Disclosures: Helen Hollingsworth, MD Nothing to disclose. April F Eichler, MD, MPH Equity Ownership/Stock Options: Johnson & Johnson [Dementia (galantamine), Epilepsy (topiramate)]. Geraldine Finlay, MD Nothing to disclose.
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.
Warning about use of non-prescription asthma treatments (April 2015)
The US Food and Drug Administration (FDA) released a consumer warning about the potential health risks of over-the-counter (OTC) homeopathic products for asthma . The efficacy and safety of OTC products are not evaluated by the FDA. In addition, there is evidence that some non-prescription therapies, such as racemic epinephrine inhaler (sold as Asthmanefrin) and systemic ephedrine (sold as Bronkaid and Primatene tablets), are less effective than standard therapies for asthma and have a higher rate of side effects. Thus, OTC products are not recommended for the routine care of asthma, particularly acute asthma symptoms. These warnings are an important reminder for clinicians to ask their patients about use of OTC products. (See "Asthma in children younger than 12 years: Rescue treatment for acute symptoms", section on 'Nonstandard therapies' and "Alternative and experimental agents for the treatment of asthma", section on 'Risks associated with inhaled epinephrine' and "Alternative and experimental agents for the treatment of asthma", section on 'Homeopathic agents' and "Homeopathy", section on 'Specific diseases'.)
Safety of inhaled long-acting beta agonist/glucocorticoid for asthma during pregnancy (February 2015)
An important clinical question for pregnant women with asthma is whether using a combination long-acting beta-agonist (LABA) plus inhaled glucocorticoid confers an increased risk for adverse fetal outcomes, compared with monotherapy using a higher dose of the inhaled glucocorticoid. In a study of 1302 pregnant women with asthma, the risk for a major congenital malformation was not increased when a LABA plus low dose inhaled glucocorticoid was compared with a medium dose inhaled glucocorticoid, or when a LABA plus medium-dose inhaled glucocorticoid was compared with a high-dose inhaled glucocorticoid . (See "Management of asthma during pregnancy", section on 'Long-acting beta-adrenergic agents'.)
Safety of omalizumab for asthma during pregnancy (February 2015)
The safety of omalizumab exposure during pregnancy in humans has not been formally evaluated, but outcomes from an omalizumab registry have been published . There were 169 pregnancies with known outcomes: 156 live births (160 infants), 1 fetal death/stillborn, and 11 spontaneous abortions. The rate of preterm birth was 14 percent, and 11 percent of infants were small for gestational age. Congenital anomalies were present in 13 percent, and 4 percent had a major anomaly. While the sample size is small, these results are similar to findings from other studies of pregnant women with asthma. Further data are needed to more fully characterize outcomes of omalizumab use in pregnancy. (See "Management of asthma during pregnancy", section on 'Anti-immunoglobulin E'.)
Novel glucocorticoid receptor agonist for asthma (February 2015)
The investigational agent AZD5423 is a nonsteroidal compound that binds to the glucocorticoid receptor in a different manner from that of traditional glucocorticoids. It suppresses production of proinflammatory proteins (like traditional glucocorticoids), but with reduced adverse effects in animal models. An inhaled dry powder formulation of AZD5423 was assessed in a trial that randomly assigned 20 subjects with mild allergic asthma to pretreatment with AZD5423, budesonide, or placebo for seven days followed by allergen-bronchoprovocation . AZD5423 attenuated the fall in forced expiratory volume in one second (FEV1) during the late phase asthmatic response compared with budesonide or placebo, but did not affect the early decrease in FEV1. AZD5423 also decreased allergen-induced sputum eosinophilia and allergen-induced airway hyperresponsiveness at 24 hours and was well-tolerated. Additional studies are needed to determine the safety and efficacy of AZD5423 compared with inhaled glucocorticoids. (See "Alternative and experimental agents for the treatment of asthma", section on 'Novel glucocorticoid receptor agonist'.)
Aspirin therapy for aspirin-exacerbated respiratory disease (October 2014)
Aspirin desensitization followed by daily aspirin therapy is used in the treatment of aspirin-exacerbated respiratory disease (AERD). The utility of aspirin therapy in patients who have asthma and chronic polypoid rhinosinusitis but who tolerate aspirin has been unclear. In a small trial, 20 patients with AERD and 14 patients with asthma and CRS with nasal polyposis, but without aspirin intolerance, were randomized to receive aspirin therapy or placebo . Aspirin therapy improved several asthma and rhinitis outcomes and led to lower maintenance doses of inhaled glucocorticoids in patients with aspirin intolerance, but was not beneficial in patients without aspirin intolerance. Although small, the findings of this trial support the clinical impression that aspirin's benefits are limited to patients with intolerance. (See "Aspirin-exacerbated respiratory disease: NSAID challenge and desensitization", section on 'Efficacy of aspirin therapy in AERD'.)
Roflumilast reduces exacerbations in severe COPD (April 2015)
Roflumilast is an oral medication that is occasionally used in severe chronic obstructive pulmonary disease (COPD). In a multicenter trial, nearly 2000 patients with COPD, severe airflow obstruction, and at least two exacerbations in the prior year were randomly assigned to oral roflumilast or placebo for one year . All patients used a combination inhaled glucocorticoid and long acting beta-agonist inhaler in addition to study medication. Tiotropium was also allowed. Moderate-to-severe COPD exacerbations were 14 percent lower among those taking roflumilast compared with those taking placebo. Severe exacerbations requiring hospital admission were decreased by 24 percent, although confidence intervals approached no effect. Roflumilast may help to reduce COPD exacerbations when added to other respiratory medications, although the effect appears to be modest. (See "Management of stable chronic obstructive pulmonary disease", section on 'PDE-4 inhibitors'.)
Combination of varenicline and nicotine patch improves smoking cessation rates (October 2014)
In a randomized trial, 435 smokers were assigned to treatment with varenicline combined with either a nicotine or a placebo patch . Nicotine or placebo patches were started two weeks before the quit day and varenicline was started one week before the quit day. Both patches and varenicline were continued for 12 weeks. Treatment with varenicline and the nicotine patch resulted in a higher rate of continuous abstinence compared with varenicline and the placebo patch (49 versus 33 percent) at six months after the end of drug treatment. Prior studies have also shown higher rates of abstinence with the combination of nicotine replacement therapy (NRT) and bupropion, and with the combination of varenicline and bupropion. We continue to suggest initiating therapy with medication from a single class (eg, varenicline, bupropion, or NRT), given the increased cost and additional side effects with combining therapies, but combining medication classes is a reasonable option for patients who have failed initial therapy. (See "Pharmacotherapy for smoking cessation in adults", section on 'Patients who fail to quit'.)
Bronchoscopic lung volume reduction with nitinol coils in severe emphysema (October 2014)
Bronchoscopic placement of nitinol coils is an experimental method to treat emphysema. When the coils are deployed in areas of emphysema, they resume their coiled shape, collecting and collapsing the surrounding lung tissue and thereby reducing hyperinflation. In a multicenter, observational study, 60 patients with severe heterogeneous emphysema underwent bronchoscopic placement of nitinol coils (55 bilateral, 5 unilateral) with a median of 10 coils per lobe . Serious adverse events included seven COPD exacerbations, four pneumothoraces, and one episode of hemoptysis. The remaining patients experienced modest but sustained improvements in quality of life and lung function at six and 12 months. Randomized trials with a longer duration of follow-up are needed to confirm these findings. (See "Emerging therapies for COPD: Bronchoscopic treatment of emphysema", section on 'Coils'.)
Mortality is unchanged in severe sepsis with early goal-directed therapy (April 2015)
Early goal-directed therapy (EGDT) is the administration of intravenous fluids to patients with severe sepsis or septic shock within the first six hours of presentation using physiologic targets to guide fluid management. Although EGDT is widely accepted, the impact on mortality is unclear. In three multicenter randomized trials involving 1300 patients (ProCESS) , 1600 patients (ARISE) , and 2160 patients (ProMISe) , EGDT, compared with usual care, did not improve mortality at 60 days or 90 days. The early administration of fluids and antibiotics prior to randomization in these trials likely biased the results. However, they suggest that strict adherence to an aggressive EGDT protocol is not required in every patient with severe sepsis. (See "Evaluation and management of severe sepsis and septic shock in adults", section on 'Protocol-directed therapy'.)
Increased mortality with delayed treatment for spontaneous bacterial peritonitis (April 2015)
Patients with spontaneous bacterial peritonitis (SBP) who develop septic shock have high mortality rates, but early initiation of antimicrobial therapy may result in improved outcomes. In a retrospective study of patients with cirrhosis and SBP-associated septic shock, the risk of mortality nearly doubled (1.9-fold increase) with every hour delay in administering antimicrobial therapy . In patients with suspected SBP-associated sepsis, ascitic fluid cultures should be obtained immediately and empiric antimicrobial therapy initiated to maximize the patient's chance of survival. (See "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis", section on 'Prognosis'.)
No effect of blood storage duration on transfusion outcomes (April 2015)
Observational studies have come to differing conclusions regarding the effect of red blood cell (RBC) storage duration on transfusion outcomes. Two new randomized trials addressing this question now demonstrate that blood storage duration does not affect clinical outcomes. The Age of BLood Evaluation (ABLE) trial evaluated critically ill adults requiring an RBC transfusion, and the REd CEll Storage duration Study (RECESS) evaluated patients undergoing complex cardiac surgery [13,14]. Neither trial found a difference in primary outcome (90-day mortality or change in multi-organ dysfunction score [MODS], respectively), or in a variety of secondary outcomes or adverse events. These data, along with a previously published randomized trial in premature infants, provide strong evidence in support of current transfusion practice that does not take into account RBC storage duration. (See "Red blood cell transfusion in adults: Storage, specialized modifications, and infusion parameters", section on 'Clinical relevance of storage time'.)
Transfusion threshold for patients who have undergone cardiac surgery (March 2015)
For patients undergoing cardiac surgery, significant postoperative anemia is associated with worse outcomes. However, transfusion of red blood cells carries with it significant risks and burdens. In the TITRe2 trial, 2007 patients who underwent cardiac surgery were randomly assigned to a restrictive transfusion threshold (hemoglobin <7.5 g/dL) or a liberal threshold (<9 g/dL) . There was no difference in the rate of the primary combined outcome of serious infection or an ischemic event. We suggest a transfusion threshold of 7.5 to 8 g/dL for these patients. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Blood transfusion'.)
Warfarin reversal for urgent surgery: four-factor prothrombin complex concentrate versus Fresh Frozen Plasma (February 2015)
Patients receiving warfarin will occasionally require an urgent or emergent procedure, necessitating rapid reversal of anticoagulation. Available options include prothrombin complex concentrates (PCCs) and Fresh Frozen Plasma (FFP). In a trial that randomly assigned 181 such patients to receive 4-factor PCC or FFP, those receiving the PCC had better hemostasis, without increased toxicity . This finding supports the use of a 4-factor PCC in this setting. Because of potential toxicities from all rapid reversal products, PCCs should be reserved for individuals with bleeding or high risk of bleeding. These products work transiently and thus should be accompanied by vitamin K administration for more prolonged reversal. (See "Correcting excess anticoagulation after warfarin", section on 'Surgery/invasive procedure'.)
Ketamine for intubation in patients with elevated intracranial pressure (February 2015)
The use of ketamine as an induction agent for rapid sequence intubation (RSI) in patients with head trauma has been debated because some observational studies suggest it elevates intracranial pressure (ICP). However, a systematic review of 10 trials involving 953 critically ill patients, all managed with intubation and mechanical ventilation, concluded that the use of intravenous ketamine did not adversely affect patient outcomes, including mortality . Most studies included in the review had methodological limitations, but two randomized, double-blinded controlled trials comparing the effects of prolonged ketamine and sufentanil infusions in patients with traumatic brain injury found no differences in mean daily ICP and cerebral perfusion pressures. The findings of this systematic review support our view that ketamine is an appropriate induction agent for RSI in patients with suspected ICP elevation and normal blood pressure or hypotension. (See "Sedation or induction agents for rapid sequence intubation in adults", section on 'Elevated intracranial pressure'.)
Driving pressure in acute respiratory distress syndrome predicts survival (February 2015)
Limiting pressure and over distension of mechanically ventilated lung improves survival in patients with acute respiratory distress syndrome (ARDS). Lung protective ventilation strategies traditionally use low tidal volume (VT) and plateau pressure (pPlat) with or without high positive end expiratory pressure (PEEP) to achieve this goal. One retrospective statistical analysis of nine trials compared driving pressure (ΔP; ie, difference between pPlat and applied PEEP) with the standard variables, VT, pPlat, and PEEP to predict survival in 3562 patients mechanically ventilated for ARDS . Among ventilator variables, ΔP was the best predictor of survival. Even in patients who were ventilated using a lung protective strategy, small increases in ΔP resulted in a 30 to 40 percent increase in mortality. However, because ΔP is largely determined by VT, pPlat, and PEEP, we suggest the continued use of these standard variables rather than ΔP to manage ventilator settings in patients with ARDS. Use of ΔP will need to be tested in a large randomized trial before it can be routinely used in this population. (See "Mechanical ventilation of adults in acute respiratory distress syndrome", section on 'Driving pressure'.)
Adjunctive glucocorticoids for hospitalized patients with community-acquired pneumonia (January 2015)
There has been interest in using glucocorticoids as adjunctive therapy to antibiotics in hospitalized patients with community-acquired pneumonia (CAP) in an attempt to reduce the inflammatory response, which is likely to contribute to the morbidity of the disease. There are conflicting data on this approach, but the largest randomized trial suggests a modest benefit. In the trial, which included 785 hospitalized adults with CAP, prednisone 50 mg daily for seven days shortened the time to clinical stability by approximately one day compared with placebo, without an increase in complications . In another randomized trial that included 120 patients in Spain with severe CAP and a high inflammatory response, there was less treatment failure among patients who received methylprednisolone 0.5 mg/kg every 12 hours for five days than in those who received placebo, but no difference in the rate of in-hospital mortality . Pending the results of a larger trial evaluating mortality rates in severe CAP, we do not favor the routine use of adjunctive glucocorticoids in adults with CAP. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)
Prophylactic antibiotics do not benefit patients with acute liver failure (October 2014)
The role of prophylactic antibiotics in the treatment of patients with acute liver failure is controversial. In a retrospective study of 1551 patients with acute liver failure, antimicrobial prophylaxis was not associated with a lower incidence of bloodstream infection or death . Our approach to antibiotic prophylaxis is to give antibiotics only if there is evidence of active infection, positive surveillance culture results, or clinical deterioration. (See "Acute liver failure in adults: Management and prognosis", section on 'Infection surveillance and prevention'.)
Antibiotic decontamination of the digestive tract in the ICU and antimicrobial resistance (October 2014)
The use of prophylactic antibiotics to decontaminate the oropharyngeal and/or digestive tracts of critically ill patients and reduce the risk of infection confers a modest mortality benefit but is not widely used, in part, because of concern that it can promote antimicrobial resistance. A large multicenter cluster-randomized trial in intensive care units in the Netherlands compared resistance rates with selective oropharyngeal decontamination (SOD; antibiotics applied to the oropharynx only) and selective digestive decontamination (SDD; antibiotics applied to the oropharynx and through a nasogastric tube plus a different intravenous antibiotic) . Rates of rectal colonization with highly resistant bacteria were overall lower with SDD than SOD, but colonization with aminoglycoside-resistant gram-negative bacilli increased more over time with SDD than SOD. Given the very low baseline rate of antimicrobial resistance in the Netherlands and the absence of a control group that received no prophylactic antibiotics, these findings do not sufficiently allay concerns about long-term antimicrobial resistance with antibiotic use for decontamination of the gastrointestinal tract. (See "Epidemiology and prevention of infections and antimicrobial resistance in the intensive care unit", section on 'Decontamination of the digestive tract'.)
Restrictive transfusion threshold safe in septic shock (October 2014)
Blood transfusion using a lower (restrictive) hemoglobin threshold has been adopted in a variety of settings, including hemodynamically stable patients in the intensive care unit. However, debate has remained regarding the safety of this approach in patients with septic shock. A new randomized trial has shown that a restrictive hemoglobin threshold of 7 g/dL can be used in this setting. The Transfusion Requirements in Septic Shock (TRISS) trial randomly assigned 998 patients with septic shock to a restrictive or a liberal transfusion strategy (hemoglobin threshold of 7 or 9 g/dL) . All outcomes were similar between the two groups at 90 days, including mortality, cardiac ischemia, and transfusion reactions. We and other experts agree that for most patients with septic shock, red blood cell transfusion should be reserved for those with a hemoglobin of ≤7 g/dL. (See "Evaluation and management of severe sepsis and septic shock in adults", section on 'Red blood cell transfusions' and "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Intensive care unit/septic shock'.)
Enteral versus parenteral nutrition in critically ill patients (October 2014)
In critically ill patients, the benefits of enteral nutrition compared with parenteral nutrition are unclear, with small randomized trials suggesting marginal benefit to enteral nutrition in surgical patients. One large multicenter randomized trial compared enteral nutrition with parenteral nutrition in 2400 critically ill patients, most of whom had medical rather than surgical illnesses . There was no difference in mortality or rates of infections between the groups. These findings support the continued use of enteral nutrition in both medical and surgical patients who are critically ill, when feasible. (See "Nutrition support in critically ill patients: An overview", section on 'Enteral versus parenteral'.)
INTERSTITIAL LUNG DISEASE
Novel variants in telomerase pathway associated with familial interstitial pneumonia (March 2015)
Several genes that maintain chromosome telomeres have been associated with idiopathic pulmonary fibrosis (IPF). In a study of 25 kindreds of familial interstitial pneumonia (FIP), the familial form of IPF, nine rare loss-of-function variants were identified in the gene that encodes the regulator of telomere elongation helicase 1 (RTEL1), which helps regulate telomere replication and stability . The rare variants identified in this study segregate with FIP in genetic studies and are associated with very short telomeres in peripheral blood mononuclear cells. In 163 additional FIP kindreds, heterozygous variants of RTEL1 were found in eight families (approximately 5 percent). These observations further support the role of genes affecting telomeres in FIP. (See "Pathogenesis of idiopathic pulmonary fibrosis", section on 'Genetic predisposition'.)
PULMONARY VASCULAR DISEASE
Two distinct phenotypes in patients with idiopathic pulmonary artery hypertension (January 2015)
Vasoconstriction and luminal obstruction from plexiform lesions are both thought to play a role in the pathogenesis of idiopathic pulmonary artery hypertension (IPAH). A minority of patients responds to pulmonary vasodilators (responders), suggesting vasoconstriction may be more important in the pathogenesis of the disease in these patients compared with non-responders. Functional capillary surface area (FCSA) is a measurement of the amount of available pulmonary flow (ie, pulmonary reserve) that can be recruited during vasodilatation for improved gas exchange and hemodynamics. In an observational study of 14 patients with IPAH, FSCA response to a vasodilator challenge was compared between responders and non responders. Responders had a higher FCSA which increased during vasodilator testing, supporting the hypothesis that vasoconstriction, rather than luminal obstruction, was the dominant pathogenetic process in this population . Further exploration of this theory with larger numbers of patients is warranted. (See "Pathogenesis of pulmonary hypertension", section on 'Pathophysiology'.)
Negative D-dimer does not predict recurrence risk in unprovoked VTE (January 2015)
Indefinite anticoagulation is preferred in patients with a first episode of unprovoked venous thromboembolism (VTE). The D-dimer assay has been proposed as a test to identify patients in whom anticoagulant therapy may be safely discontinued. However, a prospective study that measured the VTE recurrence rate in 319 patients with a first episode of unprovoked VTE who had two consecutive negative D-dimer levels does not support this indication for d-dimer testing . The first level was drawn following completion of a standard course of anticoagulant therapy and the second after one month off anticoagulation. The two year recurrence rate was 7 percent per patient-year, with higher rates reported in men (10 percent per patient year) compared with women (5 percent per patient year). These rates are sufficiently high that they support the current recommendation of indefinite anticoagulation in this population; D-dimer measurements do not appear to be useful in identifying candidates for more limited treatment. (See "Rationale and indications for indefinite anticoagulation in patients with venous thromboembolism", section on 'Elevated D-dimer'.)
Novel anticoagulant strategies with potentially lower bleeding risk (December 2014)
Anticoagulants reduce the risk of thromboembolism, but this benefit is balanced by an increased risk of bleeding. Two new strategies for anticoagulation are in development that may carry a lower risk of bleeding compared with currently available agents. The first uses an antisense oligonucleotide to reduce production of coagulation factor XI (FXI-ASO). In patients undergoing knee replacement, treatment with FXI-ASO was associated with a 3 percent risk of venous thromboembolism, compared with approximately 30 percent with low molecular weight heparin, without increasing bleeding . However, the duration of anticoagulation was long and injection site reactions were common. The second strategy targets polyphosphate, a pro-thrombotic substance released from activated platelets or microbes . In preclinical models, polyphosphate inhibitors have shown reduced arterial thrombosis without increased bleeding. Additional studies are awaited to determine the role of these new strategies in clinical practice. (See "Anticoagulation with direct thrombin inhibitors and direct factor Xa inhibitors", section on 'Anticoagulants in development'.)
Herbal products for treatment of insomnia (March 2015)
A variety of herbal products are purported to be useful for insomnia. There is little evidence from randomized controlled trials about the efficacy of many herbals, however, and for those that have been well studied (eg, valerian), there is little evidence of benefit. A meta-analysis of 14 randomized trials in over 1600 patients found no significant difference between any herbal medicine and placebo on any clinical insomnia outcome measure . The majority of the trials (11 out of 14) studied valerian; chamomile, kava, and wuling were studied in one trial each. Unlike other herbals in the study, valerian was associated with a greater number of adverse events per person compared with placebo. (See "Treatment of insomnia", section on 'Over-the-counter'.)
Risk factors for neurodegeneration in REM sleep behavior disorder (March 2015)
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia in which individuals act out their dreams due to loss of REM sleep paralysis. RBD has been increasingly recognized as a prodromal symptom of alpha-synuclein neurodegeneration (eg, Parkinson disease, dementia with Lewy bodies, and multiple system atrophy). In a 10-year prospective cohort study of 89 patients with idiopathic RBD, the rate of conversion to one of these disorders was 30 percent at 3 years and 66 percent at 7.5 years . The strongest risk factors for conversion were subtle motor dysfunction, abnormal color vision, olfactory dysfunction, and nonuse of antidepressants. These characteristics may prove useful for identifying candidates for novel, early-intervention neuroprotective trials in Parkinson disease and related disorders. (See "Rapid eye movement sleep behavior disorder", section on 'Prognosis and counseling'.)
OTHER PULMONARY MEDICINE
Pneumococcal conjugate vaccine in adults ≥65 years of age (September 2014, MODIFIED March 2015)
The CAPiTA trial, which is the largest trial to assess the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13) in adults, compared PCV13 to placebo in approximately 85,000 immunocompetent adults ≥65 years of age in the Netherlands who had not received a pneumococcal vaccine previously . The trial demonstrated 46 percent efficacy of PCV13 against vaccine-type pneumococcal pneumonia, 45 percent efficacy against vaccine-type nonbacteremic pneumococcal pneumonia, and 75 percent efficacy against vaccine-type invasive pneumococcal disease. Efficacy persisted for the duration of the trial (mean follow-up four years). However, some concern has been raised that since this trial began before PCV13 was used routinely in infants in the Netherlands, it might not answer the question of whether its use in adults is efficacious in countries that routinely vaccinate infants. (See "Pneumococcal vaccination in adults", section on 'Efficacy'.)
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many years in the United States for all adults ≥65 years of age. In September 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending PCV13 for all adults ≥65 years of age . The ACIP revision was prompted by results from the CAPiTA trial. Current recommendations for individuals ≥65 years of age who have not previously received either PCV13 or PPSV23 are to administer PCV13 followed 6 to 12 months later by PPSV23 (algorithm 1). In patients who have already received PPSV23, at least one year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Indications'.)
Approval of the direct factor Xa inhibitor edoxaban (January 2015)
The US Food and Drug Administration has approved the oral direct factor Xa inhibitor edoxaban (Savaysa; Lixiana in Japan) for the prevention of stroke in nonvalvular atrial fibrillation and the treatment of venous thromboembolism, based upon earlier randomized trials demonstrating non-inferiority to warfarin [34-36]. Dosing is once daily at a fixed dose without monitoring. There are Boxed Warnings regarding avoidance of edoxaban in patients with atrial fibrillation who have a creatinine clearance >95 mL/minute, spinal/epidural hematoma in patients undergoing neuraxial procedures, and ischemic events following premature discontinuation. (See "Atrial fibrillation: Anticoagulant therapy to prevent embolization" and "Lower extremity deep venous thrombosis: Long-term anticoagulation (10 days to three months)" and "Anticoagulation in acute pulmonary embolism" and "Anticoagulation with direct thrombin inhibitors and direct factor Xa inhibitors", section on 'Edoxaban'.)
Rituximab as maintenance therapy in ANCA-associated vasculitis (November 2014)
Azathioprine and methotrexate are conventionally considered the preferred drugs for maintenance therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trial compared rituximab with azathioprine as maintenance therapy in 115 patients who had achieved remission after induction therapy with cyclophosphamide and glucocorticoids . Major relapse rates at 28 months were lower for rituximab (5 versus 29 percent). Rates of adverse events were also similar. However, the dosing of azathioprine in this trial was not consistent with the practice of many experts, and this may have contributed to the excess relapse rate. In addition, most patients had GPA, a positive PR3-ANCA, and were newly diagnosed rather than relapsed patients. It is not clear whether or not these data apply to other groups of patients with ANCA-associated vasculitis or to patients induced with rituximab rather than cyclophosphamide. Thus, either rituximab or azathioprine (or methotrexate although it was not evaluated in this trial) can be used as maintenance therapy in patients with GPA or MPA while awaiting further data to confirm these findings. (See "Maintenance immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis", section on 'Rituximab'.)
Lower risk of fatal bleeding with target specific oral anticoagulants versus warfarin (November 2014)
All anticoagulants carry a risk of bleeding, and the lack of an antidote for direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran increases concerns about this risk. Reassuringly, a meta-analysis of 12 randomized trials in patients with atrial fibrillation or venous thromboembolism that compared bleeding risk with these agents versus vitamin K antagonists found lower rates of fatal bleeding, major bleeding, and intracranial bleeding with the direct factor Xa and direct thrombin inhibitors . Individual patient factors continue to play a role in anticoagulant choice and the development of reversal agents for the factor Xa and thrombin inhibitors is underway. (See "Management of bleeding in patients receiving target-specific oral anticoagulants", section on 'Risk of bleeding'.)
Investigational agent for reversal of multiple anticoagulants (November 2014)
Reversal agents for the target specific oral anticoagulants are lacking. In a study of 80 healthy volunteers given a therapeutic dose of the direct factor Xa inhibitor edoxaban, a reversal agent under development (PER977) normalized the whole blood clotting time within 10 minutes; in contrast, normalization of the clotting time took 12 to 15 hours in individuals given edoxaban followed by placebo . In addition to binding direct factor Xa inhibitors, PER977 also binds the direct thrombin inhibitor dabigatran, as well as unfractionated and low molecular weight heparins. (See "Management of bleeding in patients receiving target-specific oral anticoagulants", section on 'Antidotes under development'.)
Infection prevention measures for cystic fibrosis (October 2014)
Evidence is accumulating that a variety of respiratory pathogens can be transmitted among individuals with cystic fibrosis (CF) within the health care system. In particular, highly transmissible strains of Pseudomonas aeruginosa have been reported. Compared with sporadic strains of P. aeruginosa, infection with highly transmissible strains is associated with increased need for health care and antibiotics. To minimize risk of transmission, the CF Foundation has published updated guidelines for infection prevention and control to be applied to all individuals with CF, regardless of respiratory tract culture results . The guidelines include the following measures:
●Clinicians should use contact precautions (gown and surgical masks) at all times when caring for patients with CF.
●Patients with CF should wear surgical masks in the health care setting.
●Patients with CF should not congregate within or outside of the health care setting, should remain at least six feet away from other patients with CF, and be cared for in single-patient rooms when they require admission.
- Over-the-Counter Asthma Products Labeled as Homeopathic: FDA Statement - Consumer Warning About Potential Health Risks. http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm439014.htm.
- Eltonsy S, Forget A, Beauchesne MF, Blais L. Risk of congenital malformations for asthmatic pregnant women using a long-acting β₂-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy. J Allergy Clin Immunol 2015; 135:123.
- Namazy J, Cabana MD, Scheuerle AE, et al. The Xolair Pregnancy Registry (EXPECT): the safety of omalizumab use during pregnancy. J Allergy Clin Immunol 2015; 135:407.
- Gauvreau GM, Boulet LP, Leigh R, et al. A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med 2015; 191:161.
- Świerczyńska-Krępa M, Sanak M, Bochenek G, et al. Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study. J Allergy Clin Immunol 2014; 134:883.
- Martinez FJ, Calverley PM, Goehring UM, et al. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet 2015; 385:857.
- Koegelenberg CF, Noor F, Bateman ED, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. JAMA 2014; 312:155.
- Deslee G, Klooster K, Hetzel M, et al. Lung volume reduction coil treatment for patients with severe emphysema: a European multicentre trial. Thorax 2014; 69:980.
- ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370:1683.
- ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:1496.
- Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372:1301.
- Karvellas CJ, Abraldes JG, Arabi YM, et al. Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study. Aliment Pharmacol Ther 2015; 41:747.
- Lacroix J, Hébert PC, Fergusson DA, et al. Age of Transfused Blood in Critically Ill Adults. N Engl J Med 2015.
- Steiner ME, Ness PM, Assmann SF, et al. Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med 2015; 372:1419.
- Murphy GJ, Pike K, Rogers CA, et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015; 372:997.
- Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet 2015.
- Cohen L, Athaide V, Wickham ME, et al. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med 2015; 65:43.
- Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015; 372:747.
- Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015.
- Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 2015; 313:677.
- Karvellas CJ, Cavazos J, Battenhouse H, et al. Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study. Clin Gastroenterol Hepatol 2014; 12:1942.
- Oostdijk EA, Kesecioglu J, Schultz MJ, et al. Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial. JAMA 2014; 312:1429.
- Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014; 371:1381.
- Harvey SE, Parrott F, Harrison DA, et al. Trial of the route of early nutritional support in critically ill adults. N Engl J Med 2014; 371:1673.
- Cogan JD, Kropski JA, Zhao M, et al. Rare Variants in RTEL1 Are Associated with Familial Interstitial Pneumonia. Am J Respir Crit Care Med 2015; 191:646.
- Langleben D, Orfanos SE, Giovinazzo M, et al. Acute vasodilator responsiveness and microvascular recruitment in idiopathic pulmonary arterial hypertension. Ann Intern Med 2015; 162:154.
- Kearon C, Spencer FA, O'Keeffe D, et al. D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study. Ann Intern Med 2015; 162:27.
- Büller HR, Bethune C, Bhanot S, et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med 2015; 372:232.
- Travers RJ, Shenoi RA, Kalathottukaren MT, et al. Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis. Blood 2014; 124:3183.
- Leach MJ, Page AT. Herbal medicine for insomnia: A systematic review and meta-analysis. Sleep Med Rev 2014; 24C:1.
- Postuma RB, Gagnon JF, Bertrand JA, et al. Parkinson risk in idiopathic REM sleep behavior disorder: Preparing for neuroprotective trials. Neurology 2015; 84:1104.
- Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015; 372:1114.
- Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014; 63:822.
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf (Accessed on January 09, 2015).
- Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369:2093.
- Hokusai-VTE Investigators, Büller HR, Décousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369:1406.
- Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371:1771.
- Chai-Adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014; 124:2450.
- Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014; 371:2141.
- Saiman L, Siegel JD, LiPuma JJ, et al. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol 2014; 35 Suppl 1:S1.