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Social jetlag, which is the mismatch between endogenous rhythm and social timing, is prevalent among the working population. Social jetlag may result in mood changes; however, evidence of relationship between social jetlag and depressive disorders has not been fully verified. Hence, this study aimed to investigate the association between social jetlag and depressive symptoms in a representative working population of South Korea.This study included 5447 Korean employees in the Korea National Health and Nutrition Examination Survey. Social jetlag was calculated as the difference between the midpoint of sleep time on weekdays and free days. Depressive symptoms were assessed using Patient Health Questionnaire-9. Multiple logistic regression was used to estimate the odds ratio after adjusting for confounding factors. Moreover, social jetlag and continuous depression scores were evaluated using linear regression and generalized additive models.The proportion of the participants who had2 h of social jetlag was 10.26 %. Depressive symptoms increased as social jetlag increased. Multiple logistic regression analysis showed that the adjusted OR (95 % confidence interval) for 1 to 2 h of social jetlag was 1.355 (0.891-2.059) and for2 h was 1.859 (1.084-3.187), which1 h was reference.This study used a cross-sectional design and measurements were based on self-reported scales.This study found that social jetlag and depressive symptoms were significantly related in the Korean working population.

Purpose Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.Materials and Methods Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.Results A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

We aimed to evaluate the efficacy of postoperative adjuvant pemetrexed plus cisplatin (Pem-Cis) in pathologic stage IB-IIIA lung adenocarcinoma (LUAD) patients.A prospective, phase II study was performed in seven institutions in South Korea. Patients with completely resected stage IB-IIIA LUAD received pemetrexed (500 mg/mBetween August 2015 and February 2018, 105 patients were enrolled in this study. Approximately 31.4% (n=33), 43.8% (n=46), and 24.8% (n=26) of patients had pathologic stage IB, II, and IIIA, respectively. Most of the patients underwent lobectomy (n=98, 93.3%). Moreover, 41.1% and 12.1% of the patients had epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase rearrangement. Four cycles of Pem-Cis were administered in 99 patients (94.3%). At a median follow-up of 57.7 months, the 2-year DFSR was 78.1%. Multivariable analysis showed that pathologic stage IIIA and EGFR mutation were significant risk factors for DFS. Grade 3 adverse events occurred in 10 patients (9.5%), and leukopenia (n=3, 2.9%) was the most common adverse event.Adjuvant Pem-Cis is superior to historical control without adjuvant treatment in terms of 2-year DFSR; the proportion of patients with stage IB and driver mutations were higher than that of patients in previous trials. Pem-Cis showed favorable tolerability as adjuvant chemotherapy (clinicaltrial.gov; Identifier: NCT02498860).

Background Studies on the application of targeted therapies for patients with non‐small cell lung cancer (NSCLC) who harbor rare genetic mutations are ongoing. In the present study, we investigated the real‐world data of NSCLC patients who harbor rare mutations. Methods We retrospectively analyzed patients with advanced or metastatic nonsquamous NSCLC aged >20 years with confirmed rare mutations (BRAF, ROS1, MET, RET, HER2, FGFR, and NTRK) from January 2015 to September 2020 at nine tertiary hospitals. In addition, we validated the lung cancer PCR panel kit in patients with confirmed mutations by NGS. Results Among 118 patients included, 88 received platinum‐based chemotherapy as first‐line chemotherapy. The progression‐free survival of patients with BRAF, ERBB2, MET, RET, and ROS1 mutations was 10.9 months (95% confidence interval [CI]: 1.3–20.5), 5.3 months (95% CI: 3.0–7.5), 7.2 months (95% CI: 3.6–10.9), 11.4 months (95% CI: 9.2–13.6), and 10.0 months (95% CI: 3.7–16.4) respectively (p = 0.041). The median overall survival (OS) was not reached in patients with ROS1 mutations; however, in BRAF, ERBB2, MET, and RET mutant patients, median OS was 14.1 months (95% CI: 10.1–14.1), 34.5 months (95% CI: 13.2–36.9), 22.7 months (95% CI: 1.7–24.0), and 29.8 months (95% CI: 28.9–61.3), respectively (p = 0.006). Of the 27 tissue samples, 26 (96.3%) showed the same PCR panel kit result with NGS. Conclusions First‐line platinum‐based chemotherapy showed durable benefit in patients with advanced or metastatic nonsquamous NSCLC harboring rare genetic mutation other than EGFR or ALK., This study shows real‐world data of NSCLC patients with rare genetic mutations, and the majority of patients were treated primarily with platinum‐based chemotherapy. First‐line platinum‐based chemotherapy showed durable benefit in patients with advanced or metastatic nonsquamous NSCLC harboring rare genetic mutations other than EGFR or ALK.

Malignant melanoma is responsible for 3.0 and 1.7% of cases of tumor incidence and tumor-associated mortality, respectively, in the Caucasian population. Melanoma is a type of skin cancer that occurs when melanocytes mutate and divide uncontrollably.

The inflammatory defense response of macrophages is a natural protective reaction in the immune system. Antioxidant and anti-inflammatory activities are closely related. In addition, the cell signaling pathway regulating inflammation is associated with MAPK and NF-κB signaling pathway phosphorylation. The present study aimed to evaluate whether the ethyl acetate fraction from

The leaf and stem extracts of Boehmeria nivea (BN) collected from three different regions in Korea were screened for their antioxidant, neuroprotective, estrogenic, insulin secretion, and α-glucosidase inhibitory activity. We also examined whether BN extracts regulate cancer cell growth, inflammatory-related gene expression, and lipid accumulation in cellular system. Leaf extracts possessed greater antioxidant, anti-proliferative in cancer cells, neuroprotective, estrogenic activity, and inhibitory effect on pro-inflammatory gene expression than stem extracts. Leaf and stem extracts inhibited lipid accumulation in three T3-L1 adipocytes but did not affect glucose-stimulated insulin secretion in INS-1 cells. We isolated and identified the phytochemical constituents in the n-butanol and ethyl acetate fractions of BN leaves by combining silica gel column chromatography with mass spectrometry and

The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N-acetyltransferase 2 (NAT2) acetylator phenotype, i.e., rapid, intermediate, and slow. Consequently, a uniform INH dose in the current clinical practice may lead to treatment failure and drug resistance emergence. There is a lack of studies on specific doses of INH for different NAT2 acetylator phenotypes among tuberculosis patients. Therefore, we aimed to provide insight into the optimal dosing of INH for each NAT2 acetylator phenotype with respect to the probability of achieving a pharmacokinetic (PK)/pharmacodynamic target. PK, NAT2 genotype, and clinical data were collected in a multicenter prospective cohort study conducted at 13 clinical centers in Korea. Population PK modeling and simulation were carried out. Data from 454 TB patients were divided into a training dataset and a test dataset with a ratio of 4 to 1. The PK of the training data were best described by a two-compartment model with allometric scaling for the body size effect. Importantly, NAT2 acetylator phenotypes significantly affected the apparent clearance. Our model provided better predictive performance compared to previously published models, which was evaluated by external validation using the test set. The simulation for assessing the target efficacy and toxicity indicated that the best INH dosing regimens for Korean tuberculosis patients were once-daily doses of 400, 300, and 200 mg for rapid, intermediate, and slow acetylators, respectively. In conclusion, our study provides a step forward in precision dosing for anti-tuberculosis management. This article is protected by copyright. All rights reserved.

Objectives The optimal sequence for the administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non‐small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. Materials and methods Electronic records of patients with EGFR‐mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan–Meier method and log‐rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results Of the 737 patients who received frontline afatinib treatment, 324 with complete records were selected (group A: 126, group B: 198). All patients in group A were T790M positive after afatinib, while patients in group B were all negative or unknown. The median TOT was 35.4 months (95% confidence interval [CI]: 27.7−45.6) in group A and 20.8 months (95% CI: 19.4−24.0) in group B. The median TOT with afatinib was 13.0 months (95% CI: 12.0−13.9) overall and 15.7 months (95% CI: 13.9−17.3) in group A. The 2‐ and 3‐year survival rates were 86.0 and 69.3% in group A and 75.9 and 55.3% in group B, respectively. Conclusion Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies., Our study evaluated the real‐world efficacy of sequential treatment of afatinib and osimertinib, and compared it with other chemotherapies as a second‐line treatment. Promising real‐world data on first‐line afatinib and second‐line osimertinib may maximize sustained clinical benefit with avoiding chemotherapy and may warrant consideration, though tailored personalized approaches are necessary.

Shift work that interferes with normal sleep patterns, is known to be a cause of sleep disturbance and has been studied through various occupational groups. However, it is not known which shift type is better for sleep health.This study included 568 firefighters. Sleep quality was evaluated using Pittsburgh Sleep Quality Index. Sleep quality was categorized into 2 groups; good quality (≤ 5 points) and poor quality (≥ 6 points). Demographic variables, depression, anxiety, type of shift, and job were collected by self-reported questionnaires. The χThree hundred thirty-seven firefighters (59.3%) have poor sleep quality. Compared to day workers, the odds ratios (ORs) of poor sleep quality were 2.169 (95% confidence interval: 1.137-4.134) in 6-day cycle, 2.161 (1.150-4.062) in 9-day cycle, 1.805 (1.087-2.997) in 21-day cycle, and 1.485 (0.718-3.069) in 3-day cycle. The ORs of poor sleep quality were 1.697(1.021-2.823) in fire suppression and 2.325 (1.213-4.455) in emergency medical service compared to administration.All shift work type except for the 3-day cycle was associated with poor sleep quality compared to day work.

Background In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR‐tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy. Methods This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR‐TKIs were included. Results Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR‐TKI treatment duration (OR, 1.039; p, In this multicenter retrospective study, whereas exon 19 deletion, the absence of L858R, previous EGFR‐TKI treatment duration and brain metastasis at initial diagnosis were associated with acquired T790M mutation, a previous EGFR‐TKI treatment duration was independently associated with acquired T790M mutation. However, the acquired T790M mutation group had improved survival compared to the T790M mutation‐negative group. In particular, the osimertinib user group had a better one‐year survival than the nonuser group among patients with acquired T790M mutation.

Background:The response of 1st-line EGFR-TKI treatment in advanced EGFR-mutated lung adenocarcinoma patients are highly effective, but its sustainability and clinical course are quite variable from patient to patient. In this study, we investigated the clinical impact of concomitant genetic mutations analyzed by targeted NGS on PFS and acquired resistance in advanced EGFR-mutated lung adenocarcinoma patients. Methods: Eighty-five advanced NSCLC patients harboring EGFR mutations were enrolled prospectively in multi-centers from 2019 to 2022 (NCT04122833). We performed the targeted next generation sequencing on 324 cancer-related genes by Foundation One CDx with pre-treated tumor samples. First- or second-generation EGFR-TKIs(gefitinib, afatinib, or erlotinib) were administered in 1st-line setting. After the progression, tissue re-biopsy or plasma liquid biopsy (FoundationOne Liquid CDx) for NGS if tissue biopsy is difficult or risk was performed. Results: Of the 85 patients (70.6% of female, 65.8% of nonsmoker, 56.4% of E19del and 38.8% of E21 L858R mutation), 50 patients experienced a disease progression in November, 2022. The median PFS was 20 months (95 %CI: 15.2-24.8). The most frequent co-mutations were TP53 (47.1%), CDKN2A/B loss (34.1%), MTAP loss (20%), NKX2-1amp(15.3%), MDM2amp (14.1%), RMB10, CCNE/CCND1 amp, NFKB1 amp (11.8%) and CDK4/6 amp (10.6%). Patients with TP53, CDK4/6 amp and MYC amp were independently associated with shorter PFS. In a multivariate analysis, tumors with copy number alterations such as CDK4/6 amp or Myc amp were also independently associated with shorter PFS. However, the CDKN2A/2B loss, MTAP loss, and MDM amp were not related with the PFS. In the number of co-mutations, patients harboring ≥5 co-mutations identified by NGS had shorter median PFS than patients with 0-1 or 2-4 co-mutations. (mPFS 0-1: 2-4: ≥5 co-mutations=35: 18: 9.3 months, p Conclusion: We have demonstrated that concomitant mutations detected by targeted NGS analysis provide significant impact on the drug response and clinical course of advanced EGFR-mutated adenocarcinoma patients treated by 1st-line EGFR-TKIs. It is suggested that targeted NGS along with PCR-based detection will be necessary for precision medicine-based individualized practice of 1st-line EGFR-TKI-based combination treatment. Citation Format: In Ae Kim, Seung Joon Kim, Sung Yong Lee, Chang Min Choi, Jae Cheol Lee, Tae Won Jang, Seung Hun Jang, Chan Kwon Park, Wan Seop Kim, Jae Young Hur, Hee Joung Kim, Young Whan Kim, Key Young Lee. Analysis of concomitant genetic alterations in advanced EGFR-mutated lung adenocarcinoma by targeted NGS: A multicenter prospective and real world study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3886.

Background Mutation analysis of circulating tumor DNA (ctDNA) is used for diagnosing lung cancer. This trial aimed to assess the efficacy of afatinib in treatment‐naïve patients with lung cancer harboring epidermal growth factor receptor mutations (EGFRm, exon 19 deletions or exon 21 point mutations) detected based on ctDNA. Methods The primary objective was the objective response rate (ORR) in the response evaluable (RE) population. EGFRm analysis of ctDNA was performed using PANA Mutype. Of the 331 patients screened, ctDNA was positive in 21% (68/331) in the detection of activating EGFRm. Among 81 subjects with tumor EGFRm, 48 showed matched EGFRm in their ctDNA (59% sensitivity). Results Therapy with afatinib 40 mg was initiated in 21 (female, 17; adenocarcinoma, 20) patients (intention‐to‐treat, ITT); dose modifications were made in 15 (71%). The ORR was 74% in the RE population (14/19); 11 patients showed EGFRm only in ctDNA (Group A), whereas 10 exhibited the same EGFRm in their ctDNA and tumor DNA (Group B). There was no significant difference in ORR between Groups A and B (80% and 67% RE, respectively). Median progression‐free survival (PFS) was 12.0 months, and no significant difference was observed according to the final afatinib dose, type of EGFRm, and Group A versus B. After progression, T790M mutation was found in 40% (6/15) of patients, and osimertinib was used as a second‐line treatment. Conclusions Afatinib showed similar ORR and PFS in patients with lung cancer harboring EGFRm in their ctDNA regardless of tumor EGFRm results. Key points Significant findings of the study Afatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first‐line treatment of EGFR‐mutated non‐small cell lung cancer based on tumor genotyping. What this study adds Our findings emphasize that the survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real‐world setting., Afatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first‐line treatment of EGFR‐mutated NSCLC based on tumor genotyping. The survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real‐world setting

We aimed to investigate the association between working hours and poor glycemic control using a cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES). The participants who were medically diagnosed with diabetes mellitus by a physician were defined as diabetic patients, and patients with hemoglobin A1c (HbA1c) levels >9.0% were considered as “poorly controlled”. The association of HbA1c level with working hours was examined by linear regression plot, using local regression line and logistic regression analyses. The local regression plot showed a smooth increasing pattern: the longer were the working hours, the higher were the HbA1c levels, even though it was not statistically significant. Odds ratios of working hours over 52 h per week were higher with the criterion of poor diabetic control (HbA1c >9.0%). The results were significant in elderly female workers (odds ratio 3.30, 95% confidence interval 1.19–9.18). Long working hours were associated with poor glycemic control, specifically among elderly female workers with diabetes.

Several studies have reported health or safety risk of temporary agency workers (TAW). Since most of the studies are just cross-sectional studies, we intended to identify the risk of occupational injury in TAW, using longitudinal study design.The Korea Health Panel 2009-2018 data were used in the study. For the statistical analysis of this study, we used a panel logit model to identify the risk of occupational injury in TAW compared to direct contract workers (DCW).There was no significant difference in risk of occupational injury between TAW and DCW among the overall population (adjusted OR 0.920, 95% CI 0.600-1.411). However, there was a significant increase in occupational injury in women (adjusted OR 2.134, 95% CI 1.092-4.170) and the "19-34" age group (adjusted OR 2.744, 95% CI 1.103-6.825) of TAW.This study provides evidence for vulnerable groups such as women and younger age groups in the relationship between TAW and occupational injury.

The “fourth industrial revolution” (FIR) is an age of advanced technology based on information and communication. FIR has a more powerful impact on the economy than in the past. However, the prospects for the labor environment are uncertain. The purpose of this study is to anticipate and prepare for occupational health and safety (OHS) issues.In FIR, nonstandard employment will be common. As a result, it is difficult to receive OHS services and compensation. Excessive trust in new technologies can lead to large-scale or new forms of accidents. Global business networks will cause destruction of workers' biorhythms, some cancers, overwork, and task complexity. The social disconnection because of an independent work will be a risk for worker's mental health. The union bonds will weaken, and it will be difficult to apply standardized OHS regulations to multinational enterprises.To cope with the new OHS issues, we need to establish new concepts of ''decent work” and standardize regulations, which apply to enterprises in each country, develop public health as an OHS service, monitor emerging OHS events and networks among independent workers, and nurture experts who are responsible for new OHS issues. Keywords: Fourth industrial revolution, Occupational health and safety, Workers' compensation, Workers' health

Purpose Sleep disturbances are prevalent in firefighters, but the relationship between patterns of shift work and sleep disturbances has not yet been investigated. Here, this relationship has been evaluated in Korean firefighters. Methods A cross-sectional study was conducted using an online questionnaire, which captured demographic, psychosocial and work-related characteristics. Sleep disturbance was assessed using the insomnia severity index (ISI). The relationship between insomnia and work-related factors (including type of shift work and the frequency of emergency events and off-duty work which means overtime work on off days) was analyzed. Results A total of 9810 firefighters completed the survey, representing approximately 21.5% of all Korean firefighters; data from 9738 subjects were included in the analysis. All firefighter roles were significantly associated with insomnia; the odds ratio (OR) was 2.456 (95% confidence interval [CI] 1.461–4.128) for fire suppression and 1.871 (95% CI 1.105–3.167) for the emergency medical services and rescue. However, the pattern of shift work did not show a statistically significant relationship. The OR increased along with the frequency of emergency events and off-duty work (p value for trend Conclusions This study found a significant association between the frequency of emergency and off-duty work and insomnia in Korean firefighters, whereas the pattern of shift work showed no significant relationship. Therefore, measures to reduce the frequency of emergency and off-duty work are required to prevent sleep disturbances in firefighters.

Non-small cell lung cancers (NSCLCs) harboring uncommon epidermal growth factor receptor (EGFR) mutations are heterogeneous and show variable prevalence and clinical responses to EGFR tyrosine kinase inhibitors. We investigated the characteristics of uncommon EGFR mutations and the clinical efficacy of afatinib in patients with NSCLC harboring uncommon EGFR mutations.In this multicenter, retrospective study, we analyzed patients with NSCLC with uncommon EGFR mutations in 16 South Korean institutes. Mutations were categorized according to their incidence: 1) major uncommon mutations (G719X and L861Q), 2) compound mutations, and 3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M).Of 703 patients with EGFR-mutant NSCLC, 64 (9.1%) had uncommon EGFR mutations. Afatinib demonstrated activity against tumors harboring major uncommon mutations [median time of treatment (TOT): 20.3 months, 95% confidence interval (CI)=15.1-25.5; overall survival (OS): 30.6 months, 95% CI=26.3-34.8] and compound mutations (median TOT: 12.3 months, 95% CI=7.7-17.0; OS: 29.1 months, 95% CI=20.4-37.7) but not against tumors harboring minor uncommon mutations (median TOT: 3.8 months, 95% CI=1.7-6.0; OS: 8.5 months, 95% CI=5.2-11.7). The S768I mutation was present in 14 patients (1.99%). The median TOT and OS were not significantly different between S768I mutations and resistant exon 20 mutations.Afatinib is effective in patients with NSCLC harboring major uncommon and compound EGFR mutations.

One of the Korean endemic plants, Abeliophyllum distichum Nakai (Oleaceae), contains acteoside, which is a glycoside exhibiting neuroprotective, anti-inflammation effects and antibacterial capacities. We conducted an investigation on the effects of the callus of A. distichum (cultivar Okhwang 1, CAO) on pro-inflammatory mediators released following nuclear factor-кB (NF-кB), phosphatidylinositol 3-kinase/Akt (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signal activation in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Immunoblotting was employed to find out the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), and activation of MAPK molecules, NF-κB and Akt. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. High-performance liquid chromatography revealed that CAO was rich in acteoside and isoacteoside. As a result, CAO inhibited the generation of NO, cytokines, COX-2, and iNOS expression. Further, translocation to the nuclear of NF-κB p65 and degradation of the inhibitor of NF-кB (IкB) were alleviated by suppressing phosphorylation. Additionally, CAO significantly impacted MAPK pathway activation by potentially reducing phosphorylation of MAPKs. These results indicate that the anti-inflammatory effect of CAO is mediated via the inhibition of MAPK, PI3K/Akt, and NF-κB signaling pathways, probably via glycosides, phenolics, and flavonoids bioactivity derived from plants. CAO can serve as a potential anti-inflammatory agent, which alleviates inflammation factors and act through specific cell signaling pathways.

Objectives Immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor-1 and its ligand have achieved impressive success in treating patients with advanced-stage non-small cell lung cancer (NSCLC) after failed first-line cytotoxic chemotherapy. However, knowledge on clinical biomarkers that could help select patients who will respond well to second-line ICI therapy is limited. Patients and methods Medical records of patients with NSCLC treated with first-line platinum-based chemotherapy and subsequent second-line ICI were collected from 6 medical centers between January 2018 and June 2020. Clinical information, pathologic variables, and radiologic findings of the data collected were reviewed. The patients were followed up until the date of the last visit, the death of any cause, or the end of data recording (December 31, 2020). Results A total of 181 patients with NSCLC were treated with second-line ICI following first-line platinum-based doublet chemotherapy. The median progression-free survival was 2.0 months (interquartile range, 1.0 to 5.5 mo), and the median overall survival was 12.0 months (interquartile range, 6.0 to 20.0 mo). Low body mass index (BMI) was independently associated with progression-free survival (odds ratio [OR], 0.826; 95% confidence interval [CI], 0.723-0.945; P=0.005). Similarly, a low BMI (OR, 0.839; 95% CI, 0.740-0.952; P=0.005) and a high number of metastatic organs (OR, 1.682; 95% CI, 1.156-2.448; P=0.007) were independently associated with the overall survival after second-line ICI therapy. Conclusion BMI and the number of metastatic sites were significantly associated with second-line ICI therapy outcomes in patients with NSCLC receiving first-line platinum-based chemotherapy.

This study investigated the association between exercise and cardiovascular load in Korean mail carriers with high occupational physical activity (OPA). A total of 36 subjects completed a questionnaire, and their heart rates were measured for 3 consecutive days. Treadmill tests were used determine maximal oxygen uptake (VO

Background: This cross-sectional study assessed the sleep quality using the ActiGraph and investigated the relationship between the parameters of sleep assessment and the type of shift work in Korean firefighters. Methods: The participants were 359 firefighters: 65 day workers (control group) and 294 shift workers (shift work group: 77 firefighters with 3-day shift, 72 firefighters with 6-day shift, 65 firefighters with 9-day shift, and 80 firefighters with 21-day shift). Sleep assessments were performed using the ActiGraph (wGT3X-BT) for 24 hours during day shift (control and shift work group) and night shift and rest day (shift work group). The participants recorded bed time and sleep hours during the measurement period. Results: Sleep efficiency, total sleep time, and percentage of wake after sleep onset during night work were lower in the shift work group than control group (p

Afatinib, a second-generation, irreversible pan-HER inhibitor, shows better suppression of T790M-positive lung cancer cells than gefitinib in preclinical studies. However, whether the effect of afatinib on T790M acquisition differs from that of gefitinib when used clinically as first-line therapy remains unclear. To reaffirm the preclinical efficacy of afatinib on T790M-positive lung cancer cells, H1975 cells and established PC-9 cells resistant to gefitinib and erlotinib by T790M were used. In total, 398 patients with second biopsy at progression with stage IIIB/IV non–small cell lung cancer with EGFR mutation, treated with afatinib or gefitinib as first-line therapy, were retrospectively reviewed. Propensity score matching was used to balance covariates. Afatinib inhibited the growth of lung cancer cells with low T790M allele frequencies, which are resistant to gefitinib, but not those with high T790M allele frequencies. Afatinib and gefitinib showed similar efficacy in terms of progression-free survival (PFS) (11.5 vs 13.4 months, P = .08) and overall survival (OS) (29.3 vs 28.5 months, P = .76). T790M patients had better PFS and OS than those without T790M. There was no significant difference in the cumulative T790M acquisition ratio over time between afatinib and gefitinib (48.8% vs 59.3%, P = .317). The median time to acquire T790M was 12.9 months for afatinib and 15.7 months for gefitinib (P = .342). Although afatinib inhibited the growth of lung cancer cells with low T790M allele frequencies in preclinical studies, this could not be translated into clinical efficacy in terms of lowering the rate or delaying the time of T790M acquisition.

This study investigates whether workers with long working hours as well as shift workers perceive higher unmet dental care needs, and whether there is a gender difference in the associations. We used the Korea Health Panel (2009, 2011–2014) involving 20,451 person-wave observations from 5567 individuals. Perceived unmet dental care needs was defined when the participants reported that they perceived a need for dental treatment or check-up but had failed to receive dental care services during the past year. Fixed effects logit models were applied to examine how changes in weekly working hours or shift work status were linked to changes in perceived unmet dental needs within each individual. Among participants, 15.9–24.7% reported perceived unmet dental needs and the most common reason was time scarcity. We found that long working hours (&gt, 52 h/week) was significantly associated with perceived unmet dental needs due to time scarcity in both men (OR = 1.42, 95% CI 1.13–1.78) and women (OR = 1.35, 95% CI 1.03–1.79) compared workers working 40–52 h per week. Shift work was also a significant risk factor, but only in women (OR = 1.57, 95% CI 1.06–2.32). These findings provide evidence for labor policies to reduce working hours in order to improve access to dental care services.

The optimal sequence for administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non-small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. Electronic records of patients with EGFR-mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and October 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Of the 737 patients who received frontline afatinib treatment, 360 with complete records were selected (group A:154, group B: 206). The median TOT was 33.9 months (95% confidence interval [CI]: 24.5−43.3) in group A and 21.3 months (95% CI: 19.4−23.1) in group B. The median TOT with afatinib was 12.9 months (95% CI: 11.8−14.0) overall, and 15.2 months (95% CI: 13.2−17.1) in group A. The 2- and 3-year survival rates were 86.0% and 69.3% in group A and 75.9% and 55.3% in group B, respectively. Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies. Therefore, this sequential treatment strategy may offer clinical benefits to patients with EGFR-mutated NSCLC.

Shift work disorder (SWD), which is characterized by insomnia and excessive sleepiness related with shift work, is one of the most common health problems in shift workers. Shift work disorder causes insomnia, fatigue, worse work performance, an increased likelihood of accidents, and a poor quality of life. In addition, SWD is associated with decreased productivity and increased economic costs. The correct management of SWD is important to prevent sleep disturbances and maintain work performance in shift workers. To diagnose and evaluate SWD, it is necessary to take detailed medical histories, assess the severity of sleep disturbances, and evaluate shift workers’ sleep using a sleep diary and actigraphy. The work-fitness evaluation should include recommendations on how shift workers can reduce their sleep disturbances and increase work performance, as well as the assessment of work performance. This paper reviews previous research on the evaluation, diagnosis, and management of SWD and summarizes the work-fitness evaluation of SWD.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a standard of care in the first-line treatment of patients with EGFR mutation-positive metastatic non-small-cell lung cancer (NSCLC). EGFR mutations are relatively common in Asian patients with NSCLC, and there is an increasing number of studies supporting the effectiveness of the second-generation TKI afatinib in routine clinical practice in Asia. This article reviews these real-world studies investigating afatinib as first-line treatment for EGFR mutation-positive NSCLC in Asian patients. Evidence from real-world studies with afatinib in this patient population supports findings from randomized controlled trials (RCTs) showing that afatinib is associated with more favorable outcomes compared with the first-generation EGFR TKIs. The effectiveness of afatinib has also been shown in real-world studies in Asian patients with poor prognostic factors, who are often under-represented or excluded from RCTs, such as those with uncommon EGFR mutations, brain metastases, or poor performance status, and elderly patients. The tolerability profile of afatinib in the real-world setting reflects that seen in RCTs, with no new safety signals reported in real-world studies in Asian patients with EGFR mutation-positive NSCLC. Dose-modification strategies also seem to be effective in the real world, with results of the RealGido study, which included 44% Asian patients, confirming findings from prospective clinical trials showing that tolerability-guided afatinib dose modifications can reduce the incidence of adverse events without adversely affecting clinical outcomes. While further research, including clinical trial data, is needed, real-world data have also demonstrated the feasibility of sequential afatinib followed by the third-generation TKI osimertinib in T790M-positive EGFR mutation-positive patients, which showed longer overall survival. Together, these real-world results demonstrate the real-world clinical effectiveness of afatinib as first-line treatment for patients with EGFR mutation-positive NSCLC., Plain Language Summary Some patients with non-small-cell lung cancer (NSCLC) have a mutation in the EGFR gene, whose normal function is to regulate cell division. The proportion of NSCLC patients with these EGFR mutations is particularly high in Asian populations. Treatment of patients with EGFR mutation-positive NSCLC has changed markedly in recent years following the development of drugs called EGFR tyrosine kinase inhibitors (TKIs). Several EGFR TKIs have been developed, and clinical trial data have shown that the second-generation TKI afatinib and the third-generation TKI osimertinib are more effective than the first-generation TKIs erlotinib and gefitinib. However, these clinical trials, known as randomized controlled trials (RCTs), are highly selective, and many patients, such as elderly patients or those in poor health and/or with underlying diseases, are excluded. Consequently, less is known about how well TKIs work in these patients. Therefore, other less-selective studies, known as observational or ‘real-world’ studies, are used to provide information on the safety and effectiveness of EGFR TKIs across all patient groups seen in the clinic, not just those included in RCTs. In this article, we review the real-world evidence for the TKI afatinib as a treatment for Asian patients with EGFR mutation-positive NSCLC. Evidence from these real-world studies confirms that afatinib is more effective than erlotinib and gefitinib in real-world patients in Asia. Importantly, the efficacy and safety of afatinib is seen in groups of Asian patients often excluded from clinical trials including the elderly, those with brain metastases, and frail patients or those with other underlying diseases. Importantly, the safety profile of afatinib was similar to that seen in RCTs, and no additional side effects were identified in real-world patients. Also, importantly, real-world studies show that side effects can be effectively controlled by reducing the dose of afatinib. Real-world studies have also been used to demonstrate the feasibility and effectiveness of the sequential use of EGFR TKIs, particularly in Asian patients.

Objectives This study aimed to investigate the relationship between working hours and lifestyle behaviors using data from a large nationally representative panel survey. Methods We used the Korea Health Panel Study (KHPS) data from 2011 to 2014. Weekly working hours and lifestyle risk factors were assessed by questionnaires. Comparing to the reference group, the weekly working hours were 40 h per week, odds ratios and 95% confidence intervals for smoking status, alcohol consumption status, and regular exercise status of other weekly working hours groups (52) were calculated, using generalized estimating equation models considering repeated measures. Results Our findings clearly showed a relationship between long working hours and unhealthy lifestyles, such as cigarette smoking, alcohol consumption, physical inactivity, and insufficient sleep. Additionally, weekly working hours are positively associated with the amount of smoking and drinking, and inversely associated with sleep duration among those who worked 40 h or more per week. Conclusion Long working hours are associated with unhealthy lifestyles, such as cigarette smoking, alcohol consumption, physical inactivity, and insufficient sleep.

Background: Firefighters are vulnerable to irregular sleep patterns and sleep disturbance due to work characteristics such as shift work and frequent dispatch. However, there are few studies investigating intervention targeting sleep for firefighters. This preliminary study aimed to develop and test a sleep intervention, namely FIT-IN (Firefighter’s Therapy for Insomnia and Nightmares), which was based on existing evidence-based treatment tailored to firefighters in consideration of their occupational characteristics. Methods: This study implemented a single-group pre-post study design, utilizing an intervention developed based on brief behavior therapy for insomnia with imagery rehearsal therapy components. FIT-IN consisted of a total of three sessions (two face-to-face group sessions and one telephone session). Participants were recruited from Korean fire stations, and a total of 39 firefighters participated. Participants completed a sleep diary for two weeks, as well as the following questionnaires to assess their sleep and psychological factors: insomnia severity index (ISI), disturbing dream and nightmare severity index (DDNSI), Epworth sleepiness scale (ESS), depressive symptom inventory-suicidality subscale (DSI), and Patient Health Questionnaire-9 (PHQ-9). These questionnaires were administered before the first session and at the end of the second session. Results: The FIT-IN program produced improvements in sleep indices. There was a significant increase in sleep efficiency (p &lt, 0.01), and a decrease in sleep onset latency, number of awakenings, and time in bed (p &lt, 0.05), as derived from weekly sleep diaries. In addition, significant decreases were shown for insomnia (p &lt, 0.001) and nightmare severity (p &lt, 0.01). Conclusion: There were significant improvements in sleep and other clinical indices (depression, PTSD scores) when comparing pre-and post-intervention scores. FIT-IN may be a feasible and practical option in alleviating sleep disturbance in this population. Further studies will be needed to ascertain FIT-IN’s effectiveness.

Background: Recent research indicates that shift work is associated with neurocognitive function. However, studies that examine the association between shift work and neurocognitive function in firefighters have not yet been performed. We examined the effect of shift work on neurocognitive function in firefighters by measuring and comparing neurocognitive function before and after night shift. Methods: 352 firefighters from eight fire stations in South Korea were included in this study. We performed neurocognitive function test using central nervous system vital signs (CNSVS) during daytime work and on the next day after night work. We performed paired t-tests to assess differences between neurocognitive function before and after night work. We also compared neurocognitive function in insomnia and depression. We used a general linear model to analyze the associations between shiftwork schedule and the changes in neurocognitive function. Results: The neurocognitive function significantly decreased in six domains (composite memory, verbal memory, visual memory, complex attention, psychomotor speed, and motor speed) as did the neurocognitive index on the next day after night work compared with during day work. These decreased domains were the same following night work regardless of the type of shift work. Conclusion: Night work in firefighters may cause neurocognitive decline.