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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
Evaluation for occult cancer in unprovoked venous thromboembolism (August 2017)
Whether patients with a diagnosis of unprovoked venous embolism (VTE) should be evaluated for occult cancer with an extensive or more limited strategy is controversial. In a meta-analysis of 10 prospective studies (over 2000 patients with unprovoked VTE), the prevalence of cancer at one year was 5 percent . Extensive screening, performed in nearly 60 percent of patients, detected more cancer initially than limited evaluation, but the difference was not significant at one year. The effect on long-term mortality is unknown. Until the benefits of extensive evaluation strategies are proven, we suggest evaluating patients with a single episode of unprovoked VTE using a limited strategy (clinical examination, routine laboratory studies, chest radiography, and age-appropriate screening) for the detection of occult cancer. (See "Evaluating patients with established venous thromboembolism for acquired and inherited risk factors", section on 'First episode of uncomplicated unprovoked VTE'.)
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 "Prevention and management of side effects in patients receiving opioids for chronic pain".)
HOSPITAL CARDIOVASCULAR MEDICINE
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'.)
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'.)
Early refeeding in acute pancreatitis (August 2017)
The optimal timing of refeeding in acute pancreatitis is uncertain. In a systematic review of 11 randomized trials that included 948 patients with acute pancreatitis, early refeeding (≤48 hours after hospitalization) did not increase adverse effects or exacerbate symptoms compared with delayed refeeding . In four of seven trials that included patients with mild to moderate pancreatitis, it reduced length of hospital stay. However, there was significant heterogeneity in feeding protocols and reported outcomes, and several studies had a high risk of bias. Additional randomized trials are needed to define the benefits of early enteral nutrition in acute pancreatitis. (See "Management of acute pancreatitis", section on 'Oral'.)
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'.)
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 [15,16]. 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'.)
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 [17,18]. 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) [20,21]. 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'.)
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
Guidelines for mechanical ventilation in patients with ARDS (August 2017)
Guidelines were issued by the American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine for mechanical ventilation strategies in patients with acute respiratory distress syndrome (ARDS) . Key aspects included recommendations in favor of the use of low tidal volume ventilation (all ARDS patients) and prone positioning (severe ARDS). They also promoted the use of high levels of positive end expiratory pressure (PEEP) and recruitment maneuvers in select patients and recommended against the use of high frequency oscillatory ventilation (HFOV). No recommendations were made on the use of extracorporeal membrane oxygenation. (See "Prone ventilation for adult patients with acute respiratory distress syndrome" and "High-frequency ventilation in adults" and "Extracorporeal membrane oxygenation (ECMO) in adults" and "Mechanical ventilation of adults in acute respiratory distress syndrome", section on 'Low tidal volume ventilation'.)
Vasopressor blood pressure targets in critically ill patients with shock (July 2017)
Hemodynamic support with continuous infusion of a vasopressor agent may be necessary in patients with shock if administration of intravenous fluids fails to restore adequate blood pressure and/or tissue perfusion. In a systematic review of two randomized trials that included 894 critically ill adults with hypotension requiring vasopressor therapy, higher mean arterial pressure (MAP) target values (80 to 85 mmHg in one trial and 75 to 80 mmHg in the other) did not result in a mortality benefit and increased the risk of cardiac arrhythmias, compared with lower targets (65 to 70 mmHg and 60 to 65 mmHg) . We suggest a target MAP of 65 to 70 mmHg, rather than a higher target, in critically ill adults with hypotension who require vasopressor support. Similar MAP target values were recommended in a recent guideline of the Canadian Critical Care Society and the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (CCCS-SSAI) . (See "Intraoperative management of shock in adults", section on 'Initial interventions'.)
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'.)
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