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What's new in pulmonary and critical care medicine
Official reprint from UpToDate® ©2015 UpToDate®
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What's new in pulmonary and critical care medicine

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.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2015. | This topic last updated: Nov 20, 2015.

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.


New biologic therapy approved for severe eosinophilic asthma (November 2015)

Mepolizumab, a monoclonal antibody to interleukin (IL)-5, has been approved by the US Food and Drug Administration for add-on, maintenance treatment of severe asthma in patients who are age 12 or older, have frequent asthma exacerbations, and have an eosinophilic phenotype [1]. One marker of an eosinophilic phenotype is a blood absolute eosinophil count of ≥150/microL. Mepolizumab is administered subcutaneously at four-week intervals. Studies in patients with severe eosinophilic asthma have shown that mepolizumab reduces the rate of exacerbations and enables a reduction in the oral glucocorticoid dose. Based on limited data, we suggest that patients who meet criteria for vaccination receive the varicella-zoster vaccine at least four weeks prior to initiation of mepolizumab. Mepolizumab will likely be commercially available in early 2016. (See "Treatment of severe asthma in adolescents and adults", section on 'Anti-IL-5 therapy'.)

Soy isoflavone supplementation does not improve asthma control (June 2015)

Patients with asthma often request guidance on dietary alterations that might improve asthma control. Preliminary studies suggested that soy isoflavone supplementation might fill this role, possibly by a reduction in eosinophil leukotriene synthesis. However, in a 24-week multicenter trial that included 386 adults and children age 12 or older with poorly controlled asthma, isoflavone supplementation did not significantly improve pulmonary function, symptom scores, episodes of poor asthma control, or exhaled nitric oxide [2]. High-quality studies are essential to determining the efficacy of dietary adjustments; this study demonstrates that soy isoflavone supplements are not useful in poorly controlled asthma. (See "Complementary, alternative, and integrative therapies for asthma", section on 'Dietary changes and supplements'.)

Investigational agent shows promise in asthma (June 2015)

GATA3 is a transcription factor that is essential for Th2 lymphocyte differentiation and activation. An investigational synthetic DNA molecule (SB010) has been developed that uniquely binds to GATA3 messenger RNA and cleaves it. The effect of SB010 was assessed in 43 patients with mild allergic asthma who were randomly assigned to inhalation of SB010 or placebo once daily for 28 days [3]. The early and late asthmatic responses to allergen bronchoprovocation were significantly attenuated by SB010. The degree of suppression of the late response was similar to that of inhaled glucocorticoids. This study supports a potential role for disruption of GATA3 (and thus Th2 cytokines) in asthma. (See "Investigational agents for asthma", section on 'GATA3-specific DNAzyme'.)


Augmentation therapy in alpha-1 antitrypsin deficiency (June 2015)

“Augmentation therapy” consisting of regular infusions of alpha-1 antiprotease obtained from pooled human plasma is an accepted therapy for alpha-1 antitrypsin (AAT) deficiency, although high-quality studies demonstrating efficacy have been lacking. In the RAPID trial, patients with AAT deficiency were randomly assigned to weekly intravenous augmentation therapy (93 patients) or placebo (87 patients) for 24 months [4]. The rate of loss of lung density, as measured by computed tomography (CT) at full inspiration, was lower among augmentation recipients than placebo recipients. No significant differences were observed in other measures of lung function, quality of life, or exacerbation frequency. The effect on lung density suggests that augmentation therapy for AAT deficiency may slow progression of emphysema. (See "Treatment of alpha-1 antitrypsin deficiency", section on 'Clinical efficacy'.)


Reversal agent for factor Xa inhibitors (November 2015)

Lack of reversal agents for the direct oral anticoagulants has been a concern. Andexanet alfa is a recombinant protein designed to reverse factor Xa inhibitors by binding to the drugs and sequestering them away from endogenous factor Xa. In a randomized trial in healthy volunteers, an andexanet bolus reduced anti-factor Xa activity by 94 percent and 92 percent for volunteers taking apixaban or rivaroxaban, respectively, compared with reductions of 21 and 18 percent for a placebo bolus [5]. A study evaluating andexanet efficacy in patients with factor Xa inhibitor-associated bleeding is ongoing. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antidotes under development'.)

Adjunctive glucocorticoids for adults with severe community-acquired pneumonia (August 2015, Modified November 2015)

For hospitalized patients with community-acquired pneumonia (CAP), glucocorticoids as adjunctive therapy to antibiotics have the potential to reduce the inflammatory response and decrease morbidity. A 2015 meta-analysis of randomized trials that included hospitalized patients with CAP suggested a modest mortality benefit for adjunctive glucocorticoids [6]. A reduction in all-cause mortality was of borderline statistical significance (relative risk [RR] 0.67, 95% CI 0.45-1.01; risk difference 2.8 percent). Rates of mechanical ventilation and acute respiratory distress syndrome were decreased, as were time to clinical stability and duration of hospitalization; rates of hyperglycemia requiring treatment increased.

For hospitalized patients with CAP who require intensive care unit admission, we recommend adjunctive glucocorticoids. For other hospitalized patients with CAP, we suggest adjunctive glucocorticoids. Clinicians should make the decision whether or not to give glucocorticoids on a case-by-case basis, especially in patients with an elevated risk of adverse effects. Limited evidence suggests that infections caused by certain pathogens (eg, influenza virus, Aspergillus spp) may be associated with worse outcomes in the setting of glucocorticoid use [7,8]; given these concerns, we avoid adjunctive glucocorticoids if one of these pathogens is detected. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Glucocorticoids'.)

No benefit from buffered crystalloids in critically ill patients (October 2015)

Crystalloid solutions (typically isotonic saline) are commonly used for fluid resuscitation for non-trauma patients in the intensive care unit (ICU). However, whether buffered crystalloids (eg, lactated-Ringers solution) should be used instead of isotonic saline is unknown. In a randomized trial of over 2000 mostly postoperative ICU patients, buffered crystalloids, when used as the initial resuscitative fluid, did not reduce the rate of acute kidney injury or renal replacement therapy when compared with normal saline; the effect on mortality was inadequately assessed [9]. However, patients in this trial were not severely ill and did not require large volumes of resuscitative fluid. Thus, further trials will be needed to examine the efficacy of buffered solutions before they can be routinely recommended over isotonic saline for fluid resuscitation in non-trauma ICU patients. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Buffered crystalloid'.)

Chlorhexidine-alcohol for site preparation before intravascular catheter insertion (October 2015)

Skin antiseptic preparation with chlorhexidine-alcohol prior to intravascular catheter insertion provides greater protection against short-term catheter-related infection than povidone iodine-alcohol. In a large randomized trial including 2349 patients (5159 catheters), use of chlorhexidine–alcohol resulted in a lower incidence of catheter-related infections than povidone iodine-alcohol (0.28 versus 1.77 per 1000 catheter-days) [10]. We continue to recommend use of chlorhexidine-alcohol prior to catheter insertion, in conjunction with other measures for prevention of intravascular catheter-related infections. (See "Prevention of intravascular catheter-related infections", section on 'Insertion site preparation'.)

Dabigatran reversal agent approved (October 2015)

The lack of a specific reversal agent for the direct thrombin inhibitor dabigatran has been a persistent concern in its use for patients with atrial fibrillation or venous thromboembolism. Idarucizumab (Praxbind) is a reversal agent for dabigatran that was approved by the US Food and Drug Administration in October 2015 to reverse dabigatran effect in the setting of life-threatening or uncontrolled bleeding or emergency surgery [11,12]. Approval was based on studies in healthy volunteers and an interim analysis of the RE-VERSE AD trial, which included a cohort of 90 older adult patients who had clinically significant bleeding or the need for an urgent invasive procedure while taking dabigatran for atrial fibrillation [13]. Idarucizumab produced rapid normalization of clotting times and/or surgical hemostasis; there were five thrombotic events and 18 deaths. Without a control group it is unclear how these outcomes would compare with similar patients who did not receive idarucizumab. For patients with life-threatening bleeding, we would use idarucizumab, if available, along with other measures to decrease bleeding risk, but we would not combine idarucizumab with procoagulant products such as an activated prothrombin complex concentrate (aPCC). Idarucizumab is an antibody-based therapy and does not have known activity against direct factor Xa inhibitors or other anticoagulants. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)

Direct diaphragmatic pacing potentially harmful in patients with amyotrophic lateral sclerosis (August 2015)

Noninvasive ventilation (NIV) is first-line therapy for patients with amyotrophic lateral sclerosis (ALS) who have ventilatory failure. Based upon preliminary studies in this population that suggested a delay in the need for full mechanical ventilation and improved survival, direct diaphragmatic pacing stimulation (DPS) was approved for humanitarian use. However, a randomized trial of 74 patients with respiratory failure from ALS reported reduced survival when DPS was used in combination with NIV, compared with patients treated with NIV alone (11 versus 23 months) [14]. Thus, we suggest that NIV continues as first-line therapy in this population and that DPS remain investigational until larger randomized trials clarify whether or not it has true benefit. (See "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications", section on 'Amyotrophic lateral sclerosis'.)

Oxygen not helpful in normoxic STEMI patients (June 2015)

Small studies have raised the possibility of harm from supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI). In the AVOID study, 441 normoxic patients with confirmed STEMI were randomly assigned to either supplemental oxygen (8 L/min) or no oxygen [15]. The trial showed no improvement in the primary end point of a diminution in infarct size with oxygen and perhaps evidence of a larger infarct. For STEMI patients who are not hypoxic, we suggest not administering supplemental oxygen. (See "Overview of the acute management of ST elevation myocardial infarction", section on 'Oxygen'.)

Permissive underfeeding in critically ill adults (May 2015)

Meeting the complete caloric needs of critically ill patients is potentially associated with harm due to overfeeding, so standard feeding regimens in this population are typically designed to meet 70 percent of their caloric requirements. However, the optimal caloric goal for critically ill adults remains unclear. In a randomized trial of 894 critically ill patients (medical, surgical, trauma; PermiT), standard enteral feeding (70 to 100 percent of caloric requirements) was compared with 14 days of permissive underfeeding (40 to 60 percent of caloric requirements), while keeping the protein content the same in both groups [16]. There were no significant differences in mortality, gastrointestinal intolerance, infectious complications, or length of hospital stay between the two groups. This trial supports the continued practice of underfeeding in critically ill adults. Further trials are needed to confirm the optimal balance of protein and nonprotein calories in this population. (See "Nutrition support in critically ill patients: An overview", section on 'Calories'.)

High-flow oxygen therapy by nasal cannula for acute hypoxemic respiratory failure in adults (May 2015)

In adults with acute hypoxemic respiratory failure without hypercapnia, high-flow oxygen therapy by nasal cannula is a reasonable alternative to standard oxygen therapy or noninvasive positive pressure ventilation. Such patients should be managed in settings with appropriate monitoring (eg, emergency departments or intensive care units). In a multicenter trial of 310 adults with hypoxemic respiratory failure without hypercapnia that compared high-flow oxygen therapy by nasal cannula with standard oxygen therapy by face mask or noninvasive positive pressure ventilation (NPPV), the intubation rate was not significantly different for patients receiving high-flow oxygen compared with standard therapy or NPPV [17]. Patients who received high-flow oxygen therapy had significantly lower 90-day mortality and fewer days of mechanical ventilation than the other two groups, although patients receiving NPPV might have had a greater degree of baseline lung injury. (See "Continuous oxygen delivery systems for infants, children, and adults", section on 'High flow'.)

Use of high-flow nasal oxygen in postoperative care (May 2015)

Oxygen delivered via high-flow nasal cannula (HFNC) can oxygenate patients as well as provide small amounts of positive airway pressure. It is unknown whether HFNC is an effective therapy for the treatment of postoperative acute hypoxemic respiratory failure. One study of 830 patients who were at risk of or who developed acute respiratory failure following cardiothoracic surgery were randomly assigned to receive either continuous HFNC or noninvasive ventilation (NIV) with bilevel positive airway pressure (delivered for at least four hours per day) [18]. HFNC and NIV had similar rates of treatment failure (eg, reintubation) and mortality but skin breakdown was more commonly encountered with NIV. Although this study suggested that HFNC and NIV were comparable, methodologic flaws in study design may have affected the outcome, and additional randomized studies will be necessary before HFNC can be routinely used as first-line therapy for the treatment or prevention of postoperative respiratory failure. However, it may be an alternative to NIV, particularly for those in whom NIV is not tolerated. HFNC is not routinely available in all institutions for adult use and it should only be administered by staff educated in its application. (See "Overview of the management of postoperative pulmonary complications", section on 'Postoperative respiratory failure'.)


Everolimus for pulmonary lymphangioleiomyomatosis (October 2015)

The mechanistic target of rapamycin (mTOR) inhibitor, sirolimus, is approved for the treatment of moderate-to-severe pulmonary lymphangioleiomyomatosis (LAM), but not all patients are able to tolerate it. The effect of everolimus, another mTOR inhibitor, was assessed in a 26-week, multicenter, open-label study of 24 women with pulmonary LAM [19]. The forced expiratory volume in one second (FEV1) and the six-minute walk distance both improved from baseline, while the forced vital capacity (FVC) remained stable. Adverse effects were similar to sirolimus, most commonly, stomatitis and mouth ulcers, but also peripheral edema, pneumonia, cardiac failure, and Pneumocystis jirovecii infection. Everolimus appears to have benefits that are comparable to sirolimus and may expand treatment options for pulmonary LAM. (See "Pulmonary lymphangioleiomyomatosis", section on 'Everolimus'.)

Sirolimus approved for use in pulmonary lymphangioleiomyomatosis (June 2015)

Pulmonary lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung disease associated with mutations in proteins of the mechanistic target of rapamycin (mTOR) complex. Sirolimus (also known as rapamycin) has been approved by the US Food and Drug Administration for the treatment of moderate-to-severe pulmonary LAM [20]. Approval was based on an earlier trial in which sirolimus slowed the decline in pulmonary function, quality of life, and functional performance compared with placebo. (See "Pulmonary lymphangioleiomyomatosis", section on 'mTOR inhibition'.)


BRAF inhibition in non-small cell lung cancer (August 2015)

BRAF inhibition may be an effective strategy in the treatment of the 1 to 3 percent of non-small cell lung cancers (NSCLC) that harbor a BRAF V600 mutation. In a phase II trial, responses were seen in 8 of the 19 patients with BRAF V600 mutation-positive NSCLC treated with the oral BRAF inhibitor vemurafenib [21]. This study supports our suggestion to use BRAF inhibitors as second-line therapy rather than single-agent chemotherapy in patients with a BRAF V600 mutated cancer. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'BRAF mutation'.)

Gefitinib approved for EGFR mutation-positive non-small cell lung cancer in the United States (July 2015)

Epidermal growth factor receptor (EGFR) inhibitors have an established role in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and a driver mutation in EGFR. Gefitinib was approved outside the United States when the importance of EGFR mutations was identified and has now been approved by the US Food and Drug Administration for patients whose tumor contains an EGFR exon 19 deletion or the exon 21 (L858R) substitution mutation [22]. Gefitinib now provides an additional option for the treatment of patients in the United States with advanced NSCLC and an EGFR driver mutation. (See "Systemic therapy for advanced non-small cell lung cancer with an activating mutation in the epidermal growth factor receptor", section on 'Gefitinib'.)

Stereotactic body radiation therapy for stage I non-small cell lung cancer (May 2015)

Stereotactic body radiation therapy (SBRT) was compared with surgery in two randomized trials but both were prematurely closed because of poor patient accrual. A combined analysis of these trials found that overall survival was superior with SBRT at three years, although there were no differences in rates of locoregional recurrence or distant metastasis [23]. SBRT is an alternative that has growing evidence to support comparable outcomes in selected stage I patients. (See "Management of stage I and stage II non-small cell lung cancer", section on 'Stereotactic body radiation therapy'.)


Promising outcomes after lung transplantation for advanced hypersensitivity pneumonitis (July 2015)

Lung transplantation may be a reasonable option for patients with advanced chronic hypersensitivity pneumonitis (HP) that is refractory to avoidance of known allergens and immunosuppressive medications. In a case series of 31 such patients, lung transplantation was associated with 96 and 89 percent survival at one and five years, respectively [24]. The inciting allergen was identifiable in 12 patients (birds, mold, wood bark), but not in the remaining nine. Two patients with known culprit allergens experienced a recurrence of HP in the allograft due to repeat exposure, but improved after more meticulous allergen avoidance. (See "Treatment and prognosis of hypersensitivity pneumonitis (extrinsic allergic alveolitis)", section on 'Lung transplantation'.)


Warning against combining phosphodiesterase-5 inhibitors and guanylate cyclase stimulants in PAH (September 2015)

Patients with pulmonary arterial hypertension (PAH) are often treated with dual agent therapy, which may include a variety of agent classes. The safety of combining sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, and riociguat, a guanylate cyclase stimulant, was examined in a randomized trial [25]. Although no adverse effects were reported during the 12-week study period, three deaths and high rates of discontinuation due to hypotension were reported following termination of the study. As a consequence, the US Food and Drug Administration issued a warning against combining PDE-5 inhibitors and guanylate cyclase stimulants [26]. We agree that in patients with PAH, this combination is contraindicated due to an unfavorable safety profile and should not be administered. (See "Treatment of pulmonary hypertension in adults", section on 'Combination therapy'.)

Combination therapy with ambrisentan and tadalafil for pulmonary arterial hypertension (September 2015)

Typically, patients with group 1 pulmonary arterial hypertension (PAH) who have World Health Organization (WHO) class II or III symptoms are treated with single agent advanced therapy. In a randomized trial, the combination of ambrisentan (a selective endothelin receptor A antagonist) and tadalafil (a cyclic GMP phosphodiesterase type 5 [PDE5] inhibitor) was associated with a significant reduction in the rate of clinical failure when compared with either agent alone [27]. The improved clinical outcome was driven primarily by reduction in the rate of hospitalizations for progressive PAH, a factor that portends poor prognosis, rather than by improved survival or WHO functional class. We now suggest this combination as first-line therapy for newly diagnosed patients with group 1 PAH and functional class II or III symptoms, who have either a negative vasoreactivity test or who are vasoreactive but fail to respond to calcium channel blocker therapy (algorithm 1). (See "Treatment of pulmonary hypertension in adults", section on 'Combination therapy'.)

Extended anticoagulation for pulmonary embolism (July 2015)

Patients with unprovoked pulmonary embolism (PE) are at high risk of recurrence once anticoagulation is discontinued. Whether anticoagulation beyond a conventional course is beneficial was investigated in a randomized trial of 371 adult patients with a first episode of symptomatic unprovoked PE who had completed six months of warfarin therapy [28]. Rates of recurrent thrombosis were seven times higher in patients treated with placebo compared with those who continued anticoagulant therapy. However, rates of major bleeding were higher with extended anticoagulation, and once discontinued, the benefit of reduced recurrence was not maintained. These results reflect similar data derived from patients with deep venous thrombosis treated with extended anticoagulant therapy. Clinicians should continue to evaluate patients with unprovoked venous thromboembolism on an individual basis and weigh the benefits of extended anticoagulation against the risk of major bleeding. (See "Rationale and indications for indefinite anticoagulation in patients with venous thromboembolism", section on 'Recurrence with and without anticoagulation'.)

Limited occult cancer screening for venous thromboembolism (June 2015)

Occult cancer is associated with venous thromboembolism (VTE). However, evidence to support a specific evaluation strategy is limited. In a randomized trial of 854 patients with a first unprovoked episode of VTE, a limited strategy for the evaluation of cancer (basic laboratory testing, chest radiography, and breast, cervical, and prostate cancer screening) was compared with a more comprehensive strategy (the limited strategy plus CT of the abdomen and pelvis) [29]. Both strategies identified a low incidence of cancer (approximately 4 percent) and cancer-related mortality at one year was low (1 percent) in both groups. Thus, the addition of CT of the abdomen and pelvis did not improve cancer detection, and the study supports our practice of adopting a limited approach to evaluation in patients with a first episode of unprovoked VTE. (See "Evaluating patients with established venous thromboembolism for acquired and inherited risk factors", section on 'First episode of uncomplicated unprovoked VTE'.)


Cognitive-behavioral therapy for insomnia (August 2015)

Cognitive-behavioral therapy for insomnia (CBT-I) is a safe and effective alternative to medication in patients with chronic insomnia. A 2015 meta-analysis identified 20 randomized trials of CBT-I in over 1100 participants with chronic insomnia; CBT-I approaches incorporated at least three of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation [30]. Compared with inactive control conditions, CBT-I improved sleep on a variety of outcome measures, including sleep onset latency, wake time after sleep onset, and sleep efficiency. CBT-I is a particularly good option for patients who are more susceptible to side effects of medication (eg, older adults, patients with multiple medical comorbidities). (See "Treatment of insomnia", section on 'Cognitive behavioral therapy'.)

Increased mortality in heart failure patients treated with adaptive servo-ventilation for central sleep apnea (May 2015)

Adaptive servo-ventilation (ASV) is a type of noninvasive positive airway pressure therapy that is sometimes used in patients with symptomatic central sleep apnea (CSA) who fail or do not tolerate continuous positive airway pressure (CPAP). However, results of a randomized trial indicate that increased caution is now warranted when considering use of ASV in patients with CSA, particularly those with CSA associated with Cheyne-Stokes breathing due to symptomatic heart failure [31]. In the SERVE-HF trial, 1325 patients with moderate to severe CSA due to symptomatic heart failure (ejection fraction ≤45 percent) were randomly assigned to ASV plus standard medical therapy or medical therapy alone. While the study found no difference in the primary outcome of time to all-cause mortality, lifesaving cardiovascular intervention, or unplanned hospitalization due to heart failure, there was a 6 percent increase in the absolute risk of all-cause mortality in patients randomly assigned to ASV (35 versus 29 percent). Cardiovascular mortality was also increased. Based on these results, we recommend not using ASV to treat CSA due to heart failure with reduced ejection fraction; in such patients, supplemental oxygen during sleep may be the next best option to CPAP. (See "Central sleep apnea: Treatment", section on 'Adaptive servo-ventilation (ASV)'.)


Revised schedule for pneumococcal vaccination in older adults (September 2015)

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 2014, the United States Advisory Committee on Immunization Practices (ACIP) began also recommending the 13-valent pneumococcal conjugate vaccine (PCV13) for adults ≥65 years of age [32]. In September 2015, the ACIP changed the recommended interval between administration of PCV13 and PPSV23 for immunocompetent adults ≥65 years of age from 6-12 months to ≥1 year to simplify the administration schedule (algorithm 2) [33]. In patients who have already received PPSV23, at least 1 year should elapse before they are given PCV13. (See "Pneumococcal vaccination in adults", section on 'Schedule for dual vaccination'.)

Lumacaftor-ivacaftor for patients with cystic fibrosis and homozygous for the F508del mutation (August 2015)

Lumacaftor-ivacaftor is a combination of two cystic fibrosis transmembrane conductance regulator (CFTR) modulators that was approved by the US Food and Drug Administration in July 2015. The approval was based on two randomized trials with 1100 homozygous F508del subjects ages 12 years and older [34]. Compared with placebo, the groups receiving lumacaftor-ivacaftor for 24 weeks had small but statistically significant improvements in percent predicted FEV1 and body mass index (BMI), and reduced frequency of pulmonary exacerbations. Adverse effects included chest discomfort and dyspnea and were more common in subjects with worse baseline lung function. The improvement in absolute FEV1 from baseline compared with placebo (2.6 to 4 percentage points) is similar in magnitude to that achieved by treatments with inhaled dornase alfa or tobramycin. We suggest use of lumacaftor-ivacaftor for F508del homozygotes because it has modest short-term benefits and is tolerated by most patients. However, the expense of the drug and drug-drug interactions should be considered when deciding on its use. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Efficacy'.)

Bridging anticoagulation in patients who require warfarin interruption for surgery (July 2015)

Perioperative management of a patient receiving an anticoagulant is challenging because the risks of bleeding and thromboembolism are both increased. Not all patients require anticoagulant interruption. For those who do require interruption of their anticoagulant, the risks and benefits of bridging (use of a short-acting parenteral agent, typically a low molecular weight [LMW] heparin) have been unclear. The BRIDGE trial randomly assigned patients with atrial fibrillation to receive the LMW heparin dalteparin or placebo during warfarin interruption for surgery or an invasive procedure [35]. The risk of thromboembolism was similar in those who received dalteparin or placebo for bridging. However, patients bridged with dalteparin had a greater risk of bleeding. As a result of the BRIDGE trial, we suggest not using bridging for most individuals who require warfarin interruption. We continue to suggest bridging in certain high-risk individuals, including those with a mechanical mitral valve, thromboembolic event within the previous 12 weeks, atrial fibrillation and very high risk of stroke, recent coronary stenting, or previous thromboembolism during interruption of chronic anticoagulation. (See "Perioperative management of patients receiving anticoagulants", section on 'Whether to use bridging'.)

Causes of community-acquired pneumonia in adults in the United States (July 2015)

As molecular tests have become more widely available, viruses are being detected with increasing frequency in patients with community-acquired pneumonia (CAP). In the Etiology of Pneumonia in the Community (EPIC) study, an active Centers for Disease Control and Prevention (CDC) surveillance study of adults requiring hospitalization for CAP, one or more viruses were detected in 23 percent of cases, bacteria in 11 percent, bacteria and viruses in 3 percent, and fungi or mycobacteria in 1 percent; an etiology was not identified in 62 percent of cases [36]. The most commonly identified organisms were rhinovirus (in 9 percent), influenza virus (in 6 percent), and S. pneumoniae (in 5 percent). In a related study, detection of rhinovirus was associated with CAP in adults, but not in children [37]. These results add to accumulating evidence that rhinovirus is likely to play a role in CAP in adults. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Rhinovirus' and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiologic diagnosis'.)

Practice tool for managing direct oral anticoagulants (July 2015)

The direct oral anticoagulants ([DOACs]; dabigatran, rivaroxaban, apixaban, edoxaban) generally are used without routine laboratory monitoring of coagulation times; this lack of monitoring requirement is considered a major advantage over vitamin K antagonists. However, the DOACs have short half-lives, and one or two missed doses can be sufficient to eliminate their anticoagulant effect. A practice tool has been published to help clinicians ensure that patients are taking their DOAC correctly and are minimizing risks of thromboembolism and bleeding [38]. Counseling strategies are focused on minimizing gaps in therapy and avoiding medication interactions. Monitoring of renal function and treatment of hypertension are also emphasized. (See "Anticoagulation with direct thrombin inhibitors and direct factor Xa inhibitors", section on 'Comparison with heparin and warfarin'.)

Pulmonary manifestations in adults with chronic granulomatous disease (June 2015)

Pulmonary complications remain the most common manifestation of chronic granulomatous disease (CGD) in adulthood. In a series of 67 adults with CGD, two-thirds had at least one infectious or noninfectious pulmonary event, and about half had manifestations involving the gastrointestinal tract or skin [39]. Most patients with invasive pulmonary fungal infections were on itraconazole prophylaxis, although serum azole concentrations were low in the majority of the patients tested. One-third of patients with pulmonary complications, including invasive fungal infections, were asymptomatic. Serial screening for elevated inflammatory markers, such as C-reactive protein (CRP), followed by imaging of the suspected organ(s) involved if levels are elevated, are suggested to monitor for and diagnose infection. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Sites of infection' and "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Pulmonary' and "Chronic granulomatous disease: Treatment and prognosis", section on 'Antifungal prophylaxis' and "Pulmonary complications of primary immunodeficiencies", section on 'Chronic granulomatous disease' and "Chronic granulomatous disease: Treatment and prognosis", section on 'Monitoring and diagnosis'.)

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