Measuring intersectional HIV, sexual diversity, and gender non-conformity stigma among healthcare workers in Ghana: scale validation and correlates of stigma.

BACKGROUND: Men who have sex with men (MSM) are at heightened risk for HIV acquisition, yet they may delay or avoid HIV testing due to intersectional stigma experienced at the healthcare facility (HCF). Few validated scales exist to measure intersectional stigma, particularly amongst HCF staff. We developed the Healthcare Facility Staff Intersectional Stigma Scale (HCF-ISS) and assessed factors associated with stigma in Ghana. METHODS: We analyzed baseline data from HCF staff involved in a study testing a multi-level intervention to reduce intersectional stigma experienced by MSM. Data are from eight HCFs in Ghana (HCF Staff n = 200). The HCF-ISS assesses attitudes and beliefs towards same-sex relationships, people living with HIV (PLWH) and gender non-conformity. Exploratory factor analysis assessed HCF-ISS construct validity and Cronbach's alphas assessed the reliability of the scale. Multivariable regression analyses assessed factors associated with intersectional stigma. RESULTS: Factor analysis suggested an 18-item 3-factor scale including: Comfort with Intersectional Identities in the Workplace (6 items, Cronbach's alpha = 0.71); Beliefs about Gender and Sexuality Norms (7 items, Cronbach's alpha = 0.72); and Beliefs about PLWH (5 items, Cronbach's alpha = 0.68). Having recent clients who engage in same-gender sex was associated with greater comfort with intersectional identities but more stigmatizing beliefs about PLWH. Greater religiosity was associated with stigmatizing beliefs. Infection control training was associated with less stigma towards PLWH and greater comfort with intersectional identities. CONCLUSIONS: Achieving the goal of ending AIDS by 2030 requires eliminating barriers that undermine access to HIV prevention and treatment for MSM, including HCF intersectional stigma. The HCF-ISS provides a measurement tool to support intersectional stigma-reduction interventions.

Measuring and Addressing Stigma Within HIV Interventions for People Who Use Drugs: a Scoping Review of Recent Research.

PURPOSE OF REVIEW: Persistent stigma remains a crucial barrier to HIV prevention and treatment services among people who use drugs (PWUD), particularly for those living with or at-risk for HIV. This scoping review examines the current state of science with regard to approaches for measuring and addressing stigma within HIV interventions among PWUD. RECENT FINDINGS: Sixteen studies fit the inclusion criteria for this review. Half the studies originated within the USA, and the remaining represented four different regions. Within these studies, stigma was measured using various quantitative, qualitative, and mixed methods. The studies primarily focused on HIV stigma, including value-based judgments, anticipated stigma, and perceived stigma domains. Information-based and skills building approaches at the individual level were the most common for the stigma reduction interventions. Adoption of systematic evaluations is needed for measuring stigma, including intersectional stigma, within HIV interventions among PWUD. Future studies should focus on developing multilevel intersectional stigma reduction interventions for PWUD with and at-risk for HIV globally.

COVID-19 Vaccine Effectiveness: A Review of the First 6 Months of COVID-19 Vaccine Availability (1 January-30 June 2021).

Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines.

Majority of Fortune 500 Companies in 2018 Did Not Recognize Risk of Epidemics Such as COVID-19.

Infectious disease threats, like the 2002 severe acute respiratory syndrome coronavirus (SARS-CoV) disease, 2009 pandemic influenza A (H1N1), and the current coronavirus disease 2019 (COVID-19), pose multisectoral risk with the potential for wide-ranging socioeconomic disruption. In our globally intertwined economy, the impact of such events can elicit economic shock waves that reach far beyond the country of origin. Review of the 2018 Fortune 500 company 10-K filings shows the majority did not document perceived risks associated with epidemics, outbreaks, or pandemics. Enhanced engagement and investment of the public and private sectors in advancing global health security is needed to effectively prevent, detect, and respond to infectious disease events and ensure U.S. economic security.

Lessons learned from the rapid development of a statewide simulation model for predicting COVID-19's impact on healthcare resources and capacity.

The first case of COVID-19 was detected in North Carolina (NC) on March 3, 2020. By the end of April, the number of confirmed cases had soared to over 10,000. NC health systems faced intense strain to support surging intensive care unit admissions and avert hospital capacity and resource saturation. Forecasting techniques can be used to provide public health decision makers with reliable data needed to better prepare for and respond to public health crises. Hospitalization forecasts in particular play an important role in informing pandemic planning and resource allocation. These forecasts are only relevant, however, when they are accurate, made available quickly, and updated frequently. To support the pressing need for reliable COVID-19 data, RTI adapted a previously developed geospatially explicit healthcare facility network model to predict COVID-19's impact on healthcare resources and capacity in NC. The model adaptation was an iterative process requiring constant evolution to meet stakeholder needs and inform epidemic progression in NC. Here we describe key steps taken, challenges faced, and lessons learned from adapting and implementing our COVID-19 model and coordinating with university, state, and federal partners to combat the COVID-19 epidemic in NC.

Multiple-ancestry genome-wide association study identifies 27 loci associated with measures of hemolysis following blood storage.

BackgroundThe evolutionary pressure of endemic malaria and other erythrocytic pathogens has shaped variation in genes encoding erythrocyte structural and functional proteins, influencing responses to hemolytic stress during transfusion and disease.MethodsWe sought to identify such genetic variants in blood donors by conducting a genome-wide association study (GWAS) of 12,353 volunteer donors, including 1,406 African Americans, 1,306 Asians, and 945 Hispanics, whose stored erythrocytes were characterized by quantitative assays of in vitro osmotic, oxidative, and cold-storage hemolysis.ResultsGWAS revealed 27 significant loci (P < 5 × 10-8), many in candidate genes known to modulate erythrocyte structure, metabolism, and ion channels, including SPTA1, ALDH2, ANK1, HK1, MAPKAPK5, AQP1, PIEZO1, and SLC4A1/band 3. GWAS of oxidative hemolysis identified variants in genes encoding antioxidant enzymes, including GLRX, GPX4, G6PD, and SEC14L4 (Golgi-transport protein). Genome-wide significant loci were also tested for association with the severity of steady-state (baseline) in vivo hemolytic anemia in patients with sickle cell disease, with confirmation of identified SNPs in HBA2, G6PD, PIEZO1, AQP1, and SEC14L4.ConclusionsMany of the identified variants, such as those in G6PD, have previously been shown to impair erythrocyte recovery after transfusion, associate with anemia, or cause rare Mendelian human hemolytic diseases. Candidate SNPs in these genes, especially in polygenic combinations, may affect RBC recovery after transfusion and modulate disease severity in hemolytic diseases, such as sickle cell disease and malaria.

Modeling inpatient and outpatient antibiotic stewardship interventions to reduce the burden of Clostridioides difficile infection in a regional healthcare network.

Antibiotic exposure can lead to unintended outcomes, including drug-drug interactions, adverse drug events, and healthcare-associated infections like Clostridioides difficile infection (CDI). Improving antibiotic use is critical to reduce an individual's CDI risk. Antibiotic stewardship initiatives can reduce inappropriate antibiotic prescribing (e.g., unnecessary antibiotic prescribing, inappropriate antibiotic selection), impacting both hospital (healthcare)-onset (HO)-CDI and community-associated (CA)-CDI. Previous computational and mathematical modeling studies have demonstrated a reduction in CDI incidence associated with antibiotic stewardship initiatives in hospital settings. Although the impact of antibiotic stewardship initiatives in long-term care facilities (LTCFs), including nursing homes, and in outpatient settings have been documented, the effects of specific interventions on CDI incidence are not well understood. We examined the relative effectiveness of antibiotic stewardship interventions on CDI incidence using a geospatially explicit agent-based model of a regional healthcare network in North Carolina. We simulated reductions in unnecessary antibiotic prescribing and inappropriate antibiotic selection with intervention scenarios at individual and network healthcare facilities, including short-term acute care hospitals (STACHs), nursing homes, and outpatient locations. Modeled antibiotic prescription rates were calculated using patient-level data on antibiotic length of therapy for the 10 modeled network STACHs. By simulating a 30% reduction in antibiotics prescribed across all inpatient and outpatient locations, we found the greatest reductions on network CDI incidence among tested scenarios, namely a 17% decrease in HO-CDI incidence and 7% decrease in CA-CDI. Among intervention scenarios of reducing inappropriate antibiotic selection, we found a greater impact on network CDI incidence when modeling this reduction in nursing homes alone compared to the same intervention in STACHs alone. These results support the potential importance of LTCF and outpatient antibiotic stewardship efforts on network CDI burden and add to the evidence that a coordinated approach to antibiotic stewardship across multiple facilities, including inpatient and outpatient settings, within a regional healthcare network could be an effective strategy to reduce network CDI burden.

Creation of a Geospatially Explicit, Agent-based Model of a Regional Healthcare Network with Application to Clostridioides difficile Infection.

Agent-based models (ABMs) describe and simulate complex systems comprising unique agents, or individuals, while accounting for geospatial and temporal variability among dynamic processes. ABMs are increasingly used to study healthcare-associated infections (ie, infections acquired during admission to a healthcare facility), including Clostridioides difficile infection, currently the most common healthcare-associated infection in the United States. The overall burden and transmission dynamics of healthcare-associated infections, including C difficile infection, may be influenced by community sources and movement of people among healthcare facilities and communities. These complex dynamics warrant geospatially explicit ABMs that extend beyond single healthcare facilities to include entire systems (eg, hospitals, nursing homes and extended care facilities, the community). The agents in ABMs can be built on a synthetic population, a model-generated representation of the actual population with associated spatial (eg, home residence), temporal (eg, change in location over time), and nonspatial (eg, sociodemographic features) attributes. We describe our methods to create a geospatially explicit ABM of a major regional healthcare network using a synthetic population as microdata input. We illustrate agent movement in the healthcare network and the community, informed by patient-level medical records, aggregate hospital discharge data, healthcare facility licensing data, and published literature. We apply the ABM output to visualize agent movement in the healthcare network and the community served by the network. We provide an application example of the ABM to C difficile infection using a natural history submodel. We discuss the ABM's potential to detect network areas where disease risk is high; simulate and evaluate interventions to protect public health; adapt to other geographic locations and healthcare-associated infections, including emerging pathogens; and meaningfully translate results to public health practitioners, healthcare providers, and policymakers.

Iron status and risk factors for iron depletion in a racially/ethnically diverse blood donor population.

BACKGROUND: The optimal approach for reducing iron depletion (ID) in blood donors may vary depending on biologic or behavioral differences across donors. STUDY DESIGN AND METHODS: More than 12,600 successful whole blood donors were enrolled from four US blood centers for ferritin testing. The study population was enriched for racial/ethnic minorities (1605 African American, 1616 Asian, 1023 Hispanic). Subjects completed questionnaires on ID risk factors. Logistic regression identified predictors of absent iron stores (AIS; ferritin <12 ng/mL) and low ferritin (LF; ferritin <26 ng/mL). RESULTS: Across all subjects, 19% had AIS and 42% had LF, with a sharp increase in risk observed with increasing donation intensity and among women a large decrease in risk in those more than 50 years old. When other factors were controlled for, African American and Asian donors showed 20% to 25% decreased risk for AIS compared to non-Hispanic Caucasian donors, while Hispanic donors had 25% higher risk. Daily iron supplementation reduced risk for LF and AIS by 30% to 40%, respectively, while the benefit from less frequent use was lower (7%-19% protection). Regular antacid use was associated with at least 20% increment to risk. Use of oral contraceptives or estrogen in females reduced risk by 16% to 22%, while males who reported supplemental testosterone use had a 50% to 125% greater risk for LF and AIS. CONCLUSIONS: This study confirms high prevalence of LF and AIS in US donors and the principal risk factors of age, sex, and donation frequency. Additional demographic and behavioral risk factors of secondary importance might allow for refinement of ID mitigation strategies.

Blood, sweat, and tears: Red Blood Cell-Omics study objectives, design, and recruitment activities.

BACKGROUND: The Red Blood Cell (RBC)-Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the patients transfused with their donated RBCs. STUDY DESIGN AND METHODS: The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte-reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures. RESULTS: A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high-intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort. CONCLUSIONS: The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.

Frequent blood donations alter susceptibility of red blood cells to storage- and stress-induced hemolysis.

BACKGROUND: Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors. STUDY DESIGN: Leukoreduced RBC concentrate-derived samples from 13,403 donors were stored for 39 to 42 days (1-6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self-reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject. RESULTS: Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self-reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both). CONCLUSIONS: Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron-deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.

Intradonor reproducibility and changes in hemolytic variables during red blood cell storage: results of recall phase of the REDS-III RBC-Omics study.

BACKGROUND: Genetic determinants may underlie the susceptibility of red blood cells (RBCs) to hemolyze in vivo and during routine storage. This study characterized the reproducibility and dynamics of in vitro hemolysis variables from a subset of the 13,403 blood donors enrolled in the RBC-Omics study. STUDY DESIGN AND METHODS: RBC-Omics donors with either low or high hemolysis results on 4°C-stored leukoreduced (LR)-RBC samples from enrollment donations stored for 39 to 42 days were recalled 2 to 12 months later to donate LR-RBCs. Samples of stored LR-RBCs from the unit and from transfer bags were evaluated for spontaneous and stress-induced hemolysis at selected storage time points. Intradonor reproducibility of hemolysis variables was evaluated in transfer bags over two donations. Hemolysis data at serial storage time points were generated on LR-RBCs from parent bags and analyzed by site, sex, race/ethnicity, and donation frequency. RESULTS: A total of 664 donors were successfully recalled. Analysis of intradonor reproducibility revealed that osmotic and oxidative hemolysis demonstrated good and moderate reproducibility (Pearson's r = 0.85 and r = 0.53, respectively), while spontaneous hemolysis reproducibility was poor (r = 0.40). Longitudinal hemolysis in parent bags showed large increases over time in spontaneous (508.6%) and oxidative hemolysis (399.8%) and smaller increases in osmotic (9.4%) and mechanical fragility (3.4%; all p < 0.0001). CONCLUSION: Spontaneous hemolysis is poorly reproducible in donors over time and may depend on site processing methods, while oxidative and osmotic hemolysis were reproducible in donors and hence could reflect consistent heritable phenotypes attributable to genetic traits. Spontaneous and oxidative hemolysis increased over time of storage, whereas osmotic and mechanical hemolysis remained relatively stable.

Development and evaluation of a transfusion medicine genome wide genotyping array.

BACKGROUND: Many aspects of transfusion medicine are affected by genetics. Current single-nucleotide polymorphism (SNP) arrays are limited in the number of targets that can be interrogated and cannot detect all variation of interest. We designed a transfusion medicine array (TM-Array) for study of both common and rare transfusion-relevant variations in genetically diverse donor and recipient populations. STUDY DESIGN AND METHODS: The array was designed by conducting extensive bioinformatics mining and consulting experts to identify genes and genetic variation related to a wide range of transfusion medicine clinical relevant and research-related topics. Copy number polymorphisms were added in the alpha globin, beta globin, and Rh gene clusters. RESULTS: The final array contains approximately 879,000 SNP and copy number polymorphism markers. Over 99% of SNPs were called reliably. Technical replication showed the array to be robust and reproducible, with an error rate less than 0.03%. The array also had a very low Mendelian error rate (average parent-child trio accuracy of 0.9997). Blood group results were in concordance with serology testing results, and the array accurately identifies rare variants (minor allele frequency of 0.5%). The array achieved high genome-wide imputation coverage for African-American (97.5%), Hispanic (96.1%), East Asian (94.6%), and white (96.1%) genomes at a minor allele frequency of 5%. CONCLUSIONS: A custom array for transfusion medicine research has been designed and evaluated. It gives wide coverage and accurate identification of rare SNPs in diverse populations. The TM-Array will be useful for future genetic studies in the diverse fields of transfusion medicine research.

Piloting and implementation of quality assessment and quality control procedures in RBC-Omics: a large multi-center study of red blood cell hemolysis during storage.

BACKGROUND: The major aims of the RBC-Omics study were to evaluate the genomic and metabolomic determinants of spontaneous and stress-induced hemolysis during RBC storage. This study was unique in scale and design to allow evaluation of RBC donations from a sufficient number of donors across the spectrum of race, ethnicity, sex, and donation intensity. Study procedures were carefully piloted, optimized, and controlled to enable high-quality data collection. METHODS: The enrollment goal of 14,000 RBC donors across four centers, with characterization of RBC hemolysis across two testing laboratories, required rigorous piloting and optimization and establishment of a quality assurance (QA) and quality control (QC) program. Optimization of WBC elution from leukoreduction (LR) filters, development and validation of small-volume transfer bags, impact of manufacturing and sample-handling procedures on hemolysis parameters, and testing consistency across laboratories and technicians and over time were part of this quality assurance/quality control program. RESULTS: LR filter elution procedures were optimized for obtaining DNA for analysis. Significant differences between standard and pediatric storage bags led to use of an alternative LR-RBC transfer bag. The impact of sample preparation and freezing methods on metabolomics analyses was evaluated. Proficiency testing monitored and documented testing consistency across laboratories and technicians. CONCLUSION: Piloting and optimization, and establishment of a robust quality assurance/quality control program documented process consistency throughout the study and was essential in executing this large-scale multicenter study. This program supports the validity of the RBC-Omics study results and a sample repository that can be used in future studies.

Lessons learned from twelve years of HIV Seroprevalence and Behavioral Epidemiology Risk Survey (SABERS) development and implementation among foreign militaries.

Circumstances within the military environment may place military personnel at increased risk of contracting sexually transmitted infections including HIV. Since 2005, RTI International has provided technical assistance to the Seroprevalence and Behavioral Epidemiology Risk Surveys (SABERS) program and supported the development and implementation of SABERS survey instruments in 18 countries. RTI staff collaborated with the Department of Defense HIV/AIDS Prevention Program and host country military and health care leadership to develop a fully tested, culturally appropriate survey and data collection instrument and build local capacity by identifying and training local interviewers. We summarize the critical steps, challenges faced, and lessons learned from 12 years' experience developing, testing, and implementing SABERS instruments among military populations in Africa, Asia, and the Caribbean.