Using design thinking to strengthen the community pharmacist's role in epilepsy care.

OBJECTIVE: To use design thinking to develop a community pharmacist-led intervention for people living with epilepsy (PWE) with desirable, feasible, and viable features. METHODS: This study used design thinking. Three patient personas were created based on previous research: a newly diagnosed PWE, a well-controlled PWE, and a complex PWE with uncontrolled seizures. An intervention prototype was developed for each of the three personas. Structured interviews were conducted with pharmacists, pharmacy students, patients with diagnosed epilepsy, and caregivers to elicit feedback on which features of each intervention prototype were desirable, feasible, and viable. Interviews were analyzed using rapid content analysis. A multidisciplinary advisory group and the research team prioritized features of the prototypes to include in the final intervention. RESULTS: The following four features were identified as desirable, feasible, and viable for a pharmacist-led intervention for PWE: (1) pharmacist-patient consultations, (2) care plan development, (3) regular check-ins, and (4) care coordination with other health care providers. SIGNIFICANCE: This study identified evidence-based features for a community pharmacist intervention to support epilepsy care using design thinking. A pilot study to evaluate this intervention on the quality of life (QoL), health outcomes and satisfaction of PWE can inform the implementation and feasibility of such patient services.

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed. METHODS: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185). RESULTS: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons. CONCLUSION: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

Data collection systems for active safety surveillance of vaccines during pregnancy in low- and middle-income countries: developing and piloting an assessment tool (VPASS).

BACKGROUND: There is an urgent need for active safety surveillance to monitor vaccine exposure during pregnancy in low- and middle-income countries (LMICs). Existing maternal, newborn, and child health (MNCH) data collection systems could serve as platforms for post-marketing active surveillance of maternal immunization safety. To identify sites using existing systems, a thorough assessment should be conducted. Therefore, this study had the objectives to first develop an assessment tool and then to pilot this tool in sites using MNCH data collection systems through virtual informant interviews. METHODS: We conducted a rapid review of the literature to identify frameworks on population health or post-marketing drug surveillance. Four frameworks that met the eligibility criteria were identified and served to develop an assessment tool capable of evaluating sites that could support active monitoring of vaccine safety during pregnancy. We conducted semi-structured interviews in six geographical sites using MNCH data collection systems (DHIS2, INDEPTH, and GNMNHR) to pilot domains included in the assessment tool. RESULTS: We developed and piloted the "VPASS (Vaccines during Pregnancy - sites supporting Active Safety Surveillance) assessment tool" through interviews with nine stakeholders, including central-level systems key informants and site-level managers from DHIS2 and GNMNHR; DHIS2 in Kampala (Uganda) and Kigali (Rwanda); GNMNHR from Belagavi (India) and Lusaka (Zambia); and INDEPTH from Nanoro (Burkina Faso) and Manhica (Mozambique). The tool includes different domains such as the system's purpose, the scale of implementation, data capture and confidentiality, type of data collected, the capability of integration with other platforms, data management policies and data quality monitoring. Similarities among sites were found regarding some domains, such as data confidentiality, data management policies, and data quality monitoring. Four of the six sites met some domains to be eligible as potential sites for active surveillance of vaccinations during pregnancy, such as a routine collection of MNCH individual data and the capability of electronically integrating individual MNCH outcomes with information related to vaccine exposure during pregnancy. Those sites were: Rwanda (DHIS2), Manhica (IN-DEPTH), Lusaka (GNMNHR), and Belagavi (GNMNHR). CONCLUSION: This study's findings should inform the successful implementation of active safety surveillance of vaccines during pregnancy by identifying and using active individual MNCH data collection systems in LMICs.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

Stakeholder perceptions of community pharmacist population health management of people living with epilepsy.

OBJECTIVE: To identify the predisposing, enabling, and reinforcing factors influencing the integration of community pharmacists in population health approaches to epilepsy care. METHODS: Key informant interviews were conducted with 32 stakeholders, including five people living with epilepsy (PWE), ten caregivers of PWE, seven epileptologists, one neurologist, one epilepsy nurse, and eight community pharmacists in Washington State and Oregon from September 2019 to February 2020. Interviews were audio recorded, transcribed, and analyzed using a rapid content analysis approach guided by the PRECEDE-PROCEED Model to identify predisposing, enabling, and reinforcing factors influencing integration of community pharmacists in population health approaches to epilepsy care. RESULTS: Four predisposing, four enabling, three positive reinforcing factors, and two negative reinforcing factors emerged as influencing integration of community pharmacists in a population health approach to epilepsy care across all stakeholder groups. Predisposing factors included patient advocacy, medication adherence, medication monitoring, and medication education. Enabling factors were a shared vision, collaboration structure, efficient communication, and pharmacist attributes (knowledge, experience, and attitude). Positive reinforcing factors included a team approach, easy to access support, and medication adherence. Negative reinforcing factors were duplicate or conflicting care and limited time and resources. SIGNIFICANCE: This study identified several predisposing, enabling, and reinforcing factors influencing integration of community pharmacists in population health approaches to epilepsy care based on stakeholder perceptions. Community pharmacists may consider these factors when implementing services for patients with epilepsy.

Global antibiotic consumption and usage in humans, 2000-18: a spatial modelling study.

BACKGROUND: Antimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption. METHODS: In this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years. FINDINGS: We analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3 (95% uncertainty interval 13·2-15·6) defined daily doses (DDD) per 1000 population per day in 2018 (40·2 [37·2-43·7] billion DDD), an increase of 46% from 9·8 (9·2-10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8-5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia. INTERPRETATION: To our knowledge, this is the first study that incorporates antibiotic usage and consumption data and uses geostatistical modelling techniques to estimate antibiotic consumption for 204 countries from 2000 to 2018. Our analysis identifies both high rates of antibiotic consumption and a lack of access to antibiotics, providing a benchmark for future interventions. FUNDING: Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill & Melinda Gates Foundation.

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

BACKGROUND: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. METHODS: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). RESULTS: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes.

BACKGROUND: We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783). METHODS: We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables. RESULTS: We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks. CONCLUSION: This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review.

BACKGROUND: Pregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed. METHODS: We conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus. RESULTS: We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures during the three trimesters of pregnancy.The most frequent exposure was to AS03 adjuvant in the context of A/H1N1 pandemic influenza vaccines (n=24), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03) - corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines that were selected for review by the COVAX MIWG or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted given their novelty. Our findings support current WHO guidelines recommending that pregnant women may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

Maternal and neonatal data collection systems in low- and middle-income countries for maternal vaccines active safety surveillance systems: A scoping review.

BACKGROUND: Most post-licensure vaccine pharmacovigilance in low- and middle-income countries (LMICs) are passive reporting systems. These have limited utility for maternal immunization pharmacovigilance in LMIC settings and need to be supplemented with active surveillance. Our study's main objective was to identify existing perinatal data collection systems in LMICs that collect individual information on maternal and neonatal health outcomes and could be developed to inform active safety surveillance of novel vaccines for use during pregnancy. METHODS: A scoping review was performed following the Arksey and O'Malley six-stage approach. We included studies describing electronic or mixed paper-electronic data collection systems in LMICs, including research networks, electronic medical records, and custom software platforms for health information systems. Medline PubMed, EMBASE, Global Health, Cochrane Library, LILACS, Bibliography of Asian Studies (BAS), and CINAHL were searched through August 2019. We also searched grey literature including through Google and websites of existing relevant perinatal data collection systems, as well as contacted authors of key studies and experts in the field to validate the information and identify additional sources of relevant unpublished information. RESULTS: A total of 11,817 records were identified. The full texts of 264 records describing 96 data collection systems were assessed for eligibility. Eight perinatal data collection systems met our inclusion criteria: Global Network's Maternal Newborn Health Registry, International Network for the Demographic Evaluation of Populations and their Health; Perinatal Informatic System; Pregnancy Exposure Registry & Birth Defects Surveillance; SmartCare; Open Medical Record System; Open Smart Register Platform and District Health Information Software 2. These selected systems were qualitatively characterized according to seven different domains: governance; system design; system management; data management; data sources, outcomes and data quality. CONCLUSION: This review provides a list of active maternal and neonatal data collection systems in LMICs and their characteristics as well as their outreach, strengths, and limitations. Findings could potentially help further understand where to obtain population-based high-quality information on outcomes to inform the conduct of maternal immunization active vaccine safety surveillance activities and research in LMICs.

Community pharmacists' role in caring for people living with epilepsy: A scoping review.

OBJECTIVE: To identify and describe studies about pharmacist-provided services for people with epilepsy and their caregivers. METHODS: PubMed/MEDLINE and EMBASE were searched for articles that were: (1) written in English, (2) published in 1985 or later, (3) a peer-reviewed empirical study or practice report, and (4) describing an intervention provided by a pharmacist for people with epilepsy and/or their caregivers in an outpatient pharmacy setting. The abstracts and full text, when necessary, were reviewed by two investigators to assess eligibility. Data were extracted from each article by two investigators using a standardized abstraction form based on the Pharmacist Patient Care Services Intervention Reporting (PaCIR) checklist. Data elements of interest included components of service, mode of service delivery, frequency, number and duration of sessions for the service, roles and responsibilities of the community pharmacist, type of community pharmacy, outcomes and measures evaluated along with data sources, and findings and results. Risk of bias was not assessed due to the descriptive nature of the review. RESULTS: Twelve articles were included, seven of which reported services conducted in the United States. The most common service reported was medication management (n = 7) followed by education and counseling (n = 4). One article described a care coordination documentation tool that could be used by pharmacists and physicians in epilepsy care. Most interventions were evaluated using observational designs (n = 5) or did not have an evaluation component (n = 4). SIGNIFICANCE: This review provides examples of community pharmacists providing care to people living with epilepsy that extend beyond dispensing medications. Findings demonstrate that there is little published evidence on community pharmacists' contributions to epilepsy care and suggest opportunities for further exploration and innovation. This review serves as the first step in a project that seeks to develop a stakeholder-driven community pharmacist integrated population health intervention for people living with epilepsy.

Medication utilization pattern among outpatients during the Hajj mass gathering.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) provides free healthcare, including medications, for the over 2 million Muslim pilgrims who attend Hajj every year. Information on drug utilization patterns at the Hajj is important to strengthen the supply chain for medicines, avert stock-outs, identify inappropriate use, and support public health planning for the event. METHOD: We investigated drug utilization pattern among outpatients in eight seasonal Holy sites hospitals in Makkah, KSA, during the 2018 Hajj. Data on medication prescribed and dispensed were retrieved from the hospitals' electronic records. Data were also used to calculate six of the WHO indicators for drug use at these facilities. RESULTS: A total of 99,117 medications were prescribed for 37,367 outpatients during 37,933 encounters. Outpatients were mainly older males and originated from 134 countries. Twenty medications accounted for 72.8% of the 323 different medications prescribed. These were mainly nonsteroidal anti-inflammatory drugs, analgesics and antipyretics, and antibacterial medicines for systemic use. Outpatients were prescribed an average of 2.6 (SD = 1.2) drugs per consultation and polypharmacy (≥5 medications) was observed in 4.8% of the encounters. Antibiotics and an injection were prescribed in 46.9% and 6.5% of encounters, respectively. Nearly 90% of the prescribed drugs were actually dispensed. On average, medications were dispensed 16.4 (SD = 119.8) minutes from the time they were prescribed for the patient. All hospitals had a copy of the essential drugs list available and all of the prescribed drugs appeared on that list. CONCLUSION: Nonsteroidal anti-inflammatory drugs, analgesics and antibiotics are the most common medications prescribed to outpatient during Hajj. Our results, including the calculated WHO drug use indicators, can form a basis for further investigations into appropriate drug use at the Hajj and for planning purposes. These results could also guide the development of reference values for medications prescribing and use indicators at mass gatherings.

Maternal and neonatal data collection systems in low- and middle-income countries: scoping review protocol.

Background: Pregnant women and neonates represent one of the most vulnerable groups, especially in low- and middle-income countries (LMICs). A recent analysis reported that most vaccine pharmacovigilance systems in LMICs consist of spontaneous (passive) adverse event reporting. Thus, LMICs need effective active surveillance approaches, such as pregnancy registries. We intend to identify currently active maternal and neonatal data collection systems in LMICs, with the potential to inform active safety electronic surveillance for novel vaccines using standardized definitions. Methods: A scoping review will be conducted based on established methodology. Multiple databases of indexed and grey literature will be searched with a specific focus on existing electronic and paper-electronic systems in LMICs that collect continuous, prospective, and individual-level data from antenatal care, delivery, neonatal care (up to 28 days), and postpartum (up to 42 days) at the facility and community level, at the national and district level, and at large hospitals. Also, experts will be contacted to identify unpublished information on relevant data collection systems. General and specific descriptions of Health Information Systems (HIS) extracted from the different sources will be combined and duplicated HIS will be removed, producing a list of unique statements. We will present a final list of Maternal, Newborn, and Child Health systems considered flexible enough to be updated with necessary improvements to detect, assess and respond to safety concerns during the introduction of vaccines and other maternal health interventions. Selected experts will participate in an in-person consultation meeting to select up to three systems to be further explored in situ. Results and knowledge gaps will be synthesized after expert consultation.