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Community-acquired pneumonia

imagePurpose of reviewThis review examines the epidemiology, diagnosis, prognosis, treatment and prevention of community-acquired pneumonia (CAP) in adults. Recent findingsCAP is a significant cause of morbidity and mortality. Streptococcus pneumoniae is the most common CAP pathogen; however, microbial cause varies by geographic location and host factors. Identification of a microbial cause in CAP remains challenging – 30–65% of cases do not have a pathogen isolated. The use of molecular techniques in addition to culture, serology and urinary antigen testing has improved diagnostic yield. Scoring systems are useful for CAP prognostication and site of care decisions. Studies evaluating novel biomarkers including pro-B-type natriuretic peptide and procalcitonin suggest potential adjunctive roles in CAP prognosis. Guideline-based treatment for CAP has changed little in recent years. Effective and timely antimicrobial therapy is crucial in optimizing outcomes and should be based on local antimicrobial susceptibility patterns. Macrolides may have additional anti-inflammatory properties and a mortality benefit in severe CAP. Preventive strategies include immunization and modification of specific patient risk factors. SummaryCAP is common and causes considerable morbidity and mortality. A comprehensive approach including advanced diagnostic testing, effective and timely antimicrobial therapy and prevention is required to optimize CAP outcomes.

Tuberculosis: clinical trials and new drug regimens

imagePurpose of reviewRecent advances in the development of new drugs and regimens provide hope that well tolerated, effective, and shorter-duration treatments for tuberculosis (TB) will become available. This review covers the recent trials of new TB drugs and regimens. Recent findingsMoxifloxacin and levofloxacin have equally good efficacy and safety in the early phase of treatment of multidrug-resistant TB (MDR-TB), and linezolid has the potential to cure refractory cases of MDR-TB. Bedaquiline and delamanid may be the best drug candidates for enhancing treatment options for MDR-TB. New chemicals, such as sutezolid, AZD5847, PA-824, SQ109, and BTZ043, show potent activity against Mycobacterium tuberculosis. Late-generation fluoroquinolones in combination with the first-line and second-line anti-TB drugs have been used to shorten the treatment duration in drug-susceptible and MDR-TB. SummaryNew drugs and new combination regimens in clinical trials are expected to increase therapeutic efficacy and shorten treatment duration in both drug-susceptible and drug-resistant TB.

Once-daily fluticasone furoate (FF)/vilanterol reduces risk of severe exacerbations in asthma versus FF alone

Background

Combination therapy with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) is recommended for patients with asthma symptomatic on ICS alone. However, there is ongoing debate regarding the risk-benefit ratio of using LABA in asthma.

 Objective

To evaluate the effect of the addition of a novel LABA, vilanterol (VI), to a once-daily ICS, fluticasone furoate (FF), on the risk of severe asthma exacerbations in patients with uncontrolled asthma.

 Methods

This randomised double-blind comparative study of variable duration (≥24–78 weeks) was designed to finish after 330 events (each patient's first on-treatment severe asthma exacerbation). 2019 patients with asthma aged ≥12 years with ≥1 recorded exacerbation within 1 year were randomised and received FF/VI 100/25 μg or FF 100 μg, administered once daily in the evening. The primary endpoint was time to first severe exacerbation; secondary endpoints were rate of severe asthma exacerbations per patient per year and change in trough evening forced expiratory volume in 1 s (FEV1) from baseline.

 Results

Compared with FF, FF/VI delayed the time to first severe exacerbation (HR 0.795, 95% CI 0.642 to 0.985) and reduced the annualised rate of severe exacerbations (rate reduction 25%, 95% CI 5% to 40%). Significantly greater improvements in trough FEV1 (p<0.001) were observed with FF/VI than with FF at weeks 12, 36, 52 and at endpoint. Both treatments were well tolerated with similar rates of treatment-related adverse events and on-treatment serious adverse events.

 Conclusions

Once-daily FF/VI reduced the risk of severe asthma exacerbations and improved lung function compared with FF alone, with good tolerability and safety profile in adolescents and adults with asthma currently receiving ICS.

 ClinicalTrials.gov No

NCT01086384

Dispensation of long-acting {beta} agonists with or without inhaled corticosteroids, and risk of asthma-related hospitalisation: a population-based study

Background

The role of long-acting β-agonists (LABA) added to inhaled corticosteroids (ICS) in the management of asthma is extensively debated. We thought to assess the risk of asthma-related hospitalisation in individuals who regularly filled prescriptions for ICS+LABA compared to those who regularly filled prescriptions for ICS alone or LABA alone, and compared to those who did not regularly fill such medications.

 Methods

Using administrative health databases of the province of British Columbia (BC), Canada, from 1997 to 2012, we conducted a nested case-control analysis of a cohort of asthma patients. Cases were defined as those who experienced asthma-related hospitalisation after the first year of their entry into the cohort. For each case, up to 20 controls were matched based on age, sex, date of cohort entry, and several measures of asthma severity. We categorised individuals as regularly exposed, irregularly exposed, or non-exposed to ICS alone, LABA alone, or ICS+LABA based on dispensation records in the past 12 months. The primary outcome measures were the rate ratio (RR) of the asthma-related hospitalisation among categories of regular exposure.

 Results

3319 cases were matched to 43 023 controls. The RR for regular dispensation of ICS+LABA was 1.14 (95% CI 0.93 to 1.41) compared with regular dispensation of ICS alone and 0.45 (95% CI 0.29 to 0.70) compared with regular dispensation of LABA alone. Those who regularly dispensed LABA had to dispense an ICS for at least three quarters of a year to reduce their risk to that of those who did not dispense LABA.

 Conclusions

Regular dispensation of ICS+LABA was not associated with an increased risk of asthma-related hospitalisation compared with regular dispensation of ICS alone. Adherence to ICS in patients who regularly receive ICS+LABA seems to be an important factor in the prevention of adverse asthma-related outcomes.

Nodal upstaging after thoracoscopic versus open lobectomy

In this nationwide database study from Denmark, nodal upstaging and survival after thoracoscopic and open lobectomy for clinical stage I non-small cell lung cancer (NSCLC) was investigated. Clinical data for all patients diagnosed with lung cancer in Denmark are obligatorily reported to the national Danish Lung Cancer Registry (DLCR). Cross-linkage with the DLCR and other national registers is used to validate completeness of data and survival status is obtained from the Centralised Civil Registry. Surgery for lung cancer in Denmark is only performed by thoracic surgeons at four university hospitals.

The DLCR was used to identify 1513 patients who underwent lobectomy for clinical stage I NSCLC between 2007 and 2011. Thoracoscopic lobectomy was performed in 47% and thoracotomy was used in 53%. The use of a minimally invasive approach increased gradually during the study period. Information regarding sex, age, Charlson comorbidity index, use of positron-emission tomography, the preoperative staging...

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