Trends in lipid-modifying agent use in 83 countries

Background and aims: Lipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations. / Methods: This cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018 for 83 countries from the IQVIA Multinational Integrated Data Analysis System and total and non-high-density lipoprotein (non-HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. Compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time. / Results: From 2008 to 2018, use of LMAs increased from 7,468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). An estimated 173 million people used LMAs in 2018. Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and mean total and non-HDL cholesterol concentrations in 2008 versus 2018. / Conclusions: Since 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non-HDL cholesterol varied considerably

Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.Martin Donnelley, Kaye S. Morgan, Karen K. W. Siu, Nigel R. Farrow, Charlene S. Stahr, Richard C. Boucher, Andreas Fouras & David W. Parson

Clinical Characteristics and Transmission of COVID-19 in Children and Youths During 3 Waves of Outbreaks in Hong Kong

IMPORTANCE: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths. OBJECTIVE: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021. MAIN OUTCOMES AND MEASURES: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections. RESULTS: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post–COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts. CONCLUSIONS AND RELEVANCE: his cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small

Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways

Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.M Donnelley, KKW Siu, RA Jamison and DW Parson

Mapping structural changes in breast tissue disease using x-ray scattering

Spread of invasive carcinoma throughout breast tissue is believed to occur at supramolecular levels, beyond the range of standard histopathology identification. Small angle x-ray scattering (SAXS) is capable of characterizing the structural properties of collagen and tissue found in the breast at the scale of tens to hundreds of nanometers. Fifty-six patients who were treated with wide-local excision or mastectomy had tissue biopsy samples analyzed at 2 cm intervals along two perpendicular axes over their excised mass, up to 6 cm away from the primary site of the tumor. Two SAXS parameters, the integrated amorphous scatter and the third order collagen axial d spacing, showed significant differences between the center (0 cm) and distant tissues (2, 4, or 6 cm from the primary lesion). There was no evidence of directional trends (superior, inferior, or lateral sides of the nipple) of these two parameters over the breast. Mapping of these two variables over a two-dimensional grid showed good matching with independent histopathology diagnosis. These results suggest that SAXS may be capable of identifying areas of invasion or directional spread of disease as well as providing more information at the supramolecular level for aiding tissue diagnosis

A questionnaire survey on attitudes and understanding towards mental disorders

OBJECTIVES. To obtain information about basic knowledge towards mental disorders and to evaluate public attitudes towards mental disorders in the Hong Kong Chinese population. METHODS. Questionnaires which collected basic demographic information, opinions about potential stigmas and myths, and knowledge on case vignettes depicting fictional characters with symptoms of mental illness were delivered to subjects in a secondary school, 2 homes for the elderly, a private housing estate, and a public housing estate in Hong Kong. RESULTS. Completed questionnaires were collected from 1035 subjects. In general, the participants' acceptance of mental illness was good. Regular contacts with such patients were associated with better knowledge (t = -2.71, p < 0.01) and better acceptance (t = 2.77, p < 0.01) of mental illness. Younger participants aged 15 to 19 years had a lower level of knowledge about mental health problems compared with other age-groups (p < 0.001). CONCLUSIONS. Personal contact with people with mental illness may help to improve knowledge and acceptance. Younger people in secondary school should be the target and prioritised group for mental health education. Apart from the delivery of mental health knowledge, strategies to increase social contact of the public with people having mental illness could be considered in the design and implementation of anti-stigma programmes.link_to_OA_fulltex

Classification of breast tissue using a laboratory system for small-angle x-ray scattering (SAXS)

Structural changes in breast tissue at the nanometre scale have been shown to differentiate between tissue types using synchrotron SAXS techniques. Classification of breast tissues using information acquired from a laboratory SAXS camera source could possibly provide a means of adopting SAXS as a viable diagnostic procedure. Tissue samples were obtained from surgical waste from 66 patients and structural components of the tissues were examined between q = 0.25 and 2.3 nm⁻¹. Principal component analysis showed that the amplitude of the fifth-order axial Bragg peak, the magnitude of the integrated intensity and the full-width at half-maximum of the fat peak were significantly different between tissue types. A discriminant analysis showed that excellent classification can be achieved; however, only 30% of the tissue samples provided the 16 variables required for classification. This suggests that the presence of disease is represented by a combination of factors, rather than one specific trait. A closer examination of the amorphous scattering intensity showed not only a trend of increased scattering intensity with disease severity, but also a corresponding decrease in the size of the scatterers contributing to this intensity

A rare cause of infective endocarditis; Lactococcus garvieae

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Small Angle X-Ray Scattering Signatures for Breast Cancer Detection: Direct Comparison of Synchrotron and Laboratory X-Ray Sources

Scattering signatures from human breast tissue acquired on a synchrotron x-ray source and a laboratory instrument have been directly compared. We have previously established that the amorphous scatter intensity is extremely sensitive to disease status, able to detect the molecular changes in healthy tissue from patients with verified disease before the conventional histological markers of cancer are visible. SAXS images of tissue samples from 130 patients were imaged on a synchrotron source, and matched samples from 66 of these patients were also imaged on a laboratory source. The results indicate that not only does the integrated amorphous scattering intensity increase with disease severity for both sources, but that the size of the predominant scatterers also appears to decrease with disease progression

A rare cause of infective endocarditis; Lactococcus garvieae

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