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1.
Br Paramed J ; 9(1): 1-9, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946738

RESUMO

Introduction: Intravenous thrombolysis and mechanical thrombectomy are effective time-sensitive treatments for selected cases of acute ischaemic stroke. While thrombolysis is widely available, thrombectomy can only be provided at facilities with the necessary equipment and interventionists. Suitable patients admitted to other hospitals require secondary transfer, causing delays to treatment. Pre-hospital ambulance redirection to thrombectomy facilities may improve access but treatment eligibility cannot be confirmed pre-hospital. Some redirected patients would travel further and be displaced without receiving thrombectomy. This study aimed to elicit stroke survivor and carer/relative views about the possible consequences of introducing a conceptual, idealised ambulance redirection pathway. Methods: Focus groups were undertaken using a topic guide describing four hypothetical ambulance redirection scenarios and their possible consequences: earlier treatment with thrombectomy; delayed diagnosis of non-stroke 'mimic' conditions; delayed thrombolysis treatment; and delayed diagnosis of haemorrhagic stroke. Meetings were audio recorded, transcribed verbatim and data analysed thematically using emergent coding. Results: Fifteen stroke survivors and carers/relatives participated in three focus groups. There was wide acceptance of possible low-risk consequences of ambulance redirection, including extended travel time, being further from home and experiencing longer hospital stays. Participants were more uncertain about higher-risk consequences, including delays in diagnosis/treatment for patients unsuitable for thrombectomy, but remained positive about ambulance redirection overall. Participants rationalised acceptance of higher-risk consequences by recognising that redirected patients would still access appropriate treatment, even if delayed. In addition, acceptance of ambulance redirection would be increased if there were robust clinical evidence showing net benefit over secondary transfer pathways. Conclusions: Participant views were generally supportive of ambulance redirection to facilitate access to thrombectomy. Further research is needed to demonstrate overall benefit in an NHS context.

2.
Diagn Microbiol Infect Dis ; 109(3): 116269, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38692201

RESUMO

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Hemocultura , Testes de Sensibilidade Microbiana , Humanos , Hemocultura/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Farmacorresistência Bacteriana/genética , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Genótipo
3.
J Clin Pharmacol ; 64(7): 860-865, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38497326

RESUMO

Daptomycin is an antibiotic with Gram-positive activity, including methicillin-resistant Staphylococcus aureus, for which optimal pediatric dosing is unknown. This study aimed to evaluate daptomycin exposures achieved with package label dosing and to identify dosing regimens necessary to enhance efficacy and minimize toxicity in children with S. aureus bacteremia. Monte Carlo simulations were performed to determine probability of target attainment (PTA) for six pediatric age cohorts. Area under the curve to minimum inhibitory concentration ratio (AUC0-24:MIC) ≥666 was used to determine the PTA for efficacy (PTAE). Minimum concentration (Cmin) ≥24.3 mg/L determined the PTA for toxicity (PTAT). Acceptable dosing regimens were those which achieved the combined target of ≥90% PTAE and ≤5% PTAT. Package label dosing of daptomycin yielded insufficient efficacy with only 26.3% PTAE in children 13-24 months, 39.5% PTAE in children 2-6 years, 30.1% PTAE in children 7-11 years, and 50.1% PTAE in adolescents ≥12 years. To achieve the combined efficacy and safety target, doses of 18-24 mg/kg in children 3-12 months, 20-24 mg/kg in children 13-24 months, 19-24 mg/kg in children 2-6 years, 17-19 mg/kg in children 7-11 years, and 10-14 mg/kg in adolescents ≥12 years are necessary. Package label dosing resulted in suboptimal exposure for the majority of pediatric patients in all age groups evaluated. If targeting validated efficacy and safety endpoints, daily daptomycin doses of at least 20 mg/kg in children ≤6 years, 17 mg/kg in children 7-11 years, and 10 mg/kg in adolescents ≥12 years are necessary. Clinical studies evaluating these higher doses are needed.


Assuntos
Antibacterianos , Bacteriemia , Daptomicina , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Infecções Estafilocócicas , Humanos , Daptomicina/farmacocinética , Daptomicina/administração & dosagem , Daptomicina/farmacologia , Criança , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Pré-Escolar , Adolescente , Lactente , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Masculino , Feminino , Relação Dose-Resposta a Droga , Staphylococcus aureus/efeitos dos fármacos , Área Sob a Curva , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
4.
J Cell Sci ; 137(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469748

RESUMO

Equal cell division relies upon astral microtubule-based centering mechanisms, yet how the interplay between mitotic entry, cortical force generation and long astral microtubules leads to symmetric cell division is not resolved. We report that a cortically located sperm aster displaying long astral microtubules that penetrate the whole zygote does not undergo centration until mitotic entry. At mitotic entry, we find that microtubule-based cortical pulling is lost. Quantitative measurements of cortical pulling and cytoplasmic pulling together with physical simulations suggested that a wavelike loss of cortical pulling at mitotic entry leads to aster centration based on cytoplasmic pulling. Cortical actin is lost from the cortex at mitotic entry coincident with a fall in cortical tension from ∼300pN/µm to ∼100pN/µm. Following the loss of cortical force generators at mitotic entry, long microtubule-based cytoplasmic pulling is sufficient to displace the aster towards the cell center. These data reveal how mitotic aster centration is coordinated with mitotic entry in chordate zygotes.


Assuntos
Sêmen , Fuso Acromático , Masculino , Humanos , Microtúbulos , Citoplasma , Divisão Celular
5.
Pharmacotherapy ; 44(4): 294-300, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38533999

RESUMO

INTRODUCTION: The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC0-24) over minimum concentration (Cmin) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC0-24 in pediatric patients are lacking. OBJECTIVES: To describe the interplay of vancomycin dose, AUC0-24, and Cmin using first-order equations within four pediatric age groups. METHODS: This is a single-center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1-12 years), and adolescents (13-17 years). First-order equations were utilized to estimate pharmacokinetic parameters and AUC0-24. RESULTS: Overall, 219 patients (median age of 6 years [IQR 1-12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median Cmin and AUC0-24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC0-24 values outside of the therapeutic range (400-600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between Cmin and AUC0-24. However, 71% of patients with Cmin values of 5-10 mg/L had an AUC0-24 within the therapeutic range of 400-600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC0-24 had a Cmin value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury. CONCLUSIONS: Our data describe the relationship between vancomycin dose, Cmin, and AUC0-24 in pediatric patients. We demonstrated the feasibility of using first-order equations to estimate AUC0-24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC0-24 and Cmin, which indicates that Cmin should not be used as a surrogate marker for a therapeutic AUC0-24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC0-24 for efficacy and safety monitoring.


Assuntos
Antibacterianos , Área Sob a Curva , Vancomicina , Humanos , Vancomicina/farmacocinética , Vancomicina/administração & dosagem , Criança , Pré-Escolar , Lactente , Estudos Retrospectivos , Adolescente , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Masculino , Feminino , Recém-Nascido , Monitoramento de Medicamentos/métodos , Estudos de Coortes , Relação Dose-Resposta a Droga , Administração Intravenosa
6.
Artigo em Inglês | MEDLINE | ID: mdl-38156206

RESUMO

Objective: Vancomycin therapy is associated with an increased risk of acute kidney injury (AKI). Previous studies suggest that area under the curve (AUC) monitoring reduces the risk of AKI, but literature is lacking to support this in patients receiving longer durations of vancomycin therapy. Design: Retrospective cohort study. Method: Patients ≥18 years old, admitted between August 2015 and July 2017 or October 2017 and September 2019, and received at least 14 days of intravenous (IV) vancomycin therapy were included in the study. Our primary outcome was the incidence of AKI between trough monitoring and AUC monitoring groups using Kidney Disease Improving Global Outcomes criteria. Secondary outcomes included inpatient mortality, median inpatient length of stay, and median intensive care unit length of stay. Results: Overall, 582 patients were included in the study, with 318 patients included in the trough monitoring group and 264 included in the AUC monitoring group. The median duration of vancomycin therapy was 23 days (interquartile range, 16-39). Patients within the trough monitoring group had a higher incidence of AKI compared to the AUC monitoring group (45.6% vs 28.4%, p < 0.001). Furthermore, logistic regression analysis showed that AUC monitoring was associated with a 54% lower incidence of AKI (OR 0.46, 95% CI [0.31-0.69]). All-cause inpatient mortality was numerically higher in the trough monitoring group (12.9% vs 8.3%, p = 0.078). Conclusions: In patients who received at least 14 days of IV vancomycin therapy, AUC monitoring was associated with a lower incidence of AKI.

8.
Heart Lung Circ ; 32(2): 184-196, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36599791

RESUMO

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.


Assuntos
Ablação por Cateter , Isquemia Miocárdica , Taquicardia Ventricular , Humanos , Antiarrítmicos/uso terapêutico , Volume Sistólico , Estudos Prospectivos , Resultado do Tratamento , Função Ventricular Esquerda , Austrália/epidemiologia , Taquicardia Ventricular/cirurgia , Taquicardia Ventricular/etiologia , Isquemia Miocárdica/cirurgia , Ablação por Cateter/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
9.
Artigo em Inglês | MEDLINE | ID: mdl-36483380

RESUMO

We assessed breakpoint changes of 13,101 Enterobacterales and Pseudomonas aeruginosa isolates from the past decade. All ß-lactams and fluoroquinolones demonstrated decreased susceptibilities following breakpoint changes. Enterobacter cloacae experienced the largest average decrease in susceptibility amongst the Enterobacterales at 5.3% and P. aeruginosa experienced an average decrease in susceptibility of 9.3%.

10.
Circ Arrhythm Electrophysiol ; 15(12): e011129, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36399370

RESUMO

BACKGROUND: Ventricular tachycardia (VT) storm is associated with significantly increased morbidity, mortality, and exponential healthcare utilization. Although catheter ablation (CA) may be curative, there are limited data directly comparing outcomes of early CA with initial medical therapy. METHODS: We compared outcomes of patients presenting with VT storm treated with initial CA versus those treated with initial medical therapy during their first storm presentation in an observational study. Retrospective data from the host institution from January 2014 to April 2020 of 129 patients with their first VT storm presentation were analyzed (58 underwent initial CA, 71 underwent treatment with initial medical therapy). Outcomes were compared in follow-up. RESULTS: Median time to initial CA was 6 days. Over a median follow-up of 702 days, patients who underwent initial CA compared with those treated with initial medical therapy had significantly less: (i) VA recurrence (43% versus 92%; P=0.002); (ii) VT storm recurrence (28% versus 73%; P<0.001); (iii) composite end point of death, heart transplant, VT storm recurrence, and VT-related hospitalization (47% versus 89%; P=0.002); (iv) iatrogenic complications (at 12 months: 17% versus 45%; P<0.001); (v) cardiovascular-related hospitalizations (50% versus 89%; P=0.01); (vi) total number of hospitalizations (median 1 versus 4; P<0.001); and (vi) cumulative days in hospital (median 0.5 versus 18; P<0.001). There were no intraprocedural deaths in patients treated with early CA. CONCLUSION: In an observational setting in which patients presenting with storm, early CA appears superior to initial medical therapy in terms of VT recurrence, storm recurrence, iatrogenic complications, cardiovascular hospitalizations, and cumulative days in hospital in follow-up.


Assuntos
Ablação por Cateter , Taquicardia Ventricular , Humanos , Resultado do Tratamento , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Estudos Retrospectivos , Ablação por Cateter/efeitos adversos , Doença Iatrogênica , Recidiva
11.
Pharmacotherapy ; 42(4): 284-291, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35134264

RESUMO

INTRODUCTION: Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC24 :MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC24 , there are currently no large studies directly comparing these methods. OBJECTIVE: To compare calculated vancomycin AUC24 using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations. METHODS: This was a single-center, retrospective cohort study of 978 adult hospitalized patients receiving intravenous vancomycin between 2017 and 2019. Patients were included if they received at least 72 h of vancomycin and had two-serum drug concentrations obtained. AUC24 was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx™ software platform was used to calculate Bayesian AUC24 . Pearson's correlation and clinical agreement (based on AUC24  classified as subtherapeutic, therapeutic, or supratherapeutic) were used to assess agreement between methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA). RESULTS: Excellent agreement was observed between linear and Bayesian two-concentration methods (r = 0.963, clinical agreement = 87.4%) and Bayesian two-concentration and one-concentration methods (r = 0.931, clinical agreement = 88.5%); however, a degree of variability was noted with 95% LOA -99 to 76 (MD = -11.5 mg*h/L) and -92 to 113 (MD = -10.4 mg*h/L), for the respective comparisons. The agreement between linear and Bayesian one-concentration approaches was less than prior comparisons (r = 0.823, clinical agreement = 76.8%) and demonstrated the greatest amount of variability with 95% LOA -197 to 153 (MD = -21.9 mg*h/L). CONCLUSIONS: Linear and Bayesian two-concentration methods demonstrated high-level agreement with acceptable variability and may be considered comparable to estimate vancomycin AUC24 . As linear and Bayesian one-concentration methods demonstrated significant variability and suboptimal agreement, concerns exist surrounding the interchangeability of these methods in clinical practice, particularly at higher extremes of AUC24 .


Assuntos
Infecções Estafilocócicas , Vancomicina , Adulto , Antibacterianos/uso terapêutico , Área Sob a Curva , Teorema de Bayes , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico
12.
J Vasc Access ; 23(4): 615-623, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35164597

RESUMO

BACKGROUND: In 1953, Swedish radiologist Sven Seldinger introduced a technique for blood vessel or hollow organ access using a needle, guide wire and catheter. Over the last two decades, this technique has been used for Peritoneal Dialysis (PD) catheter placement, "Seldinger PD" (SPD). To improve the safety and accuracy of SPD, ultrasound, X-ray guidance, contrast imaging and micropuncture techniques have been incorporated to a greater or lesser extent. METHODS: This manuscript describes a new and rigorous technique of SPD developed at our unit and results in the first 64 cases. One of our goals was to replace emergency Central Vein Catheter Hemodialysis with "Urgent-Start" PD. We therefore sought to develop a procedure that was ultra-safe, minimally invasive and readily done on the sickest patients under Local Anesthetic. As the technique was new to our unit, and because of progressive modifications of the technique, some of the results reflect our "learning curve." In addition, 55% of the patients referred to our program had "crashed" into renal failure, 32% were deemed "unfit for General Anaesthesia" by the Anaesthetists and 53% were moderately to severely obese, resulting in a very morbid and vulnerable cohort. RESULTS: Despite this, we had no procedure related mortality, no organ injury and no significant bleeding. Technical success was 97% (intention-to-treat). Urgent Start PD was used in 36%; overall, 3/61 catheters placed experienced PD fluid leak. Correct catheter tip placement - in the Pelvic Pouch - was documented in all cases; significant catheter migration was seen in 18% of those with imaging follow-up, only two requiring revision. Most catheter migrations occurred early in our series before our low peritoneal puncture technique became standard. CONCLUSIONS: We believe this SPD technique is safe, precise, clinically and financially cost-effective and can replace other forms of PD placement in most situations.


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Algoritmos , Cateterismo/efeitos adversos , Cateterismo/métodos , Cateteres de Demora , Humanos , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos
13.
Antimicrob Agents Chemother ; 66(1): e0088621, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34633843

RESUMO

Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-h area under the concentration-time curve (AUC24) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with body mass indices (BMI) ≥30 kg/m2, admitted between August 2015 and July 2017 or October 2017 and September 2019, who received vancomycin for ≥72 h and had level(s) drawn within 96 h of initiation were included. The primary outcome was incidence of AKI. Secondary outcomes included inpatient mortality rate, median inpatient length of stay, median vancomycin trough concentration, and median vancomycin AUC24. AKI was identified using the highest serum creatinine value compared with the value immediately prior to vancomycin initiation based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Overall, 1,024 patients met inclusion criteria, with 142 out of 626 patients in the trough group and 65 out of 398 patients in the AUC24 group meeting criteria for AKI (22.7% versus 16.3%, P = 0.008). Logistic regression of the data to account for confounding factors maintained significance for the reduction in incidence of AKI with AUC24 monitoring compared to trough monitoring (P = 0.010). Monitoring of vancomycin with AUC24 was associated with a decreased risk of AKI when compared with trough monitoring in obese patients.


Assuntos
Injúria Renal Aguda , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Injúria Renal Aguda/tratamento farmacológico , Antibacterianos/efeitos adversos , Área Sob a Curva , Humanos , Testes de Sensibilidade Microbiana , Obesidade/tratamento farmacológico , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/efeitos adversos
14.
Exp Astron (Dordr) ; 54(2-3): 473-519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36915623

RESUMO

The smallest characteristic scales, at which electron dynamics determines the plasma behaviour, are the next frontier in space and astrophysical plasma research. The analysis of astrophysical processes at these scales lies at the heart of the research theme of electron-astrophysics. Electron scales are the ultimate bottleneck for dissipation of plasma turbulence, which is a fundamental process not understood in the electron-kinetic regime. In addition, plasma electrons often play an important role for the spatial transfer of thermal energy due to the high heat flux associated with their velocity distribution. The regulation of this electron heat flux is likewise not understood. By focussing on these and other fundamental electron processes, the research theme of electron-astrophysics links outstanding science questions of great importance to the fields of space physics, astrophysics, and laboratory plasma physics. In this White Paper, submitted to ESA in response to the Voyage 2050 call, we review a selection of these outstanding questions, discuss their importance, and present a roadmap for answering them through novel space-mission concepts.

15.
J Clin Pharmacol ; 62(4): 479-485, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34614542

RESUMO

ß-Lactams are the most commonly used antibiotics in intensive care units (ICUs). As critically ill patients often experience pharmacokinetic aberrations, and rates of antimicrobial resistance vary between hospital settings, reliance on tertiary sources or package labeling to guide empiric dosing often results in suboptimal ß-lactam exposure. The primary objective was to identify ß-lactam regimens capable of achieving ≥90% cumulative fraction of response (CFR) against 7 Gram-negative pathogens within 4 ICUs at our institution. Unit-specific minimal inhibitory concentration (MIC) distribution data was used in combination with published pharmacokinetic parameters in critically ill patients to perform Monte Carlo simulations. The percentage of time for which the unbound concentration of antibiotic remained above the MIC (%ƒT > MIC) was used as the pharmacodynamic target: 70%ƒT >MIC for cefepime, 40%ƒT > MIC for meropenem, and 50%ƒT > MIC for piperacillin/tazobactam. Regimens were modeled to determine the likelihood of achieving ≥90% CFR. Overall, intermittently dosed cefepime, meropenem, and piperacillin/tazobactam failed to achieve ≥90% CFR for every organism. Cefepime 2 g intermittent bolus every 8 hours failed to achieve ≥90% CFR for Klebsiella pneumoniae or Enterobacter cloacae despite susceptibility rates exceeding 90%. Piperacillin/tazobactam 4.5 g prolonged infusion (PI) every 6 hours achieved <85% CFR for Pseudomonas aeruginosa and <50% CFR for Acinetobacter baumannii in every ICU. Meropenem 2 g PI every 8 hours and meropenem 2 g PI every 6 hours were the only regimens capable of achieving ≥90% CFR for P aeruginosa in all units. Use of Monte Carlo simulations, with incorporation of local MIC distribution data, provides a mechanism to effectively predict optimal agent and dose selection within specific hospital systems, thereby enhancing pharmacokinetic/pharmacodynamic optimization and improving clinical efficacy.


Assuntos
Estado Terminal , beta-Lactamas , Antibacterianos , Cefepima/farmacologia , Humanos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Piperacilina/farmacocinética , Pseudomonas aeruginosa , Tazobactam/farmacologia
17.
Transfusion ; 62(2): 406-417, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34951486

RESUMO

BACKGROUND: Early plasma transfusion is life-saving for bleeding trauma patients. Freeze-dried plasma (FDP) provides unique formulation advantages for infusion in the prehospital setting. We describe characterization and clinical safety data of the first, next-generation FDP stored in plastic bags with rapid reconstitution. STUDY DESIGN AND METHODS: Coagulation and chemistry parameters on 155 pairs of fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a first-in-human, dose-escalation safety evaluation of FDP, involving 24 healthy volunteers who donated either whole blood or apheresis plasma to create autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and adverse events (AEs) were monitored. Cohort 3 was randomized, double-blind with a cross-over arm that compared FDP versus FFP using descriptive analysis for AEs, coagulation, hematology, and chemistry parameters. RESULTS: FDP coagulation factors, clotting times, and product quality (pH, total protein, and osmolality) post-lyophilization were preserved. FDP infusions, of up to 810 ml per subject, were found to be safe and with no serious AEs (SAEs) related to FDP. The average time to reconstitute FDP was 67 s (range: 43-106). No differences in coagulation parameters or thrombin activation were detected in subjects infused with 810 ml of FDP compared with FFP. CONCLUSION: This first next-generation FDP product preserves the potency and safety of FFP in a novel rugged, compressible, plastic container, for rapid transfusion, allowing rapid access to plasma in resuscitation protocols for therapy in acute traumatic hemorrhage.


Assuntos
Transfusão de Componentes Sanguíneos , Plasma , Liofilização/métodos , Hemorragia/terapia , Humanos , Ressuscitação/métodos
18.
Artigo em Inglês | MEDLINE | ID: mdl-36712472

RESUMO

Objective: The objective of this study was to determine antibiotic appropriateness based on Loeb minimum criteria (LMC) in patients with and without altered mental status (AMS). Design: Retrospective, quasi-experimental study assessing pooled data from 3 periods pertaining to the implementation of a UTI management guideline. Setting: Academic medical center in Lexington, Kentucky. Patients: Adult patients aged ≥18 years with a collected urinalysis receiving antimicrobial therapy for a UTI indication. Methods: Appropriateness of UTI management was assessed in patients prior to an institutional UTI guideline, after guideline introduction and education, and after implementation of a prospective audit-and-feedback stewardship intervention from September to November 2017-2019. Patient data were pooled and compared between patients noted to have AMS versus those with classic UTI symptoms. Loeb minimum criteria were used to determine whether UTI diagnosis and treatment was warranted. Results: In total, 600 patients were included in the study. AMS was one of the most common indications for testing across the 3 periods (19%-30.5%). Among those with AMS, 25 patients (16.7%) met LMC, significantly less than the 151 points (33.6%) without AMS (P < .001). Conclusions: Patients with AMS are prescribed antibiotic therapy without symptoms indicative of UTI at a higher rate than those without AMS, according to LMC. Further antimicrobial stewardship efforts should focus on prescriber education and development of clearly defined criteria for patients with and without AMS.

19.
ACS Macro Lett ; 10(7): 907-913, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34306821

RESUMO

We show that a surface-grafted polymer brush, 1-n-butyl-3-vinyl imidazolium bromide-based poly(ionic liquids), is able to reduce the interfacial friction by up to 66% and 42% in dodecane and water, respectively. AFM-based force spectroscopy reveals that the polymer brush adopts distinctively different interfacial conformations: swollen in water but collapsed in dodecane. Minimal surface adhesion was observed with both polymer conformations, which can be attributed to steric repulsion as the result of a swollen conformation in water or surface solvation when the hydrophobic fraction of the polymer was exposed to the dodecane. The work brings additional insight on the polymer lubrication mechanism, which expands the possible design of the polymer architecture for interfacial lubrication and modification.

20.
Proc Natl Acad Sci U S A ; 118(21)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34006642

RESUMO

The interaction of collisionless shocks with fully developed plasma turbulence is numerically investigated. Hybrid kinetic simulations, where a turbulent jet is slammed against an oblique shock, are employed to address the role of upstream turbulence on plasma transport. A technique, using coarse graining of the Vlasov equation, is proposed, showing that the particle transport strongly depends on upstream turbulence properties, such as strength and coherency. These results might be relevant for the understanding of acceleration and heating processes in space plasmas.

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