Publications by authors named "Robert J F Laheij"

63 Publications

Microbiota diversity and bacterial load after successful treatment of infection with honey lavage in 4 patients.

Biosci Microbiota Food Health 2022 30;41(1):1-3. Epub 2021 Sep 30.

Department of Gastroenterology and Hepatology, St. Elisabeth-TweeSteden Hospital, Hilvarenbeekseweg 60, Noord-Brabant Tilburg 5022 GC, Netherlands.

In this letter, an experimental therapy in four patients with therapy-resistant infection is described. These four patients were treated with Manuka honey via colon lavage. First, the patients received a three-day fidaxomicin treatment. The colon lavage was performed on the third day. During a subsequent ileocolonoscopy, 300 mL 15% Manuka honey was applied via a spray catheter. Patients remained in bed for two hours after the procedure and did not defecate. The patient's microbiomes were tested before treatment, after the fidaxomicin treatment, and after honey lavage. A decrease in load was found in their microbiomes. Additionally, restoration of microbiota diversity after the honey lavage was also noted. The four patients experienced complete cessation of watery stools and remain symptom free. These results indicate the need for more clinical research into this matter.
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http://dx.doi.org/10.12938/bmfh.2021-047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727055PMC
September 2021

Urgent endoscopic retrograde cholangiopancreatography with sphincterotomy versus conservative treatment in predicted severe acute gallstone pancreatitis (APEC): a multicentre randomised controlled trial.

Lancet 2020 07;396(10245):167-176

Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, Netherlands.

Background: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis.

Methods: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.

Findings: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group.

Interpretation: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis.

Funding: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.
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http://dx.doi.org/10.1016/S0140-6736(20)30539-0DOI Listing
July 2020

Successful Treatment of Lymphocytic Colitis With a Honey Lavage.

Inflamm Bowel Dis 2020 03;26(4):e25

Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands.

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http://dx.doi.org/10.1093/ibd/izz332DOI Listing
March 2020

Development of esophageal squamous cell cancer in patients with FAMMM syndrome: Two clinical reports.

Eur J Med Genet 2020 Mar 7;63(3):103840. Epub 2020 Jan 7.

Department of Surgery, Erasmus MC - University Medical Center, Rotterdam, the Netherlands.

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary syndrome characterized by multiple dysplastic nevi and melanoma. Patients with FAMMM may have a heterozygous, inactivating, pathogenic germline variant in the CDKN2A gene, especially the NM_000077.4: c.225_243del19 (p.p75fs) variant, also known as p16-Leiden variant. Patients with this variant are at high risk for developing melanomas and pancreatic cancer due to somatic inactivation of the wild-type CDKN2A allele. The combination of an inactivating germline CDKN2A mutation and somatic inactivation of the wild-type CDKN2A allele in the same cell results in tumor formation. It has been suggested that carriers of a germline CDKN2A mutation are also at increased risk for several other cancer types, including esophageal cancer. Here, we describe two unrelated patients with the p16-Leiden variant who developed esophageal squamous cell cancer. Evidence of loss of the wild-type CDKN2A allele was obtained in the tumor tissue of both patients indicating biallelic inactivation of p16 in the tumor cells. These results suggest that these patients developed esophageal squamous cell cancer in the context of FAMMM syndrome.
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http://dx.doi.org/10.1016/j.ejmg.2020.103840DOI Listing
March 2020

Successful treatment of persistent Clostridium difficile infection with manuka honey.

Int J Antimicrob Agents 2017 04 28;49(4):522-523. Epub 2017 Feb 28.

Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital, Hilvarenbeekse Weg 60, 5022GC Tilburg, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.ijantimicag.2017.02.005DOI Listing
April 2017

Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial.

Lancet Respir Med 2016 Mar 16;4(3):194-202. Epub 2016 Feb 16.

Department of Intensive Care Medicine, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands.

Background: Disturbed circadian rhythm is a potentially modifiable cause of delirium among patients in intensive-care units (ICUs). Bright-light therapy in the daytime can realign circadian rhythm and reduce the incidence of delirium. We investigated whether a high-intensity dynamic light application (DLA) would reduce ICU-acquired delirium.

Methods: This was a randomised, controlled, single-centre trial of medical and surgical patients admitted to the ICU of a teaching hospital in the Netherlands. Patients older than 18 years, expected to stay in the ICU longer than 24 h and who could be assessed for delirium were randomised to DLA or normal lighting (control), according to a computer-generated schedule. The DLA was administered through ceiling-mounted fluorescent tubes that delivered bluish-white light up to 1700 lux between 0900 h and 1600 h, except for 1130-1330 h, when the light was dimmed to 300 lux. The light could only be turned off centrally by investigators. Control light levels were 300 lux and lights could be turned on and off from inside the room. The primary endpoint was the cumulative incidence of ICU-acquired delirium. Analyses were by intention to treat and per protocol. The study was terminated prematurely after an interim analysis for futility. This study is registered with Clinicaltrials.gov, number NCT01274819.

Findings: Between July 1, 2011, and Sept 9, 2013, 734 patients were enrolled, 361 in the DLA group and 373 in the control group. Delirium occurred in 137 (38%) of 361 DLA patients and 123 (33%) of 373 control patients (odds ratio 1·24, 95% CI 0·92-1·68, p=0·16). No adverse events were noted in patients or staff.

Interpretation: DLA as a single intervention does not reduce the cumulative incidence of delirium. Bright-light therapy should be assessed as part of a multicomponent strategy.

Funding: None.
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http://dx.doi.org/10.1016/S2213-2600(16)00025-4DOI Listing
March 2016

Low fecal calprotectin predicts sustained clinical remission in inflammatory bowel disease patients: a plea for deep remission.

J Crohns Colitis 2015 Jan 26;9(1):50-5. Epub 2014 Nov 26.

University Medical Center Utrecht, Department of Gastroenterology and Hepatology, Utrecht, Netherlands

Background And Aims: Mucosal healing has become the treatment goal in patients with ulcerative colitis (UC) and Crohn's disease (CD). Whether low fecal calprotectin levels and histological healing combined with mucosal healing is associated with a further reduced risk of relapses is unknown.

Methods: Patients with CD, UC or inflammatory bowel disease-unclassified (IBD-U) scheduled for surveillance colonoscopy collected a stool sample prior to bowel cleansing. Only patients with mucosal healing (MAYO endoscopic score of 0) were included. Fecal calprotectin was measured using a quantitative enzyme-linked immunosorbent assay (R-Biopharm, Germany). Biopsies were obtained from four colonic segments, and histological disease severity was assessed using the Geboes scoring system. Patients were followed until the last outpatient clinic visit or the development of a relapse, which was defined as IBD-related hospitalization, surgery or step-up in IBD medication.

Results: Of the 164 patients undergoing surveillance colonoscopy, 92 patients were excluded due to active inflammation or missing biopsies. Of the remaining 72 patients (20 CD, 52 UC or IBD-U), six patients (8%) relapsed after a median follow-up of 11 months (range 5-15 months). Median fecal calprotectin levels at baseline were significantly higher for patients who relapsed compared with patients who maintained remission (284 mg/kg vs. 37 mg/kg. p < 0.01). Fecal calprotectin below 56 mg/kg was found to optimally predict absence of relapse during follow-up with 64% sensitivity, 100% specificity, 100% negative predictive value and 20% positive predictive value. The presence or absence of active inflammation determined by Geboes cut-off score of 3.1 was less strongly associated with the risk of relapse (64% sensitivity, 33% specificity, 9% negative predictive value and 92% positive predictive value.

Conclusion: Low calprotectin levels identify IBD patients who remain in stable remission during follow-up.
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http://dx.doi.org/10.1093/ecco-jcc/jju003DOI Listing
January 2015

Fecal calprotectin testing can identify ineffective colorectal cancer surveillance procedures in patients with longstanding colitis.

Inflamm Bowel Dis 2014 Jun;20(6):1079-84

Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.

Background: Active colitis impairs neoplasia detection during colonoscopic surveillance for colorectal cancer in patients with inflammatory bowel disease. We investigated whether fecal calprotectin testing before surveillance colonoscopy might identify ineffective surveillance procedures.

Methods: All consecutive patients with Crohn's disease or ulcerative colitis scheduled for surveillance colonoscopy were asked to collect a stool sample before the start of bowel cleansing. Ineffective surveillance was defined as at least 1 colonic segment with moderate or severe inflammation. Calprotectin was analyzed using an enzyme-linked immunosorbent assay (Ridascreen; R-Biopharm). Receiver operator characteristics statistics were used to determine the optimal cutoff for calprotectin.

Results: A total of 176 surveillance colonoscopies were performed in 164 patients, of which 83 had Crohn's disease and 81 had ulcerative colitis or inflammatory bowel disease-unclassified. Complete endoscopic remission or mild inflammation categorized as effective surveillance was observed in 151 colonoscopies (86%), whereas moderate or severe inflammation categorized as ineffective surveillance was observed in 25 colonoscopies (14%). Median calprotectin levels for the effective and ineffective surveillance group were 84 mg/kg (range, 20-4609) and 1605 mg/kg (range, 66-26,336), respectively (P < 0.01). A cutoff of 539 mg/kg identified patients with ineffective surveillance with 84% sensitivity, 89% specificity, 55% positive predictive value, 97% negative predictive value, and an area under the curve of 0.89.

Conclusions: Low fecal calprotectin accurately identifies inflammatory bowel disease patients without colonic inflammation in whom colorectal cancer surveillance is most effective.
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http://dx.doi.org/10.1097/MIB.0000000000000054DOI Listing
June 2014

Fecal hemoglobin and calprotectin are equally effective in identifying patients with inflammatory bowel disease with active endoscopic inflammation.

Inflamm Bowel Dis 2014 Feb;20(2):307-14

Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Fecal calprotectin can be used as a noninvasive tool to assess inflammation in patients with inflammatory bowel disease (IBD). However, the diagnostic accuracy of calprotectin is modest, and therefore additional markers are needed. We compared the efficacy of fecal hemoglobin and calprotectin as markers for endoscopic inflammation in patients with IBD.

Methods: Consecutive patients with Crohn's disease or ulcerative colitis scheduled for surveillance colonoscopy collected a stool sample before bowel preparation. Experienced endoscopists assessed the presence of inflammation in each colonic segment. Fecal calprotectin and hemoglobin were analyzed with an enzyme-linked immunosorbent assay. Receiver operator characteristic statistics were used to determine cutoff values for calprotectin and hemoglobin.

Results: A total of 176 surveillance colonoscopies were performed in 164 patients, of which 83 patients had Crohn's disease, 74 had ulcerative colitis, and 7 IBD-unclassified. Median (interquartile range) calprotectin and hemoglobin concentrations were 137 mg/kg (interquartile range, 33-494) and 0.51 μg/g (interquartile range, 0.18-8.50), respectively. For calprotectin, a cutoff value of 140 mg/kg predicted endoscopic inflammation with 86% sensitivity, 72% specificity, 64% positive predictive value, 90% negative predictive value, and an area under the curve of 0.87. For hemoglobin, a cutoff value of 1.51 μg/g indicated endoscopic inflammation with 74% sensitivity, 84% specificity, 72% positive predictive value, 84% negative predictive value, and an area under the curve of 0.81. Combining both tests did not increase the predictive accuracy substantially compared with calprotectin or hemoglobin alone (area under the curve, 0.88).

Conclusions: Fecal hemoglobin can identify patients with IBD with active inflammation with a predictive accuracy similar to calprotectin.
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http://dx.doi.org/10.1097/01.MIB.0000438428.30800.a6DOI Listing
February 2014

Antidepressants and gastrointestinal symptoms in the general Dutch adult population.

J Clin Psychopharmacol 2014 Feb;34(1):66-71

From the *Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen; †Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht; ‡Department of Cardiology, Radboud University Medical Center, Nijmegen; §Department of Gastroenterology and Hepatology, Elkerliek Hospital, Helmond; and ∥Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands; and ¶Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Background: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general adult population.

Methods: We assessed gastrointestinal symptoms, medication use, and comorbidity through structured questionnaires in randomly selected individuals. We compared presence of gastrointestinal symptoms in respondents who reported antidepressant use with those who did not. We used multivariable regression analysis to verify the association between antidepressant use and gastrointestinal symptoms.

Results: In total, 16,758 questionnaires were returned and eligible for analysis. Antidepressant use was reported by 701 respondents (4.2%). Gastrointestinal symptoms were more frequently reported by antidepressant users compared with nonusers (40% vs 25%, P < 0.01). This apparent association between antidepressant use and gastrointestinal symptoms did not remain after adjusting for demographic factors, comorbidity, and use of other medications (adjusted odds ratio, 0.94; 95% confidence interval, 0.74-1.18).

Conclusions: In our cross-sectional population-based study, we did not find an association between antidepressant use and gastrointestinal symptoms.
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http://dx.doi.org/10.1097/JCP.0000000000000055DOI Listing
February 2014

Symptoms associated with finding colorectal cancer during colonoscopy.

Eur J Gastroenterol Hepatol 2013 Nov;25(11):1295-9

Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Patients with an increased risk of having colorectal cancer (CRC) should have priority on the colonoscopy list.

Objective: To investigate whether presenting symptoms of patients referred for colonoscopy could help in identifying patients with an increased risk of CRC.

Patients And Methods: Between February 2007 and November 2010, random outpatients referred for colonoscopy were asked to fill out a questionnaire with respect to symptoms for which the colonoscopy was performed. Informed consent was obtained to review the colonoscopy and histology reports. Multivariate logistic regression was performed to identify predictors for CRC.

Results: In total, 1458 (21%) patients returned the questionnaire, of whom 925 (63.4%) had undergone previous sigmoidoscopy or colonoscopy. CRC was detected in 41 patients (2.8%). Age over 50 years [adjusted odds ratio (aOR) 3.00; 95% confidence interval (CI) 1.30-6.91] and presenting symptoms of rectal blood loss (aOR 4.62; 95% CI 2.31-9.22) and a change in bowel habits (aOR 3.33; 95% CI 1.50-7.40) were associated independently with an increased risk of finding CRC. Previous sigmoidoscopy or colonoscopy (aOR 0.24; 95% CI 0.12-0.49) and fatigue as presenting symptoms (aOR 0.22; 95% CI 0.09-0.56) were associated with a decreased risk of CRC. Weight loss, self-reported anemia, and abdominal pain were not associated with CRC in this study.

Conclusion: Patients presenting with rectal blood loss, change in bowel habits, and those older than 50 years of age have an increased risk of a finding of CRC during colonoscopy. We recommend that these risk groups should be prioritized on the colonoscopy list over patients who have undergone a previous endoscopy or who are presenting with fatigue.
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http://dx.doi.org/10.1097/MEG.0b013e3283640fdfDOI Listing
November 2013

Gastrointestinal symptoms are still prevalent and negatively impact health-related quality of life: a large cross-sectional population based study in The Netherlands.

PLoS One 2013 29;8(7):e69876. Epub 2013 Jul 29.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population.

Methods: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms.

Results: A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43-1.77), asthma/COPD (aOR 1.47, 95% CI 1.21-1.79), use of paracetamol (aOR 1.33, 95% CI 1.20-1.47), antidepressants (aOR 1.56, 95% CI 1.22-2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65-0.87), and use of statins (aOR 0.75, 95% CI 0.61-0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SD = 0.21) compared to 0.92 (SD = 0.14) for persons without gastrointestinal symptoms (P<0.01).

Conclusions: Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069876PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726702PMC
March 2014

Nurse-led follow-up at home vs. conventional medical outpatient clinic follow-up in patients with incurable upper gastrointestinal cancer: a randomized study.

J Pain Symptom Manage 2014 Mar 20;47(3):518-30. Epub 2013 Jul 20.

Erasmus MC University Medical Center Rotterdam, The Netherlands.

Context: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic.

Objectives: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer.

Methods: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months.

Results: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits.

Conclusion: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits.
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http://dx.doi.org/10.1016/j.jpainsymman.2013.04.006DOI Listing
March 2014

Dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of Legionnaires' disease.

PLoS One 2013 30;8(4):e62265. Epub 2013 Apr 30.

Department of Emergency Medicine and Intensive Care, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.

Study Objective: Absolute lymphocytopenia is recognised as an important hallmark of the immune response to severe infection and observed in patients with Legionnaires' disease. To explore the immune response, we studied the dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of LD.

Methods And Results: EDTA-anticoagulated blood was obtained from eight patients on the day the diagnosis was made through detection of L. pneumophila serogroup 1 antigen in urine. A second blood sample was obtained in the subacute phase. Multiparametric flow cytometry was used to calculate lymphocyte counts and values for B-cells, T-cells, NK cells, CD4+ and CD8+ T-cells. Expression of activation markers was analysed. The values obtained in the subacute phase were compared with an age and gender matched control group. Absolute lymphocyte count (×10⁹/l, median and range) significantly increased from 0.8 (0.4-1.6) in the acute phase to 1.4 (0.8-3.4) in the subacute phase. B-cell count showed no significant change, while T-cell count (×10⁶/l, median and range) significantly increased in the subacute phase (495 (182-1024) versus 979 (507-2708), p = 0.012) as a result of significant increases in both CD4+ and CD8+ T-cell counts (374 (146-629) versus 763 (400-1507), p = 0.012 and 119 (29-328) versus 224 (107-862), p = 0.012). In the subacute phase of LD, significant increases were observed in absolute counts of activated CD4+ T-cells, naïve CD4+ T-cells and memory CD4+ T-cells. In the CD8+ T-cell compartment, activated CD8+ T-cells, naïve CD8+ T-cell and memory CD8+ T-cells were significantly increased (p<0.05).

Conclusion: The acute phase of LD is characterized by absolute lymphocytopenia, which recovers in the subacute phase with an increase in absolute T-cells and re-emergence of activated CD4+ and CD8+ T cells. These observations are in line with the suggested role for T-cell activation in the immune response to LD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062265PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640018PMC
November 2013

CT-colonography after incomplete colonoscopy: what is the diagnostic yield?

Dis Colon Rectum 2013 May;56(5):593-9

Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands.

Background: Computed tomography-colonography is a diagnostic modality that can be used when the colon is not completely intubated during colonoscopy. It may have the additional advantage that information on extracolonic lesions can be obtained.

Objective: The aim of this study was to investigate the yield of CT-colonography of relevant intra- and extracolonic findings in patients after incomplete colonoscopy.

Design: This was an observational, retrospective study.

Data Sources: Data were be obtained from standardized radiology and endoscopy reports and electronic medical records.

Study Selection: In total, 136 consecutive CT-colonographies performed after incomplete colonoscopy were evaluated.

Main Outcome Measures: All intra- and extracolonic findings on CT-colonography were recorded and interpreted for clinical relevance, and it was determined whether further diagnostic and/or therapeutic workup was indicated.

Results: Major indications for colonoscopy included iron-deficiency anemia (25.7%), hematochezia (20.6%), change in bowel habits (18.4%), and colorectal cancer screening or surveillance (11.0%). Major reasons for incomplete colonoscopy were a fixed colon (34.6%) and strong angulation of the sigmoid colon (17.6%). Introduction of the colonoscope was limited to the left-sided colon in 53.7% of cases. Incomplete colonoscopy detected colorectal cancer in 12 (8.8%) patients and adenomatous polyps in 27 (19.9%) patients. CT-colonography after incomplete colonoscopy additionally revealed 19 polyps in 15 (11.0%) and a nonsynchronous colorectal cancer in 4 (2.9%) patients. CT-colonography also detected extracolonic findings with clinical consequences in 8 (5.9%) patients, including fistulizing diverticulitis (n = 3), gastric tumor (n = 2), liver abscess (n = 1), osteomyelitis (n = 1), and an infected embolus in both renal arteries (n = 1).

Limitations: This study was limited by the lack of confirmation of intraluminal CT-colonography findings in a subset of patients.

Conclusions: Computed tomography-colonography can be of added value in patients with incomplete colonoscopy, because it revealed 27 relevant additional (both intra- and extracolonic) lesions in 19.1% of patients. In cases where CT-colonography detected colorectal cancer after incomplete colonoscopy, it can also be used for staging purposes.
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http://dx.doi.org/10.1097/DCR.0b013e3182781668DOI Listing
May 2013

Similar fecal immunochemical test results in screening and referral colorectal cancer.

World J Gastroenterol 2012 Oct;18(38):5397-403

Department of Gastroenterology and Hepatology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.

Aim: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts.

Methods: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage).

Results: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10).

Conclusion: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.
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http://dx.doi.org/10.3748/wjg.v18.i38.5397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471108PMC
October 2012

The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia.

PLoS One 2012 1;7(10):e46561. Epub 2012 Oct 1.

Department of Emergency Medicine and Intensive Care, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands.

Study Objective: The neutrophil-lymphocyte count ratio (NLCR) has been identified as a predictor of bacteremia in medical emergencies. The aim of this study was to investigate the value of the NLCR in patients with community-acquired pneumonia (CAP).

Methods And Results: Consecutive adult patients were prospectively studied. Pneumonia severity (CURB-65 score), clinical characteristics, complications and outcomes were related to the NLCR and compared with C-reactive protein (CRP), neutrophil count, white blood cell (WBC) count. The study cohort consisted of 395 patients diagnosed with CAP. The mean age of the patients was 63.4 ± 16.0 years. 87.6% (346/395) of the patients required hospital admission, 7.8% (31/395) patients were admitted to the Intensive Care Unit (ICU) and 5.8% (23/395) patients of the study cohort died. The NLCR was increased in all patients, predicted adverse medical outcome and consistently increased as the CURB-65 score advanced. NLCR levels (mean ± SD) were significantly higher in non-survivors (23.3 ± 16.8) than in survivors (13.0 ± 11.4). The receiver-operating characteristic (ROC) curve for NLCR predicting mortality showed an area under the curve (AUC) of 0.701. This was better than the AUC for the neutrophil count, WBC count, lymphocyte count and CRP level (0.681, 0.672, 0.630 and 0.565, respectively).

Conclusion: Admission NLCR at the emergency department predicts severity and outcome of CAP with a higher prognostic accuracy as compared with traditional infection markers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046561PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462173PMC
February 2013

Acute gastrointestinal bleeding from a submucosal gastric mass.

Ann Gastroenterol 2012 ;25(1):76-78

Department of Gastroenterology, University Medical Center of Utrecht, The Netherlands.

We report a case of a 44-year-old male patient who presented with melena and hemodynamic instability. The endoscopic investigation of the upper and lower gastrointestinal tract was initially negative, but a repeat gastroduodenoscopy revealed a submucosal mass in the lesser curvature of the stomach with central erosion, primarily perceived as ectopic pancreas, but it was later discovered that it pertained to a gastrointestinal stromal tumor.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959352PMC
January 2012

Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis.

Int J Cancer 2011 Apr;128(8):1908-17

Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized-controlled trial to compare cost-effectiveness of screening with either one round of immunochemical fecal occult blood testing (I-FOBT; OC-Sensor®), one round of guaiac FOBT (G-FOBT; Hemoccult-II®) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third-party payer perspective in a Markov model with first- and second-order Monte Carlo simulation. Costs were measured in Euros (€), effects in life-years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I-FOBT dominated the alternatives: after one round of I-FOBT screening, a hypothetical person would on average gain 0.003 life-years and save the health care system €27 compared with G-FOBT and 0.003 life years and €72 compared with no screening. Overall, in 4,460,265 Dutch aged 50-75 years, after one round I-FOBT screening, 13,400 life-years and €320 million would have been saved compared with no screening. I-FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I-FOBT dominated G-FOBT and no screening with or without accounting for uncertainty.
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http://dx.doi.org/10.1002/ijc.25530DOI Listing
April 2011

Comparison of guaiac and immunological fecal occult blood tests in colorectal cancer screening: the patient perspective.

Scand J Gastroenterol 2010 Nov 21;45(11):1345-9. Epub 2010 Jun 21.

Department of Social Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Objective: Colorectal cancer (CRC) screening programs can decide upon the type of fecal occult blood test (FOBT): the guaiac FOBT (g-FOBT) or the immunological FOBT (i-FOBT). The effectiveness of any screening program depends not only on the diagnostic performance of the screening test but also on the compliance and general acceptance of the test by the public. Any decision on the type of FOBT for CRC screening should also take acceptation and perception into account. The aim of the present study was to study differences in patient perception between i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups in a population based study.

Material And Methods: Differences in patient perception of i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups were investigated (n = 20,623) by sending a short questionnaire to all invited to the first Dutch CRC screening trial.

Results: i-FOBT was perceived significantly more favorable than g-FOBT. About 1275 (32%) participants reported the g-FOBT not easy to use, not easy to perform, disgusting or shameful compared to 742 (16%) for the i-FOBT (p < 0.001). The participation rate was significantly higher in those who received i-FOBT compared to the g-FOBT group: 6159 of 10,322 (60%) versus 4839 of 10,301 (47%) (p < 0.001).

Conclusions: These findings support the selection of i-FOBT as the more appropriate test for population screening programs.
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http://dx.doi.org/10.3109/00365521.2010.497937DOI Listing
November 2010

Genetic polymorphisms in GSTA1, GSTP1, GSTT1, and GSTM1 and gastric cancer risk in a Vietnamese population.

Oncol Res 2010 ;18(7):349-55

Department of Gastroenterology, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam.

Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.
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http://dx.doi.org/10.3727/096504010x12626118080064DOI Listing
May 2010

Comparison of incident dyspepsia between low-dose plain aspirin and enteric-coated aspirin.

Clin Gastroenterol Hepatol 2010 Apr 13;8(4):395; author reply 395-6. Epub 2009 Oct 13.

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http://dx.doi.org/10.1016/j.cgh.2009.10.006DOI Listing
April 2010

Genetic polymorphisms in UDP-glucuronosyltransferase 1A6 are not associated with NSAIDs-related peptic ulcer haemorrhage.

Drug Metab Lett 2009 Aug;3(3):199-204

Department of Gastroenterology & Hepatology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.

UDP-glucuronosyltransferase 1A6 (UGT1A6) is involved in metabolizing non-steroidal anti-inflammatory drugs (NSAIDs). Genotype variation in UGT1A6 may influence the metabolism of NSAIDs and we studied whether this might modulate the gastrointestinal toxicity of NSAIDs. UGT1A6 genotypes of 114 patients with peptic ulcer haemorrhage were compared with those of two subsets of controls: 158 cardiology patients using similar amounts of NSAIDs and 140 healthy controls, hardly using NSAIDs. Risk factors for peptic ulcer bleeding were male gender (Odds ratio (OR) 2.66, 95% confidence interval (CI) 1.7-4.2), age above 60 years (OR 2.15, 95% CI 1.4-3.4) and use of NSAIDs/aspirin (OR 4.50, 95% CI 2.8-7.3). UGT1A6 genotype frequencies did not differ between patients with peptic ulcer and the two control groups (p=0.76). We conclude that polymorphic UGT1A6 is not implicated in the pathogenesis of NSAIDs-related peptic ulcer disease.
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http://dx.doi.org/10.2174/187231209789352111DOI Listing
August 2009

[Colorectal cancer screening: immunological test for faecal occult blood preferred].

Ned Tijdschr Geneeskd 2009 ;153:A474

Universitair Medisch Centrum St Radboud, afd. Maag-, Darm- en Leverziekten, Nijmegen, The Netherlands.

In 2003, the European Commission advised the Member States to start colorectal cancer screening. More than 12 million Europeans have been tested to date, not only by means of faecal occult blood testing but often also by opportunistic endoscopy. Nearly all of the screening programmes concerned were opportunistic in nature. The Dutch government is currently considering the implementation of an organised screening programme for the detection of colorectal cancer. The question no longer seems to be whether a screening programme should be started but rather which screening test should be used. We argue that an immunological faecal occult blood test is to be preferred over other screening tests, such as endoscopy.
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December 2009

False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening.

Int J Cancer 2009 Aug;125(4):746-50

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling and laboratory delivery on iFOBT performance. IFOBT positivity (>or=50 ng/ml hemoglobin) in colorectal cancer screening participants without delay between sampling and laboratory delivery (<5 days), was compared with positivity in participants with >or=5 and >or=7 days delay. Additionally, positive tests were stored at room temperature and retested 5 times within 10-14 days. The sampling date was reported by 61% (n = 3,767) of the participants: in 19% delay was >or=5 days and in 5% >or=7 days. Compared with no-delay, the adenoma detection rate was already significantly decreased after >or=5 days delay (OR 0.6; 95%CI 0.4-0.9). We retested iFOBT samples of 170 positives of which 139 (82%) had a colonoscopy: 45 (32%) had advanced adenomas (not colorectal cancer) and 8 (6%) had colorectal cancer. Mean daily fecal hemoglobin decrease was 29 ng/ml (S.D. 38 and median 11 ng/ml). In patients with advanced adenomas, hemoglobin in the sample was <50 ng/ml in 5 (11%) 2-3 days after the initial test and in 16 (36%) after 10-14 days. Seven days after the initial test, 2 (25%) colorectal cancer patients became false negative. Both had stage I colorectal cancer and initial values below 100 ng/ml, where the average for stage I is 532 ng/ml. Delay in sample return increased false negative immunochemical FOBT's. Mainly precursor lesions, but also colorectal cancer, will be missed due to delayed sample return.
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http://dx.doi.org/10.1002/ijc.24458DOI Listing
August 2009

Effect of genetic polymorphisms in UDP-glucuronosyltransferase 1A6 (UGT1A6) on acetylsalicylic acid metabolism in healthy female volunteers.

Pharmacology 2009 5;83(4):237-42. Epub 2009 Mar 5.

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Objective: To compare plasma concentrations of acetylsalicylic acid (ASA) and its metabolites between genetic polymorphisms in the gene encoding for UDP-glucuronosyltransferase 1A6 (UGT1A6), an enzyme involved in ASA metabolism.

Methods: Five UGT1A6*1 and 4 UGT1A6*2 homozygote females were given 320 mg ASA once daily for 8 days. During the first and last day of treatment, several blood samples were taken over a 10-hour time period and analyzed for plasma levels of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), using a validated HPLC method. The pharmacokinetic data were assessed with the Time Constant Approach and both genotypes were compared using the Mann-Whitney U test.

Results: ASA and SUA showed similar pharmacokinetic parameters in the two UGT1A6 genotypes. However, pharmacokinetic parameters for SA differed significantly: the mean area under the pharmacokinetic curve for the UGT1A6*1 and UGT1A6*2 homozygotes was 136 and 94 microg/ml.h (p = 0.04), and median C(max) was 23 and 17 microg/ml (p = 0.01), respectively.

Conclusion: In females receiving ASA, the presence of the UGT1A6*2 compared to the UGT1A6*1 homozygote genotype is associated with lower plasma levels of SA, indicating faster pharmacokinetics.
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http://dx.doi.org/10.1159/000205824DOI Listing
June 2009

Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial.

Lancet 2009 Jan;373(9659):215-25

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.

Background: Substantial physician workload and high costs are associated with the treatment of dyspepsia in primary health care. Despite the availability of consensus statements and guidelines, the most cost-effective empirical strategy for initial management of the condition remains to be determined. We compared step-up and step-down treatment strategies for initial management of patients with new onset dyspepsia in primary care.

Methods: Patients aged 18 years and older who consulted with their family doctor for new onset dyspepsia in the Netherlands were eligible for enrolment in this double-blind, randomised controlled trial. Between October, 2003, and January, 2006, 664 patients were randomly assigned to receive stepwise treatment with antacid, H(2)-receptor antagonist, and proton pump inhibitor (step-up; n=341), or these drugs in the reverse order (step-down; n=323), by use of a computer-generated sequence with blocks of six. Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcomes were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was by intention to treat (ITT); the ITT population consisted of all patients with data for the primary outcome at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00247715.

Findings: 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0.92, 95% CI 0.7-1.3). The average medical costs were lower for patients in the step-up group than for those in the step-down group (euro228 vs euro245; p=0.0008), which was mainly because of costs of medication. One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group. All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste.

Interpretation: Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care.
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http://dx.doi.org/10.1016/S0140-6736(09)60070-2DOI Listing
January 2009

Functional dyspepsia: not all roads seem to lead to rome.

J Clin Gastroenterol 2009 Feb;43(2):118-22

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Background: The Rome criteria have been introduced to create order in the heterogeneity of functional dyspepsia. The applicability of these symptom-based classification systems remains controversial.

Goal: To evaluate the successive Rome criteria for functional dyspepsia in a large pool of patients with endoscopically verified functional dyspepsia.

Study: Patients referred to a secondary care district hospital were asked to fill out a questionnaire on gastrointestinal symptoms 2 weeks before upper gastrointestinal endoscopy. Patients were classified according to the Rome I, II, and III criteria for functional dyspepsia.

Results: Nine hundred and twelve (70%) patients had no organic disorder explaining their symptoms. According to the Rome I, II, and III criteria, 371 (41%), 735 (81%), and 551 (60%) of these patients had functional dyspepsia, respectively. Twenty-five percent of patients had functional dyspepsia according to all 3 Rome criteria, whereas 15% was not classifiable at all. Forty-four percent and 42% of the patients, respectively, had epigastric pain syndrome and postprandial distress syndrome according to the Rome III criteria; however, 26% of all patients met both criteria and 40% was not classified at all.

Conclusions: The symptom-based Rome classification of functional dyspepsia does not lead to an easily applicable and consistent system that is useful in clinical practice or scientific research.
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http://dx.doi.org/10.1097/MCG.0b013e31815591f7DOI Listing
February 2009

Prognostic value of free plasma homocysteine levels in patients hospitalized with acute coronary syndrome.

Am J Cardiol 2008 Jul 28;102(2):135-9. Epub 2008 May 28.

Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Elevated total plasma homocysteine is an established risk factor for cardiovascular disease. Experimental evidence suggests that non-protein-bound free homocysteine is particularly hazardous to the vascular endothelium. This study evaluates the predictive role of free plasma homocysteine levels on cardiovascular endpoints in patients with acute coronary syndrome (ACS). In a cohort of 379 hospitalized patients with a diagnosis of myocardial infarction or unstable angina pectoris, total and free plasma homocysteine levels were measured by high performance liquid chromatography. The patients were followed for a median 2.7 years. The primary endpoint was a composite of cardiovascular death, myocardial infarction and stroke during follow-up. Stepwise Cox regression was used for multivariate analysis. Primary outcome events occurred in 82 patients (22%) with a median time to event of 6 months. The unadjusted hazard ratio for a free homocysteine level >4.11 micromol/L was 2.16 (95% confidence intervals [CI] 1.36 to 3.42) compared with the 4 lower quintiles. After adjusting for the covariates the hazard ratio was 2.25 (95% CI 1.41 to 3.58, p = 0.01). Compared with the lower 4 quintiles, patients with a total homocysteine level >22.4 micromol/L had a 2.09-fold higher risk (95% CI 1.31 to 3.35) for an event during follow-up. Adjusted for age, discharge diagnosis, serum creatinine, history of atherothrombotic events, and diabetes mellitus, the adjusted hazard ratio was 1.37 (95% CI 0.83 to 2.25, p = 0.22). In conclusion, plasma free homocysteine levels >4.11 micromol/L are a significant and independent risk factor for recurrent cardiovascular events in patients hospitalized for ACS, although total plasma homocysteine levels have no predictive value.
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http://dx.doi.org/10.1016/j.amjcard.2008.03.022DOI Listing
July 2008

Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial.

Clin Gastroenterol Hepatol 2008 Jul 18;6(7):746-52; quiz 718. Epub 2008 Apr 18.

Department of Gastroenterology & Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Background & Aims: Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects. Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome. This study aimed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia.

Methods: This was a multi-center, randomized, double-blind, placebo-controlled trial. Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities. They were randomly assigned to receive 8 weeks of treatment with either venlafaxine XR (2 weeks 75 mg once daily, 4 weeks 150 mg once daily, and 2 weeks 75 mg once daily) or placebo. Symptoms, health-related quality of life, anxiety, and depression were assessed before and at 4, 8, 12, and 20 weeks after inclusion.

Results: One hundred sixty patients were randomized; 56% and 73% of participants completed treatment with venlafaxine or placebo, respectively, according to protocol. There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion, with venlafaxine in comparison to placebo (37% and 39%, respectively; odds ratio [OR], 0.8; 95% confidence interval [CI], 0.3-2.1; and 42% and 41%, respectively; OR, 3.1; 95% CI, 0.9-12.6). Per-protocol analysis did not reveal any differences between venlafaxine and placebo either (38% and 39% symptom-free, respectively; OR, 1.0; 95% CI, 0.4-2.4 at 8 weeks).

Conclusions: Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia.
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http://dx.doi.org/10.1016/j.cgh.2008.02.051DOI Listing
July 2008
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