We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease “hot spots.” Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.

IntroductionThere is an outbreak of COVID-19 worldwide. As there is no effective therapy or vaccine yet, rigorous implementation of traditional public health measures such as isolation and quarantine remains the most effective tool to control the outbreak. When an asymptomatic individual with COVID-19 exposure is being quarantined, it is necessary to perform temperature and symptom surveillance. As such surveillance is intermittent in nature and highly dependent on self-discipline, it has limited effectiveness. Advances in biosensor technologies made it possible to continuously monitor physiological parameters using wearable biosensors with a variety of form factors.ObjectiveTo explore the potential of using wearable biosensors to continuously monitor multidimensional physiological parameters for early detection of COVID-19 clinical progression.MethodThis randomised controlled open-labelled trial will involve 200–1000 asymptomatic subjects with close COVID-19 contact under mandatory quarantine at designated facilities in Hong Kong. Subjects will be randomised to receive a remote monitoring strategy (intervention group) or standard strategy (control group) in a 1:1 ratio during the 14 day-quarantine period. In addition to fever and symptom surveillance in the control group, subjects in the intervention group will wear wearable biosensors on their arms to continuously monitor skin temperature, respiratory rate, blood pressure, pulse rate, blood oxygen saturation and daily activities. These physiological parameters will be transferred in real time to a smartphone application called Biovitals Sentinel. These data will then be processed using a cloud-based multivariate physiology analytics engine called Biovitals to detect subtle physiological changes. The results will be displayed on a web-based dashboard for clinicians’ review. The primary outcome is the time to diagnosis of COVID-19.Ethics and disseminationEthical approval has been obtained from institutional review boards at the study sites. Results will be published in peer-reviewed journals.

Background: SARS-CoV-2 infection is associated with myocardial injury, but there is a paucity of experimental platforms for the condition.Methods and Results: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected by SARS-CoV-2 for 3 days ceased beating and exhibited cytopathogenic changes with reduced viability. Active viral replication was evidenced by an increase in supernatant SARS-CoV-2 and the presence of SARS-CoV-2 nucleocaspid protein within hiPSC-CMs. Expressions of BNP, CXCL1, CXCL2, IL-6, IL-8 and TNF-α were upregulated, while ACE2 was downregulated. Conclusions:Our hiPSC-CM-based in-vitro SARS-CoV-2 myocarditis model recapitulated the cytopathogenic effects and cytokine/ chemokine response. It could be exploited as a drug screening platform.

IntroductionCurrent international guidelines recommend non-vitamin K oral anticoagulants (NOACs) for stroke prevention among patients with non-valvular atrial fibrillation (AF) at significant ischaemic stroke risk given the superior safety and comparable efficacy of NOACs over warfarin. Nonetheless, the safety and effectiveness of NOACs have not been evaluated in patients with AF with underlying moderate or severe mitral stenosis (MS), hence the recommended stroke prevention strategy remains warfarin therapy.Method and analysisMS remains disproportionately prevalent in Asian countries compared with the developed countries. This prospective, randomised, open-label trial with blinded endpoint adjudication aims to evaluate the safety and efficacy of dabigatran for stroke prevention in AF patients with moderate or severe MS. Patients with AF aged ≥18 years with moderate or severe MS not planned for valvular intervention in the coming 12 months will be randomised in a 1:1 ratio to receive dabigatran 110 mg or 150 mg two times per day or warfarin with international normalised ratio 2–3 in an open-label design. Patients with estimated creatinine clearance <30 mL/min, or with a concomitant indication for antiplatelet therapy will be excluded. The primary outcome is a composite of stroke and systemic embolism. Secondary outcomes are ischaemic stroke, systemic embolism, haemorrhagic stroke, intracranial haemorrhage, major bleeding and death. The estimated required sample size is approximately 686 participants.Ethics and disseminationThe study protocol has been approved by the Institutional Review Board of the University of Hong Kong and Hong Kong West Cluster, Hospital Authority, Hong Kong for Fung Yiu King Hospital, Grantham Hospital, Queen Mary Hospital and Tung Wah Hospital in Hong Kong. Results will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov Registry (NCT04045093); pre-results.

BackgroundLittle is known about the impact of the provision of handheld point-of-care ultrasound (POCUS) devices on physical examination skills of medical students.MethodsWe describe an educational initiative that comprised a POCUS workshop followed by allocation of a POCUS device to medical students for use over the subsequent 8 weeks. They were encouraged to scan patients and correlate their physical examination findings. A mobile instant messaging group discussion platform was set to provide feedback from instructors. Physical examination skills were assessed by means of clinical examination.Results210 final-year medical students from the University of Hong Kong participated in the programme. 46.3% completed the end of programme electronic survey: 74.6% enjoyed using the POCUS device, 50.0% found POCUS useful to validate physical examination findings and 47.7% agreed that POCUS increased their confidence with physical examination. 93.9% agreed that the programme should be incorporated into the medical curriculum and 81.9% would prefer keeping the device for longer time from 16 weeks (45.6%) to over 49 weeks (35.3%). Medical students who participated in the POCUS programme had a higher mean score for abdominal examination compared with those from the previous academic year with no POCUS programme (3.65±0.52 vs 3.21±0.80, p=0.014), but there was no statistically significant difference in their mean score for cardiovascular examination (3.62±0.64 vs 3.36±0.93, p=0.203).ConclusionThe POCUS programme that included provision of a personal handheld POCUS device improved students’ attitude, confidence and ability to perform a physical examination.

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Background Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. Objective To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019. Methods We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R0 was obtained from previous clinical studies. Results Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary, apart from having complete border closure. Conclusions Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.

Despite the extraordinary success of immune checkpoint inhibitors (ICIs) in cancer treatment, their use is associated with a high incidence of immune-related adverse events (IRAEs), resulting from therapy-related autoimmunity against various target organs. ICI-induced myocarditis is one of the most severe forms of IRAE, which is associated with risk of hemodynamic compromise and mortality. Despite increasing recognition and prompt treatment by clinicians, there remain significant gaps in knowledge regarding the pathophysiology, diagnosis and treatment of ICI-induced myocarditis. As the newly emerged disease entity is relatively rare, it is challenging for researchers to perform studies involving patients at scale. Alternatively, mouse models have been developed to facilitate research understanding of the pathogenesis of ICI-induced myocarditis and drug discovery. Transgenic mice with immune checkpoint genes knocked out allow induction of myocarditis in a highly reproducible manner. On the other hand, it has not been possible to induce ICI-induced myocarditis in wild type mice by injecting ICIs monotherapy alone. Additional interventions such as combinational ICI, tumor inoculation, cardiac sarcomere immunization, or cardiac irradiation are necessary to mimic the underlying pathophysiology in human cancer patients and to induce ICI-induced myocarditis successfully. This review focuses on the immunopathogenesis of ICI-induced myocarditis, drawing insights from human studies and animal models, and discusses the potential implications for treatment.