Telemedicine acceptance by older adults in Hong Kong during a hypothetical severe outbreak and after the COVID-19 pandemic: a cross-sectional cohort survey.

INTRODUCTION: Telemedicine services worldwide have experienced unprecedented growth since the early days of the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have shown that telemedicine is an effective alternative to conventional in-person patient care. This study explored the public perception of telemedicine in Hong Kong, specifically among older adults who are most vulnerable to COVID-19. METHODS: Medical students from The Chinese University of Hong Kong conducted in-person surveys of older adults aged ≥60 years. Each survey collected socio-demographic information, medical history, and concerns regarding telemedicine use. Univariate and multivariate logistic regression analyses were conducted to identify statistically significant associations. The primary outcomes were acceptance of telemedicine use during a hypothetical severe outbreak and after the COVID-19 pandemic. RESULTS: There were 109 survey respondents. Multivariate logistic regression analyses revealed that the expectation of government subsidies for telemedicine services was the strongest common driver and the only positive independent predictor of telemedicine use during a hypothetical severe outbreak (P=0.016) and after the COVID-19 pandemic (P=0.003). No negative independent predictors of telemedicine use during a hypothetical severe outbreak were identified. Negative independent predictors of telemedicine use after the COVID-19 pandemic included older age and residence in the New Territories (both P=0.001). CONCLUSION: Government support, such as telemedicine-specific subsidies, will be important for efforts to promote telemedicine use in Hong Kong during future severe outbreaks and after the COVID-19 pandemic. Robust dissemination of information regarding the advantages and disadvantages of telemedicine for the public, especially older adults, is needed.

Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

Family medicine vocational training and career satisfaction in Hong Kong.

BACKGROUND: Postgraduate vocational training in family medicine (FM) is essential for physicians to build capacity and develop quality primary care. Inadequate standards in training and curriculum development can contribute to poor recruitment and retention of doctors in primary care. This study aimed to investigate: 1) the satisfaction level of doctors regarding vocational training in family medicine and associated demographics; and 2) the satisfaction level of doctors regarding their family medicine career and associated factors. METHOD: This is a cross sectional study of all family medicine physicians across all government-funded primary care clinics (GOPCs). The study questionnaire consisted of items from a standardized and validated physician survey named the Physician Worklife Survey (PWS) (Konrad et al., Med Care, 1999). We selected three scales (7 items) relating to global job satisfaction, global career satisfaction and global specialty (family medicine) satisfaction with additional items on training and demographics. All significant variables in bivariate analyses were further examined using stepwise logistic regression. RESULTS: Out of 424 eligible family medicine physicians, 368 physicians successfully completed the questionnaire. The response rate was 86.8%. Most participants were male (52.6%), were aged between 35 and 44 years (55.5%), were FM specialists (42.4%), graduated locally (86.2%), and had postgraduate qualifications. Eighty-two percent (82%) of participants were satisfied with their training. Having autonomy and protected time for training were associated with satisfaction with FM training. Satisfaction with family medicine as a career was correlated with physicians' satisfaction with their current job. Doctors who did not enroll in training (p < 0.001) and physicians who were older (p = 0.023) were significantly less satisfied. Stepwise multivariate regression showed that doctors who subjectively believed their training as "broad and in depth' had higher career satisfaction (p < 0.001). CONCLUSION: Overall, the satisfaction level of physicians on current family medicine training in Hong Kong was high. Having autonomy and protected time for training is associated with higher training satisfaction levels. Perceiving FM training as "broad and in-depth" is associated with higher family medicine career satisfaction.

Injuries and envenomation by exotic pets in Hong Kong.

INTRODUCTION: Exotic pets are increasingly popular in Hong Kong and include fish, amphibians, reptiles, and arthropods. Some of these exotic animals are venomous and may cause injuries to and envenomation of their owners. The clinical experience of emergency physicians in the management of injuries and envenomation by these exotic animals is limited. We reviewed the clinical features and outcomes of injuries and envenomation by exotic pets recorded by the Hong Kong Poison Information Centre. METHODS: We retrospectively retrieved and reviewed cases of injuries and envenomation by exotic pets recorded by the Hong Kong Poison Information Centre from 1 July 2008 to 31 March 2017. RESULTS: There were 15 reported cases of injuries and envenomation by exotic pets during the study period, including snakebite (n=6), fish sting (n=4), scorpion sting (n=2), lizard bite (n=2), and turtle bite (n=1). There were two cases of major effects from the envenomation, seven cases with moderate effects, and six cases with mild effects. All major effects were related to venomous snakebites. There were no mortalities. CONCLUSION: All human injuries from exotic pets arose from reptiles, scorpions, and fish. All cases of major envenomation were inflicted by snakes.

Beta blockers and improved progression-free survival in patients with advanced HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study.

BACKGROUND: Recent retrospective studies suggest that beta-adrenergic blocking drugs (BB) are associated with improved outcomes in patients with a range of cancers. Although limited and discordant data suggest that BB may increase overall survival (OS) in localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC. PATIENTS AND METHODS: To explore the association between BB use and BC outcomes, we retrospectively reviewed ROSE/TRIO-012, a double-blinded, multinational phase III trial that randomized 1144 patients with HER2-negative advanced BC to first-line docetaxel in combination with ramucirumab or placebo. We compared progression-free survival (PFS), OS, overall response rate, and clinical benefit rate in patients who received BB to those who did not. RESULTS: 153/1144 (13%) patients received BB; 62% prior to enrolment and 38% began after enrolment. Median PFS in BB treated patients was longer than in patients who did not receive them (10.3 versus 8.3 months; HR 0.81; 95% CI 0.66-0.99; P = 0.038). Patients treated with BB only after enrolment had even higher median PFS (15.5 versus 8.3 months, P < 0.001). In the TNBC subset, median PFS was 13.0 months with BB, compared to 5.2 months without BB (HR 0.52; 95% CI 0.34-0.79; P = 0.002). The benefit of BB intake in PFS was independent of treatment-emergent hypertension (P = 0.476) but associated with treatment arm (P = 0.037). The test for interactions between BB and treatment arm was not significant (P = 0.276). No differences were seen in OS, overall response rate, or clinical benefit rate. A validation dataset analysis had consistent but less substantial improved outcomes for women with node positive operable breast cancer receiving BB in the BCIRG-005 trial. CONCLUSIONS: In this exploratory analysis, BB intake was associated with significant improvement in PFS, particularly in patients with TNBC and patients not previously exposed to BB. CLINICAL TRIAL NUMBER: NCT00703326.

Best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review.

INTRODUCTION: Hand, foot, and mouth disease continues to cause seasonal epidemics in the Asia-Pacific Region. Since the current Enterovirus 71 vaccines do not provide cross-protection for all Enterovirus species that cause hand, foot, and mouth disease, there is an urgent need to identify appropriate detection tools and best practice to prevent its transmission and to effectively control its outbreaks. This systematic review aimed to identify characteristics of outbreak and assess the impact and effectiveness of detection tools and public health preventive measures to interrupt transmission. The findings will be used to recommend policy on the most effective responses and interventions in Hong Kong to effectively minimise and contain the spread of the disease within childcare facilities. METHODS: We searched the following databases for primary studies written in Chinese or English: MEDLINE, EMBASE, Global Health, WHO Western Pacific Region Index Medicus database, China National Knowledge Infrastructure Databases, and Chinese Scientific Journals Database. Studies conducted during or retrospective to outbreaks of hand, foot, and mouth disease caused by Enterovirus 71 from 1980 to 2012 within childcare facilities and with a study population of 0 to 6 years old were included. RESULTS: Sixteen studies conducted on outbreaks in China showed that hand, foot, and mouth disease spread rapidly within the facility, with an outbreak length of 4 to 46 days, especially in those with delayed notification (after 24 hours) of clustered outbreak (with five or more cases discovered within the facility) to the local Center for Disease Control and Prevention and delayed implementation of a control response. The number of classes affected ranged from 1 to 13, and the attack rate for children ranged from 0.97% to 28.18%. CONCLUSIONS: Communication between key stakeholders about outbreak confirmation, risk assessment, and surveillance should be improved. Effective communication facilitates timely notification (within 24 hours) of clustered outbreaks to a local Center for Disease Control and Prevention. Timely implementation of a control response is effective in minimising incidence and length of an outbreak in childcare facilities. The government should provide incentives for childcare facilities to train infection control specialists who can serve as the first contact, knowledge, and communication points, as well as facilitate exchange of information and provision of support across stakeholders during a communicable disease epidemic.

Comparison of green pit viper and Agkistrodon halys antivenom in inhibition of coagulopathy due to Trimeresurus albolabris venom: an in-vitro study using human plasma.

INTRODUCTION: There are two antivenoms that may be administered in Hong Kong following a bite by Trimeresurus albolabris: the green pit viper antivenom from the Thai Red Cross Society in Thailand and the Agkistrodon halys antivenom from the Shanghai Institute of Biological Products in China. Both are recommended by the Central Coordinating Committee of Accident and Emergency Services of the Hospital Authority for treating patients with a bite by Trimeresurus albolabris. The choice of which antivenom to use is based on physician preference. This study aimed to compare the relative efficacy of the two antivenoms. METHODS: This in-vitro experimental study was carried out by a wildlife conservation organisation and a regional hospital in Hong Kong. Human plasma from 40 adult health care worker volunteers was collected. The Trimeresurus albolabris venom was added to human plasma and the mixture was assayed after incubation with each antivenom (green pit viper and Agkistrodon halys) using saline as a control. Fibrinogen level and clotting time in both antivenom groups were studied. RESULTS: The mean fibrinogen level was elevated from 0 g/L to 2.86 g/L and 1.11 g/L after the addition of green pit viper antivenom and Agkistrodon halys antivenom, respectively. When mean clotting time was measured, the value was 6.70 minutes in the control, prolonged to more than 360 minutes by green pit viper antivenom and to 19.06 minutes by Agkistrodon halys antivenom. CONCLUSIONS: Green pit viper antivenom was superior to Agkistrodon halys antivenom in neutralisation of the thrombin-like and hypofibrinogenaemic activities of Trimeresurus albolabris venom.

Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies.

The nuclear export receptor, Exportin 1 (XPO1), mediates transport of growth-regulatory proteins, including tumor suppressors, and is overactive in many cancers, including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and aggressive lymphomas. Oral selective inhibitor of nuclear export (SINE) compounds that block XPO1 function were recently identified and hold promise as a new therapeutic paradigm in many neoplasms. One of these compounds, KPT-330 (selinexor), has made progress in Phase I/II clinical trials, but systemic toxicities limit its administration to twice-per-week and requiring supportive care. We designed a new generation SINE compound, KPT-8602, with a similar mechanism of XPO1 inhibition and potency but considerably improved tolerability. Efficacy of KPT-8602 was evaluated in preclinical animal models of hematological malignancies, including CLL and AML. KPT-8602 shows similar in vitro potency compared with KPT-330 but lower central nervous system penetration, which resulted in enhanced tolerability, even when dosed daily, and improved survival in CLL and AML murine models compared with KPT-330. KPT-8602 is a promising compound for further development in hematological malignancies and other cancers in which upregulation of XPO1 is seen. The wider therapeutic window of KPT-8602 may also allow increased on-target efficacy leading to even more efficacious combinations with other targeted anticancer therapies.

Domestic dog health worsens with socio-economic deprivation of their home communities.

Dogs play an important role in infectious disease transmission as reservoir hosts of many zoonotic and wildlife pathogens. Nevertheless, unlike wildlife species involved in the life cycle of pathogens, whose health status might be a direct reflection of their fitness and competitive abilities, dog health condition could be sensitive to socio-economic factors impacting the well-being of their owners. Here, we compare several dog health indicators in three rural communities of Panama with different degrees of socio-economic deprivation. From a total of 78 individuals, we collected blood and fecal samples, and assessed their body condition. With the blood samples, we performed routine hematologic evaluation (complete blood counts) and measured cytokine levels (Interferon-γ and Interleukin-10) through enzyme-linked immunosorbent assays. With the fecal samples we diagnosed helminthiases. Dogs were also serologically tested for exposure to Trypanosoma cruzi and canine distemper virus, and molecular tests were done to assess T. cruzi infection status. We found significant differences between dog health measurements, pathogen prevalence, parasite richness, and economic status of the human communities where the dogs lived. We found dogs that were less healthy, more likely to be infected with zoonotic pathogens, and more likely to be seropositive to canine distemper virus in the communities with lower economic status. This study concludes that isolated communities of lower economic status in Panama may have less healthy dogs that could become major reservoirs in the transmission of diseases to humans and sympatric wildlife.

Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes.

Development of lipid-based adjuvant formulations to enhance the immunogenicity of recombinant vaccine antigens is a focus of modern vaccine research. Characterizing interactions between vaccine antigens and formulation excipients is important for establishing compatibility between the different components and optimizing vaccine stability and potency. Cryogenic transmission electron microscopy (TEM) is a highly informative analytical technique that may elucidate various aspects of protein- and lipid-based structures, including morphology, size, shape, and phase structure, while avoiding artifacts associated with staining-based TEM. In this work, cryogenic TEM is employed to characterize a recombinant tuberculosis vaccine antigen, an anionic liposome formulation, and antigen-liposome interactions. By performing three-dimensional tomographic reconstruction analysis, the formation of a population of protein-containing flattened liposomes, not present in the control samples, was detected. It is shown that cryogenic TEM provides unique information regarding antigen-liposome interactions not detectable by light-scattering-based methods. Employing a suite of complementary analytical techniques is important to fully characterize interactions between vaccine components.

Voiding urosonography with second-generation ultrasound contrast versus micturating cystourethrography in the diagnosis of vesicoureteric reflux.

Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.

Highly efficient beamline and spectrometer for inelastic soft X-ray scattering at high resolution.

The design, construction and commissioning of a beamline and spectrometer for inelastic soft X-ray scattering at high resolution in a highly efficient system are presented. Based on the energy-compensation principle of grating dispersion, the design of the monochromator-spectrometer system greatly enhances the efficiency of measurement of inelastic soft X-rays scattering. Comprising two bendable gratings, the set-up effectively diminishes the defocus and coma aberrations. At commissioning, this system showed results of spin-flip, d-d and charge-transfer excitations of NiO. These results are consistent with published results but exhibit improved spectral resolution and increased efficiency of measurement. The best energy resolution of the set-up in terms of full width at half-maximum is 108 meV at an incident photon energy tuned about the Ni L3-edge.

Environmental variabilities and the distribution of octocorals and black corals in Hong Kong.

A recent comprehensive survey covering 125 sites in Hong Kong waters recorded 29 soft coral species in 14 genera, 38 species of gorgonians in 19 genera and six species of black corals in two genera. Environmental variabilities based on water quality data collected by Hong Kong Environmental Protection Department were analyzed using multivariate statistics to find variables that are significantly correlated with coral distribution patterns. Eleven water quality zones with similar environmental variabilities were recognized, which could further be classified into five groups, namely Inner Bay, Outer Bay, Eastern, Western and Southern waters. LINKTREE analysis provided an overall trend indicating the importance of salinity, sediment and nutrient loadings in affecting octocoral and black coral distribution from west to east of Hong Kong waters, and from inner to outer bays. Furthermore, water turbidity and wave exposure could also affect the coral distribution patterns from north, northeast to southern waters.

In vitro evaluation of TLR4 agonist activity: formulation effects.

Effective in vitro evaluation of vaccine adjuvants would allow higher throughput screening compared to in vivo studies. However, vaccine adjuvants comprise a wide range of structures and formulations ranging from soluble TLR agonists to complex lipid-based formulations. The effects of formulation parameters on in vitro bioactivity assays and the correlations with in vivo adjuvant activity is not well understood. In the present work, we employ the Limulus amebocyte lysate assay and a human macrophage cellular cytokine production assay to demonstrate the differences in in vitro bioactivity of four distinct formulations of the synthetic TLR4 agonist GLA: an aqueous nanosuspension (GLA-AF), an oil-in-water emulsion (GLA-SE), a liposome (GLA-LS), and an alum-adsorbed formulation (GLA-Alum). Furthermore, we demonstrate the importance of the localization of GLA on in vitro potency. By comparing to previous published reports on the in vivo bioactivity of these GLA-containing formulations, we conclude that the most potent activators of the in vitro systems may not be the most potent in vivo adjuvant formulations. Furthermore, we discuss the formulation considerations which should be taken into account when interpreting data from in vitro adjuvant activity assays.

Optimizing manufacturing and composition of a TLR4 nanosuspension: physicochemical stability and vaccine adjuvant activity.

BACKGROUND: Nanosuspensions are an important class of delivery system for vaccine adjuvants and drugs. Previously, we developed a nanosuspension consisting of the synthetic TLR4 ligand glucopyranosyl lipid adjuvant (GLA) and dipalmitoyl phosphatidylcholine (DPPC). This nanosuspension is a clinical vaccine adjuvant known as GLA-AF. We examined the effects of DPPC supplier, buffer composition, and manufacturing process on GLA-AF physicochemical and biological activity characteristics. RESULTS: DPPC from different suppliers had minimal influence on physicochemical and biological effects. In general, buffered compositions resulted in less particle size stability compared to unbuffered GLA-AF. Microfluidization resulted in rapid particle size reduction after only a few passes, and 20,000 or 30,000 psi processing pressures were more effective at reducing particle size and recovering the active component than 10,000 psi. Sonicated and microfluidized batches maintained good particle size and chemical stability over 6 months, without significantly altering in vitro or in vivo bioactivity of GLA-AF when combined with a recombinant malaria vaccine antigen. CONCLUSIONS: Microfluidization, compared to water bath sonication, may be an effective manufacturing process to improve the scalability and reproducibility of GLA-AF as it advances further in the clinical development pathway. Various sources of DPPC are suitable to manufacture GLA-AF, but buffered compositions of GLA-AF do not appear to offer stability advantages over the unbuffered composition.

Observation of new Rydberg series in the many-electron transition region of N2.

Fluorescence excitation spectra produced through photoexcitation of N(2) using synchrotron radiation in the spectral region between 50 and 62.5 nm have been obtained with a resolution of 0.004 nm. A broadband detector (in the 115-180 nm region) was employed to monitor fluorescence originated from neutral excited atomic nitrogen fragments which are produced through direct dissociation processes and predissociation from the well-known many-electron excited Rydberg states. We have identified a new Rydberg series (2 (2)Π(g)) 4sσ, a better resolved Rydberg (D (2)Π(g)) npσ series, and also the prominent Codling series converging to the D (2)Π(g), and C (2)Σ(u)(+) states of N(2)(+), respectively. By normalizing our relative fluorescence intensities to previously measured absolute fluorescence cross-section data we obtain the cross-section data of undispersed fluorescence in the 115-180 nm region. The fluorescence quantum yields for the present photodissociative excitation processes are found to be less than 0.05. The present results may provide important data for our understanding of competitions among the various decay channels of the many-electron transition states of N(2).

Green pit viper antivenom from Thailand and Agkistrodon halys antivenom from China compared in treating Cryptelytrops albolabris envenomation of mice.

OBJECTIVE: To compare the relative efficacy of the green pit viper antivenom from Thailand and Agkistrodon halys antivenom from China. DESIGN. In-vivo experimental study. SETTING: A wildlife conservation organisation, a university, a poison information centre, and a regional hospital in Hong Kong. MAIN OUTCOME MEASURES: Pre- and post-antivenom lethal dose 50 (LD50) of the Cryptelytrops albolabris venom, median effective dose (ED50) of green pit viper antivenom and Agkistrodon halys antivenom against a lethal dose of the venom. SUBJECTS. Adult mice. RESULTS: The intraperitoneal LD50 of the venom from locally caught Cryptelytrops albolabris was 0.14 microL. After post-exposure treatment with 10 microL of antivenom, it was elevated to 0.36 microL and 0.52 microL by the green pit viper antivenom and the Agkistrodon halys antivenom, respectively. The ED50 was 32.02 microL for green pit viper antivenom and 6.98 microL for Agkistrodon halys antivenom. Both green pit viper antivenom and Agkistrodon halys antivenom ameliorated the lethality of Cryptelytrops albolabris venom in mice. CONCLUSION: The overall superior neutralisation capacity of Agkistrodon halys antivenom over green pit viper antivenom may be related to the geographic proximity of the venoms used for antivenom preparation. The results point towards the need for further comparison of the two antivenoms on protein or immunoglobulin weight basis, and with respect to non-lethal clinically significant toxicities.