Fracture risk in Parkinson's disease according to its severity and duration.

Fracture risk was elevated in Parkinson's disease (PD) patients compared with controls in this nationwide study. Among PD patients, the risk of fracture increased linearly with PD severity, whereas no difference in fracture risk was observed according to PD duration. INTRODUCTION: Parkinson's disease (PD) is reported to be associated with a high risk of fractures. Several studies found an association between severity and duration of PD and falls or bone mineral density, but those factors have not been considered in most previous research. The aim of this study was to determine the fracture risk in PD patients according to their disease severity and duration. METHODS: This population-based, retrospective cohort study used data from the Korean National Health Insurance Service database. The study population included 10,333 patients with prevalent PD and 6,501,464 comparison cohort. Fracture risks according to the prevalence, severity, and duration of PD were evaluated using Cox proportional hazard methods. RESULTS: Fracture risk was elevated in PD patients at all sites compared with controls (adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.44-1.56 for any fracture). When comparing fracture sites, hip fractures showed the largest risk increase in PD patients (aHR 2.16, 95% CI 1.95-2.38). Among PD patients, the risk of any fracture increased linearly with PD severity and was highest in patients with severe disease (aHR 1.65, 95% CI 1.53-1.79 compared with controls). Meanwhile, no significant association was observed between PD duration and fracture risk. CONCLUSIONS: The prevalence of PD was related to an increased risk of fractures in this nationwide study, and PD severity was linearly associated with fracture risk. PD prevalence and severity should be considered when evaluating the risk factors of fracture in clinical practice.

Association of Change in Alcohol Consumption With Risk of Ischemic Stroke.

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.

Associations Between Kidney Function, Proteinuria, and the Risk of Kidney Cancer: A Nationwide Cohort Study Involving 10 Million Participants.

Chronic kidney disease in its later stages is associated with increased risk of kidney cancer. We investigated whether chronic kidney disease at milder stages is associated with increased kidney cancer risk, using a retrospectively selected cohort of 9,809,317 adults in the Republic of Korea who participated in a nationwide health screening (2009-2016). We examined the impact of estimated glomerular filtration rate (eGFR), dipstick proteinuria, and interactive associations between the 2 factors on the risk of incident kidney cancer. During a median follow-up period of 7.3 years, 10,634 kidney cancers were identified. After adjustment for multiple confounders, participants with a reduced eGFR had an increased risk of kidney cancer (for eGFR <30 mL/minute/1.73 m2, adjusted hazard ratio = 1.18 (95% confidence interval: 1.01, 1.39); for eGFR 30-59 mL/minute/1.73 m2, adjusted hazard ratio = 1.22 (95% confidence interval: 1.14, 1.31)) compared with those with an eGFR of 60-89 mL/minute/1.73 m2. A dose-response relationship between the severity of proteinuria and incident kidney cancer was observed. Analyses of joint effects of eGFR and dipstick proteinuria showed that with the presence of proteinuria, kidney cancer incidence was markedly increased along with decreasing eGFR. Reduced eGFR and proteinuria are significantly associated with subsequent risk of kidney cancer, possibly in a synergistic manner.

Association between physical performance and incidence of end-stage renal disease in older adults: a national wide cohort study.

BACKGROUND: Physical frailty has previously been associated with adverse clinical outcomes in patients with end-stage renal disease (ESRD). This study aimed to determine whether impaired physical performance at baseline is associated with the incidence of ESRD, using a nationwide database. METHODS: The timed up-and-go (TUG) test was used to assess physical frailty in 1,552,781 66-year-old individuals, using health examination database records from the Korean National Health Insurance Service. As a primary endpoint, incident ESRD was defined operationally using healthcare claims data from the Korean Health Insurance Review and Assessment Service. RESULTS: Our results showed that baseline kidney function was significantly worse in individuals with TUG results of > 10 s compared to individuals with an intact TUG performance (≤10 s). Kaplan-Meier analysis showed a stepwise dose-response relationship between baseline physical performance and the incidence rate of ESRD (log-rank test P-value of < 0.001). An increasing ESRD incidence rate trend with poor physical performance remained significant after adjusting for characteristics such as baseline glomerular filtration rate and proteinuria. CONCLUSION: Poor baseline physical performance was associated with an increased risk of ESRD, suggesting possible interactions between systemic frailty and vascular aging processes.

Potentially modifiable blood triglyceride levels by the control of conventional risk factors.

BACKGROUNDS: Triglyceride (TG) is known to be regulated by multiple lifestyle factors rather than genetic factors. This cross-sectional and community-based study (Healthy Twin study in Korea) aimed to estimate the "modifiable TG level" by identifying non-genetic risk factors of TG. METHODS: Participants were recruited between 2006 and 2011 who fulfilled health examinations and detail surveys: 3079 Korean adults including 949 monozygotic twins and 222 dizygotic twins. In order to investigate conventional risk factors, a mixed model accounting for family as a random effect was performed. In addition, we conducted a co-twin control analysis for 452 monozygotic twin (MZ) pairs, to examine non-genetic risk factors and potentially modifiable serum triglyceride levels. RESULTS: After excluding patients on dyslipidemia or diabetes medication, 2672 individuals (1029 men, with mean age of 43.9; and 1643 women with mean age of 43.3; 949 MZ pairs, 222 dizygotic twin pairs, and 1501sibling pairs) were analyzed. Fasting blood sugar (FBS), lipid panel, height, weight, waist (WC) and hip circumference, body mass index (BMI), amount of dietary intake and amount of physical activity was examined after adjusting for age and sex. For conventional analysis, WC, fat %, and BMI were identified as significant factors influencing serum triglyceride levels. Examination of non-genetic factors from the Co-twin control study revealed BMI (beta coefficient 9.94 with C.I. 3.42 to 16.46) and amount of alcohol intake (beta coefficient 0.08 with C.I. 0.02 to 0.14) as significant factors. CONCLUSION: Our findings suggest that controlling body weight and alcohol intake might be effective to control TG; moderate weight control (BMI 1 reduction) and reducing alcohol consumption by 50 g/week (about two glassed of beer) might reduce TG level by 9.94 and 4.0 mg/dL.

Sugar-sweetened carbonated beverage consumption and coronary artery calcification in asymptomatic men and women.

BACKGROUND: Sugar-sweetened carbonated beverage consumption has been linked to obesity, metabolic syndrome, type 2 diabetes, and clinically manifest coronary heart disease, but its association with subclinical coronary heart disease remains unclear. We investigated the relationship between sugar-sweetened carbonated beverage consumption and coronary artery calcium (CAC) in a large study of asymptomatic men and women. METHODS: This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1). RESULTS: The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk. CONCLUSION: Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.

Cold exposure lowers energy expenditure at the cellular level.

Mitochondrial function is intimately involved in various metabolic processes and is therefore essential to maintain cell viability. Of particular importance is the fact that mitochondrial membrane potential (ΔΨm ) is coupled with oxidative phosphorylation to drive adenosine triphosphate (ATP) synthesis. We have examined the effects of cold temperature stress on ΔΨm and the role of cold temperature receptor expression on ΔΨm . Human bronchial endothelial cell line, BEAS-2B, and human embryonic kidney, HEK293, cell line were transfected with the gene for cold temperature responsive receptor protein TRPM8 or TRPA1, and exposed to cold temperature. ΔΨm was monitored using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazoyl carbocyanine iodide derivative (JC-10), a ΔΨm probe. While cold temperatures significantly increased ΔΨm and mitochondrial ATP levels in cells transfected with temperature responsive receptor TRPM8 or TRPA1, no change was noted in wild-type cells. Moreover, the change in ΔΨm and ATP level was a dynamic process. ΔΨm was raised to peak levels within 10 min of cold exposure, followed by a return to baseline levels at 30 min. Our findings suggest that cold temperature exposure increased mitochondrial ΔΨm via a mechanism involving cold temperature receptors.

Blood pressure and dementia risk by physical frailty in the elderly: a nationwide cohort study.

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.

Changes in smoking, alcohol consumption, and the risk of Parkinson's disease.

Objective: There have been no studies on the association between changes in smoking and alcohol consumption or combined changes in smoking and alcohol consumption frequencies and PD risk. To assess the influence of changes in smoking and alcohol consumption on the risk of Parkinson's disease (PD). Methods: National Health Insurance Service (NHIS) database between January 2009 to December 2011 was analyzed. A total of 3,931,741 patients were included. Study participants were followed up for the incidence of PD until December 2017. Results: Compared to the sustained non-smokers, sustained light smokers (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.75-0.85), sustained moderate smokers (aHR 0.54, 95% CI 0.47-0.61), and sustained heavy smokers (aHR 0.49, 95% CI 0.44-0.55) had a lower risk of PD. Compared to those who sustained non-drinking, sustained light drinkers (aHR 0.85 95% CI 0.89-0.91), sustained moderate drinkers (aHR 0.68, 95% CI 0.60-0.78), and sustained heavy drinkers (aHR 0.77, 95% CI 0.68-0.87) showed decreased risk of PD. Among non-drinkers, those who started drinking to a light level were at decreased risk of PD (aHR 0.84, 95% CI 0.77-0.91). Among non-smoking and non-drinking participants, those who initiated smoking only (aHR 0.78, 95% CI 0.70-0.86), drinking only (aHR 0.77, 95% CI 0.68-0.87), and both smoking and drinking (aHR 0.69, 95% CI 0.58-0.82) showed decreased risk of PD. Conclusion: Smoking is associated with decreased risk of PD with a dose-response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.

Streptonigrin inhibits ß-Catenin/Tcf signaling and shows cytotoxicity in ß-catenin-activated cells.

BACKGROUND: Activation of ß-catenin/T-cell factor (Tcf) signaling plays a role in human carcinogenesis. This suggests a possibility that the ß-catenin/Tcf signaling activated by the accumulation of ß-catenin in the nucleus is related to some type of human carcinogenesis. Therefore, if ß-catenin's transcriptional activity can be markedly down-regulated, tumor growth will be suppressed in ß-catenin activated types of cancer. METHODS: To investigate the activation or suppression of ß-catenin/Tcf transcription, we established a transiently transfected cell line with a constitutively active ß-catenin mutant gene whose product is not degraded. This cell line was also co-transfected with luciferase reporter gene constructs containing either an optimized (TOPflash) or mutant (FOPflash) Tcf-binding element. RESULTS: We identified the inhibitory effect of streptonigrin against ß-catenin/Tcf signaling in ß-catenin activated cells. Streptonigrin inhibited the transcriptional activity of ß-catenin/Tcf in SW480 cells and HEK293 cells transiently transfected with a constitutively active mutant ß-catenin gene. The growth inhibitory effect of streptonigrin was more evident in ß-catenin-activated cancer cells than in non-activated cancer cells. The electrophoresis mobility shift assay showed that the binding of Tcf complexes with their specific DNA-binding sites was suppressed by streptonigrin. CONCLUSION: Streptonigrin is a negative regulator of ß-catenin/Tcf signaling, and their inhibitory mechanism is related to the proliferation inhibitory effect on ß-catenin-activated cancer cells. GENERAL SIGNIFICANCE: This report reveals a molecular mechanism underlying the anti-tumor effect of streptonigrin from the perspective ß-catenin/Tcf signaling. Given its function in inhibiting ß-catenin/Tcf signaling, streptonigrin may be of interest as a leading compound for chemotherapeutic agent against ß-catenin-activated tumorigenesis.

Association between Kidney Function, Proteinuria and the Risk of Multiple Myeloma: A Population-Based Retrospective Cohort Study in South Korea.

PURPOSE: While renal impairment is one of the first clinical manifestations of multiple myeloma (MM), declined renal function may conversely be a risk factor for cancers including MM. In this study, we investigated the relationship between chronic kidney disease and MM at a population level. MATERIALS AND METHODS: A total of 9,809,376 adults who participated in a nationwide health screening program and had no MM, cancer or end-stage renal disease at baseline were investigated for incidence of MM. The impact of estimated glomerular filtration rate (eGFR) and random urine dipstick proteinuria, and interactive associations of the two factors on the MM incidence were evaluated. RESULTS: The general incidence of MM was 4.8 per 100,000 person-years (mean follow-up of 8.3 years). Participants with eGFR < 60 mL/min/1.73 m2 (5.8% of participants) had higher MM incidence than those with eGFR ≥ 60 mL/min/1.73 m2 (adjusted hazard ratio, 1.29; 95% confidence interval, 1.17 to 1.43). When eGFR was graded into five levels, there was a significant inverse dose-response relationship between eGFR level and MM incidence at the lower eGFR levels (reference: eGFR 60-89 mL/min/1.73 m2). A dose-response relationship was also found with degree of dipstick proteinuria and incidence of MM. CONCLUSION: Adults with decreased renal function indicated either by decreased eGFR or presence of proteinuria are at a higher risk of developing MM compared to those without, and there is a dose-response relationship between the severity of renal impairment and MM incidence.

Smoking, Alcohol Consumption, and the Risk of Thyroid Cancer: A Population-Based Korean Cohort Study of 10 Million People.

Background: It is unclear if cigarette smoking and alcohol consumption are associated with thyroid cancer risk. Our aim was to explore for any associations between cigarette smoking and alcohol consumption with thyroid cancer, after adjusting for potential confounders. Methods: Using data from the Korean National Health Insurance database, we retrospectively identified individuals aged ≥20 years who participated in the 2009 health screening program and were followed until 2017. We estimated the adjusted hazard ratio (aHR) for the risk of thyroid cancer using a Cox proportional hazard model, adjusted for age, sex, regular exercise, monthly income, body mass index, diabetes mellitus, and dyslipidemia. Results: During a mean follow-up period of 8.33 ± 0.57 years, of 9,699,104 participants, 89,527 (0.9%) were diagnosed with thyroid cancer. Compared with those who never smoked, current smokers had a lower risk of thyroid cancer (aHR: 0.74, 95% confidence interval [CI]: 0.72-0.76), while ex-smokers did not (aHR: 0.98, 95% CI: 0.96-1.01). There was no significant dose-response relationship with regard to daily amount smoked, duration of smoking, or pack-years. A reduced risk of thyroid cancer was observed in subjects who reported the following categories of alcohol intake (compared with none): mild (aHR: 0.92, 95% CI: 0.90-0.93), moderate (aHR: 0.86, 95% CI: 0.84-0.89), and heavy (aHR: 0.86, 95% CI: 0.82-0.89). Inverse associations with thyroid cancer risk were observed regarding the number of drinking episodes per week and the number of drinks per occasion. A submultiplicative effect of smoking and alcohol consumption was observed (p-interaction <0.001). Conclusions: We observed that thyroid cancer risk was inversely associated with smoking and alcohol consumption, with a significant interaction between these variables.

Impact of Frailty on the Relationship between Blood Pressure and Cardiovascular Diseases and Mortality in Young-Old Adults.

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 (<10, 10−14, or ≥15 s). A similar pattern of increased risks was found in those who took antihypertensive drugs and who did not, however they were more pronounced in those who did not. The findings support the need to achieve the same BP target in young-old adults with or without frailty to lower the risk of MI, stroke, and mortality.

Association Between Changes in Alcohol Consumption and Cancer Risk.

Importance: Although numerous studies have shown an association between alcohol consumption and cancer, how changes in drinking behavior increase or decrease the incidence of cancer is not well understood. Objective: To investigate the association between the reduction, cessation, or increase of alcohol consumption and the development of alcohol-related cancers and all cancers. Design, Setting, and Participants: This population-based cohort study analyzed adult beneficiaries in the Korean National Health Insurance Service. Participants (aged ≥40 years) included those who underwent a national health screening in both 2009 and 2011 and had available data on their drinking status. Data were analyzed from April 16 to July 6, 2020. Exposures: Alcohol consumption level, which was self-reported by participants in health screening questionnaires, was categorized into none (0 g/d), mild (<15 g/d), moderate (15-29.9 g/d), and heavy (≥30 g/d) drinking. Based on changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, sustainer, increaser, quitter, and reducer. Main Outcomes and Measures: The primary outcome was newly diagnosed alcohol-related cancers (including cancers of the head and neck, esophagus, colorectum, liver, larynx, and female breast), and the secondary outcome was all newly diagnosed cancers (except for thyroid cancer). Results: Among the 4 513 746 participants (mean [SD] age, 53.6 [9.6] years; 2 324 172 [51.5%] men), the incidence rate of cancer was 7.7 per 1000 person-years during a median (IQR) follow-up of 6.4 (6.1-6.6) years. Compared with the sustainer groups at each drinking level, the increaser groups had a higher risk of alcohol-related cancers and all cancers. The increased alcohol-related cancer incidence was associated with dose; those who changed from nondrinking to mild (adjusted hazard ratio [aHR], 1.03; 95% CI, 1.00-1.06), moderate (aHR, 1.10; 95% CI, 1.02-1.18), or heavy (aHR, 1.34; 95% CI, 1.23-1.45) drinking levels had an associated higher risk than those who did not drink. Those with mild drinking levels who quit drinking had a lower risk of alcohol-related cancer (aHR, 0.96; 95% CI, 0.92-0.99) than those who sustained their drinking levels. Those with moderate (aHR, 1.07; 95% CI, 1.03-1.12) or heavy (aHR, 1.07; 95% CI, 1.02-1.12) drinking levels who quit drinking had a higher all cancer incidence than those who sustained their levels, but when quitting was sustained, this increase in risk disappeared. Compared with sustained heavy drinking, reduced heavy drinking levels to moderate levels (alcohol-related cancer: aHR, 0.91 [95% CI, 0.86-0.97]; all cancers: aHR, 0.96 [95% CI, 0.92-0.99]) or mild levels (alcohol-related cancer: aHR, 0.92 [95% CI, 0.86-0.98]; all cancers: aHR, 0.92 [95% CI, 0.89-0.96]) were associated with decreased cancer risk. Conclusions and Relevance: Results of this study showed that increased alcohol consumption was associated with higher risks for alcohol-related and all cancers, whereas sustained quitting and reduced drinking were associated with lower risks of alcohol-related and all cancers. Alcohol cessation and reduction should be reinforced for the prevention of cancer.

Population-wide impacts of aspirin, statins, and metformin use on prostate cancer incidence and mortality.

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.

Changes in Smoking, Alcohol Consumption, and the Risk of Thyroid Cancer: A Population-Based Korean Cohort Study.

To elucidate potential causality between smoking and alcohol intake on thyroid cancer incidence, we explored the effect of changes in smoking and alcohol consumption habits. From the Korean National Health Insurance database, we identified 4,430,070 individuals who participated in the national health screening program in 2009 and 2011. The level of smoking and alcohol consumption was measured twice, once in 2009 and again in 2011. The risk of thyroid cancer according to their changes was estimated using the Cox proportional hazard model. During the mean follow-up period of 6.32 ± 0.72 years, 29,447 individuals were diagnosed with thyroid cancer. Compared to those who sustained not smoking, non-smokers who initiated smoking to light (adjusted hazard ratio (aHR) 0.96, 95% confidence interval (CI) 0.81-1.15), moderate (aHR 0.90, 95% CI 0.78-1.04), and heavy level (aHR 0.81, 95% CI 0.69-0.96) had a decreased risk of thyroid cancer. Heavy smokers who quit smoking had an increased risk of thyroid cancer (aHR 1.23, 95% CI 1.06-1.42) compared to those who sustained heavy smoking. Change in drinking status was not significantly associated with thyroid cancer risk compared to drinking at the same level, although a non-significant trend of increased risk was noted in quitters. Participants who initiated both smoking and drinking (HR 0.80, 95% CI 0.69-0.93) had a lower risk of thyroid cancer compared with those who continued not to smoke and drink. Our findings provide further evidence that smoking, and possibly alcohol consumption, would have true protective effects on the development of thyroid cancer.

Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study.

OBJECTIVE: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. RESEARCH DESIGN AND METHODS: We enrolled 930,055 postmenopausal women aged 40-74 years who participated in a biennial National Health Screening Program in 2009-2010 and 2011-2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. RESULTS: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06-1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26-1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04-1.19) in the transition to MetS group, 1.05 (0.96-1.14) in the transition to non-MetS group, and 1.18 (1.12-1.25) in the sustained MetS group. CONCLUSIONS: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

The Timed Up and Go test and the ageing heart: Findings from a national health screening of 1,084,875 community-dwelling older adults.

AIM: This study aimed to evaluate the relationship between Timed Up and Go test performance and the incidence of older adult heart diseases and mortality. METHODS: This was a retrospective cohort study of 1,084,875 older adults who participated in a national health screening program between 2009-2014 (all aged 66 years old). Participants free of myocardial infarction, congestive heart failure, and atrial fibrillation at baseline were included and were divided into Group 1 (<10 s), Group 2 (10-20 s) and Group 3 (≥20 s) using the Timed Up and Go test scores. The endpoints were incident myocardial infarction, congestive heart failure, atrial fibrillation, and all-cause mortality. RESULTS: During mean follow-up of 3.6 years (maximum 8.0 years), 8885 myocardial infarctions, 10,617 congestive heart failures, 15,322 atrial fibrillations, and 22,189 deaths occurred. Compared with participants in Group 1, Group 2 and Group 3 participants had higher incidences of myocardial infarction (Group 3: adjusted hazard ratio = 1.40, 95% confidence interval = 1.11-1.77), congestive heart failure (Group 3: adjusted hazard ratio = 1.59, 95% confidence interval = 1.31-1.94) and total mortality (Group 3: adjusted hazard ratio=1.93, 95% confidence interval = 1.69-2.20). The additional risks remained after adjusting for multiple conventional risk factors. For atrial fibrillation, a linear trend of increased risk was observed with slower Timed Up and Go test speed, but was statistically marginal (Group 3: adjusted hazard ratio=1.17, 95% confidence interval=0.96-1.44). CONCLUSION: Slower Timed Up and Go test speed is associated with increased risk of developing myocardial infarction, congestive heart failure, and mortality in older adults.

Smoking, alcohol consumption, and the risk of thyroid cancer: a population-based Korean cohort study of 10 million people.

BACKGROUND: The association between smoking, alcohol consumption, and thyroid cancer has been evaluated in observational studies, yet the results remain controversial. In the present investigation, we analyzed a longitudinal cohort study with representative data to determine the association between smoking, alcohol consumption, and thyroid cancer risk, allowing for risk modification due to age and sex. METHODS: From the Korean National Health Insurance database, .subjects aged ≥20 who participated in health screening program in 2009 were identified and followed-up till 2017. The adjusted hazard ratio (aHR) for the risk of thyroid cancer was estimated by Cox proportional hazard model Results: During a mean follow-up period of 8.33 ± 0.57 years, out of 9,699,104 participants, 89,527 (0.9%) were diagnosed with thyroid cancer. In comparison with those who never smoked, current smokers [aHR: 0.74, 95% confidence interval (CI): 0.72-0.76)] had a decreased risk of thyroid cancer even though ex-smokers (aHR: 0.98, 95% CI: 0.96-1.01) did not. There was no dose-response relationship when the participants were examined with regard to the daily amount of smoking, duration of smoking, and pack-years. A decrease in the risk of thyroid cancer was observed according to both the number of drinking episodes per week and the number of glasses per once drinking (HR: 0.81, 95% CI: 0.74-0.88 for drinks consumed 7 times/week and HR: 0.87, 95% CI: 0.82-0.92 for ≥ 15 glasses once drinking vs. nondrinkers). A certain degree of alcohol consumption seemed to provoke a decreased risk of thyroid cancer as compared to those who did not drink (HR: 0.85, 95% CI: 0.81-0.89 for ≥ 40 g/week). The interaction of smoking and alcohol consumption was found to be significant (p-interaction < 0.0001), and sub-multiplicative. CONCLUSIONS: We found that the risk of thyroid cancer incidence was inversely associated with smoking and alcohol consumption. A sub-multiplicative interaction between smoking and alcohol intake on the risk of thyroid cancer was found. Further studies are needed to elucidate exactly how smoking and alcohol are related to the pathogenesis and the modification their effects may have on thyroid cancer development.

Timed up-and-go test is a useful predictor of fracture incidence.

PURPOSE: The timed up-and-go (TUG) test is a validated screening tool to assess fall risk. This study evaluated the association between the TUG test and future fractures, which are a tangible clinical complication of falling. METHODS: We included 1,070,320 participants who participated in the National Screening Program for Transitional Ages for Koreans aged 66 years old from 2009 to 2014. Among them, 355,753 women underwent dual-energy X-ray absorptiometry. TUG times were classified as <10 s or ≥10 s. The incidence of fractures, including vertebral, hip, and other sites, was determined using claims data from the National Health Information database. RESULTS: During the mean follow-up period of 4.4 ±â€¯1.8 years, participants with slow TUG times had a significantly increased risk of fractures compared with those who had normal TUG times: any fractures (adjusted hazard ratio [aHR] = 1.08, 95% confidence interval [CI] = 1.06-1.10), vertebral fracture (aHR = 1.14, 95% CI = 1.11-1.16), hip fracture (aHR = 1.21, 95% CI = 1.13-1.29), and other fractures (upper arm, forearm, and lower leg; aHR = 1.02, 95% CI = 1.00-1.05). Among women with bone mineral density (BMD) results, slow TUG performance was associated with an increased risk of fracture independent of BMD. CONCLUSIONS: The TUG test, as an indicator of physical performance, can provide information about future fracture risk above that provided by BMD. Conducting the TUG test to assess fracture risk should be considered to improve fracture risk assessment and propose interventions to improve physical performance, thereby reducing fracture risk.