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Objective: To develop a population-based proband-oriented pedigree information system that can be easily applied to various diseases in genetic epidemiological studies, making allowance for the capture of theoretical family relationships. DESIGNS AND MEASUREMENTS: A population-based proband-oriented pedigree information system with ties of consanguinity based on both population-based household registry data and Keelung Community Integrated Screening data was proposed to build a comprehensive extended family pedigree structure to accommodate a series of genetic studies on different diseases. We also developed an algorithm to efficiently assess how well theoretical family relationships affecting the occurrence of diseases across three generations with respect to the relative relationship score, a quantitative indicator of genetic influence, were captured.Results: We applied this population-based proband-oriented pedigree information system to estimate the rate of hypertension with various relative relationships given the selection of probands. The degree of capturing complete familial relationships was assessed for three generations. The risk for early onset of hypertension was proportional to the proband-oriented relative relationship score with 2% increased risk and 1% correction for incomplete capture.Conclusions: The population-based proband-oriented pedigree information system is powerful and can support various genetic descriptive and analytic epidemiological studies. [ABSTRACT FROM AUTHOR]

To elucidate the effect of metabolic syndrome (MetS) on oral pre-malignancy (OPM) and also to examine whether the effect is independent of areca nut chewing. We enrolled a total of 79,940 subjects aged 20years or older undergoing both oral mucous examination and health check-up for MetS within the Keelung Community-based Integrated Screening program between 2003 and 2008. We identified 368 leukoplakia, 72 erythroleukoplakia, and 69 oral submucous fibrosis. The multi-variable logistic regression was used to assess the association between MetS and OPM with adjustment of age, gender, areca nut chewing, smoking, and alcohol drinking. Subjects with MetS were at increased risk for OPM (adjusted odds ratio (aOR)=1.68, 95% confidence interval (CI): 1.39-2.04) compared with those without MetS after taking all explanatory factors into account. Among the five components of MetS, subjects with hypertriglyceride (aOR=1.43, 95% CI: 1.17-1.75) and hyperglycemia (aOR=1.30, 95% CI: 1.02-1.67) had higher risk of presenting OPM compared with those within normal ranges. The association between MetS and OPM still persisted even in non-chewers (aOR=1.85, 95% CI: 1.42-2.40) while other risk factors were controlled. We demonstrate a positive association between MetS and OPM, which is independent of areca nut chewing and other confounding factors. This finding provides an insight into a new direction of preventing OPM in contrast to conventional viewpoint focusing on the most important factor of area nut chewing. [ABSTRACT FROM AUTHOR]

Woman have lower rate of hypertension than man but it is still elusive how such gender difference can be explained by kinetic epidemiological curves. The aim of this paper was to develop a multi-state model for delineating the kinetic epidemiology of hypertension according to the Seventh Report of the Joint National Committee (JNC 7) classification criteria by gender, and to derive gender-specific kinetic curves. We used data from a population-based screening programme with 42 027 participants to fit a four-state Markov model corresponding to the classification of hypertension from the JNC 7. The young man had higher progression rate but lower regression rate for the movement between normal and pre-hypertension than the young woman. Such gender difference disappeared after 50 years old. The mean sojourn time of pre- and stage 1 hypertension for man and stage 1 for woman was approximately 5 years. However, the corresponding figure for pre-hypertension for woman was 25 years at age 30, 10 years at age 40 and 5 years afterwards. Elucidating the kinetic epidemiological curves of hypertension explains higher prevalence rate in young man than woman. These findings fit with the role of sex hormones regulating blood pressure demonstrated in the animal model. [ABSTRACT FROM AUTHOR]

The efficacy of acupressure in relieving pain has been documented; however, its effectiveness for chronic headache compared to the muscle relaxant medication has not yet been elucidated. To address this, a randomized, controlled clinical trial was conducted in a medical center in Southern Taiwan in 2003. Twenty-eight patients suffering chronic headache were randomly assigned to the acupressure group (n = 14) or the muscle relaxant medication group (n = 14). Outcome measures regarding self-appraised pain scores (measured on a visual analogue scale; VAS) and ratings of how headaches affected life quality were recorded at baseline, 1 month after treatment, and at a 6-month follow-up. Pain areas were recorded in order to establish trigger points. Results showed that mean scores on the VAS at post-treatment assessment were significantly lower in the acupressure group (32.9±26.0) than in the muscle relaxant medication group (55.7±28.7) (p = 0.047). The superiority of acupressure over muscle relaxant medication remained at 6-month follow-up assessments (p = 0.002). The quality of life ratings related to headache showed similar differences between the two groups in the post treatment and at six-month assessments. Trigger points BL2, GV20, GB20, TH21, and GB5 were used most commonly for etiological assessment. In conclusion, our study suggests that 1 month of acupressure treatment is more effective in reducing chronic headache than 1 month of muscle relaxant treatment, and that the effect remains 6 months after treatment. Trigger points help demonstrate the treatment technique recommended if a larger-scale study is conducted in the future. [ABSTRACT FROM AUTHOR]

Objective: Few studies have been conducted to investigate the influence of recombinant human erythropoietin (rhEPO) on the long-term prognosis of end-stage renal disease (ESRD).Design: A retrospective cohort study.Setting: The largest regional hospital renowned for haemodialysis in northern Taiwan.Subjects: A total of 702 ESRD patients undergoing haemodialysis between 1993 and 2002 were evaluated.Results: The rate of overall use of rhEPO, vitamin D3 or Fe therapy was 62 %. The 10-year survival rate in patients with rhEPO supplementation was statistically more favourable than that in patients without rhEPO (hazard ratio (HR) = 0.38, 95 % CI 0.30, 0.47, P < 0.0001). Similar findings were noted for patients receiving vitamin D3 (HR = 0.36, 95 % CI 0.21, 0.64, P = 0.0004) and Fe (HR = 0.45, 95 % CI 0.33, 0.61, P < 0.0001). After adjusting for age, education and aetiology, the administration of rhEPO resulted in statistically significant improvements in long-term survival rate either with (HR = 0.30, 95 % CI 0.22, 0.42) or without (HR = 0.48, 95 % CI 0.38, 0.61) combined use of Fe or vitamin D3.Conclusions: We demonstrated a reduction in long-term mortality related to supplementation therapy with rhEPO, vitamin D3 and Fe. The findings provide a justification for the administration of combined supplement therapy in patients undergoing haemodialysis. [ABSTRACT FROM AUTHOR]

Purpose We aimed to quantify the mortality reduction by which the early detection of Parkinson's disease (PD) within a community-based study could reduce the number of advanced cases. Methods Data used in this study were derived from two community-based surveys and from a clinical series of PD cases identified from a medical centre. The cumulative survival by Hoehn-Yahr (H-Y) scale was estimated and the mortality reduction derived from a community-based survey was predicted. Results A total of 117 PD patients were detected through two community-based approaches. By comparing the H-Y stage distribution of screen-detected cases with those from the clinical series, a 22.5% excess in the number of early PD (H-Y stage I and stage II) were identified with screening. The risk ratios of being H-Y stage III or severe for community-based detected cases versus clinical series were 0.49 (95% confidence interval: 0.30-0.78). The total death rate adjusted by H-Y stage distribution was 21% and 28% for cases from community and clinical series, respectively. Conclusions The present study revealed that early detection of PD through a community-based survey may reduce 51% incidence of stage III or more severe PD at diagnosis, leading to a 25% reduction in mortality. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the change of seasonal pattern of Japanese encephalitis (JE) cases in the post-vaccination period and to elucidate whether the lagged climate variables (precipitation and temperature) were associated with occurrence of JE after adjustment for seasonal pattern, time trend, geographic areas, pig density, vaccination coverage rate for humans, and time dependence of time-series numbers of JE cases. A total of 287 confirmed JE cases between 1991 and 2005 were collected, together with monthly data on socio-ecological archival data including climate, pig density and vaccination. A time-series generalized autoregressive Poisson regression model was used to achieve the objectives. The rate of JE increased from 1998 onwards. The seasonal pattern on occurrence of JE cases clustered between May and August during the period from 1991 to 2005 in Taiwan. In each geographic area, monitoring temperature and precipitation, two possible proxy variables for mosquito density, in conjunction with seasonal factors and pig density is of assistance in forecasting JE epidemics. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The natural course of Parkinson's disease (PD), as measured on the Hoehn-Yahr (H-Y) scale, and the impact that early detection would have on prognosis for those with the disease, has barely been addressed since the introduction of L-dopa. This study aimed to elucidate the natural history of PD and effectiveness of early detection in reducing advanced disability and mortality. METHOD: A total of 21 362 participants aged 40 years or older were invited to two community-based programmes for the early detection of PD. The step-by-step annual progression rates from H-Y stage I to stage IV or V, and cumulative survival rates, by the H-Y scale, were estimated and applied to simulated data to assess the impact of different screening intervals upon stage at diagnosis and subsequent survival. RESULTS: The average duration in stages I, II and III was estimated as 2.83, 6.62 and 1.41 years, respectively. The average delay time before deteriorating into H-Y stage III was 9.45 year. Application of these parameters to simulated model predicted a 36% (95% CI: 28-39%), 26% (95% CI: 20-32%) and 19% (95% CI: 13-24%) reduction in death for annual, 5-yearly and 10-yearly screening programmes, respectively. CONCLUSION: The present study recommended a 5-yearly screening programme, with 74% of PD cases prevented from progressing to H-Y stage III or worse within 10 years of diagnosis, and leading to a corresponding 26% reduction in mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Betel-quid chewing, a recognized risk factor for oral cancer, was shown to be a contributory cause of metabolic syndrome in humans, which implies a greater likelihood of developing cardiovascular disease (CVD) among those with the betel habit. OBJECTIVE: This study investigated the effect of betel chewing on the risk of developing overt CVD. DESIGN: We used the prospective cohort data derived from a community-population-registry-based integrated screening program to quantify the effect of betel-quid chewing on the incidence of newly diagnosed CVD by classifying the study population into either exposed or nonexposed groups according to chewing status at baseline. We then followed the group free of CVD at recruitment for 2.72 y (SD=1.52 y) to learn of new cardiovascular events. Proportional hazards regression modeling was used to estimate the magnitude of the effect of betel-quid chewing on CVD. RESULTS: After control for age and education level, ever chewers had a 23% (95% CI: 11%, 37%) greater risk of developing CVD than did never chewers; ever chewers were still at greater risk of developing CVD by 24% (95% CI: 11%, 39%) after further adjustment for age, education, and other significant confounders. Significant dose-response relations were found for betel-quid chewing (P<0.05, trend test) after adjustment for other significant variables. CONCLUSION: The habit of chewing betel nut was shown to have independent dose effects to predict increases in the risk of CVD in men, with the use of a prospective community-population-registry-based cohort study. Copyright © 2008 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all. Methods We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of $13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective. Results Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were $9,794, $9,335, and $7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters. Conclusion In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.

The annual cervical screening programme using the Papanicolaou (Pap) smear test was launched for women aged 30 years and over from 1995 in Taiwan. This study aimed to evaluate the Taiwanese cervical screening policy and to make recommendations based on the empirical findings from cervical screening data between 1995 and 1998. We used a stochastic process to model the natural history of precancerous lesions and cervical cancer. Based on the estimated results, Monte-Carlo computer simulation was used to evaluate the effectiveness in terms of the reduction in incidence of and mortality from cervical cancer for screening regimes with different screening intervals. Annual Pap smear screening with 100% compliance was estimated to lead to an approximate 80% reduction in deaths from cervical cancer. With 50% compliance, around a 40% reduction was expected. Triennial screening with high compliance was as effective as annual screening with low compliance, and more cost-effective. Based on the observed Taiwan Pap smear-screening programme between 1995 and 1998, with 44.5% women attending at least once, there was an estimated reduction of 16% in deaths from cervical carcinoma. The estimated effectiveness was greater when the period was extended to 2001, in which period 61% of women attended at least once. The screening programme by 2001 was estimated to reduce cervical cancer mortality by 50% (95% confidence interval: 29-65%). The incremental cost-effectiveness was estimated as 8174 dollars per additional life-year gained. In conclusion, triennial screening targeting women aged 30-69 is recommended, along with efforts to enhance the compliance rate. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Screening for cancer and other chronic conditions tends to be conducted in independent programmes; that is, screening for one disease at a time. The Keelung community-based multiple disease screening programme, developed in Keelung city, Taiwan, is a notable exception. Here, we report on the Keelung programme's ethos and development within the community, focusing on equity of delivery of the service, and community involvement. In addition, we present some preliminary cost-effectiveness analyses of multiple disease screening. METHODS: The Keelung programme offers screening for breast, colorectal and liver cancers, cervical and oral neoplasia, all of which have an evidence base for their efficacy, and for diabetes, hypertension, osteoporosis and hyperlipidaemia, which are of unknown efficacy. We assessed variability of coverage rates of the Keelung Community-based Integrated Screening (KCIS) programme with age and socioeconomic status, availability of facilities for referral of positive screenees, and numbers of community social workers, general practitioners and local hospitals involved in the programme. We also assessed in qualitative terms how the programme interacts with non-health agencies. Finally, we simulated activities and costs for a variety of single- and multiple-disease screening situations. RESULTS: Between 1999 and 2003, coverage increased overall from 14.7 to 34.4%, and increased most dramatically in people aged 60-79 years (from around 30 to 60%) and in those of lower educational status (from around 40 to 70%). There was a significant growth in the involvement of social workers and volunteers in the programme, and an increase in the availability of local diagnostic and care facilities for those screened positive. In addition, there was substantial involvement of non-health agencies in publicizing the programme. In the health economic simulations, compared with no screening, the extra costs to gain an additional life year were estimated as 667 US dollars, 608 US dollars, 4227 and 4789 US dollars for multiple screening with 100% attendance, multiple screening with 70% attendance, single disease screening with 100% attendance and single disease screening with 30% attendance at each programme (i.e. 74% attendance for at least one out of four programmes), respectively. CONCLUSIONS: The innovative design and outreach procedures of the KCIS have led to a growth in delivery of screening services to groups sometimes overlooked (equity), community involvement in health care (participation) and the use of non-health organizations for publicity and health education (collaboration). Simulation studies indicate that multiple disease screening may be more cost-effective than single disease screening. [ABSTRACT FROM AUTHOR]

BACKGROUND: Given increasing rates of colorectal cancer (CRC) in countries with intermediate incidence rates, the decision to implement population-based screening must consider the trade-off between high costs and a relatively low yield. In Taiwan, we proposed community-based CRC screening using faecal occult blood tests (FOBT) within a multiple disease screening programme. AIMS: Based on early results from the screening programme, we aimed to compare the projected efficacies, in terms of reductions in CRC mortality, achieved with multiple disease screening, single disease screening and no screening programmes. METHODS: Annual FOBT has been included in the Keelung multiple disease screening programme. A total of 26,008 subjects were offered screening. Early indicators have been estimated to assess the potential effectiveness of this programme, including the Dukes' stage distribution of screen-detected cases, the proportionate incidence and the prevalence/incidence ratio. Transition rates according to adenoma size and Dukes' stage have been estimated from an eight-state Markov model. The projected mortality reductions based on this disease natural history have been estimated using Markov Chain Monte Carlo simulation for both multiple screening and single screening. RESULTS: The overall attendance rate was 82% at the first screen and 87% at the second screen. At the first screen, 70% of screen-detected cases were localized (i.e. Dukes' stage A or B). The corresponding figure for the second screen was 80%. Approximately three-quarters of detected adenomas were smaller than 1 cm. The estimated mean transition times from diminutive adenoma to small adenoma, from small adenoma to large adenoma and from large adenoma to pre-clinical Dukes' A or B invasive carcinoma were 14.4, 5.4 and 5.6 years, respectively. Estimated reductions in CRC mortality, based on annual screening, are 23 and 33% for the single and multiple disease screening programmes, respectively. Multiple screening with an annual screening regime may lead to a further 13% reduction in mortality when compared to conventional single screening. CONCLUSION: Early indications suggest that population-based screening for CRC with FOBT, implemented through a multi-disease screening programme, is both feasible and efficacious. Further evaluation of the programme, through longer follow-up and cost-effectiveness analysis, is now required. [ABSTRACT FROM AUTHOR]

Although multistate progression models for gastric cancer have been proposed, estimation of quantitative parameters of such models is yet to be done. The present study was conducted to elucidate risk factors for gastric cancer and its precursors, and to model the progression rates from superficial gastritis to gastric cancer. Data were derived from a community-based screening programme for gastric cancer in the Matzu region of Taiwan. A total of 2184 residents participated in a two-stage screening project. Subjects testing positive for Helicobacter pylori infection or pepsinogen (PGI or PII/PGII ratio) and immunoglobulin G (IgG), and subjects with a history of peptic ulcer or other upper gastrointestinal disease or with a family history of gastric cancer were referred to endoscopy. We identified 325 biopsy-proven precursors and gastric cancers, including 148 superficial gastritis (SG), 42 atrophic gastritis (AG), 117 intestinal metaplasia (IM) and two gastric cancers. Three further cancers were diagnosed on endoscopy alone and 14 were later diagnosed in those who did not comply with referral to endoscopy. A Markov process model was used to estimate the progression rates from superficial gastritis through to gastric cancer, with exponential regression to assess the effect of covariates on progression rates. The annual progression rate from SG to AG was 0.0670 (95% confidence interval [CI] 0.0446-0.0895). Annual progression rates from AG to IM and from IM to gastric cancer were 0.2775 (0.1665-0.3884) and 0.2265 (0.1315-0.3214), respectively. This gives average dwelling times in AG and IM of 3.60 years and 4.42 years, respectively. Progression from no disease to SG was significantly accelerated in those testing positive for H. pylori, those testing positive for PGI and in subjects with a family history of gastric cancer or a personal history of upper gastrointestinal disease. Further progression to AG and IM was significantly accelerated in those testing positive for PGI and in those with a history of upper gastrointestinal disease. [ABSTRACT FROM AUTHOR]

Background: Hepatitis is a serious global health issue. To reduce mortality, early screening for liver disease has been recommended in community health policies, particularly for asymptomatic individuals., Aim: This study explored the link between liver function biomarkers and how quickly people adopt a new multiple cancer screening program, using the diffusion of innovation (DOI) Theory., Methods: The study included 57,939 participants from a community-based screening program in Keelung, Taiwan, between January 1, 2001, and December 31, 2010. Data on demographics and lifestyle habits were collected through questionnaires, and blood samples were analyzed to measure biomarkers related to liver function., Results: On average, participants took 3.48 years to accept the new screening program. People with healthier lifestyles, such as those who drank alcohol less often, were more likely to adopt the screening early. Additionally, those with higher levels of liver-related biomarkers like albumin, total protein, and ALT joined even sooner. In conclusion, using DOI theory, the study found that personal lifestyle and liver function play a role in how quickly individuals adopt a new screening system., Conclusion: These insights can help healthcare providers improve early screening efforts, particularly for people at risk of hepatitis and liver cancer, potentially reducing related deaths., (© 2024 Wiley Periodicals LLC.)

Importance: Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown., Objective: To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality., Design, Setting, and Participants: A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020., Intervention: Invitation for testing for H pylori stool antigen., Main Outcomes and Measures: The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized., Results: Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%)., Conclusions and Relevance: Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone., Trial Registration: ClinicalTrials.gov Identifier: NCT01741363.

Background: Previous studies have highlighted the importance of viral shedding using cycle threshold (Ct) values obtained via reverse transcription polymerase chain reaction to understand the epidemic trajectories of SARS-CoV-2 infections. However, it is rare to elucidate the transition kinetics of Ct values from the asymptomatic or presymptomatic phase to the symptomatic phase before recovery using individual repeated Ct values., Objective: This study proposes a novel Ct-enshrined compartment model to provide a series of quantitative measures for delineating the full trajectories of the dynamics of viral load from infection until recovery., Methods: This Ct-enshrined compartment model was constructed by leveraging Ct-classified states within and between presymptomatic and symptomatic compartments before recovery or death among people with infections. A series of recovery indices were developed to assess the net kinetic movement of Ct-up toward and Ct-down off recovery. The model was applied to (1) a small-scale community-acquired Alpha variant outbreak under the "zero-COVID-19" policy without vaccines in May 2021 and (2) a large-scale community-acquired Omicron variant outbreak with high booster vaccination rates following the lifting of the "zero-COVID-19" policy in April 2022 in Taiwan. The model used Bayesian Markov chain Monte Carlo methods with the Metropolis-Hastings algorithm for parameter estimation. Sensitivity analyses were conducted by varying Ct cutoff values to assess the robustness of the model., Results: The kinetic indicators revealed a marked difference in viral shedding dynamics between the Alpha and Omicron variants. The Alpha variant exhibited slower viral shedding and lower recovery rates, but the Omicron variant demonstrated swifter viral shedding and higher recovery rates. Specifically, the Alpha variant showed gradual Ct-up transitions and moderate recovery rates, yielding a presymptomatic recovery index slightly higher than 1 (1.10), whereas the Omicron variant had remarkable Ct-up transitions and significantly higher asymptomatic recovery rates, resulting in a presymptomatic recovery index much higher than 1 (152.5). Sensitivity analysis confirmed the robustness of the chosen Ct values of 18 and 25 across different recovery phases. Regarding the impact of vaccination, individuals without booster vaccination had a 19% higher presymptomatic incidence rate compared to those with booster vaccination. Breakthrough infections in boosted individuals initially showed similar Ct-up transition rates but higher rates in later stages compared to nonboosted individuals. Overall, booster vaccination improved recovery rates, particularly during the symptomatic phase, although recovery rates for persistent asymptomatic infection were similar regardless of vaccination status once the Ct level exceeded 25., Conclusions: The study provides new insights into dynamic Ct transitions, with the notable finding that Ct-up transitions toward recovery outpaced Ct-down and symptom-surfacing transitions during the presymptomatic phase. The Ct-up against Ct-down transition varies with variants and vaccination status. The proposed Ct-enshrined compartment model is useful for the surveillance of emerging infectious diseases in the future to prevent community-acquired outbreaks., (©Ting-Yu Lin, Amy Ming-Fang Yen, Sam Li-Sheng Chen, Chen-Yang Hsu, Chao-Chih Lai, Dih-Ling Luh, Yen-Po Yeh, Tony Hsiu-Hsi Chen. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 19.09.2024.)

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., (© 2024. The Author(s).)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Predicting mortality in the emergency department (ED) is imperative to guide palliative care and end-of-life decisions. However, the clinical usefulness of utilizing the existing screening tools still leaves something to be desired., Methods: We advanced the screening tool with the A-qCPR (Age, qSOFA (quick sepsis-related organ failure assessment), cancer, Performance Status Scale, and DNR (Do-Not-Resuscitate) risk score model for predicting one-year mortality in the emergency department of Taipei City Hospital of Taiwan with the potential of hospice need and evaluated its performance compared with the existing screening model. We adopted a large retrospective cohort in conjunction with in-time (the trained and the holdout validation cohort) for the development of the A-qCPR model and out-of-time validation sample for external validation and model robustness to variation with the calendar year., Results: A total of 10,474 patients were enrolled in the training cohort and 33,182 patients for external validation. Significant risk scores included age (0.05 per year), qSOFA ≥ 2 (4), Cancer (5), Eastern Cooperative Oncology Group (ECOG) Performance Status score ≥ 2 (2), and DNR status (2). One-year mortality rates were 13.6% for low (score ≦ 3 points), 29.9% for medium (3 < Score ≦ 9 points), and 47.1% for high categories (Score > 9 points). The AUROC curve for the in-time validation sample was 0.76 (0.74-0.78). However, the corresponding figure was slightly shrunk to 0.69 (0.69-0.70) based on out-of-time validation. The accuracy with our newly developed A-qCPR model was better than those existing tools including 0.57 (0.56-0.57) by using SQ (surprise question), 0.54 (0.54-0.54) by using qSOFA, and 0.59 (0.59-0.59) by using ECOG performance status score. Applying the A-qCPR model to emergency departments since 2017 has led to a year-on-year increase in the proportion of patients or their families signing DNR documents, which had not been affected by the COVID-19 pandemic., Conclusions: The A-qCPR model is not only effective in predicting one-year mortality but also in identifying hospice needs. Advancing the screening tool that has been widely used for hospice in various scenarios is particularly helpful for facilitating the end-of-life decision-making process in the ED., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aim: Currently, some countries still acknowledge double-contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)-based Taiwan Colorectal Cancer Screening Program., Methods: Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders., Results: A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person-years) and 368 CRCs (7.6 per 1000 person-years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI = 2.51-3.14)., Conclusions: In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Large gatherings of people on cruise ships and warships are often at high risk of COVID-19 infections. To assess the transmissibility of SARS-CoV-2 on warships and cruise ships and to quantify the effectiveness of the containment measures, the transmission coefficient (β), basic reproductive number (R 0 ), and time to deploy containment measures were estimated by the Bayesian Susceptible-Exposed-Infected-Recovered model. A meta-analysis was conducted to predict vaccine protection with or without non-pharmaceutical interventions (NPIs). The analysis showed that implementing NPIs during voyages could reduce the transmission coefficients of SARS-CoV-2 by 50%. Two weeks into the voyage of a cruise that begins with 1 infected passenger out of a total of 3,711 passengers, we estimate there would be 45 (95% CI:25-71), 33 (95% CI:20-52), 18 (95% CI:11-26), 9 (95% CI:6-12), 4 (95% CI:3-5), and 2 (95% CI:2-2) final cases under 0%, 10%, 30%, 50%, 70%, and 90% vaccine protection, respectively, without NPIs. The timeliness of strict NPIs along with implementing strict quarantine and isolation measures is imperative to contain COVID-19 cases in cruise ships. The spread of COVID-19 on ships was predicted to be limited in scenarios corresponding to at least 70% protection from prior vaccination, across all passengers and crew.

Background: Although early dementia detection is crucial to optimize the treatment outcomes and the management of associated symptoms, the published literature is scarce regarding the effectiveness of active screening protocols in enhancing dementia awareness and increasing the rate of early detection. The present study compared the detection ratio of an active community-based survey for dementia detection with the detection ratio of passive screening during routine clinical practice. Data for passive screening were obtained from the National Health Insurance (NHI) system, which was prospectively collected during the period from 2000 to 2003., Design: A population-based cohort study with historical control., Setting: Taiwan., Participants: A total of 183 participants aged 65 years or older were involved in a community-based survey. Data from 1,921,308 subjects aged 65 years or older were retrieved from the NHI system., Measurements: An adjusted detection ratio, defined as a ratio of dementia prevalence to incidence was used., Results: The results showed that the dementia prevalence during the 2000-2003 period was 2.91% in the elderly population, compared with a prevalence of 6.59% when the active survey was conducted. The incidence of dementia in the active survey cohort was 1.83%. Overall, the dementia detection ratio was higher using active surveys [4.23, 95% confidence interval (CI): 2.68-6.69] than using passive detection (1.45, 95% CI: 1.43-1.47) for those aged 65-79 years. Similar findings were observed for those aged 80 years and older., Conclusion: The implementation of an active community-based survey led to a 3-fold increase in the detection rate of early dementia detection compared to passive screening during routine practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Wu, Jeng, Lee, Hsu, Yen, Pan, Chen, Chen, Chen and Liou.)

Background: Little is known about long-term effectiveness of COVID-19 vaccine in reducing severity and deaths associated with Omicron VOC not perturbed by prior infection and independent of oral anti-viral therapy and non-pharmaceutical (NPI)., Methods: A retrospective observational cohort study was applied to Taiwan community during the unprecedent large-scale outbreaks of Omicron BA.2 between April and August, 2022. Primary vaccination since March, 2021 and booster vaccination since January, 2022 were offered on population level. Oral Anti-viral therapy was also offered as of mid-May 2022. The population-based effectiveness of vaccination in reducing the risk of moderate and severe cases of and death from Omicron BA.2 with the consideration of NPI and oral anti-viral therapy were assessed by using Bayesian hierarchical models., Results: The risks of three clinical outcomes associated with Omicron VOC infection were lowest for booster vaccination, followed by primary vaccination, and highest for incomplete vaccination with the consistent trends of being at increased risk for three outcomes from the young people aged 12 years or below until the elderly people aged 75 years or older with 7 age groups. Before the period using oral anti-viral therapy, complete primary vaccination with the duration more than 9 months before outbreaks conferred the statistically significant 47 % (23-64 %) reduction of death, 48 % (30-61 %) of severe disease, and 46 % (95 % CI: 37-54 %) of moderate disease after adjusting for 10-20 % independent effect of NPI. The benefits of booster vaccination within three months were further enhanced to 76 % (95 % CI: 67-86 %), 74 % (95 % CI: 67-80 %), and 61 % (95 % CI: 56-65 %) for three corresponding outcomes. The additional effectiveness of oral anti-viral therapy in reducing moderate disease was 13 % for the booster group and 5.8 % for primary vaccination., Conclusions: We corroborated population effectiveness of primary vaccination and its booster vaccination, independent of oral anti-viral therapy and NPI, in reducing severe clinical outcomes associated with Omicron BA.2 naïve infection population., Competing Interests: Competing interests Authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: This study is aimed at estimating the unbiased effectiveness of population-based breast cancer service screening based on case survival information alone rather than large-scale individual screening data pursuant to the intention-to-treat principle of a randomized-controlled trial., Methods: A novel time-dependent switched design with two modalities of cancer detection (screen-detected vs clinically detected) was proposed to evaluate the effectiveness of breast cancer screening. We used data on 767 patients from Kopparberg in the Swedish Two-County trial and on 78 587 patients in the Taiwan population-based service screening. We estimated the relative rate of the screen-detected vs the clinically detected with adjustment for both truncation and lead-time biases. The absolute effectiveness in terms of the number needed to screen (NNS) for averting one death from breast cancer was estimated., Results: The relative rate of effectiveness was estimated as 33%, which was consistent with the 37% reported from the original Swedish randomized-controlled trial. The corresponding estimate for the Taiwan screening programme was 42%, which was also very close to that estimated using individual screening history data (41%). Both relative estimates were further applied to yield 446 and 806 of NNS for averting one death from breast cancer for the corresponding two data sets., Conclusion: The proposed time-dependent switched design and analysis with two modalities of case survival information provides a very efficient means for estimating the unbiased estimates of relative and absolute effectiveness of population-based breast cancer service screening dispensing with a large amount of individual screening history data., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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., (©Amy Ming-Fang Yen, Tony Hsiu-Hsi Chen, Wei-Jung Chang, Ting-Yu Lin, Grace Hsiao-Hsuan Jen, Chen-Yang Hsu, Sen-Te Wang, Huong Dang, Sam Li-Sheng Chen. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 25.11.2022.)

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.

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 m 2 ( 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 m 2 and 322 (6.9%) in the cohort of eGFR 59-30 mL/min/1.73 m 2 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsai, Lin, Hsu, Yen, Chen, Chiu and Hwang.)

Purpose: As we have previously demonstrated, breast cancers originating in the major lactiferous ducts and propagating through the process of neoductgenesis are a distinct subtype of invasive breast cancers, although by current practice they are placed within the group termed ductal carcinoma in situ (DCIS) and are consequently underdiagnosed and undertreated. Imaging biomarkers provide a reliable indication of the site of origin of this breast cancer subtype (Ductal Adenocarcinoma of the breast, DAB) and have excellent concordance with long-term patient outcome. In the present paper, the imaging biomarkers of DAB are described in detail to encourage and facilitate its recognition as a distinct, invasive breast cancer subtype., Methods: Correlation of breast imaging biomarkers with the corresponding histopathological findings using large format technology, with additional evidence from subgross, thick section histopathology to demonstrate the complex three-dimensional structure of the newly formed duct-like structures, neoducts., Results: There are six imaging biomarkers (mammographic tumour features) of DAB. Four subgroups have characteristic malignant-type calcifications on the mammogram. Two of these are characterized by intraluminal necrosis producing fragmented or dotted casting type calcifications on the mammogram; another two subgroups are characterized by intraductal fluid production which may eventually calcify, producing skipping stone-like or string of pearl-like calcifications. A fifth DAB subgroup presents with bloody or serous nipple discharge and is usually occult on mammography but is detectable with galactography and magnetic resonance imaging (MRI). The sixth subgroup presents as architectural distortion on the mammogram without associated calcifications., Conclusions: Radiologists can use these well-defined imaging biomarkers to readily detect Ductal Adenocarcinoma of the Breast, DAB. Immunochemical biomarkers are generally not determined from the DAB itself, due to the erroneous assumption that DAB is non-invasive. MRI plays a crucial role in determining disease extent and guiding surgical management. The accumulating evidence that this disease subtype is, in fact, an invasive cancer, necessitates an urgent re-evaluation of the diagnostic and management criteria for this poorly understood malignancy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion., Method: All breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome., Results: Breast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article., Conclusions: Neoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To use mammographic tumour features (imaging biomarkers) to identify and investigate breast cancers originating from the terminal ductal lobular units (TDLUs) of the breast in order to overcome the confusion arising from the current histopathology terminology, which calls cancers arising from the TDLUs either "ductal" or "lobular"., Method: Prospectively collected data from a randomized controlled mammography screening trial with more than four decades of follow up, and data from the subsequent population-based service screening program in Dalarna County, Sweden, provided the database necessary for studying nonpalpable, primarily screen-detected breast cancer cases in their earliest detectable phases. Large format thick (subgross) and thin section histopathologic images of breast cancers originating from the TDLUs were correlated with their mammographic tumour features (imaging biomarkers) and long-term patient outcome., Results: This systematic correlation indicates that imaging biomarkers can reliably determine the site of origin of breast cancers arising from the terminal ductal lobular units (TDLUs). This breast cancer subgroup has four specific mammographic tumour features: the in situ carcinomas developing from the TDLUs appear as powdery or crushed stone-like calcifications, while the invasive carcinomas appear as stellate/spiculated or circular/oval shaped tumour masses. These features are easily identified with breast imaging, either alone or in combination, unifocal or multifocal. We propose calling breast cancers of TDLU origin acinar adenocarcinoma of the breast (AAB)., Conclusions: The era of early detection necessitates rectifying the current, confusing histopathological nomenclature to one that is based on the anatomical site of origin of breast cancers. Invasive cancers originating from the TDLUs are either stellate/spiculated or circular, irrespective of the complex WHO histopathologic terminology. The mortality reduction accomplished by participation in mammography screening is mostly accomplished by identifying and treating the AABs in their non-palpable, early phase. AABs detected when < 15 mm diameter with no associated carcinoma originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB) have a good to excellent long-term outcome, irrespective of the current terminology, which tends to lead to overtreatment of these early invasive tumours. The conventionally used prognostic factors, including immunohistochemical biomarkers, fail to identify those 1-14 mm invasive AABs tumours that are eventually fatal. This identification can be made preoperatively by including the characteristic mammographic tumour features, imaging biomarkers, in primary diagnosis, treatment planning, and predicting long-term patient outcome. Forthcoming articles will address breast malignancies originating from structures of the breast other than the TDLUs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effect of the periodontal primary care (PPC) on the improvement of periodontal probing depth based on a periodontist's 30-year practice., Materials and Methods: We enrolled a total of 2,894 patients who underwent periodontal basic treatment between 1987 and 2017 with 84.5% retention rate. The study population was composed of 80% (n = 1,946) of retained patients with complete re-evaluation up to five-year follow-up. The outcome was measured by the improvement of probing depths (graded as 1:1-3 mm; 2:4-6 mm; 3: ≥7 mm) before and after PPC on both sextant and patient levels. Whether a better improvement was seen in the surgical group and the non-smoker group opposed to their comparators was assessed with various multi-variable regression models., Results: On patient (sextant) level, 82% (38%) improved, 13% (59%) unchanged, and 5% (3%) deteriorated. Adjusted better improvement of probing depth was noted for the surgical group by 63% and non-smoker by 31% compared with their counterparts. The similar findings were found for the outcomes based on continuous probing depth scores., Conclusions: We demonstrate the improvement of probing depth scores with a periodontal primary care offered for the retained patients and larger effect for the surgical group and non-smoker patients., (© 2021 Wiley Periodicals LLC.)

Facing the emerging COVID viral variants and the uneven distribution of vaccine worldwide, imported pre-symptomatic COVID-19 cases play a pivotal role in border control strategies. A stochastic disease process and computer simulation experiments with Bayesian underpinning was therefore developed to model pre-symptomatic disease progression during incubation period on which we were based to provide precision strategies for containing the resultant epidemic caused by imported COVID-19 cases. We then applied the proposed model to data on 1051 imported COVID-19 cases among inbound passengers to Taiwan between March 2020 and April 2021. The overall daily rate (per 100,000) of pre-symptomatic COVID-19 cases was estimated as 106 (95% credible interval (CrI): 95-117) in March-June 2020, fell to 37 (95% CrI: 28-47) in July-September 2020 (p < 0.0001), resurged to 141 (95% CrI: 118-164) in October-December 2020 (p < 0.0001), and declined to 90 (95% CrI: 73-108) in January-April 2021 (p = 0.0004). Given the median dwelling time, over 82% cases would progress from pre-symptomatic to symptomatic phase in 5-day quarantine. The time required for quarantine given two real-time polymerase chain reaction (RT-PCR) tests depends on the risk of departing countries, testing and quarantine strategies, and whether the passengers have vaccine jabs. Our proposed four-compartment stochastic process and computer simulation experiments design underpinning Bayesian MCMC algorithm facilitated the development of precision strategies for imported COVID-19 cases., (© 2022. The Author(s).)

Purpose: To use mammographic tumour features (imaging biomarkers) to classify breast cancer according to its apparent anatomic site of origin in the new era where tumours are found at their nonpalpable, earliest detectable phase., Method: Large format, subgross, three-dimensional histopathologic images of breast cancer subtypes and their corresponding imaging biomarkers were correlated with large format thin section histopathology and long-term patient outcome., Results: This systematic correlation indicates that breast cancers arise from three separate fibroglandular tissue components: the terminal ductal lobular units (TDLUs), the major lactiferous ducts, and in the stem cells of the mesenchyme. The resulting three cancer subgroups have distinctly different clinical, histopathological and mammographic presentations and different long-term outcomes. The relative frequency of these three breast cancer subgroups is approximately 75%, 20% and 5%, respectively. Classification of breast cancers according to their anatomic site of origin, as demonstrated with breast imaging and confirmed by subgross histopathology, correlates closely with the long-term patient outcome., Conclusions: Classification of breast cancers according to their site of origin helps overcome the inconsistencies in the current histopathologic terminology with its ductal-lobular dichotomy. The ability of the imaging biomarkers to determine the site of tumour origin and serve as a prognostic indicator emphasizes the increasingly crucial role of breast imaging in the management of breast cancer. Basing breast cancer management upon anatomically relevant terminology challenges the conventional mindset. Our proposals are based on research results from an unprecedented number of prospectively collected nonpalpable breast cancers diagnosed at their earliest detectable phases and followed up for several decades. This article is a general introduction to a series of forthcoming articles describing in detail the breast malignancies originating from the three sites of origin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

The purpose of this research is to elucidate whether metabolic syndrome affects the rate of adoption of a new multiple cancer screening programme, based on the Diffusion of Innovation theory. The time to attend the screening programme, conducted in Keelung, Taiwan, within 10 years was assessed by innovativeness (innovators, early adaptors, early majority, late majority and laggard) using data from 79,303 residents, with the information on metabolic syndrome accrued from routine adult health check-ups. The median time of adopting the programme and the relative rates of early adoption by metabolic syndrome and its severity score were estimated. The results show that the estimated times to adopt the programme ranged from 3 months for innovators to 10 years for the laggard. The rate of early adoption was 34% higher for participants without metabolic syndrome than for those with the disease, and the gradient relationship of disease severity was noted. The adjusted median time to adopt innovativeness was 0.82 years earlier for participants who were disease-free than those with the disease. Meanwhile, the adjusted median time was wider by up to 2.25 years for those with severe disease. The study suggests that innovation should prioritise the potential risk of the metabolic syndrome population., (© 2022 Wiley Periodicals LLC.)

Introduction: Pityrosporum folliculitis (PF) is a common skin condition that can be easily misdiagnosed, especially by non-dermatologists. While the initial diagnosis is often made clinically, skin microscopy may help to confirm the same. However, there is scant literature regarding the clinical epidemiology of PF. To our knowledge, in Singapore, only one prior epidemiological study was performed in 1987. Through the present study, we aimed to provide an update regarding the epidemiology, diagnosis and treatment of patients with PF in Singapore., Methods: We performed a retrospective review of patients with clinical presentations compatible with PF who presented to the dermatology clinic at the National University Hospital, Singapore, between 1 January 2011 and 31 December 2015. The medical records of patients identified as having clinical presentations that resembled PF were reviewed via written and electronic databases. Information regarding the demographics and clinical presentation of the patients was collected., Results: Of the 375 patients identified, 214 (57.1%) were confirmed as having PF based on Gram-stain microscopy. Most (35.0%) of these 214 patients were aged between 21 and 30 years, with a male-to-female ratio of 3:1. The lesions predominantly occurred on the trunk and the back. The majority of patients presented with symptoms that lasted more than one month. 128 (59.8%) patients received oral antifungal treatment, whereas 82 (38.3%) patients were treated with topical antifungal treatment alone., Conclusion: A typical Singapore patient with PF is a young man aged 21-30 years, with erythematous follicular papules or pustules over the trunk and the back., (Copyright: © Singapore Medical Association.)

COVID-19 pandemic has severely affected regular public health interventions including population-based cancer screening. Impacts of such screening delays on the changes in structure and screening process and the resultant long-term outcomes are unknown. It is therefore necessary to develop a systematic framework to assess theses impacts related to these components of quality. Using population-based cancer screening with fecal immunochemical test (FIT) as an illustration, the main analysis was to assess how various scenarios of screening delays were associated with the capacity for primary screening and full time equivalent (FTE) for colonoscopy and impact long-term outcomes based on a Markov decision tree model on population level. The second analysis was to quantify how the extent of COVID-19 epidemic measured by social distancing index affected capacity and FTE that were translated to delays with an exponential relationship. COVID-19 epidemic led to 25%, 29%, 34%, and 39% statistically significantly incremental risks of late cancer for the delays of 0.5-year, 1-year,1.5-year, and 2-year, respectively compared with regular biennial FIT screening. The corresponding statistically findings of four delayed schedules for death from colorectal cancer (CRC) were 26%, 28%, 29%, and 30%, respectively. The higher social distancing index led to a lower capacity of uptake screening and a larger reduction of FTE, resulting in longer screening delay and longer waiting time, which further impacted long-term outcomes as above. In summary, a systematic modelling approach was developed for demonstrating the strong impact of screening delays caused by COVID-19 epidemic on long-term outcomes illustrated with a Taiwan population-based FIT screening of CRC., (Copyright © 2021. Published by Elsevier Inc.)