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OBJECTIVES: The paediatric intensive care unit changed heparin infusion dosing from a variable weight-based concentration to a fixed concentration strategy, when smart pump-based drug library was introduced. This change meant significantly lower rates of infusion were needed for the same dose of heparin in the neonatal population. We performed a safety and efficacy assessment of this change. METHODS: We performed a retrospective single-centre evaluation based on data from respiratory VA-extracorporeal membrane oxygenation (ECMO) patients weighing ≤5 kg, pre and post the change to fixed strength heparin infusion. Efficacy was analysed by distribution of activated clotting times (ACT) and heparin dose requirements between the groups. Safety was analysed using thrombotic and haemorrhagic event rates. Continuous variables were reported as median, interquartile ranges, and non-parametric tests were used. Generalised estimating equations (GEE) were used to analyse associations of heparin dosing strategy with ACT and heparin dose requirements in the first 24 h of ECMO. Incidence rate ratios of circuit related thrombotic and haemorrhagic events between groups were analysed using Poisson regression with offset for run hours. RESULTS: 33 infants (20 variable weight-based, 13 fixed concentration) were analysed. Distribution of ACT ranges and heparin dose requirements were similar between the two groups during the ECMO run and this was confirmed by GEE. Incidence rate ratios of thrombotic (fixed v weight-based) (1.9 [0.5-8], p = .37), and haemorrhagic events (0.9 [0.1-4.9], p = .95) did not show statistically significant differences. CONCLUSIONS: Fixed concentration dosing of heparin was at least equally effective and safe compared to a weight-based dosing.
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BACKGROUND: Repeatedly, too low MIC results were obtained in Bacteroides fragilis quality assessment strains, using gradient strip tests with a ratio of amoxicillin:clavulanic acid of 2:1. We aimed to find the most accurate available gradient strip tests for susceptibility testing of amoxicillin/clavulanic acid in B. fragilis in comparison with agar dilution with EUCAST methodology and breakpoints. METHODS: Twenty-seven clinical B. fragilis isolates were investigated using gold standard EUCAST amoxicillin/clavulanic acid agar dilution (fixed clavulanic acid concentration at 2 mg/L, with increasing amoxicillin concentrations) as well as three commercial gradient strip tests: XL (ratio), AUG (ratio) or AMC (fixed concentration). RESULTS: Using agar dilution (fixed concentration), 19 isolates were susceptible, 1 isolate was susceptible increased exposure (I) and 7 isolates were resistant. Categorical agreement of the gradient strip tests with agar dilution (fixed concentration) was 70% for XL (ratio), 71% for AUG (ratio) and 89% for AMC (fixed concentration). Very major error rates in comparison with agar dilution (fixed concentration) were 100%, 0%, and 0%, respectively. CONCLUSIONS: EUCAST breakpoint usage in amoxicillin/clavulanic acid susceptibility tests for B. fragilis should be accompanied by EUCAST methodology. When using alternative methods such as gradient strip tests, a higher degree of alignment with EUCAST methodology, such as using fixed clavulanic acid concentrations, improves precision.
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Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Bacteroides/tratamento farmacológico , Bacteroides fragilis/efeitos dos fármacos , Bacteroides fragilis/genética , Testes de Sensibilidade Microbiana/métodos , Fitas Reagentes , Variação Genética , Genótipo , HumanosRESUMO
OBJECTIVES: This study aimed to explore the use of standard concentration infusions for intravenous infusions (SCI) in paediatric and neonatal units in the United Kingdom (UK). This included how many units use SCI, variation and overlap in concentrations, devices in use for administration and how the infusions were provided. METHODS: Paediatric and neonatal units in the UK were surveyed using a self-administered web-based survey tool. Respondents were accessed through professional networks over a one-month period in summer 2016. KEY FINDINGS: Thirty-one units (40%) used SCI. Twenty-one units provided information on presentation and administration of SCI. Forty-six medicines were used as SCI with 143 different concentrations. 'Smart' pump technology was most commonly used in the administration of SCI, and SCI were predominantly prepared by nurses in the near-patient setting. CONCLUSIONS: The majority of paediatric and neonatal units in the UK used traditional weight-based methods for IV infusions and only 40% of responding units had established SCI. This local implementation of SCI resulted in a wide variation of presentations and concentrations and thus there is no true 'standardisation'. Further research should be conducted on harmonising these SCI across neonatal and paediatric care to facilitate adoption across all units.
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Infusões Intravenosas/instrumentação , Infusões Intravenosas/métodos , Infusões Intravenosas/normas , Unidades de Terapia Intensiva Neonatal/normas , Unidades de Terapia Intensiva Pediátrica/normas , Humanos , Inquéritos e Questionários , Reino UnidoRESUMO
Acute inhalation studies are conducted in animals as part of chemical hazard identification and for classification and labelling. Current methods employ death as an endpoint (Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 403 and TG436) while the recently approved fixed concentration procedure (FCP) (OECD TG433) uses fewer animals and replaces lethality as an endpoint with evident toxicity. Evident toxicity is the presence of clinical signs that predict that exposure to the next highest concentration will cause severe toxicity or death in most animals. Approval of TG433 was the result of an international initiative, led by the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), which collected data from six laboratories on clinical signs recorded for inhalation studies on 172 substances. This paper summarises previously published data and describes the additional analyses of the dataset that were essential for approval of the TG.
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Testes de Toxicidade Aguda/métodos , Administração por Inalação , Alternativas ao Uso de Animais/métodos , Animais , Feminino , MasculinoRESUMO
OBJECTIVES: The objective of this study was to examine the frequency of psychoactive drugs and alcohol in drivers under suspicion of driving under the influence of drugs and alcohol in 2015 and 2016 in the eastern part of Denmark. The trends in the number of traffic cases sent for drug analysis since 2000 and alcohol analysis since 2011 are also discussed. METHODS: Blood samples from drivers suspected of being under the influence of alcohol and/or medication and/or illicit drugs in 2015 and 2016 were investigated as requested by the police. The blood samples were screened for alcohol and/or tetrahydrocannabinol (THC) alone, for other drugs (covering all drugs, except THC, listed in the Danish list of narcotic drugs), or for THC and other drugs. Age and gender were also recorded. The number of drug traffic cases since 2000 and the number of alcohol cases since 2011 were extracted from our Laboratory Information Management System (LIMS). RESULTS: In total, 11,493 traffic cases were investigated. Alcohol and/or drugs exceeded the legal limit in 9,657 (84%) cases. Men constituted 95% of the drivers investigated for drugs and 88% of the alcohol cases. The drivers investigated for drugs consisted primarily of young men, whereas drivers investigated for alcohol were older. The frequency was higher for positive alcohol cases above the legal limit (87%) than for drug cases (76%) above the fixed concentration limit. THC (67-69%) was the most frequently detected drug above the legal limit, followed by cocaine (27-28.5%), amphetamine (17%), and clonazepam (6-7%) in both years. Morphine (5.4%), included among the 5 most frequent drugs in 2015, was replaced by methadone (4.6%) in 2016. Few new psychoactive drugs (NPS) were detected. The number of traffic cases sent for drug analysis has increased more than 30-fold since 2000-2006, and the number of traffic cases submitted in 2016 for drug analysis was higher than the number for alcohol analysis; the latter has decreased since 2011. CONCLUSION: Overall, alcohol was the most frequent compound detected above the legal limit in both years, followed by the well-known illicit drugs THC, cocaine, and amphetamine. NPS were seldom seen. One consequence of the increased focus on drugs in traffic has been an immense increase in drug traffic cases sent for analysis since 2006 in the eastern part of Denmark. Although this survey revealed only minimal changes compared to earlier investigations, surveys like this are invaluable for monitoring abuse patterns and trends in drugged and drunken driving.
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Dirigir sob a Influência/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Dronabinol/sangue , Etanol/sangue , Feminino , Humanos , Drogas Ilícitas/sangue , Masculino , Pessoa de Meia-Idade , Entorpecentes/sangue , Psicotrópicos/sangue , Adulto JovemRESUMO
Acute inhalation studies are conducted in animals as part of chemical hazard identification and characterisation, including for classification and labelling purposes. Current accepted methods use death as an endpoint (OECD TG403 and TG436), whereas the fixed concentration procedure (FCP) (draft OECD TG433) uses fewer animals and replaces lethality as an endpoint with 'evident toxicity.' Evident toxicity is defined as clear signs of toxicity that predict exposure to the next highest concentration will cause severe toxicity or death in most animals. A global initiative including 20 organisations, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has shared data on the clinical signs recorded during acute inhalation studies for 172 substances (primarily dusts or mists) with the aim of making evident toxicity more objective and transferable between laboratories. Pairs of studies (5 male or 5 female rats) with at least a two-fold change in concentration were analysed to determine if there are any signs at the lower dose that could have predicted severe toxicity or death at the higher concentration. The results show that signs such as body weight loss (>10% pre-dosing weight), irregular respiration, tremors and hypoactivity, seen at least once in at least one animal after the day of dosing are highly predictive (positive predictive value > 90%) of severe toxicity or death at the next highest concentration. The working group has used these data to propose changes to TG433 that incorporate a clear indication of the clinical signs that define evident toxicity.