Subjects with a positive faecal immunochemical test (FIT) have a much higher likelihood of advanced neoplasms than the general population. Whether FIT-positive subjects with negative colonoscopy ...should receive subsequent FIT screening remain unclear.
Subjects with a negative colonoscopy after positive FIT in the first screening in the Taiwanese Colorectal Cancer (CRC) Screening Program 2004-2009 were followed until the end of 2014. CRC incidence was compared between those who did and did not receive subsequent FIT screening. Cox regression analysis was conducted, adjusting for major confounders to investigate whether subsequent FIT was associated with lower risk of incident CRC.
The study cohort was comprised of 9179 subjects who had negative diagnostic colonoscopy after positive FIT in 2004-2009, of whom 6195 received subsequent FIT during the study period. The CRC incidence (per 1000 person years) was 1.34 in those who received subsequent FIT and 2.69 in those who did not, with corresponding adjusted HR (aHR) of 0.47 (95% CI 0.31 to 0.71). Lower adenoma detection rate of diagnostic colonoscopy was associated with higher risk of incident CRC but became non-significant in multivariable analysis after adjustment for subsequent FIT. Higher baseline faecal haemoglobin concentration (FHbC, μg haemoglobin/g faeces) was associated with increased risk of incident CRC (reference: FHbC=20-39; aHR=1.93 (1.04-3.56), 0.95 (0.45-2.00), 2.26 (1.16-4.43) and 2.44 (1.44-4.12) for FHbC=40-59, 60-99, 100-149 and ≥150, respectively).
Subsequent FIT should be scheduled after negative colonoscopy to detect missed neoplasms and reduce the risk of incident CRC in a national FIT screening programme.
ObjectivesWe aimed to assess the effect of metabolic syndrome (MetS) on incident oral potentially malignant disorder (OPMD).DesignWe conducted a prospective cohort study of the Changhua ...community-based integrated screening (CHCIS) programme and nationwide oral cancer screening programme during the period between 2005 and 2014.SettingCHCIS, Taiwan.ParticipantsWe enrolled 17 590 participants aged 30 years and older.Main outcomes and measuresWe assessed the impact of MetS on the outcome measured by incident OPMD.ResultsThe incidences of OPMD among subjects with and without MetS were 7.68 ‰ and 5.38 ‰, respectively. After adjusting for confounders, subjects with MetS exhibited a statistically greater risk of developing OPMD compared with those who were free of MetS by 33% (adjusted rate ratio, aRR=1.33, 95% CI 1.14 to 1.55). Individual components of MetS still remained significant, including central obesity (aRR=1.22, 95% CI 1.04 to 1.44), hypertriglyceridaemia (aRR=1.26, 95% CI 1.07 to 1.49) and hyperglycaemia (aRR=1.20, 95% CI 1.02 to 1.41). Central obesity and hypertriglyceridaemia were also statistically associated with a subtype of OPMD, namely, leukoplakia.ConclusionThe temporal influence of MetS on the risk of incident OPMD was noted in our prospective cohort study. Therefore, promoting an MetS prevention and control programme might reduce the occurrence of OPMD and oral cancer.
Population-based colorectal cancer (CRC) screening programs that use a fecal immunochemical test (FIT) are often faced with a noncompliance issue and its subsequent waiting time (WT) for those FIT ...positives complying with confirmatory diagnosis. We aimed to identify factors associated with both of the correlated problems in the same model.
A total of 294,469 subjects, either with positive FIT test results or having a family history, collected from 2004 to 2013 were enrolled for analysis. We applied a hurdle Poisson regression model to accommodate the hurdle of compliance and also its related WT for undergoing colonoscopy while assessing factors responsible for the mixture of the two outcomes.
The effect on compliance and WT varied with contextual factors, such as geographic areas, type of screening units, and level of urbanization. The hurdle score, representing the risk score in association with noncompliance, and the WT score, reflecting the rate of taking colonoscopy, were used to classify subjects into each of three groups representing the degree of compliance and the level of health awareness.
Our model was not only successfully applied to evaluating factors associated with the compliance and the WT distribution, but also developed into a useful assessment model for stratifying the risk and predicting whether and when screenees comply with the procedure of receiving confirmatory diagnosis given contextual factors and individual characteristics.
Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths ...up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.
Abstract
Background
Data on hepatitis C virus (HCV) reinfection in East Asian people with HIV after treatment-induced sustained virologic response (SVR) are limited.
Methods
HIV/HCV-coinfected ...patients in Taiwan who achieved SVR12 with interferon (IFN) or direct-acting antivirals (DAAs) between 2005 and 2021 underwent HCV RNA measurements at SVR24 and then biannually. HCV reinfection was defined as the detection of different HCV strains beyond SVR12. HIV-negative, low-risk individuals with SVR12 served as reference patients. Crude reinfection rates and secular trends were assessed. Multivariate Cox regression analysis was performed to identify baseline factors associated with HCV reinfection.
Results
A total of 216 HIV-positive and 1589 reference patients were recruited, with median follow-up durations of 3.0 and 6.0 years, respectively. During a total of 772 person-years of follow-up (PYFU), the HCV reinfection rate in HIV-positive patients was 4.02 per 100 PYFU (95% CI, 2.85–5.65), while the HCV reinfection rate in reference patients was 0.14 per 100 PYFU (95% CI, 0.09–0.23) during 10 862 PYFU. HIV-positive patients had a higher risk of HCV reinfection than reference patients (hazard ratio HR, 17.63; 95% CI, 7.10–43.80; P < .001). No baseline factors were predictive of HCV reinfection in HIV-positive patients. The incidence of HCV reinfection in HIV-positive patients increased after 2015, when DAAs were made available in Taiwan.
Conclusions
The risk of HCV reinfection remains high in HIV/HCV-coinfected patients with treatment-induced SVR12. In addition to mass screening and treatment scale-up, strategies to reduce reinfection are needed for HCV microelimination in HIV-positive patients in Taiwan.
博士
國立臺灣大學
流行病學與預防醫學研究所
107
Introduction While an ordinal biological biomarker has gained popularity in the role of the screening method for early detection of cancer its statistical characteristics ...become the major concern. These include skewness, censoring, correlation, dynamics, and their correlation with the state of carcinogenesis for which statistical analysis become complex and intractable. Such an advance also motivates the links between different types of stochastic process, named as meta-stochastic process (hereafter). One of applications pertains to population-based screening for colorectal cancer with fecal immunological test (FIT) wherein fecal hemoglobin (f-Hb) concentration has been deemed as a dose-response relationship with colorectal neoplasia.
Aims To study the property of percentile and the dynamics of f-Hb and its effects on the phenotypes of preclinical detectable phase (PCDP) and clinical phase (CP) with Bayesian quantile-based method and the meta-stochastic model combing continuous-state (random walk model and diffusion process) and discrete-state Markov regression.
Methods Bayesian quantile-based method was used to estimate the risk of colorectal neoplasia by percentile of f-Hb. Bayesian generalized random-walk and diffusion regression model was then developed by estimating forward probability (p) and backward probability (q) using appropriate link function with the incorporation of three disease outcomes (normal, adenoma, and CRC) in commensuration with the change of f-Hb from empirical screening data in order to calculate the probability of and the time required for reaching absorbing barrier (threshold of colorectal neoplasia) following Gambler’s ruin probability theorem. The effect of f-Hb on the initiator responsible for the onset of PCDP and the promoter for the transition from PCDP to CP was also modelled by three-state Markov regression model. In order to link two types of stochastic processes as meta-stochastic process, Bayesian directed acyclic graph (DAG) model was developed to quantify respective effects of drift (p-q) on the incidence rate of PCDP and the transition rate from PCDP to CP by linking p and q, following two binomial distributions from the random walk model and diffusion process, with two transition parameters, from the three-state Markov process. Estimation of parameters was pursuant to Bayesian Markov Chain Monte Carlo (MCMC) procedure.
Application This meta-stochastic process was applied to data derived from nationwide biennial screening program for colorectal cancer screening with FIT that are divided into two periods, 2004-2009 and 2010-2014. In terms of Bayesian statistical viewpoint, the parameters estimated from 2004 to 2009 were regarded as the prior distributions and the data from 2010 to 2014 were treated as likelihood functions. Both were formed as posterior distributions for estimation of parameters.
Results The risk of colorectal neoplasia stratified by the percentile of f-Hb was estimated. After the simulation of identifying logistic link as an appropriate link function of Bayesian generalized random walk model, the forward (p) and backward (q) was 0.867 (95% CI:0.853-0.880), and 0.134 (95% CI: 0.120-0.148) for CRC, 0.797 (95% CI:0.768-0.824), and 0.203 (95% CI: 0.176-0.232) for advanced adenoma, 0.732 (95% CI:0.715-0.750) and 0.268 (95% CI: 0.250-0.285) for nonadvanced adenoma, and 0.297(95% CI:0.296-0.298) and 0.703 (95% CI: 0.702-0.704) for the normal subjects. Time (steps) required increased from 2.46(95% CI:2.45-2.47) for normal state, 204 (95% CI:199-209) for non-advanced adenoma, 251(95% CI:242-260) for advanced adenoma and to 462(95% CI: 454-469) for CRC. Three-state Markov regression model identified baseline rather than updated f-Hb as a significant role of the initiator in a dose-response manner but not in the transition from PCDP to CP. The results of Bayesian meta-stochastic model show both baseline and the drift of f-Hb made significant contribution to the increased incidence of PCDP but not in the transition from PCDP to CP.
Conclusions This thesis proposed a novel meta-stochastic model by linking the random-walk model or diffusion process for dealing with dynamics of ordinal biomarker data type with continuous-time Markov process for dealing with multi-state disease progression. The proposed model was successfully applied to f-Hb measured through FIT used for early detection of CRC in population-based organized service screening.
碩士
國立臺灣大學
流行病學與預防醫學研究所
103
Background As fecal hemoglobin concentration (f-Hb) is a good predictor for colorectal cancer (CRC) incidence and mortality, the dynamics of f-Hb is therefore of great ...interest in the face of large population-based screening data on periodical examination of f-Hb. Modeling the evolution of f-Hb is intractable as it is an ordinal property and often involves with correlated, censoring, truncating, and dynamic movement with absorbing barriers in the province of the random walk model.
Aims This thesis was first to assess the values of f-Hb across three groups (normal, adenoma, and CRC), estimate the effective median f-Hb concentration (f-Hb50) and its threshold when the adenoma and CRC were detected. The second aim was to apply the random walk model to quantify the dynamic change of f-Hb considering the upper limit because of occurrence of adenoma and CRC.
Methods Conventional survival analysis was employed to test the difference in the mean (or median) value of f-Hb across three groups. The Cox proportional hazards (PH) regression model, making allowance for correlated property, was applied to estimating the hazard ratio (HR) of reaching the ranking of f-Hb across three groups after controlling for relevant covariates. The non-parametric method was used to estimate effective median value of f-Hb (f-Hb50) and the threshold value of f-Hb to hit colorectal adenoma and CRC.
To consider the dynamic (stochastic) property, a random walk model with asymptotic distribution and multi-nominal distribution was further developed to elucidate the evolution (repeated measurement) of f-Hb data to estimate the forward probability (p) and backward probability (q) by three types of diseases status. These parameters were also exploited for calculating the gambler’s ruin probabilities of hitting adenoma and CRC.
Results The result of ANOVA shows that the differences in the mean value of f-Hb across three groups were statistically significant. The result of Cox PH regression after adjusting for other covariates (gender, age, family history and brand), compared to the normal group, the HR of the CRC group was 0.181 (0.178, 0.184) and the adenoma group was 0.204 (0.202, 0.205), which suggest that screenee who had higher f-Hb may have higher probability to be diagnosed with disease. The estimated results on the random walk logistic regression model is that the drift rate (p-q) was the highest in the CRC patients followed by adenoma, and the lowest in subjects free of colorectal neoplasia. With the random walk logistics regression model merely considering forward (p) and backward probability, the calculation probabilities gave 0.733 and 0.267 for patents diagnosed as CRC, 0.575 and 0.425 of p and q for patients diagnosed as adenoma, and 0.358 and 0.642 of p and q for the normal subjects. Compared with the normal group, the odds ratio of moving forward was 4.923 for CRC and 2.426 for adenoma. If we set 400 μg/g for CRC, 300 μg/g for adenoma and 20 μg/g for normal as the absorbing barrier the gambler’s ruin probability of reaching the barrier was 0.867, which was higher than 0.455 of adenoma whereas the ruin probability for the normal subject was very low. If the initial value (x) was set 1 it takes, on average, 740 steps for CRC, 893 steps for adenoma, and 7.05 steps for normal to reach absorbing barrier.
Conclusions The thesis has applied the Cox PH regression model and developed a random walk regression model to accommodate the ordinal data with long tail distribution at extremely high value, undetectable circumstance at extremely low value, and missing values and also in relation to multi-state outcome. These proposed models have been applied to nationwide population-based screening for CRC with FIT to estimate the hazard ratio for CRC and adenoma as opposed to the normal subjects, also to estimate the f-Hb50 and threshold of developing CRC and adenoma, and get a better understanding of how f-Hb moves forward and backward with time, providing what is the chance of having gambler’s ruin (reaching to the barriers of f-Hb) and how many steps are expected to be taken before ruining. These findings provide a new insight into policy-making for colorectal cancer screening and also the surveillance of early-detected colorectal cancer.
Many animals improve their foraging success by producing signals that exploit the sensory biases of potential prey, but the specific properties that make these sensory traps effective remain unclear.
...We combine field experiments with phylogenetic comparative analyses to investigate the visual luring properties of different signal designs in web‐building spiders. Our field experiments used cardboard spider models to examine the effects of area of colour patches, colour and pattern on the foraging success of the colourful giant wood spider, Nephila pilipes. These experiments revealed that both the colour (yellow) and pattern (yellow and black mosaic) are essential for luring prey in a high ambient light environment.
We subsequently used phylogenetic comparative analyses to demonstrate an evolutionary association between prey viewing environment and spider ventral signal among 63 species of orb‐weavers from 53 genera.
Combined, our data show that (a) the colour of the bright body parts of orb‐weavers is essential for both diurnal and nocturnal prey attraction, whereas the pattern and area of colour patches are important for diurnal foraging and (b) the evolution of these visual lures is associated with the viewing environment, specifically ambient light intensity.
We conclude that the effectiveness of colour luring might be a major driver of the convergent evolution of yellow mosaic patterns in phylogenetically divergent orb‐weavers.
Our discoveries indicate that prey colour preferences and signal efficacy play a significant role in the evolution of visually mediated prey‐luring systems.
A free Plain Language Summary can be found within the Supporting Information of this article.
摘要
許多動物可藉由體色傳遞誘引訊號, 利用獵物的感官偏好, 增加自身的捕食成功率。然而, 是哪些具體特質使此一欺騙訊號得以有效, 至今尚未明瞭。
本研究結合田野實驗與親緣比較方法, 探討結網性蜘蛛的視覺誘引特徵。在田野實驗中, 我們製作人面蜘蛛的色紙模型, 探討色斑的面積, 和顏色與排列形式, 對捕食成功率的影響。結果顯示, 在高光源環境下, 訊號的顏色 (黃色), 和排列形式 (黃色與黑色交錯之斑紋), 是誘引昆蟲獵物的關鍵因子。
使用親緣比較方法, 我們分析53屬63種結網性蜘蛛的自然史資料, 證實蜘蛛腹部體色的演化, 與獵物視覺環境相關。
整合田野實驗與親緣比較方法之結果, 我們得知 (一) 結網性蜘蛛體表斑紋的顏色, 為誘引日行和夜行性獵物的必要因素, 而排列形式和面積對於日間捕食活動極其重要； (二) 黃色與黑色交錯之斑紋, 此項表徵能有效誘引昆蟲, 且其演化歷程與視覺環境相關, 尤其是環境光源強度。
我們推論, 誘引獵物之效果, 是驅使親緣關係歧異的結網性蜘蛛, 演化出黃色與黑色交錯斑紋的主要因子。
我們的研究結果指出, 獵物的視覺偏好和誘引獵物之功效, 在欺騙訊號的演化中扮演重要角色。
A free Plain Language Summary can be found within the Supporting Information of this article.
Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown.
Compared ...to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ T
cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin
-cresyl sulfate.
Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.
Detecting megadalton matrix-assisted laser desorption/ionization (MALDI) ions in an ion trap mass spectrometer is a technical challenge. In this study, megadalton protein and polymer ions were ...successfully measured by MALDI linear ion trap mass spectrometer (LIT-MS) for the first time. The LIT-MS is comprised of a Thermo linear ion trap mass analyzer and a highly sensitive charge-sensing particle detector (CSPD). A newly designed radio frequency (rf) scan mode with dipolar resonance ejection techniques is proposed to extend the mass range of LIT-MS up to one million Thomson (Th). We analyze high mass ions with mass-to charge (m/z) ratios ranging from 100 kTh to 1 MTh, including thyroglobulin, alpha-2-macroglobulin, immunoglobulins (e.g., IgG and IgM), and polymer (∼ 940 kTh) ions. Besides, it is also very challenging for ion trap mass spectrometry to detect megadalton ions at low concentrations. By adopting high affinity carboxylated/oxidized detonation nanodiamonds (oxDNDs) to enrich IgM molecules and form antibody-nanodiamond conjugates, we have successfully reached ∼ 5 nM (5 μg/mL) concentration which is better than that by the other techniques.
Three-section linear ion trap (LIT) mass analyzer coupled with charge-sensing particle detector (CSPD) can successfully analyze multiply charged immunoglobulin M ions at nanomolar concentrations. Display omitted
•MALDI linear ion trap mass spectrometer.•Charge-sensing particle detector.•Detection of megadalton MALDI ions at low concentrations.
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