Children's exposure to brominated flame retardants in the home: The TESIE study.

Due to differences in chemical properties and half-lives, best practices for exposure assessment may differ for legacy versus novel brominated flame retardants (BFRs). Our objective was to identify the environment matrix that best predicted biomarkers of children's BFR exposures. Paired samples were collected from children aged 3-6 years and their homes, including dust, a small piece of polyurethane foam from the furniture, and a handwipe and wristband from each child. Biological samples collected included serum, which was analyzed for 11 polybrominated diphenyl ethers (PBDEs), and urine, which was analyzed for tetrabromobenzoic acid (TBBA), a metabolite of 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB). Significant positive correlations were typically observed between BFRs measured in dust, handwipes and wristbands, though wristbands and handwipes tended to be more strongly correlated with one another than with dust. PBDEs, EH-TBB and BEH-TEBP were detected in 30% of the sofa foam samples, suggesting that the foam was treated with PentaBDE or Firemaster® 550/600 (FM 550/600). PBDEs were detected in all serum samples and TBBA was detected in 43% of urine samples. Statistically significant positive correlations were observed between the environmental samples and serum for PBDEs. Urinary TBBA was 6.86 and 6.58 times more likely to be detected among children in the highest tertile of EH-TBB exposure for handwipes and wristbands, respectively (95 % CI: 2.61, 18.06 and 1.43, 30.05 with p < 0.001 and 0.02, respectively). The presence of either PentaBDE or FM 550/600 in furniture was also associated with significantly higher levels of these chemicals in dust, handwipes and serum (for PBDEs) and more frequent detection of TBBA in urine (p = 0.13). Our results suggest that children are exposed to a range of BFRs in the home, some of which likely originate from residential furniture, and that silicone wristbands are a practical tool for evaluating external exposure to both legacy and novel BFRs.

Experience With Four-Month Rifapentine and Moxifloxacin-Based Tuberculosis Treatment in San Francisco.

Background: A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. Methods: In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. Results: From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14-86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Conclusions: Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen.

Online and Offline Prioritization of Chemicals of Interest in Suspect Screening and Non-targeted Screening with High-Resolution Mass Spectrometry.

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typically required in targeted analysis. However, to determine the presence of chemicals of interest that may pose an overall impact on ecological and human health, prioritization strategies must be used to effectively and efficiently highlight chemicals for further investigation. Prioritization can be based on a chemical's physicochemical properties, structure, exposure, and toxicity, in addition to its regulatory status. This Perspective aims to provide a framework for the strategies used for chemical prioritization that can be implemented to facilitate high-quality research and communication of results. These strategies are categorized as either "online" or "offline" prioritization techniques. Online prioritization techniques trigger the isolation and fragmentation of ions from the low-energy mass spectra in real time, with user-defined parameters. Offline prioritization techniques, in contrast, highlight chemicals of interest after the data has been acquired; detected features can be filtered and ranked based on the relative abundance or the predicted structure, toxicity, and concentration imputed from the tandem mass spectrum (MS2). Here we provide an overview of these prioritization techniques and how they have been successfully implemented and reported in the literature to find chemicals of elevated risk to human and ecological environments. A complete list of software and tools is available from https://nontargetedanalysis.org/.

Characterizing azobenzene disperse dyes and related compounds in house dust and their correlations with other organic contaminant classes.

Azobenzene disperse dyes are the fastest-growing category of commercial dyestuffs and are implicated in the literature as potentially allergenic. In the indoor environment, these dyes may be shed from various textiles, including clothing and upholstery and accumulate in dust particles potentially leading to exposure in young children who have higher exposure to chemicals associated with dust due to their crawling and mouthing behaviors. Children may be more vulnerable to dye exposure due to their developing immune systems, and therefore, it is critical to characterize azobenzene disperse dyes in children's home environments. Here, we investigate azobenzene disperse dyes and related compounds in house dust samples (n = 124) that were previously analyzed for flame retardants, phthalates, pesticides and per- and polyfluoroalkyl substances (PFAS). High-resolution mass spectrometry was used to support both targeted and suspect screening of dyes in dust. Statistical analyses were conducted to determine if dye concentrations were related to demographic information. Detection frequencies for 12 target dyes ranged from 11% to 89%; of the dyes that were detected in at least 50% of the samples, geometric mean levels ranged from 32.4 to 360 ng/g. Suspect screening analysis identified eight additional high-abundance azobenzene compounds in dust. Some dyes were correlated to numerous flame retardants and several antimicrobials, and statistically higher levels of some dyes were observed in homes of non-Hispanic Black mothers than in homes of non-Hispanic white mothers. To our knowledge, this is the most comprehensive study of azobenzene disperse dyes in house dust to date. Future studies are needed to quantify additional dyes in dust and to examine exposure pathways of dyes in indoor environments where children are concerned.

Complex Mixtures and Multiple Stressors: Evaluating Combined Chemical Exposures and Cumulative Toxicity.

The problem of chemical mixtures in the environment encompasses biological, analytical, logistical, and regulatory challenges, among others [...].

A Call to Action for Gender Equity in Climate Leadership.

Climate action is not advancing quickly enough to prevent catastrophic harm. Understanding why might require looking at existing leadership structures and the inequitable gender representation therein. Critically examining dominant power structures could pave the way toward more comprehensive, innovative, and expedient environmental solutions-and we argue that elevating women's climate leadership is key to safeguarding planetary health. Women have historically been left out of climate science and governance leadership. Women are disproportionately impacted by the health effects of climate change, particularly in Indigenous and low- and middle-income settings. Therefore, our call for women's climate leadership is both an issue of justice and a matter of effectiveness, given evidence that inclusive leadership rooted in gender justice leads to more equitable outcomes. Here, we present evidence for why gender equity in climate leadership matters along with considerations for how to attain it across sectors and stakeholders.

Associations Among Clinical Factors and Occupational Therapy Service Utilization in Children With Autism Spectrum Disorder.

IMPORTANCE: Limited research has elucidated factors predicting occupational therapy-specific service utilization by children with autism. Such research is needed to inform reasons for receipt of services. OBJECTIVE: To examine factors associated with occupational therapy service utilization by children with autism. We hypothesized that elevated sensory hyperresponsiveness; greater sensory interests, repetitions, and seeking; and lower adaptive behavior would predict more service utilization. DESIGN: Analysis of extant data from a prospective, longitudinal survey study about autism symptom severity, adaptive behavior, sensory features, and demographic and service utilization information of children with autism ages 3 to 13 yr. SETTING: Online parent survey regarding child behaviors during daily activities and contexts. PARTICIPANTS: 892 parents of children with autism from 50 U.S. states. OUTCOMES AND MEASURES: We used scores on the Vineland Adaptive Behavior Scale-Second Edition, the Social Responsiveness Scale, and the Sensory Experiences Questionnaire Version 3.0 and responses to a demographic questionnaire. We formulated hypotheses after data collection but before analysis. RESULTS: Predictors of higher occupational therapy service utilization were lower enhanced perception; lower adaptive behavior; elevated sensory interests, repetitions, and seeking behaviors; younger child age; and higher household income. CONCLUSION AND RELEVANCE: Results partially support our hypotheses. Sensory interests, repetitions, and seeking behavior predicted occupational therapy service utilization, whereas other sensory response patterns did not, suggesting a possible referral bias for certain sensory response patterns. Occupational therapy practitioners can educate parents and teachers about the scope of practice, which includes addressing sensory features beyond sensory interests, repetitions, and seeking behaviors. What This Article Adds: Children with autism who have impairments in adaptive functioning and high levels of sensory interests, repetitions, and seeking behaviors receive more occupational therapy services. Occupational therapy practitioners should be well trained to address such concerns and advocate for the profession's role in mitigating the impact of sensory features on daily life.

Assessment Fidelity of Parents Implementing a Standardized Telehealth Infant Autism Screener.

Telehealth is effective for service delivery in pediatric occupational therapy across ages and diagnoses. Remote parent coaching provides unique benefits for both parents and infants. As a result of COVID-19, practitioners and researchers pivoted to remote assessment and intervention without much preparation or training. It is critical that we evaluate the quality of these telehealth services. One important component of remote evaluations is assessment fidelity. To examine assessment fidelity of a telehealth-delivered observational autism screening tool for infants. An assessment fidelity checklist was applied as the primary outcome measure. Parents conducted assessments with 82% adherence to the fidelity checklist. Implications: A parent coaching telehealth approach may be valid for assessment in pediatric telehealth. Continually monitoring the assessment fidelity of a tool is critical for the valid administration of remote services.

Demonstrating the Use of Non-targeted Analysis for Identification of Unknown Chemicals in Rapid Response Scenarios.

Several thousand intentional and unintentional chemical releases occur annually in the U.S., with the contents of almost 30% being of unknown composition. When targeted methods are unable to identify the chemicals present, alternative approaches, including non-targeted analysis (NTA) methods, can be used to identify unknown analytes. With new and efficient data processing workflows, it is becoming possible to achieve confident chemical identifications via NTA in a timescale useful for rapid response (typically 24-72 h after sample receipt). To demonstrate the potential usefulness of NTA in rapid response situations, we have designed three mock scenarios that mimic real-world events, including a chemical warfare agent attack, the contamination of a home with illicit drugs, and an accidental industrial spill. Using a novel, focused NTA method that utilizes both existing and new data processing/analysis methods, we have identified the most important chemicals of interest in each of these designed mock scenarios in a rapid manner, correctly assigning structures to more than half of the 17 total features investigated. We have also identified four metrics (speed, confidence, hazard information, and transferability) that successful rapid response analytical methods should address and have discussed our performance for each metric. The results reveal the usefulness of NTA in rapid response scenarios, especially when unknown stressors need timely and confident identification.

Impact of diabetes (type 2) and glycemic control on health-related outcomes of patients receiving chemotherapy for non-metastatic breast cancer: a retrospective analysis.

PURPOSE: To examine the impact of diabetes (type 2) and glycemic control on healthcare-related outcomes (healthcare utilization, adverse effects, and treatment modifications) in non-metastatic breast cancer (NMBC) patients during chemotherapy treatment. METHODS: This was a retrospective study of 243 NMBC patients (stages 1-3) with/without diabetes receiving neoadjuvant or adjuvant cytotoxic chemotherapy. The primary study endpoint was to compare healthcare utilization between NMBC patients with and without diabetes. Secondary study endpoints included adverse events and chemotherapy treatment modifications. Additional analyses were conducted to compare these health-related outcomes by glycemic control status. RESULTS: NMBC patients with diabetes had higher utilization of emergency department (ED) services (52% vs. 33%, p = 0.013) and a higher frequency of unplanned inpatient admissions (35% vs. 19%, p = 0.014). Additionally, NMBC patients with diabetes had a higher incidence of infection and treatment modifications. NMBC patients, regardless of diabetes diagnosis, who had poor glycemic control, specifically hyperglycemia (per random blood glucose), during the study period also had increased healthcare utilization, adverse effects, and treatment modifications. Patients with a baseline HbA1c ≥ 7 had a greater number of ED visits and a higher incidence of infection than those without diabetes. CONCLUSION: Diabetes and glycemic control may impact the health-related outcomes of NMBC patients. Additional studies are needed to confirm these findings and determine optimal monitoring and management strategies for NMBC patients with diabetes and/or poor glycemic control during cytotoxic chemotherapy.

Nivolumab/Relatlimab: A Novel Addition to Immune Checkpoint Inhibitor Therapy in Unresectable or Metastatic Melanoma.

OBJECTIVE: The aim of this article is to assess available data regarding use of nivolumab/relatlimab for adult and pediatric patients 12 years of age and older with unresectable or metastatic melanoma. DATA SOURCES: A search of PubMed conducted from August 2019 to August 2022 with the search terms Opdualag, nivolumab AND relatlimab, and BMS-986016 resulted in 14 publications. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials written in English language were analyzed. DATA SYNTHESIS: Nivolumab/relatlimab was approved by the Food and Drug Administration following results of a phase 1/2 trial and phase 2/3 RELATIVITY-047 trial. Nivolumab/relatlimab demonstrated a median progression free survival (PFS) of 10.1 months in the first-line setting without new safety signals. The PFS benefits appear greatest in those with programmed cell death-ligand 1 (PD-L1) <1% and lymphocyte activation gene-3 (LAG-3) ≥1%. Adverse effects commonly experienced were immune related in nature and require early identification and prompt management. Grade 3 or 4 adverse effects occurred in 18.9% of patients. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: For patients 12 years of age and older with unresectable or metastatic melanoma, nivolumab/relatlimab offers a new first-line treatment option. Evaluation of PD-L1 expression along with concomitant use of medications with potential interactions should be evaluated when deciding if nivolumab/relatlimab is the most appropriate treatment option. CONCLUSIONS: Nivolumab/relatlimab adds an additional first-line treatment option demonstrating promising improved PFS for patients with unresectable or metastatic melanoma, particularly those with PD-L1 <1% and/or LAG 3 ≥1%. Additional uses of nivolumab/relatlimab may be on the horizon as further clinical trials are ongoing.

Adverse Events Associated With Treatment for Pan-Susceptible Tuberculosis in San Francisco.

Of 373 patients treated for drug-susceptible tuberculosis, 35.4% (46.2% aged ≥65 years) developed moderate/severe adverse events that required treatment interruption (34.8%), first-line drug discontinuation (26.2%, primarily pyrazinamide), second-line drug initiation (30.0%), and treatment duration up to 3.8 months longer. More safe and effective options are needed, including for the elderly.

Outcomes and Management of Immune Checkpoint Inhibitor-Induced Hypothyroidism: A Retrospective Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) used in cancer treatment cause immune-related adverse effects (irAEs), including thyroiditis leading to hypothyroidism. The management and outcomes of this irAE are not well established. OBJECTIVE: The purpose of this analysis is to describe the onset, management, and outcomes of patients experiencing hypothyroidism from ICI. METHODS: A retrospective study was conducted of adults receiving ICI therapy at a community cancer center between January 1, 2017, and February 1, 2020. The primary endpoint was to describe onset (timing) of hypothyroidism (thyroid-stimulating hormone [TSH] > 10 µIU/mL). Secondary outcomes included describing hypothyroidism symptoms and levothyroxine use, time to documented disease progression, and occurrence of additional adverse effects (AEs). RESULTS: Of the 200 patients included in the study, 19% developed clinical hypothyroidism (TSH > 10 µIU/mL, or required initiation of or dose increase in levothyroxine). Median time to TSH higher than 10 µIU/mL was 13.3 weeks and symptoms of hypothyroidism occurred in 34% of patients developing clinical hypothyroidism. The median final daily levothyroxine dose was 88 mcg (0.88 mcg/kg). Time to disease progression was longer in those with clinical hypothyroidism (27.4 months vs. 6.8 months, respectively, P = .015). Additional AEs occurred in 68% of those developing hypothyroidism versus 49% without hypothyroidism (P = .029). CONCLUSION AND RELEVANCE: Patients with clinical hypothyroidism during ICI treatment may have improved cancer outcomes, but they also are more likely to develop other AEs. Patients requiring thyroid replacement therapy with levothyroxine may benefit from a starting dose between 50 and 100 mcg/day, approximately 0.88 mcg/kg/day.

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

A Framework for Utilizing High-Resolution Mass Spectrometry and Nontargeted Analysis in Rapid Response and Emergency Situations.

Unknown chemical releases constitute a large portion of the rapid response situations to which the US Environmental Protection Agency is called on to respond. Workflows used to address unknown chemical releases currently involve screening for a large array of known compounds using many different targeted methods. When matches are not found, expert analytical chemistry knowledge is used to propose possible candidates from the available data, which generally includes low-resolution mass spectra and situational clues such as the location of the release, nearby industrial operations, and other field-reported facts. The past decade has witnessed dramatic improvements in capabilities for identifying unknown compounds using high-resolution mass spectrometry (HRMS) and nontargeted analysis (NTA) approaches. Complementary developments in cheminformatics tools have further enabled an increase in NTA throughput and identification confidence. Together with the expanding availability of HRMS instrumentation in monitoring laboratories, these advancements make NTA highly relevant to rapid response scenarios. In this article, we introduce the concept of NTA as it relates to rapid response needs and describe how it can be applied to address unknown chemical releases. We advocate for the consideration of HRMS-based NTA approaches to support future rapid response scenarios. Environ Toxicol Chem 2022;41:1117-1130. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

An Introduction to the Benchmarking and Publications for Non-Targeted Analysis Working Group.

Non-targeted analysis (NTA) encompasses a rapidly evolving set of mass spectrometry techniques aimed at characterizing the chemical composition of complex samples, identifying unknown compounds, and/or classifying samples, without prior knowledge regarding the chemical content of the samples. Recent advances in NTA are the result of improved and more accessible instrumentation for data generation and analysis tools for data evaluation and interpretation. As researchers continue to develop NTA approaches in various scientific fields, there is a growing need to identify, disseminate, and adopt community-wide method reporting guidelines. In 2018, NTA researchers formed the Benchmarking and Publications for Non-Targeted Analysis Working Group (BP4NTA) to address this need. Consisting of participants from around the world and representing fields ranging from environmental science and food chemistry to 'omics and toxicology, BP4NTA provides resources addressing a variety of challenges associated with NTA. Thus far, BP4NTA group members have aimed to establish a consensus on NTA-related terms and concepts and to create consistency in reporting practices by providing resources on a public Web site, including consensus definitions, reference content, and lists of available tools. Moving forward, BP4NTA will provide a setting for NTA researchers to continue discussing emerging challenges and contribute to additional harmonization efforts.

Nontargeted Analysis Study Reporting Tool: A Framework to Improve Research Transparency and Reproducibility.

Non-targeted analysis (NTA) workflows using mass spectrometry are gaining popularity in many disciplines, but universally accepted reporting standards are nonexistent. Current guidance addresses limited elements of NTA reporting-most notably, identification confidence-and is insufficient to ensure scientific transparency and reproducibility given the complexity of these methods. This lack of reporting standards hinders researchers' development of thorough study protocols and reviewers' ability to efficiently assess grant and manuscript submissions. To overcome these challenges, we developed the NTA Study Reporting Tool (SRT), an easy-to-use, interdisciplinary framework for comprehensive NTA methods and results reporting. Eleven NTA practitioners reviewed eight published articles covering environmental, food, and health-based exposomic applications with the SRT. Overall, our analysis demonstrated that the SRT provides a valid structure to guide study design and manuscript writing, as well as to evaluate NTA reporting quality. Scores self-assigned by authors fell within the range of peer-reviewer scores, indicating that SRT use for self-evaluation will strengthen reporting practices. The results also highlighted NTA reporting areas that need immediate improvement, such as analytical sequence and quality assurance/quality control information. Although scores intentionally do not correspond to data/results quality, widespread implementation of the SRT could improve study design and standardize reporting practices, ultimately leading to broader use and acceptance of NTA data.