The non-pharmaceutical interventions may affect the advantage in transmission of mutated variants during epidemics: A conceptual model for COVID-19.

As the COVID-19 pandemic continues, genetic mutations in SARS-CoV-2 emerge, and some of them are found more contagious than the previously identified strains, acting as the major mechanism for many large-scale epidemics. The transmission advantage of mutated variants is widely believed as an innate biological feature that is difficult to be altered by artificial factors. In this study, we explore how non-pharmaceutical interventions (NPI) may affect transmission advantage. A two-strain compartmental epidemic model is proposed and simulated to investigate the biological mechanism of the relationships among different NPIs, the changes in transmissibility of each strain and transmission advantage. Although the NPIs are effective in flattening the epidemic curve, we demonstrate that NPIs probably lead to a decline in transmission advantage, which is likely to occur if the NPIs become intensive. Our findings uncover the mechanistic relationship between NPIs and transmission advantage dynamically, and highlight the important role of NPIs not only in controlling the intensity of epidemics but also in slowing or even containing the growth of the proportion of variants.

Excess deaths from Alzheimer's disease and Parkinson's disease during the COVID-19 pandemic in the USA.

BACKGROUND: COVID-19 pandemic has indirect impacts on patients with chronic medical conditions, which may increase mortality risks for various non-COVID-19 causes. This study updates excess death statistics for Alzheimer's disease (AD) and Parkinson's disease (PD) up to 2022 and evaluates their demographic and spatial disparities in the USA. METHODS: This is an ecological time-series analysis of AD and PD mortality in the USA from January 2018 to March 2022. Poisson log-linear regressions were utilised to fit the weekly death data. Excess deaths were calculated with the difference between the observed and expected deaths under a counterfactual scenario of pandemic absence. RESULTS: From March 2020 to March 2022, we observed 41,115 and 10,328 excess deaths for AD and PD, respectively. The largest percentage increases in excess AD and PD deaths were found in the initial pandemic wave. For people aged ≥85 years, excess mortalities of AD and PD (per million persons) were 3946.0 (95% confidence interval [CI]: 2954.3, 4892.3) and 624.3 (95% CI: 369.4, 862.5), which were about 23 and 9 times higher than those aged 55-84 years, respectively. Females had a three-time higher excess mortality of AD than males (182.6 vs. 67.7 per million persons). The non-Hispanic Black people experienced larger increases in AD or PD deaths (excess percentage: 31.8% for AD and 34.6% for PD) than the non-Hispanic White population (17.1% for AD and 14.7% for PD). CONCLUSION: Under the continuing threats of COVID-19, efforts should be made to optimise health care capacity for patients with AD and PD.

Indoor Environmental Factors and Acute Respiratory Illness in a Prospective Cohort of Community-Dwelling Older Adults.

BACKGROUND: Ambient environmental factors have been associated with respiratory infections in ecological studies, but few studies have explored the impact of indoor environmental factors in detail. The current study aimed to investigate the impact of indoor environment on the risk of acute respiratory illness (ARI) in a subtropical city. METHOD: A prospective cohort study was conducted in 285 community-dwelling older adults from December 2016 through May 2019. Individual household indoor environment data and ARI incidence were continuously collected. A time-stratified case-crossover analysis was conducted to estimate the excess risk of ARI associated with per-unit increase of daily mean indoor temperature, relative humidity, and absolute humidity (AH). RESULT: In total, 168 episodes of ARI were reported with an average risk of 36.8% per year. We observed a negative association of ARI with indoor AH up to 5 lag days in cool seasons, with a 6-day cumulative excess risk estimate of -9.0% (95% confidence interval, -15.9% to -1.5%). Negative associations between household temperature or relative humidity and ARI were less consistent across warm and cool seasons. CONCLUSIONS: Lower indoor AH in household was associated with a higher risk of ARI in the community-dwelling older adults in Hong Kong during cold seasons.

Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case-Control Study.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia. METHODS: We conducted a case-control study to compare clinical characteristics and maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia. RESULTS: During the period 24 January-29 February 2020, there were 16 pregnant women with confirmed COVID-19 pneumonia and 18 suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest were cesarean delivery. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest computed tomographic images of COVID-19 pneumonia. Compared to the controls, patients with COVID-19 pneumonia had lower counts of white blood cells (WBCs), neutrophils, C-reactive protein (CRP), and alanine aminotransferase on admission. Increased levels of WBCs, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. Three (18.8%) of the mothers with confirmed COVID-19 pneumonia and 3 (16.7%) with suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than in the control group. None experienced respiratory failure during their hospital stay. COVID-19 infection was not found in the newborns, and none developed severe neonatal complications. CONCLUSIONS: Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal or cesarean delivery. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

Long-Term Exposure to Ambient Fine Particulate Matter and Mortality From Renal Failure: A Retrospective Cohort Study in Hong Kong, China.

Numerous studies have indicated that ambient particulate matter is closely associated with increased risk of cardiovascular disease, yet the evidence for its association with renal disease remains underrecognized. We aimed to estimate the association between long-term exposure to fine particulate matter, defined as particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5), and mortality from renal failure (RF) among participants in the Elderly Health Service Cohort in Hong Kong, China, from 1998 to 2010. PM2.5 concentration at the residential address of each participant was estimated based on a satellite-based spatiotemporal model. We used Cox proportional hazards regression to estimate risks of overall RF and cause-specific mortality associated with PM2.5. After excluding 5,373 subjects without information on residential address or relevant covariates, we included 61,447 participants in data analyses. We identified 443 RF deaths during the 10 years of follow-up. For an interquartile-range increase in PM2.5 concentration (3.22 µg/m3), hazard ratios for RF mortality were 1.23 (95% confidence interval: 1.06, 1.43) among all cohort participants and 1.42 (95% confidence interval: 1.16, 1.74) among patients with chronic kidney disease. Long-term exposure to atmospheric PM2.5 might be an important risk factor for RF mortality in the elderly, especially among persons with existing renal diseases.

Smoking and Influenza-associated Morbidity and Mortality: A Systematic Review and Meta-analysis.

BACKGROUND: Although smoking has been recognized as a risk factor for many respiratory diseases, its effects of influenza-associated morbidity and mortality remain controversial. We conducted a systematic review and meta-analysis to assess the impact of smoking on influenza-associated hospital admissions, intensive care unit (ICU) admissions, and deaths. METHODS: We searched the databases of PubMed, CINAHL, EMBASE, and the China National Knowledge Infrastructure for all observational studies published between 1 January 2000 and 30 November 2017 on ever-active/secondhand smoking and influenza-associated hospital admissions, ICU admissions, and deaths. We pooled data using random effect models. RESULTS: The initial search retrieved 7495 articles, of which 20 studies were included for systematic review, and 12 studies (eight case-control studies, two cohort studies, and two cross-sectional studies) with 18612 subjects were included in meta-analysis. The overall quality of selected studies was moderate. Ever-active smokers had higher odds of hospital admissions (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.3, 1.7) and ICU admissions (OR 2.2; 95% CI = 1.4, 3.4) after influenza infections, as compared with never smokers. No association was observed between ever-active smoking and influenza-associated deaths. We found a positive association between secondhand smoking and influenza-associated hospital admissions, but only in children below 15 years of age. CONCLUSIONS: The literature evidence showed that smoking was consistently associated with higher risk of hospital admissions after influenza infection, but the results for ICU admissions and deaths were less conclusive because of the limited number of studies.

Associations of long-term exposure to low-level PM2.5 and brain disorders in 260,922 middle-aged and older adults.

Long-term exposure to high-level ambient PM2.5 was associated with increased risks of brain disorders, while the associations remain uncertain of the exposure lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM2.5 exposure on the brain system in the population with annual mean concentrations ≤15 µg/m3. We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM2.5 concentrations ≤15 µg/m3, each interquartile range (IQR, 1.28 µg/m3) increment in PM2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval (CI): 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction=0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (ß=-0.036; 95% CI: -0.050, -0.022), white matter (-0.030; -0.046, -0.014), grey matter (-0.030; -0.042, -0.017), respectively. The findings suggest long-term exposure to ambient PM2.5 at low-level still has an adverse impact on the neuro-psychiatric system. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM2.5 following the World Health Organization Air Quality Guidelines 2021.

Hypoxia and Singlet Oxygen Dual-Responsive Micelles for Photodynamic and Chemotherapy Therapy Featured with Enhanced Cellular Uptake and Triggered Cargo Delivery.

Introduction: Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer. Methods: The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model. Results: The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model. Conclusion: The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.

Projection of dengue fever transmissibility under climate change in South and Southeast Asian countries.

Vector-borne infectious disease such as dengue fever (DF) has spread rapidly due to more suitable living environments. Considering the limited studies investigating the disease spread under climate change in South and Southeast Asia, this study aimed to project the DF transmission potential in 30 locations across four South and Southeast Asian countries. In this study, weekly DF incidence data, daily mean temperature, and rainfall data in 30 locations in Singapore, Sri Lanka, Malaysia, and Thailand from 2012 to 2020 were collected. The effects of temperature and rainfall on the time-varying reproduction number (Rt) of DF transmission were examined using generalized additive models. Projections of location-specific Rt from 2030s to 2090s were determined using projected temperature and rainfall under three Shared Socioeconomic Pathways (SSP126, SSP245, and SSP585), and the peak DF transmissibility and epidemic duration in the future were estimated. According to the results, the projected changes in the peak Rt and epidemic duration varied across locations, and the most significant change was observed under middle-to-high greenhouse gas emission scenarios. Under SSP585, the country-specific peak Rt was projected to decrease from 1.63 (95% confidence interval: 1.39-1.91), 2.60 (1.89-3.57), and 1.41 (1.22-1.64) in 2030s to 1.22 (0.98-1.51), 2.09 (1.26-3.47), and 1.37 (0.83-2.27) in 2090s in Singapore, Thailand, and Malaysia, respectively. Yet, the peak Rt in Sri Lanka changed slightly from 2030s to 2090s under SSP585. The epidemic duration in Singapore and Malaysia was projected to decline under SSP585. In conclusion, the change of peak DF transmission potential and disease outbreak duration would vary across locations, particularly under middle-to-high greenhouse gas emission scenarios. Interventions should be considered to slow down global warming as well as the potential increase in DF transmissibility in some locations of South and Southeast Asia.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Metal-Organic Framework for Hypoxia/ROS/pH Triple-Responsive Cargo Release.

Nanoparticulate antitumor photodynamic therapy (PDT) is suffering from a very short lifetime, limited diffusion distance of reactive oxygen species (ROS). Herein, a hypoxia/ROS/pH triple-responsive metal-organic framework (MOF) is designed to facilitate the on-demand release of photosensitizers and hence enhanced PDT efficacy. Tailored azo-containing imidazole ligand is coordinated with zinc to form MOF where photosensitizer (Chlorin e6/Ce6) is encapsulated. Azo can be reduced by overexpressed azoreductase in hypoxic tumor cells, resulting in depletion of glutathione (GSH) and thioredoxin (Trx) which are major antioxidants against ROS oxidative damage in PDT, resulting in rapid cargo release and additional efficacy amplification. The imidazole ionization causes a proton sponge effect to ensure the disintegration of the nanocarriers in acidic organelles, allowing the rapid release of Ce6 through lysosome escape. Under light irradiation, ROS produced by Ce6 may oxidize imidazole to urea, resulting in rapid cargo release. All of the triggers are expected to show interactive synergism. The pH- and hypoxia-responsiveness can improve the release rate of Ce6 for enhanced PDT therapy, whereas the consumption of oxygen by PDT may induce elevated hypoxia and hence in turn enhanced cargo release. This work highlights the role of triple-responsive nanocarriers for triggered photosensitizer release and improved antitumor PDT efficacy.

Temporal variation of excess deaths from diabetes during the COVID-19 pandemic in the United States.

BACKGROUND: Although the COVID-19 pandemic has persisted for more than two years with the evident excess mortality from diabetes, few studies have investigated its temporal patterns. This study aims to estimate the excess deaths from diabetes in the United States (US) during the COVID-19 pandemic and evaluate the excess deaths by spatiotemporal pattern, age groups, sex, and race/ethnicity. METHODS: Diabetes as one of multiple causes of death or an underlying cause of death were both considered into analyses. The Poisson log-linear regression model was used to estimate weekly expected counts of deaths during the pandemic with adjustments for long-term trend and seasonality. Excess deaths were measured by the difference between observed and expected death counts, including weekly average excess deaths, excess death rate, and excess risk. We calculated the excess estimates by pandemic wave, US state, and demographic characteristic. RESULTS: From March 2020 to March 2022, deaths that diabetes as one of multiple causes of death and an underlying cause of death were about 47.6 % and 18.4 % higher than the expected. The excess deaths of diabetes had evident temporal patterns with two large percentage increases observed during March 2020, to June 2020, and June 2021 to November 2021. The regional heterogeneity and underlying age and racial/ethnic disparities of the excess deaths were also clearly observed. CONCLUSIONS: This study highlighted the increased risks of diabetes mortality, heterogeneous spatiotemporal patterns, and associated demographic disparities during the pandemic. Practical actions are warranted to monitor disease progression, and lessen health disparities in patients with diabetes during the COVID-19 pandemic.

Comparison of the prevalence of opioid use among U.S. adults with cardiac conditions before and during the COVID-19 pandemic.

Limited data are available on the prevalence of prescription opioid use among patients with cardiac conditions who were exposed to increased risks of cardiac events including myocardial failure and cardiac arrest. According to the U.S. National Health Interview Survey, we evaluated the prevalence of opioid use in patients with cardiac conditions who reported prescription opioid use in the past 12 months and 3 months in 2019 and 2020, respectively, and further estimated the prevalence of opioid use for acute pain or chronic pain. We also analyzed the stratified prevalence by demographical characteristics. Our results showed that there was no statistically significant change in the prevalence of opioid use in the past 12 months (26.5% in 2019 vs. 25.7% in 2020) or the past 3 months (66.6% in 2019 vs. 62.5% in 2020) before and during the COVID-19 pandemic. However, there was a significant decline in the prevalence of opioid use for acute pain, from 64.2% (95% confidence interval [CI] 57.6% to 70.3%) in 2019 to 49.6% (95% CI 40.1% to 59.0%) in 2020 (P = 0.012), particularly in the subgroups of men, non-Hispanic white people, adults with education below high school, those with an income-to-poverty ratio ranging from 1.0 to 1.9, and those covered with health insurance. Our findings suggest that monitoring opioid use in the era of living with COVID-19 is important, which will help inform healthcare providers to develop care strategies to reduce health loss for vulnerable individuals.

Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States.

Objectives: To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic. Methods: We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases. Results: From March 2020 to September 2022, the increased mortality (measured by excess risks) for Clostridium difficile colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4-2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for C. difficile colitis. Conclusion: The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community.

Impact of climate change on dengue fever epidemics in South and Southeast Asian settings: A modelling study.

The potential for dengue fever epidemic due to climate change remains uncertain in tropical areas. This study aims to assess the impact of climate change on dengue fever transmission in four South and Southeast Asian settings. We collected weekly data of dengue fever incidence, daily mean temperature and rainfall from 2012 to 2020 in Singapore, Colombo, Selangor, and Chiang Mai. Projections for temperature and rainfall were drawn for three Shared Socioeconomic Pathways (SSP126, SSP245, and SSP585) scenarios. Using a disease transmission model, we projected the dengue fever epidemics until 2090s and determined the changes in annual peak incidence, peak time, epidemic size, and outbreak duration. A total of 684,639 dengue fever cases were reported in the four locations between 2012 and 2020. The projected change in dengue fever transmission would be most significant under the SSP585 scenario. In comparison to the 2030s, the peak incidence would rise by 1.29 times in Singapore, 2.25 times in Colombo, 1.36 times in Selangor, and >10 times in Chiang Mai in the 2090s under SSP585. Additionally, the peak time was projected to be earlier in Singapore, Colombo, and Selangor, but be later in Chiang Mai under the SSP585 scenario. Even in a milder emission scenario of SSP126, the epidemic size was projected to increase by 5.94%, 10.81%, 12.95%, and 69.60% from the 2030s-2090s in Singapore, Colombo, Selangor, and Chiang Mai, respectively. The outbreak durations in the four settings were projected to be prolonged over this century under SSP126 and SSP245, while a slight decrease is expected in 2090s under SSP585. The results indicate that climate change is expected to increase the risk of dengue fever transmission in tropical areas of South and Southeast Asia. Limiting greenhouse gas emissions could be crucial in reducing the transmission of dengue fever in the future.

Relationship between temperature variability and daily hospitalisations in Hong Kong over two decades.

Background: Studies have highlighted the impacts of temperature variability (TV) on mortality from respiratory diseases and cardiovascular diseases, with inconsistent results specifically in subtropical urban areas than temperate ones. We aimed to fully determine TV-associated health risks over a spectrum of diseases and various subgroups in a subtropical setting. Methods: Using inpatient data from all public hospitals in Hong Kong from 1999 to 2019, we examined the TV-hospitalisation associations by causes, ages, and seasons by fitting a quasi-Poisson regression. We presented the results as estimated percentage changes of hospitalisations per interquartile range (IQR) of TV. Results: TVs in exposure days from 0-5 days (TV0-5) to 0-7 days (TV0-7) had detrimental effects on hospitalisation risks in Hong Kong. The overall population was significantly affected over TV0-5 to TV0-7 in endocrine, nutritional and metabolic (from 0.53% to 0.58%), respiratory system (from 0.38% to 0.53%), and circulatory systems diseases (from 0.47% to 0.56%). While we found no association with seasonal disparities, we did observe notable disparities by age, highlighting older adults' vulnerability to TVs. For example, people aged ≥65 years experienced the highest change of 0.88% (95% CI = 0.34%, 1.41%) in hospitalizations for injury and poisoning per IQR increase in TV0-4. Conclusions: Our population-based study highlighted that TV-related health burden, usually regarded as minimal compared to other environmental factors, should receive more attention and be addressed in future relevant health policies, especially for vulnerable populations during the cold seasons.