451 links to  free full text

Abstract: BACKGROUND: Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn's disease and ulcerative colitis. Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission. The aim of this randomized, placebo-controlled trial was to determine the effect of oral Lactobacillus GG (L. GG) to induce or maintain medically induced remission. METHODS: Eleven patients with moderate to active Crohn's disease were enrolled in this trial to receive either L. GG (2 x 10(9) CFU/day) or placebo for six months. All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated. The primary end point was sustained remission, defined as freedom from relapse at the 6 months follow-up visit. Relapse was defined as an increase in CDAI of >100 points. RESULTS: 5/11 patients finished the study, with 2 patients in each group in sustained remission. The median time to relapse was 16 +/- 4 weeks in the L. GG group and 12 +/- 4.3 weeks in the placebo group (p = 0.5). CONCLUSION: In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD.

Timmer A, Kemptner D, Bauer A, Takses A, Ott C, Fürst A. · Department of Medical Biometry and Statistics, University Hospital of Freiburg, Stefan-Meier Strasse 26, 79104, Freiburg, Germany. · BMC Gastroenterol. · Pubmed #18834529 links to  free full text

Abstract: BACKGROUND: Sexual function is impaired in women with inflammatory bowel disease (IBD) as compared to normal controls. We examined disease specific determinants of different aspects of low sexual function. METHODS: Women with IBD aged 18 to 65 presenting to the university departments of internal medicine and surgery were included. In addition, a random sample from the national patients organization was used (separate analyses). Sexual function was assessed by the Brief Index of Sexual Function in Women, comprising seven different domains of sexuality. Function was considered impaired if subscores were <-1 on a z-normalized scale. Results are presented as age adjusted odds ratios with 95% CI based on multiple logistic regression. RESULTS: 336 questionnaires were included (219 Crohn's disease, 117 ulcerative colitis). Most women reported low sexual activity (63%; 17% none at all, 20% moderate or high activity). Partnership satisfaction was high in spite of low sexual interest in this group. Depressed mood was the strongest predictor of low sexual function scores in all domains. Urban residency and higher socioecomic status had a protective effect. Disease activity was moderately associated with low desire (OR 1.8, 95% CI 1.0 to 3.2). Severity of the disease course impacted most on intercourse frequency (OR 2.3, 95% CI 1.4 to 4.7). Lubrication problems were more common in smokers (OR 2.5, 95% CI 1.3 to 5.1). CONCLUSION: Mood disturbances and social environment impacted more on sexual function in women with IBD than disease specific factors. Smoking is associated with lubrication problems.

Ott C, Obermeier F, Thieler S, Kemptner D, Bauer A, Schölmerich J, Rogler G, Timmer A. · Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #18794607 No free full text.

Abstract: OBJECTIVE: Although important advances in understanding the aetiology and pathogenesis of inflammatory bowel disease (IBD) have been made, many questions remain unanswered. As the most recent data available on the incidence of IBD in Germany were collected about 15 years ago, we set up a new population-based cohort to determine current incidence data for a defined region in Germany and to establish a basic cohort for prospective follow-up. METHODS: All patients living in the region of Oberpfalz newly diagnosed with IBD between 1 January 2004 and 31 December 2006 were included in this study by setting up a network of reporting clinicians and general practitioners in hospitals as well as in private practices. Demographic and clinical characteristics such as age at first diagnosis, localization of the disease, extraintestinal manifestations or family history on IBD were documented. Age-adjusted incidence rates are presented with 95% Poisson confidence intervals (CIs), based on the European standard population. RESULTS: In total, 286 newly diagnosed patients with IBD were reported in this region, 168 patients suffering from Crohn's disease (CD), 105 patients with ulcerative colitis. Age-standardized incidence rates were 11.0/10(5) (95% CI: 9.1-11.6) for IBD, 6.6/10(5) (95% CI: 5.6-7.7) for CD and 3.9/10(5) (95% CI: 3.2-4.7) for ulcerative colitis. Peak incidences were found in the age interval of 16-24 years for both diseases, predominantly for CD. Age at first diagnosis was lower, extraintestinal manifestations and a positive family history on IBD were more common in patients with CD. CONCLUSION: The incidence rate in IBD seems to be stable in Germany as compared with previously reported data, as is the remarkable predominance of CD. Prospective follow-up studies will be based on this incidence cohort.

Hafner S, Timmer A, Herfarth H, Rogler G, Schölmerich J, Schäffler A, Ehrenstein B, Jilg W, Ott C, Strauch UG, Obermeier F. · Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #18467916 No free full text.

Abstract: BACKGROUND: Environmental factors are likely to be involved in the pathogenesis of inflammatory bowel disease (IBD), as the incidence of both Crohn's disease (CD) and ulcerative colitis (UC) increased with improved living standards in Europe after World War II. On the basis of earlier reports suggesting that hygienic standards may also play a role in the pathogenesis of IBD, we investigated the influence of hepatitis A seroprevalence as an indicator for poorer hygienic conditions and worm infestations in IBD. METHODS: Hepatitis A seroprevalence was examined in patients with UC and CD. Patients with minor endocrinological disorders served as controls. All patients were questioned about immunizations, parasitic infections (worms), contact with animals, living on a farm, and ever traveling abroad. Patients were excluded for active hepatitis A immunization or recent passive immunization. Results are presented as Mantel-Haenszel odds ratios with 95% confidence interval, adjusted for age group. RESULTS: The sample included 307 patients (73 CD, 48 UC, and 186 controls). Hepatitis A seroprevalence was strongly associated with age older than 50 years. Age adjusted Mantel-Haenszel odds ratios were 0.25 (0.09-0.71) for UC and 0.75 (0.38-1.46) for CD versus controls. For parasitic infections, the odds ratios were 1.15 (0.52-2.53) for UC and 0.34 (0.13-0.89) for CD. CONCLUSION: We were able to demonstrate a negative association of hepatitis A infection with UC only. In contrast, a novel finding was a strong protective effect of worm infestations for the occurrence of CD, but not UC.

Timmer A. · Deutsches Cochrane-Zentrum, Universitätsklinikum Freiburg. · Z Gastroenterol. · Pubmed #17503319 No free full text.

This publication has no abstract.

Spoettl T, Hausmann M, Klebl F, Dirmeier A, Klump B, Hoffmann J, Herfarth H, Timmer A, Rogler G. · Department of Internal Medicine I, University of Regensburg, Germany. · Inflamm Bowel Dis. · Pubmed #17260368 links to  free full text

Abstract: BACKGROUND: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine and an important mediator in the pathophysiology of inflammatory bowel disease (IBD). The effects of TNFalpha are mediated by 2 specific receptors, a 55-kDa protein (TNF-RI) and a 75-kDa receptor (TNF-RII), which are usually bound to the cell surface. Soluble TNF receptors I and II (sTNF-RI + II) are released by proteolytic cleavage of the extracellular domains of these receptors. Soluble TNF-Rs act as TNF antagonists and can inhibit TNFalpha-mediated proinflammatory effects. METHODS: Levels of sTNF-RI + II were measured using commercially available enzyme-linked immunosorbent assays (ELISAs). Serum levels of sTNF-RI + II of 76 healthy volunteers were compared to serum levels of 373 clinically well-characterized patients with Crohn's disease (CD) and 118 patients with ulcerative colitis (UC) with different disease activity from the German IBD competence network serum bank. CD patient subgroups were defined according to the Vienna Classification. RESULTS: The serum levels of sTNF-RI were significantly increased in all groups (active, chronic active, and remission) of CD and UC patients compared to healthy controls. sTNF-RII levels were significantly higher in active CD patients compared to UC patients with no overlap of the 95% confidence interval. Significantly higher values of sTNF-RII compared to controls were also observed in CD patients and UC patients in remission. There was no statistically significant difference in sTNF-RI or sTNF-RII levels when patient subgroups were analyzed according to disease behavior or disease localization. CONCLUSION: sTNF-RI is upregulated in the serum of IBD patients compared to healthy controls and could be used as a marker for disease activity. sTNF-RII levels are significantly more elevated in serum of active CD patients as compared to UC and could be used as an additional parameter to discriminate both diseases.

Timmer A, Goebell H. · Medizinische Klinik, Abteilung für Gastroenterologie, Universitätsklinikum Essen. · Z Gastroenterol. · Pubmed #10604221 No free full text.

Abstract: A prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995 to determine the incidence of ulcerative colitis in an urban area in Germany. Patients with proctitis were excluded from this analysis. 74 (1980-84) and 76 (1991-95) patients newly diagnosed with ulcerative colitis were identified. A slight rise in the age- and sex-standardized incidence rate from 2.4/10(5) in 1980-84 (95% CI 1.8/10(5) to 3.0/10(5)) to 3.0 (95% CI 2.4/10(5) to 3.7/10(5)) in 1991-95 was primarily due to a significant increase of the disease in young woman. A male preponderance in the earlier time period was hereby leveled out. There were no differences in the extent of the disease and the severity of symptoms. However, the time from onset of symptoms to diagnosis was reduced from a median of nine months in the 1980s to two months in the more recent period.