General Synthetic Approach to Diverse Taxane Cores.

Chemical synthesis of natural products is typically inspired by the structure and function of a target molecule. When both factors are of interest, such as in the case of taxane diterpenoids, a synthesis can both serve as a platform for synthetic strategy development and enable new biological exploration. Guided by this paradigm, we present here a unified enantiospecific approach to diverse taxane cores from the feedstock monoterpenoid (S)-carvone. Key to the success of our approach was the use of a skeletal remodeling strategy which began with the divergent reorganization and convergent coupling of two carvone-derived fragments, facilitated by Pd-catalyzed C-C bond cleavage tactics. This coupling was followed by additional restructuring using a Sm(II)-mediated rearrangement and a bioinspired, visible-light induced, transannular [2 + 2] photocycloaddition. Overall, this divergent monoterpenoid remodeling/convergent fragment coupling approach to complex diterpenoid synthesis provides access to structurally disparate taxane cores which have set the stage for the preparation of a wide range of taxanes.

Risk of intracranial injury after minor head trauma in patients with pre-injury use of clopidogrel.

BACKGROUND: Clopidogrel is an adenosine diphosphate receptor antagonist. The risk of intracranial hemorrhage following minor head trauma in patients with pre-injury use of clopidogrel has not been fully determined. METHODS: This case-controlled study examined the effects of pre-injury use of clopidogrel in adult (age 14 years and older) patients with minor head trauma. RESULTS: During the study period, 1660 patients head computed tomography scans were performed in the emergency department, of which 658 met inclusion criteria. Intracranial hemorrhage was noted in 30% of patients on clopidogrel, compared with 2.2% of those patients without pre-injury use of clopidogrel. After performing a logistic regression analysis for confounders, the pre-injury use of clopidogrel was significantly associated with intracranial hemorrhage in this study population (OR 16.7; 95% CI 1.71-162.7). CONCLUSION: The use of clopidogrel is associated with a significantly increased risk of developing intracranial hemorrhage following minor trauma.

Testing a persuasive health communication intervention (PHCI) for emergency department patients who declined rapid HIV/HCV screening: a randomised controlled trial study protocol.

INTRODUCTION: Previous studies have shown that substantial percentages of emergency department (ED) patients in the USA recommended for HIV or hepatitis C (HCV) decline testing. Evidence-based and cost-effective interventions to improve HIV/HCV testing uptake are needed, particularly for people who inject drugs (PWIDs) (currently or formerly), who comprise a group at higher risk for these infections. We developed a brief persuasive health communication intervention (PHCI) designed to convince ED patients who had declined HIV/HCV testing to agree to be tested. In this investigation, we will determine if the PHCI is more efficacious in convincing ED patients to be tested for HIV/HCV when delivered by a video or in person, and whether efficacy is similar among individuals who currently, previously or never injected drugs. METHODS AND ANALYSIS: We will conduct a multisite, randomised controlled trial comparing PHCIs delivered by video versus in person by a health educator to determine which delivery method convinces more ED patients who had declined HIV/HCV testing instead to be tested. We will stratify randomisation by PWID status (current, former or never/non-PWID) to permit analyses comparing the PHCI delivery method by injection-drug use history. We will also perform a cost-effectiveness analysis of the interventions compared with current practice, examining the incremental cost-effectiveness ratio between the two interventions for the ED population overall and within individual strata of PWID. As an exploratory analysis, we will assess if a PHCI video with captions confers increased or decreased acceptance of HIV/HCV testing, as compared with a PHCI video without captions. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of the Icahn School of Medicine. The results will be disseminated at international conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05968573.

Association Between Social Determinants of Health and Traumatic Brain Injury: A Scoping Review.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Disparities exist in the populations that acquire TBIs, however, with a greater burden and poorer outcomes associated with communities of color and lower socioeconomic status. To combat health inequities such as these, institutions have begun to target social determinants of health (SDoH), which are environmental factors that affect health outcomes and risks. The SDoH may play a role in sustaining a TBI and provide modifiable targets for action to reduce the risk of TBI, especially in high-risk communities. In this study, we describe the existing literature regarding SDoH and their association with sustaining a TBI. We performed a scoping review with a comprehensive search of the Ovid MEDLINE/Embase databases. To summarize the literature, this review adapts the World Health Organization's Commission on SDoH's conceptual framework. Fifty-nine full-text articles, including five focusing on lower and middle-income countries, met our study criteria. Results of the scoping review indicate that several structural determinants of health were associated with TBI risk. Lower educational attainment and income levels were associated with higher odds of TBI. In addition, multiple studies highlight that minority populations were identified as having higher odds of TBI than their White counterparts. Literature highlighting intermediate determinants of health examined in this review describes associations between sustaining a TBI and rurality, work environment, medical conditions, medication/substance use, and adversity. Recommended exploration into lesser-researched SDoH is discussed, and the expansion of this review to other aspects of the TBI continuum is warranted.

Prevalence of hypokalemia in ED patients with diabetic ketoacidosis.

OBJECTIVE: Although patients with diabetic ketoacidosis (DKA) are expected to have total body potassium depletion, measured levels may be normal or elevated due to extracellular shifts of potassium secondary to acidosis. Because insulin therapy decreases serum potassium levels, which creates potential to precipitate a fatal cardiac arrhythmia in a patient with hypokalemia, the American Diabetes Association (ADA) recommends obtaining a serum potassium level before giving insulin. Although the ADA guidelines are clear, the evidence on which they are based is largely anecdotal. The purpose of this study was to estimate the prevalence of hypokalemia in patients with DKA before initiation of fluid resuscitation and insulin therapy. METHODS: This is a prospective cross-sectional descriptive study of patients with a capillary blood glucose level of 250 mg/dL or higher (at risk for DKA) seen in an urban county emergency department over a 1-year period. Those who consented provided basic demographic information and had a venous blood gas and chemistry panel drawn. Diabetic ketoacidosis and hypokalemia were defined using ADA recommendations. RESULTS: The mean age in our sample was 40.2 years, and 81% of patients were Hispanic. Of 503 analyzable patients with hyperglycemia, 54 (10.7%) met all criteria for DKA. Of patients with DKA, 3 (5.6%) of 54 (95% confidence interval, 1.2%-15.4%) had hypokalemia. Two of these patients had values of 3.0 mmol/L, and 1 had a value of 2.8 mmol/L. CONCLUSION: Hypokalemia was observed in 5.6% of patients with DKA. These findings support the ADA recommendation to obtain a serum potassium before initiating intravenous insulin therapy in a patient with DKA.

Legionnaires' Disease Causing Severe Rhabdomyolysis and Acute Renal Failure: A Case Report.

INTRODUCTION: Legionnaires' disease is a multisystem disease involving respiratory, gastrointestinal, and neurologic systems. This is a case of a previously healthy 44-year-old man who was diagnosed with Legionella pneumonia causing acute kidney failure and rhabdomyolysis. CASE REPORT: The patient presented with four days of chills, shortness of breath, chest discomfort, diarrhea, and myalgias. Laboratory testing revealed hyponatremia, leukocytosis, elevated inflammatory markers, renal failure, and rhabdomyolysis. He was admitted to the intensive care unit for acute hypoxemic respiratory failure, received a course of antibiotics, and more than two weeks of intermittent hemodialysis with full recovery of renal function. The pathophysiologic mechanisms by which Legionella causes rhabdomyolysis and acute kidney failure are not fully understood, although numerous mechanisms have been proposed including direct invasion of myocytes and renal tubular cells. CONCLUSION: Legionnaires' disease is one of several infections that can cause rhabdomyolysis and kidney failure. Although rarely described in the literature, it is important for emergency physicians to be aware of this clinical entity in order to implement early diagnostic testing and empiric treatment.

Risk of deaths due to injuries in travellers: a systematic review.

BACKGROUND: Annual global travel reached an all-time high of 1.4 billion international tourist visits in 2019. It is estimated that injury accounts for close to 25% of deaths in travellers, most of which are theoretically preventable. However, there are limited data available on injury occurrence and outcomes in travellers. Our objective was to better understand the relative risk of dying from injury that arises from the novel environments and behavioural changes associated with foreign travel. METHODS: A systematic literature review was conducted (PubMed, Embase and Scopus) according to PRISMA guidelines that included studies published in English since 1990 that reported injury deaths in tourists per 100 000-person years or as a proportion of total tourist deaths in comparison to a non-traveller population. We also included studies that reported data allowing calculation of these rates. Relative rates or proportions of overall injury mortality, mortality due to traffic accidents, drowning and homicide were summarized. RESULTS: In total, 1847 articles were identified, 105 underwent full-text review, and 10 articles were suitable for data extraction. There was great variability of relative risk reported, but overall, travellers appear to have a higher risk of injury mortality than domestic populations, with relative rates of injury death ranging from 1.04 to 16.7 and proportionate mortality ratios ranging from 1.43 to 3. CONCLUSIONS: Tourists should be aware of the increased risk of dying from road traffic hazards, drowning and homicide while traveling abroad. Specific geographies and activities associated with higher risk should be emphasized. Travel medicine practitioners and organizations that send people abroad should counsel travellers regarding these risks and seek ways to reduce them, including encouraging potential risk-mitigating behaviours. There is a need to improve systems of data collection and reporting on injury deaths in travellers and to study the impact of pre-travel and institutional interventions aimed at reducing this risk.

Impact of a focused trauma course on retention of provider skills, knowledge and confidence at a regional hospital in the Dominican Republic.

INTRODUCTION: Road traffic accidents are a public health epidemic, causing significant morbidity and mortality in low- and middle-income countries. The Dominican Republic (DR) ranks among the highest road traffic fatality rates in the world. There is no formalized trauma curriculum in the DR. A short trauma course was implemented at a San Pedro de Macoris, DR hospital with pre-, post- and retention evaluation of the knowledge, skills and confidence of the providers. METHODS: A 4-day trauma course was developed for medical students and residents. On days 1 and 4, providers completed pre- and post-training assessments consisting of a 40-question written exam, 1 simulation case and a trauma confidence questionnaire. Simulation cases were evaluated using a critical actions checklist and a non-technical skills scale (TNOTECHS). Assessments were repeated in 2 months to evaluate for knowledge, skill and confidence retention. A repeated measures ANOVA model was used to evaluate pre-, post- and retention training differences in the written exam, non-technical skills and critical actions scores. Confidence scores were assessed using a cumulative logistic regression model. RESULTS: A total of 65 people participated (36 medical students, 22 EM and 7 family medicine residents). Of the 65 participants, 39, 22 and 21 participants had complete scores for pre-post, pre-retention and post-retention comparisons respectively. Mean test scores for the written exam were 37.2, 63.5 and 52.2 for pre, post and retention results respectively. Comparisons between pre and post as well as pre and retention showed statistically significant differences (p=0.0001). Mean TNOTECHS total scores were 15.8, 21.3 and 20.8 for pre-, post- and retention results respectively with a significant difference found between pre- and post- training and pre- and retention training (p <0.05). Simulation mean checklist scores were 57.7%, 67.8% and 74.1% for pre-, post- and retention training respectively with a significant difference established between pre- and retention scores (p<0.05). Provider opinion that their ED patients received best care possible and patients' needs were identified and addressed showed statistically significant increases. CONCLUSION: A short trauma course can improve trauma specific knowledge, skills and confidence with significant retention at two months. A longitudinal trauma curriculum may bolster retention.

Effects of ethylene oxide chain length on crystallization of polysorbate 80 and its related compounds.

As a result of the synthesis protocol polyoxyethylene sorbitan monooleate (polysorbate 80, PS80) is a highly complex mixture of compounds. PS80 was therefore separated into its main constituents, e.g. polyoxyethylene isosorbide esters and polyoxyethylene esters, as well as mono- di- and polyesters using preparative high-performance liquid chromatography. In this comprehensive study the individual components and their ethoxylation level were verified by matrix assisted laser desorption/ionization time-of-flight and their thermotropic behavior was analyzed using differential scanning calorimetry and X-ray diffraction. A distinct correlation was found between the average length of the ethylene oxide (EO) chains in the headgroup and the individual compounds' ability to crystallize. Importantly, a critical number of EO units required for crystallization of the headgroup was determined (6 EO units per chain or 24 per molecule). The investigation also revealed that the hydrocarbon tails only crystallize for polyoxyethylene sorbitan esters if saturated. PS80 is synthesized by reacting with approximately 20 mol of EO per mole of sorbitol, however, the number of EO units in the sorbitan ester in commercial PS80 products is higher than the expected 20 (5 EO units per chain). The complex behavior of all tested compounds revealed that if the amount of several of the linear by-products is reduced, the number of EO units in the chains will stay below the critical number and the product will not be able to crystallize by the EO chains.

Sinusitis Update.

Rhinosinusitis affects many pediatric patients as well as 1 in 6 adults in any given year, resulting in ambulatory care, pediatric, and emergency department visits. Uncomplicated rhinosinusitis requires no imaging or testing and does not require antibiotic treatment. Using strict clinical diagnostic criteria may minimize unnecessary antibiotics. When indicated, amoxicillin with or without clavulanate for 5 to 10 days remains the first-line antibiotic, despite increasing incidence of staphylococcal sinusitis in the post-pneumococcal conjugate vaccine era. Emergency providers also need to recognize atypical cases in which uncommon but serious complications of sinusitis cause both morbidity and mortality.

Preparation of the Core Structure of Aspidosperma and Strychnos Alkaloids from Aryl Azides by a Cascade Radical Cyclization.

A novel approach to prepare the core structure of Aspidosperma and Strychnos alkaloids is described. The strategy is based on a cyclization cascade involving the formation of quaternary carbon center followed by trapping of the radical intermediate by an aryl azide to build the 5-membered ring of the pyrrolocarbazole system. This reaction is run with triethylborane without the need for any hydrogen atom donor such as a tin hydride or tris(trimethylsilyl)silane, and it furnishes the tetracyclic framework as a single diastereomer. The influence of different N-protecting groups on the starting iodoacetamide has been examined.