Sex differences in the intensity of statin prescriptions at initiation in a primary care setting.

BACKGROUND: Current guidelines for the prevention and management of cardiovascular diseases (CVD) provide similar recommendations for the use of statins in both women and men. In this study, we assessed sex differences in the intensity of statin prescriptions at initiation and in the achievement of treatment targets, among individuals without and with CVD, in a primary care setting. METHODS: Electronic health record data from statin users were extracted from the PHARMO Data Network. Poisson regressions were used to investigate sex differences in statin intensity and in the achievement of treatment targets. Analyses were stratified by age group, disease status and/or CVD risk category. RESULTS: We included 82 714 individuals (46% women) aged 40-99 years old. In both sexes, the proportion of individuals with a dispensed prescription for high-intensity statin at initiation increased between 2011 and 2020. Women were less likely to be prescribed high-intensity statins as compared with men, both in the subgroups without a history of CVD (risk ratio (RR) 0.69 (95% CI: 0.63 to 0.75)) and with CVD (RR 0.77 (95% CI: 0.74 to 0.81)). Women were less likely than men to achieve target levels of low-density lipoprotein cholesterol following statin initiation in the subgroup without CVD (RR 0.98 (95% CI: 0.97 to 1.00)) and with a history of CVD (RR 0.94 (95% CI: 0.89 to 0.98)). CONCLUSION: Compared with men, women were less likely to be prescribed high-intensity statins at initiation and to achieve treatment targets, both in people without and with a history of CVD, and independent of differences in other individual and clinical characteristics.

COVID-19 and pregnancy: A European study on pre- and post-infection medication use.

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

Building a Sustainable Learning Health Care System for Pregnant and Lactating People: Interview Study Among Data Access Providers.

BACKGROUND: In many areas of health care, learning health care systems (LHSs) are seen as promising ways to accelerate research and outcomes for patients by reusing health and research data. For example, considering pregnant and lactating people, for whom there is still a poor evidence base for medication safety and efficacy, an LHS presents an interesting way forward. Combining unique data sources across Europe in an LHS could help clarify how medications affect pregnancy outcomes and lactation exposures. In general, a remaining challenge of data-intensive health research, which is at the core of an LHS, has been obtaining meaningful access to data. These unique data sources, also called data access providers (DAPs), are both public and private organizations and are important stakeholders in the development of a sustainable and ethically responsible LHS. Sustainability is often discussed as a challenge in LHS development. Moreover, DAPs are increasingly expected to move beyond regulatory compliance and are seen as moral agents tasked with upholding ethical principles, such as transparency, trustworthiness, responsibility, and community engagement. OBJECTIVE: This study aims to explore the views of people working for DAPs who participate in a public-private partnership to build a sustainable and ethically responsible LHS. METHODS: Using a qualitative interview design, we interviewed 14 people involved in the Innovative Medicines Initiative (IMI) ConcePTION (Continuum of Evidence from Pregnancy Exposures, Reproductive Toxicology and Breastfeeding to Improve Outcomes Now) project, a public-private collaboration with the goal of building an LHS for pregnant and lactating people. The pseudonymized transcripts were analyzed thematically. RESULTS: A total of 3 themes were identified: opportunities and responsibilities, conditions for participation and commitment, and challenges for a knowledge-generating ecosystem. The respondents generally regarded the collaboration as an opportunity for various reasons beyond the primary goal of generating knowledge about medication safety during pregnancy and lactation. Respondents had different interpretations of responsibility in the context of data-intensive research in a public-private network. Respondents explained that resources (financial and other), scientific output, motivation, agreements collaboration with the pharmaceutical industry, trust, and transparency are important conditions for participating in and committing to the ConcePTION LHS. Respondents also discussed the challenges of an LHS, including the limitations to (real-world) data analyses and governance procedures. CONCLUSIONS: Our respondents were motivated by diverse opportunities to contribute to an LHS for pregnant and lactating people, primarily centered on advancing knowledge on medication safety. Although a shared responsibility for enabling real-world data analyses is acknowledged, their focus remains on their work and contribution to the project rather than on safeguarding ethical data handling. The results of our interviews underline the importance of a transparent governance structure, emphasizing the trust between DAPs and the public for the success and sustainability of an LHS.

Sex Differences in the Primary Prevention of Cardiovascular Diseases in a Dutch Primary Care Setting.

Background: Sex differences in the primary prevention of cardiovascular diseases (CVD) have been shown, but the evidence is mixed and fragmented. In this study, we assessed sex differences in cardiovascular risk factors assessment, risk factor levels, treatment, and meeting of treatment targets, within a Dutch primary care setting. Methods: Data were obtained from individuals aged 40 to 70 years old, without prior CVD, registered during the entire year in 2018 at one of the 51 general practices participating in the Julius General Practitioner's Network (JGPN). History of CVD was defined based on the International Classification of Primary Care (ICPC). Linear and Poisson regressions were used to investigate sex differences in risk factor assessment, risk factor levels, treatment, and meeting of treatment targets. Results: We included 83,903 individuals (50% women). With the exception of glycated hemoglobin (HbA1c), all risk factors for CVD were more often measured in women than in men. Lipid measurements and body mass index values were higher in women, while blood pressure (BP) and HbA1c levels were higher in men, along with estimated glomerular filtration rate (eGFR) levels. Among individuals with elevated BP or cholesterol levels, no sex difference was observed in the prescription of antihypertensive medications (RR 1.00, 95% CI: 0.94-1.06) but women were less likely than men to receive lipid-lowering medications (RR 0.87, 95% CI: 0.79-0.95). Among treated individuals, women were more likely than men to meet adequate levels of blood pressure (RR 1.17, 95% CI: 1.09-1.25) and less likely to meet target levels of cholesterol (RR 0.90, 95% CI: 0.83-0.98). Conclusion: While women were more likely to have their CVD risk factors measured, they were less likely to be prescribed lipid-lowering medications and to meet target levels. When treated, men were less likely to achieve adequate blood pressure control.

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic: Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS).

INTRODUCTION: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. MATERIAL AND METHODS: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. RESULTS: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27-1.02) per 1000 maternities, with notable heterogeneity across countries (I2 = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%-13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%-55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. CONCLUSIONS: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

COVID-19 Vaccine Safety Monitoring Studies in Low- and Middle-Income Countries (LMICs)-A Systematic Review of Study Designs and Methods.

BACKGROUND: Post-marketing vaccine safety surveillance aims to monitor and quantify adverse events following immunization in a population, but little is known about their implementation in low- and middle-income countries (LMICs). We aimed to synthesize methodological approaches used to assess adverse events following COVID-19 vaccination in LMICs. METHODS: For this systematic review, we searched articles published from 1 December 2019 to 18 February 2022 in main databases, including MEDLINE and Embase. We included all peer-reviewed observational COVID-19 vaccine safety monitoring studies. We excluded randomized controlled trials and case reports. We extracted data using a standardized extraction form. Two authors assessed study quality using the modified Newcastle-Ottawa Quality Assessment Scale. All findings were summarized narratively using frequency tables and figures. RESULTS: Our search found 4254 studies, of which 58 were eligible for analysis. Many of the studies included in this review were conducted in middle-income countries, with 26 studies (45%) in lower-middle-income and 28 (48%) in upper-middle-income countries. More specifically, 14 studies were conducted in the Middle East region, 16 in South Asia, 8 in Latin America, 8 in Europe and Central Asia, and 4 in Africa. Only 3% scored 7-8 points (good quality) on the Newcastle-Ottawa Scale methodological quality assessment, while 10% got 5-6 points (medium). About 15 studies (25.9%) used a cohort study design and the rest were cross-sectional. In half of them (50%), vaccination data were gathered from the participants' self-reporting methods. Seventeen studies (29.3%) used multivariable binary logistic regression and three (5.2%) used survival analyses. Only 12 studies (20.7%) performed model diagnostics and validity checks (e.g., the goodness of fit, identification of outliers, and co-linearity). CONCLUSIONS: Published studies on COVID-19 vaccine safety surveillance in LMICs are limited in number and the methods used do not often address potential confounders. Active surveillance of vaccines in LMICs are needed to advocate vaccination programs. Implementing training programs in pharmacoepidemiology in LMICs is essential.

Assessing vaccine safety during a pandemic: Recent experience and lessons learned for the future.

During the roll out of vaccines during a pandemic, questions regarding vaccine safety often arise. This was surely true during the SARS-CoV-2 pandemic. Different tools and capabilities exist during the pre-authorization phase and post introduction each with its strengths and limitations. Here we review the various tools and their strengths and limitations and discuss what functioned well in high income settings and the limitations that unequal vaccine safety pharmacovigilance capacity imposed upon middle and low income countries.

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort.

AIM: The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS: Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS: We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION: Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy.

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries.

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.

A Learning Healthcare System for pregnant and breastfeeding women: what do women during preconception, pregnancy, and nursing think? - A qualitative study : A contribution from the ConcePTION project.

BACKGROUND: Most medications lack evidence-based information about its safety and efficacy during pregnancy and breastfeeding, because pregnant women are often not included in clinical research. Another way to generate evidence is by using a Learning Healthcare System (LHS) approach. In an LHS, care and research are aligned in such a way that it can accelerate evidence generation and outcomes for patients, based on real-life medication use. For the development of an ethically responsible and sustainable LHS, it is of crucial importance to understand what women think of such an alternative approach to knowledge generation. Therefore, this paper explores their views on an LHS for pregnant and breastfeeding women. METHOD: For this qualitative study, we interviewed 20 women during preconception, pregnancy, or nursing to explore their views on an ethically responsible LHS for pregnant and breastfeeding women. The pseudonymized transcripts were analyzed thematically. RESULTS: We identified four main themes describing women's views on LHSs. The first theme describes that respondents were positive about learning healthcare systems, and considered them to function as a central point for information about their medication, which they felt is currently lacking. The second theme shows that respondents want to contribute to and engage in generating new information because they want to help others and contribute to scientific research. Respondents also mentioned that, currently, not every woman is aware of the risks of the lack of evidence for medication used in pregnancy. The third theme shows that respondents regard their healthcare professional as essential for the translation and interpretation of information, regardless of a learning healthcare system. The last theme describes that respondents will trust a learning healthcare system more if the medical community supports it, and when data collection and processing is transparent. CONCLUSION: Women during preconception, pregnancy and nursing agree that an LHS could be a viable alternative to help close the knowledge gap on the safety of medication used during pregnancy and breastfeeding. The obtained insights from our interviews provide valuable stepping-stones for the development of an ethically responsible and sustainable LHS, as well as for the engagement of women in an LHS.

Challenges Associated with the Safety Signal Detection Process for Medical Devices.

BACKGROUND: Previous safety issues involving medical devices have stressed the need for better safety signal detection. Various European Union (EU) national competent authorities have started to focus on strengthening the analysis of vigilance data. Consequently, article 90 of the new EU regulation states that the European Commission shall put in place systems and processes to actively monitor medical device safety signals. METHODS: A systematic literature review was conducted to synthesize the current state of knowledge and investigate the present tools used for medical device safety signal detection. An electronic literature search was performed in Embase, Medline, Cochrane, Web of science, and Google scholar from inception until January 2017. Articles that included terms related to medical devices and terms associated with safety were selected. A further selection was based on the abstract review. A full review of the remaining articles was conducted to decide on which articles finally to consider relevant for this review. Completeness was assessed based on the content of the articles. RESULTS: Our search resulted in a total of 20,819 articles, of which 24 met the inclusion criteria and were subject to data extraction and completeness scoring. A wide range of data sources, especially spontaneous reporting systems and registries, used for the detection and assessment of product problems and patient harms associated with the use of medical devices, were studied. Coding is remarkably heterogeneous, no agreement on the preferred methods for signal detection exists, and no gold standard for signal detection has been established thus far. CONCLUSION: Data source harmonization, the development of gold standard signal detection methodologies and the standardization of coding dictionaries are amongst the recommendations to support the implementation of a new proactive approach to signal detection. The new safety surveillance system will be able to use real-world evidence to support regulatory decision-making across all jurisdictions.

Incidence Rates of Autoimmune Diseases in European Healthcare Databases: A Contribution of the ADVANCE Project.

INTRODUCTION: The public-private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data. METHODS: Event rates were calculated for the following outcomes: acute disseminated encephalomyelitis, Bell's palsy, Guillain-Barré syndrome, immune thrombocytopenia purpura, Kawasaki disease, optic neuritis, narcolepsy, systemic lupus erythematosus, and transverse myelitis. Cases were identified by diagnosis codes. Participating organizations/databases originated from Denmark, Italy, Spain, and the UK. The source population comprised all persons registered, with at least 1 year of data prior to the study start, or follow-up from birth. Stratified incidence rates were computed per database over the period 2003 to 2014. RESULTS: Between 2003 and 2014, 148,947 incident cases of nine autoimmune diseases were identified. Crude incidence rates were highest for Bell's palsy [23.8/100,000 person-years (PYs), 95% confidence interval (CI) 23.6-24.1] and lowest for Kawasaki disease (0.7/100,000 PYs, 95% CI 0.6-0.7). Specific patterns were observed by sex, age, calendar time, and data sources. Rates were comparable with published estimates. CONCLUSION: A range of autoimmune events could be identified in the ADVANCE system. Estimation of rates indicated consistency across selected European healthcare databases, as well as consistency with US published data.

Introduction or Discontinuation of Additional Risk Minimisation Measures During the Life Cycle of Medicines in Europe.

INTRODUCTION: Additional risk minimisation measures (aRMMs) may be required to minimise important risks of medicines. aRMMs may be required at the time of authorisation, but may also be introduced or discontinued during the product life cycle as new safety information arises. The aim of this study is to describe post-authorisation introductions of new aRMMs and discontinuations of existing aRMMs for medicines authorised in the European Union (EU). METHODS: We performed a retrospective cohort study that included all new active substances authorised through the EU centralised procedure between January 1st 2006 and December 31st 2017. Data was extracted from European Public Assessment Reports available on the website of the European Medicines Agency (ema.europa.eu). Medicines were followed up from the date of marketing authorisation (MA) until first introduction or discontinuation of aRMMs, excluding Direct Healthcare Professional Communications (DHPCs), withdrawal/suspension/revocation of the MA, or July 1st 2018, when data extraction took place. Descriptive statistics were used to analyse frequency data, and survival analysis was used to calculate 5- and 10-year probability of introduction or discontinuation of aRMMs. RESULTS: A total of 476 medicines were authorised during the study period. The probability of getting aRMMs after authorisation for products authorised without aRMMs was 3.5% [95% confidence interval (CI) 1.2-5.7] within 5 years after authorisation and 6.9% (95% CI 2.6-11) within 10 years after authorisation. For products authorised with aRMMs, the probability of discontinuation of aRMMs was 0.9% (95% CI 0-2.6) within 5 years and 8.3% (95% CI 0-16.1) within 10 years after authorisation. CONCLUSIONS: We found low probabilities of introduction and discontinuation of aRMMs (excluding DHPCs) during the product life cycle for medicines authorised between 2006 and 2017. The low rate of discontinuation may potentially be due to a lack of robust data on effectiveness of aRMMs. Further research is needed to get more insight into the dynamics of aRMMs during the medicine life cycle.

Dissemination of Direct Healthcare Professional Communications on Medication Errors for Medicinal Products in the EU: An Explorative Study on Relevant Factors.

INTRODUCTION: When serious medication errors (ME) are identified, communication to the field may be necessary. In the EU, communication of serious safety issues, such as medication errors associated with adverse drug reactions, is done through direct healthcare professional communications (DHPCs). We aimed to identify how often DHPCs about medication errors are distributed, and we explored factors associated with these ME DHPCs. METHODS: We performed a descriptive study of all centrally authorised products (CAPs) approved before 1 May 2019 in the EU. All DHPCs issued between 1 January 2001 and 1 May 2019 were reviewed for ME content. Characteristics of CAPs were collected from the website of the European Medicines Agency. A Kaplan-Meier survival analysis was performed to estimate the 5- and 10-year probability of the occurrence of a first ME DHPC. A logistic regression was performed to explore risk factors for ME DHPCs. RESULTS: A total of 678 CAPs were included, of which 35 required an ME DHPC during the study period. The 5-year probability for a CAP to have a first ME DHPC was 2.5% (95% CI 1.1-3.9) and the 10-year probability was 4.4% (95% CI 2.2-6.5). Among products with an ME DHPC, the 5-year probability of a second ME DHPC was 21.3% (95% CI 0.2-38.0). The risk of ME DHPCs was increased for products with multiple pharmaceutical formulations, enteral liquid or parenteral injection preparations, and products classified as nervous system agents or antineoplastic and immunomodulating agents. CONCLUSIONS: The absolute number of ME DHPCs for CAPs is low and does not give rise to immediate concern. We identified potential risk factors for ME DHPCs that should be taken into account during approval procedures or line extensions.

Vaccines safety and maternal knowledge for enhanced maternal immunization acceptability in rural Uganda: A qualitative study approach.

BACKGROUND: Maternal immunization is a successful and cost-effective public health strategy. It protects pregnant women and their infants from vaccine-preventable diseases. Uganda is exploring new vaccines for pregnant women like replacing Tetanus Toxoid (TT) with Tetanus-Diphtheria (Td). Research on knowledge, attitudes, beliefs, and willingness among pregnant women is needed before the introduction of vaccines for pregnant women. This study was aimed at exploring maternal knowledge, attitudes, willingness, and beliefs towards maternal immunization among pregnant women in rural Uganda. METHODS: This was a qualitative descriptive study. Ten focus group discussions (FGDs) were conducted at antenatal care (ANC) clinics and in a rural community of Uganda. Five key informant interviews (KIIs) were done with health workers, for triangulation. Considering context and research characteristics, data were collected and thematically analyzed. RESULTS: Women were familiar with the importance of maternal vaccines, had positive attitudes, and expressed willingness to take them. Acceptance of a new vaccine could be affected by worries of pregnant women and that of their partners, who influence health seeking decisions in a home concerning adverse events, following the maternal immunization (AEFI). There were misconceptions about introduction of vaccines such as the belief that vaccines treat malaria and general body weakness, and being used as guinea pigs to test for the vaccine before its introduction to the larger population. CONCLUSION: A range of diverse sentiments and beliefs may affect uptake and acceptability of vaccines that are introduced in communities. For instance, ignoring vaccine safety concerns may impede maternal immunization acceptability, because pregnant women and their husbands are concerned about AEFI. Moreover, husbands make all health-seeking decisions at home, and their opinion is key, when considering such interventions.

Blockchain technology applications to postmarket surveillance of medical devices.

INTRODUCTION: The amount of mandatory data that needs to be analyzed as part of a medical device postmarket surveillance (PMS) system has grown exponentially in recent times. This is a consequence of increasingly demanding and complex regulatory requirements from Health Authorities, aimed at a better understanding of the medical device safety evaluation. Proactive approaches to PMS processes are becoming more necessary as regulators increase the scrutiny of device safety. New technologies have been explored to address some of the challenges associated with this changing regulatory environment. AREAS COVERED: This paper focuses on the different technical aspects of blockchain and how this new technology has the potential to support the ongoing efforts to improve the PMS system for medical devices. EXPERT OPINION: To address these challenges, we suggest to generate a private PMS data permissioned blockchain with a proof-of-authority consensus mechanism, to which only a restricted number of designated and audited participants have authorization to validate transactions and add them to the PMS data blockchain ledger. Blockchain has the potential to support a more efficient approach, which could offer many advantages to the different stakeholders involved in the PMS process, such as supporting with new regulatory initiatives.

Descriptive analysis of postmarket surveillance data for hip implants.

PURPOSE: Recent safety issues involving medical devices have highlighted the need for better postmarket surveillance (PMS) evaluation. This article aims to describe and to assess the quality of the PMS data for a medical device and, finally, to provide recommendations to improve the data gathering process. METHODS: A descriptive analysis of medical device reports (MDRs) on the use of MRA, a specific type of hip implant replacement submitted to the Food and Drug Administration Manufacturer and User Facility Device Experience database from 1 January 2008 to 31 December 2017. The number of reports was described as the number of MDRs per unique MDR number and stratified by different variables. The quality was assessed by the level of completeness of the collected PMS data. RESULTS: The total number of reports related to MRA was 2377, and the number of MDRs per year ranged between 84 in 2009 and 452 in 2017. Most of the reports were reported by manufacturer Depuy Johnson & Johnson and were reported by a physician. In 44.9% of the reports, the device problem was reported as "Unknown." When the device problem was known, in the majority of cases, it was related to an implant fracture. The quality of the collected data was assessed as low due to missing information. CONCLUSION: The underlying data should meet high quality standards to generate more evidence and to ensure a timely signal generation. This case study shows that the completeness and quality of the MDRs can be improved. The authors propose the development of tools to ensure a more dynamic complaint data collection to contribute to this enhancement.

Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study.

BACKGROUND: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma. METHODS: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013. Asthma was defined as ≥1 asthma-specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high-dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. RESULTS: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient-years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3-45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. CONCLUSIONS: In a real-world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma.