Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions.

In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 µg of chloroquine or 7.99 µg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping. Based on the model predictions, inhaling emitted doses comprising 1.5 mg of chloroquine or 3.3 mg hydroxychloroquine three times a day may yield therapeutically effective concentrations in the lung. Inhalation of higher doses further increased effective concentrations in the lung while maintaining lower systemic concentrations. Given the theoretically favorable risk/benefit ratio, the clinical significance for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 needs to be established in rigorous safety and efficacy studies. Graphical abstract.

The European Federation of Clinical Chemistry and Laboratory Medicine syllabus for postgraduate education and training for Specialists in Laboratory Medicine: version 5 - 2018.

Although laboratory medicine practise varies across the European Union's (EU) member states, the extent of overlap in scope is such that a common syllabus describing the education and training associated with high-quality, specialist practise can be identified. In turn, such a syllabus can help define the common set of skills, knowledge and competence in a Common Training Framework (CTF) for non-medical Specialists in Laboratory Medicine under EU Directive 2013/55/EU (The recognition of Professional Qualifications). In meeting the requirements of the directive's CTF patient safety is particularly enhanced when specialists seek to capitalise on opportunities for free professional migration across EU borders. In updating the fourth syllabus, the fifth expands on individual discipline requirements, new analytical techniques and use of statistics. An outline structure for a training programme is proposed together with expected responsibilities of trainees and trainers; reference is provided to a trainee's log book. In updating the syllabus, it continues to support national programmes and the aims of EU Directive 2013/55/EU in providing safeguards to professional mobility across European borders at a time when the demand for highly qualified professionals is increasing in the face of a disparity in their distribution across Europe. In support of achieving a CTF, the syllabus represents EFLM's position statement for the education and training that underpins the framework.

Trace metal determination as it relates to metallosis of orthopaedic implants: Evolution and current status.

In utilising metal surfaces that are in constant contact with each other, metal-on-metal (MoM) surgical implants present a unique challenge, in the sense that their necessity is accompanied by the potential risk of wear particle generation, metal ion release and subsequent patient toxicity. This is especially true of orthopaedic devices that are faulty and subject to failure, where the metal surfaces undergo atypical degradation and release even more unwanted byproducts, as was highlighted by the recent recall of orthopaedic surgical implants. The aim of this review is to examine the area of metallosis arising from the wear of MoM articulations in orthopaedic devices, including how the surgical procedures and detection methods have advanced to meet growing performance and analytical needs, respectively.

Establishing trimester-specific maternal thyroid function reference intervals.

BACKGROUND: Thyroid disorders are common in women of childbearing age and are associated with adverse pregnancy outcomes. Physiological changes in pregnancy and the lack of pregnancy-specific reference ranges make managing thyroid disorders in pregnancy challenging. Our aim was to establish trimester-specific thyroid function reference intervals throughout pregnancy, and to examine the prevalence of thyroid autoimmunity in otherwise euthyroid women. METHOD: This was a prospective, cross-sectional study of thyroid function tests (TFTs) in pregnant women attending a large, tertiary referral maternity hospital. Patients with known thyroid disorders, autoimmune disease, recurrent miscarriage, hyperemesis gravidarum and pre-eclampsia were excluded. TFTs were analysed in the CUH biochemistry laboratory using Roche Modular E170 electrochemiluminescent immunoassay. Trimester-specific reference ranges (2.5th, 50th and 97.5th centiles) were calculated. RESULTS: Three-hundred-and-fifty-one women were included into the analysis. Median maternal age was 30. Thyroid-stimulating hormone concentrations showed slightly increasing median centile throughout gestation. Free thyroxine (T4) and T3 decreased throughout gestation. Table 1 demonstrates the calculated percentiles according to gestational weeks. CONCLUSION: We established pregnancy-specific thyroid function reference intervals for our pregnant population, for use in clinical practice.

Clinical unity and community empowerment: the use of smartphone technology to empower community management of chronic venous ulcers through the support of a tertiary unit.

BACKGROUND: Chronic ulcers affect roughly 60,000 Irish people, at a total cost of €600,000,000, or €10,000 per patient annually. By virtue of their chronicity, these ulcers also contribute a significant burden to tertiary outpatient vascular clinics. OBJECTIVE: We propose utilizing mobile phone technology to decentralise care from tertiary centres to the community, improving efficiency and patient satisfaction, while maintaining patient safety. METHODS: Bespoke mobile software was developed for Apples iPhone 4 platform. This allowed for the remote collection of patient images prospectively and their transmission with clinical queries, from the primary healthcare team to the tertiary centre. Training and iPhones were provided to five public health nurses in geographically remote areas of the region. Data were uploaded securely and user end software was developed allowing the review and manipulation of images, along with two way communication between the teams. Establishing reliability, patients were reviewed clinically as well as remotely, and concordance analysed. Qualitative data were collected through focus group discussion. RESULTS: From October to December 2011 eight patients (61-83 yrs, mean 75.3 yrs) with chronic venous ulceration and their five public health nurses were recruited. Data were transmitted using 3 G, Edge, GPRS and WiFi, at a mean speed of 69.03 kps. Concordance was 100% for wound bed assessment, 80% for skin integrity/colour and 60% for exudate assessment. Focus group analysis explored the concept, practicalities and future applications of the system. CONCLUSIONS: With an evolving national data network, the secure transmission of clinical images is a safe alternative to regular clinic appointments for patients with chronic venous ulceration. With further development, and packaged as a freely downloadable application, this has the potential to support the community care of chronic wounds.

Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet.

OBJECTIVE: Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. METHODS: We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. RESULTS: Breast related topics had significantly more posts per day compared to others (mean 66.7, p < 0.01). Most posts were on media sites (65.8%). Accuracy levels were high (87.5%) but significantly lower where posted on blogs and discussion forums (p < 0.001). Anonymous posts were common (55%) and less likely to be accurate (p < 0.001). Use of discussion forums has exponentially increased over the last five years (p < 0.001). CONCLUSIONS: The internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves.

The EC4 European syllabus for post-graduate training in clinical chemistry and laboratory medicine: version 4--2012.

Laboratory medicine's practitioners across the European community include medical, scientific and pharmacy trained specialists whose contributions to health and healthcare is in the application of diagnostic tests for screening and early detection of disease, differential diagnosis, monitoring, management and treatment of patients, and their prognostic assessment. In submitting a revised common syllabus for post-graduate education and training across the 27 member states an expectation is set for harmonised, high quality, safe practice. In this regard an extended 'Core knowledge, skills and competencies' division embracing all laboratory medicine disciplines is described. For the first time the syllabus identifies the competencies required to meet clinical leadership demands for defining, directing and assuring the efficiency and effectiveness of laboratory services as well as expectations in translating knowledge and skills into ability to practice. In a 'Specialist knowledge' division, the expectations from the individual disciplines of Clinical Chemistry/Immunology, Haematology/Blood Transfusion, Microbiology/ Virology, Genetics and In Vitro Fertilisation are described. Beyond providing a common platform of knowledge, skills and competency, the syllabus supports the aims of the European Commission in providing safeguards to increasing professional mobility across European borders at a time when demand for highly qualified professionals is increasing and the labour force is declining. It continues to act as a guide for the formulation of national programmes supplemented by the needs of individual country priorities.

The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: guide to the Register, version 3-2010.

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article.

The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: Code of Conduct, Version 2--2008.

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 10 years, more than 2000 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Federation of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). A Code of Conduct was adopted in 2003 and a revised and updated version, taking account particularly of the guidelines of the Conseil Européen des Professions Libérales (CEPLIS) of which EFCC is a member, is presented in this article. The revised version was approved by the EC4 Register Commission and by the EFCC Executive Board in Paris on 6 November, 2008.