Joost P H Drenth's scientific contributionswhile working at Radboud University Medical Centre (Radboudumc), Nymegen, Gelderland, Netherlandsand other institutions

Publications (460)

  • [Show abstract] [Hide abstract] ABSTRACT: Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment. We hypothesise that decreased plasma concentrations were not caused by a DDI but were an indirect result of the clearance of the HCV infection. During chronic HCV infection, pro-inflammatory cytokines may inhibit cytochrome P450 (CYP) enzymes, which are primary responsible for tacrolimus metabolism. If this is true, then with clearance of the virus the activity of these enzymes will normalise and tacrolimus metabolism increases. These changes were clinically relevant because the tacrolimus dosage needed to be adjusted. Therefore, physicians should be aware that CYP substrates with narrow therapeutic ranges might require dose adaption during HCV therapy with DAAs.
    Article · Feb 2017 · International journal of antimicrobial agents
  • Article · Feb 2017 · Clinical Pharmacology &#38 Therapeutics
  • [Show abstract] [Hide abstract] ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) patients can suffer from chronic pain that can be refractory to conventional treatment, resulting in a wish for nephrectomy. This study aimed to evaluate the effect of a multidisciplinary treatment protocol with sequential nerve blocks on pain relief in ADPKD patients with refractory chronic pain. As a first step a diagnostic, temporary celiac plexus block with local anesthetics was performed. If substantial pain relief was obtained, the assumption was that pain was relayed via the celiac plexus and major splanchnic nerves. When pain recurred, patients were then scheduled for a major splanchnic nerve block with radiofrequency ablation. In cases with no pain relief, it was assumed that pain was relayed via the aortico-renal plexus, and catheter-based renal denervation was performed. Sixty patients were referred, of which 44 were eligible. In 36 patients the diagnostic celiac plexus block resulted in substantial pain relief with a change in the median visual analogue scale (VAS) score pre-post intervention of 50/100. Of these patients, 23 received a major splanchnic nerve block because pain recurred, with a change in median VAS pre-post block of 53/100. In 8 patients without pain relief after the diagnostic block, renal denervation was performed in 5, with a borderline significant change in the median VAS pre-post intervention of 20/100. After a median follow-up of 12 months, 81.8% of the patients experienced a sustained improvement in pain intensity, indicating that our treatment protocol is effective in obtaining pain relief in ADPKD patients with refractory chronic pain.
    Article · Jan 2017 · Kidney International
  • Aura A J van Esch · Joost P H Drenth · John J Hermans
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP. Methods: We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging). Results: We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency. Conclusions: In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.
    Article · Jan 2017 · Pancreas
  • Floor A.C. Berden · Fanny E.R. Vuik · Joost P.H. Drenth · Wietske Kievit
    Article · Jan 2017 · Digestive and Liver Disease
  • Anna Simon · Jos W.M. Van Der Meer · Joost P.H. Drenth
    Chapter · Jan 2017
  • Titus F. M. Wijnands · Maxime Ronot · Tom J. G. Gevers · [...] · Joost P. H. Drenth
    File available · Data · Jan 2017
  • File available · Data · Jan 2017
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    [Show abstract] [Hide abstract] ABSTRACT: Introduction and AimsThe DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18–60 years, estimated glomerular filtration rate 30–60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. ResultsWe included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48–55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41–58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk–benefit ratio. identifierNCT 01616927.
    Full-text available · Article · Dec 2016 · Drug Safety
  • T.E.H. Römkens · K. Gijsbers · W. Kievit · [...] · J.P.H. Drenth
    [Show abstract] [Hide abstract] ABSTRACT: Background & Aims: Recently, treatment goals in inflammatory bowel disease (IBD) in clinical trials have shifted from mainly symptom-based to more mucosa-driven. Real world data on treatment priorities are lacking. We aimed to investigate the current practice and most commonly used definitions of IBD treatment targets among Dutch gastroenterologists. Methods: Dutch gastroenterologists were asked to participate in a computer-based nation-wide survey. We asked questions on demographics, opinion and current practice regarding IBD treatment targets. Results: Twenty-four percent (134/556) of the respondents completed the survey. For both Crohn’s disease (CD) (47.3%, 61/129) and ulcerative colitis (UC)(45%, 58/129) the main treatment goal was to achieve and maintain deep remission, defined as clinical, biochemical and endoscopic remission. Seventy-six percent of the participants use mucosal healing (MH) as a potential treatment target for IBD, whereas 22.6% use histological remission. There is no single definition for MH in IBD. The majority use Mayo score ≤ 1 in UC (52%) and ‘macroscopic normal mucosa’ in CD (66%). Conclusion: More stringent and mucosa-driven treatment targets as ‘deep remission’ and ‘mucosal healing’ have found traction in clinical practice. The most commonly used definition for MH in routine practice is endoscopic MAYO score ≤ 1 in UC and ‘macroscopic normal mucosa’ in CD. © 2016, Romanian Society of Gastroenterology. All rights reserved.
    Article · Dec 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Background Five to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. Design and methods The SECURE-trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy. Patients in the usual care group will be treated according to the physician’s knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3-monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months. The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients’ symptoms and treatment and work performance, and ultimately, cost-effectiveness. Discussion The SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012) Trial registration The Netherlands National Trial Register NTR4022
    Full-text available · Article · Dec 2016 · BMC Surgery
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    Mark W. Hess · Jeroen H.F. de Baaij · Mark M.T.J. Broekman · [...] · Joost P.H. Drenth
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Proton pump inhibitors (PPIs) are effective drugs for the treatment of gastric acid-related disorders. Serious adverse events are rare for PPIs, but recent data suggest that PPIs cause hypomagnesemia. The aim of this study was to estimate the frequency of PPI-induced hypomagnesemia and to define the risk factors for its development. Materials and methods: A total of 133 chronic users of PPIs were enrolled and patients were distinguished on the basis of their serum Mg concentrations. Common single nucleotide polymorphisms (SNPs) in the candidate gene, transient receptor potential melastatin type 6 (TRPM6), were screened. Results: Seventeen out of 133 patients had PPI-induced hypomagnesemia. The duration of PPI use was longer in those with hypomagnesemia (7.7 vs. 5.2 years). Two common SNPs in TRPM6 (rs3750425 and rs2274924) increased the risk for PPI-induced hypomagnesemia by 5.8-fold. Conclusion: We found hypomagnesemia in 13% of PPI users. SNPs in TRPM6 drive the risk of developing hypomagnesemia during chronic PPI use.
    Full-text available · Article · Dec 2016 · Pharmacogenetics and Genomics
  • Titus F M Wijnands · Alena P M Görtjes · Tom J G Gevers · [...] · Joost P H Drenth
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Aspiration sclerotherapy is a percutaneous procedure indicated for treatment of symptomatic simple hepatic cysts. The efficacy and safety of this procedure have been sources of debate and disagreement for years. The purpose of this study was to assess the long-term efficacy and safety of aspiration sclerotherapy in a systematic review of the literature. Materials and methods: A systematic search was conducted of the electronic databases PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library (until August 2015). Studies of proportional volume or diameter reduction after aspiration sclerotherapy of simple hepatic cysts were included for full-text evaluation. Case reports and case series were excluded. Risk of bias was assessed by use of the Newcastle-Ottawa scale. Results: From 9357 citations, 100 were selected for full-text assessment. We included 16 studies, which included 526 patients with a total of 588 treated cysts. Overall, risk of bias was high, with 12 of 16 studies having a score of poor. Proportional cyst volume reduction ranged between 76% and 100% after a median follow-up period of 1-54 months. Change in symptoms was evaluated in 10 studies: 72-100% of patients reported symptom reduction, and 56-100% reported disappearance. Postprocedural pain occurred most frequently, at a rate of 5-90% among studies. Ethanol intoxication occurred in up to 93% of cases and was reported more frequently in studies with either high ethanol volumes (133.7-138.3 mL) or long sclerotherapy duration (120-180 minutes). Conclusion: We found excellent results with respect to long-term efficacy and safety after aspiration sclerotherapy of hepatic cysts. Nevertheless, because of the high risk of bias in the included studies, definite conclusions regarding efficacy cannot be drawn.
    Article · Nov 2016 · American Journal of Roentgenology
  • Floor A.C. Berden · Bryan R.R.Z. Aaldering · Hans Groenewoud · [...] · Joost P.H. Drenth
    [Show abstract] [Hide abstract] ABSTRACT: Background & aims: Direct-acting antivirals (DAA) are effective in treatment of chronic hepatitis C virus (HCV) infection, although results for patients infected with genotype 3 are suboptimal. There are several regimens available but direct comparisons have not been made and are unlikely to occur. We aimed to identify the most effective DAA regimen for patients infected with HCV genotype 3 and to assess the role of ribavirin. Methods: We conducted a systematic search of Pubmed, Embase and Web of Science databases through March 2016. We performed a Bayesian network meta-analysis using a random effects model to indirectly compare regimens in patients with and without cirrhosis. We calculated mean estimated sustained virologic response (SVR) with 95% credible intervals (95% CrI) per regimen and effect of ribavirin as odds ratio. We focused on current recommended regimens and regimens under evaluation by regulatory authorities. Results: Our search identified 2167 articles; 27 studies (comprising 3415 patients) were included. Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%; 95% CrI, 98%-100%) and without ribavirin (97%; 95% CrI, 95%-99%), sofosbuvir + daclatasvir + ribavirin (96%; 95% CrI, 92%-98%), and sofosbuvir + peginterferon + ribavirin (95%; 95% CrI, 91%-98%), all for 12 weeks. Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%; 95% CrI, 92%-99%), sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%; 95% CrI, 87%-98%), and sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%; 95% CrI, 86%-98%). Ribavirin increases efficacy in patients with and without cirrhosis (odds ratio, 2.6-4.5). Conclusion: An indirect comparison of DAA-based treatments, using Bayesian network meta-analysis, found regimens containing sofosbuvir and velpatasvir to be the best option for patients with HCV genotype 3 infection. Our analyses indicate that ribavirin significantly increases rates of SVR and should be considered if tolerated.
    Article · Nov 2016 · Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association
  • [Show abstract] [Hide abstract] ABSTRACT: Background Atazanavir is boosted with the cytochrome P450 (CYP) 3A4 inhibitor ritonavir. When combined with the CYP3A4 substrate daclatasvir, the daclatasvir dosage should be reduced from 60 to 30 mg once daily. Recently, cobicistat was licensed as a CYP3A booster and used with atazanavir. Objectives To determine whether the fixed-dose combination of atazanavir/cobicistat has an influence on daclatasvir pharmacokinetics comparable to that of the separate agents atazanavir and ritonavir. Methods A prospective, open-label, two-period, randomized, cross-over trial was performed in 16 healthy subjects (NCT02565888). Treatment consisted of 300/100 mg of atazanavir/ritonavir plus 30 mg of daclatasvir once daily (reference) and a second period of 300/150 mg of atazanavir/cobicistat plus 30 mg of daclatasvir once daily (test). A 24 h pharmacokinetic, steady-state curve was recorded for all drugs. Geometric mean ratios (GMRs) with 90% CI were calculated for daclatasvir and atazanavir AUCτ and Cmax to compare the effect of both treatments (test versus reference). Laboratory safety and adverse events were evaluated throughout the trial. Results All 16 healthy subjects completed the study. Median (range) age and BMI were 48.5 (21–55) years and 24.5 (19.0–29.2) kg/m², respectively. Pharmacokinetic parameters of ritonavir and cobicistat were comparable to those in the literature. The GMRs (90% CI) of daclatasvir AUCτ and Cmax (test versus reference) were 101% (92%–111%) and 97% (89%–106%), respectively. Atazanavir GMRs (90% CI) of AUCτ and Cmax were 82% (75%–79%) and 74% (68%–81%), respectively. No serious adverse events were reported. Conclusions Atazanavir/cobicistat and atazanavir/ritonavir had a similar influence on daclatasvir pharmacokinetics in healthy volunteers. Daclatasvir at 30 mg once daily is the correct dose when combined with atazanavir/cobicistat.
    Article · Oct 2016 · Journal of Antimicrobial Chemotherapy
  • Hedwig M.A. D'Agnolo · Wietske Kievit · Kim N van Munster · [...] · Joost P.H. Drenth
    [Show abstract] [Hide abstract] ABSTRACT: Background: Polycystic liver disease (PLD) is a rare genetic disorder with progressive cyst growth as the primary phenotype. Therapy consists of volume reduction through invasive surgical or radiological procedures. In order to understand the process of treatment decision, our aim was to identify factors that increased the likelihood of treatment. Study design: We performed a cross-sectional study using an international population of PLD patients. We collected data on the following therapies: liver transplantation, resection, fenestration and aspiration sclerotherapy. Data on the potential determinants: sex, center, autosomal dominant polycystic kidney disease (ADPKD), autosomal dominant polycystic liver disease (ADPLD), age at diagnosis, symptoms and phenotype were included. We corrected for follow-up time. Results: We included 578 patients in our study and 35% underwent invasive therapy. Multivariate regression analysis showed that number of symptoms) and age at diagnosis of PLD increased the likelihood of treatment (respectively RR 1.4, p<0.001 and RR =1.4, p=0.03). The choice for liver transplantation or aspiration sclerotherapy was center-dependent (RR 0.7, p<0.001 and RR 1.1, p=0.03 respectively). Conclusion: The results of our international cross-sectional study suggests that a higher number of symptoms and every 10 years of PLD diagnosis increases the risk to undergo treatment by 40%. The choice to elect a particular modality is center dependent. This article is protected by copyright. All rights reserved.
    Article · Oct 2016 · Transplant International
  • Rianne A. Weersink · Joost P.H. Drenth · Sander D. Borgsteede
    Article · Oct 2016 · Gastroenterology
  • [Show abstract] [Hide abstract] ABSTRACT: Introduction Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. Methods and analysis For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Ethics and dissemination Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings.
    Article · Oct 2016 · BMJ Open
  • Edgar S Wills · Joost P H Drenth
    Article · Sep 2016 · Gut
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    Mark P. Lamberts · Cihan Özdemir · Joost P. H. Drenth · [...] · Wietske Kievit
    [Show abstract] [Hide abstract] ABSTRACT: Background: The aim of this study was to determine the cost-effectiveness of a new strategy for the preoperative detection of patients that will likely benefit from a cholecystectomy, using simple criteria that can be applied by surgeons. Criteria for a cholecystectomy indication are: (1) having episodic pain; (2) onset of pain 1 year or less before the outpatient clinic visit. Methods: The cost-effectiveness of the new strategy was evaluated against current practice using a decision analytic model. The incremental cost-effectiveness of applying criteria for a cholecystectomy for a patient with abdominal pain and gallstones was compared to applying no criteria. The incremental cost-effectiveness ratio (ICER) was expressed as extra costs to be invested to gain one more patient with absence of pain. Scenarios were analyzed to assess the influence of applying different criteria. Results: The new strategy of applying one out of two criteria resulted in a 4 % higher mean proportion of patients with absence of pain compared to current practice with similar costs. The 95 % upper limit of the ICER was €4114 ($4633) per extra patient with relief of upper abdominal pain. Application of two out of two criteria resulted in a 3 % lower mean proportion of patients with absence of pain with lower costs. Conclusion: The new strategy of using one out of two strict selection criteria may be an effective but also a cost-effective method to reduce the proportion of patients with pain after cholecystectomy.
    Full-text available · Article · Sep 2016 · Surgical Endoscopy


  • 2011
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands
  • 2009
    • Laboratorium Zeeuws-Vlaanderen B.V.
      'Ulst, Zeeland, Netherlands
  • 2008
    • Yale University
      New Haven, Connecticut, United States
  • 2004
    • Slingeland Ziekenhuis
      Doetinchem, Gelderland, Netherlands
  • 2000-2004
    • Radboud University Nijmegen
      • Department of Gastroenterology and Hepatology
      Nijmegen, Provincie Gelderland, Netherlands

Publication Stats

10k Citations