1. Fluticasone Furoate, Vilanterol and Lung Function Decline in Patients with Moderate COPD and Heightened Cardiovascular Risk.
- The Study to Understand Mortality and Morbidity (SUMMIT), evaluated the effect of Fluticasone Furoate 100 μg (FF) alone or in combination with Vilanterol 25 μg (VI) compared with placebo in patients with Moderate COPD (FEV1 50 -70%) and heightened cardiovascular risk. This multicenter, double blind, randomized placebo-controlled trial of a pretty large group of patients (n= 16485) found no mortality or cardiovascular outcomes difference but reduced exacerbations. The impact of drug therapy on the rate of decline of FEV1 was of one the key secondary outcomes; FF alone or in combination with VI appears to slow down the decline compared with placebo. VI alone had no effect. Although the differences were statistically significant, they were rather small (8 mL per year). Not surprising the FEV1 decline was faster in current smokers but also in patients with lower body-mass index, males and those with established cardiovascular disease.
2. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomized, double-blind, placebo-controlled trial.
- There is a growing body of evidence supporting the role of azithromycin as an immunomodulator and its beneficial effects on different chronic lung disorders is well supported. The effect of this antibiotic in a group of patients (n= 420) with uncontrolled persistent asthma despite therapy with medium-to-high dose inhaled corticosteroid (ICS) plus a long-acting bronchodilator was evaluated. The chosen dose was 500 mgs three times per week and the patients enrolled did not have hearing issues or QTc prolongation. After 4 years, a clinically and statistically significant reduction of exacerbations and improvement of quality of life was observed compared with placebo. Diarrhea developed more frequently on those taking the study drug. The reduction in the rate of exacerbations was seen in patients with eosinophilic and non-eosinophilic asthma and the mechanisms that mediate this benefit remained to be elucidated.
3. Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted Temperature Management: A Multicenter Study on 1,053 Patients.
- The clinical findings and laboratory tests that help to predict neurologic outcome after cardiac arrest and cardiopulmonary resuscitation were systematically analyzed by the American Academy of Neurology in their evidence-based review from 2006. Neuron-specific enolase (NSE) is an easily available prognostic biomarker. Recent studies looking at its value have yielded controversial results. This study evaluated the NSE serum concentrations 72 hours after non-traumatic in-hospital and out-of-hospital cardiac arrest. Patients were treated at 33°C for 24 hours. A concentration greater than 90 μg/L was a reliable predictor of poor outcome at ICU discharge; its accuracy was better for out-of-hospital cardiac arrest than for in-hospital events. In parallel concentrations less than or equal to 17 μg/L argue against hypoxic-ischemic encephalopathy incompatible with reawakening. Confounders of NSE elevation should be considered; including NSE-producing tumors, acute brain diseases and hemolysis to avoid false positives.
4. Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy.
- The APEX trial, a multicenter, double-blind, randomized controlled trial showed significant reduction in venous thromboembolism (VTE) when betrixaban, a direct factor Xa inhibitor was given for an extended period (35 to 42 days) compared with a standard enoxaparin regimen (10±4 days) in patients hospitalized with an acute medical illness. In this post hoc analysis a composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, acute myocardial infarction, pulmonary embolism and ischemic stroke) was evaluated. Treatment with betrixaban was associated with a ≈30% reduction events compared with standard-duration enoxaparin. The number needed to treat to prevent 1 fatal or irreversible event versus enoxaparin was 65. Overall this fairly novel oral factor Xa inhibitor appears as a very effective and practical option for VTE prophylaxis in acutely ill medical patients in particular those with increased risk (elevated D-dimer and ≥75 years of age).
5. Frailty and Subsequent Disability and Mortality among Patients with Critical Illness.
- Frailty is a non-specific state of increasing risk, which reflects multisystem physiological change.
The Clinical Frailty Scale (CFS) is a measure of fitness and frailty based on clinical judgment described by Rockwood et al. in 2005. It ranges from 1 (very fit) to 7 (complete functional dependence on others) and is a simple evaluation tool that can easily be measured in critically ill patients at the time of hospital discharge. This study evaluated 1040 patients with a median age of 62. In a multivariate regression analysis, greater CFS scores were independently associated with higher mortality at 3 (P = 0.01) and 12 months (P < 0.001 ) and with greater odds of disability in instrumental activities of daily living at 3 (P = 0.04 and 12 months ( P = 0.002 ). CFS scores were not associated with disability in basic activities of daily living or with cognition.Routine screening of clinical frailty in critically ill patients of all ages may allow the development of interventions that may reduce mortality and disability among those patients with higher vulnerability.