Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial.

BACKGROUND: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products. STUDY DESIGN AND METHODS: MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. RESULTS: After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). DISCUSSION: This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.

SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.

Impact of different pathogen reduction technologies on the biochemistry, function, and clinical effectiveness of platelet concentrates: An updated view during a pandemic.

Standard platelet concentrates (PCs) stored at 22°C have a limited shelf life of 5 days. Because of the storage temperature, bacterial contamination of PCs can result in life-threatening infections in transfused patients. The potential of blood components to cause infections through contaminating pathogens or transmitting blood-borne diseases has always been a concern. The current safety practice to prevent pathogen transmission through blood transfusion starts with a stringent screening of donors and regulated testing of blood samples to ensure that known infections cannot reach transfusion products. Pathogen reduction technologies (PRTs), initially implemented to ensure the safety of plasma products, have been adapted to treat platelet products. In addition to reducing bacterial contamination, PRT applied to PCs can extend their shelf life up to 7 days, alleviating the impact of their shortage, while providing an additional safety layer against emerging blood-borne infectious diseases. While a deleterious action of PRTs in quantitative and qualitative aspects of plasma is accepted, the impact of PRTs on the quality, function, and clinical efficacy of PCs has been under constant examination. The potential of PRTs to prevent the possibility of new emerging diseases to reach cellular blood components has been considered more hypothetical than real. In 2019, a coronavirus-related disease (COVID-19) became a pandemic. This episode should help when reconsidering the possibility of future blood transmissible threats. The following text intends to evaluate the impact of different PRTs on the quality, function, and clinical effectiveness of platelets within the perspective of a developing pandemic.

Public Policy Impact of the COVID-19 Pandemic on Blood Supply in the United States.

The COVID-19 pandemic has precipitated an acute blood shortage for medical transfusions, exacerbating an already tenuous blood supply system in the United States, contributing to the public health crisis, and raising deeper questions regarding emergency preparedness planning for ensuring blood availability. However, these issues around blood availability during the pandemic are related primarily to the decline in supply caused by reduced donations during the pandemic rather than increased demand for transfusion of patients with COVID-19.The challenges to ensure a safe blood supply during the pandemic will continue until a vaccine is developed, effective treatments are available, or the virus goes away. If this virus or a similar virus were capable of transmission through blood, it would have a catastrophic impact on the health care system, causing a future public health emergency that would jeopardize the national blood supply.In this article, we identify the impact of the COVID-19 pandemic on blood supply adequacy, discuss the public health implications, propose recovery strategies, and present recommendations for preparing for the next disruption in blood supply driven by a public health emergency.

Ride-Hailing Services and Alcohol Consumption: Longitudinal Analysis.

BACKGROUND: Alcohol consumption is associated with a wide range of adverse health consequences and a leading cause of preventable deaths. Ride-hailing services such as Uber have been found to prevent alcohol-related motor vehicle fatalities. These services may, however, facilitate alcohol consumption generally and binge drinking in particular. OBJECTIVE: The goal of the research is to measure the impact of ride-hailing services on the extent and intensity of alcohol consumption. We allow these associations to depend on population density as the use of ride-hailing services varies across markets. METHODS: We exploit the phased rollout of the ride-hailing platform Uber using a difference-in-differences approach. We use this variation to measure changes in alcohol consumption among a local population following Uber's entry. Data are drawn from Uber press releases to capture platform entry and the Behavioral Risk Factor Surveillance Systems (BRFSS) Annual Survey to measure alcohol consumption in 113 metropolitan areas. Models are estimated using fixed-effects Poisson regression. Pre- and postentry trends are used to validate this approach. RESULTS: Ride-hailing has no association with the extent of alcohol consumption in high (0.61 [95% CI -0.05% to 1.28%]) or low (0.61 [95% CI -0.05% to 1.28%]) density markets, but is associated with increases in the binge drinking rate in high-density markets (0.71 [95% CI 0.13% to 1.29%]). This corresponds to a 4% increase in binge drinking within a Metropolitan Statistical Area. CONCLUSIONS: Ride-hailing services are associated with an increase in binge drinking, which has been associated with a wide array of adverse health outcomes. Drunk driving rates have fallen for more than a decade, while binge drinking continues to climb. Both trends may be accelerated by ride-hailing services. This suggests that health information messaging should increase emphasis on the direct dangers of alcohol consumption and binge drinking.

The United States' potential blood donor pool: updating the prevalence of donor-exclusion factors on the pool of potential donors.

BACKGROUND/CASE STUDIES: Despite decreased blood use, there are supply limitations. Therefore, it is important to determine the number of people potentially eligible to donate blood. This study updates an analysis from 2007 to estimate the pool of eligible blood donors in the United States. STUDY DESIGN/METHODS: We developed a revised epidemiologic model to account for changes in donor exclusion factors based on AABB standards. Donor exclusionary factors were identified and epidemiologic databases selected to enumerate the population prevalence of the donor exclusion factors. Prevalence data were adjusted for age, duration of exclusion, and comorbidities. The number of excluded individuals is calculated to estimate the current size of the eligible blood donor pool. The current study incorporates changes in demographic characteristics that have altered the pool of eligible blood donors. RESULTS/FINDINGS: The pool of eligible blood donors increased by approximately 93.9 million from 111 million persons in 2007 to 204.9 million persons in 2018, while the population of the United States increased by 34 million persons (from 293 million to 327 million). The number of donor exclusion factors increased from 31 to 38. Overall, the pool of eligible blood donors increased from 37.9% to 62.6% of the total population. The single largest change impacting the pool of eligible blood donors is the inclusion of individuals 65 years and older, increasing the eligible blood donor pool by 51 million of the new 93.9 million persons However, this increase in number of potential donors 65 years and older is offset by a corresponding increase in the prevalence of donor exclusion factor impact in individuals aged 65 years and above. CONCLUSION: A very large number of people are potentially eligible to donate blood. Therefore, blood supply limitations appear to be due to other factors. We suggest that these factors are differences in social commitments by changing demographic populations and the elimination of high-cost blood collection operations by blood suppliers.

Treatment for emerging viruses: Convalescent plasma and COVID-19.

Use of convalescent plasma transfusions could be of great value in the current pandemic of coronavirus disease (COVID-19), given the lack of specific preventative and therapeutic options. This convalescent plasma therapy is of particular interest when a vaccine or specific therapy is not yet available for emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. This report summarizes existing literature around convalescent plasma as a therapeutic option for COVID-19. It also includes recommendations for establishing a convalescent plasma program, enhancement considerations for convalescent plasma, and considerations around pathogen reduction treatment of convalescent plasma. Time is of the essence to set up protocols for collection, preparation, and administration of apheresis-collected convalescent plasma in response to the current pandemic. The immediate use of convalescent plasma provides prompt availability of a promising treatment while specific vaccines and treatments are evaluated and brought to scale. Further development of improved convalescent plasma, vaccines and other therapeutics depends on quick generation of additional data on pathogenesis and immune response. Additionally, given the lack of information around the natural history of this disease, PRT should be considered to add a layer of safety to protect recipients of convalescent plasma.

The Digitization of Patient Care: A Review of the Effects of Electronic Health Records on Health Care Quality and Utilization.

Electronic health records (EHRs) adoption has become nearly universal during the past decade. Academic research into the effects of EHRs has examined factors influencing adoption, clinical care benefits, financial and cost implications, and more. We provide an interdisciplinary overview and synthesis of this literature, drawing on work in public and population health, informatics, medicine, management information systems, and economics. We then chart paths forward for policy, practice, and research.

Platelet in vitro assays: their correspondence with their in vivo hemostatic potential.

Developments during the past few years have resulted in multiple kinds of platelet products for transfusion. This involves different collection methods, containers, preservative solutions, modifications of storage temperatures and durations, and additional treatments such as pathogen reduction. Much experience has been obtained testing these processes in vitro to seek indications of in vivo effectiveness. Availability of an in vitro method that correlated with in vivo effectiveness would be extremely valuable for these different kinds of platelet products and as more innovation in platelet preparation occurs in the future. This report reviews the methods for in vitro platelet testing with a view to their in vivo implications and whether such testing could be helpful in projecting the clinical effectiveness of different platelet products.

Effects of red-cell storage duration on patients undergoing cardiac surgery.

BACKGROUND: Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS: We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS: The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS: The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

Pathogen reduction combined with rapid diagnostic tests to reduce the risk of transfusion-transmitted infections in Uganda.

BACKGROUND: Blood safety and transfusion-transmitted infections (TTIs) are a major concern in low-resource areas. Laboratory screening of donors, a key contributor to blood safety, is usually done by enzyme-linked immunosorbent assay (ELISA) methods, which use expensive reagents and necessitate complex instruments and sophisticated laboratory staff. Rapid diagnostic tests (RDTs) are less expensive and easier to perform but have less sensitivity. Pathogen reduction technology (PRT) reduces transfusion transmission of malaria and may be effective in decreasing other TTIs. We explored the potential to improve blood safety by combining PRT and RDTs in comparison with current ELISA testing. STUDY DESIGN AND METHODS: We identified the sensitivity of RDTs available in Uganda and the sensitivity of currently used ELISA. Data from a riboflavin-and-UV-based photochemical treatment PRT were used. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and malaria were studied. Probability models were developed for estimation of the number of infectious units of blood for each of these four infections using either current ELISA or the combination of RDT and PRT. RESULTS: Compared to currently used ELISA, the combination of RDTs and PRT could reduce the rate of infectious units by 100, 20, 98, and 83% for HIV, HBV, HCV, and malaria, respectively, and would prevent use of 758 units of infectious blood per 10,000 units transfused. CONCLUSION: The combination of RDTs and PRT may improve blood safety in low-resource areas.

WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic granulocyte transfusions.

BACKGROUND: Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. STUDY DESIGN AND METHODS: One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. RESULTS: Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments. CONCLUSION: The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.

An International Registry of Granulocyte Transfusions.

INTRODUCTION: Granulocyte transfusions are used to either treat or prevent life-threatening infections in neutropenic patients. Current evidence from clinical trials does not support or reject efficacy, nor guide practice. METHODS: A group of investigators have led the efforts to create an online registry to gather information on granulocyte transfusion practices from as broad a range of international settings. The data forms were adapted from an on-going study in England for electronic data management. Data is collected at the time of the request for granulocytes, weekly, at 28 days, and at 6 months. Information collected includes donor, granulocyte unit, patient and illness characteristics, and outcomes. RESULTS: The PROspective GRanulocyte usage and outcomEs Survey (ProGrES) is currently open for data entry. Centres across the UK have collected data on 80 subjects. Five institutions from 4 countries (2 from the US, 1 each from Brazil, and national services in Canada and France) are in the process of joining the study. Other countries have expressed interest. CONCLUSION: It is feasible to develop an international registry of granulocyte transfusions to characterise current practices and describe outcomes. This registry would provide a platform to explore the relationship between intervention and outcomes, and to generate evidence to inform granulocyte transfusion efficacy.

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection.

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/µL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 10(9) granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 10(9) granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.

Progress in the blood supply of Afghanistan.

BACKGROUND: The blood supply system in Afghanistan was badly damaged by years of conflict. In 2009, the Afghanistan National Blood Safety and Transfusion Service (ANBSTS) was established. STUDY DESIGN AND METHODS: For 6 years, we collaborated to assist with policy and infrastructure development; blood bank operations; blood collection, testing, and component production; transfusion practices; and training of technicians, nurses, midwives, and physicians. RESULTS: Policies were established, infrastructure was strengthened, and capable staff was acquired and trained. Standard operating procedures were developed, testing was improved, and quality systems were established. Thirty trainings were held for blood center staff. Four additional formal trainings were held for 39 physicians, 36 nurses and/or midwives, and 38 laboratory technicians. During 5 years of this project, blood collection increased by 40%. CONCLUSION: The ANBSTS has made impressive progress developing infrastructure, personnel, procedures, quality systems, and training programs and increasing blood collection. Knowledge of transfusion medicine was improved through structured training.

The effect of implant macro-thread design on implant stability in the early post-operative period: a randomized, controlled pilot study.

INTRODUCTION: Available literature suggests there is a transient drop in implant stability from approximately week 0 to week 3-4 as a result of peri-implant bone remodeling as it transitions from a primary, mechanical stability to a secondary, biological stability. Research investigating the influence of macro-thread design on this process is scant. AIM: The specific aim of this study was to evaluate the role of macro-thread design on implant stability in the early post-operative healing period using resonance frequency analysis (RFA). MATERIAL AND METHODS: Seven patients, each missing at least two posterior teeth in the same arch, were included in the study. Three patients qualified for four implants resulting in a total of 10 matched pairs. All sites were healed (>6 months), non-grafted sites with sufficient bone to place implants. Each site in a matched pair was randomly assigned to receive either a control (Megagen EZ Plus Internal; EZ) or test (Megagen AnyRidge; AR) implant. The test implant incorporates a novel thread design with a wide thread depth and increased thread pitch. RFA was used to determine implant stability quotient (ISQ) values for each implant at the time of placement and weekly for the first 8 weeks. RESULTS: Implants consistently achieved a relatively high insertion torque (30-45 N/cm) and high initial ISQ value (79.8 ± 1.49). Baseline ISQ values for test (AR; 79.55 ± 1.61) and control (EZ; 80.05 ± 1.37) implants were similar. A general pattern of stability from baseline through all eight follow-up evaluations was observed for the test implants. A pattern of decreasing ISQ values was observed for the control implants across the early follow-up evaluations up to week four, where the value plateaued. There was a statistically significant main effect due to implant type (P < 0.01) and a statistically significant interaction between implant type and time (P < 0.01), indicating that the test and control implants performed differently at certain time points. CONCLUSIONS: Within the limitations of this study, macro-thread design appears to play a role in implant stability in the early post-operative healing period as assessed by RFA. These findings may have important implications related to immediate or early loading protocols.

Cord blood banking and quality issues.

BACKGROUND: Food and Drug Administration guidelines are designed to assure the quality and safety of the cord blood product used for transplantation. It is valuable to determine whether the actions called for in these guidelines are effective. STUDY DESIGN AND METHODS: We applied our cell therapy quality system to all cord blood units shipped into our cellular therapy laboratory for transplant at the University of Minnesota between 2011 and 2013. The quality issues were categorized as likely, potentially, or unlikely to have a clinical impact. RESULTS: A total of 249 units of umbilical cord blood (UCB) were received from 16 cord blood banks. A total of 159 units (64%) had a total of 245 issues. Of these, 117 (48%) pertained to medical history, 120 (49%) to quality control, and eight (3%) to labeling and documentation. Units with quality issues were no more likely to fail to engraft, and no specific kind of quality issue was associated with failure to engraft. Compared to a similar study 10 years ago, there was a decrease in the number of issues per unit. DISCUSSION: The cost of collecting, testing, processing, and storing UCB is very high. However, there may be activities that do not contribute to the quality or safety of the cord blood. The guidelines could be reviewed to determine their value based on years of experience.

Blood transfusions and pulmonary complications after hematopoietic cell transplantation.

BACKGROUND: Transfusion of blood products is an essential component of the hematopoietic cell transplantation (HCT) process. Blood transfusion carries several risks including, but not limited to, lung injury. The effect of transfusions on lung complications after HCT has not been previously investigated. STUDY DESIGN AND METHODS: We retrospectively studied 215 adult allogeneic HCT recipients at the University of Minnesota and examined the association between transfusion of blood components and development of lung complications after HCT. Patients without lung complications were used as the control group. RESULTS: A total of 113 (58%) of the patients developed lung injury events before Day 180 after HCT. Six-month survival was significantly lower in the lung event group (52%) versus the controls (78%; p = 0.01). Patients who eventually developed lung events received more transfusion episodes per week in the first month after HCT (median, 4.3 vs. 2.7 for controls), platelet units per week (3.5 vs. 2.0), and RBC units per week (1.8 vs. 1.4; p < 0.01) for all. In a multivariable analysis, each additional transfusion before Day +30 was associated with a 2.7% higher risk of lung complication (95% confidence interval, 0.8-4.8; p = 0.01), adjusting for time to engraftment, conditioning intensity, and donor type. Blood utilization increased after the lung event and remained high for several months relative to controls. CONCLUSION: Our data suggest that transfusion of blood products is associated with and may further complicate lung complications after HCT. Cautious use of blood components in the post HCT period is recommended.