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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.
GENERAL HOSPITAL MEDICINE
Stress ulcer prophylaxis in critically ill patients (June 2017)
The benefits and harms of stress ulcer prophylaxis in critically ill patients have recently been questioned, with concerns about possible increased risk of pneumonia and Clostridium difficile infection associated with use of proton pump inhibitors (PPIs). A preliminary randomized trial in 91 patients reported no difference in the rate of upper gastrointestinal bleeding, pneumonia, or C. difficile infection in mechanically ventilated receiving pantoprazole (a PPI) or placebo . Also included as part of the study was a meta-analysis of five trials comparing PPIs to placebo that reported no difference in the rates of bleeding, infections, or mortality. These data justify the feasibility of larger placebo-controlled trials to replicate these findings before revising recommendations for stress ulcer prophylaxis in critically ill patients. (See "Stress ulcer prophylaxis in the intensive care unit", section on 'Efficacy'.)
Rivaroxaban for treatment of superficial vein thrombosis (May 2017)
Short-term anticoagulation is recommended for treatment of superficial vein thrombosis (SVT) in patients at high risk for venous thromboembolism (VTE). The phase 3b SURPRISE trial randomly assigned over 400 patients with SVT to oral rivaroxaban (a direct factor Xa inhibitor) or subcutaneous fondaparinux and found that both groups had similar rates of symptomatic VTE, progression or recurrence of SVT, and all-cause mortality at 45 days . There were no major bleeds in either group, but clinically relevant nonmajor bleeding occurred more often in the rivaroxaban group. Thus, rivaroxaban appears to be an effective anticoagulant for patients with SVT and may be a more convenient and less expensive option than subcutaneous therapy. (See "Phlebitis and thrombosis of the superficial lower extremity veins", section on 'Increased risk for thromboembolism'.)
Naldemedine for opioid-induced constipation (March 2017)
The benefit of naldemedine, an oral peripherally acting opioid receptor antagonist, for opioid-induced constipation (OIC) was shown in two identically designed 12-week phase III randomized trials conducted in patients with noncancer chronic pain and OIC . In a preliminary report, naldemedine, compared with placebo, decreased constipation and was well tolerated with no signs or symptoms of opioid withdrawal or decrease in opioid analgesic efficacy. Naldemedine has been approved in the United States for OIC in adult patients with chronic noncancer pain . However, efficacy has also been shown for treatment of OIC in cancer patients , and naldemedine can be used off label in this population. The European Medicines Agency has approved naldemedine for treatment of OIC without restriction to noncancer pain . (See "Cancer pain management with opioids: Prevention and management of side effects", section on 'Other oral agents'.)
MRI in patients with pacemakers or implantable cardioverter-defibrillators (March 2017)
Potential risks of magnetic resonance imaging (MRI) in patients with permanent pacemakers or implantable cardioverter-defibrillators (ICDs) include programming changes, pacing abnormalities, and induced currents in lead wires. In a prospective multicenter trial, 1500 nonthoracic MRI examinations were performed in a 1.5T magnet on patients with a non-MRI-conditional pacemaker or ICD that had been programmed according to a standardized protocol; no device or lead failures were observed . While these reports are reassuring, the presence of a pacemaker or ICD is still generally considered a strong relative contraindication to routine MRI. (See "Principles of magnetic resonance imaging", section on 'Permanent pacemakers and implantable cardioverter-defibrillators'.)
Early initiation of palliative care and survival (February 2017)
When initiated early in the disease course, palliative care improves clinical and quality of care outcomes; randomized trials in patients with cancer or advanced lung disease also report a survival advantage, although more diverse palliative care populations have not been studied. A meta-analysis of seven randomized trials involving 2184 patients concluded that there was no association between early initiation of palliative care and overall survival . Previous reports of a possible survival advantage may have reflected bias in patient selection; only one of the seven trials was rated as having a low risk of bias. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)
The qSOFA prediction score and in-hospital mortality (January 2017)
Two recent studies have evaluated the quick sepsis-related organ failure assessment score (qSOFA) as a simple bedside tool to facilitate early identification of patients at risk of dying from sepsis [9,10]. In one study of patients presenting to the emergency department with suspected infection, the predictive validity of qSOFA for in-hospital mortality was similar to that of the full SOFA score . In contrast, qSOFA was inferior to SOFA in a retrospective analysis of intensive care unit (ICU) patients with an infection-related diagnosis . We believe that qSOFA is a valuable bedside tool in predicting death from sepsis outside the ICU. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Identification of early sepsis (qSOFA)'.)
Anticoagulant thromboprophylaxis not warranted in nonmajor lower limb orthopedic surgery (January 2017)
Whether anticoagulation thromboprophylaxis is indicated for patients with lower leg immobilization from below knee casting or undergoing arthroscopy was evaluated in a randomized trial . The rate of symptomatic venous thromboembolism (VTE) was low (<2 percent) and not affected by the administration of anticoagulant prophylaxis. Risk factors in addition to the surgery itself were present among the few patients who did develop thrombus. This trial supports the current recommendation that, for patients with lower leg immobilization due to below knee casting or arthroscopy who do not have additional risk factors for VTE, anticoagulant prophylaxis is not warranted. (See "Prevention of venous thromboembolic disease in surgical patients", section on 'Orthopedic surgery'.)
HOSPITAL CARDIOVASCULAR MEDICINE
Rapid aspirin desensitization in patients with acute coronary syndrome (April 2017)
There are well-established protocols for elective desensitization to aspirin, but fewer studies of approaches in patients needing urgent treatment. In a multicenter observational study of 330 consecutive patients with acute coronary syndrome and past hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), 95 percent were successfully desensitized to low-dose aspirin using a protocol that could be completed within six hours . The procedure was aborted in 5 percent because symptoms developed during the protocol. While useful, we prefer our own approach because it does not exclude patients who react during the protocol. (See "Diagnostic challenge and desensitization protocols for NSAID reactions", section on 'Our approach'.)
Withholding ACE-I/ARB prior to noncardiac surgery (April 2017)
In many patients undergoing noncardiac surgery, angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) is withheld prior to the procedure out of a concern for the potential of perioperative hypotension. In a prospective cohort analysis of over 3000 patients undergoing noncardiac surgery taking these medications, the composite risk of all-cause death, stroke, or myocardial injury and the risk of intraoperative hypotension was lower among those in whom ACE-I/ARB was withheld . We omit these during the 24 hours prior to surgery in many patients. (See "Management of cardiac risk for noncardiac surgery", section on 'ACE inhibitor or ARB'.)
Targeting natriuretic peptide level in treatment of acute heart failure (February 2017)
Since natriuretic peptides have relatively short half-lives, it has been postulated that serial measurements might help guide management of acute heart failure. A systematic review found low-quality evidence supporting an association between achievement of natriuretic predischarge thresholds and reduced acute heart failure mortality and readmission . However, a randomized trial studying the effect of treating to a target natriuretic peptide level found no improvement in outcomes with a natriuretic peptide-guided strategy, although a reduction in natriuretic peptide during hospitalization was associated with better outcomes [15,16]. Thus, natriuretic peptide levels have prognostic value in patients with acute heart failure, but evidence does not support targeting lower levels as a means of improving outcomes. (See "Natriuretic peptide measurement in heart failure", section on 'Acute HF'.)
ACG guidelines on the treatment of H. pylori (May 2017)
The American College of Gastroenterology has published updated guidelines on the treatment of Helicobacter pylori . According to these guidelines, the choice of initial antibiotic regimen to treat H. pylori should be guided by risk factors for macrolide resistance and penicillin allergy. Risk factors for macrolide resistance include prior exposure to macrolides and local clarithromycin rates ≥15 percent (assumed in the United States). In patients with risk factors for macrolide resistance, bismuth quadruple therapy is a first-line treatment option. (See "Treatment regimens for Helicobacter pylori", section on 'Approach to selecting an antibiotic regimen'.)
ACG guidelines on the evaluation of abnormal liver chemistries (January 2017)
The American College of Gastroenterology has published new guidelines on the evaluation of abnormal liver chemistries . These guidelines define normal alanine aminotransferase (ALT) ranges as 29 to 33 international units/L for males and 19 to 25 international units/L for females, which are lower than the reference ranges of many clinical laboratories. They recommend that ALT levels repeatedly above these upper limits of normal be evaluated. In addition, they provide a framework for the evaluation of elevated ALT, aspartate aminotransferase (AST), and alkaline phosphatase levels (which should be characterized as liver chemistries or tests rather than markers of liver function) based on the degree and pattern of elevations. (See "Approach to the patient with abnormal liver biochemical and function tests", section on 'Aminotransferases'.)
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'.)
New oral direct factor Xa inhibitor betrixaban approved (June 2017)
The US Food and Drug administration has approved a new oral direct factor Xa inhibitor, betrixaban, for venous thromboembolism prophylaxis in acutely ill medical patients . Betrixaban (brand name Bevyxxa) is taken at a dose of 160 mg on day 1 followed by 80 mg once daily for the duration of thromboprophylaxis. In a trial in which over 7500 patients hospitalized for an acute medical illness were randomly assigned to receive betrixaban or the low molecular weight heparin enoxaparin for 35 to 42 days, betrixaban was associated with a trend towards greater efficacy and a similar risk of bleeding compared with enoxaparin. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects" and "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)
PLASMIC score for TTP (March 2017)
Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening condition in which platelet microthrombi can cause organ injury and infarction. Most patients with TTP have severely reduced activity of the von Willebrand factor cleaving protease ADAMTS13, but results of ADAMTS13 testing may take days to receive. The PLASMIC score was developed to predict the likelihood of ADAMTS13 activity <10 percent in adults with suspected TTP. In three cohorts involving over 500 patients, a high PLASMIC score was predictive of ADAMTS13 <10 percent [21,22]. This score cannot be used to confirm or exclude the diagnosis of TTP, but it may be helpful when there is lack of clarity regarding the most likely diagnosis and/or the need to initiate TTP therapy. (See "Acquired TTP: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)
Underdosing of direct oral anticoagulants (February 2017)
The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban (collectively called direct oral anticoagulants [DOACs]) have been available for several years. A real-world study of over 1500 patients with venous thromboembolism (VTE) who were treated with a DOAC found that dosing differed from the recommended product dosing in 20 to 50 percent of cases, depending on the agent . These deviations (mostly underdosing) correlated with an increased frequency of VTE recurrence. Clinicians should familiarize themselves with prescribing information to avoid adverse outcomes. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Clinician familiarity with dosing'.)
HOSPITAL INFECTIOUS DISEASES
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 [24,25]. 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'.)
Recombinant hemagglutinin influenza vaccine in older adults (June 2017)
Recombinant hemagglutinin influenza vaccines (Flublok and Flublok Quadrivalent) are produced using recombinant DNA technology and a baculovirus expression system rather than the traditional egg-based methods. In a randomized trial that included adults ≥50 years of age, Flublok Quadrivalent was more effective than the quadrivalent standard-dose inactivated vaccine for preventing influenza . Flublok Quadrivalent has not been compared directly with the high-dose inactivated vaccine, which has been found to be more effective than the standard dose inactivated vaccine in older adults (including a mortality benefit). Flublok Quadrivalent is a reasonable alternative to the high-dose vaccine for older adults. (See "Seasonal influenza vaccination in adults", section on 'Recombinant hemagglutinin vaccine'.)
Healthcare-associated Candida auris infections in the United States (June 2017)
The emergence of a multidrug-resistant Candida species, Candida auris, was first reported from the United States and United Kingdom in 2016. It has been detected in over a dozen countries on five continents and has been associated with healthcare-associated outbreaks. As of July 2017, in the United States, 98 cases have been reported, with most cases occurring in New York (68 cases) and New Jersey (20 cases) [27,28]. The most common site of infection has been the bloodstream. Nearly all patients have had multiple underlying conditions and exposure to healthcare facilities. An echinocandin (anidulafungin, caspofungin, or micafungin) is the treatment of choice for C. auris infection . (See "Epidemiology and pathogenesis of candidemia in adults", section on 'Emergence of C. auris' and "Treatment of candidemia and invasive candidiasis in adults", section on 'C. auris'.)
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'.)
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'.)
Ultraviolet environmental disinfection and in-hospital transmission of resistant organisms (January 2017)
Ultraviolet (UV) radiation may be a useful adjunctive tool for surface disinfection to reduce in-hospital transmission of multidrug-resistant organisms. One cluster-randomized crossover study evaluated the addition of UV light to standard disinfection alone (quaternary ammonium for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or multidrug-resistant Acinetobacter, and bleach for Clostridium difficile) for rooms from which a patient on contact precautions for these pathogens was discharged . Among over 20,000 patients subsequently admitted to these rooms, UV light reduced the overall incidence of colonization or infection with these pathogens by 30 percent, but it did not substantially reduce the individual incidence of C. difficile infection. (See "Infection prevention: General principles", section on 'Healthcare environment: Cleaning and disinfection'.)
Early versus late initiation of dialysis for acute kidney injury (March 2017)
Randomized trials have yielded conflicting results regarding a possible benefit of early initiation of dialysis (ie, before there are clear electrolyte or fluid balance indications) among patients with acute kidney injury (AKI). A meta-analysis of 10 randomized trials showed no benefit of early dialysis initiation on mortality, risk of dialysis dependence, length of hospital stay, or recovery of renal function . The quality of the analysis was low, in part because of heterogeneity due to varying definitions of early versus late initiation. Nevertheless, we do not electively initiate dialysis for AKI unless electrolyte or fluid balance abnormalities have reached a particular threshold. (See "Renal replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Timing of elective initiation'.)
HOSPITAL PULMONOLOGY AND CRITICAL CARE MEDICINE
YEARS algorithm for the diagnosis of pulmonary embolism (June 2017)
Algorithms that integrate pretest probability (PTP) assessment using Wells criteria with a fixed cutoff level for D-dimer (<500 ng/mL) are typically used to target which patients with suspected pulmonary embolism (PE) should undergo computed tomography pulmonary angiography (CTPA). Compared with this typical approach, an alternative strategy using the YEARS items (clinical signs of deep venous thrombosis, hemoptysis, and PE as the most likely diagnosis) together with varying cutoff levels of D-dimer resulted in a 14 percent reduction in the number of CTPA scans performed, without increasing the risk of PE during a three-month follow-up . While encouraging, this algorithm requires further validation before it is routinely used in practice. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'D-dimer'.)
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'.)
Extubation during nighttime hours may be harmful (January 2017)
It is unclear whether patients who are mechanically ventilated can be safely extubated during nighttime hours. One recent retrospective study reported that, compared with patients extubated during daytime hours, patients who were extubated at nighttime (after 7:00 pm) had increased intensive care unit mortality . These data support the typical practice of safe extubation during daytime hours, when personnel are usually more readily available for re-intubation. However, methodologic flaws (eg, incomplete capture of the circumstances surrounding extubation and analysis of older data) and incongruent results compared with earlier studies suggest that these findings should not prohibit clinicians from extubating select patients who are suitable for extubation at night (eg, terminal patients). (See "Extubation management", section on 'Timing of extubation'.)
Guidelines for weaning critically ill patients from mechanical ventilation (January 2017)
The American Thoracic Society and American College of Chest Physicians recently issued joint guidelines regarding weaning critically ill patients from mechanical ventilation [37-39]. Recommendations focus on the use of sedation, liberation, and early mobilization protocols in patients who were mechanically ventilated for more than 24 hours. Additional recommendations include the use of low-level inspiratory pressure support during spontaneous breathing trials, the application of noninvasive ventilation immediately following extubation in patients at high risk of extubation failure, and cuff leak testing and/or glucocorticoid administration in those at high risk of post-extubation stridor due to laryngeal edema. These guidelines are consistent with our current recommendations for weaning patients from mechanical ventilation. (See "Extubation management" and "Methods of weaning from mechanical ventilation" and "Weaning from mechanical ventilation: Readiness testing" and "Post-intensive care syndrome (PICS)", section on 'Prevention'.)
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- Beyer-Westendorf J, Schellong SM, Gerlach H, et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol 2017; 4:e105.
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- Freund Y, Lemachatti N, Krastinova E, et al. Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department. JAMA 2017; 317:301.
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- Rossini R, Iorio A, Pozzi R, et al. Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease). Circ Cardiovasc Interv 2017; 10.
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- McQuade CN, Mizus M, Wald JW, et al. Brain-Type Natriuretic Peptide and Amino-Terminal Pro-Brain-Type Natriuretic Peptide Discharge Thresholds for Acute Decompensated Heart Failure: A Systematic Review. Ann Intern Med 2017; 166:180.
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- Tsay S, Welsh RM, Adams EH, et al. Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities - United States, June 2016-May 2017. MMWR Morb Mortal Wkly Rep 2017; 66:514.
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- Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 2017; 43:304.
- Anderson DJ, Chen LF, Weber DJ, et al. Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. Lancet 2017; 389:805.
- Bhatt GC, Das RR. Early versus late initiation of renal replacement therapy in patients with acute kidney injury-a systematic review & meta-analysis of randomized controlled trials. BMC Nephrol 2017; 18:78.
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- Seymour CW, Gesten F, Prescott HC, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med 2017; 376:2235.
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- Ouellette DR, Patel S, Girard TD, et al. Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation. Chest 2017; 151:166.
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