[Show abstract][Hide abstract]ABSTRACT: Recently, we reported that earlier stages of Alzheimer’s disease (AD) can be categorized into three following anatomical subtypes using a hierarchical cluster analysis of cortical thickness across the entire brain: medial-temporal-dominant (MT), parietal-dominant (P) and diffuse atrophy (D). The goal of this study was to investigate the rates of cognitive decline in these anatomical subtypes. Of the patients included in the prior study, 100 AD patients (MT, n=36; P, n=20; D, n=44) who underwent follow-up neuropsychological assessments over a three-year period were included. A linear mixed model analysis was performed to compare the longitudinal changes in neuropsychological test scores. The P subtype exhibited the most rapid cognitive decline in attention, language, visuospatial, memory, and frontal-executive function, while MT and D subtypes did not differ in their longitudinal decline. When repeating the analyses with early-onset AD, which is known to progress faster than late-onset AD, only the P subtype showed such rapid progression. The P subtype appears to be a unique subtype of AD characterized by an aggressive rate of progression.
[Show abstract][Hide abstract]ABSTRACT: Previous epidemiological studies have suggested that uric acid is an independent risk factor for incident hypertension, whereas few studies have evaluated the effect of hyperuricemia on blood pressure control in hypertensive patients. We investigated whether hyperuricemia predicts uncontrolled hypertension through a large-scale prospective cohort study with hypertensive patients treated with fimasartan in the Republic of Korea (the Kanarb-Metabolic Syndrome study).Of the 10,601 hypertensive patients who were recruited from 582 private clinics and 11 university hospitals at baseline, 7725 completed the follow-up after 3 months of fimasartan medication, and 6506 were included in the analysis after excluding those with missing values. We estimated the risk of uncontrolled hypertension after 3 months (≥130/80 mm Hg in those with diabetes or chronic renal failure and ≥140/90 mm Hg in the remaining patients) related with baseline hyperuricemia (serum uric acid ≥7 mg/dL in males ≥6 mg/dL in females) using multiple logistic regression models.Hyperuricemia increased the risk of uncontrolled hypertension after 3 months of fimasartan medication (odds ratio, 1.247; 95% confidence interval, 1.063-1.462). Males in the highest quartile of uric acid level were at a 1.322 (95% confidence interval, 1.053-1.660) times higher risk of uncontrolled hypertension in reference to the lowest quartile; the same analyses in females were not significant. Patients without metabolic syndrome had significantly higher odds of uncontrolled hypertension with hyperuricemia (odds ratio, 1.328; 95% confidence interval, 1.007-1.751).Hyperuricemia predicted uncontrolled hypertension even after 3 months of fimasartan treatment in hypertensive patients.
[Show abstract][Hide abstract]ABSTRACT: Background:
In keeping with increasing interest in dementia, few recent studies suggest that clinical course of mild cognitive impairment vary across different studies with hospital-based subjects showing higher rates of conversion than community-based subjects.
The main objective of the present study was to assess whether the clinical conversion or reversion rates differ according to recruitment source.
The baseline study subjects comprised of patients who were diagnosed with mild cognitive impairment in community-based GDEMCIS or hospital-based CREDOS. The two studies had nearly the same protocol and were performed over a similar period. We used propensity score matching for baseline comparability. After that, Cox proportional hazards regression analyses were conducted to estimate the hazard ratios and 95% confidence intervals of clinical conversion or reversion.
Based on 89 GDEMCIS subjects, 1 : 4 propensity score matching was conducted and 356 CREDOS subjects were selected. After adjusting for covariates including baseline demographics, comorbidity, depression, disability, and neuropsychological result, Cox proportional hazard regression analysis for time to clinical conversion indicated that recruitment from hospital-based CREDOS exhibited hazard ratio of 2.13 (95% CI, 1.08-4.21), as compared to recruitment from community-based GDEMCIS. Similarly, Cox proportional hazard regression analysis for time to reversion indicated that recruitment from hospital-based CREDOS exhibited hazard ratio of 0.34 (95% CI, 0.20-0.59), as compared to recruitment from community-based GDEMCIS.
The present study demonstrated that even after the matching process and adjustments for baseline covariates, recruitment source greatly affected the course of mild cognitive impairment.
Article · May 2016 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract]ABSTRACT: Background:
We compared the validity of models of subcortical ischemic depression (SID) and depression-executive dysfunction syndrome (DED) in predicting functional disability in the elderly.
We obtained data from elderly Korean subjects (n=1356) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A generalized estimating equation (GEE) model was constructed to measure functional disability using instrumental activity of daily living as a primary outcome. A risk factor of interest was SID and DED evaluated by a visual rating scale of deep white matter hyperintensity in MRI, Stroop test and Geriatric Depression Scale (GDS) score. Receiver-operating-characteristic plots and area under the curve (AUC) test were applied to examine the difference of the two definitions of vascular depression with predicted values of functional disability outcome.
The mean (SD) follow-up duration of the participants was 1.7 (0.9) years. The GEE model showed that presence of SID at baseline predicted functional disability compared to non-depressed subjects (GDS score: Odds ratio [OR] 1.76; 95% CI 1.23, 2.53; p=0.002). The association was also statistically significant among the DED group (OR 1.48; 95% CI 1.15, 1.92; p=0.003). There were no significant differences in predicting functional disability (95% CI: -0.003 to 0.009, p=0.366) according to AUC differences between SID and DED.
The results will be useful in evaluating the cardinal features of the vascular depression hypothesis in predicting functional disability.
Full-text Article · Apr 2016 · Archives of gerontology and geriatrics
[Show abstract][Hide abstract]ABSTRACT: Although the incidence and mortality for most cancers such as lung and colon are decreasing in several countries, they are increasing in several developed countries because of an unhealthy western lifestyles including smoking, physical inactivity and consumption of calorie-dense food. The incidences for lung and colon cancers in a few of these countries have already exceeded those in the United States and other western countries. Among them, lung cancer is the main cause of cancer death in worldwide. The cumulative survival rate at five years differs between 13 and 21 % in several countries. Although the most important risk factors are smoking for lung cancer, however, the increased incidence of lung cancer in never smokers(LCINS) is necessary to improve knowledge concerning other risk factors. Environmental factors and genetic susceptibility are also thought to contribute to lung cancer risk. Patients with lung adenocarcinoma who have never smoking frequently contain mutation within tyrosine kinase domain of the epidermal growth factor receptor(EGFR) gene. Also, K-ras mutations are more common in individuals with a history of smoking use and are related with resistance to EFGR-tyrosine kinase inhibitors. Recently, radon(Rn), natural and noble gas, has been recognized as second common reason of lung cancer. In this review, we aim to know whether residential radon is associated with an increased risk for developing lung cancer and regulated by several genetic polymorphisms.
[Show abstract][Hide abstract]ABSTRACT: Background:
Lung cancer was the second highest absolute cancer incidence globally and the first cause of cancer mortality in 2014. Indoor radon is the second leading risk factor of lung cancer after cigarette smoking among ever smokers and the first among non-smokers. Environmental burden of disease (EBD) attributable to residential radon among non-smokers is critical for identifying threats to population health and planning health policy.
To identify and retrieve literatures describing environmental burden of lung cancer attributable to residential radon, we searched databases including Ovid-MEDLINE, -EMBASE from 1980 to 2016. Search terms included patient keywords using 'lung', 'neoplasm', exposure keywords using 'residential', 'radon', and outcomes keywords using 'years of life lost', 'years of life lost due to disability', 'burden'. Searching through literatures identified 261 documents; further 9 documents were identified using manual searching. Two researchers independently assessed 271 abstracts eligible for inclusion at the abstract level. Full text reviews were conducted for selected publications after the first assessment. Ten studies were included in the final evaluation.
Global disability-adjusted life years (DALYs)(95 % uncertainty interval) for lung cancer were increased by 35.9 % from 23,850,000(18,835,000-29,845,000) in 1900 to 32,405,000(24,400,000-38,334,000) in 2000. DALYs attributable to residential radon were 2,114,000(273,000-4,660,000) DALYs in 2010. Lung cancer caused 34,732,900(33,042,600 ~ 36,328,100) DALYs in 2013. DALYs attributable to residential radon were 1,979,000(1,331,000-2,768,000) DALYs for in 2013. The number of attributable lung cancer cases was 70-900 and EBD for radon was 1,000-14,000 DALYs in Netherland. The years of life lost were 0.066 years among never-smokers and 0.198 years among ever-smoker population in Canada.
In summary, estimated global EBD attributable to residential radon was 1,979,000 DALYs for both sexes in 2013. In Netherlands, EBD for radon was 1,000-14,000 DALYs. Smoking population lost three times more years than never-smokers in Canada. There was no study estimating EBD of residential radon among never smokers in Korea and Asian country. In addition, there were a few studies reflecting the age of building, though residential radon exposure level depends on the age of building. Further EBD study reflecting Korean disability weight and the age of building is required to estimate EBD precisely.
[Show abstract][Hide abstract]ABSTRACT: Lung cancer is a leading cause of cancer-related death in the world. Smoking is definitely the most important risk factor for lung cancer. Radon ((222)Rn) is a natural gas produced from radium ((226)Ra) in the decay series of uranium ((238)U). Radon exposure is the second most common cause of lung cancer and the first risk factor for lung cancer in never-smokers. Case-control studies have provided epidemiological evidence of the causative relationship between indoor radon exposure and lung cancer. Twenty-four case-control study papers were found by our search strategy from the PubMed database. Among them, seven studies showed that indoor radon has a statistically significant association with lung cancer. The studies performed in radon-prone areas showed a more positive association between radon and lung cancer. Reviewed papers had inconsistent results on the dose-response relationship between indoor radon and lung cancer risk. Further refined case-control studies will be required to evaluate the relationship between radon and lung cancer. Sufficient study sample size, proper interview methods, valid and precise indoor radon measurement, wide range of indoor radon, and appropriate control of confounders such as smoking status should be considered in further case-control studies.
[Show abstract][Hide abstract]ABSTRACT: Exposure to radon gas is the second most common cause of lung cancer after smoking. A large number of studies have reported that exposure to indoor radon, even at low concentrations, is associated with lung cancer in the general population. This paper reviewed studies from several countries to assess the attributable risk (AR) of lung cancer death due to indoor radon exposure and the effect of radon mitigation thereon. Worldwide, 3-20 % of all lung cancer deaths are likely caused by indoor radon exposure. These values tend to be higher in countries reporting high radon concentrations, which can depend on the estimation method. The estimated number of lung cancer deaths due to radon exposure in several countries varied from 150 to 40,477 annually. In general, the percent ARs were higher among never-smokers than among ever-smokers, whereas much more lung cancer deaths attributable to radon occurred among ever-smokers because of the higher rate of lung cancers among smokers. Regardless of smoking status, the proportion of lung cancer deaths induced by radon was slightly higher among females than males. However, after stratifying populations according to smoking status, the percent ARs were similar between genders. If all homes with radon above 100 Bq/m(3) were effectively remediated, studies in Germany and Canada found that 302 and 1704 lung cancer deaths could be prevented each year, respectively. These estimates, however, are subject to varying degrees of uncertainty related to the weakness of the models used and a number of factors influencing indoor radon concentrations.
[Show abstract][Hide abstract]ABSTRACT: Radiation from natural sources is one of causes of the environmental diseases. Radon is the leading environmental cause of lung cancer next to smoking. To investigate the relationship between indoor radon concentrations and lung cancer, researchers must be able to estimate an individual's cumulative level of indoor radon exposure and to do so, one must first be able to assess indoor radon concentrations. In this article, we outline factors affecting indoor radon concentrations and review related mathematical models based on the mass balance equation and the differential equations. Furthermore, we suggest the necessities of applying time-dependent functions for indoor radon concentrations and developing stochastic models.
[Show abstract][Hide abstract]ABSTRACT: Background Palliative resection of stage IV pancreatic ductal adenocarcinoma (PDAC) has not shown its benefit until now. In our retrospective review, we compared the results of palliative resection to non-resection. Methods Between 2000 and 2009, metastasis of PDAC was confirmed in the operating room in 150 patients. 35 underwent palliative resection (resection group; R) and 115 did bypass or biopsy. 35 patients (biopsy or bypass group: NR) in the 115 patients were matched with the patients undergoing resection for tumor size and the metastasis of peritoneal seeding. Demographic, clinical, operative data and survival were analyzed. Results There was no significant difference of major complication (Clavien–Dindo classification 3–5) between two groups. There was no 30-day mortality in either group. More patients in R received postoperative chemotherapy (82.9% vs. 57.1%; P = 0.019). Multivariate analysis showed resection and postoperative chemotherapy as independent factor related to survival (hazard ratio, 0.44; 95% CI, 0.25–0.76; P = 0.003). Patients in R showed better survival rates compared to those in NR (P < 0.001). Conclusion Our study suggests resection for stage IV PDAC can be associated with increased survival. In patients of stage IV PDAC, palliative resection with chemotherapy could have some benefit in selected patients.
[Show abstract][Hide abstract]ABSTRACT: Purpose
The association between liver enzymes and death from external causes has not been examined. We investigated the association between serum aminotransferase levels and external-cause mortality in a large prospective cohort study.
Materials and Methods
A total of 142322 subjects of 35-59 years of age who completed baseline examinations in 1990 and 1992 were enrolled. Mortalities were identified using death certificates. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were categorized into quintiles. Sub-distribution hazards ratios and 95% confidence intervals (CIs) were estimated using a competing risks regression model in which deaths from other causes were treated as competing risks.
Of 8808 deaths, 1111 (12.6%) were due to external causes. Injury accounted for 256 deaths, and suicide accounted for 255. After adjusting for covariates, elevated ALT and AST were significantly associated with an increased risk of all external-cause mortalities, as well as suicide and injury. Sub-distribution hazards ratios (95% CIs) of the highest versus the lowest quintiles of serum ALT and AST were, respectively, 1.57 (1.26-1.95) and 1.45 (1.20-1.76) for all external causes, 2.73 (1.68-4.46) and 1.75 (1.15-2.66) for suicide, and 1.79 (1.10-2.90) and 1.85 (1.21-2.82) for injury. The risk of external-cause mortality was also significantly higher in the fourth quintile of ALT (21.6-27.5 IU/L) than in its first quintile.
Elevated aminotransferase levels, even within the normal range, were significantly associated with increased risk of all external-cause mortalities, including suicide, and injury.
Full-text Article · Nov 2015 · Yonsei Medical Journal
[Show abstract][Hide abstract]ABSTRACT: Objective:
According to most prospective studies, being underweight (BMI<18·5 kg/m2) is associated with significantly higher mortality than being of normal weight, especially among smokers. We aimed to explore in a generally lean population whether being underweight is significantly associated with increased all-cause mortality.
Prospective cohort study.
Korea Medical Insurance Corporation study with 14 years of follow-up.
After excluding deaths within the first 5 years of follow-up (1993-1997) to minimize reverse causation and excluding participants without information about smoking and health status, 94 133 men and 48 496 women aged 35-59 years in 1990 were included.
We documented 5411 (5·7 %) deaths in men and 762 (1·6 %) in women. Among never smokers, hazard ratios (HR) for underweight individuals were not significantly higher than those for normal-weight individuals (BMI=18·5-22·9 kg/m2): HR=0·87 (95 % CI 0·41, 1·84, P=0·72) for underweight men and HR=1·12 (95 % CI 0·76, 1·65, P=0·58) for underweight women. Among ex-smokers, HR=0·86 (95 % CI 0·38, 1·93, P=0·72) for underweight men and HR=3·77 (95 % CI 0·42, 32·29, P=0·24) for underweight women. Among current smokers, HR=1·60 (95 % CI 1·28, 2·01, P<0·001) for underweight men and HR=2·07 (95 % CI 0·43, 9·94, P=0·36) for underweight women.
The present study does not support that being underweight per se is associated with increased all-cause mortality in Korean men and women.
[Show abstract][Hide abstract]ABSTRACT: Aromatase inhibitors (AIs), the standard therapy for estrogen receptor- or progesterone receptor-positive breast cancer in postmenopausal women, lead to increased hip fractures in breast cancer patients. To investigate the mechanism of increased incidence of hip fractures in breast cancer patients treated with AIs, we evaluated bone mineral density (BMD) in the cortical and trabecular compartments and assessed femoral geometry using quantitative computed tomography (QCT) in breast cancer patients. In total, 249 early breast cancer patients who underwent QCT in their fifties (mean age 54.3 years) were retrospectively analyzed. Proximal femoral BMD and geometrical parameters were compared. In all regions of the proximal femur, cortical areal BMDs were lower in the AI group than in the non-AI group (p < 0.05). Cortical thickness of the femoral neck, trochanter, and total hip was significantly lower in the AI group compared with the non-AI group (p < 0.05). Analysis of the narrowest section of the femoral neck showed significantly thinner cortical bone and smaller cortical area in the AI group than in the non-AI group (p < 0.05), especially in the superoposterior quadrant. Bone strength parameters in the femoral neck, such as the section modulus and cross-sectional moment of inertia, were significantly lower in the AI group than in the non-AI group (p < 0.05). In conclusion, AI treatment in breast cancer patients is associated with deterioration of femoral cortical BMD and geometry, which could contribute in site-specific weakened bone strength and increased incidence of hip fractures.
Article · Aug 2015 · Calcified Tissue International
[Show abstract][Hide abstract]ABSTRACT: Although inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population.
Plasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status.
Fibrinogen levels were positively associated with IMT-max (standardized β=0.25, p=0.021) and IMT-tpm (standardized β=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers.
Our findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations.
Full-text Article · Jul 2015 · Yonsei medical journal
[Show abstract][Hide abstract]ABSTRACT: Objectives:
Eisenmenger syndrome (ES) is commonly associated with depressive symptoms and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). We investigated the predictive value of depressive symptoms and NTproBNP levels for long-term outcomes in patients with ES.
Blood was drawn to measure NT-proBNP, and depressive symptoms were measured using the Korean version of the Beck Depression Inventory (BDI) in an outpatient clinic sample of 64 patients with ES (67% female; median age = 41.5 years [range, 21.0-74.8 years]). Cardiac events (hospitalization, emergency department visits, and cardiac death) were monitored during 3 years of follow-up.
During the follow-up period, 15 (23.4%) patients experienced a cardiac event. The combination of depressive symptoms and NT-proBNP levels better predicted future cardiac events than either variable alone. Patients with NT-proBNP > 510 pg/ml and a total BDI score > 10 had a 9.6 times higher risk for cardiac events than did patients with NT-proBNP ≤ 510 pg/ml or total BDI score ≤ 10 (p < .001).
Depressive symptoms and NT-proBNP levels are both associated with adverse clinical outcomes in ES.