Clinical and Economic Value of a Biosimilar Portfolio to Stakeholders: An Integrative Literature Review.

Purpose: While the value of individual biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings between biosimilars and originators. Stakeholders may consider the value of a manufacturer's biosimilar portfolio, especially when negotiating portfolio-based contracts or other rebate programs. However, little is known about what other types of value, in addition to financial benefits, decision-makers perceive regarding a manufacturer with a biosimilar portfolio compared to those without one. The objective of this integrative literature review was to describe a conceptual framework consisting of themes that may help define the value of a biosimilar portfolio. Methods: An integrative literature review was conducted using Excerpta Medica Database (Embase) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Grey literature searches of search engines, journals not indexed in Embase or MEDLINE, healthcare payers, health technology assessment bodies, value frameworks, and non-pharmaceutical industry analogs were also conducted. Eligible studies reported on the value of a biosimilar portfolio in decision-making by stakeholders. Apart from the literature, insights were gained from clinical experience and observation. Results: No studies investigating biosimilar portfolio value were identified; however, several themes were identified that may help define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; and transaction costs. Several non-pharmaceutical industry analogs were identified: Product line length and single-supplier versus multiple-supplier procurement. Several themes were identified through other sources: Science credibility and research. Based on these themes, we developed a conceptual framework for biosimilar portfolio value. Conclusion: To our knowledge, this is the first study to systematically assess and create a framework for biosimilar portfolio value. The conceptual framework described here could be tested to quantify the clinical and economic value associated with a biosimilar portfolio.

Though the value of single biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings incurred between biosimilars and originators.We identified seven themes that may help to define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; transaction costs; science credibility; and research.These themes may be integrated into a conceptual framework that may form a basis to help quantify the clinical and economic benefit of a biosimilar portfolio to stakeholders.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

BACKGROUND: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. METHODS: We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. RESULTS: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. CONCLUSIONS: Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

Neighborhood socioeconomic disadvantages influence outcomes following rotator cuff repair in the non-Medicaid population.

BACKGROUND: Prior investigations have utilized various surrogate markers of socioeconomic status to assess how health care disparities impact outcomes after rotator cuff repair (RCR). When taken as individual markers, these factors have inconsistent associations. Medicaid insurance status is an accessible marker that has recently been correlated with less optimal outcomes after RCR. Socioeconomic disparities exist within the non-Medicaid population as well and are arguably more difficult to characterize. The Area Deprivation Index (ADI) uses seventeen socioeconomic variables to establish a spectrum of neighborhood health care disparity. The purpose of this study was to determine the influence of neighborhood socioeconomic disadvantages, quantified by ADI, on 2-year patient reported outcome scores following RCR in the non-Medicaid population. METHODS: A retrospective review of patients who underwent RCR from 2015 to 2020 was performed. All procedures were performed by a group of 7 surgeons at a large academic center. Patient demographics and comorbidities were collected from charts. Rotator cuff tear size was assessed from arthroscopic pictures. ADI scores were calculated based on patients' home addresses using the Neighborhood Atlas tool. The primary outcome measure was American Shoulder and Elbow Surgeons (ASES) score with a minimum follow-up of 2 years. A linear regression analysis with covariate control for age and patient comorbidities was performed. RESULTS: There were 287 patients with a mean age of 60.11 years. The linear regression model between ADI and 2-year ASES score was significant (P = .02). When controlling for both age and patient comorbidities, every 0.9-point reduction in ADI resulted in a 1-point increase in the ASES score (P = .03). Patients with an ADI of 8, 9, or 10 had lower mean 2-year ASES scores than those with an ADI of 1 (87.08 vs. 93.19, P = .04), but both groups had similar change from preoperative ASES score (40.17 vs. 32.88, P = .12). The change in ASES score at 2-years in our study surpassed all established minimal clinically important difference values irrespective of ADI. CONCLUSION: Patients with greater levels of disparity in their home neighborhoods have worse final ASES scores at 2 years, but patients significantly improve from their preoperative state regardless of social disadvantages. This is the first study to the authors' knowledge that examines ADI and outcomes following RCR. Providers should be aware that patients with higher ADI scores may have inferior preoperative shoulder function. The results of this study support the utilization of primary RCR in applicable tears regardless of socioeconomic status.

The Clinical Anatomy Fellowship: Revolutionizing curricular experiences for faculty and students.

Fellows completing the Clinical Anatomy Fellowship at Kansas City University assist Anatomy faculty in the Gross Anatomy laboratory, complete robust research projects, and support other departments. The program's positive impact on participants has been reported; however, the impact on individuals interfacing with Fellows has not been investigated. A follow-up, survey-based (Likert scale, multiple-choice, open-ended) study was conducted to evaluate faculty, staff, and student perceptions of the program. Ninety-five percent of surveyed faculty and staff (n = 22) perceived the Fellows as beneficial to students, faculty, and the university (p < 0.05) by acting as role models (95%) and mentors (90%), contributing to educational processes (90%), and reducing faculty work burden (81%) (p < 0.05). Student responses (n = 95) were also positive: 97% perceived interactions with Fellows as beneficial (p < 0.05). A passion for Anatomy (mean, 4.6; p < 0.05) and the opportunity to increase competitiveness for residency (mean, 4.5; p < 0.05) were the most important factors driving interest in the Fellowship (Cronbach's alpha, 0.766). In contrast, diverting a year from the school's curriculum (mean, 4.4; p < 0.05) and delaying clinical experiences (mean, 4.3; p < 0.05) were the most important deterrents (Cronbach's alpha, 0.505). Additionally, the financial investment required by the program is lower than that associated with hiring full-time faculty. Analysis comparing employment of Fellows versus associate-level faculty identified annual net savings of $370,000. Not only does the Fellowship augment faculty and student experiences at the university, but it also allows for substantial cost savings. Collectively, these data are evidence for other health professional institutions to consider adopting a similar program.

The Role of Individual Discrimination and Structural Stigma in the Mental Health of Sexual Minority Youth.

OBJECTIVE: Sexual minority (SM) youth experience a greater mental health burden compared with their heterosexual peers. This study aimed to characterize mental health disparities among SM compared with non-SM youth, test main and interactive associations of SM identity and stressors targeting SM youth at the individual level (interpersonal SM discrimination) and structural level (state-level structural SM stigma) with youth mental health, and explore the contribution of interpersonal SM discrimination to the mental health burden of SM youth. METHOD: Participants included 11,622 youth (ages 9-13; 47.6% assigned female at birth) from the Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effects models tested main and interactive associations of SM identity, interpersonal SM discrimination, and structural SM stigma with mental health measures (self-reported overall psychopathology, suicidal ideation, and suicide attempts), adjusting for demographics and other interpersonal stressors not specific to SM (other discrimination types, peer victimization, and cyberbullying). Longitudinal mediation models tested whether interpersonal SM discrimination mediated the associations between SM identity and mental health measures. RESULTS: SM youth (n = 1,051) experienced more interpersonal SM discrimination and overall psychopathology compared with their non-SM peers (n = 10,571). Adjusting for demographics, there were significant associations (main effects) of interpersonal SM discrimination and structural SM stigma with overall psychopathology. When further adjusting for other non-SM-related stressors, the main effect of structural SM stigma was no longer significant. Interpersonal SM discrimination was also significantly associated with suicidal ideation and attempt, accounting for demographics, while structural SM stigma was not. Accounting for both demographics and other non-SM stressors, there was a significant interaction between SM identity and structural SM stigma in association with psychopathology (p = .02), such that, compared with their peers, SM youth showed a greater association between structural SM stigma and psychopathology. Longitudinal mediation revealed that interpersonal SM discrimination was a significant mediator explaining approximately 10% to 15% of the variance of the pathways between SM identity and all mental health outcomes. CONCLUSION: Results delineate contributions of interpersonal discrimination and structural stigma targeting SM youth to their heightened mental health burden in early adolescence. These findings underscore the need to address microlevel and macrolevel SM discrimination and structural stigma when caring for this population. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

The clinical anatomy fellowship: A participants' perspective.

Kansas City University offers a Clinical Anatomy Fellowship which enrolls nine medical students during each academic year and provides training in research, teaching, and advanced anatomical topics. The Fellows practice as novice educators, working alongside Anatomy faculty to teach medical students in the Gross Anatomy laboratory. However, little has been reported related to Fellowship participation and success outcomes. This survey-based study was designed to explore (1) student motivation(s) for pursuing the Fellowship, (2) benefits of participation, and (3) the perceived impact on residency applications and career success. Three unique populations were surveyed. The most important factors driving application to the Fellowship were a desire to increase competitiveness in the residency application process (Likert mean score 4.7-5.0) and a passion for Anatomy (Likert mean score 4.3-4.7). Taking a year away from the College of Osteopathic Medicine curriculum (Likert mean score 4.4) and delaying clinical exposure (Likert mean score 4.2) were the most important deterrents to application. The most reported benefits after program completion included opportunities to build a strong residency application (44% and 50% of Fellows), conduct research (44% and 45% of Fellows), and participate in teaching (11% and 50% of Fellows). 73% of past Fellows matched into their top specialty of choice. Flexibility in the program allows participants to individualize their Fellowship experience to address their personal goals related to residency applications and careers as future physicians. As the results suggest, the Clinical Anatomy Fellowship benefits Fellows, signaling other medical institutions to consider adopting a similar program.

Trauma as a Public Health Moment: Addressing Vaccine Uptake in Trauma Patients.

Objective: Our objective was to identify factors associated with COVID-19 vaccination in trauma patients and to provide an opportunity for patients to engage in conversations about vaccination. Background: The trauma surgery service offers a unique opportunity to promote preventative health interventions in hard-to-reach populations. Methods: Trauma inpatients in Chicago, IL were recruited for this mixed-methods study from February 2022 to April 2022. Participants completed a survey on demographics, COVID-19 vaccination status, and Experiences of Discrimination Scale adapted for medical settings. Differences between vaccinated and unvaccinated patients were analyzed using the Wilcoxon-rank sum test. A semistructured, qualitative interview was completed. Qualitative data was transcribed and analyzed using Grounded Theory Methodology. Results: Fifty-eight trauma patients were surveyed, representing 88% of patients approached. Only 23 (40%) patients reported full vaccination to COVID-19. Previous vaccination (at least 1 dose) was associated with greater concern for COVID-19 (OR 3.47, 95% CI 1.987-6.964, P < 0.001) and higher income (OR 1.21, 95% CI 1.02-1.44, P = 0.03). Higher Experiences of Discrimination Scale scores were associated with decreased likelihood of prior vaccination (OR 0.97, 95% CI 0.95-0.99, P = 0.04). On qualitative analysis, recurrent themes included vaccination motivated by either community-based or personal health-related values, and disinterest in vaccination based on perceived low need or skepticism of experimentation. Fifteen patients (26%) eligible for a vaccine dose consented to onsite vaccination after the survey. Conclusions: Trauma patients who have experienced more discrimination in medical settings have lower rates of COVID-19 vaccination. Vaccination rates in our population were over 2 times lower than citywide rates, but admission to the trauma service can increase comprehensive care.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery. Families are consented for sharing of sequence and phenotype data with researchers, allowing development of a Critical Assessment of Genome Interpretation (CAGI) community challenge, placing variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods: Predictors were provided a dataset of phenotype terms and variant calls from GS of 175 RGP individuals (65 families), including 35 solved training set families, with causal variants specified, and 30 test set families (14 solved, 16 unsolved). The challenge tasked teams with identifying the causal variants in as many test set families as possible. Ranked variant predictions were submitted with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on rank position of true positive causal variants and maximum F-measure, based on precision and recall of causal variants across EPCR thresholds. Results: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performing teams recalled the causal variants in up to 13 of 14 solved families by prioritizing high quality variant calls that were rare, predicted deleterious, segregating correctly, and consistent with reported phenotype. In unsolved families, newly discovered diagnostic variants were returned to two families following confirmatory RNA sequencing, and two prioritized novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant, in an unsolved proband with phenotype overlap with asparagine synthetase deficiency. Conclusions: By objective assessment of variant predictions, we provide insights into current state-of-the-art algorithms and platforms for genome sequencing analysis for rare disease diagnosis and explore areas for future optimization. Identification of diagnostic variants in unsolved families promotes synergy between researchers with clinical and computational expertise as a means of advancing the field of clinical genome interpretation.

BaM-seq and TBaM-seq, highly multiplexed and targeted RNA-seq protocols for rapid, low-cost library generation from bacterial samples.

The ability to profile transcriptomes and characterize global gene expression changes has been greatly enabled by the development of RNA sequencing technologies (RNA-seq). However, the process of generating sequencing-compatible cDNA libraries from RNA samples can be time-consuming and expensive, especially for bacterial mRNAs which lack poly(A)-tails that are often used to streamline this process for eukaryotic samples. Compared to the increasing throughput and decreasing cost of sequencing, library preparation has had limited advances. Here, we describe bacterial-multiplexed-seq (BaM-seq), an approach that enables simple barcoding of many bacterial RNA samples that decreases the time and cost of library preparation. We also present targeted-bacterial-multiplexed-seq (TBaM-seq) that allows for differential expression analysis of specific gene panels with over 100-fold enrichment in read coverage. In addition, we introduce the concept of transcriptome redistribution based on TBaM-seq that dramatically reduces the required sequencing depth while still allowing for quantification of both highly and lowly abundant transcripts. These methods accurately measure gene expression changes with high technical reproducibility and agreement with gold standard, lower throughput approaches. Together, use of these library preparation protocols allows for fast, affordable generation of sequencing libraries.

Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort.

BACKGROUND: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. OBJECTIVE: We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs. METHODS: First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86). RESULTS: Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations. SIGNIFANCE: We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs. IMPACT: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.

Social Media Use Among Parents and Women of Childbearing Age in the US.

Many parents and pregnant women in the US use social media to access health-related information. Estimates of current use of different platforms among these populations are needed. We used data from a 2021 Pew Research Center survey to describe use of commercial social media platforms by US parents and US women aged 18 to 39 years. Most US parents and women of childbearing age use YouTube, Facebook, and Instagram, with most engaging daily. Understanding social media use patterns can help public health professionals, health care systems, and researchers reach selected populations with evidence-based health information and health promotion programs.

Diagnostic quality model (DQM): an integrated framework for the assessment of diagnostic quality when using AI/ML.

BACKGROUND: Laboratory medicine has reached the era where promises of artificial intelligence and machine learning (AI/ML) seem palpable. Currently, the primary responsibility for risk-benefit assessment in clinical practice resides with the medical director. Unfortunately, there is no tool or concept that enables diagnostic quality assessment for the various potential AI/ML applications. Specifically, we noted that an operational definition of laboratory diagnostic quality - for the specific purpose of assessing AI/ML improvements - is currently missing. METHODS: A session at the 3rd Strategic Conference of the European Federation of Laboratory Medicine in 2022 on "AI in the Laboratory of the Future" prompted an expert roundtable discussion. Here we present a conceptual diagnostic quality framework for the specific purpose of assessing AI/ML implementations. RESULTS: The presented framework is termed diagnostic quality model (DQM) and distinguishes AI/ML improvements at the test, procedure, laboratory, or healthcare ecosystem level. The operational definition illustrates the nested relationship among these levels. The model can help to define relevant objectives for implementation and how levels come together to form coherent diagnostics. The affected levels are referred to as scope and we provide a rubric to quantify AI/ML improvements while complying with existing, mandated regulatory standards. We present 4 relevant clinical scenarios including multi-modal diagnostics and compare the model to existing quality management systems. CONCLUSIONS: A diagnostic quality model is essential to navigate the complexities of clinical AI/ML implementations. The presented diagnostic quality framework can help to specify and communicate the key implications of AI/ML solutions in laboratory diagnostics.

Association between Asthma and Suicidality in 9-12-Year-Old Youths.

PURPOSE: Suicidal ideation and attempts in youth are a growing health concern, and more data are needed regarding their biological underpinnings. Asthma is a common chronic inflammatory disorder in youth and has been associated with suicidal ideation and attempts in adolescent and adult populations, but data in younger children and early adolescents are lacking. We wished to study associations of asthma with childhood suicidality considering asthma's potential as a clinically relevant model for childhood chronic immune dysregulation. METHODS: Using data from the Adolescent Brain Cognitive Development (ABCD) Study (n = 11,876, 47.8% female, mean age 9.9 years at baseline assessment and 12.0 years at two-year follow-up), we assessed associations between asthma and suicidal ideation and attempts through baseline to two-year follow-up. RESULTS: Asthma history as defined by parent report (n = 2282, 19.2% of study population) was associated with suicide attempts (SA) (odds ratio (OR) = 1.44, p = 0.01), and this association remained significant even when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.46, p = 0.028). History of asthma attacks was associated with both suicidal ideation (SI) and SA when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.27, p = 0.042; OR = 1.83, p = 0.004, respectively). The association of asthma attack with SA remained significant when controlling for self-reported psychopathology (OR = 1.92, p = 0.004). The total number of asthma attacks was associated with both SI and SA (OR = 1.03, p = 0.043; OR = 1.06, p = 0.05, respectively). CONCLUSIONS: Findings suggest an association between asthma and suicidality in early adolescence. Further research is needed to investigate mechanisms underlying this relationship.

COVID-19-related financial strain and adolescent mental health.

Background: The COVID-19 pandemic and associated responses have induced a host of crises worldwide, including an economic recession and a global mental health crisis. The specific effects of recession on youth mental health are understudied. We aimed to examine the mechanisms by which pandemic-related financial strain may affect mental health in a diverse sample of American adolescents. Methods: We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD Study®), a large, longitudinal study of diverse US adolescents which collected data before and during the pandemic (N = 9,720, mean age 12.9 years, 18.2% Black). Linear mixed-effects models tested associations of financial strain (parent-reported household wage loss and youth-reported financial stress) with depressive symptomatology over time, covarying for multiple confounders including pre-pandemic socioeconomic status and psychopathology, and pandemic-related environmental factors. Longitudinal mediation analyses examined potential mechanisms leading from wage loss to youth mental health. Findings: Financial strain was highly prevalent, especially among low-income participants, with >70% of the total sample reporting lost wages. Both wage loss and subjective financial stress were associated with depressive symptomatology over time (Estimate = 0.04, P = 0.014; Estimate = 0.17, P < 0.001; respectively). The association between financial stress and depressive symptomatology was robust to the addition of multiple environmental confounders (Estimate = 0.16, P < 0.001). Both family-level (family conflict) and individual-level (financial stress) factors mediated the relationship between wage loss and depressive symptomatology. Interpretation: The financial effects of COVID-19 (and worldwide responses to it) have taken a significant toll on youth mental health. In families that lost wages, youth-reported financial stress and familial factors mediated the relationship between wage loss and mental health over time. Findings highlight financial stress as a key driver of youth mental health burden and identify familial factors as critical targets for intervention to mitigate mental health risks in periods of economic crises. Funding: This study was supported by the National Institute of Mental Health [grant numbers K23MH120437 (RB), R01MH117014 (TMM)]; the Lifespan Brain Institute of Children's Hospital of Philadelphia and Penn Medicine, University of Pennsylvania.

The "Our Voice" Method: Participatory Action Citizen Science Research to Advance Behavioral Health and Health Equity Outcomes.

Citizen science research that more fully engages the community can systematically involve people from under-resourced groups to create practical health-enhancing improvements across physical, social and food environments. Exemplary health equity-focused outcomes include key health behaviors (e.g., healthy eating or physical activity) and community-level changes (e.g., public transit to food shops) that are central to health promotion while being demonstrably impacted by local environmental contexts. Yet, few examples of this approach are readily available for application within complex, community-based settings. In this paper, we present the Our Voice (OV) four-step method to demonstrate an integrated participatory citizen science approach and its usability for action-focused researchers and community health practitioners. In addition, we present a summary of the major research, processes, and community outcomes, with examples drawn from nutrition and healthy food access areas, among others. Finally, we explore the hallmark features of the OV method that effectively engage citizen scientists, empowering action and fostering solution-building across social and environmental structures impacting community health. Expanding research that marries participatory research philosophies with innovative citizen science methods, supported by systematic data collection, visualization, and delivery technologies, in turn provides a powerful toolkit for tackling local to global health equity challenges.

An open-source, low-cost voluntary running activity tracking tool for in vivo rodent studies.

In vivo rodent behavioral and physiological studies often benefit from measurement of general activity. However, many existing instruments necessary to track such activity are high in cost and invasive within home cages, some even requiring extensive separate cage systems, limiting their widespread use to collect data. We present here a low-cost open-source alternative that measures voluntary wheel running activity and allows for modulation and customization, along with a reproducible and easy to set-up code pipeline for setup and analysis in Arduino IDE and R. Our robust, non-invasive scalable voluntary running activity tracker utilizes readily accessible magnets, Hall effect sensors, and an Arduino microcontroller. Importantly, it can interface with existing rodent home cages and wheel equipment, thus eliminating the need to transfer the mice to an unfamiliar environment. The system was validated both for accuracy by a rotating motor used to simulate mouse behavior, and in vivo. Our recorded data is consistent with results found in the literature showing that the mice run between 3 to 16 kilometers per night, and accurately captures speed and distance traveled continuously on the wheel. Such data are critical for analysis of highly variable behavior in mouse models and allow for characterization of behavioral metrics such as general activity. This system provides a flexible, low-cost methodology, and minimizes the cost, infrastructure, and personnel required for tracking voluntary wheel activity.

Association between racial/ethnic discrimination and pubertal development in early adolescence.

Racial health disparities in the United States are a major concern, with Black or African Americans experiencing more morbidity and mortality at earlier ages compared to White Americans. More data is needed on the biological underpinnings of this phenomenon. One potential explanation for racial health disparities is that of accelerated aging, which is associated with increased stress exposure. Black Americans face disproportionate levels of environmental stress, specifically racial/ethnic discrimination. Here we investigated associations between self-reported experiences of discrimination and pubertal development (PD) in a diverse sample of young American adolescents (N = 11,235, mean age 10.9 years, 20.5% Black participants) from the Adolescent Brain Cognitive Development (ABCD) Study. Compared to their non-Black counterparts, Black youth experienced more racial/ethnic discrimination in the past year (10.4% vs 3.1%) and had a greater likelihood of being in late/post-pubertal status (3.6% vs 1.5% in boys, 21.3% vs 11.4% in girls). In both sexes, multivariable regression models run in the full sample revealed a cross-sectional association of experiences of racial/ethnic discrimination with pubertal development (boys: standardized beta [ß]=0.123, P < .001; girls: ß = 0.110, P < .001) covarying for demographics, BMI, and dietary habits. Associations remained significant when controlling for multiple other environmental confounders including other forms of (non-racial/ethnic) discrimination and other environmental adversities including poverty and negative life events, and when using parent-reported assessment of pubertal development. Furthermore, racial/ethnic discrimination was associated with elevated estradiol levels in girls (ß = 0.057, P = .002). Findings suggest an association between experiences of discrimination and pubertal development that is independent of multiple environmental stressors. Future longitudinal studies are warranted to establish causal mechanism.

Economic and Humanistic Burden of Triple-Negative Breast Cancer: A Systematic Literature Review.

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs). It is more commonly diagnosed in younger women and often has a less favorable prognosis compared with other BC subtypes. OBJECTIVE: The objective of this study was to provide a literature-based extensive overview of the economic and humanistic burden of TNBC to assist medical decisions for healthcare payers, providers, and patients. METHODS: A systematic literature review was performed using multiple databases, including EMBASE, MEDLINE, Econlit, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from database inception to 16 May 2021. In addition, a targeted search was performed in the Northern Light Life Sciences Conference Abstracts database from 2016 through June 2021. The bibliographies of included articles were reviewed to identify other potentially relevant publications. Quality assessment of the included studies was conducted. RESULTS: The review identified 19 studies assessing the economic burden and 10 studies assessing the humanistic burden of TNBC. Studies varied widely in study design, settings, patient populations, and time horizons. The estimates of mean per-patient annual direct medical costs ranged from around $20,000 to over $100,000 in stage I-III TNBC and from $100,000 to $300,000 in stage IV TNBC. Healthcare costs and resource utilization increased significantly with disease recurrence, progression, and increased cancer stage or line of therapy. Compared with the costs of systemic anticancer therapy, cancer management costs comprised a larger portion of total direct costs. The estimates of indirect costs due to productivity loss ranged from $207 to $1573 per patient per month (all costs presented above were adjusted to 2021 US dollars). Cancer recurrence led to significantly reduced productivity and greater rates of leaving the workforce. A rapid deterioration of health utility associated with disease progression was observed in TNBC patients. Treatment with pembrolizumab or talazoparib showed significantly greater improvements in health-related quality of life (HRQoL) compared with chemotherapy, as measured by EORTC QLQ-C30, QLQ-BR23, and FACT-B. CONCLUSION: TNBC is associated with a substantial economic burden on healthcare systems and societies and considerably reduced productivity and HRQoL for patients. This study synthesized the published literature on the economic and humanistic burden of TNBC and highlighted the need for continued research due to the rapidly changing landscape of TNBC care.

Assessment of metabolic perturbations associated with exposure to phthalates among pregnant African American women.

BACKGROUND: Phthalates have been linked with numerous harmful health effects. Limited data are available on the molecular mechanism underlying phthalate toxicity on human health. In this study, we measured urinary phthalate metabolites and used high-resolution metabolomics (HRM) to identify biological perturbations associated with phthalate exposures among pregnant African American (AA) women, who are disproportionately exposed to high phthalates levels. METHODS: We used untargeted HRM profiling to characterize serum samples collected during early (8-14 weeks gestation) and late (24-30 weeks gestation) pregnancy from 73 participants from the Atlanta AA Maternal-Child cohort. We measured eight urinary phthalate metabolites in early and late pregnancy, including Monoethyl phthalate (MEP), Mono(2-ethlyhexyl) phthalate (MEHP), and Mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), to assess maternal exposures to phthalates. Metabolite and metabolic pathway perturbation were evaluated using an untargeted HRM workflow. RESULTS: Geometric mean creatinine-adjusted levels of urinary MEP, MEHP, and MEHHP were 67.3, 1.4, and 4.1 µg/g creatinine, respectively, with MEP and MEHP higher than the mean levels of non-Hispanic blacks in the general US population (2015-2016). There were 73 and 1435 metabolic features significantly associated with at least one phthalate metabolite during early and late pregnancy (p < 0.005), respectively. Pathway enrichment analysis revealed perturbations in four inflammation- and oxidative-stress-related pathways associated with phthalate metabolite levels during both early and late pregnancy, including glycerophospholipid, urea cycle, arginine, and tyrosine metabolism. We confirmed 10 metabolites with level-1 evidence, which are associated with urinary phthalates, including thyroxine and thiamine, which were negatively associated with MEP, as well as tyramine and phenethylamine, which were positively associated with MEHP and MEHHP. CONCLUSION: Our results demonstrated that urinary phthalate levels were associated with perturbations in biological pathways connected with inflammation, oxidative stress, and endocrine disruption. The findings support future targeted investigations on molecular mechanisms underlying the impact of maternal phthalates exposure on adverse health outcomes.