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

Sexual function and reproduction can be impaired in men with rheumatic diseases: A systematic review

Information about the possible effect of rheumatic diseases on male sexual function and reproduction (sexual health) is scarce and difficult to summarize. Factors known to impair sexual health, such as inflammation, medication use and hypogonadism can be present in a significant proportion of male patients with rheumatic diseases. Objectives: The objective of our study was to systematically review the literature for the influence of paternal rheumatic disease on sexual health, such as sexual function, reproductive hormones, male fertility, pregnancy and offspring outcomes. Data sources: English language articles identified through Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Google Scholar and the Clinical trial registries of Europe and the USA published until February 2019. Study appraisal and synthesis methods: Literature was synthesized in narrative form and in summary tables. Outcomes were categorized as: sexual function, reproductive hormones, fertility and pregnancy and offspring outcomes. Results are presented per category and per disease. Results: 9735 articleswere identified with our search strategy. After removal of duplicates, excluding articles by screening titles and abstracts and assessing eligibility by reading 289 fulltext articles, 87 articles fulfilled the eligibility criteria. All included studies enrolled patients diagnosed with a rheumatic disease and had results at least on one of the outcome categories. Sexual function was the most common category, followed by reproductive hormones, fertility and pregnancy and offspring outcomes. Sexual function is impaired in a high proportion of patients with rheumatic diseases. This was statistically significant in most of the studies where a control group was available. Clinically relevant abnormalities in reproductive hormones were mainly identified in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and a positive correlation with disease activity were reported. Semen quality inmen with rheumatic diseases can be impaired in patients with SLE, SpA, sarcoidosis, BD and MWS. Sperm count and motility were the most common semen quality parameters affected. No negative effect of paternal RA and vasculitis on pregnancy outcomes were reported in 3 studies. No studies reporting the effect of paternal disease on offspring outcomes were identified. Limitations: Most of the studies included in this review suffer from an inconsistent methodological quality, definitions of outcomes varied in several studies, a wide variety of screening questionnaires and/or diagnostic tools were used and results might only apply to the specific populations that were studied. Conclusions: This systematic review suggests that sexual health is impaired in men with rheumatic diseases. The degree and extent of sexual health impairment vary per disease. More research is needed to fully understand the link between rheumatic diseases and impaired male sexual health. Meanwhile, rheumatologists should be aware of this association and discuss it with their patients. Implications of key findings: Sexual health of men with rheumatic diseases can be impaired by the disease itself. Especially in men trying to conceive, information on sexual function, reproductive hormones and sperm quality are needed to identify these problems. Treatment resulting in lower disease activity can improve overall sexual health in man with rheumatic diseases and facilitate their journey to fatherhoo

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 sexua

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

#35 Paternal exposure to immunosuppressive drugs:possible influence on pregnancy outcome and infant's health, a systematic review

Introduction: Although there are theoretical concerns about the possible influence on fertility, pregnancy outcome or complications and health of the offspring, preconceptional paternal drug exposure has not been studied significantly. This applies to immunosuppressive drugs like methotrexate and mycophenolic acid. As start of a research project on paternal immunosuppressive drugs and/or autoimmune diseases and their possible influence on fertility, pregnancy outcomes and child health we performed two systematic reviews, one on drugs and one on diseases. Here we give an overview of the pregnancy and infant outcomes of immunosuppressive drugs from the initial search. Methods: The protocol for this systematic review is written according to the PRISMA-P statement and registered in PROSPERO. A systematic literature search was performed in Embase and MEDLINE. Additional sources included Cochrane Central register of Controlled Trials, Web of Science and Google Scholar. The initial search was done in April 2018. For each database a search profile was developed including keywords regarding male fertility, paternal exposure, pregnancy outcomes and complications and infant's health. This was combined with immunosuppressive drugs. The literature search was limited to the English language and human subjects. The following type of studies were included: case control studies, cohort studies, cross-sectional studies, case reports and case series. The methodological quality of the studies was assessed with the Newcastle Ottawa Scale. Results: After deduplication 3720 publications were eligible for title and abstract screening. Full text reading was done for 260 publications, which resulted in inclusion of 41 references on pregnancy and infant related outcomes. Since 2016, 7 population-based cohort studies were published based on the Danish registries, with potential overlap in included pregnancies. The Norwegian registries were used in 2 population-based cohort studies. Other cohort studies used data from Teratology Information Services, the USA National Transplant Pregnancy Registry or hospitals. Case series were mostly based on hospital records. Most studies looked at azathioprine and/or 6-mercaptopurine (n = 8) or methotrexate (n = 5). Other drugs in studies were TNA-alpha blockers, calcineurin inhibitors, mycophenolic acid or colchicine. The most frequently reported outcomes were pregnancy outcome (e.g. miscarriage, live birth), preterm birth (gestational age), low birthweight (birth weight) and congenital abnormalities, in general no major differences between exposed and the comparison group were reported. Conclusions: Paternal use of immunosuppressive drugs preconceptionally has received more attention in the last years. Preliminary data of the systematic review implies that the reported outcomes after immunosuppressive drug use do not differ significantly from the comparison group. The numbers in the different publications, and also the total number of pregnancies included, are still low. The quality of the publications ranges between high and low