Combined strategy of upfront CTCA and optimal treatment for stable chest pain: rationale and design of the CLEAR-CAD trial.

Background: Patients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac events.

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions.

Background: Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest").

Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults.

Background: Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection.

Methods: In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01-adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season.

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation : Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups.

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.

Unsupervised Reconstruction of Analyte-Specific Mass Spectra Based on Time-Domain Morphology with a Modified Cross-Correlation Approach.

Concomitant species that appear at the same or very similar times in a mass-spectral analysis can clutter a spectrum because of the coexistence of many analyte-related ions (.., molecular ions, adducts, fragments).

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial.

Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness.

Ten-Year Antibody Persistence and Booster Response to MenACWY-TT Vaccine After Primary Vaccination at 1-10 Years of Age.

This phase 3B, open-label, extension study (NCT01962207) evaluated long-term persistence of antibodies induced by the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) compared with the meningococcal serogroup C vaccine conjugated to CRM (MenC-CRM) and the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS) 6 to 10 y after primary vaccination in toddlers (aged 1-<2 y; MenACWY-TT and MenC-CRM) and children (aged 2-<11 y; MenACWY-TT and MenACWY-PS). Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by serum bactericidal antibody assays using rabbit (rSBA) or human (hSBA) complement. A MenACWY-TT booster dose at Year 10 was given to all eligible subjects regardless of the primary vaccine received.

A phase 2b/3b MenACWY-TT study of long-term antibody persistence after primary vaccination and immunogenicity and safety of a booster dose in individuals aged 11 through 55 years.

Background: A previous phase 2 study demonstrated the immunogenicity of a single dose of meningococcal A, C, W, Y-tetanus toxoid conjugate (MenACWY-TT) or polysaccharide (MenACWY-PS) vaccine for up to 5 years in individuals aged 11-55 years. This follow-up study evaluated long-term antibody persistence up to 10 years and the immunogenicity and safety of a single MenACWY-TT booster dose given 10 years after primary vaccination.

Methods: Blood draws were conducted annually in Years 7-10.

Efficacy and safety of a booster dose of the meningococcal A, C, W, Y-tetanus toxoid conjugate vaccine administered 10 years after primary vaccination and long-term persistence of tetanus toxoid conjugate or polysaccharide vaccine.

A previous phase 3, randomized, multicenter study showed the immunogenicity of a primary vaccination of subjects aged 11 to 17 years with the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) or the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS). This extension study evaluated the safety and immunogenicity of a MenACWY-TT booster 10 years after receiving a primary dose of either MenACWY-TT or MenACWY-PS. The primary immunogenicity endpoint was booster response, evaluated using serum bactericidal antibody assays with rabbit complement (rSBA), 1 month postbooster.

Long-term antibody persistence after a booster dose of quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine in healthy 5-year-old children.

Background: To provide continuing protection, available meningococcal vaccines must provide long-term persistence of circulating functional antibodies against prevalent serogroups causing invasive meningococcal disease (IMD). This study assessed antibody persistence and safety of the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) and the meningococcal serogroup C vaccine conjugated to Corynebacterium diphtheriae CRM protein (MenC-CRM) for up to 6 years after booster dosing in children.

Methods: In the primary vaccination study, children were vaccinated at age 12 to 23 months.

Correction to: Guidelines for the management of myocardial infarction/injury with non-obstructive coronary arteries (MINOCA): a position paper from the Dutch ACS working group.

Correction to: Neth Heart J 2019 https://doi.org/10.1007/s12471-019-01344-6 The reference to the term acute coronary syndrome with normal or near-normal (non-obstructive) coronary arteries (ACSNNOCA) from Manolis et al.

Guidelines for the management of myocardial infarction/injury with non-obstructive coronary arteries (MINOCA): a position paper from the Dutch ACS working group.

Patients with myocardial infarction and non-obstructive coronary arteries (MINOCA), defined as angiographic stenosis <50%, represent a conundrum given the many potential underlying aetiologies. Possible causes of MINOCA can be subdivided into coronary, myocardial and non-cardiac disorders. MINOCA is found in up to 14% of patients presenting with an acute coronary syndrome.

Immunogenicity and Safety of a Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine 6 Years After MenC Priming as Toddlers.

Background: We assessed immunogenicity, antibody persistence and safety of the meningococcal serogroups A, C, W and Y-tetanus toxoid (TT) conjugate vaccine (MenACWY-TT) in children primed as toddlers with MenC vaccine.

Methods: This open, multicenter extension study enrolled children 84-95 months of age who had received one dose of the combined Haemophilus influenzae type b (Hib)-MenC-TT conjugate vaccine (HibMenC group) or Hib-TT and monovalent MenC (MCC)-CRM197 vaccines (Hib+MCC group) at 12-18 months of age, in the primary study. All participants received one dose of MenACWY-TT.

Chimeric Hemagglutinin-Based Influenza Virus Vaccines Induce Protective Stalk-Specific Humoral Immunity and Cellular Responses in Mice.

The high variation of the influenza virus hemagglutinin (HA), particularly of its immunodominant head epitopes, makes it necessary to reformulate seasonal influenza virus vaccines every year. Novel influenza virus vaccines that redirect the immune response toward conserved epitopes of the HA stalk domain should afford broad and durable protection. Sequential immunization with chimeric HAs (cHAs) that express the same conserved HA stalk and distinct exotic HA heads has been shown to elicit high levels of broadly cross-reactive Abs.

Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III, randomized study.

Background: This study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults.

Methods: In this phase III, randomized, partially-blind study (NCT01767376), healthy 11-25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA).

MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial.

Background: Co-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women.

Methods: In this phase IIIb study (NCT01755689), 1300 healthy 9-25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6.

Immunogenicity and safety of MenACWY-TT, a meningococcal conjugate vaccine, co-administered with routine childhood vaccine in healthy infants: A phase III, randomized study.

Background: Invasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants.

Methods: In this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15-18 months; group ACWY3+1); 1+1 (at 6 and 15-18 months; group ACWY1+1) or single-dose at 15-18 months (group ACWY1).

Antibody persistence and booster response 68 months after vaccination at 2-10 years of age with one dose of MenACWY-TT conjugate vaccine.

Background: We evaluated antibody persistence up to 68 months (M) post-vaccination with a quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) or a licensed monovalent MenC conjugate vaccine (MenC-CRM) and subsequent booster responses to MenACWY-TT in healthy European children.

Methods: In the initial study (NCT00674583), healthy children, 2-10 years of age, were randomized to receive a single dose of either MenACWY-TT or MenC-CRM. In the follow-up study, we present the persistence at 32, 44, 56, and 68 M post-vaccination, overall and stratified by age (2-5 and 6-10 years), and the immunogenicity and safety of MenACWY-TT administered to all study participants at M68 post-primary vaccination.

Immunogenicity and Reactogenicity of DTPa-HBV-IPV/Hib and PHiD-CV When Coadministered With MenACWY-TT in Infants: Results of an Open, Randomized Trial.

Background: This study evaluated the immunogenicity and reactogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus virus-Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) and a 10-valent pneumococcal conjugate vaccine (PHiD-CV) coadministered with a quadrivalent meningococcal conjugate vaccine (MenACWY-TT) in infants/toddlers.

Methods: In this open, controlled, phase III study (NCT01144663), 2095 healthy infants were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age or MenACWY-TT, MenC-CRM197, or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age.

Comparison of Outcomes and Intervention Among Patients With Non-ST-Segment Elevation Acute Myocardial Infarction of Those With a Left Circumflex Versus Those With a Non-Left Circumflex-Related Coronary Artery (From the ELISA-3 Trial).

Previous studies found that patients with an acute coronary syndrome (ACS) due to occlusion of the left circumflex (LC) coronary artery often present without ST-elevation, leading to a delay in diagnosis and revascularization, a larger infarct size, and a worse prognosis. In this subgroup analysis of the ELISA-3 study (early or late intervention in high-risk non-ST-segment elevation acute coronary syndromes [NSTE-ACS]) incidence, characteristics and prognosis of LC-related NSTE-ACS was investigated, and the outcome of early versus late invasive strategy was compared. In 383 of 542 patients the culprit vessel could be identified, with the LC artery in 112 (29%) of them.

Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study.

Background: Individuals with functional or anatomic asplenia are at high risk for meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2 doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid-conjugate vaccine (MenACWY-TT) in this high-risk population.

Methods: This phase III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17-year-olds with impaired splenic activity (high-risk group) and age-matched healthy controls (control group).

Two-year outcome after early or late Intervention in non-ST elevation acute coronary syndrome.

Objective: To compare long-term outcome of an early to a delayed invasive strategy in high-risk patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

Methods: This prospective, multicentre trial included patients with NSTE-ACS and at least two out of three of the following high-risk criteria: (1) evidence of extensive myocardial ischaemia on ECG, (2) elevated biomarkers for myocardial necrosis and (3) age above 65 years. Patients were randomised to either an early (angiography and revascularisation if appropriate <12 hours) or a delayed invasive strategy (>48 hours after randomisation).