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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

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: Jan 2016. | This topic last updated: Feb 04, 2016.

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 an absolute eosinophil count in peripheral blood of ≥150/microL. Studies in patients with severe eosinophilic asthma have shown that mepolizumab reduces the rate of exacerbations [2] and enables a reduction in the oral glucocorticoid dose. Mepolizumab is administered subcutaneously at four-week intervals. Based on a small increase in herpes zoster in treated adults, we suggest that patients who meet criteria for the varicella-zoster vaccine be immunized 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'.)


Bronchoscopic therapies for severe emphysema (December 2015, Modified January 2016)

Two investigational devices, endobronchial valves and nitinol coils, can provide benefit by deflating areas of emphysematous lung that compromise function.

The STELVIO trial included 68 patients with severe emphysema, favorable anatomy, and no evidence of collateral ventilation [3]. Subjects were randomly assigned to receive bronchoscopic endobronchial valve (EBV) placement (average four per lobe) or standard medical care. After six months, the increases in lung function and exercise tolerance in the EBV group were greater than in the usual care group. However, serious adverse events occurred in the EBV group, including one death, six pneumothoraces, and the necessity for valve removal in seven patients, compared with five serious adverse events and no deaths in the control group.

The REVOLENS trial included 100 patients with severe emphysema, of whom two-thirds had homogeneous emphysema, considered an unfavorable pattern for either surgery or endobronchial valve placement. Patients were randomly assigned to undergo endobronchial deployment of nitinol coils or usual care [4]. The coil group had significant improvements in lung function and quality of life at 6 and 12 months. Pneumonia was the most frequent serious adverse event.

Taken together, these studies show that endobronchial valves or nitinol coils can improve lung function, exercise tolerance, and quality of life in carefully selected patients with severe emphysema who are willing to accept the associated risks. (See "Emerging therapies for COPD: Bronchoscopic treatment of emphysema", section on 'Endobronchial valves' and "Emerging therapies for COPD: Bronchoscopic treatment of emphysema", section on 'Coils'.)

Combination glycopyrrolate-indacaterol approved for use in COPD (December 2015)

A twice daily, dry powder inhaler containing glycopyrrolate-indacaterol (15.6 mcg-27.5 mcg) has been approved by the US Food and Drug Administration for the treatment of chronic obstructive pulmonary disease (COPD) [5]. The United States preparation, which contains lower medication doses than the product approved in Europe and Japan (table 1), was examined in 2038 patients with moderate-to-severe COPD in parallel randomized trials [6]. Significant benefits were noted in lung function, health-related quality of life, and dyspnea in the combination group compared with the individual components or placebo. (See "Management of stable chronic obstructive pulmonary disease", section on 'Combined therapy'.)


FDA approval of sugammadex for reversal of neuromuscular blockade (January 2016)

Neuromuscular blockade due to rocuronium (or vecuronium) can be rapidly reversed with sugammadex, a novel chelating agent. Several trials have demonstrated that, compared with neostigmine, administration of sugammadex at the end of surgery results in faster complete reversal of neuromuscular blockade due to rocuronium or vecuronium, with shorter time to discharge from the operating room. Use of rocuronium with sugammadex reversal may be especially useful for potentially difficult or rapid sequence intubations, since sugammadex also results in a faster recovery of neuromuscular function compared with spontaneous recovery after succinylcholine administration. Sugammadex has been available in many countries for several years and was approved by the US Food and Drug Administration (FDA) in December 2015 [7]. (See "Induction of general anesthesia", section on 'Sugammadex' and "Management of the difficult airway for general anesthesia" and "Overview of complications occurring in the post-anesthesia care unit" and "Neuromuscular blocking agents (NMBA) for rapid sequence intubation in adults".)

Venous thromboembolism risk with central versus peripheral insertion of central venous catheters (January 2016)

There is accumulating evidence that peripherally-inserted central venous catheters (PICCs) are associated with a greater risk for upper extremity deep vein thrombosis (UEDVT) compared with centrally-inserted central venous catheters (CICCs). The Medical Inpatients and Thrombosis (MITH) Study evaluated catheter use in 299 venous thromboembolism cases compared with controls without venous thromboembolism at a single institution [8]. Central catheter use was associated with a 14-fold increased risk for UEDVT, without a significantly increased risk for pulmonary embolism. PICCs were associated with a higher cumulative risk compared with CICCs (8.1 versus 4.8 per 1000 admissions). Given the higher risk for UEDVT with PICCs, we generally avoid them in patients for whom maintaining vascular patency and integrity for long-term vascular access options (eg, future hemodialysis access) is essential. (See "Catheter-related upper extremity venous thrombosis", section on 'Peripheral versus central insertion' and "Overview of central venous access".)

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 [9]. 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 [10]. 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 [11,12]; 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 [13]. 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) [14]. 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 [15,16]. 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 [17]. 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) [18]. 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'.)


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'.)


FDA approval for alectinib in crizotinib-resistant ALK-positive NSCLC (December 2015)

Alectinib was recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have progressed on or are intolerant of crizotinib. This approval was based on the results of two single-arm phase II studies in patients with crizotinib-resistant ALK-positive, locally advanced or metastatic NSCLC that suggested a 50 percent response rate to alectinib [20,21]. Among patients with brain metastases, the majority of whom had received prior radiation therapy, the objective central nervous system (CNS) response rate was 57 percent in one study and 75 percent in the other, and the median duration of CNS response was 10 and 11 months, respectively. These data support the use of alectinib in patients with crizotinib refractory ALK-positive NSCLC and demonstrate its efficacy for managing both systemic and brain metastases. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer", section on 'Alectinib'.)

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 [22]. 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'.)


Small versus large chest tubes for malignant effusion pleurodesis (January 2016)

The optimal diameter chest tube for malignant effusion pleurodesis is uncertain. Smaller diameter tubes are assumed to be more comfortable, but larger diameter tubes may provide better drainage. Nonrandomized studies suggest there is no difference. A multicenter trial compared pleurodesis failure rates and pain scores among 100 patients treated using either a small (12 Fr) or large (24 Fr) chest tube [23]. At three months of follow-up, pleurodesis failure rates were not statistically different for smaller versus larger tubes (30 versus 24 percent). Pain scores were slightly lower for patients receiving smaller chest tubes. The small sample size for the tube diameter comparison may have limited the ability to detect a difference in pleurodesis failure rates, if one existed. Until a larger trial is available, we continue to use a smaller bore catheter (8 to 18 Fr) chest tube placed under imaging guidance for initial malignant effusion pleurodesis. (See "Placement and management of thoracostomy tubes", section on 'Malignant effusion' and "Management of malignant pleural effusions", section on 'Chest tube size'.)


Oral prostacyclin receptor agonist in pulmonary arterial hypertension (January 2016)

Prostanoids are highly effective agents for group 1 pulmonary arterial hypertension (PAH), but have only been available in parenteral formulations and are typically reserved for those with the most severe disease (World Health Organization [WHO] class IV). Less severe PAH (WHO class II or III) is usually treated with oral non-prostanoid pulmonary vasodilators. Selexipag is a selective prostacyclin receptor agonist, with actions similar to prostanoids, which is now available in an oral formulation and was evaluated in a randomized trial in 1156 patients with group 1 PAH, WHO class II or III [24]. Selexipag was associated with a significant benefit compared with placebo, which was largely driven by a reduction in hospitalizations and disease progression, rather than by improved survival. Adverse effects were mostly mild and consistent with the known side effects of prostanoids, including headache, diarrhea, nausea, and jaw pain. We consider selexipag as a useful alternative to other oral agents for the treatment of patients with group 1 PAH, WHO class II or III. Parenteral prostanoids should remain the mainstay of therapy for WHO class IV disease. (See "Treatment of pulmonary hypertension in adults", section on 'Selexipag'.)

Warfarin associated with worse survival in systemic sclerosis-associated pulmonary arterial hypertension (December 2015)

Early studies suggested a possible mortality benefit for anticoagulation with warfarin in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). However, a post-hoc analysis of a PAH registry study reported a trend towards worse survival in patients with SSc-PAH who received anticoagulant therapy compared with those not receiving anticoagulant therapy [25]. A subsequent analysis of a separate registry of PAH patients also reported an increased mortality in the same population, even after adjustment for confounders including disease severity [26]. Based on findings of these studies, we suggest that anticoagulant therapy not be administered to patients with systemic sclerosis-associated PAH. (See "Treatment of pulmonary hypertension in adults", section on 'Anticoagulation'.)

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 [27]. 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 [28]. 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 [29]. 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'.)


Mandibular advancement devices lower blood pressure in sleep apnea (December 2015)

Improved blood pressure control is a benefit associated with continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA) and hypertension. However, it is unclear whether therapeutic modalities other than CPAP result in the same benefit. One meta-analysis of 51 studies of patients with hypertension and OSA reported that compared with patients on placebo or not receiving therapy, mandibular advancement devices (MADs) were associated with a significant reduction in systolic and diastolic blood pressure [30]. The level of reduction was similar to that reported in patients treated with CPAP. While this study does not alter the indications for either therapy, it suggests that patients with OSA who are treated with MADs may derive similar positive effects on blood pressure control as those treated with CPAP. (See "Obstructive sleep apnea and cardiovascular disease", section on 'Impact of treatment'.)

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 [31]. 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'.)


IDSA guidelines on the management of candidiasis (January 2016)

The Infectious Diseases Society of America released updated guidelines for the management of patients with candidiasis [32]. A substantial change compared with previous versions is the preference for echinocandins (anidulafungin, caspofungin, micafungin) as first-line therapy for candidemia and invasive candidiasis. As an example, for both nonneutropenic and neutropenic patients with candidemia, an echinocandin is the preferred choice for initial therapy (table 2). This change is due to an increase in fluconazole-resistant Candida infections, the favorable safety profile of the echinocandins, and accumulating efficacy data and clinical experience to support the echinocandins. Important exceptions include Candida central nervous system, eye, and urinary tract infections, for which other antifungals are preferred. (See "Treatment of candidemia and invasive candidiasis in adults", section on 'Nonneutropenic patients'.)

Adjuvanted influenza vaccine approved for elderly adults in the United States (November 2015)

There has been interest in using adjuvants in influenza vaccines in elderly individuals, who have reduced immune responses to influenza vaccines; adjuvants are substances that amplify the immune response to an antigen. In November 2015, an adjuvanted trivalent inactivated influenza vaccine (Fluad) was approved for use in individuals ≥65 years of age in the United States [33]. It is the first adjuvanted seasonal influenza vaccine to be approved in the United States, but it has been approved already in >35 other countries. The vaccine is formulated with the adjuvant MF59, an oil-in-water emulsion of squalene oil. Studies have shown that the MF59-adjuvanted vaccine has comparable [33] or higher immunogenicity compared with unadjuvanted vaccines [34-36]. Until further data are available, we continue to suggest the non-adjuvanted high-dose inactivated vaccine for individuals ≥65 years of age. (See "Seasonal influenza vaccination in adults", section on 'Adjuvanted vaccine' and "Seasonal influenza vaccination in adults", section on 'Vaccine formulations'.)

Statins and influenza vaccine immunogenicity and effectiveness (November 2015)

Statins are used commonly in older adults with hyperlipidemia and are known to have immunomodulatory effects, which could affect vaccine responses. In an observational study conducted in the context of a randomized trial that evaluated influenza vaccines in individuals >65 years of age, hemagglutination inhibition (HAI) geometric mean titers to various influenza strains were substantially lower in those receiving chronic statin therapy than in those not receiving it [37]. In addition, in the adjusted analysis of a large retrospective cohort study, statin use was associated with reduced influenza vaccine effectiveness against medically attended acute respiratory illness [38]. The observed associations between statin use and vaccine effectiveness could be due to confounding, as patients receiving statins are likely to be at differing baseline risk of influenza from those not receiving statins. Although these studies raise the possibility that older patients receiving statins are less likely to be protected by the influenza vaccine, such individuals should still receive statins, when indicated, as well as an influenza vaccine annually. (See "Seasonal influenza vaccination in adults", section on 'Efficacy'.)

Updated guidelines for the diagnosis and management of primary immunodeficiency (November 2015)

A revised “Practice parameter for the diagnosis and management of primary immunodeficiency,” developed by the three national allergy and immunology societies in the United States, has been published to aid allergy/immunology specialists and other practitioners in the recognition, diagnosis, and general management of these disorders [39]. Highlights include screening and advanced laboratory tests for the different components of immune function, characteristic clinical manifestations and laboratory findings for a number of disorders, internet resources, antibiotic prophylaxis, and indications for hematopoietic cell transplantation or gene therapy. There are now more than 200 genetically distinct disorders of immune function that are classified using the system devised by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS). Consultation with an immunology specialist with experience in diagnosing and managing primary immunodeficiencies is recommended. Our approach is consistent with that outlined in this practice parameter. (See "Approach to the child with recurrent infections" and "Laboratory evaluation of the immune system" and "Medical management of immunodeficiency".)

Influenza vaccination and influenza-associated pneumonia (October 2015)

Many studies have demonstrated that influenza vaccination decreases the incidence of laboratory-confirmed influenza infection, but few have evaluated the effect on the serious complications of influenza. Recent data suggest that vaccination is associated with a reduced risk of influenza pneumonia. In a case-control study of adult and pediatric patients hospitalized for community-acquired pneumonia (CAP), those with laboratory-confirmed influenza-associated pneumonia had lower odds of having received an influenza vaccine during the same influenza season compared with those with CAP not associated with influenza [40]. The estimated vaccine effectiveness for preventing influenza-associated pneumonia was 57 percent. (See "Seasonal influenza vaccination in adults", section on 'Trivalent inactivated vaccines' and "Seasonal influenza in children: Prevention with vaccines", section on 'Indications'.)

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 [41]. 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) [42]. 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 [43]. 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'.)

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