Extensive red blood cell matching considering patient alloimmunization risk

Background and Objectives: Red blood cell (RBC) transfusions pose a risk of alloantibody development in patients. For patients with increased alloimmunization risk, extended preventive matching is advised, encompassing not only the ABO-D blood groups but also the most clinically relevant minor antigens: C, c, E, e, K, Fya, Fyb, Jka, Jkb, S and s. This study incorporates patient-specific data and the clinical consequences of mismatching into the allocation process. Materials and Methods: We have redefined the MINimize Relative Alloimmunization Risks (MINRAR) model to include patient group preferences in selecting RBC units from a finite supply. A linear optimization approach was employed, considering both antigen immunogenicity and the clinical impact of mismatches for specific patient groups. We also explore the advantages of informing the blood bank about scheduled transfusions, allowing for a more strategic blood distribution. The model is evaluated using historical data from two Dutch hospitals, measuring shortages and minor antigen mismatches. Results: The updated model, emphasizing patient group-specific considerations, achieves a similar number of mismatches as the original, yet shifts mismatches among patient groups and antigens, reducing expected alloimmunization consequences. Simultaneous matching for multiple hospitals at the distribution centre level, considering scheduled demands, led to a 30% decrease in mismatches and a 92% reduction in shortages. Conclusion: The reduction of expected alloimmunization consequences by incorporating patient group preferences demonstrates our strategy's effectiveness for patient health. Substantial reductions in mismatches and shortages with multi-hospital collaboration highlights the importance of sharing information in the blood supply chain

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Many-analysts Approach to the Relation Between Religiosity and Well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

Preventing alloimmunization using a new model for matching extensively typed red blood cells

Background and Objectives: Alloimmunization is a well-known adverse event associated with red blood cell (RBC) transfusions, caused by phenotype incompatibilities between donor and patient RBCs that may lead to haemolytic transfusion reactions on subsequent transfusions. Alloimmunization can be prevented by transfusing fully matched RBC units. Advances in RBC genotyping render the extensive typing of both donors and patients affordable in the foreseeable future. However, the exponential increase in the variety of extensively typed RBCs asks for a software-driven selection to determine the ‘best product for a given patient’. Materials and Methods: We propose the MINimize Relative Alloimmunization Risks (MINRAR) model for matching extensively typed RBC units to extensively typed patients to minimize the risk of alloimmunization. The key idea behind this model is to use antigen immunogenicity to represent the clinical implication of a mismatch. Using simulations of non-elective transfusions in Caucasian donor and patient populations, the effect on the alloimmunization rate of the MINRAR model is compared with that of a baseline model that matches antigens A, B and RhD only. Results: Our simulations show that with the MINRAR model, even for small inventories, the expected number of alloimmunizations can be reduced by 78.3% compared with a policy of only matching on antigens A, B and RhD. Furthermore, a reduction of 93.7% can be achieved when blood is issued from larger inventories. Conclusion: Despite an exponential increase in phenotype variety, matching of extensively typed RBCs can be effectively implemented using our MINRAR model, effectuating a substantial reduction in alloimmunization risk without introducing additional outdating or shortages

Abstract P086: Metabolic Risk, Galectin-3 And Heart Failure: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Diabetes and metabolic syndrome (MetS) confer an increased risk of heart failure (HF) through poorly understood mechanisms. Galectin-3 (Gal-3) is a marker of fibrosis linked to greater HF risk. The inter-relationships among diabetes, MetS and Gal-3, and related implications for HF risk, are not well understood. Hypothesis: Diabetes and MetS are associated with elevated Gal-3, and high Gal-3 indicates greater HF risk among those with diabetes or MetS. Methods: We included 8,445 participants (mean age 63, 59% male, 21% Black) at ARIC Visit 4 (1996-1999) without baseline HF. We categorized participants by metabolic risk (no diabetes/no MetS; MetS only; diabetes with or without MetS), and Gal-3 levels (gender-specific quartiles). We assessed the associations of metabolic risk categories with high Gal-3 (≥75 th percentile) using logistic regression. We used Cox regression to evaluate associations of cross-categories of metabolic risk group and Gal-3 quartiles with incident HF. Results: In cross-sectional analyses, those with MetS were more likely to have elevated Gal-3 levels than those with no diabetes or MetS (OR 1.29, 95%CI 1.13-1.47). The additional presence of diabetes did not change the likelihood of elevated Gal-3 (OR 1.29, 95%CI 1.08-1.55). Over 20.5 years of follow-up, there were 1,611 HF events. Higher Gal-3 was associated with higher HF risk in each metabolic risk group, and higher metabolic risk group was associated with greater HF risk in each Gal-3 quartile. There was no interaction between Gal-3 and metabolic risk group on HF risk ( P =0.15). The combination of diabetes &MetS and high Gal-3 was associated with an almost 5-fold higher risk of incident HF (HR 4.93; 95% CI: 3.77 - 6.44) than the combination of no diabetes/MetS and low Gal-3 (first quartile) ( Table ). Conclusions: MetS was associated with higher levels of Gal-3. Metabolic risk group and Gal-3 provided powerful complementary prognostic information regarding HF risk. Fibrosis likely plays a role in the development of HF linked to metabolic risk

Obesity, Galectin-3, and Incident Heart Failure: The ARIC Study

Background Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin-3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996-1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin-3 (≥75th sex-specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin-3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin-3 (odds ratio [OR], 2.32; 95% CI, 1.88-2.86) for severe obesity ([BMI ≥35 kg/m ] versus normal weight [BMI 18.5-<25 kg/m ]). There were stronger associations of BMI with elevated galectin-3 among women versus men and White versus Black participants (both -for-interaction 4-fold higher risk of HF (HR, 4.19; 95% CI, 2.98-5.88) than those with normal weight and galectin-3 <25th percentile. Conclusions Obesity is strongly associated with elevated galectin-3. Additionally, the combination of obesity and elevated galectin-3 is associated with marked HF risk, underscoring the importance of elucidating pathways linking obesity with cardiac inflammation and fibrosis

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported beta = 0.120). For the second research question, this was the case for 65% of the teams (median reported beta = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates