Hospital Burden of Chronic Obstructive Pulmonary Disease in Hong Kong - The Trend from 2006 to 2014.

Background: Chronic obstructive pulmonary disease (COPD) is a common cause for hospital admission. This study aims to review the hospital burden of COPD in Hong Kong (HK) and the trend from year 2006 to 2014. Methods: A multi-center, retrospective study of the characteristics of COPD patients discharged from the public hospitals of HK from year 2006 to 2014. Anonymized data retrieval and analysis were performed. The demographic data of the subjects, use of health-care resources, ventilatory support, medications used and mortality of the subjects were analyzed. Results: Total patient headcount (HC) and admission number reduced from 10,425 and 23,362 in year 2006 to 9613 and 19,771, respectively, in 2014. There was a progressive reduction of female COPD HC from 2193 (21%) in year 2006 to 1517 (16%) in 2014. The utilization of non-invasive ventilation (NIV) increased rapidly and peaked in 2010 (29%) and decreased thereafter. There was a rapid increase in the prescription of long-acting bronchodilators (from 15% to 64%). COPD and pneumonia were the top causes of death, but death due to pneumonia was rapidly increasing while death due to COPD was progressively decreasing over the period. Conclusion: COPD HC and admission number (particularly in female patients) decreased progressively from year 2006 to 2014. There was also a decreasing trend of severity of disease as reflected by lower NIV use (after year 2010) and lower mortality rate due to COPD. Reduced smoking prevalence and tuberculosis (TB) notification rate in the community in the past might have reduced the incidence and severity of COPD and the hospital burden of disease. We observed an increasing trend of mortality due to pneumonia in COPD patients. Appropriate and timely vaccination programs are recommended for COPD patients as in the general elderly population.

A multicenter retrospective cohort study on predicting the risk for amiodarone pulmonary toxicity.

BACKGROUND: Amiodarone is one of the most commonly used anti-arrhythmic agents. Amiodarone pulmonary toxicity is a potentially fatal adverse effect associated with amiodarone use. Previous studies on the epidemiology and risk factors for amiodarone pulmonary toxicity showed diverse results. METHODS: A multicenter retrospective cohort study was conducted to identify clinic-epidemiologic markers associated with amiodarone pulmonary toxicity for development of a prediction rule. Patients taking amiodarone who were managed in 3 centres in Hong Kong from 2005 to 2015 were included in this study. Penalized logistic regression was used to model the outcome as it is rare. RESULTS: A total of 34 cases with amiodarone pulmonary toxicity were identified among 1786 patients taking amiodarone for at least 90 days from 2005 to 2015. The incidence of amiodarone pulmonary toxicity was estimated to be 1.9%. The risk factors for amiodarone pulmonary toxicity included advanced age (OR 1.047, 95% CI 1.010-1.085, p = 0.013), ventricular arrhythmia (OR 2.703, 95% CI 1.053-6.935, p = 0.039), underlying lung disease (OR 2.511, 95% CI 1.146-5.501, p = 0.021) and cumulative dose of amiodarone (OR 4.762, 95% CI 1.310-17.309 p = 0.018). CONCLUSIONS: The incidence of amiodarone pulmonary toxicity in Chinese patients in Hong Kong is estimated to be 1.9% in this study. Age, underlying lung disease, ventricular arrhythmia and cumulative dose of amiodarone are associated with the development of amiodarone pulmonary toxicity. A prediction rule was developed to inform the risk of developing amiodarone pulmonary toxicity.

Mass Screening Is Associated with Low Rates of Acute Kidney Injury among COVID-19 Patients in Hong Kong.

INTRODUCTION: Renal involvement in COVID-19 is less well characterized in settings with vigilant public health surveillance, including mass screening and early hospitalization. We assessed kidney complications among COVID-19 patients in Hong Kong, including the association with risk factors, length of hospitalization, critical presentation, and mortality. METHODS: Linked electronic records of all patients with confirmed COVID-19 from 5 major designated hospitals were extracted. Duplicated records due to interhospital transferal were removed. Primary outcome was the incidence of in-hospital acute kidney injury (AKI). Secondary outcomes were AKI-associated mortality, incident renal replacement therapy (RRT), intensive care admission, prolonged hospitalization and disease course (defined as >90th percentile of hospitalization duration [35 days] and duration from symptom onset to discharge [43 days], respectively), and change of estimated glomerular filtration rate (GFR). Patients were further stratified into being symptomatic or asymptomatic. RESULTS: Patients were characterized by young age (median: 38.4, IQR: 28.4-55.8 years) and short time (median: 5, IQR: 2-9 days) from symptom onset to admission. Among the 591 patients, 22 (3.72%) developed AKI and 4 (0.68%) required RRT. The median time from symptom onset to in-hospital AKI was 15 days. AKI increased the odds of prolonged hospitalization and disease course by 2.0- and 3.5-folds, respectively. Estimated GFR 24 weeks post-discharge reduced by 7.51 and 1.06 mL/min/1.73 m2 versus baseline (upon admission) in the AKI and non-AKI groups, respectively. The incidence of AKI was comparable between asymptomatic (4.8%, n = 3/62) and symptomatic (3.7%, n = 19/519) patients. CONCLUSION: The overall rate of AKI among COVID-19 patients in Hong Kong is low, which could be attributable to a vigilant screening program and early hospitalization. Among patients who developed in-hospital AKI, the duration of hospitalization is prolonged and kidney function impairment can persist for up to 6 months post-discharge. Mass surveillance for COVID-19 is warranted in identifying asymptomatic subjects for earlier AKI management.

Development and validation of risk prediction models for COVID-19 positivity in a hospital setting.

OBJECTIVES: To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. METHODS: Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer-Lemeshow (H-L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880-0.941]). The second model developed has the same variables except contact history (AUC = 0.880 [CI = 0.844-0.916]). Both were externally validated on the H-L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. CONCLUSION: Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.

Posterior Oropharyngeal Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. METHODS: The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between 1 February 2020 and 15 April 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. RESULTS: A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 nasopharyngeal specimens (NPsp). Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% confidence interval [CI] 55.1-67.6%) and 53.3% (95% CI 46.8-59.6%). The overall, negative and positive percent agreement were 76.0% (95% CI 70.2-80.9%), 65.4% (95% CI 55.5-74.2%), 85.2% (95% CI 77.4-90.8%). Better positive percent agreement was observed in POPS-NPsp obtained within 7 days (96.6%, 95% CI 87.3-99.4%) compared with after 7 days of symptom onset (75.0%, 95% CI 61.4-85.2%). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to -14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the 2 specimen types. CONCLUSIONS: POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.

SARS-CoV-2 shedding and seroconversion among passengers quarantined after disembarking a cruise ship: a case series.

BACKGROUND: A cruise ship is a closed-off environment that simulates the basic functioning of a city in terms of living conditions and interpersonal interactions. Thus, the Diamond Princess cruise ship, which was quarantined because of an onboard outbreak of COVID-19 in February, 2020, provides an opportunity to define the shedding pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient antibody responses before and after the onset of symptoms. METHODS: We recruited adult (≥18 years) passengers from Hong Kong who had been on board the Diamond Princess cruise ship docked in Yokohama, Japan in February, 2020. All participants had been found to be negative for SARS-CoV-2 by RT-PCR 4 days before disembarking and were transferred to further quarantine in a public estate in Hong Kong, where they were recruited. Participants were prospectively screened by quantitative RT-PCR (RT-qPCR) of nasopharyngeal and throat swabs, and serum IgG and IgM against internal nucleoprotein and the surface spike receptor-binding protein (RBD) of SARS-CoV-2 at baseline (upon entering quarantine) and on days 4, 8, and 12 of quarantine. FINDINGS: On Feb 22, 2020, 215 adults were recruited, of whom nine (4%; 95% CI 2-8) were positive for SARS-CoV-2 by RT-qPCR or serology and were hospitalised. Of these nine patients, nasopharyngeal swab RT-qPCR was positive in eight patients (89%; 57-99) at baseline. All nine patients were positive for anti-RBD IgG by day 8. Eight (89%; 57-99) were simultaneously positive for nasopharyngeal swab RT-PCR and anti-RBD IgG. One patient who was positive for anti-RBD IgG and had a negative viral load had multifocal peripheral ground-glass changes on high-resolution CT that were typical of COVID-19. Five patients (56%; 27-81) with ground-glass changes on high-resolution CT were found to have higher anti-nucleoprotein-IgG OD values on day 8 and 12 and anti-RBD IgG OD value on day 12 than patients without ground-glass changes. Six (67%; 35-88) patients remained asymptomatic throughout the 14-day quarantine period. INTERPRETATION: Patients with COVID-19 can develop asymptomatic lung infection with viral shedding and those with evidence of pneumonia on imaging tend to have an increased antibody response. Positive IgG or IgM confirmed infection of COVID-19 in both symptomatic and asymptomatic patients. A combination of RT-PCR and serology should be implemented for case finding and contact tracing to facilitate early diagnosis, prompt isolation, and treatment. FUNDING: Shaw Foundation Hong Kong; Sanming-Project of Medicine (Shenzhen); High Level-Hospital Program (Guangdong Health Commission).

Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial.

BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

Comorbidities, mortality, and management of chronic obstructive pulmonary disease patients who required admissions to public hospitals in Hong Kong - computerized data collection and analysis.

Background: COPD is a common cause for hospital admission. Conventional studies of the epidemiology of COPD involved large patient number and immense resources and were difficult to be repeated. The present study aimed at assessing the utilization of a computerized data management system in the collection and analysis of the epidemiological and clinical data of a large COPD cohort in Hong Kong (HK). Patients and methods: It was a computerized, multicenter, retrospective review of the characteristics of patients discharged from medical departments of the 16 participating hospitals with the primary discharge diagnosis of COPD in 1 year (2012). Comparison was made between the different subgroups in the use of medications, ventilatory support, and other health care resources. The mortality of the subjects in different subgroups was traced up to December 31, 2014. The top 10 causes of death were analyzed. Results: In total, 9,776 subjects (82.6% men, mean age = 78 years) were identified. Of the 1,918 subjects with lung function coding, 85 (4.4%), 488 (25.5%), 808 (42.1%), and 537 (28.0%) subjects had the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 2, 3, and 4 classes, respectively. Patients with higher GOLD classes had higher number of hospital admissions, longer hospital stay, increased usage of noninvasive mechanical ventilation (NIV), combinations of long-acting bronchodilators, and higher mortality. Of the 9,776 subjects, 2,278 (23.3%) received NIV, but invasive mechanical ventilation was uncommon (134 of 9,776 subjects [1.4%]); 4,427 (45.3%) subjects had died by the end of 2014. The top causes of death were COPD, pneumonia, lung cancer, and other malignancies. Conclusion: Patients admitted to hospitals for COPD in HK had significant comorbidities, mortality, and imposed heavy burden on health care resources. It is possible to collect and analyze data of a large COPD cohort through a computerized system. Suboptimal coding of lung function results was observed, and underutilization of long-acting bronchodilators was common.

Left ventricular performance in patients with severe acute respiratory syndrome: a 30-day echocardiographic follow-up study.

BACKGROUND: Severe acute respiratory syndrome (SARS) is characterized by an overaggressive immune response. Myocardial performance may be impaired in cytokine-mediated immune reactions. METHODS AND RESULTS: Forty-six patients with established clinical diagnosis of SARS were studied prospectively. Transthoracic echocardiographic examinations were done at the acute stage of infection and 30 days later. Among them, 14 patients required mechanical ventilation. The clinical course, laboratory data, SARS-CoV antibody titers, and results of reverse transcriptase-polymerase chain reaction were studied. Significantly higher left ventricular index of myocardial performance (IMP) (0.42+/-0.13 versus 0.33+/-0.09, P<0.001), longer isovolumic relaxation time (102.9+/-15.7 versus 81.6+/-14.7 ms, P<0.001), lower flow propagation velocity (69.6+/-15.7 versus 83.8+/-19.7 cm/s, P=0.011), and Doppler-derived cardiac output (4.69+/-1.01 versus 5.49+/-1.04 L/min, P<0.001) were observed during acute infection when compared with those at 30 days. No significant valvular disease or pulmonary hypertension was found. At baseline, a lower mean left ventricular ejection fraction (LVEF) (65.3+/-12.8% versus 71.4+/-5.7%, P=0.03) and a higher mean IMP (0.51+/-0.11 versus 0.40+/-0.12, P=0.017) were found in patients who required mechanical ventilation. A decrease in LVEF correlated moderately with an elevated lactate dehydrogenase level (r=-0.605, P<0.001), whereas a higher IMP correlated weakly with an increase in creatine kinase level (r=0.38, P=0.016). Histological examination of the heart in the patient with the lowest EF (30.2%) revealed no interstitial lymphocytic infiltrate or myocyte necrosis. CONCLUSIONS: Subclinical diastolic impairment without systolic involvement was observed in patients with SARS. This impairment may be reversible on clinical recovery.