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Background/Aims Functional lumen imaging probe (FLIP) Panometry has demonstrated utility in the assessment of esophageal motility as a complement to existing methodologies like high-resolution manometry. However, as FLIP is typically performed with sedation during routine endoscopy, there is potential for impact of sedation agents on esophageal motility. We aim to examine the effects of conscious sedation with midazolam and fentanyl on FLIP Panometry metrics and classification. Methods A cross-over study was conducted on 12 healthy, asymptomatic volunteers that completed FLIP while sedated with intravenous fentanyl and midazolam and while awake on a separate day. FLIP was performed in the same manner in both conditions with transoral placement of the FLIP and stepwise FLIP filling. During awake FLIP, subjects also rated the presence and intensity of esophageal perception. Results In both experimental conditions, all subjects demonstrated normal motility. The esophagogastric junction distensibility index was lower (median [interquartile range]: 5.8 [5.15-6.85] vs 8.9 [7.68-9.38] mm2/mmHg; P = 0.025), and the FLIP pressure was higher (46.5 [38.125-52.5] vs 33 [26-36.8] mmHg; P = 0.010) in the sedated condition compared to the awake condition. Maximum esophagogastric junction diameter and body distensibility plateau were no different between conditions (P = 0.999 and P = 0.098, respectively). Perception of esophageal sensation during awake FLIP was reported in 7/12 (58%) subjects. Conclusions While numeric differences in FLIP Panometry metrics were observed between sedated and awake FLIP in healthy subjects, these differences did not change the FLIP Panometry diagnosis. Sedated FLIP offers a well-tolerated method to assess esophageal motility during endoscopy. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 45-year-old male who was envenomated by his pet Trimeresurus insularis, a blue Indonesian pit viper. The patient presented to an emergency department in the United States and consultation with a poison center and medical toxicologist was obtained. Although Thai green pit viper antivenom is not approved by the US FDA, it was recommended based on in vitro data. The patient was transferred to another hospital to acquire the antivenom and received multiple doses, resulting in improvement in pain and swelling. Challenges in managing exotic snake envenomation in the US were highlighted, including the need for reimbursement to lending institutions and the regulatory requirements for using foreign antivenoms. Preemptive relationship development between poison centers, hospital pharmacies, IRBs, and venom lending facilities was suggested to navigate these challenges. [Extracted from the article]

Management of patients with salicylate toxicity frequently requires urine alkalinization to enhance excretion of salicylate. One strategy for determining when to stop urine alkalinization is to wait for two consecutive serum salicylate concentrations to be less than 300 mg/L (2.17 mmol/L) and declining. When alkalinization of the urine ceases, a rebound in serum salicylate concentration can occur from tissue redistribution or delayed gastrointestinal absorption. Whether this can lead to rebound toxicity is not well understood. This was a single-center, retrospective review of cases with a primary ingestion of acetylsalicylic acid reported to the local poison center over a five-year period. Cases were excluded if the product was not listed as the primary ingestion or if there was no serum salicylate concentration documented after discontinuation of intravenous sodium bicarbonate infusion. The primary outcome was the incidence of serum salicylate rebound to a concentration greater than 300 mg/L (2.17 mmol/L) after discontinuation of intravenous sodium bicarbonate infusion. A total of 377 cases were included. Of these, eight (2.1%) had a serum salicylate concentration increase (rebound) after stopping the sodium bicarbonate infusion. All these cases were acute ingestions. Five of the eight cases had rebound serum salicylate concentrations that were greater than 300 mg/L (2.17 mmol/L). Of these five patients, only one reported recurrent symptoms (tinnitus). Prior to stopping urinary alkalinization, the last or the last two serum salicylate concentrations were less than 300 mg/L (2.17 mmol/L) in three and two cases, respectively. In patients with salicylate toxicity, the incidence of rebound in serum salicylate concentration after cessation of urine alkalinization, is low. Even if serum salicylate rebounds to supratherapeutic concentrations, symptoms are often absent or mild. Routine repeat serum salicylate concentrations after urine alkalinization is stopped may be unnecessary unless symptoms recrudesce. [ABSTRACT FROM AUTHOR]

Acetaminophen is undetectable in plasma from more than half of patients believed to have acute liver failure due to overdose. Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: A case series. B SELF-ASSESSMENT QUESTIONS b Access to the Self-Assessment Questions for purchase of CPE or BCPS credit: https://bit.ly/2nKnnjl A pharmacist staffing a poison control center (PCC) is contacted by an ED physician regarding a patient with iron overdose. PSAP in JACCP features are developed from activities presented as part of the Pharmacotherapy Self-Assessment Program (PSAP). [Extracted from the article]

Study objective: The objective of this study was to evaluate clinical outcomes associated with time to administration and dose of four‐factor prothrombin complex concentrate (4F‐PCC) in patients with ICH on warfarin. Design: This was a single‐center retrospective analysis of patients with ICH on warfarin who received 4F‐PCC. Setting: The site of the study was a large, Level I trauma, academic medical center with a dedicated neurologic intensive care unit and an emergency department (ED) that has approximately 72,000 visits annually. Patients: Patients were included if they were ≥18 years of age, diagnosed with ICH, had an INR >1 due to warfarin use, and received both 4F‐PCC and IV vitamin K for anticoagulation reversal. Exclusion criteria included patients who were less than 18 years of age, were not currently taking warfarin, had a bleeding site other than ICH, were pregnant or incarcerated, had an inadequate medical record, had a left ventricular assist device, had known liver disease with Child‐Pugh Class C, received anticoagulation with heparin therapy within 24 h of anticoagulation reversal, or did not receive vitamin K within 24 h of hospital admission. Intervention: Our primary outcome was a composite of hematoma expansion or death due to neurologic injury. Treatment groups were defined as receipt of 4F‐PCC within 0–30, 31–60, 61–90, 91–120 min, or greater than 120 min. Hematoma expansion was defined as any increase in hematoma size as assessed by a radiologist via standard 6‐h CT. Death due to neurologic injury was defined as death prior to a repeat CT being performed or documentation of a neurologic cause of death. Adequate INR reversal (INR ≤1.3 on repeat INR) vs. inadequate INR reversal and weight‐based vs. fixed‐dose 4F‐PCC were also assessed. Measurements and Main Results: A total of 94 patients met the inclusion criteria. Forty‐one patients (43.6%) met the composite endpoint, including 60% of the 31–60 min group, 47.6% of the 61–90 min group, 71.4% of the 91–120 min group, and 30.6% of the >120‐min group. A significant difference in primary outcome occurred between the 91–120 min and >120‐min groups (71.4% vs. 30.6%; p= 0.005), but this difference was not observed when accounting for disparities in Glasgow Coma Scale (GCS). Patients with adequate INR reversal were less likely to meet the primary endpoint than those with inadequate INR reversal (28.1% vs. 58.6%; p= 0.0059). There was less failure of anticoagulation reversal with weight‐based dosing compared with fixed dosing (24.2% vs. 65.0%; p< 0.001). Conclusions: No difference in clinical outcomes among 4F‐PCC dosing strategies or time windows to administration was observed in patients with GCS <15. Rates of repeat INR ≤1.3 were higher with weight‐based dosing, suggesting investigation of populations in which fixed dosing may be inappropriate is warranted. [ABSTRACT FROM AUTHOR]

Background:Teleneurology has been well described for acute stroke, but outpatient use has been limited. At home, virtual visits have the potential to improve access to neurological care. Introduction:This study reports on the use of a personal device videoconferencing platform for outpatient neurologic follow-up visits. Materials and Methods:This is a cross-sectional study that identified all virtual neurologic follow-up visits completed by patients ≥18 years at a single institution over 4 years. Virtual visits were conducted by personal smartphone or computer via videoconferencing with a provider. Patients were asked to rate their overall experience with the visit and provider (five-point scale). Travel distance from the institution was calculated using patient's home addresses. Results:Three thousand nine hundred thirteen patients completed 5,581 virtual visits during the study (mean age 49.4 ± 17.0 years, 58.7% female). Number of virtual visits increased from 30 in year 1 to 4,468 in year 4. Virtual visits were completed in all outpatient neurologic subspecialties. A total of 30.1% of patients were local (<50 miles), 25.9% were near regional (50–150 miles), 21.7% were far regional (151–270 miles), and 22.2% were remote (>270 miles). A distance of 1,327,128 miles of travel was prevented across the 5,581 visits. On average, patients rated their overall virtual visit experience 4.7/5 ± 0.89 and rated their provider 4.9/5 ± 0.48. Discussion:Virtual visits prevented a substantial amount of travel and resulted in high patient satisfaction. The sizable proportion of local patients may indicate that teleneurology provides important access for reasons beyond travel distance. Conclusion:This study demonstrates the feasibility of implementing outpatient teleneurology services. [ABSTRACT FROM AUTHOR]

Background: Exposures to bromethalin rodenticides have increased since restrictions were placed on long acting anticoagulant rodenticide (LAAR) registrations in 2008. Bromethalin works, in part, by uncoupling mitochondrial oxidative phosphorylation. Toxicity in humans is not well characterized and no antidote is available. Methods: This retrospective observational study analyzed data from the National Poison Data System (NPDS). The data set was derived from single substance bromethalin ingestions followed to a known medical outcome that were reported to US poison centers from 01/01/2008 to 12/31/2017. Results: There were 2674 bromethalin exposures in the NPDS database that met inclusion criteria. Of these exposures 2227 (83.28%) were pediatric, aged 16 days–12 years. Within this population, no effects were seen in 2143 (96.38%) of the exposures, 74 (3.32%) had minor effects, and 10 (0.45%) had moderate effects. No major clinical effects or deaths occurred in pediatric patients, although one patient with a major effect was of unknown age. Exposures in patients >12 years encompassed 391 patients aged 13–94 years. No effect was seen amongst 257 (65.73%) of the patients, 100 (25.58%) had minor effects, 23 (5.88%) had moderate effects, nine (2.30%) had major effects, and two (0.51%) patients died. Intentional ingestions among these patients accounted for one (0.25%) death and four (1.02%) major effects. Case details of the intentional ingestion death suggest the possibility of a miscoded long acting coagulant rodenticide. Conclusions: No major effects or deaths were seen in pediatric exposures. A majority of the possible bromethalin exposures involving adults reported to poison centers resulted in minor or no effects, though seizures, death and one questionable case of coagulopathy were documented. This dataset suffers from its retrospective nature, reliance on caller information, selection bias, information bias, and miscoding. It is possible that one or both deaths attributed to bromethalin exposure were not actually due to bromethalin. [ABSTRACT FROM AUTHOR]

The synthesis of asymmetric (-)-laulimalide by exploiting the asymmetric glycolate alkylation reaction is described. Laulimalide is a potent cell growth inhibitor and inhibits proliferation of multidrug-resistant cell line.

Background: The coronavirus disease of 2019 (COVID-19) pandemic and the need for social distancing have dramatically changed health care delivery. There is an urgent need to continue to deliver outpatient care for chronic neurological disease and teleneurology has the potential to fulfill this gap. Introduction: This study reports the implementation and utilization of teleneurology across all neurological subspecilities during the COVID-19 pandemic. Materials and Methods: This is a retrospective observational study that identified all in-person and teleneurology outpatient nonprocedural visits from January 5 to April 4, 2020, across neurological specialties at a single academic center. Visit volumes were assessed weekly and practice patterns were compared before and after March 15, 2020, as this was the date of a major statewide stay-at-home order in Ohio. Results: Before March 15 the mean in-person visit per week was 5129.4 and decreased to 866.7 after that date. The mean teleneurology visits per week increased from 209.1 to 2619.3 for the same time period. The overall teleneurology visit volume in the 3 weeks after March 15 increased by 533%. Discussion: In a relatively short time frame of 3 weeks, a single academic center was able to dramatically increase teleneurology visits to provide outpatient neurological care. Conclusions: This study demonostrates that teleneruology can be a solution for outpatient neurological care in the context of COVID-19. The increased utilization of teleneurology during this crisis has the potential to expand teleneurology and improve access to neurological care in the future outside the pandemic setting. [ABSTRACT FROM AUTHOR]

Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability. [ABSTRACT FROM AUTHOR]

The determination of forming limit curves and deformation features of AA5754 aluminium alloy are studied in this article. The robust and repeatable experiments were conducted at a warm forming temperature range of 200 °C-300 °C and at a forming speed range of 20-300 mm/s. The forming limit curves of AA5754 at elevated temperatures with different high forming speeds have been obtained. The effects of forming speed and temperature on limiting dome height, thickness variation and fracture location are discussed. The results show that higher temperatures and lower forming speeds are beneficial to increasing forming limits of AA5754; however, lower temperatures and higher forming speeds contribute to enhancing the thickness uniformity of formed specimens. The decreasing forming speed and increasing temperature result in the locations of fracture to move away from the apexes of formed specimens. It is found that the analysis of deformation features can provide a guidance to understand warm forming process of aluminium alloys. [ABSTRACT FROM AUTHOR]

Dear Editor In recent years, much discussion surrounds higher dosing of intravenous (IV) n-acetylcysteine (NAC) in acetaminophen toxicity [[1]]. Commonly, this is described as a "three-bag" method for IV NAC administration, implying that, over each dosing interval a separate NAC dose is injected into its own bag of IV fluid and then given as a separate infusion. For example, a hospital may be instructed to administer the "one-bag" NAC regimen and logically conclude they should administer the three-bag regimen's daily dosing as a single, continuous infusion. [Extracted from the article]

Dear Editor, Ethosuximide (ESM) is an antiepileptic used for the treatment of absence seizures. A single case series in patients with chronic renal disease who underwent iHD after one therapeutic dose of ESM showed a reduction in drug concentration by 38.8-52.4% [[6]]. [Extracted from the article]

Species distribution models have great potential to efficiently guide management for threatened species, especially for those that are rare or cryptic. We used MaxEnt to develop a regional-scale model for the koala Phascolarctos cinereus at a resolution (250 m) that could be used to guide management. To ensure the model was fit for purpose, we placed emphasis on validating the model using independently-collected field data. We reduced substantial spatial clustering of records in coastal urban areas using a 2-km spatial filter and by modeling separately two subregions separated by the 500-m elevational contour. A bias file was prepared that accounted for variable survey effort. Frequency of wildfire, soil type, floristics and elevation had the highest relative contribution to the model, while a number of other variables made minor contributions. The model was effective in discriminating different habitat suitability classes when compared with koala records not used in modeling. We validated the MaxEnt model at 65 ground-truth sites using independent data on koala occupancy (acoustic sampling) and habitat quality (browse tree availability). Koala bellows ( n = 276) were analyzed in an occupancy modeling framework, while site habitat quality was indexed based on browse trees. Field validation demonstrated a linear increase in koala occupancy with higher modeled habitat suitability at ground-truth sites. Similarly, a site habitat quality index at ground-truth sites was correlated positively with modeled habitat suitability. The MaxEnt model provided a better fit to estimated koala occupancy than the site-based habitat quality index, probably because many variables were considered simultaneously by the model rather than just browse species. The positive relationship of the model with both site occupancy and habitat quality indicates that the model is fit for application at relevant management scales. Field-validated models of similar resolution would assist in guiding management of conservation-dependent species. [ABSTRACT FROM AUTHOR]

While the exact incidence of this type of exposure is not entirely known due to reporting limitations, clinicians should be aware of potential medical termination methods and should inquire about specific pregnancy termination procedures for treatment optimization. While cardiocentesis with potassium chloride is a more common method of feticide, digoxin has also been used off label by intra-amniotic (IA) or intra-fetal (IF) injection to induce fetal demise in late second-trimester pregnancy termination [[1]]1 [1]. In 2016, most abortions (91%) were performed at less than 13 weeks' gestation; a smaller number of abortions (7.7%) were performed at 14-20 weeks' gestation, and even fewer (1.2%) were performed at >= 21 weeks' gestation [[5]]. [Extracted from the article]

BACKGROUND: Tapentadol (Nucynta) is indicated for the treatment of moderate to severe pain in adults. Tapentadol's mechanism of action consists of acting as an agonist on the m-opioid receptor and by inhibiting the reuptake of norepinephrine. There are no published reports on the toxicity of tapentadol in pediatric patients. The goals of this study are to describe the incidence, medical outcomes, clinical effects, and treatment secondary to tapentadol exposure. METHODS: This retrospective observational study used data from the National Poison Data System. Inclusion criteria were exposure to tapentadol from November 1, 2008 to December 31, 2013; age 0 to 17 years; single ingestion; and followed to a known outcome. RESULTS: There were 104 patients who met the inclusion criteria. Eighty patients were aged ≤6, 2-year-olds the most common age group (60.6%). There were 52 male and 52 female patients. Of the 104 patients, 93 had unintentional exposures. No deaths were reported. Sixty-two of the patients had no effect, 34 had minor effects, 6 had moderate and 2 had major effects. Thirty patients reported drowsiness and lethargy. Other effects reported included nausea, vomiting, miosis, tachycardia, respiratory depression, dizziness/vertigo, coma, dyspnea, pallor, vomiting, edema, hives/welts, slurred speech, pruritus, and hallucinations/delusions. Fifty-three patients were reported to have no medical intervention. CONCLUSIONS: This is the first study examining the toxic effects of tapentadol in a pediatric population. Although a majority of the patients in this review developed no effect from their exposure, two had life-threatening events. The most common effects reported were opioidlike. [ABSTRACT FROM AUTHOR]