Cost-Effectiveness Analysis of Personalized Hypertension Prevention.

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

Breast cancers originating from the terminal ductal lobular units: In situ and invasive acinar adenocarcinoma of the breast, AAB.

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.

Community-based multiple screening for metabolic syndrome by innovative theory: A longitudinal study.

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.

Economic evaluation for mass vaccination against COVID-19.

BACKGROUND: Vaccine is supposed to be the most effective means to prevent COVID-19 as it may not only save lives but also reduce productivity loss due to resuming pre-pandemic activities. Providing the results of economic evaluation for mass vaccination is of paramount importance for all stakeholders worldwide. METHODS: We developed a Markov decision tree for the economic evaluation of mass vaccination against COVID-19. The effectiveness of reducing outcomes after the administration of three COVID-19 vaccines (BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and AZD1222 (Oxford-AstraZeneca)) were modelled with empirical parameters obtained from literatures. The direct cost of vaccine and COVID-19 related medical cost, the indirect cost of productivity loss due to vaccine jabs and hospitalization, and the productivity loss were accumulated given different vaccination scenarios. We reported the incremental cost-utility ratio and benefit/cost (B/C) ratio of three vaccines compared to no vaccination with a probabilistic approach. RESULTS: Moderna and Pfizer vaccines won the greatest effectiveness among the three vaccines under consideration. After taking both direct and indirect costs into account, all of the three vaccines dominated no vaccination strategy. The results of B/C ratio show that one dollar invested in vaccine would have USD $13, USD $23, and USD $28 in return for Moderna, Pfizer, and AstraZeneca, respectively when health and education loss are considered. The corresponding figures taking value of the statistical life into account were USD $176, USD $300, and USD $443. CONCLUSION: Mass vaccination against COVID-19 with three current available vaccines is cost-saving for gaining more lives and less cost incurred.

Estimating global burden of COVID-19 with disability-adjusted life years and value of statistical life metrics.

BACKGROUND: Global burden of COVID-19 has not been well studied, disability-adjusted life years (DALYs) and value of statistical life (VSL) metrics were therefore proposed to quantify its impacts on health and economic loss globally. METHODS: The life expectancy, cases, and death numbers of COVID-19 until 30th April 2021 were retrieved from open data to derive the epidemiological profiles and DALYs (including years of life lost (YLL) and years loss due to disability (YLD)) by four periods. The VSL estimates were estimated by using hedonic wage method (HWM) and contingent valuation method (CVM). The estimate of willingness to pay using CVM was based on the meta-regression mixed model. Machine learning method was used for classification. RESULTS: Globally, DALYs (in thousands) due to COVID-19 was tallied as 31,930 from Period I to IV. YLL dominated over YLD. The estimates of VSL were US$591 billion and US$5135 billion based on HWM and CVM, respectively. The estimate of VSL increased from US$579 billion in Period I to US$2160 billion in Period IV using CVM. The higher the human development index (HDI), the higher the value of DALYs and VSL. However, there exits the disparity even at the same level of HDI. Machine learning analysis categorized eight patterns of global burden of COVID-19 with a large variation from US$0.001 billion to US$691.4 billion. CONCLUSION: Global burden of COVID-19 pandemic resulted in substantial health and value of life loss particularly in developed economies. Classifications of such health and economic loss is informative to early preparation of adequate resource to reduce impacts.

Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers.

OBJECTIVE: To measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening. DESIGN: A prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features. RESULTS: FIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80). CONCLUSION: A large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.

Classifying interval cancers as false negatives or newly occurring in fecal immunochemical testing.

OBJECTIVE: To classify interval colorectal cancers as false negatives or newly occurring cases in a biennial Fecal immunochemical test (FIT) screening program and by various interscreening intervals. SETTING: Data from the Taiwanese biennial colorectal cancer screening program involving FIT from 2004 to 2014 were used to estimate the incidence rate of asymptomatic colorectal cancer and the rate of its subsequent progression to clinical mode. METHODS: The sensitivity of detecting asymptomatic colorectal cancers excluding newly developed colorectal cancers was compared to the conventional estimate of sensitivity, the complementary FIT interval cancer rate as a percentage of the expected incidence rate ((1-I/E)%). The relative contribution of newly developed or false-negative cases to FIT interval colorectal cancers was estimated by age and interscreening intervals. RESULTS: The Taiwanese biennial fecal immunochemical test screening program had a conventional sensitivity estimate of 70.2%. After newly developed colorectal cancers were separated from FIT interval cancers, the ability to detect asymptomatic colorectal cancers increased to 75.5%. FIT interval colorectal cancers from the biennial program mainly resulted from newly developed colorectal cancers (68.8%). The corresponding figures decreased to 61.1% for the annual program but increased to 74.7% for the triennial program. The preponderance of newly developed colorectal cancers among FIT interval cancers was more prominent in screenees aged 50-59 than in those aged 60-69. CONCLUSIONS: Newly developed colorectal cancers showed a predominance among the FIT interval colorectal cancers in particular in the younger population screened. It is desirable to identify high-risk individuals to offer them a short interscreening interval or advanced detection methods to reduce their odds of developing interval cancer.

Impact of treatment delay on survival of oral/oropharyngeal cancers: Results of a nationwide screening program.

BACKGROUND: To assess the impact of treatment delay on survival of oral/oropharyngeal cancer (OSCC). METHODS: We followed 5743 OSCCs between 2004 and 2009 from a population-based screening program and ascertained death until the end of 2012. RESULTS: The hazard ratios (HRs) of mortality from OSCC were 1.46 (1.30-1.65) and 1.18 (1.04-1.33) in univariable and multivariable analyses, respectively, for treatment delay longer than 6 weeks compared with that shorter than 3 weeks. The corresponding figures were 1.12 (1.01-1.24) and 1.00 (0.91-1.11) for treatment delay between 3 and 6 weeks. Advancing age (1.01), higher stage (stage II: 1.84, stage III: 2.97, stage IV: 6.33), cancer in tongue (1.37), or hard palate (1.63) had higher HR of mortality (P < .05). However, treatment at medical center had a lower mortality (0.83, 0.75-0.91) than local/regional hospital. CONCLUSIONS: Treatment delay longer than 6 weeks for OSCCs detected via a population-based screening program had unfavorable survival.

Early detection of breast cancer rectifies inequality of breast cancer outcomes.

OBJECTIVES: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome. METHODS: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression. RESULTS: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range. CONCLUSIONS: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.

Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands.

OBJECTIVE: Although mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear. DESIGN: Mass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively. RESULTS: After six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI -14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori. CONCLUSION: Population-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period. TRIAL REGISTRATION NUMBER: NCT00155389.

Precision Science on Incidence and Progression of Early-Detected Small Breast Invasive Cancers by Mammographic Features.

The aim was to evaluate how the inter-screening interval affected the performance of screening by mammographic appearances. This was a Swedish retrospective screening cohort study with information on screening history and mammography features in two periods (1977-1985 and 1996-2010). The pre-clinical incidence and the mean sojourn time (MST) for small breast cancer allowing for sensitivity by mammographic appearances were estimated. The percentage of interval cancer against background incidence (I/E ratio) was used to assess the performance of mammography screening by different inter-screening intervals. The sensitivity-adjusted MSTs (in years) were heterogeneous with mammographic features, being longer for powdery and crushed stone-like calcifications (4.26, (95% CI, 3.50-5.26)) and stellate masses (3.76, (95% CI, 3.15-4.53)) but shorter for circular masses (2.65, (95% CI, 2.06-3.55)) in 1996-2010. The similar trends, albeit longer MSTs, were also noted in 1977-1985. The I/E ratios for the stellate type were 23% and 32% for biennial and triennial screening, respectively. The corresponding figures were 32% and 43% for the circular type and 21% and 29% for powdery and crushed stone-like calcifications, respectively. Mammography-featured progressions of small invasive breast cancer provides a new insight into personalized quality assurance, surveillance, treatment and therapy of early-detected breast cancer.

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

BACKGROUND: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death. METHODS: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression. RESULTS: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]). CONCLUSIONS: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.

Cost-Effectiveness Analysis of Deep Brain Stimulation for Parkinson Disease in Taiwan.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for Parkinson disease (PD). However, cost-effectiveness analysis is required because most patients are older adults and decision makers must therefore consider whether the long-term effectiveness outweighs the initial cost. METHODS: A Markov decision model was constructed on the basis of a societal perspective. The Hoehn and Yahr scale and Unified PD Rating Scale motor score were used in the polytomous logistic regression model. Markov Chain Monte Carlo simulation was used to initiate the probabilistic cost-effectiveness analysis. RESULTS: The life-year gained (LYG) in the STN-DBS group and medication group was, respectively, 2.937 and 2.632 years at the 3-year follow-up and 7.417 and 5.971 years at the 10-year follow-up. The quality-adjusted life-year (QALY) gained in the STN-DBS and medication groups was, respectively, 1.739 and 1.220 at the 3-year follow-up and 4.189 and 2.88 at the 10-year follow-up. The incremental cost-effectiveness ratio of STN-DBS compared with medication was $147,065 per LYG and $123,436 per QALY gained at the 3-year follow-up and $36,833 and $69,033 at the 10-year follow-up, respectively. STN-DBS is an optimal strategy when the willingness to pay is $150,000 per LYG and over $90,000 per QALY gained in 3 years and when the willingness to pay is over $38,000 per LYG and over $41,000 per QALY gained in 10 years. CONCLUSIONS: This study provided data comparing STN-DBS and medical treatment for PD with respect to LYG and QALY gained. STN-DBS was more cost-effective in terms of LYG and QALY gained according to the current gross domestic product of Taiwan.

Low ambient temperature as the only meteorological risk factor of seizure occurrence: A multivariate study.

BACKGROUND: The onset of epileptic seizures is influenced by weather, which is multifactorial. It is unknown which specific weather factors affect the occurrence of seizures. OBJECTIVES: We studied the correlation between the onset of epileptic seizures and multiple weather parameters based on a population-based registry profile. METHODS: We determined the number of patients who visited emergency services in Taiwan diagnosed as having epilepsy. Then we used a linear regression model to analyze the monthly average number of patients who received emergency treatment for epilepsy in relation to temperature, barometric pressure, accumulated precipitation, relative humidity, and hours of sunshine. The Poisson regression model was used to analyze multiple meteorological factors in relation to the number of daily emergency visits because of epilepsy. A receiver operating characteristic curve was used to determine the cutoff temperature for the occurrence of seizures. RESULTS: Temperature appeared to be the robust factor for the onset of epilepsy. For every 1 °C decrease in temperature, there was a relative risk increase of 1.016 in the number of emergency visits as a result of epilepsy. Temperature lower than 18 °C had the best predictive value for seizure. Barometric pressure, accumulated precipitation, relative humidity, and the number of hours of sunshine were not related to the occurrence of seizures. SIGNIFICANCE: Our results suggest that temperature is the only influential meteorological factor that affects seizure occurrence.

Heterogeneity in Cost-Effectiveness Analysis of Vaccination for Mild and Moderate Alzheimer's Disease.

BACKGROUND: Immunotherapy for Alzheimer's disease(AD) has gained momentum in recent years. One of the concerns over its application pertains to Cost-Effectiveness Analysis (CEA) from population average and specific subgroup differences, as such a therapy is imperative for health decisionmakers to allocate limited resources. However, this sort of CEA model considering heterogeneous population with risk factors adjustment has been rarely addressed. METHODS: We aimed to show the heterogeneity of CEA in immunotherapy for AD in comparison with the comparator without intervention. Economic evaluation was performed via incremental Cost- Effectiveness Ratio (ICER) and Cost-Effectiveness Acceptability Curve (CEAC) in terms of the Quality- Adjusted Life Years (QALY). First, population-average CEA was performed with and without adjustment for age and gender. Secondly, sub-group CEA was performed with the stratification of gender and age based on Markov process. RESULTS: Given the threshold of $20,000 of willingness to pay, the results of ICER without and with adjustment for age and gender revealed similar results ($14,691/QALY and $17,604/QALY). The subgroup ICER results by different age groups and gender showed substantial differences. The CEAC showed that the probability of being cost-effective was only 48.8%-53.3% in terms of QALY at population level but varied from 83.5% in women aged 50-64 years, following women aged 65-74 years and decreased to 0.2% in men≥ 75 years. CONCLUSION: There were considerable heterogeneities observed in the CEA of vaccination for AD. As with the development of personalized medicine, the CEA results assessed by health decision-maker should not only be considered by population-average level but also specific sub-group levels.

Quantile-based fecal hemoglobin concentration for assessing colorectal neoplasms with 1,263,717 Taiwanese screenees.

BACKGROUND: Although fecal hemoglobin concentration (f-Hb) was highly associated with the risk of colorectal neoplasms, current studies on this subject are hampered by skewedness of the data and the ordinal property of f-Hb has not been well studied yet. Our aim was to develop a quantile-based method to estimate adjusted percentiles (median) of fecal hemoglobin concentration and their derived prediction for the risk of multistage outcomes of colorectal disease. METHODS: We used a 6-year follow-up cohort of Taiwanese nationwide colorectal screening program with fecal immunochemical testing (FIT) to obtain fecal hemoglobin concentration and applied accelerated failure time multi-variable analyses to make the comparison of adjusted median and other percentitles of fecal hemoglobin across four categories of colorectal carcinogenesis. We then predicted the risk of colorectal neoplasms on the basis of the corresponding percentile values by using accelerated failure time model with Bayesian inversion method. RESULTS: The adjusted median fecal hemoglobin concentration of nonadvanced adenoma, advanced adenoma, and colorectal cancer were 57, 82, and 163 µg/g feces as opposed to 0 µg/g feces for the normal group. At 90 µg/g of f-Hb, the highly suspected cut-off for colorectal disease, the risks were 17% for non-advanced adenoma, 6% for advanced adenoma, and 9% for CRC. Life-time risks of each colorectal neoplasm were derived by percentiles of fecal hemoglobin concentration. CONCLUSION: Covariate-adjusted risk stratification for multistage outcomes of colorectal neoplasia were provided by using the quantiles of fecal hemoglobin concentration, yielding the estimated life-time risks of 25th to 75th quantitles, ranging from 0.5 to 44% for colorectal cancer, 0.2 to 46% for non-advanced adenoma, and 0.1 to 20% for advanced adenoma.

Impact of Overdiagnosis on Long-Term Breast Cancer Survival.

Elucidating whether and how long-term survival of breast cancer is mainly due to cure after early detection and effective treatment and therapy or overdiagnosis resulting from the widespread use of mammography provides a new insight into the role mammography plays in screening, surveillance, and treatment of breast cancer. Given information on detection modes, the impact of overdiagnosis due to mammography screening on long-term breast cancer survival was quantitatively assessed by applying a zero (cured or overdiagnosis)-inflated model design and analysis to a 15-year follow-up breast cancer cohort in Dalarna, Sweden. The probability for non-progressive breast cancer (the zero part) was 56.14% including the 44.34% complete cure after early detection and initial treatment and a small 11.80% overdiagnosis resulting from mammography screening program (8.94%) and high awareness (2.86%). The 15-year adjusted cumulative survival of breast cancer was dropped from 88.25% to 74.80% after correcting for the zero-inflated part of overdiagnosis. The present findings reveal that the majority of survivors among women diagnosed with breast cancer could be attributed to the cure resulting from mammography screening and accompanying effective treatment and therapy and only a small fraction of those were due to overdiagnosis.

Elucidating bidirectional relationship between metabolic syndrome and elevated faecal haemoglobin concentration: a Taiwanese community-based cohort study.

OBJECTIVES: To elucidate the bidirectional temporal relationship between elevated faecal haemoglobin (f-Hb) concentration and metabolic syndrome (MetS). DESIGN: A longitudinal cohort study was conducted by utilising data on community-based periodical screening for colorectal cancer with faecal immunochemical test (FIT) and health check-up for MetS. SETTING: Population-based organised integrated service screening in Keelung city, Taiwan. PARTICIPANTS: We enrolled a total of 62,293 community residents aged 40-79 years. MAIN OUTCOMES AND MEASURES: Bidirectional outcomes of FIT-positive and MetS were measured. RESULTS: The presence of MetS at baseline led to a statistically significant 31% elevated risk of being incident FIT-positive (adjusted HR, (aHR)=1.31, 95% CI: 1.14 to 1.51) whereas the effect of those with FIT-positive at baseline on incident MetS was not statistically significant (aHR=1.06, 95% CI: 0.89 to 1.25) after adjusting for relevant confounders. Such an effect was particularly noted for three individual components (abnormal waist circumference, higher fasting plasma glucose and lower high-density lipoprotein). CONCLUSIONS: Our finding on the presence of MetS before FIT-positive based on bidirectional relationship assessment suggests the control of MetS may contribute to reducing the risk of colorectal neoplasia through the early surveillance of f-Hb. However, such a temporal epidemiological finding still needs to be verified by using other external data.

Hurdle Poisson Regression Model for Identifying Factors Related to Noncompliance and Waiting Time for Confirmatory Diagnosis in Colorectal Cancer Screening.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Risk for a second primary hypopharyngeal and esophageal cancer after an initial primary oral cancer.

OBJECTIVE: To investigate the risk for second primary cancer in the hypopharynx and esophagus (SPC-HE) among individuals with an initial oral/oropharyngeal cancer. MATERIALS AND METHODS: Mass screening data from Taiwan (2004-2009) included individuals who were ≥18 years old and smoked cigarettes and/or chewed betel quid. Occurrence of SPC-HE was monitored until December 31, 2014. Results were expressed as adjusted relative risk (aRR) and 95% confidence interval (CI). RESULTS: One hundred and fifty-eight out of 4,494 subjects with oral cancer developed SPC-HE (incidence rate: 6.47 per 1,000 person-years). Relative to patients with primary cancers in the lip, the risk of an SPC-HE was higher in patients with primary cancers in oropharynx (aRR: 19.98, 95% CI: 4.72-84.55), floor of mouth (aRR: 12.13, 95% CI: 2.67-55.15), and hard palate (aRR: 7.31, 95% CI: 1.65-32.37), but not in patients with cancers in tongue (aRR: 3.67, 95% CI: 0.89-15.17) or gum (aRR: 3.99, 95% CI: 0.92-17.35). Regression analyses also showed the risk of an SPC-HE was greater in alcohol drinkers than those who did not (aRR: 1.65, 95% CI: 1.10-2.48). CONCLUSIONS: Compared with the initial cancer in the lip, patients with a cancer in the oropharynx, floor of mouth, and hard palate had a higher risk for the SPC-HE.