The effect of antiarrhythmic medications on the risk of cardiovascular outcomes in patients with atrial fibrillation and coronary artery disease.

BACKGROUND: While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice. METHODS: This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes. RESULTS: Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio [HR] 1.531, 95% confidence interval [CI] 1.112-2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174-1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation. CONCLUSION: For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF.

Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients.

OBJECTIVE: Individuals with hyperthyroidism are at an increased risk of atrial fibrillation (AF), but the association between autoantibodies and AF or cardiovascular mortality in individuals who have returned to normal thyroid function remains unclear. METHODS: The study utilized electronic medical records from National Taiwan University Hospital between 2000 and 2022. Each hyperthyroidism patient had at least 1 thyrotropin-binding inhibiting immunoglobulin (TBII) measurement. The relationship between TBII levels and the risk of AF and cardiovascular mortality was assessed using multivariable Cox regression models and Kaplan-Meier survival analysis. RESULTS: Among the 14 618 enrolled patients over a 20-year timeframe, 173 individuals developed AF, while 46 experienced cardiovascular mortality. TBII values exceeding 35% were significantly associated with an elevated risk of AF for both the first TBII (hazard ratio {HR} 1.48 [1.05-2.08], P = .027) and mean TBII (HR 1.91 [1.37-2.65], P < .001). Furthermore, after free T4 levels had normalized, a borderline association between first TBII and AF (HR 1.59 [0.99-2.56], P = .056) was observed, while higher mean TBII increased AF (HR 1.78 [1.11-2.85], P = .017). Higher first and mean TBII burden continued to significantly impact the incidence of cardiovascular mortality (HR 6.73 [1.42-31.82], P = .016; 7.87 [1.66-37.20], P = .009). Kaplan-Meier analysis demonstrated that elevated TBII levels increased the risk of AF and cardiac mortality (log-rank P = .035 and .027, respectively). CONCLUSION: In euthyroid individuals following antithyroid treatment, elevated circulating TBII levels and burden are associated with an elevated risk of long-term incident AF and cardiovascular mortality. Further reduction of TBII level below 35% will benefit to clinical outcomes.

Prediabetes increases the risk of major limb and cardiovascular events.

BACKGROUND: Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated with a similar risk of complications as diabetes, but its relationship with peripheral arterial disease remains underexplored. METHODS: We conducted a retrospective cohort study involving 36,950 adult patients, utilizing electronic medical records from the National Taiwan University Hospital between 2014 and 2019. We employed multivariable Cox regression and Kaplan-Meier analysis with the log-rank test to analyze major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in relation to normal glucose regulation (NGR) and prediabetes. RESULTS: During the 131,783 person-years follow-up, 17,754 cases of prediabetes and 19,196 individuals with normal glucose regulation (NGR) were identified. Kaplan-Meier analysis revealed an increased incidence of both MALE and MACE in individuals with prediabetes. (log-rank p = 0.024 and < 0.001). Prediabetes exhibited a significant association with an elevated risk of MALE (adjusted hazard ratio (aHR) 1.26 [95% CI 1.10-1.46], p = 0.001) and MACE (aHR 1.46 [1.27-1.67], p < 0.001). Furthermore, in individuals with prediabetes, the elevation in the risk of MALE commenced before HbA1c levels surpassed 5.0% (for HbA1c 5.0-5.5%: aHR 1.78 (1.04-3.04), p = 0.036; HbA1c 5.5-6.0%: aHR 1.29 [1.06-1.58], p = 0.012; aHbA1c 6.0-6.5%: aHR 1.39 [1.14-1.70], p < 0.001). Similarly, the onset of increased MACE risk was observed when HbA1c levels exceeded 5.5% (for HbA1c 5.5-6.0%: aHR 1.67 [1.39-2.01], p < 0.001; HbA1c 6.0-6.5%: HR 2.10 [1.76-2.51], p < 0.001). Factors associated with both MALE and MACE in prediabetes include advanced age, male gender, higher body mass index, and a history of heart failure or atrial fibrillation. CONCLUSION: We demonstrated higher susceptibility to MALE and MACE in prediabetes compared to normoglycemic counterparts, notwithstanding lower HbA1c levels. Complications may manifest at an earlier prediabetes trajectory. Intensive lifestyle modification may improve the prognosis of severe prediabetes.

A cross-sectional study for prevalence and risk factors of peri-implant marginal bone loss.

STATEMENT OF PROBLEM: Progressive peri-implant marginal bone loss and peri-implantitis have become a growing problem, but cross-sectional studies on their prevalence and risk factors are sparse. PURPOSE: The purpose of this cross-sectional clinical study was to investigate the prevalence of peri-implant marginal bone loss (MBL) and to identify systemic and local risk factors. MATERIAL AND METHODS: All adult patients who had received dental implants at the National Taiwan University Hospital (NTUH) during 2009 or 2010 were included. Their medical records were collected from the NTUH-integrative Medical Database. Consecutive follow-up radiographs were accessed for severity of MBL. The influence of each factor on MBL was estimated by using generalized estimating equations (GEEs). RESULTS: A total of 732 participants with 1873 implants were analyzed (mean follow-up: 5.30 years). The prevalence of MBL was 59.15% at the individual level and 49.55% at the implant level. The risk indicators identified for the presence of MBL were follow-up period of more than 2 years, diagnosis of diabetes within 12 months, radiation therapy (2 years after implant placement), implant location at maxillary canine (compared with mandibular molar), and implants from the Nobel Biocare brands (Brånemark System and NobelActive). A second multivariate GEE model confirmed the association of progressive MBL with implant location at the maxillary canine and mandibular incisor and implant brand or design. CONCLUSIONS: The identified risk indicators for MBL were longer follow-up period, diagnosis of diabetes, radiation therapy, implant location at maxillary canine, and implant brand or design.

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

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

Long-Term Visit-to-Visit Glycemic Variability as a Predictor of Major Adverse Limb and Cardiovascular Events in Patients With Diabetes.

Background Peripheral arterial disease (PAD) is a severe complication in patients with type 2 diabetes. Glycemic variability (GV) is associated with increased risks of developing microvascular and macrovascular diseases. However, few studies have focused on the association between GV and PAD. Methods and Results This cohort study used a database maintained by the National Taiwan University Hospital, a tertiary medical center in Taiwan. For each individual, GV parameters were calculated, including fasting glucose coefficient of variability (FGCV) and hemoglobin A1c variability score (HVS). Multivariate Cox regression models were constructed to estimate the relationships between GV parameters and composite scores for major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs). Between 2014 and 2019, a total of 45 436 adult patients with prevalent type 2 diabetes were enrolled for analysis, and GV was assessed during a median follow-up of 64.4 months. The average number of visits and time periods were 13.38 and 157.87 days for the HVS group and 14.27 and 146.59 days for the FGCV group, respectively. The incidence rates for cardiac mortality, PAD, and critical limb ischemia (CLI) were 5.38, 20.11, and 2.41 per 1000 person-years in the FGCV group and 5.35, 20.32, and 2.50 per 1000 person-years in HVS group, respectively. In the Cox regression model with full adjustment, the highest FGCV quartile was associated with significantly increased risks of MALEs (hazard ratio [HR], 1.57 [95% CI, 1.40-1.76]; P<0.001) and MACEs (HR, 1.40 [95% CI, 1.25-1.56]; P<0.001). Similarly, the highest HVS quartile was associated with significantly increased risks of MALEs (HR, 1.44 [95% CI, 1.28-1.62]; P<0.001) and MACEs (HR, 1.28 [95% CI, 1.14-1.43]; P<0.001). The highest FGCV and HVS quartiles were both associated with the development of PAD and CLI (FGCV: PAD [HR, 1.57; P<0.001], CLI [HR, 2.19; P<0.001]; HVS: PAD [HR, 1.44; P<0.001], CLI [HR, 1.67; P=0.003]). The Kaplan-Meier analysis showed significantly higher risks of MALEs and MACEs with increasing GV magnitude (log-rank P<0.001). Conclusions Among individuals with diabetes, increased GV is independently associated with the development of MALEs, including PAD and CLI, and MACEs. The benefit of maintaining stable glycemic levels for improving clinical outcomes warrants further studies.

Mass screening and eradication of Helicobacter pylori as the policy recommendations for gastric cancer prevention.

Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.

Incidence, risk factors and predictors of cardiovascular mortality for aortic stenosis among patients with diabetes mellitus.

AIMS: To find the incidence, risk factors and predictors of cardiovascular (CV) mortality for aortic stenosis (AS) in patients with type 2 diabetes mellitus (T2DM). METHODS: Between 2014 and 2019, 20,979 patients with T2DM who underwent echocardiography were enrolled for analysis. The mean follow-up period was 34 months. Multiple risk factors and outcomes for patients with and without AS were presented. RESULTS: AS was present in 776 (3.70%) patients. Age, female, chronic kidney disease, hyperlipidemia, and peripheral arterial disease statistically increased risk of AS. The CV mortality (adjusted hazard ratio [aHR] = 1.97; 95% confidence interval [CI] 1.336 - 2.906, p < 0.001) and risk of hospitalization for heart failure (HHF) (aHR = 1.73, 95% CI 1.442-2.082, p < 0.001) were significantly increased in patients with AS, without significant differences in acute myocardial infarction and stroke. Severity of AS, body mass index (<27 kg/m2), hypertension, hyperuricemia, left ventricular dysfunction (ejection fraction < 50%), and hematocrit (<38%) were significantly associated with increased CV mortality and HHF. CONCLUSIONS: AS was associated with an increased risk of CV mortality and HHF in patients with T2DM.

Quality assurance of integrative big data for medical research within a multihospital system.

BACKGROUND: The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored. METHODS: Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006-2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning. RESULTS: Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P < 0.05) were found in 34 (58.6%), of which 15 were caused by changes in diagnostic codes, wrong accounts, or modified orders. For the rest, the differences were related to accumulation of hospital visits over time. In the remaining 24 tables (41.4%) without significant differences, three were revised because of incorrect computer programming or wrong accounts. For the rest, the programming was correct and absolute differences were negligible. The applicability was confirmed using the data of 2,730,883 patients and 15,647,468 patient-visits transmitted during 2017-2018, in which 10 (3.5%) tables were corrected. CONCLUSION: Significant magnitude of inconsistent data does exist during the transmission of big data from diverse sources. Systematic validation is essential. Comparing the number of data tabulated using the primary keys allow us to rapidly identify and correct these scattered errors.

Underweight is a major risk factor for atrial fibrillation in Asian people with type 2 diabetes mellitus.

BACKGROUND: Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Obesity commonly accompanies T2DM, and increases the risk of AF. However, the dose-relationship between body mass index (BMI) and AF risk has seldom been studied in patients with diabetes. METHODS: This cohort study utilized a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, 64,339 adult patients with T2DM were enrolled for analysis. BMI was measured and categorized as underweight (BMI < 18.5), normal (18.5 ≤ BMI < 24), overweight (24 ≤ BMI < 27), obesity class 1 (27 ≤ BMI < 30), obesity class 2 (30 ≤ BMI < 35), or obesity class 3 (BMI ≥ 35). Multivariate Cox regression and spline regression models were employed to estimate the relationship between BMI and the risk of AF in patients with T2DM. RESULTS: The incidence of AF was 1.97 per 1000 person-years (median follow-up, 70.7 months). In multivariate Cox regression, using normal BMI as the reference group, underweight (HR 1.52, 95% CI 1.25-1.87, p < 0.001) was associated with a significantly higher risk of AF, while overweight was associated with significantly reduced risk of AF (HR 0.82, 95% CI 0.73-0.89, p < 0.001). Kaplan-Meier analysis showed AF risk was highest in the underweight group, followed by obesity class 3, while the overweight group had the lowest incidence of AF (log-rank test, p < 0.001). The cubic restrictive spline model revealed a "J-shaped" or "L-shaped" relationship between BMI and AF risk. CONCLUSIONS: Underweight status confers the highest AF risk in Asian patients with T2DM.

Higher long-term visit-to-visit glycemic variability predicts new-onset atrial fibrillation in patients with diabetes mellitus.

BACKGROUND: Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Glycemic variability (GV) is associated with risk of micro- and macrovascular diseases. However, whether the GV can increase the risk of AF remains unknown. METHODS: The cohort study used a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, a total of 27,246 adult patients with T2DM were enrolled for analysis. Each individual was assessed to determine the coefficients of variability of fasting glucose (FGCV) and HbA1c variability score (HVS). The GV parameters were categorized into quartiles. Multivariate Cox regression models were employed to estimate the relationship between the GV parameters and the risk of AF, transient ischemic accident (TIA)/ischemic stroke and mortality in patients with T2DM. RESULTS: The incidence rates of AF and TIA/ischemic stroke were 21.31 and 13.71 per 1000 person-year respectively. The medium follow-up period was 70.7 months. In Cox regression model with full adjustment, the highest quartile of FGCV was not associated with increased risk of AF [Hazard ratio (HR): 1.12, 95% confidence interval (CI) 0.96-1.29, p = 0.148] or TIA/ischemic stroke (HR: 1.04, 95% CI 0.83-1.31, p = 0.736), but was associated with increased risk of total mortality (HR: 1.33, 95% CI 1.12-1.58, p < 0.001) and non-cardiac mortality (HR: 1.41, 95% CI 1.15-1.71, p < 0.001). The highest HVS was significantly associated with increased risk of AF (HR: 1.29, 95% CI 1.12-1.50, p < 0.001), total mortality (HR: 2.43, 95% CI 2.03-2.90, p < 0.001), cardiac mortality (HR: 1.50, 95% CI 1.06-2.14, p = 0.024) and non-cardiac mortality (HR: 2.80, 95% CI 2.28-3.44, p < 0.001) but was not associated with TIA/ischemic stroke (HR: 0.98, 95% CI 0.78-1.23, p = 0.846). The Kaplan-Meier analysis showed significantly higher risk of AF, cardiac and non-cardiac mortality according to the magnitude of GV (log-rank test, p < 0.001). CONCLUSIONS: Our data demonstrate that high GV is independently associated with the development of new-onset AF in patients with T2DM. The benefit of maintaining stable glycemic levels to improve clinical outcomes warrants further studies.

Long Term Outcome of Postoperative Atrial Fibrillation After Cardiac Surgery-A Propensity Score-Matched Cohort Analysis.

Background: Postoperative atrial fibrillation (POAF) results in a longer hospital stay and excess mortality. However, whether POAF would increase stroke rate has been debated for years. When and how long should anticoagulation be used to prevent stroke are unknown. In the study, we planned to investigate the clinical demographics and long-term outcomes of POAF after cardiac surgery in a single-center cohort. Methods: The cohort study used a database from National Taiwan University Hospital, a single tertiary medical center in Taiwan, between 2007 and 2017, to identify patients with prior normal sinus rhythm developing POAF after cardiac surgery. Patients without POAF after cardiac surgery were used as controls. Propensity score matching with 1:1 ratio and Cox regression models were employed to estimate the risk of transient ischemic accident (TIA) or ischemic stroke. Results: From 2007 to 2017, a total of 8,374 patients received open-heart surgery, in which 1,585 patients with a history of AF were excluded. The overall incidence of TIA/ischemic stroke was 3.9% in a median 9.2-years of follow-up. After propensity matching, 1,965 matched paired subjects were included for analysis. Postoperative atrial fibrillation was associated with an increased risk of future AF [Hazard ratio (HR) 1.40, 95% confidence interval (95%CI) = 1.09-1.79, p = 0.008] and heart failure (HF) hospitalization (HR 1.58, 95%CI 1.23-2.04, p < 0.001); however, POAF did not significantly correlate with the risk of TIA/ischemic stroke (HR 1.17, 95%CI 0.85-1.60, p = 0.043). Kaplan-Meier analysis showed that POAF was a significant predictor for future AF, HF hospitalization, and overall mortality, but not for TIA/ischemic stroke. Conclusion: In the Asian population, POAF after cardiac surgery increased the risk of future AF, HF, and overall mortality, but was not associated with future TIA/ischemic stroke.

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.

Planning mass eradication of Helicobacter pylori infection for indigenous Taiwanese peoples to reduce gastric cancer.

BACKGROUND AND AIM: The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in Indigenous communities. METHODS: First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006-2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy. RESULTS: Gastric cancer incidence (24.4 vs 12.3 per 100 000 person-years) and mortality rates (15.8 vs 6.8 per 100 000 person-years) were higher in Indigenous than in non-Indigenous, with 2.19-fold (95% confidence interval [CI]: 2.06-2.33) and 2.47-fold (2.28-2.67) increased risk, respectively. In Indigenous communities, H. pylori infection was more prevalent in Indigenous than in non-Indigenous (59.4% vs 31.5%, P < 0.01). Regression analyses consistently showed that either the mountain or plain Indigenous had 1.89-fold (95% CI: 1.34-2.66) and 1.73-fold (95% CI: 1.24-2.41) increased risk for H. pylori infection, respectively, as compared with non-Indigenous, adjusting for other baseline characteristics. The high infection rates were similarly seen in young, middle-aged, and older adults. Program eradication rates using clarithromycin-based triple therapy were suboptimal (73.7%, 95% CI: 70.0-77.4%); the habits of smoking (1.70-fold, 95% CI: 1.01-2.39) and betel nut chewing (1.54-fold, 95% CI: 0.93-2.16) were associated with the higher risk of treatment failure. CONCLUSION: Gastric cancer burden is higher in Indigenous Taiwanese peoples than in their non-Indigenous counterparts. Eliminating the prevalent risk factor of H. pylori infection is a top priority to reduce this health disparity.

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.

Impact of varying anatomic sites on advanced stage and survival of oral cancer: 9-year prospective cohort of 27 717 cases.

BACKGROUND: To elucidate the impact of varying anatomic sites on advanced stage of and death from oral cancer. METHODS: A total of 27 717 oral cancers mainly from a population-based visual inspection program in Taiwan from 2004 to 2009 was followed until the end of 2012. RESULTS: Using lip cancer as reference, the odds ratios (95% confidence interval [CI]) of advanced stage of cancer were 2.20 (1.92-2.51) for tongue, 2.60 (2.28-2.97) for buccal, 2.68 (2.20-3.28) for floor of mouth, 2.96 (2.52-3.47) for hard palate, 6.04 (5.17-7.05) for gingiva, and 10.83 (9.20-12.74) for oropharynx. The estimated hazard ratios (95% CI) for oral cancer death increased from 1.48 (1.31-1.67) in buccal, 1.61 (1.43-1.82) in tongue, 1.68 (1.41-1.99) in floor of mouth, 1.79 (1.57-2.05) in gingiva, 1.97 (1.71-2.26) in hard palate, and 2.15 (1.89-2.45) in oropharynx. CONCLUSION: Different anatomic sites had variations in advanced stage of and death from oral cancer and need vigilant surveillance.

Effects of screening and universal healthcare on long-term colorectal cancer mortality.

BACKGROUND: To evaluate the time trends of colorectal cancer (CRC) affected by a Nationwide Colorectal Cancer Screening (NCCS) programme with biennial faecal immunochemical testing (FIT) and Nationwide Healthcare Insurance (NHI). METHODS: Data from the national registries on cancer and death in Taiwan were separated into years 1984-1993, 1994-2003 and 2004-2013 based on the implementations of NHI (starting 1995) and NCCS (starting 2004). The adult population was divided into three age groups (young, 30-49; middle-aged, 50-69; and old, 70-84 years); only the middle-aged were eligible for NCCS. Crude and adjusted effects of NCCS and NHI were quantified by percentage change and 95% confidence interval (CI) with respect to CRC mortality, according to the attributions from incidence and survival. RESULTS: Within 335 million person-years of follow-up, 204 362 incident CRCs and 80 771 CRC-related deaths were identified. Increasing mortality trends were noted for 1994-2003 (post-NHI) vs 1984-1993 due to remarkable increasing incidence trends that could not be offset by improved survival as a result of NHI. During 2004-13 (post-NCCS), mortality continued to increase by 15% (95% CI: 10-21%) in young adults (30-49 years) and 8% (95% CI: 6-11%) in older adults (70-84 years), whereas middle-aged adults (50-69 years) had a reduction of 7% (95% CI: 5-9%) due to a remarkable stage shift and subsequent improvement in survival. In the middle-aged adults, increased incidence was less but survival improvement was more compared with other age groups. CONCLUSIONS: Whereas universal healthcare insurance led to improvement in CRC survival, FIT-based screening has made an even greater contribution to reducing CRC mortality.

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.

Malignant transformation to oral cancer by subtype of oral potentially malignant disorder: A prospective cohort study of Taiwanese nationwide oral cancer screening program.

OBJECTIVES: To elucidate the risk of malignant transformation to invasive oral cancer by subtypes of oral potentially malignant disorders (OPMD) and to examine the independent effects of risk factors, particularly alcohol drinking, by subtype based on a nationwide oral cancer screening program targeting at general population with habits of smoking and/or betel quids chewing. MATERIALS AND METHODS: The total of 8501 subjects diagnosed as different subtypes of OPMDs from the Taiwanese screening program between 2004 and 2009 were followed up over time to ascertain the occurrence of invasive oral cancer. The hazard ratios of malignant transformation were estimated by using Cox proportional hazards regression model. RESULTS: The overall malignant rate (per 1000 person-years) to oral cancer was 8.4 (407 incident cases with an average of 5.7 years of follow-up). The highest rate was noted in exophytic verrucous hyperplasia (33), followed by erythroplakia (11.8), erythroleukoplakia (10.7), oral submucous fibrosis (OSF) (8.6), and leukoplakia (5.4). After adjusting for confounders, exophytic verrucous hyperplasia still had a 5.69 (4.47-7.24) times risk compared with leukoplakia. The corresponding figures for erythroplakia, erythroleukoplakia, and OSF were 2.25 (1.31-3.89), 2.00 (1.13-3.53), and 1.63 (1.29-2.06), respectively. Alcohol drinking elevated the overall risk of malignant transformation by 23% (1-52% and also triggered a higher risk in OSF (aHR = 1.62 (1.06-2.47)). The higher risk attributed to betel quids chewing was noted for exophytic verrucous hyperplasia (aHR = 4.23 (1.55-11.55)). CONCLUSIONS: The risk of malignant transformation to oral cancer varied with the subtypes of OPMD and was elevated in OSF and verrucous hyperplasia attributed to alcohol drinking and betel quids, respectively.