Summary Background Chikungunya virus—a mosquito-borne alphavirus—is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for ...treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine. Methods VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults aged 18–50 years who were enrolled at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Participants were assigned to sequential dose level groups to receive vaccinations at 10 μg, 20 μg, or 40 μg on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov , NCT01489358. Findings 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 μg (n=5), 20 μg (n=10), and 40 μg (n=10). The protocol was completed by all five participants at the 10 μg dose, all ten participants at the 20 μg dose, and eight of ten participants at the 40 μg dose; non-completions were for personal circumstances unrelated to adverse events. 73 vaccinations were administered. All injections were well tolerated, with no serious adverse events reported. Neutralising antibodies were detected in all dose groups after the second vaccination (geometric mean titres of the half maximum inhibitory concentration: 2688 in the 10 μg group, 1775 in the 20 μg group, and 7246 in the 40 μg group), and a significant boost occurred after the third vaccination in all dose groups (10 μg group p=0·0197, 20 μg group p<0·0001, and 40 μg group p<0·0001). 4 weeks after the third vaccination, the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 μg group, 4525 for the 20 μg group, and 5390 for the 40 μg group. Interpretation The chikungunya VLP vaccine was immunogenic, safe, and well tolerated. This study represents an important step in vaccine development to combat this rapidly emerging pathogen. Further studies should be done in a larger number of participants and in more diverse populations. Funding Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.
FPA@rcp.ac.uk Salisbury discusses important issues raised by the death of a woman debated in parliament in reference to physician associates (PAs).12 We hope we can agree on the benefits of ...multidisciplinary practice in healthcare, recognising the importance of appropriate training, role boundaries, and supervision. 6 Health Education England has published guidance for PAs working in primary care,7 as has NHS England,8 and there are multiple resources on the faculty website relating to supervision in practice. Physician associates: the case for regulation. 29 Jul 2022. https://www.fparcp.co.uk/file/image/media/633da06a23641_FPA_Regulate_PA_s_Now_Policy_Paper_FINAL.pdf 4 Department of Health and Social Care.
Despite widespread use of Pegylated forms of Inteferon in the management of Myeloproliferative Neoplasms (MPN), most clinicians have experience predominantly with peginterferon alfa-2a (Pegasys). ...Third generation pegylated IFNα, ropeginterferon alfa-2b (ropegIFN; Besremi), was recommended by the European Medicine Authority (EMA) for treatment of Polycythaemia Vera (PV) following a Phase III trial (PROUD-PV / CONTINUATION-PV). FDA approval for PV, regardless of treatment history, was subsequently granted in November 2021. We hereby demonstrate the safety and tolerability of ropegIFN in a series of MPN patients at variable doses. It corroborates reports of efficacy of ropegIFN in patients with PV and use in pregnancy.
Challenges to breast cancer control in low-and middle-income countries exist because of constrained access to care, including pathology services. Immunohistochemistry (IHC)-based estrogen receptor ...(ER) analysis is limited-nonexistent because of few and inadequately staffed and equipped pathology laboratories. We have identified N
-hydroxy-L-Arginine (NOHA) as a blood-based biomarker to distinguish ER status in US patients with breast cancer. Here, we examine NOHA's clinical utility as an ER IHC alternative in Tanzanian patients.
Following informed consent, 70 newly diagnosed, known or suspected patients with breast cancer were enrolled at Kilimanjaro Christian Medical Center; basic, deidentified clinical and sociodemographic data were collected. For each, a needle prick amount of blood was collected on a Noviplex plasma card and stored at -80°C. Plasma cards and unstained tumor pathology slides were shipped regularly to US laboratories for NOHA, histologic and IHC analysis. NOHA and IHC assay operators were blinded to each other's result and patient clinical status. Paired NOHA and IHC results were compared.
Slides from 43 participants were available for pathological analysis in the United States. Of those with confirmed malignancy (n = 39), 44%, 51%, 5% were ER-positive, ER-negative, and ER inconclusive, respectively. NOHA levels were available among 33 of 43 of those with pathological data and showed distinct threshold levels correlating 100% to tumor ER IHC and disease categorization where a level below 4 nM, from 4 to 8 nM, and above 8 nM signified ER-negative, ER-positive, and no cancer, respectively.
The results are consistent with findings from US patients and suggest NOHA's clinical utility as an accessible IHC replacement in determining ER status among low-and middle-income country patients with breast cancer, promising to extend access to cost-efficient, available hormonal agents and improve outcomes.
Cybercrime activity is growing fast and evolving at a rapid pace, becoming both more technically proficient and aggressive. The Office for National Statistics (ONS) estimates that there were two ...million computer misuse offences experienced in England and Wales in the 12 months to March 2016. Precise figures for the total cost of cybercrime are hard to establish, but a National Crime Agency (NCA) Assessment published in July 2016 estimated the cost to the UK economy to be in the order of billions of pounds per annum.
Tackling the threat of cybercrime requires a broad-based strategy that recognises the diversity of offences, actors and motivations. It requires the right balance between the 'Four Ps' of the UK Serious and Organised Crime Strategy - PURSUE, PREVENT, PROTECT, PREPARE. Critically, it requires close working between law enforcement, government, international partners and industry.
This paper sets out the UK approach to tackling cybercrime and outlines some of the successes that have been achieved to date. It recognises that government, law enforcement agencies and other bodies have all increased efforts to tackle cybercrime, but concludes that these efforts alone cannot fully address the challenge. A number of areas are identified that need to be strengthened if, collectively, we are to have a lasting impact on the threat.
Haematological emergencies Curto-Garcia, Natalia; Saunders, Jamie; Doyle, Andrew
Medicine (Abingdon. 1995, UK ed.),
20/May , Letnik:
49, Številka:
5
Journal Article
Recenzirano
This article summarizes the management of common haematological emergencies. Patients with haematological disorders may have associated co-morbidities and/or be being given chemotherapy treatment, ...which can be daunting to doctors who have not previously encountered these clinical situations. Laboratory data interpretation, familiarity with disease-associated complications and good clinical skills are essential for the diagnosis and management of haematological emergencies. This review aims to discuss the key concepts in the diagnosis and management of frequently encountered emergencies in these patients.
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