Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative.

BACKGROUND: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative. METHODS: We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC-transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012-2018. RESULTS: There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC-transfused patients had 1 (~46%) or 2-5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte-reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities. DISCUSSION: ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities.

Changes in transfusion-transmissible infection prevalence and demographics among US blood donors during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic impacted the US blood supply. We compared blood donor demography and infectious disease prevalence before and during the pandemic using a large multicenter database. METHODS: Data were categorized as "Before COVID-19" (March 2018-February 2020) or "During COVID-19" (March 2020-February 2022). Donor demographics, donation frequency, and infectious marker prevalence of HIV, HBV, and HCV were compared for the two time periods. The odds of a donor testing positive for these infections among the two time periods were calculated using multivariable logistic regression. RESULTS: Our study assessed a total of 26,672,213 donations including 13,430,380 before and 13,241,833 during COVID-19. There were significantly more donations from donors who were female, aged 40 and older, white, and repeat, during COVID-19. Donation frequency comparison quantified the increase in donations from donors who were white, female, older, and repeat during the pandemic. The prevalence of HIV and HCV decreased significantly during COVID-19 compared to before, but not for HBV. For HIV, the adjusted odds of infection during the pandemic did not differ but for HBV, the odds were significantly more likely during the pandemic and were significantly lower for HCV. DISCUSSION: Demographics and infectious disease marker prevalence changed during the COVID-19 pandemic in the United States. Prevalence of each infection in the donor population will continue to be monitored to determine if changes were specific to the pandemic period.

How we forecast tomorrow's haemovigilance.

The field of haemovigilance continues to develop, building on more than forty years of international experience. This review considers the current scope and activities of haemovigilance around the world and explores aspects of preparation for the advent of new blood products and alternative therapies to transfusion; new tools for data acquisition (including patient- and donor-reported outcomes, and data from 'wearables') and the analysis and communication of haemovigilance results.

Haemovigilance resources available for everyone: A report from the International Haemovigilance Tools Collaborative Project.

BACKGROUND AND OBJECTIVES: Haemovigilance systems are intended to collect and analyse data, and report findings relating to transfusion complications, such as blood product safety, procedural incidents, and adverse reactions in donors and patients. A common problem among developing haemovigilance programs is the lack of resources and tools available to countries striving to establish or enhance their haemovigilance system. MATERIALS AND METHODS: World Health Organization, in collaboration with International Society for Blood Transfusion (ISBT), International Haemovigilance Network and other haemovigilance experts embarked on a Haemovigilance Tools Project to collect and provide materials and resources to assist with the stepwise implementation of haemovigilance. RESULTS AND CONCLUSIONS: Resources are housed as a virtual compendium on the ISBT website under the Haemovigilance Working Party. These are managed by a subcommittee of the Working Party and are freely available and downloadable to all without requiring ISBT membership.

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.

Background rates for severe cutaneous reactions in the US: Contextual support for safety assessment of COVID-19 vaccines and novel biologics.

The global COVID-19 public health crisis has resulted in extraordinary collaboration to expeditiously develop vaccines and therapeutics. The safety of these biologics is closely monitored by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Novel products may have limited safety data, and although serious medical outcomes associated with vaccination are rare, knowledge of background incidence rates of medical conditions in the US population puts reported adverse events (AEs) in perspective for further study. Although relatively minor vaccination skin reactions are common, rare instances of severe delayed hypersensitivity reactions such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome may occur. To aid in the assessment of these events, we performed a literature search in PubMed and Web of Science on the background incidence of EM, SJS, SJS/TEN, and TEN in the US population and on published reports of these conditions occurring post-vaccination. The US background annual incidence rates per million individuals of all ages ranged from 5.3 to 63.0 for SJS, from 0.4 to 5.0 for TEN, and from 0.8 to 1.6 for SJS/TEN. Since these conditions may overlap, some studies reported rates for EM/SJS/TEN combined, however we did not find studies with exclusive EM incidence rates. The published literature, including studies of reports submitted to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS), describes post-vaccination EM, SJS, SJS/TEN and/or TEN as rare occurrences. The vaccines most frequently associated with these conditions were measles, mumps, and rubella; diphtheria, tetanus, and pertussis; and varicella. The majority of VAERS reports of EM, SJS, SJS/TEN, or TEN occurred in children within 30 days of vaccination. This review summarizes background rates of these disorders in the general population and published AEs among vaccine recipients, to support safety surveillance of COVID-19 vaccines and other biologics.

HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

Novel computational methods on electronic health record yields new estimates of transfusion-associated circulatory overload in populations enriched with high-risk patients.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety. STUDY DESIGN AND METHODS: This retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO. Novel natural language processing methods, now made publicly available on GitHub, were developed to extract ARs from 3178 transfusion reaction reports. Other patient-level data were extracted computationally from UCSF EHR between 2012 and 2022. The odds ratio estimates of risk factors were calculated using a multivariate logistic regression analysis with case-to-control matched on sex and age at a ratio of 1:5. RESULTS: A total of 56,208 patients received transfusions (total 573,533 units) at UCSF during the study period and 102 patients developed TACO. The prevalence of TACO was estimated to be 0.2% per patient (102/total 56,208). Patients with a history of coagulopathy (OR, 1.36; 95% CI, 1.04-1.79) and transplant (OR, 1.99; 95% CI, 1.48-2.68) were associated with increased odds of TACO. DISCUSSION: While TACO is a serious AR, events remained rare, even in populations enriched with high-risk patients. Novel computational methods can be used to find and continually surveil for transfusion ARs. Results suggest that patients with history or presence of coagulopathy and organ transplant should be carefully monitored to mitigate potential risks of TACO.

A Retrospective Review of Center for Biologics Evaluation and Research Advisory Committee Meetings in the Context of the FDA's Benefit-Risk Framework.

The US FDA Center for Biologics Evaluation and Research (CBER) is responsible for the regulation of biologically derived products. FDA has established Advisory Committees (AC) as vehicles to seek external expert advice on scientific and technical matters related to the development and evaluation of products regulated by the agency. We aimed to identify and evaluate common topics discussed in CBER AC meetings during the regulatory decision-making process for biological products and medical devices. We analyzed the content of 119 CBER-led AC meetings between 2009 and 2021 listed on the FDA AC webpage. We reviewed publicly available meeting materials such as briefing documents, summaries, and transcripts. Using a structured review codebook based on FDA benefit-risk guidance, we identified important considerations within the benefit-risk dimensions discussed at the AC meetings: therapeutic context, benefit, risk and risk management, and benefit-risk trade-off, where evidence and uncertainty are critical parts of the FDA benefit-risk framework. Based on a detailed review of 24 topics discussed in 23 selected AC meetings conducted between 2016 and 2021, the two most frequently discussed considerations were "Uncertainty about assessment of the safety profile" and "Uncertainty about assessment of the benefit based on clinical trial data" (16/24 times each) as defined in our codebook. Most of the reviewed meetings discussed Investigational New Drug or Biologics License Applications of products. This review could help sponsors better plan and design studies by contextualizing how the benefit-risk dimensions were embedded in the AC discussions and the considerations that went into the final AC recommendations.

Modeling the Risk of HIV Transfusion Transmission.

BACKGROUND: Blood donations are routinely screened for HIV to prevent an infectious unit from being released to the blood supply. Despite improvements to blood screening assays, donations from infected donors remain undetectable during the window period (WP), when the virus has not yet replicated above the lower limit of detection (LOD) of a screening assay. To aid in the quantitative risk assessments of WP donations, a dose-response model describing the probability of transfusion-transmission of HIV over a range of viral RNA copies was developed. METHODS: An exponential model was chosen based on data fit and parsimony. A data set from a HIV challenge study using a nonhuman primate model and another data set from reported human blood transfusions associated with HIV infected donors were separately fit to the model to generate parameter estimates. A Bayesian framework using No-U-Turn Sampling (NUTS) and Monte Carlo simulations was performed to generate posterior distributions quantifying uncertainty in parameter estimation and model predictions. RESULTS: The parameters of the exponential model for both nonhuman primate and human data were estimated with a mean (95% credible intervals) of 2.70 × 10 -2 (7.74 × 10 -3 , 6.06 × 10 -2 ) and 7.56 × 10 -4 (3.68 × 10 -4 , 1.31 × 10 -3 ), respectively. The predicted ID 50 for the animal and human models was 26 (12, 90) and 918 (529, 1886) RNA copies transfused, respectively. CONCLUSION: This dose-response model can be used in a quantitative framework to estimate the probability of transfusion-transmission of HIV through WP donations. These models can be especially informative when assessing risk from blood components with low viral load.

Detection of allergic transfusion-related adverse events from electronic medical records.

BACKGROUND: Transfusion-related adverse events can be unrecognized and unreported. As part of the US Food and Drug Administration's Center for Biologics Evaluation and Research Biologics Effectiveness and Safety initiative, we explored whether machine learning methods, such as natural language processing (NLP), can identify and report transfusion allergic reactions (ARs) from electronic health records (EHRs). STUDY DESIGN AND METHODS: In a 4-year period, all 146 reported transfusion ARs were pulled from a database of 86,764 transfusions in an academic health system, along with a random sample of 605 transfusions without reported ARs. Structured and unstructured EHR data were retrieved, including demographics, new symptoms, medications, and lab results. In unstructured data, evidence from clinicians' notes, test results, and prescriptions fields identified transfusion ARs, which were used to extract NLP features. Clinician reviews of selected validation cases assessed and confirmed model performance. RESULTS: Clinician reviews of selected validation cases yielded a sensitivity of 67.9% and a specificity of 97.5% at a threshold of 0.9, with a positive predictive value (PPV) of 84%, estimated to 4.5% when extrapolated to match transfusion AR incidence in the full transfusion dataset. A higher threshold achieved sensitivity of 43% with specificity/PPV of 100% in our validation set. Essential features predicting ARs were recognized transfusion reactions, administration of antihistamines or glucocorticoids, and skin symptoms (e.g., hives and itching). Removal of NLP features decreased model performance. DISCUSSION: NLP algorithms can identify transfusion reactions from the EHR with a reasonable level of precision for subsequent clinician review and confirmation.

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.

Regulatory considerations for study of infant protection through maternal immunization.

Childhood Immunization is one of the critical strategies to decrease infant morbidity and mortality due to infectious diseases, but primary immunization schedules for infants in most countries start at 2 months of age. Childhood vaccines therefore begin providing adequate protection later in life, leaving infants vulnerable to infectious diseases and creating an immunity gap that results in higher morbidity and mortality among younger infants. Maternal immunization, the practice of vaccinating individuals during pregnancy, reduces the risk of infant infection primarily through the transfer of protective maternal antibodies to the fetus during late pregnancy. Although much progress has been made in public health policies to support maternal immunization research, inclusion of pregnant individuals and children in clinical trials remains challenging. This has resulted in paucity of evidence regarding safety and effectiveness of vaccines to support licensure of products intended for use during pregnancy and lactation to prevent disease in the infant. In addition, although safeguards for clinical research in pregnancy are supportive, experimental vaccines, e.g., Respiratory Syncytial Virus, are more complicated to study because data on safety, efficacy, and dosing are limited. This requires randomized controlled trials with safety monitoring for the mother, the fetus, and the infant with follow-up for at least 1 year or longer to assess long-term health outcomes that may be associated with peripartum vaccine exposure. The goal of this paper is to discuss the general regulatory considerations for clinical research to evaluate safety and effectiveness of vaccines administered during pregnancy to protect infants from disease. This could be useful to inform future vaccine trials. This discussion is not intended to provide agency guidance nor to articulate agency policy.

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.

Analyzing real world data of blood transfusion adverse events: Opportunities and challenges.

BACKGROUND: Blood transfusions are a vital component of modern healthcare, yet adverse reactions to blood product transfusions can cause morbidity, and rarely result in mortality. Therefore, accurate reporting of transfusion related adverse events (TRAEs) is paramount to improved transfusion practice. This study aims to investigate real-world data (RWD) on TRAEs by evaluating differences between ICD 9/10-based electronic health records (EHR) and blood bank-specific reporting. STUDY DESIGN AND METHODS: TRAE data were retrospectively collected from a blood bank-specific database between Jan 2015 and June 2019 as the reference data source and compared it to ICD 9/10 diagnostic codes corresponding to various TRAEs. Seven reactions that have corresponding ICD 9/10 diagnostic codes were evaluated: Transfusion related circulatory overload (TACO), transfusion related acute lung injury (TRALI), febrile non-hemolytic reaction (FNHTR), transfusion-related anaphylactic reaction (TRA), acute hemolytic transfusion reaction (AHTR), delayed hemolytic transfusion reaction (DHTR), and delayed serologic reaction (DSTR). These accounted for 33% of the TRAEs at an academic institution during the study period. RESULTS: Among 18637 adult blood transfusion recipients, there were 229 unique patients with 263 TRAE related ICD codes in the EHR, while there were 191 unique patients with 287 TRAEs identified in the blood bank database. None of the categories of reaction we investigated had perfect alignment between ICD 9/10 codes and blood bank specific diagnoses. DISCUSSION: Multiple systemic challenges were identified that hinder effective reporting of TRAEs. Identifying factors causing inconsistent reporting between blood banks and EHRs is paramount to developing effective workability between these electronic systems, as well as across clinical and laboratory teams.

Early administration of COVID-19 convalescent plasma with high titer antibody content by live viral neutralization assay is associated with modest clinical efficacy.

The efficacy of COVID-19 convalescent plasma (CCP) as a treatment for hospitalized patients with COVID-19 remains somewhat controversial; however, many studies have not evaluated CCP documented to have high neutralizing antibody titer by a highly accurate assay. To evaluate the correlation of the administration of CCP with titer determined by a live viral neutralization assay with 7- and 28-day death rates during hospitalization, a total of 23 118 patients receiving a single unit of CCP were stratified into two groups: those receiving high titer CCP (>250 50% inhibitory dilution, ID50; n = 13 636) or low titer CCP (≤250 ID50; n = 9482). Multivariable Cox regression was performed to assess risk factors. Non-intubated patients who were transfused with high titer CCP showed 1.1% and 1.7% absolute reductions in overall 7- and 28-day death rates, respectively, compared to those non-intubated patients receiving low titer CCP. No benefit of CCP was observed in intubated patients. The relative benefit of high titer CCP was confirmed in multivariable Cox regression. Administration of CCP with high titer antibody content determined by live viral neutralization assay to non-intubated patients is associated with modest clinical efficacy. Although shown to be only of modest clinical benefit, CCP may play a role in the future should viral variants develop that are not neutralized by other available therapeutics.

Risk of Guillain-Barré Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries.

Importance: Guillain-Barré syndrome can be reported after vaccination. This study assesses the risk of Guillain-Barré syndrome after administration of recombinant zoster vaccine (RZV or Shingrix), which is administered in 2 doses 2 to 6 months apart. Objective: Use Medicare claims data to evaluate risk of developing Guillain-Barré syndrome following vaccination with zoster vaccine. Design, Setting, and Participants: This case series cohort study included 849 397 RZV-vaccinated and 1 817 099 zoster vaccine live (ZVL or Zostavax)-vaccinated beneficiaries aged 65 years or older. Self-controlled analyses included events identified from 2 113 758 eligible RZV-vaccinated beneficiaries 65 years or older. We compared the relative risk of Guillain-Barré syndrome after RZV vs ZVL, followed by claims-based and medical record-based self-controlled case series analyses to assess risk of Guillain-Barré syndrome during a postvaccination risk window (days 1-42) compared with a control window (days 43-183). In self-controlled analyses, RZV vaccinees were observed from October 1, 2017, to February 29, 2020. Patients were identified in the inpatient, outpatient procedural (including emergency department), and office settings using Medicare administrative data. Exposures: Vaccination with RZV or ZVL vaccines. Main Outcomes and Measures: Guillain-Barré syndrome was identified in Medicare administrative claims data, and cases were assessed through medical record review using the Brighton Collaboration case definition. Results: Amongst those who received RZV vaccinees, the mean age was 74.8 years at first dose, and 58% were women, whereas among those who received the ZVL vaccine, the mean age was 74.3 years, and 60% were women. In the cohort analysis we detected an increase in risk of Guillain-Barré syndrome among RZV vaccinees compared with ZVL vaccinees (rate ratio [RR], 2.34; 95% CI, 1.01-5.41; P = .047). In the self-controlled analyses, we observed 24 and 20 cases during the risk and control period, respectively. Our claims-based analysis identified an increased risk in the risk window compared with the control window (RR, 2.84; 95% CI, 1.53-5.27; P = .001), with an attributable risk of 3 per million RZV doses (95% CI, 0.62-5.64). Our medical record-based analysis confirmed this increased risk (RR, 4.96; 95% CI, 1.43-17.27; P = .01). Conclusions and Relevance: Findings of this case series cohort study indicate a slightly increased risk of Guillain-Barré syndrome during the 42 days following RZV vaccination in the Medicare population, with approximately 3 excess Guillain-Barré syndrome cases per million vaccinations. Clinicians and patients should be aware of this risk, while considering the benefit of decreasing the risk of herpes zoster and its complications through an efficacious vaccine, as risk-benefit balance remains in favor of vaccination.

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.

Neonatal and pediatric blood bank practice in the United States: Results from the AABB pediatric transfusion medicine subsection survey.

BACKGROUND: There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. STUDY DESIGN AND METHODS: The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74-question survey to capture neonatal and pediatric BB practices in the United States. RESULTS: Thirty-five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small-volume (SV) and large-volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV = 60%, LV = 67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte-reduced (LR) for neonates and 97% for non-neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single-donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma-containing products (20% for platelets and 9.1% for plasma). CONCLUSIONS: Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.