Contemporary Practice of Anemia Treatment Among Dialysis Patients in the United States.

Introduction: The treatment of anemia is a major activity in the care of patients undergoing maintenance hemodialysis (HD). The comparative effectiveness of new pharmacologic treatments, relative to erythropoiesis-stimulating agents (ESAs), should be anticipated on the bases of controlled trials and current practice. We describe the contemporary practice of anemia treatment in a national cohort of patients undergoing maintenance HD. Methods: We analyzed the United States Renal Data System (USRDS) data to identify adult patients undergoing in-facility HD in 2016 to 2019. Using the Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb) dataset, we identified hemoglobin and ESA utilization (agent and cumulative dose) during each patient-month, as well as intravenous (IV) iron utilization, ferritin, and transferrin saturation. We compared ESA dosing during the study era to dosing in the Normal Hematocrit Cardiac Trial (NHCT), conducted in the 1990s. We assessed ESA hyporesponsiveness by estimating the prevalence of the following: (i) high erythropoietin resistance index (ERI) and (ii) either 3 or 6 consecutive months with hemoglobin <10 g/dl. Results: Nearly two-thirds of patient-months had hemoglobin of 10.0 to 11.9 g/dl. Mean ESA utilization was 76.7% per month, with increasing use of pegylated epoetin beta. ESA dosing was stable; epoetin alfa dosing was slightly lower than in the low-target arm of the NHCT. The prevalence of ESA hyporesponsiveness was 22.2% if defined by high ERI, but only 2.1% to 6.0% if defined by 3 to 6 consecutive months with hemoglobin <10 g/dl. Median transferrin saturation was 22.3% with high ERI and persistently low hemoglobin. Conclusion: Hemoglobin and ESA dosing distributions are stable, with epoetin alfa dosing below the low-target arm of the NHCT. Persistently low hemoglobin occurs infrequently and may reflect iron depletion.

Etelcalcetide Versus Cinacalcet in Hemodialysis Patients in the United States: A Facility Calcimimetic Approach to Assess Real-World Effectiveness.

Rationale & Objective: Some US hemodialysis (HD) facilities switched from oral cinacalcet to intravenous etelcalcetide as the primary calcimimetic therapy to control parathyroid hormone (PTH) levels after the introduction of etelcalcetide in 2017. Although clinical trials have demonstrated the superior efficacy of etelcalcetide versus cinacalcet, evidence comparing real-world effectiveness is lacking. Study Design: Prospective cohort. Setting & Participants: Patients receiving HD enrolled in US Dialysis Outcomes and Practice Patterns Study facilities. Exposure: We classified HD facilities on the basis of whether >75% of calcimimetic users were prescribed etelcalcetide ("etelcalcetide-first") or cinacalcet ("cinacalcet-first") from March-August 2019. Outcomes: PTH, calcium, and phosphorus levels among calcimimetic users, all averaged in the 6 months after the exposure assessment period. Analytical Approach: We used adjusted linear regression to compare outcomes using 2 approaches: (1) cross-sectional comparison of etelcalcetide-first and cinacalcet-first HD facilities; (2) pre-post comparison of HD facilities that switched from cinacalcet-first to etelcalcetide-first using facilities that remained cinacalcet-first as a comparison group. Results: We identified 45 etelcalcetide-first and 67 cinacalcet-first HD facilities; etelcalcetide-first (vs cinacalcet-first) facilities were more likely to be from small or independent dialysis organizations (86% vs 22%) and had higher total calcimimetic use (43% vs 29%) and lower active vitamin D use (66% vs 82%). In the cross-sectional analysis comparing etelcalcetide-first and cinacalcet-first HD facilities, the adjusted mean difference in PTH levels was -115 pg/mL (95% CI, -196 to -34) and the prevalence of a PTH level of >600 pg/mL was lower (prevalence difference, -11.4%; 95% CI, -19.3% to -3.5%). Among facilities that switched to etelcalcetide-first, the mean PTH level decreased from 671 to 484 pg/mL and the prevalence of a PTH level of >600 pg/mL decreased from 39% to 21%. Among facilities that remained cinacalcet-first, the mean PTH level increased from 632 to 698 pg/mL and the prevalence of a PTH level of >600 pg/mL increased from 37% to 43%. The adjusted difference-in-difference between the switch to etelcalcetide-first and the continuation of cinacalcet-first was -169 pg/mL (-249 to -90 pg/mL) for the mean PTH and -14.4% (-22.0% to -6.8%) for a PTH level of >600 pg/mL. We also observed slightly lower serum calcium levels and minimal differences in serum phosphorus levels between the etelcalcetide-first and the cinacalcet-first facilities. Limitations: Residual confounding. Conclusions: We observed better PTH control in HD facilities that switched from using cinacalcet to etelcalcetide as the primary calcimimetic therapy. Further research is needed to investigate how the greater real-world effectiveness of intravenous etelcalcetide (vs oral cinacalcet) may affect clinical outcomes.

10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea.

BACKGROUND: In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015. METHODS: BMD was classified as normal (T-score ≥-1.0 standard deviation [SD]), osteopenia (T-score <-1.0 SD and >-2.5 SD), and osteoporosis (T score ≤-2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD. RESULTS: Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD. CONCLUSION: Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

Adolescent overweight and obesity and the risk of papillary thyroid cancer in adulthood: a large-scale case-control study.

This study aimed to investigate the association between adolescent overweight and obesity and PTC risk in adulthood. We conducted a case-control study in the Republic of Korea with 1,549 PTC patients and 15,490 controls individually matched for age and sex. We estimated body mass index (BMI) at age 18 years from self-reported weight at this age. Compared with BMI < 23.0 at age 18 years, BMI ≥ 25.0 at age 18 years was associated with higher PTC risk (odds ratio [OR] = 4.31, 95% confidence interval [CI]: 3.57, 5.22). The association between BMI ≥ 25.0 at age 18 years and PTC risk was stronger among men (OR = 6.65, 95% CI: 4.78, 9.27) than among women (OR = 3.49, 95% CI: 2.74, 4.43), and stronger among individuals with current BMI ≥ 25.0 (OR = 8.21, 95% CI: 6.34, 10.62) than among those with current BMI < 25.0 (OR = 2.21, 95% CI: 1.49, 3.27). Among PTC patients, BMI ≥ 25.0 at age 18 years was associated with extra-thyroidal extension and T stage ≥2, but not with N stage ≥1 or BRAFV600E mutation. Adolescent overweight and obesity was associated with higher risk of PTC in adulthood. Our results emphasise the importance of weight management in adolescence to decrease the PTC risk.

Low-density lipoprotein cholesterol goal attainment rates in high-risk patients with cardiovascular diseases and diabetes mellitus in Korea: a retrospective cohort study.

BACKGROUND: Real-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS). METHODS: This was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD). RESULTS: Overall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015). CONCLUSIONS: LDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.

Active and Passive Smoking, BRAFV600E Mutation Status, and the Risk of Papillary Thyroid Cancer: A Large-Scale Case-Control and Case-Only Study.

PURPOSE: The association between tobacco smoking and thyroid cancer remains uncertain. We evaluated the associations of active and passive smokingwith the risk of papillary thyroid cancer (PTC), the most common type of thyroid cancer, and with the BRAFV600E mutation, the most common oncogenic mutation in PTC related to poor prognosis. MATERIALS AND METHODS: We conducted this study with newly diagnosed PTC patients (n=2,142) and community controls (n=21,420) individually matched to cases for age and sex. Information on active and passive smoking and potential confounders were obtained from structured questionnaires, anthropometric measurements, and medical records. BRAFV600E mutation status was assessed in PTC patients. We evaluated the associations of active and passive smoking with PTC and BRAFV600E mutation risk using conditional and unconditional logistic regression models, respectively. RESULTS: We did not find associations between exposure indices of active and passive smoking and PTC risk in both men and women, except for the association between current smoking and lower PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAFV600E mutation risk in male PTC patients (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.30 to 1.00). The CI for the association was wider in female PTC patients (OR, 0.23; 95% CI, 0.02 to 2.62), possibly owing to a smaller sample size in this stratum. CONCLUSION: We did not find consistent associations between active and passive smoking and PTC risk. Cumulative smoking ≥ 20 pack-years was associated with lower BRAFV600E mutation risk in male PTC patients.

Association between Body Mass Index and Gastric Cancer Risk According to Effect Modification by Helicobacter pylori Infection.

PURPOSE: Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information. MATERIALS AND METHODS: We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model. RESULTS: Increased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori. CONCLUSION: This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

Corrigendum: Author's Name Correction. Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro).

This corrects the article on p. 278 in vol. 33, PMID: 29947183.

Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro).

BACKGROUND: The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups. METHODS: This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis. RESULTS: Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014). CONCLUSION: The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Health and Prevention Enhancement (H-PEACE): a retrospective, population-based cohort study conducted at the Seoul National University Hospital Gangnam Center, Korea.

PURPOSE: The Health and Prevention Enhancement (H-PEACE) study was designed to investigate the association of diagnostic imaging results, biomarkers and the predisease stage of non-communicable diseases (NCDs), such as malignancies and metabolic diseases, in an average-risk population in Korea. PARTICIPANTS: This study enrolled a large-scale retrospective cohort at the Healthcare System Gangnam Center, Seoul National University Hospital, from October 2003 to December 2014. FINDINGS TO DATE: The baseline and follow-up information collected in the predisease stage of NCDs allows for evaluation of an individual's potential NCD risk, which is necessary for establishing personalised prevention strategies. A total of 91 336 health examinees were included in the cohort, and we repeatedly measured and collected information for 50.9% (n=46 484) of the cohort members. All participants completed structured questionnaires (lifestyle, medical history, mini-dietary assessment index, sex-specific variables and psychiatric assessment), doctors' physical examinations, laboratory blood and urine tests and digital chest X-ray imaging. For participants with available data, we also obtained information on specific diagnostic variables using advanced diagnostic tests, including coronary CT for coronary calcium scores, colonoscopy and brain MRI. Furthermore, 17 455 of the participants who provided informed consent and donated blood samples were enrolled into the Gene-environmental interaction and phenotype study, a subcohort of the H-PEACE, from October 2013, and we analysed genome-wide single-nucleotide polymorphism array data for 6579 of these blood samples. FUTURE PLANS: The data obtained from this cohort will be used to facilitate advanced and accurate diagnostic techniques related to NCDs while considering various phenotypes. Potential collaborators can access the dataset after receiving approval from our institutional review board. Applications can be submitted on the study homepage (http://en-healthcare.snuh.org/HPEACEstudy).

Associations of urinary sodium levels with overweight and central obesity in a population with a sodium intake.

BACKGROUND: Previous studies have reported an association between dietary sodium intake and overweight/central obesity. However, dietary survey methods were prone to underestimate sodium intake. Therefore, this study investigated the associations of calculated 24-h urinary sodium excretion, an index of dietary sodium intake, with various obesity parameters including body mass index (BMI) and waist circumference (WC) in a population with a relatively high sodium intake. METHODS: A total of 16,250 adults (aged ≥19 years) and 1476 adolescents (aged 10-18 years), with available information on spot urine sodium levels and anthropometric measurements from the Korea National Health and Nutrition Examination Survey (KNHANES) were included in this study. We calculated 24-h urine sodium excretion levels from spot urine sodium levels using the Tanaka formula. RESULTS: In adults, those with high sodium excretion levels (≥ 3200 mg) showed increased odds of overweight and central obesity compared to those with low urinary sodium excretion level (< 2200 mg) (odds ratio [OR] = 2.17, 95% confidence interval [CI] = 1.90-2.49 for overweight; OR = 2.50, 95% CI = 2.13-2.94 for central obesity). These associations were also observed in adolescents (OR = 5.80, 95% CI = 3.17-10.60 for overweight; OR = 4.19, 95% CI = 1.78-9.89 for central obesity). CONCLUSIONS: The present study suggests that reducing salt intake might be important for preventing overweight and central obesity, especially in adolescents. However, because the present study was conducted with cross-sectional study design, further longitudinal studies are warranted to confirm the causal relationship between urinary sodium excretion and overweight/central obesity.

Effectiveness of Gastric Cancer Screening on Gastric Cancer Incidence and Mortality in a Community-Based Prospective Cohort.

PURPOSE: This study was performed to investigate the effectiveness of gastric cancer (GC) screening methods in a community-based prospective cohort of the Korean Multi-center Cancer Cohort (KMCC) with over a 10-year follow-up. MATERIALS AND METHODS: A total 10,909 and 4,773 subjects from the KMCC with information on gastroendoscopy (GE) and upper gastrointestinal series (UGIS) were included in this study. Cox proportional hazard model adjusted for age, sex, Helicobacter pylori infection, cigarette smoking, and alcohol drinking was used to estimate the hazard ratios (HRs) and 95% confidence interval (CI). RESULTS: The GE screened subjects had almost half the risk of GC-specific death than that of unscreened subjects (HR, 0.58; 95% CI, 0.36 to 0.94). Among the GC patients, GE screenees had a 2.24-fold higher survival rate than that of the non-screenees (95% CI, 1.61 to 3.11). In particular, GE screenees who underwent two or more screening episodes had a higher survival rate than that of the non-screenees (HR, 13.11; 95% CI, 7.38 to 23.30). The effectiveness of GE screening on reduced GC mortality and increased survival rate of GC patients was better in elderly subjects (≥ 65 years old) (HR, 0.47; 95% CI, 0.24 to 0.95 and HR, 8.84; 95% CI, 3.63 to 21.57, respectively) than that in younger subjects (< 65 years old) (HR, 0.66; 95% CI, 0.34 to 1.29 and HR, 1.83; 95% CI, 1.24 to 2.68, respectively). In contrast, UGIS screening had no significant relation to GC mortality and survival. CONCLUSION: The findings of this study suggest that a decreased GC-specific mortality and improved survival rate in GC patients can be achieved through GE screening.

Predictors of all-cause mortality among 514,866 participants from the Korean National Health Screening Cohort.

BACKGROUND: There is not enough evidence regarding how information obtained from general health check-ups can predict individual mortality based on long-term follow-ups and large sample sizes. This study evaluated the applicability of various health information and measurements, consisting of self-reported data, anthropometric measurements and laboratory test results, in predicting individual mortality. METHODS: The National Health Screening Cohort included 514,866 participants (aged 40-79 years) who were randomly selected from the overall database of the national health screening program in 2002-2003. Death was determined from causes of death statistics provided by Statistics Korea. We assessed variables that were collected at baseline and repeatedly measured for two consecutive years using traditional and time-variant Cox proportional hazards models in addition to random forest and boosting algorithms to identify predictors of 10-year all-cause mortality. Participants' age at enrollment, lifestyle factors, anthropometric measurements and laboratory test results were included in the prediction models. We used c-statistics to assess the discriminatory ability of the models, their external validity and the ratio of expected to observed numbers to evaluate model calibration. Eligibility of Medicaid and household income levels were used as inequality indexes. RESULTS: After the follow-up by 2013, 38,031 deaths were identified. The risk score based on the selected health information and measurements achieved a higher discriminatory ability for mortality prediction (c-statistics = 0.832, 0.841, 0.893, and 0.712 for Cox model, time-variant Cox model, random forest and boosting, respectively) than that of the previous studies. The results were externally validated using the community-based cohort data (c-statistics = 0.814). CONCLUSIONS: Individuals' health information and measurements based on health screening can provide early indicators of their 10-year death risk, which can be useful for health monitoring and related policy decisions.

The Association between Type 2 Diabetes Mellitus and Thyroid Cancer.

AIM: The incidence of thyroid cancer is increasing worldwide. The prevalence of type 2 diabetes mellitus (T2DM) is also increasing. Therefore, we aimed to analyze the effect of T2DM on thyroid cancer. METHODS: A case-control study was performed. A total of 415 healthy controls with thyroid ultrasound screening and physician consultation were selected from the Thyroid Cancer Longitudinal Study (T-CALOS). Among patients with thyroid cancer who were enrolled in T-CALOS, 415 patients were matched to the control group according to age and sex. We assessed the effects of T2DM, T2DM duration, and T2DM medication on thyroid cancer. RESULTS: Women with T2DM had lower odds of thyroid cancer than women without T2DM (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.20-0.81). Individuals receiving T2DM medication had higher odds of thyroid cancer compared to those without T2DM medication (OR: 5.21, 95% CI: 1.58-17.15). Individuals with T2DM duration <6 years had lower odds of thyroid cancer compared to those without T2DM (OR: 0.58, 95% CI: 0.34-0.97). CONCLUSIONS: Individuals with early T2DM are presumed to have a low incidence of thyroid cancer, and this effect seems to last up to 6 years after diagnosis of T2DM.

Relationship between iodine levels and papillary thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND: Iodine excess has been suggested as an exogenous risk factor of papillary thyroid cancer (PTC). We performed a systematic review and meta-analysis to assess the relationship between iodine exposure measured in various forms and PTC prevalence. METHODS: We searched MEDLINE, Embase, and the Cochrane Library for case-control studies on iodine and PTC published up to December 2015. Exposure to iodine was compared between PTC and control groups. RESULTS: From the 16 selected studies, the odds ratio (OR) for the overall effect size between high iodine exposure and PTC risk was 1.418 (95% confidence interval [CI] 1.054-1.909). Based on 7 studies conducted in high iodinated regions, a positive association between iodine exposure and PTC was observed (OR 2.200; 95% CI 1.389-3.483). CONCLUSION: This study demonstrated a higher exposure to iodine in patients with PTC compared with controls, especially for patients from high iodinated regions.

The Effect of Breastfeeding Duration and Parity on the Risk of Epithelial Ovarian Cancer: A Systematic Review and Meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). METHODS: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p<0.01; Q=59.46; I2=47.9%). Fifteen studies had breastfeeding categories of <6 months, 6-12 months, and >13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p=0.17; Q=18.79, I2=25.5%). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. CONCLUSIONS: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk.

Association between Exposure to Smartphones and Ocular Health in Adolescents.

PURPOSE: Smartphone use has dramatically increased in recent years. Smartphones may have adverse health effects, particularly on the eyes, because users stare at the screen for a much longer time than they do with ordinary mobile phones. The objective of this study was to elucidate the relationship between smartphone use and ocular symptoms among adolescents. METHODS: Information on smartphone use and ocular symptoms (blurring, redness, visual disturbance, secretion, inflammation, lacrimation and dryness) related to eye fatigue and strain from 715 adolescent subjects from three cities in Korea was obtained using a structured questionnaire. Ocular health was scored using number of ocular symptoms. Odds ratios (ORs), 95% confidence intervals (95% CIs) and p-values for ocular symptoms were calculated with binomial and multinomial logistic regression models. RESULTS: Higher prevalence rates for ocular symptoms were observed in groups with greater exposure to smartphones (p < 0.05). Longer daily smartphone use was associated with a higher likelihood of having multiple ocular symptoms (5-7 symptoms out of 7 symptoms; p = 0.005). Excessive/intermittent use (>2 hours daily and ≤2 hours continuously) and excessive/persistent use (>2 hours daily and >2 hours continuously) compared to shorter use (<2 hours daily) were associated with multiple ocular symptoms (OR 2.18, 95% CI 1.09-4.39; OR 2.26, 95% CI 1.11-4.57, respectively). A higher lifetime exposure to smartphones was associated with a higher likelihood of having multiple ocular symptoms (OR 3.05, 95% CI 1.51-6.19; p = 0.001). CONCLUSION: Increasing exposure to smartphones can have a negative impact on ocular health in adolescents.

Attribution to Heterogeneous Risk Factors for Breast Cancer Subtypes Based on Hormone Receptor and Human Epidermal Growth Factor 2 Receptor Expression in Korea.

We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors.Using matched case-control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes.The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%-69.8%]; luminal B, 21.4% [95% CI = 18.6-24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%-74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%-32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (P heterogeneity  ≤  0.001). The contribution of modifiable reproductive factors to luminal A type in premenopausal women was higher than that of the other subtypes (18.2% for luminal A; 3.1%, 8.1%, and -3.1% for luminal B, HER2-overexpression, and TN subtypes, respectively; P heterogeneity  ≤  0.001). Physical activity had the highest impact preventing 32.6% of luminal A, 14.5% of luminal B, 38.0% of HER2-overexpression, and 26.9% of TN subtypes (P heterogeneity = 0.014). Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, -3.1%; P heterogeneity  ≤  0.001).Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.

Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea.

BACKGROUND: This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC). METHODS: The Thyroid Cancer Longitudinal Study (T-CALOS) included 2,258 DTC patients (449 men and 1,809 women) and 22,580 healthy participants (4,490 men and 18,090 women) who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional regression models. RESULTS: While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion) was associated with increased risks in men (OR = 2.22, 95%CI = 1.27-3.87) and women (OR = 3.61, 95%CI = 1.52-8.58) compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31-40 years: OR = 1.58, 95%CI = 1.10-2.28; 41+ years: OR = 3.46, 95%CI = 2.06-5.80) and women (31-40 years: OR = 2.18, 95%CI = 1.62-2.92; 41+ years: OR = 2.71, 95%CI = 1.36-5.05) compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage. CONCLUSION: The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.