A nationwide real-world study for evaluation of effectiveness and safety of T-DM1 in patients with HER2-positive metastatic breast cancer in Korea (KCSG BR19-15).

Purpose: This study aimed to investigate clinical practices and factors related to the outcomes of T-DM1 use in patients with HER2-positive metastatic breast cancer (mBC). Methods: We included patients with HER2-positive mBC who received T-DM1 as a palliative therapy between August 2017 and December 2018. The safety and outcomes of T-DM1, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) for mortality or progression to HER2-positive mBC. Results: In total, 824 patients were enrolled during the study period. The mean age of patients was 58 years, and 516 (62.6%) patients relapsed after curative treatment. Excluding a history of endocrine therapy, 341 (41.4%) patients previously received none or first-line chemotherapy, 179 (21.7%) received second-line therapy, and 303 (36.9%) received third-or later-line chemotherapy before T-DM1 therapy. During a median follow-up of 16.8 months, the ORR was 35%, the median PFS was 6.6 months, and the median OS was not reached. The clinical factors associated with the hazard of progression were age (<65 years), poor performance status (⩾2), advanced line of palliative chemotherapy (⩾2), prior pertuzumab use, and treatment duration of palliative trastuzumab (<10 months). Common grade 3-4 adverse events were thrombocytopenia (n = 107, 13.2%), neutropenia (n = 23, 2.8%), anemia (n = 21, 2.6%), and elevated liver enzyme (n = 20, 2.5%). Hypokalemia (⩽3.0 mmol/L) and any-grade bleeding events occurred in 25 (3.1%) and 94 (22.6%) patients, respectively. Conclusion: This is the first nationwide real-world study of T-DM1 use in patients with HER2-positive mBC in Korea. The effectiveness and toxicity profiles of T-DM1 in real-world practice were comparable to those in randomized trials. Moreover, patient factors and previous anti-HER2 therapy could predict the outcomes of T-DM1 therapy.

Data collection framework for electronic medical record-based real-world data to evaluate the effectiveness and safety of cancer drugs: a nationwide real-world study of the Korean Cancer Study Group.

Background: Electronic medical records (EMRs) have the highest value among real-world data (RWD). The aim of the present study was to propose a data collection framework of EMR-based RWD to evaluate the effectiveness and safety of cancer drugs by conducting a nationwide real-world study based on the Korean Cancer Study Group. Methods: We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Standard operating procedures for systematic data collection were prospectively developed. Investigator reliability was evaluated using the concordance rate between the recommended input value for representative fictional cases and the input value of each investigator. Reliability of collected data was evaluated twice during the study period at three institutions randomly selected using the concordance rate between the previously collected data and data collected by an independent investigator. The reliability results of the investigators and collected data were used for revision of the electronic data capture system and site training. Results: Between the starting date of medical insurance coverage and December 2018, a total of 1063 patients at 56 institutions in the RAM/PTX cohort and 824 patients at 60 institutions in the T-DM1 cohort were included. Mean investigator reliability in the RAM/PTX and T-DM1 cohorts was 73.5% and 71.9%, respectively. Mean reliability of collected data in the RAM/PTX and T-DM1 cohort was 90.0% for both cohorts in the first analysis and 89.0% and 84.0% in the second analysis, respectively. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively. Conclusion: This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs.

Ramucirumab plus paclitaxel as a second-line treatment in HER2-positive gastric cancer: subgroup analysis of a nationwide, real-world study in Korea (KCSG-ST19-16).

BACKGROUND: A subgroup analysis of data from a nationwide study (KCSG-ST19-16) was performed to evaluate the efficacy and safety of second-line ramucirumab plus paclitaxel treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma. METHODS: The KCSG-ST19-16 study enrolled a total of 1063 patients from 56 hospitals in South Korea with advanced gastric or GEJ adenocarcinoma, who had received second-line treatment with ramucirumab plus paclitaxel. HER2 status was known for 994 (93.5%) of these patients, who were thus included in the subgroup analysis. RESULTS: In total, 163 of 994 patients (16.4%), had HER2-positive gastric or GEJ adenocarcinoma. The objective response rate to ramucirumab plus paclitaxel treatment was significantly higher in patients with HER2-positive disease compared to those with HER2-negative disease (23.0% [95% confidence interval (CI), 15.9-30.1] vs. 15.1% [95% CI, 12.3-17.9], p = 0.025). The median progression-free survival was longer in patients with HER2-positive versus HER2-negative disease, but the difference was not statistically significant (4.3 months [95% CI, 3.7-5.3] vs 3.7 months [95% CI, 3.4-4.0], p = 0.054). There was no statistically significant difference in median overall survival (OS) between the groups (9.8 months [95% CI, 8.9-12.3] vs 10.1 months [95% CI, 9.2-10.9], p = 0.564). CONCLUSIONS: In patients with HER2-positive gastric or GEJ adenocarcinoma, the objective response rate to second-line treatment with ramucirumab plus paclitaxel was significantly higher compared to patients with HER2-negative disease. However, an increased response to treatment was not associated with an improvement in OS.

Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma: a nationwide real-world outcomes in Korea study (KCSG-ST19-16).

BACKGROUND: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, real-world data from large study cohorts focused on ramucirumab plus paclitaxel in gastric cancer are limited. METHODS: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between 1 May 2018 and 31 December 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy. RESULTS: In total, 1063 patients were included in the present study. The objective response rate and disease control rate were 15.1% and 57.7%, respectively. The median progression-free survival was 4.03 months (95% confidence interval, 3.80-4.27) and the median overall survival was 10.03 months (95% confidence interval, 9.33-10.73). Grade 3 or higher treatment-related adverse events with incidence of ⩾5% were neutropenia (35.1%) and anemia (10.5%). Based on multivariable analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ⩾2, weight loss ⩾10% in the previous 3 months, GEJ of primary tumor, poor or unknown histologic grade, number of metastatic sites ⩾3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment <6 months. CONCLUSION: Our large-scale, nationwide, real-world data analysis of an unselected real-world population adds evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

Association between body mass index, missing data, and mortality risk among critically ill patients: the role of missing-data imputation.

BACKGROUND: We aimed to investigate the association between body mass index (BMI) at the time of intensive care unit (ICU) admission and 90-day mortality risk in complete-case datasets that ignore missing data as well as in datasets with multiple imputation for missing data. METHODS: This retrospective study analysed the medical records of adult patients admitted to ICUs in a single tertiary academic hospital. For BMI analysis, data were classified into four groups: underweight (<20 kg/m2 ), normal (20-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). RESULTS: A total of 24,928 patients were examined. Among them, 5,916 (23.7%) patients had missing BMI data at ICU admission, and the missing mechanism was not missing completely at random. In the multivariable Cox regression analysis, the 90-day mortality risk of underweight patients in the complete-case group increased by 1.49 times compared with that of normal BMI patients with a hazard ratio (HR) of 1.49 (95% confidence interval: 1.34-1.66; P<0.001), whereas the 90-day mortality risk of underweight patients in the multiple imputation group increased by 1.36 times compared with that of normal BMI patients (HR: 1.36, 95% confidence interval: 1.24-1.49; P<0.001). CONCLUSIONS: We showed that the occurrence of missing BMI data at ICU admission could affect the prediction of 90-day mortality in critically ill patients. Particularly, missing BMI data had the potential to slightly overestimate the 90-day mortality of underweight patients. Therefore, multiple imputation for missing BMI data can be an appropriate statistical option to reduce bias.

Psychological characteristics and associations between living kidney transplantation recipients and biologically related or unrelated donors.

BACKGROUND: Although recipients and donors in living kidney transplantation experience psychological distress-including depression and anxiety-during the pre-operative period, very few studies have evaluated the related psychological reactions. This study aimed to determine the characteristics and correlations of the mood states and personality of recipients and donors (genetically related and unrelated) of living kidney transplantations. METHODS: A total of 66 pairs of living donors and recipients were enrolled from April 2008 to June 2019 in this study, of whom 53 eligible pairs of living donors and recipients were included in the retrospective analysis of their psychological assessments in the pre-transplantation states. While participants' personality patterns were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), mood states were evaluated via both the State-Trait Anxiety Inventory (STAI) and The Center for Epidemiologic Studies Depression Scale (CES-D). Statistical analysis was performed using paired t-tests and Spearman's correlation analyses. RESULTS: The recipient group showed significantly higher scores for Hypochondriasis (t = - 4.49, p = .0001), Depression (t = - 3.36, p = .0015), and Hysteria (t = - 3.30, p = .0018) of MMPI-2 and CES-D (t = - 3.93, p = .0003) than the donor group. The biologically unrelated recipient group reported higher scores of Hypochondriasis (t = - 3.37, p = .003) and Depression (t = - 2.86, p = 0.0098) than the unrelated donor group. Higher scores for Hypochondriasis (t = - 3.00, p = 0.0054) and CES-D (t = - 3.53, p = .0014) were found in the related recipient group. A positive association was found for Hypomania (r = .40, p = .003) of MMPI-2, STAI-S (r = .36, p = .009), and CES-D (r = .36, p = .008) between the recipient and donor groups. CONCLUSIONS: Recipients suffered from a higher level of depression and somatic concerns than donors before living kidney transplantation. Psychological problems like depression and anxiety can occur in both living kidney transplantation donors and recipients. This study suggests that clinicians must pay attention to mood states not only in recipients but also in donors because of emotional contagion.

Effectiveness of a Smartphone App With a Wearable Activity Tracker in Preventing the Recurrence of Mood Disorders: Prospective Case-Control Study.

BACKGROUND: Smartphones and wearable devices can be used to obtain diverse daily log data related to circadian rhythms. For patients with mood disorders, giving feedback via a smartphone app with appropriate behavioral correction guides could play an important therapeutic role in the real world. OBJECTIVE: We aimed to evaluate the effectiveness of a smartphone app named Circadian Rhythm for Mood (CRM), which was developed to prevent mood episodes based on a machine learning algorithm that uses passive digital phenotype data of circadian rhythm behaviors obtained with a wearable activity tracker. The feedback intervention for the CRM app consisted of a trend report of mood prediction, H-score feedback with behavioral guidance, and an alert system triggered when trending toward a high-risk state. METHODS: In total, 73 patients with a major mood disorder were recruited and allocated in a nonrandomized fashion into 2 groups: the CRM group (14 patients) and the non-CRM group (59 patients). After the data qualification process, 10 subjects in the CRM group and 33 subjects in the non-CRM group were evaluated over 12 months. Both groups were treated in a similar manner. Patients took their usual medications, wore a wrist-worn activity tracker, and checked their eMoodChart daily. Patients in the CRM group were provided with daily feedback on their mood prediction and health scores based on the algorithm. For the CRM group, warning alerts were given when irregular life patterns were observed. However, these alerts were not given to patients in the non-CRM group. Every 3 months, mood episodes that had occurred in the previous 3 months were assessed based on the completed daily eMoodChart for both groups. The clinical course and prognosis, including mood episodes, were evaluated via face-to-face interviews based on the completed daily eMoodChart. For a 1-year prospective period, the number and duration of mood episodes were compared between the CRM and non-CRM groups using a generalized linear model. RESULTS: The CRM group had 96.7% fewer total depressive episodes (n/year; exp ß=0.033, P=.03), 99.5% shorter depressive episodes (total; exp ß=0.005, P<.001), 96.1% shorter manic or hypomanic episodes (exp ß=0.039, P<.001), 97.4% fewer total mood episodes (exp ß=0.026, P=.008), and 98.9% shorter mood episodes (total; exp ß=0.011, P<.001) than the non-CRM group. Positive changes in health behaviors due to the alerts and in wearable device adherence rates were observed in the CRM group. CONCLUSIONS: The CRM app with a wearable activity tracker was found to be effective in preventing and reducing the recurrence of mood disorders, improving prognosis, and promoting better health behaviors. Patients appeared to develop a regular habit of using the CRM app. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088657; https://clinicaltrials.gov/ct2/show/NCT03088657.

Temporal association between zolpidem medication and the risk of suicide: A 12-year population-based, retrospective cohort study.

There have been concerns about abuse and unnecessary chronic administration of zolpidem, and zolpidem's relation to suicide risk. To investigate the temporal association of zolpidem with the risk of suicide, we conducted a 12-year, population-based, retrospective cohort study on the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Data were collected from 2002 to 2013 from the NHIS-NSC, and data cleaning was performed for 1,125,691 subjects. Cox proportional hazards regression analysis was used to investigate the correlation over time between zolpidem medication and suicide. Over intervals commencing after 80 months of observation, the adjusted hazard ratio of suicides associated with the use of the zolpidem was 2.01 (95% CI: 1.58-2.56; p < 0.001). The mean cumulative number of days of zolpidem prescription was significantly longer in the suicide group than in the non-suicide group after log-transformation (p = 0.005). Cases of chronic use of zolpidem (over six months or one year) were significantly more common in the suicide group compared to the non-suicide group (p = 0.002 and 0.005, respectively). Subjects who received zolpidem medication had a significantly higher risk of suicide after at least 80 months of observation, suggesting a long-term increased suicide risk associated with insomnia exposed to zolpidem medication.

Preadmission Statin Use and 90-day Mortality in the Critically Ill: A Retrospective Association Study.

BACKGROUND: This study aimed to examine the association between preadmission statin use and 90-day mortality in critically ill patients and to investigate whether this association differed according to statin type and dose. We hypothesized that preadmission statin use was associated with lower 90-day mortality. METHODS: This retrospective cohort study analyzed the medical records of all adult patients admitted to the intensive care unit in a single tertiary academic hospital between January 2012 and December 2017. Data including preadmission statin use, statin subtype, and daily dosage were collected, and the associations between these variables and 90-day mortality after intensive care unit admission were examined. The primary endpoint was 90-day mortality. RESULTS: A total of 24,928 patients (7,396 statin users and 17,532 non-statin users) were included. After propensity score matching, 5,354 statin users and 7,758 non-statin users were finally included. The 90-day mortality rate was significantly higher in non-statin users (918 of 7,758; 11.8%) than in statin users (455 of 5,354; 8.5%; P < 0.001). In Cox regression analysis, the 90-day mortality rate was lower among statin users than among non-statin users (hazard ratio: 0.70, 95% CI: 0.63 to 0.79; P < 0.001). Rosuvastatin use was associated with 42% lower 90-day mortality (hazard ratio: 0.58, 95% CI: 0.47 to 0.72; P < 0.001). There were no specific significant differences in the association between daily statin dose and 90-day mortality. In competing risk analysis, the risk of noncardiovascular 90-day mortality in statin users was 32% lower than that in non-statin users (hazard ratio: 0.68, 95% CI: 0.60 to 0.78; P < 0.001). Meanwhile, cardiovascular 90-day mortality was not significantly associated with statin use. CONCLUSIONS: Preadmission statin use was associated with a lower 90-day mortality. This association was more evident in the rosuvastatin group and with noncardiovascular 90-day mortality; no differences were seen according to daily dosage intensity.

Preadmission chronic opioid usage and its association with 90-day mortality in critically ill patients: a retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the association of chronic opioid usage with 90-day mortality in critically ill patients after admission to the ICU. METHODS: This retrospective cohort study analysed the medical records of adult patients admitted to ICUs in a tertiary academic hospital between January 2012 and December 2017. Patients taking opioids regularly for more than 4 weeks before ICU admission were defined as chronic opioid users, whereas the others were defined as opioid-naïve patients. RESULTS: We selected 18 409 patients for this study, including 757 (4.1%) chronic opioid users. After propensity matching, 2990 patients (chronic opioid users, 757; opioid-naïve, patient: 2233) were included in the analysis. The odds of 90-day mortality were higher in chronic opioid users than in opioid-naïve patients using both the generalised estimating equation model for the propensity-matched cohort (odds ratio=1.90; 95% confidence interval, 1.57-2.31; P<0.001) and the multivariable logistic regression model for the entire cohort (odds ratio=2.20; 95% confidence interval, 1.81-2.66; P<0.001). Additionally, this association was significant in cancer patients and non-chronic kidney disease (CKD) patients and was not significant in non-cancer and CKD patients. CONCLUSIONS: Our results suggest that in a cohort of critically ill adult patients, chronic opioid use is associated with an increase in 90-day mortality. This association was more evident in cancer patients and non-CKD patients.

Retrospective analysis of 30-day unplanned readmission after major abdominal surgery with reversal by sugammadex or neostigmine.

BACKGROUND: Sugammadex is associated with fewer postoperative complications, but its impact on 30-day unplanned readmission is unclear. METHODS: This was a single-centre retrospective observational study of patients after major abdominal surgery between 2010 and 2017, where rocuronium was the only neuromuscular blocker used. The primary endpoint was the difference in incidence of 30-day unplanned readmission between reversal with sugammadex or neostigmine. The secondary endpoints were the length of hospital stay after surgery and related hospital charges (total charges excluding those related to surgery and anaesthesia). Analysis included propensity score matching and generalised mixed-effects modelling. RESULTS: Mixed-effects logistic regression analysis of 1479 patients (sugammadex: 355; neostigmine: 1124) showed that the incidence of 30-day unplanned readmission was 34% lower (odds ratio [OR]: 0.66, 95% confidence interval [CI]: 0.46-0.96, P=0.031), the length of hospital stay was 20% shorter (exponential regression coefficient: 0.80, 95% CI: 0.77-0.83, P<0.001), and related hospital charges were 24% lower (exponential regression coefficient: 0.76, 95% CI: 0.67-0.87, P<0.001) in the sugammadex group than in the neostigmine group. For patients living ≥50 km from the hospital, the incidence of 30-day unplanned readmission was 68% lower in the sugammadex group than in the neostigmine group (OR: 0.32, 95% CI: 0.13-0.79, P=0.014), while it was not significant for patients living <50 km from the hospital (P=0.319). CONCLUSIONS: Compared with neostigmine, reversal of rocuronium with sugammadex after major abdominal surgery was associated with a lower incidence of 30-day unplanned readmission, a shorter hospital stay, and lower related hospital charges.

Intimate partner violence and incidence of depression in married women: A longitudinal study of a nationally representative sample.

BACKGROUND: Intimate partner violence (IPV) has a serious detrimental effect on mental health outcomes. We aimed to investigate the association of verbal or physical IPV with incidence of depressive symptoms in both married women and men according to the victim-perpetrator role. The potential mediating role of verbal or physical IPV in the association between satisfaction level with family relationships or childhood adversity and the incidence of depressive symptoms in married adults was also explored. METHODS: The Korea Welfare Panel Study (KOWEPS) in 2006 and 2007 dataset was analyzed for 9217 married respondents aged 19 years or older. Physical and verbal IPV was assessed according to victim-perpetrator role in 2006. Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression Scale, 11-item version in 2006 and 2007. Association of IPV with incidental depressive symptoms was investigated with logistic regression analysis fully-adjusted for all potential confounding factors. RESULTS: The bidirectional role of verbal IPV and victimization by physical IPV led to incidence of depressive symptoms in married women. Verbal IPV significantly mediated the association between satisfaction level with the family relationship and incidental depressive symptoms in women. LIMITATIONS: We did not investigate the influence of premorbid depressive symptoms on new-onset IPV. CONCLUSIONS: This study is the first to demonstrate that gender and the victim-perpetrator role are critical moderating factors in the association between IPV and depressive symptom incidence using a nationally representative sample.

Social capital, socioeconomic status, and depression in community-living elderly.

A growing body of evidence has suggested that social capital is an upstream social determinant of mental health. We investigated the association of cognitive social capital, including interpersonal trust and reciprocity, with depressive symptoms in the elderly. We also explored the mediating role of cognitive social capital in the association between socioeconomic status (SES) and depressive symptoms and the moderating effect of SES on the relationship between social capital and depressive symptoms. Data from the 2012 Korea Welfare Panel Study (KOWEPS) was analyzed for 5969 participants aged 60 years or older. Cognitive components of social capital, including interpersonal trust and reciprocity, were evaluated using single-item questionnaires. Socioeconomic and health-related characteristics were investigated and depressive symptoms were evaluated by an 11-item version of the Center for Epidemiologic Studies Depression Scale. Low interpersonal trust and reciprocity levels were significantly associated with depressive symptoms in the elderly. Reciprocity level mediated the association between household income level and depressive symptoms. We did not observe any significant moderating effect of SES on the association between cognitive social capital and depressive symptoms. A significant association between cognitive social capital and depressive symptoms in Korean elderly was found. We elucidated how SES interacted with depressive symptoms through the mediation pathway of cognitive social capital using a representative sample of the Korean elderly population.

Effects of Astragalus Extract Mixture HT042 on Height Growth in Children with Mild Short Stature: A Multicenter Randomized Controlled Trial.

HT042 is a standardized functional food ingredient approved by Korean Food and Drug Administration with a claim 'HT042 can help height growth of children'. We aimed to evaluate the safety and efficacy of HT042 on height growth in children with mild short stature. A multicenter, randomized, double-blind, placebo-controlled parallel study was performed on children aged 6-8 years with height ranked below the 25th percentile. In 129 children, height gain was significantly higher in HT042 group than placebo group after 24 weeks (mean difference, 0.29 cm; 95% CI, 0.01 to 0.57 cm; p = 0.027). The difference was elevated when the efficacy analysis was restricted to children below the 10th percentile (mean difference, 0.45 cm; 95% CI, 0.04 to 0.87 cm; p = 0.031). Because bone age advancement was lower in HT042 group, height standard deviation score gain for bone age was higher in HT042 group and the difference was significant in children below the 10th percentile (mean difference, 0.20 score; 95% CI, 0.00 to 0.39 points; p = 0.045). Serum IGF-1 and IGFBP-3 levels were significantly increased compared with baseline within HT042 group, but group difference was not significant. HT042 supplementation helped to increase height growth in children without skeletal maturation and was more effective in much shorter children. The effects might be mediated by increases in serum IGF-1 and IGFBP-3 levels. Copyright © 2017 John Wiley & Sons, Ltd.

Correlation of occupational stress with depression, anxiety, and sleep in Korean dentists: cross-sectional study.

BACKGROUND: This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea. METHODS: A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis. RESULTS: The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t = 3.93, P < 0.0001; t = 4.05, P < 0.0001; t = 4.18, P < 0.0001, respectively). In particular, patient factors and clinical responsibility/judgment factors were significantly associated with depression (t = 2.80, P = 0.0056; t = 4.93, P < 0.0001, respectively), anxiety (t = 2.35, P = 0.0195; t = 5.11, P < 0.0001, respectively), and sleep (t = 3.78, P = 0.0002; t = 4.30, P < 0.0001, respectively), whereas work factors were not associated with any mental health state. CONCLUSIONS: This study confirms that dentists as professions experience more severe mental states. For successful mental health care among dentists, stress management focusing on interpersonal relationship with patients and responsibility as an expert rather than the intensity of work should be considered.

Solar radiation increases suicide rate after adjusting for other climate factors in South Korea.

OBJECTIVE: Previous studies have indicated that suicide rates have significant seasonal variations. There is seasonal discordance between temperature and solar radiation due to the monsoon season in South Korea. We investigated the seasonality of suicide and assessed its association with climate variables in South Korea. METHOD: Suicide rates were obtained from the National Statistical Office of South Korea, and climatic data were obtained from the Korea Meteorological Administration for the period of 1992-2010. We conducted analyses using a generalized additive model (GAM). First, we explored the seasonality of suicide and climate variables such as mean temperature, daily temperature range, solar radiation, and relative humidity. Next, we identified confounding climate variables associated with suicide rate. To estimate the adjusted effect of solar radiation on the suicide rate, we investigated the confounding variables using a multivariable GAM. RESULTS: Suicide rate showed seasonality with a pattern similar to that of solar radiation. We found that the suicide rate increased 1.008 times when solar radiation increased by 1 MJ/m2 after adjusting for other confounding climate factors (P < 0.001). CONCLUSION: Solar radiation has a significant linear relationship with suicide after adjusting for region, other climate variables, and time trends.

The safety of progestogen in the prevention of preterm birth: meta-analysis of neonatal mortality.

BACKGROUND: The safety of preventive progestogen therapy for preterm birth remains to be established. This meta-analysis aimed to evaluate the effects of preventive progestogen therapy on neonatal mortality. METHODS: Randomized controlled trials (RCTs) on the preventive use of progestogen therapy, published between October 1971 and November 2015, were identified by searching MEDLINE/PubMed, EMBASE, Scopus, ClinicalTrials.gov, Cochrane Library databases, CINAHL, POPLINE, and LILACS using "progesterone" and "preterm birth" as key terms. We conducted separate analyses according to the type of progestogen administered and plurality of the pregnancy. RESULTS: Twenty-two RCTs provided data on 11,188 neonates. Preventive progestogen treatment in women with a history of preterm birth or short cervical length was not associated with increased risk of neonatal death compared to placebo in all analyzed progestogen types and pregnancy conditions. The pooled relative risks (95% confidence interval) of neonatal mortality were 0.69 (0.31-1.54) for vaginal progestogen in singleton pregnancies, 0.6 (0.33-1.09) for intramuscular progestogen in singleton pregnancies, 0.96 (0.51-1.8) for vaginal progestogen in multiple pregnancies, and 0.96 (0.49-1.9) for intramuscular progestogen in multiple pregnancies. CONCLUSIONS: The results of this meta-analysis suggest that administration of preventive progestogen treatment to women at risk for preterm birth does not appear to negatively affect neonatal mortality in single or multiple pregnancies regardless of the route of administration.

Advanced Circadian Phase in Mania and Delayed Circadian Phase in Mixed Mania and Depression Returned to Normal after Treatment of Bipolar Disorder.

Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7hour advanced (equivalent to ~17hour delayed). Phases of 21 out of these 23 cases returned to normal by ~7hour delay along with treatment, but two out of 23 cases returned to normal by ~17hour advance. In three cases of mixed manic episodes, the phases were ~6-7hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~4-5hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD.

In vivo (1)H-MRS hepatic lipid profiling in nonalcoholic fatty liver disease: an animal study at 9.4 T.

The applicability of the in vivo proton magnetic resonance spectroscopy hepatic lipid profiling (MR-HLP) technique in nonalcoholic fatty liver disease was investigated. Using magnetic resonance spectroscopy, the relative fractions of diunsaturated (fdi), monounsaturated (fmono), and saturated (fsat) fatty acids as well as total hepatic lipid content were estimated in the livers of 8 control and 23 CCl4-treated rats at 9.4 T. The mean steatosis, necrosis, inflammation, and fibrosis scores of the treated group were all significantly higher than those of the control group (P < 0.01). There was a strong correlation between the histopathologic parameters and the MR-HLP parameters (r = 0.775, P < 0.01) where both steatosis and fibrosis are positively correlated with fmono and negatively correlated with fdi. Both necrosis and inflammation, however, were not correlated with any of the MR-HLP parameters. Hepatic lipid composition appears to be changed in association with the severity of steatosis and fibrosis in nonalcoholic fatty liver disease, and these changes can be depicted in vivo by using the MR-HLP method at 9.4 T. Thus, while it may not likely be that MR-HLP helps differentiate between steatohepatitis in its early stages and simple steatosis, these findings altogether are in support of potential applicability of in vivo MR-HLP at high field in nonalcoholic fatty liver disease.