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.

[Self-reported maternal adverse events of covid-19 vaccination during pregnancy]. / Maternale bijwerkingen na covid-19-vaccinatie in de zwangerschap.

OBJECTIVE: To describe the self-reported maternal adverse events (AEs) of covid-19 vaccination during pregnancy. DESIGN: The Dutch Pregnancy Drug Register ("Moeders van Morgen"), is a prospective cohort study among pregnant women in the Netherlands. METHOD: Using online questionnaires, women reported whether they received a covid-19 vaccination and the self-perceived AEs after vaccination. We included women who received their first covid-19 vaccination during pregnancy. We assessed the maternal AEs by vaccine dose, type of vaccine (BioNTech/Pfizer, Moderna, AstraZeneca, and Janssen) and moment of vaccination in pregnancy. RESULTS: 4348 women received their first covid-19 vaccination during pregnancy and were included. Of these, 2787 women also reported a second dose during pregnancy. After the first dose, AEs were less often reported for BioNTech/Pfizer (56% ≥1 AE), compared to Moderna (68% ≥1 AE) or AstraZeneca (87% ≥1 AE). After the second dose, AEs were less often reported for BioNTech/Pfizer (44% ≥1 AE) compared to Moderna (76% ≥1 AE). Injection site reactions, myalgia and fatigue were reported most frequently. There was large variation in the percentage reporting pyrexia/fever between the different vaccines (3%, 22%, and 10% after the second dose of BioNTech/Pfizer, Moderna, and Astrazeneca respectively). There were no major differences in the rates of AEs between vaccination in the first, second, or third trimester. CONCLUSION: The adverse event profile among women who were vaccinated against covid-19 during pregnancy do not indicate any safety concerns. Considering the reported maternal AEs, the BioNTech/Pfizer vaccine seems best for vaccination during pregnancy.

Male Sexual Health and Reproduction in Cutaneous Immune-Mediated Diseases: A Systematic Review.

INTRODUCTION: Information about the possible effects of cutaneous immune-mediated diseases (cIMDs) on male sexual function and reproduction is scarce. Factors known to impair sexual health and reproduction, such as inflammation, medication use, and hypogonadism, can be present in a significant proportion of male patients with cIMD. OBJECTIVES: To systematically review the literature for the influence of paternal cIMD on many aspects of male sexual and reproductive health, such as sexual function, reproductive hormones, fertility, and pregnancy and offspring outcomes. METHODS: A systematic literature search was performed. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes, and offspring's health with a list of cIMDs. RESULTS: The majority of the identified studies included patients with psoriasis (22 of 27), and sexual function was the most common outcome of interest (20 of 27). For patients diagnosed with psoriasis, the prevalence of male sexual dysfunction reported in these studies ranged from 34 to 81%. Hypogonadism in patients with psoriasis was reported in 2 of 3 studies. Sperm analysis abnormalities in patients with psoriasis were reported in 3 of 4 studies. No information about the effect of paternal disease on pregnancy and offspring outcomes was identified. CONCLUSIONS: Disease activity in psoriasis might play an important role in the development of sexual dysfunction, hypogonadism, and abnormal sperm quality. For the other cIMD included in this review, there is insufficient information regarding male sexual and reproductive health to draw firm conclusions. More research is needed to understand the association between cIMD and impaired male sexual and reproductive health. Perez-Garcia LF, Dolhain R, te Winkel B, et al. Male Sexual Health and Reproduction in Cutaneous Immune-Mediated Diseases: A Systematic Review. Sex Med Rev 2021;9:423-433.

Insight in the safety profile of antidiabetic agents glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors in daily practice from the patient perspective.

PURPOSE: The primary aim of this study was to gain insight in the safety profile of the new antidiabetic agents glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in daily practice. The secondary aim was to compare reported adverse drug reactions (ADRs) with information described in the Summary of Product Characteristics (SPC) and to generate knowledge about characteristics, like time to onset and outcome of ADRs. This knowledge is important for drug regulators and clinical practice to understand and manage ADRs better. METHODS: A prospective, observational web-based cohort event monitoring study among first-time users of GLP-1 agonists and DPP-4 inhibitors. Patients were recruited through community pharmacies from 2008 to 2016. Participants were invited to complete six web-based questionnaires over a 1-year periods after start of the antidiabetic agent. Questions were posed about patient characteristics, drug use, and ADRs. Data were analyzed using descriptive statistics. RESULTS: Then, 743 patients were included. Also 62% of all GLP-1 agonist users (total n = 119) and 33% of DPP-4 inhibitor users (total n = 624) experienced an ADR. Of the 10 most reported ADRs, for GLP-1 agonist all, and for DPP-4 inhibitors 8 were described in the drug's SPC. For 45 (91%) ADRs, the patients recovered without discontinuation of the GLP-1 agonist and 79 (73%) ADRs without discontinuation of the DPP-4 inhibitor therapy. CONCLUSIONS: This study gives insight in the safety profile and ADR characteristics of the new antidiabetic agents. This study provides important knowledge for healthcare professionals in managing ADRs and can be directly applied in consultations in daily practice.

Assessment of medication use during pregnancy by Web-based questionnaires, pharmacy records and serum screening.

OBJECTIVE: To compare assessment of early pregnancy medication exposure using three methods of data collection. METHODS: Serum samples were obtained from 752 women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study before gestational week 17. For 52 women using medication at the date of blood sampling according to Web-based questionnaires or pharmacy records, we analysed serum samples using untargeted liquid chromatography time-of-flight spectrometry. RESULTS: Medication was detected in 18 serum samples (35%). Medications taken orally for chronic conditions reported in the questionnaire were detected in serum and vice versa. Pharmacy records did not identify additional exposed women, but missed exposure in 5 women mainly due to unavailability. We observed substantial discordance between the three methods for inhaled medication, dermatological preparations, and medications for short-term use, which went often undetected in serum. CONCLUSIONS: It remains challenging to assess medication use in large-scale studies as no 'gold standard' is currently available.

Aim and Design of pREGnant, the Dutch Pregnancy Drug Register.

Information on the safety of medication use during pregnancy and breastfeeding is scarce, yet use of medication among pregnant and breastfeeding women is widespread. The pREGnant, the Dutch Pregnancy Drug Register, was set up to obtain insight into medication use among pregnant and breastfeeding women and potential effects on maternal and fetal/infant health. The systematically documented, good quality data on medication use during pregnancy and lactation in pREGnant will be used in signal detection, epidemiologic studies and counseling of healthcare providers and patients. The register has a prospective cohort design. The population is derived from pregnant women throughout the Netherlands. Data collection started in April 2014 and enrollment of women is continuous and is characterized by a relative high proportion of women born in the Netherlands with a high education compared with the general Dutch pregnant population. Data on current pregnancy, obstetric history, maternal lifestyle, health and medication use, delivery, and infant health are collected through web-based questionnaires completed by the participating women (three times during pregnancy and three times during the infant's first year of life). If permission is given, the self-reported data can be complemented with information retrieved from Perined, the perinatal registry of the Netherlands, and from obstetric and medical records, and/or pharmacy records. Here, we provide detailed information on the design of the pREGnant, the Dutch Pregnancy Drug Register, as well as descriptive information on characteristics of the participants so far. Currently, steps are being taken to implement the register on a large scale in the Netherlands.

Using Web-Based Questionnaires to Assess Medication Use During Pregnancy: A Validation Study in 2 Prospectively Enrolled Cohorts.

Medication use is often underreported in paper-based questionnaires or interviews. Web-based questionnaires may improve recall of medication use, but data on their validity are currently lacking. Participants in the Pregnancy and Infant Development (PRIDE) Study (2014-2016; n = 557) and the Pregnancy Drug Registry (pREGnant) (2015-2016; n = 169) completed a 6-week paper-based medication diary during gestational weeks 19-24 or 26-31. In week 34, they completed a Web-based questionnaire with questions on medication names, time period and frequency of use, and quantity taken. To assess the degree of underreporting, we calculated the questionnaire's sensitivity using the medication diary as the reference standard. Sensitivity was high for many medication groups, including antiepileptic medication (sensitivity (Sn) = 0.96, 95% confidence interval (CI): 0.89, 1.00), antacids (Sn = 0.89, 95% CI: 0.86, 0.93), and iron preparations (Sn = 0.81, 95% CI: 0.64, 0.98). However, medications for short-term use were underreported more frequently, with sensitivities of 0.54 (95% CI: 0.35, 0.72) for antihistamines, 0.63 (95% CI: 0.57, 0.69) for analgesic and antipyretic agents, and 0.57 (95% CI: 0.51, 0.64) for acetaminophen. Shortening the period of time between exposure and questionnaire administration increased sensitivity substantially. In conclusion, underreporting in Web-based questionnaires is limited for many medication groups. In prospective studies, underreporting of medications for short-term use may be reduced by decreasing the interval between consecutive questionnaires.

Web-based questionnaires to assess perinatal outcome proved to be valid.

OBJECTIVES: The objective of this study was to validate a Web-based questionnaire completed by the mother to assess perinatal outcome used in a prospective cohort study. STUDY DESIGN AND SETTING: For 882 women with an estimated date of delivery between February 2012 and February 2015 who participated in the PRegnancy and Infant DEvelopment (PRIDE) Study, we compared data on pregnancy outcome, including mode of delivery, plurality, gestational age, birth weight and length, head circumference, birth defects, and infant sex, from Web-based questionnaires administered to the mothers 2 months after delivery with data from obstetric records. For continuous variables, we calculated intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs), whereas sensitivity and specificity were determined for categorical variables. RESULTS: We observed only very small differences between the two methods of data collection for gestational age (ICC, 0.91; 95% CI, 0.90-0.92), birth weight (ICC, 0.96; 95% CI, 0.95-0.96), birth length (ICC, 0.90; 95% CI, 0.87-0.92), and head circumference (ICC, 0.88; 95% CI, 0.80-0.93). Agreement between the Web-based questionnaire and obstetric records was high as well, with sensitivity ranging between 0.86 (termination of pregnancy) and 1.00 (four outcomes) and specificity between 0.96 (term birth) and 1.00 (nine outcomes). CONCLUSION: Our study provides evidence that Web-based questionnaires could be considered as a valid complementary or alternative method of data collection.