BACKGROUND: Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. OBJECTIVES: To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. MAIN RESULTS: Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I(2) = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I(2) = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I(2) = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence).Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in da...

The β1-adrenergic antagonist metoprolol improves cardiac function in animals and patients with chronic heart failure, isolated mitral regurgitation (MR), and ischemic heart disease, though the molecular mechanisms remain incompletely understood. Metoprolol has been reported to upregulate cardiac expression of β3-adrenergic receptors (β3AR) in animal models. Myocardial β3AR signaling via neuronal nitric oxide synthase (nNOS) activation has recently emerged as a cardioprotective pathway. We tested whether chronic β1-adrenergic blockade with metoprolol enhances myocardial β3AR coupling with nitric oxide-stimulated cyclic guanosine monophosphate (β3AR/NO-cGMP) signaling in the MR-induced, volume-overloaded heart. We compared the expression, distribution, and inducible activation of β3AR/NO-cGMP signaling proteins within myocardial membrane microdomains in dogs (canines) with surgically induced MR, those also treated with metoprolol succinate (MR+βB), and unoperated controls. β3AR mRNA transcripts, normalized to housekeeping gene RPLP1, increased 4.4 × 103- and 3.2 × 102-fold in MR and MR+βB hearts, respectively, compared to Control. Cardiac β3AR expression was increased 1.4- and nearly twofold in MR and MR+βB, respectively, compared to Control. β3AR was detected within caveolae-enriched lipid rafts (Cav3+LR) and heavy density, non-lipid raft membrane (NLR) across all groups. However, in vitro selective β3AR stimulation with BRL37344 (BRL) triggered cGMP production within only NLR of MR+βB. BRL induced Ser1412 phosphorylation of nNOS within NLR of MR+βB, but not Control or MR, consistent with detection of NLR-specific β3AR/NO-cGMP coupling. Treatment with metoprolol prevented MR-associated oxidation of NO biosensor soluble guanylyl cyclase (sGC) within NLR. Metoprolol therapy also prevented MR-induced relocalization of sGCβ1 subunit away from caveolae, suggesting preserved NO-sGC-cGMP signaling, albeit without coupling to β3AR, within MR+βB caveolae. Chronic β1-blockade is associated with myocardial β3AR/NO-cGMP coupling in a microdomain-specific fashion. Our canine study suggests that microdomain-targeted enhancement of myocardial β3AR/NO-cGMP signaling may explain, in part, β1-adrenergic antagonist-mediated preservation of cardiac function in the volume-overloaded heart.

As antiretroviral therapy continues to improve health outcomes for patients with HIV, there needs to be a shift in focus of care toward chronic noncommunicable diseases. Among cardiovascular disease-complicating chronic HIV infection, HIV-PAH is a severe progressive disease that leads to right heart failure and death. Currently available treatment strategies are effective, however, furthering our understanding of HIV-PAH will be critical as it is likely to become the commonest cause of PAH worldwide.

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Catheter-based treatment of VTE is a viable adjunct to anticoagulant therapy and is being rapidly adopted around the United States. Early data suggest that these therapies reduce postthrombotic sequelae and improve quality of life, but bleeding events are still frequent, particularly at low-volume centers. Protocols need to be standardized to improve patient care.

C atheter-directed thrombolysis (CDT) is increasingly used in patients with lower-extremity deep vein thrombosis (LE-DVT), with recent literature revealing significant reductions in lifestyle-limiting postthrombotic complications of acute LE-DVT with CDT compared with anticoagulation alone.1,2 These complications include chronic pain, swelling, heaviness, fatigue of the affected limb, stasis dermatitis, and skin ulceration (called the postthrombotic syndrome), leading to significant impairment in quality of life.3,4 However, CDT was noted to be associated with increased bleeding rates and procedure-related complications. 5,6Clinical Perspective on p 1135In a recent report, we noted a higher incidence of adverse events such as intracranial hemorrhage, need for blood transfusions, and inferior vena cava (IVC) filter placements with CDT use compared with anticoagulation alone.5 These findings point toward possible safety hazards with widespread CDT use. However, we also noticed a 3-fold increase in CDT use nationwide from 2005 to 2010. It is therefore critical to identify and understand modifiable factors that drive CDTrelated morbidity and mortality.One such factor is institutional volume. Given that earlier literature on other invasive procedures suggests an inverse association between institutional volume and adverse patient outcomes,

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