The Impact of Inter-Hospital Transfer on Clinical Outcomes following Endovascular Treatment for Acute Ischemic Stroke

PURPOSE Hospitals designated as primary stroke centers offer noninvasive treatment for acute ischemic stroke, but only comprehensive stroke centers are equipped to provide endovascular treatment. When stroke patients needing endovascular treatment present to the emergency department at a primary stroke center, they then require inter-hospital transfer to a comprehensive center for definitive treatment. Recent studies have found significant treatment delays and poor clinical outcomes in patients requiring inter-hospital transfer1,2. The primary aim of this study is to determine if inter-hospital transfer impacts clinical outcomes after endovascular treatment for acute ischemic stroke. A secondary aim is to determine whether inter-hospital transfer coincides with any significant treatment delay. METHODS This study involves retrospective chart review for 107 patients undergoing endovascular treatment for acute ischemic stroke at one of three hospitals in Austin, Texas from October 2016 to September 2018. 26 patients required inter-hospital transfer, while 81 (the control group) presented directly to a hospital offering endovascular treatment. Two-tailed T- and U-tests were used for analysis of parametric and non-parametric variables pertaining to time intervals and baseline characteristics. Odds ratios were calculated to compare dichotomized outcomes between groups, with significance determined by chi-square. RESULTS Inter-hospital transfer significantly prolonged onset to groin (mean difference = 37.2 min, p=.02). The transfer group was more likely to experience intracranial hemorrhage (53.9% > 22.2%, p<.01). Clinical outcomes did not significantly differ between groups. CONCLUSIONS Although observed trends in these data suggest poor outcomes for transfer patients, small sample size limits the significance of these findings. However, the significant treatment delay seen in the transfer group warrants a discussion on city protocol changes regarding patient transport via emergency services. Protocol changes favoring direct delivery of patients to comprehensive stroke centers may reduce treatment delay and yield improved clinical outcomes.Dell Medical Schoo

LDLR-Gene therapy for familial hypercholesterolaemia: Problems, progress, and perspectives

Coronary artery diseases (CAD) inflict a heavy economical and social burden on most populations and contribute significantly to their morbidity and mortality rates. Low-density lipoprotein receptor (LDLR) associated familial hypercholesterolemia (FH) is the most frequent Mendelian disorder and is a major risk factor for the development of CAD. To date there is no cure for FH. The primary goal of clinical management is to control hypercholesterolaemia in order to decrease the risk of atherosclerosis and to prevent CAD. Permanent phenotypic correction with single administration of a gene therapeutic vector is a goal still needing to be achieved. The first ex vivo clinical trial of gene therapy in FH was conducted nearly 18 years ago. Patients who had inherited LDLR gene mutations were subjected to an aggressive surgical intervention involving partial hepatectomy to obtain the patient's own hepatocytes for ex vivo gene transfer with a replication deficient LDLR-retroviral vector. After successful re-infusion of transduced cells through a catheter placed in the inferior mesenteric vein at the time of liver resection, only low-level expression of the transferred LDLR gene was observed in the five patients enrolled in the trial. In contrast, full reversal of hypercholesterolaemia was later demonstrated in in vivo preclinical studies using LDLR-adenovirus mediated gene transfer. However, the high efficiency of cell division independent gene transfer by adenovirus vectors is limited by their short-term persistence due to episomal maintenance and the cytotoxicity of these highly immunogenic viruses. Novel long-term persisting vectors derived from adeno-associated viruses and lentiviruses, are now available and investigations are underway to determine their safety and efficiency in preparation for clinical application for a variety of diseases. Several novel non-viral based therapies have also been developed recently to lower LDL-C serum levels in FH patients. This article reviews the progress made in the 18 years since the first clinical trial for gene therapy of FH, with emphasis on the development, design, performance and limitations of viral based gene transfer vectors used in studies to ameliorate the effects of LDLR deficiency

Conjugative transfer frequencies of mef(A)-containing Tn1207.3 to macrolide-susceptible Streptococcus pyogenes belonging to different emm types

The aim of this study was to examine the gene transfer potential of mef(A)-containing Tn120.3 to macrolide-susceptible Streptococcus pyogenes belonging to different emm types. Using the filter mating technique, Tn1207.3 was transferred by conjugation to 23 macrolide-susceptible recipients representing 11 emm types. PCR analysis confirmed the presence of the mef(A) gene and the comEC junction regions of the Tn1207.3 insertion in resultant transconjugants. Significant variation was found in the transfer frequency of Tn1207.3 to different Strep. pyogenes strains, and this phenomenon may contribute to the differences in mef(A) frequency observed among clinical isolates. Significance and Impact of the Study: The spread of antimicrobial resistance among pathogenic bacteria is an important problem, but the mechanisms of horizontal transfer between strains and species are often poorly understood. For instance, little is known on how macrolide resistance spreads between strains of the human pathogen Strep. pyogenes and why certain strains more commonly display resistance than others. Here, we show that Strep. pyogenes strains vary greatly in their ability to acquire a transposon encoding macrolide resistance by horizontal gene transfer in vitro. These data provide a novel insight into the transfer of antibiotic resistance between bacterial strains and offer an explanation for the differences in the frequency of resistance determinates and resistance seen among clinical isolates. © 2014 The Authors Letters in Applied Microbiology

Ethics of modifying the mitochondrial genome

Recent preclinical studies have shown the feasibility of specific variants of nuclear transfer to prevent mitochondrial DNA disorders. Nuclear transfer could be a valuable reproductive option for carriers of mitochondrial mutations. A clinical application of nuclear transfer, however, would entail germ-line modification, more specifically a germ-line modification of the mitochondrial genome. One of the most prominent objections against germ-line modification is the fear that it would become possible to alter 'essential characteristics' of a future person, thereby possibly violating the child's right to an open future. As only the nuclear DNA would contain the ingredients for individual characteristics, modification of the mtDNA is often considered less controversial than modification of the nuclear DNA. This paper discusses the tenability of this dichotomy. After having clarified the concept of germ-line modification, it argues that modification of the mtDNA is not substantively different from modification of the nuclear DNA in terms of its effects on the identity of the future person. Subsequently the paper assesses how this conclusion affects the moral evaluation of nuclear transfer to prevent mtDNA disorders. It concludes that the moral acceptability of germ-line modification does not depend on whether it alters the identity of the future child-all germ-line modifications do-but on whether it safeguards the child's right to an open future. If nuclear transfer to prevent mtDNA disorders becomes safe and effective, then dismissing it because it involves germ-line modification is unjustified

Diversifying the Healthcare Workforce: Transition of the Combat Medic to Baccalaureate-Prepared Nurse

Purpose The creation of a combat medic to accelerated Bachelor of Science in Nursing (BSN) program may offer a way to positively contribute to the nursing workforce. Therefore, the purpose of this feasibility project was to combine the four sub-roles of expert practitioner, educator, researcher, and consultant1, to design a new pathway for military combat medic entry into nursing. Methods A comparative analysis elucidated gaps in 219 different nursing skills, didactic and general education requirements, clinical hours, and transfer credits between combat medic training and the BSN curriculum at a Vermont university. Identified gaps were compared to nursing licensure requirements. A sample of combat medics was surveyed for interest level in pursuing a BSN, desired employment setting, and intent to work at the bedside for two years or longer. Feedback was collected from faculty and administrators and at schools with similar existing programs. Results Two program plans of study for 24- and 32-month completion were developed, (dependent on transfer credits and demonstrated skill competencies). Participating combat medics (84%) reported being “very interested” and 16% reported being “interested” in pursuing an accelerated program in nursing. Combat medic participants (100%) indicated that they would remain at the bedside for two years or longer. Conclusion The proposed program pathway was well-received and may offer a way to alleviate medic unemployment rates and contribute to the nursing workforce. Plans for further research include a cost-benefit analysis, more precise sampling to gauge interest levels, and determinants of requisite supplies, physical space, clinical placements, and faculty. Keywords: Nurse, Military, Medic, BSN, RN References Manley, K. (1997). A conceptual framework for advanced practice: An action research project operationalizing an advanced practitioner/consultant nurse role. Journal of Clinical Nursing, 6, 179–190