Nationwide Population-based Database Research Articles

Epidemiology and demographics of slipped capital femoral epiphysis in South Korea: A nationwide cohort study.

This study investigated the epidemiology and demographics of slipped capital femoral epiphysis (SCFE) in South Korea using a nationwide population-based database. Information on sex, age at onset, endocrine comorbidities, history of growth hormone therapy, history of radiation therapy, surgical methods, and complications in patients with SCFE aged younger than 18 years between 2007 and 2019 was retrieved from the Korean Health Insurance Review and Assessment Service database. Data were available for 586 children (429 boys, 157 girls). The average age at onset was 11.1 ± 1.8 years (boys, 11.3 ± 1.9; girls, 10.6 ± 1.5). Five hundred and twenty-nine (90.3%) patients were aged 9-14 years; the incidence rate in this age group was 6.0/100,000 (95% confidence interval, 5.5-6.6) and significantly higher in boys (8.4 vs 3.5, p<0.001). There was a significant increase in the annual incidence rate from 0.96/100,000 in 2009 to 2.05/100,000 in 2019 (p = 0.006). Ninety-five patients (16.2%) had endocrine comorbidities or a history of hormone/radiation therapy. Osteotomy and internal fixation were performed in 59 patients and in situ pinning in 527. Seventy-six patients developed postoperative complications. The annual incidence rate of SCFE in South Korea has increased since 2009.

Impact of abdominal obesity on the risk of glioma development in patients with diabetes: A nationwide population-based cohort study in Korea.

Abdominal obesity has been suggested as a risk factor for glioma; however, it is unclear whether this association applies to people with diabetes. This study examined the association between abdominal obesity and the risk of developing gliomas in diabetic patients. We conducted a retrospective cohort study using the National Health Insurance System of South Korea from 2009 to 2012. The primary outcome was the incidence of newly diagnosed gliomas according to waist circumference (WC), and subgroup analyses were performed according to demographic characteristics and diabetes status including disease duration, number of oral hypoglycemic agents, and insulin use. Of a total of 1,893,057 participants, 1,846 (0.10%) cases of gliomas occurred. After adjusting for confounding factors, WC ≥90 cm (men)/85 cm (women) was associated with significantly higher risks of gliomas (adjusted HR [95% CI]; 1.279 [1.053, 1.554], 1.317 [1.048, 1.655], and 1.369 [1.037, 1.807] in the WC <95 cm (men)/90 cm (women) group, WC <100 cm (men)/95 cm (women) group, and WC ≥100 cm (men)/95 cm (women) group, respectively). Subgroup analysis showed that patients with larger WC had a consistently higher incidence of glioma than their lean counterparts, except for insulin users (insulin user vs. nonuser, P for interaction = .03). Abdominal obesity was associated with the development of gliomas in diabetic patients in a nationwide population-based database. Further study is needed in diabetic patients to stratify the risk for glioma development according to WC and to establish the underlying mechanism of carcinogenesis.

Descriptive Study of Mastitis in Postpartum Women in Taiwan: Incidence and Related Factors.

Background: Mastitis is a common disorder among postpartum women. The discomfort and pain caused by mastitis may lead to the discontinuation of breastfeeding. Large-scale epidemiological studies examining mastitis are limited. Accordingly, the present study used a nationwide population-based database to collect information about all postpartum women in Taiwan to determine the incidence of and related factors for mastitis. Materials and Methods: This retrospective population-based study used the National Health Insurance Research Database to collect records of patients with mastitis during 2008-2017 and then linked the collected data to the Taiwan Birth Registry. We included women diagnosed as having lactational mastitis within 6 months of delivery. A multivariable logistic regression model was used to compare the risk of mastitis between parity in multiparous women. Results: We identified 1,686,167 deliveries in 1,204,544 women. 19,794 women with 20,163 deliveries had a medical claim for mastitis. The incidence proportion of mastitis for 6 months postpartum was ∼1.19% and highest during the first month after delivery. Multivariable logistic regression revealed that multiparous women with a history of mastitis were likely to experience mastitis again after subsequent deliveries (adjusted odds ratio = 5.86; 95% confidence interval = 5.21-6.58). The Kaplan-Meier curve indicated that primiparous women had a higher risk of mastitis than did multiparous women (log-rank test, p < 0.001). Conclusion: Mastitis generally occurred during the first month postpartum, and primiparous women had a higher risk of mastitis than did multiparous women. Furthermore, multiparous women with a history of mastitis had a 5.86-fold increased risk of recurrence during subsequent deliveries.

Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort

ObjectiveThe main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database. MethodsWe conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups—those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause. ResultsAfter PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81–0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70–0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56–1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34–0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55–0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis. ConclusionOur results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes.Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176–183.

Pregnancy Outcomes Associated With Biologic Agent Exposure in Patients With Several Rheumatic Diseases and Inflammatory Bowel Diseases.

This study aimed to analyze pregnancy outcomes based on biologic agents use in women using the nationwide population-based database. The study used the claims database to identify women of childbearing age with several rheumatic (rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis) and inflammatory bowel diseases (Crohn's disease and ulcerative colitis) who had pregnancy-related codes between January 2010 and December 2019. We analyzed live births and adverse pregnancy outcomes based on the previous use of biologics. We also stratified the patients according to duration of biologic agent exposure before pregnancy and the use of biologics during pregnancy to analyze the pregnancy outcomes by subgroups. We identified 4,787 patients with pregnancy events. Among them, 1,034 (21.6%) used biologics before pregnancy. Live birth rate was not different between the biologics group and biologics naïve group (75.0% vs. 75.2%). Multivariate analyses showed that biologics use was associated with higher risk of intrauterine growth retardation (odds ratio [OR], 1.780) and lower risk of gestational diabetes mellitus (OR, 0.776) compared with biologics naïve. Biologics use during pregnancy was associated with higher risk of preterm delivery (OR, 1.859), preeclampsia/eclampsia (OR, 1.762), intrauterine growth retardation (OR, 3.487), and cesarean section (OR, 1.831), but lower risk of fetal loss (OR, 0.274) compared with biologics naïve. Although there was no difference in live birth rate between the biologics group and biologics naïve group, biologics use seems to be associated with several adverse pregnancy outcomes, especially in patients with biologics during pregnancy. Therefore, patients with biologics during pregnancy need to be carefully observed for adverse pregnancy outcomes.

Better Oral Hygiene Is Associated with a Decreased Risk of Meniere's Disease: A Nationwide Cohort Study.

To investigate the association of the oral health parameters with Meniere’s disease in a nationwide population-based longitudinal cohort database. The data of the participants who underwent an oral health screening by dentists in 2003 (n = 2,415,963) were retrieved from the National Health Insurance Database of the Korean National Health Insurance Service. The main outcome was the occurrence of Meniere’s disease, defined as two or more claims of the diagnostic code H810 with a previous audiometric examination. The occurrence of Meniere’s disease was analyzed using a Cox proportional hazard model according to the presence of periodontitis and the oral health examination findings, including missing teeth, the frequency of tooth brushing and dental scaling. Overall, the analysis included 2,240,282 participants. During a median follow-up of 16.7 years, Meniere’s disease developed in 112,106 (5.0%) participants. Poor oral health status was characterized by the presence of periodontitis (adjusted hazard ratio [aHR]: 1.18, 95% confidence interval [CI]: 1.14−1.22, p < 0.001) and an increased number of missing teeth (≥15; aHR: 1.25, 95% CI: 1.18−1.32, p < 0.001) was associated with an increased risk of Meniere’s disease. Better oral hygiene behaviors, such as frequent tooth brushing (≥3 per day; aHR: 0.75, 95% CI: 0.73−0.76, p < 0.001) and dental scaling within 1 year (aHR: 0.98, 95% CI: 0.97−0.99, p = 0.003) were negatively associated with the occurrence of Meniere’s disease. The presence of periodontitis and an increased number of missing teeth may augment the risk of the occurrence of Meniere’s disease. However, maintaining good oral hygiene through tooth brushing and dental scaling may be associated with a decreased risk of Meniere’s disease. Further studies should confirm the association between oral health and Meniere’s disease.

Proteinuria and Risk for Heart Failure in 55,191 Patients Having History of Cancer

Introduction: We examined the association of proteinuria with the risk for heart failure (HF) and other cardiovascular disease (CVD) events in patients with prior history of breast, colorectal, or stomach cancer using a nationwide population-based database. Methods: We conducted this retrospective observation study using the JMDC Claims Database and analyzed 55,191 patients with prior history of breast, colorectal, or stomach cancer. The median age was 54 (48–60) years, and 20,665 participants (37.4%) were men. Using urine dipstick data at baseline, 3,945 and 1,521 participants were categorized as having trace and positive proteinuria, respectively. Using Cox proportional hazards models, we examined the relationship of proteinuria with the incidence of HF and other CVD events. Results: Over a mean follow-up of 2.8 ± 2.2 years, 1,597 HF, 124 myocardial infarction, 1,342 angina pectoris, 719 stroke, and 361 atrial fibrillation events were recorded. Kaplan-Meier curves showed that the cumulative incidence for HF increased with proteinuria category (log-rank p < 0.001). After multivariable adjustment, hazard ratios of trace and positive proteinuria for HF were 1.24 (95% CI, 1.04–1.47) and 1.62 (95% CI, 1.30–2.02), respectively. The presence of proteinuria was also associated with a higher risk for angina pectoris and atrial fibrillation. Discussion: Proteinuria was associated with a greater risk of developing HF and other CVD events in patients with prior history of cancer. The optimal management strategy for patients with proteinuria and cancer needs to be established for the prevention of HF in cancer patients.

Fetal heart rate patterns complicated by chorioamnionitis and subsequent cerebral palsy in Japan.

This retrospective study was performed to investigate whether certain fetal heart rate patterns were associated with subsequent cerebral palsy (CP) in infants with chorioamnionitis at or near term. We used cases registered by the Japan Obstetric Compensation System for CP, which is a nationwide population-based database. Among them, 133 infants with chorioamnionitis who were born at ≥34 weeks of gestation were enrolled. All infants underwent magnetic resonance imaging (MRI), and all fetal heart rate charts had been interpreted according to the National Institute of Child Health and Human Development criteria, focusing on antepartum and immediately before delivery. The incidence of CP after chorioamnionitis at ≥34 weeks of gestation was 0.3 per 10 000 in Japan. Between the clinical (24%) and subclinical groups (76%), the incidence of abnormal fetal heart rate patterns did not differ. According to the MRI classification, 88% of the infants with CP showed hypoxic-ischemic encephalopathy. Half of the infants with CP experienced terminal bradycardia, leading to severe acidosis and exclusively to hypoxic-ischemic encephalopathy. In another half, who did not experience bradycardia, 80% had moderate acidosis (pH7.00-7.20) resulting in hypoxic-ischemic encephalopathy, and the remaining 20% showed non-acidosis resulting in brain damage other than hypoxic-ischemic encephalopathy. The fetal heart rate patterns before the terminal bradycardia showed that the incidence rates of late deceleration or decreased variability were high (>60%). Fifty percent of pregnant women with chorioamnionitis-related CP had terminal bradycardia that exclusively resulted in hypoxic-ischemic encephalopathy.

Decreased trends of using dental amalgam filling for decayed teeth in Taiwan from 1997 to 2013

Background/purposeMercury within dental amalgam has been criticized for the potential toxicity and environmental hazard. Phasing down the use of dental amalgam is the transition for amalgam free dentistry. However, little is known about dental amalgam filling (AMF) in Taiwan. In this study, time trends of AMF were measured by using National Health Insurance Research Database (NHIRD). Materials and methodsA retrospective study was conducted to analyze the AMF data in registered database compiled by Taiwanese NHIRD from 1997 to 2013. The AMF data were further analyzed according to sex, age, and geographic location, respectively. Time trends of dental visits for AMF and medical expenses for AMF were also evaluated. ResultsThe average annual AMF ratio was 8.965% of nationwide population in Taiwan. The prevalence of AMF was significantly decreased both in male and female from 1997 to 2013 (P for trend <0.0001). The decreased pattern of AMF was found by the age stratification (P for trend <0.0001). The significant fall of AMF was also displayed in six districts (P for trend <0.0001). The number of dental visits were ranged from 821,749 in 1997 to 1,313,734 in 2013. However, time trends of dental visits for AMF were significantly decreased (P for trend <0.0001). The medical expenses for AMF were simultaneous significantly decreased from 1997 to 2013 (P for trend <0.0001). ConclusionForm the results of this nationwide population-based database, a significant decrease of AMF in Taiwan was observed during past 17 years.

Abstract 12325: Burden of Premature Ventricular Complex is Associated With New-Onset Atrial Fibrillation

Introduction: Large burden of premature ventricular complex (PVC)lead to more cardiovascular mortality. A recent nationwide population-based database demonstrated that presence of PVC is associated with increased risk of atrial fibrillation. The relationship between burden of PVC and new onset of atrial fibrillation (AF), however, has never been investigated. Hypothesis: The purpose of the study is to clarify whether burden of PVC is associated with more new-onset AF. Methods: We designed a single-center, retrospective, and large population-based cohort to clarify the role of PVC burden and new-onset atrial fibrillation in Taiwan. PVC patients without history of atrial fibrillation with were divided into low burden group (&lt;1000/day) and moderate to high burden group (≥1000/day) based on the report of 24-h Holter ECG. New-onset AF was defined as new or first detectable events presenting as either persistent or paroxysmal AF. Results: A total of 16030 AF-naïve patients who underwent 24-h Holter ECG were enrolled in this study with a mean follow-up time of 973 days. A propensity-score matched analysis demonstrated moderate to high burden PVC group had a higher risk to have new-onset AF in comparison with low burden (4.96% vs 2.79%, p&lt;0.001). Multivariate Cox regression analysis showed that moderate to high burden of PVC is an independent risk factor to develop new-onset AF. A Kaplan-Meier analysis also showed that patients with moderate to high burden of PVC is associated with more new-onset AF (log rank p&lt;0.001). Conclusions: Burden of PVC is associated with new-onset atrial fibrillation. Patients with moderate to high burden PVC are at a higher risk to have new-onset atrial fibrillation.

Mortality and Causes of Death among Individuals Diagnosed with Human Immunodeficiency Virus in Korea, 2004-2018: An Analysis of a Nationwide Population-Based Claims Database.

The mortality rate and causes of death among individuals diagnosed with human immunodeficiency virus (HIV) infection in Korea were described and compared to those of the general population of Korea using a nationwide population-based claims database. We included 13,919 individuals aged 20–79 years newly diagnosed with HIV between 2004 and 2018. The patients’ vital status and cause of death were linked until 31 December 2019. Standardized mortality ratios (SMRs) for all-cause death and specific causes of death were calculated. By the end of 2019, 1669 (12.0%) of the 13,919 HIV-infected participants had died. The survival probabilities of HIV-infected individuals at 1, 5, 10, and 15 years after diagnosis in Korea were 96.2%, 91.6%, 85.9%, and 79.6%, respectively. The main causes of death during the study period were acquired immunodeficiency syndrome (AIDS; 59.0%), non-AIDS-defining cancer (8.2%), suicide (7.4%), cardiovascular disease (4.9%), and liver disease (2.7%). The mortality rate of men and women infected with HIV was 5.60-fold (95% CI = 5.32–5.89) and 6.18-fold (95% CI = 5.30–7.09) that of men and women in the general population, respectively. After excluding deaths due to HIV, the mortality remained significantly higher, with an SMR of 2.16 (95% CI = 1.99–3.24) in men and 3.77 (95% CI = 3.06–4.48) in women. HIV-infected individuals had a higher overall mortality than the general population, with AIDS the leading cause of mortality. Additionally, mortality due to non-AIDS-related causes was higher in HIV-infected individuals.

Quality of Life of Survivors of Thyroid Cancer Is Not Inferior to That in Subjects without Cancer: Long-Term after Over 5 Years.

BackgroundPatients with thyroid cancer undergo less extensive surgery and additional therapies compared to those with other cancers. We aimed to compare the quality of life (QoL) between patients with thyroid cancer and healthy subjects using representative data from Korea. Differences in QoL of thyroid cancer survivors according to the duration after cancer diagnosis was also evaluated.MethodsThis population-based cohort study included 50,278 subjects who participated in the Korea National Health and Nutrition Examination Survey between 2007 and 2017. QoL was compared between patients with thyroid cancer and healthy subjects using self-reported data from the EuroQoL (EQ)-5 dimension (5D) and EQ-visual analog scale (VAS). Propensity score matching was used to match thyroid cancer survivors to healthy subjects (1:5 matching).ResultsLinear regression with univariate analysis showed that the presence of thyroid cancer was positively correlated with better EQ-5D index scores (β-coefficient=0.010, P=0.046). After adjusting for multiple covariables, statistical significance was maintained. EQ-VAS fails to demonstrate any significant correlation. Among the EQ-5D categories, patients with thyroid cancer showed better self-care than healthy subjects. Thyroid cancer duration did not correlate with the EQ-5D index score. In subgroup analyses, compared to patients with thyroid cancer duration of <5 years, no significant difference was observed in the correlation between the EQ-5D index score and survival duration in those with thyroid cancer duration of 5 to 9 years and ≥10 years.ConclusionUsing a large-scale nationwide population-based database, our study demonstrated better QoL, especially in terms of self-care, among thyroid cancer survivors than among healthy subjects without cancer.

Breast Cancer Incidence among Female Workers by Different Occupations and Industries: A Longitudinal Population-Based Matched Case–Control Study in Taiwan

Background: Breast cancer is the leading cause of cancer incidence worldwide and in Taiwan. The relationship between breast cancer and occupational types remains unclear. This study aimed to investigate lifetime breast cancer incidence by different occupational industries among female workers in Taiwan. Methods: A population-based retrospective case–control study was conducted using three nationwide population-based databases. Matched case and control groups were identified with 1-to-4 exact matching among 103,047 female workers with breast cancer diagnosed in 2008–2017 and those without breast cancer. Their lifetime labor enrollment records were tracked using the National Labor Insurance Database, 1950–2017. Conditional logistic regression was used to analyze the association between types of occupational industries and risk of incident breast cancer. Results: Our study found slightly significant breast cancer risk among the following major occupational classifications: manufacturing (OR: 1.027, 95% CI: 1.011–1.043); wholesale and retail trade (OR: 1.068, 95% CI: 1.052–1.084); information and communication (OR: 1.074, 95% CI: 1.043–1.105); financial and insurance activities (OR: 1.109, 95% CI: 1.086–1.133); real estate activities (OR: 1.050, 95% CI: 1.016–1.085); professional, scientific, and technical activities (OR: 1.118, 95% CI: 1.091–1.145); public administration, defense, and social security (OR: 1.054, 95% CI: 1.023–1.087), education (OR: 1.199, 95% CI: 1.168–1.230); and human health and social work activities (OR: 1.125, 95% CI: 1.096–1.156). Conclusions: Greater percentages of industrial occupations (i.e., manufacturing, wholesale and retail, or health professionals) were associated with slightly increased breast cancer risk. Further studies should investigate the possible risk factors among female workers in those industries with slightly higher incidence of breast cancer.

Cancer Incidence Among Adults With HIV in a Population-Based Cohort in Korea

In combination with a decreased risk of AIDS-defining cancers and improved survival of people infected with HIV, the burden of non-AIDS-defining cancer has increased markedly. Although a substantial number of studies have measured the cancer risk among people with HIV in developed countries, little research has been conducted on the risk of cancer in HIV-infected people in Asia. To examine the cancer incidence and the estimated risk of cancer among people in Korea infected with HIV compared with the general population. This retrospective cohort study evaluated patients without cancer newly diagnosed with HIV from January 1, 2006, to December 31, 2018, using a nationwide population-based claims database embedded in the National Health Insurance Service database. Data were analyzed between December 6, 2021, and February 28, 2022. Infection with HIV. Cancer incidence and standardized incidence rate (SIR) through indirect standardization. A total of 11 552 individuals without cancer (10 444 male [90.4%]; mean [SD] age, 39.9 [11.2] years) diagnosed with HIV were identified. The SIR for all cancers was 1.68 (95% CI, 1.50-1.87) in men and 1.26 (95% CI, 0.89-1.64) in women. In men, the highest SIRs were for Kaposi sarcoma (SIR, 349.10; 95% CI, 196.10-502.20) and anal cancer (SIR, 104.20; 95% CI, 55.56-149.90). The incidence of non-Hodgkin lymphoma (SIR, 15.62; 95% CI, 11.85-19.39), Hodgkin lymphoma (SIR, 16.67; 95% CI, 4.32-29.02), and oropharyngeal cancer (SIR, 2.97; 95% CI, 1.36-4.58) in men infected with HIV was higher than in the general population. In women infected with HIV, an increased incidence of cervical cancer (SIR, 4.98; 95% CI, 1.29-8.66) and non-Hodgkin lymphoma (SIR, 11.78; 95% CI, 2.35-21.21) compared with the general population was observed. The SIR of thyroid cancer in patients with HIV was lower than in the general population in both men (SIR, 0.63; 95% CI, 0.27-0.99) and women (SIR, 0.48; 95% CI, 0.06-0.90). In this cohort study, cancer risks, especially AIDS-defining cancer and virus-related cancer, were elevated in people with HIV. Efforts for cancer prevention, screening, and better accessibility to medical care in HIV-infected people are warranted.

External Validation of Two Established Clinical Risk Scores Predicting Outcome after Local Treatment of Colorectal Liver Metastases in a Nationwide Cohort.

Simple SummaryPatients with colorectal liver metastases (CRLM) are able to achieve long-term survival when they receive local treatment of CRLM (resection or tumor ablation). Existing clinical risk scores (CRSs) predicting prognosis of patients after resection of colorectal liver metastases were developed in highly specialized centers and thus may not function in the general population. We validated the Fong and GAME CRSs in a large population-based cohort, including two important subgroups: young/elderly and with/without perioperative chemotherapy. Both CRSs showed predictive ability. However, they were not able to discriminate preoperative risk sufficiently for clinical decision-making and, thus, require improvement.Optimized surgical techniques and systemic therapy have increased the number of patients with colorectal liver metastases (CRLM) eligible for local treatment. To increase postoperative survival, we need to stratify patients to customize therapy. Most clinical risk scores (CRSs) which predict prognosis after CRLM resection were based on the outcome of studies in specialized centers, and this may hamper the generalizability of these CRSs in unselected populations and underrepresented subgroups. We aimed to externally validate two CRSs in a population-based cohort of patients with CRLM. A total of 1105 patients with local treatment of CRLM, diagnosed in 2015/2016, were included from a nationwide population-based database. Survival outcomes were analyzed. The Fong and more recently developed GAME CRS were externally validated, including in pre-specified subgroups (≤70/>70 years and with/without perioperative systemic therapy). The three-year DFS was 22.8%, and the median OS in the GAME risk groups (high/moderate/low) was 32.4, 46.7, and 68.1 months, respectively (p < 0.005). The median OS for patients with versus without perioperative therapy was 47.6 (95%CI [39.8, 56.2]) and 54.9 months (95%CI [48.8, 63.7]), respectively (p = 0.152), and for below/above 70 years, it was 54.9 (95%CI [49.3–64.1]) and 44.2 months (95%CI [37.1–54.3]), respectively (p < 0.005). The discriminative ability for OS of Fong CRS was 0.577 (95%CI [0.554, 0.601]), and for GAME, it was 0.596 (95%CI [0.572, 0.621]), and was comparable in the subgroups. In conclusion, both CRSs showed predictive ability in a population-based cohort and in predefined subgroups. However, the limited discriminative ability of these CRSs results in insufficient preoperative risk stratification for clinical decision-making.

Medication-Naïve Blood Pressure and Incident Cancers: Analysis of 2 Nationwide Population-Based Databases.

Results of preceding studies on the relationship between blood pressure (BP) and cancers have been confounded due to individuals taking antihypertensive medications or shared risk factors. We assessed whether medication-naïve high BP is a risk factor for incident cancers. This retrospective observational study included 1,388,331 individuals without a prior history of cancer and not taking antihypertensive medications enrolled in the JMDC Claims Database between 2005 and 2018. The primary outcome was 16 cancers. The median [interquartile range] age was 45 [40-52] years and 56.2% were men. Mean systolic BP (SBP) and diastolic BP (DBP) were 117.7 ± 15.8 and 72.8 ± 11.6 mm Hg. Multivariate Cox regression analysis demonstrated that SBP per 1-SD was associated with a higher incidence of thyroid (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.03-1.16), esophageal (HR: 1.15, 95% CI: 1.07-1.24), colorectal (HR: 1.04, 95% CI: 1.01-1.07), liver (HR: 1.11, 95% CI: 1.03-1.20), and kidney (HR: 1.22, 95% CI: 1.14-1.31) cancers, but with a lower incidence of stomach cancer (HR: 0.94, 95% CI: 0.91-0.98). These associations remained significant after adjustment for multiple testing. DBP was associated with higher incidences of thyroid, esophageal, colorectal, kidney, and corpus uteri cancers, but with a lower incidence of stomach cancer. The associations between SBP and incidences of thyroid, esophageal, colorectal, liver, and kidney cancers were confirmed in the Korean National Health Insurance Service database. Medication-naïve BP was associated with higher incidences of thyroid, esophageal, colorectal, liver, and kidney cancers. Uncovering the underlying mechanisms for our results may help identify novel therapeutic approach for hypertension and cancer.

Proton pump inhibitors reduce the survival of advanced lung cancer patients with therapy of gefitinib or erlotinib

Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for advanced non-small-cell lung cancer. However, co-administration of either drug with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may reduce TKI’s bioavailability. Therefore, we aimed to investigate the effects of these drug–drug interactions. We surveyed nationwide population-based databases between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced lung adenocarcinoma who received first-line gefitinib or erlotinib were identified. Effects on overall survival (OS) and time to next treatment (TTNT) association between PPIs or H2RAs and co-administrated gefitinib or erlotinib were evaluated. PPIs or H2RAs users were defined if the period overlapped with TKIs by ≥ 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. PPI group had the shortest median OS and TTNT compared to the H2RA and non-user groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P < 0.0001, TTNT: 8.47 vs. 10.78 vs. 10.33 months; P < 0.0001); (in erlotinib cohort: OS: 16.97 vs. 20.07 vs. 23.92 months; P < 0.0001, TTNT: 9.06 vs. 11.85 vs. 10.90 months; P = 0.0808). Compared with the non-user group, the adjusted hazard ratio (aHR) of the PPI group in the gefitinib was 1.58 on OS (95% CI 1.42–1.76), 1.37 on TTNT (95% CI 1.24–1.52); in the erlotinib was 1.54 on OS (95% CI 1.30–1.82) and 1.19 on TTNT (95% CI 1.01–1.39). Concurrent use of PPIs with first-line gefitinib or erlotinib therapy was associated with a worse OS and TTNT in patients with lung adenocarcinoma harboring EGFR mutations.

Association between proteinuria and incident colorectal cancer: analysis of a nationwide population-based database

ObjectivesThis study aimed to assess whether adults with proteinuria were at a higher risk of incident colorectal cancer (CRC) than those without proteinuria using a large-scale population-based database.DesignA retrospective observational...

Change in Cardiovascular Health Metrics and Risk for Proteinuria Development: Analysis of a Nationwide Population-Based Database

Introduction: Evidence is lacking regarding the association between cardiovascular health (CVH) metrics and the risk for proteinuria. Methods: We performed this observational cohort study including 865,087 participants (median age, 46 years, 60.7% men) with negative proteinuria at the initial health check-up, who underwent repeated health check-ups within 4 years. Ideal CVH metrics included nonsmoking, body mass index <25 kg/m², physical activity at goal, eating breakfast, blood pressure <120/80 mm Hg, fasting plasma glucose <100 mg/dL, and total cholesterol <200 mg/dL. The primary outcome was incident proteinuria, defined as ≥1 + on the urine dipstick test. Results: Participants were categorized as having low CVH metrics defined as having 0–2 ideal CVH metrics (n = 84,439), middle CVH metrics defined as having 3–4 ideal CVH metrics (n = 335,773), and high CVH metrics defined as having 5–7 ideal CVH metrics (n = 444,875). Compared with low CVH metrics, middle CVH metrics (odds ratio (OR): 0.61, 95% CI: 0.59–0.63) and high CVH metrics (OR: 0.45, 95% CI: 0.43–0.46) were associated with a lower risk of proteinuria. The OR of a one-point increase in the ideal number of CVH metrics was 0.83 (95% CI: 0.82–0.83). All CVH metrics components except for ideal total cholesterol were associated with a decreased risk of proteinuria. A one-point improvement in the number of ideal CVH metrics at 1 year after the initial health check-up was associated with a decreased incidence of proteinuria (OR: 0.90, 95% CI: 0.89–0.92). Conclusion: Not only maintaining better CVH metrics but also improving CVH metrics would prevent developing proteinuria in a general population.

Association of retinal atherosclerosis assessed using Keith-Wagener-Barker system with incident heart failure and other atherosclerotic cardiovascular disease: Analysis of 319,501 individuals from the general population

Background and aimsIt is not known whether the presence of retinal atherosclerosis (RA) is associated with incident heart failure (HF) in the general population. We aimed to investigate the relationship between RA and the risk of HF development using a nationwide population-based database. MethodsWe studied 319,501 adults without a history of cardiovascular disease (CVD) and with available data on retinoscopy at health check-up registered in the JMDC Claims Database between January 2005 and April 2020. We performed Cox regression analyses to assess the relationship of RA, defined as Keith-Wagener-Barker system grade ≥1, with incident HF and other CVD, including myocardial infarction (MI), angina pectoris (AP), and stroke. ResultsThe median age (interquartile range) was 47 (41–54) years, and 159,710 participants (50.0%) were men. RA was observed in 26,168 participants (8.2%). During a median (interquartile range) follow-up of 2.9 (1.6–4.6) years, 6,821 (2.1%) HF, 692 (0.2%) MI, 7,016 (2.2%) AP and 3,584 (1.1%) stroke events occurred. After adjustment for potential confounders, multivariable Cox regression analyses showed that RA was associated with a greater incidence of HF (hazard ratio 1.13, 95% confidence interval [CI] 1.05–1.21) and other CVDs. Hazard ratios of RA for MI, AP, and stroke were 1.17 (95% CI, 0.95–1.44), 1.13 (95% CI, 1.05–1.21), and 1.25 (95% CI, 1.14–1.37), respectively. This association was present in all subgroups. ConclusionsThe assessment of RA may be useful to identify people at high-risk for the development of HF and other atherosclerotic CVD events in a general population.