Characteristics and outcomes of patients with COVID-19 who return to the emergency department: a multicentre observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

OBJECTIVE: Unplanned return emergency department (ED) visits can reflect clinical deterioration or unmet need from the original visit. We determined the characteristics and outcomes of patients with COVID-19 who return to the ED for COVID-19-related revisits. METHODS: This retrospective observational study used data for all adult patients visiting 47 Canadian EDs with COVID-19 between 1 March 2020 and 31 March 2022. Multivariable logistic regression assessed the characteristics associated with having a no return visit (SV=single visit group) versus at least one return visit (MV=return visit group) after being discharged alive at the first ED visit. RESULTS: 39 809 patients with COVID-19 had 44 862 COVID-19-related ED visits: 35 468 patients (89%) had one visit (SV group) and 4341 (11%) returned to the ED (MV group) within 30 days (mean 2.2, SD=0.5 ED visit). 40% of SV patients and 16% of MV patients were admitted at their first visit, and 41% of MV patients not admitted at their first ED visit were admitted on their second visit. In the MV group, the median time to return was 4 days, 49% returned within 72 hours. In multivariable modelling, a repeat visit was associated with a variety of factors including older age (OR=1.25 per 10 years, 95% CI (1.22 to 1.28)), pregnancy (1.86 (1.46 to 2.36)) and presence of comorbidities (eg, 1.72 (1.40 to 2.10) for cancer, 2.01 (1.52 to 2.66) for obesity, 2.18 (1.42 to 3.36) for organ transplant), current/prior substance use, higher temperature or WHO severe disease (1.41 (1.29 to 1.54)). Return was less likely for females (0.82 (0.77 to 0.88)) and those boosted or fully vaccinated (0.48 (0.34 to 0.70)). CONCLUSIONS: Return ED visits by patients with COVID-19 within 30 days were common during the first two pandemic years and were associated with multiple factors, many of which reflect known risk for worse outcomes. Future studies should assess reasons for revisit and opportunities to improve ED care and reduce resource use. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04702945.

Brain-derived neurotrophic factor as a biomarker in cancer-related cognitive impairment among adolescent and young adult cancer patients.

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15-39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p < 0.001) and 6-months post-baseline (median: 8.2 vs 15.3, p = 0.001) compared to non-cancer controls. Through linear mixed modelling adjusted for sociodemographic variables, baseline cognition, fatigue, psychological distress, and time, we observed that among cancer participants, lower baseline BDNF levels were associated with worse attention (p = 0.029), memory (p = 0.018) and self-perceived cognitive abilities (p = 0.020) during cancer treatment. Met/Met was associated with enhanced executive function compared to Val/Val (p = 0.012). Plasma BDNF may serve as a predictive biomarker of cancer-related cognitive impairment.

Impact of a high sensitivity troponin accelerated diagnostic protocol on the safety and emergency department length of stay of chest pain in an academic tertiary hospital: a quality improvement study.

PURPOSE: High-sensitivity troponin (hsTn) accelerated diagnostic protocols are highly recommended for evaluating acute coronary syndromes. Our goal was to improve care for chest pain patients through the safe adoption of an accelerated diagnostic protocol in our academic Emergency Department (ED) with an aim to reduce mean ED length of stay for chest pain patients by 1 h over 1.5 years. Pre-accelerated diagnostic protocol, our mean ED length of stay for chest pain patients was 9.0 h. METHODS: Using the Model for Improvement, we implemented a two-hour accelerated diagnostic protocol and conducted two Plan-Do-Study-Act cycles and education efforts to improve accelerated diagnostic protocol compliance and decrease ED length of stay. Using control charts, we measured the mean monthly ED length of stay for chest pain patients to look for special cause evidence of improvement. Process measures measured compliance with the accelerated diagnostic protocol. Balancing measures included the ED length of stay for abdominal pain patients and the number of admissions and deaths at 7 days for chest pain patients. RESULTS: Mean ED length of stay for chest pain patients decreased from 9.0 to 8.2 h post-accelerated diagnostic protocol. The mean time between troponins decreased from 3.9 to 3.0 h, and the percentage of second troponins repeated at < 2.75 h increased from 22.3% to 58.6%. For abdominal pain patients, ED length of stay decreased from 10.8 to 10.5 h. No chest pain patients died within 7 days pre- or post-accelerated diagnostic protocol. Pre-accelerated diagnostic protocol, 0.84% (41/4,905) were admitted within 7 days. Post-accelerated diagnostic protocol and accelerated diagnostic protocol compliant, 0.70% (13/1,844) were admitted. Post-accelerated diagnostic protocol and accelerated diagnostic protocol non-compliant, 1.1% (13/1,183) were admitted. CONCLUSION: We safely introduced a hsTn accelerated diagnostic protocol in an academic ED. ED length of stay decreased for chest pain patients but did not meet our 1-h goal.

RéSUMé : OBJECTIF : Les protocoles de diagnostic accélérés à haute sensibilité de la troponine (hsTn) sont fortement recommandés pour évaluer les syndromes coronariens aigus. Notre objectif était d'améliorer les soins pour les patients souffrant de douleurs thoraciques grâce à l'adoption en toute sécurité d'un protocole de diagnostic accéléré dans notre service d'urgence universitaire (ED) dans le but de réduire la durée moyenne de séjour des patients souffrant de douleurs thoraciques d'une heure sur 1,5 an. Protocole de diagnostic pré-accéléré, notre durée moyenne de séjour aux urgences pour les patients souffrant de douleurs thoraciques était de 9 heures. MéTHODES: À l'aide du Modèle d'amélioration, nous avons mis en œuvre un protocole de diagnostic accéléré de deux heures et mené deux cycles Plan-Do-Study-Act et des efforts d'éducation pour améliorer la conformité du protocole de diagnostic accéléré et réduire la durée du séjour aux urgences. À l'aide de tableaux de contrôle, nous avons mesuré la durée moyenne mensuelle du séjour aux urgences pour les patients souffrant de douleurs thoraciques afin de rechercher des preuves d'amélioration de cause spéciale. Le processus mesure la conformité au protocole de diagnostic accéléré. Les mesures d'équilibrage comprenaient la durée du séjour aux urgences pour les patients souffrant de douleurs abdominales et le nombre d'admissions et de décès à sept jours pour les patients souffrant de douleurs thoraciques. RéSULTATS: La durée moyenne du séjour aux urgences chez les patients souffrant de douleurs thoraciques a diminué de 9,0 à 8,2 heures après le protocole de diagnostic accéléré. Le temps moyen entre les troponines a diminué de 3,9 à 3,0 heures, et le pourcentage de deuxième troponines répétées à moins de 2,75 heures a augmenté de 22,3 % à 58,6 %. Pour les patients souffrant de douleurs abdominales, la durée du séjour aux urgences a diminué de 10,8 à 10,5 heures. Aucun patient souffrant de douleurs thoraciques n'est décédé dans les sept jours précédant ou suivant le protocole de diagnostic accéléré. Protocole de diagnostic pré-accéléré, 0,84 % (41/4905) ont été admis dans les sept jours. Protocole de diagnostic post-accéléré et protocole de diagnostic accéléré conforme, 0,70% (13/1844) ont été admis. Le protocole diagnostique post-accéléré et le protocole diagnostique accéléré non conforme, 1,1% (13/1,183) ont été admis. CONCLUSION: Nous avons introduit en toute sécurité un protocole de diagnostic accéléré hsTn dans un ED académique. La durée de séjour des patients souffrant de douleurs thoraciques a diminué, mais n'a pas atteint notre objectif d'une heure.

Drivers of Emergency Department Use Among Oncology Patients in the Era of Novel Cancer Therapeutics: A Systematic Review.

BACKGROUND: Patients diagnosed with cancer are frequent users of the emergency department (ED). While many visits are unavoidable, a significant portion may be potentially preventable ED visits (PPEDs). Cancer treatments have greatly advanced, whereby patients may present with unique toxicities from targeted therapies and are often living longer with advanced disease. Prior work focused on patients undergoing cytotoxic chemotherapy, and often excluded those on supportive care alone. Other contributors to ED visits in oncology, such as patient-level variables, are less well-established. Finally, prior studies focused on ED diagnoses to describe trends and did not evaluate PPEDs. An updated systematic review was completed to focus on PPEDs, novel cancer therapies, and patient-level variables, including those on supportive care alone. METHODS: Three online databases were used. Included publications were in English, from 2012-2022, with sample sizes of ≥50, and reported predictors of ED presentation or ED diagnoses in oncology. RESULTS: 45 studies were included. Six studies highlighted PPEDs with variable definitions. Common reasons for ED visits included pain (66%) or chemotherapy toxicities (69.1%). PPEDs were most frequent amongst breast cancer patients (13.4%) or patients receiving cytotoxic chemotherapy (20%). Three manuscripts included immunotherapy agents, and only one focused on end-of-life patients. CONCLUSION: This updated systematic review highlights variability in oncology ED visits during the last decade. There is limited work on the concept of PPEDs, patient-level variables and patients on supportive care alone. Overall, pain and chemotherapy toxicities remain key drivers of ED visits in cancer patients. Further work is needed in this realm.

Cognitive impairment in adolescent and young adult cancer patients: Pre-treatment findings of a longitudinal study.

BACKGROUND: There is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study. METHODS: Newly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]). RESULTS: We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self-perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10 and IFN-γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function. CONCLUSION: With the pre-existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (ClinicalTrials.gov Identifier: NCT03476070).

Development and pilot testing of a decision aid for navigating breast cancer survivorship care.

BACKGROUND: The predominant oncologist-led model in many countries is unsustainable to meet the needs of a growing cohort of breast cancer survivors (BCS). Despite available alternative models, adoption rates have been poor. To help BCS navigate survivorship care, we aimed to systematically develop a decision aid (DA) to guide their choice of follow-up care model and evaluate its acceptability and usability among BCS and health care providers (HCPs). METHODS: We recruited BCS aged ≥ 21 years who have completed primary treatment and understand English. BCS receiving palliative care or with cognitive impairment were excluded. HCPs who routinely discussed post-treatment care with BCS were purposively sampled based on disciplines. Each participant reviewed the DA during a semi-structured interview using the 'think aloud' approach and completed an acceptability questionnaire. Descriptive statistics and directed content analysis were used. RESULTS: We conducted three rounds of alpha testing with 15 BCS and 8 HCPs. All BCS found the final DA prototype easy to navigate with sufficient interactivity. The information imbalance favouring the shared care option perceived by 60% of BCS in early rounds was rectified. The length of DA was optimized to be 'just right'. Key revisions made included (1) presenting care options side-by-side to improve perceived information balance, (2) creating dedicated sections explaining HCPs' care roles to address gaps in health system contextual knowledge, and (3) employing a multicriteria decision analysis method for preference clarification exercise to reflect the user's openness towards shared care. Most BCS (73%) found the DA useful for decision-making, and 93% were willing to discuss the DA with their HCPs. Most HCPs (88%) agreed that the DA was a reliable tool and would be easily integrated into routine care. CONCLUSIONS: Our experience highlighted the need to provide contextual information on the health care system for decisions related to care delivery. Developers should address potential variability within the care model and clarify inherent biases, such as low confidence levels in primary care. Future work could expand on the developed DA's informational structure to apply to other care models and leverage artificial intelligence to optimize information delivery.

Artificial intelligence significantly improves the diagnostic accuracy of deep myxoid soft tissue lesions in histology.

Deep myxoid soft tissue lesions have posed a diagnostic challenge for pathologists due to significant histological overlap and regional heterogeneity, especially when dealing with small biopsies which have profoundly low accuracy. However, accurate diagnosis is important owing to difference in biological behaviors and response to adjuvant therapy, that will guide the extent of surgery and the need for neo-adjuvant therapy. Herein, we trained two convolutional neural network models based on a total of 149,130 images representing diagnoses of extra skeletal myxoid chondrosarcoma, intramuscular myxoma, low-grade fibromyxoid sarcoma, myxofibrosarcoma and myxoid liposarcoma. Both AI models outperformed all the pathologists, with a significant improvement of accuracy up to 97% compared to average pathologists of 69.7% (p < 0.00001), corresponding to 90% reduction in error rate. The area under curve of the best AI model was on average 0.9976. It could assist pathologists in clinical practice for accurate diagnosis of deep soft tissue myxoid lesions, and guide clinicians for precise and optimal treatment for patients.

Intraoperative Frozen Section Biopsy of Uterine Smooth Muscle Tumors: A Clinicopathologic Analysis of 112 Cases With Emphasis on Potential Diagnostic Pitfalls.

Frozen sections of uterine smooth muscle tumors are infrequently required, and related diagnostic difficulties are seldom discussed. We analyzed the clinicopathologic features of 112 frozen sections of uterine smooth muscle tumors and determined the accuracy, reasons for deferrals, and causes of interpretational errors. Most patients (median age, 45 y) presented with pelvic mass symptoms (53%). The main reasons for a frozen section examination were an abnormal gross appearance including loss of the usual whorled pattern of leiomyoma (36 cases, 32.1%), and intraoperative discovery of an abnormal growth pattern and extrauterine extension of a uterine tumor (28 cases, 25%). There were 9 leiomyosarcomas and 103 leiomyomas, including 18 benign histologic variants. An accurate diagnosis of malignancy was achieved in all leiomyosarcomas, with the exception of a myxoid leiomyosarcoma. In 99 cases (88%), the frozen section diagnosis concurred with the permanent section diagnosis (false positives, 0.9%; false negatives, 0%). Misinterpretation of stromal hyalinization as tumor cell necrosis in a leiomyoma with amianthoid-like fibers was a major discrepancy. Two minor discrepancies did not lead to a change in management. The diagnosis was deferred in 10 cases (8.9%) because of stromal alterations, unusual cellular morphology, uncertain type of necrosis, and abnormal growth patterns. Thus, although various stromal and cellular alterations can cause diagnostic uncertainty, leading to deferrals, frozen section diagnosis of uterine smooth muscle tumors has a high accuracy rate. While a definitive frozen section diagnosis of malignancy may be made when there is unequivocal atypia, indisputable mitotic figures, and tumor cell necrosis, it is important to remember that nonmyogenic mesenchymal tumors may also mimic uterine smooth muscle tumors. In a frozen section setting, it would be sufficient to issue a diagnosis of "malignant mesenchymal tumor." For tumors that do not meet the criteria for malignancy, issuing a frozen section diagnosis of "atypical mesenchymal tumor and defer the histologic subtyping to the permanent sections" is appropriate.

Swallowing disorders following free jejunal flap reconstruction of circumferential pharyngeal defect: Does Botox help?

OBJECTIVES: Free jejunal flap for circumferential pharyngeal reconstruction is associated with late-onset dysphagia, regurgitation and prolonged transit time. This study aims to assess the feasibility and efficacy of Botulinum toxin A (Botox) in alleviating such swallowing dysfunction. MATERIALS AND METHODS: Twenty-six consecutive patients underwent free jejunal flap for circumferential pharyngeal reconstruction between January 2012 and December 2018. Outcomes were compared at 6, 12 and 24 months. RESULTS: In the non-Botox group (n = 13), video-fluoroscopic and manometry studies demonstrated asynchronous contractions and retrograde propulsion. All patients complained of nasal regurgitation on thin fluids at 6, 12 and 24 months. Bolus residue accumulation along jejunal mucosal folds resulted in prolonged transit time. In the Botox group (n = 13), amplitude of asynchronous contractions were lower: 25.4 mmHg vs. 52.1 mmHg (p = 0.037) for thin fluids at 12 months. Three patients complained of nasal regurgitation on thin fluids at 6 months. All 3 were asymptomatic at 12 months. Transit time was shortened overall. Functional Oral Intake Scale was higher. MD Anderson Dysphagia Inventory global (72.5% vs 45.7%, p = 0.003) and functional (62.0% vs 40.6%, p = 0.012) subscales were significantly improved at 24 months. CONCLUSION: Botox safely and effectively alleviates swallowing dysfunction associated with free jejunal flap for circumferential pharyngeal reconstruction.

Adaptation and validation of Mandarin Chinese version of the pediatric Voice Handicap Index (pVHI).

OBJECTIVE: The aim of this study was to adapt and validate the English version of pediatric voice handicap index (pVHI) into Mandarin Chinese. METHODS: A cross-sectional study was performed from May 2016 to April 2017. A total of 367 parents participated in this study, and 338 parents completed the translated questionnaire without missing data, including 213 parents of children with voice disorders (patients group), and 125 parents of children without voice disorders (control group). The internal consistency, test-retest reliability, contents validity, construct validity, clinical validity, and cutoff point were calculated. RESULTS: The most common voice disorder in the patients group was vocal fold nodules (77.9%), followed by chronic laryngitis (18.8%), and vocal fold polyps (3.3%). The prevalence for voice disorders was higher in boys (67.1%) than girls (32.9%). The most common vocal misuse and abuse habit was shouting loudly (n = 186, 87.3%), followed by speaking for a long time (n = 158, 74.2%), and crying loudly (n = 99, 46.5%). The internal consistency for the Mandarin Chinese version of pVHI was excellent in patients group (Cronbach α = 0.95). The inter-class correlation coefficient indicated strong test-retest reliability (ICC = 0.99). The principal-component analysis demonstrated three-factor eigenvalues greater than 1, and the cumulative proportion was 66.23%. The mean total scores and mean subscales scores were significantly higher in the patients group than the control group (p < 0.05). The physical domain had the highest mean score among the three subscales (functional, physical and emotional) in the patients group. The optimal cutoff point of the Mandarin Chinese version of pVHI was 9.5 points with a sensitivity of 80.3% and a specificity of 84.8%. CONCLUSION: The Mandarin Chinese version of pVHI was a reliable and valid tool to assess the parents' perception about their children's voice disorders. It is recommended that it can be used as a screening tool for discriminating between children with and without dysphonia.

Outcomes of Carotid Endarterectomy with Primary Closure.

Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid artery stenosis, although the optimal surgical technique is debated. The literature suggests that patch angioplasty reduces complication risk, although primary closure shortens cross-clamp time and eliminates complications associated with grafts. The objective of this study was to assess the complication rate after CEA with primary closure. Retrospective review of 240 consecutive patients between 2002 and 2010. Of these patients, 70% returned for follow-up visits for at least 2 or more years. Primary closure was used in all patients. The average cross-clamp time was 18 minutes. Complications in the immediate postoperative period within 30 days were as follows: stroke (n = 3; 1.1%), transient ischemic attack (TIA; n = 4; 1.5%), myocardial infarction (MI; n = 3; 1.1%), and death (n = 1; 0.4%). Short-term follow-up revealed eight patients who were found to have significant restenosis (>80%) by carotid duplex imaging. Two to ten year postoperative complication rates were as follows: stroke (n = 7; 4.2%), TIA (n = 7; 4.2%), amaurosis fugax (n = 1; 0.6%), MI (n = 8; 4.8%), and death (n = 28; 17%). Mortality was due to stroke or heart attack (n = 2; 1.2%), cancer (n = 7; 4.2%), and unknown causes (n = 19; 11%). This study presents our experience with complications after primary closure after CEA. In our experience, CEA is a safe and effective surgical means of preventing stroke in the short term. Well-designed prospective studies are needed to confirm specific patient characteristics in which primary closure and patch angioplasty are indicated.

Canadian Academy of Sport and Exercise Medicine position statement: athletes at high altitude.

Many sports incorporate training at altitude as a key component of their athlete training plan. Furthermore, many sports are required to compete at high altitude venues. Exercise at high altitude provides unique challenges to the athlete and to the sport medicine clinician working with these athletes. These challenges include altitude illness, alterations in training intensity and performance, nutritional and hydration difficulties, and challenges related to the austerity of the environment. Furthermore, many of the strategies that are typically utilized by visitors to altitude may have implications from an anti-doping point of view.This position statement was commissioned and approved by the Canadian Academy of Sport and Exercise Medicine. The purpose of this statement was to provide an evidence-based, best practices summary to assist clinicians with the preparation and management of athletes and individuals travelling to altitude for both competition and training.

Implementing wait-time reductions under Ontario government benchmarks (Pay-for-Results): a Cluster Randomized Trial of the Effect of a Physician-Nurse Supplementary Triage Assistance team (MDRNSTAT) on emergency department patient wait times.

BACKGROUND: Internationally, emergency departments are struggling with crowding and its associated morbidity, mortality, and decreased patient and health-care worker satisfaction. The objective was to evaluate the addition of a MDRNSTAT (Physician (MD)-Nurse (RN) Supplementary Team At Triage) on emergency department patient flow and quality of care. METHODS: Pragmatic cluster randomized trial. From 131 weekday shifts (8:00-14:30) during a 26-week period, we randomized 65 days (3173 visits) to the intervention cluster with a MDRNSTAT presence, and 66 days (3163 visits) to the nurse-only triage control cluster. The primary outcome was emergency department length-of-stay (EDLOS) for patients managed and discharged only by the emergency department. Secondary outcomes included EDLOS for patients initially seen by the emergency department, and subsequently consulted and admitted, patients reaching government-mandated thresholds, time to initial physician assessment, left-without being seen rate, time to investigation, and measurement of harm. RESULTS: The intervention's median EDLOS for discharged, non-consulted, high acuity patients was 4:05 [95th% CI: 3:58 to 4:15] versus 4:29 [95th% CI: 4:19-4:38] during comparator shifts. The intervention's median EDLOS for discharged, non-consulted, low acuity patients was 1:55 [95th% CI: 1:48 to 2:05] versus 2:08 [95th% CI: 2:02-2:14]. The intervention's median physician initial assessment time was 0:55 [95th% CI: 0:53 to 0:58] versus 1:21 [95th% CI: 1:18 to 1:25]. The intervention's left-without-being-seen rate was 1.5% versus 2.2% for the control (p = 0.06). The MDRNSTAT subgroup analysis resulted in significant decreases in median EDLOS for discharged, non-consulted high (4:01 [95th% CI: 3:43-4:16]) and low acuity patients (1:10 95th% CI: 0:58-1:19]), as well as physician initial assessment time (0:25 [95th% CI: 0:23-0:26]). No patients returned to the emergency department after being discharged by the MDRNSTAT at triage. CONCLUSIONS: The intervention reduced delays and left-without-being-seen rate without increased return visits or jeopardizing urgent care of severely ill patients. TRIAL REGISTRATION NUMBER: NCT00991471 ClinicalTrials.gov.