Association of nirmatrelvir-ritonavir with post-acute sequelae and mortality in patients admitted to hospital with COVID-19: a retrospective cohort study.

BACKGROUND: Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong. METHODS: This retrospective cohort study used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. Patients aged 18 years and older who tested positive for SARS-CoV-2 between March 11, 2022, and Oct 10, 2023, and who were admitted to hospital with COVID-19 were included. The treatment group included patients prescribed nirmatrelvir-ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir-ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. Standardised mortality ratio weights were applied to balance covariates, and Cox proportional hazards regression was used to investigate the relationship between nirmatrelvir-ritonavir and outcomes. FINDINGS: 136 973 patients were screened for inclusion, among whom 50 055 were eligible and included in the analysis (24 873 [49·7%] were female and 25 182 [50·3%] were male). 15 242 patients were prescribed nirmatrelvir-ritonavir during acute COVID-19 and 23 756 patients were included in the control group; 11 057 patients did not meet our definition for the exposed and unexposed groups. Patients were followed up for a median of 393 days (IQR 317-489). In the nirmatrelvir-ritonavir group compared with the control group, there was a significantly lower hazard of post-acute inpatient death (hazard ratio 0·62 [95% CI 0·57-0·68]; p<0·0001), congestive heart failure (0·70 [0·58-0·85]; p=0·0002), atrial fibrillation (0·63 [0·52-0·76]; p<0·0001), coronary artery disease (0·71 [0·59-0·85]; p=0·0002), chronic pulmonary disease (0·68 [0·54-0·86]; p=0·0011), acute respiratory distress syndrome (0·71 [0·58-0·86]; p=0·0007), interstitial lung disease (0·17 [0·04-0·75]; p=0·020), and end-stage renal disease (0·37 [0·18-0·74]; p=0·0049). There was no evidence indicating difference between the groups in deep vein thrombosis, seizure, anxiety, post-traumatic stress disorder, acute kidney injury, and pancreatitis. INTERPRETATION: This study showed extended benefits of nirmatrelvir-ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. Further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae. FUNDING: Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund.

Metabolic dysfunction-associated profiles and subsequent site-specific risk of obesity-related cancers among Chinese patients with diabetes: a retrospective cohort study.

OBJECTIVES: To compare metabolic dysfunction-associated profiles between patients with diabetes who developed different obesity-related site-specific cancers and those who remained free of cancer during follow-up. DESIGN: Retrospective cohort study. SETTING: Public general outpatient clinics in Hong Kong. PARTICIPANTS: Patients with diabetes without a history of malignancy (n=391 921). PRIMARY OUTCOME MEASURES: The outcomes of interest were diagnosis of site-specific cancers (colon and rectum, liver, pancreas, bladder, kidney and stomach) during follow-up. Cox proportional hazards regression was applied to assess the associations between metabolic dysfunction and other clinical factors with each site-specific cancer. RESULTS: Each 0.1 increase in waist-to-hip ratio was associated with an 11%-35% elevated risk of colorectal, bladder and liver cancers. Each 1% increase in glycated haemoglobin was linked to a 4%-9% higher risk of liver and pancreatic cancers. While low-density lipoprotein cholesterol and triglycerides were inversely associated with the risk of liver and pancreatic cancers, high-density lipoprotein cholesterol was negatively associated with pancreatic, gastric and kidney cancers, but positively associated with liver cancer. Furthermore, liver cirrhosis was linked to a 56% increased risk of pancreatic cancer. No significant association between hypertension and cancer risk was found. CONCLUSIONS: Metabolic dysfunction-associated profiles contribute to different obesity-related cancer outcomes differentially among patients with diabetes. This study may provide evidence to help identify cancer prevention targets during routine diabetes care.

Impact of Environment on Pain among the Working Poor: Making Use of Random Forest-Based Stratification Tool to Study the Socioecology of Pain Interference.

Pain interferes with one's work and social life and, at a personal level, daily activities, mood, and sleep quality. However, little research has been conducted on pain interference and its socioecological determinants among the working poor. Noting the clinical/policy decision needs and the technical challenges of isolating the intricately interrelated socioecological factors' unique contributions to pain interference and quantifying the relative contributions of each factor in an interpretable manner to inform clinical and policy decision-making, we deployed a novel random forest algorithm to model and quantify the unique contribution of a diverse ensemble of environmental, sociodemographic, and clinical factors to pain interference. Our analyses revealed that features representing the internal built environment of the working poor, such as the size of the living space, air quality, access to light, architectural design conducive to social connection, and age of the building, were assigned greater statistical importance than other more commonly examined predisposing factors for pain interference, such as age, occupation, the severity and locations of pain, BMI, serum blood sugar, and blood pressure. The findings were discussed in the context of their benefit in informing community pain screening to target residential areas whose built environment contributed most to pain interference and informing the design of intervention programs to minimize pain interference among those who suffered from chronic pain and showed specific characteristics. The findings support the call for good architecture to provide the spirit and value of buildings in city development.

Risk of Dementia Among Patients With Diabetes in a Multidisciplinary, Primary Care Management Program.

Importance: Although poorly controlled diabetes is associated with a higher incidence of dementia, few studies have examined the association of diabetes management interventions with dementia incidence. Objective: To examine the association of receiving a multidisciplinary diabetes management program (the Risk Assessment and Management Program-Diabetes Mellitus [RAMP-DM]) that enables better glycemic control with subsequent risk of dementia incidence and the association of dementia with glycemic control. Design, Setting, and Participants: This territory-wide, retrospective, matched cohort study with more than 8 years of follow-up was conducted using electronic health care records from all the patients who used public health care services in Hong Kong from 2011 to 2019. Eligible participants included all patients with type 2 diabetes (T2D) who were managed in primary care settings. Patients who received RAMP-DM were matched in a 1:1 ratio with patients who received usual care only. Data analysis occurred from April 2023 to July 2023. Exposures: Diagnosis of T2D, hemoglobin A1C (HbA1C) level, and attendance at a general outpatient clinic or family medicine clinic. Patients received either RAMP-DM or usual care. Main Outcomes and Measures: Incidence of all-cause dementia and subtypes of dementia were compared between the RAMP-DM and usual care participants using a Cox proportional hazard model with other baseline characteristics, biomarkers, and medication history adjusted. HbA1C levels were measured as a secondary outcome. Results: Among the 55 618 matched participants (mean [SD] age, 62.28 [11.90] years; 28 561 female [51.4%]; 27 057 male [48.6%]), including the 27 809 patients in the RAMP-DM group and 27 809 patients in the usual care group, patients had been diagnosed with T2D for a mean (SD) of 5.90 (4.20) years. During a median (IQR) follow-up period of 8.4 (6.8-8.8) years, 1938 patients in the RAMP-DM group (6.97%) and 2728 patients in the usual care group (9.81%) received a diagnosis of dementia. Compared with those receiving usual care, RAMP-DM participants had a lower risk of developing all-cause dementia (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.68-0.77; P < .001), Alzheimer disease (aHR, 0.85; 95% CI, 0.76-0.96; P = .009), vascular dementia (aHR, 0.61; 95% CI, 0.51-0.73; P < .001), and other or unspecified dementia (aHR, 0.71; 95% CI, 0.66-0.77; P < .001). Compared with having a mean HbA1C level during the first 3 years after cohort entry between 6.5% and 7.5%, a higher risk of dementia incidence was detected for patients with a 3-year mean HbA1C level greater than 8.5% (aHR, 1.54; 95% CI, 1.31-1.80]), between 7.5% and 8.5% (aHR, 1.33; 95% CI, 1.19-1.48), between 6% and 6.5% (aHR, 1.17; 95% CI, 1.07-1.29), and 6% or less (aHR, 1.39; 95% CI, 1.24-1.57). Conclusions and Relevance: In this cohort study of patients with T2D, the findings strengthened evidence of an association of glycemic control with dementia incidence, and revealed that a multidisciplinary primary care diabetes management program was associated with beneficial outcomes for T2D patients against dementia and its major subtypes. A moderate glycemic control target of HbA1C between 6.5% and 7.5% was associated with lower dementia incidence.

Barriers and Facilitators to Implementing Interventions for Reducing Avoidable Hospital Readmission: Systematic Review of Qualitative Studies.

BACKGROUND: Avoidable hospital readmission is a major problem among health systems. Although there are effective peri-discharge interventions for reducing avoidable hospital readmission, successful implementation is challenging. This systematic review of qualitative studies aimed to identify barriers and facilitators to implementing peri-discharge interventions from providers' and service users' perspectives. METHODS: We searched four databases for potentially eligible qualitative studies from databases' inception to March 2020, and updated literature search for studies published between January 2020 to October 2021. Barriers and facilitators to implementing peri-discharge interventions were identified and mapped onto the Consolidated Framework for Implementation Research (CFIR) constructs. Inductive analysis of the CFIR constructs was performed to yield thematic areas that illustrated the relationship between various facilitators and barriers, generating practical insights to key implementation issues. RESULTS: Thirteen qualitative studies were included in this systematic review. Key issues were clustered in the CFIR constructs of Design Quality and Complexity of the intervention, strength of Network and Communication, being responsive to Patient Needs with sufficient Resource support, and External Incentives. The three thematic areas were rationality of the interventions, readiness and effort of multidisciplinary implementation teams, and influence of external stakeholders. Common barriers included (i) limited resources, (ii) poor communication among team members, (iii) incompatibility between the new intervention and existing work routine, (iv) complicated implementation process, (v) low practicality of supporting instruments, and (vi) lack of understanding about the content and effectiveness of the new interventions. Common facilitators were (i) information sharing via regular meetings on implementation issues, (ii) organizational culture that values quality and accountability, (iii) financial penalties for hospitals with high avoidable readmissions rates, (iv) external support offered via quality improvement programs and community resources, and (v) senior leadership support. CONCLUSION: This study synthesized commonly-presenting barriers and facilitators to implementing peri-discharge interventions among different healthcare organizations. Findings may inform development of implementation strategies in different health systems after appropriate tailoring, based on a consensus-based formative research process.

Effectiveness of BNT162b2 and Sinovac vaccines against the transmission of SARS-CoV-2 during Omicron-predominance in Hong Kong: A retrospective cohort study of COVID-19 cases.

BACKGROUND: In 2022, SARS-CoV-2 Omicron variants circulated globally, generating concerns about increased transmissibility and immune escape. Hong Kong, having an infection-naive population with a moderate 2-dose vaccine coverage (63% by the end of 2021), experienced a COVID-19 epidemic largely seeded by Omicron BA.2 variants that led to the greatest outbreak in the region to date. Little remains known about the protection of commonly-administered vaccines against transmission of Omicron BA.2 variants. METHODS: In this retrospective cohort study, we identified 17 535 laboratory-confirmed COVID-19 cases using contact tracing information during the Omicron-predominant period between January and June 2022 in Hong Kong. Demographic characteristics, time from positive test result to case reporting, isolation, or hospital admission, as well as contact tracing history and contact setting were extracted. Transmission pairs were reconstructed through suspected epidemiological links according to contact tracing history, and the number of secondary cases was determined for each index case as a measurement for risk of transmission. The effectiveness of mRNA vaccine (BNT162b2) and inactivated vaccine (Sinovac) against transmission of BA.2 variants was estimated using zero-inflated negative binomial regression models. RESULTS: Vaccine effectiveness against transmission for patients who received the 2-dose BNT162b2 vaccine was estimated at 56.2% (95% CI: 14.5, 77.6), 30.6% (95% CI: 13.0, 44.6), and 21.3% (95% CI: 2.9, 36.2) on 15 - 90, 91 - 180, and 181 - 270 days after vaccination, respectively, showing a significant decrease over time. For 3-dose vaccines, vaccine effectiveness estimates were 41.0% (95% CI: 11.3, 60.7) and 41.9% (95% CI: 6.1, 64.0) on 15 - 180 days after booster doses of Sinovac and BNT162b2, respectively. Although significant vaccine effectiveness was detected in household settings, no evidence of such protective association was detected in non-household settings for either Sinovac or BNT162b2. CONCLUSION: Moderate and significant protection against Omicron BA.2 variants' transmission was found for 2 and 3 doses of Sinovac or BNT162b2 vaccines. Although protection by 2-dose BNT162b2 may evidently wane with time, protection could be restored by the booster dose. Here, we highlight the importance of continuously evaluating vaccine effectiveness against transmission for emerging SARS-CoV-2 variants.

Contextualizing evidence-based nurse-led interventions for reducing 30-day hospital readmissions using GRADE evidence to decision framework: A Delphi study.

BACKGROUND: High 30-day readmission rates increase hospital costs and negatively impact patient outcomes in many healthcare systems, including Hong Kong. Evidence-based and local adaptable nurse-led interventions have not been established for reducing 30-day hospital readmissions among general medical patients in Hong Kong's public healthcare system. AIMS: The aim of this study was to select and refine evidence-based nurse-led interventions for reducing 30-day hospital readmissions among general medical patients in Hong Kong's public healthcare system using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) framework. METHODS: Eighteen local healthcare stakeholders were recruited to carry out a two-step process. In step 1, stakeholders were invited to prioritize nurse-led interventions which were supported by existing evidence and suggest important combinations of different interventions. For all interventions prioritized in step 1, step 2 involved stakeholders performing a two-round Delphi questionnaire aiming to generate consensus-based interventions appropriate to the local context. GRADE EtD framework was applied to guide the decision-making process, taking into account certainty of evidence, benefits and harms, resource use, equity, acceptability, and feasibility. RESULTS: Four out of eight nurse-led interventions reached a positive consensus with percentage agreement ranging from 70.6% to 82.4%. GRADE EtD criteria ratings showed that over 70% of stakeholders agreed these four interventions were probably acceptable and feasible, though the certainty of evidence was low or moderate. Half of stakeholders believed their desirable effects compared to undesirable effects were large. However, the resources required and how these nurse-led interventions might affect health inequities when implemented were uncertain. Preliminary implementation issues included high complexity of delivering multiple nurse-led intervention components, and challenges of coordinating different involved parties in delivering the interventions. Appropriate resource allocation and training should be provided to address these potential problems, as suggested by stakeholders. LINKING EVIDENCE TO ACTION: Using the GRADE EtD framework, four nurse-led interventions were recommended by healthcare stakeholders as possible strategies for reducing 30-day hospital readmissions among general medical patients in Hong Kong. To address preliminary implementation issues, nurses' role as care coordinators should also be strengthened to ensure smooth delivery of nurse-led intervention components, and to facilitate multidisciplinary collaboration during service delivery.

Relationship between antidepressants and severity of SARS-CoV-2 Omicron infection: a retrospective cohort study using real-world data.

Background: Few studies have used real-world data to evaluate the impact of antidepressant use on the risk of developing severe outcomes after SARS-CoV-2 Omicron infection. Methods: This is a retrospective cohort study using propensity-score matching to examine the relationship between antidepressant use and COVID-19 severity. Inpatient and medication records of all adult COVID-19 patients in Hong Kong during the Omicron-predominated period were obtained. Severe clinical outcomes including intensive care unit admission and inpatient death after the first positive results of reverse transcription polymerase chain reaction as well as a composite outcome of both were studied. Cox proportional hazard models were applied to estimate the crude and adjusted hazard ratios (HR). Findings: Of 60,903 hospitalised COVID-19 patients admitted, 40,459 were included for matching, among which 3821 (9.4%) were prescribed antidepressants. The rates of intensive care unit admission, inpatient death, and the composite event were 3.9%, 25.5%, and 28.3% respectively in the unexposed group, 1.3%, 20.0%, and 21.1% respectively in the exposed group, with adjusted HR equal to 0.332 (95% CI, 0.245-0.449), 0.868 (95% CI, 0.800-0.942), and 0.786 (95% CI, 0.727-0.850) respectively. The result was generally consistent when stratified by selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. Antidepressants with functional inhibition of acid sphingomyelinase activity, specifically fluoxetine, were also negatively associated with the outcomes. The effect of antidepressants was more apparent in female and fully vaccinated COVID-19 patients. Interpretation: Antidepressant use was associated with a lower risk of severe COVID-19. The findings support the continuation of antidepressants in patients with COVID-19, and provide evidence for the treatment potential of antidepressants for severe COVID-19. Funding: This research was supported by Health and Medical Research Fund [grant numbers COVID190105, COVID19F03, INF-CUHK-1], Collaborative Research Fund of University Grants Committee [grant numbers C4139-20G], National Natural Science Foundation of China (NSFC) [71974165], and Group Research Scheme from The Chinese University of Hong Kong.

Changes in all-cause and cause-specific excess mortality before and after the Omicron outbreak of COVID-19 in Hong Kong.

Background: While coronavirus 2019 (COVID-19) deaths were generally underestimated in many countries, Hong Kong may show a different trend of excess mortality due to stringent measures, especially for deaths related to respiratory diseases. Nevertheless, the Omicron outbreak in Hong Kong evolved into a territory-wide transmission, similar to other settings such as Singapore, South Korea, and recently, mainland China. We hypothesized that the excess mortality would differ substantially before and after the Omicron outbreak. Methods: We conducted a time-series analysis of daily deaths stratified by age, reported causes, and epidemic wave. We determined the excess mortality from the difference between observed and expected mortality from 23 January 2020 to 1 June 2022 by fitting mortality data from 2013 to 2019. Results: During the early phase of the pandemic, the estimated excess mortality was -19.92 (95% confidence interval (CI) = -29.09, -10.75) and -115.57 (95% CI = -161.34, -69.79) per 100 000 population overall and for the elderly, respectively. However, the overall excess mortality rate was 234.08 (95% CI = 224.66, 243.50) per 100 000 population overall and as high as 928.09 (95% CI = 885.14, 971.04) per 100 000 population for the elderly during the Omicron epidemic. We generally observed negative excess mortality rates of non-COVID-19 respiratory diseases before and after the Omicron outbreak. In contrast, increases in excess mortality were generally reported in non-respiratory diseases after the Omicron outbreak. Conclusions: Our results highlighted the averted mortality before 2022 among the elderly and patients with non-COVID-19 respiratory diseases, due to indirect benefits from stringent non-pharmaceutical interventions. The high excess mortality during the Omicron epidemic demonstrated a significant impact from the surge of COVID-19 infections in a SARS-CoV-2 infection-naive population, particularly evident in the elderly group.

Estimation of Vaccine Effectiveness of CoronaVac and BNT162b2 Against Severe Outcomes Over Time Among Patients With SARS-CoV-2 Omicron.

Importance: Few studies have evaluated the waning of vaccine effectiveness against severe outcomes caused by SARS-CoV-2 Omicron infection. Hong Kong is providing inactivated and mRNA vaccines, but the population had limited protection from natural infections before the Omicron variant emerged. Objective: To examine the change in vaccine effectiveness against hospitalization and mortality due to the Omicron variant over time. Design, Setting, and Participants: This case-control study included adults with SARS-CoV-2 Omicron variant infection who died or were hospitalized in Hong Kong from January 1 to June 5, 2022 (ie, case participants), and adults with SARS-CoV-2 Omicron, sampled from the public health registry during the study period (ie, control participants), who were matched to case participants by propensity score. Exposures: Vaccination status of the individuals. Main Outcomes and Measures: Estimated vaccine effectiveness against death, death or hospitalization, and death among hospitalized patients. Vaccine effectiveness was calculated as 1 - adjusted odds ratio obtained by conditional logistic regression adjusted with covariates for each period following vaccination. Results: There were 32 823 case participants (25 546 [77.8%] ≥65 years; 16 930 [47.4%] female) and 131 328 control participants (100 041 [76.2%] ≥65 years; 66 625 [46.6%] female) in the sample analyzed for the death or hospitalization outcome. Vaccine effectiveness against death or hospitalization was maintained for at least 6 months after the second dose of both CoronaVac (74.0%; 95% CI, 71.8%-75.8%) and BNT162b2 (77.4%; 95% CI, 75.5%-79.0%) vaccines. Vaccine effectiveness against death in those aged 18 to 49 years was 86.4% (95% CI, 85.8%-87.0%) and 92.9% (95% CI, 92.6%-93.2%) for those receiving 2 doses of CoronaVac and BNT162b2, respectively, while for patients aged 80 years or older, it dropped to 61.4% (95% CI, 59.8%-63.2%) and 52.7% (95% CI, 50.2%-55.6%) for CoronaVac and BNT162b2, respectively. Nevertheless, overall vaccine effectiveness against death at 4 to 6 months after the third dose was greater than 90% for CoronaVac, BNT162b2, and the mixed vaccine schedule (eg, mixed vaccines: vaccine effectiveness, 92.2%; 95% CI, 89.2%-95.1%). Conclusions and Relevance: While vaccines were generally estimated to be effective against severe outcomes caused by SARS-CoV-2 Omicron infection, this analysis found that protection in older patients was more likely to wane 6 months after the second dose. Hence, a booster dose is recommended for older patients to restore immunity. This is especially critical in a setting like Hong Kong, where third-dose coverage is still insufficient among older residents.

Dining-Out Behavior as a Proxy for the Superspreading Potential of SARS-CoV-2 Infections: Modeling Analysis.

BACKGROUND: While many studies evaluated the reliability of digital mobility metrics as a proxy of SARS-CoV-2 transmission potential, none examined the relationship between dining-out behavior and the superspreading potential of COVID-19. OBJECTIVE: We employed the mobility proxy of dining out in eateries to examine this association in Hong Kong with COVID-19 outbreaks highly characterized by superspreading events. METHODS: We retrieved the illness onset date and contact-tracing history of all laboratory-confirmed cases of COVID-19 from February 16, 2020, to April 30, 2021. We estimated the time-varying reproduction number (Rt) and dispersion parameter (k), a measure of superspreading potential, and related them to the mobility proxy of dining out in eateries. We compared the relative contribution to the superspreading potential with other common proxies derived by Google LLC and Apple Inc. RESULTS: A total of 6391 clusters involving 8375 cases were used in the estimation. A high correlation between dining-out mobility and superspreading potential was observed. Compared to other mobility proxies derived by Google and Apple, the mobility of dining-out behavior explained the highest variability of k (ΔR-sq=9.7%, 95% credible interval: 5.7% to 13.2%) and Rt (ΔR-sq=15.7%, 95% credible interval: 13.6% to 17.7%). CONCLUSIONS: We demonstrated that there was a strong link between dining-out behaviors and the superspreading potential of COVID-19. The methodological innovation suggests a further development using digital mobility proxies of dining-out patterns to generate early warnings of superspreading events.

A statistical framework for tracking the time-varying superspreading potential of COVID-19 epidemic.

Timely detection of an evolving event of an infectious disease with superspreading potential is imperative for territory-wide disease control as well as preventing future outbreaks. While the reproduction number (R) is a commonly-adopted metric for disease transmissibility, the transmission heterogeneity quantified by dispersion parameter k, a metric for superspreading potential is seldom tracked. In this study, we developed an estimation framework to track the time-varying risk of superspreading events (SSEs) and demonstrated the method using the three epidemic waves of COVID-19 in Hong Kong. Epidemiological contact tracing data of the confirmed COVID-19 cases from 23 January 2020 to 30 September 2021 were obtained. By applying branching process models, we jointly estimated the time-varying R and k. Individual-based outbreak simulations were conducted to compare the time-varying assessment of the superspreading potential with the typical non-time-varying estimate of k over a period of time. We found that the COVID-19 transmission in Hong Kong exhibited substantial superspreading during the initial phase of the epidemics, with only 1 % (95 % Credible interval [CrI]: 0.6-2 %), 5 % (95 % CrI: 3-7 %) and 10 % (95 % CrI: 8-14 %) of the most infectious cases generated 80 % of all transmission for the first, second and third epidemic waves, respectively. After implementing local public health interventions, R estimates dropped gradually and k estimates increased thereby reducing the risk of SSEs to approaching zero. Outbreak simulations indicated that the non-time-varying estimate of k may overlook the possibility of large outbreaks. Hence, an estimation of the time-varying k as a compliment of R as a monitoring of both disease transmissibility and superspreading potential, particularly when public health interventions were relaxed is crucial for minimizing the risk of future outbreaks.

Evaluation of SARS-CoV-2 transmission in COVID-19 isolation wards: On-site sampling and numerical analysis.

Although airborne transmission has been considered as a possible route for the spread of SARS-CoV-2, the role that aerosols play in SARS-CoV-2 transmission is still controversial. This study evaluated the airborne transmission of SARS-CoV-2 in COVID-19 isolation wards at Prince of Wales Hospital in Hong Kong by both on-site sampling and numerical analysis. A total of 838 air samples and 1176 surface samples were collected, and SARS-CoV-2 RNA was detected using the RT-PCR method. Testing revealed that 2.3% of the air samples and 9.3% of the surface samples were positive, indicating that the isolation wards were contaminated with the virus. The dispersion and deposition of exhaled particles in the wards were calculated by computational fluid dynamics (CFD) simulations. The calculated accumulated number of particles collected at the air sampling points was closely correlated with the SARS-CoV-2 positive rates from the field sampling, which confirmed the possibility of airborne transmission. Furthermore, three potential intervention strategies, i.e., the use of curtains, ceiling-mounted air cleaners, and periodic ventilation, were numerically investigated to explore effective control measures in isolation wards. According to the results, the use of ceiling-mounted air cleaners is effective in reducing the airborne transmission of SARS-CoV-2 in such wards.

Risk of air and surface contamination of SARS-CoV-2 in isolation wards and its relationship with patient and environmental characteristics.

Air and surface contamination of the SARS-CoV-2 have been reported by multiple studies. However, the evidence is limited for the change of environmental contamination of this virus in the surrounding of patients with COVID-19 at different time points during the course of disease and under different conditions of the patients. Therefore, this study aims to understand the risk factors associated with the appearance of SARS-CoV-2 through the period when the patients were staying in the isolation wards. In this study, COVID-19 patients admitted to the isolation wards were followed up for up to 10 days for daily collection of air and surface samples in their surroundings. The positivity rate of the environmental samples at different locations was plotted, and multiple multi-level mixed-effect logistic regressions were used to examine the association between the positivity of environmental samples and their daily health conditions and environmental factors. It found 6.6 % of surface samples (133/2031 samples) and 2.1 % of air samples (22/1075 samples) were positive, and the positivity rate reached to peak during 2-3 days after admission to the ward. The virus was more likely to present at bedrail, patients' personal items and medical equipment, while less likely to be detected in the air outside the range of 2 m from the patients. It also revealed that higher positivity rate is associated with lower environmental temperature, fever and cough at the day of sampling, lower Ct values of latest test for respiratory tract samples, and pre-existing respiratory or cardiovascular conditions. The finding can be used to guide the hospital infection control strategies by identifying high-risk areas and patients. Extra personal hygiene precautions and equipment for continuously environmental disinfection can be used for these high-risk areas and patients to reduce the risk of hospital infection.

Effectiveness of different types and levels of social distancing measures: a scoping review of global evidence from earlier stage of COVID-19 pandemic.

OBJECTIVE: Social distancing is one of the main non-pharmaceutical interventions used in the control of the COVID-19 pandemic. This scoping review aims to synthesise research findings on the effectiveness of different types and levels of social distancing measures in the earlier stage of COVID-19 pandemic without the confounding effect of mass vaccination. DESIGN: Scoping review. DATA SOURCES: MEDLINE, Embase, Global Health and four other databases were searched for eligible studies on social distancing for COVID-19 published from inception of the databases to 30 September 2020. STUDY SELECTION AND DATA EXTRACTION: Effectiveness studies on social distancing between individuals, school closures, workplace/business closures, public transport restrictions and partial/full lockdown were included. Non-English articles, studies in healthcare settings or not based on empirical data were excluded. RESULTS: After screening 1638 abstracts and 8 additional articles from other sources, 41 studies were included for synthesis of findings. The review found that the outcomes of social distancing measures were mainly indicated by changes in Rt , incidence and mortality, along with indirect indicators such as daily contact frequency and travel distance. There was adequate empirical evidence for the effect of social distancing at the individual level, and for partial or full lockdown at the community level. However, at the level of social settings, the evidence was moderate for school closure, and was limited for workplace/business closures as single targeted interventions. There was no evidence for a separate effect of public transport restriction. CONCLUSIONS: In the community setting, there was stronger evidence for the combined effect of different social distancing interventions than for a single intervention. As fatigue of preventive behaviours is an issue in public health agenda, future studies should analyse the risks in specific settings such as eateries and entertainment to implement and evaluate measures which are proportionate to the risk.

Integrated Care for Multimorbidity Population in Asian Countries: A Scoping Review.

Background: The complex needs of patients with multiple chronic diseases call for integrated care (IC). This scoping review examines several published Asian IC programmes and their relevant components and elements in managing multimorbidity patients. Method: A scoping review was conducted by searching electronic databases encompassing Medline, Embase, Scopus, and Web of Science. Three key concepts - 1) integrated care, 2) multimorbidity, and 3) Asian countries - were used to define searching strategies. Studies were included if an IC programme in Asia for multimorbidity was described or evaluated. Data extraction for IC components and elements was carried out by adopting the SELFIE framework. Results: This review yielded 1,112 articles, of which 156 remained after the title and abstract screening and 27 studies after the full-text screening - with 23 IC programmes identified from seven Asian countries. The top 5 mentioned IC components were service delivery (n = 23), workforce (n = 23), leadership and governance (n = 23), monitoring (n = 15), and environment (n = 14); whist financing (n = 9) was least mentioned. Compared to EU/US countries, technology and medical products (Asia: 40%, EU/US: 43%-100%) and multidisciplinary teams (Asia: 26%, EU/US: 50%-81%) were reported less in Asia. Most programmes involved more micro-level elements that coordinate services at the individual level (n = 20) than meso- and macro-level elements, and programmes generally incorporated horizontal and vertical integration (n = 14). Conclusion: In the IC programmes for patients with multimorbidity in Asia, service delivery, leadership, and workforce were most frequently mentioned, while the financing component was least mentioned. There appears to be considerable scope for development. Highlights: First scoping review to synthesise the key components and elements of integrated care programmes for multimorbidity in Asia.All programmes emphasized 'distinctive service delivery', 'leadership', and 'workforce' components.'Financing' component was least mentioned in identified integrated care programmes.

Evaluation of Length of Stay, Care Volume, In-Hospital Mortality, and Emergency Readmission Rate Associated With Use of Diagnosis-Related Groups for Internal Resource Allocation in Public Hospitals in Hong Kong.

Importance: Hong Kong's internal resource allocation system for public inpatient care changed from a global budget system to one based on diagnosis-related groups (DRGs) in 2009 and returned to a global budget system in 2012. Changes in patient and hospital outcomes associated with moving from a DRG-based system to a global budget system for inpatient care have rarely been evaluated. Objective: To examine associations between the introduction and discontinuation of DRGs and changes in length of stay, volume of care, in-hospital mortality rates, and emergency readmission rates in the inpatient population in acute care hospitals overall, stratified by age group, and across 5 medical conditions. Design, Setting, and Participants: This cross-sectional study included data from patients aged 45 years or older who were hospitalized in public acute care settings in Hong Kong before the introduction (April 2006 to March 2009), during implementation (April 2009 to March 2012), and after discontinuation (April 2012 to November 2014) of the DRG scheme. Data analysis was conducted from January to June 2021. Exposures: Public hospitals transitioned from a global budget payment system to a DRG-based system in April 2009 and returned to a global budget system in April 2014. Main Outcomes and Measures: The main outcome was the association of use of DRGs with patient-level length of stay, in-hospital mortality rate, 1-month emergency readmission rate, and population-level number of admissions per month. An interrupted time series design was used to estimate changes in the level and slope of outcome variables after introduction and discontinuation of DRGs, accounting for pretrends. Results: This study included 7 604 390 patient episodes. Overall, the mean (SD) age of patients was 68.97 (13.20) years, and 52.17% were male. The introduction of DRGs was associated with a 1.77% (95% CI, 1.23%-2.32%) decrease in the mean length of stay, a 2.90% (95% CI, 2.52%-3.28%) increase in the number of patients admitted, a 4.12% (95% CI, 1.89%-6.35%) reduction in in-hospital mortality, and a 2.37% (95% CI, 1.28%-3.46%) decrease in emergency readmissions. Discontinuation of the DRG scheme was associated with a 0.93% (95% CI, 0.42%-1.44%) increase in the mean length of stay and a 1.82% (95% CI, 1.47%-2.17%) reduction in the number of patients treated after adjusting for covariates; no statistically significant change was observed in in-hospital mortality (-0.14%; 95% CI, -2.29% to 2.01%) or emergency readmission rate (-0.29%; 95% CI, -1.30% to 0.71%). Conclusions and Relevance: In this cross-sectional study, the introduction of DRGs was associated with shorter lengths of stay and increased hospital volume, and discontinuation was associated with longer lengths of stay and decreased hospital volume. In-hospital mortality and emergency readmission rates did not significantly change after discontinuation of DRGs.

Effectiveness of Peri-Discharge Complex Interventions for Reducing 30-Day Readmissions among COPD Patients: Overview of Systematic Reviews and Network Meta-Analysis.

BACKGROUND: An overview of systematic reviews(SRs) and network meta-analysis(NMA) were conducted to evaluate the comparative effectiveness of peri-discharge complex interventions for reducing 30-day readmissions among chronic obstructive pulmonary disease(COPD) patients. METHODS: Five databases were searched for SRs of randomized controlled trials(RCTs). An additional search was conducted for updated RCTs from database inception until Jun 2020. Pooled effect of peri-discharge complex interventions was assessed using random-effect pairwise meta-analyses. Comparative effectiveness across different peri-discharge complex interventions was evaluated using NMA. RESULTS: Nine SRs and 11 eligible RCTs(n = 1,422) assessing eight different peri-discharge complex interventions were included. For reducing 30-day all-cause readmissions, pairwise meta-analysis showed no significant difference between peri-discharge complex interventions and usual care, while NMA indicated no significant differences among different peri-discharge complex interventions as well as usual care. For reducing 30-day COPD-related readmissions, peri-discharge complex interventions were significantly more effective than usual care (pooled RR = 0.45, 95% CI:0.24-0.84). CONCLUSIONS: Peri-discharge complex interventions may not differ from usual care in reducing 30-day all-cause readmissions among COPD patients but some are more effective for lowering 30-day COPD-related readmission. Thus, complex intervention comprising core components of patient education, self-management, patient-centred discharge instructions, and telephone follow up may be considered for implementation, but further evaluation is warranted.

Characterization of Unlinked Cases of COVID-19 and Implications for Contact Tracing Measures: Retrospective Analysis of Surveillance Data.

BACKGROUND: Contact tracing and intensive testing programs are essential for controlling the spread of COVID-19. However, conventional contact tracing is resource intensive and may not result in the tracing of all cases due to recall bias and cases not knowing the identity of some close contacts. Few studies have reported the epidemiological features of cases not identified by contact tracing ("unlinked cases") or described their potential roles in seeding community outbreaks. OBJECTIVE: For this study, we characterized the role of unlinked cases in the epidemic by comparing their epidemiological profile with the linked cases; we also estimated their transmission potential across different settings. METHODS: We obtained rapid surveillance data from the government, which contained the line listing of COVID-19 confirmed cases during the first three waves in Hong Kong. We compared the demographics, history of chronic illnesses, epidemiological characteristics, clinical characteristics, and outcomes of linked and unlinked cases. Transmission potentials in different settings were assessed by fitting a negative binomial distribution to the observed offspring distribution. RESULTS: Time interval from illness onset to hospital admission was longer among unlinked cases than linked cases (median 5.00 days versus 3.78 days; P<.001), with a higher proportion of cases whose condition was critical or serious (13.0% versus 8.2%; P<.001). The proportion of unlinked cases was associated with an increase in the weekly number of local cases (P=.049). Cluster transmissions from the unlinked cases were most frequently identified in household settings, followed by eateries and workplaces, with the estimated probability of cluster transmissions being around 0.4 for households and 0.1-0.3 for the latter two settings. CONCLUSIONS: The unlinked cases were positively associated with time to hospital admission, severity of infection, and epidemic size-implying a need to design and implement digital tracing methods to complement current conventional testing and tracing. To minimize the risk of cluster transmissions from unlinked cases, digital tracing approaches should be effectively applied in high-risk socioeconomic settings, and risk assessments should be conducted to review and adjust the policies.