Double-contrast barium enema is no longer justified as a backup examination for colonoscopy in the population screening program: Population study in an organized fecal immunochemical test-based screening program.

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.

Integrating the clinical frailty scale with emergency department triage systems for elder patients: A prospective study.

BACKGROUND: This prospective study investigated whether integrating the Clinical Frailty Scale (CFS) with a triage system would improve triage for older adult emergency department (ED) patients. METHODS: We enrolled ED patients aged 65 years or older at 5 study sites in Taiwan between December 2020 and April 2021. All eligible patients were assigned a triage level by using the Taiwan Triage and Acuity Scale (TTAS) in accordance with usual practice. A CFS score was collected from them. The primary outcome was critical events, defined as ICU admission or in-hospital mortality. The secondary outcomes were ED medical expenditures, number of orders in the ED, and length of hospital stay (LOS). We applied a reclassification concept and integrated the CFS and TTAS to create the Triage Frailty Acuity Scale (TFAS). We compared the outcomes achieved between the TTAS and TFAS. RESULTS: Of 1023 screened ED patients, 890 were enrolled. The majority were assigned to TTAS level 3 (73.26%) and had CFS scores of 4 to 9 (55.96%). The primary outcomes were better predicted by the TFAS than the TTAS (area under the curve [AUC] 0.82 vs. 064). Using multivariable approach, TTAS level 1 (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.7-13.4) and CFS score (OR, 5.8; 95% CI, 1.9-17.2) were significantly associated with the primary outcomes. For older adults at the highest triage level, the TFAS was not associated with an increase in the primary outcomes compared with the TTAS; however, the TFAS was associated with a significant decrease in the number of older ED patients assigned to triage levels 3 to 5. In addition, TFAS had a longer average LOS but did not have a higher average number of orders or ED medical expenditures compared to TTAS. CONCLUSIONS: The TFAS identified more older ED patients who had been triaged as less emergent but proceeded to need ICU admission or in-hospital death. Incorporating the CFS into triage may reduce the under-triage of older adults in the ED.

Validity of the Taiwan Triage and Acuity Scale in mainland China: a retrospective observational study.

OBJECTIVES: The Taiwan Triage and Acuity Scale (TTAS), developed for use in EDs, has been shown to be an excellent tool for triaging patients with high predictive performance, with an area under the receiver operating curve (AUROC) of 0.75. TTAS has been widely used in hospitals in Taiwan since 2010, but its utility has not been studied outside of Taiwan. Thus, the aim of this study was to evaluate the validity of using the TTAS in the ED of a tertiary hospital in mainland China to predict patient outcomes. METHODS: A retrospective observational study was performed on patients 14 years of age or older attending the ED of a tertiary hospital in mainland China between 1 January 2016 and 31 March 2016. The validity of the TTAS in predicting hospital admission, intensive care unit (ICU) admission, death, ED length of stay (LOS) and ED resource utilisation was evaluated by determining the correlation of these outcomes with the TTAS, AUROC and test characteristics. RESULTS: A total of 7843 patients were included in this study. There were significant differences between the TTAS categories in disposition, ED LOS and ED resource utilisation (p<0.0001). The TTAS was significantly correlated with patient disposition at discharge, hospital admission, ICU admission and death in the ED (Kendall rank correlations were 0.254, -0.254, -0.079 and -0.071, respectively; p=0.001). The AUROCs for the prediction of hospital admissions, ICU admissions and deaths in the ED were 0.749 (95% CI 0.732 to 0.765), 0.869 (95% CI 0.797 to 0.942) and 0.998 (95% CI 0.995 to 1.000), respectively. Our results demonstrated better performance using the TTAS for predictions of ICU admission and death. CONCLUSIONS: The TTAS had good validity in predicting patient outcomes and ED resource utilisation in a tertiary hospital in mainland China. Compared with the performance of the TTAS in Taiwan, our results suggest that the TTAS can usefully be applied outside of Taiwan.

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.

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.

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.

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; P < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Stephen A. Feig in this issue.

Risk stratification for gastric cancer after Helicobacter pylori eradication: A population-based study on Matsu Islands.

BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.

Clinical and novel application of FibroScan, FIB-4 and aspartate aminotransferase-to-platelet ratio index in liver fibrosis evaluation in patients with hepatocellular carcinoma and their roles in oesophageal variceal prediction.

BACKGROUND: Non-invasive techniques for liver fibrosis diagnosis are very important for clinician especially in high-risk patients for liver biopsy. We further explored the diagnostic accuracy of FibroScan, FIB-4 and aminotransferase-to-platelet ratio index (APRI) in identifying liver fibrosis and assess their predictive role for oesophageal varices in patients with hepatocellular carcinoma (HCC). METHODS: In total, 380 patients who underwent surgery for HCC were included based on retrospective study design. Liver fibrosis was pathologically diagnosed using the Ishak scoring system. Liver stiffness parameters were measured using FibroScan. APRI and FIB-4 were calculated. Among those, 121 patients who received oesophagogastroduodenoscopic examination underwent variceal evaluation. RESULTS: For liver cirrhosis diagnosis with FibroScan, the optimal cut-off values for the patients with HCC overall, left HCC and right HCC were 8.85, 11.75 and 8.70 kPa (the accuracy were 78.7%, 78.4% and 79.2%, respectively). They had high areas under the receiver operating characteristic curve of 0.84, 0.84 and 0.85. The combined FibroScan, APRI and FIB-4 had very high specificity (more than 92%) for cirrhosis diagnosis. The optimal cut-off liver stiffness values for the diagnosis of varices were all 11.2 kPa. For predicting varices, the optimal cut-off values of FIB-4 and APRI were 2.64 and 0.71, their accuracy were 64.3%-78.4%, 69.4% and 72.7%, respectively. CONCLUSIONS: FibroScan, FIB-4 and APRI have moderate accuracy for liver fibrosis diagnosis and oesophageal varices prediction in patients with hepatoma. This is a study of these non-invasive techniques applied in specific hepatoma patients and with inevitable limitations and need future more studies for validation.

Pregnancy weight gain may affect perinatal outcomes, quality of life during pregnancy, and child-bearing expenses: an observational cohort study.

PURPOSE: We aimed to examine the effect of gestational weight gain (GWG) on perinatal outcomes, quality of life (QoL) during pregnancy, and medical costs of childbirth. METHODS: The observational cohort comprised 2210 pregnant women who were classified into three groups based on their pre-pregnancy body mass index (BMI) and GWG in relation to the 2020 Institute of Medicine (IOM) recommendations. The data were collected on perinatal outcomes, urinary incontinence (UI) during pregnancy, changes in sexual function, and medical costs of hospitalization for delivery. Univariate and multivariable logistic regression models were employed to explore those associations. RESULTS: Only 42.1% of women met the 2020 IOM guidelines. After adjustments for potential confounding factors, women with above-normal GWG had adverse pregnancy outcomes, including a large fetal head circumference and macrosomia, and women with below-normal GWG were more likely to deliver low-birthweight fetuses preterm than women with normal GWG. Only 16.8% of women reported sexual activity during pregnancy. There were not significant differences in sexual activity and satisfaction, or QoL among the three GWG groups. Child-bearing expenses were higher for women with above-normal GWG than for women with normal GWG. Although the child-bearing expenses were higher for the above-normal GWG, the proportion of women with expenses above the median increased according to pre-pregnancy BMI. CONCLUSION: Our results show that inappropriate GWG is associated with a greater risk of adverse perinatal outcomes and increased medical expenses for delivery. Healthcare providers are advised to counsel women to maintain their GWG following the 2020 IOM recommendations throughout pregnancy.

Continental transmission of emerging COVID-19 on the 38° north latitude.

BACKGROUND: As COVID-19 has become a pandemic emerging infectious disease it is important to examine whether there was a spatiotemporal clustering phenomenon in the globe during the rapid spread after the first outbreak reported from southern China. MATERIALS AND METHODS: The open data on the number of COVID-19 cases reported at daily basis form the globe were used to assess the evolution of outbreaks with international air link on the same latitude and also including Taiwan. The dynamic Susceptible-Infected-Recovered model was used to evaluate continental transmission from December 2019 to March 2020 before the declaration of COVID-19 pandemic with basic reproductive number and effective reproductive number before and after containment measurements. RESULTS: For the initial COVID-19 outbreak in China, the estimated reproductive number was reduced from 2.84 during the overwhelming outbreaks in early January to 0.43 after the strict lockdown policy. It is very surprising to find there were three countries (including South Korea, Iran, and Italy) and the Washington state of the USA on the 38° North Latitude involved with large-scale community-acquired outbreaks since the first imported COVID-19 cases from China. The propagation of continental transmission was augmented from hotspot to hotspot with higher reproductive number immediately before the declaration of pandemic. By contrast, there was not any large community-acquired outbreak in Taiwan. CONCLUSION: The propagated spatiotemporal transmission from China to other hotspots may explain the emerging pandemic that can only be exempted by timely border control and preparedness of containment measurements according to Taiwan experience.

Classification of community-acquired outbreaks for the global transmission of COVID-19: Machine learning and statistical model analysis.

BACKGROUND: As Coronavirus disease 2019 (COVID-19) pandemic led to the unprecedent large-scale repeated surges of epidemics worldwide since the end of 2019, data-driven analysis to look into the duration and case load of each episode of outbreak worldwide has been motivated. METHODS: Using open data repository with daily infected, recovered and death cases in the period between March 2020 and April 2021, a descriptive analysis was performed. The susceptible-exposed-infected-recovery model was used to estimate the effective productive number (Rt). The duration taken from Rt > 1 to Rt < 1 and case load were first modelled by using the compound Poisson method. Machine learning analysis using the K-means clustering method was further adopted to classify patterns of community-acquired outbreaks worldwide. RESULTS: The global estimated Rt declined after the first surge of COVID-19 pandemic but there were still two major surges of epidemics occurring in September 2020 and March 2021, respectively, and numerous episodes due to various extents of Nonpharmaceutical Interventions (NPIs). Unsupervised machine learning identified five patterns as "controlled epidemic", "mutant propagated epidemic", "propagated epidemic", "persistent epidemic" and "long persistent epidemic" with the corresponding duration and the logarithm of case load from the lowest (18.6 ± 11.7; 3.4 ± 1.8)) to the highest (258.2 ± 31.9; 11.9 ± 2.4). Countries like Taiwan outside five clusters were classified as no community-acquired outbreak. CONCLUSION: Data-driven models for the new classification of community-acquired outbreaks are useful for global surveillance of uninterrupted COVID-19 pandemic and provide a timely decision support for the distribution of vaccine and the optimal NPIs from global to local community.

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.

Novel Toilet Paper-Based Point-Of-Care Test for the Rapid Detection of Fecal Occult Blood: Instrument Validation Study.

BACKGROUND: Colorectal cancer screening by fecal occult blood testing has been an important public health test and shown to reduce colorectal cancer-related mortality. However, the low participation rate in colorectal cancer screening by the general public remains a problematic public health issue. This fact could be attributed to the complex and unpleasant operation of the screening tool. OBJECTIVE: This study aimed to validate a novel toilet paper-based point-of-care test (ie, JustWipe) as a public health instrument to detect fecal occult blood and provide detailed results from the evaluation of the analytic characteristics in the clinical validation. METHODS: The mechanism of fecal specimen collection by the toilet-paper device was verified with repeatability and reproducibility tests. We also evaluated the analytical characteristics of the test reagents. For clinical validation, we conducted comparisons between JustWipe and other fecal occult blood tests. The first comparison was between JustWipe and typical fecal occult blood testing in a central laboratory setting with 70 fecal specimens from the hospital. For the second comparison, a total of 58 volunteers were recruited, and JustWipe was compared with the commercially available Hemoccult SENSA in a point-of-care setting. RESULTS: Adequate amounts of fecal specimens were collected using the toilet-paper device with small day-to-day and person-to-person variations. The limit of detection of the test reagent was evaluated to be 3.75 µg of hemoglobin per milliliter of reagent. Moreover, the test reagent also showed high repeatability (100%) on different days and high reproducibility (>96%) among different users. The overall agreement between JustWipe and a typical fecal occult blood test in a central laboratory setting was 82.9%. In the setting of point-of-care tests, the overall agreement between JustWipe and Hemoccult SENSA was 89.7%. Moreover, the usability questionnaire showed that the novel test tool had high scores in operation friendliness (87.3/100), ease of reading results (97.4/100), and information usefulness (96.1/100). CONCLUSIONS: We developed and validated a toilet paper-based fecal occult blood test for use as a point-of-care test for the rapid (in 60 seconds) and easy testing of fecal occult blood. These favorable characteristics render it a promising tool for colorectal cancer screening as a public health instrument.

The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening.

BACKGROUND: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? METHODS: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection. RESULTS: The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34-0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44-0.63) compared with the corresponding risks for nonparticipants. CONCLUSIONS: Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.

Time to Colonoscopy and Risk of Colorectal Cancer in Patients With Positive Results From Fecal Immunochemical Tests.

BACKGROUND & AIMS: In patients with positive results from a fecal immunochemical test (FIT), failure to receive a timely follow-up colonoscopy may be associated with higher risks of colorectal cancer (CRC) and advanced-stage CRC. We evaluated the prevalence of any CRC and advanced-stage CRC associated with delays in follow-up colonoscopies for patients with positive results from a FIT. METHODS: We collected data from 39,346 patients (age, 50-69 years) who participated in the Taiwanese Nationwide Screening Program from 2004 through 2012 and had completed a colonoscopy more than 1 month after a positive result from a FIT. Risks of any CRC and advanced-stage CRC (stage III-IV) were evaluated using logistic regression models and results expressed as adjusted odds ratios (aORs) and corresponding 95% CIs. RESULTS: In our cohort, 2003 patients received a diagnosis of any CRC and 445 patients were found to have advanced-stage disease. Compared with colonoscopy within 1-3 months (cases per 1000 patients: 50 for any CRC and 11 for advanced-stage disease), risks were significantly higher when colonoscopy was delayed by more than 6 months for any CRC (aOR, 1.31; 95% CI, 1.04-1.64; 68 cases per 1000 patients) and advanced-stage disease (aOR, 2.09; 95% CI, 1.43-3.06; 24 cases per 1000 patients). The risks continuously increased when colonoscopy was delayed by more than 12 months for any CRC (aOR, 2.17; 95% CI, 1.44-3.26; 98 cases per 1000 patients) and advanced-stage disease (aOR, 2.84; 95% CI, 1.43-5.64; 31 cases per 1000 patients). There were no significant differences for colonoscopy follow up at 3-6 months for risk of any CRC (aOR, 0.98; 95% CI, 0.86-1.12; 49 cases per 1000 patients) or advanced-stage disease (aOR, 0.95; 95% CI, 0.72-1.25; 10 cases per 1000 patients). CONCLUSIONS: In an analysis of data from the Taiwanese Nationwide Screening Program, we found that among patients with positive results from a FIT, risks of CRC and advanced-stage disease increase with time. These findings indicate the importance of timely colonoscopy after a positive result from a FIT.

Serum Pepsinogen as a Predictor for Gastric Cancer Death: A 16-Year Community-based Cohort Study.

GOALS: The purpose of this article is to validate the long-term association between initial serum pepsinogen (PG) measurements and subsequent gastric cancer-specific deaths from a long-term longitudinal cohort. BACKGROUND: Endoscopic surveillance can be effective and efficient in reducing gastric cancer mortality if a biomarker such as serum PG is available to identify high-risk individuals and if the biomarker also is specific to gastric cancer risk. STUDY: Between 1995 and 1998, a gastric cancer-screening program was conducted in a high-risk population: The first stage involved PG testing, and the second stage involved upper endoscopy. The outcome was gastric cancer death, which was monitored until December 31, 2010; results were expressed as the hazard ratio (HR) and corresponding 95% confidence interval (CI) using the Cox proportional hazards regression model. Other causes of death were used as comparators. RESULTS: Among participants (n=3514) aged ≥30 years, 1682 (47.9%) were screened to determine serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori serological positivity showed that PG-I <30 µg/L and PG-I <30 µg/L or PG-I/II ratio <3 were significantly associated with the risk of gastric cancer death (HR, 3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In contrast, there were no significant associations between PG and other causes of death, including neoplastic and non-neoplastic diseases. CONCLUSION: This long-term cohort study shows the usefulness of PG measurement as a biomarker that is specific to the risk of gastric cancer death.

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.

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.

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.