Assessing Excess Mortality of Baby Boomers from the COVID-19 Pandemic: Taiwan Omicron-naïve Cohort.

BACKGROUND: Asia's elderly Baby Boomer demographic (born between 1946 and 1964) faced a huge problem during the COVID-19 pandemic due to increased all-cause mortality. We aimed to provide a unique Taiwan situation regarding the impact of Baby Boomers on excess mortalities from all causes relative to non-Baby Boomers throughout distinct times of SARS-CoV-2 mutations during the COVID-19 pandemic. METHODS: We used the Poisson time series design with a Bayesian directed acyclic graphic approach to build the background mortality prior to the COVID-19 pandemic between 2015 and 2019. It was then used for predicting the expected all-cause deaths compared to the reported figures during the COVID-19 pandemic period based on Taiwan residents, an Omicron-naïve cohort. RESULTS: Baby Boomers experienced a 2% negative excess mortality in 2020 (Wuhan/D614G) and a 4% excess mortality in 2021 (Alpha/Delta) with a rising background mortality trend whereas non-Baby Boomers showed the corresponding figures of 4% negative excess and 1% excess with a stable trend. Baby Boomer and non-Baby Boomer excess mortality soared to 9% (95% CI: 7-10%) and 10% (95% CI: 9-11%), respectively, during the epidemic Omicron period from January to June 2022. Surprisingly, Baby Boomers aged 58-76 experienced the same 9% excess mortality as non-Baby Boomers aged 77 and beyond. Non-COVID-19 deaths were more prevalent among Baby Boomers than non-Baby Boomers (33% vs. 29%). CONCLUSION: Baby Boomers were more likely to die from COVID-19 in early pandemic and had more non-COVID-19 deaths in late pandemic than older non-Baby Boomers demonstrated in Taiwan Omicron-naïve cohort. For this vulnerable population, adequate access to medical care and medical capacity require more consideration.

Precision Colorectal Cancer Fecal Immunological Test Screening With Fecal-Hemoglobin-Concentration-Guided Interscreening Intervals.

Importance: Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy. Objective: To demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening. Design, Setting, and Participants: A retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes. Main Outcomes and Measurements: A spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023. Results: Using data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening. Conclusion and Relevance: The gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.

New insights into three trajectories of omicron-related all-cause death reduced by COVID-19 booster vaccination.

BACKGROUND: The trajectories of all-cause deaths linked to omicron infections are rarely studied, especially in relation to the efficacy of booster shots. For assessing three epidemiological death trajectories, including dying from COVID-19, dying with COVID-19, and non-COVID-19 death, we offer a new COVID-19-and-death competing risk model that deals with the primary pathway (e.g., dying from COVID-19) competing with two other pathways. METHODS: We applied this model to track three trajectories: deaths directly from COVID-19, deaths with COVID-19 as a contributing factor, and indirect non-COVID-19 deaths. The study used data from a Taiwanese cohort, covering periods of Omicron subvariants BA.2, BA.5, and BA.2.75. It focused on the effectiveness of monovalent and bivalent booster vaccines against these death trajectories. RESULTS: The highest mortality was observed during the BA.2 phase, which decreased in the BA.5 period and increased again in the BA.2.75 period. Analyzing each trajectory, we noted similar trends in deaths directly from and with COVID-19, while non-COVID-19 deaths remained stable across subvariants. Booster vaccines reduced all-cause mortality by 58% (52%-62%) for BA.2, 70% (65%-75%) for BA.5%, and 75% (70%-80%) for BA.2.75, compared to incomplete vaccination. The reduction in deaths directly from COVID-19 was 66% (61%-72%) for BA.2, 78% (72%-84%) for BA.5%, and 85% (76%-93%) for BA.2.75. For deaths with COVID-19, the figures were 46% (36%-55%), 76% (68%-84%), and 90% (86%-95%). Additionally, the booster shots decreased non-COVID-19 deaths by 64% (63%-66%) for BA.2, 38% (36%-40%) for BA.5, and 19% (17%-21%) for BA.2.75. CONCLUSION: Our competing risk analysis is effective for monitoring all-cause death trajectories amidst various Omicron infections. It provides insights into the impact of booster vaccines, especially bivalent ones, and highlights the consequences of inadequate healthcare for vulnerable groups.

Do abnormal screening results for chronic diseases motivate inactive people to start exercising? A community-based prospective cohort study in Changhua, Taiwan.

OBJECTIVE: Exercise improves health, but illnesses can cause changes in exercise behavior, including starting or stopping. This study investigated the effects of chronic disease screening on inactive individuals' exercise behavior and analyzed the impact of age and chronic disease history on this relationship using stratified analysis. METHODS: Using a community-based prospective observational cohort design and data from the Changhua Community-Based Integrated Screening (CHCIS) dataset from 2005 to 2020, we examined 12,038 people who were screened at least twice and self-reported having never exercised at their first screening. Changes in exercise behavior were classified as "initiating exercise" and "remaining inactive." We obtained chronic disease screening results from CHCIS records, which included measurements of waist circumference, blood glucose, blood pressure, triglycerides, and high-density lipoproteins. SAS version 9.4 was used for COX proportional hazards regression. RESULTS: The findings indicated that abnormal waist circumference and blood pressure increased the likelihood of initiating exercise compared to normal results. Age stratification showed that those aged 40-49 with abnormal results were more likely to start exercising than normal participants, but not those under 40 or over 65. When stratified by chronic disease history, abnormal screening results correlated with exercise initiation only in groups without chronic disease history, except for those with a history of hyperlipidemia. CONCLUSIONS: This is the first study to demonstrate that abnormal screening results may influence exercise initiation in individuals who have never exercised, and this association varies by screening item, age, and disease history.

Beneficial effect of repeated participation in breast cancer screening upon survival.

OBJECTIVES: The benefit of mammography screening in reducing population mortality from breast cancer is well established. In this paper, we estimate the effect of repeated participation at scheduled screens on case survival. METHODS: We analysed incidence and survival data on 37,079 women from nine Swedish counties who had at least one to five invitation(s) to screening prior to diagnosis, and were diagnosed with breast cancer between 1992 and 2016. Of these, 4564 subsequently died of breast cancer. We estimated the association of survival with participation in up to the most recent five screens before diagnosis. We used proportional hazards regression to estimate the effect on survival of the number of scheduled screens in which subjects participated prior to the diagnosis of breast cancer. RESULTS: There was successively better survival with an increasing number of screens in which the subject participated. For a woman with five previous screening invitations who participated in all five, the hazard ratio was 0.28 (95% confidence interval (CI) 0.25-0.33, p < 0.0001) compared to a woman attending none (86.9% vs 68.9% 20-year survival). Following a conservative adjustment for potential self-selection factors, the hazard ratio was 0.34 (95% CI 0.26-0.43, p < 0.0001), an approximate three-fold reduction in the hazard of dying from breast cancer. CONCLUSION: For those women who develop breast cancer, regular prior participation in mammography screening confers significantly better survival.

Planning, implementing, and evaluating Hepatitis C virus elimination via collaborative community-based care cascade: age-period-cohort model for estimating demand from antecedent anti-HCV survey.

BACKGROUND: Estimating the demand for HCV care cascade plays an important role in planning, monitoring, and assessing the performance of introducing a new community-based hepatitis C virus (HCV) elimination program but such an analytic and systematic approach has been barley addressed. METHODS: A new collaborative care program for HCV elimination in the Changhua Community of Taiwan has been offered to a total of 895,353 residents since 2018. To grasp the variation of demand for HCV care cascade across demographic and geographic features in the planning stage, we applied the age-period-cohort spatial model to the antecedent anti-HCV survey enrolling 123,617 participants aged 30 years or older between 2005 and 2018. Based on this precise denominator, we then employed a "before-and-after" study design to routinely evaluate whether the WHO criteria of 90% RNA positive diagnosis and 80% successful treatments could be reached. RESULTS: The overall demand for HCV care cascade was 4.28% (HCV infection) of the underlying population but a declining trend was noted. The early cohort had a higher demand, whereas the demand of the young cohort decreased with each passing year. The demand also differed by township. The demand, allowing for these variations, for antiviral treatment was 22,362, yielding the WHO target of 12,880 for achieving HCV elimination. With 11,844 successful treatments, the effectiveness of elimination has already reached 92% (11,844/12,880) by the end of 2022. CONCLUSIONS: The demand for HCV care cascade allows health care decision-makers to timely and properly assess the performance of a novel community-based collaborative care program in achieving HCV elimination.

Performance measures of 8,169,869 examinations in the National Breast Cancer Screening Program in Taiwan, 2004-2020.

BACKGROUND: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods. METHODS: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. RESULTS: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period. CONCLUSIONS: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

Community-Based Digital Contact Tracing of Emerging Infectious Diseases: Design and Implementation Study With Empirical COVID-19 Cases.

BACKGROUND: Contact tracing for containing emerging infectious diseases such as COVID-19 is resource intensive and requires digital transformation to enable timely decision-making. OBJECTIVE: This study demonstrates the design and implementation of digital contact tracing using multimodal health informatics to efficiently collect personal information and contain community outbreaks. The implementation of digital contact tracing was further illustrated by 3 empirical SARS-CoV-2 infection clusters. METHODS: The implementation in Changhua, Taiwan, served as a demonstration of the multisectoral informatics and connectivity between electronic health systems needed for digital contact tracing. The framework incorporates traditional travel, occupation, contact, and cluster approaches and a dynamic contact process enabled by digital technology. A centralized registry system, accessible only to authorized health personnel, ensures privacy and data security. The efficiency of the digital contact tracing system was evaluated through a field study in Changhua. RESULTS: The digital contact tracing system integrates the immigration registry, communicable disease report system, and national health records to provide real-time information about travel, occupation, contact, and clusters for potential contacts and to facilitate a timely assessment of the risk of COVID-19 transmission. The digitalized system allows for informed decision-making regarding quarantine, isolation, and treatment, with a focus on personal privacy. In the first cluster infection, the system monitored 665 contacts and isolated 4 (0.6%) cases; none of the contacts (0/665, 0%) were infected during quarantine. The estimated reproduction number of 0.92 suggests an effective containment strategy for preventing community-acquired outbreak. The system was also used in a cluster investigation involving foreign workers, where none of the 462 contacts (0/462, 0%) tested positive for SARS-CoV-2. CONCLUSIONS: By integrating the multisectoral database, the contact tracing process can be digitalized to provide the information required for risk assessment and decision-making in a timely manner to contain a community-acquired outbreak when facing the outbreak of emerging infectious disease.

Imaging biomarkers are underutilised but highly predictive prognostic factors for the more fatal breast cancer subtypes.

PURPOSE: The development and refinement of breast imaging modalities offer a wealth of diagnostic information such as imaging biomarkers, which are primarily the mammographic appearance of the various breast cancer subtypes. These are readily available preoperatively at the time of diagnosis and can enhance the prognostic value of currently used molecular biomarkers. In this study, we investigated the relative utility of the molecular and imaging biomarkers, both jointly and independently, when predicting long-term patient outcome according to the site of tumour origin. METHODS: We evaluated the association of imaging biomarkers and conventional molecular biomarkers, (ER, PR, HER-2, Ki67), separately and combined, with long-term patient outcome in all breast cancer cases having complete data on both imaging and molecular biomarkers (n = 2236) diagnosed in our Institute during the period 2008-2019. Large format histopathology technique was used to document intra- and intertumoural heterogeneity and select the appropriate foci for evaluating molecular biomarkers. RESULTS: The breast cancer imaging biomarkers were strongly predictive of long-term patient outcome. The molecular biomarkers were predictive of outcome only for unifocal acinar adenocarcinoma of the breast (AAB), but less reliable in the multifocal AAB cases due to variability of molecular biomarkers in the individual tumour foci. In breast cancer of mesenchymal origin (BCMO), conventionally termed classic invasive lobular carcinoma, and in cancers originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB), the molecular biomarkers misleadingly indicated favourable prognosis, whereas the imaging biomarkers in BCMO and DAB reliably indicated the high risk of breast cancer death. Among the 2236 breast cancer cases, BCMO and DAB comprised 21% of the breast cancer cases, but accounted for 45% of the breast cancer deaths. CONCLUSIONS: Integration of imaging biomarkers into the diagnostic workup of breast cancer yields a more precise, comprehensive and prognostically accurate diagnostic report. This is particularly necessary in multifocal AAB cases having intertumoural heterogeneity, in diffuse carcinomas (DAB and BCMO), and in cases with combined DAB and AAB. In such cases, the imaging biomarkers should be prioritised over molecular biomarkers in planning treatment because the latter fail to predict the severity of the disease. In combination with the use of the large section histopathology technique, imaging biomarkers help alleviate some of the current problems in breast cancer management, such as over- and under-assessment of disease extent, which carry the risk of overtreatment and undertreatment.

Cost-Effectiveness Analysis of Personalized Hypertension Prevention.

BACKGROUND: While a population-wide strategy involving lifestyle changes and a high-risk strategy involving pharmacological interventions have been described, the recently proposed personalized medicine approach combining both strategies for the prevention of hypertension has increasingly gained attention. However, a cost-effectiveness analysis has been hardly addressed. This study was set out to build a Markov analytical decision model with a variety of prevention strategies in order to conduct an economic analysis for tailored preventative methods. METHODS: The Markov decision model was used to perform an economic analysis of four preventative strategies: usual care, a population-based universal approach, a population-based high-risk approach, and a personalized strategy. In all decisions, the cohort in each prevention method was tracked throughout time to clarify the four-state model-based natural history of hypertension. Utilizing the Monte Carlo simulation, a probabilistic cost-effectiveness analysis was carried out. The incremental cost-effectiveness ratio was calculated to estimate the additional cost to save an additional life year. RESULTS: The incremental cost-effectiveness ratios (ICER) for the personalized preventive strategy versus those for standard care were -USD 3317 per QALY gained, whereas they were, respectively, USD 120,781 and USD 53,223 per Quality-Adjusted Life Year (QALY) gained for the population-wide universal approach and the population-based high-risk approach. When the ceiling ratio of willingness to pay was USD 300,000, the probability of being cost-effective reached 74% for the universal approach and was almost certain for the personalized preventive strategy. The equivalent analysis for the personalized strategy against a general plan showed that the former was still cost-effective. CONCLUSIONS: To support a health economic decision model for the financial evaluation of hypertension preventative measures, a personalized four-state natural history of hypertension model was created. The personalized preventive treatment appeared more cost-effective than population-based conventional care. These findings are extremely valuable for making hypertension-based health decisions based on precise preventive medication.

Multifocal and diffusely infiltrating breast cancers are highly fatal subgroups needing further improvement in diagnostic and therapeutic strategies.

Physicians treating breast cancer patients often wonder why this dreaded disease is still fatal in some women despite our best diagnostic and therapeutic efforts. Our own studies on prospectively documented cases spanning several decades have given us new insights for approaching this problem. By using imaging biomarkers to classify breast cancer subtypes according to their apparent site of origin, we found that a majority of breast cancer deaths (71%) occur in a minority of breast cancers (45%). Breast cancer deaths are significantly more likely to occur in women with multifocal acinar adenocarcinoma of the breast, AAB (13.1%), diffusely invasive breast cancers of ductal origin, DAB (24 %) and breast malignancies of mesenchymal hybrid cell origin, BCMO (33.7%) compared with women having unifocal invasive breast cancers (6.1%). Preventing more of these fatal events will require a re-evaluation of the current imperfect histopathologic terminology of breast cancer with special attention to the diffuse breast cancer subtypes, intensification of multimodality imaging and multidisciplinary management, as well as application of image guided large format histopathology.

Prediabetes as a risk factor for new-onset atrial fibrillation: the propensity-score matching cohort analyzed using the Cox regression model coupled with the random survival forest.

BACKGROUND: The glycemic continuum often indicates a gradual decline in insulin sensitivity leading to an increase in glucose levels. Although prediabetes is an established risk factor for both macrovascular and microvascular diseases, whether prediabetes is independently associated with the risk of developing atrial fibrillation (AF), particularly the occurrence time, has not been well studied using a high-quality research design in combination with statistical machine-learning algorithms. METHODS: Using data available from electronic medical records collected from the National Taiwan University Hospital, a tertiary medical center in Taiwan, we conducted a retrospective cohort study consisting 174,835 adult patients between 2014 and 2019 to investigate the relationship between prediabetes and AF. To render patients with prediabetes as comparable to those with normal glucose test, a propensity-score matching design was used to select the matched pairs of two groups with a 1:1 ratio. The Kaplan-Meier method was used to compare the cumulative risk of AF between prediabetes and normal glucose test using log-rank test. The multivariable Cox regression model was employed to estimate adjusted hazard ratio (HR) for prediabetes versus normal glucose test by stratifying three levels of glycosylated hemoglobin (HbA1c). The machine-learning algorithm using the random survival forest (RSF) method was further used to identify the importance of clinical factors associated with AF in patients with prediabetes. RESULTS: A sample of 14,309 pairs of patients with prediabetes and normal glucose test result were selected. The incidence of AF was 11.6 cases per 1000 person-years during a median follow-up period of 47.1 months. The Kaplan-Meier analysis revealed that the risk of AF was significantly higher in patients with prediabetes (log-rank p < 0.001). The multivariable Cox regression model indicated that prediabetes was independently associated with a significant increased risk of AF (HR 1.24, 95% confidence interval 1.11-1.39, p < 0.001), particularly for patients with HbA1c above 5.5%. The RSF method identified elevated N-terminal natriuretic peptide and altered left heart structure as the two most important risk factors for AF among patients with prediabetes. CONCLUSIONS: Our study found that prediabetes is independently associated with a higher risk of AF. Furthermore, alterations in left heart structure make a significant contribution to this elevated risk, and these structural changes may begin during the prediabetes stage.

Assessing overdiagnosis of fecal immunological test screening for colorectal cancer with a digital twin approach.

Evaluating the magnitude of overdiagnosis associated with stool-based service screening for colorectal cancer (CRC) beyond a randomized controlled trial is often intractable and understudied. We aim to estimate the proportion of overdiagnosis in population-based service screening programs for CRC with the fecal immunochemical test (FIT). The natural process of overdiagnosis-embedded disease was first built up to learn transition parameters that quantify the pathway of non-progressive and progressive screen-detected cases calibrated with sensitivity, while also taking competing mortality into account. The Markov algorithms were then developed for estimating these transition parameters based on Taiwan FIT service CRC screening data on 5,417,699 residents aged 50-69 years from 2004 to 2014. Following the digital twin design with the parallel universe structure for emulating the randomized controlled trial, the screened twin, mirroring the control group without screening, was virtually recreated by the application of the above-mentioned trained parameters to predict CRC cases containing overdiagnosis. The ratio of the predicted CRCs derived from the screened twin to the observed CRCs of the control group minus 1 was imputed to measure the extent of overdiagnosis. The extent of overdiagnosis for invasive CRCs resulting from FIT screening is 4.16% (95% CI: 2.61-5.78%). The corresponding figure is increased to 9.90% (95% CI: 8.41-11.42%) for including high grade dysplasia (HGD) and further inflated to 15.83% (95% CI: 15.23-16.46%) when the removal adenoma is considered. The modest proportion of overdiagnosis modelled by the digital twin method, dispensing with the randomized controlled trial design, suggests the harm done to population-based FIT service screening is negligible.

A new approach to modeling pre-symptomatic incidence and transmission time of imported COVID-19 cases evolving with SARS-CoV-2 variants.

There is paucity of the statistical model that is specified for data on imported COVID-19 cases with the unique global information on infectious properties of SARS-CoV-2 variant different from local outbreak data used for estimating transmission and infectiousness parameters via the established epidemic models. To this end, a new approach with a four-state stochastic model was proposed to formulate these well-established infectious parameters with three new parameters, including the pre-symptomatic incidence rate, the median of pre-symptomatic transmission time (MPTT) to symptomatic state, and the incidence (proportion) of asymptomatic cases using imported COVID-19 data. We fitted the proposed stochastic model to empirical data on imported COVID-19 cases from D614G to Omicron with the corresponding calendar periods according to the classification GISAID information on the evolution of SARS-CoV-2 variant between March 2020 and Jan 2022 in Taiwan. The pre-symptomatic incidence rate was the highest for Omicron followed by Alpha, Delta, and D614G. The MPTT (in days) increased from 3.45 (first period) ~ 4.02 (second period) of D614G until 3.94-4.65 of VOC Alpha but dropped to 3.93-3.49 of Delta and 2 days (only first period) of Omicron. The proportion of asymptomatic cases increased from 29% of D-614G period to 59.2% of Omicron. Modeling data on imported cases across strains of SARS-CoV-2 not only bridges the link between the underlying natural infectious properties elucidated in the previous epidemic models and different disease phenotypes of COVID-19 but also provides precision quarantine and isolation policy for border control in the face of various emerging SRAS-CoV-2 variants globally.

The Preventive Role of mRNA Vaccines in Reducing Death among Moderate Omicron-Infected Patients: A Follow-Up Study.

Very few studies have been conducted to assess the potential preventive role of vaccines, particularly mRNA vaccines, in the improvement of survival among moderate and severe hospitalized patients with COVID-19. After community-acquired outbreaks of the Omicron variant from 18 March until 31 May 2022, occurred in Taiwan, this retrospective cohort of 4090 moderate and 1378 severe patients admitted to hospital was classified according to whether they were administered an mRNA-based vaccine, and followed up to ascertain rates of death in both the vaccinated (≥2 doses) and unvaccinated (no or 1 dose) groups. The age-adjusted hazard ratio (aHR) of less than 1 was used to assess the preventive role of mRNA vaccines in reducing deaths among moderate and severe Omicron-infected patients. Survival was statistically significantly better for the ≥2 dose jab group (aHR, 0.75, 95% confidence interval [CI], 0.60 to 0.94) and even higher among those who had received a booster jab (aHR, 0.71; 95% CI, 0.55 to 0.91) compared with the unvaccinated group among moderate patients, but not among severe patients. In conclusion, unveiling the role of mRNA vaccines in preventing moderate but not severe COVID-19 patients from death provides new insights into how mRNA vaccines play a role in the pathway leading to a severe outcome due to Omicron COVID-19.

The Effectiveness of Population Mass Screening to Oral Cancer: A Simulation Study.

Background: Mass screening of high-risk populations for oral cancer has proven to be effective in reducing oral cancer mortality. However, the magnitude of the effectiveness of the various screening scenarios has rarely been addressed. Methods: We developed a simulation algorithm for a prospective cohort under various oral cancer screening scenarios. A hypothetical cohort of 8 million participants aged ≥30 years with cigaret smoking and/or betel quid chewing habits was constructed based on parameters extracted from studies on oral cancer screening. The results of a population-based screening program in Taiwan and a randomized controlled trial in India were used to validate the fitness; then, the effectiveness of the model was determined by changing the screening parameters. Results: There was a reduction in the risk of advanced oral cancer by 40% (relative risk [RR] = 0.60, 95% confidence interval [CI]:0.59-0.62) and oral cancer mortality by 29% (RR = 0.71, 95% CI: 0.69-0.73) at the 6-year follow-up in a screening scenario similar to the biennial screening in Taiwan, with a 55.1% attendance rate and 92.6% referral rate. The incremental effect in reducing advanced oral cancer was approximately 5% with a short 1-year screening frequency, and the corresponding reduction in mortality was, on average, 6.5%. The incremental reduction in advanced oral cancer per 10% increase in the compliance rate was 3% to 4%, while only 1% to 2% reduction was noted per 10% increase in the referral rate. The effectiveness of screening in reducing advanced oral cancer was 5% to 6% less when both betel quid chewing and alcohol drinking habits were present. Conclusion: Our computer simulation model demonstrated the effect of screening on the reduction in oral cancer mortality under various scenarios. The results provide screening policymakers with the necessary guidance to implement screening programs to save lives.

Autonomic modulation and the risk of dementia in a middle-aged cohort: A 17-year follow-up study.

BACKGROUND: Altered autonomic modulation, measured by heart rate variability (HRV), has been found to be associated with dementia risk in the elderly. However, long-term follow-up study evaluating the association between autonomic modulation from middle-age and the incidence of dementia has been limited. METHODS: This retrospective cohort analyzed data from Taiwan's National Health Insurance Database covering the period from 2001 to 2017, with a linkage to citywide health examinations conducted by Tainan Metropolitan City, Taiwan. We included subjects aged 45-64 years. The mean follow-up period was 15.75 ± 3.40 years. The measurements of HRV included resting heart rate, high frequency (HF), low frequency (LF), standard deviation of normal-to-normal R-R intervals (SDNN), ratio between the 30th and 15th R-R interval after standing up from the supine position (30/15 ratio), ratio between the R-R intervals during expiration and inspiration, and the ratio between the high- and low-frequency components (LF/HF). The main study outcome was the incidence of dementia. We performed multivariable Cox proportional hazard regression models to compare the risk of dementia among different HRV subgroups. RESULTS: We included 565 participants with a mean age of 53 (SD: 6) years, of whom 44% were male. The risk of dementia was significantly increased in association with lower parasympathetic HRV modulation, including SDNN (HR: 3.23, 95% CI: 1.55-6.73) and 30/15 ratio (HR: 3.52, 95%CI: 1.67-7.42). Moreover, the risk of dementia was increased in subjects with higher LF/HF ratios (HR: 2.05, 95% CI: 1.12-3.72). CONCLUSIONS: Lower parasympathetic activity and higher sympathetic-vagal imbalance in middle-age were associated with dementia risk.

New Surveillance Metrics for Alerting Community-Acquired Outbreaks of Emerging SARS-CoV-2 Variants Using Imported Case Data: Bayesian Markov Chain Monte Carlo Approach.

BACKGROUND: Global transmission from imported cases to domestic cluster infections is often the origin of local community-acquired outbreaks when facing emerging SARS-CoV-2 variants. OBJECTIVE: We aimed to develop new surveillance metrics for alerting emerging community-acquired outbreaks arising from new strains by monitoring the risk of small domestic cluster infections originating from few imported cases of emerging variants. METHODS: We used Taiwanese COVID-19 weekly data on imported cases, domestic cluster infections, and community-acquired outbreaks. The study period included the D614G strain in February 2020, the Alpha and Delta variants of concern (VOCs) in 2021, and the Omicron BA.1 and BA.2 VOCs in April 2022. The number of cases arising from domestic cluster infection caused by imported cases (Dci/Imc) per week was used as the SARS-CoV-2 strain-dependent surveillance metric for alerting local community-acquired outbreaks. Its upper 95% credible interval was used as the alert threshold for guiding the rapid preparedness of containment measures, including nonpharmaceutical interventions (NPIs), testing, and vaccination. The 2 metrics were estimated by using the Bayesian Monte Carlo Markov Chain method underpinning the directed acyclic graphic diagram constructed by the extra-Poisson (random-effect) regression model. The proposed model was also used to assess the most likely week lag of imported cases prior to the current week of domestic cluster infections. RESULTS: A 1-week lag of imported cases prior to the current week of domestic cluster infections was considered optimal. Both metrics of Dci/Imc and the alert threshold varied with SARS-CoV-2 variants and available containment measures. The estimates were 9.54% and 12.59%, respectively, for D614G and increased to 14.14% and 25.10%, respectively, for the Alpha VOC when only NPIs and testing were available. The corresponding figures were 10.01% and 13.32% for the Delta VOC, but reduced to 4.29% and 5.19% for the Omicron VOC when NPIs, testing, and vaccination were available. The rapid preparedness of containment measures guided by the estimated metrics accounted for the lack of community-acquired outbreaks during the D614G period, the early Alpha VOC period, the Delta VOC period, and the Omicron VOC period between BA.1 and BA.2. In contrast, community-acquired outbreaks of the Alpha VOC in mid-May 2021, Omicron BA.1 VOC in January 2022, and Omicron BA.2 VOC from April 2022 onwards, were indicative of the failure to prepare containment measures guided by the alert threshold. CONCLUSIONS: We developed new surveillance metrics for estimating the risk of domestic cluster infections with increasing imported cases and its alert threshold for community-acquired infections varying with emerging SARS-CoV-2 strains and the availability of containment measures. The use of new surveillance metrics is important in the rapid preparedness of containment measures for averting large-scale community-acquired outbreaks arising from emerging imported SARS-CoV-2 variants.

Factors associated with renal function state transitions: A population-based community survey in Taiwan.

Background: Understanding renal function state transition risk and associated factors in community residences is vital for appropriate preventive and care actions. We aim to investigate factors affecting renal function state transitions through 10-year longitudinal community screening surveys. Methods: The prospective cohort study included participants who attended the screening program ≥2 times from 2001 to 2009 and were divided into two cohorts: those with baseline estimated glomerular filtration rate (eGFR) ≥60 (n = 46,278) and those with eGFR 59-30 mL/min/1.73 m2 (n = 4,656). We applied the illness-death model to identify associated factors with eGFR <60 and death for the cohort with baseline eGFR ≥60 and eGFR <30 and death for that with baseline eGFR ≥59-30. Results: Among the followed-up participants, 3,018 (6.5%) in the cohort of baseline eGFR ≥60 mL/min/1.73 m2 and 322 (6.9%) in the cohort of eGFR 59-30 mL/min/1.73 m2 experienced renal function state transition during a median over 7-year follow-up. Besides eGFR and grade of proteinuria, diabetes mellitus (adding nearly 50% hazard rate) is the main factor associated with both state transitions. Other early-phase eGFR state transition risk factors were metabolic syndrome score, triglyceride, uric acid, fasting blood sugar, and high-density lipoprotein cholesterol. Males, poor hemoglobin, high triglyceride, and high low-density lipoprotein cholesterol were all linked with the late-phase eGFR state transition hazard rate. Conclusion: The study developed the state transition functions for community participants with varying renal function levels. Further actions to develop precision screening plans and services that incorporate personal risk factors and state transition risks are necessary.