Moderation Effects of Daily Behavior on Associations between Symptoms and Social Participation Outcomes after Burn Injury: A 6-month Digital Phenotyping Study.

OBJECTIVE: To examine the moderation effects of daily behavior on the associations between symptoms and social participation outcomes after burn injury DESIGN: A 6-month prospective cohort study SETTING: Community PARTICIPANTS: 24 adult burn survivors INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Symptoms and social participation outcomes were assessed weekly using smartphone surveys, including symptoms of pain (Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity and Pain Interference), anxiety (PROMIS Anxiety), and depression (Patient Health Questionnaire (PHQ-8)), as well as outcomes of social interactions and social activities (Life Impact Burn Recovery Evaluation (LIBRE) Social Interactions and Social Activities). Daily behaviors were automatically recorded by a smartphone application and smartphone logs, including physical activity (steps, travel miles, and activity minutes), sleep (sleep hours), and social contact (number of phone call and message contacts). RESULTS: Multilevel models controlling for demographic and burn injury variables examined the associations between symptoms and social participation outcomes, and the moderation effects of daily behaviors. Lower (worse) LIBRE Social Interactions and LIBRE Social Activities scores were significantly associated with higher (worse) PROMIS Pain Intensity, PROMIS Pain Interference, PROMIS Anxiety, and PHQ-8 scores (p<0.05). Additionally, daily steps and activity minutes were associated with LIBRE Social Interactions and LIBRE Social Activities (p<0.05), and significantly moderated the association between PROMIS Anxiety and LIBRE Social Activities (p<0.001). CONCLUSIONS: Social participation outcomes are associated with pain, anxiety, and depression symptoms after burn injury, and are buffered by daily physical activity. Future interventions studies should examine physical activity promotion on improving social recovery after burns.

Beyond surviving: A scoping review of collaborative care models to inform the future of post-discharge trauma care.

ABSTRACT: Trauma centers demonstrate an impressive ability to save lives, as reflected by inpatient survival rates of over 95% in the United States. Nevertheless, we fail to allocate sufficient effort and resources to ensure that survivors and their families receive the necessary care and support after leaving the trauma center. The objective of this scoping review is to systematically map the research on collaborative care models (CCM) that have been put forward to improve trauma survivorship. Of 833 articles screened, we included 16 studies evaluating eight collaborative care programs, predominantly in the U.S. The majority of the programs offered care coordination and averaged 9-months in duration. Three-fourths of the programs incorporated a mental health provider within their primary team. Observed outcomes were diverse: some models showed increased engagement (e.g., Center for Trauma Survivorship, trauma quality-of-life follow-up clinic), while others presented mixed mental health outcomes and varied results on pain and healthcare utilization. The findings of this study indicate that collaborative interventions may be effective in mental health screening, PTSD and depression management, effective referrals, and improving patient satisfaction with care. A consensus on core elements and cost-effectiveness of CCMs is necessary to set the standard for comprehensive care in post-trauma recovery.

A novel missense variant at the NKX2-1 homeodomain prevents the transcriptional rescue by TAZ.

Background Brain-Lung-Thyroid syndrome (BLTS) is caused by NKX2-1 haploinsufficiency, resulting in chorea/choreoathetosis, respiratory problems and hypothyroidism. Genes interacting with NKX2-1 mutants influence its phenotypic variability. We report a novel NKX2-1 missense variant and the modifier function of TAZ/WWTR1 in BLTS. Methods A child with BLTS underwent NGS panel testing for thyroid disorders. His family was genotyped for NKX2-1 variants and screened for germline mosaicism. Mutant NKX2-1 was generated and transactivation assays were performed on three NKX2-1 target gene promoters. DNA binding capacity and protein-protein interaction were analyzed. Results The patient had severe BLTS and carried a novel missense variant c.632A>G (p.N211S) in NKX2-1, which failed to bind to specific DNA promoters, reducing their transactivation. TAZ co-transfection did not significantly increase transcription of these genes, although the variant retained its ability to bind to TAZ. Conclusions We identify a novel pathogenic NKX2-1 variant that causes severe BLTS and is inherited through germline mosaicism. The mutant lacks DNA binding capacity, impairing transactivation and suggesting that NKX2-1 binding to DNA is essential for TAZ-mediated transcriptional rescue.

Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

BACKGROUND: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). OBJECTIVES: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. METHODS: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. RESULTS: Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. CONCLUSION: Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Critical appraisal of the Colombian clinical practice guide for the prevention, diagnosis and treatment of suicidal ideation and/or behaviour (adoption).

INTRODUCTION: Suicide is a complex, global public health problem. The Colombian clinical practice guideline provides relevant input for its prevention, diagnosis and treatment. The objective was to evaluate the methodological quality, credibility and applicability of the Colombian clinical practice guideline for suicidal behaviour. METHODS: An academic group of 12 evaluators was established to assess the guide and its recommendations in a standardised way, using the AGREE-II and AGREE-REX instruments. The evaluations were given in the range of 0.0-1.0 with 0.7 as a cut-off point for appropriate quality. RESULTS: The global assessment of the AGREE-II was greater than 0.7 in the dimensions: "scope and objective" (0.86), "clarity of presentation" (0.89), "applicability" (0.73) and "editorial independence" (0.89). The lowest scores were for "participation of those involved" (0.67) and "rigour in preparation" (0.69). With the AGREE-REX, the results in all dimensions were below 0.70, which indicates lower quality and suitability for use. CONCLUSIONS: The adoption process of the Colombian guideline for suicidal behaviour was a rigorous methodological process, while the practice recommendations were valued as of low applicability due to low support in local evidence. It is necessary to strengthen the generation and synthesis of evidence at the national level to give greater support and applicability to the practice recommendations.

Psychiatric and Substance Use Disorders and Their Association With Clinical Outcomes in Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome.

BACKGROUND AND OBJECTIVE: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are life-threatening conditions that send nearly 180,000 patients to the intensive care unit each year, with mortality rates up to 5-10%. Little is known about the impact of concurrent psychiatric disorders on specific DKA/HHS outcomes. Identifying these relationships offers opportunities to improve clinical management, treatment planning, and mitigate associated morbidity and mortality. METHODS: We conducted a retrospective review including adult DKA/HHS admissions within a large Massachusetts hospital system from 2010 to 2019. We identified patients admitted inpatient for DKA or HHS, then filtered by International Classification of Disease-9-CM and International Classification of Disease-10-CM codes for psychiatric diagnoses that were present in patients electronic medical record at any point in this observational period. Outcomes included the number of inpatient admissions for DKA/HHS, age of death, rates of discharging against medical advice (AMA) from any inpatient admission, and end-stage renal disease/dialysis status. Multivariate regression was conducted using R software to control for variables across patients and evaluate relationships between outcomes and concurrent psychiatric disorders. Significance was set at P < 0.05. RESULTS: Seven thousand seven hundred fifty-six patients were admitted for DKA or HHS, 66.9% of whom had a concurrent psychiatric disorder. Of these patients, 54.5% were male, 70.4% were White, and they had an average age of 61.6 years. This compares with 26.1% with concurrent psychiatric condition within the general diabetes population, 52.1% of whom were male, 72.1% were White, and an average age of 68.2 years. A concurrent psychiatric disorder was associated with increased odds of rehospitalization (adjusted odds ratio [aOR] = 1.62 95% confidence interval [CI] 1.35-1.95, P < 0.001), of being diagnosed with end-stage renal disease and on dialysis (aOR = 1.02 95% CI 1.002-1.035, P = 0.02), and of leaving AMA (aOR = 6.44 95% CI 4.46-9.63, P < 0.001). The average age of death for those with a concurrent psychiatric disorder had an adjusted mean difference in years of -7.5 years (95% CI -9.3 to 5.8) compared to those without a psychiatric disorder. CONCLUSIONS: Of patients with DKA/HHS, 66.9% have a concurrent psychiatric disorder. Patients with a concurrent psychiatric disorder admitted for DKA/HHS were more likely to have multiple admissions, to leave AMA, to be on renal dialysis, and to have a lower age of mortality.

Emergence of lingual dystonia and strabismus in early-onset SCN8A self-limiting familial infantile epilepsy.

Pathogenic variants in SCN8A are associated with a broad phenotypic spectrum, including Self-Limiting Familial Infantile Epilepsy (SeLFIE), characterized by infancy-onset age-related seizures with normal development and cognition. Movement disorders, particularly paroxysmal kinesigenic dyskinesia typically arising after puberty, may represent another core symptom. We present the case of a 1-year-old girl with a familial disposition to self-limiting focal seizures from the maternal side and early-onset orofacial movement disorders associated with SCN8A-SeLFIE. Brain MRI was normal. Genetic testing revealed a maternally inherited SCN8A variant [c.4447G > A; p.(Glu1483Lys)]. After the introduction of valproic acid, she promptly achieved seizure control as well as complete remission of strabismus and a significant decrease in episodes of tongue deviation. Family history, genetic findings, and epilepsy phenotype are consistent with SCN8A-SeLFIE. Movement disorders are an important part of the SCN8A phenotypic spectrum, and this case highlights the novel early-onset orofacial movement disorders associated with this condition. The episodes of tongue deviation and protrusion suggest focal oromandibular (lingual) dystonia. Additionally, while infantile strabismus or esophoria is a common finding in healthy individuals, our case raises the possibility of an ictal origin of the strabismus. This study underscores the importance of recognizing and addressing movement disorders in SCN8A-SeLFIE patients, particularly the rare early-onset orofacial manifestations. It adds to the growing body of knowledge regarding the diverse clinical presentations of SCN8A-associated disorders and suggests potential avenues for clinical management and further research.

Telehealth in Informal Caregivers of Stroke Survivors: A Systematic Review.

Background: There has been an increase in people with disabilities who require continuous care, which often falls to informal carers (ICs). Stroke is one of the conditions where ICs are most needed. Therefore, it is necessary for ICs to improve their caregiving skills and self-care capacity. Telehealth (TH) can facilitate them. The aim of this systematic review is to summarize the evidence of the effects of interventions on ICs of stroke patients. Methods: The search was conducted in Pubmed, Scopus, Web of Science, CINALH, Psychology and Behavioral Sciences Collection, and APA PsycInfo. Key search terms included "stroke", "informal caregiver" and "telemedicine". Only randomised clinical trials were included. Results: A total of 2031 articles were found in the databases, 476 were screened and 19 clinical trials met the eligibility criteria. Different TH programmes have evaluated many outcomes related to physical and emotional health. The TH tools included phone, videophone, web-based interventions, and social media. The most investigated outcome was depression; although contradictory results were found, the TH may have helped to prevent an increase in depressive symptoms. There were inconsistent results on the caregiving burden and the preparedness of the IC. However, TH has positive effects on the health of the ICs, reducing the number of unhealthy days, anxiety, task difficulty perception, and improving psychological health. Conclusions: TH may be a useful tool to improve the abilities and health of ICs of SS. No adverse effects have been reported. More quality studies evaluating the effects of telemedicine on the ICs of stroke survivors, as well as the most appropriate doses, are needed.

An Executive Summary of the National Trauma Research Action Plan (NTRAP).

ABSTRACT: The National Trauma Research Action Plan (NTRAP) project successfully engaged multidisciplinary experts to define opportunities to advance trauma research and has fulfilled the recommendations related to trauma research from the National Academies of Sciences, Engineering and Medicine (NASEM) report. These panels identified more than 4,800 gaps in our knowledge regarding injury prevention and the optimal care of injured patients and laid out a priority framework and tools to support researchers to advance this field. Trauma research funding agencies and researchers can use this executive summary and supporting manuscripts to strategically address and close the highest priority research gaps. Given that this is the most significant public health threat facing our children, young adults, and military service personnel, we must do better in prioritizing these research projects for funding and providing grant support to advance this work. Through the Coalition for National Trauma Research (CNTR), the trauma community is committed to a coordinated, collaborative approach to address these critical knowledge gaps and ultimately reduce the burden of morbidity and mortality faced by our patients.

Additional effects of therapeutic exercise and education on manual therapy for chronic temporomandibular disorders treatment: a randomized clinical trial.

BACKGROUND: Previous studies have evaluated the implementation of behavioral approaches in individuals with chronic temporomandibular disorders (TMDs). OBJECTIVE: To evaluate the benefits of a behavioral approach to craniofacial pain. Second, we assessed the benefits of kinesiophobia, catastrophizing, mouth opening without pain, and forward head posture. METHODS: Individuals with chronic TMDs were treated for five weeks. The intervention group (n = 17) underwent pain neuroscience education, manual therapy, and therapeutic exercise, whereas the control group (n = 17) underwent manual therapy only. Outcomes were evaluated immediately, at seven and 19 weeks follow-up. The assessment tools used were the Craniofacial Pain Disability Inventory, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, Mandibular Range of Motion Scale, and Cervical Range of Motion Tool. RESULTS: The interventions did not influence the differences in the improvements between the groups observed for craniofacial pain disability (inter-subject p 0.4). The intervention had a moderate influence on the improvement of kinesiophobia and catastrophizing (Inter-subject p 0.09 and 0.1 respectively) with a clinically significant effect size (Estimated mean (EM) -8.6 standard deviation (SD) ±3.48 p 0.019; and EM -7.6 SD ± 5.11 p 0.15 respectively). CONCLUSION: The behavioral approach improved catastrophizing and kinesiophobia outcomes in individuals with chronic TMDs.

Determinants of long-term physical and mental health outcomes after intensive care admission for trauma survivors.

INTRODUCTION: Collectively, studies from medical and surgical intensive care units (ICU) suggest that long-term outcomes are poor for patients who have spent significant time in an ICU. We sought to identify determinants of post-intensive care physical and mental health outcomes 6-12 months after injury. METHODS: Adult trauma patients [ISS ≥9] admitted to one of three Level-1 trauma centers were interviewed 6-12 months post-injury to evaluate patient-reported outcomes. Patients requiring ICU admission â€‹≥ â€‹3 days ("ICU patients") were compared with those who did not require ICU admission ("non-ICU patients"). Multivariable regression models were built to identify factors associated with poor outcomes among ICU survivors. RESULTS: 2407 patients were followed [598 (25%) ICU and 1809 (75%) non-ICU patients]. Among ICU patients, 506 (85%) reported physical or mental health symptoms. Of them, 265 (52%) had physical symptoms only, 15 (3%) had mental symptoms only, and 226 (45%) had both physical and mental symptoms. In adjusted analyses, compared to non-ICU patients, ICU patients were more likely to have new limitations for ADLs (OR â€‹= â€‹1.57; 95% CI â€‹= â€‹1.21, 2.03), and worse SF-12 mental (mean Δ â€‹= â€‹-1.43; 95% CI â€‹= â€‹-2.79, -0.09) and physical scores (mean Δ â€‹= â€‹-2.61; 95% CI â€‹= â€‹-3.93, -1.28). Age, female sex, Black race, lower education level, polytrauma, ventilator use, history of psychiatric illness, and delirium during ICU stay were associated with poor outcomes in the ICU-admitted group. CONCLUSIONS: Physical impairment and mental health symptoms following ICU stay are highly prevalent among injury survivors. Modifiable ICU-specific factors such as early liberation from ventilator support and prevention of delirium are potential targets for intervention.

Patients Lost to Follow-up After Injury: Who are They and What are Their Long-Term Outcomes?

INTRODUCTION: Trauma patients are at high risk for loss to follow-up (LTFU) after hospital discharge. We sought to identify risk factors for LTFU and investigate associations between LTFU and long-term health outcomes in the trauma population. METHODS: Trauma patients with an Injury Severity Score ≥9 admitted to one of three Level-I trauma centers, 2015-2020, were surveyed via telephone 6 mo after injury. Univariate and multivariate analyses were performed to assess factors associated with LTFU and several long-term outcomes. RESULTS: Of 3609 patients analyzed, 808 (22.4%) were LTFU. Patients LTFU were more likely to be male (71% versus 61%, P = 0.001), Black (22% versus 14%, P = 0.003), have high school or lower education (50% versus 42%, P = 0.003), be publicly insured (23% versus 13%, P < 0.001), have a penetrating injury (13% versus 8%, P = 0.006), have a shorter length of stay (3.64 d ± 4.09 versus 5.06 ± 5.99, P < 0.001), and be discharged home without assistance (79% versus 50%, P < 0.001). In multivariate analyses, patients who followed up were more likely to require assistance at home (6% versus 11%; odds ratio [OR] 2.23, 1.26-3.92, P = 0.005), have new functional limitations (11% versus 26%; OR 2.91, 1.97-4.31, P = < 0.001), have daily pain (30% versus 48%; OR 2.11, 1.54-2.88, P = < 0.001), and have more injury-related emergency department visits (7% versus 10%; OR 1.93, 1.15-3.22, P = 0.012). CONCLUSIONS: Vulnerable populations are more likely to be LTFU after injury. Clinicians should be aware of potential racial and socioeconomic disparities in follow-up care after traumatic injury. Future studies investigating improvement strategies in follow-up care should be considered.

A new blood DNA methylation signature for Koolen-de Vries syndrome: Classification of missense KANSL1 variants and comparison to fibroblast cells.

Pathogenic variants in KANSL1 and 17q21.31 microdeletions are causative of Koolen-de Vries syndrome (KdVS), a neurodevelopmental syndrome with characteristic facial dysmorphia. Our previous work has shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes have identifiable patterns of DNA methylation (DNAm) change: DNAm signatures or episignatures. Given the role of KANSL1 in histone acetylation, we tested whether variants underlying KdVS are associated with a DNAm signature. We profiled whole-blood DNAm for 13 individuals with KANSL1 variants, four individuals with 17q21.31 microdeletions, and 21 typically developing individuals, using Illumina's Infinium EPIC array. In this study, we identified a robust DNAm signature of 456 significant CpG sites in 8 individuals with KdVS, a pattern independently validated in an additional 7 individuals with KdVS. We also demonstrate the diagnostic utility of the signature and classify two KANSL1 VUS as well as four variants in individuals with atypical clinical presentation. Lastly, we investigated tissue-specific DNAm changes in fibroblast cells from individuals with KdVS. Collectively, our findings contribute to the understanding of the epigenetic landscape related to KdVS and aid in the diagnosis and classification of variants in this structurally complex genomic region.

The invisible scars: Unseen financial complications worsen every aspect of long-term health in trauma survivors.

BACKGROUND: Trauma survivors are susceptible to experiencing financial toxicity (FT). Studies have shown the negative impact of FT on chronic illness outcomes. However, there is a notable lack of data on FT in the context of trauma. We aimed to better understand prevalence, risk factors, and impact of FT on trauma long-term outcomes. METHODS: Adult trauma patients with an Injury Severity Score (ISS) ≥9 treated at Level I trauma centers were interviewed 6 months to 14 months after discharge. Financial toxicity was considered positive if patients reported any of the following due to the injury: income loss, lack of care, newly applied/qualified for governmental assistance, new financial problems, or work loss. The Impact of FT on Patient Reported Outcome Measure Index System (PROMIS) health domains was investigated. RESULTS: Of 577 total patients, 44% (254/567) suffered some form of FT. In the adjusted model, older age (odds ratio [OR], 0.4; 95% confidence interval [95% CI], 0.2-0.81) and stronger social support networks (OR, 0.44; 95% CI, 0.26-0.74) were protective against FT. In contrast, having two or more comorbidities (OR, 1.81; 95% CI, 1.01-3.28), lower education levels (OR, 1.95; 95% CI, 95%, 1.26-3.03), and injury mechanisms, including road accidents (OR, 2.69; 95% CI, 1.51-4.77) and intentional injuries (OR, 4.31; 95% CI, 1.44-12.86) were associated with higher toxicity. No significant relationship was found with ISS, sex, or single-family household. Patients with FT had worse outcomes across all domains of health. There was a negative linear relationship between the severity of FT and worse mental and physical health scores. CONCLUSION: Financial toxicity is associated with long-term outcomes. Incorporating FT risk assessment into recovery care planning may help to identify patients most in need of mitigative interventions across the trauma care continuum to improve trauma recovery. Further investigations to better understand, define, and address FT in trauma care are warranted. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

A new early-diverging probainognathian cynodont and a revision of the occurrence of cf. Aleodon from the Chañares Formation, northwestern Argentina: New clues on the faunistic composition of the latest Middle-?earliest Late Triassic Tarjadia Assemblage Zone.

The Chañares Formation (Ischigualasto-Villa Unión Basin) is worldwide known by its exquisitely preserved fossil record of latest Middle-to-early Late Triassic tetrapods, including erpetosuchids, "rauisuchians," proterochampsids, gracilisuchids, dinosauromorphs, pterosauromorphs, kannemeyeriiform dicynodonts, and traversodontid, chiniquodontid and probainognathid cynodonts, coming from the Tarjadia (bottom) and Massetognathus-Chanaresuchus (top) Assemblage Zones of its lower member. Regarding cynodonts, most of its profuse knowledge comes from the traditional layers discovered by Alfred Romer and his team in the 1960s that are now enclosed in the Massetognathus-Chanaresuchus Assemblage Zone (AZ). In this contribution we focus our study on the probainognathian cynodonts discovered in levels of the Tarjadia Assemblage Zone. We describe a new chiniquodontid cynodont with transversely broad postcanine teeth (Riojanodon nenoi gen. et sp. nov.) which is related to the genus Aleodon. In addition, the specimen CRILAR-Pv 567 previously referred to cf. Aleodon is here described, compared, and included in a phylogenetic analysis. It is considered as an indeterminate Aleodontinae nov., a clade here proposed to included chiniquodontids with transversely broad upper and lower postcanines, by having a cuspidated sectorial labial margin and a lingual platform that is twice broader than a lingual cingulum. Cromptodon mamiferoides, from the Cerro de Las Cabras Formation (Cuyo Basin), was also included in the phylogenetic analysis and recovered as an Aleodontinae. The new cynodont and the record of Aleodontinae indet. reinforce the faunal differentiation between the Tarjadia and Massetognathus-Chanaresuchus Assemblage Zones, in the lower member of the Chañares Formation, and inform on the diverse chiniquodontid clade with both sectorial and transversely broad postcanine teeth.

Developing a National Trauma Research Action Plan: Results from the regulatory challenges Delphi survey.

BACKGROUND: In 2016, the National Academies of Sciences, Engineering, and Medicine issued a report calling for a National Trauma Research Action Plan (NTRAP) requiring a resourced, coordinated, joint approach to trauma care research. The National Academies of Sciences, Engineering, and Medicine report recommended the identification of regulatory barriers to trauma research. The NTRAP Regulatory Challenges Panel of trauma researchers and regulatory professionals was convened to identify the most challenging aspects of regulatory processes involved in conducting research. METHODS: Trauma researchers and regulatory experts were recruited to identify and rate challenging regulatory issues in 2021 to 2022. Challenge statements were developed from a comprehensive scoping review. Panelists rated the challenge level for each statement on a 9-point Likert scale. The Delphi survey was conducted over three online rounds. Consensus was defined a priori as ≥60% agreement. Results of the Delphi survey were presented to the panel during a webinar. Panel participants then participated in breakout sessions to strategize solutions, share lessons learned, and identify where more regulatory guidance is needed. RESULTS: Thirty-eight subject matter experts rated 175 regulatory challenges, of which 141 (81%) reached the consensus threshold. Of the consensus-reaching challenge statements, 42 had a challenge rating of 6 or higher. Among the highest-rated challenges were issues pertaining to conducting prehospital research, exception from informed consent, mistrust of research among various racial and ethnic groups, and issues specific to conducting pediatric trauma research. CONCLUSION: This Delphi survey rated challenges culled from a regulatory literature scoping review. The panel identified the most challenging aspects of human subjects protection while conducting trauma research and recommended strategies and best practices to address them. The findings from this study were used to develop the NTRAP Investigator Toolkit, which is available on the internet as a resource for trauma researchers. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.