Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

Association between urinary iodine concentration and the risk of papillary thyroid cancer by sex and age: a case-control study.

Previous studies on dietary iodine intake and the risk of papillary thyroid cancer (PTC) have demonstrated inconsistent results. We aimed to evaluate the association between urinary iodine concentration (UIC), a surrogate biomarker for dietary iodine intake, and the risk of thyroid cancer stratified by sex and age in an iodine-sufficient area. A hospital-based case-control study was conducted in Seoul, South Korea. A total of 492 cases of newly diagnosed PTC and 595 controls were included. Compared with the lowest quartile of creatine-adjusted UIC (< 159.3 µg/gCr), the highest quartile (≥ 1037.3 µg/gCr) showed an increased risk of PTC (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.04-2.13), especially in those who were < 45 years old (ptrend = 0.01) compared with those who were ≥ 45 years old (ptrend = 0.48). For those who were < 45 years old, a positive association between creatinine-adjusted UIC and the risk of PTC was observed in both men (q4 vs. q1, OR 4.27, 95% CI 1.14-18.08) and women (OR 1.97, 95% CI 1.04-3.78). For those who were ≥ 45 years old, no association was found in any sex. Creatinine-adjusted UIC was positively associated with the risk of PTC, especially in those who were younger than 45 years for both men and women.

Early psychiatric referral after attempted suicide helps prevent suicide reattempts: A longitudinal national cohort study in South Korea.

Introduction: Although people who attempted suicide tend to repeat suicide attempts, there is a lack of evidence on the association between psychiatric service factors and suicide reattempt among them. Methods: We used a nationwide, population-based medical record database of South Korea to investigate the use of psychiatric services before and after the index suicide attempt and the association between psychiatric service factors after the index suicide attempt with the risk of suicide reattempt. Results: Among 5,874 people who had attempted suicide, the all-cause mortality within 3 months after the suicide attempt was 11.6%. Among all subjects who attempted suicide, 30.6% of them had used psychiatric services within 6 months before the suicide attempt; 43.7% of them had used psychiatric services within 3 months after the suicide attempt. Among individuals who had visited clinics following attempted suicide, the cumulative incidence of suicide reattempt over a mean follow-up period of 5.1 years was 3.4%. About half of suicide reattempts occurred within 1 year after the index suicide attempt. Referral to psychiatric services within 7 days was associated with a decreased risk of suicide reattempt (adjusted hazard ratio, 0.51; 95% confidence intervals, 0.29-0.89). Conclusion: An early psychiatric referral within 1 week after a suicide attempt was associated with a decreased risk of suicide reattempt.

Association of Marital Status With Total and Cause-Specific Mortality in Asia.

Importance: Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. Objective: To examine the association of marital status with total and cause-specific mortality. Design, Setting, and Participants: This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. Exposures: Marital status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 623 140 participants (326 397 women [52.4%] and 296 743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123 264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years. Conclusions and Relevance: This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.

Association between body mass index and oesophageal cancer mortality: a pooled analysis of prospective cohort studies with >800 000 individuals in the Asia Cohort Consortium.

BACKGROUND: The association between body mass index (BMI) and oesophageal cancer (OC) has been consistently negative among Asians, whereas different associations based on histological OC subtypes have been observed in Europeans and North Americans. We examined the association between BMI and OC mortality in the Asia Cohort Consortium. METHODS: We performed a pooled analysis to evaluate the association between BMI and OC mortality among 842 630 Asians from 18 cohort studies. Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A wide J-shaped association between BMI and overall OC mortality was observed. The OC mortality risk was increased for underweight (BMI <18.5 kg/m2: HR = 2.20, 95% CI 1.80-2.70) and extreme obesity (BMI ≥35 kg/m2: HR = 4.38, 95% CI 2.25-8.52) relative to the reference BMI (23-25 kg/m2). This association pattern was confirmed by several alternative analyses based on OC incidence and meta-analysis. A similar wide J-shaped association was observed in oesophageal squamous cell carcinoma (OSCC). Smoking and alcohol synergistically increased the OC mortality risk in underweight participants (HR = 6.96, 95% CI 4.54-10.67) relative to that in reference BMI participants not exposed to smoking and alcohol. CONCLUSION: Extreme obesity and being underweight were associated with an OC mortality risk among Asians. OC mortality and BMI formed a wide J-shaped association mirrored by OSCC mortality. Although the effect of BMI on OSCC and oesophageal adenocarcinoma mortality can be different in Asians, further research based on a large case-control study is recommended.

Associations of fasting glucose and glycated hemoglobin with vitamin D levels according to diabetes mellitus status in Korean adults.

OBJECTIVES: According to previous studies, vitamin D deficiency might increase the risk of type 2 diabetes mellitus (DM). However, few studies have examined whether vitamin D continues to affect glucose control after DM diagnosis. Therefore, we examined the association between vitamin D and glucose levels in individuals with and without DM. METHODS: We analyzed data for 32,943 adults aged 19 years and older from the 2008 to 2014 Korea National Health and Nutrition Examination Survey. Patients were classified into 3 groups according to the 25-hydroxyvitamin D concentration. DM was defined as a fasting glucose level ≥126 mg/dL, current use of DM medications or insulin injections, or a self-reported diagnosis of DM by a doctor. RESULTS: In male DM patients, the hemoglobin A1c (HbA1c) level increased significantly as vitamin D levels became severely deficient. In male and postmenopausal female with abnormal HbA1c, those with severe vitamin D deficiency had significantly higher HbA1c levels (p for trend=0.004 and 0.022 for male and postmenopausal female, respectively). Significant differences were found between participants with normal and abnormal HbA1c levels in both male and female. However, regardless of sex or menopausal status, there was no significant association between vitamin D and fasting glucose in any of the fasting glucose subgroups. CONCLUSIONS: Male and female with abnormal HbA1c levels showed markedly elevated blood glucose when they also had vitamin D deficiency. A more distinct difference was observed in the HbA1c subgroups than in the fasting glucose subgroups.

Comparing warning signs of suicide between suicide decedents with depression and those non-diagnosed psychiatric disorders.

OBJECTIVE: Early recognition of a high-risk group impending suicide is important. We aimed to compare warning signs depending on the nature of the psychiatric disorder and whether it was a documented diagnosis. METHODS: Data of suicide decedents were collected from police records from 2013 to 2017. We evaluate psychiatric symptoms and warning signs in three aspects (language, behavior, and affect) using the Korea-Psychological Autopsy Checklist for Police Records (K-PAC-PR). RESULTS: A total of 13,265 suicide decedents were recruited for this study. Of them, 66.9% of females and 46.7% of males diagnosed psychiatric disorders, with depressive disorder being the most common one. Warning signs were observed in 93.0% of suicide decedents. They were observed more in those who were diagnosed with psychiatric disorders, especially in those with a depressive disorder. "Talking about dying or suicide" was the most common warning sign in all groups, and "apathetic behavior" was the most related warning sign for depressive disorder. Especially for "talking about dying or suicide," the proportion of observed "within a week" was high, making it valuable as a warning sign. CONCLUSION: Warning signs were commonly found in suicide decedents regardless of gender. They were more common among the decedents diagnosed with psychiatric disorders, especially among those with a depressive disorder.

Psychological autopsy study comparing suicide decedents with and without a history of suicide attempts in a nationwide sample of South Korea.

The majority of suicide decedents die on their initial attempt. To bring attention to suicide decedents without a suicide attempt history, the current study explored their demographic, clinical, and suicide-related characteristics. The data were derived from the Korea National Investigation of Suicide Victims Study, which assessed all suicide cases from 2013 to 2017 recorded in police investigation reports. We compared suicide decedents with and without a history of nonfatal attempts using the Korea Psychological Autopsy Checklist for Police Records (K-PAC). Out of 5228 cases included in our study, 3147 (60.2%) died on their first suicide attempt. Demographically, those who were male, older than 65, employed, and married/widowed were more likely to die on their initial attempt. Clinically, those who died on their initial attempt were more likely to have never been diagnosed with psychiatric disorders, whereas those who died on a repeated attempt were more likely to have been diagnosed with mood disorders. In terms of suicide-related factors, experiencing relationship problems and complaining about physical discomfort were associated with dying on an initial attempt. Depressed affect, self-harming behaviors, and talking about suicide or death were associated with repeated attempts.

Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Predictive Factors Associated With Methods of Suicide: The Korean National Investigations of Suicide Victims (The KNIGHTS Study).

Background: Because the suicide mortality depends on the lethality of suicide methods, the identification and prediction of suicide methods are important for suicide prevention. Methods: Examination data of suicide decedents were collected based on police reports. Suicide decedents were divided into groups according to the suicide methods (hanging, gas poisoning, pesticide poisoning, jumping, drug poisoning, and drowning) they used. Predictive factors for each suicide method in comparison to other suicide methods were identified. Results: Among 23,647 subjects, hanging was the most common method of suicide. Regarding gas poisoning, the history of previous suicide attempt was a risk factor and being age of 65 or older was a protective factor. Being age of 65 or older showed a highly strong association with suicide by pesticide poisoning. Being age of 18 or younger and the presence of schizophrenia were associated with jumping. A history of psychiatric outpatient treatment was a risk factor for drug poisoning. Regarding suicide by drowning, schizophrenia was a risk factor, while being age of 65 or older was a protective factor. Limitations: Only eight out of a total of 17 regions in South Korea were examined and included in the data of this study. Also, the methods of suicide were defined as one method that directly caused the death, which could undermine other less fatal methods used. Conclusions: There were differences in predictive factors according to the method of suicide. Predicting the method of suicide in people at high risk for suicide stands to be an important strategy for suicide prevention in clinical settings.

Cost-Effectiveness of a Multi-Disciplinary Emergency Consultation System for Suicide Attempts by Drug Overdose in Young People and Adult Populations.

The purpose of this study was to compare the characteristics of suicide attempts by drug overdose between young people and adults, and evaluate the cost-effectiveness of a multi-disciplinary emergency consultation system (MECS) for suicide attempters with drug overdose. It was verified by comparing and analyzing data from June 1, 2017 to May 31, 2018 (before the MECS was implemented; pre-MECS), and from June 1, 2018 to May 31, 2019 (after the MECS was implemented; post-MECS). The data were retrospectively reviewed for a total of 251 such patients with suicide attempts by drug overdose who visited the emergency room of a university hospital in Seoul during the period. The young people group were shown to be more likely to use painkillers and less likely to use psychoactive drugs for a suicide attempt (p < 0.01), had more unplanned attempts than planned ones (p < 0.01), and had lower levels of intentionality for suicide (p = 0.04) and of suicide lethality (p = 0.02), compared to the adult group. We defined suicide attempts as being "serious" when there was both high intentionality and lethality. On this basis, the young people group had less serious suicide attempts, compared to the adult group (p = 0.02). Young people in the post-MECS group had lower intensive care unit (ICU) costs (p = 0.01) and lower costs in the 6-months after the suicide attempt (p = 0.02) compared to those in the pre-MECS group. Young people, both with serious (p < 0.01) and non-serious attempts (p < 0.01) in the post-MECS group had lower ICU costs compared to those in the pre-MECS group. Adults with non-serious attempts in the post-MECS group had lower ICU costs (p < 0.01) compared to those in the pre-MECS group. Therefore, it can be concluded that fast and precise cooperation from the multidisciplinary departments for patients who attempted suicide by drug overdose reduced unnecessary ICU treatment and costs, especially in young attempters and those with lower levels of intentionality and lethality.

Increased risk of depression before and after unilateral or bilateral oophorectomy: A self-controlled case series study using a nationwide cohort in South Korea.

BACKGROUND: There is insufficient evidence of the association between oophorectomy and depression. METHODS: A nationwide medical records database of South Korea was used to investigate incidence rate ratios (IRRs) of major depressive disorder before and after oophorectomy (n = 36,284) using a self-controlled case series design. Outcomes before and after hysterectomy (n = 25,415) were identified to compare with those around oophorectomy. RESULTS: In all oophorectomy and hysterectomy groups, the risk of depression was increased before and after surgery, peaking immediately before or after the operation, with no significant difference in the pattern of the results according to type of surgery. In the bilateral oophorectomy group, the IRR was increased between 2-3 months before the surgery, peaking immediately before surgery at 1.39 (95% CI: 1.30-1.49, p < .0001), and remained heightened for one-year postexposure. Subgroup analyses performed according to ovarian cancer, age group, and hormone replacement therapy produced results similar to those of the main outcome. LIMITATIONS: Because we used claims data, the detailed clinical information related to oophorectomy is lacking. There is possibility that time-varying confounder besides age and season might have affected the results CONCLUSIONS: The risk of depression increased before and after oophorectomy. The increase in risk of depression started before oophorectomy and peaked immediately before or after the operation, but no significant differences between unilateral and bilateral surgery and cancer and noncancer or among age groups were noted.

Risk of Suicide Attempt after Thyroidectomy: A Nationwide Population Study in South Korea.

OBJECTIVE: To investigate the association between thyroidectomy and suicide attempt. METHODS: A nationwide population-based electronic medical records database of South Korea between January 1, 2009 and June 30, 2016 was used to investigate incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts before and after thyroidectomy using a self-controlled case series design. RESULTS: In 2,986 patients who attempted suicide or probable suicide, the IRRs of suicidal behaviors during risk periods one year before and after thyroidectomy were investigated. Generally, after thyroidectomy, there was no increase in IRR compared to the non-risk period. When data were analyzed according to thyroidectomy type, after partial thyroidectomy, IRR increased up to 1.43 (95% CI: 1.03-1.98, p=0.032) in the days 91-181 period. In the subgroup with major depressive disorder (MDD), the IRR increased up to 1.74 (95% CI: 1.21-2.51, p=0.003) before thyroidectomy, and increased up to 1.67 (95% CI: 1.16-2.41, p=0.006) after thyroidectomy. CONCLUSION: Although the general risk of suicide attempt was not increased after thyroidectomy, patients with MDD showed increased risk of suicide attempt before and after thyroidectomy. These results suggest that suicidality should be evaluated when depressive symptoms are present in patients who have undergone thyroidectomy.

Quantifying the association of low-intensity and late initiation of tobacco smoking with total and cause-specific mortality in Asia.

BACKGROUND: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts. METHODS: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis. FINDINGS: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence. CONCLUSIONS: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice.

Predictive factors of diagnostic conversion from major depressive disorder to bipolar disorder in young adults ages 19-34: A nationwide population study in South Korea.

BACKGROUND: Predicting patients who convert to bipolar disorder is important for deciding appropriate treatment for young adults with major depressive disorder (MDD). We focused on the predictive factors of bipolar conversion in a large population of young adults. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment service of South was used to investigate adjusted hazard ratio (HR) of each potential predictor of the bipolar converter group compared to the non-converter group using Cox regression analysis including age of onset, medication use, clinical features, comorbid disorders, admission, self-harm, and negative life events in childhood. RESULTS: Among 291,721 subjects who were initially diagnosed with MDD in young adults, 12,376 subjects experienced diagnostic conversion to bipolar disorder. The cumulative incidence was 6.46% during the average 3.26 years of follow-up. Among the predictive factors during diagnosis of MDD, antipsychotic use (HR 3.12, 95%CI, 2.99-3.26, p < 0.0001) and mood stabilizers (HR 2.45, 95%CI, 2.35-2.55, p < 0.0001) showed the strongest association with diagnostic conversion to bipolar disorder. In addition, female sex, younger age of onset, mood stabilizer use, recurrent depression, psychotic symptoms, and admission to a psychiatric ward during diagnosis of MDD were also associated with diagnostic conversion to bipolar disorder. CONCLUSION: In young adults with MDD, antipsychotic and mood stabilizer use during diagnosis of MDD were the strongest predictive factors with diagnostic conversion to bipolar disorder during follow-up. If young adults with MDD need antipsychotics or mood stabilizer, patients should be carefully evaluated for possibility of bipolar disorder.

Risks of suicide attempts after prescription of zolpidem in people with depression: a nationwide population study in South Korea.

OBJECTIVES: To investigate the association between zolpidem prescription and suicide attempts in people with depression. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment Service of South was used to investigate the incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts in people with depression before and after zolpidem prescription using self-controlled case series design. RESULTS: In a total of 445 people who attempted suicide and 23 141 people who attempted probable suicide attempt, the IRRs of suicidal behavior during the risk periods before and after zolpidem prescription increased compared with those at the baseline. The IRRs gradually increased and peaked immediately before the prescription of zolpidem. The IRR was 70.06 (95% CI: 25.58-191.90) on day 2 before zolpidem prescription and 63.35 (95% CI: 22.99-174.59) on day 1 after zolpidem prescription in the suicide attempt group. The IRR was 24.07 (95% CI: 20.50-28.26) on the day before zolpidem prescription and 14.96 (95% CI: 12.21-18.34) on the day after zolpidem prescription in the probable suicide attempt group. The ratios declined eventually after zolpidem was prescribed. CONCLUSIONS: Although zolpidem prescription was associated with an increased risk of suicide attempts in people with depression, the risk increased and peaked immediately before zolpidem prescription. The risk declined gradually thereafter. This result indicates that the risk of suicide attempts increases at the time of zolpidem prescription. However, zolpidem prescription does not contribute to additional increase in the risk of suicide attempts.