Real-world treatment patterns for palbociclib plus an aromatase inhibitor, or an aromatase inhibitor alone, for patients with metastatic breast cancer in the Flatiron Database.

There are limited real-world comparative effectiveness data for palbociclib plus an aromatase inhibitor (AI) as a first-line (1L) treatment examining endpoints that require long term follow-up and post 1L progression. The Flatiron Health Analytic Database was used to characterize treatment and dosing patterns in patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) receiving palbociclib plus an AI vs an AI alone in routine US clinical practice. In addition, time to chemotherapy (TTC) and real-world progression-free survival (rwPFS) when combining 1L and second-line of therapy (rwPFS2) were assessed. Of 1324 patients who received palbociclib plus an AI between February 3, 2015 and March 31, 2020, 1110 (83.8%) started palbociclib at the recommended 125 mg/day dose. After stabilized inverse probability treatment-weighting (sIPTW), median TTC in patients treated with palbociclib plus an AI and AI alone was 37.4 months (95% confidence interval [CI], 33.7-40.7) and 29.2 months (95% CI, 26.8-33.5), respectively (hazard ratio [HR] = 0.77 [95% CI, 0.69-0.86], P < .0001); median rwPFS2 was 32.6 months (95% CI, 29.4-35.2) and 20.7 months (95% CI, 18.9-22.6), respectively (HR = 0.62 [95% CI, 0.54-0.70], P < .0001). Sensitivity analyses with propensity score matching showed similar results to sIPTW analyses. Results from this large real-world study examining additional effectiveness outcomes beyond 1L rwPFS and overall survival support the use of palbociclib plus an AI as a 1L treatment for patients with HR+/HER2- mBC.

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

Prolonging the lives of African-Americans with metastatic breast cancer by adding palbociclib to an aromatase inhibitor in routine clinical practice: a plain language summary of a real-world database study.

WHAT IS THIS SUMMARY ABOUT?: This summary is about a study that was published in the medical journal The Oncologist in July 2023. The combination of palbociclib with an aromatase inhibitor (AI) was approved by the FDA in 2015 as a treatment for people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, the effectiveness of palbociclib in African-Americans with MBC is not well studied. The goal of this study was to find out whether adding palbociclib to an AI helped African-Americans with HR+/HER2- MBC live longer. WHAT ARE THE KEY TAKEAWAYS?: This study used de-identified medical information from the Flatiron Database. This database contains healthcare information on people with cancer treated by doctors in the United States but personal information is removed to maintain privacy. Medical information for people who received certain treatments in routine clinical practice or real-world setting was included in the study.This study showed that in the real-world setting, African-Americans with HR+/HER2- MBC lived longer when receiving palbociclib with an AI than with an AI alone. Also, the study showed that African-Americans treated with palbociclib plus an AI lived longer without their cancer getting worse than those treated with an AI alone. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: These results support the use of palbociclib with an AI as a first treatment for African-Americans with HR+/HER2- MBC.Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Effectiveness of palbociclib plus an aromatase inhibitor in African Americans with metastatic breast cancer in routine clinical practice: a plain language summary.

Starting a Romantic Relationship, Breakups, and Sleep: A Longitudinal Study of Chinese Adolescents.

BACKGROUND: Epidemiological data on the association between romantic experiences and sleep in adolescents are limited. This study examined the associations of starting a romantic relationship (SRR) and romantic breakups with insomnia symptoms and sleep duration in adolescents. METHODS: A total of 7,072 Chinese adolescents were surveyed in November-December 2015 and 1 year later. A self-administered questionnaire was used to assess SRR, romantic breakups, sleep duration, insomnia symptoms, depressive symptoms, substance use, and demographics. RESULTS: The mean age of the sample was 14.58 (SD = 1.46) years and half were female. SRR only, breakups only, and both (SRR + breakups) in the past year were reported by 7.0%, 8.4%, and 15.4% of the sample, respectively. At the baseline and 1-year follow-up, 15.2% and 14.7% of the sample had insomnia symptoms and 47.7% and 42.1% reported short sleep duration (<7 h/night), respectively. After adjusting for depressive symptoms, substance use, and demographics, SRR and breakups were significantly associated with 35-45% increased odds of insomnia symptoms at baseline. SRR + breakups were significantly associated with short sleep duration (OR = 1.28, 95%CI = 1.05-1.56). SRR (OR = 1.61, 95%CI = 1.16-2.23) and breakups (OR = 1.43, 95%CI = 1.04-1.96) were significantly associated with increased odds of incident insomnia symptoms at 1-year follow-up. These associations were stronger in younger adolescents (<15 years) than in older adolescents (≥15 years), especially in girls. CONCLUSIONS: The findings suggest that SRR and breakups are associated with insomnia symptoms and short sleep duration, underscoring the importance of romantic relationships education and management of romantic stress for healthy sleep especially in early adolescent girls.

Bidirectional associations between short sleep duration, insomnia symptoms, and psychotic-like experiences in adolescents.

This study investigates the prospective associations between short sleep duration, insomnia symptoms, and psychotic-like experiences (PLEs) in a large sample of Chinese adolescents. This study utilized a three-timepoint repeated cross-sectional survey with two nested longitudinal subsamples. A total of 17,722 adolescents were assessed at baseline (April 21 to May 12, 2021) and six months later (December 17 to 26, 2021). Out of these, 15,694 adolescents provided complete responses to the questions at baseline and one year later (May 17 - June 6, 2022). A self-administered questionnaire was used to measure sample characteristics (at baseline), sleep duration, insomnia symptoms, and PLEs (at each assessment), and negative life events (at two follow-ups). Baseline short sleep duration and insomnia symptoms predicted frequent PLEs at both follow-up assessments. Additionally, baseline frequent PLEs also predicted insomnia symptoms at six months and one year later. However, when controlling for confounders, PLEs at baseline only predicted short sleep duration at six months, and not at one year. This study reveals bidirectional prospective relationships between short sleep duration, insomnia symptoms, and PLEs, even after controlling for covariates. Therefore, it is crucial to assess both sleep patterns and PLEs in order to promote optimal sleep and mental health among adolescents.

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

BACKGROUND: Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations. PATIENTS AND METHODS: This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020. RESULTS: Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199). CONCLUSION: This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings. TRIAL NUMBER: NCT05361655.

Prolonging the life of people with metastatic breast cancer in routine clinical practice by adding palbociclib to an aromatase inhibitor from a real-world database analysis: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article about a study called "P-REALITY X" that was published in the medical journal npj Breast Cancer in October 2022. "P-REALITY X" stands for Palbociclib REAl-world first-LIne comparaTive effectiveness studY eXtended. This study used information from a database to look at whether adding a second treatment (palbociclib) to an aromatase inhibitor (AI) helped people with a certain type of breast cancer to live longer. The type of breast cancer is metastatic hormone receptor-positive/human epidermal growth factor-negative breast cancer, also called HR-positive (or HR+)/HER2-negative (or HER2-) breast cancer. The study used information from the Flatiron Database. This database contains unidentified health care information collected from people seen by doctors in the USA. Only data from people who did not participate in a clinical trial were used. When people are treated outside of a clinical trial, this is called the real-world setting, or routine clinical practice. In clinical trials, people lived longer without their disease worsening if they were treated with palbociclib plus an AI versus being treated with an AI only. Based on the results of clinical trials, treatment with palbociclib plus an AI is already approved and recommended for people with HR+/HER2- breast cancer. This study looked at whether people lived longer if they were treated with palbociclib plus an AI versus being treated with an AI only in routine clinical practice as well. WHAT WERE THE RESULTS?: This study showed that, in routine clinical practice, people treated with the medicine palbociclib plus an AI lived longer than people treated with only an AI. WHAT DO THE RESULTS MEAN?: These results support the continued use of palbociclib plus an AI as the standard first medicine to be given to people with metastatic HR+/HER2- breast cancer. Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Effect of Octacalcium Phosphate Crystals on the Osteogenic Differentiation of Tendon Stem/Progenitor Cells In Vitro.

Synthetic octacalcium phosphate (OCP) activates bone tissue-related cells, such as osteoblasts, osteoclasts, and vascular endothelial cells. However, the effect of OCP on tendon-related cell activation remains unknown. This study examined the response of rat tendon stem/progenitor cells (TSPCs) to OCP and related calcium phosphate crystals in vitro. TSPCs were cultured with OCP and Ca-deficient hydroxyapatite (CDHA) obtained from the original OCP hydrolysis to assess the activity of alkaline phosphatase (ALP) and the expression of osteogenesis-related genes. Compared with CDHA, the effect of OCP on promoting the osteogenic differentiation of TSPCs was apparent: the ALP activity and mRNA expression of RUNX2, Col1a1, OCN, and OPN were higher in OCP than in CDHA. To estimate the changes in the chemical environment caused by OCP and CDHA, we measured the calcium ion (Ca2+) and inorganic phosphate (Pi) ion concentrations and pH values of the TSPCs medium. The results suggest that the difference in the osteogenic differentiation of the TSPCs is related to the ionic environment induced by OCP and CDHA, which could be related to the progress of OCP hydrolysis into CDHA. These results support the previous in vivo observation that OCP has the healing function of rabbit rotator cuff tendon in vivo.

Prevalence and Associated Factors of Premenstrual Syndrome in Chinese Adolescent Girls.

Epidemiological data on premenstrual syndrome (PMS) in Chinese adolescents are limited. This study reported the prevalence and associated factors of PMS in a large sample of Chinese adolescents. A total of 5099 adolescent girls who had menarche participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort study in Shandong, China. A self-administered questionnaire was used to ask about PMS, age at menarche, menstrual cycle interval, menstrual flow length, menstrual regularity, period pain, body weight and height, trait anger, stressful life events, and demographics. The mean age of the sample was 15.19 years (SD = 1.32). The overall prevalence of PMS was 24.6%. The prevalence rates of PMS-anxiety, PMS-water retention, PMS-craving, and PMS-depression were 18.9%, 4.0%, 7.9%, and 11.5%, respectively. The most common symptoms were premenstrual irritability (54%) and fatigue (52.5%). Stepwise logistic regression showed that high levels of life stress (OR 2.26), high levels of trait anger (OR 4.65), alcohol consumption (OR 1.28), menstrual cycle interval ≤ 24 days (OR 1.45), and mild (OR 1.50), moderate (OR 2.57) or severe period pain (OR 4.84) were all significantly associated with increased likelihood of PMS. In conclusion, approximately 1 in 4 Chinese adolescent girls suffered from PMS. Multiple psychosocial and menstrual factors were associated with PMS. Further research is needed to understand developmental changes of PMS and its long-term impacts on psychosocial wellbeing in Chinese adolescent girls.

Prevalence and associated factors of suicidal ideation among college students during the COVID-19 pandemic in China: a 3-wave repeated survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China. METHODS: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors. RESULTS: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation. CONCLUSION: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students.

Nightmare frequency and psychopathological problems in a large sample of Chinese adolescents.

PURPOSE: Nightmares are common, especially in pediatric populations and psychiatric patients. Nightmares are associated with daytime distress and negative health outcomes. The data on the prevalence and psychopathological profiles of nightmares in Chinese adolescents are limited. This study examined age and gender differences in nightmare frequency and associated psychopathological problems in a large sample of Chinese adolescents. METHODS: A total of 11,831 adolescent students (mean age = 14.9, 12-18 years) participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort. Participants completed a self-administered questionnaire to report their nightmare frequency, trait anger, hopelessness, and multiple domains of behavioral/emotional problems. Univariate and multivariate analyses were performed to examine psychopathological problems in relation to nightmare frequency. RESULTS: Of the sample, 45.2% reported having nightmares at least once in the past month and 7.9% at least once/week. Girls reported more frequent nightmares than boys. Nightmare frequency significantly declined with age for both boys and girls. Mean scores on trait anger, hopelessness, attention, internalizing problems, and externalizing problems significantly increased with nightmare frequency. Frequent nightmares (at least once/week) were significantly associated with 2-4-fold increased likelihood of behavioral/emotional problems after adjusting for adolescent and family covariates. CONCLUSION: Nightmares are prevalent in Chinese adolescents. Frequent nightmares are associated with multiple domains of psychopathological problems. Assessment and intervention of frequent nightmares should be incorporated into routine clinical practice and mental health services in adolescents.

A Longitudinal Study of Insomnia, Daytime Sleepiness, and Academic Performance in Chinese Adolescents.

BACKGROUND: Longitudinal data on the associations between sleep disturbances, daytime sleepiness, and daily functioning are limited in the general adolescent population. This study examined the cross-sectional and longitudinal associations between insomnia, excessive daytime sleepiness (EDS), and subject-specific academic performance in a large sample of Chinese adolescents. METHOD: Data were derived from the Shandong Adolescent Behavior and Health Cohort (n = 7,072) study. A self-administered questionnaire was used to assess insomnia, EDS, academic performance (overall, Chinese, mathematics, and English), behavioral and emotional problems, and family demographics. The cross-sectional analysis was conducted with baseline data while the longitudinal analysis was conducted with both baseline and 1-year follow-up data. Logistic regression analyses and mediation models were performed to examine the associations between insomnia, EDS, and academic performance. RESULTS: Logistic regression analyses revealed that insomnia and EDS had significant cross-sectional associations with overall performance and mathematics performance after controlling for age, gender, ever smoking, ever alcohol drinking, frequent snore, sleep duration, chronic disease, anxious/depressive symptoms, parents' education, parents' occupation, and family economic status. Both insomnia (OR = 1.20, 95% CI: 1.00-1.45) and EDS (OR = 1.22, 95% CI: 1.03-1.45) at baseline were significantly associated with poor mathematics performance 1 year later. The effect of insomnia at baseline on poor academic performance 1 year later was mediated by EDS except for the Chinese subject after controlling for the covariates. CONCLUSIONS: Insomnia and daytime sleepiness are significantly associated with poor academic performance, particularly in mathematics. EDS mediates the association between insomnia and poor academic performance. Further research is warranted to investigate the effects of sleep disturbance and daytime sleepiness on the learning process and performance across academic subjects.

Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice.

BACKGROUND: Findings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (MBC) treated in routine clinical practice in the USA. PATIENTS AND METHODS: This was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed. RESULTS: After sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2-34.9) in the palbociclib group and 23.3 months (IQR, 12.7-34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9 months; hazard ratio [HR], 0.58; 95% CI, 0.49-0.69; P < 0.0001). Median OS was not reached in the palbociclib group and was 43.1 months with letrozole alone (HR, 0.66; 95% CI, 0.53-0.82; P = 0.0002). The 2-year OS rate was 78.3% in the palbociclib group and 68.0% with letrozole alone. A propensity score matching analysis showed similar results. CONCLUSIONS: In this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting. TRIAL REGISTRATION: Clinicaltrials.gov; NCT04176354.

Repeat self-harm among Chinese adolescents: 1-year incidence and psychosocial predictors.

PURPOSE: Self-harm in adolescents is prevalent and is the most significant predictor of future self-harm and suicide. Longitudinal data on the incidence and predictors of repeat self-harm in the general population of adolescents are limited. This study investigated 1-year incidence and psychosocial predictors of repeat self-harm in Chinese adolescents. METHODS: Shandong Adolescent Behavior and Health Cohort is a longitudinal study of behavior and health in adolescents in Shandong Province, China. Of 7072 participants who were assessed in 2015 and again 1 year later in 2016, 1879 reported a history of self-harm at the baseline survey and were included for this analysis. A self-administered structured questionnaire was used to assess behavioral and emotional problems, sleep, life stress, previous history of self-harm and suicidal thought, and family factors at baseline and self-harm at 1-year follow-up. RESULTS: Mean age of the sample was 14.86 (SD 1.36) years and 54.6% were female. At 1-year follow-up, 22.1% participants engaged in repeat self-harm. Multiple logistic regression analyses showed that female gender (OR 1.45, 95% CI 1.11-1.89), alcohol use (OR 1.95, 95% CI 1.48-2.57), frequent nightmares (OR 1.61, 95% CI 1.14-2.28), elevated depression score (OR 1.59, 95% CI 1.05-2.42), and prior suicidal thought (OR 1.79, 95% CI 1.37-2.34) were independently and significantly associated with an increased risk of repeat self-harm. CONCLUSION: More than one in five Chinese adolescents who had a history of self-harm engaged in self-harm at 1-year follow-up. Multiple psychosocial factors including female gender, alcohol use, frequent nightmares, depression, and prior suicidal thought appeared to be significant predictors of repeat self-harm. Our findings highlight the importance of comprehensive psychosocial assessment and intervention of repeat self-harm in adolescents.

Early Childhood Co-Sleeping Predicts Behavior Problems in Preadolescence: A Prospective Cohort Study.

OBJECTIVE/BACKGROUND: Co-sleeping is common practice around the globe. The relationship between early childhood co-sleeping and adolescent behavior problems remains uncertain. We aim to identify whether early childhood co-sleeping can predict behavior problems in preadolescence. PARTICIPANTS: A cohort of 1,656 Chinese preschool children were followed up in adolescence. METHODS: Prospective cohort study design involving two waves of data collection from the China Jintan Cohort (1,656 children aged 3-5 years). Co-sleeping history was collected at 3-5-years-old via parent-reported questionnaire at wave I data collection. Behavior problems were measured twice in childhood and preadolescence, respectively. Adolescent behavior problems were measured by integrating data from self-report, parent-report and teacher-report using the Achenbach System of Empirically Based Assessment. Predictions were assessed using the general linear model with mixed effects on the inverse probability weight propensity-matched sample. RESULTS: 1,656 children comprising 55.6% boys aged 4.9 ± 0.6 were initially enrolled in the first wave of data collection. In the second wave of data collection, 1,274 children were 10.99 ± 0.74 (76.9%) aged 10-13 years were retained. Early childhood co-sleeping is significantly associated with increased behavior problems in childhood (Odds Ratio [OR] 1.22-2.06, ps<0.03) and preadolescence (OR 1.40-2.27, ps<0.02). Moreover, co-sleeping history significantly predicted multiscale increase in internal (OR 1.63-2.61, ps<0.02) and external behavior problems in adolescence. CONCLUSIONS: Early childhood co-sleeping is associated with multiple behavioral problems reported by parents, teachers, and children themselves. Early childhood co-sleeping predicts preadolescent internalizing and externalizing behavior after controlling for baseline behavior problems.

Analysis of lncRNA-mRNA networks after MEK1/2 inhibition based on WGCNA in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) responds poorly to treatment. Efforts have been exerted to prolong the survival time of PDA, but the 5-year survival rates remain disappointing. Understanding the molecular mechanisms of PDA development is significant. MEK/ERK pathway signaling has been proven to be important in PDA. lncRNA-mRNA networks have become a vital part of molecular mechanisms in the MEK/ERK pathway. Herein, weighted gene coexpression network analysis was used to investigate the coexpressed lncRNA-mRNA networks in the MEK/ERK pathway based on GSE45765. Differently expressed long noncoding RNA (lncRNA) and messenger RNA (mRNA) were found and 10 modules were identified based on coexpression profiles. Gene ontology and Kyoto Encyclopedia of Genes and Genomes were then performed to analyze the coexpressed lncRNA and mRNA in different modules. PDA cells and tissues were used to validate the analysis results. Finally, we found that NONHSAT185150.1 and B4GALT6 were negatively correlated with MEK1/2. By analyzing GSE45765, the genome-wide profiles of lncRNA-mRNA network after MEK1/2 was established, which might aid the development of drug-targeting MEK1/2 and the investigation of diagnostic markers.

Cytotoxic gelsedine-type indole alkaloids from Gelsemium elegans.

A chemical investigation on the 95% ethanol extract of the aerial part of Gelsemium elegans resulted in the isolation of three new gelsedine-type indole alkaloids, 14ß-hydroxygelselenidine (1), 11-methoxygelseziridine (2), and 14ß-hydroxygelsedethenine (3). Structural elucidation of all the compounds was accomplished by spectral methods such as 1 D and 2 D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against five human non-small-cell lung cancer cell lines. Consequently, alkaloid 3 exhibited cytotoxic activities for all tested tumor cell lines with IC50 values from 8.3 to 9.8 µM. [Formula: see text].

Testing Syndromes of Psychopathology in Parent and Youth Ratings Across Societies.

As societies become increasingly diverse, mental health professionals need instruments for assessing emotional, behavioral, and social problems in terms of constructs that are supported within and across societies. Building on decades of research findings, multisample alignment confirmatory factor analyses tested an empirically based 8-syndrome model on parent ratings across 30 societies and youth self-ratings across 19 societies. The Child Behavior Checklist for Ages 6-18 and Youth Self-Report for Ages 11-18 were used to measure syndromes descriptively designated as Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-Breaking Behavior, and Aggressive Behavior. For both parent ratings (N = 61,703) and self-ratings (N = 29,486), results supported aggregation of problem items into 8 first-order syndromes for all societies (configural invariance), plus the invariance of item loadings (metric invariance) across the majority of societies. Supported across many societies in both parent and self-ratings, the 8 syndromes offer a parsimonious phenotypic taxonomy with clearly operationalized assessment criteria. Mental health professionals in many societies can use the 8 syndromes to assess children and youths for clinical, training, and scientific purposes.

Menarche and menstrual problems are associated with non-suicidal self-injury in adolescent girls.

Menstrual problems and non-suicidal self-injury (NSSI) are common in adolescent girls. This study examined whether onset of menstruation and menstrual problems were related to NSSI in Chinese female adolescents. A total of 5696 adolescent girls participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort (SABHC) study in Shandong, China. A structured questionnaire was used to ask about participants' lifetime and last-year NSSI, age at menarche, menstrual cycle interval, menstrual flow length, menstrual irregularity, period pain, body weight and height, and demographics. Impulsivity was assessed by the Eysenck I7 impulsiveness scale. Internalizing and externalizing problems were measured by the Youth Self-Report of Child Behavior Checklist. The mean age of the sample was 15.0 years (SD = 1.4). The prevalence of lifetime and last year NSSI were 28.1% and 21.4% in Chinese adolescent girls. After adjusting for adolescent and family covariates (age, body mass index, impulsivity, internalizing and externalizing problems, paternal education, and family economic status), onset of menstruation was significantly associated with increased risk of lifetime NSSI (OR = 1.62, 95%CI = 1.20-2.20) and last year NSSI (OR = 1.92, 95%CI = 1.37-2.67). Among adolescent girls who had menarche, often irregular menstruation and period pain were significantly and independently associated with lifetime NSSI (OR = 1.36, 95%CI = 1.03-1.79; OR = 1.29, 95%CI = 1.05-1.58) and last year NSSI (OR = 1.46, 95%CI = 1.07-1.98; OR = 1.29, 95%CI = 1.03-1.61). Our findings suggest that onset of menarche, irregular periods, and period pain appear to be associated with increased risk of NSSI. These findings highlight the importance of menstruation hygiene education and treatment of menstrual problems to reduce the risk of NSSI among adolescent girls.

Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation: Assessment via a Large Insurance Database.

BACKGROUND AND PURPOSE: Stroke risk may increase shortly after warfarin initiation in nonvalvular atrial fibrillation patients. Because of the brief period and limited number of events, large samples are needed to study this effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial fibrillation patients initiating warfarin to nonwarfarin comparators using an insurance claims database. METHODS: We identified nonvalvular atrial fibrillation patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan database, January 1, 2009, to December 31, 2010. We studied patients initiating warfarin using prescription claims and 1:1 matched 22 669 initiators to comparators based on age, sex, diagnosis date, and warfarin propensity score. Follow-up began on initiation date; patients were censored at discontinuation/switch of therapy, disenrollment, or end of the study. The median follow-up was 415 days. Cox regression was used to study differences in ischemic stroke risks between warfarin initiators and comparators while controlling for important prognostic factors. RESULTS: Warfarin initiators were generally similar to comparators in clinical features but had higher CHADS2 scores (1.26 versus 1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837); P=0.18) but lower subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248]; P=0.002). Multivariable regression confirmed a significant interaction between follow-up and warfarin use with the adjusted hazard ratios (95% confidence intervals) for warfarin/comparator as 1.46 (0.80-2.65) in the first 30 days and 0.70 (0.57-0.85) afterward. CONCLUSIONS: Warfarin effect was qualitatively different in the first 30 days after initiation than subsequently. This is consistent with a modest increase in stroke risk occurring briefly after starting warfarin.