Theo P. G. M. de Vries

Teaching clinical pharmacology and therapeutics with an emphasis on the therapeutic reasoning of undergraduate medical students

BackgroundThe rational prescribing of drugs is an essential skill of medical doctors. Clinical pharmacologists play an important role in the development of these skills by teaching clinical pharmacology and therapeutics (CP&T) to undergraduate medical students. Although the approaches to teaching CP&T have undergone many changes over the last decennia, it is essential that the actual teaching of CP&T continues to be a major part of the undergraduate medical curriculum.ObjectivesThe learning objectives of CP&T teaching in terms of developing the therapeutic competencies of undergraduate medical students are described, with an emphasis on therapeutic decision-making. On the basis of current theories of cognitive psychology and medical education, context-learning is presented as an effective approach by which to achieve therapeutic competencies. An example of a CP&T curriculum is presented.

The Prominent Role of the Liver in the Elimination of Asymmetric Dimethylarginine (ADMA) and the Consequences of Impaired Hepatic Function

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), the enzyme which converts the amino acid arginine into nitric oxide (NO). ADMA has been identified as an important risk factor for cardiovascular diseases. Besides the role of ADMA in cardiovascular diseases, it also seems to be an important determinant in the development of critical illness, (multiple) organ failure, and the hepatorenal syndrome. ADMA is eliminated from the body by urinary excretion, but it is mainly metabolized by the dimethylarginine dimethylaminohydrolase (DDAH) enzymes that convert ADMA into citrulline and dimethylamine. DDAH is highly expressed in the liver, which makes the liver a key organ in the regulation of the plasma ADMA concentration. The prominent role of the liver in the elimination of ADMA and the consequences of impaired hepatic function on ADMA levels will be discussed in this article.

Low arginine/asymmetric dimethylarginine ratio deteriorates systemic hemodynamics and organ blood flow in a rat model

Objective:Both arginine and asymmetric dimethylarginine (ADMA) play a crucial role in the arginine–nitric oxide pathway. Low arginine and high ADMA levels can be found in critically ill patients after major surgery. The aim of this study was to evaluate the effects of low arginine plasma concentrations in combination with high ADMA plasma concentrations on hemodynamics and organ blood flow. Design:Randomized, placebo-controlled animal laboratory investigation. Subjects:Male Wistar rats (n = 21), anesthetized. Interventions:Rats were randomly assigned to three groups: a control group, an ADMA group, or an arginase (ASE)/ADMA group. In the control group, rats received (at t = 0) an intravenous (IV) infusion of 1.5 mL 0.9% NaCl during a 20-minute period. After 60 minutes (t = 60), rats received an IV bolus of 1.0 mL 0.9% NaCl. In the ADMA group, rats received an IV infusion of 1.5 mL 0.9% NaCl during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). In the ASE/ADMA group, rats received an IV infusion of 1.5 mL ASE (3200 IU) solution during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). Measurements and Main Results:Infusion of ADMA (20 mg/kg) and ASE (3200 IU) resulted in increased plasma ADMA levels and decreased arginine levels. During the whole experiment, systemic hemodynamics (heart rate, mean arterial pressure [MAP], and cardiac output) were measured. In addition, organ blood flow was measured at t = 90 and t = 180 minutes, using fluorescent microspheres. Compared with the control group, MAP and systemic vascular resistance were increased after infusion of ADMA. Infusion of ASE in combination with ADMA significantly deteriorated systemic hemodynamics (MAP, cardiac output, stroke volume, and systemic vascular resistance) and organ blood flow through the kidney and spleen. In addition, an initial decrease in arterial flow, followed by a later major increase, and panlobular apoptosis and necrosis of the liver was observed. Conclusions:The current study shows that low arginine plasma levels in combination with high ADMA plasma levels deteriorates systemic hemodynamics and reduces blood flow through the kidney and spleen and liver. These data suggest that a diminished nitric oxide production may be involved in the onset of organ failure.

Factors related to high and low levels of drug adherence according to patients with type 2 diabetes

Objective Adherence to medication in patients with type 2 diabetes varies widely, yet the factors that influence adherence according to patients are not fully known. The aim of this study is to explore both factors related to high and lower levels of adherence that patients with type 2 diabetes experienced in their medication use. Setting Primary care in the Netherlands. Method Qualitative, semi-structured interviews were performed in 20 patients with type 2 diabetes. Interviews were audio-taped and transcribed verbatim. Transcripts were coded and analysed using content analysis and constant comparison. Main outcome measure experiences and opinions of patients concerning factors related to high and lower levels of adherence. Results Comparable aspects influenced drug adherence in more and less adherent patients. Four aspects that influenced adherence to medication emerged from the interviews: (1) information about the prescribed medication, (2) experience with medication and complications with use, (3) social support for medication behaviour and (4) routines in medication behaviour. Experience with medication and social support for medication behaviour were related to high levels of adherence in some patients, and to lower levels of adherence in others. Complicated medication regimens were mainly related to lower adherence, while social support and routines in medication behaviour were related to higher adherence. Conclusions Routines in medication behaviour were related to higher drug adherence. Patient education should not only address information about the disease and medication, but also more practical issues concerning drug intake. Hence, to improve drug adherence in patients with type 2 diabetes, pharmaceutical care might be aimed at the counselling of patients to organise drug use in their daily schedule.

Plasma ADMA concentrations at birth and mechanical ventilation in preterm infants: A prospective pilot study

Nitric oxide (NO) produced in the lung is an important mediator of normal lung development, vascular smooth muscle relaxation, and ventilation perfusion matching. NO is synthesized from arginine by the action of NO‐synthase (NOS). Asymmetric dimethylarginine (ADMA), an endogenous derivate of arginine, inhibits NOS and is thereby a determinant of NO synthesis. We compared ADMA and arginine levels in preterm infants requiring mechanical ventilation with preterm infants who did not require mechanical ventilation and determined the relation between ADMA and the length of mechanical ventilation in these infants.

The effect of different levels of realism of context learning on the prescribing competencies of medical students during the clinical clerkship in internal medicine: an exploratory study

PurposeThe aim of this study is to evaluate the effect of different levels of realism of context learning on the prescribing competencies of medical students during the clinical clerkship in internal medicine.MethodsBetween 2001 and 2007, 164 medical students took part in the prospective explorative study during their clinical clerkship in internal medicine at the VU University Medical Center, Amsterdam, The Netherlands. In a fixed order, each student had to formulate a treatment plan for a real patient in three situations of increasing realism: a minimal level (studying a patient record), medium level (preparing for a therapeutic consultation), and optimal level (preparing for and performing a therapeutic consultation with the patient).ResultsIn comparison to studying a patient record (minimal context level), preparing a therapeutic consultation (medium context) improved four of the six steps of the WHO six-step plan. Preparing and performing a therapeutic consultation with a real patient (optimal context) further improved three essential prescribing competencies, namely checking for contraindications and interactions, prescription writing, and instructions to the patient.Conclusion and recommendationsThe results of this first explorative study suggest that enrichment of the learning context (responsibility for patient care) might be an important factor to improve the training of rational prescribing skills of medical students during their clinical clerkship in internal medicine. Clinical (pharmacology) teachers should be aware that seemingly small adaptations in the learning context of prescribing training during clinical clerkships (i.e., with or without involvement with and responsibility for patient care) may have relatively large impact on the development of prescribing competencies of our future doctors.

Motivation and competence of participants in a learner-centered student-run clinic: an exploratory pilot study

BackgroundThe Learner-Centered Student-run Clinic (LC-SRC) was designed to teach and train prescribing skills grounded in a real-life context, to provide students with early clinical experience and responsibility. The current studies’ theoretical framework was based on the Self-determination Theory. According to the Self-determination Theory, early involvement in clinical practice combined with a high level of responsibility makes the LC-SRC an environment that can stimulate intrinsic motivation. We investigated the different types of motivation and the proficiency in CanMEDS competencies of the participating students.MethodType of motivation was measured using the Academic Motivation Scale and Intrinsic Motivation Inventory. CanMEDS competencies were evaluated by faculty using a mini-clinical examination and by the students themselves using a post-participation questionnaire.ResultsThe 29 participating students were highly intrinsic motivated for this project on all subscales of the Intrinsic Motivation Inventory. Motivation for medical school on the Academic Motivation Scale was high before and was not significantly changed after participation. Students considered that their CanMEDS competencies “Collaborator”, “Communicator”, “Academic”, and “Medical expert” had improved. Their actual clinical team competence was judged by faculty to be at a junior doctor level.ConclusionStudents showed a high level of intrinsic motivation to participate in the LC-SRC and perceived an improvement in competence. Furthermore their actual clinical competence was at junior doctor level in all CanMEDS competencies. The stimulating characteristics of the LC-SRC, the high levels of intrinsic motivation and the qualitative comments of the students in this study makes the LC-SRC an attractive place for learning.

What should Junior Doctors Know about the Drugs they frequently prescribe? A Delphi Study among Physicians in The Netherlands

The aim of this study was to identify the information about commonly prescribed drugs that junior doctors should know in order to prescribe rationally in daily practice, defined as essential drug knowledge (EDK). A two‐round Internet Delphi study was carried out involving general practitioners from one practice cluster, and registrars and consultants from two Dutch academic and eight teaching hospitals. A preliminary list of 377 potential EDK items for three commonly prescribed drugs was assessed on a dichotomous scale; an item was considered EDK if at least 80% consensus was reached. The consensus list of EDK items was discussed by the research team to identify similarities between the three drugs, with a view to forming a list of general EDK items applicable to other commonly prescribed drugs. Sixty experts considered 93 of the 377 items (25%) as EDK. These items were then used to form a list of 10 general EDK items. The list of EDK items identified by primary and secondary care doctors could be used in medical curricula and training programmes and for assessing the prescribing competence of future junior doctors. Further research is needed to evaluate the generalizability of this list for other commonly prescribed drugs.

Structure, importance and recording of therapeutic information in the medical record: a multicentre observational study.

RATIONALE, AIMS AND OBJECTIVES Structuring the diagnostic section of the medical record (MR) improves diagnosis and communication between doctors. However, little is known about the therapeutic section of the MR. The aim of this study was to gain insight into the extent to which MRs are structured for therapeutic information, to determine which therapeutic data registrars and clinical consultants consider should be recorded in the MR and to what extent registrars record this information themselves. METHODS A multicentre observational study was carried out in the internal medicine outpatient clinics of five teaching hospitals in the Netherlands. Preformatted structure, importance and actual recording of therapeutic information was compared with a reference list of 35 therapeutic items based on the WHO Guide to Good Prescribing (e.g. drug name, indication for drug). RESULTS The preformatted structure of four paper MRs and one electronic MR was assessed. Eight of the 35 therapeutic items were listed in the paper MRs and 18 items in the electronic MR. Registrars and consultants agreed on the importance of recording most of the therapeutic items in the MR, 25 and 27 out of the 35 items, respectively; however, registrars recorded only 11 of the 35 items in the paper MR and 20 of the 35 items in the electronic MR. CONCLUSIONS The structure and content of paper and electronic MRs are not adequate. While both registrars and consultants agree on the importance of recording therapeutic items in the MR, registrars fail to record most of this information in practice. The results of this study can be used as starting point for the discussion regarding the necessity of structured recording of therapeutic information in the MR and its possible benefits with regard to medication safety and training of the new generation of prescribers.