Dynamics of detailed components of metabolic syndrome associated with the risk of cardiovascular disease and death.

Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1-2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95-46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77-30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89-6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46-1.79%) for FMD, 4.74% (95% CI 4.52-4.96%) for MMD, to 20.22% (95% CI 19.52-20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6-7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.

Chronic hepatitis B exhibited higher rate of hepatocellular carcinoma occurrence than hepatitis C in cirrhotic patients after effective antiviral treatment.

BACKGROUND/PURPOSE: Effective antiviral-therapy can reduce the risk of liver cirrhosis related hepatocellular carcinoma in patients with chronic hepatitis B and hepatitis C. Yet, the difference of hepatocellular carcinoma development in chronic hepatitis B and hepatitis C patients with cirrhosis after effective antiviral therapy treatment is unknown. In this study, We comprehensive explored the difference among them. METHODS: 1363 patients with cirrhosis and hepatitis B virus treated with nucleos(t)ide analogues (NUCs) with completely suppressed virus, and patients with cirrhosis and hepatitis C virus treated with pegylated interferon (peg-IFN)/ribavirin (RBV) combination therapy who achieved sustained virologic response were enrolled. RESULTS: Total 261 developed hepatocellular carcinoma within a median follow-up of 4.25 years. Univariate analysis, patients developed hepatocellular carcinoma tended to be of older age, and had lower platelet counts, were chronic hepatitis B carriers, and had higher serum alfa-fetoprotein (AFP) (≥20 ng/mL), FIB-4 index and APRI scores. Subsequent multivariate analysis revealed older age, lower platelet counts, high AFP levels and chronic hepatitis B carriers were independent risk factors of hepatocellular carcinoma. CONCLUSION: Our findings identify that chronic hepatitis B patients were with a higher risk of hepatocellular carcinoma compared to chronic hepatitis C patients after achieving virological response. Special attention should be paid to those patients.

Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals.

BACKGROUND/AIMS: Taiwan has the highest incidence of end-stage renal disease, which requires renal replacement therapy. Chronic kidney disease (CKD) contributes to this burden. However, the current data on the epidemiologic features of CKD in Taiwan are incomplete. Therefore, we aimed to investigate the prevalence and incidence of CKD in a population-based study and then estimate the average dwelling time (ADT) in the main clinical burden of CKD (stages 3-5). METHODS: A prospective cohort study was designed with an integrated community-based multiple screening program of 106,094 individuals aged ≥20 years in Keelung, Taiwan, in 1999-2009. Prevalence was estimated as the percentage of CKD stages among individuals attending the first screening, and incidence was expressed as the ratio of total desired events in the following period to the total observational time. Finally, ADT was estimated from the ratio of prevalence to incidence. RESULTS: The participants' mean age was 47.7 ± 15.4 years. The estimated prevalence was 15.46% for total CKD and 9.06% for CKD stages 3-5. The incidence was 27.21/1,000 person-years (PY) for total CKD and 16.89/1,000-PY for CKD stages 3-5. Older patients, males, and those patients with comorbidities of diabetes mellitus (DM), hypertension, and metabolic syndrome (MetS) exhibited higher prevalence and incidence rates than their opposing counterparts. Moreover, the ADT of CKD stages 3-5 was 5.37 years (95% CI 5.17-5.57). Males and those with comorbidities of DM or MetS had shorter ADTs in CKD stages 3-5 than their opposing counterparts. Interestingly, the ADT of participants with hypertension was longer than those without. CONCLUSIONS: The prevalence and incidence of CKD in Taiwan are high. Moreover, ADT in CKD stages 3-5 varied according to sex, age, and comorbidity. Further exploration of the factors associated with the shifting of this duration will shed light on effective CKD management.

Bayesian negative-binomial-family-based multistate Markov model for the evaluation of periodic population-based cancer screening considering incomplete information and measurement errors.

Population-based cancer screening is often asked but hardly addressed by a question: "How many rounds of screening are required before identifying a cancer of interest staying in the pre-clinical detectable phase (PCDP)?" and also a similar one related to the number of screens required for stopping screening for the low risk group. It can be answered by using longitudinal follow-up data on repeated rounds of screen, namely periodic screen, but such kind of data are rather complicated and fraught with intractable statistical properties including correlated multistate outcomes, unobserved and incomplete (censoring or truncation) information, and imperfect measurements. We therefore developed a negative-binomial-family-based discrete-time stochastic process, taking sensitivity and specificity into account, to accommodate these thorny issues. The estimation of parameters was implemented with Bayesian Markov Chain Monte Carlo method. We demonstrated how to apply this proposed negative-binomial-family-based model to the empirical data similar to the Finnish breast cancer screening program.

Fuzzy set regression method to evaluate the heterogeneity of misclassifications in disease screening with interval-scaled variables: application to osteoporosis (KCIS No. 26).

Although the trade-off between the two misclassifications (false-positive fraction and false-negative fraction), corresponding to type I and type II error in statistical hypothesis testing based on Neyman-Pearson lemma, to determine the optimal cutoff in the province of evaluating the accuracy of medical diagnosis and disease screening using interval-scaled biomarkers has been attempted by the receiver operating characteristic (ROC) curve, the heterogeneity of the two misclassifications in relation to the utility or individual preference for relative weights between the two errors has been barely addressed and has increasingly gained attention in disease screening when the optimal subject-specific or subgroup-specific cutoff (the heterogeneity of ROC curve) is underscored. We proposed a fuzzy set regression method to achieve such a purpose. The proposed method was illustrated with data on screening for osteoporosis with bone mineral density.

Does non-central nervous system tuberculosis increase the risk of ischemic stroke? A population-based propensity score-matched follow-up study.

BACKGROUND: Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. METHODS: We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. RESULTS: During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73-1.14, P = 0.4299). CONCLUSIONS: Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.

Increased risk of ischemic stroke in young patients with ankylosing spondylitis: a population-based longitudinal follow-up study.

BACKGROUND: Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS. METHODS: A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates. RESULTS: During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20-3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16-3.20; p = 0.0110). CONCLUSION: Our study showed an increased risk of developing ischemic stroke in young patients with AS.

Parkinson's disease is related to an increased risk of ischemic stroke-a population-based propensity score-matched follow-up study.

OBJECTIVE: The risk of stroke in patients with Parkinson's disease (PD) remains controversial. The purpose of this population-based propensity score-matched longitudinal follow-up study was to determine whether there is an increased risk of ischemic stroke after PD. METHODS: We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 2204 patients with at least two ambulatory visits with the principal diagnosis of PD in 2001 was enrolled in the PD group. The non- PD group consisted of 2204, propensity score-matched subjects without PD. The ischemic stroke-free survival rates of the two groups were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression with patients matched on propensity score was used to estimate the effect of PD on the occurrence of ischemic stroke. RESULTS: During the three-year follow-up period, 328 subjects in the PD group and 156 subjects in the non-PD group developed ischemic stroke. The ischemic stroke-free survival rate of the PD group was significantly lower than that of the non-PD group (P<0.0001). The hazard ratio (HR) of stroke for the PD group was 2.37 (95% confidence interval [CI], 1.92 to 2.93, P<0.0001) compared to the non- PD group. CONCLUSIONS: This study shows a significantly increased risk of ischemic stroke in PD patients. Further studies are required to investigate the underlying mechanism.

Increased risk of hemorrhagic stroke in patients with migraine: a population-based cohort study.

OBJECTIVE: Previous studies on the association between migraine and the risk of developing hemorrhagic stroke (HS) have generated inconsistent results. The aim of the present population-based, age- and sex- matched follow-up study was to investigate whether migraine is associated with an increased risk of HS. METHOD: A total of 20925 persons with at least two ambulatory visits in 2001 with the principal diagnosis of migraine were enrolled in the migraine group. The non-migraine group consisted of 104625, age- and sex- matched, randomly sampled subjects without migraine. The two-year HS-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the effect of migraine on the occurrence of HS. RESULTS: During the 2 year follow-up, 113 subjects in the migraine group (0.54%) and 255 in the non-migraine group (0.24%) developed HS. The crude hazard ratio (HR) for developing HS in the migraine group was 2.22 compared to the non-migraine group (95% confidence interval [CI]: 1.78-2.77, p<0.0001) and the adjusted HR was 2.13 (95% CI: 1.71-2.67, p<0.0001) after controlling for demographic characteristics and comorbid medical disorders. CONCLUSIONS: This population-based age- and sex- matched cohort study shows that migraine was linked to an increased risk of HS.

Association of diabetes mellitus with the risk of developing adhesive capsulitis of the shoulder: a longitudinal population-based followup study.

OBJECTIVE: Although it has been suggested that diabetes mellitus (DM) is a risk factor for developing adhesive capsulitis of the shoulder (ACS), data on the temporal association between these 2 conditions are sparse. The purpose of this population-based age- and sex-matched cohort study was to investigate the risk of developing ACS in patients with newly diagnosed DM. METHODS: A total of 78,827 subjects with at least 2 ambulatory care visits with a principal diagnosis of DM in 2001 were recruited for the DM group. The non-DM group comprised 236,481 age- and sex-matched randomly sampled subjects without DM. The 3-year cumulative risk of ACS was calculated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to estimate the crude and adjusted hazard ratio (HR) of developing ACS. RESULTS: During a 3-year followup period, 946 subjects (1.20%) in the DM group and 2,254 subjects (0.95%) in the non-DM group developed ACS. The crude HR of developing ACS for the DM group compared to the non-DM group was 1.333 (95% confidence interval [95% CI] 1.236-1.439, P < 0.0001), whereas the adjusted HR was 1.321 (95% CI 1.224-1.425, P < 0.0001) after adjustment for age, sex, and dyslipidemia. CONCLUSION: This longitudinal population-based followup study showed that there is a significantly increased risk of developing ACS after developing DM.

Increased risk of stroke after trigeminal neuralgia--a population-based follow-up study.

BACKGROUND: There are no reports on the risk of stroke after trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether the occurrence of TN is associated with a higher risk of developing stroke. METHODS: A total of 1453 people with at least three ambulatory visits in 2001 with the principal diagnosis of TN were enrolled in the TN cohort. The non-TN cohort consisted of 5812 age- and sex-matched, randomly sampled subjects without TN. The 2-year stroke-free survival rate between the two groups was compared using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of stroke after adjustment for demographic and clinical covariates. RESULTS: In the TN cohort, 73 patients developed stroke during follow-up, while in the non-TN cohort, 157 subjects suffered a stroke. The crude hazard ratio of stroke for the subjects with TN was 1.86 (95% CI, 1.41-2.45; p<0.0001). The adjusted hazard ratio was 1.76 (95% CI, 1.33-2.33; p<0.0001) after adjusting for demographic characteristics and comorbid medical disorders. CONCLUSION: This study showed a significantly increased risk of developing stroke after TN. Further studies are needed to investigate the underlying mechanism of this association.

Different prevalence rates of Parkinson's disease in urban and rural areas: a population-based study in Taiwan.

BACKGROUND: Rural living has long been debated as a risk factor for idiopathic Parkinson's disease (IPD). But few community-based studies compared this difference between urban and rural areas. METHODS: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. RESULTS: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551-864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620-646) for people aged 40 and over and 230 (95% CI: 227-234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). CONCLUSIONS: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.

Mortality of Parkinson's disease by Hoehn-Yahr stage from community-based and clinic series [Keelung Community-based Integrated Screening (KCIS) no. 17)].

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

Impact of chewing betel-nut (Areca catechu) on liver cirrhosis and hepatocellular carcinoma: a population-based study from an area with a high prevalence of hepatitis B and C infections.

BACKGROUND: Chewing betel-nuts (Areca catechu) is carcinogenic but the risk for hepatocellular carcinoma (HCC) and liver cirrhosis (LC) is little considered. Worldwide 600 million people chew betel, including emigrants from palm-growing countries. OBJECTIVE: We aimed to assess the relationships and dose-response effects of betel chewing on LC and HCC risks, since habit cessation could reduce the increased risks of HCC and LC found in such communities. SUBJECTS: Screening 60 326 subjects aged 30-79 years in a population-based study in Taiwan identified LC in 588 and HCC in 131 subjects. Demographic features, hepatitis B/C infections, other risk factors and betel chewing were noted. Multiple Cox regression models were used to assess independent relationships, interactions and synergisms between age, betel chewing and hepatitis B/C. RESULTS: Betel chewing increased LC and HCC risk 4.25-fold (95 % CI 2.9, 6.2) in current chewers and 1.89-fold (95 % CI 1.13, 3.16) in ex-chewers v. never-chewers, with dose effects for quantity, duration and cumulative exposure in chewers. Subjects without hepatitis B/C infections had 5.0-fold (95 % CI 2.87, 9.03) increased risk of LC/HCC v. never-chewers, and betel chewing had an additive synergistic effect on hepatitis B/C-related risks. Risk reduction with betel habit cessation could exceed that expected from immunization programmes for hepatitis B and C. CONCLUSION: Increased risks of cirrhosis and hepatocellular cancer were found in betel chewers free of hepatitis B/C infection, and these risks were synergistically additive to those of hepatitis B/C infections. Estimated risk reduction from effective anti-betel chewing programmes would be sizeable.

Elevation of C-reactive protein level is associated with synchronous and advanced colorectal neoplasm in men.

OBJECTIVES: Chronic inflammation has been implicated in the development of colorectal cancer (CRC). The presence of low-grade systemic inflammation, as determined by an elevation of high-sensitivity C-reactive protein (CRP), has been associated with an increased risk of cardiovascular diseases and cancers. However, previous studies of CRP and CRC in cohorts that comprised different genders have yielded conflicting results and little is known about CRP levels in individuals with colorectal adenomas, the precursor lesion of CRC. This study aims to elucidate the association of CRP and colorectal neoplasia. METHODS: Plasma CRP levels were examined using a cross-sectional design in 6,695 consecutive ethnic Chinese adults who had undergone a complete colonoscopy following a thorough routine health evaluation. Logistic regression analysis was used to correlate the risk of colorectal neoplasia with CRP levels. RESULTS: Plasma CRP levels were significantly higher in subjects with colorectal neoplasia than in those without neoplasia (1.85 mg/L vs 1.55 mg/L, P= 0.04). The presence of synchronous neoplasia, advanced neoplasia, and concurrent synchronous and advanced neoplasia were associated with elevated levels of plasma CRP, after adjustment for other risk factors. Gender stratification revealed a positive association between elevated CRP levels and the risk of colorectal neoplasia in men, but no such corresponding association existed in women. CONCLUSIONS: Elevated plasma CRP levels are independently associated with an increased risk of colorectal neoplasia in men, but not in women. These data support the association between chronic inflammation and colorectal neoplasia in men and provide new insights into the underlying mechanisms that warrant further investigation.

First- or second-line therapy with gefitinib produces equal survival in non-small cell lung cancer.

RATIONALE: Gefitinib is effective in treating patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Deletions in exon 19 and L858R in exon 21 are the best-documented EGFR mutations that are associated with effective gefitinib responsiveness. OBJECTIVES: To clarify the influence of gefitinib timing, we conducted a study to compare the outcomes of different lines of gefitinib treatment in patients with exon 19 deletions or L858R. METHODS: We surveyed the clinical data and mutational studies of patients with NSCLC with EGFR mutations in the National Taiwan University Hospital (Taipei, Taiwan). MEASUREMENTS AND MAIN RESULTS: Three hundred and twenty-eight patients, who received gefitinib for stage IIIb or IV NSCLC, were adequately sequenced for EGFR mutations; 192 patients had mutant EGFR, including 77 patients with exon 19 deletions and 75 patients with L858R. The 152 patients with exon 19 deletions or L858R and who were receiving gefitinib were classified into a chemonaive group (91 patients) or a chemotherapy-treated group (61 patients). Chemonaive status before gefitinib and female sex were associated with clinical response to gefitinib (P = 0.006 and 0.053, respectively). Neither overall survival after the start of antitumor therapy nor progression-free survival after gefitinib therapy was significantly different between these two groups (P = 0.207 and 0.804, respectively). Clinical response to gefitinib was the only factor associated with better overall survival (P = 0.001). CONCLUSIONS: This study suggests that gefitinib is effective in patients with EGFR mutations. The gefitinib response rate in chemonaive patients is higher than in chemotherapy-treated patients; however, there is no difference in overall survival.

Community-based randomized intervention trial for periodontal disease after 18-month follow-up [Keelung Community-based Integrated Screening (KCIS) No. 4].

OBJECTIVES: As periodontal disease preponderates in adults, early detection and interventional regime is urgently needed. However, there is lack of evidence-based data on evaluation of population-based intervention programme related to periodontal disease. The aim of this study was to assess the efficacy of intervention regime on early periodontal disease identified from a community-based periodontal survey. METHOD: By randomization, 60 subjects were allocated to the intervention group and 49 to the control group respectively. Status on periodontal disease of participants was evaluated at entry and re-evaluated after intervention at 1-month and 18-month follow-up respectively. Primary outcome evaluated was based on Community Periodontal Index and Loss of Attachment on sextant level. RESULTS: The efficacy of intervention was significant in Community Periodontal Index (P<0.001) but not in Loss of Attachment (P=0.53) at 1-month and 18-month follow-up. CONCLUSION: The improvement of periodontal disease owing to intervention regime was seen in Community Periodontal Index but not Loss of Attachment as yet at 18-month follow-up after intervention.

Natural history and effectiveness of early detection of Parkinson's disease: results from two community-based programmes in Taiwan (KCIS no. 11).

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

Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response.

PURPOSE: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases. EXPERIMENTAL DESIGN: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival. RESULTS: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates to WBRT compared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival. CONCLUSIONS: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.

A prospective community-population-registry based cohort study of the association between betel-quid chewing and cardiovascular disease in men in Taiwan (KCIS no. 19).

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