Our analysis of data collected from multiple epidemics in Hong Kong indicated a shorter serial interval and generation time of infections with the SARS-CoV-2 Omicron variant. The age-specific ...case-fatality risk for Omicron BA.2.2 case-patients without complete primary vaccination was comparable to that of persons infected with ancestral strains in earlier waves.
Influenza viruses may cause severe human infections leading to hospitalization or death. Linear regression models were fitted to population-based data on hospitalizations and deaths. Surveillance ...data on influenza virus activity permitted inference on influenza-associated hospitalizations and deaths. The ratios of these estimates were used as a potential indicator of severity. Influenza was associated with 431 (95% CrI: 358-503) respiratory deaths and 12,700 (95% CrI: 11,700-13,700) respiratory hospitalizations per year. Majority of the excess deaths occurred in persons ≥65 y of age. The ratios of deaths to hospitalizations in adults ≥65 y were significantly higher for influenza A(H1N1) and A(H1N1)pdm09 compared to A(H3N2) and B. Substantial disease burden associated with influenza viruses were estimated in Hong Kong particularly among children and elderly in 1998-2013. Infections with influenza A(H1N1) was suggested to be more serious than A(H3N2) in older adults.
Abstract
Influenza viruses are associated with a substantial global burden of morbidity and mortality every year. Estimates of influenza-associated mortality often vary between studies due to ...differences in study settings, methods, and measurement of outcomes. We reviewed 103 published articles assessing population-based influenza-associated mortality through searches of PubMed and Embase, and we identified considerable variation in the statistical methods used across studies. Studies using regression models with an influenza activity proxy applied 4 approaches to estimate influenza-associated mortality. The estimates increased with age and ranged widely, from −0.3–1.3 and 0.6–8.3 respiratory deaths per 100,000 population for children and adults, respectively, to 4–119 respiratory deaths per 100,000 population for older adults. Meta-regression analysis identified that study design features were associated with the observed variation in estimates. The estimates increased with broader cause-of-death classification and were higher for older adults than for children. The multiplier methods tended to produce lower estimates, while Serfling-type models were associated with higher estimates than other methods. No “average” estimate of excess mortality could reliably be made due to the substantial variability of the estimates, partially attributable to methodological differences in the studies. Standardization of methodology in estimation of influenza-associated mortality would permit improved comparisons in the future.
When new vaccine components or platforms are developed, they will typically need to demonstrate noninferiority or superiority over existing products, resulting in the assessment of relative vaccine ...effectiveness (rVE). This review aims to identify how rVE evaluation is being performed in studies of influenza to inform a more standardized approach.
We conducted a systematic search on PubMed, Google Scholar, and Web of Science for studies reporting rVE comparing vaccine components, dose, or vaccination schedules. We screened titles, abstracts, full texts, and references to identify relevant articles. We extracted information on the study design, relative comparison made, and the definition and statistical approach used to estimate rVE in each study.
We identified 63 articles assessing rVE in influenza virus. Studies compared multiple vaccine components (n = 38), two or more doses of the same vaccine (n = 17), or vaccination timing or history (n = 9). One study compared a range of vaccine components and doses. Nearly two-thirds of all studies controlled for age, and nearly half for comorbidities, region, and sex. Assessment of 12 studies presenting both absolute and relative effect estimates suggested proportionality in the effects, resulting in implications for the interpretation of rVE effects.
Approaches to rVE evaluation in practice is highly varied, with improvements in reporting required in many cases. Extensive consideration of methodologic issues relating to rVE is needed, including the stability of estimates and the impact of confounding structure on the validity of rVE estimates.
Many locations around the world have used real-time estimates of the time-varying effective reproductive number (Formula: see text) of COVID-19 to provide evidence of transmission intensity to inform ...control strategies. Estimates of Formula: see text are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the latent period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by RT-qPCR cycle threshold values) and estimates of Formula: see text based on case counts. We demonstrate that cycle threshold values could be used to improve real-time Formula: see text estimation, enabling more timely tracking of epidemic dynamics.
The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to ...estimate the influenza-associated excess respiratory mortality in mainland China for the 2010–11 through 2014–15 seasons.
We obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005–15. Disease surveillance points with an annual average mortality rate of less than 0·4% between 2005 and 2015 or an annual mortality rate of less than 0·3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age <60 years and ≥60 years) and aggregated by province. The overall annual population data of each province and national annual respiratory mortality data were compiled from the China Statistical Yearbook. Influenza surveillance data on weekly proportion of samples testing positive for influenza virus by type or subtype for 31 provinces were extracted from the National Sentinel Hospital-based Influenza Surveillance Network. We estimated influenza-associated excess respiratory mortality rates between the 2010–11 and 2014–15 seasons for 22 provinces with valid data in the country using linear regression models. Extrapolation of excess respiratory mortality rates was done using random-effect meta-regression models for nine provinces without valid data for a direct estimation of the rates.
We fitted the linear regression model with the data from 22 of 31 provinces in mainland China, representing 83·0% of the total population. We estimated that an annual mean of 88 100 (95% CI 84 200–92 000) influenza-associated excess respiratory deaths occurred in China in the 5 years studied, corresponding to 8·2% (95% CI 7·9–8·6) of respiratory deaths. The mean excess respiratory mortality rates per 100 000 person-seasons for influenza A(H1N1)pdm09, A(H3N2), and B viruses were 1·6 (95% CI 1·5–1·7), 2·6 (2·4–2·8), and 2·3 (2·1–2·5), respectively. Estimated excess respiratory mortality rates per 100 000 person-seasons were 1·5 (95% CI 1·1–1·9) for individuals younger than 60 years and 38·5 (36·8–40·2) for individuals aged 60 years or older. Approximately 71 000 (95% CI 67 800–74 100) influenza-associated excess respiratory deaths occurred in individuals aged 60 years or older, corresponding to 80% of such deaths.
Influenza was associated with substantial excess respiratory mortality in China between 2010–11 and 2014–15 seasons, especially in older adults aged at least 60 years. Continuous and high-quality surveillance data across China are needed to improve the estimation of the disease burden attributable to influenza and the best public health interventions are needed to curb this burden.
National Science Fund for Distinguished Young Scholars, National Science and Technology Major Project of China, National Institute of Health Research, the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences, and the China-US Collaborative Program on Emerging and Re-emerging Infectious Disease.
Abstract
Background
Understanding severity of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is crucial to inform public health measures. Here we used ...coronavirus disease 2019 (COVID-19) patient data from Hong Kong to characterize the severity profile of COVID-19.
Methods
Time-varying and age-specific effective severity measured by case hospitalization risk and hospitalization fatality risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through 26 October 2022 over 6 epidemic waves. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections.
Results
With 32 222 COVID-19 hospitalizations and 9669 deaths confirmed over 6 epidemic waves, the time-varying hospitalization fatality risk dramatically increased from <10% before the largest fifth wave of Omicron BA.2 to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, fatality risk was highest among older unvaccinated patients.
Conclusions
Omicron has comparable intrinsic severity to the ancestral Wuhan strain, although the effective severity is substantially lower in Omicron cases due to vaccination.
Evaluating changes in COVID-19 severity over time is crucial when novel variants emerge. Intrinsic fatality risk was similar between Omicron and ancestral strains. Risk was inversely proportional to number of doses received, and higher risk was observed in older ages.
Abstract Estra‐4,9‐diene‐3,17‐dione (dienedione) is an anabolic‐androgenic steroid (AAS) available on the market as a dietary supplement for bodybuilding. It is prohibited in both human and equine ...sports due to its potential performance‐enhancing effect. With the rare presence of the 4,9‐diene configuration in endogenous steroids, dienedione has been considered as a synthetic AAS. Nevertheless, the reoccurring detection of dienedione in entire male horse urine samples led to the investigation of its possible endogenous nature in horses, and its endogenous nature in entire male horses has been recently confirmed and reported by the authors' laboratory. While dienedione is not detected in castrated horses (geldings), it is essential to study its elimination and identify its metabolites for its effective control. To study the elimination and biotransformation of dienedione, administration experiments were performed by giving three castrated horses (geldings) each single oral dose of 1500 mg of dienedione powder for seven consecutive days. The postulated in vivo metabolites included 17‐hydroxyestra‐4,9‐dien‐3‐one (M1a and M1b), hydroxylated dienedione (M2a, M2b, M3a, M3b, M4, M5) and hydroxylated M1 (M6a, M6b, M7a, M7b, M8a and M8b), formed from hydroxylation and reduction of dienedione. To control the misuse of dienedione in geldings, M3a and M3b are the potential targets that gave the longest detection time, which could be detected for up to 2–5 days in urine and 0.4–4 days in plasma.
Background
Human influenza virus infections cause a considerable burden of morbidity and mortality worldwide each year. Understanding regional influenza‐associated outpatient burden is crucial for ...formulating control strategies against influenza viruses.
Methods
We extracted the national sentinel surveillance data on outpatient visits due to influenza‐like‐illness (ILI) and virological confirmation of sentinel specimens from 30 provinces of China from 2006 to 2015. Generalized additive regression models were fitted to estimate influenza‐associated excess ILI outpatient burden for each individual province, accounting for seasonal baselines and meteorological factors.
Results
Influenza was associated with an average of 2.5 excess ILI consultations per 1000 person‐years (py) in 30 provinces of China each year from 2006 to 2015. Influenza A(H1N1)pdm09 led to a higher number of influenza‐associated ILI consultations in 2009 across all provinces compared with other years. The excess ILI burden was 4.5 per 1000 py among children aged below 15 years old, substantially higher than that in adults.
Conclusions
Human influenza viruses caused considerable impact on population morbidity, with a consequent healthcare and economic burden. This study provided the evidence for planning of vaccination programs in China and a framework to estimate burden of influenza‐associated outpatient consultations.
Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from ...1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04–0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94–2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.
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