Chikungunya virus infections among travellers returning to Spain, 2008 to 2014

Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers

Antibiotic Prescribing for Lower Respiratory Tract Infections and Community-Acquired Pneumonia: An Italian Pediatric Emergency Department’s Real-Life Experience

Background: Lower respiratory tract infections (LRTIs) and community-acquired pneumonia (CAP) are among the most frequent reasons for referrals to the pediatric emergency department (PED). The aim of this study is to describe the management of antibiotic prescription in febrile children with LRTI or CAP admitted to a third-level PED and to investigate the different variables that can guide physicians in this decision-making. Methods: This is an observational, retrospective, monocentric study including patients < 14 years old who were presented to the PED for a febrile LRTI or CAP during the first six months of the year 2017. Demographic and clinical data, PED examinations, recommended therapy, and discharge modality were considered. Two multivariate logistic regression analyses were performed on patients with complete profiles to investigate the impact of demographic, laboratory, and clinical variables on antibiotic prescription and hospital admission. Results: This study included 584 patients with LRTI (n = 368) or CAP (n = 216). One hundred and sixty-eight individuals (28.7%) were admitted to the hospital. Lower age, higher heart rate, and lower SpO2 were associated with an increased risk of hospitalization. Antibiotics were prescribed to 495 (84.8%) patients. According to the multivariate logistic regression, the diagnosis and duration of fever were substantially linked with antibiotic prescription. Conclusions: The present study reports real-life data about our PED experience. A high rate of antibiotic prescription was noted. In the future, it is necessary to improve antibiotic stewardship programs to increase clinical adherence to guidelines

The mass donor of Scorpius X-1 revealed

We present the first detection of the mass donor star in the prototype X-ray binary Scorpius X-1. Phase resolved spectroscopy revealed narrow emission lines components from the irradiated secondary star. Radial velocity fits to the Bowen blend emission are used to establish an absolute orbital ephemeris and derive an accurate value for the systemic velocity; gamma= -113.8 +/- 0.6 km/s. Emission from the irradiated front side of the secondary leads to solid limits to the radial velocity of the mass donor of 87 < K_2 < 148 km/s. In conjunction with an upper limit to the velocity of the primary K_1 < 53 km/s, we derive a firm limit on the mass ratio of Sco X-1 of q < 0.61. % A likely set of system parameters satisfying the various constraints as well as the recent inclination estimate by Fomalont et al. (2001) is K_1=40 km/s, K_2=133 km/s, q=0.30 corresponding to component masses of M_1=1.4M_sun, M_2=0.42 M_sun for an orbital inclination of 38 degrees.Comment: 11 pages, 5 figures, accepted for publication in Ap

Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis:results from the WILLOW trial

Background: Brensocatib is an oral, selective, reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), responsible for activating neutrophil serine proteases (NSPs) including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG). In chronic inflammatory lung diseases such as non-cystic fibrosis bronchiectasis (NCFBE), neutrophils accumulate in the airways resulting in excess active NSPs that cause damaging inflammation and lung destruction.Methods: The 24-week WILLOW trial (NCT03218917) was a randomized, double-blind, placebo-controlled, parallel-group trial in patients with NCFBE conducted at 116 sites across 14 countries. In this trial, treatment with brensocatib was associated with improvements in clinical outcomes including time to first exacerbation, reduction in exacerbation frequency and a reduction in NE activity in sputum. An exploratory analysis of NE activity in white blood cell (WBC) extracts and NE, PR3 and CatG activity in sputum was conducted to further characterize brensocatib's effect and identify potential correlated effects.Results: NE, PR3 and CatG activities were reduced in sputum and NE activity was reduced in WBC extracts in a dose-dependent manner after four weeks of brensocatib treatment, with a return to baseline four weeks after the end of treatment. Brensocatib produced the greatest reduction in the sputum activity of CatG, followed by NE and then PR3. Positive correlations among the sputum NSPs were observed both at baseline and in response to treatment, with the strongest correlation among the sputum NSPs for NE and CatG.Conclusions: These results suggest a broad anti-inflammatory effect of brensocatib underlying its clinical efficacy observed in NCFBE patients.Trial registration: The study was approved by the corresponding ethical review boards of all participating centers. The trial was approved by the Food and Drug Administration and registered at clinicaltrials.gov (NCT03218917) on July 17, 2017 and approved by the European Medicines Agency and registered at the European Union Clinical trials Register (EudraCT No. 2017-002533-32). An independent, external data and safety monitoring committee (comprising physicians with pulmonary expertise, a statistician experienced in the evaluation of clinical safety, and experts in periodontal disease and dermatology) reviewed all adverse events.</p

Care of the old—A matter of ethics, organization and relationships

The world stands on the threshold of a demographic revolution called global ageing. According to the World Health Organization (WHO), the population aged 60 and over is expected to increase from today's 650 million to an estimated 2 billion by 2050. Alongside demographic changes, dramatic changes can also be observed in older people's services. The shift has resulted in reduced government spending on caring for ill and frail older people in health care. Today, many governments have developed strategies to keep older people living well in their private home for as long as possible and have replaced long-term care institutions with residential homes. The aim of this study was to illuminate the meaning of caring for older people as experienced by health care students and professionals working in this field. Interviews were carried out with 17 women and one man, aged 21–65 years; six were Registered Nurses (RN), six were Enrolled Nurses (EN) and six were nursing students. The interviews were analyzed with a phenomenological hermeneutical approach and provided three themes and eight sub-themes: Ethical moral self with sub-themes “meeting the needs of the old”, “pliability towards the old”, and “difficulties in meeting aggressiveness”; Organizational and co-workers ethical moral actions with sub-themes, “co-workers who are offensive”, and “supportive and non-supportive leaders”: The relation with the old persons and their relatives with sub-themes “fellowship and closeness in the relation”, “uncertainty and fear in the relation”, and, “demands from the older persons’ close relatives”

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

<p>Abstract</p> <p>Background</p> <p>Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.</p> <p>Methods/Design</p> <p>The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express²paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.</p> <p>Discussion</p> <p>The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at <url>http://www.clinicaltrials.gov</url>, identification numbers NCT00484315 and NCT00489541.</p

Postnatal Development of Hepatic Innate Immune Response

The liver is an immunocompetent organ that plays a key role in the immune response to infections, and the development of hepatic immune function during early postnatal stages has not been thoroughly characterized. This study analyzed the constitutive expression of complement factors, namely C3 and C9, and pattern recognition receptors, namely CD14, toll-like receptor (TLR)-4, and lipopolysaccharide binding protein (LBP), in the liver of postnatal day (P)1, P21, and P70 rats, and compared the kinetics of induction of cytokines and chemokines in the liver of P 1 and P 21 animals. Our studies found that while the mRNA expression of C3, C9, CD14, and TLR-4 was lower in P1 animals, the mRNA level of LBP was higher in P1 animals as compared to older animals, and that the kinetics of induction of cytokines and chemokines was significantly delayed in P1 as compared to P21 liver following LPS stimulation. Our data suggest that hepatic innate immunity is deficient in the neonates and undergo significant development during early postnatal life