Options for possible changes to the blood donation service: health economics modelling

BackgroundEvidence is required on the cost-effectiveness of alternative changes to the blood collection service.Objectives(1) To estimate the cost-effectiveness of alternative minimum interdonation intervals between whole-blood donations. (2) To investigate donors’ frequency of whole-blood donation according to alternative changes to the blood collection service. (3) To estimate the cost-effectiveness of alternative strategies for maintaining the supply of whole blood.MethodsWe undertook a within-trial cost-effectiveness analysis (CEA) of the INTERVAL trial, stated preference (SP) surveys to elicit donor preferences and a CEA of different strategies for blood collection. The strategies considered were reduced minimum intervals between whole-blood donations, introduction of a donor health report and changes to appointment availability and opening times at blood collection venues. The within-trial CEA included 44,863 donors, with men randomly assigned to 12- versus 10- versus 8-week interdonation intervals, and women to 16- versus 14- versus 12-week interdonation intervals. We undertook a SP survey of non-INTERVAL donors (100,000 invitees). We asked donors to state the frequency with which they would be willing to donate blood, according to the service attribute and level. The CEA compared changes to the blood service with current practice by combining the survey estimates with information from the NHS Blood and Transpant database (PULSE) and cost data. The target population was existing whole-blood donors in England, of whom approximately 85% currently donate whole blood at mobile (temporary) blood collection venues, with the remainder donating at static (permanent) blood collection centres. We reported the effects of the alternative strategies on the number of whole-blood donations, costs and cost-effectiveness.ResultsThe reduced donation interval strategies had higher deferral rates caused by low haemoglobin (Hb), but increased frequency of successful donation. For men in the 8- versus 12-week arm of the INTERVAL trial [Di Angelantonio E, Thompson SG, Kaptoge S, Moore C, Walker M, Armitage J,et al.Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors.Lancet2017;390:2360–71], the Hb-related deferral rate was 5.7% per session versus 2.6% per session, but the average number of donations over 2 years increased by 1.71 (95% confidence interval 1.60 to 1.80). A total of 25,187 (25%) donors responded to the SP survey. For static donor centres, extending appointment availability to weekday evenings or weekends, or reduced intervals between blood donations, increased stated donation frequency by, on average, 0.5 donations per year. The CEA found that reducing the minimum interval, extending opening times to weekday evenings and extending opening times to weekends in all static donor centres would provide additional whole blood at a cost per additional unit of £10, £23 and £29, respectively, with similar results for donors with high-demand blood types.LimitationsThe study did not consider the long-term rates at which donors will leave the donation register, for example following higher rates of Hb-related deferral.ConclusionsExtending opening hours for blood donation to weekday evenings or weekends for all static donor centres are cost-effective ways of increasing the supply of high-demand blood types.Future workTo monitor the effects of new strategies on long-term donation frequency.FundingThe National Institute for Health Research Health Services and Delivery Research programme.</jats:sec

The Synthesis Analysis and Application of Tritiated Compounds.

As the title suggests this thesis is concerned with the synthesis of tritiated compounds and their subsequent use in addressing various problems in physical-organic chemistry. Hence in chapter one the stereoselectivity shown by the base-catalysed ionisation of the C10 axial and equatorial hydrogens of a tetracyclic drug,Mianserin,for a wide range of highly basic DMSO-H[2]O-OH solutions, was investigated by using tritium as a hydrogen-tracer to determine the kinetics of this reaction. The stereoselectivity is discussed in terms of the stereochemical relationship between the axial C10 hydrogen and the lone-pair of electrons of the N5 atom. The effect of high-basicity on transition-state geometry and the stereoselectivity is also discussed. Similar tracer techniques were employed in chapter two to study the conformational effects of small to medium sized alicyclic rings on the base-catalysed ionisation of a series of methylcycloalkylketones under aqueous base conditions. The nature of the reaction intermediate is discussed in terms of the observed kinetic behaviour. Chapter three represents a complete departure from the kinetic theme of the previous chapters in that it is concerned with the isolation and tritiation of chrysophanolanthrone a natural product suspected to possess valuable pharmaceutical properties

The Synthesis Analysis and Application of Tritiated Compounds.

As the title suggests this thesis is concerned with the synthesis of tritiated compounds and their subsequent use in addressing various problems in physical-organic chemistry. Hence in chapter one the stereoselectivity shown by the base-catalysed ionisation of the C10 axial and equatorial hydrogens of a tetracyclic drug,Mianserin,for a wide range of highly basic DMSO-H[2]O-OH solutions, was investigated by using tritium as a hydrogen-tracer to determine the kinetics of this reaction. The stereoselectivity is discussed in terms of the stereochemical relationship between the axial C10 hydrogen and the lone-pair of electrons of the N5 atom. The effect of high-basicity on transition-state geometry and the stereoselectivity is also discussed. Similar tracer techniques were employed in chapter two to study the conformational effects of small to medium sized alicyclic rings on the base-catalysed ionisation of a series of methylcycloalkylketones under aqueous base conditions. The nature of the reaction intermediate is discussed in terms of the observed kinetic behaviour. Chapter three represents a complete departure from the kinetic theme of the previous chapters in that it is concerned with the isolation and tritiation of chrysophanolanthrone a natural product suspected to possess valuable pharmaceutical properties

High-Temperature Illumination-Induced Metastability in Undoped Semi-Insulating GaN Grown by Metalorganic Vapor Phase Epitaxy

High-temperature (high-T) illumination-induced metastability in undoped semi-insulating (SI) GaN grown on a-plane sapphire by metalorganic vapor phase epitaxy has been studied using thermally stimulated current (TSC) spectroscopy, photocurrent (PC) and persistent photocurrent (PPC) measurements. The metastability can be induced by illumination at 390\u3eT\u3e300K (using either white or 360-nm light), followed by cooling the sample to 83 K in the dark. Without high-T illumination, the SI-GaN sample stays in its normal state (“off” state), and shows at least six TSC traps, B (0.63 eV), Bx (0.51 eV), C1 (0.44 eV), C (0.32 eV), D (0.23 eV), and E (0.16 eV). However, after high-T illumination the sample goes into a metastable state (“on” state), and shows a strong increase in both the PC at 83 K and the TSC of traps D, C, and E, accompanied by significant change in their relative densities. PPC at 83 K in the “on” state lasts much longer than that in the “off” state. Association of possible point defects and dislocations with the metastability behavior will be discussed

High-Temperature Illumination-Induced Metastability in Undoped Semi-Insulating GaN Grown by Metalorganic Vapor Phase Epitaxy

High-temperature (high-T) illumination-induced metastability in undoped semi-insulating (SI) GaN grown on a-plane sapphire by metalorganic vapor phase epitaxy has been studied using thermally stimulated current (TSC) spectroscopy, photocurrent (PC) and persistent photocurrent (PPC) measurements. The metastability can be induced by illumination at 390\u3eT\u3e300K (using either white or 360-nm light), followed by cooling the sample to 83 K in the dark. Without high-T illumination, the SI-GaN sample stays in its normal state (“off” state), and shows at least six TSC traps, B (0.63 eV), Bx (0.51 eV), C1 (0.44 eV), C (0.32 eV), D (0.23 eV), and E (0.16 eV). However, after high-T illumination the sample goes into a metastable state (“on” state), and shows a strong increase in both the PC at 83 K and the TSC of traps D, C, and E, accompanied by significant change in their relative densities. PPC at 83 K in the “on” state lasts much longer than that in the “off” state. Association of possible point defects and dislocations with the metastability behavior will be discussed

Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells

BACKGROUND: Cigarette smoke induces a pro-inflammatory response in airway epithelial cells but it is not clear which of the various chemicals contained within cigarette smoke (CS) should be regarded as predominantly responsible for these effects. We hypothesised that acrolein, nicotine and acetylaldehyde, important chemicals contained within volatile cigarette smoke in terms of inducing inflammation and causing addiction, have immunomodulatory effects in primary nasal epithelial cell cultures (PNECs). METHODS: PNECs from 19 healthy subjects were grown in submerged cultures and were incubated with acrolein, nicotine or acetylaldehyde prior to stimulation with Pseudomonas aeruginosa lipopolysaccharide (PA LPS). Experiments were repeated using cigarette smoke extract (CSE) for comparison. IL-8 was measured by ELISA, activation of NF-κB by ELISA and Western blotting, and caspase-3 activity by Western blotting. Apoptosis was evaluated using Annexin-V staining and the terminal transferase-mediated dUTP nick end-labeling (TUNEL) method. RESULTS: CSE was pro-inflammatory after a 24 h exposure and 42% of cells were apoptotic or necrotic after this exposure time. Acrolein was pro-inflammatory for the PNEC cultures (30 μM exposure for 4 h inducing a 2.0 fold increase in IL-8 release) and also increased IL-8 release after stimulation with PA LPS. In contrast, nicotine had anti-inflammatory properties (0.6 fold IL-8 release after 50 μM exposure to nicotine for 24 h), and acetylaldehyde was without effect. Acrolein and nicotine had cellular stimulatory and anti-inflammatory effects respectively, as determined by NF-κB activation. Both chemicals increased levels of cleaved caspase 3 and induced cell death. CONCLUSIONS: Acrolein is pro-inflammatory and nicotine anti-inflammatory in PNEC cultures. CSE induces cell death predominantly by apoptotic mechanisms