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Article ; Online: Estimating the risks of prehospital transfusion of D-positive whole blood to trauma patients who are bleeding in England.

Cardigan, Rebecca / Latham, Tom / Weaver, Anne / Yazer, Mark / Green, Laura

2022 Volume 117, Issue 5, Page(s) 701–707

Abstract: Background and objectives: D-negative red cells are transfused to D-negative females of childbearing potential (CBP) to prevent haemolytic disease of the foetus and newborn (HDFN). Transfusion of low-titre group O whole blood (LTOWB) prehospital is ... ...

Abstract	Background and objectives: D-negative red cells are transfused to D-negative females of childbearing potential (CBP) to prevent haemolytic disease of the foetus and newborn (HDFN). Transfusion of low-titre group O whole blood (LTOWB) prehospital is gaining interest, to potentially improve clinical outcomes and for logistical benefits compared to standard of care. Enhanced donor selection requirements and reduced shelf-life of LTOWB compared to red cells makes the provision of this product challenging. Materials and methods: A universal policy change to the use of D-positive LTOWB across England was modelled in terms of risk of three specific harms occurring: risk of haemolytic transfusion reaction now or in the future, and the risk of HDFN in future pregnancies for all recipients or D-negative females of CBP. Results: The risk of any of the three harms occurring for all recipients was 1:14 × 10 Conclusion: These data suggest that the risk of transfusing RhD-positive blood is low in the prehospital setting and must be balanced against its potential benefits.
MeSH term(s)	ABO Blood-Group System ; Blood Transfusion ; Emergency Medical Services ; England ; Erythroblastosis, Fetal ; Female ; Hemorrhage/etiology ; Hemorrhage/therapy ; Humans ; Infant, Newborn ; Pregnancy ; Resuscitation ; Transfusion Reaction/prevention & control
Chemical Substances	ABO Blood-Group System
Language	English
Publishing date	2022-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	80313-3
ISSN	1423-0410 ; 0042-9007
ISSN (online)	1423-0410
ISSN	0042-9007
DOI	10.1111/vox.13249
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Article ; Online: A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects.

Sadaf, Alina / Dong, Min / Pfeiffer, Amanda / Latham, Teresa / Kalfa, Theodosia / Vinks, Alexander A / Ware, Russell E / Quinn, Charles T

Clinical pharmacokinetics

2024 Volume 63, Issue 3, Page(s) 357–365

Abstract: Background and objective: L-Glutamine is a treatment for children and adults with sickle cell disease. A comprehensive evaluation of the pharmacokinetics of L-glutamine in sickle cell disease has not been conducted. We aimed to assess the effects of ... ...

Abstract	Background and objective: L-Glutamine is a treatment for children and adults with sickle cell disease. A comprehensive evaluation of the pharmacokinetics of L-glutamine in sickle cell disease has not been conducted. We aimed to assess the effects of long-term dosing, multiple dose levels, and food intake on L-glutamine exposure in patients with sickle cell disease compared to normal participants. Methods: We conducted an open-label dose-ascending trial of L-glutamine in pediatric and adult participants with sickle cell disease (N = 8) and adult healthy volunteers (N = 4), providing a total of 400 plasma L-glutamine concentrations. Each participant received three ascending oral doses (0.1 and 0.3 g/kg twice daily and 0.6 g/kg once daily) over 3 weeks. Plasma L-glutamine concentrations were quantified using ion exchange chromatography. Both a non-compartmental pharmacokinetic analysis and a population pharmacokinetic analysis were performed. Results: L-glutamine had rapid absorption and elimination, and there was no significant change in the baseline (pre-dose) L-glutamine concentration throughout the study, indicating no drug accumulation. Pharmacokinetics was best described by a one-compartment model with first-order kinetics. The dose-normalized peak concentration decreased with dose escalation, indicating the capacity-limited non-linear pharmacokinetics of oral L-glutamine. A covariate analysis showed that baseline L-glutamine concentrations correlated negatively with glutamine clearance, whereas dose positively correlated with volume of distribution. Food intake did not significantly affect glutamine clearance, indicating that L-glutamine can be taken with or without food. Conclusions: We report the first pharmacokinetic study of multiple-dose, long-term oral L-glutamine therapy and the first population pharmacokinetic analysis of L-glutamine for sickle cell disease. These findings may permit optimized dosing of L-glutamine for patients with sickle cell disease to maximize treatment benefits. Clinical trial registration: This trial is registered at ClinicalTrials.gov (NCT04684381).
MeSH term(s)	Adult ; Child ; Humans ; Anemia, Sickle Cell/drug therapy ; Area Under Curve ; Glutamine/pharmacokinetics
Chemical Substances	Glutamine (0RH81L854J)
Language	English
Publishing date	2024-02-24
Publishing country	Switzerland
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-024-01349-4
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Article ; Online: Reducing transfusion utilization for children with sickle cell anemia in sub-Saharan Africa with hydroxyurea: Analysis from the phase I/II REACH trial.

Power-Hays, Alexandra / Tomlinson, George A / Tshilolo, Leon / Santos, Brígida / Williams, Thomas N / Olupot-Olupot, Peter / Smart, Luke R / Aygun, Banu / Lane, Adam / Stuber, Susan E / Latham, Teresa / Ware, Russell E

American journal of hematology

2024 Volume 99, Issue 4, Page(s) 625–632

Abstract: Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion ... ...

Abstract	Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two-month pre-treatment screening period followed by 6 months of fixed-dose hydroxyurea (15-20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person-years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person-years was 43.2 before hydroxyurea, 21.7 on fixed-dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre-treatment (IRR 0.25, 95% confidence interval [CI] 0.18-0.35, p < .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39-0.63, p < .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub-Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply.
MeSH term(s)	Child ; Humans ; Hydroxyurea/therapeutic use ; Antisickling Agents/therapeutic use ; Anemia, Sickle Cell/complications ; Anemia, Sickle Cell/drug therapy ; Uganda ; Kenya
Chemical Substances	Hydroxyurea (X6Q56QN5QC) ; Antisickling Agents
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Clinical Trial, Phase II ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27244
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Article: The relationship between irrigation-induced electrical loads and antecedent weather conditions in Tasmania, Australia

Latham, Tom / Christopher J. White / Tomas A. Remenyi

Irrigation science. 2018 May, v. 36, no. 3

2018

Abstract: Over the past decade in Australia, there has been a general trend towards the introduction of electrical motors to operate irrigation pumps. While electrical motors provide many advantages over the alternatives, electrical loads can aggregate in some ... ...

Abstract	Over the past decade in Australia, there has been a general trend towards the introduction of electrical motors to operate irrigation pumps. While electrical motors provide many advantages over the alternatives, electrical loads can aggregate in some areas to become large peaks, which challenge the existing electrical distribution networks. This is especially true during extreme hot or dry periods, when irrigators collectively demand significant electrical resources at the same time. While there is an inherent link between weather conditions and the amount of electricity used for irrigation, this relationship is poorly understood. Previous studies have either focused on localised data related to concurrent temperature, rainfall and soil moisture, or they have annualised summaries over large areas. In this study, we compare intensive irrigation periods with the drought factor at a case study irrigation scheme in Tasmania, Australia, finding a strong relationship between electrical load and periods when the drought factor is > 6. This relatively simple relationship may be useful for managers of electricity supply and distribution, managers of water resources, and irrigators, as it may be used to minimise the risk of exceeding the capacity of the electricity network, improve water availability and optimise irrigation scheduling.
Keywords	case studies ; drought ; electric energy consumption ; electric motors ; electricity ; irrigation rates ; irrigation scheduling ; managers ; pumps ; rain ; risk ; soil water ; temperature ; water resources ; Tasmania
Language	English
Dates of publication	2018-05
Size	p. 167-178.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	133938-2
ISSN	1432-1319 ; 0342-7188
ISSN (online)	1432-1319
ISSN	0342-7188
DOI	10.1007/s00271-018-0573-0
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Modelling the outcomes of different red blood cell transfusion strategies for the treatment of traumatic haemorrhage in the prehospital setting in the United Kingdom.

Roberts, Barnaby / Green, Laura / Ahmed, Venus / Latham, Tom / O'Boyle, Peter / Yazer, Mark H / Cardigan, Rebecca

Vox sanguinis

2022 Volume 117, Issue 11, Page(s) 1287–1295

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Humans ; Female ; Middle Aged ; Erythrocyte Transfusion/adverse effects ; United Kingdom ; Blood Transfusion/methods ; Erythrocytes ; Hemorrhage/therapy
Language	English
Publishing date	2022-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	80313-3
ISSN	1423-0410 ; 0042-9007
ISSN (online)	1423-0410
ISSN	0042-9007
DOI	10.1111/vox.13359
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Article ; Online: Sustained and Boosted Antibody Responses in Breast Milk After Maternal SARS-CoV-2 Vaccination.

Ware, Julie / McElhinney, Kathryn / Latham, Teresa / Lane, Adam / Dienger-Stambaugh, Krista / Hildeman, David / Spearman, Paul / Ware, Russell E

Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine

2022 Volume 18, Issue 8, Page(s) 612–620

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adolescent ; Adult ; Female ; Humans ; Antibodies, Viral ; Antibody Formation ; Breast Feeding ; Cohort Studies ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Lactation ; Milk, Human ; Prospective Studies ; SARS-CoV-2 ; Vaccination ; Infant
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin A, Secretory ; Immunoglobulin G
Language	English
Publishing date	2022-10-19
Publishing country	United States
Document type	Clinical Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2234680-6
ISSN	1556-8342 ; 1556-8253
ISSN (online)	1556-8342
ISSN	1556-8253
DOI	10.1089/bfm.2023.0106
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Article ; Online: Haemolytic transfusion reaction in a Gy(a-) patient with anti-Gy

Dwight, M / Bullock, T / Dowling, K / Ricks, J / Jenner, M / Boyce, S / Narayanan, S / Latham, T

Transfusion medicine (Oxford, England)

2019 Volume 29, Issue 3, Page(s) 211–213

MeSH term(s)	Aged ; Anemia/blood ; Anemia/immunology ; Anemia/therapy ; Blood Group Antigens/blood ; Blood Group Antigens/immunology ; Blood Group Incompatibility/blood ; Blood Group Incompatibility/immunology ; Erythrocyte Transfusion ; Female ; Humans ; Transfusion Reaction/blood ; Transfusion Reaction/immunology
Chemical Substances	Blood Group Antigens
Language	English
Publishing date	2019-02-27
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	1067989-3
ISSN	1365-3148 ; 0958-7578
ISSN (online)	1365-3148
ISSN	0958-7578
DOI	10.1111/tme.12583
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Article ; Online: Spectroscopic identification of Ca-bearing uranyl silicates formed in C-S-H systems.

Yorkshire, Antonia S / Stennett, Martin C / Walkley, Brant / Provis, John L / Townsend, Luke T / Haigh, Latham T / Hyatt, Neil C / Mottram, Lucy M / Corkhill, Claire L

Scientific reports

2023 Volume 13, Issue 1, Page(s) 3374

Abstract: Portland cement-based grouts used for radioactive waste immobilisation contain a Ca- and Si-rich binder phase, known as calcium-silicate-hydrate (C-S-H). Depending on the blend of cement used, the Ca/Si ratio can vary considerably. A range of C-S-H ... ...

Abstract	Portland cement-based grouts used for radioactive waste immobilisation contain a Ca- and Si-rich binder phase, known as calcium-silicate-hydrate (C-S-H). Depending on the blend of cement used, the Ca/Si ratio can vary considerably. A range of C-S-H minerals with Ca/Si ratios from 0.6 to 1.6 were synthesised and contacted with aqueous U(VI) at 0.5 mM and 10 mM concentrations. Solid-state
Language	English
Publishing date	2023-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-30024-0
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Article ; Online: Large red cell-derived membrane particles are major contributors to hypercoagulability in sickle cell disease.

Smith, Rachel A / Mankelow, Tosti J / Drizou, Despoina / Bullock, Thomas / Latham, Tom / Trompeter, Sara / Blair, Allison / Anstee, David J

Scientific reports

2021 Volume 11, Issue 1, Page(s) 11035

Abstract: Sickle cell disease (SCD) is one of the most common inherited single gene disorders. Polymerisation of sickle hemoglobin results in erythrocytes that are inflexible and adherent, leading to coagulation, vascular and cellular activation and resultant ... ...

Abstract	Sickle cell disease (SCD) is one of the most common inherited single gene disorders. Polymerisation of sickle hemoglobin results in erythrocytes that are inflexible and adherent, leading to coagulation, vascular and cellular activation and resultant blood vessel blockage. Previous studies have observed elevated numbers of red cell-derived particles (RCDP), also denoted extracellular vesicles, in SCD plasma. Here, imaging flow cytometry was used to quantify all RCDP in SCD plasma. A more heterogenous population of RCDP was observed than previously reported. Significantly, large right side-out red cell macrovesicles (MaV), 7 µm in diameter, were identified. Most RCDP were right side-out but a minor population of inside-out vesicles was also present. Electron micrographs confirmed the heterogenous nature of the RCDP detected. All MaV are decorated with prothrombotic phosphatidylserine (PS) and their removal from plasma lengthened clotting times by more than three-fold. Removal of all right side-out RCDP from SCD patient plasma samples resulted in a seven-fold increase in clotting time. These results indicate that MaV comprise a large area of prothrombotic membrane and are thus major contributors to hypercoagulation in SCD. Consequently, controlled removal of MaV and PS exposed RCDP from plasma could provide a novel therapy for managing this disease.
MeSH term(s)	Anemia, Sickle Cell ; Blood Coagulation ; Erythrocyte Membrane ; Phosphatidylserines/metabolism ; Thrombin/metabolism ; Thrombophilia
Chemical Substances	Phosphatidylserines ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2021-05-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-90477-z
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Article ; Online: Use of cffDNA to avoid administration of anti-D to pregnant women when the fetus is RhD-negative: implementation in the NHS.

Soothill, P W / Finning, K / Latham, T / Wreford-Bush, T / Ford, J / Daniels, G

BJOG : an international journal of obstetrics and gynaecology

2015 Volume 122, Issue 12, Page(s) 1682–1686

Abstract: Objective: To determine whether a policy of offering cffDNA testing to all RhD-negative women at about 16 weeks' gestation to avoid anti-D administration when the fetus is RhD-negative could be implemented successfully in the NHS without additional ... ...

Abstract	Objective: To determine whether a policy of offering cffDNA testing to all RhD-negative women at about 16 weeks' gestation to avoid anti-D administration when the fetus is RhD-negative could be implemented successfully in the NHS without additional funding. Design: Prospectively planned observational service implementation pilot and notes audit. Setting: Three maternity services in the South West of England. Population: All RhD-negative women in a 6-month period. Methods: Prospective, intervention, cross-sectional observational study, using pre-intervention data as controls. Main outcome measures: Proportion of suitable women who offered and accepted the test. Accuracy of the cffDNA result as assessed by cord blood group result. Fall in anti-D doses administered. Results: 529 samples were received; three were unsuitable. The results were reported as RhD-positive (n = 278), RhD-negative (n = 185) or inconclusive, treat as positive (n = 63). Cord blood results were available in 502 (95%) and the only incorrect result was one case of a false positive (cffDNA reported as positive, cord blood negative - and so given anti-D unnecessarily). The notes audit showed that women who declined this service were correctly managed and that anti-D was not given when the fetus was predicted to be RhD-negative. The total use of anti-D doses fell by about 29% which equated to about 35% of RhD-negative women not receiving anti-D in their pregnancy unnecessarily. Conclusions: We recommend this service is extended to all UK NHS services.
MeSH term(s)	Administration, Intravenous ; Adult ; Anemia, Hemolytic/prevention & control ; Cross-Sectional Studies ; Female ; Health Policy ; Humans ; Immunologic Factors/administration & dosage ; Isoantibodies/administration & dosage ; Practice Guidelines as Topic ; Pregnancy ; Prospective Studies ; Rh Isoimmunization/blood ; Rh-Hr Blood-Group System/genetics ; State Medicine
Chemical Substances	Immunologic Factors ; Isoantibodies ; Rh-Hr Blood-Group System
Language	English
Publishing date	2015-11
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2000931-8
ISSN	1471-0528 ; 0306-5456 ; 1470-0328
ISSN (online)	1471-0528
ISSN	0306-5456 ; 1470-0328
DOI	10.1111/1471-0528.13055
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