Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Routine prophylactic antibiotics do not improve clinically important outcomes in survivors of out-of-hospital cardiac arrest (April 2017)
Many survivors of out-of-hospital cardiac arrest (OHCA) go on to develop pneumonia, but the value of prophylactic antibiotics is unproven. In a single-center clinical trial involving 60 comatose OHCA patients without obvious evidence of tracheobronchial aspiration on admission, random assignment to prophylactic antibiotics versus clinically-driven antibiotic therapy reduced the number of positive broncho-alveolar lavage cultures on hospital day 3, but did not improve survival or other patient-important outcomes . We do not suggest routine prophylactic treatment with antibiotics in these patients. (See "Post-cardiac arrest management in adults", section on 'Antibiotic therapy and prophylaxis'.)
2016 sepsis guidelines (March 2017)
Updated sepsis guidelines were issued by the Surviving Sepsis Campaign/Society of Critical Care Medicine/European Society of Intensive Care Medicine . Major differences, compared with the 2012 iteration, include: the administration of intravenous antibiotics within one hour of presentation, with emphasis on source control and antibiotic stewardship; infusion of crystalloid solution at a rate at 30 mL/kg/hour within three hours for early fluid resuscitation; and movement away from previously recommended early goal-directed therapy targets (eg, central venous pressure) to use of dynamic predictors of fluid responsiveness, when feasible. Norepinephrine remains the vasopressor of first choice. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Hemodynamic'.)
GENERAL ADULT EMERGENCY MEDICINE
Urgency of diuretic therapy in patients with acute heart failure (August 2017)
Only retrospective data have been available, until now, to evaluate the importance of time to initiation of diuretic therapy for management of acute heart failure. A multicenter, prospective observational study of 1291 patients with acute heart failure treated with intravenous furosemide within 24 hours of arrival in an emergency department found that treatment within one hour was associated with a lower in-hospital mortality than later treatment . Thus, the expeditious initiation of an intravenous loop diuretic regimen may improve in-hospital outcomes, in addition to controlling symptoms of volume overload. (See "Treatment of acute decompensated heart failure: Components of therapy", section on 'Diuretics'.)
Mixed data regarding icatibant in ACE inhibitor-induced angioedema (August 2017)
Although the bradykinin receptor antagonist icatibant has proven efficacy in hereditary angioedema, particularly when given soon after onset of symptoms, evidence is mixed regarding its utility in angiotensin-converting enzyme inhibitor-associated angioedema (AceIA). In a randomized trial of 121 patients with AceIA of the head or neck, icatibant did not decrease the time to discharge relative to placebo . Therefore, careful airway management, rather than icatibant, remains the primary intervention for most cases of AceIA, although icatibant may have a role in rare instances when patients present very early. (See "ACE inhibitor-induced angioedema", section on 'Icatibant'.)
Home use of topical anesthesia to control pain from corneal abrasions (August 2017)
In a retrospective study of 444 patients with corneal abrasions given a 24-hour supply of topical tetracaine at the initial emergency department visit, there were no documented serious complications or uncommon adverse events . However, definitive outcomes were only known for 120 patients who returned for rechecks. Patients receiving topical tetracaine were more likely to return for emergency department reevaluation compared with patients who did not receive tetracaine. Topical analgesia was prescribed inappropriately in one-third of patients, for lesions other than simple corneal abrasion (eg, large corneal abrasions, retained rust rings, herpes keratitis, anterior uveitis, and corneal erosions). Because of the possibility of overuse (ie, use beyond 24 hours) and the risk of inappropriate administration, we favor other means of pain control and discourage the prescribing of topical anesthetic agents. More evidence is needed to establish the safety of this practice in patients with simple corneal abrasions. (See "Corneal abrasions and corneal foreign bodies: Management", section on 'Pain control'.)
Timing of coronary angiography in patients with NSTEACS (August 2017)
Unlike patients with ST-elevation myocardial infarction who should undergo coronary angiography and revascularization within a few hours of symptom onset, the optimal timing of angiography in patients with non-ST elevation acute coronary syndromes (NSTEACS) is not known. A 2017 meta-analysis evaluated mortality in eight randomized trials that compared early to delayed invasive treatment . There was no difference in mortality between the two strategies. However, subgroup analysis suggested benefit from early intervention in patients at high risk. We generally perform coronary angiography in most NSTEACS patients within 24 hours of presentation. (See "Coronary angiography and revascularization for unstable angina or non-ST elevation acute myocardial infarction", section on 'Timing'.)
ACC/AHA/HRS guideline for the evaluation and management of syncope (July 2017)
In 2017 the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) published guidelines on evaluation and management of patients with syncope, the first major new syncope guidelines in eight years . The guidelines present an approach to the evaluation and management of patients with syncope that is consistent with the approach advocated by UpToDate experts. Both UpToDate and the ACC/AHA/HRS guidelines emphasize the importance of a detailed medical history, physical examination, and review of an electrocardiogram as the initial evaluation in all patients. An echocardiogram should be performed in patients with known or suspected structural heart disease, with selected additional testing directed by the results of the initial evaluation. (See "Syncope in adults: Clinical manifestations and diagnostic evaluation", section on 'Initial evaluation'.)
Confirmatory data on idarucizumab for dabigatran reversal (July 2017)
Idarucizumab (pronounced "I-dare-you-cizumab") is a monoclonal antibody fragment against dabigatran that can reverse the anticoagulant effect within minutes. A preliminary report suggested good efficacy in patients with dabigatran-associated bleeding or those undergoing emergency surgery. In a new report of over 500 patients treated with idarucizumab, most had cessation of bleeding or underwent surgery without abnormal bleeding . We continue to suggest idarucizumab for clinically significant bleeding or emergency surgery in patients on dabigatran with a history or laboratory testing that suggest they are actively anticoagulated. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)
Opana ER withdrawn from the US market (July 2017)
A long-acting abuse-deterrent formulation of oxymorphone, Opana ER, is being voluntarily withdrawn from the United States (US) market at the request of the US Food and Drug Administration due to concerns related to injection abuse, including reports of thrombotic microangiopathy (TMA) when the oral formulation is injected intravenously (IV) [9-11]. The TMA is thought to be due to an inert component that was added to the formulation to make it crush-resistant and thus deter IV injection. Generic extended-release oxymorphone products remain on the US market. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Oxycodone, hydrocodone, hydromorphone, and oxymorphone' and "Drug-induced thrombotic microangiopathy", section on 'Drugs of abuse'.)
Antibiotic therapy for skin abscess (July 2017)
Management of skin abscess consists of incision and drainage; the role of antibiotic therapy depends on individual clinical circumstances, including abscess size. In a randomized trial including more than 780 patients with skin abscess ≤5 cm (most were larger than 2 cm) who underwent incision and drainage, higher cure rates were observed among those who received antibiotic therapy with methicillin-resistant Staphylococcus aureus (MRSA) coverage (trimethoprim-sulfamethoxazole or clindamycin) than those who received placebo (82 or 83 percent versus 69 percent); MRSA was isolated in 49 percent of cases . These findings support our approach to management of patients with skin abscess, in which we suggest antibiotic therapy in addition to incision and drainage for patients with skin abscess ≥2 cm. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Role of antibiotic therapy'.)
Delafloxacin for treatment of skin and soft tissue infections (July 2017)
Delafloxacin, a fluoroquinolone, has been approved by the US Food and Drug Administration for treatment of bacterial skin and soft tissue infections. It has activity against staphylococci (including methicillin-resistant strains), gram-negative bacteria (including Pseudomonas aeruginosa and Enterobacteriaceae), and some anaerobes (including Clostridium difficile) but does not have activity against enterococci. In two phase III clinical trials, the drug was statistically noninferior to the combination of vancomycin and aztreonam at the endpoint of early clinical response at 48 to 72 hours [13,14]. Given limited clinical experience with delafloxacin, at this time its use should be reserved for patients who do not respond to or do not tolerate first-line antimicrobial agents. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections", section on 'Delafloxacin'.)
Countering the high cost of epinephrine autoinjectors (June 2017)
Physicians and patients in the United States have been struggling with the high cost of epinephrine autoinjectors, and alternatives, as well as ways to maximize the utility of expensive devices, have begun to appear:
●A prefilled syringe (Symjepi) containing 0.3 mg epinephrine per dose was approved by the US Food and Drug Administration (FDA) in June 2017 and should offer a more affordable alternative to autoinjectors . It will be available in upcoming months in just one dose, labeled for use in patients weighing ≥30 kg (66 lbs). (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Prefilled syringes'.)
●A study of 31 expired autoinjectors (EpiPens) found that devices as much as four years past the expiration date still contained 84 to 88 percent of the intended epinephrine dose . Thus, patients should understand that expired devices retain most of their potency and that if anaphylaxis develops, using an outdated device is preferable to not injecting epinephrine at all. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)
Treatment of nonpurulent cellulitis (June 2017)
Empiric antibiotic therapy for nonpurulent cellulitis (ie, with no purulent drainage and no associated abscess) should be active against beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) but not necessarily methicillin-resistant S. aureus (MRSA). This approach is supported by a randomized trial of nearly 500 patients with nonpurulent cellulitis, in which cephalexin plus placebo (active against beta-hemolytic streptococci and MSSA) and cephalexin plus trimethoprim-sulfamethoxazole (TMP-SMX, which adds activity against MRSA) resulted in statistically similar clinical cure rates (69 versus 76 percent) . Although there was a trend toward higher cure rates with the addition of TMP-SMX, the results were likely skewed by a relatively large number of patients who did not complete the full course of therapy. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Cellulitis'.)
Glucocorticoids not necessary for simple acute urticaria (May 2017)
Although patients with urticaria and symptoms involving other organ systems are treated with epinephrine given the likelihood of anaphylaxis, H1 antihistamines are the initial treatment for those with isolated urticaria. For such patients, the additive benefit of glucocorticoids is not well defined. In a randomized trial of 100 adults presenting to the emergency department with isolated urticaria (without angioedema, anaphylaxis, or fever) of ≤24 hours duration, patients received the H1 antihistamine levocetirizine plus either prednisone or placebo for four days . There was no significant difference in the rate of symptom resolution, and most patients were symptom-free within two days. This study supports our suggestion to reserve glucocorticoids for those patients with new urticaria who have prominent angioedema or whose symptoms persist despite antihistamines. (See "New-onset urticaria", section on 'Glucocorticoids'.)
Time to treatment and mortality in sepsis (May 2017)
Timely administration of fluids and antibiotics is the cornerstone of therapy for patients with sepsis and septic shock. A recent database study of patients with sepsis reported increased mortality in association with the delayed administration of antibiotics (greater than three hours) but not with a longer time to completion of a fluid bolus (greater than six hours) . This study further validates international guideline recommendations that antibiotics be administered within the first three hours, and preferably within the first hour after presentation in patients with sepsis and septic shock. We also continue to recommend infusion of intravenous fluids within the first three hours of presentation. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial resuscitative therapy'.)
GENERAL PEDIATRIC EMERGENCY MEDICINE
Identification of children with low-risk past penicillin reactions (August 2017)
Many children who have mild adverse reactions to penicillins, such as maculopapular rash, hives, or gastrointestinal symptoms, are not allergic and can safely receive this class of antibiotics in the future. In a study of children presenting to an urban emergency department with histories of past penicillin reactions, nearly 600 parents/caregivers completed a questionnaire about the child’s past reaction . The questionnaire included hives as a low-risk feature (for true allergy), but considered facial angioedema as a high-risk feature. One hundred of 434 patients with low-risk reactions were referred to an allergist for evaluation. Ninety-seven had negative skin tests, while three initially had positive skin tests that were negative upon later repeat testing. Ultimately, all 100 children passed oral challenge to amoxicillin. Despite these results, we consider both hives and angioedema as high-risk features and would advocate that children with past reactions involving either of these symptoms be referred to an allergy specialist to determine if penicillins can be safely used again. (See "Penicillin allergy: Delayed hypersensitivity reactions", section on 'Studies in children'.)
The Pediatric Sedation State Scale to assess pediatric procedural sedation (July 2017)
The Pediatric Sedation State Scale (PSSS) identifies six levels of sedation based on patient behavior (including patient interference with the procedure and need for restraint) and physiologic parameters (table 1). The PSSS is derived from expert opinion and has been validated, using a small sample of patients and observers, with high inter- and intra-observer agreement . Scales that simply measure the depth of sedation track only one aspect of this practice and do not assess key findings that identify whether the goals of procedural sedation are met. We suggest the use of the PSSS to provide a simple and rapid means of effectively documenting and communicating the quality of pediatric sedation. (See "Procedural sedation in children outside of the operating room", section on 'Sedation state'.)
Low yield of lumbar puncture after complex febrile seizure (July 2017)
After a febrile seizure, lumbar puncture to assess for infection can be avoided in most well-appearing children who have returned to their baseline, even when the febrile seizure has complex features (ie, focal onset, >15 minutes in duration, or recurrent within 24 hours). In a multicenter cohort study of more than 800 children age six months to five years presenting to a pediatric emergency department with a complex febrile seizure, rates of bacterial meningitis and herpes simplex encephalitis were 0.7 and 0 percent, respectively . All five cases of infection occurred in children with a clinical examination suggestive of meningitis. (See "Clinical features and evaluation of febrile seizures", section on 'Lumbar puncture'.)
Delay of appendectomy up to 24 hours not related to appendiceal perforation in children with appendicitis (June 2017)
In the past, appendicitis has been considered a surgical emergency that requires prompt appendectomy to avoid perforation and other complications. In a multicenter, prospective observational study of 955 children 3 to 18 years of age, all of whom were treated with appendectomy for appendicitis within 24 hours of arrival to the emergency department, duration of time between initial evaluation and operation was not associated with an increase in appendiceal perforation . This study adds to a growing body of evidence that suggests that adverse outcomes are not increased for children who receive timely administration of antibiotics and undergo appendectomy less than 24 hours after diagnosis. (See "Acute appendicitis in children: Management", section on 'Timing of operation'.)
Safety and efficacy of nonoperative treatment of pediatric appendicitis (March 2017)
In a systematic review of 10 studies that provided outcomes for over 400 children undergoing nonoperative treatment (NOT, antibiotics without immediate surgery) of early, uncomplicated appendicitis, initial treatment was effective in 88 to 99 percent of patients and was associated with no appendectomy at reported follow-up in 62 to 92 percent of patients . Complications and total length of hospital stay appeared similar during follow-up for NOT and appendectomy. Pooled estimates were performed by the investigators but, given the underlying variation in methodology of the included studies, may be misleading, particularly given subsequent evidence suggesting that patient selection strongly influences outcomes of NOT for appendicitis [25-27]. Although appendectomy remains the treatment of choice for most children with early, uncomplicated appendicitis, NOT is an alternative for selected patients based upon caregiver preference. Additional research is needed to determine which patients are least likely to fail nonoperative treatment. (See "Acute appendicitis in children: Management", section on 'Nonoperative management'.)
ACCM practice parameters for management of pediatric and neonatal septic shock (August 2017)
The American College of Critical Care Medicine (ACCM) has published new practice parameters for hemodynamic support of pediatric and neonatal septic shock that continue to emphasize timely fluid administration, early initiation of broad-spectrum antibiotics, and, in patients with fluid refractory shock, prompt administration of vasoactive drug infusions (algorithm 1) . After resuscitation, management is targeted to improving physiologic indicators of perfusion and vital organ function within the first six hours of care (table 2). The guidelines also recommend that each pediatric institution develop multidisciplinary approaches or "bundles" designed to increase adherence to these guidelines, decrease time to therapy, and improve outcomes in pediatric septic shock. (See "Septic shock in children: Rapid recognition and initial resuscitation (first hour)" and "Septic shock in children: Ongoing management after resuscitation".)
Antivenom treatment for patients with mild, non-progressive copperhead envenomation (August 2017)
In a randomized trial of 74 patients with confirmed copperhead bites (88 percent with mild envenomation), patients who received polyvalent Crotalinae ovine immune Fab (FabAV) antivenom therapy, compared with placebo, had modestly better limb function at 14 days, lower use of opioid analgesia, but no significant difference in time to return of normal function . Patients who received antivenom had more minor adverse events (36 versus 10 percent), but there were no serious adverse events. Current expert guidelines recommend antivenom treatment only for patients with moderate or severe envenomations or mild envenomation with progressive effects . While this study suggests that patients with mild, non-progressive copperhead envenomation may also benefit from antivenom administration, larger trials are needed to establish the safety and efficacy of FabAV antivenom for these patients. The use of antivenom for patients with mild, non-progressive envenomation should be individualized on a case by case basis with the input from a medical toxicologist or other snakebite expert. (See "Evaluation and management of Crotalinae (rattlesnake, water moccasin [cottonmouth], or copperhead) bites in the United States", section on 'Indications'.)
Interpretation of blood lead levels <5 mcg/dL (0.24 micromol/L) (August 2017)
Interpretation of blood lead levels <5 mcg/dL (0.24 micromol/L) is complicated by an increased risk of specimen contamination arising from blood collection equipment (eg, needles, blood collection tubes, or cryovials) causing false positives and the inability for many laboratories to quantify low levels of blood lead resulting in false negatives . However, any detectable lead <5 mcg/dL (0.24 micromol/L) warrants careful patient evaluation and an attempt at determining the source of lead exposure. (See "Childhood lead poisoning: Management", section on 'Detectable BLL <5 mcg/dL (current reference level)'.)
Medical use of prescription opioid medications and misuse in adolescents (May 2017)
Surveys of high school seniors in the United States over 40 years show that the use of prescription opioids is strongly correlated with misuse in adolescents and that misuse typically follows medical use by the patient . Thus, health care providers should follow safe prescribing guidance for prescription opioids, including use of alternatives (eg, acetaminophen or ibuprofen) to control pain whenever possible, using the lowest effective dose and minimum quantity of prescription opioid medications when they are needed, and utilizing prescription drug monitoring programs, where available, to identify patients or caregivers who might be misusing (ie, abusing or diverting) prescription opioid medications. (See "Opioid intoxication in children and adolescents", section on 'Safe prescribing'.)
Safe storage of prescription opioids (May 2017)
Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications . In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age . These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)
Persistence of neurotoxicity of childhood lead poisoning into adulthood (May 2017)
Detectable blood lead levels (BLLs) are associated with irreversible neurocognitive deficits in children and a BLL lower limit for this toxicity has not been established. Previous studies had shown that this effect persists into adolescence. In a longitudinal cohort study of over 1000 patients, lead exposure, based upon BLLs obtained at 11 years of age, was associated in a dose-dependent fashion with lower intelligence quotient (IQ) and lower socioeconomic status at age 38 years after adjustment for maternal IQ, child IQ, and childhood socioeconomic status . Thus, childhood lead exposure causes neurotoxicity that persists into adulthood. Primary prevention of lead exposure, including in pregnant women, can prevent these effects. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Neurologic'.)
Immunoassay for acetaminophen-induced liver injury (May 2017)
Establishing the diagnosis of acetaminophen (APAP) poisoning in patients who present greater than 24 hours to several days after ingestion, when a serum APAP level may no longer be detectable, can be difficult. However, a recent observational cohort study found excellent performance for a rapid immunoassay that measures serum APAP-protein adducts in identifying patients with APAP-induced acute liver injury (ALI) . In this study, a point of care immunoassay (AcetaSTAT) had 100 percent sensitivity and 100 percent negative predictive value, compared with results of high performance liquid chromatography as a reference standard, for identifying patients with such injury. If these results are validated in future clinical trials, this assay may provide a rapid means to distinguish APAP-induced ALI from other causes, and to begin appropriate management quickly. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis", section on 'Evaluation following delayed presentation'.)
Asymptomatic cervical spine fracture in older adults with trauma (August 2017)
Under-triage and unrecognized injuries remain a major problem in the management of elder trauma patients. Both the history and the physical examination are often less sensitive for detecting injuries in older trauma patients compared with their younger counterparts. In a recent retrospective study of 173 patients over the age of 55 with cervical spine fractures identified on diagnostic imaging, 36 (21 percent) reported no neck pain and no midline cervical tenderness at presentation . All patients had a Glasgow Coma Score of 15. We continue to advocate for a low threshold for obtaining advanced imaging studies in older trauma patients at risk of injury. (See "Geriatric trauma: Initial evaluation and management", section on 'Cervical spine injury'.)
Consensus statement from 5th International Conference on Concussion in Sport (July 2017)
Recently, the 5th International Conference on Concussion in Sport published a consensus statement . Concussion remains a clinical diagnosis that is best approached through multidimensional testing. The consensus statement endorses the new 5th edition of the Sport Concussion Assessment Tool (SCAT5) for sideline assessment of athletes 13 and older, and the Child SCAT5 for athletes 5 to 12 years old. Consistent with prior iterations, the statement emphasizes immediate removal from play followed by a careful systematic evaluation whenever concussion is suspected. Athletes diagnosed with a concussion should rest, but strict absolute rest is not necessary, and patients can be encouraged to become more active in a gradual manner as their symptoms permit. (See "Sideline evaluation of concussion" and "Concussion in children and adolescents: Clinical manifestations and diagnosis" and "Concussion and mild traumatic brain injury" and "Sideline evaluation of concussion", section on 'Assessment instruments'.)
Focused Assessment with Sonography for Trauma (FAST) does not change outcomes in hemodynamically stable children with blunt torso trauma (June 2017)
Focused Assessment with Sonography for Trauma (FAST) is routinely used to rapidly identify pericardial effusion or intraabdominal hemorrhage in hemodynamically unstable pediatric patients with blunt trauma. Its utility in hemodynamically stable children after trauma is less clear. In an unblinded, randomized trial of 925 hemodynamically stable children evaluated for blunt torso trauma, FAST combined with standard emergency assessment, compared with standard care alone, did not lower missed intraabdominal injury (IAI) rates, frequency of abdominal computed tomography (CT), mean emergency department length of stay, or hospital charges . Negative results on ultrasonography did lower the managing physician's clinical suspicion for IAI but did not decrease the use of abdominal CT. Thus, routine use of FAST in stable trauma patients does not appear to alter important clinical outcomes.(See "Trauma management: Approach to the unstable child", section on 'FAST (Focused Assessment with Sonography for Trauma)' and "Approach to the initially stable child with blunt or penetrating injury", section on 'Abdominal trauma'.)
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