Virtual urgent care is here to stay: driving toward safe, equitable, and sustainable integration within emergency medicine.

BACKGROUND: Virtual care in Canada rapidly expanded during the COVID-19 pandemic in a low-rules environment in response to pressing needs for ongoing access to care amid public health restrictions. Emergency medicine specialists now face the challenge of advising on which virtual urgent care services ought to remain as part of comprehensive emergency care. Consideration must be given to safe, quality, and appropriate care as well as issues of equitable access, public demand, and sustainability (financial and otherwise). The aim of this project was to summarize current literature and expert opinion and formulate recommendations on the path forward for virtual care in emergency medicine. METHODS: We formed a working group of emergency medicine physicians from across Canada working in a variety of practice settings. The virtual care working group conducted a scoping review of the literature and met monthly to discuss themes and develop recommendations. The final recommendations were circulated to stakeholders for input and subsequently presented at the 2023 Canadian Association of Emergency Physicians (CAEP) Academic Symposium for discussion, feedback, and refinement. RESULTS: The working group developed and reached unanimity on nine recommendations addressing the themes of system design, equity and accessibility, quality and patient safety, education and curriculum, financial models, and sustainability of virtual urgent care services in Canada. CONCLUSION: Virtual urgent care has become an established service in the Canadian health care system. Emergency medicine specialists are uniquely suited to provide leadership and guidance on the optimal delivery of these services to enhance and complement emergency care in Canada.

RéSUMé: CONTEXTE: Les soins virtuels au Canada ont rapidement pris de l'ampleur pendant la pandémie de COVID-19 dans un environnement où les règles sont peu strictes, en réponse aux besoins urgents d'accès continu aux soins dans un contexte de restrictions en santé publique. Les spécialistes de la médecine d'urgence sont maintenant confrontés au défi de conseiller sur les services de soins d'urgence virtuels qui devraient rester dans le cadre des soins d'urgence complets. Il faut tenir compte des soins sécuritaires, de qualité et appropriés, ainsi que des questions d'accès équitable, de la demande publique et de la durabilité (financière et autre). L'objectif de ce projet était de résumer la littérature actuelle et l'opinion d'experts et de formuler des recommandations sur la voie à suivre pour les soins virtuels en médecine d'urgence. MéTHODES: Nous avons formé un groupe de travail composé de médecins urgentistes de partout au Canada qui travaillent dans divers milieux de pratique. Le groupe de travail sur les soins virtuels a effectué un examen de la portée de la documentation et s'est réuni chaque mois pour discuter des thèmes et formuler des recommandations. Les recommandations finales ont été distribuées aux intervenants pour obtenir leurs commentaires, puis présentées au symposium universitaire 2023 de l'Association canadienne des médecins d'urgence (ACMU) pour discussion, rétroaction et perfectionnement. RéSULTATS: Le groupe de travail a élaboré et atteint l'unanimité sur neuf recommandations portant sur les thèmes de la conception du système, de l'équité et de l'accessibilité, de la qualité et de la sécurité des patients, de l'éducation et des programmes, des modèles financiers et de la viabilité des services virtuels de soins d'urgence au Canada. CONCLUSION : Les soins d'urgence virtuels sont devenus un service établi dans le système de santé canadien. Les spécialistes en médecine d'urgence sont particulièrement bien placés pour fournir un leadership et des conseils sur la prestation optimale de ces services afin d'améliorer et de compléter les soins d'urgence au Canada.

Bipolar seesaw control on last interglacial sea level.

Our current understanding of ocean-atmosphere-cryosphere interactions at ice-age terminations relies largely on assessments of the most recent (last) glacial-interglacial transition, Termination I (T-I). But the extent to which T-I is representative of previous terminations remains unclear. Testing the consistency of termination processes requires comparison of time series of critical climate parameters with detailed absolute and relative age control. However, such age control has been lacking for even the penultimate glacial termination (T-II), which culminated in a sea-level highstand during the last interglacial period that was several metres above present. Here we show that Heinrich Stadial 11 (HS11), a prominent North Atlantic cold episode, occurred between 135 ± 1 and 130 ± 2 thousand years ago and was linked with rapid sea-level rise during T-II. Our conclusions are based on new and existing data for T-II and the last interglacial that we collate onto a single, radiometrically constrained chronology. The HS11 cold episode punctuated T-II and coincided directly with a major deglacial meltwater pulse, which predominantly entered the North Atlantic Ocean and accounted for about 70 per cent of the glacial-interglacial sea-level rise. We conclude that, possibly in response to stronger insolation and CO2 forcing earlier in T-II, the relationship between climate and ice-volume changes differed fundamentally from that of T-I. In T-I, the major sea-level rise clearly post-dates Heinrich Stadial 1. We also find that HS11 coincided with sustained Antarctic warming, probably through a bipolar seesaw temperature response, and propose that this heat gain at high southern latitudes promoted Antarctic ice-sheet melting that fuelled the last interglacial sea-level peak.

Rapid coupling between ice volume and polar temperature over the past 150,000 years.

Current global warming necessitates a detailed understanding of the relationships between climate and global ice volume. Highly resolved and continuous sea-level records are essential for quantifying ice-volume changes. However, an unbiased study of the timing of past ice-volume changes, relative to polar climate change, has so far been impossible because available sea-level records either were dated by using orbital tuning or ice-core timescales, or were discontinuous in time. Here we present an independent dating of a continuous, high-resolution sea-level record in millennial-scale detail throughout the past 150,000 years. We find that the timing of ice-volume fluctuations agrees well with that of variations in Antarctic climate and especially Greenland climate. Amplitudes of ice-volume fluctuations more closely match Antarctic (rather than Greenland) climate changes. Polar climate and ice-volume changes, and their rates of change, are found to covary within centennial response times. Finally, rates of sea-level rise reached at least 1.2 m per century during all major episodes of ice-volume reduction.

Definitive radiotherapy for early (T1-T2) glottic squamous cell carcinoma: a 20 year Cleveland Clinic experience.

PURPOSE: To report our 20 yr experience of definitive radiotherapy for early glottic squamous cell carcinoma (SCC). METHODS AND MATERIALS: Radiation records of 141 patients were retrospectively evaluated for patient, tumor, and treatment characteristics. Cox proportional hazard models were used to perform univariate (UVA) and multivariate analyses (MVA). Cause specific survival (CSS) and overall survival (OS) were plotted using cumulative incidence and Kaplan-Meir curves, respectively. RESULTS: Of the 91% patients that presented with impaired voice, 73% noted significant improvement. Chronic laryngeal edema and dysphagia were noted in 18% and 7%, respectively. The five year LC was 94% (T1a), 83% (T1b), 87% (T2a), 65% (T2b); the ten year LC was 89% (T1a), 83% (T1b), 87% (T2a), and 53% (T2b). The cumulative incidence of death due to larynx cancer at 10 yrs was 5.5%, respectively. On MVA, T-stage, heavy alcohol consumption during treatment, and used of weighted fields were predictive for poor outcome (p < 0.05). The five year CSS and OS was 95.9% and 76.8%, respectively. CONCLUSIONS: Definitive radiotherapy provides excellent LC and CSS for early glottis carcinoma, with excellent voice preservation and minimal long term toxicity. Alternative management strategies should be pursued for T2b glottis carcinomas.

Novel bacterial NAD+-dependent DNA ligase inhibitors with broad-spectrum activity and antibacterial efficacy in vivo.

DNA ligases are indispensable enzymes playing a critical role in DNA replication, recombination, and repair in all living organisms. Bacterial NAD+-dependent DNA ligase (LigA) was evaluated for its potential as a broad-spectrum antibacterial target. A novel class of substituted adenosine analogs was discovered by target-based high-throughput screening (HTS), and these compounds were optimized to render them more effective and selective inhibitors of LigA. The adenosine analogs inhibited the LigA activities of Escherichia coli, Haemophilus influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Staphylococcus aureus, with inhibitory activities in the nanomolar range. They were selective for bacterial NAD+-dependent DNA ligases, showing no inhibitory activity against ATP-dependent human DNA ligase 1 or bacteriophage T4 ligase. Enzyme kinetic measurements demonstrated that the compounds bind competitively with NAD+. X-ray crystallography demonstrated that the adenosine analogs bind in the AMP-binding pocket of the LigA adenylation domain. Antibacterial activity was observed against pathogenic Gram-positive and atypical bacteria, such as S. aureus, S. pneumoniae, Streptococcus pyogenes, and M. pneumoniae, as well as against Gram-negative pathogens, such as H. influenzae and Moraxella catarrhalis. The mode of action was verified using recombinant strains with altered LigA expression, an Okazaki fragment accumulation assay, and the isolation of resistant strains with ligA mutations. In vivo efficacy was demonstrated in a murine S. aureus thigh infection model and a murine S. pneumoniae lung infection model. Treatment with the adenosine analogs reduced the bacterial burden (expressed in CFU) in the corresponding infected organ tissue as much as 1,000-fold, thus validating LigA as a target for antibacterial therapy.

A comparison of fluorescamine and naphthalene-2,3-dicarboxaldehyde fluorogenic reagents for microplate-based detection of amino acids.

The use of appropriate fluorometric derivatization procedures is of considerable importance for accurate determination of amino acids in biological samples and in metal-assisted peptide hydrolysis reactions. It is especially critical for the relative fluorescence intensities (RFI) of equal amounts of amino acids to be as similar as possible. While fluorescamine and naphthalene-2,3-dicarboxaldehyde (NDA) have proven to be excellent fluorogenic reagents for amino acid detection, the effects of various factors such as organic solvent, buffer, and pH have never been rigorously evaluated with respect to normalizing the relative fluorescence intensities of individual amino acids. To this end, here we describe optimized fluorescamine and NDA derivatization reactions that enhance the accuracy of microplate-based detection of amino acids. For both fluorescamine and NDA, we have shown that the RFI values of 16 of 19 amino acids are greater than 70%. Although determination of tryptophan is problematic, this difficulty is overcome by the addition of beta-cyclodextrin to the NDA reaction. In principle, the optimized fluorescamine and NDA microplate procedures reported here can be utilized as complementary techniques for the detection of 19 of 20 naturally occurring amino acids.

The use of dietary supplements in pediatrics: a study of echinacea.

Alternative medical therapies are commonly used and have increased in popularity. Although patients may not always disclose the use of alternative therapies, they may seek advice regarding their use, especially for children. Regulation and standardization of these modalities, especially botanicals, is incomplete. The University of Arizona has initiated a study of the use of echinacea in the prevention of recurrent otitis media. A review of echinacea preparations was undertaken, and this report discusses the complexities surrounding the use of this dietary supplement. The number and diversity of echinacea preparations are detailed; the role of the physician as "botanical" advisor to patients and families is examined.

Chromium and exercise training: effect on obese women.

Chromium supplementation may affect various risk factors for coronary artery disease (CAD) and non-insulin-dependent diabetes mellitus (NIDDM), including body weight and composition, basal plasma hormone and substrate levels, and response to an oral glucose load. This study examined the effects of chromium supplementation (400 micrograms.d-1), with or without exercise training, on these risk factors in young, obese women. Chromium picolinate supplementation resulted in significant weight gain in this population, while exercise training combined with chromium nicotinate supplementation resulted in significant weight loss and lowered the insulin response to an oral glucose load. We conclude that high levels of chromium picolinate supplementation are contraindicated for weight loss in young, obese women. Moreover, our results suggest that exercise training combined with chromium nicotinate supplementation may be more beneficial than exercise training alone for modification of certain CAD and NIDDM risk factors.

Human intestinal folate transport: cloning, expression, and distribution of complementary RNA.

BACKGROUND & AIMS: Despite intensive investigations, very little is known about the molecular identity(ies) of the intestinal folate transport system(s), especially in humans. The aim of this study was to isolate a functional human intestinal folate carrier complementary DNA (cDNA) clone and determine the distribution of complementary RNA at the tissue and cellular levels. METHODS: Hybridization screening, modified Marathon cDNA amplification, expression in Xenopus oocytes, Northern analysis, and in situ hybridization were used. RESULTS: The hIFC-1 cDNA contains an open reading frame for 591 amino acids (relative molecular mass = 64,826, pI = 9.4, 12 transmembrane domains, three protein kinase C phosphorylation sites, and one N-glycosylation site) with 74% DNA and 66% amino acid sequence homologies with the mouse cDNA counterpart. Xenopus oocytes injected with hIFC-1 cRNA show induced folate uptake that was (1) saturable with substrate concentration (apparent Michaelis constant = 0.71 +/- 0.06 micromol/L; maximum velocity = 128 +/- 3 fmol x h(-1) x oocyte(-1)), (2) inhibited by methotrexate, folinic acid, and folic acid (Ki = 0.84 micromol/L, 0.71 micromol/L, and 10 micromol/L, respectively), and (3) sensitive to 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (Ki = 0.29 mmol/L). Northern analysis showed wide distribution of hIFC1-complementary messenger RNA species in various human tissues. In situ hybridization on sections of human jejunum showed preferential hIFC-1 expression in epithelial cells, especially in the upper half of the villi. CONCLUSIONS: These results represent the first molecular characterization of a human small intestinal folate carrier.

Gasoline injection.

Injection of petroleum distillates is rare. We recently cared for a man with a long history of drug abuse who attempted intravenous injection with gasoline into a right forearm vein in order to "get high." We believe he accomplished an intramuscular and subcutaneous injection of gasoline which resulted in a severe impairment of the right hand and forearm from damage to the right median, ulnar, and radial nerves.

Photochemotherapy of psoriasis with methoxsalen and longwave ultraviolet light (PUVA).

The effectiveness of methoxsalen and ultraviolet light (PUVA) in treating is reviewed. The use of this therapy, its mechanism of action, pharmacology, pharmacokinetics, adverse reactions, dosage, and comparison with other forms of therapy, are discussed. Administered orally, methoxsalen in combination with long-range ultraviolet light (UVA) is effective in treating patients with moderate to severe forms of psoriasis. Although the short-term risks associated with PUVA therapy are minimal, the long-term risks of oncogenicity have not been evaluated thoroughly. Common adverse reactions to methoxsalen and UVA are nausea, pruritus, and erythema, but usually they can be managed by minor modifications in the treatment regimen. Methoxsalen and UVA therapy should be reserved for patients with moderate to severe forms of psoriasis that do not respond to other forms of therapy until the long-term risks of oncogenicity are evaluated.