Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption.

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study.

AIMS: Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers. METHODS AND RESULTS: Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group. CONCLUSION: Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers.

In this study of 19 425 participants, we investigated whether alcohol consumption reduction was associated with lower risk of incident atrial fibrillation (AF) in individuals with chronic heavy alcohol consumption. The absolute abstinence significantly reduced incident AF, but reducing alcohol consumption was not associated with a lower incident AF. The benefit of absolute abstinence for incidence of AF was significantly identified in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease.

Association Between Migraine and Ischemic Cardio-Cerebrovascular Disease (CCVD) and Effects of Triptans and Ergotamine on the Risk of Ischemic CCVD in Patients with Migraine in the Korean NHIS-HEALS Cohort.

BACKGROUND AND OBJECTIVES: Triptans and ergotamine are commonly used to treat migraine, a risk factor for ischemic stroke. This study aimed to investigate the association between migraine and ischemic cardio-cerebrovascular disease (CCVD). Further analyses were performed to examine whether symptom-relieving treatment of migraine with triptans and ergotamine reduces ischemic CCVD in migraineurs. METHODS: Participants from the Korean NHIS-HEALS cohort database were divided into patients reporting headache without migraine (HA), migraineurs who received at least one prescription for triptans or ergotamine (TE), and migraineurs who were prescribed neither triptans nor ergotamine (NTNE). Ischemic CCVDs comprised ischemic cerebrovascular diseases and cardiovascular diseases. Using cox proportional hazards regression models, primary and secondary analysis for risk of ischemic CCVDs was compared. RESULTS: Among 62,272 patients diagnosed with migraine or HA, men with migraine or HA numbered 14,747 and 8935, respectively, while the numbers of women were 27,836 and 10,754, respectively. The median follow-up was 6.65 years. The overall incidence rate of CCVDs was 4728/38,590 (12.25%) in females and 3158/23,682 (13.33%) in males. Compared with the HA group, the hazard ratios (HRs) (95% CIs) of the TE and NTNE groups for ischemic CCVDs were 1.18 (1.01-1.39) and 1.39 (1.28-1.50), respectively, in males, and 1.22 (1.09-1.37) and 1.53 (1.42-1.65), respectively, in females, after full adjustment for confounding variables. Compared with the NTNE group, the HRs (95% CIs) of the TE group for ischemic CCVDs were 0.86 (0.73-0.999) in males and 0.80 (0.72-0.88) in females. CONCLUSIONS: Migraine increased the risk of ischemic CCVDs in both sexes, and migraineurs treated with triptans and ergotamine were at lower risk of ischemic CCVDs than migraineurs who did not take those medications, especially in women.

Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort.

BACKGROUND: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor. RESEARCH DESIGN AND METHODS: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models. RESULTS: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20). CONCLUSIONS: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.

Recent trends in opioid prescriptions in Korea from 2002 to 2015 based on the Korean NHIS-NSC cohort.

OBJECTIVES: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. METHODS: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). RESULTS: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. CONCLUSIONS: Consumption of opioids greatly increased in Korea over the 14-year study period.

Statin Use and Incidence of Chronic Kidney Disease in Hypercholesterolemia Patients with Normal Renal Function.

INTRODUCTION: Dyslipidemia is a known risk factor for chronic kidney disease (CKD). The effects of statins on CKD have already been studied in patients with CKD; however, data on the general population are limited. This study aimed to determine the relationship between statin use and the incidence of CKD in patients with hypercholesterolemia having normal renal function. METHODS: A total of 7,856 participants aged 40-79 years at baseline (2009-2010) were included in the final analyses. The participants were divided into statin users (n = 4,168) and statin nonusers (n = 3,668), according to the statin usage. The Cox proportional hazard regression model was used to evaluate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CKD. RESULTS: The median follow-up duration was 5.8 years. A total of 543 cases of CKD (285 cases in males and 258 cases in females) occurred during the study period. The estimated cumulative incidence of CKD was significantly different between male statin nonusers and users (p < 0.001), while it was not statistically significant between female statin nonusers and users (p = 0.126). Compared with statin nonusers, the fully adjusted HRs (95% CIs) for CKD in statin users were 1.014 (0.773-1.330) in males and 1.117 (0.843-1.481) in females. CONCLUSION: Dyslipidemia is an obvious risk factor for CKD; however, statin use in patients with hypercholesterolemia having normal renal function does not demonstrate a clear relationship with the incidence of CKD.

Clinical Practice Guidelines for Managing Frailty in Community-Dwelling Korean Elderly Adults in Primary Care Settings.

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and "healthy aging" become more and more important, these guidelines are also expected to increase in clinical usefulness.

Beneficial Effects of a Specially Designed Home Meal Replacement on Cardiometabolic Parameters in Individuals with Obesity: Preliminary Results of a Randomized Controlled Clinical Trial.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention (p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

The ratio of triglycerides to high-density lipoprotein cholesterol is associated with the risk of chronic kidney disease in Korean men.

Dyslipidemia is nephrotoxic and can result in the development of chronic kidney disease (CKD). The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is well-correlated with insulin resistance and cardiovascular events. The aim of this study is to examine the association between the TG/HDL-C ratio and CKD in Korean adults. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening cohort. Seventy three thousand and fifty-two participants aged between 40 and 79 years old at baseline (2009-2010) were included in the final analyses. The study population was classified into three tertile groups (T1 , T2 , and T3 ) according to the TG/HDL-C ratio by sex. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were calculated using Cox proportional hazard regression models. The median follow-up duration was 5.9 years. Higher tertile groups of the TG/HDL-C ratio had lower estimated glomerular filtration rates in both sexes. The cumulative incidence of CKD of T1 , T2 , and T3 was 11.89%, 12.90%, and 12.91%, respectively, in men and 10.17%, 10.61%, and 14.87%, respectively, in women (all p values < 0.001). Compared with T1 of the TG/HDL-C ratio, the HRs (95% CIs) of T2 and T3 for CKD were 1.212 (1.118-1.315) and 1.183 (1.087-1.287), respectively, in men and 0.895 (0.806-0.994) and 1.038 (0.937-1.150), respectively, in women after being fully adjusted. Higher TG/HDL-C ratios were positively associated with CKD development in men, while middle levels of TG/HDL ratios reduced the CKD incidence in women.

Association between Second-hand Smoke Exposure and Urinary NNAL Level in Korean Adolescents.

BACKGROUND: The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers. Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents. METHODS: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels. RESULTS: The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58-4.53), 31.02 (9.46-101.74), and 1.89 (1.12-3.17) in boys; and 6.50 (3.22-13.11), 20.09 (7.08-57.04), and 3.94 (1.98-7.77) in girls, respectively. CONCLUSION: SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure. These findings remind us of the need to protect adolescents from SHS.

Metformin use in cancer survivors with diabetes reduces all-cause mortality, based on the Korean National Health Insurance Service between 2002 and 2015.

ABSTRACT: Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan-Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models.The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683-0.850) and 1.055 (0.966-1.152) in men and 0.805 (0.649-0.999), and 1.049 (0.873-1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839-1.071) and 0.530 (0.452-0.621) in men and 1.163 (0.921-1.469) and 0.439 (0.323-0.596) in women, respectively.Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality.Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates.

Increased Omega-3 Fatty Acid Intake Is Inversely Associated with Subclinical Inflammation in Healthy Elderly Men, Based on the 2015-2018 Korean National Health and Nutrition Examination Survey.

(1) Background: Subclinical inflammation as a risk factor of cardiovascular diseases was clinically measured using C-reactive protein (CRP) level. (2) Methods: This study was cross-sectionally designed based the 2015-2018 Korean National Health and Nutrition Examination Survey (KNHANES). The ratio of daily omega-3 fatty acids to energy intake (ω3FA ratio) was classified into four quartile groups (Q1, <0.3%; Q2, 0.3%-<0.6%; Q3, 0.6%-<1.0%; and Q4, ≥1.0% in both sexes). Logistic regression analysis was conducted to investigate the association between the ω3FA ratio and subclinical inflammation defined as CRP levels ≥3 mg/dL. (3) Results: The ω3FA ratio in subjects without and with subclinical inflammation was 0.8% and 0.7% in men (p-value = 0.001), and 0.8% and 0.8% in women (p-value = 0.491), respectively. The prevalence of subclinical inflammation in males decreased with increasing quartile of ω3FA ratio (12.9%, 9.6%, 7.4%, and 7.7%, p-value = 0.033), while female prevalence was not significant among quartile groups. Compared to Q1, odds ratios (95% confidence intervals) for subclinical inflammation of Q2, Q3, and Q4 were 0.740 (0.465-1.177), 0.564 (0.341-0.930), and 0.549 (0.317-0.953) in males, and 1.066 (0.653-1.741), 1.105 (0.600-1.718), and 0.934 (0.556-1.571) in females after full adjustment. (4) Conclusion: The ω3FA ratio is associated with subclinical inflammation in men.

Metformin usage and the risk of colorectal cancer: a national cohort study.

PURPOSE: This study aimed to investigate the association between metformin usage and the risk of colorectal cancer (CRC) using data from the Korean National Health Insurance Service-National Health Screening Cohort database. METHODS: Data from the NHIS-HEALS cohort between 2002 and 2015 were longitudinally analyzed. Subjects were divided into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and no DM group. CRC was defined using the ICD-10 code (C18.0-C20.0) at the time of admission. Cox proportional hazard regression models were adopted after stepwise adjustment for confounders to investigate the association between metformin usage and colorectal cancer risk. RESULTS: During the follow-up period, of the total 323,430 participants, 2341 (1.33%) of the 175,495 males and 1204 (0.81%) of the 147,935 females were newly diagnosed with CRC. The estimated cumulative incidence of CRC was significantly different among the three groups based on Kaplan-Meier's survival curve (p values < 0.05 in both sexes). Compared with metformin non-users, hazard ratios (95% CIs) of metformin users and the no DM group were 0.66 (0.51-0.85) and 0.72 (0.61-0.85) in males and 0.59 (0.37-0.92) and 0.93 (0.66-1.29) in females, respectively, after being fully adjusted. CONCLUSIONS: Metformin users with diabetes appear to have a significantly lower risk of CRC compared with metformin non-users.

Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort.

AIMS: The aim of this study is to investigate the association between metformin usage and dementia in an elderly Korean population. METHODS: Participants were divided into five groups: metformin non-users with diabetes mellitus (DM), metformin users with DM (low-, mid-, and high-users), and non-diabetic Individuals. Dementia was defined with primary diagnostic dementia codes according to the 10th edition of the International Classification of Diseases. To compare the incidence rate of dementia among the five groups, Kaplan-Meier estimates and log-rank test were employed. Also, to control the confounding factors, Cox proportional hazards regression models were fitted in a sequential adjustment. RESULTS: The median follow-up was 12.4 years. The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73-1.28), 0.77 (0.58-1.01), 0.48 (0.35-0.67), and 0.98 (0.84-1.15), respectively, in men, respectively, and 0.90 (0.65-0.98), 0.61 (0.50-0.76), 0.46 (0.36-0.58), and 0.92 (0.81-1.04), respectively, in women, after full adjustment of confounding variables. CONCLUSIONS: Metformin use in an elderly population with DM reduced dementia risk in a dose-response manner.

Metformin use reduced the overall risk of cancer in diabetic patients: A study based on the Korean NHIS-HEALS cohort.

BACKGROUND AND AIM: Several studies have reported the preventive effect of metformin on cancer development. This study aimed to investigate the relationship between use of metformin and risk of cancer in Koreans. METHODS AND RESULTS: This study was designed retrospectively using the National Health Insurance Service-National Health Screening Cohort conducted between 2002 and 2015. 40 to 69-year-old subjects who received a health screening examination from 2002 to 2003 were enrolled. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer were estimated in a multivariate Cox proportional regression analysis. A total of 323,430 subjects was enrolled (301,905 individuals without diabetes [No DM], 8643 diabetic patients with metformin treatment [metformin users], and 12,882 diabetic patients without metformin treatment [metformin non-users]). The median follow-up period was 12.7 years. Cumulative incidence of overall cancer was 7.9% (7.7, 10.3, and 11.1% in No DM, metformin users and non-users, respectively). Compared to metformin non-users, the fully adjusted HRs (95% CIs) of metformin users and No DM for overall cancer incidence were 0.73 (0.66-0.81) and 0.75 (0.64-0.88), respectively, in men and 0.83 (0.78-0.89) and 0.81 (0.72-0.92) in women. CONCLUSIONS: Diabetic patients receiving metformin treatment, and individuals without diabetes were at lower risk for cancer incidence than diabetic patients without metformin treatment.

Diabetes, Metformin, and Lung Cancer: Retrospective Study of the Korean NHIS-HEALS Database.

BACKGROUND: Metformin is the first option in managing type 2 diabetes mellitus (DM) and has pleotropic effects. We studied the incidence of lung cancer in patients who received metformin therapy. PATIENTS AND METHODS: This study was retrospectively designed and based on the Korean National Health Insurance Service-National Health Screening Cohort to determine whether metformin reduces lung cancer risk in the diabetic population. At baseline, all participants were 40 to 69 years old and were categorized into 3 groups: metformin nonrecipients with DM, metformin recipients with DM, and the nondiabetic group. RESULTS: A total of 336,168 individuals were included in the final analysis (314,291 nondiabetic individuals, 8806 metformin recipients, and 13,071 metformin nonrecipients). The study median follow-up period was 12.86 years. The estimated cumulative lung cancer incidence of metformin nonrecipients, metformin recipients, and the nondiabetic group was 1.80%, 1.97%, and 1.24% in men and 1.87%, 0.61%, and 0.41% in women, respectively (P < .05). Compared to metformin nonrecipients, the hazard ratios (95% confidence intervals) for lung cancer incidence of metformin recipients and the nondiabetic group were 1.287 (0.979-1.691) and 0.835 (0.684-1.019) in men and 0.664 (0.374-1.177) and 0.553 (0.359-0.890) in women, respectively. The hazard ratios (95% confidence intervals) were statistically significant in male ever smokers (0.784 [0.627-0.979]) and female nonsmokers (0.498 [0.320-0.774]) after stratification according to smoking status. CONCLUSION: Metformin therapy did not reduce lung cancer incidence in the diabetic population. However, individuals without DM were at a lower risk of lung cancer, especially in male ever smokers and female nonsmokers.

Regional variation in states' naloxone accessibility laws in association with opioid overdose death rates-Observational study (STROBE compliant).

Though overall death from opioid overdose are increasing in the United States, the death rate in some states and population groups is stabilizing or even decreasing. Several states have enacted a Naloxone Accessibility Laws to increase naloxone availability as an opioid antidote. The extent to which these laws permit layperson distribution and possession varies. The aim of this study is to investigate differences in provisions of Naloxone Accessibility Laws by states mainly in the Northeast and West regions, and the impact of naloxone availability on the rates of drug overdose deaths.This cross-sectional study was based on the National Vital Statistics System multiple cause-of-death mortality files. The average changes in drug overdose death rates between 2013 and 2017 in relevant states of the Northeast and West regions were compared according to availability of naloxone to laypersons.Seven states in the Northeast region and 10 states in the Western region allowed layperson distribution of naloxone. Layperson possession of naloxone was allowed in 3 states each in the Northeast and the Western regions. The average drug overdose death rates increased in many states in the both regions regardless of legalization of layperson naloxone distribution. The average death rates of 3 states that legalized layperson possession in the West region decreased (-0.33 per 100,000 person); however, in states in the West region that did not allow layperson possession and states in the Northeast region regardless of layperson possession increased between 2013 and 2017.The provision to legalize layperson possession of naloxone was associated with decreased average opioid overdose death rates in 3 states of the West region.

Inverse Association between Statin Use and Stomach Cancer Incidence in Individuals with Hypercholesterolemia, from the 2002-2015 NHIS-HEALS Data.

Purpose: To investigate the association between statin use and stomach cancer incidence in individuals with hypercholesterolemia. Materials and methods: To examine the cumulative effect of statins, we defined a statin user as one who used statins during 2002-2003 at baseline. Statin users were further classified into high and low users according to the medication possession rate. Statin non-users consisted of participants who had never used statins during the entire period of 2002-2015, despite having hypercholesterolemia (total cholesterol level ≥250 mg/dL at baseline). Ultimately, 17,737 statin users and 13,412 statin non-users were used in the analysis. We performed survival analyses, considering the diagnosis of stomach cancer as an event of interest. Results: Median follow-up duration was 12.9 years. The cumulative incidence rates of stomach cancer were lowest in high users (1.90% in men and 0.98% in women). Compared to non-users, hazard ratios (95% confidential intervals) for stomach cancer of low users and high users were 0.953 (0.755-1.203) and 0.526 (0.399-0.693) in men and 0.629 (0.457-0.865) and 0.370 (0.256-0.535) in women, respectively, after adjusting for possible confounders. Conclusions: We observed an inverse association between statin use and stomach cancer incidence in participants with hypercholesterolemia.

Statin use increased new-onset diabetes in hypercholesterolemic individuals: Data from the Korean National Health Insurance Service-National Health Screening Cohort database (NHIS-HEALS).

AIM: We investigated the association between statin use and new-onset diabetes (NODM) in Korean adults with hypercholesterolemia. METHODS: This study performed based on data from the National Health Insurance Service-National Health Screening Cohort for the years from 2002 to 2015. Statin users classified as high- or low- users according to medication possession ratio. Statin non-users consisted of hypercholesterolemic participants who never used statin over the entire follow-up period. 21,469 participants (10,880 statin users, 10,589 statin non-users) with a median follow-up period of 12.5 years were included. We estimated the NODM risk based on the survival analyses. In particular, to adjust for confounding effects, we considered Cox proportional hazards regression models over three stages. RESULTS: Compared to non-users, statin users had a significantly higher risk for NODM. The fully adjusted hazard ratios (aHRs) (95% confidential intervals [95% CIs]) of statin users for NODM were 1.43 (1.31-1.57) in men, and 1.86 (1.66-2.10) in women, respectively after adjusted confounding factors including age and lifestyle factors. Compared to high-users, aHRs (95% CIs) of low-users for NODM were 1.16 (1.03-1.30) and 1.28 (1.16-1.43) in men and women, respectively. CONCLUSIONS: In hypercholesterolemic patients, statin users have a higher risk of NODM than non-users.

Association between statin use and all-cause mortality in cancer survivors, based on the Korean health insurance service between 2002 and 2015.

BACKGROUND AND AIMS: Cancer is the number one cause of death in Korea. This study aimed to investigate if statin use in cancer survivors was inversely associated with all-cause mortality. METHODS AND RESULTS: Data from the 2002 to 2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) were used. The Kaplan-Meier estimator was used to estimate the survival function according to statin usage. Cox proportional hazards regression models were adopted after stepwise adjustment for potential confounders to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The median follow-up duration was 10.0 years. Statin users had a higher percentage of diabetes and hypertension in both sexes. Survival rates of statin users were higher than non-users (p-values <0.001 in men and 0.021 in women). Compared to non-users, the HRs (95% CIs) of statin users for all-cause mortality were 0.327 (0.194-0.553) in men and 0.287 (0.148-0.560) in women after adjustment for potential confounding factors. CONCLUSIONS: Statin users in cancer survivors had higher survival rate than non-users in both sexes.