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1.  Elderly Peritoneal Dialysis Compared with Elderly Hemodialysis Patients and Younger Peritoneal Dialysis Patients: Competing Risk Analysis of a Korean Prospective Cohort Study 
PLoS ONE  2015;10(6):e0131393.
The outcomes of peritoneal dialysis (PD) in elderly patients have not been thoroughly investigated. We aimed to investigate the clinical outcomes and risk factors associated with PD in elderly patients. We conducted a prospective observational nationwide adult end-stage renal disease (ESRD) cohort study in Korea from August 2008 to March 2013. Among incident patients (n = 830), patient and technical survival rate, quality of life, and Beck’s Depression Inventory (BDI) scores of elderly PD patients (≥65 years, n = 95) were compared with those of PD patients aged ≤49 years (n = 205) and 50~64 years (n = 192); and elderly hemodialysis (HD) patients (n = 315). The patient death and technical failure were analyzed by cumulative incidence function. Competing risk regressions were used to assess the risk factors for survival. The patient survival rate of elderly PD patients was inferior to that of younger PD patients (P<0.001). However, the technical survival rate was similar (P = 0.097). Compared with elderly HD patients, the patient survival rate did not differ according to dialysis modality (P = 0.987). Elderly PD patients showed significant improvement in the BDI scores, as compared with the PD patients aged ≤49 years (P = 0.003). Low albumin, diabetes and low residual renal function were significant risk factors for the PD patient survival; and peritonitis was a significant risk factor for technical survival. Furthermore, low albumin and hospitalization were significant risk factors of patient survival among the elderly. The overall outcomes were similar between elderly PD and HD patients. PD showed the benefit in BDI and quality of life in the elderly. Additionally, the technical survival rate of elderly PD patients was similar to that of younger PD patients. Taken together, PD may be a comparable modality for elderly ESRD patients.
doi:10.1371/journal.pone.0131393
PMCID: PMC4488000  PMID: 26121574
2.  Non-Linear Concentration-Response Relationships between Ambient Ozone and Daily Mortality 
PLoS ONE  2015;10(6):e0129423.
Background
Ambient ozone (O3) concentration has been reported to be significantly associated with mortality. However, linearity of the relationships and the presence of a threshold has been controversial.
Objectives
The aim of the present study was to examine the concentration-response relationship and threshold of the association between ambient O3 concentration and non-accidental mortality in 13 Japanese and Korean cities from 2000 to 2009.
Methods
We selected Japanese and Korean cities which have population of over 1 million. We constructed Poisson regression models adjusting daily mean temperature, daily mean PM10, humidity, time trend, season, year, day of the week, holidays and yearly population. The association between O3 concentration and mortality was examined using linear, spline and linear-threshold models. The thresholds were estimated for each city, by constructing linear-threshold models. We also examined the city-combined association using a generalized additive mixed model.
Results
The mean O3 concentration did not differ greatly between Korea and Japan, which were 26.2 ppb and 24.2 ppb, respectively. Seven out of 13 cities showed better fits for the spline model compared with the linear model, supporting a non-linear relationships between O3 concentration and mortality. All of the 7 cities showed J or U shaped associations suggesting the existence of thresholds. The range of city-specific thresholds was from 11 to 34 ppb. The city-combined analysis also showed a non-linear association with a threshold around 30-40 ppb.
Conclusion
We have observed non-linear concentration-response relationship with thresholds between daily mean ambient O3 concentration and daily number of non-accidental death in Japanese and Korean cities.
doi:10.1371/journal.pone.0129423
PMCID: PMC4468145  PMID: 26076447
3.  Korean research project on the integrated exposure assessment of hazardous substances for food safety 
Objectives:
This survey was designed to conduct the first nationwide dietary exposure assessment on hazardous substances including the intakes of functional food and herbal medicine. In this paper, we introduced the survey design and the results of the dietary exposure status and internal exposure levels of lead (Pb), cadmium (Cd), and mercury (Hg).
Methods:
We selected 4867 subjects of all ages throughout Korea. We conducted a food survey, dietary survey, biomonitoring, and health survey.
Results:
Pb and Cd were the highest (median value) in the seaweed (94.2 μg/kg for Pb; 594 μg/kg for Cd), and Hg was the highest in the fish (46.4 μg/kg). The dietary exposure level (median value) of Pb was 0.14 μg/kg body weight (bw)/d, 0.18 μg/kg bw/d for Cd, and 0.07 μg/kg bw/d for Hg. Those with a blood Pb level of less than 5.00 μg/dL (US Centers for Disease Control and Prevention, reference value for those 1 to 5 years of age) were 99.0% of all the subjects. Those with a blood Cd level with less than 0.30 μg/L (German Federal Environmental Agency, reference value for non-smoking children) were 24.5%. For those with a blood Hg level with less than 5.00 μg/L (human biomonitoring I, references value for children and adults, German Federal Environmental Agency) was 81.0 % of all the subjects.
Conclusions:
The main dietary exposure of heavy metals occurs through food consumed in a large quantity and high frequency. The blood Hg level and dietary exposure level of Hg were both higher than those in the European Union.
doi:10.5620/eht.e2015004
PMCID: PMC4509523  PMID: 26184046
Food intake; Hazardous substances; Heavy metal; Integrated dietary exposure assessment; Survey design
4.  Recalibration and Validation of the Charlson Comorbidity Index in Korean Incident Hemodialysis Patients 
PLoS ONE  2015;10(5):e0127240.
Background
Weights assigned to comorbidities to predict mortality may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in incident hemodialysis patients (mCCI-IHD), thereby improving risk stratification for mortality.
Methods
Data on 24,738 Koreans who received their first hemodialysis treatment between 2005 and 2008 were obtained from the Korean Health Insurance dataset. The mCCI-IHD score were calculated by summing up the weights which were assigned to individual comorbidities according to their relative prognostic significance determined by multivariate Cox proportional hazards model. The modified index was validated in an independent nationwide prospective cohort (n=1,100).
Results
The Cox proportional hazards model revealed that all comorbidities in the CCI except ulcers significantly predicted mortality. Thus, the mCCI-IHD included 14 comorbidities with re-assigned severity weights. In the validation cohort, both the CCI and the mCCI-IHD were correlated with mortality. However, the mCCI-IHD showed modest but significant increases in c statistics compared with the CCI at 6 months and 1 year. The analyses using continuous net reclassification improvement revealed that the mCCI-IHD improved net mortality risk reclassification by 24.6% (95% CI, 2.5-46.7; P=0.03), 26.2% (95% CI, 1.0-51.4; P=0.04) and 42.8% (95% CI, 4.9-80.8; P=0.03) with respect to the CCI at 6 months and 1 and 2 years, respectively.
Conclusions
The mCCI-IHD facilitates better risk stratification for mortality in incident hemodialysis patients compared with the CCI, suggesting that it may be a preferred index for use in clinical practice and the statistical analysis of epidemiological studies.
doi:10.1371/journal.pone.0127240
PMCID: PMC4436150  PMID: 25984790
5.  Global variation in the effects of ambient temperature on mortality: a systematic evaluation 
Epidemiology (Cambridge, Mass.)  2014;25(6):781-789.
Background
Studies have examined the effects of temperature on mortality in a single city, country or region. However, less evidence is available on the variation in the associations between temperature and mortality in multiple countries, analyzed simultaneously.
Methods
We obtained daily data on temperature and mortality in 306 communities from 12 countries/regions (Australia, Brazil, Thailand, China, Taiwan, Korea, Japan, Italy, Spain, United Kingdom, United States and Canada). Two-stage analyses were used to assess the non-linear and delayed relationship between temperature and mortality. In the first stage, a Poisson regression allowing over-dispersion with distributed lag non-linear model was used to estimate the community-specific temperature-mortality relationship. In the second stage, a multivariate meta-analysis was used to pool the non-linear and delayed effects of ambient temperature at the national level, in each country.
Results
The temperatures associated with the lowest mortality were around the 75th percentile of temperature in all the countries/regions, ranging from 66th (Taiwan) to 80th (UK) percentiles. The estimated effects of cold and hot temperatures on mortality varied by community and country. Meta-analysis results show that both cold and hot temperatures increased the risk of mortality in all the countries/regions. Cold effects were delayed and lasted for many days, while hot effects appeared quickly and did not last long.
Conclusions
People have some ability to adapt to their local climate type, but both cold and hot temperatures are still associated with the risk of mortality. Public health strategies to alleviate the impact of ambient temperatures are important, in particular in the context of climate change.
doi:10.1097/EDE.0000000000000165
PMCID: PMC4180721  PMID: 25166878
6.  Assessment of Climate-sensitive Infectious Diseases in the Federated States of Micronesia 
Tropical Medicine and Health  2014;43(1):29-40.
Background: The health impacts of climate change are an issue of growing concern in the Pacific region. Prior to 2010, no formal, structured, evidence-based approach had been used to identify the most significant health risks posed by climate change in Pacific island countries. During 2010 and 2011, the World Health Organization supported the Federated States of Micronesia (FSM) in performing a climate change and health vulnerability and adaptation assessment. This paper summarizes the priority climate-sensitive health risks in FSM, with a focus on diarrheal disease, its link with climatic variables and the implications of climate change.
Methods: The vulnerability and adaptation assessment process included a review of the literature, extensive stakeholder consultations, ranking of climate-sensitive health risks, and analysis of the available long-term data on climate and climate-sensitive infectious diseases in FSM, which involved examination of health information data from the four state hospitals in FSM between 2000 and 2010; along with each state’s rainfall, temperature and El Niño-Southern Oscillation data. Generalized linear Poisson regression models were used to demonstrate associations between monthly climate variables and cases of climate-sensitive diseases at differing temporal lags.
Results: Infectious diseases were among the highest priority climate-sensitive health risks identified in FSM, particularly diarrheal diseases, vector-borne diseases and leptospirosis. Correlation with climate data demonstrated significant associations between monthly maximum temperature and monthly outpatient cases of diarrheal disease in Pohnpei and Kosrae at a lag of one month and 0 to 3 months, respectively; no such associations were observed in Chuuk or Yap. Significant correlations between disease incidence and El Niño-Southern Oscillation cycles were demonstrated in Kosrae state.
Conclusions: Analysis of the available data demonstrated significant associations between climate variables and climate-sensitive infectious diseases. This information should prove useful in implementing health system and community adaptation strategies to avoid the most serious impacts of climate change on health in FSM.
doi:10.2149/tmh.2014-17
PMCID: PMC4361343  PMID: 25859151
infectious diseases; climate; Federated States of Micronesia
7.  The efficacy and safety of acupuncture for cerebral vasospasm after subarachnoid hemorrhage: study protocol for a randomized controlled trial 
Trials  2015;16:68.
Background
Subarachnoid hemorrhage (SAH) is a neurological disease with a high mortality rate. Several serious complications frequently arise after successful surgery for this condition. Cerebral vasospasm, one such complication, occurs in 50 to 70% of SAH patients. These patients suffer neurological symptoms known as delayed ischemic neurological deficit (DIND); however, the effect of treatment of vasospasm is limited. The major pathogenesis of cerebral vasospasm is the reduction of nitric oxide (NO) and activation of vasoconstrictors. Acupuncture is known to increase the production and activity of vascular endothelial cell-derived NO and improve endothelium-dependent vasodilatation. A preliminary retrospective case study to investigate the ability of acupuncture to prevent the occurrence of cerebral vasospasm has been conducted. However, no randomized, controlled clinical trials have been carried out to evaluate the efficacy of acupuncture for cerebral vasospasm.
Methods/Design
This trial will be a single-center, randomized, placebo-controlled, parallel group, patient-assessor-blinded clinical trial. A total of 80 patients with SAH will be randomized into two groups: a study group given acupuncture, electroacupuncture, and intradermal acupuncture, and a control group given mock transcutaneous electrical nerve stimulation and sham intradermal acupuncture. Intervention will start within 96 h after SAH, and a total of 12 sessions will be performed during a 2-week period. The primary outcome measure will be the occurrence of DIND, and the secondary outcomes will be vasospasm as measured by cerebral angiography, transcranial Doppler, clinical symptoms, vasospasm-related infarcts, NO and endothelin-1 plasma levels, mortality, and modified Rankin Scale scores.
Discussion
This trial will examine the efficacy and safety of acupuncture for cerebral vasospasm after SAH. The placebo effect will be excluded and the mechanism of action of the treatments will be evaluated through blood testing.
Trial registration
ClinicalTrials.gov NCT02275949, Registration date: 26 October 2014.
doi:10.1186/s13063-015-0591-7
PMCID: PMC4352281  PMID: 25886483
Subarachnoid hemorrhage; Vasospasm; Delayed ischemic neurological deficit; Acupuncture
8.  Not Early Referral but Planned Dialysis Improves Quality of Life and Depression in Newly Diagnosed End Stage Renal Disease Patients: A Prospective Cohort Study in Korea 
PLoS ONE  2015;10(2):e0117582.
Background
Health-related quality of life (HRQOL) has recently become an important issue. It reportedly affects morbidity and mortality in patients with end-stage renal disease (ESRD). In this study, we investigated whether early referral and planned dialysis improve the HRQOL and depression of patients with ESRD.
Methods
We prospectively enrolled newly diagnosed patients with ESRD, from 31 hospitals in Korea, who completed questionnaires at 3 months after dialysis. We also got follow-up survey at 1 year after dialysis. To measure HRQOL and depression, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) and Beck’s Depression Inventory (BDI) were utilized.
Results
A total of 643 patients were analyzed. Referral type did not affect either KDQOL-36 or BDI scores. However, the planned dialysis group showed significantly better scores in 4 of 5 KDQOL-36 domains than did the unplanned group at 3 months after dialysis and partly, the effect was sustained for 1 year after dialysis. The benefit of planned dialysis was significant after adjusting for age, sex, type of dialysis, marital status, educational attainment, occupation, modified Charlson comorbidity index, albumin, and hemoglobin levels. BDI scores were also lower which indicate less depressive mood in planned dialysis group than those in unplanned group both at 3 months and 1 year after dialysis.
Conclusions
Not early referral but planned dialysis improved both the short- and long-term HRQOL and depression of patients with ESRD. Nephrologists should try to help patients to initiate dialysis in a planned manner.
doi:10.1371/journal.pone.0117582
PMCID: PMC4338188  PMID: 25706954
9.  Heat-Attributable Deaths between 1992 and 2009 in Seoul, South Korea 
PLoS ONE  2015;10(2):e0118577.
Background
Climate change may significantly affect human health. The possible effects of high ambient temperature must be better understood, particularly in terms of certain diseases’ sensitivity to heat (as reflected in relative risks [RR]) and the consequent disease burden (number or fraction of cases attributable to high temperatures), in order to manage the threat.
Purpose
This study investigated the number of deaths attributable to abnormally high ambient temperatures in Seoul, South Korea, for a wide range of diseases.
Method
The relationship between mortality and daily maximum temperature using a generalized linear model was analyzed. The threshold temperature was defined as the 90th percentile of maximum daily temperatures. Deaths were classified according to ICD-10 codes, and for each disease, the RR and attributable fractions were determined. Using these fractions, the total number of deaths attributable to daily maximum temperatures above the threshold value, from 1992 to 2009, was calculated. Data analyses were conducted in 2012–2013.
Results
Heat-attributable deaths accounted for 3,177 of the 271,633 deaths from all causes. Neurological (RR 1.07; 95% CI, 1.04–1.11) and mental and behavioral disorders (RR 1.04; 95% CI, 1.01–1.07) had relatively high increases in the RR of mortality. The most heat-sensitive diseases (those with the highest RRs) were not the diseases that caused the largest number of deaths attributable to high temperatures.
Conclusion
This study estimated RRs and deaths attributable to high ambient temperature for a wide variety of diseases. Prevention-related policies must account for both particular vulnerabilities (heat-sensitive diseases with high RRs) and the major causes of the heat mortality burden (common conditions less sensitive to high temperatures).
doi:10.1371/journal.pone.0118577
PMCID: PMC4334895  PMID: 25692296
10.  Heat-related mortality risk model for climate change impact projection 
Objectives
We previously developed a model for projection of heat-related mortality attributable to climate change. The objective of this paper is to improve the fit and precision of and examine the robustness of the model.
Methods
We obtained daily data for number of deaths and maximum temperature from respective governmental organizations of Japan, Korea, Taiwan, the USA, and European countries. For future projection, we used the Bergen climate model 2 (BCM2) general circulation model, the Special Report on Emissions Scenarios (SRES) A1B socioeconomic scenario, and the mortality projection for the 65+-year-old age group developed by the World Health Organization (WHO). The heat-related excess mortality was defined as follows: The temperature–mortality relation forms a V-shaped curve, and the temperature at which mortality becomes lowest is called the optimum temperature (OT). The difference in mortality between the OT and a temperature beyond the OT is the excess mortality. To develop the model for projection, we used Japanese 47-prefecture data from 1972 to 2008. Using a distributed lag nonlinear model (two-dimensional nonparametric regression of temperature and its lag effect), we included the lag effect of temperature up to 15 days, and created a risk function curve on which the projection is based. As an example, we perform a future projection using the above-mentioned risk function. In the projection, we used 1961–1990 temperature as the baseline, and temperatures in the 2030s and 2050s were projected using the BCM2 global circulation model, SRES A1B scenario, and WHO-provided annual mortality. Here, we used the “counterfactual method” to evaluate the climate change impact; For example, baseline temperature and 2030 mortality were used to determine the baseline excess, and compared with the 2030 excess, for which we used 2030 temperature and 2030 mortality. In terms of adaptation to warmer climate, we assumed 0 % adaptation when the OT as of the current climate is used and 100 % adaptation when the OT as of the future climate is used. The midpoint of the OTs of the two types of adaptation was set to be the OT for 50 % adaptation.
Results
We calculated heat-related excess mortality for 2030 and 2050.
Conclusions
Our new model is considered to be better fit, and more precise and robust compared with the previous model.
doi:10.1007/s12199-013-0354-6
PMCID: PMC3890078  PMID: 23928946
Heat-related mortality; Excess deaths; Climate change; Projection; Adaptation
11.  The effect of community-level smoke-free ordinances on smoking rates in men based on Community Health Surveys 
Epidemiology and Health  2014;36:e2014037.
OBJECTIVES:
As one of smoke-free policies, communities have established the smoke-free ordinances since August 2010. Thus, this study aimed to evaluate the effects of community-level smoke-free ordinances (SFO) on smoking rates in men using multiyear Community Health Survey (CHS) data.
METHODS:
Data on community-level SFO were collected from a website on Enhanced Local Laws and Regulation Information System. Regional smoking-related data were obtained from CHS data from 2008 to 2012 and the age-standardized rates of current smoking in men, attempts to quit smoking, and smoke-free campaign experiences including the mean number of cigarettes smoked (smoking amount) were calculated. Repeated measures analysis of variance was performed to evaluate the effects of regional implementation of SFO and the duration on change of smoking rates.
RESULTS:
Overall current smoking rates and daily mean cigarettes smoked were lower in community where SFO had been implemented compared to those without implementation, and there was a significant difference in smoking rates between 2010 and 2008. Cross-sectional analysis of the effects of regional SFO revealed clear difference in rate of current smoking, but longitudinal analysis showed no significant differences. Stratifying by age groups, however, showed that groups less than 30 years of age had low smoking rates in community with ordinance compared to those without SFO since 2010. Yearly surveys measuring the number of cigarettes smoked, attempts to quit smoking, and experiences of smoke-free campaigns showed regional differences in the duration of implementation, but these differences were not significant in longitudinal analysis. Furthermore, there was a difference in regional socioeconomic characteristics between community with and without SFO implementation.
CONCLUSIONS:
For effective smoking control, it is necessary to evaluate current policies and develop indices to evaluate the practical implementation of ordinances. As more communities to pass the SFO, long-term observation and assessments required.
doi:10.4178/epih/e2014037
PMCID: PMC4371388  PMID: 25758213
Smoke-free ordinance; Ecological study; Smoking; South Korea
12.  Structure-activity relationships of the intramolecular disulfide bonds in coprisin, a defensin from the dung beetle 
BMB Reports  2014;47(11):625-630.
Defensins, which are small cationic molecules produced by organisms as part of their innate immune response, share a common structural scaffold that is stabilized by three disulfide bridges. Coprisin is a 43-amino acid defensin-like peptide from Copris tripartitus. Here, we report the intramolecular disulfide connectivity of cysteine-rich coprisin, and show that it is the same as in other insect defensins. The disulfide bond pairings of coprisin were determined by combining the enzymatic cleavage and mass analysis. We found that the loss of any single disulfide bond in coprisin eliminated all antibacterial, but not antifungal, activity. Circular dichroism (CD) analysis showed that two disulfide bonds, Cys20-Cys39 and Cys24-Cys41, stabilize coprisin’s α-helical region. Moreover, a BLAST search against UniProtKB database revealed that coprisin’s α-helical region is highly homologous to those of other insect defensins. [BMB Reports 2014; 47(11): 625-630]
doi:10.5483/BMBRep.2014.47.11.262
PMCID: PMC4281341  PMID: 24393527
Antimicrobial peptide; Circular dichroism; Coprisin; disulfide connectivity; Insect defensin
13.  Role of NADH: quinone oxidoreductase-1 in the tight junctions of colonic epithelial cells 
BMB Reports  2014;47(9):494-499.
NADH:quinone oxidoreductase 1 (NQO1) is known to be involved in the regulation of energy synthesis and metabolism, and the functional studies of NQO1 have largely focused on metabolic disorders. Here, we show for the first time that compared to NQO1-WT mice, NQO1-KO mice exhibited a marked increase of permeability and spontaneous inflammation in the gut. In the DSS-induced colitis model, NQO1-KO mice showed more severe inflammatory responses than NQO1-WT mice. Interestingly, the transcript levels of claudin and occludin, the major tight junction molecules of gut epithelial cells, were significantly decreased in NQO1-KO mice. The colons of NQO1-KO mice also showed high levels of reactive oxygen species (ROS) and histone deacetylase (HDAC) activity, which are known to affect transcriptional regulation. Taken together, these novel findings indicate that NQO1 contributes to the barrier function of gut epithelial cells by regulating the transcription of tight junction molecules. [BMB Reports 2014;47(9): 494-499]
doi:10.5483/BMBRep.2014.47.9.196
PMCID: PMC4206724  PMID: 24393524
Barrier dysfunction of epithelial cells; Chromosome condensation; Claudin-1; Gut epithelial cell tight junction; Gut inflammation; Histone acetylation/deacetylation; NQO1 knockout mice; Occludin; Transcription
14.  Ordinary kriging approach to predicting long-term particulate matter concentrations in seven major Korean cities 
Objectives
Cohort studies of associations between air pollution and health have used exposure prediction approaches to estimate individual-level concentrations. A common prediction method used in Korean cohort studies is ordinary kriging. In this study, performance of ordinary kriging models for long-term particulate matter less than or equal to 10 μm in diameter (PM10) concentrations in seven major Korean cities was investigated with a focus on spatial prediction ability.
Methods
We obtained hourly PM10 data for 2010 at 226 urban-ambient monitoring sites in South Korea and computed annual average PM10 concentrations at each site. Given the annual averages, we developed ordinary kriging prediction models for each of the seven major cities and for the entire country by using an exponential covariance reference model and a maximum likelihood estimation method. For model evaluation, cross-validation was performed and mean square error and R-squared (R2) statistics were computed.
Results
Mean annual average PM10 concentrations in the seven major cities ranged between 45.5 and 66.0 μg/m3 (standard deviation=2.40 and 9.51 μg/m3, respectively). Cross-validated R2 values in Seoul and Busan were 0.31 and 0.23, respectively, whereas the other five cities had R2 values of zero. The national model produced a higher crossvalidated R2 (0.36) than those for the city-specific models.
Conclusions
In general, the ordinary kriging models performed poorly for the seven major cities and the entire country of South Korea, but the model performance was better in the national model. To improve model performance, future studies should examine different prediction approaches that incorporate PM10 source characteristics.
doi:10.5620/eht.e2014012
PMCID: PMC4178540  PMID: 25262773
Exposure prediction; Health effect; Kriging; Long-term exposure; Particulate matter
15.  Effects of Air Pollution on Asthma Hospitalization Rates in Different Age Groups in Metropolitan Cities of Korea 
Air quality, atmosphere, & health  2013;6(3):10.1007/s11869-013-0195-x.
Many studies have shown associations between air pollution and asthma admissions in Korea, but have not reported whether these effects differ by age classification. The purpose of this study was to determine whether air pollution effects on asthmatic hospital admissions are different by three age groups (years): children (less than 15), adults (15–64; reference group), and the elderly (over 65). Daily time-series data from seven metropolitan cities in South Korea were analyzed in two stages. In the first stage, relative asthma morbidity rates associated with air pollution were estimated for each city and age group, using semi-parametric log-linear regression. In the second stage, estimates from all seven cities were combined by age group using Bayesian hierarchical modeling. The effects of exposure to particulate matter <10 micrometers in aerodynamic diameter (PM10), carbon monoxide (CO) and nitrogen dioxide (NO2) varied significantly by age groups. Using adults as the referent, the relative rate (RR) of asthma admissions with 10μg/m3 increase of PM10 is 1.5% (95%CI: 0.1–2.8%) lower for children, and 1.3% (95% CI: 0.7–1.9%) higher for the elderly; RR with 1ppm increase of CO is 1.9% (95% CI: 0.3–3.8%) lower for children; RR with 1ppb increase of NO2(1ppb) is 0.5% (95% CI: 0.3–0.7%) higher for the elderly. No significant age group difference in relative rate was found for ozone or sulfur dioxide.
doi:10.1007/s11869-013-0195-x
PMCID: PMC3821782  PMID: 24223075
16.  Tropical influenza and weather variability among children in an urban low-income population in Bangladesh 
Global Health Action  2014;7:10.3402/gha.v7.24413.
Background
Influenza seasonality in the tropics is poorly understood and not as well documented as in temperate regions. In addition, low-income populations are considered highly vulnerable to such acute respiratory disease, owing to limited resources and overcrowding. Nonetheless, little is known about their actual disease burden for lack of data. We therefore investigated associations between tropical influenza incidence and weather variability among children under five in a poor urban area of Dhaka, Bangladesh.
Design
Acute respiratory illness data were obtained from a population-based respiratory and febrile illness surveillance dataset of Kamalapur, a low-income urban area in southeast Dhaka. Analyzed data were from January 2005 through December 2008. Nasopharyngeal wash specimens were collected from every fifth eligible surveillance participant during clinic visits to identify influenza virus infection with viral culture and reverse transcriptase–polymerase chain reaction. Time series analysis was conducted to determine associations between the number of influenza cases per week and weather factors. Zero-inflated Poisson and generalized linear Poisson models were used in the analysis for influenza A and B, respectively.
Results
Influenza A had associations with minimum temperature, relative humidity (RH), sunlight duration, and rainfall, whereas only RH was associated with influenza B. Although associations of the other weather factors varied between the two subtypes, RH shared a similar positive association when humidity was approximately 50–70%.
Conclusions
Our findings of a positive RH association is consistent with prior studies, and may suggest the viral response in the tropics. The characteristics of settlement areas, population demographics, and typical overcrowding of urban poverty may also contribute to different impacts of rainfall from higher economic population. Further investigations of associations between tropical influenza and weather variability for urban low-income populations are required for better understanding.
doi:10.3402/gha.v7.24413
PMCID: PMC4134673  PMID: 25128806
influenza; tropics; weather; low-income; poor; urban; children; time series
17.  The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods 
BMC Pulmonary Medicine  2014;14:109.
Background
This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases.
Methods/Design
The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.
The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child’s neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child’s microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures.
Discussion
The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.
doi:10.1186/1471-2466-14-109
PMCID: PMC4099383  PMID: 24990471
Cohort study; Gene-environment interaction; Allergy; Microbiota; Nutritional Status; Psychologic stress
18.  Diffuse Infiltrative Primary Cardiac Lymphoma with Delayed Extracardiac Involvement 
Chonnam Medical Journal  2014;50(1):27-30.
Primary cardiac lymphoma (PCL) is an extremely rare and fatal neoplasm of the heart. Traditionally, it is defined as lymphoma involving the heart or pericardium. PCL has a poor prognosis because of the diagnostic difficulty and its location. We present the case of a 48-year-old man who presented with pericardial effusion and diffuse cardiac wall thickening. We first suspected infiltrative heart disease. However, even after performing a biopsy, we could not establish an accurate diagnosis. After 20 months, primary cardiac diffuse large B cell lymphoma (DLBCL) was diagnosed by cervical lymph node biopsy. In this case, after chemotherapy, the DLBCL lesions, including cardiac wall thickening, improved. The treatment outcome suggests that the diagnosis was diffuse infiltrative PCL with delayed extracardiac involvement.
doi:10.4068/cmj.2014.50.1.27
PMCID: PMC4022795  PMID: 24855605
Heart; Lymphoma; Diagnosis
19.  Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-α Therapy 
Yonsei Medical Journal  2014;55(2):442-448.
Purpose
Anti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea.
Materials and Methods
We retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected.
Results
A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn's disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results.
Conclusion
Serious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.
doi:10.3349/ymj.2014.55.2.442
PMCID: PMC3936648  PMID: 24532516
Tumor necrosis factor-alpha; tuberculosis; infection
20.  An Association Rule Mining-Based Framework for Understanding Lifestyle Risk Behaviors 
PLoS ONE  2014;9(2):e88859.
Objectives
This study investigated the prevalence and patterns of lifestyle risk behaviors in Korean adults.
Methods
We utilized data from the Fourth Korea National Health and Nutrition Examination Survey for 14,833 adults (>20 years of age). We used association rule mining to analyze patterns of lifestyle risk behaviors by characterizing non-adherence to public health recommendations related to the Alameda 7 health behaviors. The study variables were current smoking, heavy drinking, physical inactivity, obesity, inadequate sleep, breakfast skipping, and frequent snacking.
Results
Approximately 72% of Korean adults exhibited two or more lifestyle risk behaviors. Among women, current smoking, obesity, and breakfast skipping were associated with inadequate sleep. Among men, breakfast skipping with additional risk behaviors such as physical inactivity, obesity, and inadequate sleep was associated with current smoking. Current smoking with additional risk behaviors such as inadequate sleep or breakfast skipping was associated with physical inactivity.
Conclusion
Lifestyle risk behaviors are intercorrelated in Korea. Information on patterns of lifestyle risk behaviors could assist in planning interventions targeted at multiple behaviors simultaneously.
doi:10.1371/journal.pone.0088859
PMCID: PMC3923836  PMID: 24551181
21.  Non-Linear Relationship between Serum 25-Hydroxyvitamin D and Hemoglobin in Korean Females: The Korean National Health and Nutrition Examination Survey 2010–2011 
PLoS ONE  2013;8(8):e72605.
Background
Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population.
Methods
Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status.
Results
The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1st quintile but not the 2nd, 3rd, and 4th quintiles were significantly different from the 5th quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males.
Conclusions
This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.
doi:10.1371/journal.pone.0072605
PMCID: PMC3755993  PMID: 24015265
22.  Genome-Wide Association Study of Lung Cancer in Korean Non-Smoking Women 
Journal of Korean Medical Science  2013;28(6):840-847.
Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (P < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, P = 0.027). OR and P value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed P value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.
doi:10.3346/jkms.2013.28.6.840
PMCID: PMC3677999  PMID: 23772147
Lung Neoplasms; Genome-Wide Association Study; Non-Smoking Women
23.  Early Referral to a Nephrologist Improved Patient Survival: Prospective Cohort Study for End-Stage Renal Disease in Korea 
PLoS ONE  2013;8(1):e55323.
The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3±58.9 versus 2.9±3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27–4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73–13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.
doi:10.1371/journal.pone.0055323
PMCID: PMC3555934  PMID: 23372849
24.  Susceptibility to air pollution effects on mortality in Seoul, Korea: A case-crossover analysis of individual-level effect modifiers 
Air pollution’s mortality effects may differ by subpopulation; however, few studies have investigated this issue in Asia. We investigated susceptibility to air pollutants on total, cardiovascular, and respiratory mortality in Seoul, Korea for the period 2000 – 2007. We applied time-stratified case-crossover analysis, which allows direct modeling of interaction terms, to estimate susceptibility based on sex, age, education, marital status, and occupation. An interquartile range increase in pollution was associated with odds ratios of 0.94 (95% confidence interval, 0.25 – 1.62), 2.27 (1.03–3.53), 1.94 (0.80 – 3.09), and 2.21 (1.00 – 3.43) for total mortality and 1.95 (0.64 – 3.27), 4.82 (2.18 – 7.54), 3.64 (1.46 – 5.87), and 4.32 (1.77 – 6.92) for cardiovascular mortality for PM10, nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), respectively. Ozone effect estimates were positive, but not statistically significant. Results indicate that some populations are more susceptible than others. For total or cardiovascular mortality, associations were higher for males, those 65 – 74 years, and those with no education or manual occupation for some pollutants. For example, the odds ratio for SO2 and cardiovascular mortality was 1.19 (1.03 – 1.37) times higher for those with manual occupations than professional occupations. Our findings provide evidence that some populations are more susceptible to the effects of air pollution than others, which has implications for public policy and risk assessment for susceptible subpopulations.
doi:10.1038/jes.2012.6
PMCID: PMC3543153  PMID: 22395258
air pollution; effect modifiers; mortality; time-stratified case–crossover analysis; susceptible subpopulations
25.  Epidemiological Characteristics of Novel Influenza A (H1N1) in Antiviral Drug Users in Korea 
PLoS ONE  2012;7(10):e47634.
Soon after the first novel influenza A (H1N1) death was documented in Korea on August 15, 2009, prompt treatment with antiviral drugs was recommended when an infection was suspected. Free antiviral drugs were distributed to patients who met the case definition in the treatment guidelines, and patients prescribed the antiviral drugs were included in the Antiviral Drug Surveillance System (ADSS). A total of 2,825,821 patients were reported to the ADSS from September 1 to December 31, 2009. Odds ratios were calculated to compare the risks of severe diseases, as indicated by general hospital admissions or intensive care unit (ICU) admissions according to demographic characteristics, underlying medical conditions, and behavioral factors. Approximately 6% of the total population received antiviral drugs during the study period. Of these, 2,709,611 (95.9%) were outpatients, 114,840 (4.06%) were hospitalized, and 1,370 (0.05%) were admitted to the ICU. Children aged 0–9 yr accounted for 33.94% of all reported cases, whereas only 3.89% of the patients were ≥ 60 yr. The estimated incidence of novel influenza A (H1N1) during the pandemic was 5.68/100 of all reported cases. Mortality due to influenza A (H1N1) during the pandemic was 0.33/100,000, with the highest mortality of 1.31/100,000 for patients aged ≥ 60 years. Severe pandemic H1N1 influenza was associated with the presence of one or more underlying medical conditions in elderly aged ≥ 60 years and with lower economic status. Moreover, influenza A (H1N1) appeared to be age-specific in terms of mortality. Although the incidence and admission rates of influenza A (H1N1) were higher in younger age groups, fatal cases were much more likely to occur in the elderly (≥60 years). In contrast to earlier influenza A (H1N1) reports, the risks of a severe outcome were elevated among those who were underweight (body mass index < 18.5 kg/m2).
doi:10.1371/journal.pone.0047634
PMCID: PMC3474727  PMID: 23082184

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