Reported adverse drug reactions during the use of inhaled steroids in children with asthma in the Netherlands

Objective: Inhaled corticosteroids (ICS) are widely used in the treatment of asthma. We studied the suspected adverse drug reactions (sADRs) reported during the use of ICS in the Netherlands. Methods: In the Netherlands, health professionals and patients can report suspected ADRs to the Pharmacovigilance Centre Lareb. All reported sADRs on ICS were categorised and assessed as to whether these were likely to be associated with use of the steroid. Age and gender adjusted Reported Odds Ratios (RORs) and Naranjo Scores (NS) were computed for sADRs reported more than 3 times. Results: Since 1984, sADRs of ICS were reported in 89 children (mean age 6 years), 48 (54%) were boys. Suspected drugs were fluticasone in 46 children (52%), budesonide in 21 (24%), and beclomethasone in 22 cases (24%). Psychiatric symptoms were reported in 19 children (21%; ROR 3.8, NS 3.6), growth retardation in 6 children (7%; ROR 47.8, NS 3.0) and rashes in 6 cases (7%; ROR 0.7, NS 2.4). There were 7 reports (8%; ROR 2.1, NS 3.4) concerning abnormalities of the teeth, 4 reports of alopecia (4%; ROR 3.3, NS 3.5), and 3 reports of hirsutism and hypertrichosis (NS 4.0). Non-fatal adrenal insufficiency was reported once. Conclusion: Alteration of behaviour was the most frequently reported sADR. There are more indications that alterations of behaviour could be a real sADR of ICS. Non-fatal adrenal insufficiency was the only reported possible life threatening sADR. The association of hypertrichosis and teeth abnormalities after ICS in children has not been reported in the literature before

The Dutch Pregnancy Drug Register:Suitable to Study Paternal Drug Exposures?

Paternal medication use around the time of conception is common, but information about its effects on pregnancy outcome and the health of the child is generally limited. The aim of this study is to examine the feasibility of studying paternal exposure in the Dutch Pregnancy Drug Register by using immunosuppressants as a proof of concept. In 113 of 15,959 pregnancies, long-term paternal immunosuppressant use was reported 3 months before conception. In total, 134 immunosuppressants were used. Pregnancy outcome was known for 54 cases and was in accordance with previous findings. Two spontaneous abortions, two premature births, six small for gestational age babies, and two major congenital malformations were reported. Time to pregnancy (TTP) was known for 9548 pregnancies, including 89 with paternal immunosuppressant use. TTP analysis did not show a difference in pregnancies with paternal immunosuppressant use compared to the control group. Moreover, the number of fertility treatments in the paternal immunosuppressant group was similar to the control group. In our opinion, it is feasible to use the Dutch Pregnancy Drug Register to study the effects of paternal exposure on pregnancy outcome. However, to study the potential effects on fertility, more information is needed, particularly since the beginning of pregnancy attempts.</p

The Dutch Pregnancy Drug Register:Suitable to Study Paternal Drug Exposures?

Paternal medication use around the time of conception is common, but information about its effects on pregnancy outcome and the health of the child is generally limited. The aim of this study is to examine the feasibility of studying paternal exposure in the Dutch Pregnancy Drug Register by using immunosuppressants as a proof of concept. In 113 of 15,959 pregnancies, long-term paternal immunosuppressant use was reported 3 months before conception. In total, 134 immunosuppressants were used. Pregnancy outcome was known for 54 cases and was in accordance with previous findings. Two spontaneous abortions, two premature births, six small for gestational age babies, and two major congenital malformations were reported. Time to pregnancy (TTP) was known for 9548 pregnancies, including 89 with paternal immunosuppressant use. TTP analysis did not show a difference in pregnancies with paternal immunosuppressant use compared to the control group. Moreover, the number of fertility treatments in the paternal immunosuppressant group was similar to the control group. In our opinion, it is feasible to use the Dutch Pregnancy Drug Register to study the effects of paternal exposure on pregnancy outcome. However, to study the potential effects on fertility, more information is needed, particularly since the beginning of pregnancy attempts.</p

The potential of training specialist oncology nurses in real-life reporting of adverse drug reactions

Specialist oncology nurses (SONs) have the potential to play a major role in monitoring and reporting adverse drug reactions (ADRs); and reduce the level of underreporting by current healthcare professionals. The aim of this study was to investigate the long term clinical and educational effects of real-life pharmacovigilance education intervention for SONs on ADR reporting. This prospective cohort study, with a 2-year follow-up, was carried out in the three postgraduate schools in the Netherlands. In one of the schools, the prescribing qualification course was expanded to include a lecture on pharmacovigilance, an ADR reporting assignment, and group discussion of self-reported ADRs (intervention). The clinical value of the intervention was assessed by analyzing the quantity and quality of ADR-reports sent to the Netherlands Pharmacovigilance Center Lareb, up to 2 years after the course and by evaluating the competences regarding pharmacovigilance of SONs annually. Eighty-eight SONs (78% of all SONs with a prescribing qualification in the Netherlands) were included. During the study, 82 ADRs were reported by the intervention group and 0 by the control group. This made the intervention group 105 times more likely to report an ADR after the course than an average nurse in the Netherlands. This is the first study to show a significant and relevant increase in the number of well-documented ADR reports after a single educational intervention. The real-life pharmacovigilance educational intervention also resulted in a long-term increase in pharmacovigilance competence. We recommend implementing real-life, context- and problem-based pharmacovigilance learning assignments in all healthcare curricula

Electronic Health Record-Triggered Research Infrastructure Combining Real-world Electronic Health Record Data and Patient-Reported Outcomes to Detect Benefits, Risks, and Impact of Medication:Development Study

BACKGROUND: Real-world data from electronic health records (EHRs) represent a wealth of information for studying the benefits and risks of medical treatment. However, they are limited in scope and should be complemented by information from the patient perspective. OBJECTIVE: The aim of this study is to develop an innovative research infrastructure that combines information from EHRs with patient experiences reported in questionnaires to monitor the risks and benefits of medical treatment. METHODS: We focused on the treatment of overactive bladder (OAB) in general practice as a use case. To develop the Benefit, Risk, and Impact of Medication Monitor (BRIMM) infrastructure, we first performed a requirement analysis. BRIMM’s starting point is routinely recorded general practice EHR data that are sent to the Dutch Nivel Primary Care Database weekly. Patients with OAB were flagged weekly on the basis of diagnoses and prescriptions. They were invited subsequently for participation by their general practitioner (GP), via a trusted third party. Patients received a series of questionnaires on disease status, pharmacological and nonpharmacological treatments, adverse drug reactions, drug adherence, and quality of life. The questionnaires and a dedicated feedback portal were developed in collaboration with a patient association for pelvic-related diseases, Bekkenbodem4All. Participating patients and GPs received feedback. An expert meeting was organized to assess the strengths, weaknesses, opportunities, and threats of the new research infrastructure. RESULTS: The BRIMM infrastructure was developed and implemented. In the Nivel Primary Care Database, 2933 patients with OAB from 27 general practices were flagged. GPs selected 1636 (55.78%) patients who were eligible for the study, of whom 295 (18.0% of eligible patients) completed the first questionnaire. A total of 288 (97.6%) patients consented to the linkage of their questionnaire data with their EHR data. According to experts, the strengths of the infrastructure were the linkage of patient-reported outcomes with EHR data, comparison of pharmacological and nonpharmacological treatments, flexibility of the infrastructure, and low registration burden for GPs. Methodological weaknesses, such as susceptibility to bias, patient selection, and low participation rates among GPs and patients, were seen as weaknesses and threats. Opportunities represent usefulness for policy makers and health professionals, conditional approval of medication, data linkage to other data sources, and feedback to patients. CONCLUSIONS: The BRIMM research infrastructure has the potential to assess the benefits and safety of (medical) treatment in real-life situations using a unique combination of EHRs and patient-reported outcomes. As patient involvement is an important aspect of the treatment process, generating knowledge from clinical and patient perspectives is valuable for health care providers, patients, and policy makers. The developed methodology can easily be applied to other treatments and health problems