Adolescent psychopathic traits and adverse environments: Associations with socially adaptive outcomes.

Researchers have suggested that psychopathic traits among adults may be, at least in part, an adaptive and/or a learned response for securing socially adaptive outcomes in adverse environments, but there is a lack of developmental evidence supporting this hypothesis among adolescents. Therefore, we examined the indirect links from self-perceived adverse environments (parental neglect, socioeconomic status, school competition, neighborhood violence) to evolutionarily relevant social outcomes (social power, dating behavior) through psychopathic traits. A community sample of 396 adolescents completed measures for the study (Mage = 14.64, SD = 1.52). As predicted, there were significant indirect effects from higher levels of parental neglect, school competition, and neighborhood violence to both forms of socially adaptive outcomes through psychopathic traits, but unexpectedly, there were no indirect effects with socioeconomic status. There were also direct effects between environment and socially adaptive outcomes. Results support the hypothesis that psychopathic traits may be, in part, an adaptive and/or learned response to cues from adverse social environments as a means to acquire evolutionarily relevant social outcomes. Interventions could be designed to target the adverse social issues that might be facilitating the development of psychopathy and should be sensitive to the social outcomes adolescents may acquire from these traits.

Social Media Friendship Jealousy.

A new measure to assess friendship jealousy in the context of social media was developed. This one-factor, seven-item measure was psychometrically sound, showing evidence of validity and reliability in three samples of North American adults (Study 1, n = 491; Study 2, n = 494; Study 3, n = 415) and one-, two-, and three-year stability (Study 3). Women reported more social media friendship jealousy than men (Studies 2 and 3) and younger women had the highest levels of social media friendship jealousy (compared with younger men and older men and women; Study 2). Social media friendship jealousy was associated with lower friendship quality (Study 1) and higher social media use and trait jealousy (Study 2). The relation between social media friendship jealousy and internalizing symptoms indicated positive within time associations and longitudinal bidirectional relations (Study 3). Specifically, social media friendship jealousy predicted increases in internalizing problems, and internalizing problems predicted greater social media friendship jealousy accounting for gender and trait levels of social media friendship jealousy and internalizing problems. Anxious and depressed adults may be predisposed to monitor threats to their friendships via social media and experience negative consequences because of this behavior. Although social media interactions can be associated with positive well-being and social connectedness, our results highlight that they can also undermine friendships and mental health due to jealousy.

Anxiety symptoms before and during the COVID-19 pandemic: A longitudinal examination of Canadian young adults.

The COVID-19 pandemic has resulted in many changes that may impact anxiety symptoms (i.e., general anxiety and somatization), particularly for young adults who were at higher risk for anxiety than older adults. We examined anxiety symptoms before (age 19, 20, 21, and 22) and during the pandemic (age 23 and 24) in a cohort of Canadian young adults (n = 396). Latent growth curve models were performed for general anxiety and somatization and the pandemic time points were estimated as structured residuals to quantify the change from participants' expected trajectories. We also examined whether fear of COVID-19 predicted the changes in anxiety symptoms during the pandemic. Results indicated that a history of general anxiety and somatization positively predicted fear of COVID-19 during the pandemic and negatively predicted pandemic change from predicted values for both general anxiety and somatization. Increased COVID-19 fear was related within time to increases in general anxiety at ages 23 and 24 and increases in somatization at age 24. We also found that the proportion of individuals in the subclinical/clinical range of somatization was higher from age 23-24, but not from age 22-23 and there were no differences for general anxiety. Results highlight the need to consider within-person change and development in evaluating anxiety symptom changes and predictors of changes in anxiety symptoms.

Bullying before and during the COVID-19 pandemic.

The rates of bullying during the COVID-19 pandemic, a time of unprecedented public health and social restrictions, were compared to earlier times when students attended school in person. Several studies indicated a notable decrease in the prevalence of bullying victimization and perpetration during the pandemic, particularly when online learning was implemented. But studies from countries with fewer social restrictions indicated increases in rates of bullying during the pandemic. Mixed results regarding prevalence rates for some bullying forms (e.g., cyberbullying) were also found. Racialized youth and LGBTQ+ youth reliably reported higher rates of bullying victimization during the pandemic, consistent with pre-pandemic patterns. Reasons for the inconsistencies in findings likely relate to diverse methods, timeframes, and sampling techniques, as well as different experiences with pandemic social restrictions. More longitudinal studies are needed to assess whether bullying involvement did in fact "change" during, compared to before, the pandemic. The findings point to the importance of peer relationships and hint at the potential of increased teacher supervision as a bullying prevention strategy.

Bullying involvement and the transition to high school: A brief report.

School transitions are common educational experiences for children and adolescents and many of them worry about being bullied during this type of major life-changing point. In a sample of 701 Canadians assessed yearly from grade 5 (age 10) to grade 12 (age 18), we examined heterogeneous patterns of bullying involvement while statistically accounting for the transition into high school. Gender differences were also examined. Results indicated that on average, bullying victimization declined over time with a significant drop noted between grade 8 and grade 9 (the transition into high school), with few differences between girls and boys. Bullying perpetration also declined for most students (no gender differences), with a notable drop found at the transition into high school. However, for a subset of adolescents, the transition into high school was accompanied by an increase in bullying perpetration. These varied experiences highlight the need to model heterogeneity when examining the impact of school transitions on bullying, a neglected focus of inquiry to date. Our results suggest that moving into high school is beneficial for most adolescents involved in bullying, but not for all.

Loneliness and Well-Being in Children and Adolescents during the COVID-19 Pandemic: A Systematic Review.

Concerns have been raised about the loneliness and well-being of children and adolescents during the COVID-19 pandemic. The extent to which the ongoing pandemic has impacted loneliness and the association between loneliness and well-being is unclear. Therefore, a systematic review of empirical studies on the COVID-19 pandemic was conducted to examine the (1) prevalence of loneliness in children and adolescents, (2) associations between loneliness and indicators of well-being, and (3) moderators of these associations. Five databases (MEDLINE, Embase, PsycInfo, Web of Science, ERIC) were searched from 1 January 2020 to 28 June 2022 and 41 studies met our inclusion criteria (cross-sectional: n = 30; longitudinal: n = 11; registered on PROSPERO: CRD42022337252). Cross-sectional prevalence rates of pandemic loneliness varied, with some finding that over half of children and adolescents experienced at least moderate levels of loneliness. Longitudinal results reflected significant mean increases in loneliness compared to pre-pandemic levels. Cross-sectional results indicated that higher levels of loneliness were significantly associated with poorer well-being, including higher depression symptoms, anxiety symptoms, gaming addiction, and sleep problems. Longitudinal associations between loneliness and well-being were more complex than cross-sectional associations, varying by assessment timing and factors in the statistical analyses. There was limited diversity in study designs and samples, preventing a thorough examination of moderating characteristics. Findings highlight a broader challenge with child and adolescent well-being that predates the pandemic and the need for future research to examine underrepresented populations across multiple timepoints.

Normal Ranges of Right Atrial Strain: A Systematic Review and Meta-Analysis.

BACKGROUND: Standard measures for the clinical assessment of right atrial (RA) function are lacking. OBJECTIVES: In this systematic review and meta-analysis, the authors sought to report a reference range for RA deformation parameters in healthy subjects and to identify factors that contribute to reported variations. METHODS: The authors conducted a comprehensive search of MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; Embase; Scopus; and the Cochrane Central Register of Controlled Trials from database inception through October 2021. Studies were included if they reported RA strain or strain rate (SR) using 2-dimensional speckle-tracking echocardiography in healthy volunteers or apparently healthy control patients. Data were extracted by 1 reviewer and then reviewed by 2 independent reviewers. Conflicts were resolved through consensus. Data were combined using the method developed by Siegel and adjusted using the restricted maximum likelihood random-effects model. The normal range was defined as the 95% CI of the mean. Heterogeneity was assessed by the Cochran Q-statistic and the inconsistency index (I2). The quality of the included studies and publication bias were assessed. Effects of clinical variables were sought in a metaregression. RESULTS: The search identified 4,111 subjects from 21 studies. The average RA reservoir strain was 44% (95% CI: 25%-63%), contractile strain was 17% (95% CI: 2%-32%), and conduit strain was 18% (95% CI: 7%-28%), with significant between-study heterogeneity and inconsistency. The systolic SR was 2.1 s-1 (95% CI: 0.9-3.4 s-1), early-diastolic SR was -2.0 s-1 (95% CI: -3.3 to -0.8 s-1), and late-diastolic SR was -1.9 s-1 (95% CI: -2.4 to -1.3 s-1), with nonsignificant heterogeneity and inconsistency. Ranges remained wide in healthy volunteers. The metaregression identified only age as significantly associated with systolic SR and no other significant determinants of variation among normal ranges of strain. CONCLUSIONS: There are wide reference ranges for RA deformation, and these may limit the utility of this test in clinical practice.

Indirect aggression, anxiety, and empathy: Disaggregating between and within person longitudinal associations during childhood and adolescence.

Although indirectly aggressive behavior and anxiety symptoms can co-occur, it is unclear whether anxiety is an antecedent or outcome of indirect aggression at the individual level and whether other personality traits can contribute to these longitudinal associations. Therefore, the between- and within-person associations among indirect aggression, anxiety symptoms, and empathic concern were examined across adolescence from ages 11 to 16 in a cohort of individuals followed annually (N = 700; 52.9% girls; 76.0% White) controlling for direct aggression and demographic variables. Results of autoregressive latent trajectory models with structured residuals supported an acting out model at the within-person level. Specifically, anxiety symptoms positively predicted indirect aggression and indirect aggression negatively predicted empathic concern at each adjacent time point. These findings suggest that methods of reducing worries about the self and increasing healthy self-confidence could prevent indirect aggression and help build concern and compassion toward others.

Epigenetic Silencing of RIPK3 in Hepatocytes Prevents MLKL-mediated Necroptosis From Contributing to Liver Pathologies.

BACKGROUND & AIMS: Necroptosis is a highly inflammatory mode of cell death that has been implicated in causing hepatic injury including steatohepatitis/ nonalcoholic steatohepatitis (NASH); however, the evidence supporting these claims has been controversial. A comprehensive, fundamental understanding of cell death pathways involved in liver disease critically underpins rational strategies for therapeutic intervention. We sought to define the role and relevance of necroptosis in liver pathology. METHODS: Several animal models of human liver pathology, including diet-induced steatohepatitis in male mice and diverse infections in both male and female mice, were used to dissect the relevance of necroptosis in liver pathobiology. We applied necroptotic stimuli to primary mouse and human hepatocytes to measure their susceptibility to necroptosis. Paired liver biospecimens from patients with NASH, before and after intervention, were analyzed. DNA methylation sequencing was also performed to investigate the epigenetic regulation of RIPK3 expression in primary human and mouse hepatocytes. RESULTS: Identical infection kinetics and pathologic outcomes were observed in mice deficient in an essential necroptotic effector protein, MLKL, compared with control animals. Mice lacking MLKL were indistinguishable from wild-type mice when fed a high-fat diet to induce NASH. Under all conditions tested, we were unable to induce necroptosis in hepatocytes. We confirmed that a critical activator of necroptosis, RIPK3, was epigenetically silenced in mouse and human primary hepatocytes and rendered them unable to undergo necroptosis. CONCLUSIONS: We have provided compelling evidence that necroptosis is disabled in hepatocytes during homeostasis and in the pathologic conditions tested in this study.

A problem of proportions: estimates of metabolic associated fatty liver disease and liver fibrosis in Australian adults in the nationwide 2012 AusDiab Study.

Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34-97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00-1.02)), male (OR 1.37 (95% CI 1.17-1.59)), have ALT elevation (OR 3.21 (95% CI 2.59-3.99)), diabetes (OR 3.39 (95% CI 2.61-4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12-0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05-1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59-2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7-0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.

Childhood Predictors of Adolescent Joint Trajectories: A Multi-Informant Study on Bullying Perpetration and Hypercompetitiveness.

OBJECTIVE: Bullying perpetration has been proposed to be a strategic behavior used by adolescents to compete for social resources, yet the co-development of bullying perpetration and trait hypercompetitiveness is understudied. The joint developmental trajectories of self-rated bullying perpetration and parent-rated hypercompetitiveness were investigated in a sample of adolescents and childhood social, emotional, and physical predictors were explored. METHOD: In a sample of 607 adolescents (Mage = 13.02 years in Grade 7 [SD = 0.38]; 54.4% girls; 76.4% White) self-rated bullying perpetration and parent-rated hypercompetitiveness were assessed across six years of development (Grades 7 to 12). Childhood (i.e., Grades 5 and 6) social, emotional, and physical predictors of trajectory group membership were also examined. RESULTS: Using latent class growth analyses, the three expected joint trajectory groups of primary interest were found: (1) a pattern of moderate stable bullying perpetration and high increasing hypercompetitiveness (high-risk group), (2) a pattern of low decreasing bullying and high increasing hypercompetitiveness (hypercompetitive only group), and (3) a pattern of low decreasing bullying and low stable hypercompetitiveness (low-risk group). Adolescents reflecting the high-risk joint trajectory pattern were differentiated from adolescents reflecting the other two trajectory patterns by having more adverse childhood social, emotional, and physical predictors. CONCLUSIONS: Findings indicate that bullying is a developmental and context-dependent behavior that can reflect trait hypercompetitiveness. Bullying prevention efforts should focus on reducing emphasis on outcompeting peers and instead facilitate a sense of self-acceptance, awareness, and accomplishment within prosocial school and family environments.

Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses.

PURPOSE: To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy. METHODS: We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4,482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies. RESULTS: In trial-level analyses, association between HR for OS and OR for CR was moderate (R2 = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R2 = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R2 = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37). CONCLUSION: On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect.

ASH Research Collaborative: a real-world data infrastructure to support real-world evidence development and learning healthcare systems in hematology.

The ASH Research Collaborative is a nonprofit organization established through the American Society of Hematology's commitment to patients with hematologic conditions and the science that informs clinical care and future therapies. The ASH Research Collaborative houses 2 major initiatives: (1) the Data Hub and (2) the Clinical Trials Network (CTN). The Data Hub is a program for hematologic diseases in which networks of clinical care delivery sites are developed in specific disease areas, with individual patient data contributed through electronic health record (EHR) integration, direct data entry through electronic data capture, and external data sources. Disease-specific data models are constructed so that data can be assembled into analytic datasets and used to enhance clinical care through dashboards and other mechanisms. Initial models have been built in multiple myeloma (MM) and sickle cell disease (SCD) using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) and Fast Healthcare Interoperability Resources (FHIR) standards. The Data Hub also provides a framework for development of disease-specific learning communities (LC) and testing of health care delivery strategies. The ASH Research Collaborative SCD CTN is a clinical trials accelerator that creates efficiencies in the execution of multicenter clinical trials and has been initially developed for SCD. Both components are operational, with the Data Hub actively aggregating source data and the SCD CTN reviewing study candidates. This manuscript describes processes involved in developing core features of the ASH Research Collaborative to inform the stakeholder community in preparation for expansion to additional disease areas.

Safety and efficacy of endoscopic cyanoacrylate injection in the management of gastric varices: A systematic review and meta-analysis.

BACKGROUND AND AIM: Bleeding from gastric varices is a catastrophic event and poses difficulty in management. The efficacy and safety of cyanoacrylate injection remain unclear. We performed a systematic review and meta-analysis to evaluate the effect of endoscopic cyanoacrylate injection in the management of gastric varices. METHODS: We conducted a comprehensive search of MEDLINE, Embase, Web of Science, Scopus databases, and Cochrane Database of Systematic Reviews through November 2020 and manually reviewed the literature. Trial-specific risk ratios (RRs) were estimated and pooled using random-effect model meta-analysis. RESULTS: We included seven randomized controlled trials (six for secondary prophylaxis and one for primary prophylaxis) at low risk of bias in which 126 deaths were reported among 583 patients with gastric varices. All studies reported the use of N-butyl-2-cyanoacrylate glue. Cyanoacrylate use was associated with significantly lower all-cause mortality (RR, 0.59; 95% confidence interval [CI], 0.36-0.98; I2 = 41%) and rebleeding rate after hemostasis (RR, 0.49; 95% CI, 0.35-0.68, I2 = 0%) compared with any other treatment approach not involving cyanoacrylate. When cyanoacrylate was compared with each individual treatment approach (propranolol only, band ligation, sclerotherapy with alcohol or ethanolamine), data comprised sparse limited comparative conclusions. The use of cyanoacrylate injection was not associated with an increase in serious adverse events. The quality of evidence is moderate, graded down due to the small number of events and wide CIs. CONCLUSION: The use of endoscopic cyanoacrylate injection therapy for gastric varices may be associated with lower all-cause mortality and better hemostasis compared with other therapies.

Systematic Review of PD-1/PD-L1 Inhibitors in Oncology: From Personalized Medicine to Public Health.

BACKGROUND: To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as PD-[L]1 inhibitors) over a 6-year period and corresponding companion/complementary diagnostic assays. MATERIALS AND METHODS: To determine the indications and pivotal trials eligible for inclusion, approval letters and package inserts available on Drugs@FDA were evaluated for approved PD-[L]1 inhibitors to identify all new indications granted from the first approval of a PD-[L]1 inhibitor on September 4, 2014, through September 3, 2020. The corresponding FDA drug and device reviews from the marketing applications for the approved indications were identified through FDA internal records. Two reviewers independently extracted information for the endpoints, efficacy data, basis for approval, type of regulatory approval, and corresponding in vitro diagnostic device test. The results were organized by organ system and tumor type. RESULTS: Of 70 Biologic Licensing Application or supplement approvals that resulted in new indications, 32 (46%) were granted based on response rate (ORR) and durability of response, 26 (37%) on overall survival, 9 (13%) on progression-free survival, 2 (3%) on recurrence-free survival, and 1 (1%) on complete response rate. Most ORR-based approvals were granted under the accelerated approval provisions and were supported with prolonged duration of response. Overall, 21% of approvals were granted with a companion diagnostic. Efficacy results according to tumor type are discussed. CONCLUSION: PD-[L]1 inhibitors are an effective anticancer therapy in a subset of patients. This class of drugs has provided new treatment options for patients with unmet need across a wide variety of cancer types. Yet, the modest response rates in several tumor types signal a lack of understanding of the biology of these diseases. Further preclinical and clinical investigation may be required to identify a more appropriate patient population, particularly as drug development continues and additional treatment alternatives become available. IMPLICATIONS FOR PRACTICE: The number of PD-[L]1 inhibitors in drug development and the associated companion and complementary diagnostics have led to regulatory challenges and questions regarding generalizability of trial results. The interchangeability of PD-L1 immunohistochemical assays between PD-1/PD-L1 drugs is unclear. Furthermore, robust responses in some patients with low levels of PD-L1 expression have limited the use of PD-L1 as a predictive biomarker across all cancers, particularly in the setting of diseases with few alternative treatment options. This review summarizes the biomarker thresholds and assays approved as complementary and companion diagnostics and provides regulatory perspective on the role of biomarkers in oncology drug development.

School bullying before and during COVID-19: Results from a population-based randomized design.

We examined the impact of COVID-19 on bullying prevalence rates in a sample of 6578 Canadian students in Grades 4 to 12. To account for school changes associated with the pandemic, students were randomized at the school level into two conditions: (1) the pre-COVID-19 condition, assessing bullying prevalence rates retrospectively before the pandemic, and (2) the current condition, assessing rates during the pandemic. Results indicated that students reported far higher rates of bullying involvement before the pandemic than during the pandemic across all forms of bullying (general, physical, verbal, and social), except for cyber bullying, where differences in rates were less pronounced. Despite anti-Asian rhetoric during the pandemic, no difference was found between East Asian Canadian and White students on bullying victimization. Finally, our validity checks largely confirmed previous published patterns in both conditions: (1) girls were more likely to report being bullied than boys, (2) boys were more likely to report bullying others than girls, (3) elementary school students reported higher bullying involvement than secondary school students, and (4) gender diverse and LGTBQ + students reported being bullied at higher rates than students who identified as gender binary or heterosexual. These results highlight that the pandemic may have mitigated bullying rates, prompting the need to consider retaining some of the educational reforms used to reduce the spread of the virus that could foster caring interpersonal relationships at school such as reduced class sizes, increased supervision, and blended learning.