Treatment patterns and outcomes following disease progression on anti-PD-1 therapies for advanced melanoma

Background: Anti-PD-1-based therapies prolong survival in advanced melanoma, but disease progression is common. This study evaluated treatment patterns and overall survival (OS) after anti-PD-1 progression. Methods: Retrospective data from patients with advanced melanoma and progression on anti-PD-1 treatment between 2014 and 2019 were taken from Flatiron Health, which reflects largely community practice. Treatment patterns and OS were analyzed for BRAF mutant (mt) and wild-type (wt) subgroups; OS was also examined across all patients. Results: Progression following anti-PD-1 was recorded for 679 patients. Median OS ranged from 5.0 to 11.3 months. Of 275 BRAFmt and 374 BRAFwt patients, 113 (41.1%) and 228 (61.0%) received no subsequent therapy, respectively. However, 48.4% of BRAFmt and 57.8% of BRAFwt patients continued anti-PD-1 treatment beyond progression. Conclusion: This real-world study underscores the need for effective treatments for advanced melanoma post-progression on anti-PD-1 therapy

Burden of asthma exacerbations and health care utilization in pediatric patients with asthma in the US and England.

BACKGROUND: Data on asthma burden in pediatric patients are limited; this real-world study investigated exacerbation frequency and health care resource utilization (HCRU) in pediatric asthma patients from the US and England. METHODS: Data from pediatric patients (aged 6-17 years) in the Optum claims database (US) or Clinical Practice Research Datalink with linkage to Hospital Episode Statistics (England) were analyzed. Patients were categorized into four hierarchical groups: treated asthma (patients with ≥1 baseline asthma medication), severe asthma (plus Global Initiative for Asthma Step 4/5), severe refractory asthma ([SRA] plus ≥2 baseline severe asthma exacerbations), and eosinophilic SRA (SRA plus blood eosinophil count ≥150 cells/µL). Exacerbation frequency and HCRU during the 12 months postindex were described. RESULTS: Of 151 549 treated asthma patients in the US, 18 086 had severe asthma, 2099 SRA, and 109 eosinophilic SRA. There were 32 893 treated asthma patients in England, of whom 2711 had severe asthma, 265 SRA, and 8 eosinophilic SRA. In the 12 months postindex, ≥1 exacerbation occurred in 12.4% and 10.8% of patients with severe asthma, and 32.6% and 42.6% with SRA in the US and England, respectively. The proportions of patients with ≥1 asthma hospitalization in the 30 days after the first asthma exacerbation were 2.7% and 4.4% (treated), 3.5% and 8.2% (severe asthma), and 6.0% and 16.8% (SRA) in the US and England, respectively. CONCLUSION: This study provides insights into current asthma management practices in the US and England and indicates that some patients with severe disease have an unmet need for effective management

Attrition in a Multi-Component Smoking Cessation Study for Females

Limiting attrition (i.e., participant dropout before the conclusion of a study) is a major challenge faced by researchers when implementing clinical trials. Data from a smoking cessation trial for females (N = 246) were analyzed in order to identify baseline smoking-related, demographic and psychological characteristics affecting likelihood of early (i.e., before the quit attempt) and late (i.e., after the quit attempt) dropout. There were a number of significant demographic predictors of attrition. Participants with at least one child living at home were at increased risk of both early and late dropout. Non-Whites were at increased risk of early dropout, while not having a college degree put one at increased risk of late dropout. Age was found to be a protective factor in that the older a participant was, the less likely she was to drop out in the early stages of the trial. With respect to psychological variables, weight concerns increased risk of attrition, as did the experience of guilt. In terms of smoking-related variables, mean cigarettes per day was not a significant predictor of attrition, although length of longest prior quit attempt was a significant predictor of early dropout when age was removed from the regression

Disruptions in Liver Function among Cancer Patients and Patients Treated with Tyrosine Kinase Inhibiting Drugs: Comparisons of Two Population-Based Databases

Liver toxicity is a recognized adverse event associated with small molecule tyrosine kinase inhibitors (TKIs). Electronic Medical Record (EMR) databases offer the most precise data to investigate the rate of liver function test (LFT) elevations; however, they can be limited in sample size and costly to access and analyze. Health insurance claims databases often contain larger samples sizes but may lack key health information. We evaluated the feasibility of utilizing a large claims database to calculate incidence rates (IRs) of LFT elevations among a general cohort of cancer patients and a cohort of patients treated with TKIs by comparing the results to a “gold standard” oncology-specific EMR database. IRs for the TKI cohorts were very similar between the two databases; however, IRs were higher in the EMR database for the cancer cohorts. Possible explanations for these differences include lack of specificity when defining a cancer case, poor capture of laboratory data, or inaccurate assessment of person-time in the insurance claims database. This study suggests that insurance claims data may provide reliable results when investigating liver toxicities associated with oncology drug exposure; however, there are limitations when assessing laboratory outcomes for cohorts defined solely by disease status

Allelic Variation and Environmental Lead Exposure in Urban Children

The advent of the Human Genome Project has allowed for increased understanding and sophistication in diagnosis, treatment methods, and overall care planning on the part of healthcare providers for children with genetic disorders. Genetics research dealing with polymorphic changes within a genome has opened the door to awareness of how dormant genetic alleles may become active when coupled with certain environmental insults. Such genetic aberrations may place a child at a higher risk for health disparities when exposed to environmental toxins. It has been posited that such exposure in children with an arylsulfatase-A (ASA) allelic variation is associated with increased risk for neurodevelopmental damage. This initial study contributes to this new field and supports development of finer-tuned methods to prevent ominous outcomes of lead exposure. The purpose of this study was to explore the incidence of children in a representative sample from a Midwest metropolitan city with positive test results for the ASA allelic variation who have been exposed to the environmental toxin lead. In this corollary study of 107 children, part of a parent study on the behavior of African American children prenatally exposed to cocaine, 45% were found to be heterozygous, 11% mutant homozygous, and 44% normal in terms of ASA allele or alleles. Further studies on neurodeficiencies, low-level exposure to environmental toxins, and allelic variations must be conducted before a relation between ASA allelic variance and environmental lead can be determined

The Association Between Caregiver Substance Abuse and Self-Reported Violence Exposure Among Young Urban Children

This study examined the relative importance of caregiver substance abuse as a correlate of child-reported exposure to violence. A total of 407 female African-American primary caregivers and their children age 6 to 7 were evaluated. The association between child report of violence and exposure to substance abuse by others (both within and outside the home) was considered after controlling for variance accounted for by child characteristics, caregiver characteristics, home environment, and neighborhood environment (including neighborhood crime). Caregiver alcohol abuse, children\u27s witnessing of drug use in the home, and children\u27s witnessing of drug deals all explained significant additional variance in violence exposure. These findings suggest that for early elementary-age children, meaningful prevention of violence exposure may be possible via addressing their exposure to substance abuse in their home and community