534 research outputs found

    Perel, Pablo

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    Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial.

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    OBJECTIVE: To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings. METHODS: The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ()perLY.Bothdeterministicandprobabilisticsensitivityanalyseswereperformedtotesttherobustnessoftheresultstomodelassumptions.FINDINGS:AdministeringTXAtobleedingtraumapatientswithinthreehoursofinjurysavedanestimated372,315and755LYsper1,000traumapatientsinTanzania,IndiaandtheUKrespectively.ThecostofgivingTXAto1,000patientswas) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. FINDINGS: Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was 17,483 in Tanzania, 19,550inIndiaand19,550 in India and 30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was 18,025inTanzania,18,025 in Tanzania, 20,670 in India and 48,002intheUK.TheestimatedincrementalcostperLYgainedofadministeringTXAis48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is 48, 66and66 and 64 in Tanzania, India and the UK respectively. CONCLUSION: Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings. TRIAL REGISTRATION: This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.govNCT00375258 and South African Clinical Trial Register DOH-27-0607-1919

    The risk of transfusion-transmitted infections in sub-Saharan Africa.

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    BACKGROUND: Blood transfusions carry the risk of transmitting infections. This risk has been studied in detail in high-income countries but not in sub-Saharan Africa. This study estimates the risks of acquiring human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) from a single unit of blood in sub-Saharan Africa. STUDY DESIGN AND METHODS: A mathematical model was constructed to quantify transfusion risks across 45 sub-Saharan African countries using three components: the risk of a contaminated unit entering the blood supply, the risk that the unit will be given to a susceptible patient, and the risk that receipt of the unit will lead to infection in the recipient. Variables included prevalence of infection in donors, extent of blood testing, test sensitivity, and susceptibility of recipients. Data from the World Health Organization (WHO) African Region and a systematic review of the literature were used to parameterize the model. Uncertainty in the risk estimates was quantified using probabilistic sensitivity analysis. RESULTS: The median overall risks of becoming infected with HIV, HBV, and HCV from a blood transfusion in sub-Saharan Africa were 1, 4.3, and 2.5 infections per 1000 units, respectively. If annual transfusion requirements projected by the WHO were met, transfusions alone would be responsible for 28,595 HBV infections, 16,625 HCV infections, and 6650 HIV infections every year. Sensitivity analysis suggests that the true risks may be even higher. CONCLUSIONS: This study is the first to systematically quantify the risks of transfusion-transmitted infections across sub-Saharan Africa. Although the results are limited by the quality and quantity of available data, these may be the most reliable estimates at this time

    CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury - a nested, randomised, placebo-controlled trial

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    Background: Tranexamic acid (TXA) has been shown to reduce blood loss in surgical patients and the risk of death in patients with traumatic bleeding, with no apparent increase in vascular occlusive events. These findings raise the possibility that it might also be effective in traumatic brain injury (TBI). Objective: The Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Intracranial Bleeding Study (CRASH-2 IBS) was conducted to quantify the effect of an early short course of TXA on intracranial haemorrhage and new focal cerebral ischaemic lesions in patients with TBI. Design: CRASH-2 IBS was a prospective randomised controlled trial nested within the CRASH-2 trial. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight. We used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical. The pack number was recorded on the entry form, which was sent to the international trial co-ordinating centre in London, UK. Once the treatment pack number was recorded, the patient was included in the trial whether or not the treatment pack was opened or the allocated treatment started. All site investigators and trial co-ordinating centre staff were masked to treatment allocation. Setting: Ten hospitals: (India) Aditya Neuroscience Centre, Sanjivani Hospital, CARE Hospital, Christian Medical College, Medical Trust Hospital, Jeevan Jyoti Hospital and (Colombia) Hospital Universitario San Vicente de Paul, Hospital Pablo Tobon Uribe, Hospital Universitario San Jose de Popayan and Fundacion Valle del Lili. Participants: The trial was conducted in a subset of 270 CRASH-2 trial participants. Patients eligible for inclusion in the CRASH-2 IBS fulfilled the inclusion criteria for the CRASH-2 trial, and also had TBI [Glasgow Coma Scale score of <= 14 and a brain computerised tomography (CT) scan compatible with TBI]. Pregnant women and patients for whom a second brain CT scan was not possible were excluded. Interventions: Participants were randomly allocated to receive either a loading dose of 1g of TXA infused over 10 minutes followed by an intravenous infusion of 1g over 8 hours or matching placebo. Main outcome measure: The primary outcome was the increase in size of intracranial haemorrhage growth between a CT scan at hospital admission and a second scan 24-48 hours later. Results: One hundred and thirty-three patients were allocated to TXA and 137 to placebo, of whom information on the primary (imaging) outcome was available for 123 (92%) and 126 (92%) respectively. The analysis suggested that TXA was likely to be associated with a reduction in haemorrhage growth [adjusted difference -3.8 ml, 95% credibility interval (CrI) -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CrI 0.20 to 1.46] and fewer deaths (adjusted OR 0.49, 95% CrI 0.22 to 1.06). Conclusions: This was the first randomised controlled study to evaluate the effect of TXA in TBI patients and it found that neither moderate benefits nor moderate harmful effects can be excluded. However, although uncertainty remains, our analyses suggest that TXA administration might improve outcome in TBI patients and provide grounds for evaluating this hypothesis in future research

    Giving tranexamic acid to reduce surgical bleeding in sub-Saharan Africa: an economic evaluation.

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    BACKGROUND: The identification of safe and effective alternatives to blood transfusion is a public health priority. In sub-Saharan Africa, blood shortage is a cause of mortality and morbidity. Blood transfusion can also transmit viral infections. Giving tranexamic acid (TXA) to bleeding surgical patients has been shown to reduce both the number of blood transfusions and the volume of blood transfused. The objective of this study is to investigate whether routinely administering TXA to bleeding elective surgical patients is cost effective by both averting deaths occurring from the shortage of blood, and by preventing infections from blood transfusions. METHODS: A decision tree was constructed to evaluate the cost-effectiveness of providing TXA compared with no TXA in patients with surgical bleeding in four African countries with different human immunodeficiency virus (HIV) prevalence and blood donation rates (Kenya, South Africa, Tanzania and Botswana). The principal outcome measures were cost per life saved and cost per infection averted (HIV, Hepatitis B, Hepatitis C) averted in 2007 International dollars ().TheprobabilityofreceivingabloodtransfusionwithandwithoutTXAandtheriskofbloodborneviralinfectionwereestimated.Theimpactofuncertaintyinmodelparameterswasexploredusingonewaydeterministicsensitivityanalyses.ProbabilisticsensitivityanalysiswasperformedusingMonteCarlosimulation.RESULTS:Theincrementalcostperlifesavedis). The probability of receiving a blood transfusion with and without TXA and the risk of blood borne viral infection were estimated. The impact of uncertainty in model parameters was explored using one-way deterministic sensitivity analyses. Probabilistic sensitivity analysis was performed using Monte Carlo simulation. RESULTS: The incremental cost per life saved is 87 for Kenya and $93 for Tanzania. In Botswana and South Africa, TXA administration is not life saving but is highly cost saving since fewer units of blood are transfused. Further, in Botswana the administration of TXA averts one case of HIV and four cases of Hepatitis B (HBV) per 1,000 surgical patients. In South Africa, one case of HBV is averted per 1,000 surgical patients. Probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: An economic argument can be made for giving TXA to bleeding elective surgical patients. In countries where there is a blood shortage, TXA would be a cost effective way to reduce mortality. In countries where there is no blood shortage, TXA would reduce healthcare costs and avert blood borne infections

    Web tool for prognosis of patients with head injury (CRASH trial) (reproduced from Perel et al [7] with permission).

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    <p>Web tool for prognosis of patients with head injury (CRASH trial) (reproduced from Perel et al <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001381#pmed.1001381-Perel1" target="_blank">[7]</a> with permission).</p

    Selenium-based self-assembled monolayers: the nature of adsorbate-surface interactions

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    In recent years, self-assembled monolayers (SAMs) of selenols have been characterized using electrochemistry, scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), thermal desorption spectroscopy, and other experimental approaches. Interest in the relative stability and conductance of the Se - Au interface as compared to S-Au prompted different investigations which have led to contradictory results. From the theoretical side, on the other hand, the study of selenol-based SAMs has concentrated on the investigation of the electron transport across the Se-Au contact, whereas the structural and the thermodynamic features of the monolayer were essentially neglected. In this Article, we examine the binding of selenols to the Au(111) surface using density functional theory with plane wave basis sets and periodic boundary conditions. Our calculations provide insights on the geometry of the headgroup, the stability of the monolayer, and the electronic properties of the bond. In particular, we propose that the presence of a conjugated backbone might be a major factor determining the relative conductance at the monolayer, by differentially enhancing the intramolecular electron transport in selenols with respect to thiols. This surmise, if confirmed, would explain the conflictive data coming from the available experimentsFil: de la Llave, Ezequiel Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Scherlis Perel, Damian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

    Role of confinement and surface affinity on filling mechanisms and sorption hysteresis of water in nanopores

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    The liquid-vapor transition in cylindrical pores is studied as a function of pore size and hydrophilicity through molecular dynamics simulations with the mW coarse-grained model of water. We identify two distinct filling mechanisms, depending on whether the water-pore interaction is smaller or larger than the water-water interaction. In the former case (that we term hydrophobic pore), the formation of the condensed phase proceeds gradually with filling, through the nucleation of a water cluster which grows toward the center of the cavity. In hydrophilic pores, instead, the condensed phase develops in conditions of supersaturation, which in principle become more extreme with increasing pore radius and surface affinity. For highly hydrophilic interfaces (those with adsorption energy for water above 10 kcal/mol), the equilibrium and dynamical properties of water in confinement turn out to be practically independent of water affinity.Fil: de la Llave, Ezequiel Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Molinero, Valeria. University of Utah; Estados UnidosFil: Scherlis Perel, Damian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentin

    Blood-free risk scores and neuropathy assessment tools to detect undiagnosed type 2 diabetes in Peru.

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    The prevalence of type 2 diabetes mellitus is rising, especially in low- and middle-income countries, where the situation is worsened because around half of cases are unaware of the disease. Universal screening utilizing blood markers can be challenging in resource-constrained settings. The identification of these individuals can be potentially addressed using risk scores and neuropathy assessment tools. This study aimed to assess the diagnostic accuracy of the FINDRISC, a blood-free risk score, three neuropathy assessment tools (EZSCAN, pupillometer, and biothesiometer), alone and in combination. A population-based study was conducted enrolling a sex-stratified random sample of participants from Tumbes, a semiurban area in the north of Peru. Undiagnosed T2DM was the outcome, defined using WHO OGTT thresholds. Diagnostic accuracy of the FINDRISC and neuropathy tools was evaluated using the area under the ROC curve (aROC) and respective 95% confidence intervals (95%CI). Data from 1609 participants were analysed, mean age 48.2 (SD: 10.6) years, 810 (50.3%) females. A total of 176 (10.9%) individuals had T2DM, and only 71 (4.7%) had undiagnosed T2DM. The diagnostic accuracy of the FINDRISC was aROC = 0.69 (95% CI: 0.64–0.74), with a sensitivity of 69% and specificity of 67%. Among devices, the EZSCAN (aROC = 0.59; 95%CI: 0.53–0.66; sensitivity of 59% and specificity of 54%) and biothesiometer in the third metatarsal head (aROC = 0.60; 95%CI: 0.53–0.67; sensitivity of 31% and specificity of 85%) performed best. A combination of the FINDRISC and the biothesiometer had the best diagnostic accuracy, with a similar aROC of FINDRISC alone (AROC = 0.69; 95%CI: 0.68–0.78), with a sensitivity of 79% and a specificity of 59%. Our results confirm that combination of the FINDRISC and biothesiometer can improve diagnostic accuracy of the FINDRISC and biothesiometer alone, increasing sensitivity without affecting specificity or the area under the ROC curve
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