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Understanding sex-related variation in health and illness requires rigorous and precise approaches to revealing underlying mechanisms. A first step is to recognize that sex is not in and of itself a causal mechanism; rather, it is a classification system comprising a set of categories, usually assigned according to a range of varying traits. Moving beyond sex as a system of classification to working with concrete and measurable sex-related variables is necessary for precision. Whether and how these sex-related variables matter-and what patterns of difference they contribute to-will vary in context-specific ways. Second, when researchers incorporate these sex-related variables into research designs, rigorous analytical methods are needed to allow strongly supported conclusions. Third, the interpretation and reporting of sex-related variation require care to ensure that basic and preclinical research advance health equity for all.
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Investigación Biomédica , Equidad en Salud , Sexo , HumanosRESUMEN
Technological advances have enabled the rapid generation of health and genomic data, though rarely do these technologies account for the values and priorities of marginalized communities. In this commentary, we conceptualize a blockchain genomics data framework built out of the concept of Indigenous Data Sovereignty.
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Cadena de Bloques , Seguridad Computacional , Genómica , TecnologíaRESUMEN
Cancer mortality rates have declined during the last 28 years, but that process is not equitably shared. Disparities in cancer outcomes by race, ethnicity, socioeconomic status, sexual orientation and gender identity, and geographic location persist across the cancer care continuum. Consequently, community outreach and engagement (COE) efforts within National Cancer Institute-Designated Cancer Center (NCI-DCC) catchment areas have intensified during the last 10 years as has the emphasis on COE and catchment areas in NCI's Cancer Center Support Grant applications. This review article attempts to provide a historic perspective of COE within NCI-DCCs. Improving COE has long been an important initiative for the NCI, but it was not until 2012 and 2016 that NCI-DCCs were required to define their catchment areas rigorously and to provide specific descriptions of COE interventions, respectively. NCI-DCCs had previously lacked adequate focus on the inclusion of historically marginalized patients in cancer innovation efforts. Integrating COE efforts throughout the research and operational aspects of the cancer centers, at both the patient and community levels, will expand the footprint of COE efforts within NCI-DCCs. Achieving this change requires sustained commitment by the centers to adjust their activities and improve access and outcomes for historically marginalized communities.
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Instituciones Oncológicas , Relaciones Comunidad-Institución , National Cancer Institute (U.S.) , Neoplasias , Humanos , Estados Unidos/epidemiología , Neoplasias/terapia , Neoplasias/epidemiología , Instituciones Oncológicas/organización & administración , Disparidades en Atención de SaludRESUMEN
There remains a need to synthesize linkages between social determinants of health (SDOH) and cancer screening to reduce persistent inequities contributing to the US cancer burden. The authors conducted a systematic review of US-based breast, cervical, colorectal, and lung cancer screening intervention studies to summarize how SDOH have been considered in interventions and relationships between SDOH and screening. Five databases were searched for peer-reviewed research articles published in English between 2010 and 2021. The Covidence software platform was used to screen articles and extract data using a standardized template. Data items included study and intervention characteristics, SDOH intervention components and measures, and screening outcomes. The findings were summarized using descriptive statistics and narratives. The review included 144 studies among diverse population groups. SDOH interventions increased screening rates overall by a median of 8.4 percentage points (interquartile interval, 1.8-18.8 percentage points). The objective of most interventions was to increase community demand (90.3%) and access (84.0%) to screening. SDOH interventions related to health care access and quality were most prevalent (227 unique intervention components). Other SDOH, including educational, social/community, environmental, and economic factors, were less common (90, 52, 21, and zero intervention components, respectively). Studies that included analyses of health policy, access to care, and lower costs yielded the largest proportions of favorable associations with screening outcomes. SDOH were predominantly measured at the individual level. This review describes how SDOH have been considered in the design and evaluation of cancer screening interventions and effect sizes for SDOH interventions. Findings may guide future intervention and implementation research aiming to reduce US screening inequities.
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Neoplasias Pulmonares , Determinantes Sociales de la Salud , Humanos , Detección Precoz del Cáncer , Disparidades en el Estado de Salud , EscolaridadRESUMEN
Manipulation of a patient's genome for therapeutic ends is being attempted through numerous methods, some of which have resulted in disease-modifying interventions. The much anticipated promise of somatic gene therapy is starting to pay off; however, there remain many scientific unknowns, including concerns about safety and durability. A significant ethical concern is that of access to these novel interventions, an issue that is normally framed in terms of the high costs of approved products. I describe how access issues permeate gene therapy long before there is any commercial product and how even upstream decisions-such as choices of indication to pursue, viral vector, and where to site a trial-have significant implications for access to resultant products in both the developmental and commercial stages.
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Terapia Genética , Humanos , Terapia Genética/ética , Vectores GenéticosRESUMEN
The ethical standards for the responsible conduct of human research have come a long way; however, concerns surrounding equity remain in human genetics and genomics research. Addressing these concerns will help society realize the full potential of human genomics research. One outstanding concern is the fair and equitable sharing of benefits from research on human participants. Several international bodies have recognized that benefit-sharing can be an effective tool for ethical research conduct, but international laws, including the Convention on Biological Diversity and its Nagoya Protocol on Access and Benefit-Sharing, explicitly exclude human genetic and genomic resources. These agreements face significant challenges that must be considered and anticipated if similar principles are applied in human genomics research. We propose that benefit-sharing from human genomics research can be a bottom-up effort and embedded into the existing research process. We propose the development of a "benefit-sharing by design" framework to address concerns of fairness and equity in the use of human genomic resources and samples and to learn from the aspirations and decade of implementation of the Nagoya Protocol.
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Genómica , Humanos , Genómica/ética , Genómica/métodos , Genoma Humano , Investigación Genética/ética , Investigación Genética/legislación & jurisprudenciaRESUMEN
Next-generation sequencing has revolutionized the speed of rare disease (RD) diagnoses. While clinical exome and genome sequencing represent an effective tool for many RD diagnoses, there is room to further improve the diagnostic odyssey of many RD patients. One recognizable intervention lies in increasing equitable access to genomic testing. Rural communities represent a significant portion of underserved and underrepresented individuals facing additional barriers to diagnosis and treatment. Primary care providers (PCPs) at local clinics, though sometimes suspicious of a potential benefit of genetic testing for their patients, have significant constraints in pursuing it themselves and rely on referrals to specialists. Yet, these referrals are typically followed by long waitlists and significant delays in clinical assessment, insurance clearance, testing, and initiation of diagnosis-informed care management. Not only is this process time intensive, but it also often requires multiple visits to urban medical centers for which distance may be a significant barrier to rural families. Therefore, providing early, "direct-to-provider" (DTP) local access to unrestrictive genomic testing is likely to help speed up diagnostic times and access to care for RD patients in rural communities. In a pilot study with a PCP clinic in rural Kansas, we observed a minimum 5.5 months shortening of time to diagnosis through the DTP exome sequencing program as compared to rural patients receiving genetic testing through the "traditional" PCP-referral-to-specialist scheme. We share our experience to encourage future partnerships beyond our center. Our efforts represent just one step in fostering greater diversity and equity in genomic studies.
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Pruebas Genéticas , Genómica , Accesibilidad a los Servicios de Salud , Enfermedades Raras , Población Rural , Humanos , Pruebas Genéticas/métodos , Enfermedades Raras/genética , Enfermedades Raras/diagnóstico , Genómica/métodos , Niño , Masculino , Secuenciación de Nucleótidos de Alto Rendimiento , FemeninoRESUMEN
There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.
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Pruebas Genéticas , Enfermedades Raras , Secuenciación Completa del Genoma , Humanos , Masculino , Enfermedades Raras/genética , Enfermedades Raras/diagnóstico , Femenino , Niño , Pruebas Genéticas/métodos , Preescolar , Adolescente , Adulto , Lactante , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/diagnósticoRESUMEN
Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.
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Advancements in genomic technologies have shown remarkable promise for improving health trajectories. The Human Genome Project has catalyzed the integration of genomic tools into clinical practice, such as disease risk assessment, prenatal testing and reproductive genomics, cancer diagnostics and prognostication, and therapeutic decision making. Despite the promise of genomic technologies, their full potential remains untapped without including individuals of diverse ancestries and integrating social determinants of health (SDOHs). The NHGRI launched the 2020 Strategic Vision with ten bold predictions by 2030, including "individuals from ancestrally diverse backgrounds will benefit equitably from advances in human genomics." Meeting this goal requires a holistic approach that brings together genomic advancements with careful consideration to healthcare access as well as SDOHs to ensure that translation of genetics research is inclusive, affordable, and accessible and ultimately narrows rather than widens health disparities. With this prediction in mind, this review delves into the two paramount applications of genetic testing-reproductive genomics and precision oncology. When discussing these applications of genomic advancements, we evaluate current accessibility limitations, highlight challenges in achieving representativeness, and propose paths forward to realize the ultimate goal of their equitable applications.
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Genómica , Medicina de Precisión , Humanos , Genómica/métodos , Medicina de Precisión/métodos , Genoma Humano , Pruebas Genéticas , Neoplasias/genética , Accesibilidad a los Servicios de SaludRESUMEN
Despite prevalent diversity and inclusion programs in STEM, gender biases and stereotypes persist across educational and professional settings. Recognizing this enduring bias is crucial for achieving transformative change on gender equity and can help orient policy toward more effective strategies to address ongoing disparities.
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Sexismo , Humanos , Femenino , Masculino , Estereotipo , Ciencia , Ingeniería , MatemáticaRESUMEN
Although cancer mortality rates declined in the United States in recent decades, some populations experienced little benefit from advances in cancer prevention, early detection, treatment, and survivorship care. In fact, some cancer disparities between populations of low and high socioeconomic status widened during this period. Many potentially preventable cancer deaths continue to occur, and disadvantaged populations bear a disproportionate burden. Reducing the burden of cancer and eliminating cancer-related disparities will require more focused and coordinated action across multiple sectors and in partnership with communities. This article, part of the American Cancer Society's Cancer Control Blueprint series, introduces a framework for understanding and addressing social determinants to advance cancer health equity and presents actionable recommendations for practice, research, and policy. The article aims to accelerate progress toward eliminating disparities in cancer and achieving health equity.
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Equidad en Salud/normas , Política de Salud , Disparidades en el Estado de Salud , Neoplasias/epidemiología , Determinantes Sociales de la Salud/normas , Terapia Combinada , Salud Global , Humanos , Morbilidad/tendencias , Neoplasias/terapia , Tasa de Supervivencia/tendenciasRESUMEN
Equity is core to sustainability, but current interventions to enhance sustainability often fall short in adequately addressing this linkage. Models are important tools for informing action, and their development and use present opportunities to center equity in process and outcomes. This Perspective highlights progress in integrating equity into systems modeling in sustainability science, as well as key challenges, tensions, and future directions. We present a conceptual framework for equity in systems modeling, focused on its distributional, procedural, and recognitional dimensions. We discuss examples of how modelers engage with these different dimensions throughout the modeling process and from across a range of modeling approaches and topics, including water resources, energy systems, air quality, and conservation. Synthesizing across these examples, we identify significant advances in enhancing procedural and recognitional equity by reframing models as tools to explore pluralism in worldviews and knowledge systems; enabling models to better represent distributional inequity through new computational techniques and data sources; investigating the dynamics that can drive inequities by linking different modeling approaches; and developing more nuanced metrics for assessing equity outcomes. We also identify important future directions, such as an increased focus on using models to identify pathways to transform underlying conditions that lead to inequities and move toward desired futures. By looking at examples across the diverse fields within sustainability science, we argue that there are valuable opportunities for mutual learning on how to use models more effectively as tools to support sustainable and equitable futures.
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Polygenic scores (PGSs) aggregate the effects of variants across the genome to estimate genetic liability, but have lower performance in external study populations. A new study by Ding et al. has applied a novel framework to estimate the individual-level predictive accuracy of PGSs, and demonstrates that performance reduction occurs linearly with genetic distance.
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The need for rapid and ambitious conservation and restoration is widely acknowledged, yet concern exists that the widespread reallocation of land to nature would disproportionately affect the world's poor. Conservation and restoration may limit nutrition and livelihood options and thus negatively affect social development objectives. Although much research looks into global-scale scenarios and planning of conservation and restoration, spatial evaluations of these trade-offs in terms of equity remain limited. We fill this gap by identifying areas where conservation or restoration under different future scenarios and prioritization maps expand nature into landscapes that likely support land-dependent communities in their local food security. By contrasting the expansion of nature into areas supporting land-dependent communities vs. places where the food system is supported by regional to global markets, we highlight the need for disaggregated indicators that reflect the diversity of human land-use needs in order to identify more equitable pathways. Conservation prioritizations were found to result in more equitable land-use outcomes than the land-use outcomes of widely used socioeconomic scenarios. Accounting for differentiated social impacts in model-based conservation and restoration planning and global scale scenario assessment can help achieve a more inclusive transition to sustainability as well as reduce barriers to meaningful change.
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Biodiversidad , Conservación de los Recursos Naturales , Humanos , Cambio Social , EcosistemaRESUMEN
Leveraging a scientific infrastructure for exploring how students learn, we have developed cognitive and statistical models of skill acquisition and used them to understand fundamental similarities and differences across learners. Our primary question was why do some students learn faster than others? Or, do they? We model data from student performance on groups of tasks that assess the same skill component and that provide follow-up instruction on student errors. Our models estimate, for both students and skills, initial correctness and learning rate, that is, the increase in correctness after each practice opportunity. We applied our models to 1.3 million observations across 27 datasets of student interactions with online practice systems in the context of elementary to college courses in math, science, and language. Despite the availability of up-front verbal instruction, like lectures and readings, students demonstrate modest initial prepractice performance, at about 65% accuracy. Despite being in the same course, students' initial performance varies substantially from about 55% correct for those in the lower half to 75% for those in the upper half. In contrast, and much to our surprise, we found students to be astonishingly similar in estimated learning rate, typically increasing by about 0.1 log odds or 2.5% in accuracy per opportunity. These findings pose a challenge for theories of learning to explain the odd combination of large variation in student initial performance and striking regularity in student learning rate.
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There is a growing need for solid organ transplantation (SOT) for people living with human immunodeficiency virus (HIV). With the advent of antiretroviral therapy, people living with HIV are experiencing increased life expectancies and are, therefore, developing more comorbidities, including end-stage organ disease. In cases of advanced organ failure, SOT is often the best therapeutic option to improve quality of life and overall survival. As organ shortages persist, transplantation of organs from donors with HIV to recipients with HIV has become a potential therapeutic option. This article first reviews the current state of organ transplantation from donors without HIV to recipients with HIV (HIV D-/R+) by organ and discusses key lessons learned from these transplant trials, including those about drug-drug interactions, rejection, and opportunistic infections. It then explores transplantation from donors with HIV to recipients with HIV (HIV D+/R+), a new frontier. Finally, it investigates challenges of implementation, including public awareness and regulatory requirements, and explores future directions for SOT in people living with HIV.
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Infecciones por VIH , Trasplante de Órganos , Humanos , VIH , Calidad de Vida , Infecciones por VIH/tratamiento farmacológico , Donantes de TejidosRESUMEN
Every 10 years, the American Heart Association (AHA) Emergency Cardiovascular Care Committee establishes goals to improve survival from cardiac arrest. These goals align with broader AHA Impact Goals and support the AHA's advocacy efforts and strategic investments in research, education, clinical care, and quality improvement programs. This scientific statement focuses on 2030 AHA emergency cardiovascular care priorities, with a specific focus on bystander cardiopulmonary resuscitation, early defibrillation, and neurologically intact survival. This scientific statement also includes aspirational goals, such as establishing cardiac arrest as a reportable disease and mandating reporting of standardized outcomes from different sources; advancing recognition of and knowledge about cardiac arrest; improving dispatch system response, availability, and access to resuscitation training in multiple settings and at multiple time points; improving availability, access, and affordability of defibrillators; providing a focus on early defibrillation, in-hospital programs, and establishing champions for debriefing and review of cardiac arrest events; and expanding measures to track outcomes beyond survival. The ability to track and report data from these broader aspirational targets will potentially require expansion of existing data sets, development of new data sets, and enhanced integration of technology to collect process and outcome data, as well as partnerships of the AHA with national, state, and local organizations. The COVID-19 (coronavirus disease 2019) pandemic, disparities in COVID-19 outcomes for historically excluded racial and ethnic groups, and the longstanding disparities in cardiac arrest treatment and outcomes for Black and Hispanic or Latino populations also contributed to an explicit focus and target on equity for the AHA Emergency Cardiovascular Care 2030 Impact Goals.
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COVID-19 , Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco , Paro Cardíaco Extrahospitalario , Estados Unidos/epidemiología , Humanos , American Heart Association , Objetivos , Paro Cardíaco/terapia , COVID-19/terapia , Paro Cardíaco Extrahospitalario/terapiaRESUMEN
Our research investigates the societal implications of access to glucagon-like peptide-1 (GLP-1) agonists, particularly in light of recent clinical trials demonstrating the efficacy of semaglutide in reducing cardiovascular mortality. A decade-long analysis of Google Trends indicates a significant increase in searches for GLP-1 agonists, primarily in North America. This trend contrasts with the global prevalence of obesity. Given the high cost of GLP-1 agonists, a critical question arises: Will this disparity in medication accessibility exacerbate the global health equity gap in obesity treatment? This viewpoint explores strategies to address the health equity gap exacerbated by this emerging medication. Because GLP-1 agonists hold the potential to become a cornerstone in obesity treatment, ensuring equitable access is a pressing public health concern.
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Receptor del Péptido 1 Similar al Glucagón , Equidad en Salud , Obesidad , Humanos , Obesidad/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/uso terapéutico , Disparidades en Atención de Salud , Accesibilidad a los Servicios de Salud , Fármacos Antiobesidad/uso terapéutico , Hipoglucemiantes/uso terapéutico , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
Nearly 56% of the global population lives in cities, with this number expected to increase to 6.6 billion or >70% of the world's population by 2050. Given that cardiometabolic diseases are the leading causes of morbidity and mortality in people living in urban areas, transforming cities and urban provisioning systems (or urban systems) toward health, equity, and economic productivity can enable the dual attainment of climate and health goals. Seven urban provisioning systems that provide food, energy, mobility-connectivity, housing, green infrastructure, water management, and waste management lie at the core of human health, well-being, and sustainability. These provisioning systems transcend city boundaries (eg, demand for food, water, or energy is met by transboundary supply); thus, transforming the entire system is a larger construct than local urban environments. Poorly designed urban provisioning systems are starkly evident worldwide, resulting in unprecedented exposures to adverse cardiometabolic risk factors, including limited physical activity, lack of access to heart-healthy diets, and reduced access to greenery and beneficial social interactions. Transforming urban systems with a cardiometabolic health-first approach could be accomplished through integrated spatial planning, along with addressing current gaps in key urban provisioning systems. Such an approach will help mitigate undesirable environmental exposures and improve cardiovascular and metabolic health while improving planetary health. The purposes of this American Heart Association policy statement are to present a conceptual framework, summarize the evidence base, and outline policy principles for transforming key urban provisioning systems to heart-health and sustainability outcomes.