Publications by authors named "Jeroen Jaspers Focks"

8 Publications

  • Page 1 of 1

Rivaroxaban Plasma Levels and Levetiracetam.

Ann Intern Med 2020 11;173(9):770-771

Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, the Netherlands (F.W.V.).

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November 2020

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial.

BMJ 2016 Jun 15;353:i2868. Epub 2016 Jun 15.

Department of Cardiology, Radboud University Nijmegen Medical Centre, PO box 9101, 6500 HB Nijmegen, Netherlands.

Objective:  To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation.

Design:  Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)-a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011.

Participants:  18 201 ARISTOTLE trial participants.

Interventions:  In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years.

Main Outcome Measures:  Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country).

Results:  Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs (Pinteraction=0.82). A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs (Pinteraction=0.017). Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin.

Conclusions:  In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe.Trial registration ARISTOTLE trial, NCT00412984.
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June 2016

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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February 2014

Novel antithrombotic challenges: head, heart, and guts.

Gastroenterology 2013 Nov 21;145(5):1163-4. Epub 2013 Sep 21.

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

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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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March 2014

Assessment of plasma aminothiol levels and the association with recurrent atherothrombotic events in patients hospitalized for an acute coronary syndrome: a prospective study.

Clin Chem Lab Med 2013 Nov;51(11):2187-93

Background: The aminothiols homocysteine and, to a lesser extent, cysteine have been associated with adverse cardiovascular outcome, whereas glutathione, as an antioxidant, may protect against atherosclerosis and thrombosis. Potentially, the combined assessment of these aminothiols may provide a more accurate association with future cardiovascular outcome. We evaluated the association between recurrent atherothrombotic events and the concentration of total plasma cysteine, homocysteine, and glutathione and their combination.

Methods: Respective aminothiols were measured by high-performance liquid chromatography in blood plasma of consecutive first-day survivors admitted for an acute coronary syndrome between April 2002 and January 2004. The combined score was calculated using the combination of the individual aminothiols. The end point was the composite of cardiovascular death, myocardial infarction, and/or stroke.

Results: A cohort of 375 consecutive patients (median age 66 years, 66% male) were followed for a median duration of 2.7 years. The end point occurred in 82 patients (22%). In univariate analyses, all aminothiols were significantly associated with the composite end point. After correction for possible confounders, only cysteine and glutathione remained significantly associated. The strongest association with the end point was observed for the combined score (adjusted hazard ratio, 1.40 per standard deviation increase; p=0.005).

Conclusions: Although homocysteine is generally considered the aminothiol of interest with respect to cardiovascular disease, in our prospective study, only cysteine and glutathione appeared independently associated with recurrent atherothrombotic events. Moreover, we showed that an imbalance in the combination of aminothiols could be of more importance than investigating the individual metabolites.
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November 2013

Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review.

Heart 2013 Apr 31;99(8):520-7. Epub 2012 Jul 31.

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

Background: Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel the controversy on this issue.

Purpose: Systematic review of the impact of the addition of PPIs to clopidogrel on platelet function and cardiovascular outcome.

Data Sources: PubMed, Web-of-Science, Cochrane Database and reference lists of related articles.

Study Selection: Published articles on controlled studies addressing the addition of PPIs to clopidogrel. Platelet function studies describe patients as well as healthy volunteers. Clinical studies concern patients using clopidogrel for acute coronary syndromes or because of stent implantation for stable coronary disease.

Data Extraction: Two investigators independently reviewed the identified articles for eligibility, and one author extracted the data.

Data Synthesis: In 70% (7/10) of the laboratory studies examining healthy volunteers on clopidogrel, addition of PPIs resulted in a significant reduction in platelet inhibition. For patients, this was observed in 11/18 (61%) studies. The 33 clinical studies showed significant heterogeneity in observed outcomes, with risk ratios for major adverse cardiovascular events varying from 0.64 to 4.58 in the case of PPI use, which was randomly allocated in only two studies. Consequently, imbalances between prognosticators at baseline and PPI prescription bias markedly contributed to the variability in results.

Conclusions: Despite indications of reduced antiplatelet activity ex vivo in the case of PPI administration in clopidogrel users, data on the clinical consequences are controversial. With the accumulating evidence from better designed, prospective clinical studies, an adverse effect of PPI use on clinical outcome in patients on clopidogrel cannot be substantiated. This review challenges the validity of conclusions based on quantitative analyses of predominantly non-randomised data.
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April 2013

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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April 2010