Prediction of Early Neurological Deterioration in Individuals With Minor Stroke and Large Vessel Occlusion Intended for Intravenous Thrombolysis Alone.

Importance: The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy. Objective: To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO. Design, Setting, and Participants: This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019. Main Outcomes and Measures: ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause. Results: Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively. Conclusions and Relevance: The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

Platelet-to-neutrophil Ratio after Intravenous Thrombolysis Predicts Unfavorable Outcomes in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Platelet-to-neutrophil ratio (PNR) was suggested to be an independent protective predictor for 90-days outcomes in acute ischemic stroke (AIS) patients in previous studies. This study aims to investigate the association between PNR and outcomes of AIS in intravenous thrombolysis (IVT) group. METHODS: Data on acute ischemic stroke patients who received intravenous thrombolysis from April 2015 to March 2019 were collected. We defined the PNR value at admission as pre-IVT PNR and after IVT within 24 h was defined as post-IVT PNR. Clinical outcome indicators included early neurological deterioration (END), hemorrhagic transformation (HT), delayed neurological deterioration (DND), and poor 3-month outcome (3m-mRS >2). RESULTS: A total of 581 patients were enrolled in the final analysis. The age was 61(53-69) years, and 423(72.8%) were males. Post-IVT PNR was independently associated with hemorrhagic transformation (OR = 0.974; 95%CI = 0.956-0.992; P=0.006), early neurological deterioration (OR = 0.939; 95%CI = 0.913-0.966; P = 0.01), delayed neurological deterioration (OR = 0.949; 95%CI = 0.912- 0.988; P = 0.011), and poor outcome (OR = 0.962; 95%CI = 0.948-0.976; P<0.001). PNR level was identified as high (at the cut-off value or above) or low (below the cut-off value) according to receiver operating curve (ROC) analyses on each endpoint. Comparison of early neurological deterioration, hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome (3m-mRS >2) between patients at high and low levels for platelet-to-neutrophil ratio (PNR) showed statistical differences (p<0.001). CONCLUSION: Post-IVT PNR was independently associated with early neurological deterioration, hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome. Lower PNR can predict a worse outcome.

Uso del hierro intravenoso en la clínica actual / Use of intravenous iron in the current clinical practice

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Brinquedo terapêutico na administração de medicação endovenosa em crianças: estudo exploratório / Use of therapeutic play during intravenous drug administration in children: exploratory study / Juguete terapéutico en la administración de medicamentos intravenoso en niños: estudio exploratorio

OBJETIVO: Identificar reações de crianças na administração de medicação endovenosa, realizada anterior e posteriormente à técnica do Brinquedo Terapêutico, e analisar percepção dos acompanhantes em relação à influência da técnica no preparo para administração da medicação endovenosa. MÉTODO: Estudo exploratório, com abordagem qualitativa, realizado por meio de observações de administração medicamentosa endovenosa e das sessões de Brinquedo Terapêutico com crianças, e entrevista semiestruturada com acompanhantes. Os dados foram submetidos à análise temática. RESULTADOS: Crianças com dificuldade em aceitar a medicação endovenosa apresentaram mudanças positivas no comportamento após realização Brinquedo Terapêutico, principalmente aquelas entre 4 e 6 anos. Acompanhantes recomendam a realização dessa prática para melhoria do cuidado e redução do estresse durante a administração. CONCLUSÃO: Brinquedo terapêutico é uma relevante intervenção de enfermagem para minimizar as reações da criança durante o uso de medicações endovenosas, sendo importante a capacitação dos enfermeiros e o fomento da técnica para qualificação da assistência.

AIM: To identify the reactions of children during intravenous drug administration before and after the use of therapeutic play technique and to analyse their companions' perceptions regarding the technique's effects on the child's preparation for intravenous drug administration. METHOD: An exploratory study with a qualitative approach conducted through observations of intravenous drug administration and therapeutic play sessions with children and semi-structured interviews with their companions. The data were subjected to thematic analysis. RESULTS: Children who had difficulty accepting intravenous medication, especially those between 4 and 6 years, presented positive behavioural changes after the use of therapeutic play. The children's companions recommended the use of this technique to improve care and reduce stress during drug administration. CONCLUSION: Therapeutic play is a relevant nursing intervention for minimizing children's reactions during intravenous drug administration, and the training of nurses and the promotion of technique are important for improving care.

OBJETIVO: Identificar reacciones de niños en la administración de medicamentos intravenoso, realizada anterior y posteriormente a la técnica del Juguete Terapéutico, y analizar percepción de los acompañantes en relación a la influencia de la técnica en el preparo para la administración del medicamento intravenoso. MÉTODO: Estudio exploratorio, con enfoque cualitativo, realizado por medio de observaciones de administración medicamentosa intravenosa y de las sesiones de Juguete Terapéutico con niños, y entrevista semiestructurada con acompañantes. Los datos fueron sometidos al análisis temático. RESULTADOS: Niños con dificultad en aceptar el medicamento intravenoso presentaron cambios positivos en el comportamiento después la realización Juguete Terapéutico, principalmente aquellas entre 4 y 6 años. Acompañantes recomiendan la realización de esa práctica para mejora del cuidado y reducción del estrés durante la administración. CONCLUSIÓN: Juguete terapéutico es una relevante intervención de enfermería para minimizar las reacciones del niño durante el uso de medicamentos intravenosa, siendo importante la capacitación de los enfermeros y el fomento de la técnica para cualificación de la asistencia.

Actualización de la estabilidad de los medicamentos citostáticos y otras mezclas intravenosas aplicando la metodología de la matriz de riesgo para la elaboración de medicamentos estériles / Update of the stability of drugs cytostatic drugs by applying the methodology of the matrix of risk for the manufacture of sterile drugs

Objetivo: Establecer unos plazos de validez de los viales abiertos y/o reconstituidos y de las mezclas citostáticas según su estabilidad fisicoquímica, el nivel de riesgo y los requisitos de preparación asignados por la matriz de riesgo de la Guía de Buenas Prácticas de Preparación de Medicamentos en los Servicios de Farmacia Hospitalaria. Método: Se elaboró una tabla de estabilidades con los medicamentos citostáticos. Los datos de estabilidad fisicoquímica se obtuvieron de fichas técnicas y revisiones bibliográficas. El nivel de riesgo fue asignado por la matriz de riesgo en función de los requisitos de cada preparación. Cuando la estabilidad fisicoquímica era igual o superior a la indicada por la matriz, se asumieron los plazos de validez de la matriz; en caso contrario, los plazos de validez coincidieron con el periodo máximo de estabilidad fisicoquímica. Resultados: Se revisaron 61 fármacos. Se asumió el plazo de validez físico-química en el 45,9% de los viales abiertos/ reconstituidos y en el 50,8% de las mezclas citostáticas, y el indicado por la matriz de riesgo en el resto, respectivamente. Según la matriz, el nivel de riesgo fue medio en todos los medicamentos citostáticos salvo en uno, que resultó de riesgo alto. Ningún medicamento resultó de riesgo bajo. Conclusiones: Para asignar el plazo de validez de los viales abiertos/reconstituidos y de las mezclas citostáticas no solo es necesario tener en cuenta los datos de estabilidad físico-química, sino también el nivel de riesgo y los requisitos de preparación, permitiendo unos plazos de validez más adecuados (AU)

Objective: To establish limits of validity to opened or reconstituted vials and cytostatic mixtures according to their physico-chemical stability and the level of risk and preparation requirements. The level of risk and preparation requirements were assigned by the risk matrix the Guide of Good Practice of Preparation of Drugs in Hospital Pharmacy Services. Method: A table of stabilities of cytostatic drugs was developed. Physicochemical stability data were obtained from data sheets and literature reviews. The level of risk was assigned by the matrix of risk depending on the requirements of each preparation. When the physico-chemical stability was equal to or higher than indicated by the matrix, it is assumed the terms of validity of the matrix; otherwise, validity periods coincided with the peak period of physicochemical stability. Results: 61 drugs were reviewed. It was assumed the chemical term of validity in 45.9% of opened/reconstituted vials and 50.8% of cytostatic mixtures, and indicated by the risk in the rest array, respectively. According to the matrix, the level of risk was medium in most of cytostatic drugs. Only one preparation was high risk. No preparation obtained low-risk. Conclusions: To assign the term of validity of opened/reconstituted vials and cytostatic mixtures not only it is necessary to consider physical and chemical stability. The level of risk and preparation requirements are also important, allowing more adequate validity periods (AU)

Ibuprofeno intravenoso / No disponible

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The history and evolution of outpatient parenteral antibiotic therapy (OPAT).

Outpatient parenteral antibiotic therapy (OPAT) is now a widely accepted and safe therapeutic option for carefully selected patients. Benefits include cost savings and improved patient satisfaction; risks include failure to adhere to care, unexpected changes in the underlying infection, and adverse drug and intravenous access events. We report on our 40-year experience with OPAT in a single healthcare system in the USA and highlight OPAT developments in several countries. We compared data on patients treated in our programme over two time periods: Period 1 from 1978 to 1990; and Period 2, calendar year 2014. In Period 2 paediatric patients were excluded. Between Periods 1 and 2, changes included an almost three-fold increase in the number of patients treated per year (80 vs. 229), treatment of more patients with severe orthopaedic-related infections (20% vs. 38%), a marked increase in the use of peripherally inserted central catheters to administer antibiotics (20% vs. 98%), a shorter duration of inpatient stay and a longer duration of OPAT (13 days vs. 24 days). Other changes in Period 2 included treatment of 20% of patients without antecedent hospitalisation, and use of carbapenems rather than cephalosporins as the most frequently administered agents. OPAT was safe, with rehospitalisation rates of 6% and 1% in Periods 1 and 2, respectively. We recommend increased access to structured OPAT teams and the development of standard definitions and criteria for important outcome measures (e.g. clinical 'cure' and unplanned hospital re-admissions). These steps are critical for patient safety and financial stewardship of resources.

Intravenous thrombolysis in acute ischemic stroke: standard and potential future applications.

Acute ischemic stroke is a medical emergency requiring urgent treatment. Randomized clinical trial and Phase IV data have provided unequivocal evidence that intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) improves early functional outcomes by restoring brain perfusion. Moreover, these studies have shed substantial light on the factors which are associated with more favorable outcome with tPA and are related to the highest benefit-to-risk ratio. Stroke physicians should consider vascular imaging techniques to aid decision making with thrombolytic therapy. The presence of intracranial occlusion is the target of treatment with early recanalization being the goal. Successful use of intravenous thrombolysis depends on a sound understanding of the decision-making process and organization of the treating team who strives for early treatment initiation and strict adherence to the protocol. Intravenous rt-PA within 4.5 h of onset should now be a standard treatment of acute disabling ischemic stroke throughout the world. This review also summarizes intravenous thrombolysis contraindications as well as the safety of novel reperfusion therapies including tenecteplase, sonothrombolysis and the combination of alteplase with direct thrombin inhibitors or glycoprotein IIb/IIIa receptor antagonists.

Microdosing and drug development: past, present and future.

INTRODUCTION: Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. AREAS COVERED: The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. EXPERT OPINION: Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date.

The impact of technology dependence on children and their families.

Advances in medical care and technologies have prolonged life for many children with medical complexity. These advances and their effects reinforce the need for further research to determine how children and their families are being affected by technology dependence and their quality of life. A review of the literature suggests that children, as well as their family members, are negatively affected by technology dependence in a variety of psychosocial domains. Implications for clinical care and future research of this population are discussed.