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Importance: Pulmonary embolism (PE) is characterized by occlusion of blood flow in a pulmonary artery, typically due to a thrombus that travels from a vein in a lower limb. The incidence of PE is approximately 60 to 120 per 100 000 people per year. Approximately 60 000 to 100 000 patients die from PE each year in the US.Observations: PE should be considered in patients presenting with acute chest pain, shortness of breath, or syncope. The diagnosis is determined by chest imaging. In patients with a systolic blood pressure of at least 90 mm Hg, the following 3 steps can be used to evaluate a patient with possible PE: assessment of the clinical probability of PE, D-dimer testing if indicated, and chest imaging if indicated. The clinical probability of PE can be assessed using a structured score or using clinical gestalt. In patients with a probability of PE that is less than 15%, the presence of 8 clinical characteristics (age <50 years, heart rate <100/min, an oxygen saturation level of > 94%, no recent surgery or trauma, no prior venous thromboembolism event, no hemoptysis, no unilateral leg swelling, and no estrogen use) identifies patients at very low risk of PE in whom no further testing is needed. In patients with low or intermediate clinical probability, a D-dimer level of less than 500 ng/mL is associated with a posttest probability of PE less than 1.85%. In these patients, PE can be excluded without chest imaging. A further refinement of D-dimer threshold is possible in patients aged 50 years and older, and in patients with a low likelihood of PE. Patients with a high probability of PE (ie, >40% probability) should undergo chest imaging, and D-dimer testing is not necessary. In patients with PE and a systolic blood pressure of 90 mm Hg or higher, compared with heparin combined with a vitamin K antagonist such as warfarin followed by warfarin alone, direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, are noninferior for treating PE and have a 0.6% lower rate of bleeding. In patients with PE and systolic blood pressure lower than 90 mm Hg, systemic thrombolysis is recommended and is associated with an 1.6% absolute reduction of mortality (from 3.9% to 2.3%).Conclusions and Relevance: In the US, PE affects approximately 370 000 patients per year and may cause approximately 60 000 to 100 000 deaths per year. First-line therapy consists of direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, with thrombolysis reserved for patients with systolic blood pressure lower than 90 mm Hg. [ABSTRACT FROM AUTHOR]

Importance: Acute infectious conjunctivitis is characterized by ocular redness and discharge, and is a common clinical entity. Evidence-based tools to aid the clinical diagnosis of viral vs bacterial conjunctivitis are lacking and may contribute to overprescribing of topical antibiotics.Objective: To determine the relative prevalence of viral vs bacterial conjunctivitis in adults and children, and to determine which symptoms or signs are suggestive of a viral vs bacterial etiology.Data Sources: A MEDLINE search (January 1946-March 2022) yielded 1891 articles. Included articles were rated using a quality score based on a modified Rational Clinical Examination grading system. Methodological quality levels 1 through 4 required a microbiological reference standard for diagnosis, whereas quality level 5 (the lowest quality) used a clinical reference standard for diagnosis.Study Selection: Consecutive series of patients presenting with acute infectious conjunctivitis and case series of viral or bacterial conjunctivitis alone. Thirty-two studies were included in a meta-analysis to determine prevalence and diagnostic accuracy measures; 27 used a microbiological reference standard for diagnosis and 5 used a clinical reference standard for diagnosis.Results: In studies involving children (5 studies; 881 patients; mean age, 4.7 years [age range, 1 month-18 years]), the prevalence of bacterial conjunctivitis was higher than viral conjunctivitis (71% vs 16%, respectively, P = .01). In the only study of adults (n = 207 patients; mean age, 25.7 years), the prevalence of viral conjunctivitis was higher than bacterial conjunctivitis (78% vs 16%, respectively, P < .001). For the primary analysis of level 1 (n = 6) and level 2 (n = 5) studies (1725 patients total), the clinical findings that best distinguished a viral etiology for conjunctivitis from a bacterial etiology included pharyngitis (sensitivity range, 0.55-0.58; specificity range, 0.89-0.94; positive likelihood ratio [LR] range, 5.4-9.9), preauricular lymphadenopathy (sensitivity range, 0.17-0.31; specificity range, 0.93-0.94; positive LR range, 2.5-5.6), and contact with another person with red eye (sensitivity, 0.18 [95% CI, 0.14-0.22]; specificity, 0.93 [95% CI, 0.90-0.95]; positive LR, 2.5 [95% CI, 1.6-3.7]). Mucopurulent ocular discharge (sensitivity, 0.76 [95% CI, 0.60-0.87); specificity, 0.66 [95% CI, 0.58-0.73]; positive LR, 2.1 [95% CI, 1.7-2.6]) and otitis media (sensitivity, 0.24 [95% CI, 0.20-0.29]; specificity, 0.91 [95% CI, 0.85-0.94]; positive LR, 2.5 [95% CI, 1.5-4.4]) were associated with the presence of bacterial conjunctivitis.Conclusions and Relevance: In this review, bacterial conjunctivitis was more common than viral conjunctivitis in children and viral conjunctivitis was more common than bacterial conjunctivitis in adults, although the prevalence estimates were based on limited evidence. Symptoms and signs associated with a higher likelihood of viral conjunctivitis in adults and children included concomitant pharyngitis, an enlarged preauricular node, and contact with another person with red eye, and signs associated with a higher likelihood of bacterial conjunctivitis included the presence of mucopurulent discharge and otitis media, but no single symptom or sign differentiated the 2 conditions with high certainty. [ABSTRACT FROM AUTHOR]

Importance: Approximately 23 700 US children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function.Objective: To evaluate neurocognitive outcomes of children who survive pediatric intensive care unit (PICU) hospitalization for acute respiratory failure compared with their biological siblings.Design, Setting, and Participants: Prospective sibling-matched cohort study conducted at 31 US PICUs and associated neuropsychology testing centers. Patients were 8 years or younger with a Pediatric Cerebral Performance Category score of 1 (normal) before PICU admission and less than or equal to 3 (no worse than moderate neurocognitive dysfunction) at PICU discharge, excluding patients with a history of neurocognitive deficits or who were readmitted and underwent mechanical ventilation. Biological siblings were aged 4 to 16 years at testing, with Pediatric Cerebral Performance Category score of 1 and no history of mechanical ventilation or general anesthesia. A total of 121 sibling pairs were enrolled from September 2, 2014, to December 13, 2017, and underwent neurocognitive testing starting March 14, 2015. The date of the final follow-up was November 6, 2018.Exposures: Critical illness and PICU treatment for acute respiratory failure.Main Outcomes and Measures: The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included measures of attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Evaluations occurred 3 to 8 years after hospital discharge.Results: Patients (n = 121; 55 [45%] female patients) underwent PICU care at a median (IQR) age of 1.0 (0.2-3.2) years, received a median (IQR) of 5.5 (3.1-7.7) days of invasive mechanical ventilation, and were tested at a median (IQR) age of 6.6 (5.4-9.1) years. Matched siblings (n = 121; 72 [60%] female siblings) were tested at a median (IQR) age of 8.4 (7.0-10.2) years. Patients had a lower mean estimated IQ than matched siblings (101.5 vs 104.3; mean difference, -2.8 [95% CI, -5.4 to -0.2]). Among secondary outcomes, patients had significantly lower scores than matched siblings on nonverbal memory (mean difference, -0.9 [95% CI, -1.6 to -0.3]), visuospatial skills (mean difference, -0.9 [95% CI, -1.8 to -0.1]), and fine motor control (mean difference, -3.1 [95% CI, -4.9 to -1.4]) and significantly higher scores on processing speed (mean difference, 4.4 [95% CI, 0.2-8.5]). There were no significant differences in the remaining secondary outcomes, including attention, verbal memory, expressive language, and executive function.Conclusions and Relevance: Among children, survival of PICU hospitalization for respiratory failure and discharge without severe cognitive dysfunction was associated with significantly lower subsequent IQ scores compared with matched siblings. However, the magnitude of the difference was small and of uncertain clinical importance. [ABSTRACT FROM AUTHOR]

This study compares the frequency of hospital-to-hospital transportation events and associated life-threatening deterioration during transport among patients with acute lower respiratory tract illness during vs before the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Importance: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known.Objective: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis.Design, Setting, and Participants: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019.Interventions: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days.Main Outcomes and Measures: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference.Results: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin.Conclusion and Relevance: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics.Trial Registration: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10. [ABSTRACT FROM AUTHOR]

Importance: While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown.Objective: To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy.Design, Setting, and Participants: A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed.Interventions: Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408).Main Outcomes and Measures: The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes.Results: Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%).Conclusions and Relevance: Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.Trial Registration: ClinicalTrials.gov Identifier: NCT01429415. [ABSTRACT FROM AUTHOR]

Importance: Clinical guidelines for the early management of acute heart failure in the emergency department (ED) setting are based on only moderate levels of evidence, with subsequent low adherence to these guidelines.Objective: To test the effect of an early guideline-recommended care bundle on short-term prognosis in older patients with acute heart failure in the ED.Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 15 EDs in France of 503 patients 75 years and older with a diagnosis of acute heart failure in the ED from December 2018 to September 2019 and followed up for 30 days until October 2019.Interventions: A care bundle that included early intravenous nitrate boluses; management of precipitating factors, such as acute coronary syndrome, infection, or atrial fibrillation; and moderate dose of intravenous diuretics (n = 200). In the control group, patient care was left to the discretion of the treating emergency physician (n = 303). Each center was randomized to the order in which they switched to the "intervention period." After the initial 4-week control period for all centers, 1 center entered in the intervention period every 2 weeks.Main Outcomes and Measures: The primary end point was the number of days alive and out of hospital at 30 days. Secondary outcomes included 30-day all-cause mortality, 30-day cardiovascular mortality, unscheduled readmission, length of hospital stay, and kidney impairment.Results: Among 503 patients who were randomized (median age, 87 years; 298 [59%] women), 502 were analyzed. In the intervention group, patients received a median (interquartile range) of 27.0 (9-54) mg of intravenous nitrates in the first 4 hours vs 4.0 (2.0-6.0) mg in the control group (adjusted difference, 23.8 [95% CI, 13.5-34.1]). There was a significantly higher percentage of patients in the intervention group treated for their precipitating factors than in the control group (58.8% vs 31.9%; adjusted difference, 31.1% [95% CI, 14.3%-47.9%]). There was no statistically significant difference in the primary end point of the number of days alive and out of hospital at 30 days (median [interquartile range], 19 [0- 24] d in both groups; adjusted difference, -1.9 [95% CI, -6.6 to 2.8]; adjusted ratio, 0.88 [95% CI, 0.64-1.21]). At 30 days, there was no significant difference between the intervention and control groups in mortality (8.0% vs 9.7%; adjusted difference, 4.1% [95% CI, -17.2% to 25.3%]), cardiovascular mortality (5.0% vs 7.4%; adjusted difference, 2.1% [95% CI, -15.5% to 19.8%]), unscheduled readmission (14.3% vs 15.7%; adjusted difference, -1.3% [95% CI, -26.3% to 23.7%]), median length of hospital stay (8 d in both groups; adjusted difference, 2.5 [95% CI, -0.9 to 5.8]), and kidney impairment (1% in both groups).Conclusions and Relevance: Among older patients with acute heart failure, use of a guideline-based comprehensive care bundle in the ED compared with usual care did not result in a statistically significant difference in the number of days alive and out of the hospital at 30 days. Further research is needed to identify effective treatments for acute heart failure in older patients.Trial Registration: ClinicalTrials.gov Identifier: NCT03683212. [ABSTRACT FROM AUTHOR]

Importance: Nonoperative management with antibiotics alone has the potential to treat uncomplicated pediatric appendicitis with fewer disability days than surgery.Objective: To determine the success rate of nonoperative management and compare differences in treatment-related disability, satisfaction, health-related quality of life, and complications between nonoperative management and surgery in children with uncomplicated appendicitis.Design, Setting, and Participants: Multi-institutional nonrandomized controlled intervention study of 1068 children aged 7 through 17 years with uncomplicated appendicitis treated at 10 tertiary children's hospitals across 7 US states between May 2015 and October 2018 with 1-year follow-up through October 2019. Of the 1209 eligible patients approached, 1068 enrolled in the study.Interventions: Patient and family selection of nonoperative management with antibiotics alone (nonoperative group, n = 370) or urgent (≤12 hours of admission) laparoscopic appendectomy (surgery group, n = 698).Main Outcomes and Measures: The 2 primary outcomes assessed at 1 year were disability days, defined as the total number of days the child was not able to participate in all of his/her normal activities secondary to appendicitis-related care (expected difference, 5 days), and success rate of nonoperative management, defined as the proportion of patients initially managed nonoperatively who did not undergo appendectomy by 1 year (lowest acceptable success rate, ≥70%). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between treatment groups for all outcome assessments.Results: Among 1068 patients who were enrolled (median age, 12.4 years; 38% girls), 370 (35%) chose nonoperative management and 698 (65%) chose surgery. A total of 806 (75%) had complete follow-up: 284 (77%) in the nonoperative group; 522 (75%) in the surgery group. Patients in the nonoperative group were more often younger (median age, 12.3 years vs 12.5 years), Black (9.6% vs 4.9%) or other race (14.6% vs 8.7%), had caregivers with a bachelor's degree (29.8% vs 23.5%), and underwent diagnostic ultrasound (79.7% vs 74.5%). After IPTW, the success rate of nonoperative management at 1 year was 67.1% (96% CI, 61.5%-72.31%; P = .86). Nonoperative management was associated with significantly fewer patient disability days at 1 year than did surgery (adjusted mean, 6.6 vs 10.9 days; mean difference, -4.3 days (99% CI, -6.17 to -2.43; P < .001). Of 16 other prespecified secondary end points, 10 showed no significant difference.Conclusion and Relevance: Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1% and, compared with urgent surgery, was associated with statistically significantly fewer disability days at 1 year. However, there was substantial loss to follow-up, the comparison with the prespecified threshold for an acceptable success rate of nonoperative management was not statistically significant, and the hypothesized difference in disability days was not met.Trial Registration: ClinicalTrials.gov Identifier: NCT02271932. [ABSTRACT FROM AUTHOR]

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function.Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018.Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed.Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality.Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach.Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings.Trial Registration: ISRCTN Identifier: ISRCTN45877994. [ABSTRACT FROM AUTHOR]

Importance: Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas with a prevalence of 42 to 73 per 100 000 adults in the United States.Observations: Both genetic and environmental factors are thought to contribute to the pathogenesis of CP. Environmental factors associated with CP include alcohol abuse (odds ratio [OR], 3.1; 95% CI, 1.87-5.14) for 5 or more drinks per day vs abstainers and light drinkers as well as smoking (OR, 4.59; 95% CI, 2.91-7.25) for more than 35 pack-years in a case-control study involving 971 participants. Between 28% to 80% of patients are classified as having "idiopathic CP." Up to 50% of these individuals have mutations of the trypsin inhibitor gene (SPINK1) or the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Approximately 1% of people diagnosed with CP may have hereditary pancreatitis, associated with cationic trypsinogen (PRSS1) gene mutations. Approximately 80% of people with CP present with recurrent or chronic upper abdominal pain. Long-term sequelae include diabetes in 38% to 40% and exocrine insufficiency in 30% to 48%. The diagnosis is based on pancreatic calcifications, ductal dilatation, and atrophy visualized by imaging with computed tomography, magnetic resonance imaging, or both. Endoscopic ultrasound can assist in making the diagnosis in patients with a high index of suspicion such as recurrent episodes of acute pancreatitis when imaging is normal or equivocal. The first line of therapy consists of advice to discontinue use of alcohol and smoking and taking analgesic agents (nonsteroidal anti-inflammatory drugs and weak opioids such as tramadol). A trial of pancreatic enzymes and antioxidants (a combination of multivitamins, selenium, and methionine) can control symptoms in up to 50% of patients. Patients with pancreatic ductal obstruction due to stones, stricture, or both may benefit from ductal drainage via endoscopic retrograde cholangiopancreatography (ERCP) or surgical drainage procedures, such as pancreaticojejunostomy with or without pancreatic head resection, which may provide better pain relief among people who do not respond to endoscopic therapy.Conclusions and Relevance: Chronic pancreatitis often results in chronic abdominal pain and is most commonly caused by excessive alcohol use, smoking, or genetic mutations. Treatment consists primarily of alcohol and smoking cessation, pain control, replacement of pancreatic insufficiency, or mechanical drainage of obstructed pancreatic ducts for some patients. [ABSTRACT FROM AUTHOR]

Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.Design, Setting, and Participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone.Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.Main Outcomes and Measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave.Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group).Conclusions and Relevance: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.Trial Registration: ClinicalTrials.gov Identifier: NCT01022567. [ABSTRACT FROM AUTHOR]

Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.Interventions: Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.Main Outcomes and Measures: Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.Results: Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.Conclusions and Relevance: Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.Trial Registration: clinicaltrials.gov Identifier: NCT02166476. [ABSTRACT FROM AUTHOR]

Importance: Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment.Objective: To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children.Design, Setting, and Participants: A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts.Exposures: Broad-spectrum antibiotics vs narrow-spectrum antibiotics.Main Outcomes and Measures: In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events.Results: Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%]).Conclusions and Relevance: Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections. [ABSTRACT FROM AUTHOR]

Importance: Acute mountain sickness (AMS) affects more than 25% of individuals ascending to 3500 m (11 500 ft) and more than 50% of those above 6000 m (19 700 ft). AMS may progress from nonspecific symptoms to life-threatening high-altitude cerebral edema in less than 1% of patients. It is not clear how to best diagnose AMS.Objective: To systematically review studies assessing the accuracy of AMS diagnostic instruments, including the visual analog scale (VAS) score, which quantifies the overall feeling of sickness at altitude (VAS[O]; various thresholds), Acute Mountain Sickness-Cerebral score (AMS-C; ≥0.7 indicates AMS), and the clinical functional score (CFS; ≥2 indicates AMS) compared with the Lake Louise Questionnaire Score (LLQS; score of ≥5).Data Extraction and Synthesis: Searches of MEDLINE and EMBASE from inception to May 2017 identified 1245 publications of which 91 were suitable for prevalence analysis (66 944 participants) and 14 compared at least 2 instruments (1858 participants) using a score of 5 or greater on the LLQS as a reference standard. To determine the prevalence of AMS for establishing the pretest probability of AMS, a random-effects meta-regression was performed based on the reported prevalence of AMS as a function of altitude.Main Outcomes and Measures: AMS prevalence, likelihood ratios (LRs), sensitivity, and specificity of screening instruments.Results: The final analysis included 91 articles (comprising 66 944 study participants). Altitude predicted AMS and accounted for 28% of heterogeneity between studies. For each 1000-m (3300-ft) increase in altitude above 2500 m (8200 ft), AMS prevalence increased 13% (95% CI, 9.5%-17%). Testing characteristics were similar for VAS(O), AMS-C, and CFS vs a score of 5 or greater on the LLQS (positive LRs: range, 3.2-8.2; P = .22 for comparisons; specificity range, 67%-92%; negative LRs: range, 0.30-0.36; P = .50 for comparisons; sensitivity range, 67%-82%). The CFS asks a single question: "overall if you had any symptoms, how did they affect your activity (ordinal scale 0-3)?" For CFS, moderate to severe reduction in daily activities had a positive LR of 3.2 (95% CI, 1.4-7.2) and specificity of 67% (95% CI, 37%-97%); no reduction to mild reduction in activities had a negative LR of 0.30 (95% CI, 0.22-0.39) and sensitivity of 82% (95% CI, 77%-87%).Conclusions and Relevance: The prevalence of acute mountain sickness increases with higher altitudes. The visual analog scale for the overall feeling of sickness at altitude, Acute Mountain Sickness-Cerebral, and clinical functional score perform similarly to the Lake Louise Questionnaire Score using a score of 5 or greater as a reference standard. In clinical and travel settings, the clinical functional score is the simplest instrument to use. Clinicians evaluating high-altitude travelers who report moderate to severe limitations in activities of daily living (clinical functional score ≥2) should use the Lake Louise Questionnaire Score to assess the severity of acute mountain sickness. [ABSTRACT FROM AUTHOR]

Importance: Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery.Objective: To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation.Design, Setting, and Participants: In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015).Interventions: Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%.Main Outcomes and Measures: The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement.Results: A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified.Conclusions and Relevance: Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting.Trial Registration: ISRCTN Identifier: ISRCTN52416964. [ABSTRACT FROM AUTHOR]

Importance: Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence.Objective: To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma.Design, Setting, and Participants: Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years.Interventions: Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days.Main Outcomes and Measures: The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events.Results: Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, -0.20; 95% CI, -0.40 to 0.00; P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events.Conclusions and Relevance: Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity.Trial Registration: ISRCTN.com Identifier: ISRCTN57309858. [ABSTRACT FROM AUTHOR]

Importance: Acute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment.Objective: To assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics.Design, Setting, and Participants: Double-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy.Interventions: Single oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283).Main Outcomes and Measures: Primary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events.Results: Among 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, -1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no significant differences in any other secondary outcomes.Conclusions and Relevance: Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours.Trial Registration: isrctn.org Identifier: ISRCTN17435450. [ABSTRACT FROM AUTHOR]

Importance: Readmission rates declined after announcement of the Hospital Readmission Reduction Program (HRRP), which penalizes hospitals for excess readmissions for acute myocardial infarction (AMI), heart failure (HF), and pneumonia.Objective: To compare trends in readmission rates for target and nontarget conditions, stratified by hospital penalty status.Design, Setting, and Participants: Retrospective cohort study of Medicare fee-for-service beneficiaries older than 64 years discharged between January 1, 2008, and June 30, 2015, from 2214 penalty hospitals and 1283 nonpenalty hospitals. Difference-interrupted time-series models were used to compare trends in readmission rates by condition and penalty status.Exposure: Hospital penalty status or target condition under the HRRP.Main Outcomes and Measures: Thirty-day risk adjusted, all-cause unplanned readmission rates for target and nontarget conditions.Results: The study included 48 137 102 hospitalizations of 20 351 161 Medicare beneficiaries. In January 2008, the mean readmission rates for AMI, HF, pneumonia, and nontarget conditions were 21.9%, 27.5%, 20.1%, and 18.4%, respectively, at hospitals later subject to financial penalties and 18.7%, 24.2%, 17.4%, and 15.7% at hospitals not subject to penalties. Between January 2008 and March 2010, prior to HRRP announcement, readmission rates were stable across hospitals (except AMI at nonpenalty hospitals). Following announcement of HRRP (March 2010), readmission rates for both target and nontarget conditions declined significantly faster for patients at hospitals later subject to financial penalties compared with those at nonpenalized hospitals (for AMI, additional decrease of -1.24 [95% CI, -1.84 to -0.65] percentage points per year relative to nonpenalty discharges; for HF, -1.25 [95% CI, -1.64 to -0.86]; for pneumonia, -1.37 [95% CI, -1.80 to -0.95]; and for nontarget conditions, -0.27 [95% CI, -0.38 to -0.17]; P < .001 for all). For penalty hospitals, readmission rates for target conditions declined significantly faster compared with nontarget conditions (for AMI, additional decline of -0.49 [95% CI, -0.81 to -0.16] percentage points per year relative to nontarget conditions [P = .004]; for HF, -0.90 [95% CI, -1.18 to -0.62; P < .001]; and for pneumonia, -0.57 [95% CI, -0.92 to -0.23; P < .001]). In contrast, among nonpenalty hospitals, readmissions for target conditions declined similarly or more slowly compared with nontarget conditions (for AMI, additional increase of 0.48 [95% CI, 0.01-0.95] percentage points per year [P = .05]; for HF, 0.08 [95% CI, -0.30 to 0.46; P = .67]; for pneumonia, 0.53 [95% CI, 0.13-0.93; P = .01]). After HRRP implementation in October 2012, the rate of change for readmission rates plateaued (P < .05 for all except pneumonia at nonpenalty hospitals), with the greatest relative change observed among hospitals subject to financial penalty.Conclusions and Relevance: Medicare fee-for-service patients at hospitals subject to penalties under the HRRP had greater reductions in readmission rates compared with those at nonpenalized hospitals. Changes were greater for target vs nontarget conditions for patients at the penalized hospitals but not at the other hospitals. [ABSTRACT FROM AUTHOR]

Importance: Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials.Objective: To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy.Design, Setting, and Participants: SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery.Intervention: Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy.Main Outcomes and Measures: Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]). Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety.Results: Among 150 patients (60 women [40%]; mean age, 71.5 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 16.8 at admission vs 13.6 after 24 hours; difference, -3.2 points [95% CI, -5.6 to -0.8]) vs the conscious sedation group (mean NIHSS score, 17.2 at admission vs 13.6 after 24 hour; difference, -3.6 points [95% CI, -5.5 to -1.7]); mean difference between groups, -0.4 (95% CI, -3.4 to 2.7; P = .82). Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences. In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 9.1%; difference, 9.1%; P = .008), but postinterventional complications were more frequent for hypothermia (32.9% vs 9.1%; P < .001), delayed extubation (49.3% vs 6.5%; P < .001), and pneumonia (13.7% vs 3.9%; P = .03). More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [37.0% in the general anesthesia group vs 18.2% in the conscious sedation group P = .01]). There were no differences in mortality at 3 months (24.7% in both groups).Conclusions and Relevance: Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours. The study findings do not support an advantage for the use of conscious sedation.Trial Registration: clinicaltrials.gov Identifier: NCT02126085. [ABSTRACT FROM AUTHOR]

This study uses Medicare Parts A and B claims data to compare hospitalizations for and spending on traumatic injury vs heart failure, pneumonia, stroke, and acute myocardial infarction in older adults between 2008 and 2014. [ABSTRACT FROM AUTHOR]

Importance: Acute aortic syndrome (AAS), a potentially fatal pathologic process within the aortic wall, should be suspected in patients presenting with severe thoracic pain and hypertension. AAS, including aortic dissection (approximately 90% of cases) and intramural hematoma, may be complicated by poor perfusion, aneurysm, or uncontrollable pain and hypertension. AAS is uncommon (approximately 3.5-6.0 per 100,000 patient-years) but rapid diagnosis is imperative as an emergency surgical procedure is frequently necessary.Objective: To systematically review the current evidence on diagnosis and treatment of AAS.Evidence Review: Searches of MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials for articles on diagnosis and treatment of AAS from June 1994 to January 29, 2016, were performed. Only clinical trials and prospective observational studies of 10 or more patients were included. Eighty-two studies (2 randomized clinical trials and 80 observational) describing 57,311 patients were reviewed.Findings: Chest or back pain was the most commonly reported presenting symptom of AAS (61.6%-84.8%). Patients were typically aged 60 to 70 years, male (50%-81%), and had hypertension (45%-100%). Sensitivities of computerized tomography and magnetic resonance imaging for diagnosis of AAS were 100% and 95% to 100%, respectively. Transesophageal echocardiography was 86% to 100% sensitive, whereas D-dimer was 51.7% to 100% sensitive and 32.8% to 89.2% specific among 6 studies (n = 876). An immediate open surgical procedure is needed for dissection of the ascending aorta, given the high mortality (26%-58%) and proximity to the aortic valve and great vessels (with potential for dissection complications such as tamponade). An RCT comparing endovascular surgical procedure to medical management for uncomplicated AAS in the descending aorta (n = 61) revealed no dissection-related deaths in either group. Endovascular surgical procedure was better than medical treatment (97% vs 43%, P < .001) for the primary end point of "favorable aortic remodeling" (false lumen thrombosis and no aortic dilation or rupture). The remaining evidence on therapies was observational, introducing significant selection bias.Conclusions and Relevance: Because of the high mortality rate, AAS should be considered and diagnosed promptly in patients presenting with acute chest or back pain and high blood pressure. Computerized tomography, magnetic resonance imaging, and transesophageal echocardiography are reliable tools for diagnosing AAS. Available data suggest that open surgical repair is optimal for treating type A (ascending aorta) AAS, whereas thoracic endovascular aortic repair may be optimal for treating type B (descending aorta) AAS. However, evidence is limited by the paucity of randomized trials. [ABSTRACT FROM AUTHOR]

Importance: Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection.Objective: To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing.Design, Setting, and Participants: Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection.Exposures: All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test.Main Outcomes and Measures: Number and proportion with acute HIV infections detected.Results: Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P < .001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%).Conclusions and Relevance: In a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention. [ABSTRACT FROM AUTHOR]

Importance: Interventions based on behavioral science might reduce inappropriate antibiotic prescribing.Objective: To assess effects of behavioral interventions and rates of inappropriate (not guideline-concordant) antibiotic prescribing during ambulatory visits for acute respiratory tract infections.Design, Setting, and Participants: Cluster randomized clinical trial conducted among 47 primary care practices in Boston and Los Angeles. Participants were 248 enrolled clinicians randomized to receive 0, 1, 2, or 3 interventions for 18 months. All clinicians received education on antibiotic prescribing guidelines on enrollment. Interventions began between November 1, 2011, and October 1, 2012. Follow-up for the latest-starting sites ended on April 1, 2014. Adult patients with comorbidities and concomitant infections were excluded.Interventions: Three behavioral interventions, implemented alone or in combination: suggested alternatives presented electronic order sets suggesting nonantibiotic treatments; accountable justification prompted clinicians to enter free-text justifications for prescribing antibiotics into patients' electronic health records; peer comparison sent emails to clinicians that compared their antibiotic prescribing rates with those of "top performers" (those with the lowest inappropriate prescribing rates).Main Outcomes and Measures: Antibiotic prescribing rates for visits with antibiotic-inappropriate diagnoses (nonspecific upper respiratory tract infections, acute bronchitis, and influenza) from 18 months preintervention to 18 months afterward, adjusting each intervention's effects for co-occurring interventions and preintervention trends, with random effects for practices and clinicians.Results: There were 14,753 visits (mean patient age, 47 years; 69% women) for antibiotic-inappropriate acute respiratory tract infections during the baseline period and 16,959 visits (mean patient age, 48 years; 67% women) during the intervention period. Mean antibiotic prescribing rates decreased from 24.1% at intervention start to 13.1% at intervention month 18 (absolute difference, -11.0%) for control practices; from 22.1% to 6.1% (absolute difference, -16.0%) for suggested alternatives (difference in differences, -5.0% [95% CI, -7.8% to 0.1%]; P = .66 for differences in trajectories); from 23.2% to 5.2% (absolute difference, -18.1%) for accountable justification (difference in differences, -7.0% [95% CI, -9.1% to -2.9%]; P < .001); and from 19.9% to 3.7% (absolute difference, -16.3%) for peer comparison (difference in differences, -5.2% [95% CI, -6.9% to -1.6%]; P < .001). There were no statistically significant interactions (neither synergy nor interference) between interventions.Conclusions and Relevance: Among primary care practices, the use of accountable justification and peer comparison as behavioral interventions resulted in lower rates of inappropriate antibiotic prescribing for acute respiratory tract infections.Trial Registration: clinicaltrials.gov Identifier: NCT01454947. [ABSTRACT FROM AUTHOR]

Importance: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear.Objective: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure.Design, Setting, and Participants: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015.Interventions: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183).Main Outcomes and Measures: The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay.Results: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays.Conclusions and Relevance: Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited.Trial Registration: clinicaltrials.gov Identifier: NCT01915719. [ABSTRACT FROM AUTHOR]

Importance: Low back pain (LBP) is responsible for more than 2.5 million visits to US emergency departments (EDs) annually. These patients are usually treated with nonsteroidal anti-inflammatory drugs, acetaminophen, opioids, or skeletal muscle relaxants, often in combination.Objective: To compare functional outcomes and pain at 1 week and 3 months after an ED visit for acute LBP among patients randomized to a 10-day course of (1) naproxen + placebo; (2) naproxen + cyclobenzaprine; or (3) naproxen + oxycodone/acetaminophen.Design, Setting, and Participants: This randomized, double-blind, 3-group study was conducted at one urban ED in the Bronx, New York City. Patients who presented with nontraumatic, nonradicular LBP of 2 weeks' duration or less were eligible for enrollment upon ED discharge if they had a score greater than 5 on the Roland-Morris Disability Questionnaire (RMDQ). The RMDQ is a 24-item questionnaire commonly used to measure LBP and related functional impairment on which 0 indicates no functional impairment and 24 indicates maximum impairment. Beginning in April 2012, a total of 2588 patients were approached for enrollment. Of the 323 deemed eligible for participation, 107 were randomized to receive placebo and 108 each to cyclobenzaprine and to oxycodone/acetaminophen. Follow-up was completed in December 2014.Interventions: All participants were given 20 tablets of naproxen, 500 mg, to be taken twice a day. They were randomized to receive either 60 tablets of placebo; cyclobenzaprine, 5 mg; or oxycodone, 5 mg/acetaminophen, 325 mg. Participants were instructed to take 1 or 2 of these tablets every 8 hours, as needed for LBP. They also received a standardized 10-minute LBP educational session prior to discharge.Main Outcomes and Measures: The primary outcome was improvement in RMDQ between ED discharge and 1 week later.Results: Demographic characteristics were comparable among the 3 groups. At baseline, median RMDQ score in the placebo group was 20 (interquartile range [IQR],17-21), in the cyclobenzaprine group 19 (IQR,17-21), and in the oxycodone/acetaminophen group 20 (IQR,17-22). At 1-week follow-up, the mean RMDQ improvement was 9.8 in the placebo group, 10.1 in the cyclobenzaprine group, and 11.1 in the oxycodone/acetaminophen group. Between-group difference in mean RMDQ improvement for cyclobenzaprine vs placebo was 0.3 (98.3% CI, -2.6 to 3.2; P = .77), for oxycodone/acetaminophen vs placebo, 1.3 (98.3% CI, -1.5 to 4.1; P = .28), and for oxycodone/acetaminophen vs cyclobenzaprine, 0.9 (98.3% CI, -2.1 to 3.9; P = .45).Conclusions and Relevance: Among patients with acute, nontraumatic, nonradicular LBP presenting to the ED, adding cyclobenzaprine or oxycodone/acetaminophen to naproxen alone did not improve functional outcomes or pain at 1-week follow-up. These findings do not support use of these additional medications in this setting.Trial Registration: clinicaltrials.gov Identifier: NCT01587274. [ABSTRACT FROM AUTHOR]

Importance: Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures.Objective: To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis.Design, Setting, and Participants: Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled.Interventions: Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered.Main Outcomes and Measures: The primary outcome was severe postoperative complications (Clavien-Dindo score >IIIa) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life.Results: The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage.Conclusions and Relevance: Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.Trial Registration: clinicaltrials.gov Identifier: NCT01047462. [ABSTRACT FROM AUTHOR]

The article discusses research regarding the potential relationship between acute Zika virus infections and the risks factors for the autoimmune disorder Guillain-Barré syndrome (GBS), and it mentions a Zika virus epidemic in Puerto Rico, as well as information about flavivirus transmissions involving Aedes species mosquitoes. Positive reverse transcription–polymerase chain reactions and neurologic illness diagnoses and GBS treatments.

Importance: Oral steroids are commonly used to treat acute sciatica due to a herniated disk but have not been evaluated in an appropriately powered clinical trial.Objective: To determine if oral prednisone is more effective than placebo in improving function and pain among patients with acute sciatica.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial conducted from 2008 to 2013 in a large integrated health care delivery system in Northern California. Adults (n=269) with radicular pain for 3 months or less, an Oswestry Disability Index (ODI) score of 30 or higher (range, 0-100; higher scores indicate greater dysfunction), and a herniated disk confirmed by magnetic resonance imaging were eligible.Interventions: Participants were randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral prednisone (5 days each of 60 mg, 40 mg, and 20 mg; total cumulative dose = 600 mg; n = 181) or matching placebo (n = 88).Main Outcomes and Measures: The primary outcome was ODI change at 3 weeks; secondary outcomes were ODI change at 1 year, change in lower extremity pain (measured on a 0-10 scale; higher scores indicate more pain), spine surgery, and Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (0-100 scale; higher scores better).Results: Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the placebo group, respectively. The prednisone-treated group showed an adjusted mean 6.4-point (95% CI, 1.9-10.9; P = .006) greater improvement in ODI scores at 3 weeks than the placebo group and a mean 7.4-point (95% CI, 2.2-12.5; P = .005) greater improvement at 52 weeks. Compared with the placebo group, the prednisone group showed an adjusted mean 0.3-point (95% CI, -0.4 to 1.0; P = .34) greater reduction in pain at 3 weeks and a mean 0.6-point (95% CI, -0.2 to 1.3; P = .15) greater reduction at 52 weeks. The prednisone group showed an adjusted mean 3.3-point (95% CI, 1.3-5.2; P = .001) greater improvement in the SF-36 PCS score at 3 weeks, no difference in the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3 to 5.4; P = .08), no change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI, -0.4 to 4.8; P = .10), and an adjusted 3.6-point (95% CI, 0.6-6.7; P = .02) greater improvement in the SF-36 MCS score at 52 weeks. There were no differences in surgery rates at 52-week follow-up. Having 1 or more adverse events at 3-week follow-up was more common in the prednisone group than in the placebo group (49.2% vs 23.9%; P < .001).Conclusions and Relevance: Among patients with acute radiculopathy due to a herniated lumbar disk, a short course of oral steroids, compared with placebo, resulted in modestly improved function and no improvement in pain.Trial Registration: clinicaltrials.gov Identifier: NCT00668434. [ABSTRACT FROM AUTHOR]

The article focuses on reports of unexplainable acute hepatitis among pediatric patients being investigated by the U.S. Centers for Disease Control and Prevention (CDC) in 36 states and territories.

This JAMA Patient Page describes acute cholecystitis and its risk factors, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

This Viewpoint uses clinical observations of the natural course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to propose 3 phases of illness: acute infection (what people commonly refer to with the COVID-19 designation); postacute hyperinflammatory illness (referred to clinically as multisystem inflammatory syndrome); and late inflammatory sequelae, manifest as enduring cardiac, neurological, and psychological symptoms. [ABSTRACT FROM AUTHOR]

The article focuses on a study aimed at the calculating the weaning duration in patients requiring prolonged mechanical ventilation and they are com-weaned at long-term acute care hospitals (LTACH). It states that the study was conducted in a hospital in Illinois. According to the study, patients when randomized to tracheostomy and then disconnected from the ventilator so that they can breathe through the tracheostomy then the weaning duration was interrupted. It further states that the weaning time between pressure support and tracheostomy collar was made using the log-rank test.

The article focuses on a study related to the treatment of pancreatitis with the help of lipid modification. Meta analysis method was used in the collection of several data related to randomize clinical trials. It mentions that treatment of pancreatitis that statin and ezetimibe with placebo were effective in controlling the disease and hypertriglyceridemia was reported to be the common cause of pancreatitis. A flowchart and a table are also presented related to several lipid modification trials. The author states that they were not able to differentiate pancreatitis in chronic and acute cases.

The article discusses a study on stress cardiomyopathy (SC) also known in Japanese as takotsubo conducted in Europe and North America from January 2005 to October 2010. SC is described as a transient form of acute heart failure linked with left ventricular (LV) dysfunction and triggered by stressful events. The study involved postmenopausal women, younger women and men. Four different patterns of regional ventricular ballooning were identified through data from cardiovascular magnetic resonance (CMR) imaging. Coronary angiography revealed healthy coronary arteries in 75% of the patients and an epicardial coronary artery stenosis in 6%. Also discussed are the clinical characteristics, treatment and management of SC.

The article comments on the result of a randomized clinical trial that investigated the best medical management with endoscopic intervention versus surgery for painful chronic pancreatitis. Topics discussed are efficacy of surgery over endoscopic treatment and stone lithotripsy for treatment of painful chronic pancreatitis, and effectiveness of surgery compared to endoscopy when it comes to pain relief for patients.

A correction to the article "Acute Pancreatitis: A Review" by M. A. Mederos, H. A. Reber and M. D. Girgis which appeared in the January 26, 2021 issue is presented.

Context: Diagnosis of infection with Borrelia burgdorferi, the cause of Lyme disease (LD), has been impeded by the lack of effective assays to detect active infection.Objective: To determine whether B. burgdorferi-specific immune complexes are detectable during active infection in LD.Design, Setting, and Patients: Cross-sectional analysis of serum samples from 168 patients fulfilling Centers for Disease Control and Prevention surveillance criteria for LD and 145 healthy and other disease controls conducted over 8 years. Tests were performed blinded.Main Outcome Measure: Detection of B. burgdorferi immune complexes by enzyme-linked immunosorbent assay and Western blot.Results: The B. burgdorferi immune complexes were found in 25 of 26 patients with early seronegative erythema migrans (EM) LD; 105 of 107 patients with seropositive EM LD; 6 of 10 samples that were seronegative [corrected] with culture-positive EM; 0 of 12 patients who were treated and recovered from LD; and 13 of 13 patients with neurologic LD without EM. Among 147 controls, B. burgdorferi immune complex was found in 0 of 50 healthy individuals; 0 of 40 patients with persistent fatigue; 0 of 7 individuals with frequent tick exposure; and 2 of 50 patients with other diseases.Conclusion: These data suggest that B. burgdorferi immune complex formation is a common process in active LD. Analysis of the B. burgdorferi immune complexes by a simple technique has the potential to support or exclude a diagnosis of early as well as active LD infection. [ABSTRACT FROM AUTHOR]

Context: Increased levels of homocysteine are associated with risk of cardiovascular disease. Homocysteine may cause this risk by impairing endothelial cell function.Objective: To evaluate the effect of acute hyperhomocysteinemia with and without antioxidant vitamin pretreatment on cardiovascular risk factors and endothelial functions.Design and Setting: Observer-blinded, randomized crossover study conducted at a university hospital in Italy.Subjects: Twenty healthy hospital staff volunteers (10 men, 10 women) aged 25 to 45 years.Interventions: Subjects were given each of 3 loads in random order at 1-week intervals: oral methionine, 100 mg/kg in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). Ten of the 20 subjects also ingested a placebo load with vitamins.Main Outcome Measures: Lipid, coagulation, glucose, and circulating adhesion molecule parameters, blood pressure, and endothelial functions as assessed by hemodynamic and rheologic responses to L-arginine, evaluated at baseline and 4 hours following ingestion of the loads.Results: The oral methionine load increased mean (SD) plasma homocysteine level from 10.5 (3.8) micromol/L at baseline to 27.1 (6.7) micromol/L at 4 hours (P<.001). A similar increase was observed with the same load plus vitamins (10.0 [4.0] to 22.7 [7.8] micromol/L; P<.001) but no significant increase was observed with placebo (10.1 [3.7] to 10.4 [3.2] micromol/L; P=.75). Coagulation and circulating adhesion molecule levels significantly increased after methionine ingestion alone (P<.05) but not after placebo or methionine ingestion with vitamins. While the mean (SD) blood pressure (-7.0% [2.7%]; P<.001), platelet aggregation response to adenosine diphosphate (-11.4% [4.5%]; P=.009) and blood viscosity (-3.0% [1.2%]; P=.04) declined in these parameters 10 minutes after an L-arginine load (3 g) following placebo, the increase after methionine alone (-2.3% [1.5%], 4.0% [3.0%], and 1.5% [1.0%], respectively; P<.05), did not occur following methionine load with vitamin pretreatment (-6.3% [2.5%], -7.9% [3.5%], and -1.5% [1.0%], respectively; P=.24).Conclusion: Our data suggest that mild to moderate elevations of plasma homocysteine levels in healthy subjects activate coagulation, modify the adhesive properties of endothelium, and impair the vascular responses to L-arginine. Pretreatment with antioxidant vitamin E and ascorbic acid blocks the effects of hyperhomocysteinemia, suggesting an oxidative mechanism. [ABSTRACT FROM AUTHOR]

The Jones Criteria for guidance in the diagnosis of acute rheumatic fever were first published by T. Duckett Jones, MD, in 1944 and have been revised over the years by the American Heart Association. The current guidelines are an update of these criteria. For the first time, the guidelines are designed to establish the initial attack of acute rheumatic fever. Major manifestations, minor manifestations, and supporting evidence of antecedent group A streptococcal infection are discussed. These updated guidelines expand on the available tools to diagnose streptococcal pharyngitis and clarify the available antibody tests for detecting antecedent group A streptococcal infection. At the present time echocardiography without accompanying auscultatory findings is insufficient to be the sole criterion for valvulitis in acute rheumatic fever. Finally, this article addresses overdiagnosis of rheumatic fever and lists exceptions to the Jones Criteria, including recurrent attacks in individuals with a history of rheumatic fever. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the length of a queue at a public hospital emergency department was associated with increased likelihood of patients' leaving without being seen by a physician and whether leaving adversely affected patients' health or affected their subsequent use of health care services.Design: Observational cohort. Patients were surveyed during 1 week in July 1990 and received a follow-up survey 7 to 14 days later. The responses of patients who left without being seen by a physician were compared with those who were seen by a physician.Setting: Emergency department at San Francisco (Calif) General Hospital.Patients: All English-, Spanish-, and Cantonese-speaking adults waiting for emergency care were eligible. Of 882 eligible individuals, 700 agreed to participate; 85% of enrolled subjects saw a physician and 15% left without being seen. Demographic characteristics of patients who were and who were not seen were not significantly different.Main Outcome Measures: Emergency department waiting time and changes in patients' self-reported health.Results: Patients were more likely to leave as waiting times increased. At follow-up, patients who left without being seen were twice as likely as those who were seen to report that their pain or the seriousness of their problem was worse. Only 4% of patients who left required subsequent hospitalization, but 27% returned to an emergency department.Conclusion: Many patients can appropriately decide whether their problem is truly urgent and make alternative plans in the face of long waits, but the health of some patients may be jeopardized by long queues for emergency care. [ABSTRACT FROM AUTHOR]

Objective: To determine whether patients who sought care at a public hospital emergency department and left without being seen by a physician needed immediate medical attention and whether they obtained care after leaving.Design: Follow-up study of patients who left without being seen and of patients who waited to be seen by a physician.Setting: A public hospital's emergency department in Torrance, Calif.Patients: All patients who registered for care and left without being seen (n = 186) and a 20% random sample of patients who waited until they were seen (n = 211) in a 2-week period during spring 1990.Main Outcome Measures: At time of presentation: triage nurse urgency assessment, clinical acuity rating, and self-reported health status. At follow-up: hospitalization rates.Results: Patients who left reported that they had waited 6.4 hours before leaving; those who stayed reported a 6.2-hour wait before being seen. There were no differences between those who left and those who stayed in chief complaint, triage nurse assessment, acuity ratings, or self-reported health status. Forty-six percent of those who left were judged to need immediate medical attention, and 29% needed care within 24 to 48 hours. Eleven percent of those who left were hospitalized within the next week, and three patients required emergency surgery. Nine percent of those who waited to be seen were hospitalized. Forty-nine percent of patients who left did not see a physician during the 1-week follow-up period.Conclusion: Overcrowding in this public hospital's emergency department restricts access to needed ambulatory medical care for the poor and uninsured. [ABSTRACT FROM AUTHOR]