Demonstrating the reliability of in vivo metabolomics based chemical grouping: towards best practice.

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography-mass spectrometry (LC-MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice.

Shorter Telomere Length Is Associated With Older Age, Poor Sleep Hygiene, and Orthopedic Injury, but Not Mild Traumatic Brain Injury, in a Cohort of Canadian Children.

BACKGROUND: Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI). METHODS: Saliva was collected at a postacute (median 7 days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17 years with either mTBI (n = 202) or OI (n = 90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman's correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates. RESULTS: After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio = 0.93; 95% confidence interval, 0.89-0.98; P = .003). As expected, increasing age was negatively associated with TL (Spearman's r = -0.14, P = .016). Sleep hygiene at 3 months was positively associated with TL (adjusted mean ratio = 1.010; 95% confidence interval, 1.001-1.020; P = .039). CONCLUSION: The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.

What medical-legal partnerships can do for trauma patients and trauma care.

ABSTRACT: Trauma patients are particularly vulnerable to the impact of preexisting social and legal determinants of health postinjury. Trauma patients have a wide range of legal needs, including housing, employment, debt, insurance coverage, and access to federal and state benefits. Legal support could provide vital assistance to address the social determinants of health for injured patients. Medical legal partnerships (MLPs) embed legal professionals within health care teams to improve health by addressing legal needs that affect health. Medical legal partnerships have a successful track record in oncology, human immunodeficiency virus/acquired immune deficiency syndrome, and pediatrics, but have been little used in trauma. We conducted a scoping review to describe the role of MLPs and their potential to improve health outcomes for patients with traumatic injuries. We found that MLPs use legal remedies to address a variety of social and structural conditions that could affect patient health across several patient populations, such as children with asthma and patients with cancer. Legal intervention can assist patients in obtaining stable and healthy housing, employment opportunities, debt relief, access to public benefits, and immigration assistance. Medical legal partnership structure varies across institutions. In some, MLP lawyers are employed directly by a health care institution. In others, MLPs function as partnerships between a health system and an external legal organization. Medical legal partnerships have been found to reduce hospital readmissions, increase treatment utilization by patients, decrease patient stress levels, and benefit health systems financially. This scoping review outlines the potential of MLPs to improve outcomes for injured patients. Establishing trauma-focused MLPs could be a feasible intervention for trauma centers around the country seeking to improve health outcomes and reduce disparities for injured patients.

Addressing Legal Needs as Violence Prevention: A National Survey of Legal Services Offered through Hospital-based Violence Intervention Programs.

Hospital-based violence intervention programs (HVIPs) provide comprehensive services to survivors of community violence to address social determinants of health (SDOH) as risks factors for future violence. Medical-legal partnerships (MLPs) integrate lawyers into health care teams to address SDOH through the application of the law. Despite shared purposes, it is unknown if HVIP-MLPs exist. We sought to quantify the existing landscape of legal services provided by HVIPs, identify HVIP-MLPs, and characterize barriers to formation. Surveys and interviews were conducted in 2020 with 35 HVIPs of the Health Alliance for Violence Intervention (HAVI) concerning civil legal services. Most HVIPs screened for civil legal needs though none had an official MLP. Common civil legal needs included housing, mental health, and education. Barriers included no memorandum of understanding, legal confusion, funding, and overwhelming need. In 2021, no HVIP-MLP partnerships existed within HAVI. Establishing HVIP-MLPs may further support survivors of violence and address health inequity.