Emergency department utilization by persons with rheumatoid arthritis: a population-based cohort study.

Some emergency department (ED) visits by persons with rheumatoid arthritis (RA) may be avoidable. This study aims to describe ED use by persons with RA in Alberta, Canada over a 10-year period. Using linked population-based administrative datasets, the annual frequency of ED visits, timing of visits, acuity at presentation assessed (Canadian Triage Acuity Scale (CTAS)), return visits within 72 h, and final disposition were assessed. Most responsible diagnoses assessed by the ED provider were categorized. Between 2008 and 2017, a total of 48,633 persons with RA had 416,964 unique ED visits. There was a 41% relative increase in visits over the study period and within a fiscal year 37% of persons with RA on average attended an ED. Half of the visits were assessed as CTAS 4 'Less Urgent' (31%) and CTAS 5 'Non-Urgent' (19%). No specific diagnosis could be assigned in 36% of visits and RA was listed as the most responsible diagnosis in 2.5% of all visits. Hospital admissions, occurring on average for 14% of ED visits, increased by 15% over the 10 years, and were rare for CTAS 4 (6.4%) and CTAS 5 (1.4%) presentations. Male patients (difference to female 1.2%, 95%CI 0.6, 1.7) and urban patients (difference to rural 8.4%, 95%CI 7.7, 9.2) were more frequently admitted to hospital. Persons with RA have increased ED utilization over time, with a significant volume of less urgent and non-urgent visits. Opportunities for appropriate ambulatory care provision to reduce acute care use should be identified.

In ischemic stroke upon wakening, IV thrombolysis or EVT improves functional outcome at 90 d.

SOURCE CITATION: Roaldsen MB, Lindekleiv H, Mathiesen EB. Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake-up stroke. Cochrane Database Syst Rev. 2021;12:CD010995. 34850380.

Outcomes After Recurrent Intentional Methanol Exposures Not Treated With Alcohol Dehydrogenase Inhibitors Or Hemodialysis.

BACKGROUND: Relying on a treatment threshold for methanol poisoning of 20 mg/dL (6.2 mmol/L) as a stand-alone criterion may lead to unnecessary and invasive treatment because it is likely too conservative, especially for patients with repeated, intentional methanol exposures. OBJECTIVE: We investigated how often patients with recurrent intentional methanol exposures above this threshold developed biochemical or overt clinical toxicity despite not being treated with either an alcohol dehydrogenase inhibitor (ADHi) or hemodialysis. METHODS: We identified patients with ≥3 methanol-related emergency visits from 2002 to 2015 and selected every visit in which neither ADHi nor hemodialysis were administered despite serum methanol >20 mg/dL but neither metabolic acidosis nor end organ toxicity at presentation. The primary outcome was the incidence of visual deterioration or death. RESULTS: Four patients accounted for the 17 visits that met inclusion criteria. All exposures were intentional substance misuse, and 7 of 17 were via inhalation (i.e., huffing). Initial methanol concentrations ranged from 22 mg/dL to 35 mg/dL (7-11 mmol/L). Four of these 17 visits had undetectable initial ethanol concentrations at presentation, including 1 with an initial methanol concentration of 35 mg/dL. No patients developed visual deterioration, and all were known to have survived the exposure. CONCLUSION: Following recurrent, intentional methanol exposure, isolated serum methanol concentrations as high as 35 mg/dL (11 mmol/L) appear to be well-tolerated without treatment in the absence of metabolic acidosis or end-organ toxicity. To better define the methanol treatment threshold, prospective studies are warranted in which patients are followed closely while fomepizole is withheld.

Integration of pan-cancer transcriptomics with RPPA proteomics reveals mechanisms of epithelial-mesenchymal transition.

Integrating data from multiple regulatory layers across cancer types could elucidate additional mechanisms of oncogenesis. Using antibody-based protein profiling of 736 cancer cell lines, along with matching transcriptomic data, we show that pan-cancer bimodality in the amounts of mRNA, protein, and protein phosphorylation reveals mechanisms related to the epithelial-mesenchymal transition (EMT). Based on the bimodal expression of E-cadherin, we define an EMT signature consisting of 239 genes, many of which were not previously associated with EMT. By querying gene expression signatures collected from cancer cell lines after small-molecule perturbations, we identify enrichment for histone deacetylase (HDAC) inhibitors as inducers of EMT, and kinase inhibitors as mesenchymal-to-epithelial transition (MET) promoters. Causal modeling of protein-based signaling identifies putative drivers of EMT. In conclusion, integrative analysis of pan-cancer proteomic and transcriptomic data reveals key regulatory mechanisms of oncogenic transformation.

Ethnicity and health literacy: a survey on hypertension knowledge among Canadian ethnic populations.

OBJECTIVES: With an increase and diversity in ethnic populations in Westernized countries, understanding the differences in levels of knowledge surrounding hypertension is important in planning appropriate prevention strategies. The purpose of our study was to assess levels of hypertension knowledge in Chinese, Indian and White populations in a large metropolitan Canadian city. DESIGN: A telephone survey was conducted in English, Chinese (Cantonese and Mandarin) and Indian languages (Hindi, Punjabi and Urdu). Hypertension knowledge was assessed through a 10-item validated instrument; respondents received 1 point for each correct answer. Logistic regression was used to test differences in hypertension knowledge among these three populations. RESULTS: Survey response rates were 68.7% (301) for Chinese, 61.3% (248) for Indian and 69.7% (254) for White populations. The average hypertension knowledge score for Chinese respondents was 7.23 out of 10, 7.11 for Indian respondents and 7.28 for White respondents. Compared to White respondents, Chinese respondents were less likely than White respondents to know high blood pressure can cause heart attacks (adjusted odds ratio [aOR]: .43, 95% confidence interval [CI]: .19-.96] and Indian respondents were less likely to know losing weight usually decreases blood pressure (aOR: .38, 95% CI: .21-.68). CONCLUSIONS: Hypertension knowledge levels among these three ethnic/racial populations were similar and relatively high and varied by content. Low levels of knowledge for Chinese and Indian ethnic populations were on hypertension risk factors, long-term consequences of hypertension and anti-hypertensive medication adherence. Specifically, females, recent immigrants to Canada and Chinese seniors were identified as sub-groups who should be targeted for hypertension knowledge promotion.

Prognostic association between d-dimer thresholds and 30-day pulmonary embolism diagnosis among emergency department patients with suspected SARS-CoV-2 infection: a Canadian COVID-19 Emergency Department Rapid Response Network study.

OBJECTIVE: The primary objective was to quantify the prognostic association between various D-dimer thresholds and 30-day PE diagnosis among emergency department (ED) patients with suspected SARS-CoV-2 infection. METHODS: This was a retrospective study of patients enrolled in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry from March 1, 2020 to July 2, 2021. We included consecutive adults (≥ 18 years) presenting to 49 EDs with chest pain, shortness of breath, hypoxia, syncope, presyncope, or hemoptysis who were tested for both SARS-CoV-2 and D-dimer at index ED visit. The primary outcome measure was the sensitivity, specificity, and negative predictive value of D-dimer test thresholds for the outcome of 30-day PE diagnosis. RESULTS: Among 10,837 patients included in our study, 404 (3.7%) were diagnosed with PE at 30-days. A standard D-Dimer threshold of 500 ng/mL had a sensitivity of 97.8% (95% confidence interval [CI] 95.8-99.0%), specificity of 40.9% (95% CI 39.9-41.8%), and negative predictive value of 99.8% (95% CI 99.6-99.9%). An age-adjusted D-dimer threshold had a sensitivity of 96.0% (95% CI 93.6-97.7%), specificity of 48.5% (95% CI 47.5-49.4%), and negative predictive value of 99.7% (95% CI 99.5-99.8%). D-dimer testing had slightly lower prognostic performance among SARS-CoV-2 positive compared to SARS-CoV-2 negative patients in predicting 30-day PE diagnosis. CONCLUSIONS: Among ED patients with suspected SARS-CoV-2, the standard 500 ng/mL and age-adjusted D-dimer thresholds were comparable for the prediction of PE at 30-days. The prognostic performance of D-dimer was lower among SARS-CoV-2 positive patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

RéSUMé: OBJECTIF: L'objectif principal était de quantifier l'association pronostique entre différents seuils de D-dimères et le diagnostic d'EP à 30 jours chez les patients des services d'urgence suspectés d'être infectés par le SRAS-CoV-2. MéTHODES: Il s'agissait d'une étude rétrospective des patients inscrits au registre du réseau canadien de réponse rapide aux urgences COVID-19 (CCEDRRN) du 1er mars 2020 au 2 juillet 2021. Nous avons inclus des adultes consécutifs (>18 ans) se présentant dans 49 services d'urgence pour une douleur thoracique, un essoufflement, une hypoxie, une syncope, une présyncope ou une hémoptysie et qui ont été testés à la fois pour le SRAS-CoV-2 et les D-dimères lors de la visite de référence aux urgences. Le principal critère d'évaluation était la sensibilité, la spécificité et la valeur prédictive négative des seuils du test des D-dimères pour le diagnostic de l'EP à 30 jours. RéSULTATS: Parmi les 10 837 patients inclus dans notre étude, 404 (3,7 %) ont reçu un diagnostic d'EP à 30 jours. Un seuil standard de D-Dimer de 500 ng/mL avait une sensibilité de 97,8 % (intervalle de confiance [IC] à 95 % 95,8-99,0 %), une spécificité de 40,9 % (IC à 95 % 39,9-41,8 %) et une valeur prédictive négative de 99,8 % (IC à 95 % 99,6-99,9 %). Un seuil de D-dimères ajusté à l'âge avait une sensibilité de 96,0% (IC à 95 % 93,6-97,7 %), une spécificité de 48,5% (IC à 95 % 47,5-49,4 %) et une valeur prédictive négative de 99,7 % (IC à 95 % 99,5-99,8 %). Le test des D-dimères avait une performance pronostique légèrement inférieure chez les patients positifs pour le SRAS-CoV-2 par rapport aux patients négatifs pour le SRAS-CoV-2 en ce qui concerne la prédiction du diagnostic d'EP à 30 jours. CONCLUSIONS: Chez les patients des urgences suspectés d'être atteints du SRAS-CoV-2, les seuils standard de 500 ng/ml et les seuils de D-dimères ajustés à l'âge étaient comparables pour la prédiction de l'EP à 30 jours. La performance pronostique des D-dimères était plus faible chez les patients positifs pour le SRAS-CoV-2. ENREGISTREMENT DE L'ESSAI: Clinicaltrials.gov, NCT04702945.

The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.

The expression of inducible nitric oxide synthase (iNOS; NOS2) and derived NO in various cancers was reported to exert pro- and anti-tumorigenic effects depending on the levels of expression and the tumor types. In humans, the breast cancer level of iNOS was reported to be overexpressed, to exhibit pro-tumorigenic activities, and to be of prognostic significance. Likewise, the expression of the oncogenes HER2, BRCA1, and BRCA2 has been associated with malignancy. The interrelationship between the expression of these protooncogenes and oncogenes and the expression of iNOS is not clear. We have hypothesized that there exist cross-talk signaling pathways between the breast cancer protooncogenes, the iNOS axis, and iNOS-mediated NO mutations of these protooncogenes into oncogenes. We review the molecular regulation of the expression of the protooncogenes in breast cancer and their interrelationships with iNOS expression and activities. In addition, we discuss the roles of iNOS, HER2, BRCA1/2, and NO metabolism in the pathophysiology of cancer stem cells. Bioinformatic analyses have been performed and have found suggested molecular alterations responsible for breast cancer aggressiveness. These include the association of BRCA1/2 mutations and HER2 amplifications with the dysregulation of the NOS pathway. We propose that future studies should be undertaken to investigate the regulatory mechanisms underlying the expression of iNOS and various breast cancer oncogenes, with the aim of identifying new therapeutic targets for the treatment of breast cancers that are refractory to current treatments.

Content Analysis of Stroke Teleconsultation Recordings in the Moravian-Silesian Region, Czech Republic.

Background: Direct teleconsultations between emergency medical services (EMS) crews and hospital-based stroke neurologists are mandated in the Czech Republic as triage and prenotification tool in acute stroke patients. The main aim of this study was to analyze the efficacy as well as quality of such teleconsultations in daily clinical practice. Methods: This is a descriptive analysis of teleconsultations between EMS paramedic crews and hospital-based neurologists in a geographically defined region of the Czech Republic (Moravian-Silesian region) between October 2018 to December 2018. All teleconsultations were analyzed for length and content. Content analysis included the following information: date, age, sex, prehospital neurological deficit(s), known/unknown time of symptom onset, anticoagulation status, vital signs, premorbid disability, and patient ID/insurance company number. Results: Within the study period, paramedics conducted 522 calls across 6 stroke centers. Of these, 334 (64%) calls were conducted because patients met pre-established prehospital criteria for suspected acute stroke. Median call duration was 1 min 44 s ± 56 s (minimum 50 s, maximum 5 min 5 s). Amongst the analyzed prehospital teleconsultations, stroke onset time was reported in 95% of cases, neurological deficit in 96%, significant co-morbidities in 53%, premorbid disability in 37%, and anticoagulation status in 53%. Conclusion: Teleconsultations between paramedics and hospital-based neurologists are not time-consuming. Stroke onset time and severity of neurological deficit are consistently communicated, however other important information such as comorbidities, premorbid disability, and anticoagulation status are reported inconsistently.

Meta-analysis of interventions to reduce door to needle times in acute ischaemic stroke patients.

BACKGROUND: Door-to-needle time (DTN) has an important impact on thrombolysis and reperfusion outcomes in the treatment of acute ischaemic stroke. This systematic review is a critical synthesis of studies evaluating DTN reduction strategies. METHOD: Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, CINAHL, ProQuest dissertations and LILACS were used as bibliographic databases for primary literature. CIHI, Health Quality Council of Alberta, Health Quality Ontario and websites of heart and stroke associations in Canada, USA, UK, Australia and New Zealand were used as sources of grey literature. Searched reports were screened by title and abstract, and full texts were located for review. Articles quality was evaluated using National Institute of Health's Study Quality Assessment tools. Methods for improving DTN were categorised under 13 DTN reduction strategies, primarily adapted from the Target: Stroke Phase II recommendations, and including two additional categories: Strategies not encompassed by any Target: Stroke recommendation, and Combinations of Interventions. RESULTS: 96 studies (4 randomised control trials, 1 review, 91 observational pre/post studies) were included in the review. All strategies and interventions resulted in a reduction of DTN. Approaches using combinations of interventions were the most effective at reducing DTN (33.77% DTN reduction, standard mean difference=1.857, 95% CI=1.510-2.205), and were more effective than approaches using only a single strategy (p=0.040). DTN reduction was associated with the duration of the DTN reduction programme at each facility (p=0.006). INTERPRETATION: The greatest reductions in DTN were observed when implementing combinations of DTN reduction strategies, although there was no significant advantage to implementing more than two strategies simultaneously. PROSPERO REGISTRATION NUMBER: 42016036215.

Ultrasonography versus computed tomography for initial investigation of suspected nephrolithiasis.

UNLABELLED: Clinical question Is ultrasonography a safe and practical alternative to computed tomography for the initial investigation of suspected nephrolithiasis? Article chosen Smith-Bindman R, Aubin C, Bailitz J, et al. Ultrasonography versus computed tomography for suspected nephrolithiasis. N Engl J Med 2014;371(12):1100-10. OBJECTIVE: To assess the safety and efficacy of ultrasonography as a first-line imaging investigation for patients with suspected nephrolithiasis.