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What's new in pulmonary and critical care medicine
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What's new in pulmonary and critical care medicine
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2017. | This topic last updated: Aug 16, 2017.

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.

ASTHMA

Mepolizumab for eosinophilic granulomatosis with polyangiitis (August 2017)

Mepolizumab is a monoclonal anti-interleukin-5 antibody that is approved for use in severe eosinophilic asthma. In a multicenter trial, 136 patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) were randomly assigned to receive mepolizumab 300 mg (three times the US Food and Drug Administration-approved dose of 100 mg) or placebo subcutaneously every four weeks for 52 weeks [1]. Mepolizumab led to significantly more accrued weeks of remission and a lower frequency of relapse than placebo. Among mepolizumab-treated subjects, 44 percent were able to taper prednisolone to ≤4 mg/day, compared with 7 percent on placebo. While not all patients respond, high-dose mepolizumab may be an additional option for selected patients with EGPA. (See "Treatment and prognosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Anti-IL-5 antibodies'.)

Benralizumab and glucocorticoid-sparing effect in severe asthma (June 2017)

Benralizumab, an investigational anti-IL-5 receptor alpha antibody, appears to have a glucocorticoid-sparing effect in patients requiring oral glucocorticoids to control severe asthma. In a multicenter trial, 220 patients who had ≥150 eosinophils/mL in peripheral blood AND required daily oral glucocorticoids for the previous six months were randomly assigned to one of two benralizumab treatment arms or placebo [2]. The oral glucocorticoid dose was reduced according to a predetermined program (2.5 to 5 mg every four weeks). After 28 weeks, the oral glucocorticoid dose decreased by 75 percent from baseline in the two benralizumab groups, compared with 25 percent in the placebo group. Exacerbation rates were lower in the benralizumab groups despite glucocorticoid tapering, and pulmonary function remained stable. (See "Investigational agents for asthma", section on 'Anti-IL-5 receptor alpha antibodies'.)

Tyrosine kinase inhibition and severe asthma (June 2017)

Mast cells are typically increased in asthmatic airways and are associated with greater bronchial hyperresponsiveness. The KIT tyrosine kinase inhibitor, imatinib, inhibits the major growth factor for mast cells, raising the possibility that imatinib may ameliorate severe asthma. In a proof-of-principle randomized trial, 62 adults with severe asthma were assigned to imatinib or placebo for six months [3]. Airway hyperresponsiveness, as determined by methacholine inhalation challenge, was decreased in the imatinib group, indicating a potential role for KIT-dependent processes and mast cells in severe asthma. Whether tyrosine kinase inhibition by imatinib or a related agent will prove to be a safe and effective treatment for severe asthma awaits further study. (See "Investigational agents for asthma", section on 'Tyrosine kinase inhibitors'.)

Maternal fish oil supplementation and asthma in offspring (February 2017)

Maternal supplementation with fish oil, which consists of two n-3 long chain polyunsaturated fatty acids (docosahexaenoic acid [DHA]) and eicosapentaenoic acid [EPA]), has been proposed to improve a variety of pregnancy outcomes. In a placebo-controlled randomized trial of third-trimester maternal supplementation with fish oil 2.4 grams daily (55 percent EPA and 37 percent DHA), supplementation resulted in a 7 percent reduction in the absolute risk of persistent wheeze or asthma in offspring followed to age three to five years [4]. Because of limitations in the design of this trial, UpToDate does not advise routine supplementation with this dose of fish oil, but continues to recommend that all pregnant women achieve DHA intake of at least 200 to 300 mg/day. (See "Fish consumption and docosahexaenoic acid (DHA) supplementation in pregnancy".)

Spirometry and asthma diagnosis (February 2017)

The importance of confirming reversible airflow limitation when making a diagnosis of asthma was illustrated in a study of 701 randomly selected adults who had a physician diagnosis of asthma in the previous five years [5]. Current asthma was excluded in 33 percent and, among these, less than half had previous testing to confirm airflow limitation. This observation suggests that a clinical diagnosis of asthma, if not supported by spirometry, may be incorrect and reinforces guideline recommendations that spirometry pre- and post-bronchodilator be obtained at the time of an initial diagnosis of asthma.

(See "Diagnosis of asthma in adolescents and adults", section on 'Diagnosis'.)

COPD

Nocturnal noninvasive ventilation and COPD (June 2017)

Nocturnal noninvasive ventilation (NIV) at home may reduce readmissions and improve survival in patients with hypercapnic chronic obstructive pulmonary disease (COPD). In a randomized trial, 116 patients who received NIV during a COPD exacerbation and had persistent hypercapnia (PaCO2 >53 mmHg) were assigned to nocturnal NIV or supplemental oxygen after discharge. Nocturnal NIV prolonged the median time to readmission or death compared with supplemental oxygen alone (4.3 versus 1.4 months, respectively) [6]. One reason for the success of NIV in this study may be the use of high inspiratory pressures (median 24 cm H2O) titrated to reduce transcutaneous carbon dioxide by ≥4 mmHg. (See "Nocturnal ventilatory support in COPD", section on 'Effects on hospitalization and mortality'.)

New ERS/ATS guidelines for the management of COPD exacerbations (April 2017)

The European Respiratory Society and American Thoracic Society (ERS/ATS) have published joint guidelines that address several issues in the management of chronic obstructive pulmonary disease (COPD) exacerbations. Among other recommendations, the guidelines suggest that the duration of oral glucocorticoids administered for exacerbations be ≤14 days, noting that the evidence for an exact number of days is weak [7]. UpToDate's suggestion of a 5 to 14 day course is consistent with this recommendation. (See "Management of exacerbations of chronic obstructive pulmonary disease", section on 'Systemic glucocorticoids'.)

Updated guidelines for chronic obstructive pulmonary disease (March 2017)

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published updated guidelines that focus on a combined assessment of an individual's symptoms and exacerbation history to guide therapy [8]. Symptoms are assessed using standardized instruments, such as the COPD Assessment Tool (CAT) or the modified Medical Research Council (mMRC) dyspnea scale. Future exacerbation risk is based on the number of exacerbations and hospitalizations for exacerbations in the previous 12 months. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging", section on 'GOLD system'.)

CRITICAL CARE

Guidelines for mechanical ventilation in patients with ARDS (August 2017)

Guidelines were issued by the American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine for mechanical ventilation strategies in patients with acute respiratory distress syndrome (ARDS) [9]. Key aspects included recommendations in favor of the use of low tidal volume ventilation (all ARDS patients) and prone positioning (severe ARDS). They also promoted the use of high levels of positive end expiratory pressure (PEEP) and recruitment maneuvers in select patients and recommended against the use of high frequency oscillatory ventilation (HFOV). No recommendations were made on the use of extracorporeal membrane oxygenation. (See "Prone ventilation for adult patients with acute respiratory distress syndrome" and "High-frequency ventilation in adults" and "Extracorporeal membrane oxygenation (ECMO) in adults" and "Mechanical ventilation of adults in acute respiratory distress syndrome", section on 'Low tidal volume ventilation'.)

Angiotensin II as an investigational vasopressor agent in shock (August 2017)

A randomized trial investigated the safety and efficacy of angiotensin II as a vasopressor agent for patients with vasodilatory (mostly septic) shock [10]. For patients receiving high-dose norepinephrine, the trial compared the addition of angiotensin or placebo.The increase in mean arterial pressure (MAP) was greater in the angiotensin II group. As well, less norepinephrine was required in the angiotensin II group and there was no difference in serious adverse events between the groups. These results are encouraging, but further trials are indicated to determine the role of angiotensin II for the treatment of vasodilatory shock. (See "Use of vasopressors and inotropes", section on 'Angiotensin II'.)

Vasopressor blood pressure targets in critically ill patients with shock (July 2017)

Hemodynamic support with continuous infusion of a vasopressor agent may be necessary in patients with shock if administration of intravenous fluids fails to restore adequate blood pressure and/or tissue perfusion. In a systematic review of two randomized trials that included 894 critically ill adults with hypotension requiring vasopressor therapy, higher mean arterial pressure (MAP) target values (80 to 85 mmHg in one trial and 75 to 80 mmHg in the other) did not result in a mortality benefit and increased the risk of cardiac arrhythmias, compared with lower targets (65 to 70 mmHg and 60 to 65 mmHg) [11]. We suggest a target MAP of 65 to 70 mmHg, rather than a higher target, in critically ill adults with hypotension who require vasopressor support. Similar MAP target values were recommended in a recent guideline of the Canadian Critical Care Society and the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (CCCS-SSAI) [12]. (See "Intraoperative management of shock in adults", section on 'Initial interventions'.)

Confirmatory data on idarucizumab for dabigatran reversal (July 2017)

Idarucizumab (pronounced "I-dare-you-cizumab") is a monoclonal antibody fragment against dabigatran that can reverse the anticoagulant effect within minutes. A preliminary report suggested good efficacy in patients with dabigatran-associated bleeding or those undergoing emergency surgery. In a new report of over 500 patients treated with idarucizumab, most had cessation of bleeding or underwent surgery without abnormal bleeding [13]. We continue to suggest idarucizumab for clinically significant bleeding or emergency surgery in patients on dabigatran with a history or laboratory testing that suggest they are actively anticoagulated. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)

New oral direct factor Xa inhibitor betrixaban approved (June 2017)

The US Food and Drug administration has approved a new oral direct factor Xa inhibitor, betrixaban, for venous thromboembolism prophylaxis in acutely ill medical patients [14]. Betrixaban (brand name Bevyxxa) is taken at a dose of 160 mg on day 1 followed by 80 mg once daily for the duration of thromboprophylaxis. In a trial in which over 7500 patients hospitalized for an acute medical illness were randomly assigned to receive betrixaban or the low molecular weight heparin enoxaparin for 35 to 42 days, betrixaban was associated with a trend towards greater efficacy and a similar risk of bleeding compared with enoxaparin. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects" and "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)

Stress ulcer prophylaxis in critically ill patients (June 2017)

The benefits and harms of stress ulcer prophylaxis in critically ill patients have recently been questioned, with concerns about possible increased risk of pneumonia and Clostridium difficile infection associated with use of proton pump inhibitors (PPIs). A preliminary randomized trial in 91 patients reported no difference in the rate of upper gastrointestinal bleeding, pneumonia, or C. difficile infection in mechanically ventilated receiving pantoprazole (a PPI) or placebo [15]. Also included as part of the study was a meta-analysis of five trials comparing PPIs to placebo that reported no difference in the rates of bleeding, infections, or mortality. These data justify the feasibility of larger placebo-controlled trials to replicate these findings before revising recommendations for stress ulcer prophylaxis in critically ill patients. (See "Stress ulcer prophylaxis in the intensive care unit", section on 'Efficacy'.)

Time to treatment and mortality in sepsis (May 2017)

Timely administration of fluids and antibiotics is the cornerstone of therapy for patients with sepsis and septic shock. A recent database study of patients with sepsis reported increased mortality in association with the delayed administration of antibiotics (greater than three hours) but not with a longer time to completion of a fluid bolus (greater than six hours) [16]. This study further validates international guideline recommendations that antibiotics be administered within the first three hours, and preferably within the first hour after presentation in patients with sepsis and septic shock. We also continue to recommend infusion of intravenous fluids within the first three hours of presentation. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial resuscitative therapy'.)

Immunoassay for acetaminophen-induced liver injury (May 2017)

Establishing the diagnosis of acetaminophen (APAP) poisoning in patients who present greater than 24 hours to several days after ingestion, when a serum APAP level may no longer be detectable, can be difficult. However, a recent observational cohort study found excellent performance for a rapid immunoassay that measures serum APAP-protein adducts in identifying patients with APAP-induced acute liver injury (ALI) [17]. In this study, a point of care immunoassay (AcetaSTAT) had 100 percent sensitivity and 100 percent negative predictive value, compared with results of high performance liquid chromatography as a reference standard, for identifying patients with such injury. If these results are validated in future clinical trials, this assay may provide a rapid means to distinguish APAP-induced ALI from other causes, and to begin appropriate management quickly. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis", section on 'Evaluation following delayed presentation'.)

Routine prophylactic antibiotics do not improve clinically important outcomes in survivors of out-of-hospital cardiac arrest (April 2017)

Many survivors of out-of-hospital cardiac arrest (OHCA) go on to develop pneumonia, but the value of prophylactic antibiotics is unproven. In a single-center clinical trial involving 60 comatose OHCA patients without obvious evidence of tracheobronchial aspiration on admission, random assignment to prophylactic antibiotics versus clinically-driven antibiotic therapy reduced the number of positive broncho-alveolar lavage cultures on hospital day 3, but did not improve survival or other patient-important outcomes [18]. We do not suggest routine prophylactic treatment with antibiotics in these patients. (See "Post-cardiac arrest management in adults", section on 'Antibiotic therapy and prophylaxis'.)

2011 shortage of norepinephrine in the United States and septic shock outcome (April 2017)

The impact of a shortage of norepinephrine in the United States in 2011 on vasopressor agent selection was recently highlighted in a study of 28,000 patients with sepsis. When norepinephrine (first-line agent) was in short supply, phenylephrine was the most frequent alternative agent chosen, during which time mortality rates from septic shock also rose (36 to 40 percent) [19]. While there is little guidance for selecting a second-line vasopressor agent in patients with sepsis, phenylephrine should continue to be avoided, when feasible. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Vasopressors'.)

2016 sepsis guidelines (March 2017)

Updated sepsis guidelines were issued by the Surviving Sepsis Campaign/Society of Critical Care Medicine/European Society of Intensive Care Medicine [20]. Major differences, compared with the 2012 iteration, include: the administration of intravenous antibiotics within one hour of presentation, with emphasis on source control and antibiotic stewardship; infusion of crystalloid solution at a rate at 30 mL/kg/hour within three hours for early fluid resuscitation; and movement away from previously recommended early goal-directed therapy targets (eg, central venous pressure) to use of dynamic predictors of fluid responsiveness, when feasible. Norepinephrine remains the vasopressor of first choice. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Hemodynamic'.)

Target blood glucose levels in critically ill children (March 2017)

Optimal target blood glucose levels in critically ill children are unknown. In the HALF-Pint randomized trial of intensive insulin therapy (IIT), a lower target blood glucose level (80 to 110 mg/dL [4.4 to 6.1 mmol/L] did not reduce the number of intensive care unit-free days in critically ill children when compared with a higher target level (150 to 180 mg/dL [8.3 to 10 mmol/L]) [21]. Rates of hypoglycemia and health care-associated infections were increased for the lower target group, but there was no difference in mortality. These results are consistent with trials in adults and, as in adults, we recommend against treatment with IIT regimens that target blood glucose levels between 80 to 110 mg/dL [4.4 to 6.1 mmol/L] in critically ill children. (See "Glycemic control and intensive insulin therapy in critical illness", section on 'Children'.)

The effect of tracheal intubation on in-patients with sudden cardiac arrest (February 2017)

The appropriate role for tracheal intubation during sudden cardiac arrest (SCA) remains a source of debate. In a large multicenter cohort study comparing outcomes between intubated patients and a propensity-matched group of non-intubated patients, all of whom sustained SCA while admitted to the hospital, intubated patients had lower rates of return of spontaneous circulation, survival, and survival with good functional outcome [22]. This study provides additional evidence that tracheal intubation is best withheld until the return of spontaneous circulation following SCA, unless adequate ventilation cannot be maintained with bag-mask ventilation or a supraglottic airway. (See "Advanced cardiac life support (ACLS) in adults", section on 'Airway management while performing ACLS'.)

Rapidly progressive acute chest syndrome in sickle cell disease (February 2017)

Acute chest syndrome (ACS) in individuals with sickle cell disease (SCD) encompasses a variety of clinical presentations and severities. A distinct phenotype of ACS has been characterized, referred to as rapidly progressive ACS, in which respiratory failure occurs within 24 hours of initial respiratory symptoms [23]. In a cohort of 97 children and 76 adults with SCD and at least one prior ACS episode, rapidly progressive ACS occurred more commonly in adults than children (21 versus 2 percent). Adults with rapidly progressive ACS were more likely to have multiorgan failure compared with adults without this phenotype. The only laboratory predictor of rapidly progressive ACS was a decline in platelet count on presentation. (See "Evaluation of acute pain in sickle cell disease", section on 'Acute systemic illness, diffuse pain, or both'.)

PULMONARY VASCULAR DISEASE

YEARS algorithm for the diagnosis of pulmonary embolism (June 2017)

Algorithms that integrate pretest probability (PTP) assessment using Wells criteria with a fixed cutoff level for D-dimer (<500 ng/mL) are typically used to target which patients with suspected pulmonary embolism (PE) should undergo computed tomography pulmonary angiography (CTPA). Compared with this typical approach, an alternative strategy using the YEARS items (clinical signs of deep venous thrombosis, hemoptysis, and PE as the most likely diagnosis) together with varying cutoff levels of D-dimer resulted in a 14 percent reduction in the number of CTPA scans performed, without increasing the risk of PE during a three-month follow-up [24]. While encouraging, this algorithm requires further validation before it is routinely used in practice. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'D-dimer'.)

Rivaroxaban for treatment of superficial vein thrombosis (May 2017)

Short-term anticoagulation is recommended for treatment of superficial vein thrombosis (SVT) in patients at high risk for venous thromboembolism (VTE). The phase 3b SURPRISE trial randomly assigned over 400 patients with SVT to oral rivaroxaban (a direct factor Xa inhibitor) or subcutaneous fondaparinux and found that both groups had similar rates of symptomatic VTE, progression or recurrence of SVT, and all-cause mortality at 45 days [25]. There were no major bleeds in either group, but clinically relevant nonmajor bleeding occurred more often in the rivaroxaban group. Thus, rivaroxaban appears to be an effective anticoagulant for patients with SVT and may be a more convenient and less expensive option than subcutaneous therapy. (See "Phlebitis and thrombosis of the superficial lower extremity veins", section on 'Increased risk for thromboembolism'.)

Rivaroxaban versus aspirin for indefinite treatment of venous thromboembolism (April 2017)

The optimal antithrombotic agent for patients with venous thromboembolism (VTE) who have indications for indefinite therapy to reduce the risk of recurrent VTE is unclear. A randomized trial compared rivaroxaban (a direct factor Xa inhibitor) and aspirin for long-term treatment of patients who had completed a 6- to 12-month course of therapeutic anticoagulation [26]. Rivaroxaban, either at a treatment (20 mg daily) or a prophylactic (10 mg daily) dose, was superior to aspirin in preventing VTE recurrence for up to 12 months, without increasing the risk of major bleeding. While rates of recurrence were comparable between both doses of rivaroxaban, further studies are warranted before reduced intensity regimens can be recommended. For most patients with VTE requiring long-term treatment, we suggest full intensity anticoagulation rather than low intensity regimens or aspirin. (See "Rationale and indications for indefinite anticoagulation in patients with venous thromboembolism", section on 'Factor Xa and direct thrombin inhibitors'.)

SLEEP MEDICINE

Guideline on obstructive sleep apnea diagnosis and treatment in commercial drivers (May 2017)

The American Academy of Sleep Medicine (AASM) has released consensus-based recommendations on screening, diagnosis, and management of obstructive sleep apnea (OSA) in commercial drivers [27]. The AASM recommends that drivers meeting any of the following high-risk criteria be referred to a sleep medicine specialist for clinical sleep evaluation and diagnostic testing:

Body mass index (BMI) ≥40 kg/m2

Fatigue or sleepiness during the duty period or involvement in a sleepiness-related crash or accident

BMI ≥33 kg/m2 and either hypertension requiring two or more medications to control or type 2 diabetes

The document also provides guidance on determining when to restrict driving certification based on OSA severity, symptoms, and adherence with positive airway pressure therapy. (See "Drowsy driving: Risks, evaluation, and management", section on 'Special considerations in commercial drivers'.)

Adaptive servoventilation in adults with central sleep apnea and heart failure (April 2017)

A previous randomized trial (SERVE-HF) found that adaptive servoventilation (ASV), a modified method of positive airway pressure ventilation, increased cardiovascular mortality in patients with central sleep apnea (CSA) due to symptomatic heart failure with reduced ejection fraction. In the CAT-HF trial, 126 hospitalized patients with heart failure and moderate-to-severe CSA were randomly assigned to ASV plus optimized medical therapy or medical therapy alone [28]. While the trial showed no difference between the groups in a combined endpoint (death, cardiovascular hospitalizations, and timed walk distance), the confidence intervals were wide and there was a suggestion of increased harm in the ASV group (HR 1.06, 95% CI 0.75-1.51). The trial was stopped early, in part due to results of SERVE-HF. Although this limits interpretation of the CAT-HF results, we continue to recommend against use of ASV in patients with CSA and heart failure with reduced ejection fraction. (See "Sleep-disordered breathing in heart failure", section on 'Adaptive servoventilation' and "Central sleep apnea: Treatment", section on 'Patients with ejection fraction ≤45 percent'.)

Alveolar recruitment maneuvers in postoperative mechanically ventilated patients (April 2017)

Unlike patients with acute respiratory distress syndrome (ARDS) in whom the value of alveolar recruitment maneuvers is known to be beneficial, their role in postoperative patients without ARDS is unknown. One single center study of 320 patients who had undergone elective cardiac surgery and were mechanically ventilated for hypoxemia compared an intensive recruitment strategy with a moderate strategy [29]. An intensive strategy resulted in fewer pulmonary complications as well as decreased intensive care unit length of stay and mortality, without increasing the incidence of barotrauma. This study suggests that the benefit from recruitment maneuvers in postoperative patients without ARDS may be similar to the benefit in patients with ARDS, and further investigation is warranted. (See "Positive end-expiratory pressure (PEEP)", section on 'Postoperative patients'.)

Psychiatric comorbidities in patients with narcolepsy (March 2017)

Small studies have found an increased rate of depression in patients with narcolepsy, but the risk of other psychiatric comorbidities has not been well established. In a population-based case-control study that included 9312 adults with narcolepsy and more than 45,000 age- and gender-matched controls, a broad range of psychiatric disorders were more common in patients with narcolepsy; the most prevalent were depressive disorders and anxiety, which were three to four times more common than in controls [30]. Thus, recognition and treatment of psychiatric disorders is an important component of the care of patients with narcolepsy. (See "Clinical features and diagnosis of narcolepsy in adults", section on 'Other features'.)

AASM guideline on pharmacotherapy for chronic insomnia in adults (March 2017)

The American Academy of Sleep Medicine (AASM) has released a new clinical practice guideline on the pharmacologic treatment of chronic insomnia in adults [31]. The guideline reviews evidence of effectiveness for a variety of medications (including benzodiazepines, nonbenzodiazepine hypnotics, ramelteon, doxepin, and suvorexant) and notes limitations and potential biases to the evidence, leading to low confidence in the overall estimation of risk-to-benefit ratio. The potential short-term benefits of pharmacologic therapy need to be balanced with the risk of side effects and dependence with long-term use. We continue to prefer behavioral therapy, rather than pharmacotherapy, as an initial treatment approach in most patients. (See "Treatment of insomnia in adults", section on 'Choice of an agent'.)

OTHER PULMONARY MEDICINE

Revised follow-up for a solitary pulmonary nodule (June 2017)

Fleischner Society guidelines have been updated to reflect the accumulating data on the malignancy risk of incidental pulmonary nodules and growth rates of lung cancer [32]. Important changes include guidance on identifying benign nodules with minimal follow-up imaging. For patients with a solid or subsolid (ground glass or part-solid) solitary pulmonary nodule measuring <6 mm, follow-up computed tomography (CT) is optional, but no longer required. A solitary pulmonary nodule that is solid and unchanged on serial CT over a two-year period, or subsolid and unchanged over a five-year period, is likely benign and does not need further diagnostic evaluation. Recommendations in UpToDate have been revised to reflect these new guidelines. (See "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Management strategy' and "Diagnostic evaluation and management of the solitary pulmonary nodule", section on 'Solid nodules ≤8 mm'.)

High-dose influenza vaccine in older adults (March 2017)

For influenza vaccination of adults ≥65 years of age, we recommend the high-dose inactivated influenza vaccine, which has previously been shown to be more immunogenic and modestly more effective at preventing influenza infection than the standard-dose vaccine. In a study of United States Medicare beneficiaries ≥65 years of age, the high-dose vaccine was more effective than the standard-dose vaccine for preventing postinfluenza death during the 2012-2013 influenza season, a season when circulation of H3N2 influenza A (a strain associated with severe disease) was common [33]. In contrast, it was not more effective for preventing postinfluenza death during the following season, when H1N1 influenza A (a strain associated with mild disease) predominated. This difference was likely due to the difficulty in demonstrating benefit during a mild influenza season, when death is a rare outcome. The high-dose vaccine was associated with a reduced risk of hospitalization during both seasons. (See "Seasonal influenza vaccination in adults", section on 'High-dose vaccine'.)

High-dose IV zanamivir does not improve outcomes for severe influenza (February 2017)

There has been interest in determining whether doubling the dose of a neuraminidase inhibitor improves outcomes for severe influenza. Previous studies have not demonstrated a benefit to doubling the dose of oral oseltamivir. An intravenous (IV) formulation of zanamivir has been developed but remains investigational. In a trial, patients with severe influenza were randomly assigned to receive the standard dose of either oral oseltamivir (75 mg twice daily) or IV zanamivir (300 mg twice daily) or a double dose of IV zanamivir (600 mg twice daily) for 5 to 10 days [34]. The time to clinical response (a composite of vital sign stabilization and hospital discharge) was similar in all three groups. (See "Treatment of seasonal influenza in adults", section on 'Dosing'.)

Guidelines for the diagnosis of primary ciliary dyskinesia (February 2017)

Primary ciliary dyskinesia (PCD, also called the immotile cilia syndrome) is an inherited disease that presents, often in childhood, with recurrent respiratory infections and chronic rhinosinusitis. The European Respiratory Society has published new guidelines for the diagnosis of PCD [35]. For patients with clinical features suggestive of PCD, a combination of tests is usually needed to confirm or exclude the diagnosis, given that there is no “gold standard.” The most commonly used tests are nasal nitric oxide, high-speed videomicroscopy analysis, and transmission electron microscopy. Genotyping may be useful in a small number of selected patients. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)", section on 'Diagnostic evaluation'.)

Underdosing of direct oral anticoagulants (February 2017)

The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban (collectively called direct oral anticoagulants [DOACs]) have been available for several years. A real-world study of over 1500 patients with venous thromboembolism (VTE) who were treated with a DOAC found that dosing differed from the recommended product dosing in 20 to 50 percent of cases, depending on the agent [36]. These deviations (mostly underdosing) correlated with an increased frequency of VTE recurrence. Clinicians should familiarize themselves with prescribing information to avoid adverse outcomes. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Clinician familiarity with dosing'.)

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