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Background: Recent studies have demonstrated the relevance of circulating factors in the occurrence and development of colorectal cancer (CRC); however, the causal relationship remains unclear. Methods: Summary-level data for CRC were obtained from the UK Biobank (5,657 cases and 372,016 controls), FinnGen cohort (3,022 cases and 215,770 controls), and BioBank Japan Project (BBJ, 7,062 cases and 195,745 controls). Thirty-two peripheral markers with consistent definitions were collected from the three biobanks. Mendelian randomization (MR) was used to evaluate the causal effect of circulating factors on CRC. The effects from the three consortiums were combined using trans-ancestry meta-analysis methods. Results: Our analysis provided compelling evidence for the causal association of higher genetically predicted eosinophil cell count (EOS, odds ratio [OR], 0.8639; 95% confidence interval [CI] 0.7922–0.9421) and red cell distribution width (RDW, OR, 0.9981; 95% CI, 0.9972–0.9989) levels with a decreased risk of CRC. Additionally, we found suggestive evidence indicating that higher levels of total cholesterol (TC, OR, 1.0022; 95% CI, 1.0002–1.0042) may increase the risk of CRC. Conversely, higher levels of platelet count (PLT, OR, 0.9984; 95% CI, 0.9972–0.9996), total protein (TP, OR, 0.9445; 95% CI, 0.9037–0.9872), and C-reactive protein (CRP, OR, 0.9991; 95% CI, 0.9983–0.9999) may confer a protective effect against CRC. Moreover, we identified six ancestry-specific causal factors, indicating the necessity of considering patients' ancestry backgrounds before formulating prevention strategies. Conclusions: MR findings support the independent causal roles of circulating factors in CRC, which might provide a deeper insight into early detection of CRC and supply potential preventative strategies. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals. [ABSTRACT FROM AUTHOR]

Background: The interest in re‐introducing whole blood (WB) transfusion for the management of traumatic major haemorrhage is increasing. However, due to the current leucodepletion filters used in the UK a WB component was not readily available. Instead, an alternative but similar component, leucocyte depleted red cell and plasma (LD‐RCP), which provided a unique experience in assessing the feasibility of a WB component was used whilst a WB component was being manufactured. Study Design and Methods: Between November 2018 and October 2020, LD‐RCP replaced RBC as standard of care for all trauma patients with major haemorrhage in London. The aims of the study were to assess (a) deliverability, (b) component wastage and (c) safety. Results: Over the study period a total of 1208 LD‐RCP units were delivered, of which 96.5% were delivered 'On Time In Full' (OTIF). Of the 1208 units, 733 (60.68%) were transfused and 475 (39.3%) units were wasted. Component wastage reduced significantly throughout the study (p = 0.001). A total of 177 patients had a blood group recorded, 86 were group O and 91 were non‐group O. There was no statistically significantly difference between haemoglobin (p = 0.422), or bilirubin levels (p = 0.084) between group O and non‐group O patients. Discussion: It was feasible for NHS Blood and Transplant to deliver LD‐RCP on time in full, however component wastage was high due to short shelf life and limited use of the component. Low titre group O LD‐RCP units were not associated with clinical evidence of haemolysis. [ABSTRACT FROM AUTHOR]

Background: Early blood transfusion improves survival in patients with life-threatening bleeding, but the optimal transfusion strategy in the pre-hospital setting has yet to be established. Although there is some evidence of benefit with the use of whole blood, there have been no randomised controlled trials exploring the clinical and cost effectiveness of pre-hospital administration of whole blood versus component therapy for trauma patients with life-threatening bleeding. The aim of this trial is to determine whether pre-hospital leukocyte-depleted whole blood transfusion is better than standard care (blood component transfusion) in reducing the proportion of participants who experience death or massive transfusion at 24 h. Methods: This is a multi-centre, superiority, open-label, randomised controlled trial with internal pilot and within-trial cost-effectiveness analysis. Patients of any age will be eligible if they have suffered major traumatic haemorrhage and are attended by a participating air ambulance service. The primary outcome is the proportion of participants with traumatic haemorrhage who have died (all-cause mortality) or received massive transfusion in the first 24 h from randomisation. A number of secondary clinical, process, and safety endpoints will be collected and analysed. Cost (provision of whole blood, hospital, health, and wider care resource use) and outcome data will be synthesised to present incremental cost-effectiveness ratios for the trial primary outcome and cost per quality-adjusted life year at 90 days after injury. We plan to recruit 848 participants (a two-sided test with 85% power, 5% type I error, 1-1 allocation, and one interim analysis would require 602 participants—after allowing for 25% of participants in traumatic cardiac arrest and an additional 5% drop out, the sample size is 848). Discussion: The SWiFT trial will recruit 848 participants across at least ten air ambulances services in the UK. It will investigate the clinical and cost-effectiveness of whole blood transfusion versus component therapy in the management of patients with life-threatening bleeding in the pre-hospital setting. Trial registration: ISRCTN: 23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072, 21 Dec 2021. [ABSTRACT FROM AUTHOR]

Background: Cancer is a leading cause of morbidity and mortality worldwide, and better understanding of the risk factors could enhance prevention. Methods: We conducted a hypothesis‐free analysis combining machine learning and statistical approaches to identify cancer risk factors from 2828 potential predictors captured at baseline. There were 459,169 UK Biobank participants free from cancer at baseline and 48,671 new cancer cases during the 10‐year follow‐up. Logistic regression models adjusted for age, sex, ethnicity, education, material deprivation, smoking, alcohol intake, body mass index and skin colour (as a proxy for sun sensitivity) were used for obtaining adjusted odds ratios, with continuous predictors presented using quintiles (Q). Results: In addition to smoking, older age and male sex, positively associating features included several anthropometric characteristics, whole body water mass, pulse, hypertension and biomarkers such as urinary microalbumin (Q5 vs. Q1 OR 1.16, 95% CI = 1.13–1.19), C‐reactive protein (Q5 vs. Q1 OR 1.20, 95% CI = 1.16–1.24) and red blood cell distribution width (Q5 vs. Q1 OR 1.18, 95% CI = 1.14–1.21), among others. High‐density lipoprotein cholesterol (Q5 vs. Q1 OR 0.84, 95% CI = 0.81–0.87) and albumin (Q5 vs. Q1 OR 0.84, 95% CI = 0.81–0.87) were inversely associated with cancer. In sex‐stratified analyses, higher testosterone increased the risk in females but not in males (Q5 vs. Q1 ORfemales 1.23, 95% CI = 1.17–1.30). Phosphate was associated with a lower risk in females but a higher risk in males (Q5 vs. Q1 ORfemales 0.94, 95% CI = 0.90–0.99 vs. ORmales 1.09, 95% CI 1.04–1.15). Conclusions: This hypothesis‐free analysis suggests personal characteristics, metabolic biomarkers, physical measures and smoking as important predictors of cancer risk, with further studies needed to confirm causality and clinical relevance. [ABSTRACT FROM AUTHOR]

Background Measurement error in exposures and confounders can bias exposure–outcome associations but is rarely considered. We aimed to assess random measurement error of all continuous variables in UK Biobank and explore approaches to mitigate its impact on exposure–outcome associations. Methods Random measurement error was assessed using intraclass correlation coefficients (ICCs) for all continuous variables with repeat measures. Regression calibration was used to correct for random error in exposures and confounders, using the associations of red blood cell distribution width (RDW), C-reactive protein (CRP) and 25-hydroxyvitamin D [25(OH)D] with mortality as illustrative examples. Results The 2858 continuous variables with repeat measures varied in sample size from 109 to 49 121. They fell into three groups: (i) baseline visit [529 variables; median (interquartile range) ICC = 0.64 (0.57, 0.83)]; (ii) online diet by 24-h recall [22 variables; 0.35 (0.30, 0.40)] and (iii) imaging measures [2307 variables; 0.85 (0.73, 0.94)]. Highest ICCs were for anthropometric and medical history measures, and lowest for dietary and heart magnetic resonance imaging. The ICCs (95% confidence interval) for RDW, CRP and 25(OH)D were 0.52 (0.51, 0.53), 0.29 (0.27, 0.30) and 0.55 (0.54, 0.56), respectively. Higher RDW and levels of CRP were associated with higher risk of all-cause mortality, and higher concentration of 25(OH)D with lower risk. After correction for random measurement error in the main exposure, the associations all strengthened. Confounder correction did not influence estimates. Conclusions Random measurement error varies widely and is often non-negligible. For UK Biobank we provide relevant statistics and adaptable code to help other researchers explore and correct for this. [ABSTRACT FROM AUTHOR]

BACKGROUND Previous studies have found associations of red blood cell (RBC) traits (hemoglobin and RBC count) with blood pressure; whether these associations are causal is unknown. METHODS We performed cross-sectional analyses in the Lifelines Cohort Study (n = 167,785). Additionally, we performed bidirectional 2 sample Mendelian randomization (MR) analyses to explore the causal effect of the 2 traits on systolic (SBP) and diastolic blood pressure (DBP), using genetic instrumental variables regarding hemoglobin and RBC identified in UK Biobank (n = 350,475) and International Consortium of Blood Pressure studies for SBP and DBP (n = 757,601). RESULTS In cross-sectional analyses, we observed positive associations with hypertension and blood pressure for both hemoglobin (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.16–1.20 for hypertension; B = 0.11, 95% CI: 0.11–0.12 for SBP; B = 0.11, 95% CI: 0.10–0.11 for DBP, all per SD) and RBC (OR = 1.14, 95% CI: 1.12–1.16 for hypertension; B = 0.11, 95% CI: 0.10–0.12 for SBP; B = 0.08, 95% CI: 0.08–0.09 for DBP, all per SD). MR analyses suggested that higher hemoglobin and RBC cause higher DBP (inverse-variance weighted B = 0.11, 95% CI: 0.07–0.16 for hemoglobin; B = 0.07, 95% CI: 0.04–0.10 for RBC, all per SD). Reverse MR analyses (all per SD) suggested causal effects of DBP on both hemoglobin (B = 0.06, 95% CI: 0.03–0.09) and RBC (B = 0.08, 95% CI: 0.04–0.11). No significant effects on SBP were found. CONCLUSIONS Our results suggest bidirectional causal relationships of hemoglobin and RBC with DBP, but not with SBP. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with type 2 diabetes mellitus and chronic low-grade inflammation. Although chronic inflammatory conditions and diabetes are associated with anaemia, less is known about associations of obesity and body shape, independent of each other, with erythrocyte and reticulocyte parameters. Methods: We investigated the associations of body mass index (BMI) and the allometric body shape index (ABSI) and hip index (HI), which are uncorrelated with BMI, with erythrocyte and reticulocyte parameters (all continuous, on a standard deviation (SD) scale) in UK Biobank participants without known metabolic, endocrine, or major inflammatory conditions (glycated haemoglobin HbA1c < 48 mmol/mol, C-reactive protein CRP < 10 mg/L). We examined erythrocyte count, total reticulocyte count and percent, immature reticulocyte count and fraction (IRF), haemoglobin, haematocrit, mean corpuscular haemoglobin mass (MCH) and concentration (MCHC), mean corpuscular and reticulocyte volumes (MCV, MRV), and red cell distribution width (RDW) in multivariable linear regression models. We additionally defined body shape phenotypes with dichotomised ABSI (≥ 73 women; ≥ 80 men) and HI (≥ 64 women; ≥ 49 men), including "pear" (small-ABSI-large-HI) and "apple" (large-ABSI-small-HI), and examined these in groups according to BMI (18.5–25 normal weight; 25–30 overweight; 30–45 kg/m2 obese). Results: In 105,853 women and 100,854 men, BMI and ABSI were associated positively with haemoglobin, haematocrit, and erythrocyte count, and more strongly with total reticulocyte count and percent, immature reticulocyte count and IRF. HI was associated inversely with all, but least with IRF. Associations were comparable in women and men. In groups according to obesity and body shape, erythrocyte count was ~ 0.6 SD higher for obese-"apple" compared to normal-weight-"pear" phenotype (SD = 0.31*1012/L women, SD = 0.34*1012/L men), total reticulocyte count was ~ 1.1 SD higher (SD = 21.1*109/L women, SD = 23.6*109/L men), immature reticulocyte count was ~ 1.2 SD higher (SD = 7.9*109/L women, SD = 8.8*109/L men), total reticulocyte percent was ~ 1.0 SD higher (SD = 0.48% women and men), and IFR was over 0.7 SD higher (SD = 5.7% women and men). BMI but not ABSI or HI was associated more weakly inversely with MCV, MRV, and MCH, but positively with MCHC in men and RDW in women. Conclusions: In obesity uncomplicated with diabetes, larger BMI and ABSI are associated with increased erythropoiesis and reticulocyte immaturity. [ABSTRACT FROM AUTHOR]

Trans-ethnic genome-wide association studies have revealed that many loci identified in European populations can be reproducible in non-European populations, indicating widespread trans-ethnic genetic similarity. However, how to leverage such shared information more efficiently in association analysis is less investigated for traits in underrepresented populations. We here propose a statistical framework, trans-ethnic genetic risk score informed gene-based association mixed model (GAMM), by hierarchically modeling single-nucleotide polymorphism effects in the target population as a function of effects of the same trait in well-studied populations. GAMM powerfully integrates genetic similarity across distinct ancestral groups to enhance power in understudied populations, as confirmed by extensive simulations. We illustrate the usefulness of GAMM via the application to 13 blood cell traits (i.e. basophil count, eosinophil count, hematocrit, hemoglobin concentration, lymphocyte count, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, monocyte count, neutrophil count, platelet count, red blood cell count and total white blood cell count) in Africans of the UK Biobank (n  = 3204) while utilizing genetic overlap shared in Europeans (n  = 746 667) and East Asians (n  = 162 255). We discovered multiple new associated genes, which had otherwise been missed by existing methods, and revealed that the trans-ethnic information indirectly contributed much to the phenotypic variance. Overall, GAMM represents a flexible and powerful statistical framework of association analysis for complex traits in underrepresented populations by integrating trans-ethnic genetic similarity across well-studied populations, and helps attenuate health inequities in current genetics research for people of minority populations. [ABSTRACT FROM AUTHOR]

Despite considerable variation in disease manifestations observed among coronavirus disease 2019 (COVID‐19) patients infected with severe acute respiratory syndrome coronavirus 2, the risk factors predicting disease severity remain elusive. Recent studies suggest that peripheral blood cells play a pivotal role in COVID‐19 pathogenesis. Here, we applied two‐sample Mendelian randomization (MR) analyses to evaluate the potential causal contributions of blood cell indices variation to COVID‐19 severity, using single‐nucleotide polymorphisms (SNPs) as instrumental variables for 17 indices from the UK Biobank and INTERVAL genome‐wide association studies (N = 173 480). Data on the associations between the SNPs and very severe respiratory confirmed COVID‐19 were obtained from the COVID‐19 host genetics initiative (N = 8779/1 001 875). We observed significant negative association between hematocrit (HCT; odds ratio, OR = 0.775, 95% confidence interval, CI = 0.635–0.915, p = 3.48E−04) or red blood cell count (OR = 0.830, 95% CI = 0.728–0.932, p = 2.19E−03) and very severe respiratory confirmed COVID‐19, as well as nominal negative association of hemoglobin concentration (OR = 0.808, 95% CI = 0.673–0.943, p = 3.95E−03) with very severe respiratory confirmed COVID‐19 (no effect survived multiple correction). In conclusion, the MR study supports a protective effect of high HCT and red blood cell count from very severe respiratory confirmed COVID‐19, suggesting potential strategies to ameliorate/treat clinical conditions in very severe respiratory confirmed COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Familial pseudohyperkalemia (FP) is a rare asymptomatic condition characterized by an increased rate of potassium leak from red blood cells (RBC) on refrigeration. Gamma irradiation compromises RBC membrane integrity and accelerates potassium leakage. Here, we compared the effect of irradiation, applied early or late in storage, on FP versus non‐FP RBC. Study Design: Five FP and 10 non‐FP individuals from the National Institute for Health Research Cambridge BioResource, UK, and three FP and six non‐FP individuals identified by Australian Red Cross Lifeblood consented to the study. Blood was collected according to standard practice in each center, held overnight at 18–24°C, leucocyte‐depleted, and processed into red cell concentrates (RCC) in Saline Adenine Glucose Mannitol. On Day 1, RCC were split equally into six Red Cell Splits (RCS). Two RCS remained non‐irradiated, two were irradiated on Day 1 and two were irradiated on Day 14. RBCs were tested over cold storage for quality parameters. Results: As expected, non‐irradiated FP RCS had significantly higher supernatant potassium levels than controls throughout 28 days of storage (p <.001). When irradiated early, FP RCS released potassium at similar rates to control. When irradiated late, FP RCS supernatants had higher initial post‐irradiation potassium concentration than controls but were similar to controls by the end of storage (14 days post‐irradiation). No other parameters studied showed a significant difference between FP and control. Discussion: FP does not increase the rate of potassium leak from irradiated RBCs. Irradiation may cause a membrane defect similar to that in FP RBCs. [ABSTRACT FROM AUTHOR]

• Greater proximity to greenspace was associated with larger brain volumes. • Greater proximity to natural environment was associated with larger brain volumes. • Smoking and physical activity mediated associations between greenspace and brain volumes. • Vitamin D, red blood cell indices, and creatinine were important mediators for the association. To examine the associaiton between environmental measures and brain volumes and its potential mediators. This was a prospective study. Our analysis included 34,454 participants (53.4% females) aged 40–73 years at baseline (between 2006 and 2010) from the UK Biobank. Brain volumes were measured using magnetic resonance imaging between 2014 and 2019. Greater proximity to greenspace buffered at 1000 m at baseline was associated with larger volumes of total brain measured 8.8 years after baseline assessment (standardized β (95% CI) for each 10% increment in coverage: 0.013(0.005,0.020)), grey matter (0.013(0.006,0.020)), and white matter (0.011(0.004,0.017)) after adjustment for covariates and air pollution. The corresponding numbers for natural environment buffered at 1000 m were 0.010 (0.004,0.017), 0.009 (0.004,0.015), and 0.010 (0.004,0.016), respectively. Similar results were observed for greenspace and natural environment buffered at 300 m. The strongest mediator for the association between greenspace buffered at 1000 m and total brain volume was smoking (percentage (95% CI) of total variance explained: 7.9% (5.5–11.4%)) followed by mean sphered cell volume (3.3% (1.8–5.8%)), vitamin D (2.9% (1.6–5.1%)), and creatinine in blood (2.7% (1.6–4.7%)). Significant mediators combined explained 18.5% (13.2–25.3%) of the association with total brain volume and 32.9% (95% CI: 22.3–45.7%) of the association with grey matter volume. The percentage (95% CI) of the association between natural environment and total brain volume explained by significant mediators combined was 20.6% (14.7–28.1%)). Higher coverage percentage of greenspace and environment may benefit brain health by promoting healthy lifestyle and improving biomarkers including vitamin D and red blood cell indices. [ABSTRACT FROM AUTHOR]

Background and Objectives: The limited supply and increasing demand of group O RhD‐negative red blood cells (RBCs) have resulted in other transfusion strategies being explored by blood services that carry potential risks but may still provide an overall benefit to patients. Our aim was to analyse the potential economic benefits of prehospital transfusion (PHT) against no PHT. Materials and Methods: The impact of three PHT strategies (RhD‐negative RBC, RhD‐positive RBC and no transfusion) on quality‐adjusted‐life‐years (QALYs) of all United Kingdom trauma patients in a given year and the subset of patients considered most at risk (RhD‐negative females <50 years old), was modelled. Results: For the entire cohort and the subset of patients, transfusing RhD‐negative RBCs generated the most QALYs (141,899 and 2977, respectively), followed by the RhD‐positive RBCs (141,879.8 and 2958.8 respectively), and no prehospital RBCs (119,285 and 2503 respectively). The QALY difference between RhD‐negative and RhD‐positive policies was smaller (19.2, both cohorts) than RhD‐positive and no RBCs policies in QALYs term (22,600 all cohort, 470 for a subset), indicating that harms from transfusing RhD‐positive RBCs are lower than harms associated with no RBC transfusion. A survival increase from PHT of 0.02% (entire cohort) and 0.7% (subset cohort) would still make the RhD‐positive strategy better in QALYs terms than no PHT. Conclusion: While the use of RhD‐positive RBCs carries risks, the benefits measured in QALYs are higher than if no PHT are administered, even for women of childbearing potential. Group O RhD‐positive RBCs could be considered when there is a national shortage of RhD‐negative RBCs. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the link between increased erythrocyte mean corpuscular volume (MCV) and methotrexate (MTX) use in patients with psoriatic arthritis (PsA). Topics explored include the assessment of patient response to MTX use, the evaluation of MCV as predictor of clinical response in PsA, and the observations on the longitudinal change in MCV from baseline through 24 weeks.

Background: Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate causal risk factors and etiology have not been fully understood. This study assesses the causal effects of 37 heritable clinical factors on CAD in East Asian and European populations. Methods: We collected genome-wide association summary statistics of 37 clinical factors from the Biobank Japan (42,793 to 191,764 participants) and the UK Biobank (314,658 to 442,817 participants), paired with summary statistics of CAD from East Asians (29,319 cases and 183,134 controls) and Europeans (91,753 cases and 311,344 controls). These clinical factors covered 12 cardiometabolic traits, 13 hematological indices, 7 hepatological and 3 renal function indices, and 2 serum electrolyte indices. We performed univariable and multivariable Mendelian randomization (MR) analyses in East Asians and Europeans separately, followed by meta-analysis. Results: Univariable MR analyses identified reliable causal evidence (P < 0.05/37) of 10 cardiometabolic traits (height, body mass index [BMI], blood pressure, glycemic and lipid traits) and 4 other clinical factors related to red blood cells (red blood cell count [RBC], hemoglobin, hematocrit) and uric acid (UA). Interestingly, while generally consistent, we identified population heterogeneity in the causal effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant (P < 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19, P = 3.26×10−5). Conclusions: We confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD. [ABSTRACT FROM AUTHOR]

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275–675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms. ClinicalTrials.gov: NCT03466528. [ABSTRACT FROM AUTHOR]

Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity in the UK. Visual estimation of blood loss is unreliable yet remains common practice. As part of a national quality improvement project to improve care during PPH, standardized, quantitative measurement of blood loss (QBL) for all deliveries was introduced into a tertiary obstetric unit in Cardiff, Wales. Retrospective analysis of 875 consecutive maternities between December 2017 and February 2018 was undertaken. Of these, 372 mothers had both pre- and post-partum hemoglobin (Hb) were recorded. Regression analyses were performed to investigate the relationship between change in Hb adjusted for red cell transfusion and QBL. The correlation coefficient between QBL and adjusted change in Hb for all deliveries (n = 372) was 0.57. This corresponded to an estimated fall of adjusted change in Hb of 15.3 g/L (95% CI: 13.1, 17.6) per 1000 mL blood loss. QBL has been shown to be reliable across all maternity settings, with reproducible results in theater and delivery rooms (on the obstetric unit and alongside midwifery-led unit). QBL is moderately correlated with adjusted change in Hb for all volumes of bleeding and gives clinicians more accurate knowledge of blood loss than visual estimation. This low-cost, low-fidelity intervention can influence the timely escalation of clinical care and therefore patient outcome. [ABSTRACT FROM AUTHOR]

Summary: There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster‐randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23–41%) in the intervention group vs. 81% (95%CI 70–90%) in the control group. The proportion of women receiving cryoprecipitate at any time‐point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference −0.6 units, 95%CI −1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3–1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1–1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full‐scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation. [ABSTRACT FROM AUTHOR]

Background: The IV use of human immunoglobulin (hIVIG) in dogs with primary immune‐mediated hemolytic anemia (IMHA) has been described previously, but herein we describe the use of high‐dose IgM‐enriched hIVIG (Pentaglobin). Hypothesis/Objectives: Dogs treated with high‐dose Pentaglobin will experience shorter time to remission and hospital discharge and have decreased transfusion requirements compared to dogs receiving standard treatment alone. Animals Fourteen client‐owned dogs diagnosed with primary IMHA at specialist referral hospitals in the United Kingdom. Methods: All prospectively enrolled dogs received prednisolone, dexamethasone or both along with clopidogrel. Patients were randomized to receive Pentaglobin at 1 g/kg on up to 2 occasions, or to serve as controls. No additional immunosuppressive drugs were allowed within the first 7 days of treatment. Remission was defined as stable PCV for 24 hours followed by an increase in PCV. Results: Ten of 11 dogs from the treatment group and 2 of 3 dogs from the control group achieved remission and survived until hospital discharge. Survival and time to remission were not significantly different between groups. The volume of packed red blood cells transfused, normalized for body weight, was not significantly different between groups. Potential adverse reactions to Pentaglobin occurred in 2 dogs, but their clinical signs may have been related to the underlying disease. Conclusions and Clinical Importance: Treatment with high‐dose Pentaglobin was well tolerated by dogs with primary IMHA but no significant advantage was found in this small study. Additional studies examining larger groups and subpopulations of dogs with primary IMHA associated with a poorer prognosis are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Haemolysis is considered one of the major contributors of nonconformities and sample rejection in coagulation testing. Materials and methods: Two lyophilized plasmas were distributed to 800 centres registered for prothrombin time (PT), activated partial thromboplastin time (APTT) and either Clauss fibrinogen or thrombin time (TT) in the UK NEQAS BC programme. The same pool of normal plasma was used to prepare both samples, to one of which red blood cell haemolysate was added to mimic haemolysis at 3 g/L haemoglobin concentration. Participants were asked to complete a questionnaire about their laboratory approach to dealing with haemolysed samples, including strategies used to deal with different levels of haemolysis. Results: Results for tests performed did not show great differences between the two samples. It should be noted that artificially constructed haemolysed samples may not behave in the same way as patient samples (ie, may not be commutable). However, the possibility of carrying out a large multicentre study for detection of haemolysis was demonstrated. Inconsistency in practice was observed with 226/551 (41%) of centres indicated they reject haemolysed samples solely on visual checks, and 163 (30%) using initial visual checks with further sample rejection evaluation by analyser flags. Furthermore, 333 (72%) of centres indicated that the level of haemolysis affects sample rejection decisions, while 132 (28%) stated it did not. Conclusion: Variability of responses for dealing with haemolysed samples reflects a lack of clear consistency in the pre‐analytical area of sample processing. [ABSTRACT FROM AUTHOR]

Objectives: Patients presenting to acute care settings with anaemia are at risk of inadequate investigation and inappropriate blood transfusion. In collaboration with Haematology Specialty Trainee Audit and Research (HaemSTAR), this study set out to assess current red blood cell (RBC) transfusion practice and anaemia management in acute care settings across the United Kingdom. Methods and Results: Fifteen different hospitals participated in the study over a period of a month beginning 01 January 2020. Eight‐hundred and twenty‐eight eligible patients presenting to acute care settings with anaemia received RBC transfusions during this period. Of these, 159 (19.2%) received inappropriate transfusions according to National Institute for Health and Care Excellence guidelines, and 257 (31%) could have been treated with alternatives to transfusion. One‐hundred and fifty‐four (18.6%) did not have a cause for their anaemia identified by the time they were discharged from hospital, and in over 50% of these cases that was because of inadequate investigation with blood tests, specialist investigation or referral, or both. Conclusion: This study found that the appropriateness of transfusion and investigation of anaemia in acute care settings warrant improvement and also demonstrates the value of HaemSTAR in facilitating time‐efficient collection of high‐quality data. [ABSTRACT FROM AUTHOR]

Objectives: A retrospective population‐based study to determine the incidence and prevalence of patients with the rare blood disease paroxysmal nocturnal haemoglobinuria (PNH). Methods: All patients were identified by flow cytometric detection of blood cells deficient in glycosylphosphatidylinositol (GPI) linked proteins at a single diagnostic reference laboratory that serves the Yorkshire based, Haematological Malignancy Research Network (HMRN) with a population of 3.8 million. Results: One hundred and ninety‐seven patients with detectable PNH clones at a level of >0.01% in at least two lineages of cells (neutrophils, monocytes and/or red cells) were identified over a 15‐year period (2004‐2018). Of these, 88% had aplastic anaemia (AA), 8% classical PNH and 3% myelodysplastic syndrome. The overall incidence rate was estimated at 0.35 cases per 100 000 people per year. This equates to 220 cases newly diagnosed in the United Kingdom each year. The overall prevalence rate was 3.81 per 100 000, this equates to an estimated 2400 prevalent cases in the UK. The overall and relative 5‐year survival rates were 72% and 82.7%, respectively. Conclusions: This study showed that classical haemolytic PNH is a rare disease and represents only a small proportion overall of patients with detectable PNH cells, the majority of which have aplastic anaemia. [ABSTRACT FROM AUTHOR]

Mitochondrial (MT) dysfunction is a hallmark of aging and has been associated with most aging-related diseases as well as immunological processes. However, little is known about aging, lifestyle and genetic factors influencing mitochondrial DNA (mtDNA) abundance. In this study, mtDNA abundance was estimated from the weighted intensities of probes mapping to the MT genome in 295,150 participants from the UK Biobank. We found that the abundance of mtDNA was significantly elevated in women compared to men, was negatively correlated with advanced age, higher smoking exposure, greater body-mass index, higher frailty index as well as elevated red and white blood cell count and lower mortality. In addition, several biochemistry markers in blood-related to cholesterol metabolism, ion homeostasis and kidney function were found to be significantly associated with mtDNA abundance. By performing a genome-wide association study, we identified 50 independent regions genome-wide significantly associated with mtDNA abundance which harbour multiple genes involved in the immune system, cancer as well as mitochondrial function. Using mixed effects models, we estimated the SNP-heritability of mtDNA abundance to be around 8%. To investigate the consequence of altered mtDNA abundance, we performed a phenome-wide association study and found that mtDNA abundance is involved in risk for leukaemia, hematologic diseases as well as hypertension. Thus, estimating mtDNA abundance from genotyping arrays has the potential to provide novel insights into age- and disease-relevant processes, particularly those related to immunity and established mitochondrial functions. [ABSTRACT FROM AUTHOR]

Poor nutrition is not simply implying unavailability or inaccessibility to good food which is a struggle only for the under-developed or developing countries. It is inclusive of different version of malnutrition (e.g. overweight and obesity) now endemic in the developed countries like the United Kingdom. These types of malnutrition are closely linked to non-communicable diseases like diabetes, cardiovascular diseases, hypertension and cancer. Hence, disputing the fact that availability of something to put in the mouth could prevent malnutrition. Moreover, many of the uninformed and unselective choices of food also predispose the populace to their target flights. Children and women in sub-Saharan Africa suffer more from malnutrition caused by undernutrition especially protein deficiency. Many of the commonly available protein sources are usually associated with unwanted antinutrient substances. Consumption of these proteins leads to malnutrition (overweight and obesity) in subjects. The replacement of these protein sources with 25% Moringa oleifera leaf provided sustainable improvements in some biochemical and haematological parameters of examined in this study. All the haematological indices such as red blood cells (RBC), white blood cells (WBC), haemoglobin (Hb) and packed cell volume (PCV) were observed to be significantly lower than the control before treatment, but these parameters were significantly increased after treatment with both treatment feeds. Serum concentration of albumin was significantly (P<0.05) reduced in experimental rats following feeding with low protein iso-caloric diets. This concentration however increased significantly after feeding the malnourished animals with the formulated treatment feeds, with the most significant increase in the group treated with 25% M. oleifera. The treatment feeds also produced significant changes (P<0.05) in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) is an autologous preparation that has been claimed to improve healing and mechanobiological properties of tendons both in vitro and in vivo. In this sub-study from the PATH-2 (PRP in Achilles Tendon Healing-2) trial, we report the cellular and growth factor content and quality of the Leukocyte-rich PRP (L-PRP) (N = 103) prepared using a standardized commercial preparation method across 19 different UK centers. Baseline whole blood cell counts (red cells, leukocyte and platelets) demonstrated that the two groups were well-matched. L-PRP analysis gave a mean platelet count of 852.6 x 109/L (SD 438.96), a mean leukocyte cell count of 15.13 x 109/L (SD 10.28) and a mean red blood cell count of 0.91 x 1012/L (SD 1.49). The activation status of the L-PRP gave either low or high expression levels of the degranulation marker CD62p before and after ex-vivo platelet activation respectively. TGF-β, VEGF, PDGF, IGF and FGFb mean concentrations were 131.92 ng/ml, 0.98 ng/ml, 55.34 ng/ml, 78.2 ng/ml and 111.0 pg/ml respectively with expected correlations with both platelet and leukocyte counts. While PATH-2 results demonstrated that there was no evidence L-PRP is effective for improving clinical outcomes at 24 weeks after Achilles tendon rupture, our findings support that the majority of L-PRP properties were within the method specification and performance. [ABSTRACT FROM AUTHOR]

Causal inference via Mendelian randomization requires making strong assumptions about horizontal pleiotropy, where genetic instruments are connected to the outcome not only through the exposure. Here, we present causal Graphical Analysis Using Genetics (cGAUGE), a pipeline that overcomes these limitations using instrument filters with provable properties. This is achievable by identifying conditional independencies while examining multiple traits. cGAUGE also uses ExSep (Exposure-based Separation), a novel test for the existence of causal pathways that does not require selecting instruments. In simulated data we illustrate how cGAUGE can reduce the empirical false discovery rate by up to 30%, while retaining the majority of true discoveries. On 96 complex traits from 337,198 subjects from the UK Biobank, our results cover expected causal links and many new ones that were previously suggested by correlation-based observational studies. Notably, we identify multiple risk factors for cardiovascular disease, including red blood cell distribution width. Mendelian randomization is a popular method to detect causal relationships between traits, but can be confounded by instances of horizontal pleiotropy. Here, the authors present a Mendelian randomization workflow which includes causal discovery analysis and filtering of genetic instruments based on their conditional independencies. [ABSTRACT FROM AUTHOR]

The association between international-normalised-ratio (INR) correction and mortality in patients with major bleeding on vitamin-K-antagonists (VKA) is important for evaluating the efficacy of reversal agents for oral anticoagulants. We evaluate if INR correction (defined as ≤1.3) following intervention in major bleeding on VKA is associated with better survival, and if there is a dose-response relationship between Vitamin K (VK) and INR correction. Data on patients' characteristics, haematological management and 30-day outcomes reported by 32 UK hospitals (October 2013–August 2016) were analysed. Associations between INR correction and: (a) 30-day mortality; (b) VK dose were estimated using multivariable logistic regression, using multiple imputation to handle missing INR values. Of 1771 patients, 77%, 73% and 33% received prothrombin-complex-concentrate (PCC), VK (92% intravenous) and red cells and fresh frozen plasma transfusion respectively. Proportionally more intracranial haemorrhage (ICH) cases (87%) than non-ICH cases (69%) received PCC. VK administration did not vary by ICH group, with 10 mg (33%) and 5 mg (28%) doses being the most common. Higher doses of VK (10 mg) were more likely to correct INR than lower doses (5 mg). Post-intervention INR > 1.3 in treated patients was associated with 3.2 (95%CI: 2.1–4.9) times higher odds of death within 30 days, compared with INR ≤ 1.3, with no difference between ICH and non-ICH. INR correction after intervention to manage major bleeding on VKA is associated with better survival. Higher VK doses (10 mg) improve INR correction more than lower doses (5 mg) in major bleeding, but further studies are warranted to compare the relative benefits/risks of 5 mg versus 10 mg doses. • INR correction is associated with better survival in major bleeding from warfarin. • 10 mg and 5 mg Vitamin K are commonly used; higher doses improve INR correction more. • We need trials to compare the relative benefits/risks of 10 mg versus 5 mg Vitamin K. [ABSTRACT FROM AUTHOR]

This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data were collected retrospectively from patient electronic records and hospital transfusion databases recording issue of blood products from January 2016 to December 2018. Of 134 patients with MH, 24 had activated MHP and 110 did not have activated MHP. Groups were similar for age, sex, baseline hemoglobin, platelet count, coagulation screen, and renal function with no difference in the baseline clinical characteristics. The total number of red cell units (median and [IQR]) transfused was no different in the patients with activated (7.5 [5–11.75]) versus nonactivated (9 [6–12]) MHP ( p  = 0.35). Patients in the nonactivated MHP group received significantly higher number of platelet units (median: 3 vs. 2, p  = 0.014), plasma (median: 4.5 vs. 1.5, p  = 0.0007), and cryoprecipitate (median: 2 vs. 1, p  = 0.008). However, activation of MHP was associated with higher mortality at 24 hours compared with patients with nonactivation of MHP (33.3 vs. 10.9%, p  = 0.005) and 30 days (58.3 vs. 30.9%, p  = 0.01). The total RBC and platelet (but not fresh frozen plasma [FFP]) units received were higher in deceased patients than in survivors. Increased mortality was associated with a higher RBC:FFP ratio. Only 26% of patients received tranexamic acid and these patients had higher mortality at 30 days but not at 24 hours. Deceased patients at 30 days had higher levels of fibrinogen than those who survived (median: 2.4 vs. 1.8, p  = 0.01). Patients with activated MHP had significantly higher mortality at both 24 hours and 30 days despite lack of difference in the baseline characteristics of the patients with activated MHP versus nonactivated MHP groups. The increased mortality associated with a higher RBC:FFP ratio suggests dilutional coagulopathy may contribute to mortality, but higher fibrinogen at baseline was not protective. [ABSTRACT FROM AUTHOR]

Hb Manitoba [α102(G9)Ser→Arg] is a rare α chain variant with diverse ethnic origins. It is mildly unstable with an expression of around 10.0–14.2% in the heterozygous state in most literature. In this study, 12 cases of Hb Manitoba [11 cases carried Hb Manitoba II (HBA1: c.309C>A) and one case carried Hb Manitoba IV (HBA1: c.307A>C)] were detected during a wide-spectrum study of α chain variants in the UK. Fluctuation in variant expression from 6.9 to 15.2% of total Hb on high performance liquid chromatography (HPLC) would pose a diagnostic dilemma in routine laboratories. Focusing on the variant expression, the median of Hb Manitoba was around 11.5% of total Hb in three cases, apparently with normal hemoglobin (Hb), and normal red blood cell (RBC) indices. Two cases showed a higher expression (13.9 and 15.2%) and five cases showed a lower expression (6.9–9.9%). The common α-thalassemia (α-thal) –α3.7 (rightward) deletion coexisted with one case of increased Hb Manitoba expression. Iron (or other nutrient) deficiency was likely the cause of decreased Hb Manitoba percentage in this study. The α73(EF2)Val→Val (α2) (HBA2: c.222G>T) polymorphism is published for the first time and coexisted with two cases. The Cap +14 (C>G) (HBA2: c.-24C>G) polymorphism coexisted with another case in a heterozygous state. In conclusion, the fluctuation in variant expression can cause a diagnostic dilemma, especially in routine laboratories. Screening for the common –α3.7 deletion and iron deficiency is recommended when an α chain variant is suspected. [ABSTRACT FROM AUTHOR]

Background: Microcytosis (smaller than normal red blood cells) has previously been identified as a possible early risk marker for some cancers. However, the role of microcytosis across all cancers has not been fully investigated.Aim: To examine cancer incidence in a cohort of patients with microcytosis, with and without accompanying anaemia.Design and Setting: Cohort study of patients aged ≥40 years using UK primary care electronic patient records.Method: The 1-year cancer incidence was compared between cohorts of patients with a mean red cell volume of <85 femtolitres (fL) (low) or 85-101 fL (normal). Further analyses examined sex, age group, cancer site, and haemoglobin values.Results: Of 12 289 patients with microcytosis, 497 had a new cancer diagnosis within 1 year (4.0%, 95% confidence interval [CI] = 3.7 to 4.4), compared with 1465 of 73 150 without microcytosis (2.0%, CI = 1.9 to 2.1). In males, 298 out of 4800 with microcytosis were diagnosed with cancer (6.2%, CI = 5.5 to 6.9), compared with 940 out of 34 653 without (2.7%, CI = 2.5 to 2.9). In females with microcytosis, 199 out of 7489 were diagnosed with cancer (2.7%, CI = 2.3 to 3.1), compared with 525 out of 38 497 without (1.4%, CI = 1.3 to 1.5). In patients with microcytosis but normal haemoglobin, 86 out of 2637 males (3.3%, CI = 2.6 to 4.0) and 101 out of 5055 females (2.0%, CI = 1.6 to 2.4) were diagnosed with cancer.Conclusion: Microcytosis is a predictor of underlying cancer even if haemoglobin is normal. Although a benign explanation is more likely, clinicians in primary care should consider simple testing for cancer on encountering unexplained microcytosis, particularly in males. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To determine the organisational resources in place; what blood was being transfused, why, how, where, when and by whom; whether laboratory support and policies met standards for patients with sickle cell disease (SCD). Background: SCD affects 14 000 people in the United Kingdom (UK). Standards and guidelines do not cover all aspects of transfusion in SCD and there are no data on their use; people may become very sick without warning presenting to non‐specialist hospitals; blood services are increasingly supplying units for transfusion in SCD with little data on their use. Methods: A retrospective audit of transfusion services/practice for people with SCD who had received a transfusion in January‐July 2014 in participating hospitals in the UK and Republic of Ireland (ROI). Results: Eighty‐four hospitals submitted 1290 cases, 75% of cases came from 18 hospitals submitting 25 or more cases. Transfusions (91.2% [1164/1276]) were administered to patients with HbSS, 60% (732/1227) of patients needed Rh CE negative blood. Transfusion episodes (4528) were recorded, of which 84% were elective. Stroke prevention accounted for 42% of all transfusions; adults received 56% of transfusions of which 50% were automated red cell exchange (RCE), children received 44% of transfusions of which 87% were simple transfusions. Conclusions: There was a paucity of appropriate clinical management protocols, adequately trained staff and network arrangements. The high numbers of children being transfused, disparity in transfusion modality between children and adults and the high frequency of the CE negative Rh phenotype were noted. [ABSTRACT FROM AUTHOR]

Psychiatric disorders are highly heritable and associated with a wide variety of social adversity and physical health problems. Using genetic liability (rather than phenotypic measures of disease) as a proxy for psychiatric disease risk can be a useful alternative for research questions that would traditionally require large cohort studies with long-term follow up. Here we conducted a hypothesis-free phenome-wide association study in about 300,000 participants from the UK Biobank to examine associations of polygenic risk scores (PRS) for five psychiatric disorders (major depression (MDD), bipolar disorder (BP), schizophrenia (SCZ), attention-deficit/ hyperactivity disorder (ADHD) and autism spectrum disorder (ASD)) with 23,004 outcomes in UK Biobank, using the open-source PHESANT software package. There was evidence after multiple testing (p<2.55x10-06) for associations of PRSs with 294 outcomes, most of them attributed to associations of PRSMDD (n = 167) and PRSSCZ (n = 157) with mental health factors. Among others, we found strong evidence of association of higher PRSADHD with 1.1 months younger age at first sexual intercourse [95% confidence interval [CI]: -1.25,-0.92] and a history of physical maltreatment; PRSASD with 0.01% lower erythrocyte distribution width [95%CI: -0.013,-0.007]; PRSSCZ with 0.95 lower odds of playing computer games [95%CI:0.95,0.96]; PRSMDD with a 0.12 points higher neuroticism score [95%CI:0.111,0.135] and PRSBP with 1.03 higher odds of having a university degree [95%CI:1.02,1.03]. We were able to show that genetic liabilities for five major psychiatric disorders associate with long-term aspects of adult life, including socio-demographic factors, mental and physical health. This is evident even in individuals from the general population who do not necessarily present with a psychiatric disorder diagnosis. Author summary: Psychiatric disorders are associated with a wide range of adverse health, social and economic problems. Our study investigated the association of genetic risk for five common psychiatric disorders with socio- demographics, lifestyle and health of about 330,000 participants in the UK Biobank using a systematic, hypothesis-free approach. We found that genetic risk for attention deficit/hyperactivity disorder (ADHD) and bipolar disorder were most strongly associated with lifestyle factors, such as time of first sexual intercourse and educational attainment. Genetic risks for autism spectrum disorder and schizophrenia were associated with altered blood cell counts and decreased risk of coeliac disease, respectively. Increased genetic risk for depression was associated with other mental health outcomes such as neuroticism and irritability. In general, our results suggest that genetic risk for psychiatric disorders associates with a range of health and lifestyle traits that were measured in adulthood, in individuals from the general population who do not necessarily present with a psychiatric disorder diagnosis. However, it is important to note that these associations are not necessary causal but can also represent genetic correlation or be influenced by other factors, such as socio-economic factors and selection into the cohort. The findings should inform future research using causally informative designs. [ABSTRACT FROM AUTHOR]

Summary: The International Collaboration for Transfusion Medicine Guidelines (ICTMG) has published guidance on transfusion for haemoglobinopathies. To give a UK perspective on this guidance, each of the recommendations in the ICTMG guideline were reviewed and the applicability for transfusion practice in the UK considered with reference to relevant published British Society for Haematology (BSH) guidelines and national standards. There was much consensus; however, there was disparity surrounding the recommendations for routinely extended matching in those with alloimmunisation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Responding to national and local pressures to reduce the amount of blood transfused, the haematology department of Oxford University Hospitals (OUH), UK implemented an electronic blood‐ordering system with clinical decision support. This intervention targeted junior doctors, giving regular feedback on their transfusion practices with respect to clinical guidelines. Methods: We evaluated the incremental costs of the intervention using interrupted time series methods to compare red blood cell and platelet usage before and after the intervention was implemented. Difference‐in‐differences analysis was used to control for external factors that would affect the use of blood products over time. Reductions in blood usage were balanced against intervention costs. Results: The base case analysis showed an average cost saving to the department of £89 304 annually as a result of the intervention. Scenario analyses suggested that the savings may have been greater still, had the increasing trend in blood use prior to the intervention continued in the absence of the intervention. Conclusion: An electronic blood‐ordering system with clinical decision support can reduce blood transfusions and associated healthcare costs. Focusing on improving junior doctors' transfusion practice is expected to have a knock‐on benefit in terms of dissemination of good transfusion practice both within their own department and others as they continue their training. [ABSTRACT FROM AUTHOR]

Meta‐analyses and Mendelian randomization (MR) may clarify the associations of smoking, blood cells and myeloproliferative neoplasms (MPN). We investigated the association of smoking with blood cells in the Danish General Suburban Population Study (GESUS, n = 11 083), by meta‐analyses (including GESUS) of 92 studies (n = 531 741) and MR of smoking variant CHRNA3 (rs1051730[A]) in UK Biobank, and with MPN in a meta‐analysis of six studies (n (total/cases):1 425 529/2187), totalling 2 307 745 participants. In the meta‐analysis the random‐effects standardized mean difference (SMD) in current smokers versus non‐smokers was 0·82 (0·75–0·89, P = 2·0 * 10−108) for leukocytes, 0·09 (−0·02 to 0·21, P = 0·12) for erythrocytes, 0·53 (0·42–0·64, P = 8·0 * 10−22) for haematocrit, 0·42 (0·34–0·51, P = 7·1 * 10−21) for haemoglobin, 0·19 (0·08–0·31, P = 1·2 * 10−3) for mean corpuscular haemoglobin (MCH), 0·29 (0·19–0·39, P = 1·6 * 10−8) for mean corpuscular volume (MCV), and 0·04 (−0·04 to 0·13, P = 0·34) for platelets with trends for ever/ex‐/current smokers, light/heavy smokers and female/male smokers. Analyses presented high heterogeneity but low publication bias. Per allele in CHRNA3, cigarettes per day in current smokers was associated with increased blood cell counts (leukocytes, neutrophils), MCH, red cell distribution width (RDW) and MCV. The pooled fixed‐effects odds ratio for MPN was 1·44 [95% confidence interval (CI): 1·33–1·56; P = 1·8 * 10−19; I2 = 0%] in current smokers, 1·29 (1·15–1·44; P = 8·0 * 10−6; I2 = 0%) in ex‐smokers, 1·49 (1·26–1·77; P = 4·4 * 10−6; I2 = 0%) in light smokers and 2·04 (1·74–2·39, P = 2·3 * 10−18; I2 = 51%) in heavy smokers compared with non‐smokers. Smoking is observationally and genetically associated with increased leukocyte counts and red blood cell indices (MCH, MCV, RDW) and observationally with risk of MPN in current and ex‐smokers versus non/never‐smokers. [ABSTRACT FROM AUTHOR]

Summary: Background: Acute upper gastrointestinal bleeding (UGIB) remains a major cause of hospital admission worldwide. The recent UK National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report on severe gastrointestinal bleeding used the Shock Index to assess bleeding severity and found an association between Shock Index and mortality. However, this has never been prospectively validated as a predictor of outcome in UGIB. Aims: To compare the Shock Index with existing pre‐endoscopic UGIB risk scores in predicting outcomes after UGIB Methods: In an international, prospective study of 3012 consecutive patients with UGIB, we compared the Shock Index with existing scores including the Glasgow Blatchford score (GBS), admission Rockall score, AIMS65, and the newly described "ABC" score. Pre‐determined endpoints were need for major (≥4 units red cells) transfusion, need for endoscopic therapy and 30‐day mortality. Results: The Shock Index was inferior to the GBS in predicting need for major transfusion (area under the receiver operator characteristic curve [AUROC] 0.655 vs 0.836, P < 0.001) and need for endotherapy (AUROC 0.606 vs 0.747, P < 0.001). The Shock Index was inferior to all other scores for 30‐day mortality: for example, AUROC 0.611 vs 0.863 for ABC score (P < 0.001). Adding the Shock Index to the ABC score did not improve accuracy of the ABC score in predicting mortality (AUROC 0.864 vs 0.863, P = 0.95). Conclusion: The Shock Index performed poorly with AUROCs <0.66 and was inferior to existing pre‐endoscopy scores at predicting major clinical endpoints after UGIB. We found no clear evidence that the Shock Index is clinically useful at predicting outcomes in UGIB. [Correction added on 20 December 2019, after first online publication: Summary section has been changed for clarification.] LINKED CONTENT This article is linked to Bardou and Barkun and McPherson and Hammond and Stanley papers. To view these articles, visit https://doi.org/10.1111/apt.15574 and https://doi.org/10.1111/apt.15615 and https://doi.org/10.1111/apt.15605. [ABSTRACT FROM AUTHOR]

Thrombosis and platelet activation play a central role in stroke pathogenesis, and antiplatelet and anticoagulant therapies are central to stroke prevention. However, whether haematological traits contribute equally to all ischaemic stroke subtypes is uncertain. Furthermore, identification of associations with new traits may offer novel treatment opportunities. The aim of this research was to ascertain causal relationships between a wide range of haematological traits and ischaemic stroke and its subtypes. We obtained summary statistics from 27 published genome-wide association studies of haematological traits involving over 375 000 individuals, and genetic associations with stroke from the MEGASTROKE Consortium (n = 67 000 stroke cases). Using two-sample Mendelian randomization we analysed the association of genetically elevated levels of 36 blood cell traits (platelets, mature/immature red cells, and myeloid/lymphoid/compound white cells) and 49 haemostasis traits (including clotting cascade factors and markers of platelet function) with risk of developing ischaemic (AIS), cardioembolic (CES), large artery (LAS), and small vessel stroke (SVS). Several factors on the intrinsic clotting pathway were significantly associated (P < 3.85 × 10−4) with CES and LAS, but not with SVS (e.g. reduced factor VIII activity with AIS/CES/LAS; raised factor VIII antigen with AIS/CES; and increased factor XI activity with AIS/CES). On the common pathway, increased gamma (γ′) fibrinogen was significantly associated with AIS/CES. Furthermore, elevated plateletcrit was significantly associated with AIS/CES, eosinophil percentage of white cells with LAS, and thrombin-activatable fibrinolysis inhibitor activation peptide antigen with AIS. We also conducted a follow-up analysis in UK Biobank, which showed that amongst individuals with atrial fibrillation, those with genetically lower levels of factor XI are at reduced risk of AIS compared to those with normal levels of factor XI. These results implicate components of the intrinsic and common pathways of the clotting cascade, as well as several other haematological traits, in the pathogenesis of CES and possibly LAS, but not SVS. The lack of associations with SVS suggests thrombosis may be less important for this stroke subtype. Plateletcrit and factor XI are potentially tractable new targets for secondary prevention of ischaemic stroke, while factor VIII and γ′ fibrinogen require further population-based studies to ascertain their possible aetiological roles. [ABSTRACT FROM AUTHOR]

Human-specific duplications at chromosome 16p11.2 mediate recurrent pathogenic 600 kbp BP4–BP5 copy-number variations, which are among the most common genetic causes of autism. These copy-number polymorphic duplications are under positive selection and include three to eight copies of BOLA2 , a gene involved in the maturation of cytosolic iron-sulfur proteins. To investigate the potential advantage provided by the rapid expansion of BOLA2 , we assessed hematological traits and anemia prevalence in 379,385 controls and individuals who have lost or gained copies of BOLA2 : 89 chromosome 16p11.2 BP4–BP5 deletion carriers and 56 reciprocal duplication carriers in the UK Biobank. We found that the 16p11.2 deletion is associated with anemia (18/89 carriers, 20%, p = 4e−7, OR = 5), particularly iron-deficiency anemia. We observed similar enrichments in two clinical 16p11.2 deletion cohorts, which included 6/63 (10%) and 7/20 (35%) unrelated individuals with anemia, microcytosis, low serum iron, or low blood hemoglobin. Upon stratification by BOLA2 copy number, our data showed an association between low BOLA2 dosage and the above phenotypes (8/15 individuals with three copies, 53%, p = 1e-4). In parallel, we analyzed hematological traits in mice carrying the 16p11.2 orthologous deletion or duplication, as well as Bola2 +/− and Bola2 −/− animals. The Bola2 -deficient mice and the mice carrying the deletion showed early evidence of iron deficiency, including a mild decrease in hemoglobin, lower plasma iron, microcytosis, and an increased red blood cell zinc-protoporphyrin-to-heme ratio. Our results indicate that BOLA2 participates in iron homeostasis in vivo, and its expansion has a potential adaptive role in protecting against iron deficiency. [ABSTRACT FROM AUTHOR]

Background: Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery.Study Design and Methods: Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37°C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution. A laboratory study was conducted on six pools of ABO/D-matched units made the day after donation. On Days 7, 21, and 28 of 4 ± 2°C storage, one unit per pool was rejuvenated and measured over 96 hours for volume, hematocrit, hemolysis, ATP, 2,3-DPG, supernatant potassium, lactate, and purines added (inosine) or produced (hypoxanthine) by rejuvenation. Subsequently, an operational validation (two phases of 32 units each) was undertaken, with results from the first informing a trial component specification applied to the second. Rejuvenation effects were also tested on crossmatch reactivity and RBC antigen profiles.Results: Rejuvenation raised 2,3-DPG to, and ATP above, levels of fresh cells. The final component had potassium and hemolysis values below those of standard storage Days 7 and 21, respectively, containing 1.2% exogenous inosine and 500 to 1900 μmoles/unit of hypoxanthine. The second operational validation met compliance to the trial component specification. Rejuvenation did not adversely affect crossmatch reactivity or RBC antigen profiles.Conclusion: The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials. [ABSTRACT FROM AUTHOR]

• 92 iiSNPs were mined in 4085 genome-wide association studies. • 17 significant genotype-phenotype relationships were identified. • SNP-phenotype associations do not survive empirical evaluation. • Biobanks can prioritize iiSNP-phenotype associations to test empirically. Single nucleotide polymorphisms (SNPs) are amenable to genotyping DNA from degraded, inhibited, and/or ancient substrates due to their relatively small amplicon size. Though they have clear advantages over traditional short tandem repeat (STR) typing for specific casework scenarios, the advances in massively parallel sequencing (MPS) have drastically increased the utility of this marker type. The biallelic nature of SNPs makes them individually less informative than STRs due to limited heterozygosity; however, in sufficiently large multiplexes, identity informative SNPs (iiSNPs) may produce combined random match probabilities comparable to STR typing. Multiple MPS library preparation kits now include iiSNPs and similar to STRs, these loci have been rigorously characterized during multiplex development. The relative accessibility of genome-wide association study (GWAS) summary statistics enables re-investigation of forensically relevant targets in high-quality datasets. Here, 4085 GWASs from the UK Biobank European datasets (UKB; 787 ≤ N ≤ 361,194) were mined for iiSNPs typed by the ForenSeq DNA Signature Prep Kit (Verogen). Seven iiSNPs had genome-wide association (p ≤ 5 × 10−8) with 17 phenotypes in UKB Europeans. Most notably, these relationships involve two outwardly visible characteristics: standing height (rs907100; β = 0.011, p = 1.35 × 10-10) and hair/balding patterns (rs2399332; β = −0.009, p = 3.83 × 10−8). The remaining associations involve red blood cell characteristics and measures of lung function. Though these traits are highly polygenic and the individual SNP effects described here have been refuted empirically, we describe the importance and ease of exploring high-quality, freely accessible data to continuously and robustly characterize new and existing forensically relevant loci. [ABSTRACT FROM AUTHOR]

Background There may be differences in hematological parameters between meat-eaters and vegetarians. Objective The aim of this study was to perform cross-sectional analyses of hematological parameters by diet group in a large cohort in the United Kingdom. Methods A complete blood count was carried out in all UK Biobank participants at recruitment (2006–2010). We examined hemoglobin, red and white blood cell counts, and platelet counts and volume in regular meat eaters (>3 times/wk of red/processed meat consumption, n  = 212,831), low meat eaters (n  = 213,092), poultry eaters (n  = 4815), fish eaters (n  = 10,042), vegetarians (n  = 6548), and vegans (n  = 398) of white ethnicity and meat eaters (n  = 3875) and vegetarians (n  = 1362) of British Indian ethnicity. Results In both white and British Indian populations, compared with regular meat eaters (or meat eaters in Indians), the other diet groups had up to 3.7% lower age-adjusted hemoglobin concentrations (difference not significant in white vegan women) and were generally more likely to have anemia (e.g. 8.7% of regular meat eaters compared with 12.8% of vegetarians in white premenopausal women; P  < 0.05 after Bonferroni correction). In the white population, compared with regular meat eaters, all other diet groups had lower age- and sex-adjusted total white cells, neutrophils, lymphocytes, monocytes, and eosinophils (P -heterogeneity < 0.001 for all), but basophil counts were similar across diet groups; in British Indians, there was no significant difference in any of the white blood cell counts by diet group. Compared with white regular meat eaters, the low meat eaters, poultry eaters, fish eaters, and vegans had significantly lower platelet counts and higher platelet volume, whereas vegetarians had higher counts and lower volume. Compared with British Indian meat eaters, vegetarians had higher platelet count and lower volume. Conclusions In the UK Biobank, people with low or no red meat intake generally had lower hemoglobin concentrations and were slightly more likely to be anemic. The lower white blood cell counts observed in low and non-meat eaters, and differences in mean platelet counts and volume between diet groups, warrant further investigation. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697. [ABSTRACT FROM AUTHOR]

Background and Objectives: The 30‐min rule has been used to maintain a core temperature (CT) of red‐blood‐cell (RBC) units below 10°C during transportation. We evaluated the utility of temperature‐sensitive indicators (TIs) to monitor the surface temperature (ST) of RBC units and to explore whether TIs can help with compliance with the 30‐min rule by extrapolating or correlating temperature change with time. Materials and Methods: Two US FDA‐approved TIs, Safe‐T‐Vue 10 (STV10; Temptime Corporation, Morris Plains, NJ, USA) and Timestrip Blood Temp 10 (BT10; Timestrip UK Ltd, Cambridge, UK), were attached to 50 RBC units. After issue, their colour change indicating 10°C was monitored, and temperature excursions were measured by standard reading. In additional 18 RBC units, both ST and CT were monitored simultaneously. Results: In 50 RBC units, 94% of STV10 and 100% of BT10 showed colour change indicating 10°C within 30 min; 4% of STV10 and 18% of BT10 showed it during transportation. The time for colour change indicating 10°C differed significantly between STV10 and BT10 (19·0 vs. 5·6 min, P < 0·001). In additional 18 RBC units, 83·3% of STV10, 100% of BT10 and 88·9% of CT reached 10°C within 30 min, and the time for colour change indicating 10°C was 24·4 min in STV10, 14·6 min in BT 10 and 24·2 min in CT (P < 0·001). Conclusion: In two TIs, the time for colour change indicating 10°C varied considerably. To enhance the utility of TIs, further improvement and standardization would be needed. [ABSTRACT FROM AUTHOR]

Background and Objectives: In the UK, a significant proportion of red cell units is discarded due to the 30‐min rule governing out of temperature control. Studies have shown that repeated warming to ambient temperature has little impact on red cell quality or bacterial growth. We aimed to validate extension of the rule to 60 minutes by investigation of repeated same, and different, day exposures on bacterial growth. Materials and Methods: Red cell units were seeded individually at 100‐1000 cfu/ml with Yersinia enterocolitica, Serratia liquefaciens, Pseudomonas putida, Staphylococcus epidermidis, Enterobacter cloacae and Bacillus cereus. Test units were exposed to 30°C for 30 or 60 min on a single occasion at days 15, 17 and 21, or thrice on day 15 of a 35‐day storage period. A 10‐fold increase in bacterial counts in tests versus controls maintained in cold storage was considered indicative of significant bacterial proliferation. Results: Exposure of units to 30°C for up to 60 min had no substantial impact on the growth of bacteria and all mesophiles declined steadily in tests and controls. Only P. putida showed a near significant elevation in count on exposure for 60 min at day 35. Conclusions: Extension of the out of temperature rule for red cells to 60 min will potentially not compromise patient safety, although exposures to ambient temperatures should be minimized. Units returned to storage must not be reissued for at least 6 hours and not be exposed to ambient temperatures on more than three occasions. [ABSTRACT FROM AUTHOR]

There are approximately 8.5 million Jehovah's Witnesses and around 150,000 live in Great Britain and Ireland. Based on their beliefs and core values, Jehovah's Witnesses refuse blood component transfusion (including red cells, plasma and platelets). They regard non-consensual transfusion as a physical violation. Consent to treatment is at the heart of this guideline. Refusal of treatment by an adult with capacity is lawful. The reasons why a patient might refuse transfusion and the implications are examined. The processes and products that are deemed acceptable or unacceptable to Jehovah's Witnesses are described. When a team is faced with a patient who refuses transfusion, a thorough review of the clinical situation is advocated and all options for treatment should be explored. After discussion, a plan should then be made that is acceptable to the patient and appropriate consent obtained. When agreement cannot be reached between the doctor and the patient, referral for a second opinion should be considered. When the patient is a child, the same strategy should be used but on occasion the clinical team may have to obtain legal help. [ABSTRACT FROM AUTHOR]

The aim of present study was to determine the seroprevalence and hematological changes in freerange chicken (Gallus domesticus) naturally infected with Toxoplasma gondii (T. gondii). Blood samples of chicken (n=71), were collected from Cholistan areas of Bahawalpur (Punjab), Pakistan. Serum samples were tested for toxoplasmosis with a commercial latex agglutination kit (Antec Diagnostic products, UK). The overall prevalence was 26.76%. The significant (P<0.05) higher seroprevalence was observed in males (34.28%) than in females (19.44%). For analysis of hematological parameters blood samples were collected. The mean values for hemoglobin (Hb), Packed Cell Volume (PCV), Red Blood Cells Count (RBC), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), White Blood Cells count (WBC), Heterophils (%), Eosinophils (%), Basophils(%), Monocytes(%), and Lymphocytes(%) values of negative chickens were 9.43±0.49 g/dl,, 25.81±1.34%, 1.84±0.13 x106/ìL, 151.7±11.0 fl, 3.85±0.22 pg, 39.34±2.07%, 3.98±0.13 x103/ìL, 45.71±1.26%, 2.08±0.29%, 1.54±0.17%, 2.58±0.29% and 48.10±1.36% and for positive chickens were 9.35±0.89 g/dl, 24.63±2.21%, 1.68±0.17 x106/ìL, 168.9±17.5 fl, 5.92±1.95 pg, 59.3±19.5%, 3.98±0.23 x103/ìL, 45.74±2.76%, 3.05±0.45%, 1.58±0.23%, 0.95±0.19% and 48.74±3.15, respectively. MCH, eosinophils and monocytes showed significant difference. Hb, PCV, RBC, MCV MCHC, heterophils, basophils and lymphocytes values showed non-significant difference. Furthermore, some of the hematological parameters are altered by T. gondii but not all. In literature a little information is present regarding the hematological changes due to T.gondii in chickens of Cholistan, Bahwalpur, Pakistan. This is pilot study one of a kind and need for further studies with larger populations and samples across the country. [ABSTRACT FROM AUTHOR]

The article reports that the United Kingdom has approved a groundbreaking CRISPR therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics, utilizing gene editing to treat sickle cell and beta thalassemia, demonstrating significant success in clinical trials.

Background: In an environment of limited health care resources, it is crucial for health care systems which provide blood transfusion to have accurate and comprehensive information on the costs of transfusion, incorporating not only the costs of blood products, but also their administration. Unfortunately, in many countries accurate costs for administering blood are not available. Our study aimed to generate comprehensive estimates of the costs of administering transfusions for the UK National Health Service.Study Design and Methods: A detailed microcosting study was used to cost two key inputs into transfusion: transfusion laboratory and nursing inputs. For each input, data collection forms were developed to capture staff time, equipment, and consumables associated with each step in the transfusion process. Costing results were combined with costs of blood product wastage to calculate the cost per unit transfused, separately for different blood products. Data were collected in 2014/15 British pounds and converted to US dollars.Results: A total of 438 data collection forms were completed by 74 staff. The cost of administering blood was $71 (£49) per unit for red blood cells, $84 (£58) for platelets, $55 (£38) for fresh-frozen plasma, and $72 (£49) for cryoprecipitate.Conclusions: Blood administration costs add substantially to the costs of the blood products themselves. These are frequently incurred costs; applying estimates to the blood components supplied to UK hospitals in 2015, the annual cost of blood administration, excluding blood products, exceeds $175 (£120) million. These results provide more accurate estimates of the total costs of transfusion than those previously available. [ABSTRACT FROM AUTHOR]

High red blood distribution width (RDW) is associated with decreased red blood cell deformability, and high neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and innate-adaptive immune system imbalance. Both RDW and NLR are predictors of chronic disease risk and mortality. Omega-3 index (O3I) values have previously been shown to be inversely associated with RDW and NLR levels. Our objective was to determine if total plasma long chain omega-3 fatty acids (Omega3%) measured in the UK Biobank cohort were associated with RDW and NLR values. RDW- and NLR- relationships with Omega3% were characterized in 109,191 adults (58.4% female). RDW- and NLR-Omega3% relationships were inversely associated with Omega3% (both p < 0.0001). These cross-sectional associations confirm previous findings that increasing RDW and NLR values are associated with low O3I. The hypothesis that RDW and/or NLR values can be reduced in individuals with less-than optimal long chain omega 3 values need to be tested in randomized controlled intervention trials using EPA and/or DHA., Competing Interests: Declaration of Competing Interest M.I. McBurney has or has held consulting agreements in the past 3 years with the Council for Responsible Nutrition; Church & Dwight; DSM Nutritional Products; McCormick; VitaMe Technologies; and World Health Organization. W.S. Harris holds an interest in OmegaQuant Analytics, a lab that offers omega-3 blood testing; and is a member of the RB Schiff Science and Innovation Advisory Board. N.L. Tintle has no conflicts to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Knowledge of blood utilization can assist clinicians in directing patient blood management (PBM) initiatives and can facilitate demand planning by blood services. We describe a national study of red blood cell (RBC) utilization in England and North Wales in 2014.Study Design and Methods: All hospitals that are supplied with blood components by NHS Blood and Transplant (NHSBT) were asked to provide data on the age and sex of all recipients of transfusions of RBCs, and the clinical indication for every unit transfused, for two separate weeks in 2014. Clinical indication categories were derived from those used in previous studies in an English region. Completeness of data collection was checked against NHSBT issue and wastage data.Results: Data on 46,111 RBC units were collected, representing 73% of all RBCs issued by NHSBT during the weeks surveyed. A total of 67% of RBC units were transfused for a medical indication, with 27 and 6% being transfused for surgical and obstetric/gynecologic indications, respectively. For comparison, figures from a study in the North of England in 2009, on which this national study was based, showed that 64% of RBCs were transfused to medical patients. All but 20 units could be ascribed to a broad clinical heading, for example, "gastrointestinal bleeding."Conclusion: Our findings confirm the previous regional finding that the percentage of RBC units that are transfused to surgical patients in England and North Wales is now much lower than for medical patients and suggest that PBM initiatives should now focus on medical patients. [ABSTRACT FROM AUTHOR]