Search

Background: The effect of serial change in alcohol consumption on stroke risk has been limitedly evaluated. We investigated the association of change in alcohol consumption with risk of stroke. Methods: This study is a population-based retrospective cohort study from National Health Insurance Service database of all Koreans. Four lakh five hundred thirteen thousand seven hundred forty-six participants aged ≥40 years who underwent 2 subsequent national health examinations in both 2009 and 2011. Alcohol consumption was assessed by average alcohol intake (g/day) based on self-questionnaires and categorized into non-, mild, moderate, and heavy drinking. Change in alcohol consumption was defined by shift of category from baseline. Cox proportional hazards model was used with adjustment for age, sex, smoking status, regular exercise, socioeconomic information, and comorbidities, Charlson Comorbidity Index, systolic blood pressure, and laboratory results. Subgroup analysis among those with the third examination was conducted to reflect further change in alcohol consumption. Results: During 28 424 497 person-years of follow-up, 74 923 ischemic stroke events were identified. Sustained mild drinking was associated with a decreased risk of ischemic stroke (adjusted hazard ratio, 0.88 [95% CI, 0.86–0.90]) compared with sustained nondrinking, whereas sustained heavy drinking was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.06 [95% CI, 1.02–1.10]). Increasing alcohol consumption was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.11 [95% CI, 1.06–1.17] from mild to moderate; adjusted hazard ratio, 1.28 [95% CI, 1.19–1.38] from mild to heavy) compared with sustained mild drinkers. Reduction of alcohol consumption from heavy to mild level was associated with 17% decreased risk of ischemic stroke through 3× of examinations. Conclusions: Light-to-moderate alcohol consumption is associated with a decreased risk of ischemic stroke, although it might be not causal and could be impacted by sick people abstaining from drinking. Reduction of alcohol consumption from heavy drinking is associated with a decreased risk of ischemic stroke.

ImportanceAlthough it has been postulated that chronic inflammation caused by rheumatoid arthritis (RA) contributes to the development of Parkinson disease (PD), the association between these 2 conditions has yet to be determined.ObjectiveTo evaluate the association between RA and subsequent PD risk.Design, Setting, and ParticipantsThis retrospective cohort study used the Korean National Health Insurance Service database to collect population-based, nationally representative data on patients with RA enrolled from 2010 to 2017 and followed up until 2019 (median follow-up, 4.3 [IQR, 2.6-6.4] years after a 1-year lag). A total of 119 788 patients who were first diagnosed with RA (83 064 with seropositive RA [SPRA], 36 724 with seronegative RA [SNRA]) were identified during the study period and included those who underwent a national health checkup within 2 years before the RA diagnosis date (64 457 patients). After applying exclusion criteria (eg, age ExposuresRheumatoid arthritis as defined using International Classification of Diseases, Tenth Revision codes M05 for SPRA and M06 (except M06.1 and M06.4) for SNRA; prescription of any disease-modifying antirheumatic drug; and enrollment in the Korean Rare and Intractable Diseases program.Main Outcomes and MeasuresThe main outcome was newly diagnosed PD. Data were analyzed from May 10 through August 1, 2022, using Cox proportional hazards regression analyses.ResultsFrom the 328 080 individuals analyzed (mean [SD] age, 58.6 [10.1] years; 74.9% female and 25.1% male), 1093 developed PD (803 controls and 290 with RA). Participants with RA had a 1.74-fold higher risk of PD vs controls (95% CI, 1.52-1.99). An increased risk of PD was found in patients with SPRA (adjusted hazard ratio [aHR], 1.95; 95% CI, 1.68-2.26) but not in patients with SNRA (aHR, 1.20; 95% CI, 0.91-1.57). Compared with the SNRA group, those with SPRA had a higher risk of PD (aHR, 1.61; 95% CI, 1.20-2.16). There was no significant interaction between covariates on risk of PD.Conclusions and RelevanceIn this study, RA was associated with an increased risk of PD, and seropositivity of RA conferred an augmented risk of PD. The findings suggest that physicians should be aware of the elevated risk of PD in patients with RA and promptly refer patients to a neurologist at onset of early motor symptoms of PD without synovitis.

Figure S1 shows the concept of time-dependent survival analysis.

Supplementary tables show the results of subgroup analyses stratified by sex, age, body mass index, smoking status, and alcohol consumption.

Anticancer effects of aspirin, metformin, and statins against gastric cancer, one of the most common cancers in the world, have been reported. This retrospective cohort study aimed to investigate independent associations of aspirin, metformin, and statin use with gastric cancer incidence and mortality after adjustment for concomitant use of other drugs, using pooled cohort data extracted from the Korean National Health Insurance claim database. Follow-up started on January 1, 2004 and ended at the date of gastric cancer diagnosis, death, or December 31, 2013. Exposures to drugs were defined as cumulative duration of use for aspirin and cumulative defined daily dose for metformin and statin, and were entered as time-dependent variables in Cox analysis models to avoid immortal time bias. Use of aspirin for longer than 182.5 and 547.5 days during 2-year interval was associated with reduced risks of gastric cancer incidence and mortality, respectively. Patients with diabetes were at higher risk of gastric cancer incidence and mortality than nondiabetic people, regardless of metformin treatment. However, metformin use among patients with diabetes was associated with a reduction in gastric cancer mortality in a dose-response manner. Statin use was also associated with a reduction of gastric cancer mortality in the general population, but not with gastric cancer incidence. In conclusion, long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population, but metformin or statin use was only associated with a reduction of gastric cancer mortality in patients with diabetes and in the general population, respectively.Prevention Relevance:Long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population. Metformin or statin use, however, was only associated with a reduction of gastric cancer mortality in diabetic patients and in the general population in a dose-response manner, respectively.

Background Midlife hypertension has been recognized as a modifiable risk factor for dementia, but association between blood pressure (BP) in late life and dementia has been inconclusive. In addition, few studies have investigated effects of BP control on dementia incidence in the frail elderly. Thus, this study aimed to investigate the association of BP and dementia incidence with concomitant consideration of physical frailty in the young elderly population. Methods Using the Korean National Health Information Database, we identified 804,024 subjects without history of dementia at age 66. Dementia diagnosis was defined with prescription records of anti-dementia drugs and dementia-related diagnostic codes. Physical frailty was measured using the Timed Up and Go test. Association of BP and dementia incidence with concomitant consideration of physical frailty was investigated using Cox hazards analyses. Results The risks of Alzheimer’s and vascular dementia increased from systolic BP ≥ 160 and 130–139 mmHg, respectively; a significant association of dementia incidence with low BP was not observed. In the analyses stratified by the physical frailty status, low BP was not associated with increased risks of dementia within the groups both with and without physical frailty. Conclusions High BP was associated with increased risks of dementia, especially for vascular dementia, while low BP was not associated with increased risks of any type of dementia in young elderly people, even in those with physical frailty. This study suggests the need for tight BP control in young elderly people, irrespective of frailty status, to prevent dementia and supports the current clinical guidelines of hypertension treatment.

We evaluated the association between aspirin, statins, and metformin use and prostate cancer (PC) incidence and mortality using a large population-based dataset. 388,760 men who participated in national health screening program in Korea during 2002–2003 were observed from 2004 to 2013. Hazard ratios of aspirin, statins, and metformin use for PC incidence and PC mortality were calculated with adjustment for simultaneous drug use. Cumulative use of each drug was inserted as time-dependent variable with 2-year time windows. Aspirin use ≥ 1.5 year (per 2-year) was associated with borderline decrease in PC mortality when compared to non-users (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.50–1.02). Statins use was not associated with either PC incidence or PC mortality. Metformin ever-use was associated with decreased PC incidence compared with non-diabetics (aHR 0.86, 95% CI 0.77–0.96). Diabetics who were not using metformin or using low cumulative doses had higher PC mortality than non-diabetics (aHR 2.01, 95% CI 1.44–2.81, and aHR 1.70, 95% CI 1.07–2.69, respectively). However, subjects with higher cumulative doses of metformin did not show increased PC mortality. In conclusion, metformin use was associated with lower PC incidence. Use of aspirin and that of metformin among diabetic patients were associated with lower PC mortality.

This study aimed to determine the dose–response relationship between the levels of statin exposure and the incidence of Alzheimer’s disease (AD). We included 119,013 Korean adults (≥ 60 years old) using a database from the Korean National Health Insurance Service (2002–2013). Statin exposure was treated as a time-varying variable. Incidence of AD was defined by the first claim code for AD with anti-Alzheimer drugs. AD occurred in 9467 cases during a median 7.2 years of follow-up. Overall, statin use was not associated with an increased risk of AD incidence [adjusted hazard ratio (aHR) = 1.04; 95% confidence interval (CI) = 0.99–1.10]. When examined by level of statin exposure, statin prescription

The optimal blood pressure (BP) target in older people according to frailty status remains uncertain. This article investigates how frailty affects the association between BP and cardiovascular diseases or mortality, specifically in young-old adults. A retrospective cohort was created for 708,964 older adults with a uniform age of 66 years. The association between BP and myocardial infarction (MI), stroke, or mortality was analyzed using Cox proportional hazards models. The Timed Up and Go test (TUG) was used as a measure of physical frailty. Mean follow-up was 6.8 years, detecting 38,963 (5.5%) events. There was a linear association between increasing systolic BP (SBP) or diastolic BP (DBP) and increased risk of incident MI and stroke, compared to the reference BP (SBP, 110–119 mmHg or DBP, 80–89 mmHg). The risk patterns with high BP remained similar in each TUG group (

BACKGROUND Sarcopenia is an important health problem, the risk factors of which a few studies have reported on. The purpose of this study was to evaluate the correlation between sarcopenia and the ratio of total energy intake to basal metabolic rate (BMR) as well as physical activity, and determine whether the relationship was different between younger and older age groups using data from the 2008-2011 Korea National Health and Nutrition Examination Survey. METHODS We analyzed 16,313 subjects older than 19 years who had dual energy X-ray absorptiometry data. Sarcopenia was defined as an appendicular lean mass/weight (%) ratio of 1 standard deviation below the sex-specific mean value for a younger reference group, and BMR was calculated using the Harris-Benedict equation. A chi-squared test and logistic regression analyses were performed to evaluate the factors associated with sarcopenia. RESULTS In this study, 15.2% of males and 15.4% of females had sarcopenia. Energy intake/BMR as well as physical activity was negatively related to sarcopenia risk. In stratified analysis by age and sex, strength exercises showed an inverse association with sarcopenia only in males under the age of 50 years (odds ratio, 0.577; P

PURPOSE Although smoking has a significant impact on mortality and morbidity of cancer patients, many patients continue to smoke post-diagnosis. The purpose of this study was to investigate prevalence and predictors of sustained smoking among male cancer survivors. Materials and Methods The Korean National Health Insurance Service-National Health Screening Cohort database was used for this population-based, retrospective study. Study subjects were 15,141 men who were diagnosed with their first incident cancer between 2004 and 2011. Changes in smoking status before and after a cancer diagnosis were investigated. For patients who were current smokers pre-diagnosis, association between post-diagnosis sustained smoking and demographic, socioeconomic, and clinical variables were examined. RESULTS Of the 4,657 pre-diagnosis smokers, 2,255 (48%) had quit after cancer diagnosis, while 2,402 (51.6%) continued to smoke. In a multivariate logistic regression analysis, younger age at cancer diagnosis (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.21 to 1.55; p < 0.001), low socioeconomic status (aOR, 1.29; 95% CI, 1.15 to 1.45; p ≤ 0.001), pre-diagnosis heavy smoking (aOR, 1.24; 95% CI, 1.09 to 1.41; p=0.001), diagnosis of non-smoking- related cancer (aOR, 1.67; 95% CI, 1.42 to 1.96; p < 0.001), and high serum glucose level (aOR, 1.23; 95% CI, 1.03 to 1.46; p=0.019) were associated with sustained smoking after a cancer diagnosis. CONCLUSION Almost half of the male smokers continue to smoke after a cancer diagnosis. Targeted interventions for smoking cessation should be considered for patients with younger age, low socioeconomic status, heavy smoking history, non-smoking-related cancer, and high blood glucose levels.

Aims The aim of this study was to assess the association of smoking cessation and reduction with risk of cardiovascular disease (CVD). Methods and results A total of 897 975 current smokers aged ≥40 years who had undergone two consecutive national health examinations (in 2009 and 2011) were included. Participants were classified as quitters (20.6%), reducers I (≥50% reduction, 7.3%), reducers II (20–50% reduction, 11.6%), sustainers (45.7%), and increasers (≥20% increase, 14.5%). During 5 575 556 person-years (PY) of follow-up, 17 748 stroke (3.2/1000 PY) and 11 271 myocardial infarction (MI) (2.0/1000 PY) events were identified. Quitters had significantly decreased risk of stroke [adjusted hazard ratio (aHR) 0.77 95% confidence interval (CI) 0.74–0.81; absolute risk reduction (ARR) −0.37, 95% CI −0.43 to −0.31] and MI (aHR 0.74, 95% CI 0.70–0.78; ARR −0.27, 95% CI −0.31 to −0.22) compared to sustainers after adjustment for demographic factors, comorbidities, and smoking status. The risk of stroke and MI incidence in reducers I (aHR 1.02, 95% CI 0.97–1.08 and aHR 0.99, 95% CI 0.92–1.06, respectively) and reducers II (aHR 1.00, 95% CI 0.95–1.05 and aHR 0.97, 95% CI 0.92–1.04, respectively) was not significantly different from the risk in sustainers. Further analysis with a subgroup who underwent a third examination (in 2013) showed that those who quit at the second examination but had starting smoking again by the third examination had 42–69% increased risk of CVD compared to sustained quitters. Conclusions Smoking cessation, but not reduction, was associated with reduced CVD risk. Our study emphasizes the importance of sustained quitting in terms of CVD risk reduction.

Anticancer effects of aspirin, metformin, and statins against gastric cancer, one of the most common cancers in the world, have been reported. This retrospective cohort study aimed to investigate independent associations of aspirin, metformin, and statin use with gastric cancer incidence and mortality after adjustment for concomitant use of other drugs, using pooled cohort data extracted from the Korean National Health Insurance claim database. Follow-up started on January 1, 2004 and ended at the date of gastric cancer diagnosis, death, or December 31, 2013. Exposures to drugs were defined as cumulative duration of use for aspirin and cumulative defined daily dose for metformin and statin, and were entered as time-dependent variables in Cox analysis models to avoid immortal time bias. Use of aspirin for longer than 182.5 and 547.5 days during 2-year interval was associated with reduced risks of gastric cancer incidence and mortality, respectively. Patients with diabetes were at higher risk of gastric cancer incidence and mortality than nondiabetic people, regardless of metformin treatment. However, metformin use among patients with diabetes was associated with a reduction in gastric cancer mortality in a dose-response manner. Statin use was also associated with a reduction of gastric cancer mortality in the general population, but not with gastric cancer incidence. In conclusion, long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population, but metformin or statin use was only associated with a reduction of gastric cancer mortality in patients with diabetes and in the general population, respectively. Prevention Relevance: Long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population. Metformin or statin use, however, was only associated with a reduction of gastric cancer mortality in diabetic patients and in the general population in a dose-response manner, respectively.

Adherence to antihypertensive medication is a critical factor to control blood pressure and prevent complications. However, cognitive impairment can negatively affect medication adherence. In this study, we investigated the association between cognitive function and antihypertensive medication adherence among elderly hypertensive patients using the Korean National Health Insurance Service National Sample Cohort Data of the Elderly Cohort. The study included 20,071 elderly hypertensive patients and the prevalence of poor medication adherence to antihypertensive medications was 16.4%. A multivariate logistic regression analysis showed that lower cognitive function was associated with poor medication adherence (adjusted odds ratio 0.980, 95% confidence interval 0.961–0.999). Additionally, high income levels, living in metropolitan areas, and comorbidities (such as stroke, coronary heart disease, diabetes, and dyslipidemia) were positively associated with medication adherence, while patients diagnosed with cancers showed poor medication adherence. Our study demonstrated that cognitive impairment is a possible risk factor for poor antihypertensive medication adherence, even in patients without dementia. Thus, clinicians involved with geriatric care should monitor patients’ cognitive function and medication adherence. And if a patient shows cognitive impairment, clinicians need to educate patients and caregivers about the importance of proper adherence, and consider proper interventions to optimize the cognitive function of elderly patients.

Smoking cessation reduces the risk of cardiovascular disease (CVD), but also elevates fasting serum glucose (FSG) levels. The effect of post-cessation hyperglycemia on cardiovascular disease is unknown. The study population consisted of 127,066 men without type 2 diabetes from the Korean National Health Insurance System – Health Screening Cohort database. Change in smoking habits and FSG was determined by the difference in smoking status and FSG levels from the first (2002 and 2003) and second (2004 and 2005) health examinations. Continual smokers, quitters, ex-smokers, and never smokers were stratified according to FSG elevation. The study participants were followed-up for CVD and CVD-related death from 2006 to 2013. Compared to continual smokers, quitters had decreased risk of CVD among those without FSG elevation (hazard ratio, HR, 0.76, 95% confidence interval, CI, 0.66–0.86) and with FSG elevation (HR 0.83, 95% CI 0.72–0.96). Similarly, quitters had a tendency towards reduced risk of CVD-related death among those without FSG elevation (HR 0.74, 95% CI 0.51–1.09) and with FSG elevation (HR 0.68, 95% CI 0.46–1.03). Post-cessation hyperglycemia did not attenuate the beneficiary risk-reducing effects of quitting on CVD and CVD-related death.

Alcohol consumption is a major risk factor for head and neck cancer (HNC), yet little data exist examining drinking patterns and HNC risk. In this population-based, retrospective cohort study, 11,737,467 subjects were recruited from the Korean National Health Insurance Service database. The risks of overall HNC and HNC subtypes according to average alcohol consumption, drinking frequency, and daily amount were examined using Cox proportional hazard models. Over the median follow-up of 6.4 years, 15,832 HNC cases were identified. HNC risk linearly increased with drinking frequency (p-trend &lt, 0.01, adjusted hazard ratio [aHR] 1.55, 95% confidence interval [CI] 1.45–1.67 in subjects who drank 7 days/week). HNC risk also increased according to daily amount of alcohol consumption (p-trend &lt, 0.01), but plateaued from 5–7 units/occasion (aHR 1.25, 95% CI 1.19–1.31) to &gt, 14 units/occasion (aHR 1.26, 95% CI 1.13–1.40). When stratified by average alcohol consumption, drinking frequency, but not daily amount, showed a linear relationship with HNC risk in moderate and heavy drinkers. When comparing the HNC subtypes, similar tendencies were observed in cancers of the oral cavity, pharynx, and larynx, but not in the salivary gland. In conclusion, drinking frequency is a stronger risk factor for HNC, especially for cancer of the oral cavity, pharynx, and larynx, than the daily amount of alcohol consumption.

Purpose Suboptimal frequency of glycosylated hemoglobin (HbA1c) monitoring is associated with poor diabetes control. We aimed to analyze compliance to HbA1c testing guidelines and explore associated individual and area-level determinants, focusing on regional variation. Methods This cross-sectional study between the period of 2012–2013 was conducted by using the Korean National Health Insurance Research Database, and included 45,634 patients diagnosed with diabetes mellitus, who were prescribed any anti-diabetic medications, including insulin. We calculated the proportion of each HbA1c testing frequency (≥1, ≥2, or ≥4 times per year) stratified by 17 administrative regions. Multilevel and multivariate logistic analyses were performed with regional (proportion of farmer population) and individual characteristics (age, sex, income level, duration of diabetes, and most visited medical institution). Results Overall, 67.3% of the patients received ≥ 1 HbA1c test per year; 37.8% and 6.1% received ≥2 and ≥4 tests per year, respectively. Those managed in secondary-level hospitals or clinics and those living in rural areas were less likely to receive HbA1c testing. Even after adjusting for individual and regional level characteristics, significant area level variation was observed (variance participant coefficients were 7.91%, 9.58%, and 14.43% for testing frequencies of ≥1, ≥2, and ≥4 times a year, respectively). Conclusions The frequency of HbA1c monitoring is suboptimal in Korea, especially in rural areas. Moreover, significant regional variation was observed, implying a contextual effect. This suggests the need for developing policy actions to improve HbA1c monitoring. In particular, access to HbA1c testing in rural primary care clinics must be improved.

Background The combined effect of transitions of metabolic health and weight on cardiovascular disease ( CVD ) remains unclear. We aimed to examine the association of concurrent changes of metabolic health and weight on CVD over time. Methods and Results The study population consisted of 205 394 from the Korean National Health Insurance Service. Metabolic health was determined by fasting serum glucose, total cholesterol, and blood pressure levels, while obesity was determined by body mass index. All participants were divided into either metabolically healthy nonobese ( MHNO ), metabolically healthy obese, metabolically unhealthy nonobese, or metabolically unhealthy obese for each of the first (2002–2003) and second (2004–2005) health screening periods, after which participants were followed‐up for CVD from 2006 to 2015. Cox proportional hazards regression was used to determine adjusted hazard ratios ( aHR s) and 95% CI s. Among initial MHNO participants, those who became metabolically healthy obese ( aHR , 1.25; 95% CI , 1.10–1.41), metabolically unhealthy nonobese ( aHR , 1.23; 95% CI , 1.15–1.31), and metabolically unhealthy obese ( aHR , 1.34; 95% CI , 1.12–1.61) had elevated risk for CVD compared with those who remained MHNO . Conversely, improving metabolic health and obesity were associated with reduced CVD risk among initially metabolically unhealthy nonobese to secondary MHNO ( aHR , 0.79; 95% CI , 0.73–0.84), metabolically unhealthy obese to MHNO ( aHR , 0.68; 95% CI , 0.58–0.81), and metabolically unhealthy obese to metabolically healthy obese ( aHR, 0.73; 95% CI , 0.66–0.80) participants. Conclusions Changes toward metabolically unhealthy or obese states resulted in increased CVD risk. Improving metabolic health along with reducing weight may lead to decreased risk of CVD .

We examined effects of smoking habit change on fracture risk in men. Long-term quitters and never smokers showed decreased risk for overall fractures, lumbar fractures, and other site fractures. Short-term quitters did not show decreased risk. Longer time since smoking cessation may lead to decreased fracture risk in men. Cigarette smoking is a well-known modifiable risk factor of osteoporosis and fractures. This study investigated the effects of change in smoking habits on risks of all types of fractures in men using a nationwide health claims database. Retrospective study was performed using the Korean National Health Insurance Service-National Sample Cohort Data. Cox proportional hazards regression analyses were performed to estimate risks of all types of hospitalized fractures, hip fractures, lumbar fractures, and other site fractures (all other fractures excluding the lumbar and hip areas). Compared to continued smokers, long-term quitters and never smokers showed decreased risk for all types of fractures (adjusted hazard ratio (aHR) 0.83, 95% confidence interval (CI) 0.78–0.88 and aHR 0.84, 95% CI 0.80–0.89, respectively). According to skeletal site, long-term quitters and never smokers showed decreased risk for lumbar fractures (aHR 0.82, 95% CI 0.68–0.98 and aHR 0.85, 95% CI 0.73–0.99, respectively) and other site fractures (aHR 0.83, 95% CI 0.78–0.89 and aHR 0.85, 95% CI 0.81–0.90, respectively). Hip fractures were decreased in never smokers (aHR 0.77, 95% CI 0.62–0.94). Short-term quitters did not show decreased risk for fractures. Longer time since smoking cessation in men may lead to decreased risk for fractures, especially lumbar and other site fractures. Physicians should counsel patients at risk for fractures both to quit smoking and to maintain abstinence from smoking. Further studies may be required to help comprehend how smoking cessation can affect fracture risk.

Background While smoking elevates the risk for cardiovascular disease (CVD) among atrial fibrillation (AF) patients, whether smoking cessation after AF diagnosis actually leads to reduced CVD risk is unclear. We aimed to determine the association of smoking cessation after AF diagnosis with subsequent CVD Risk among South Korean men. Methods This retrospective cohort study included 2372 newly diagnosed AF male patients during 2003–2012 from the Korean National Health Insurance Service database. Self-reported smoking status within 2 years before and after diagnosis date were determined, after which the participants were divided into continual smokers, quitters (smokers who quit after AF diagnosis), sustained-ex smokers (those who quit prior to AF diagnosis), and never smokers. Participants were followed up from 2 years after AF diagnosis until 31 December 2015 for CVD. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for CVD according to the change in smoking habits before and after AF diagnosis. Results The mean (standard deviation, minimum-maximum) age of the study subjects was 62.5 (8.6, 41–89) years. Among AF patients, quitters had 35% reduced risk (aHR 0.65, 95% CI 0.44–0.97) and never smokers had 32% reduced risk (aHR 0.68, 95% CI 0.52–0.90) for CVD compared to continual smokers (p for trend 0.020). Similarly, compared to continual smokers, quitters had 41% risk-reduction (aHR 0.59, 95% CI 0.35–0.99) and never smokers 34% risk-reduction (aHR 0.66, 95% CI 0.46–0.93) for total stroke (p for trend 0.047). Quitters had 50% reduction (aHR 0.50, 95% CI 0.27–0.94), sustained ex-smokers had 36% reduction (aHR 0.64, 95% CI 0.42–0.99), and never smokers had 39% reduction (aHR 0.61, 95% CI 0.41–0.91) in ischemic stroke risk (p for trend 0.047). The risk-reducing effect of quitting on CVD risk tended to be preserved regardless of aspirin or warfarin use. Conclusions Smoking cessation after AF diagnosis was associated with reduced CVD, total stroke, and ischemic stroke risk.

Background: Although guidelines recommend regular glycated hemoglobin (HbA1c) testing every 6 months for type 2 diabetes patients, whether adherence to these guidelines leads to improved health outcomes is unclear. We aimed to determine the association of HbA1c testing intervals on stroke and cardiovascular disease (CVD) risk among newly diagnosed type 2 diabetes patients. Methods: The study population consisted of 31,041 newly diagnosed type 2 diabetes patients during 2003-2011 from the Korean National Health Insurance Service. Average HbA1c testing interval was calculated during 3 years after type 2 diabetes diagnosis. Participants were categorized into average HbA1c testing intervals of ≤6, >6 to ≤12, >12 to ≤18, and >18 months, after which they were followed-up for stroke and CVD until 2015. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazards regression for the risk of stroke and CVD according to HbA1c testing interval. Results: Compared to patients with HbA1c testing intervals of ≤6 months, patients with >6 to ≤12 (aHR 1.40, 95% CI 1.10-1.78), >12 to ≤18 (aHR 1.43, 95% CI 1.12-1.84), and >18 (aHR 1.64, 95% CI 1.32-2.04) month intervals had elevated risk for stroke ( p trend 12 to ≤18 (aHR 1.28, 95% CI 1.10-1.50), and >18 (aHR 1.38, 95% CI 1.21-1.58) month intervals had increased risk for CVD ( p trend 3 to ≤6 months on stroke and CVD risk. The risk-increasing effect of stroke and CVD by longer HbA1c testing intervals was preserved among subgroups divided by fasting serum glucose, initial diabetes medication, outpatient department visits, and Charlson comorbidity index. Conclusions: HbA1c testing interval of more than 6 months was associated with increased risk of stroke and CVD among newly diagnosed type 2 diabetes patients. Type 2 diabetes patients who undergo biannual HbA1c testing may benefit from reduced stroke and CVD risk.

Supplemental Digital Content is available in the text, Many lifelong smokers establish smoking habits during young adulthood. A university can be an effective setting for early smoking cessation. We evaluated long-term predictors of smoking cessation among smokers in a university setting. We longitudinally followed a cohort of smokers enrolled in a university smoking cessation program in Seoul, South Korea. Sociodemographic factors, smoking-related variables, and changes in smoking habits were assessed during 6-week visit sessions and follow-up telephone interviews conducted 1 year or more later. A total of 205 participants were followed up (mean follow-up duration: 27.1 months). Cessation rates were 47.3% at the end of the visit sessions and 28.8% at follow-up. The long-term persistent smoking rate was significantly higher among individuals with peers who smoked (odds ratio [OR] = 8.64; 95% confidence interval [CI] = 1.75, 42.80), with family members who smoked (OR = 3.28; 95% CI = 1.20, 9.00), and who smoked 10 to 19 cigarettes/day (OR = 4.83; 95% CI = 1.49, 15.69). Conversely, persistent smoking was less likely among those who attended the program regularly (OR = 0.84 per visit; 95% CI = 0.72, 0.99) and attempted quitting more frequently (OR = 0.93 per attempt; 95% CI = 0.87, 0.99). Use of smoking cessation medications (varenicline or bupropion) was not significantly associated with long-term quitting (OR = 0.71; 95% CI = 0.26, 1.93). Peer influences were the strongest predictors of failure in long-term cessation among smokers who attempted to quit. Similarly, the existence of smokers in the family was negatively associated with successful quitting. Regular attendance at a smoking cessation program and a high number of attempts to quit were positively associated with successful quitting. Targeting peer and family smoking groups together rather than targeting individual smokers alone, implementing active cessation programs encouraging regular attendance, and providing comprehensive antismoking environments might be effective strategies in a university setting.

Background We aimed to investigate the association between weight change after smoking cessation and the risk of all-cause and cause-specific mortality among middle-aged male smokers. Methods We conducted a prospective cohort study using the National Health Insurance Service National Health Screening Cohort (NHIS-HealS) database. Male Participants (n=102,403) without critical conditions aged between 40 and 79 at baseline who underwent biennial health examination were included in this study. Participants were categorized into continued smokers, recent quitters (within 4 years), long-term quitters (more than 4 years), and never-smokers based on the self-reported smoking status. Weight change was determined by the change of Body Mass Index (BMI) between the first (2002-2003) and second (2004-2005) health examination records. We followed patients from January 1, 2006 to December, 31, 2013. To assess the risk of all-cause, cancer, cardiovascular disease (CVD) mortality, and non-cancer, non-CVD mortality according to smoking cessation and weight change, we computed Hazard Ratio (HR) and 95% Confidence Interval (95% CI) using Cox proportional hazard models. Results Severity of weight gain was more prevalent among recent quitters compared to long-term quitters. After adjusting for covariates and weight change, both recent quitters (HR:0.74; 95% CI: 0.63-0.87) and long-term quitters (HR:0.53; 95% CI:0.45-0.61) had decreased risk of all-cause mortality compared to continued smokers. Similarly, both recent and long-term quitters had decreased risk of cancer, CVD, non-cancer, and non-CVD death regardless of weight change following smoking cessation. Compared to continued smokers, non-smokers also had a lower risk of overall and cause-specific death. Conclusions Post-cessation weight change did not modify the protective association of smoking cessation with reduced risk of all-cause and cause-specific death. From a public health perspective, smoking cessation program may contribute to reducing risk of death in middle-aged male smokers despite the concern on weight change after quitting smoking.

This study aimed to investigate the effects of smoking habit change on the risks of all-cause mortality and cardiovascular diseases (CVDs) among patients with newly diagnosed diabetes using the Korean National Sample Cohort data. Survival regression analyses for the risks of all-cause mortality and CVDs were performed. Quitters without body mass index (BMI) change (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.46–1.00) and quitters with BMI loss (aHR, 1.76; 95% CI, 1.13–2.73) showed significantly reduced and substantially the increased risk of all-cause mortality, respectively, compared with sustained smokers. Smoking reduction after diabetes diagnosis may have potential positive effects. However, definite benefits on the health outcomes were not identified in this study. Participants who started smoking after diabetes diagnosis had higher risks of all-cause mortality and CVDs than those who were never smokers or ex-smokers, although not statistically significant. In conclusion, smoking cessation after diabetes diagnosis could reduce the risks of all-cause mortality and cardiovascular events among patients with newly diagnosed diabetes when accompanied by proper weight management. Therefore, physicians should advice patients with newly diagnosed type 2 diabetes on the importance of smoking cessation in combination with long-term weight management to maximize the benefits of smoking cessation.

Background While smoking cessation reduces the risk of cardiovascular disease (CVD), quitting also increases fasting serum glucose (FSG) levels. The effect of post-cessation FSG elevation on cardiovascular disease is unknown. Methods The study population consisted of 128,208 men without type 2 diabetes from the Korean National Health Insurance System - Health Screening Cohort database. Change in smoking habits and FSG was determined by the difference in smoking status and FSG levels from the first (2002 and 2003) and second (2004 and 2005) health examinations. Quitters were divided into those with FSG elevation of greater than 10.0 mg/dL and those without FSG elevation. The study participants were followed-up for cardiovascular disease and CVD-related death from 2006 to 2013. Results Compared to continual smokers, quitters without FSG elevation had decreased risk of cardiovascular disease (hazard ratio, HR, 0.77, 95% confidence interval, CI, 0.69-0.86), while quitters with FSG elevation did not (HR 0.86, 95% CI 0.74-1.01). Similarly, quitters without FSG elevation had decreased risk of CVD-related death (HR 0.71, 95% CI 0.51-0.99) while quitters with FSG elevation did not (HR 0.86, 95 % CI 0.57-1.29). Both quitters with and without FSG elevation had decreased risk of myocardial infarction, while only quitters without FSG elevation had decreased risk of total stroke. Conclusions Post-cessation FSG elevation attenuated the beneficiary risk-reducing effects of quitting on cardiovascular disease and CVD-related mortality. Extra care should be given to controlling FSG levels among quitters in order to reduce the risk of cardiovascular disease and CVD-related death.

Smoking is a major risk factor of cardiovascular disease (CVD) such as stroke and ischemic heart disease. Prior studies have observed people continued smoking even after being diagnosed with CVD. However, population-level data regarding smoking behavior changes among people who are diagnosed with CVD are still lacking. From the National Health Insurance sample cohort database, we identified 1,700 patients diagnosed as having CVD between 2003 and 2012, and underwent the national health screening examination in the year before and after the CVD event. We found that 486 (28.6%) were smokers before the CVD event. Among them, 240 (49.4%) continued to smoke despite the diagnosis. We observed that a higher smoking amount and longer smoking duration before the diagnosis were associated with persistent smoking. Our finding that approximately 50% of smokers continue smoking even after CVD events supports the need for an assessment of patients' smoking statuses during follow-up after a CVD event and for health-care providers to offer the appropriate smoking cessation interventions to those who continue smoking.

The administration of antiplatelet drugs for months after a drug-eluting stent implantation is critical in decreasing the risk of complications, and premature discontinuation of antiplatelet therapy before the recommended period is the most important predictor for late complications. Therefore, we investigated the prevalence and associated factors of premature discontinuation of antiplatelet therapy in patients in Korea. This retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort data. Patients who were treated with dual-antiplatelet therapy (DAPT) were identified with medication prescription data. The Kaplan-Meier failure time plot was used to illustrate the cumulative probability of treatment discontinuation. Cox regression analysis was conducted to compare predictors of early discontinuation of DAPT. The characteristics of the early discontinuation group were not significantly different from the guideline concordance group, except for a higher prevalence of disability and a lower rate of chronic kidney disease. In a Cox regression model, the presence of hypertension was identified as a negative predictor of early discontinuation, and disability was not a statistically significant predictor. The prevalence of early discontinuation was 31.0% and seems to be significantly higher than those reported from prospective studies, which may more accurately reflect the real-world situation. In conclusion, physicians should make more effort to educate patients on the risk associated with premature discontinuation of antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent, and further studies investigating the reasons for nonadherence of DAPT are needed to improve DAPT compliance.

Purpose Weight gain often occurs after breast cancer diagnosis and significantly impacts the general health of cancer survivors. While the number of breast cancer survivors is increasing, few studies have reported data on weight change beyond 5 years post-diagnosis. We investigated weight change and associated factors in long-term survivors of breast cancer. Patients and Methods Medical records were reviewed on 1363 breast cancer patients and a total of 822 women who had survived beyond 5 years since diagnosis were included in the final analysis. The association between demographic, anthropometric, lifestyle, cancer related factors (including time since diagnosis, treatment modality, pathologic stage, and hormone receptor status), and weight-change over 5 years were examined. Results During an average 8.2 years of follow-up time, mean weight gain was 0.32kg (p = 0.017). 175 (21.3%) patients had gained more than 5% of their weight at diagnosis and their average gain was 5.55kg. Body mass index (BMI) at diagnosis, age at diagnosis, aromatase inhibitor (AI) use, heavy drinking, and type of surgery were associated with relative weight gain (≥5%) in univariate analysis (all p-values

We herein formulated and characterized an in situ-forming chitosan gel consisting of chitosan and glycerol phosphate (GP) disodium salt, and examined its use as an in vivo scaffold for rat bone marrow mesenchymal stem cells (rBMSCs). First, the phase transition behaviors of chitosan solutions formulated with and without GP were characterized as a function of temperature. Chitosan solutions containing20 wt % GP became a gel at 37 degrees C and maintained this form for 28 days in vitro and in vivo. Next, we examined whether the chitosan gel could act as a suitable biocompatible substrate for the attachment and proliferation of rBMSCs. Immunohistochemistry clearly demonstrated that rBMSCs survived well on the scaffold created by in situ-forming chitosan gel in rats. Injection of chitosan gel alone induced macrophage accumulation in the host tissue and at the edge of the chitosan, whereas injection of chitosan gel containing rBMSCs was associated with decreased macrophage accumulation, indicating immunosuppression by the transplanted rBMSCs. Our results collectively show for the first time that chitosan gel could serve as an in situ-forming gel scaffold for entrapped rBMSCs in vivo.

The objective of this study was to deliver the DNA/PEI nano-particles into rat bone marrow stem cells (rBMSCs). The formation of nano-particles from DNA and PEI was performed by the adding of the PEI solution to the DNA solution. Gel retardation assay showed the optimal N/P charge ratio where PEI completely binds DNA. The particle size of DNA/PEI complexes measured by dynamic light scattering (DLS) showed diameters of about 200–400 nm. These results indicated that DNA was sufficiently condensed by PEI to give DNA/PEI nano-particles and the optimal packing was achieved at N/P charge ratio of 4. From AFM image, PEI completely condensed DNA into round-shaped. The diameters of the DNA/PEI nano-particles observed by AFM were in good agreement with the results of the DLS. rBMSCs viability in the presence of DNA/PEI nano-particles was evaluated by means of the MTT assay. The DNA/PEI nano-particles were transfected into rBMSCs. After gene transfection, enhanced green fluorescence protein (EGFP) was monitored by flow cytometry. Naked DNA showed no EGFP expression, whereas delivery of DNA/PEI nano-particles to rBMSCs showed EGFP expression and resulted in 2–10% transfection.

Native small intestinal submucosa (SIS) sheet was prepared by removal of inside and outside layer of porcine jejunum. The acid treated SIS sheet was also prepared by dipping of native SIS sheet in acetic acid solution. The native or acid treated SIS sheets exhibited elastic and soft property on touch. The surface of native SIS sheet appears to be covered with thin and long collagen fibers entangled into networks. The fibers and fibrils at acid treated SIS sheet disappeared due to the acidic erosion of collagen fiber. The water uptake of acid treated SIS sheet (1300%) was higher than that of the native SIS sheet (500%). The cell morphology and proliferation of human bone marrow stem cells (hBMSCs) on SIS sheet was examined. The hBMSCs on the SIS sheet showed a flattened morphology, while cells in the polyglycolic acid (PGA) mesh showed rounded cell morphology. The cell viability on native or acid treated SIS sheet was higher than that of PGA mesh. The hBMSCs in both native and acid treated SIS sheet were grown at a similar rate. The number of adhering hBMSCs increased with incubation time. Thus, we could confirm that native or acid treated SIS sheet could act as a potential scaffold to enhance the hBMSCs proliferation by providing probably natural environments.

An innate immune response is often found at the site of biomaterial implantation. Since the effective use of biomaterials in vivo requires good biocompatibility and biofunctionality, it is vital that we assess and compare the inflammatory reactions provoked by various implanted biomaterials in vivo. In the present study, we assessed the host tissue response to poly(lactic-co-glycolic acid) (PLGA)- and small intestinal submucosa (SIS)-based scaffolds subcutaneously implanted in Fischer rats. Our results revealed that the PLGA-based scaffolds resulted in severe post-implantation inflammation, whereas the SIS-based scaffolds induced only a slight post-implantation inflammation and a PLGA/SIS-based copolymer yielded intermediate results.

An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. In this study, we investigated how human bone marrow stromal cells (hBMSCs) respond to scaffold substrates. We prepared wettable polymer surfaces by exposing polymer sheets to radio frequency plasma discharge, which gradually oxidizes the polymer surface, increasing the roughness and greatly reducing the hydrophobicity. We found that hBMSCs adhered better to highly hydrophilic and rough surfaces than to hydrophobic and smooth surfaces. In addition, the cells flattened extensively on hydrophilic surfaces. Further, c-fos gene expression increased in parallel with the degree of hydrophilicity, whereas the expression of the c-myc gene was higher on hydrophobic than on hydrophilic surfaces. Finally, p53 gene expression was higher on more hydrophobic or hydrophilic surfaces than on moderately hydrophobic or hydrophilic surfaces. These results indicate that the biological signals induced by cell adhesion depend on the wettability of the surface to which the cells attach.

In this study, we developed an injectable carrier for demineralized bone matrix (DBM) which consists of chitosan and glycerol phosphate (GP). The phase transition behaviors of chitosan and GP solution characterized as a function of temperature. The chitosan and GP solutions were shown to form a sol at room temperature, and the chitosan solution with 10-20 wt% concentrations were found to undergo sol-to-gel phase transitions as the temperature was increased. In situ gel forming implant in vivo was successfully fabricated by simple subcutaneous injection of chitosan and GP solutions with demineralized bone matrix (DBM). von Kossa images of the gel implant formed from solution with DBM revealed the presence of mineral deposits.

The goal of this study was to investigate release tendency of brain-derived neurotrophic factor (BDNF) from poly(L-lactide-co-glycolide) (PLGA) and small intestine submucosa (SIS) scaffold prepared by ice-leaching method. A porous scaffold consisting of PLGA and SIS as carrier of BDNF has been prepared in the presence of ice particle. SEM image of the PLGA/SIS scaffold showed an interconnected pore structure. The release behavior of BDNF loaded PLGA/SIS scaffold was examined for 4 weeks period at phosphate buffered saline (PBS, pH 7.4) at 37 oC. The sustained release of BDNF over 4 weeks was observed from the PLGA/SIS scaffold. These results indicate that the sustained release of BDNF from PLGA/SIS scaffold can be very useful for application in the tissue engineering.

Methoxy poly(ethylene glycol) (MPEG)-b-poly(ε-caprolactone) (PCL) diblock copolymer was synthesized by ring-opening of ε-caprolactone (ε-CL) in the presence of a monomer activator with the terminal alcohol of MPEG as an initiator. The temperature sensitive behavior of the prepared MPEG-PCL diblock copolymer solution was examined. The polymer solution formed translucent sol at the room temperature. As the temperature increased from room temperature, the sol became gel, indicating that the diblock copolymer solution at room temperature can form gel at body temperature. Brain-derived neurotrophic factor (BDNF) loaded MPEG-PCL diblock copolymer solution and Pluronic solution for comparison were prepared to examine the release behavior of BDNF. Pluronic gel exhibited nearly complete release of BDNF even at 2 day, while the release of BDNF in MPEG-PCL gel showed the prolonged release profile for 21 days. In this study, we confirmed that thermosensitive MPEG-PCL diblock copolymer in this work could utilize as a potential carrier of BDNF.

Background Cardiovascular disease (CVD) has become the most common cause of mortality and morbidity worldwide. Health screening is associated with higher outpatient visits for detection and treatment of CVD-related diseases (diabetes mellitus, hypertension, and dyslipidemia). We examined the association between health screening, health utilization, and economic status. Methods A sampled cohort database from the National Health Insurance Corporation was used. We included 306,206 participants, aged over 40 years, without CVD (myocardial infarction, stroke, and cerebral hemorrhage), CVD-related disease, cancer, and chronic renal disease. The follow-up period was from January 1, 2003 through December 31, 2005. Results Totally, 104,584 participants received at least one health screening in 2003–2004. The odds ratio of the health screening attendance rate for the five economic status categories was 1.27 (95% confidence interval [CI], 1.24 to 1.31), 1.05 (95% CI, 1.02 to 1.08), 1, 1.16 (95% CI, 1.13 to 1.19) and 1.50 (95% CI, 1.46 to 1.53), respectively. For economic status 1, 3, and 5, respectively, the diagnostic rate after health screening was as follows: diabetes mellitus: 5.94%, 5.36%, and 3.77%; hypertension: 32.75%, 30.16%, and 25.23%; and dyslipidemia: 13.43%, 12.69%, and 12.20%. The outpatient visit rate for attendees diagnosed with CVD-related disease was as follows for economic status 1, 3, and 5, respectively: diabetes mellitus: 37.69%, 37.30%, and 43.70%; hypertension: 34.44%, 30.09%, and 32.31%; and dyslipidemia: 18.83%, 20.35%, and 23.48%. Conclusion Thus, higher or lower economic status groups had a higher health screening attendance rate than the middle economic status group. The lower economic status group showed lower outpatient visits after screening, although it had a higher rate of CVD diagnosis.

This study investigated the effect of switching normal diet to vegetarian diet rich in vegetables and fruits for school foodservice and home meal on the nutritional status, bowel habit improvement and stress reduction of teachers and adolescents. A total of 40 research subjects (26 students, 14 teachers) from one middle school voluntarily participated in the research. Questionnaire surveys and blood analysis were conducted before and after a 12-week vegetarian diet period. The participants were asked on their dietary habit, bowel habit and stress measurement. After 12 weeks, reduction of BMI (kg/m2) in the students (p < 0.05) and reduction of TC (mg/dL) in both teachers and students (p < 0.05) were observed. Also reduction of LDL-C (mg/dL) was observed in the teachers (p < 0.05) whereas serum calcium and Vitamin B12 was increased in the students and teachers (p < 0.005). The teacher's stress level was reduced (p < 0.05) after the 12-week vegetarian diet. As for the changes in bowel habit, the number of the students and teachers classified as experiencing functional constipation was decreased respectively from 10 to 7, from 7 to 5. Based on the result, it is considered that the vegetarian diet rich in fruits and vegetables improved general health status of study subjects suggesting that such a dietary habit would substantially contribute to improving nutritional status and bowel habit.