Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.

Prevalence and Severity of Child Impairment in a US Sample of Child Maltreatment Investigations.

OBJECTIVES: Although there is agreement that childhood disability is both a risk and result of maltreatment, the extent of disability in the child welfare system remains unclear. Our objective is to determine the prevalence and severity of child impairment in a national sample of child abuse and neglect investigations in the United States. METHODS: We used data from the National Survey of Child and Adolescent Well-Being II, a study of 2644 children older than 3 years who were subjects of child abuse and neglect investigations. Groups of children were identified by latent profile analysis using continuous standardized measures of intelligence, emotional or behavioral impairments, adaptive behaviors, and social skills. RESULTS: Whether the child remained in home or was removed to foster care after an investigation, 3 classes of children were identified: (1) slightly over one-tenth were in an intellectual disability subgroup characterized by marked intellectual impairments alongside delays in daily living functioning, (2) over one-third were in an emotional or behavioral impairment subgroup characterized by both frequent and severe internalizing and externalizing behaviors, and (3) slightly over half were in a typically developing subgroup. CONCLUSION: When using standardized measures of disability, nearly half of the children investigated by child protection in the United States are not typically developing. These findings suggest that those working for the child welfare system need to be attentive to the complex needs of children with intellectual disabilities and emotional or behavioral impairments and their families, many of whom are under significant stress.

Resting Heart Rate and Psychopathy Revisited: Findings From the Add Health Survey.

Despite the prior linkages of low resting heart rate to antisocial behavior broadly defined, less work has been done examining possible associations between heart rate to psychopathic traits. The small body of research on the topic that has been conducted so far seems to suggest an inverse relationship between the two constructs. A smaller number of studies has found the opposite result, however, and some of the previous studies have been limited by small sample sizes and unrepresentative samples. The current study attempts to help clarify the relationship between resting heart rate and psychopathic traits in a large, nationally representative sample (analytical N ranged from 14,173-14,220) using an alternative measure of psychopathic traits that is less focused on antisocial processes, and rooted in personality traits. No significant relationship between heart rate and psychopathic traits, or heart rate and a measure of cold-heartedness, was found. It is possible that previous findings of a link between heart rate and psychopathy have been driven by the inclusion of overt antisocial behavior in many traditional psychopathy measures. Further work is needed to confirm the associations (or lack thereof) between heart rate and the behavioral, affective, and personality trait aspects of psychopathy.

Gender disparity in utilization rates of substance abuse services among female ex-offenders: a population-based analysis.

BACKGROUND: The use and abuse of substances is common among offender populations. Although the female former offender population has risen substantially in recent decades, relatively little is known about their substance abuse treatment experiences. OBJECTIVE: This study examines disparities in substance abuse treatment utilization among the US population with special focus upon formerly incarcerated female offenders. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n = 43,093) collected in 2001-2002 and 2004-2005 the authors compared lifetime rates of substance abuse treatment utilization between female and male ex-offenders with the U.S. general population. The sample population covered inpatient and community based substance use treatment, detoxification and rehabilitation programs. It is a nationally representative sample of noninstitutionalized persons over the age of 18. Multinomial logistic regression was performed and likelihood of using substance use treatment and services was calculated using adjusted odds ratios (AOR). RESULTS: Compared to male ex-offenders, female ex-offenders were 52% less likely to use substance-abuse treatment services (AOR = 0.48, 95% CI = 0.26-0.89) and 51% less likely to use rehabilitation programs (AOR = 0.49, 95% CI = 0.26-0.93). Compared to females in the general population, female ex-offenders were 10 times more likely to use substance-abuse treatment services (AOR = 10.14, 95% CI = 5.71-18.00), 10.5 times more likely to use substance detoxification programs (AOR = 10. 45, 95% CI = 5.64-19.39); 8 times more likely to use inpatient wards (AOR = 8.05, 95% CI = 4.16-15.59); 9 times more likely to use outpatient wards (AOR = 9.06, 95% CI = 4.89-16.81), and 12 times more likely to use substance-abuse rehabilitation programs (AOR = 12.06, 95% CI = 6.55-22.22). CONCLUSIONS: While female ex-offenders were more likely to have used a range of substance abuse services when compared to the general population, they were less likely to use substance-abuse treatment services and rehabilitation programs than male ex-offenders.