Anti-inflammatory effects of varespladib methyl in diabetic patients with acute coronary syndrome.

Purpose: Secretory phospholipase A(2) group IIA (sPLA(2-)IIA) concentration and activity are associated with increased risk of cardiovascular events in acute coronary syndrome (ACS) patients. This study evaluated baseline differences in sPLA(2)-IIA concentration and other inflammatory markers in ACS patients with and without diabetes, and the inflammatory biomarker response to selective sPLA(2) inhibition.

Methods: The effects of the sPLA(2) inhibitor varespladib methyl 500 mg daily and placebo on serial changes in inflammatory and lipid biomarkers were examined in 624 ACS patients who were treated with standard of care including atorvastatin 80 mg daily.

A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain.

Objectives: To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain.

Methods: A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg).

Results: There were 892 participants (mean age 60.

The von Willebrand inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy: a randomized trial.

Background And Purpose: Inhibition of von Willebrand factor offers a novel approach to prevention of stroke and myocardial ischemia but has not yet been demonstrated to show efficacy on clinically relevant end points. ARC1779 is an aptamer that inhibits the prothrombotic function of von Willebrand factor by binding to the A1 domain of von Willebrand factor and thereby blocking its interaction with glycoprotein. Phase 1 studies suggest it inhibits platelet aggregation with less increase in bleeding than conventional antiplatelet agents.

Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial.

Aims: Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events.

A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat.

Background: Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections.

Methods: In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74).

A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain.

Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.

Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients.

Objectives: The purpose of this study was to investigate the effects of varespladib on cardiovascular biomarkers in acute coronary syndrome patients.

Background: Secretory phospholipase A(2) (sPLA(2)) represents a family of proatherogenic enzymes that hydrolyze lipoprotein phospholipids, increasing their affinity for intimal proteoglycans; contribute to cholesterol loading of macrophages by nonscavenger receptor mediated pathways; and activate inflammatory pathways. In prospective studies, high sPLA(2)-IIA levels predicted major adverse cardiovascular events in acute coronary syndrome (ACS) and stable coronary heart disease patients.

Effect on mode of death of heart failure treatment started with bisoprolol followed by Enalapril, compared to the opposite order: results of the randomized CIBIS III trial.

Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting.

The effect of treatment with bisoprolol-first versus enalapril-first on cardiac structure and function in heart failure.

Background: In CIBIS III, initiating chronic heart failure (CHF) treatment with bisoprolol (target dose 10 mg q.d.) followed by combination therapy with enalapril (target dose 10 mg b.

Onset of analgesia with sodium ibuprofen, ibuprofen acid incorporating poloxamer and acetaminophen--a single-dose, double-blind, placebo-controlled study in patients with post-operative dental pain.

Objective: To compare the onset of action and efficacy of sodium ibuprofen (ibuprofen sodium dihydrate) and ibuprofen acid incorporating poloxamer (ibuprofen/poloxamer) with that of acetaminophen and placebo in patients with post-operative dental pain.

Methods: A double-blind, randomised, placebo-controlled, active comparator, two-centre study assessing the analgesic efficacy of sodium ibuprofen (512 mg, equivalent to 400 mg ibuprofen acid), ibuprofen/poloxamer (containing 400 mg ibuprofen acid and 120 mg poloxamer 407), acetaminophen (1000 mg) and placebo in patients with moderate-to-severe pain after third molar extraction (n = 322). Onset of action was assessed using the two-stopwatch technique, and pain intensity and relief were measured using validated traditional descriptor scales.

Clinical effects of initial 6 months monotherapy with bisoprolol versus enalapril in the treatment of patients with mild to moderate chronic heart failure. Data from the CIBIS III Trial.

Purpose: To assess the clinical effects and safety profile of initial monotherapy with either bisoprolol or enalapril in elderly patients with heart failure (HF).

Methods: In CIBIS III, 1010 patients with mild to moderate HF and age>or=65 years were randomized to monotherapy with either bisoprolol or enalapril for 6 months.

Results: Bisoprolol had a similar effect as enalapril on the combined end-point of all-cause mortality or hospitalization (HR 1.

Ibuprofen versus paracetamol in pediatric fever: objective and subjective findings from a randomized, blinded study.

Objective: The main objective of this study was to compare the single-dose efficacy of 15 mg/kg paracetamol (acetaminophen) versus 10 mg/kg ibuprofen in a general practice setting.

Methods: Children from the age of 3 months to 12 years with a fever of non-serious origin were randomized to receive either ibuprofen or paracetamol. The first dose was given double-blind, using a double-dummy technique.

Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial.

Objectives: We sought to evaluate the safety and efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS).

Background: Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor VIIa complex that has the potential to reduce ischemic complications mediated by thrombin generation.

Methods: A total of 203 patients were randomized 4:1 to double-blinded intravenous rNAPc2 or placebo every 48 h for a total of 1 to 3 doses in 8 ascending panels (1.