Trends in RED Blood CELL Transfusions within the Biologics Effectiveness and Safety (BEST) Initiative Network, 2012-2018

The U.S. FDA Center for Biologics Evaluation and Research (CBER) recently established the Biologics Effectiveness and Safety (BEST) Initiative which is an active surveillance system for all CBER regulated products, including blood components, and which also allows for investigation of patterns in utilization. The 2015 National Blood Collection& Utilization Survey (NBCUS) Report found an overall decrease in the number of units of red blood cells (RBCs) transfused in recent years. The aim of this study is to describe the utilization of RBCs from 2012 through 2018 using electronic health records (EHR) from three data sources participating in the BEST Initiative

WHO global vaccine safety multi-country collaboration project on safety in pregnancy: Assessing the level of diagnostic certainty using standardized case definitions for perinatal and neonatal outcomes and maternal immunization.

Standardized case definitions strengthen post-marketing safety surveillance of new vaccines by improving generated data, interpretation and comparability across surveillance systems. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project developed standardized case definitions for 21 key obstetric and neonatal terms following the Brighton Collaboration (BC) methodology. In this prospective cohort study, we assessed the applicability of GAIA definitions for maternal immunization exposure and for low birth weight (LBW), preterm birth, small for gestational age (SGA), stillbirth, neonatal death, neonatal infection, and congenital microcephaly. We identified the missing data elements that prevented identified cases and exposures from meeting the case definition (level 1-3 of BC diagnostic certainty). Over a one-year period (2019-2020), all births occurring in 21 sites (mostly secondary and tertiary hospitals) in 6 Low Middle Income Countries and 1 High Income Country were recorded and the 7 perinatal and neonatal outcome cases were identified from routine medical records. Up to 100 cases per outcome were recruited sequentially from each site. Most cases recruited for LBW, preterm birth and neonatal death met the GAIA case definitions. Birth weight, a key parameter for all three outcomes, was routinely recorded at all sites. The definitions for SGA, stillbirth, neonatal infection (particularly meningitis and respiratory infection) and congenital microcephaly were found to be less applicable. The main barrier to obtaining higher levels of diagnostic certainty was the lack of sonographic documentation of gestational age in first or second trimester. The definition for maternal immunization exposure was applicable, however, the highest level of diagnostic certainty was only reached at two sites. Improved documentation of maternal immunization will be important for vaccine safety studies. Following the field-testing of these 8 GAIA definitions, several improvements are suggested that may lead to their easier implementation, increased standardization and hence comparison across studies

Trends in Influenza Vaccination Rates among a Medicaid Population from 2016 to 2021

Seasonal influenza is a leading cause of death in the U.S., causing significant morbidity, mortality, and economic burden. Despite the proven efficacy of vaccinations, rates remain notably low, especially among Medicaid enrollees. Leveraging Medicaid claims data, this study characterizes influenza vaccination rates among Medicaid enrollees and aims to elucidate factors influencing vaccine uptake, providing insights that might also be applicable to other vaccine-preventable diseases, including COVID-19. This study used Medicaid claims data from nine U.S. states (2016–2021], encompassing three types of claims: fee-for-service, major Medicaid managed care plan, and combined. We included Medicaid enrollees who had an in-person healthcare encounter during an influenza season in this period, excluding those under 6 months of age, over 65 years, or having telehealth-only encounters. Vaccination was the primary outcome, with secondary outcomes involving in-person healthcare encounters. Chi-square tests, multivariable logistic regression, and Fisher’s exact test were utilized for statistical analysis. A total of 20,868,910 enrollees with at least one healthcare encounter in at least one influenza season were included in the study population between 2016 and 2021. Overall, 15% (N = 3,050,471) of enrollees received an influenza vaccine between 2016 and 2021. During peri-COVID periods, there was an increase in vaccination rates among enrollees compared to pre-COVID periods, from 14% to 16%. Children had the highest influenza vaccination rates among all age groups at 29%, whereas only 17% were of 5–17 years, and 10% were of the 18–64 years were vaccinated. We observed differences in the likelihood of receiving the influenza vaccine among enrollees based on their health conditions and medical encounters. In a study of Medicaid enrollees across nine states, 15% received an influenza vaccine from July 2016 to June 2021. Vaccination rates rose annually, peaking during peri-COVID seasons. The highest uptake was among children (6 months–4 years), and the lowest was in adults (18–64 years). Female gender, urban residency, and Medicaid-managed care affiliation positively influenced uptake. However, mental health and substance abuse disorders decreased the likelihood. This study, reliant on Medicaid claims data, underscores the need for outreach services

Operational lessons learned in conducting an international study on pharmacovigilance in pregnancy in resource-constrained settings: The WHO Global Vaccine safety Multi-Country collaboration project.

The WHO Global Vaccine Safety Multi-Country Collaboration study on safety in pregnancy aims to estimate the minimum detectable risk for selected perinatal and neonatal outcomes and assess the applicability of standardized case definitions for study outcomes and maternal immunization in low- and middle-income countries (LMICs). This paper documents the operational lessons learned from the study. A prospective observational study was conducted across 21 hospitals in seven countries. All births occurring at sites were screened to identify select perinatal and neonatal outcomes from May 2019 to August 2020. Up to 100 cases per outcome were recruited to assess the applicability of standardized case definitions. A multi-pronged study quality assurance plan was implemented. The impact of the COVID-19 pandemic on site functioning and project implementation was also assessed. Multi-layered ethics and administrative approvals, limited clinical documentation, difficulty in identifying outcomes requiring in-hospital follow-up, and poor quality internet connectivity emerged as important barriers to study implementation. Use of electronic platforms, application of a rigorous quality assurance plan with frequent interaction between the central and site teams helped improve data quality. The COVID-19 pandemic disrupted data collection for up to 6 weeks in some sites. Our study succeeded in establishing an international hospital-based surveillance network for evaluating perinatal and neonatal outcomes using common study protocol and procedures in geographically diverse sites with differing levels of infrastructure, clinical and health-utilization practices. The enhanced surveillance capacity of participating sites shall help support future pharmacovigilance efforts for pregnancy interventions

Estimating baseline rates of adverse perinatal and neonatal outcomes using a facility-based surveillance approach: A prospective observational study from the WHO Global Vaccine Safety Multi-Country Collaboration on safety in pregnancy.

BACKGROUND: Most perinatal and neonatal deaths occur in low- and middle-income countries (LMICs), yet, quality data on burden of adverse outcomes of pregnancy is limited in such countries. METHODS: A network of 21 maternity units, across seven countries, undertook surveillance for low birthweight, preterm birth, small for gestational age (SGA), stillbirths, congenital microcephaly, in-hospital neonatal deaths, and neonatal infections in a cohort of over 85,000 births from May 2019 - August 2020. For each outcome, site-specific rates per 1,000 livebirths (or per 1,000 total births for stillbirth) and 95% confidence intervals (CI) were calculated. Descriptive sensitivity analysis was conducted to gain insight regarding underreporting of four outcomes at 16 sites. FINDINGS: Estimated rates varied across countries and sites, ranging between 43·3-329·5 and 21·4-276·6/1000 livebirths for low birthweight and preterm birth respectively and 11·8-81/1,000 livebirths for SGA. No cases of congenital microcephaly were reported by three sites while the highest estimated rate was 13/1,000 livebirths. Neonatal infection and neonatal death rates varied between 1·8-73 and 0-59·9/1000 livebirths respectively while stillbirth rates ranged between 0-57·1/1000 total births across study sites. Results from the sensitivity analysis confirmed the underreporting of congenital microcephaly and SGA in our study. INTERPRETATION: Our study establishes site-specific baseline rates for important adverse perinatal and neonatal outcomes and addresses a critical evidence gap towards improved monitoring of benefits and risks of emerging pregnancy and neonatal interventions. FUNDING: The study was sponsored by the World Health Organization with funding from the Bill and Melinda Gates Foundation

Use of a rapid electronic survey methodology to estimate blood donors' potential exposure to emerging infectious diseases: Application of a statistically representative sampling methodology to assess risk in US blood centers

UNLABELLED: Risk assessments of transfusion-transmitted emerging infectious diseases (EIDs) are complicated by the fact that blood donors demographics and behaviors can be different from the general population. Therefore, when assessing potential blood donor exposure to EIDs, the use of general population characteristics, such as U.S. travel statistics, may invoke uncertainties that result in inaccurate estimates of blood donor exposure. This may, in turn, lead to the creation of donor deferral policies that do not match actual risk. STUDY DESIGN AND METHODS: This article reports on the development of a system to rapidly assess EID risks for a nationally representative portion of the U.S. blood donor population. To assess the effectiveness of this system, a test survey was developed and deployed to a statistically representative sample frame of blood donors from five blood collecting organizations. Donors were directed to an online survey to ascertain their recent travel and potential exposure to Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: A total of 7128 responses were received from 54 256 invitations. The age-adjusted estimated total number of blood donors potentially exposed to MERS-CoV was approximately 15 640 blood donors compared to a lower U.S. general population-based estimate of 9610 blood donors. CONCLUSION: The structured donor demographic sample-based data provided an assessment of blood donors potential exposure to an emerging pathogen that was 63% larger than the U.S. population-based estimate. This illustrates the need for tailored blood donor-based EID risk assessments that provide more specific demographic risk intelligence and can inform appropriate regulatory decision making