Selective early medical treatment of the patent ductus arteriosus in extremely low gestational age infants: a pilot randomised controlled trial protocol (SMART-PDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in extremely preterm infants and is associated with poor clinical outcomes. Uncertainty exists on whether early pharmacotherapeutic treatment of a clinically symptomatic and echocardiography-confirmed haemodynamically significant PDA in extremely preterm infants improves outcomes. Given the wide variation in the approach to PDA treatment in this gestational age (GA) group, a randomised trial design is essential to address the question. Before embarking on a large RCT in this vulnerable population, it is important to establish the feasibility of such a trial. METHODS AND ANALYSIS: Design: a multi-centre, open-labelled, parallel-designed pilot randomised controlled trial. Participants: preterm infants born <26 weeks of gestation with a PDA diagnosed within 72 hours after birth. Intervention (selective early medical treatment (SMART) strategy): selective early pharmacological treatment of a moderate-severe PDA shunt (identified based on pre-defined clinical signs and routine screening echocardiography) within the first 72 postnatal hours with provision for repeat treatment if moderate-severe shunt persists. Comparison (early conservative management strategy): no treatment of PDA in the first postnatal week. Primary outcomes: (1) proportion of eligible infants recruited during the study period; (2) proportion of randomised infants treated outside of protocol-mandated therapy. Sites and sample size: the study is being conducted in seven neonatal intensive care units across Canada and the USA with a target of 100 randomised infants. Analysis: the primary feasibility outcomes will be expressed as proportions. A pre-planned Bayesian analysis will be conducted for secondary clinical outcomes such as mortality, severe intraventricular haemorrhage, procedural PDA closure and chronic lung disease to aid stakeholders including parent representatives decide on the appropriateness of enrolling this vulnerable population in a larger trial if the feasibility of recruitment in the pilot trial is established. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1027298) and six additional participating sites. On the completion of the study, results will be presented at national and international meetings, published in peer-reviewed journals and incorporated into existing systematic reviews. TRIAL REGISTRATION NUMBER: NCT05011149 (WHO Trial Registration Data Set in Appendix A). PROTOCOL VERSION: Ver 7.2 (dated July 19, 2023).

Quality of health economic evaluations in emergency medicine journals: a systematic review.

OBJECTIVE: Health economic evaluations are used in decision-making regarding resource allocation and it is imperative that they are completed with rigor. The primary objectives were to describe the characteristics and assess the quality of economic evaluations published in emergency medicine journals. METHODS: Two reviewers independently searched 19 emergency medicine-specific journals via Medline and Embase from inception until March 3, 2022. Quality assessment was completed using the Quality of Health Economic Studies (QHES) tool, and the primary outcome was the QHES score out of 100. Additionally, we identified factors that may contribute to higher-quality publications. RESULTS: 7260 unique articles yielded 48 economic evaluations that met inclusion criteria. Most studies were cost-utility analyses and of high quality, with a median QHES score of 84 (interquartile range, IQR: 72, 90). Studies based on mathematical models and those primarily designed as an economic evaluation were associated with higher quality scores. The most commonly missed QHES items were: (i) providing and justifying the perspective of the analysis, (ii) providing justification for the primary outcome, and (iii) selecting an outcome that was long enough to allow for relevant events to occur. CONCLUSIONS: The majority of health economic evaluations in the emergency medicine literature are cost-utility analyses and are of high quality. Decision analytic models and studies primarily designed as economic analyses were positively correlated with higher quality. To improve study quality, future EM economic evaluations should justify the choice of the perspective of the analysis and the selection of the primary outcome.

ABSTRAIT: OBJECTIFS: Les évaluations économiques de la santé sont utilisées dans la prise de décisions concernant l'affectation des ressources et il est impératif qu'elles soient réalisées avec rigueur. Les principaux objectifs étaient de décrire les caractéristiques et d'évaluer la qualité des évaluations économiques publiées dans les revues de médecine d'urgence. MéTHODES: Deux examinateurs ont effectué une recherche indépendante dans 19 revues spécialisées en médecine d'urgence au moyen de Medline et d'Embase, du début jusqu'au 3 mars 2022. L'évaluation de la qualité a été effectuée à l'aide de l'outil Quality of Health Economic Studies (QHES), et le résultat principal a été la note de l'QHES sur 100. De plus, nous avons relevé des facteurs qui pourraient contribuer à des publications de meilleure qualité. RéSULTATS: 7260 articles uniques ont produit 48 évaluations économiques qui répondaient aux critères d'inclusion. La plupart des études étaient des analyses coût-utilité et de haute qualité, avec un score médian de l'EPQE de 84 (plage interquartile, IQR : 72,90). Les études fondées sur des modèles mathématiques et celles conçues principalement comme une évaluation économique ont été associées à des notes de qualité supérieure. Les éléments les plus souvent omis de l'EPQH étaient : i) fournir et justifier la perspective de l'analyse, ii) fournir une justification pour le résultat principal, et iii) choisir un résultat qui était suffisamment long pour permettre aux événements pertinents de se produire. CONCLUSIONS: La majorité des évaluations économiques de la santé dans la littérature sur la médecine d'urgence sont des analyses coût-utilité et sont de grande qualité. Les modèles d'analyse décisionnelle et les études principalement conçus comme des analyses économiques ont été positivement corrélés avec une qualité supérieure. Pour améliorer la qualité des études, les futures évaluations économiques des ME devraient justifier le choix de la perspective de l'analyse et le choix du résultat principal.

Monitoring Magnesium Stearate Blending in a V-Blender Through Passive Vibration Measurements.

Process analytical technologies are implemented within the pharmaceutical manufacturing process to rectify issues associated with current sampling methods. These include inline monitoring methods such as passive vibration measurements which are non-intrusive and less costly to other methods. In the final mixing stage of the tablet manufacturing process, a lubricant is added to ensure the mixture is ejected from the tablet die cleanly. To monitor this process, an accelerometer was attached to the lid of the V-blender loaded with various particles and magnesium stearate. At a fixed fill level, the lubricant concentration and particle mass were varied to investigate the effects of changes in process parameters on the signal vibrations measured by the sensor, the coefficient of restitution, and the flowability. It was found that measured vibrations from stress waves propagated upon collisions of the particles with the V-shell respond to and can distinguish differences in particles. As well, the magnesium stearate layer around particles alters energy dissipation and subsequently the measured vibrations. A mixing endpoint of uniform distribution of magnesium stearate with primary particles can be identified from vibrations measured by an accelerometer attached to the lid of the V-blender. The flowability change was considered negligible in the particles due to their physical morphology. These findings indicate that passive vibration measurements can be a viable, non-intrusive monitoring method while providing insight into V-blender mixing behaviors as well as improving process efficiency.

An Investigation of Magnesium Stearate Mixing Performance in a V-Blender Through Passive Vibration Measurements.

Prior to compression in tablet manufacturing, a lubricant is added and mixed in a V-blender to ensure the mixture is ejected from the tablet die smoothly. Mixing is conducted batch-wise and must be analyzed offline afterwards to ensure the mixture is uniform and will produce desired tablet properties, thereby a costly and time-consuming step within the manufacturing process. To improve process efficiency, inline monitoring methods using passive acoustic emissions or vibration measurements could be implemented. Methods are non-destructive, non-invasive, and have a reduced capital cost compared to traditional methods. Using an accelerometer affixed to the lid of the V-shell, magnesium stearate was added to glass beads and monitored to determine the effect of loading configuration and fill level on mixing performance and measured vibrations. Axial loading configurations performed better than radial configurations due to the limited axial dispersion from the geometry of the V-shell. Mixing was hindered at an increased fill level due to convective and axial dispersion. The optimal fill level of a V-blender was found to be 21-23% by volume. Monitoring magnesium stearate mixing using passive vibration measurements is a non-intrusive and potentially inline method that could significantly improve pharmaceutical process efficiency.

Associations between measures of vascular structure and function and systemic circulating blood markers in humans.

Examination of relationships between systemic markers and functional measures of arterial structure and function may assist in determining alternative indices of vascular regulation and designing and evaluating interventions to improve arterial structure and function. Twenty young healthy individuals, 20 older healthy men, and 26 individuals with coronary artery disease (CAD), comprising a spectrum of vascular health, participated. Systemic markers of vascular structure and function included: pro-collagen type I C-peptide (PIP) - marker of collagen synthesis, C-telopeptide of type I collagen (CTX) - marker of collagen degradation, endothelin-1 (ET-1) - vasoconstrictor, and interleukin-6 (IL-6) - inflammatory marker. Functional measures of arterial structure and function included carotid artery distensibility and brachial artery flow-mediated dilation (FMD). Moderate positive relationships were observed between carotid distensibility and CTX and PIP (r = 0.57, P < 0.0001 and r = 0.47, P < 0.0001). A negative correlation exists between ET-1 and FMD (r = -0.44, P = 0.0004); however, no relationship was observed between IL-6 and FMD (P = 0.25). Over a broad range of vascular health, relationships were observed between markers of type I collagen turnover and arterial stiffness and between a marker of vasoconstriction and endothelial function. These results indicate that regulatory links, between the indices examined, exist. Therefore, monitoring systemic markers rather than functional vascular measures, may provide sufficient information about vascular health and should be considered in the design and evaluation of vascular interventions.

Quest for business intelligence in health care.

In an era of reform, providers are examining more forward-thinking business intelligence strategies, according to a recent study. Enterprise business intelligence tool sets offer a breadth of design and functionality that often are capable of serving the enterprise. One limitation of broader tool sets is that they may lack needed application-specific functionality or prebuilt healthcare content for a specific department.