Publications by authors named "Merel M Tielemans"

7 Publications

  • Page 1 of 1

Immunosuppressive drugs and the gastrointestinal tract in renal transplant patients.

Transplant Rev (Orlando) 2019 04 14;33(2):55-63. Epub 2018 Nov 14.

Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, the Netherlands. Electronic address:

Gastrointestinal (GI) discomfort is common after renal transplantation and can be caused by the use of various immunosuppressive drugs. GI symptoms affect the quality of life, lead to an impaired graft survival and an increased mortality. Moreover, diseases and disturbances of the GI tract also affect the pharmacokinetics of immunosuppressive drugs. This review addresses the interaction between immunosuppressive agents and GI disorders. The GI tract is involved in the metabolism of several immunosuppressive drugs. Calcineurin inhibitors, mTor inhibitors, and corticosteroids are subjected to metabolism by the intestinal cytochrome P450 (CYP3A) and by the drug efflux pump ABCB1. Mycophenolate is partly metabolized in the stomach and intestine and undergoes enterohepatic recirculation. Gastrointestinal disturbances can lead to a modified exposure to immunosuppressive drugs. In the first and second part of this review, we focus on the role of the GI tract in the pharmacokinetics of the immunosuppressive drugs and how to adjust immunosuppressive therapy in patients with vomiting, need for tube feeding, delayed gastric emptying, intestinal resection, and diarrhea. In the third part, we review the GI adverse effects of the various immunosuppressive drugs, with special attention for diarrhea and dyspepsia. Finally, we discuss the effects of drugs used for relief of GI complaints on the exposure to immunosuppressive agents.
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http://dx.doi.org/10.1016/j.trre.2018.11.001DOI Listing
April 2019

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

Online follow-up of individuals with gastroesophageal reflux disease using a patient-reported outcomes instrument: results of an observational study.

BMC Gastroenterol 2013 Oct 1;13:144. Epub 2013 Oct 1.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, PO Box 9101, Internal code 455, Nijmegen 6500 HB, The Netherlands.

Background: Many individuals with gastroesophageal reflux disease (GERD) never visit their general practitioner. Therefore, prospective data about GERD and its natural history in the general population are scarce. The aims of this study were to assess symptoms over time and consultation reasons in an Internet population with GERD.

Methods: Visitors (18-79 years) to a GERD information website who completed the GerdQ self-assessment questionnaire were invited to participate. Follow-up GerdQ questionnaires were sent after 4, 12 and 24 weeks, and those who had a total GerdQ score ≥ 8 and responded to at least the baseline and 4-week questionnaires (within 2-7 weeks) were included in the analyses. Outcome in proton pump inhibitor (PPI) and non-PPI users was classified as symptom improvement, symptom persistence/stable symptoms, or symptom relapse according to GerdQ scores.

Results: A total of 403 non-PPI users (mean age 48 years, 40% male) and 304 PPI users (mean age 51 years, 41% male) were included. After 24 weeks, symptom improvement was present in 66% of non-PPI users (45/68) and 8% of PPI users (6/73), while persisting symptoms were reported by 24% (16/68) and 89% (65/73) respectively (baseline symptoms did not influence outcome at 24 weeks). Fifty-five percent of PPI users (116/210) and 37% of non-PPI users (76/207) who intended to visit a healthcare practitioner, performed one or more healthcare visits in the interim. Most frequently reported reason for consultation was persistence of symptoms.

Conclusions: GERD symptoms were persistent in the majority of PPI users during our 24-week follow-up, while almost two thirds of non-PPI users reported symptom improvement. Online follow-up of an Internet population with GERD is feasible.
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http://dx.doi.org/10.1186/1471-230X-13-144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851875PMC
October 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

Esomeprazole relieves upper gastrointestinal symptoms in high-risk and average-risk NSAID users in daily clinical practice: results from an open-label study.

Eur J Gastroenterol Hepatol 2012 Mar;24(3):281-7

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

Objective: To investigate whether esomeprazole can provide relief for nonsteroidal anti-inflammatory drug (NSAID)-associated upper gastrointestinal symptoms in patients at different gastrointestinal risk.

Methods: A multicentre, prospective, open-label study was conducted, wherein NSAID users visiting their general practitioner for upper gastrointestinal symptoms were asked to participate. Patients were treated with 20 mg esomeprazole and treatment effect was evaluated within 8 weeks. Response was defined as a maximum of 1 day per week with gastrointestinal symptoms during the last week of treatment. Partial response was defined as more than 50% improvement in the number of days per week with symptoms compared with baseline. Patients not meeting the above-mentioned criteria were classified as nonresponders. Patients who completely responded were compared with partial responders and nonresponders and were analysed according to their baseline gastrointestinal risk.

Results: A total of 1042 patients (mean age: 57 years; standard deviation: 15; 43% male) were analysed. Complete response, partial response and nonresponse were achieved in 57, 24 and 19% of the patients, respectively. Similar response was seen in average-risk and high-risk patients (58 and 56%; P=0.46) and in nonselective NSAID and selective cyclooxygenase-2 users (57 and 53%; P=0.32).

Conclusion: Esomeprazole (20  mg) improved NSAID-associated upper gastrointestinal symptoms. Baseline gastrointestinal risk did not influence esomeprazole effectiveness.
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http://dx.doi.org/10.1097/MEG.0b013e32834f4d19DOI Listing
March 2012

Open access capture of patients with gastroesophageal reflux disease using an online patient-reported outcomes instrument.

Interact J Med Res 2012 Sep 26;1(2):e7. Epub 2012 Sep 26.

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

Background: Persons with gastroesophageal reflux disease (GERD) frequently search online for information about causes and treatment options. The GerdQ self-assessment questionnaire can be used for diagnosis of GERD and follow-up of symptoms.

Objectives: To assess whether it is feasible (1) to study the prevalence and impact of GERD in persons visiting a GERD information website, and (2) to identify partial responsiveness to proton pump inhibitor (PPI) therapy using the GerdQ.

Methods: All visitors (aged 18-79 years) to a GERD information website between November 2008 and May 2011 were invited to complete the GerdQ online. The GerdQ questionnaire consists of 6 questions (score per question: 0-3). In respondents who did not use PPIs, we used the questionnaire to identify those with GERD (total score ≥8) and assess the influence of these symptoms on their daily life, divided into low (total score <3 on impact questions) and high impact (total score ≥3 on impact questions). In PPI users, we used the GerdQ to quantify partial responsiveness by any report of heartburn, regurgitation, sleep disturbance, or over-the-counter medication use for more than 1 day in the preceding week. We subsequently asked GerdQ respondents scoring ≥8 to complete the disease-specific Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire.

Results: A total of 131,286 visitors completed the GerdQ, of whom 80.23% (n = 105,329) did not use a PPI. Of these, we identified 67,379 respondents (63.97%) to have GERD (n = 32,935; 48.88% high impact). We invited 14,028 non-PPI users to complete the QOLRAD questionnaire, of whom 1231 (8.78%) completed the questionnaire. Mean total QOLRAD scores were 5.14 (SEM 0.04) for those with high-impact GERD and 5.77 (SEM 0.04) for those with low-impact GERD (P < .001). In PPI users, 22,826 of 25,957 respondents (87.94%) reported partial responsiveness. We invited 6238 PPI users to complete the QOLRAD questionnaire, of whom 599 (9.60%) completed the disease-specific quality-of-life questionnaire. Mean total QOLRAD scores were 4.62 (SEM 0.05) for partial responders and 5.88 (SEM 0.14) for adequate responders (P < .001).

Conclusions: The GerdQ identified GERD in many website respondents and measured partial responsiveness in the majority of PPI users. Both non-PPI users with GERD and PPI users with partial responsiveness were associated with a decreased health-related quality of life. We have shown the feasibility of GERD patient identification online.
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http://dx.doi.org/10.2196/ijmr.2101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626138PMC
September 2012

Identification of NSAID users at risk for gastrointestinal complications: a systematic review of current guidelines and consensus agreements.

Drug Saf 2010 Jun;33(6):443-53

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

NSAIDs are among the most often used drugs worldwide. Numerous NSAID users are at risk for developing gastrointestinal complications. The purpose of this review was to identify and stratify risk factors for gastrointestinal complications in NSAID users documented in guidelines and consensus agreements, and to collect recommendations regarding over-the-counter (OTC) NSAID use. To facilitate this, a PubMed search from 1 January 1999 until 1 March 2009 was performed, resulting in the inclusion of nine English-language guidelines in our analysis. Risk factors were defined as 'definite' if mentioned in all guidelines; otherwise they were defined as 'controversial' risk factors. 'Definite' risk factors were a history of (complicated) peptic ulcer disease, older age (cut-off range 60-75 years), concomitant anticoagulant or corticosteroid use and multiple NSAID use, including low-dose aspirin (acetylsalicylic acid). 'Controversial' risk factors were high-dose NSAID use, concomitant clopidogrel or selective serotonin reuptake inhibitor use, a history of gastrointestinal symptoms, rheumatoid arthritis disability and cardiovascular disease. Infection with Helicobacter pylori was identified as an additive risk factor. Risk factors in OTC NSAID users were difficult to identify in the current literature. Risk factors were not all uniformly present in analysed guidelines and consensus agreements. We identified a history of (complicated) peptic ulcer disease, older age, concomitant anticoagulant or corticosteroid use and multiple NSAID use, including low-dose aspirin, as definite gastrointestinal risk factors in NSAID users.
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http://dx.doi.org/10.2165/11534590-000000000-00000DOI Listing
June 2010
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