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RATIONALE: Airway obstruction in patients with asthma is associated with airway dysfunction and inflammation. Objective measurements including sputum analysis can guide therapy, but this is often not possible in typical clinical settings. Metabolomics is the study of molecules generated by metabolic pathways. We hypothesize that airway dysfunction and inflammation in an animal model of asthma would produce unique patterns of urine metabolites measured by multivariate statistical analysis of high-resolution proton nuclear magnetic resonance ((1)H NMR) spectroscopy data. OBJECTIVES: To develop a noninvasive means of monitoring asthma status by metabolomics and urine sampling. METHODS: Five groups of guinea pigs were studied: control, control treated with dexamethasone, sensitized (ovalbumin, administered intraperitoneally), sensitized and challenged (ovalbumin, administered intraperitoneally, plus ovalbumin aerosol), and sensitized-challenged with dexamethasone. Airway hyperreactivity (AHR) to histamine (administered intravenously) and inflammation were measured. Multivariate statistical analysis of NMR spectra based on a library of known urine metabolites was performed by partial least-squares discriminant analysis. In addition, the raw NMR spectra exported as xy-trace data underwent linear discriminant analysis. MEASUREMENTS AND MAIN RESULTS: Challenged guinea pigs developed AHR and increased inflammation compared with sensitized or control animals. Dexamethasone significantly improved AHR. Using concentration differences in metabolites, partial least-squares discriminant analysis could discriminate challenged animals with 90% accuracy. Using only three or four regions of the NMR spectra, linear discriminant analysis-based classification demonstrated 80-90% separation of the animal groups. CONCLUSIONS: Urine metabolites correlate with airway dysfunction in an asthma model. Urine NMR analysis is a promising, noninvasive technique for monitoring asthma in humans. [ABSTRACT FROM AUTHOR]

Agitation is a common presenting symptom of delirium for older adults in the emergency department (ED). No medications have been found to reduce delirium severity, symptoms, or mortality, yet they may cause harm. Guidelines suggest using medications only when patients are posing a risk of harm, situations which may arise frequently in the ED. We sought to characterize prescribing patterns of medications for agitation by ED physicians in Canadian hospitals. In this multicenter study, we surveyed physicians in Vancouver, Toronto, and Sherbrooke. Descriptive statistics were used to summarize group characteristics and starting doses were compared to order sets. Fisher exact tests were used for demographic comparison. Ordinal linear regression models were run to identify a relationship between starting dose of medications and location. Of the 137 physicians invited, 77 (56%) completed the survey. Use of order sets was greatest in Sherbrooke and least in Vancouver. The most common medications used across sites were haloperidol, lorazepam, and quetiapine. Benzodiazepines were used across all sites but were used significantly more frequently in Vancouver than the other sites. Practice location was a significant predictor of starting dose of haloperidol, with Sherbrooke and Toronto having a lower starting dose than Vancouver. Higher use of order sets correlated with lower and more consistent starting doses. Benzodiazepines are used across EDs in Canada despite little evidence for efficacy in delirium and risk of harm. Implementation of order sets may be a useful way to standardize ED management of older adults experiencing hyperactive delirium., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood the Canadian Geriatrics Journal’s policy on disclosing conflicts of interest and declare that we have none., (© 2023 Author(s).)

Background: Between 75% and 80% of patients with sepsis arrive in the hospital through the emergency department. Early diagnosis is important to alter patient prognosis, but currently, there is no reliable biomarker. The innate immune response links inflammation and coagulation. Several coagulation -related biomarkers are associated with poor prognosis in the ICU. The role of coagulation biomarkers to aid in early sepsis diagnosis has not previously been investigated. The objective of our study is to determine the individual or combined accuracy of coagulation and inflammation biomarkers with standard biochemical tests to diagnose adult septic patients presenting to the emergency department., Methods: in the Emergency Department is a prospective, observational cohort study with a target enrolment of 250 suspected septic patients from two Canadian emergency departments. The emergency physicians will enroll patients with suspected sepsis. Blood samples will be collected at two time points (initial presentation and 4 hr following). Patients will be adjudicated into septic, infected, or not infected status in accordance with the Sepsis-3 definitions. Patient demographics, cultures, diagnosis, and biomarkers will be reported using descriptive statistics. Optimal cut off values with sensitivity and specificity for each biomarker will be determined using C-statistics to distinguish between septic and nonseptic patients. Stepwise multiple logistic regression analysis with exclusion of nonsignificant covariates from the final model will be used to establish a panel of biomarkers., Conclusions: Our protocol describes the processes and methods for a pragmatic observational biomarker study in the emergency department. This study will seek to determine the potential diagnostic importance of early coagulation abnormalities to identify additional tools for sepsis diagnosis., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

A previously healthy 10-year-old girl presented to the emergency department with a 1-day history of abdominal pain. She was afebrile with an elevated white blood cell count and a negative pelvic ultrasound. The pain resolved while in hospital, and the patient was discharged home. The patient returned 10 days later, and the pain now migrated from the left flank to the subumbilical region. The patient now had an elevated white blood cell count and C-reactive protein. On pelvic ultrasound, the patient had a large midline mass and a normal right ovary. The patient was taken to the operating room where she was found to have a torted and necrotic left ovary and fallopian tube, which were removed. There are few instances where pediatric ovarian torsion presents as intermittent episodes of abdominal pain. Emergency physicians should always have a high index of suspicion for ovarian torsion in any case of abdominal/pelvic pain in young girls with previous negative imaging.

Back pain is one of the most common presentations to the emergency department. Though case reports of patients presenting with increased back pain following chiropractic spinal manipulations are rare, we have identified a case rarely reported in the literature where a potential injury from chiropractic manipulation resulted in a diagnosis of multiple myeloma. We have reported a previously healthy 66-year-old male who presented with persistent lower back pain over 4 weeks. An initial evaluation with thoracolumbar radiographs revealed no significant findings. Following initial presentation to the family physician, the patient underwent three treatments of spinal manipulation from his local chiropractor, which resulted in worsening lower back pain. A re-examination and new radiographs in the hospital revealed multiple compression fractures and an underlying diagnosis of multiple myeloma. We have explored current literature examining the prevalence of lower back pain, as well as the incidence of spinal fracture following chiropractic manipulation, and have highlighted a potential complication from chiropractic manipulation in a patient with an undiagnosed underlying neoplastic disorder.

Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes. We hypothesized that animals with immunologic memory to a respiratory virus would also develop airway hyperresponsiveness in response to a UV-inactivated form of the virus if they have pre-existing allergic airway inflammation. Guinea pigs were ovalbumin-sensitized, infected with live parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re-inoculated 60 days later with live or UV-inactivated PIV. Some animals were either treated with dexamethasone prior to the second viral exposure. Lymphocytes were isolated from parabronchial lymph nodes to confirm immunologic memory to the virus. Airway reactivity was measured and inflammation was assessed using bronchoalveolar lavage and lung histology. The induction of viral immunologic memory was confirmed in infected animals. Allergen sensitized and challenged animals developed airway hyperreactivity with eosinophilic airway inflammation when re-exposed to UV-inactivated PIV, while non-sensitized animals did not. Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment with dexamethasone. We suggest that the response of allergic inflammation to virus antigen is a significant factor causing asthma exacerbation. We propose that this is one mechanism explaining how corticosteroids prevent virus-induced asthma attack.

Entamoeba histolytica infections of the gastrointestinal tract are common in the developing world but rare in North America. The authors present two cases: one involving an individual who had not travelled to an endemic area and another involving an individual who was born in Bulgaria. Both presented with severe abdominal pain and diarrhea. Endoscopic assessment revealed scattered colonic ulcerations and one patient was found to have a liver abscess on imaging. Stool ova and parasite studies were negative in both cases and both were diagnosed on review of colonic biopsies. On review of all Entamoeba cases in the Calgary Health Zone (Alberta), ova and parasite analysis found an average of 63.7 Entamoeba cases per year and a pathology database review revealed a total of seven cases of invasive E histolytica (2001 to 2011). Both patients responded well to antibiotic therapy. E histolytica should be considered in new-onset colitis, especially in individuals from endemic areas.

The new factor Xa inhibitors and direct thrombin inhibitors have offered alternatives to traditional anticoagulants, with benefits of no routine monitoring, less drug interactions, and oral administration. Current approved uses of these agents include prophylaxis of stroke in non-valvular atrial fibrillation and prevention of venous thromboembolism (VTE) following hip and knee arthroplasty. However, concern over bleeding risk in the context of having no specific antidotes available is a topic of focus for many physicians in an acute care setting. This manuscript examines the recent literature in the management of acute bleeding and the various methods of reversing anticoagulation in this setting. Literature published over the last 18 months (2011/07/01-present) was gathered from PubMed, Ovid, and Medline under a combined search strategy covering bleeding, reversal, and new oral anticoagulants, both factor Xa and direct thrombin inhibitors. The use of prothrombin complex concentrate, fresh frozen plasma, activated recombinant factor VII, activated prothrombin complex concentrate, as well as adjuncts of charcoal, hemodialysis, and antifibrinolytics are discussed. Recommendations are based on the determination of the severity of the bleed and physiological markers of anticoagulation, and involve the use of prothrombin complex concentrate, activated recombinant factor VII, and adjunctive therapy as appropriate.

Establishing the severity of hypoxic insult during the delivery of a neonate is key step in the determining the type of therapy administered. While successful therapy is present, current methods for assessing hypoxic injuries in the neonate are limited. Urine Nuclear Magnetic Resonance (NMR) metabolomics allows for the rapid non-invasive assessment of a multitude breakdown products of physiological processes. In a newborn piglet model of hypoxia, we used NMR spectroscopy to determine the levels of metabolites in urine samples, which were correlated with physiological measurements. Using PLS-DA analysis, we identified 13 urinary metabolites that differentiated hypoxic versus nonhypoxic animals (1-methylnicotinamide, 2-oxoglutarate, alanine, asparagine, betaine, citrate, creatine, fumarate, hippurate, lactate, N-acetylglycine, N-carbamoyl-β-alanine, and valine). Using this metabolomic profile, we then were able to blindly identify hypoxic animals correctly 84% of the time compared to nonhypoxic controls. This was better than using physiologic measures alone. Metabolomic profiling of urine has potential for identifying neonates that have undergone episodes of hypoxia.

Background: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheeze. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents., Objectives: The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms., Methods: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB., Results: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported., Conclusions: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

Immune modulation has been a sought after means of therapy for atopic diseases. CVT-E002 is an extract derived from North American Ginseng shown to promote T-helper-1-like responses. We determined what effect CVT-E002 could have in a mouse model of atopic asthma. We report that oral CVT-E002 inhibited the development of allergic airway inflammation and airway hyperresponsiveness. This correlated with an increased presence of interferon-γ in the lung, and also increased regulatory T cells and IL-10. The ability of CVT-E002 to induce regulatory T-cell development was also seen in human in vitro co-cultures., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Asthma is a chronic disorder of the airways involving inflammation and airway hyper-reactivity. Clinical diagnosis and monitoring of asthma must incorporate the immunological, biochemical, and histological changes of a chronic disorder, while recognizing acute phenotypic changes in order to optimally tailor therapeutics to each individual., Recent Findings: Articles published within the previous 18 months are summarized in this article in order to present an up to date review of the latest findings regarding the monitoring of asthma. The articles encompass a wide array of specialties from basic research and histology to clinical medicine as well as community medicine and nursing., Summary: Exciting new advancements in the monitoring of asthma continue to unfold. Potentially new diagnostic and monitoring tools are highlighted in this study. Continued investigations may enable a select few methodologies to reach clinical utility in the ongoing monitoring and treatment of patients with asthma.