The series of experiments herein evaluated prototype drugs representing different mechanisms of antiseizure, antinociceptive or antidepressant action in a battery of preclinical pain models in adult male CF#1 mice (formalin, writhing, and tail flick) and Sprague Dawley rats partial sciatic nerve ligation (PSNL). In the formalin assay, phenytoin (PHT, 6 mg/kg), sodium valproate (VPA, 300 mg/kg), amitriptyline (AMI, 7.5 and 15 mg/kg), gabapentin (GBP, 30 and 70 mg/kg), tiagabine (TGB, 5 and 15 mg/kg), and acetominophen (APAP, 250 and 500 mg/kg) reduced both phases of the formalin response to ≤ 25% of vehicle-treated mice. In the acetic acid induced writhing assay, VPA (300 mg/kg), ethosuximide (ETX, 300 mg/kg), morphine (MOR, 5 & 10 mg/kg), GBP (10, 30, and 60 mg/kg), TGB (15 mg/kg), levetiracetam (LEV, 300 mg/kg), felbamate (FBM, 80 mg/kg) and APAP (250 mg/kg) reduced writhing to ≤ 25% of vehicle-treated mice. In the tail flick test, MOR (1.25-5 mg/kg), AMI (15 mg/kg) and TGB (5 mg/kg) demonstrated significant antinociceptive effects. Finally, carbamazepine (CBZ, 20 and 50 mg/kg), VPA, MOR (2 and 4 mg/kg), AMI (12 mg/kg), TPM (100 mg/kg), lamotrigine (LTG, 40 mg/kg), GBP (60 mg/kg), TGB (15 mg/kg), FBM (35 mg/kg), and APAP (250 mg/kg) were effective in the PSNL model. Thus, TGB was the only prototype compound with significant analgesic effects in each of the four models, while AMI, GBP, APAP, and MOR each improved three of the four pain phenotypes. This study highlights the importance evaluating novel targets in a variety of pain phenotypes.
Acute brain injury (ABI) increases morbidity and mortality in patients with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Optimal neurologic monitoring methods have not been well-explicated. We studied the use of Near-infrared Spectroscopy (NIRS) to monitor cerebral regional oxygenation tissue saturation (rSO2) and its relation to ABI in VA-ECMO. In this prospective, observational cohort study of 39 consecutive patients, we analyzed the ability of rSO2 values from continuous bedside NIRS monitoring to predict ABI during VA-ECMO support. ABI occurred in 24 (61.5%) patients. Those with ABI had a lower pre-ECMO Glasgow Coma Scale, more blood product transfusions of pRBCs and FFP, and higher APACHEII score. Baseline rSO2 values were not significantly different between cohorts (54.25 vs 58.50, p = 0.260), while the minimum rSO2 value was lower for patients who experienced an ABI than those who did not (39.75 vs 44.50, p = 0.039). In patients with ABI, 21 (87.5%) had a drop in rSO2 of 25% from baseline, compared to only 7 (46.7%) patients without ABI (p = 0.017). By ROC analysis, we found that desaturations with >25% drop from the baseline rSO2 on VA-ECMO exhibited 86% sensitivity and 55% specificity to predict ABI, with an area under the curve of 0.68. Patients with ABI were more likely to have withdrawal of life sustaining therapy (17 vs 5, p = 0.049), while neurologic outcome and mortality were not statistically different between patients with or without ABI. Our results support that cerebral NIRS is a useful, real-time bedside neuromonitoring tool to detect ABI in VA-ECMO patients. A >25% drop from the baseline was sensitive in predicting ABI occurrence. Further research is needed to assess how to implement this knowledge to utilize NIRS in developing appropriate intervention strategy in VA-ECMO patients.
Introduction: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for those in cardiopulmonary failure, including post-cardiac arrest. Despite a high volume of ECMO patients using anti-seizure medication, there is a paucity of data concerning the dosing, levels, and clinical scenarios for their use. Case Report: We present three cases of ECMO patients post-PEA arrest who were on valproic acid (VPA) for treatment of seizure and/or myoclonus. The total and free levels of VPA are reported. Discussion: The trough levels are consistent throughout therapy, suggesting VPA is not significantly removed by the ECMO circuitry. Although the total serum levels remained below the toxic range, the free level was elevated in two patients. These patients did not develop signs of toxicity. Conclusion: VPA may be an effective anti-seizure medication in ECMO patients. Free VPA levels should be more readily available to better quantify efficacy or toxicity, especially in ECMO patients.
, it has been an exciting year for the field. However, this volume of research renders it difficult to keep abreast with the latest innovations in education. This year alone in CT surgery, there were 35 education-focused abstracts, 24 sessions oriented toward emerging technology, and more than 180 sessions devoted to surgical skills and simulations. Many studies explored the role of technology-based tools in augmenting CT surgery training. These were applied to the field broadly, within subspecialties, and at all levels of medical training from medical student to senior attending. Research also grappled with how to best enhance recruitment of students into CT surgery. It is these advances in education that will prove vital to the future of CT surgery education. Reflecting on the extensive scholarly work published and presented at the major CT surgical conferences, the aim of this paper is to explore the education highlights of the 2017 to 2018 academic year and provide commentary on where the field may be headed. EDUCATIONAL RESEARCH ACROSS THE FIELD OF CT SURGERY Structure of the Field Many researchers over the course of the year investigate how the field of CT surgery is changing and how trainees in particular are responding. The presence of physician extenders within CT surgery has increased in recent years. A national survey assessing opinions of physician extender involvement showed that overall impression is favorable but that their role can occasionally impede resident education, especially in regard to patient management on the ward. 1 In regard to training structure, residents appear to prefer traditional programs to the integrated 6-year (I-6) program. The most common reasons given for not applying to the I-6 program were lack of commitment to CT surgery as a medical student and uncertainty of adequacy of I-6 training-from the belief that general surgery training is more well-rounded. 2 For general thoracic surgery, the 4/3 and traditional programs were the preferred and more common route compared with the I-6 residents, who nearly all were set on a cardiac career (adult or congenital). 2,3 I-6 programs also increase concern about decreased general surgery operative volume, which emphasizes the need for cooperation and communication between integrated and categorical program directors to ensure adequate training for all residents. 4 Understanding the advantages and challenges of the various educational paradigms, programs continue to modify and improve their curriculum to better address the perceived needs of the specialty and those of the trainees. Support for Residents' Transition to Training and to Practice Research this year focused on understanding how to better support CT surgery residents. Throughout the conferences this year, many sessions were oriented toward
Purpose In light of highly publicized media coverage on breast implant recalls and Food and Drug Administration hearings on breast implant safety, online searches of these topics have surged. It is thus critical to determine whether such searches are providing meaningful information for those who use them. Patient/laywomen-directed online education materials on breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) must not only be comprehensible but also accurate, actionable, and culturally concordant, especially as more diverse populations turn to the internet for breast implant–related information. This study assessed the overall suitability of BIA-ALCL patient–directed educational text and video-based materials online. Methods This was a cross-sectional, multimetric investigation of online text– and video-based patient-directed educational materials for BIA-ALCL using multiple validated measures. Two reviewers assessed each resource. Kruskal-Wallis and Fisher exact analyses were used as appropriate to compare text- and video-based online resources. Results In total, 30 websites and 15 videos were evaluated, more than half (56%) of which were from academic/physician or governmental/nonprofit sources. Overall, website and video content, as well as quality, varied by source. Academic/physician or governmental/nonprofit sources tended to be more comprehensive and have higher-quality information than commercial/media outlet sources. Median actionability of websites was 38%, well below the threshold of 70% used in the literature to identify actionable resources. The median suitability score for BIA-ALCL websites was 57%, which is considered “adequate” based on published thresholds. The mean overall Cultural Sensitivity Assessment Tool score for websites was 2.4; Cultural Sensitivity Assessment Tool scores higher than 2.5 are generally regarded as culturally sensitive. In general, videos were more understandable than websites. Substantial interrater reliability across the validated tools used in this study was noted using Pearson correlation coefficients. Conclusions Online resources varied in content and quality by source. As BIA-ALCL becomes an increasingly salient topic among both providers and patients, it is important to empower women with accurate information about this implant-associated cancer. Of available resources, providers should refer patients or those seeking more information to websites from governmental/academic organizations (“.gov” or “.org” domains) and videos from academic/physician or governmental sources, given that among high-quality resources, these were most clear/comprehensible. Overall, there is a need for improved online content on this topic.
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