A Therapeutic Antigen-Presenting Cell-Targeting DNA Vaccine VB10.16 in HPV16-Positive High-Grade Cervical Intraepithelial Neoplasia: Results from a Phase I/IIa Trial.

Purpose: To evaluate the safety, immunogenicity and efficacy of a therapeutic DNA vaccine VB10.16, using a unique modular vaccine technology that is based on linking antigens to CCL3L1 targeting module, in women with HPV16-positive high-grade cervical intraepithelial neoplasia (CIN).

Patients And Methods: We conducted a first-in-human, open-label, phase I/IIa clinical trial of VB10.

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke.

Background: Most ischaemic strokes are caused by blockage of a cerebral artery by a thrombus. Intravenous administration of recombinant tissue plasminogen activator given within 4.5 hours is now standard treatment for this condition.

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

Background: Factor Xa inhibitors and vitamin K antagonists (VKAs) are now recommended in treatment guidelines for preventing stroke and systemic embolic events in people with atrial fibrillation (AF). This is an update of a Cochrane review previously published in 2013.

Objectives: To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for preventing cerebral or systemic embolic events in people with AF.

New strategies for the development of lipid-lowering therapies to reduce cardiovascular risk.

The very high occurrence of cardiovascular events presents a major public health issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels.

New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment.

Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure.

Effects of alteplase on survival after ischaemic stroke (IST-3): 3 year follow-up of a randomised, controlled, open-label trial.

Background: The effect of alteplase on patient survival after ischaemic stroke is the subject of debate. We report the effect of intravenous alteplase on long-term survival after ischaemic stroke of participants in the Third International Stroke Trial (IST-3).

Methods: In IST-3, done at 156 hospitals in 12 countries (Australia, Europe, and the UK), participants (aged >18 years) were randomly assigned with a telephone voice-activated or web-based system in a 1:1 ratio to treatment with intravenous 0·9 mg/kg alteplase plus standard care or standard care alone within 6 h of ischaemic stroke.

The European Medicines Agency approval of axitinib (Inlyta) for the treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine: summary of the scientific assessment of the committee for medicinal products for human use.

Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3. Based on the positive opinion from the European Medicines Agency (EMA), a marketing authorization valid throughout the European Union (EU) was issued for the treatment of advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine. The demonstration of clinical benefit for axitinib was based on a phase III, randomized, open-label, multicenter study of axitinib compared with sorafenib in patients with advanced RCC after failure of a prior systemic first-line regimen containing one or more of the following agents: sunitinib, bevacizumab plus interferon-α, temsirolimus, or cytokines.

Factor Xa inhibitors vs warfarin for preventing stroke and thromboembolism in patients with atrial fibrillation.

Clinical Question: Is treatment with factor Xa inhibitors associated with better efficacy and safety compared with the vitamin K antagonist warfarin for preventing strokes or other systemic embolic events in patients with atrial fibrillation?

Bottom Line: Compared with warfarin, factor Xa inhibitors are associated with a lower risk of stroke and other systemic embolic events in patients with atrial fibrillation. Factor Xa inhibitors were associated with lower rates of intracranial hemorrhage and mortality compared with warfarin. Factor Xa inhibitors were associated with a reduction in major bleeding events, but there was heterogeneity between the included studies, and the reduction was not statistically significant in a prespecified sensitivity analysis.

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

Background: Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs.

Objectives: To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF.

Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.

Background And Purpose: Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature.

Methods: We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration).

The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial.

Background: Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset.

Methods: In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control.

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.

Background: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.

Design: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke.

Causes of death by level of dependency at 6 months after ischemic stroke in 3 large cohorts.

Background And Purpose: We assessed the influence of functional status at 6 months after ischemic stroke on cause of death during long-term follow-up in 3 prospective cohorts.

Methods: The cohorts were 7710 patients from the Oxfordshire Community Stroke Project, Lothian Stroke Register, and International Stroke Trial. Functional status was assessed at 6 months after stroke onset.

Thrombolytic treatment for stroke: patient preferences for treatment, information, and involvement.

Background: Thrombolytic treatment for stroke carries the potential for a better functional outcome, but also a risk of intracranial hemorrhage and death. Ideally, the decision to treat should be based on the patient's preferences.

Methods: Study participants were 75 stroke survivors and 75 healthy, age-matched control subjects.

Third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke.

Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.

Design: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke.

Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies.

Objective: To estimate the impact on long term survival of functional status at six months after ischaemic stroke.

Design: Prospective cohort study. Settings Three cohorts: Oxfordshire community stroke project, Lothian stroke register, and the first international stroke trial (in the United Kingdom).

Haemorrhagic transformation of a recent silent cerebral infarct during thrombolytic stroke treatment.

We present a patient in her 60s who was admitted with a sudden loss of power in her right arm and leg, right sided facial weakness, and difficulties with speaking. An acute ischaemic stroke in the left hemisphere was diagnosed and the patient received intravenous thrombolytic treatment. Treatment was stopped halfway as a cerebral haemorrhage was suspected.