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Hemorrhage accounts for 40-50% of deaths in severe trauma patients. IV administration of TXA within three hours of injury reduces mortality. In this study we show IM TXA is equally efficacious as IV in treating hyperfibrinolysis in an in vivo swine model.

ABSTRACT Derivative longevity risk solutions, such as bespoke and indexed longevity swaps, allow pension schemes, and annuity providers to swap out longevity risk, but introduce counterparty credit risk, which can [...]

Rapid alkylations of thiols are performed in a packed-bed flow reactor where potassium carbonate acts as a heterogeneous base in anhydrous solvents at ambient temperature. The reaction also has a high efficiency as the removal of the solvent is the only work up required to isolate the product. The products can be used in a subsequent oxidation which was performed sequentially in semibatch mode. The alkylations of phenol and benzyl amine have been demonstrated on an array of bases, but higher temperatures and longer reaction times are required than with thiols.

BACKGROUND: Cyanide is a common toxin in structural fires and a salt that is ingested for suicide. However, most studies have focused on the effects of inhaled cyanide. The objective of this study was to describe the incidence of cyanide ingestions, symptoms, cardiac arrest and antidotal therapy used as reported to all US poison centres over 7 years. METHODS: A retrospective review of cases over 7 years as reported to 61 poison centres in the USA was performed. Sole ingestions of cyanide were identified. A trained reviewer used a standard data collection sheet within a secured electronic database. Age, intent, clinical effects, treatments, antidotes and outcomes were recorded. One investigator audited a random sample of charts. RESULTS: Out of 1741 exposures, 435 ingestions were identified. Most were male (68%) and the mean age was 34 years (range 1 month–83 years). 45% of cases were intentional, most commonly as a suicide attempt. 8.3% of cases died and 9% (38/435) of patients had cardiac arrest or hypotension. 13% of all cases and 26% of cases arriving at a healthcare facility received an antidote. In 35% of cases of cardiac arrest or hypotension, and in 74% of intentional ingestions, antidotes were not given. CONCLUSIONS: Suicide attempt was the most common reason for cyanide ingestion. Most of these patients died. Cardiac arrest or hypotension was common, but antidote use was not, particularly in critically ill patients. Research is needed to improve outcomes of cyanide-induced hypotension and cardiac arrest and to reduce barriers to antidote use.

Many biochemical and molecular details are available for soybean seed proteinase inhibitors, but little is known about the quantitative regulation of structural genes. In order to fill this gap, a complete set of diallel crosses was made between inbred lines characterised by the same inhibitor array coupled with a different inhibitor content in the raw flour. The Hayman analysis revealed the presence of different regulatory elements in the parental lines, giving rise to both additive and dominance variation. Dominant alleles were found to decrease the trypsin inhibitory activity (TI activity) shown by the raw flours and appeared to have higher frequencies than recessive alleles. Significant maternal effects were also detected, particularly in crosses of low-TI activity female × high-TI activity male; maternal effects strengthened the role of the regulatory genes transferred by the female parent to the hybrid. Data fitted the simple additive–dominance model with genes independent in both action and distribution. Narrow and broad heritability values were 54% and 82% respectively, thus indicating the feasibility of lowering TI activity through selection. © 2000 Society of Chemical Industry

Abstract: Polyethylene glycols (PEGs) of various chain length were used tocrosslink lysozyme onto an insoluble support such as oxirane. A very high degree of modification and noinactivation of lysozyme were obtained with PEG 20000, but enzymatic activity increased up to 20 times at pH 3.0, at which point the activity of the native enzyme was lower when using Leuconos tok oenus as a macromolecular substrate.

Partially delactosated and demineralized whey protein powders were purified from pooled milks of individual cows homozygous for the β-lactoglobulin (β-Lg) genetic variants A and B ( whey A and whey B). The protein composition of the two samples was similar. The two whey protein powders were dissolved in water at different pH (2, 4.5, 6.8) and NaCl concentrations (150 and 400 mmol/dm3), and emulsions were made utilizing grape-seed oil. Emulsion stability (ES), emulsion activity index (EAI) and emulsion capacity (EC) were examined. The results showed the influence of the two genetic variants of β-Lg on the functional behaviour of whey. Emulsion obtained from B powder solutions showed the higher stability at the different test conditions. The best results occurred at pH 6.8 with no significant differences between the two tested NaCl concentrations. At pH2 and 400 mmol/dm3 NaCl, both samples did not demonstrate any stability. Data on emulsion capacity indicated that whey B is less affected by the different physicochemical conditions tested (pH, NaCl concentration, heat treatment at 90°Cl5 min), while whey A gave the highest and the lowest EC values depending on the experimental conditions.

In August 2007, the Food and Drug Administration (FDA) released a public health advisory recommending that over-the-counter cough and cold medications (CCMs) not be used in children younger than 2 years. Our objective was to assess parents’ awareness and understanding of the guidelines.

Reaction of the sterically demanding ligand precursor [(CHBu^t)2(C5H2Bu^t2)2]K2 with SnCl2 in THF gave the air-stable ansa-stannocene complex rac[(CHBu^t)2(C5H2Bu^t2)2]Sn. A single-crystal X-ray structure of the ansa-stannocene revealed a C2-symmetric and slipped bent structure, with the Sn²⁺ displaced toward an η² bonding mode between bridged, highly tilted, and staggered 2,4-di-tert-butylcyclopentadienyl rings.

Purpose: We aimed to estimate the 3-year budget impact of replacing salmeterol/fluticasone with indacaterol/glycopyrronium for the treatment of chronic obstructive pulmonary disease patients in Italy.Methods: The budget impact model included patients with moderate, severe, and very severe chronic obstructive pulmonary disease and was developed using data from the FLAME study. The budget impact model considered direct medical costs from the National Healthcare System perspective over a 3-year time-horizon. Costs of drugs, adverse events, and exacerbations were estimated using public net prices for drugs and national (inpatient/outpatient) tariffs for patient management. Data on adverse events and exacerbations were derived from FLAME and other clinical trials. The model assumed an increasing uptake of indacaterol/glycopyrronium, substituting it for salmeterol/fluticasone. Two sensitivity analyses were conducted. In the first, every long-acting muscarinic antagonist/inhaled corticosteroid switch to indacaterol/glycopyrronium; in the second, drugs compliance varies from 20% to 60%.Results: The target population was estimated at 572,788 patients in the first year, increasing to 585,491 in the third year. The alternative treatment pattern, with a higher indacaterol/glycopyrronium uptake, was associated with a total cost of €1.69 billion over 3 years, while the total costs in the current treatment pattern amounted to €1.71 billion. Thus, increasing indacaterol/glycopyrronium use provided total savings of €17.3 million over 3 years. Sensitivity analysis confirmed robustness of the results.Conclusion: Increasing the uptake of indacaterol/glycopyrronium was estimated to be cost-saving for the Italian National Healthcare System, both when drug-related expenditures and total costs were considered. Savings increased with the number of patients switching to indacaterol/glycopyrronium.

Background The past few years, the Italian National Health Service (INHS) has faced the challenge of ensuring sustainable costs for antineoplastic and immunomodulating drugs. The aim of this study was to analyse expenditure trends for these drugs in two Local Health Units during the period 2009-2011.Methods Data for this retrospective study were derived from the administrative databases of two Local Health Units in Northern Italy. A sample was built up by selecting all patients with at least one antineoplastic and immunomodulating drug prescription between 2009 and 2011. The study evaluated the annual, per capita and per user drug expenditure. The antineoplastic and immunomodulating drug expenditure was also analysed by therapeutic indication.Results The number of users (annual mean rate: 12.1%) and the antineoplastic and immunomodulating drug expenditure (annual mean rate: 15.7%) were increased in the three-year period. The mean annual per capita cost was €18.40 in the first year (2009), €22.18 in the second year (2010) and €24.23 in the last year (2011). Taking into account the last year of the analysis (2011), monoclonal antibody drugs showed the highest per capita drug spending (€9.36), followed by TNF-alpha inhibitors (€6.61) and tyrosine kinase inhibitors (€5.75). The highest mean annual expenditure was on cancer drugs (€15,046,773), followed by rheumatoid arthritis (€3,596,925), psoriatic arthritis (€925,510), ankylosing spondylitis (€626,050) and psoriasis (€622,332).Conclusions Spending on antineoplastic and immunomodulating drugs increased over the three-year period of the analysis and the oncological disease was the main therapeutic indication.