Association between asthma and COVID-19 severity during Omicron epidemic: a retrospective cohort study using real-world data.

BACKGROUND: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. METHODS: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. RESULTS: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660-0·909) and 0·770 (95% CI: 0·662-0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. CONCLUSIONS: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.

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.

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.

Transcriptomic Analysis in Marine Medaka Gill Reveals That the Hypo-Osmotic Stress Could Alter the Immune Response via the IL17 Signaling Pathway.

Fish gills are the major osmoregulatory tissue that contact the external water environment and have developed an effective osmoregulatory mechanism to maintain cellular function. Marine medaka (Oryzias melastigma) has the ability to live in both seawater and fresh water environments. The present study performed a seawater (SW) to 50% seawater (SFW) transfer, and the gill samples were used for comparative transcriptomic analysis to study the alteration of hypo-osmotic stress on immune responsive genes in this model organism. The result identified 518 differentiated expressed genes (DEGs) after the SW to SFW transfer. Various pathways such as p53 signaling, forkhead box O signaling, and the cell cycle were enriched. Moreover, the immune system was highlighted as one of the top altered biological processes in the enrichment analysis. Various cytokines, chemokines, and inflammatory genes that participate in the IL-17 signaling pathway were suppressed after the SW to SFW transfer. On the other hand, some immunoglobulin-related genes were up-regulated. The results were further validated by real-time qPCR. Taken together, our study provides additional gill transcriptome information in marine medaka; it also supports the notion that osmotic stress could influence the immune responses in fish gills.

Public preference for COVID-19 vaccines in China: A discrete choice experiment.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic is sweeping across the globe, there is an urgent need to develop effective vaccines as the most powerful strategy to end the pandemic. This study aimed to examine how factors related to vaccine characteristics, their social normative influence and convenience of vaccination can affect the public's preference for the uptake of the COVID-19 vaccine in China. METHODS: An online discrete choice experiment (DCE) survey was administered to a sample of China's general population. Participants were asked to make a series of hypothetical choices and estimate their preference for different attributes of the vaccine. A mixed logit regression model was used to analyse the DCE data. Willingness to pay for each attribute was also calculated. RESULTS: Data of 1236 participants who provided valid responses were included in the analysis. There was strong public preference for high effectiveness of the vaccine, followed by long protective duration, very few adverse events and being manufactured overseas. Price was the least important attribute affecting the public preference in selecting the COVID-19 vaccine. CONCLUSIONS: The strong public preferences detected in this study should be considered when developing COVID-19 vaccination programme in China. The results provide useful information for policymakers to identify the individual and social values for a good vaccination strategy. PATIENT OR PUBLIC CONTRIBUTION: The design of the experimental choices was fully based on interviews and focus group discussions participated by 26 Chinese people with diverse socio-economic backgrounds. Without their participation, the study would not be possible.

A two years longitudinal study of a transgenic Huntington disease monkey.

BACKGROUND: A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington's disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. RESULTS: Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. CONCLUSIONS: This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.

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.

Scoring System for Predicting the Risk of Liver Cancer among Diabetes Patients: A Random Survival Forest-Guided Approach.

BACKGROUND: Most liver cancer scoring systems focus on patients with preexisting liver diseases such as chronic viral hepatitis or liver cirrhosis. Patients with diabetes are at higher risk of developing liver cancer than the general population. However, liver cancer scoring systems for patients in the absence of liver diseases or those with diabetes remain rare. This study aims to develop a risk scoring system for liver cancer prediction among diabetes patients and a sub-model among diabetes patients without cirrhosis/chronic viral hepatitis. METHODS: A retrospective cohort study was performed using electronic health records of Hong Kong. Patients who received diabetes care in general outpatient clinics between 2010 and 2019 without cancer history were included and followed up until December 2019. The outcome was diagnosis of liver cancer during follow-up. A risk scoring system was developed by applying random survival forest in variable selection, and Cox regression in weight assignment. RESULTS: The liver cancer incidence was 0.92 per 1000 person-years. Patients who developed liver cancer (n = 1995) and those who remained free of cancer (n = 1969) during follow-up (median: 6.2 years) were selected for model building. In the final time-to-event scoring system, presence of chronic hepatitis B/C, alanine aminotransferase, age, presence of cirrhosis, and sex were included as predictors. The concordance index was 0.706 (95%CI: 0.676-0.741). In the sub-model for patients without cirrhosis/chronic viral hepatitis, alanine aminotransferase, age, triglycerides, and sex were selected as predictors. CONCLUSIONS: The proposed scoring system may provide a parsimonious score for liver cancer risk prediction among diabetes patients.

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.

Outcomes and Hospital Service Use Among Patients With COPD in a Nurse- and Allied Health-Led Clinic.

Importance: Multidisciplinary disease management efforts enable the improvement in lung function among patients with chronic obstructive pulmonary disease (COPD), but there is little evidence of its association with risks of adverse health outcomes and health care service use. Objective: To examine the association between the use of a nurse- and allied health-led primary care clinic for respiratory patients, namely the Nurse and Allied Health Clinic-Respiratory Care (NAHC-Respiratory), and their risks of mortality and morbidity and health care service use. Design, Setting, and Participants: This territory-wide, population-based, propensity-matched, retrospective cohort study used data from the electronic health records of all patients who used public health care services in Hong Kong, China, from January 1, 2010, to December 31, 2019. All patients with COPD treated in public outpatient clinics between January 1, 2010, and December 31, 2014, were included. Patients who attended NAHC-Respiratory and usual care only were propensity score-matched at a 1:2 ratio. Data analyses were conducted between August 2023 and April 2024. Exposure: Attendance at NAHC-Respiratory. Main Outcomes and Measures: All-cause and cause-specific mortality, incidence of COPD complications, and use of emergency department and inpatient services until the end of 2019 were compared between the NAHC-Respiratory and usual care participants using Cox proportional hazard regression, Poisson regression, and log-link gamma regression models after matching. Results: This study included 9048 eligible patients after matching, including 3093 in the exposure group (2814 [91.0%] men; mean [SD] age, 69.8 [9.5] years) and 5955 in the reference group (5431 [91.2%] men; mean [SD] age, 69.5 [11.7] years). Compared with patients in the usual care-only group (reference), patients in the exposure group had lower risks of all-cause mortality (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90) as well as pneumonia-caused (HR, 0.85; 95% CI, 0.74-0.97), respiratory-caused (HR, 0.86; 95% CI, 0.77-0.96), and cardiovascular-caused (HR, 0.74; 95% CI, 0.59-0.93) mortality. Exposure was associated with reduced rates of emergency department visits (incidence rate ratio [IRR], 0.92; 95% CI, 0.86-0.98) and hospitalization through emergency department (IRR, 0.89; 95% CI, 0.83-0.95). Conclusions: In this cohort study, the use of a nurse- and allied health-led clinic in primary care settings was associated with reduced risks of mortality and use of hospital services among patients with COPD. These findings emphasize the important role of health care workers other than physicians in disease management in the primary care setting. The NAHC-Respiratory model and service components can be used to help improve primary care programs to benefit more patients with COPD.

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.

Association between meteorological variations and the superspreading potential of SARS-CoV-2 infections.

BACKGROUND: While many investigations examined the association between environmental covariates and COVID-19 incidence, none have examined their relationship with superspreading, a characteristic describing very few individuals disproportionally infecting a large number of people. METHODS: Contact tracing data of all the laboratory-confirmed COVID-19 cases in Hong Kong from February 16, 2020 to April 30, 2021 were used to form the infection clusters for estimating the time-varying dispersion parameter (kt), a measure of superspreading potential. Generalized additive models with identity link function were used to examine the association between negative-log kt (larger means higher superspreading potential) and the environmental covariates, adjusted with mobility metrics that account for the effect of social distancing measures. RESULTS: A total of 6,645 clusters covering 11,717 cases were reported over the study period. After centering at the median temperature, a lower ambient temperature at 10th percentile (18.2 °C) was significantly associated with a lower estimate of negative-log kt (adjusted expected change: -0.239 [95 % CI: -0.431 to -0.048]). While a U-shaped relationship between relative humidity and negative-log kt was observed, an inverted U-shaped relationship with actual vapour pressure was found. A higher total rainfall was significantly associated with lower estimates of negative-log kt. CONCLUSIONS: This study demonstrated a link between meteorological factors and the superspreading potential of COVID-19. We speculated that cold weather and rainy days reduced the social activities of individuals minimizing the interaction with others and the risk of spreading the diseases in high-risk facilities or large clusters, while the extremities of relative humidity may favor the stability and survival of the SARS-CoV-2 virus.

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.

Longitudinal transcriptomic dysregulation in the peripheral blood of transgenic Huntington's disease monkeys.

BACKGROUND: Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin (HTT) gene. The clinical features of HD are characterized by cognitive, psychological, and motor deficits. Molecular instability, a core component in neurological disease progression, can be comprehensively evaluated through longitudinal transcriptomic profiling. Development of animal models amenable to longitudinal examination enables distinct disease-associated mechanisms to be identified. RESULTS: Here we report the first longitudinal study of transgenic monkeys with genomic integration of various lengths of the human HTT gene and a range of polyQ repeats. With this unique group of transgenic HD nonhuman primates (HD monkeys), we profiled over 47,000 transcripts from peripheral blood collected over a 2 year timespan from HD monkeys and age-matched wild-type control monkeys. CONCLUSIONS: Messenger RNAs with expression patterns which diverged with disease progression in the HD monkeys considerably facilitated our search for transcripts with diagnostic or therapeutic potential in the blood of human HD patients, opening up a new avenue for clinical investigation.

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.

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.

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.

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.

Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses.

A great variety of endocrine-disrupting chemicals (EDCs) have been used extensively and become widespread in the environment nowadays. Limited mammalian studies have shown that certain EDCs may target chromosome and epigenome of the germline, leading to adverse effects in subsequent generations, despite these progenies having never been exposed to the EDC before. However, the underlying mechanisms of chromosomal changes induced by these pollutants remain poorly known. Using the human ovarian granulosa tumor cell line COV434 as a model, we investigated and compared the transcriptomic changes induced by nine EDCs with diverse chemical structures (i.e. BDE-47, BPA, BP-3, DEHP, DHP, EE2, TCS, TDCPP and NP), to inquire if there is any common epigenetic modification associated with reproductive functions induced by these EDCs. Our results showed that COV434 cells were more responsive to BP-3, NP, DEHP and EE2, and more importantly, these four EDCs altered the expression of gene clusters related to DNA damage response, cell cycle, proliferation, and chromatin remodeling, which can potentially lead to epigenetic modifications and transgenerational inheritance. Furthermore, dysregulation of similar gene clusters was common in DEHP and NP treatments. Bioinformatics analysis further revealed that BP-3 disturbed signaling pathways associated with reproductive functions, whereas alterations in telomere-related pathways were highlighted upon EE2 exposure. Overall, this study highlighted chromatin modifications caused by a class of chemicals which that may potentially lead to epigenetic changes and transgenerational reproductive impairments.

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.