New in Hospital Med

HOSPITAL CARDIOVASCULAR MEDICINE

The role of supplemental oxygen in nonhypoxic patients with acute myocardial infarction patients has not been well studied. A systematic review of three trials found no significant difference in mortality, but a trend towards worse outcomes, for hypoxic or normoxic patients with acute myocardial infarction who were randomly assigned to oxygen or no supplemental oxygen [1]. The suggestion of harm with supplemental oxygen is of concern, particularly in patients with normoxia, as a pathophysiologic basis for such harm has been articulated [2]. (See "Overview of the acute management of acute ST elevation myocardial infarction", section on 'Oxygen'.)

In patients with heart failure (HF), an elevated heart rate is associated with worse cardiovascular outcomes. The SHIFT trial randomly assigned patients with HF due to systolic dysfunction to receive the selective sinus node inhibitor ivabradine or placebo [3]. At a median follow-up of 23 months, the primary endpoint of cardiovascular death or hospital admission for worsening HF was less frequent in the ivabradine group but there was no effect on all-cause mortality. (See "Possibly effective emerging therapies for heart failure", section on 'Sinus node inhibition'.)

Based on the results of small observational studies, prophylactic intraaortic balloon pumping (IABP) has been advocated for both stable patients and those with acute coronary syndromes undergoing high-risk or complicated percutaneous coronary intervention (PCI). However, the elective placement of an IABP was not found to improve outcomes in the randomized BCIS-1 trial that involved 301 high risk patients with severe left ventricular dysfunction and complex, multivessel coronary artery disease [4]. (See "Intraaortic balloon pump counterpulsation", section on 'High-risk PCI'.)

Whether patients who are receiving chronic clopidogrel therapy require an additional loading dose prior to PCI was evaluated in the ARMYDA-4 RELOAD trial [5]. Over 500 patients on chronic clopidogrel were randomly assigned to receive clopidogrel 600 mg or placebo four to eight hours before PCI. There was no significant difference in the primary combined endpoint (30 day incidence of death, MI, or target vessel revascularization). (See "Antithrombotic therapy for intracoronary stent implantation: General use", section on 'Patients already taking clopidogrel'.)

The optimal loading and maintenance dosing regimens for either clopidogrel or aspirin in patients with acute coronary syndromes (ACS) are not known. This issue was addressed in the CURRENT-OASIS 7 trial, which randomly assigned over 25,000 patients with an ACS who were referred for an invasive strategy to differing doses of aspirin and clopidogrel in a 2 by 2 factorial design [6]. Doses were clopidogrel 600 mg followed by 150 mg daily for 6 days (and 75 mg thereafter) or clopidogrel 300 mg followed by 75 mg daily and aspirin 300 to 325 mg or 75 to 100 mg daily [6]. The following findings were noted:

* With regard to the clopidogrel comparison, the rate of the primary outcome (cardiovascular death, MI, or stroke at 30 days) was not statistically different comparing high to low dose. Major bleeding occurred significantly more often in patients who received the higher clopidogrel dose.
* With regard to the aspirin comparison, there was no significant difference in the primary outcome between those who were randomly assigned to 300 to 325 mg compared to those given 75 to 100 mg [6]. While there was no significant difference in the rate of major bleeding, the rate of minor bleeding in the subgroup of patients who received percutaneous coronary intervention was significantly higher in those who received the higher dose of aspirin [7].

(See "Antiplatelet agents in acute ST elevation myocardial infarction", section on 'Primary PCI' and "Coronary artery stent thrombosis: Prevention and management", section on 'Coronary artery stent thrombosis prevention'.)

Fondaparinux is one of four anticoagulants with demonstrated efficacy in patients with non-ST elevation ACS who undergo PCI. However, its use is limited by the fact that a second anticoagulant (unfractionated heparin [UFH]) is necessary to prevent catheter-related thrombi. The optimal dose of UFH was evaluated in the randomized FUTURA/OASIS 8, which found no difference in the rates of bleeding or access-site complications between standard and low dose UFH [8]. (See "Anticoagulant therapy in unstable angina and acute non-ST elevation myocardial infarction", section on 'Heparin dosing'.)

HOSPITAL GASTROENTEROLOGY AND HEPATOLOGY

Nonselective beta blockers are used routinely to prevent variceal bleeding in patients with cirrhosis and esophageal varices. However, a prospective observational study of patients with refractory ascites found increased mortality in patients who received beta blockers compared with those who did not, raising concerns over their safety in this population [9]. (See "Treatment of diuretic-resistant ascites in patients with cirrhosis", section on 'Safety concern with beta blockers'.)

A randomized trial of 77 patients who had bled from gastric varices confirmed a benefit of endoscopic cyanoacrylate injection [10]. Compared with the use of non-selective beta blockers, cyanoacrylate injection was associated with a significantly lower risk of rebleeding (15 versus 55 percent) and lower mortality (3 versus 25 percent). (See "Treatment of active variceal hemorrhage", section on 'Approach to patients with bleeding gastric varices'.)

HOSPITAL HEMATOLOGY

A study that examined agents possibly responsible for drug-induced thrombocytopenia (DITP) using three different methods (published case reports, documentation of drug-dependent platelet-reactive antibodies, and a search of the US Food and Drug Administration’s Adverse Event Reporting System database), identified 24 drugs that had evidence of an association with thrombocytopenia by all three methods [11]. This list of 24 identified drugs provides a valuable resource for the evaluation and management of patients with suspected DITP, although other agents that are not on this list may be causative in some patients. (See "Drug-induced thrombocytopenia", section on 'Multiple approaches for identifying drugs causing DITP'.)

Patients with multiple myeloma or the precursor lesion monoclonal gammopathy of undetermined significance (MGUS) have an increased incidence of venous thromboembolism. In addition, several studies suggest an increased risk of arterial thromboembolism in these populations as manifested by stroke, transient ischemic attack, myocardial infarction, or symptomatic peripheral arterial disease [12]. (See "Treatment of the complications of multiple myeloma", section on 'Thrombosis'.)

In a phase III trial conducted in adults with hematologic malignancies at risk for tumor lysis syndrome (TLS), normalization of serum uric acid was achieved by a significantly higher percentage of patients receiving rasburicase alone than allopurinol alone, and time to control serum uric acid was also shorter [13]. Although the study was not designed to demonstrate differences in clinical endpoints, the incidence of clinical tumor lysis syndrome was similar in both groups, as was the percentage of patients who experienced acute kidney injury following chemotherapy. There did not appear to be any benefit for combined therapy with both rasburicase and allopurinol. (See "Tumor lysis syndrome", section on 'Rasburicase'.)

HOSPITAL INFECTIOUS DISEASES

In September 2010, the US Food and Drug Administration (FDA) issued a safety announcement regarding increased mortality risk associated with the use of tigecycline compared with other drugs [14]. The increased risk was seen most clearly in patients treated for hospital-acquired pneumonia, but was also seen in patients with complicated skin and skin structure infections, complicated intraabdominal infections, and diabetic foot infections. (See "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults" and "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on 'MRSA'.)

An FDA review of cefepime safety data was initiated in 2007 following findings of a meta-analysis that raised concern regarding increased all-cause mortality associated with cefepime use [15]. The FDA reviewed these study data, conducted additional analyses based on other data, and determined that the data do not indicate a higher rate of death in cefepime-treated patients [16]. Cefepime remains an appropriate therapy for its approved indications. (See "Cephalosporins", section on 'Fourth generation'.)

Ceftaroline is a fifth generation cephalosporin that exhibits bactericidal activity against gram-positive organisms (including MRSA, vancomycin-intermediate S. aureus, and macrolide-resistant S. pyogenes) as well as gram-negative pathogens (including Enterobacteriaceae, but not Pseudomonas species or extended-spectrum beta-lactamase producers). In phase 3 trials including 1378 patients with complicated skin and skin structure infection who were randomly assigned to receive ceftaroline alone or vancomycin plus aztreonam, clinical cure rates and rates of adverse events were similar [17]. (See "Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults", section on 'Cephalosporins'.)

Enterobacteriaceae isolates carrying a novel metallo-beta-lactamase gene, the New Delhi metallo-beta-lactamase (NDM-1), were first described in December 2009 in a patient hospitalized in India with an infection due to Klebsiella pneumoniae [18]. Subsequent cases have been reported elsewhere in Asia, Europe, and North America [19]. Clinicians should be aware of the possibility of NDM-1 producing Enterobacteriaceae in patients who have received medical care in India and Pakistan. In the United States, isolates may be forwarded through state public health laboratories to the Centers for Disease Control for further characterization [19]. Therapeutic options for infections due to these organisms are limited but may include tigecycline, colistin, and aztreonam. (See "Carbapenemases", section on 'Class B beta-lactamases'.)

Rapid testing using molecular techniques can greatly improve diagnosis and control of multidrug resistant tuberculosis infection. The assay Xpert MTB/RIF is an automated nucleic acid amplification test for M. tuberculosis and rifampin resistance (rpoB gene). In a study including 1730 patients with suspected tuberculosis, the test correctly identified 98 percent with smear positive tuberculosis and 72 percent with smear negative tuberculosis [20]. The accuracy for identification of rifampin resistance was 98 percent. The assay is simple to perform with minimal training, is not prone to cross-contamination, and requires minimal biosafety facilities. (See "Diagnosis, treatment, and prevention of drug-resistant tuberculosis", section on 'Rapid testing'.)

A revised version of the HIV treatment guidelines from the International AIDS Society-USA panel has several major changes [21]:

* Antiretroviral therapy (ART) is now recommended for patients with a CD4 count less than 500 cells
* ART is also recommended for HIV-infected patients with certain comorbidities, regardless of CD4 cell count
* Raltegravir is now considered an option for use within combination antiretroviral regimens for treatment-naive patients

These recommendations are largely in agreement with the treatment guidelines from the US Department of Health and Human Services (DHHS), which were released in December 2009. (See "When to initiate antiretroviral therapy in HIV-infected patients" and "Selecting antiretroviral regimens for the treatment naive HIV-infected patient".)

The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America have endorsed a policy in which annual influenza vaccination is a condition of employment and/or professional privileges for healthcare workers [22,23]. (See "Infection control measures to prevent seasonal influenza in healthcare settings", section on 'Immunization of healthcare workers'.)

HOSPITAL NEPHROLOGY

A case-control study found that, in elderly patients being treated with an angiotensin-converting enzyme inhibitor (ACEi) or ARB, admission with hyperkalemia was associated with prior use of trimethoprim-sulfamethoxazole compared with other antibiotics [24]. (See "Etiology and treatment of hypoaldosteronism (type 4 RTA)", section on 'Antibiotics'.)

HOSPITAL NEUROLOGY

A meta-analysis of the three largest randomized trials comparing carotid artery stenting with carotid endarterectomy in patients with symptomatic carotid disease found that the proportion with stroke or death at 120 days after randomization was significantly higher for the stenting group [25]. The estimated risk of stroke or death for patients age 70 and older was approximately two-fold higher for the stenting group compared with the endarterectomy group. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Randomized trials' and "Management of symptomatic carotid atherosclerotic disease", section on 'Effect of age'.)

MRI and diffusion-weighted imaging (DWI) utilizing higher magnetic field strengths of 3 Tesla (T) units are increasingly available in clinical settings. A retrospective study found that diagnostic accuracy for early strokes, read by radiologists blinded to the machine used, was better for images taken with standard 1.5 T MRI scanners than for 3 T images [26]. Artifacts with higher magnetic field strengths may obscure early ischemic changes. (See "Neuroimaging of acute ischemic stroke", section on 'Diffusion-weighted imaging'.)

New guidelines published by the American Academy of Neurology refine the criteria for diagnosing brain death and emphasize that there are no published reports of neurologic recovery after a diagnosis of brain death using these or the 1995 criteria [27]. (See "Diagnosis of brain death".)

HOSPITAL ONCOLOGY

In a randomized trial, early integration of palliative care into the disease-specific therapies for patients with advanced non-small cell lung cancer resulted in improved quality of life and mood [28]. Although patients had less aggressive care at the end of life, median survival was significantly longer in patients who received earlier palliative care. (See "Overview of the treatment of advanced non-small cell lung cancer", section on 'Palliative care'.)

HOSPITAL PULMONARY AND CRITICAL CARE MEDICINE

Neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) has both desirable effects (improves oxygenation) and undesirable effects (prolonged neuromuscular weakness). A trial randomly assigned 340 patients with ARDS to receive cisatracurium besylate or placebo by continuous infusion for 48 hours [29]. The cisatracurium besylate group had lower 90-day mortality after adjustment for baseline risk and there was no difference in the frequency of prolonged neuromuscular weakness. (See "Supportive care and oxygenation in acute respiratory distress syndrome", section on 'Paralysis'.)

The potential for long-term psychological sequelae (eg, posttraumatic stress disorder [PTSD]) has slowed the incorporation of daily interruption of sedation into routine clinical practice for management of patients requiring mechanical ventilation. However, a randomized trial found that patients who underwent daily interruption of sedation had less cognitive impairment at three months and no increase in the frequency of PTSD at 3 or 12 months, compared to patients who did not undergo daily interruption of sedation [30]. (See "Sedative-analgesic medications in critically ill patients: Selection, initiation, maintenance, and withdrawal", section on 'Daily interruption'.)

The relative effects of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation in patients with ARDS are uncertain. A meta-analysis that compared HFOV to conventional mechanical ventilation (tidal volume <8 mL/kg) found a reduction in mortality with HFOV that was not statistically significant [31]. (See "High-frequency ventilation in adults", section on 'HF oscillatory ventilation'.)

In a randomized trial assessing treatment options for malignant pleural effusions, 58 patients were assigned to in-dwelling catheter drainage or talc pleurodesis [32]. The effusion recurrence rates were slightly lower and the quality of life scores slightly higher with catheter drainage than with pleurodesis; however, the success rate with talc pleurodesis in this trial (approximately 50 percent) was low compared with other published reports. (See "Management of malignant pleural effusions", section on 'In-dwelling pleural catheter'.)

A retrospective cohort study that evaluated follow-up computed tomography pulmonary angiograms (CT-PA) in patients with prior acute pulmonary embolism (PE) found that complete radiographic resolution of PE is common and occurs more quickly in the main and lobar pulmonary arteries than in the segmental pulmonary arteries [33]. (See "Diagnosis of acute pulmonary embolism", section on 'Time course of PE'.)