Predicting haemoglobin deferral using machine learning models: Can we use the same prediction model across countries?

BACKGROUND AND OBJECTIVES: Personalized donation strategies based on haemoglobin (Hb) prediction models may reduce Hb deferrals and hence costs of donation, meanwhile improving commitment of donors. We previously found that prediction models perform better in validation data with a high Hb deferral rate. We therefore investigate how Hb deferral prediction models perform when exchanged with other blood establishments. MATERIALS AND METHODS: Donation data from the past 5 years from random samples of 10,000 donors from Australia, Belgium, Finland, the Netherlands and South Africa were used to fit random forest models for Hb deferral prediction. Trained models were exchanged between blood establishments. Model performance was evaluated using the area under the precision-recall curve (AUPR). Variable importance was assessed using SHapley Additive exPlanations (SHAP) values. RESULTS: Across the validation datasets and exchanged models, the AUPR ranged from 0.05 to 0.43. Exchanged models performed similarly within validation datasets, irrespective of the origin of the training data. Apart from subtle differences, the importance of most predictor variables was similar in all trained models. CONCLUSION: Our results suggest that Hb deferral prediction models trained in different blood establishments perform similarly within different validation datasets, regardless of the deferral rate of their training data. Models learn similar associations in different blood establishments.

Effects of plasmapheresis frequency on health status and exercise performance in men: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Most research studies on the effects of repeated plasma donation are observational with different study limitations, resulting in high uncertainty on the link between repeated plasma donation and health consequences. Here, we prospectively investigated the safety of intensive or less intensive plasma donation protocols. MATERIALS AND METHODS: Sixty-three male subjects participated in this randomized controlled trial and were divided into low-frequency (LF, once/month, n = 16), high-frequency (HF, three times/month, n = 16), very high-frequency (VHF, two times/week, n = 16) and a placebo (P, once/month, n = 15) groups. Biochemical, haematological, clinical, physiological and exercise-related data were collected before (D0), after 1½ months (D42) and after 3 months (D84) of donation. RESULTS: In VHF, red blood cells, haemoglobin and haematocrit levels decreased while reticulocyte levels increased from D0 to D84. In both HF and VHF, plasma ferritin levels were lower at D42 and D84 compared to D0. In VHF, plasma levels of albumin, immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) dropped from D0 to D42 and remained lower at D84 than at D0. In HF, plasma IgG, IgA and IgM were lower at D42, and IgG and IgM were lower at D84, compared to D0. Few adverse events were reported in HF and VHF. Repeated plasma donation had no effect on blood pressure, body composition or exercise performance. CONCLUSION: VHF plasmapheresis may result in a large reduction in ferritin and IgG levels. HF and VHF plasmapheresis may result in little to no difference in other biochemical, haematological, clinical, physiological and exercise-related parameters.

Safety and protection of plasma donors: A scoping review and evidence gap map.

BACKGROUND AND OBJECTIVES: As part of a large-scale project to safely increase plasma collection in Europe, the current scoping review identifies the existing evidence (gaps) on adverse events (AEs) and other health effects in plasmapheresis donors, as well as factors that may be associated with such events/effects. MATERIALS AND METHODS: We searched six databases and three registries. Study characteristics (publication type, language, study design, population, outcomes, associated factors, time of assessment, duration of follow-up, number and frequency of donations, convalescent plasma [y/n], setting and location) were synthesized narratively and in an interactive evidence gap map (EGM). RESULTS: Ninety-four research articles and five registrations were identified. Around 90% were observational studies (57 controlled and 33 uncontrolled), and most of them were performed in Europe (55%) or the United States (20%). Factors studied in association with donor health included donor characteristics (e.g., sex, age) (n = 27), cumulative number of donations (n = 21), donation frequency (n = 11), plasma collection device or programme (n = 11), donor status (first time vs. repeat) (n = 10), donation volume per session (n = 8), time in donation programme (n = 3), preventive measures (n = 2) or other (n = 9). CONCLUSION: The current scoping review provides an accessible tool for researchers and policymakers to identify the available evidence (gaps) concerning plasmapheresis donation safety. Controlled prospective studies with long-term donor follow-up are scarce. Furthermore, additional experimental studies comparing the health effects of different donation frequencies are required to inform a safe upper limit for donation frequency.

Does cold storage of blood before transfusion prevent the transmission of syphilis? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Although screening of donated blood for syphilis is almost universally applied, its cost-effectiveness is questioned because of the low prevalence of transfusion-transmitted syphilis and a widespread belief that the syphilis-causing bacterium Treponema pallidum is very vulnerable to cold storage. Since the latter claim is not yet supported by a systematic review, we investigated whether syphilis can be transmitted via transfusion following prolonged (cold or room temperature) storage of blood products. MATERIALS AND METHODS: MEDLINE, PMC and NCBI bookshelf (PubMed interface), Cochrane Library, Embase, Web of Science and CINAHL were searched up to 17 January 2023. RESULTS: Nine experimental animal studies and one observational human study were included. Meta-analysis showed that storing artificially infected human (six studies; risk ratio [RR] = 0.37, 95% confidence interval [CI]: 0.22-0.64, p = 0.0003) or rabbit (two studies; RR = 0.08, 95% CI: 0.01 to 0.55, p = 0.01) blood for more than 72 h before intratesticular injection significantly decreased the number of recipient animals that develop syphilis. Nonetheless, the possibility of syphilis transmission remained for up to 7 days. Differences could not be found for rabbit plasma (p = 0.60) or naturally infected rabbit blood (p = 0.28). There was limited evidence from one study in favour of the storage of artificially infected human platelets for over 72 h at cold temperatures (RR = 0.13, 95% CI: 0.03-0.52, p = 0.004) but not at room temperature (p = 0.12). CONCLUSION: Even though the infectivity of T. pallidum-spiked blood may decrease after 72 h of cold storage, the possibility for transfusion-transmitted syphilis may remain for several days after. The evidence is very uncertain, and conclusions are hindered by a lack of sufficiently powered studies and studies in humans. In addition, T. pallidum concentrations used in animal studies may be unrealistically high.

Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Cost Effectiveness of Different Platelet Preparation, Storage, Selection and Dosing Methods in Platelet Transfusion: A Systematic Review.

BACKGROUND AND OBJECTIVE: Evidence-based guidelines on platelet transfusion therapy assist clinicians to optimize patient care, but currently do not take into account costs associated with different methods used during the preparation, storage, selection and dosing of platelets for transfusion. This systematic review aimed to summarize the available literature regarding the cost effectiveness (CE) of these methods. METHODS: Eight databases and registries, as well as 58 grey literature sources, were searched up to 29 October 2021 for full economic evaluations comparing the CE of methods for preparation, storage, selection and dosing of allogeneic platelets intended for transfusion in adults. Incremental CE ratios, expressed as standardized cost (in 2022 EUR) per quality-adjusted life-year (QALY) or per health outcome, were synthesized narratively. Studies were critically appraised using the Philips checklist. RESULTS: Fifteen full economic evaluations were identified. Eight investigated the costs and health consequences (transfusion-related events, bacterial and viral infections or illnesses) of pathogen reduction. The estimated incremental cost per QALY varied widely from EUR 259,614 to EUR 36,688,323. For other methods, such as pathogen testing/culturing, use of apheresis instead of whole blood-derived platelets, and storage in platelet additive solution, evidence was sparse. Overall, the quality and applicability of the included studies was limited. CONCLUSIONS: Our findings are of interest to decision makers who consider implementing pathogen reduction. For other preparation, storage, selection and dosing methods in platelet transfusion, CE remains unclear due to insufficient and outdated evaluations. Future high-quality research is needed to expand the evidence base and increase our confidence in the findings.

Men who have sex with men and risk for transfusion-transmissible infections in blood donors in Western countries: A systematic review update.

BACKGROUND AND OBJECTIVES: This systematic review update summarizes evidence concerning transfusion-transmissible infections (TTIs) in male blood donors reporting sex with another man (MSM) or after easing the MSM deferral period. MATERIALS AND METHODS: We searched five databases, including studies comparing MSM versus non-MSM donors (Type I), MSM deferral periods (Type II) or infected versus non-infected donors (Type III) in Western countries, and used GRADE to determine evidence certainty. RESULTS: Twenty-five observational studies were included. Four Type I studies suggest that there may be an increased risk for overall TTIs, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis in MSM donors, but the evidence is very uncertain. There was insufficient evidence of MSM with low-risk sexual behaviour. A Type II study indicates that easing the MSM deferral period to 1 year may have little to no effect on TTI risk. TTI prevalence in blood donors under 5-year, 1-year, 3-month or risk-based deferral in eight other Type II studies was too low to provide clear conclusions on the effect of easing the deferral. Three Type III studies reported that MSM may be a risk factor for HIV. Increased risk of HBV, hepatitis C virus and HTLV-I/II could not be shown. The evidence from Type III studies is very uncertain. CONCLUSION: There may be an increased risk of HIV in MSM blood donors. Shortening the deferral from permanent to 1 year may have little to no effect on TTI risk. However, there is limited, unclear evidence from observational studies concerning the impact of introducing 3-month or risk-based deferrals.

Cost-Effectiveness of Thrombopoietin Mimetics in Patients with Thrombocytopenia: A Systematic Review.

OBJECTIVES: Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. METHODS: Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. RESULTS: Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). CONCLUSIONS: Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.

Intranasal administration of convalescent plasma protects against SARS-CoV-2 infection in hamsters.

BACKGROUND: Convalescent plasma (CP) transfusion is an early option for treating infections with pandemic potential, often preceding vaccine or antiviral drug rollout. Heterogenous findings from randomized clinical trials on transfusion of COVID-19 CP (CCP) have been reported. However, meta-analysis suggests that transfusion of high titer CCP is associated with a mortality benefit for COVID-19 outpatients or inpatients treated within 5 days after symptom onset, indicating the importance of early administration. METHODS: We tested if CCP is an effective prophylactic against SARS-CoV-2 infection by the intranasal administration of 25 µL CCP/nostril (i.e. 0.01-0.06 mg anti-RBD antibodies/kg) in hamsters exposed to infected littermates. FINDINGS: In this model, 40% of CCP treated hamsters were fully protected and 40% had significantly reduced viral loads, the remaining 20% was not protected. The effect seems dose-dependent because high-titer CCP from a vaccinated donor was more effective than low-titer CCP from a donation prior to vaccine rollout. Intranasal administration of human CCP resulted in a reactive (immune) response in hamster lungs, however this was not observed upon administration of hamster CCP. INTERPRETATION: We conclude that CCP is an effective prophylactic when used directly at the site of primary infection. This option should be considered in future prepandemic preparedness plans. FUNDING: Flanders Innovation & Entrepreneurship (VLAIO) and the Foundation for Scientific Research of the Belgian Red Cross Flanders.

GPIbα shedding in platelets is controlled by strict intracellular containment of both enzyme and substrate.

BACKGROUND: A disintegrin and metalloprotease 17 (ADAM17) catalyzes platelet glycoprotein (GP) Ibα ectodomain shedding, thereby releasing glycocalicin in plasma. The spatiotemporal control over the enzyme-substrate interaction and the biological consequences of GPIbα shedding are poorly understood. OBJECTIVES: This study aimed to determine the spatiotemporal control over GPIbα shedding by ADAM17. METHODS: Transmission electron microscopy with immunogold staining, immunoprecipitation, and quantitative western blotting were used. RESULTS: Immunogold staining showed that all ADAM17 antigen is expressed intracellularly, irrespective of platelet activation. ADAM17 clustered in patches on a tortuous membrane system different from α- and dense granules. Mild activation by platelet adhesion to immobilized fibrinogen did not cause GPIbα shedding, whereas strong and sustained stimulation using thrombin and collagen (analogs) did. Glycocalicin release kinetics was considerably slower than typical hemostasis, starting at 20 minutes and reaching a plateau after 3 hours of strong stimulation. Inhibition of the ADAM17 scissile bond specifically in GPIbα receptors that reside on the platelet's extracellular surface did not prevent shedding, which is in line with the strict intracellular location of ADAM17. Instead, shedding was restricted to a large GPIbα subpopulation that is inaccessible on resting platelets but becomes partially accessible following platelet stimulation. Furthermore, the data show that proteinaceous, water-soluble ADAM17 inhibitors cannot inhibit GPIbα shedding, whereas membrane permeable small molecule ADAM inhibitors can. CONCLUSION: The data show that platelets harbor 2 distinct GPIbα subpopulations: one that presents at the platelet's surface known for its role in primary hemostasis and one that provides substrate for proteolysis by ADAM17 with kinetics that suggest a role beyond hemostasis.

An international comparison of haemoglobin deferral prediction models for blood banking.

BACKGROUND AND OBJECTIVES: Blood banks use a haemoglobin (Hb) threshold before blood donation to minimize donors' risk of anaemia. Hb prediction models may guide decisions on which donors to invite, and should ideally also be generally applicable, thus in different countries and settings. In this paper, we compare the outcome of various prediction models in different settings and highlight differences and similarities. MATERIALS AND METHODS: Donation data of repeat donors from the past 5 years of Australia, Belgium, Finland, the Netherlands and South Africa were used to fit five identical prediction models: logistic regression, random forest, support vector machine, linear mixed model and dynamic linear mixed model. Only donors with five or more donation attempts were included to ensure having informative data from all donors. Analyses were performed for men and women separately and outcomes compared. RESULTS: Within countries and overall, different models perform similarly well. However, there are substantial differences in model performance between countries, and there is a positive association between the deferral rate in a country and the ability to predict donor deferral. Nonetheless, the importance of predictor variables across countries is similar and is highest for the previous Hb level. CONCLUSION: The limited impact of model architecture and country indicates that all models show similar relationships between the predictor variables and donor deferral. Donor deferral is found to be better predictable in countries with high deferral rates. Therefore, such countries may benefit more from deferral prediction models than those with low deferral rates.

Single step method for high yield human platelet lysate production.

BACKGROUND: We aimed to develop a single step method for the production of human platelet lysate (hPL). The method must result in high hPL yields, be closed system and avoid heparin use. STUDY DESIGN AND METHODS: The method aimed at using glass beads and calcium. An optimal concentration of calcium and glass beads was determined by serial dilution. This was translated to a novel method and compared to known methods: freeze-thawing and high calcium. Quality outcome measures were transmittance, fibrinogen and growth factor content, and cell doubling time. RESULTS: An optimal concentration of 5 mM Ca2+ and 0.2 g/ml glass beads resulted in hPL with yields of 92% ± 1% (n = 50) independent of source material (apheresis or buffy coat-derived). The transmittance was highest (56% ± 9%) compared to known methods (<39%). The fibrinogen concentration (7.0 ± 1.1 µg/ml) was well below the threshold, avoiding the need for heparin. Growth factor content was similar across hPL production methods. The cell doubling time of adipose derived stem cells was 25 ± 1 h and not different across methods. Batch consistency was determined across six batches of hPL (each n = 25 constituting concentrates) and was <11% for all parameters including cell doubling time. Calcium precipitation formed after 4 days of culturing stem cells in media with hPL prepared by the high (15 mM) Ca2+ method, but not with hPL prepared by glass bead method. DISCUSSION: The novel method transforms platelet concentrates to hPL with little hands-on time. The method results in high yield, is closed system, without heparin and non-inferior to published methods.

Systematic reviews on platelet transfusions: Is there unnecessary duplication of effort? A scoping review.

BACKGROUND AND OBJECTIVES: Platelet transfusions are used across multiple patient populations to prevent and correct bleeding. This scoping review aimed to map the currently available systematic reviews (SRs) and evidence-based guidelines in the field of platelet transfusion. MATERIALS AND METHODS: A systematic literature search was conducted in seven databases for SRs on effectiveness (including dose and timing, transfusion trigger and ratio to other blood products), production modalities and decision support related to platelet transfusion. The following data were charted: methodological features of the SR, population, concept and context features, outcomes reported, study design and number of studies included. Results were synthesized in interactive evidence maps. RESULTS: We identified 110 SRs. The majority focused on clinical effectiveness, including prophylactic or therapeutic transfusions compared to no platelet transfusion (34 SRs), prophylactic compared to therapeutic-only transfusion (8 SRs), dose, timing (11 SRs) and threshold for platelet transfusion (15 SRs) and the ratio of platelet transfusion to other blood products in massive transfusion (14 SRs). Furthermore, we included 34 SRs on decision support, of which 26 evaluated viscoelastic testing. Finally, we identified 22 SRs on platelet production modalities, including derivation (4 SRs), pathogen inactivation (6 SRs), leucodepletion (4 SRs) and ABO/human leucocyte antigen matching (5 SRs). The SRs were mapped according to concept and clinical context. CONCLUSION: An interactive evidence map of SRs and evidence-based guidelines in the field of platelet transfusion has been developed and identified multiple reviews. This work serves as a tool for researchers looking for evidence gaps, thereby both supporting research and avoiding unnecessary duplication.

Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

BACKGROUND: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. RESULTS: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. CONCLUSIONS: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.

Whole blood donor return rates after deferral for tattooing or body piercing-Survey across blood donation services: The BEST collaborative study.

BACKGROUND AND OBJECTIVES: To protect transfusion recipients from transfusion-transmissible infections, blood donors are deferred from donating after recent tattooing or piercing. To explore to what extent and how this deferral impacts donor availability, we performed an international study to investigate how many donors were deferred for a recent tattoo or piercing and how many of these donors returned to donate. MATERIALS AND METHODS: We surveyed blood centre members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative and the European Blood Alliance Donor Studies Working Group on their numbers of donations, tattoo and piercing deferrals, and return rates in the year 2017. RESULTS: Eight blood centres participated. Overall, deferral rates were lower for repeat donors compared to new donors. Repeat donors were more likely to return than new donors. Women and young donors were more often deferred than male and older donors. Men were more demotivated by tattoo or piercing deferral, resulting in lower return rates compared to women. Return rates differed greatly between blood centres. CONCLUSION: Tattoo and piercing deferrals lead to missed donations and result in lower return rates. However, the numbers vary largely internationally, probably due to cultural and policy differences. Shortening deferral periods after tattooing or piercing may reduce the impact on donor availability, which should be investigated in single-centre studies.

Prevalence and associated risk factors of HIV infections in a representative transgender and non-binary population in Flanders and Brussels (Belgium): Protocol for a community-based, cross-sectional study using time-location sampling.

INTRODUCTION: HIV prevalence and sexual risk have been estimated very high for transgender people. However, the limited sampling and data collection methods used in current research on transgender people potentially led to overrepresentation and generalisation of people at risk for HIV. Current HIV prevalence estimates in transgender populations are generalised from studies mainly focusing on transgender women engaging in sex work. Moreover, studies focusing on non-binary people, who identify with a broad range of identities beyond the traditional male and female gender identities, are scarce. OBJECTIVES: To estimate the HIV prevalence rate in the Flemish and Brussels (Belgium) transgender population, including transgender women, transgender men and non-binary people, and to identify the associated risk factors. METHODS: In this community-based cross-sectional study, self-identified transgender and non-binary (TGNB) people will be recruited through a two-stage time-location sampling approach. First, community settings in which TGNB people gather will be mapped to develop an accurate sampling frame. Secondly, a multistage sampling design is applied involving a stratification based on setting type (healthcare facilities vs outreach events), a selection of clusters by systematic sampling and a simple random selection of TGNB people within each cluster. Participants will complete an electronic self-reported survey to measure sociological, sexual and drug-using behaviors (risk factors) and oral fluid aliquots will be collected and tested for HIV antibodies. Logistic regression models will be used to evaluate risk factors independently associated with HIV infection. The presented study is registered at ClinicalTrials.gov (NCT04930614). DISCUSSION: This study will be the first to investigate the HIV prevalence rates and associated risk behaviors in an accurate representation of the TGNB population in a Western European country. The findings will globally serve as a knowledge base for identifying subgroups at risk for becoming infected with HIV within TGNB people and to set up targeted prevention programs.

Impact of disasters on blood donation rates and blood safety: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Timely and adequate access to safe blood forms an integral part of universal health coverage, but it may be compromised by natural or man-made disasters. This systematic review provides an overview of the best available scientific evidence on the impact of disasters on blood donation rates and safety outcomes. MATERIALS AND METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Web of Science and CINAHL) were searched until 27 March 2020 for (un)controlled studies investigating the impact of disasters on blood donation rates and/or safety. Risk of bias and overall certainty of the evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Eighteen observational studies were identified, providing very low certainty of evidence (due to high risk of bias, inconsistency and/or imprecision) on the impact of natural (12 studies) and man-made/technological (6 studies) disasters. The available evidence did not enable us to form any generalizable conclusions on the impact on blood donation rates. Meta-analyses could not detect any statistically significant changes in transfusion-transmissible infection (TTI) rates [hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2, human T-lymphotropic virus I and II (HTLV-I/II) and syphilis] in donated blood after a disaster, either in first-time or repeat donors, although the evidence is very uncertain. CONCLUSION: The very low certainty of evidence synthetized in this systematic review indicates that it is very uncertain whether there is an association between disaster occurrence and changes in TTI rates in donated blood. The currently available evidence did not allow us to draw generalizable conclusions on the impact of disasters on blood donation rates.

Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma.

BACKGROUND: Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness. METHODS: In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT50)) ≥1/320 was the product of choice for the study. RESULTS: Between 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806-906) mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT50) ≥1/320. Median time from onset of symptoms to randomisation was 7 days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) versus control 84.05% (n=137)) (OR 0.99, 95% CI 0.59-1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%). CONCLUSIONS: Transfusion of 4 units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.