PT/
PC
PE2
Dear Colleagues,
This is the annual report for 2013 of the Units PharmacoEpidemiology &
PharmacoEconomics (PE2) and Pharmacotherapy & Pharmaceutical Care (PT/PC)
from the Department of Pharmacy, University of Groningen. The units have integrated
an important part of their educational and scientific activities.
We are part of the graduate schools of Natural Sciences and Medical Sciences
and the Research Institute SHARE. Within SHARE, we participate in the program
Methods in Medicines evaluation & Outcomes research (M2O). M2O is constituted
together with (parts of) the Epidemiology and Clinical Pharmacology departments of
the University Medical Center Groningen (UMCG). Furthermore, we participate in the
ROAHD program (Reproductive Origins of Adult Health and Disease) with
researchers from different disciplines, such as molecular biology, genetics,
epidemiology, reproductive medicine and obstetrics of the UMCG. Also, we host the
North-east regional office of the Netherlands Pharmacovigilance Centre Lareb.
Notably, next to new PhDs, this year we were very happy to welcome some new
colleagues to the units: candidate PhDs Pieter de Boer, Thang Nguyen, Didik
Setiawan, Dianna de Vries, Maarten van Wijhe, post-docs/staff Pepijn Vemer, Hans
Wouters , Marcy Liu and Prof Eric van Roon. Managing staff of PE2 consists of Prof
Maarten Postma, Prof Eelko Hak and Dr Nynke Schuiling-Veninga. Ex-heads-of-theUnits and retired Profs Lolkje de Jong-van den Berg and Koos Brouwers are still
involved in honorary positions in the areas of targeted medicine and pharmacotherapy.
The managing staff of PT/PC consists of Prof Bob Wilffert, Prof Han de Gier and Prof
Katja Taxis. In 2013, Prof Maarten Postma was appointed director of SHARE, the
research institute joining parts of UMCG and Pharmacy. With our primary
investigators in SHARE/M2O and Eelko Hak as program leader, this report presents
the M2O program on page 10.
We are looking forward to a new exciting scientific year with these new
colleagues and within the existing and extending network comprising other academic
partners, pharmacists, industries and international colleagues.
Feb 2013, Units PE2 and PT/PC
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Research Programs PharmacoEpidemiology & PharmacoEconomics
Prof MJ Postma
Unit head PE2 and program leader Pharmacoeconomics
Prof E Hak
Program leader Clinical Pharmacoepidemiology
Research Programs Pharmacotherapy & Pharmaceutical Care
Prof B Wilffert
Unit head PT/PC and program leader Pharmacotherapy & Clinical Pharmacy
Prof JJ de Gier
Program leader Pharmaceutical Care
Prof AC van Grootheest
Program leader Pharmacovigilance
Prof JGW Kosterink
Program leader Hospital & Clinical Pharmacy
Prof AJM Loonen
Program leader Psychiatric Pharmacotherapy
Prof EN van Roon
Program leader Clinical Pharmacotherapy
Prof K Taxis
Program leader Medication safety
Visiting address:
Antonius Deusinglaan 1
9713 AV Groningen
Postal address:
University of Groningen
Department of Pharmacy
Secretary: J Schoonveld
telephone: +31 50 363 7576
fax:
+31 50 363 2772
Building 3214, 4th floor
HPC XB 45
Antonius Deusinglaan 1
9713 AV Groningen
The Netherlands
e-mail:
[email protected]
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2. News from the different lines of research
Unit PharmacoEpidemiology & PharmacoEconomics (PE2)
Pharmacoeconomics & Outcomes research
In the research line of pharmacoeconomics & outcomes research, various
developments can be mentioned for the year 2013.
On cost-effectiveness and modeling in vaccines, various papers were authored in
Vaccine, PloS One and Expert Reviews, for example, on meningococcal, rotavirus and
Hepatitis A vaccines (Drss Baudioun Standaert and Auliya Suwantika). Next to a
standing co-operation with the Health Protection Agency in the UK, co-operations in
the area of vaccines were started and strengthened with Indonesia, Thailand and
Vietnam. Drs Tjalke Westra and Mehraj Parouty continued their investigations into
issues concerning discounting of health effects for HPV-vaccination within the
frameworks of complex multi-cohort and dynamical models and subsequently
defended their theses in 2013. Within other projects, involving co-operations with the
National Institute of Public Health & the Environment and National Reference
Laboratory in Amsterdam, cost-effectiveness of pneumococcal vaccines were
investigated. Drs Didik Setiawan started his research on cost-effectiveness of HPVvaccines in Indonesia courageously and initial steps were taken in 2013. Costeffectiveness studies on RSV and MenB vaccines were published by cand PhDs
Marjan Meijboom and Koen Pouwels. Cand PhD Nikos Kotsopoulos won the best
poster prize at European ISPOR for his work on HPV-vaccination.
A paper by Dianna de Vries (Value in Health accepted) illustrated the continuation of
a line of research into cost-effectiveness issues in the disease area where
cardiovascular, diabetic and kidney diseases meet. Additionally, abundant other papers
were produced during 2013 from the pharmacoeconomics and outcomes research line,
both internationally (e.g. Value in Health, Expert Reviews in Pharmacoeconomics &
Outcomes Res and PharmacoEconomics) and nationally (Pharmaceutisch Weekblad/
Wetenschappelijk Platform and bookchapters). Also, various external (cand) PhDs
contributed enormously to this flow of publications; Dr Mark Connolly and Drs HansJoerg Fugel, to name just a few. Co-operations were further strengthened and the
network was broadened both within the public and the private sector, inclusive
representation of Unit’s workers in various advisory committees and boards for the
Health Council, CVZ, WHO, consultancies and pharmaceutical industries.
IADB.nl provides an important research tool for drug utilization research. Major steps
were taken by the team of Drs Sipke Visser, Jens Bos and Bert Bijker both in terms of
extending the database with new regions as well as with additional years and
integrating within the Mondriaan project/foundation. Currently, 600,000 persons are
included with drug use up to and including 2013. All research lines benefit from this
development, inclusive pharmacoeconomics. Also, further steps were taken in
enabling the effective linkage of IADB.nl with CBS as of January 1st 2014.
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2013 brought 2 further thesis defenses in the area of pharmacoeconomics by Dr
Albert-Jan van Hoek and Dr Mark Rozenbaum. Dr Petros Pechlivanolou supervised by
a team of Prof Maarten Postma, Prof Jan Wilschut, Prof Toos Daemen, Prof Hans
Nijman (all 3 UMCG), Prof John Edmunds, Prof Liz Miller (both HPA) and Prof
Eelko Hak. Dr Petros Pechlivanoglou left the Unit for the University of Toronto, but is
still involved in specific issues of the Unit, for example, in the supervision of Drs
Jelena Stevanovic, who continued her work in the area of cardiology, in particular,
stroke prevention’s cost-effectiveness in patients with atrial fibrillation.
Various new projects were attracted from both the private and the public sector in
2013, including WHO, EU, GSK, Roche, Shire, Boehringer Ingelheim and ZonMw.
Both Dr Stefan Vegter and Drs Job van Boven contributed highly to attracting these
projects often involving the specific areas of COPD, osteoporosis and Parkinson. In
particular, they continued their work on the pharmacoeconomics of pharmaceutical
care, attracting a new grant from the KNMP, publishing in high-impact journals (JvB
and SV had 5 papers as first and last author in 2013) and lecturing at national and
international platforms.
Co-operations – inclusive joint supervision of PhDs – have been continued with the
Health Protection Agency (London), Mahidol University (Bangkok) and University of
Ghent (Belgium) and extended with Hacettepe University (Ankara) and Hanoi
Medical University (Vietnam).
Clinical Pharmacoepidemiology
Within the research line Clinical Pharmacoepidemiology the strong focus on the
conduct of methodological studies was further continued in 2013. Prof Eelko Hak,
program leader, spent his last visiting professorship at the department of Applied
Mathematics, Computer Science and Statistics, Faculty of Sciences of the University
of Ghent to review and discuss valid design and analytical approaches towards the
control of confounding in observational drug effect studies with Prof Stijn
Vansteelandt. In a formal collaboration between the two universities and with Dr
Fanny Janssen from the Department of Demography, cand PhD Maarten Bijlsma is
developing new statistical models to assess demographic changes in medicine use and
effects of medicines at a macro and micro-level. For these studies, data from the inhouse prescription database IADB.nl (see website) has been linked to Statistics
Netherlands (CBS) data on mortality and hospitalizations. Bijlsma, who almost obtains
his master degree in Statistics, also advised some investigators on statistical aspects
and, for example, developed a simulation study on the required number of outcome
measurements and consequences for statistical power and numbers of patients with Dr
Hiddo Lambers-Heerspink from the Clinical Pharmacy research unit. Bianca Mulder
successfully continued her methodological studies during a combined PharmD-PhD
trajectory and applied variations on the case-crossover study, case-control and cohort
design using more than 40,000 linked infant-mother pairs from the IADB.nl database.
Her studies into the association between gastric-acid reducing medication during
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pregnancy and asthma development in infants were presented at the ISPE congress in
Montreal and published in the influential JACI journal. Dianna de Vries, who also
combines her studies with PhD research, successfully meta-analyzed the effects of
statins in diabetes patients and applied an unique matched cohort analysis to assess the
effects of a cardiovascular event on compliance. This information will be used to build
valid cost-effectiveness models including “real world” risk and compliance data.
Further, the unique research line on geographical spread and spatio-temporal
prediction of medication use has been continued by PhD-student Aletta Dijkstra and a
report was published in Plos One. PhD student Koen Pouwels continued his work on
the empirical comparison of results from trials, case-crossover and prescription
symmetry analysis, and published in Br J Clin Pharmacy and Drug Safety. He is also
collaborating with Prof Petra Denig from the Clinical Pharmacy department to link the
primary care data on 17,000 diabetes patients with hospital data to determine the
accuracy of medication proxies and to validly estimate long-term effects taking
mediators and confounders into account. Cand PhDs Giedre Gefenaite and Maryam
Darvishian succeeded to publish an innovative bias-adjusted meta-analysis on the
effects of influenza vaccination among elderly in close collaboration with the
Cambridge Statistical Medical Research Center in the Journal of Clinical
Epidemiology. Gefenaite, in close collaboration with cand PhD Janette RahamatLangendoen, from the Virology Department conducted an innovative test-negative
case-control study in Lithuania which has been accepted by Vaccine. This project was
conducted in close collaboration with European hospital network to assess influenza
vaccine effectiveness in hospitals, coordinated by EpiConcept (Paris). In close
collaboration with Prof Edwin van den Heuvel from the Epidemiology department and
Maarten Bijlsma, Maryam Darvishian has been conducting a meta-analysis on testnegative case-control designs among elderly applying generalized mixed models to
adjust for confounding and between study differences. Also, Josien RiphagenDalhuisen (cand GP) successfully defended her thesis on development and evaluation
of intervention programs to increase influenza vaccine uptake among health care
workers. She supervised a new implementation project financed by ZONMW to install
the developed educational intervention in most hospitals in the northern region. Within
the research line many publications appeared, amongst which Q1-publications in
JACI, Drug Safety and Clin Exp Allergy. A highlight this year was the successful
awarding of the European FP7-project UNISEC coordinated by Prof Erik Frijlink, Dr
Ed Schmidt, Prof Anke Huckriede, and Prof Eelko Hak. Our research line will be
responsible for the conduct of two large multi-country phase 2 trials with promising
universal flu vaccines. Dr Marcy Heng Liu, who is a postdoc in Vaccinology, will
work in close collaboration with the Trial Coordination Center on the development
and installment of these trials. Finally, the research track in Pharmaco-epidemiology
within the two-year Master of Medical Pharmaceutical Sciences has been started in a
pilot phase. In the track all four units of the SHARE program M2O participate,
involving lectures and supervision of Master projects.
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Targeted & Personalized Drug Therapy
In 2013 we continued the data collection for the ‘diabetic cohort’ that is part of the
EUROmediCAT FP-7 research project. Dr Hao Wang is appointed as post-doc on this
project and has the lead in this research. Aiming to include at least 1200 diabetic
pregnant women, we actually were able to include 1800. Seven countries were
included in this study. We found the use of human insulin is more frequent than the
use of analogs in our study population. The data are checked and cleaned and during
2014 we will start the analyses. Use of human insulin appeared to be more prevalent
than that of analogs and subsequently the risk on major heart defects will be studied
for both groups of insulins.
In line with previous analyses in this area, we will study the relation between the use
of the new anti-epileptics (as topiramate) during pregnancy and congenital anomalies,
using the EUROCAT Antiepileptic Drug Database that covers a population of nearly
10 million births from 20 European countries. A current signal of topiramate and clefts
will be evaluated this year.
Our unit is also involved in one of the work packages of the European IMI project
PROTECT with PhD-student Priscilla Zetstra-van der Woude is the PhD student
working on this project. We try to get direct and continuous information on drug use
and life style factors in pregnancy from women themselves by using a web-based
questionnaire. Four countries are involved: UK, Denmark, Poland and the
Netherlands. Currently we have included a total of 2000 women. Additionally, Profs
Hak and Wilffert and Dr Nynke Schuiling-Veninga contribute strongly to this line of
research with analyses using IADB.nl looking into associations between maternal drug
use and outcomes in children.
Finally, screening (in pregnancy) remained an issue in this area, for example,
regarding pre-eclampsia (EU-project), HCV and HIV (publications in PloS One and
AIDS).
Next to pregnant women, further specific (vulnerable) groups considered in this line of
research are elderly, children and patients in need of orphan drugs. Notably
publications referred to the costs of ADHD in schoolchildren (Hoa Le et al in Eur
Child Adolesc Psychiatry and Kotsopoulos et al in J Mental Health Policy Econ),
vaccination against herpes zoster (de Boer et al in Vaccine) and everolimus treatment
in renal cell carcinoma (Mihajlovic et al in Clin Ther).
One of the foci in personalized medicine remained on the pharmacoepidemiological
analysis and economic impact of pharmacogenetic testing, for example, for antidepressive treatment and treatments in acute and non-acute cardiology (all 3 projects
financed by the MoH). Publications are obviously expected in 2014. Also, next year
one thesis defense is expected in the area of individualized medicine using diagnostics
for (in) fertility treatments.
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Unit Pharmacotherapy & Pharmaceutical Care (PT/PC)
Pharmaceutical care
This year, joint efforts in collaboration with the European Medicines Agency (EMA)
in London, and EU’s DG SANCO have been started for improving the patient package
inserts for medicines that impair driving and belonging to categories II and III
(moderate and severe impairment), according to the DRUID categorization system. A
research paper was published on the effectiveness of pictograms in communicating
risk about driving-impairing medicines (cand PhD Susana Monteiro). Research efforts
in 2013 have been focused on investigating the added value of using the DRUID rating
pictogram compared to the yellow-black sticker used in the Netherlands since 1973 to
warn patient about the driving impairing properties of their medicines.
A PhD thesis defense by Timothy Broesamle on the topic designing health care
services using systems thinking was considered as a landmark to initiate new research
projects in developing integrated pharmaceutical care. Several research papers by
Marlies Geurts have been published or accepted in 2013. One on using concordance
self-completion forms in providing pharmaceutical care at the start of a chronic
treatment; another one on medication assessment tools in cardiovascular patients. A
paper on the development of a web-based pharmaceutical care plan in integrated
pharmaceutical care has been accepted.
In 2013 a new PhD research project started to investigate the effectiveness of
information received by the patient at the start of and after being involved in a clinical
medication review. Next to the patient’s own needs, also the needs of the patient’s
caregivers were investigated. A new format for providing patients (and their care
givers) information after a clinical medication review has been proposed
Pharmacovigilance
Prof Kees van Grootheest is holding the chair on Pharmacovigilance. Courses in
Pharmacovigilance are given to Pharmacy students in their first, third and fourth year.
In the final phase of the study, Pharmacy students – and also medical students –
receive instructions about how to report an adverse drug reaction (ADR) and are
obliged to send in at least one adverse drug reaction, seen by them during their
internship in a (hospital) pharmacy.
Two PhD students started their PhD study in Pharmacovigilance in 2013: Léan Rolfes
and Loes de Vries in combination with their practical work in Pharmacovigilance at
the Netherlands Pharmacovigilance Centre Lareb. This work is done within a
successful co-operation between the University of Groningen and the Netherlands
Pharmacovigilance Centre Lareb, in education, research and supervision of students in
bachelor and master theses.
Also in 2013 the International Meyler Course ‘Introduction to Pharmacovigilance’ has
taken place; 23 students from 10 different countries joined this one week course.
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Hospital & Clinical Pharmacy
Prof Jos Kosterink was appointed as professor within the Unit of PT/PC in November
2011. He is also head of the Department of Hospital and Clinical Pharmacy of the
UMCG. His research focuses on personalized medicine and targeted pharmacotherapy.
This research is in strong collaboration with several other sections in a
multidisciplinary setting (pharmaceutical technology and biopharmacy,
pharmacokinetics, toxicology and targeting), departments of the UMCG (medical
oncology, cardiology, infectious diseases, hematology, nuclear medicine and
molecular imaging and of course hospital and clinical pharmacy), other Universities
(VU, UU, Radboud UN) and pharmaceutical industries. A part of the research is done
in the CTMM network. Around 15 PhD students are working on this research-line
under his (co)supervision. One specific area of research involves new
radiopharmaceuticals for molecular imaging in oncology. He is also responsible for
several educational courses within the master program: Hospital Pharmacy and
Pharmacotherapy of Cardiovascular Diseases.
Besides that he supervises students with their bachelor project, practical training or
internship hospital pharmacy. Several individual lectures are given within the bachelor
and master program.
Psychiatric Pharmacotherapy
Prof Anton Loonen continued the research with the Mental Health Research Institute
of Tomsk, Siberia (Prof SA Ivanova). This project has extended with the participation
of the department of Biological Psychiatry of the UMCG (Prof PG Luiten and Dr
ULM Eisel). The collaboration with GGZ Westelijk Noord-Brabant on methods to
improve medical and pharmaceutical care for ambulatory chronic psychiatric patients
resulted in the PhD graduation of Fenneke van Hasselt. Additionally, the collaboration
with the department of Clinical Neuropsychology of the UMCG (Prof WH Brouwer)
on the neuroscientific origin of akathisia was continued.
Clinical Pharmacotherapy
Prof Eric van Roon is holding the chair on Clinical Pharmacotherapy from June 16
2013. Courses in Clinical Pharmacotherapy within ‘Algemene Farmacotherapie’ en
‘Specialistische Farmacotherapie’ are given to Pharmacy students in their third and
sixth year. In 2013 2 BSc-project students and 10 master students in stage P and
‘Masteronderzoek’ received supervision from Prof van Roon.
Two PhD students started their PhD work in 2013 within the field of Clinical
Pharmacotherapy. K Boslooper MD started her work within the field of outcome
research in Diffuse Large B-cell Lymphoma. This PhD work is a cooperation with the
departments of Haematology of the Medisch Centrum Leeuwarden and the UMCG. M
Simoons PharmD started her PhD work in Assen on the topic of outcome monitoring
in patients treated with psychotropics in outpatient GGZ care facilities in Northern
Netherlands. Her work is a cooperation with the University Center of Psychiatry
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Groningen (Dr E Ruhé MD), the department of Clinical Pharmacy of the Wilhelmina
ziekenhuis in Assen (Dr H Mulder PharmD) and the GGZs in Drenthe, Groningen and
Friesland. JP Yska PharmD is continuing his PhD work in the field of bariatric
surgery.
Medication Safety
Prof Katja Taxis continued the research on global medication safety, particularly
focusing on interventions which are applicable in low- and middle income countries.
In this research line, we welcomed Thang Nguyen from Vietnam as a new PhD
student and, in cooperation with Dr Peter Mol, from the UMCG, Department of
Clinical Pharmacology, Derbew Fikadu Berhe from Ethiopia. Both PhD projects are in
the area of cardiovascular diseases, which present an increasing problem in those
countries. Work of Abera Berhe was presented at the International Conferenence on
Pharmacoepidemiology in Montreal, Canada. PhD student Huong Thao Nguyen nearly
completed her PhD on medication safety in Vietnamese hospitals having amongst
others a publication in BMJ Quality and Safety in Health Care. She will defend her
thesis in spring 2014. Within the Dutch hospital setting, Willem van der Veen PharmD
continued to investigate the safety of electronic prescribing systems in hospitals.
Within the area of medication safety in vulnerable patient groups (psychiatric and
nursing home patients), Irene Lako defended her PhD thesis (more information about
her project can be found elsewhere in this report). Psychologist Dr Hans Wouters
joined us in June 2013 as a postdoc to study the cost-effectiveness of medication
reviews in nursing home patients (funded by ZonMW). The project is a
multidisciplinary cooperation with nursing homes and hospital pharmacies
(Martiniziekenhuis, Wilhelmina Ziekenhuis in Assen and Diaconessenziekenhuis in
Meppel). A lot of time was spent on preparing the trial and we will start including
patients in June 2014. Furthermore, cooperations with researchers from Australia (Dr
L Pont, University of Sydney) and the UK (Prof C Anderson, University of
Nottingham) were strengthened by sending in total four Master students abroad for
their Master thesis. Amongst other projects, we completed a study on comparing
prescribing patterns between Dutch and Australian nursing homes. Some highlights of
activities within scientific societies include that Prof Taxis has become chair elect of
the SIG on Drug Utilisation Research of the International Society of
Pharmacoepidemiology. As member of the European group on drug utilisation she is
co-organiser of the EuroDURG Conference 2014 which will take place in Groningen
in August 2014 (www.eurodurg2014.com). Within the Netherlands she continues to be
president of the PRISMA network (Praktijk Research In Samenwerking Met
Apothekers) which has successfully organised a conference on pharmacy practice
research in January 2013 with another one planned in May 2014
(www.knmp.nl/agenda/prisma-symposium).
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Pharmacotherapy & Pharmacogenetics
In close collaboration with Prof Eelko Hak, Prof Maarten Postma and Prof Koos
Brouwers in his position in EPHOR, in 2011 a ZONMw grant was obtained in the
Program Priority Medicines in Elderly: “Effects and Cost-Effectiveness of
Pharmacogenetic Screening among Elderly Starters with Antidepressants: A Pragmatic
Randomized Controlled Trial.”. In September 2012 Lisette Berm started as PhD on
this project and in 2013 put a lot of energy in the inclusion of patients and extending
the participating centers. Furthermore, she started presenting and publishing data on
the developed Dried Blood Spot assays for venlafaxine and nortriptyline and wrote a
letter to the Editor of Clinical Psychiatry on Phenoconversion of cytochrome P450
2D6: The need for identifying the intermediate metabolizer genotype.
In 2013, we started 2 PhD-projects with Hao Tran (April) and Aizati Daud (October)
on pharmacogenetics in drug-induced birth defects. In their supervisers we combine
the expertise on medication in pregnancy of Dr Hao Wang of the Unit PE2 and Dr
Marian Bakker, Dr Jorieke van Kammen-Bergman, Dr Hermien de Walle, all
epidemiologists at EUROCAT at the Department of Genetics from the UMCG, with
our knowledge on pharmacology and pharmacogenetics. With the research line
Pharmacogenetics in drug-induced birth defects, we participate within SHARE in both
M2O and ROAHD. Aizati Daud is finishing a review on the role of polymorphisms of
placental transporter proteins in drug-induced birth defects and preparing a population
based case only study. Hao Tran is finishing a review on cohort studies on druginduced birth defects by drugs acting via vascular disruption and is starting up a casecontrol study in EUROCAT.
In close collaboration with Prof Petra Denig and Dr Hiddo Lambers Heerspink from
the department of Clinical Pharmacology and Prof Eelko Hak, we started a PhDproject with Doti Parameswari on pharmacogenetics and response to oral antidiabetics.
Parameswari is now finishing a systematic review on predictors of response in initial
users of metformin and sulfonylurea derivatives and started with a retrospective cohort
study in the GIANTT database (diabetes patients) on this topic.
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Research Institute SHARE (director: Prof MJ Postma)
Program: Methods in Medicines Evaluation & Outcomes research (M2O)
Program leaders
Prof P Denig (UMCG)
Prof E Hak (RUG) since Oct 2013 / Prof MJ Postma (RUG) until Oct 2013
Mission & Context
How can we grow old in good health? How can we prevent complications associated
with chronic disease? How can we increase quality of life for all and especially older
people and reduce costs of an ageing society? How can we support and maintain
participation of individuals in a rapidly changing society and for an ageing population?
The ultimate mission of M2O is to contribute to the science and understanding of
healthy ageing through development, validation and application of scientific
methodologies for (pharmacotherapeutic) interventions and implementation in health
and disease.
In particular, clinically relevant Big Data from patient cohorts are used to develop and
apply advanced methods to further expand scientific knowledge on determinants and
effects of drug treatment and other medical interventions in practice, and to support
decision making and optimal use of (pharmacotherapeutic) interventions. Scientific
research is conducted applying both experimental and non-experimental
epidemiological studies, economic evaluations, health technology assessments
(HTAs), and tools and methods to support high-quality treatment decisions.
Main Fields
Drug Utilization, Clinical and Genetic Pharmacoepidemiology, Pharmacotherapy &
Pharmacovigilance and Health Economics & Health Outcomes Research comprise the
major fields of M2O. Within these fields, the following research themes feature.
Optimizing treatment
 Analyses of drug utilization and quality of pharmacotherapy, with a focus
on multi-factorial diseases (in particular diabetes, cardiovascular and
nephrological diseases), and on monitoring and management of
medication safety and medication errors in vulnerable patient groups (e.g.
elderly and psychiatric patients)
 Personalized and targeted (drug) treatment in elderly, patients with multimorbidity, children and newborns, pregnant women and patients with
psychiatric disorders
 Conduct interventions to counter suboptimal treatment or further enhance
the quality existing interventions
 Health economics in vaccinology, (preventive) drug therapies and
medical interventions
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Development and application of advanced methodologies
 Causal research using observational individual and aggregated
population-level patient data by use of information from Big Data stored
in large databases, such as IADB, Eurocat, GIANTT, LifeLines, Lareb,
PHAMOUS, VIPP, GPRD and RNG
 Conduct of (bias-adjusted) systematic meta-analyses and mixed-treatment
comparisons
 Developing health economic models in a multidisciplinary environment
 Research into methods optimizing patient reported outcome measures
M2O is steered by two units from the Department of Pharmacy and two units from the
UMCG, i.e. PharmacoEpidemiology & PharmacoEconomics (PE2, Pharmacy),
Pharmacotherapy & Pharmaceutical Care (PT/PC, Pharmacy), Clinical Pharmacy &
Pharmacology (Drug Utilization unit, UMCG) and the Health Technology Assessment
(HTA) unit of the Department of Epidemiology (UMCG).
As part of the M2O research program, large scale medical and pharmaceutical
databases are used and research takes advantage of the presence of the unique stable
population of the Northern provinces of the Netherlands. By joining forces, major
advancements have been made in the organization and validation of existing ongoing
data collections (for example, IADB, VIPP and GIANTT) as well as through
combining ideas and methods from the different multidisciplinary units (PE2, PPC,
Drug Utilization, and HTA). We aim to stabilize and further increase the funding for
these “Big Data laboratories” and strengthen our grant positions by joint research
projects. The ageing of the population and the vast and accruing possibilities for
pharmacotherapy – both curative and preventive – pose challenges that cover a broad
range of research sectors, even beyond pharmaceutical and medical sciences. This
requires collaborations even beyond the M2O or SHARE internal structures, for
example, with fields of sciences as demographics, economics and psychology, and
ongoing projects have been started.
The M2O program ideally fits into the Health Aging theme of the University of
Groningen. One example of the focus on healthy ageing concerns the topic of
vaccination throughout the life course from childhood to adolescence and from
maternity to seniorship.
Staff involved
Prof JRBJ Brouwers
Prof E Buskens (UMCG)
Dr TL Feenstra (UMCG)
Prof FM Haaijer-Ruskamp (UMCG)
Dr FJ Janssen
Dr HJ Lambers Heerspink (UMCG)
Prof K Taxis
Prof B Wilffert
Prof P Denig (UMCG)
Prof H Groen (UMCG)
Prof E Hak
Dr PFM Krabbe (UMCG)
Prof MJ Postma
Dr Hoa Wang
Prof AC van Grootheest
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3. Thesis defenses 2013
Peter ter Horst
Promotores:
Thesis defense:
Prof B Wilffert
Prof LTW de Jong-van den Berg
January 11th 2013
“Clinical Pharmacology of Antidepressants during Pregnancy”
Antidepressants are frequently prescribed in general and also to women of fertile age.
The risks of these drugs during pregnancy are not fully known, however also the risks of
not using these drugs during pregnancy in case of major depressive disorder (MDD), are
not well understood.
In the thesis, scientific literature has been searched for possible aspects which may play
a role in using antidepressants during pregnancy. One of the main findings was that all
antidepressants pass the blood-placenta barrier, which means that antidepressants reach
the embryo, while organ systems are developing. Most antidepressants can be used
safely during pregnancy; however paroxetine may cause heart valve defects and leads to
an increased pulmonary blood pressure. Therefore paroxetine should not be prescribed
anymore during and just before pregnancy. The pharmacological effect of SSRIs for
MDD is only small. The use of SSRIs for MDD should therefore be reconsidered,
especially during pregnancy. In case of MDD one of the tricyclic antidepressants
(TCAs) should be prescribed. Antidepressants have been used in combination with other
drugs during pregnancy. It is not known whether these combinations leads to an increase
of risks, and therefore this should be further studied.
The newborn might be affected by antidepressants as neonatal withdrawal signs may
occur. The scientific literature has been screened whether dose adjustments of
antidepressants should be made, because of possible increased volume of distribution, or
a change in absorption of antidepressants from the alimentary tract, or a change in the
elimination of antidepressants by the liver. However, this kind of information was
insufficiently available, and therefore more studies are needed.
Next, pharmacokinetics of clomipramine, one of the TCAs, during pregnancy has been
studied. From pregnant women using this drug, every trimester blood samples have been
taken and the CESID score for depression. Three months after delivery, a sample was
taken to use as an estimate of the blood concentration of clomipramine before
pregnancy. We found that the clearance of clomipramine did not change during
pregnancy and that CES-D scores remain constant suggesting therapeutic concentrations
of clomipramine. From this study we concluded that pregnant women do not need
increased clomipramine doses, however the number of patients in our study was small.
Also, children in utero exposed to clomipramine were followed during the first days
after birth. Many of those children suffered from withdrawal of clomipramine, which in
general was mild and transient. Most symptoms were sleep- and eating problems, and
13
shivering’s. However in two cases we noticed cyanosis and tachycardia. These neonatal
signs and increased half-life, are reasons for a longer than 48 hours observation period
of these newborns in the hospital to be recommended, to be sure that serious withdrawal
will not happen anymore.
Finally, the scientific literature has been searched for the possibility that antidepressants
might affect the development of the a1in1entary tract. SSRIs have an influence on the
development of the early a1in1entary tract, the enteric nervous system (ENS), by
binding to the serotonin transporter (SERT) and by binding to a specific receptor
subtype (5-HT2). This might influence the development of new cells of the ENS.
Albert Jan van Hoek
Promotores:
Prof MJ Postma
Prof WJ Edmunds
Prof E Miller
Thesis defense:
February 25th 2013
“The Epidemiology and Cost-effectiveness of Vaccination Strategies against
Infectious Diseases: a Focus on Varicella Zoster, Pandemic influenza A/H1N1 2009,
Streptococcus Pneumonia”
Varicella zoster virus causes chickenpox en shingles. A vaccine is available against both
diseases. Notably, Dr van Hoek shows that vaccination of elderly against shingles is
cost-effective in England, and marginal cost-effective in the Netherlands. Next, the
question if children should be vaccinated against chickenpox is investigated. It is
suggested that when there is no chickenpox around the chance to develop shingles
increases. Therefore vaccination against chickenpox is only cost-effective on the very
long term; when everybody is less likely to develop shingles due to childhood
vaccination.
During the 2009 H1N1 pandemic the question was raised how to use the pandemic
vaccine: only vaccinating children, elderly, risk groups or a combination. In the thesis
the impact of H1N1 on the quality of life is described and a ‘real time’ cost effectiveness
analysis is presented. Van Hoek’s analysis shows that focussing on risk groups was the
best use of the vaccine in England at the time the vaccine was available.
Streptococcus pneumoniae is a bacteria with 90+ serotypes.Subsequently, the effect and
impact of serotype replacement is analysed, as the conjugate vaccine (PCV) only
protects against 7, 10 or 13 serotypes. It is shown that vaccinating risk groups with PCV
is not cost-effective, but - using serotype specific disease outcomes – it is concluded that
vaccination of children with PCV is still cost-effective.
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Mark Rozenbaum
Promotores:
Prof MJ Postma
Prof E Hak
Thesis defense:
February 25th 2013
“Cost and Effectiveness of Extended Vaccination Strategies against Pertussis and
Pneumococcal Disease”
A crowded vaccination schedule and restrained health–care budgets limit the uptake of
new vaccines into the Dutch national immunization programs (NIP). Next to many other
factors, cost-effectiveness considerations highly influence the decision whether to
introduce vaccines into Dutch NIP.
The first part of this thesis focuses on the (cost-) effectiveness of pneumococcal
vaccination. It is shown that there are large differences in the observed disease
epidemiology after implementation of paediatric pneumococcal immunization programs
between the USA and Europe. In Europe, less cases of pneumococcal disease were
avoided in unvaccinated individuals (herd effects) than in the
USA, while significant replacement was observed in Europe with strains not included in
the vaccine.
As a consequence, the 7-valent pneumococcal vaccine, which was previously used in the
Dutch NIP, was less cost-effective as predicted beforehand. More valent pneumococcal
vaccines are more likely to be considered cost-effective as more direct and herd effects
and less serotype replacement effects are expected. These potential herd effects reduce
the cost-effectiveness of elderly and adult (risk) groups vaccination in time. In
particular, a modelling study showed that vaccinating risk groups in England was
unlikely to be considered cost-effective in the base-case analysis unless the vaccine
would also offer protection against non–bacteraemic pneumonia. Evidence on whether
the latter occurs is awaited from a large Dutch clinical trial.
The second part of the thesis explores the impact of extending the childhood pertussis
vaccination program to adolescents and adults. Given the nature of the problem, the
development of a complex population dynamical model was required. The developed
dynamic model showed that the most (cost-) effective age for the introduction of an
additional booster is around 12 years. Nevertheless, this strategy only offered limited
indirect protection to the (partly) unvaccinated infants with potentially most serious
disease which might be considered the primary aim of extended pertussis vaccination.
In conclusion, the dynamics of infectious diseases makes it challenging to predict the
impact of new vaccination programs. Extending the vaccination programs against
pneumococcal disease and pertussis offers the possibility to prevent morbidity and
mortality and decrease the economic burden of disease for society.
15
Irene Lako
Promotores:
Copromotores:
Thesis defense:
Prof K Taxis
Prof D Wiersma
Dr R Bruggeman
Dr CJ Slooff
March 22nd 2013
“Depressive Symptoms in Patients with Schizophrenia. Count symptoms that Count”
Patients with schizophrenia frequently suffer from co-morbid depressive symptoms.
Antidepressants are frequently prescribed and maintained in the treatment of depressive
symptoms. In clinical practice, clinicians may have difficulties to adequately distinguish
depressive symptoms from other psychotic symptoms in this population. The use of
validated depression instruments may help the clinician in the recognition of depressive
symptoms. Systematic literature review showed that the Calgary Depression Scale for
Schizophrenia (CDSS) is the most reliable and valid depression instrument in this
population. We would recommend the clinician to use the CDSS interview for the
measurement of depressive symptoms in daily clinical practice of patients with
schizophrenia.
Depressive symptoms can be a side effect of antipsychotics. This thesis demonstrated
that especially those patients using one or more antipsychotics frequently attributed their
depressive symptoms to antipsychotics. A dose-response relationship between
depressive symptoms and dopamine D2 receptor occupancy in the brain could, however,
not be confirmed in patients using antipsychotic monotherapy. Although this research
cannot recommend the use of certain antipsychotic types or doses, we would
recommend being cautious with prescribing antipsychotic combination therapy in
patients with schizophrenia.
Furthermore, this thesis described the development of the short version of the Subjects’
Response to Antipsychotics (SRA-34) questionnaire, which can be used to evaluate
desired and undesired effects of antipsychotics. The short and easy-to-use SR-34 may
support the clinician to evaluate and address the individual needs of a patient.
Tjalke Westra
Promotores:
Thesis defense:
Prof MJ Postma
Prof JC Wilschut
Prof CAHH Daemen
Prof HW Nijman
April 17th 2013
“Health-economic modelling of human papillomavirus vaccination”
Since 2009, 12-year-old Dutch teenage girls are offered vaccination against human
papillomavirus (HPV). HPV is a sexually transmitted virus that can cause cervical
16
cancer in women. Although the available vaccines potentially provide protection against
70% of cervical cancer cases, implementation of HPV vaccination was strongly debated
in The Netherlands, because of safety issues and the high costs of vaccination.
Presumably due to this debate, the current vaccination coverage among teenage girls is
only approximately 50%.
In this thesis, health economic models were used to assess the effectiveness and costeffectiveness of HPV vaccination. HPV vaccination was found a highly effective and
cost-effective intervention for young teenage girls. In particular, despite the relatively
low vaccine uptake, approximately 50-60% of cervical cancers can be prevented by the
current HPV vaccination programme. To further reduce the burden of cervical cancer,
either vaccination of older girls/women or vaccination of boys could be considered.
Westra found that both strategies, in combination with the current vaccination
programme, are cost-effective. However, vaccination of boys is no longer cost-effective,
if vaccine uptake among girls would exceed 70%. Finally, currently two registered HPV
vaccines are available, a bivalent and a quadrivalent vaccine. The quadrivalent vaccine,
which not only protects against cervical cancer but also against anogenital warts, was
found to be slightly more cost-effective than the bivalent vaccine, despite the fact that
the latter provides superior protection against cervical cancer. For well-informed
decisions about the preferred vaccine, these considerations need to be taken into account
during new tenders.
Josta de Jong
Promotor:
Copromotor:
Thesis defense:
Prof LTW de Jong-van den Berg
Dr TW de Vries
May 31st 2013
“Antibiotic drug use in children. Pharmacoepidemiologic, practical, social en
environmental perspectives in the Netherlands”
Antibiotics are commonly used in children, their use should however be monitored
critically. Use can contribute to antibiotic resistance for bacteria, which is nowadays a
great concern. In her thesis Dr de Jong described the current use of antibiotics in
children (0-19 y). This can give us leads to prevent antibiotic resistance.
For her studies she used the IADB.nl database, a pharmacy prescription database
covering a population of approximately. 120.000 children. She mapped the antibiotic
use in children and compared that with the current guidelines and the use of antibiotics
in other European countries. As expected, she concluded that the use in the Netherlands
is comparable with other northern European countries but is less than in the southern
European countries. Also, antibiotics were more often prescribed than recommended in
guidelines. Among children below the age of 4, antibiotics use was the highest among
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children under 1 year of age, and often their use was off-label.
In the pharmacy, parents were asked on the practices and problems they encountered
while giving an antibiotic course to their child. Although the compliance was high,
adverse effects and administration problems were reported in over 20% of the children.
Dr de Jong found that in children who used antibiotics more often allergy and skin
reactions occurred.
In another part of her thesis, she studied the social and environmental factors related to
the antibiotic use of young children aged 0-5 years. In one study she compared the
medication use of parents of children using antibiotics recurrently with parents of
children not taking any antibiotic. She found that parents of children using antibiotics
recurrently, not only used more antibiotics but also analgesics and psychotropic
medication was used relatively often.
Finally, the thesis aims to relate human and animal factors. The overuse of antibiotics in
cattle in the Netherlands is suspected to be a factor causing infections of resistant
bacteria in humans, especially in those who have regular contact with cattle, such as
farmers. She compared the antibiotic use of people living in rural areas with those living
in urban areas and found differences, which could be a consequence of veterinarian
antibiotic use. In particular, more frequent need of a second antibiotic course in the rural
areas compared with the urban population was identified.
Compared to southern Europe, the Netherlands are doing relatively well in the field of
antibiotics in children. Nevertheless improvements are necessary. Improved adherence
to guidelines, reduced not-registered antibiotics in young children, increased attention to
and education of parents and decreased use of antibiotics in animal husbandry, could all
contribute to decreasing of antibiotic resistance and enhanced rational prescribing.
Timothy Broesamle
Promotores:
Prof JJ de Gier
Prof JJ van der Werf
Thesis defense:
June 6th 2013
“Designing Health Care Services Using Systems Thinking: A Theory, A Method and
their Application in the Dutch Community Pharmacy”
Providing health care services is complex. Health care services must be able to function
given multiple environmental influences. They have to take into consideration
organizational constraints stemming from multiple organizations, fit the professional
standards of those providing the service (i.e. be evidence based), meet scientific
standards, and meet the needs of the patient. This dissertation reflects on the premise
that through understanding the relationships between the different health care providers
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and the variability of patients, health care service processes can be designed which
efficiently, efficaciously, and effectively address the needs of the patients.
Using the theory of systems thinking, a theory is developed for understanding different
types of health care service system designs that address the needs of the patient based on
the amount of variation introduced by the patient. System thinking also provides a basis
for a proposed design method that combines the iterative nature of soft systems
methodology and the need to provide evidence that the service is functioning as
intended. The practicality of the proposed Health Cares Service System Design
Typology is analyzed by applying the theory in analyzing the designs of pharmaceutical
care services both in daily practice and in a pilot study of a medication review process.
Finally, an action research study was conducted with a group of first line providers in
designing a new geriatric care service using the theory developed in the first half of the
dissertation and soft systems methodology.
Hoa Dinh Vu
Promotores:
Copromotor:
Thesis defense:
Prof JRBJ Brouwers
Prof DRA Uges
Prof VH Le†/Prof DH Nguyen
Dr JWC Alffenaar
June 28th 2013
“Clinical Pharmacology of Tuberculosis Drugs and Tuberculosis Control in
Developing World. The involvement of Private Pharmacy and the individualization of
treatment using Dried blood spot”
The research of Dinh Hoa Vu emphasized the clinical pharmacology aspects related to
Tuberculosis (TB) control in the developing world, where TB epidemics are serious and
complex. Worldwide there is an alarming increase in multidrug-resistant TB (MDRTB). This increase is now emerging from Eastern Europe and Central Asia. So to attack
TB we need: knowledge by the healthcare workers and easy tests for individual
monitoring of TB therapy.
Vu performed a field study using a simulated patient method and interview, to explore
the TB control activities and knowledge of healthcare providers (HCPs) in private
pharmacies in Hanoi, Vietnam. It was common that HCPs did not refer suspected
tuberculosis patients and advised to dispense rifampicin and fluoroquinolone for the
suspected case. This may contribute to worsening the epidemic and emergence of drug
resistance. Postgraduate teaching for pharmacists in TB control is urgently needed.
Vu developed new and simple methods for monitoring anti-TB drugs in blood, which
can be applied to treatment optimization and adherence control. Only one drop of blood,
drawn by a fingerprick, is needed for analysis. The new method is called Dried Blood
Spot Method (DBS). The patient variation in blood levels of the anti-TB drugs is
variable because of differences in genetics, bodyweight, race etc. The development of
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the DBS for easily implementing therapeutic drug monitoring for MDR-TB in the
developing world is urgently needed. We developed analytical methods for the anti-TBdrugs: moxifloxacin, linezolid, rifampicin and clarithromycin. We figured out technical
and clinical aspects of the DBS analytical method which supports the application of this
tool in a clinical environment. The opportunity to apply DBS to TB control in
developing (poor) countries from the perspective of Good Global Health for all people,
is discussed.
Mehraj Parouty
Promotor:
Prof MJ Postma
Thesis defense:
September 13th 2013
“Inequality Aversion to Posterity: Discounting Human Lives”
The fact that we devalue the lives of our descendants has raised abundant ethical debates
during the past few decades. Economists are saying that, because we value the present
more than the future, this should not exclude anything, not even human lives. In an
attempt to bring ethics in symphony with economics, this thesis proposes that our
decisions depend on what we aspire for.
This thesis first points out the ethical debates around the devaluation of future health
with respect to cost-effectiveness of vaccination programs with the aim to achieve
morally correct cost-effectiveness analyses. However, ethically correct decision rules
should also be theoretically correct. Theory suggests the adoption of the Ramsey
discount rate, at least for money. For health, theoretical arguments exist that, firstly, the
pure rate is circular reasoning for human lives; secondly, the growth rate should be
based on growth in life expectancy and, thirdly, the elasticity for a life year is assumed
to derive from a linear utility function for life years which can be disputed. Considering
growth rates of GDP compared to life expectancy, suggests moderate growth in life
expectancy compared to growth in GDP and a lower discount rate per se. Given the lack
of motivation for an equal rate for costs and health, the thesis investigates whether
individuals discount health at a lower rate emprically. A questionnaire was designed that
allows us to compare discount rates for health and money, while keeping all questions,
as far as possible, similar for both money and health. Indeed differential rates were
identified, as well as differential rates among population characteristics such as health
states and in time. Given the lack of theoretical motivation for equal discounting and our
empirical results, differential discounting is strongly supported.
Majorities of national bodies however currently suggest an equal rate. Yet, a single
straightforward argument allowing for differential rate for health is the fact that the
monetary value of health need not be constant in time. Given the need for differential
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discounting, a model-consistent expectation is formed of an n-commodity economy
where each commodity grows according to their n different growth functions, rather
than 2 (money and health). Next, the theory is extended with a well-known
psychological posit on the variability of the specious present, both in a deterministic
probabilistic context. The extended n-commodity model allows further research work
into the Utopian goal of global welfare, such as how health states affect discount rates
and how that affects labour markets, GDP etcetera.
Fenneke van Hasselt
Promotores:
Prof AJM Loonen
Prof MJ Postma
Copromotores:
Dr MJT Oud
Dr PFM Krabbe
Thesis defense:
October 25th 2013
“Improving the physical health of people with severe mental illness. The need for
tailor made care and uniform evaluation of interventions”
Patients with severe mental illness (SMI) experience a 13- to 30-year reduction in life
expectancy compared with the general population. The majority of these deaths can be
attributed to an increased risk of physical health problems including cardiovascular
disease and diabetes mellitus. We showed in our studies that the specific needs of these
patients are not taken into account by health care providers.
We asked outpatients with SMI as well as family carers, general practitioners and
mental health care staff to point out the barriers to optimal care for the somatic health of
outpatients with SMI. They stated that patients have a reduced capacity to request help.
Additionally there is lack of structural professional collaboration between general
practitioners and mental health care. In my dissertation we give an overview of potential
solutions based on consensus of all four stake holder groups mentioned.
These policy advices include the advice that mental health care is responsible for the
registration of the individual capacity of every patient with SMI to organise the
necessary care for their physical health. This can be performed through a physical health
check. We develop a physical health check which includes an interview, laboratory
assessment and information from the pharmacy and general practitioner. Our study
showed that a health check intervention detects important diseases in outpatients with
SMI that were not previously known to the general practitioner at reasonable cost. This
intervention provides the opportunity to give tailor made advice to individual patients.
21
Josien Riphagen-Dalhuisen
Promotor:
Prof E Hak
Thesis defense:
October 28th 2013
“Influenza Vaccination of Healt Care Workers”
If more hospital doctors and nurses were to be given a flu jab, fewer hospital patients
would contract flu and/or develop pneumonia. This is the conclusion reached by UMCG
researcher Josien Riphagen on the basis of her research findings. She devised a
campaign that resulted in a 23.7% rise in the vaccination rate among hospital staff, while
the number of patients who contracted flu and/or developed pneumonia while in hospital
dropped from 9.7% to 3.9%. ‘So doctors and nurses who have a flu jab really do help to
prevent flu from spreading among patients’, explains Riphagen.
Riphagen developed the flu jab campaign on the basis of a questionnaire among hospital
staff. ‘This helps us to understand the factors that encourage or discourage staff from
having a flu jab.’ As an example, Riphagen cites the timing. It is important to offer flu
jabs at a convenient moment, at the time when shifts change, for example. The
vaccination campaign was supported by the V&VN Dutch Nurses’ Association
(Vereniging Verpleegkundigen en Verzorgenden Nederland).
All eight Dutch university medical centres (UMCs) took part in the study. The two
hospitals that had already introduced an effective vaccination programme for staff took
part as an external control group. Half of the remaining six hospitals launched the new
vaccination campaign and the other UMCs ran the flu campaign that they had used in
previous years. The effect of the new campaign was clear from the marked increase in
the vaccination rate among hospital staff. Riphagen then examined the number of
patients in the hospital who had been infected with the flu virus and/or developed
pneumonia during their hospital stay. She used the figures from the Internal Medicine
and Paediatrics departments in every hospital. The research was carried out during the
flu periods in 2009-2010 and 2010-2011. Riphagen ascertained that 9.7% of patients in
the Internal Medicine departments of the three control UMCs contracted flu and/or
developed pneumonia, compared with 3.9% of the patients in the UMCs that had
introduced the new vaccination campaign. This drop in the number of infections
corresponds with the higher vaccination rate among staff. The flu campaign devised and
introduced by Riphagen ultimately cuts costs. ‘The power of this sustained flu jab
campaign lies in the fact that we try to respond to the thoughts and wishes of hospital
staff. Quite often, they are simply not sufficiently aware. Doctors and nurses need to
know that the vaccination will not only help them, but also, and more importantly, their
patients’, says Riphagen. Prof Hak has now received funding from ZonMw to
implement the vaccination campaign in other hospitals in the north of the Netherlands.
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4. New PhDs & Post-docs and their projects
Pieter de Boer BSc, Cand PharmD
Supervision: Prof MJ Postma, Prof JC Wilschut (UMCG)
Cost-effectiveness of vaccination strategies against several viral infectious diseases
Pieter de Boer (1985) was born in Exmorra, studies pharmacy in Groningen
(University of Groningen) and will graduate as a pharmacist in 2014. During his
master thesis at the department of PE2, he worked on a research project assessing the
cost effectiveness of vaccination of the elderly against Herpes Zoster (shingles).
Nowadays, he combines a 3-year PhD project at the department of PE2 with the final
year of his master’s program. The PhD project focuses on cost-effectiveness of
vaccination strategies against viral infectious diseases. In particular, he models disease
spread of viral diseases in scenarios with or without vaccination, and estimates the
corresponding impact on health-related quality of life and health care/societal costs.
Currently, he is working on cost-effectiveness of an influenza vaccine and a varicella
vaccine.
Marcy, Heng Liu PhD
Supervision: Prof E Hak
Universal Influenza Vaccines Secured (UNISEC)
Heng Liu (1982) was born in Taipei, Taiwan. She obtained her PhD degree in medical
sciences from the University of Groningen in 2013. Her PhD research was focused on
improving the immunogenicity and protective efficacy of influenza vaccines. Several
key aspects were related to vaccine development, such as adjuvantation, formulation
and route of immunization.
After graduation, she joined the Unit PE2 as a postdoc and participates in the UNISEC
project. The project aims at integrating the state-of the-art knowledge and techniques
across Europe for the development and evaluation of universal influenza vaccine. It
expects to introduce influenza vaccines that are able to provide broad immunity for
cross-seasonal protection. She is involved in the phase IIb vaccine clinical trials within
UNISEC.
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Thang Nguyen MSc, PharmD
Supervision: Prof K Taxis
Prevention of inappropriate prescribing in treatment of Vietnamese patients with
cardiovascular diseases.
Thang Nguyen (1985) was born in Vietnam, studied pharmacy in Vietnam, graduated
as a pharmacist in 2008 (Can Tho University of Medicine and Pharmacy) and had a
Master degree in Clinical Pharmacology in 2012 (University of Medicine and
Pharmacy at Ho Chi Minh City). During his studies, he worked on a research project
assessing potential drug-drug interaction in treatment for patients with
multi-drug-resistant tuberculosis (MDR-TB) and proposing the way to prevent drugdrug interaction in MDR-TB patients.
After graduating, he started a 4-year PhD project at the Unit of PT/PC.
His PhD project focuses on prescribing-related problems which are aiming to design
new explicit criteria to improve appropriateness of prescribing in treatment of
Vietnamese patients with cardiovascular diseases.
Didik Setiawan MSc
Supervision: Prof MJ Postma, Prof B Wilffert, Dr J At Thobari
Health Economics of Human Papilloma Virus (HPV) vaccination in developing
countries
Didik Setiawan (1983) was born in Yogyakarta, Indonesia. Studied pharmacy in
Faculty of Pharmacy, Universitas Gadjah Mada (UGM) Indonesia and graduate as a
pharmacist in 2006. He Works as lecturer and researcher on Faculty of Pharmacy,
University of Muhammadiyah Purwokerto with interests in pharmacoeconomics and
pharmacoepidemiology. His Master was finished in 2011 in the faculty of Medicine,
UGM. During his works and studies, he focused the health economics of cancer
(breast, lung, and liver) in Indonesia.
Now, he started a 4-years PhD project at the Unit of PE2. His project focuses on the
cost and effectiveness of cervical cancer prevention programs in Indonesia, consisting
of Human Papillomavirus (HPV) vaccination and cervical cancer screening. This
study will explore cost-effective scenarios in cervical cancer prevention in Indonesia.
24
Pepijn Vemer MSc
Supervision: Prof MJ Postma
Examining the cost-effectiveness of integrated approaches to chronic disease
prevention in Europe (Economics of Chronic Diseases, EConDA)
Pepijn Vemer (1975) was born in Enter and studied Econometrics in Groningen. After
having worked at a health insurer and a consultancy company, he started to work as a
scientific researcher at iMTA in Rotterdam. He’s currently working on finalizing his
thesis, with publications on methodological issue of health economics modeling. The
thesis focuses primarily on transferability of health economic outcomes, and metaanalysis. Currently, he holds a position as scientific researcher at both PE2
(Mon&Tue) and the department of Epidemiology (UMCG, Thu&Fri). His current
projects include a study on model validation (what is it, how should it be done and
why don't people do that?) and a cost-effectiveness analysis on integrated care in
chronic diseases in Europe (EU-project ECONDA).
Dianna de Vries BSc, Cand PharmD
Supervision: Prof E Hak, Prof P Denig, Prof MJ Postma
Primary and secondary prevention of cardiovascular diseases with statins in type 2
diabetes patients.
Dianna de Vries (1989) was born in Delfzijl, she started studying pharmacy in
Groningen (University of Groningen) in 2007, since 2013 she is combining this with
her PhD and expects to graduate in 2014. For her master thesis she performed a metaanalysis on the effectiveness of statin treatment for primary prevention of
cardiovascular and cerebrovascular events in type 2 diabetes patients. She also
assessed the cost-effectiveness of statin treatment for primary prevention in newly
diagnosed type 2 diabetes patients in which real world non-adherence was taken into
account.
Her PhD project will continue on this and will focus on the secondary prevention of
cardiovascular and cerebrovascular diseases. Also, the relation between LDLcholesterol reduction and non-adherence will be determined.
25
Loes de Vries MSc
Supervision: Prof AC van Grootheest, Prof B Wilffert
Drug safety during pregnancy
Loes de Vries (1967) was born in Maastricht, the Netherlands. She obtained her
medical degree at the University of Utrecht. After some clinical work in neurology and
clinical genetics, she started in 2006 at the Dutch Teratology Information Service
(TIS), now part of the Netherlands Pharmacovigilance Centre Lareb. Aim of TIS is
optimizing pharmacotherapy during pregnancy and lactation. Her PhD will focus on
knowledge translation and flow of the teratology information in the Netherlands. She
will develop models to facilitate knowledge exchange between TIS and public health
institutes. Her ultimate goal is to enhance accessibility of adequate teratology
knowledge for health care providers in individual care.
Maarten van Wijhe MSc
Supervision: Prof MJ Postma, Dr J Wallinga (UU)
Measuring the public health benefits of vaccinations in the Netherlands
Maarten van Wijhe (1989), born in Malden, studied Epidemiology at the Radboud
University in Nijmegen. During his studies, he worked on a project at the RIVM
assessing trends in antimicrobial resistance in Escherichia coli using a dynamic
transmission model.
After his graduation in 2013, he started a 4-year PhD project at the Unit of PE2 in
collaboration with the RIVM. In the project he tries to answer the question: to what
extend have vaccines contributed to preventing infections, complications,
hospitalizations and deaths? The main focus is on developing the methodologies to
answer this question using population-based databases (inclusive CBS).
26
Hans Wouters PhD
Supervision: Prof K Taxis
Discontinuing inappropriate medication among nursing home residents
Hans Wouters (1981) studied psychology at Utrecht University. He wrote his
dissertation about adaptive cognitive testing in dementia at the Academic Medical
Center in Amsterdam. By means of adaptive testing, it is possible to select for each
individual patient only items of appropriate difficulty (H Wouters et al in J Alzheimers
Dis). He was also involved in a study about the cognitive function in later life of
people who were prenatally exposed to famine at the end of the Second World War
(PNAS 2010). As a postdoc researcher at Utrecht University, he studied amongst
others trade-off preferences with regard to endocrine therapy for prevention of breast
cancer recurrence (Wouters et al in Ann Oncol). His key interests are gerontology,
geriatric pharmacotherapy, healthy ageing, neuropsychology and medical decisionmaking. He just received a grant (in collaboration with the department of General
Practice and the Alzheimer Center of the VUMC) to develop an automated selfscreener for dementia. He is also involved in projects aimed at studying
chemotherapy-related cognitive impairment, differential diagnosis of dementia using
cognitive tests, supporting elderly patients in making the right treatment decisions and
validation of a hetero-anamnestic questionnaire for delirium. In June 2013, he joined
the department as a postdoc researcher. Under supervision of Prof Katja Taxis, he will
be working on the promising DIM NHR study. The DIM NHR study is aimed at
discontinuing inappropriate medication among frail nursing home patients. The DIM
NHR study is a cluster randomized controlled trial. At the ward level, patients will be
randomly assigned to either an optimized systematic multidisciplinary medication
review (enhanced usual care) or usual care. The primary outcome is the percentage of
nursing home residents for whom medication can be successfully discontinued.
Secondary outcomes are amongst others health care utilization, falls, and quality of
life. The medication reviews will also be qualitatively examined to identify barriers
and facilitators of medication reviewing.
27
5. Publications
Scientific International
Alsaad N, van Altena R, Pranger AD, van Soolingen D, de Lange WC, van der Werf
TS, Kosterink JG, Alffenaar JW. Evaluation of co-trimoxazole in the treatment of
multidrug-resistant tuberculosis. Eur Respir J 2013;42(2):504-12
Alsaad N, Wilffert B, van Altena R, de Lange WC, van der Werf TS, Kosterink JG,
Alffenaar JW. Potential antimicrobial agents for the treatment of MDR-TB. Eur
Respir J 2013; [Epub ahead of print]
Berm EJJ, Risselada AJ, Mulder H, Hak E, Wilffert B. Phenoconversion of
Cytochrome P450 @D6: The Need for Identifying the Intermediate Metabolizer
Genotype, J Clin Psychiatry 2013;74:1025-letter.
Bertholee D, Ter Horst PG, Hijmering ML, Spanjersberg AJ, Hospes W, Wilffert B.
Blood concentrations of cefuroxime in cardiopulmonary bypass surgery. Int J Clin
Pharm 2013; [Epub ahead of print]
Bijlsma MJ, Hak E, Bos J, De Jong-van den Berg LTW, Janssen F. Assessing the
effect of a guideline change on drug use prevalence by including the birth cohort
dimension: the case of benzodiazepines. Pharmacoepidemiol Drug Saf
2013;22(9):933-41
Bolhuis MS, Altena RV, Soolingen DV, Lange WC, Uges DR, Werf TS, Kosterink
JG, Alffenaar JW. Clarithromycin increases linezolid exposure in multidrug-resistant
tuberculosis patients. Eur Respir J 2013; [Epub ahead of print]
Bolhuis MS, van Altena R, van Hateren K, de Lange WC, Greijdanus B, Uges DR,
Kosterink JG, van der Werf TS, Alffenaar JW. Clinical validation of the analysis of
linezolid and clarithromycin in oral fluid of patients with multidrug-resistant
tuberculosis. Antimicrob Agents Chemother 2013;57(8):3676-80
Bulsink A, Imholz AL, Brouwers JRBJ, Jansman FG. Characteristics of potential
drug-related problems among oncology patients. Int J Clin Pharm 2013;35(3):401-7
Bult W, Kroeze SG, Elschot M, Seevinck PR, Beekman FJ, de Jong HW, Uges DR,
Kosterink JG, Luijten PR, Hennink WE, van Het Schip AD, Bosch JL, Nijsen JF, Jans
JJ. Intratumoral administration of holmium-166 acetylacetonate microspheres:
antitumor efficacy and feasibility of multimodality imaging in renal cancer. PLoS One
2013;8(1):e52178
Cohen D and Loonen AJ. Are immediate- and extended-release drugs
interchangeable? Acta Psychiatr Scand 2013;127(1):78-80
28
Connolly MP, Kuyvenhoven JP, Postma MJ, Nielsen SK. Cost and quality-adjusted
life year differences in the treatment of active ulcerative colitis using once-daily 4 g or
twice-daily 2 g mesalazine dosing. Journal of Crohn's and Colitis 2013; [Epub ahead
of print]
Crijns I, Mantel-Teeuwisse A, Bloemberg R, Pinas E, Straus S, de Jong-van den Berg
LTW. Healthcare professional surveys to investigate the implementation of the
isotretinoin Pregnancy Prevention Programme: a descriptive study. Expert Opin Drug
Saf 2013;12(1):29-38
Darak S, Darak T, Kulkarni S, Kulkarni V, Parchure R, Hutter I, Janssen F. Effect of
highly active antiretroviral treatment (HAART) during pregnancy on pregnancy
outcomes: experiences from a PMTCT program in western India. AIDS Patient Care
STDS 2013;27(3):163-70
de Boer PT, Pouwels KB, Cox JM, Hak E, Wilschut JC, Postma MJ. Costeffectiveness of vaccination of the elderly against herpes zoster in The Netherlands.
Vaccine 2013;31(9):1276-83
de Jonge L, Bos HJ, van Langen IM, de Jong-van den Berg LTW, Bakker MK.
Antibiotics prescribed before, during and after pregnancy in the Netherlands: a drug
utilization study. Pharmacoepidemiol Drug Saf 2013; [Epub ahead of print]
de Jonge L, Zetstra-van der Woude AP, Bos HJ, de Jong-van den Berg LTW, Bakker
MK. Identifying Associations between Maternal Medication Use and Birth Defects
Using a Case-Population Approach: An Exploratory Study on Signal Detection. Drug
Saf 2013; [Epub ahead of print]
Dijkstra A, Hak E, Janssen F. A systematic review of the application of spatial
analysis in pharmacoepidemiologic research. Ann Epidemiol 2013;23(8):504-14
Dijkstra A, Janssen F, De Bakker M, Bos J, Lub R, Van Wissen LJ, Hak E. Using
spatial analysis to predict health care use at the local level: a case study of type 2
diabetes medication use and its association with demographic change and
socioeconomic status. PLoS One 2013;8(8):e72730
Dreischulte T, Johnson J, McAnaw J, Geurts M, de Gier H, Hudson S. Medication
assessment tool to detect care issues from routine data: a pilot study in primary care.
Int J Clin Pharm 2013;35:1063-74
Gefenaite G, Tacken M, Bos J, Stirbu-Wagner I, Korevaar JC, Stolk RP, Wolters B,
Bijl M, Postma MJ, Wilschut J, Nichol KL, Hak E. Effectiveness of A(H1N1)pdm09
Influenza Vaccine in Adults Recommended for Annual Influenza Vaccination. PLoS
One 2013;8(6):e66125
Gefenaite G, Tacken M, Kolthof J, Mulder B, Korevaar JC, Stirbu-Wagner I, Bos J,
Stolk RP, Hak E. Predictors of influenza in the adult population during seasonal and
A(H1N1)pdm09 pandemic influenza periods. Epidemiol Infect 2013:1-5
29
Geurts MM, van der Flier M, de Vries-Bots AM, Brink-van der Wal TI, de Gier JJ.
Medication reconciliation to solve discrepancies in discharge documents after
discharge from the hospital. Int J Clin Pharm 2013; [Epub ahead of print]
Geurts MM, Zuydgeest IA, Walser S, Kijlstra NB, Petkova V, de Gier JJ. The
evaluation of patient self-completion concordance forms used in community
pharmacy: a comparison of two European countries. Int J Pharm Pract 2013; [Epub
ahead of print]
Hak E, de Vries TW, Hoekstra PJ, Jick SS. Association of childhood attentiondeficit/hyperactivity disorder with atopic diseases and skin infections? A matched
case-control study using the General Practice Research Database. Ann Allergy Asthma
Immunol 2013;111(2):102,106.e2
Hak E, Mulder B, Schuiling-Veninga CC, de Vries TW, Jick SS. Use of AcidSuppressive Drugs in Pregnancy and the Risk of Childhood Asthma: Bidirectional
Crossover Study using the General Practice Research Database. Drug Saf 2013; [Epub
ahead of print]
Hak E, Shea KM, Jick SS. Association of infant pneumococcal vaccination with
pneumococcal pneumonia among mothers: A nested case-control study using the
GPRD. Vaccine 2013; [Epub ahead of print]
Härmark L, Alberts S, van Puijenbroek E, Denig P, van Grootheest K.
Representativeness of diabetes patients participating in a web-based adverse drug
reaction monitoring system. Pharmacoepidemiol Drug Saf 2013;22(3):250-5
Härmark L, Lie-Kwie M, Berm L, de Gier H, van Grootheest K. Patients' motives for
participating in active post-marketing surveillance. Pharmacoepidemiol Drug Saf
2013;22(1):70-6
Härmark L, van Puijenbroek E, van Grootheest K. Intensive monitoring of duloxetine:
results of a web-based intensive monitoring study. Eur J Clin Pharmacol
2013;69(2):209-15
Härmark LV, Huls HJ, de Gier JJ, van Grootheest AC. Non-response in a pharmacy
and patient-based intensive monitoring system: a quantitative study on non-response
bias and reasons for non-response. Int J Pharm Pract 2013; [Epub ahead of print]
Hepkema H, Pouwels KB, van der Ende A, Westra TA, Postma MJ. Meningococcal
serogroup a, C, w135 and y conjugated vaccine: a cost-effectiveness analysis in the
Netherlands. PLoS One 2013;8(5):e65036
Hovens JE and Loonen AJ. Reaction on 'The aftermath of the reduction in inpatient
care and treatment II: cross-sectional study relating to the health, the need for care, the
quality of life, social functioning and the integration in society of chronic mental
patients in Amsterdam'. Tijdschr Psychiatr 2013;55(5):387-8
30
Janssen F, van Wissen LJG, Kunst AE. Life expectancy is increasing - but by how
much exactly? Population Europe - Pop Digest 2013;22-07-2013
Janssen F, van Wissen LJ, Kunst AE. Including the smoking epidemic in
internationally coherent mortality projections. Demography 2013;50(4):1341-62
Jiang Y, Gauthier A, Postma MJ, Ribassin-Majed L, Largeron N, Bresse X. A critical
review of cost-effectiveness analyses of vaccinating males against human
papillomavirus. Hum Vaccin Immunother 2013;9(11)
Kelso JK, Halder N, Postma MJ, Milne GJ. Economic analysis of pandemic influenza
mitigation strategies for five pandemic severity categories. BMC Public Health
2013;13:211
Kibele E and Janssen F. Distortion of regional old-age mortality rates due to late-life
migration in the Netherlands? Demographic Research 2013;29(5):105-32
Knol W, van Marum RJ, Jansen PA, Strengman E, Al Hadithy AF, Wilffert B,
Schobben AF, Ophoff RA, Egberts TC. Genetic Variation and the Risk of
Haloperidol-Related Parkinsonism in Elderly Patients: A Candidate Gene Approach. J
Clin Psychopharmacol 2013;33(3):405-10
Kotsopoulos N, Connolly MP, Postma MJ, Hutubessy RC. Fiscal consequences of
changes in morbidity and mortality attributed to rotavirus immunisation. Vaccine
2013; [Epub ahead of print]
Kotsopoulos N, Connolly MP, Sobanski E, Postma MJ. The fiscal consequences of
ADHD in Germany: a quantitative analysis based on differences in educational
attainment and lifetime earnings. J Ment Health Policy Econ 2013;16(1):27-33
Kotsopoulos N, Connolly MP, Sobanski E, Postma MJ. Assessing the economic
burden and benefit-cost of treating attention-deficit hyperactivity disorder in Germany.
Journal of Health Economics and Outcomes Research (JHEOR) 2013;1:212-23.
Lako IM, Bruggeman R, Liemburg EJ, van den Heuvel ER, Knegtering H, Slooff CJ,
Wiersma D, Taxis K. A brief version of the Subjects' Response to Antipsychotics
questionnaire to evaluate treatment effects. Schizophr Res 2013;147(1):175-80
Lako IM, van den Heuvel ER, Knegtering H, Bruggeman R, Taxis K. Estimating
dopamine D₂ receptor occupancy for doses of 8 antipsychotics: a meta-analysis. J Clin
Psychopharmacol. 2013 Oct;33(5):675-81
Le HH, Hodgkins P, Postma MJ, Kahle J, Sikirica V, Setyawan J, Erder MH, Doshi
JA. Economic impact of childhood/adolescent ADHD in a European setting: the
Netherlands as a reference case. Eur Child Adolesc Psychiatry 2013. [Epub ahead of
print]
31
Leendertse AJ, de Koning GH, Goudswaard AN, Belitser SV, Verhoef M, de Gier HJ,
Egberts AC, van den Bemt PM. Preventing hospital admissions by reviewing
medication (PHARM) in primary care: an open controlled study in an elderly
population. J Clin Pharm Ther 2013;38(5):379-87
Loonen AJ and Ivanova SA. New insights into the mechanism of drug-induced
dyskinesia. CNS Spectr 2013;18(1):15-20
Luttjeboer J, Westra TA, Wilschut JA, Nijman HW, Daemen T, Postma MJ. Costeffectiveness of the prophylactic HPV vaccine: An application to the Netherlands
taking non-cervical cancers and cross-protection into account. Vaccine 2013; [Epub
ahead of print]
Mapako T, Mvere DA, Chitiyo ME, Rusakaniko S, Postma MJ, van Hulst M. Human
immunodeficiency virus prevalence, incidence, and residual transmission risk in firsttime and repeat blood donations in Zimbabwe: implications on blood safety.
Transfusion 2013; [Epub ahead of print]
Meijboom MJ, Pouwels K, Luytjes W, Postma MJ, Hak E. RSV vaccine in
development: Assessing the potential cost-effectiveness in the Dutch elderly
population. Vaccine 2013. [Epub ahead of print]
Mihajlović J, Pechlivanoglou P, Miladinov-Mikov M, Zivkovic S, Postma MJ. Cancer
incidence and mortality in Serbia 1999-2009. BMC Cancer 2013;13:18-13-18
Mihajlović J, Pechlivanoglou P, Sabo A, Tomić Z, Postma MJ. Cost-Effectiveness of
Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia.
Clin Ther. 2013 Nov 13. doi:pii: S0149-2918(13)01023-0. [Epub ahead of print].
Monteiro SP, Huiskes R, Van Dijk L, Van Weert JC, de Gier JJ. How effective are
pictograms in communicating risk about driving-impairing medicines? Traffic Inj Prev
2013;14(3):299-308
Mulder B, Schuiling-Veninga CC, Bos JH, de Vries TW, Hak E. Acid-suppressive
drug use in pregnancy and the toddler's asthma risk: A crossover, case-control study. J
Allergy Clin Immunol 2013; [Epub ahead of print]
Mulder B, Schuiling-Veninga C, Bos H, De Vries T, Jick S, Hak E. Prenatal exposure
to acid-suppressive drugs and the risk of allergic diseases in the offspring: a cohort
study. Clin Exp Allergy 2013. [Epub ahead of print]
Munster JM, Leenders AC, Hamilton CJ, Meekelenkamp JC, Schneeberger PM, van
der Hoek W, Rietveld A, de Vries E, Stolk RP, Aarnoudse JG, Hak E. Routine
screening for Coxiella burnetii infection during pregnancy: a clustered randomised
controlled trial during an outbreak, the Netherlands, 2010. Euro Surveill
2013;18(24):20504
32
Nguyen HT, Pham HT, Vo DK, Nguyen TD, van den Heuvel ER, Haaijer-Ruskamp
FM, Taxis K. The effect of a clinical pharmacist-led training programme on
intravenous medication errors: a controlled before and after study. BMJ Qual Saf.
2013 Nov 6
Parouty MB, Krooshof DG, Westra TA, Pechlivanoglou P, Postma MJ. Reviewing and
piloting methods for decreasing discount rates; someone, somewhere in time. Expert
Rev Pharmacoecon Outcomes Res 2013;13(4):523-47
Pechlivanoglou P, Le HH, Daenen S, Snowden JA, Postma MJ. Mixed treatment
comparison of prophylaxis against invasive fungal infections in neutropenic patients
receiving therapy for haematological malignancies: a systematic review. J Antimicrob
Chemother 2013; [Epub ahead of print]
Postma MJ, Kappelhoff BS, van Hulst M, Brouwers JR. Author response: economic
evaluation of dabigatran etexilate. J Med Econ 2013;16(3):372-3
Postma MJ, Parouty M, Westra TA. Accumulating evidence for the case of differential
discounting. Expert Rev Clin Pharmacol 2013;6(1):1-3
Postma MJ and Standaert BA. Economics of vaccines revisited. Hum Vaccin
Immunother 2013;9(5)
Postma MJ, Westra TA, Quilici S, Largeron N. Economic evaluation of vaccines:
specificities and future challenges illustrated by recent European examples. Expert Rev
Vaccines 2013;12(5):555-65
Postma MJ, Top G, Buskens E. Healthy aging through lifelong vaccination: a tale of
two countries. Aging Health 2013;9:619-27
Pouwels KB, Hak E, van der Ende A, Christensen H, van den Dobbelsteen GP,
Postma MJ. Cost-effectiveness of vaccination against meningococcal B among Dutch
infants: Crucial impact of changes in incidence. Hum Vaccin Immunother 2013;9(5)
Pouwels KB, Visser ST, Hak E. Effect of pravastatin and fosinopril on recurrent
urinary tract infections. J Antimicrob Chemother 2013;68(3):708-14
Pouwels KB, Visser ST, Bos HJ, Hak E. Angiotensin-Converting Enzyme Inhibitor
Treatment and the Development of Urinary Tract Infections: A Prescription Sequence
Symmetry Analysis. Drug Saf 2013; [Epub ahead of print]
Rahamat-Langendoen JC, Riezebos-Brilman A, Hak E, Scholvinck EH, Niesters HG.
The significance of rhinovirus detection in hospitalized children: clinical,
epidemiological and virological features. Clin Microbiol Infect 2013; [Epub ahead of
print]
Riphagen-Dalhuisen J, Burgerhof J, Frijstein G, van der Geest-Blankert A, DanhofPont M, de Jager H, Bos A, Smeets E, de Vries M, Gallee P, Hak E. Hospital-based
33
cluster randomised controlled trial to assess effects of a multi-faceted programme on
influenza vaccine coverage among hospital healthcare workers and nosocomial
influenza in the Netherlands, 2009 to 2011. Euro Surveill 2013;18(26):20512
Riphagen-Dalhuisen J, Frijstein G, van der Geest-Blankert N, Danhof-Pont M, de
Jager H, Bos N, Smeets E, de Vries M, Gallee P, Hak E. Planning and process
evaluation of a multi-faceted influenza vaccination implementation strategy for health
care workers in acute health care settings. BMC Infect Dis 2013;13:235
Rolfes L, Wilkes S, van Hunsel F, van Puijenbroek E, van Grootheest K. Important
information regarding reporting of adverse drug reactions: a qualitative study. Int J
Pharm Pract 2013; [Epub ahead of print]
Rozenbaum MH, Pechlivanoglou P, van der Werf TS, Lo-Ten-Foe JR, Postma MJ,
Hak E. The role of Streptococcus pneumoniae in community-acquired pneumonia
among adults in Europe: a meta-analysis. Eur J Clin Microbiol Infect Dis
2013;32(3):305-16
Rozenbaum MH and Postma MJ. Response on "RE: Cost-effectiveness of pertussis
booster vaccination in the Netherlands". Vaccine 2013;31(16):2024
Standaert B, Gomez JA, Raes M, Debrus S, Velazquez FR, Postma MJ. Impact of
rotavirus vaccination on hospitalisations in belgium: comparing model predictions
with observed data. PLoS One 2013;8(1):e53864
Stoeldraijer L, van Duin C, Van Wissen LJG, Janssen F. Sensitivity of future life
expectancy at birth and at age 65 due to different mortality forecasting methods.
Demographic Research 2013;29(13):323-54
Suwantika AA, Tu HA, Postma MJ. Cost-effectiveness of rotavirus immunization in
Indonesia: Taking breastfeeding patterns into account. Vaccine 2013;31(32):3300-7
Suwantika AA, Yegenoglu S, Riewpaiboon A, Tu HA, Postma MJ. Economic
evaluations of hepatitis A vaccination in middle-income countries. Expert Rev
Vaccines 2013;12(12):1479-94
ter Horst PG, Bos HJ, de Jong-van den Berg LTW, Wilffert B. In utero exposure to
antidepressants and the use of drugs for pulmonary diseases in children. Eur J Clin
Pharmacol 2013;69(3):541-7
Tu HA, Rozenbaum MH, de Boer PT, Noort AC, Postma MJ. An update of "Costeffectiveness of rotavirus vaccination in the Netherlands: the results of a Consensus
Rotavirus Vaccine model". BMC Infect Dis 2013;13:54
Urbanus AT, van Keep M, Matser AA, Rozenbaum MH, Weegink CJ, van den Hoek
A, Prins M, Postma MJ. Is adding HCV screening to the antenatal national screening
program in Amsterdam, the Netherlands, cost-effective? PLoS One 2013;8(8):e70319
34
van Boven JF, Chavannes NH, van der Molen T, Rutten-van Mölken MP, Postma MJ,
Vegter S. Clinical and economic impact of non-adherence in COPD: A systematic
review. Respir Med 2013; [Epub ahead of print]
van Boven JF, de Boer PT, Postma MJ, Vegter S. Persistence with osteoporosis
medication among newly-treated osteoporotic patients. J Bone Miner Metab 2013;
[Epub ahead of print]
van Boven JF, de Jong-van den Berg LTW, Vegter S. Inhaled corticosteroids and the
occurrence of oral candidiasis: a prescription sequence symmetry analysis. Drug Saf
2013;36(4):231-6
van Boven JF, Hiddink EG, Stuurman-Bieze AG, Schuiling-Veninga CC, Postma MJ,
Vegter S. The pharmacists' potential to provide targets for interventions to optimize
pharmacotherapy in patients with asthma. Int J Clin Pharm 2013; [Epub ahead of
print]
van Boven JF, Vegter S, van der Molen T, Postma MJ. COPD in the Working Age
Population: The Economic Impact on Both Patients and Government. COPD 2013;
[Epub ahead of print]
van der Elst KC, Span LF, van Hateren K, Vermeulen KM, van der Werf TS,
Greijdanus B, Kosterink JG, Uges DR, Alffenaar JW. Dried blood spot analysis
suitable for therapeutic drug monitoring of voriconazole, fluconazole and
posaconazole. Antimicrob Agents Chemother 2013; [Epub ahead of print]
van der Veen W, de Gier HJ, van der Schaaf T, Taxis K., van den Bemt PM. Risk
analysis and user satisfaction after implementation of computerized physician order
entry in Dutch hospitals. Int J Clin Pharm 2013;35(2):195-201
van Gelder MM, Bos JH, Roeleveld N, de Jong-van den Berg LTW. Drugs associated
with teratogenic mechanisms. Part I: dispensing rates among pregnant women in the
Netherlands, 1998-2009. Hum Reprod 2013; [Epub ahead of print]
van Hasselt FM, Thier CSM, van Rijswijk E, Loonen AJM. Is Somatic Health
Screening in Patients With Severe Mental Illness of Added Value? Perspect Psychiatr
Care 2013;doi: 10.1111/ppc.12042
van Hasselt FM, Coehorst Y, Wilffert B, Loonen AJ. Influencing CYP enzymes to
boost psychiatric treatment: a review on clinical evidence. Pharmacopsychiatry
2013;46(2):43-6
van Hasselt FM, Krabbe PF, van Ittersum DG, Postma MJ, Loonen AJ. Evaluating
interventions to improve somatic health in severe mental illness: a systematic review.
Acta Psychiatr Scand 2013; [Epub ahead of print]
35
van Hasselt FM, Schorr SG, Mookhoek EJ, Brouwers JRBJ, Loonen AJ, Taxis K.
Gaps in health care for the somatic health of outpatients with severe mental illness. Int
J Ment Health Nurs 2013;22(3):249-55
van Hasselt FM, Oud MJT, Loonen AJM. Improvement of care for the physical health
of patients with severe mental illness: a qualitative study assessing the view of patients
and families. BMC Health Services Research.2013, 13:426
van Leeuwen RW, Brundel DH, Neef C, van Gelder T, Mathijssen RH, Burger DM,
Jansman FG. Prevalence of potential drug-drug interactions in cancer patients treated
with oral anticancer drugs. Br J Cancer 2013;108(5):1071-8
Vegter S, de Boer P, van Dijk KW, Visser ST, de Jong-van den Berg LTW. The
Effects of Antitussive Treatment of ACE Inhibitor-Induced Cough on Therapy
Compliance: A Prescription Sequence Symmetry Analysis. Drug Saf 2013; [Epub
ahead of print]
Vegter S, Tolley K, Wilson Waterworth T, Jones H, Jones S, Jewell D. Meta-analysis
using individual patient data: efficacy and durability of topical alicaforsen for the
treatment of active ulcerative colitis. Aliment Pharmacol Ther 2013;38(3):284-93
Verstappen GM, Smolders EJ, Munster JM, Aarnoudse JG, Hak E. Prevalence and
predictors of over-the-counter medication use among pregnant women: a crosssectional study in the Netherlands. BMC Public Health 2013;13:185 doi:
10.1186/1471-2458-13-185
Visser ST, Schuiling-Veninga CC, Bos JH, de Jong-van den Berg LTW, Postma MJ.
The population-based prescription database IADB.nl: its development, usefulness in
outcomes research and challenges. Expert Rev Pharmacoecon Outcomes Res
2013;13(3):285-92
Vriend HJ, Lugner AK, Xiridou M, Schim van der Loeff MF, Prins M, de Vries HJ,
Geerlings SE, Prins JM, Rijnders BJ, van Veen MG, Fennema JS, Postma MJ, van der
Sande MA. Sexually transmitted infections screening at HIV treatment centers for
MSM can be cost-effective. AIDS 2013;27(14):2281-90
Vu DH, Koster RA, Wessels AM, Greijdanus B, Alffenaar JW, Uges DR.
Troubleshooting carry-over of LC-MS/MS method for rifampicin, clarithromycin and
metabolites in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci
2013;917-918:1-4
Westra AE, van Gils EJ, Aarts F, Rodenburg GD, Veenhoven RH, Hak E, Scharloo M,
Sukhai RN, Wit JM, de Beaufort I, Sanders EL. Perceived discomfort levels in healthy
children participating in vaccine research. J Empir Res Hum Res Ethics 2013;8(3):6672
Westra TA, Stirbu-Wagner I, Dorsman S, Tutuhatunewa ED, de Vrij EL, Nijman HW,
Daemen T, Wilschut JC, Postma MJ. Inclusion of the benefits of enhanced cross36
protection against cervical cancer and prevention of genital warts in the costeffectiveness analysis of human papillomavirus vaccination in the Netherlands. BMC
Infect Dis 2013;13(1):75
Wilffert B, Swen J, Mulder H, Touw D, Maitland-Van der Zee AH, Deneer V, KNMP
working group Pharmacogenetics. From evidence based medicine to mechanism based
medicine. Reviewing the role of pharmacogenetics. Int J Clin Pharm 2013;35(3):36975
Wirtz VJ, Mol PG, Verdijk J, Vander Stichele RH, Taxis K. Use of antibacterial fixeddose combinations in the private sector in eight Latin American Countries between
1999 and 2009. Trop Med Int Health 2013; [Epub ahead of print]
Xiridou M, Vriend HJ, Lugner AK, Wallinga J, Fennema JS, Prins JM, Geerlings SE,
Rijnders BJ, Prins M, de Vries HJ, Postma MJ, van Veen MG, Schim van der Loeff
MF, van der Sande MA. Modelling the impact of chlamydia screening on the
transmission of HIV among men who have sex with men. BMC Infect Dis
2013;13(1):436
Yska JP, van der Linde S, Tapper VV, Apers JA, Emous M, Totte ER, Wilffert B, van
Roon EN. Influence of Bariatric Surgery on the Use and Pharmacokinetics of Some
Major Drug Classes. Obes Surg 2013; [Epub ahead of print]
Scientific Publications National
Härmark L, van Puijenbroek E, van Grootheest K. Het volgen van bijwerkingen in de
tijd met webbased intensive monitoring – pregabaline als voorbeeld. Pharmaceutisch
Weekblad Wetenschappelijk Platform 2013;7:a1309
Mol PG, van den Bemt PM, Dequito AB, van Doormaal JE, Zaal RJ, HaaijerRuskamp FM, Kosterink JG. Preventable and non-preventable medication-related
injuries incurred in hospitals. Ned Tijdschr Geneeskd 2013;157(3):A5051
Pouwels K and van Grootheest K. De besluitvorming over werkzaamheid en
veiligheid van rosiglitazon bij de FDA en de EMA. Wat zijn de lessen?
Pharmaceutisch Weekblad Wetenschappelijk Platform 2013;7(6):a1319
ter Horst PGJ, Bos JH, de Jong-van den Berg LTW, Wilffert B. Antidepressiva tijdens
de zwangerschap en het gebruik van luchtwegmedicatie door de nakomelingen.
Pharmaceutisch Weekblad Wetenschappelijk Platform 2013;7(9):102-7
Wilffert B. Ongeschikte medicatie bij ouderen opsporen met Nederlandse versie
STOPP en START. Pharmaceutisch Weekblad Wetenschappelijk Platform
2013;7(2):e1304
37
Wilffert B. Proteomics voor schatting nierschade bij diabetici. Pharmaceutisch
Weekblad Wetenschappelijk Platform 2013;7(1):e1305
Professional
Brouwers J.R.B.J. Calcium en vitamine D-suppletie bij ouderen: te veel en te weinig.
Ins&Ouds-Tijdschrift voor Geriatrie 2013;3:6-10
Brouwers JRBJ, Jansen PAF. Geneesmiddelen bij kwetsbare ouderen. MFMTijdschrift Praktische Farmacotherapie 2013;3:54-6
Cohen D, Loonen AJM. Substitutie vaak riskant. Psychofarmaca: pas op met
uitwisselen directe en gereguleerde afgifte. Pharmaceutisch Weekblad
2013:148(2):19-21
de Jong J. Meer aandacht voor goed gebruik antibiotica bij kinderen. Pharmaceutisch
weekblad-Nieuwsberichten;23-05-2013.
de Jong J. Minder antibioticagebruik bij kind mogelijk. Pharmaceutisch weekbladRubrieken;23-08-2013.
Härmark L, van Puijenbroek EP, de Gier H, van Grootheest AC. Lareb Intensive
Monitoring boekt succes; Systematischer inzicht in bijwerkingen. Pharmaceutisch
weekblad 2013;148(8):18-20
Hovens JE, Loonen AJM. Reactie op ‘Na de extramuralisering. II. Een crosssectionele
studie naar psychisch en sociaal functioneren en kwaliteit van leven van een
steekproef van chronische psychiatrische patiënten in de Amsterdamse GGZ. Tijdschr
Psychiatr . 2013;55(5):387-8
Keijsers CJPW, Jansen PAF, de Wildt DJ, Brouwers JRBJ. Rationeel voorschrijven bij
ouderen: innovatie in het farmacotherapieonderwijs. Tijdschr v Geriatrie- Ins&Ouds
2013;1:9-12
Lokhorst B and van Grootheest K. Acne-achtige bultjes door vitamine B12.
Pharmaceutisch weekblad 2013;148(14):16-7
Loonen AJM. Een moeder die haar kind achterliet in de ballenbak. Psyfar 2013: 8 (1;
maart):32-5
Stoeldraijer L, van Duin C, Janssen F. Bevolkingsprognose 2012-2060: Model en
veronderstellingen betreffende de sterfte. [Population forecast 2012-2060: Model and
assumptions on mortality]. Bevolkingstrends 2013;juni:1-27
Taxis K. Kleiner Nachbar ganz groß. Das Studienfach Klinische Pharmazie in den
Niederlanden. Deutsche Apotheker Zeitung 2013;36:3000-4
ter Horst PGJ, Bos JH, de Jong-van den Berg LTW, Wilffert B. Grote rol apotheker bij
depressieve zwangere. Pharmaceutisch weekblad 2013;148(34):18-20
38
van Grootheest AC. Geneesmiddelen in Afrika – een persoonlijke kijk Folia
Pharmaceutica 2013;100(2):22-3
van Ojik AL, Jansen PAF, Brouwers JRBJ, van Roon EN. Antipsychotica bij ouderen
met een delier-welk middel wel en welk niet? Tijdschr v Geriatrie- Ins&Ouds 2013:113
van Ojik AL, Jansen PAF, Brouwers JRBJ, van Roon EN. Evidence based keuze van
opioiden bij ouderen met chronische pijn. Ins&Ouds-Tijdschrift voor Geriatrie
2013;3:11-15
van Strien AM, Keijsers CJPW, Schuoten HJ, Brouwers JRBJ. Factor Xa remmers en
directe trombineremmers, nieuwe orale anticoagulantis bij kwetsbare ouderen?
Ins&Ouds-Tijdschrift voor Geriatrie 2013;3:16-23
Vegter S and Postma MJ. Zijn weesgeneesmiddelen te duur? Foliolum 2013;2:13-5
Woerdenbag HJ and Brouwers JRBJ. Traditionele geneeskunde in Vietnam. Ned
Tijdschr Fytotherapie 2013;26(1):9-13
Books
Brouwers JRBJ, Hendriks JML, Jukema GJ, van Laarhoven H. Patiënt relevantie en
validatieprocedure: Het patiënten perspectief op antistollingsbehandeling van diepe
veneuze trombose en longembolie (VTE). Uitgaaf Europe-Expro Munchen 2013, 70
blz.
de Gier JJ, Bouvy ML, Egberts ACG, de Smet PAGM. Handboek Farmaceutische
Patiëntenzorg. Achtergronden En Praktijk. Uitgaaf Prelum: Houten, 2013, 331 blz.
Loonen AJM. Het beweeglijke brein. Uitgaaf Mension Haarlem 2013; Tweede
editie:415 blz.
Chapters in Books
de Gier JJ. Medicines & driving: results of the European DRUID project
[лекарственные средства и ввждение: результаты еврвпеисквгв првекта bruib].
2013 Chapter 2:16-49
Dijkstra A, Schaafsma E. Psychologie van gedragsverandering en counseling. In: JJ de
Gier, ML Bouvy, ACG Egberts, PAGM de Smet (Eds) Handboek farmaceutische
patiëntenzorg: achtergronden en praktijk. 2013 Hoofdstuk 7:83-100
Loonen AJM. серотонин: функции, метаболи3м, рецепторы. [Serotonin: function
metabolism receptor.] In: Bokhan NA, Ivanova SA, Levchuk LA, eds.
Серотониновая Система в модуляции депрессивных и аддиктивного поведения.
2013;(Chapter 1):11-30
39
Postma MJ, Boersma C, Vegter S, Vandijck D, Annemans L. Pharmacoeconomics of
Pharmacogenetics within the Context of General Health Technology Assessments. In:
YWF Lam, LH Cavallari (Eds) Pharmacogenomics 2013 Chapter 12:429-50
van Bodegraven AA, van Weyenberg SJB, Wierdsma NJ. de Wit NJ, Brouwers JRBJ.
Diagnose en Therapie 2013-2014. Serie Praktische Huisartsen geneeskunde 2013
Hoofdstuk 12:394-431
Vegter S, van Boven JF, Hiddink EG, Postma MJ. Economische uitkomsten. In: JJ de
Gier, ML Bouvy, ACG Egberts, PAGM de Smet (Eds) Handboek farmaceutische
patiëntenzorg: achtergronden en praktijk 2013 Hoofdstuk 21:275-82
40
6. Staff profile PharmacoEpidemiology & PharmacoEconomics 2014
Bijker BJ (Bert)
Bos HJ (Jens)
Hak E (Eelko)
Hulst M van (René)
Janssen F (Fanny)
Liu H (Marcy)
Nguyen L (Lan)
Postma MJ (Maarten)
Schoonveld J (Jannie)
Schuiling-Veninga CCM (Nynke)
Vegter S (Stefan)
Vemer P (Pepijn)
Visser ST (Sipke)
Wang H (Hao)
BSc
Cand BSc
PhD, Prof
PharmD, PhD
PhD
PhD
MD, MPH
PhD, Prof
Secretary
PharmD, PhD
PharmD, PhD
MSc
MSc
MD, PhD
Candidate PhDs
Bijlsma MJ (Maarten)
Boer de P (Pieter)
Boven JFM van (Job)
Gefenaite G (Giedre)
Mulder B (Bianca)
Pouwels KB (Koen)
Setiawan D (Didik)
Stevanovic J (Jelena)
Suwantika A (Auliya)
Vries de FM (Dianna)
Wijhe van M (Maarten)
Zetstra-van der Woude AP (Priscilla)
MSc
MSc
PharmD
MSc (UMCG/RUG)
BSc
MSc
MSc
MSc
MBA
MSc
MSc
MSc
Visiting Researchers/external candidate PhDs
Boersma C (Cornelis)
Connolly MP (Mark)
Dijkstra A (Aletta)
Fugel HJ (Hans-Joerg)
Heeg BMS (Bart)
Hiddink EG (Erik)
PhD (GSK Zeist)
PhD (GMA Solutions, Switzerland)
MSc (Calco, Maarssen)
MSc (Onyx Pharm International, Switzerland)
MSc (Pharmerit, Rotterdam)
MSc (Health Base, Houten)
41
Kotsopoulos N (Nikos)
Lub R (Rene)
Mafirakureva N (Nyashadzaishe)
Mapako T (Tonderai)
Meijboom M (Marjan)
Mihajlović J (Jovan)
Standaert BACGM (Bo)
Westra TA (Tjalke)
MSc (GMA Solutions, Switzerland)
PharmD (Zuidlaren)
MSc (National Blood Service, Zimbabwe)
MSc (National Blood Service, Zimbabwe)
MSc (Achmea Amersfoort)
MSc (Novi Sad, Serbia)
MSc (GSK, België)
PhD (GSK Zeist)
7. Staff profile Pharmacotherapy & Pharmaceutical Care 2014
Brouwers JRBJ (Koos)
Gier JJ de (Han)
Grootheest AC van (Kees)
Jonge W de (Wanda)
Kosterink JGW (Jos)
Loonen AJM (Anton)
Pavlovic J (Jugo)
Postuma A (Anja)
Roon EN van (Eric)
Schoonveld J (Jannie)
Taxis K (Katja)
Wilffert B (Bob)
Wouters J (Hans)
PharmD, PhD, Prof
PharmD, PhD, Prof
MD, PhD, Prof
Secretary (Education)
PharmD, PhD, Prof
PharmD, MD, PhD, Prof
BSc
Secretary (Internships)
PharmD, PhD, Prof
Secretary (Research)
MPharm, PhD, Prof
PharmD, PhD, Prof
PhD
Candidate PhDs
Berhe A (Abera)
Berm EJJ (Lisette)
Daud A (Aizati)
Geurts MME (Marlies)
Martono D (Doti)
Monteiro SP (Susana)
Nguyen T (Thang)
Nguyen HT (Thao)
Tran YH (Hao)
MSc
MSc
MSc
MSc
MSc
MSc
MSc, PharmD
MSc
MSc
42
Visiting Researchers/external candidate PhDs
Chedoe I (Indra)
Hasselt FM van (Fenneke)
Härmark L (Linda)
Hunsel FPAM van (Florence)
Puijenbroek EP van (Eugène)
Rolfes L (Leán)
Veen W van der (Willem)
Vries L de (Loes)
Yska JP (Jan Peter)
PharmD (Isala Klinieken Zwolle)
MD (GGZ-Westelijk Noord-Brabant)
PharmD (Lareb)
MSc, MBA (Lareb)
MD (Lareb)
MSc (Lareb)
PharmD (Scheper Hospital Emmen)
MSc (Lareb)
PharmD (MCL Leeuwarden)
Educational staff /Internship
Benjamins Y (Yael)
Dantuma CM -Wering (Claudia)
Hulten RP van (Rolf)
Jansman FGA (Frank)
Moolenaar F (Frits)
Pras N (Niesko)
Schaafsma ES (Evelyn)
Sehagic E -Alickovic (Enisa)
Sillius AW (Aaldrik)
Toering DJ (Dick)
Vries C de -Vingerling (Christa)
Wieringa S (Sieto)
Zwaga S (Sabien)
PharmD
PharmD
PhD
PharmD, PhD
PharmD
PhD
PharmD
BSc
Ir
PharmD
BSc
PharmD
PharmD
43
Winners photo contest 2013
First: Jannie Schoonveld, Piccardthofplas, Groningen
Second: Lisette Berm, Esperance, Australia
The X-chromosome and Y-chromosome
'Xy' van Martin Borchert (2009) Garden RUG (A. Deusinglaan-Oostersingel)
The X-chromosome and Y-chromosome have come to represent genetic research into
the fundamental building blocks of man. The more we know about chromosomes, the
better the diagnosis and
the better able we are to
prevent and treat
disease. However,
increasing understanding
can also lead to ethically
dubious applications.
The Anniversary
illustration Xy depicts
the artist’s ambivalent
attitude towards genetic research – the relationship between the two figures is open to
interpretation.
44

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