Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare, fatal, premature aging disease caused by a toxic protein called progerin. Circulating progerin has not been previously detected, precluding research using readily available biological samples. This study aimed to develop a plasma progerin assay to evaluate progerin's quantity, response to progerin-targeted therapy, and relationship to patient survival. METHODS: Biological samples were collected by The Progeria Research Foundation Cell and Tissue Bank from a non-HGPS cohort cross-sectionally and a HGPS cohort longitudinally. HGPS donations occurred at baseline and intermittently while treated with farnesylation inhibitors lonafarnib±pravastatin and zoledronate, within 3 sequential open-label clinical trials at Boston Children's Hospital totaling >10 years of treatment. An ultrasensitive single-molecule counting progerin immunoassay was developed with prespecified performance parameters. Intra- and interpatient group statistics were descriptive. The relationship between progerin and survival was assessed by using joint modeling with time-dependent slopes parameterization. RESULTS: The assay's dynamic detection range was 59 to 30 000 pg/mL (R2=0.9987). There was no lamin A cross-reactivity. Mean plasma progerin in non-HGPS participants (n=69; 39 male, 30 female; age, 0.2-71.3 years) was 351±251 pg/mL, and in drug-naive participants with HGPS (n=74; 37 female, 37 male; age, 2.1-17.5 years) was 33 261±12 346 pg/mL, reflecting a 95-fold increase in affected children (P<0.0001). Progerin levels did not differ by sex (P=0.99). Lonafarnib treatment resulted in an average per-visit progerin decrease from baseline of between 35% to 62% (all P<0.005); effects were not augmented by adding pravastatin and zoledronate. Progerin levels fell within 4 months of therapy and remained lower for up to 10 years. The magnitude of progerin decrease positively associated with patient survival (P<0.0001; ie, 15 000 pg/mL decrease yields a 63.9% decreased risk of death). For any given decrease in progerin, life expectancy incrementally increased with longer treatment duration. CONCLUSIONS: A sensitive, quantitative immunoassay for progerin was developed and used to demonstrate high progerin levels in HGPS plasma that decreased with lonafarnib therapy. The extent of improved survival was associated with both the magnitude of progerin decrease and duration at lower levels. Thus, plasma progerin is a biomarker for HGPS whose reduction enables short- and long-term assessment of progerin-targeted treatment efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifiers: NCT00879034 and NCT00916747.

Just-relations and responsibility for planetary health: The global nurse agenda for climate justice.

There is an urgent call for nurses to address climate change, especially in advocating for those most under threat to the impacts. Social justice is important to nurses in their relations with individuals and populations, including actions to address climate justice. The purpose of this article is to present a Global Nurse Agenda for Climate Justice to spark dialog, provide direction, and to promote nursing action for just-relations and responsibility for planetary health. Grounding ourselves within the Mi'kmaw concept of Etuaptmumk (two-eyed seeing), we suggest that climate justice is both call and response, moving nurses from silence to Ksaltultinej (love as action). We review the movement for climate justice in nursing, weaving between our own stories, our relations with Mi'kmaw ways of knowing, and the stories of the movement, with considerations for the (w)holistic perspectives foundational to nursing's metaparadigm of person, environment, and health. We provide a background to the work of the Global Nurse Agenda for Climate Justice steering committee including their role at the 26th United Nations Climate Change Conference in Glasgow, 2021, and share our own stories of action to frame this agenda. We accept our Responsibility for the challenges of climate justice with humility and invite others to join us.

Pediatric septorhinoplasty: Current attitudes and practices by facial plastic and reconstructive surgeons.

OBJECTIVE: There is hesitation to offer pediatric patients rhinoplasty due to concerns about postoperative effect on midface growth. A cross-sectional survey of members of the American Academy of Facial Plastic and Reconstructive Surgery was conducted regarding practice information and attitudes towards pediatric septorhinoplasty. The goal of the study is to describe the current attitudes on pediatric septorhinoplasty. STUDY DESIGN: Cross-sectional survey. SETTING: Community members of the American Academy of Facial Plastic and Reconstructive Surgery society. METHODS: A 19-question survey was distributed to surgeons surveying background information and current attitudes towards pediatric septorhinoplasty practices. Fisher's exact tests were implemented using Monte Carlo methods. RESULTS: There were 94 total respondents. A majority believed septorhinoplasty is safe in patients <16 years of age (n = 68, 72.34 %) with most choosing either 16 years (n = 30, 31.91 %) or 14 years (n = 29, 30.85 %) as the minimum age to consider the procedure. A majority of respondents would not perform any nasal procedures in patients ≤12 years (n = 40, 43.48 %). CONCLUSION: Trends in pediatric rhinoplasty practices have evolved overtime. Despite prior beliefs and studies cautioning against performing septorhinoplasty in pediatric patients (<16 years of age), a majority of practicing facial plastic surgeons believe that pediatric septorhinoplasty can be performed in patients >14 years old. LEVEL OF EVIDENCE: IV.

Current Practices and Trends in Midface Rejuvenation.

BACKGROUND: Cosmetic approaches to midface aging are complex and vary in their treatment methodology. The nature of cosmetic surgery limits clinical trial data, forcing surgeons to rely on small studies and professional preferences when choosing an approach. Our study aimed to quantitatively assess national trends in midface rejuvenation practices. METHODS: We conducted a cross-sectional study consisting of a survey administered through the American Academy of Facial Plastic and Reconstructive Surgery and the American Society of Plastic Surgeons listservs. To evaluate trends, techniques were grouped into 2 categories: minimally invasive (injectable fillers, fat transfer, fat repositioning) or invasive (deep plane facelift, subperiosteal lift, malar/cheek alloplastic implant, bone grafting/bone advancement). RESULTS: Two hundred thirty-two survey responses were received. Of the total respondents, 46.52% were certified by the American Board of Facial Plastic and Reconstructive Surgery, and 48.26% were certified by the American Board of Plastic Surgery. Minimally invasive techniques were far more preferred (66.67%) over invasive (33.33%) techniques, with injectable fillers as the most common technique (34.88%), followed by fat transfer (20.93%). Deep plane facelift was preferred over subperiosteal lift (18.60% vs 7.91%, respectively). Surgeons board certified by the American Board of Facial Plastic and Reconstructive Surgery were more inclined to perform invasive techniques over those board certified by the American Board of Plastic Surgery (P = 0.0427). CONCLUSION: This study quantitatively assessed national trends in cosmetic approaches to midface aging. Our data suggest that trends among surgeons across the United States have shifted toward favoring minimally invasive techniques over more invasive approaches.

Evaluation of a multischool collaborative COVID-19 vaccination project.

To describe experiences of student nurses and faculty who participated in COVID-19 vaccine delivery through a multischool collaboration. Cross-sectional survey. Student nurses and faculty members from five university schools and colleges of nursing who participated in one or more COVID-19 vaccination or education events in 2021. Surveys were designed for students and faculty to document process and outcome experiences associated with project participation. Surveys were administered through an online survey platform. Overall, 648 students and 68 faculty members participated in the project. The evaluation survey was completed by 115 students (18%) and 58 faculty members (85%). Students valued increasing their clinical skills and reported the experience influenced their perspectives on nursing, fueling their passion and informing future career choices. Students reported that it was personally important to contribute to the vaccination effort. Few students reported challenges in participating in the project. Faculty reported positive experiences including gaining knowledge about public health and their communities, fueling their passion for nursing education, feeling a deeper connection with students, and experiencing personal satisfaction from contributing to the pandemic response. This project resulted in meaningful student learning opportunities, enhanced capacity for the public health emergency response, and strengthened partnerships among nursing programs and between academia and public health community partners.

Relationship Between Level of American Football Playing and Diagnosis of Chronic Traumatic Encephalopathy in a Selection Bias Analysis.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts such as those from American football. Our understanding of this association is based on research in autopsied brains, since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs to be accounted for to ensure a generalizable estimate of the association between repetitive head impacts and CTE. We evaluated the relationship between level of American football playing and CTE diagnosis after adjusting for selection bias. The sample included 290 deceased male former American football players who donated their brains to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank between 2008 and 2019. After adjustment for selection bias, college-level and professional football players had 2.38 (95% simulation interval (SI): 1.16, 5.94) and 2.47 (95% SI: 1.46, 4.79) times the risk of being diagnosed with CTE as high-school-level players, respectively; these estimates are larger than estimates with no selection bias adjustment. Since CTE is currently diagnosed only postmortem, we additionally provide plausible scenarios for CTE risk ratios for each level of play during the former players' lifetime. This study provides further evidence to support a dose-response relationship between American football playing and CTE.

Sample size determination for the association between longitudinal and time-to-event outcomes using the joint modeling time-dependent slopes parameterization.

Given their improvements in bias reduction and efficiency, joint models (JMs) for longitudinal and time-to-event data offer great potential to clinical trials. However, for JM to become more widely used, there is a need for additional development of design considerations. To this end, Chen et al previously developed two closed-form sample size formulas in the JM setting. In this current work, we expand upon this framework by utilizing the time-dependent slopes parameterization, where the change in the longitudinal outcome influences the hazard, in addition to the current value of the longitudinal process. Our extended formula for the required number of events can be used when testing significance of the association between the longitudinal and time-to-event outcomes. We find that if the data indeed are generated such that not only the current value, but also the slope of the longitudinal outcome influence the hazard of the time-to-event process, it is advisable to use the current formula developed utilizing the time-dependent slopes parameterization. In this setting, our proposed formula will provide a more accurate estimate of power compared to the method by Chen et al. To illustrate our proposed method, we present power calculations of a biomarker qualification study for Hutchinson-Gilford progeria syndrome, an ultra-rare premature aging disease.

Early findings of a nurse-led youth activist program in mind caring.

BACKGROUND: School-based youth activist programs in mind caring have been shown to support the mental health and learning needs of adolescent students. METHODS: We used collaborative action research methods to implement a nurse-led mind caring youth activist program for a rural, extended opportunity school in Thailand. The participants (N = 67) were the public health nurse assigned to the school, students willing to become youth activists (n = 42), school teachers and staff (n = 7), university psychiatric mental health nursing faculty (n = 2), and volunteer nursing students (n = 16). Qualitative thematic analyses methods were used to explore the transcripts of the participant's reflection circles and confirmatory interviews for evidence of effective program implementation. RESULTS: Major themes of change and growth were identified. Youth activists students said mind caring improved their mental health. Teachers described having a more positive attitude towards students' mental health and learning needs. Nursing students found optimistic confidence and self-awareness in the hands-on experience with the complex role responsibilities in public health nursing. CONCLUSION: These results provide early evidence of stakeholder satisfaction with the implementation of a school-based youth activist program as collaborative action for organizational change.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Admission Lymphocytopenia is Associated with Urinary Tract Infection and Nosocomial Infections in Hemorrhagic Stroke.

OBJECTIVE: Growing evidence suggests that lymphocytopenia on admission (LOA) is associated with infectious complications and poor outcomes in intracerebral hemorrhage (ICH). Whether LOA preferentially increases the risk for community acquired infections or nosocomial infections is unknown. This study investigates the relationship between LOA and nosocomial infections in a cohort of patients with ICH in a safety-net hospital. MATERIAL AND METHODS: This is a single center, observational, retrospective study of 213 patients with non-traumatic ICH admitted to the neurocritical care unit between 2008 and 2014. Patients' clinical, demographic, lab and radiologic data were retrieved from institutional electronic medical records. Nosocomial infection was defined as clinical onset 48 h after admission. RESULTS: Prevalence of LOA was 24.8%. Patients with LOA showed significant associations with mechanical ventilation (67.9% versus 49.4%; p= 0.019), higher median ICH score (2 versus 1; p=0.006), nosocomial infection (43.4% versus 28.0%; p=0.038), nosocomial UTI (24.5% versus 8.9%; p=0.003). Adjusting for baseline covariates in a multivariate logistic regression, we observed an association of LOA with nosocomial UTI (OR, 3.66 [95% CI, 1.36-9.88], p=0.010). From the Cox proportional model, patients with LOA had 1.76 times the hazard of developing of nosocomial infection, compared to those without LOA ([95% CI: 1.01, 3.07], p=0.046) and had 3.27 times the hazard of developing nosocomial UTI, compared to those without LOA ([95% CI: 1.39, 7.67], p=0.007). CONCLUSIONS: This study is the first to show that LOA is associated with nosocomial urinary tract infections and significantly shorter times to develop nosocomial infections.

Nursing strategies for environmental justice: A scoping review.

OBJECTIVE: To describe types of strategic actions nurses take to promote environmental justice (EJ) through research, education, advocacy, and practice (REAP) reported in peer-reviewed literature. DESIGN AND SAMPLE: A scoping review of literature was conducted that described EJ nursing strategies and included nurses listed as authors, subjects, partners, or organizational members. The sample consisted of 35 articles, representing 24 primary research studies and 11 nonresearch articles. Data were separately analyzed by research and nonresearch articles for a clearer understanding of evidence-based strategies within domains of REAP. RESULTS: Articles in the sample highlighted the importance of authentic community partnership and represented diversity of nursing strategies that addressed a range of environmental exposures and subsequent health and racial inequities. Climate justice, a concept that emerged from the EJ movement and intersects with planetary health, is a recent focus in professional nursing. CONCLUSIONS: This scoping review establishes an understanding of the extent of nursing knowledge and research in EJ and lays the groundwork for further research on effective EJ nursing strategies. Community-Based Participatory Research/Participatory Action Research methods are fundamental for EJ research, and further theoretical development is needed to guide evaluation of EJ nursing strategies for education, advocacy, and practice.

Documentation of medical marijuana use in cancer patients.

PURPOSE: Medical marijuana is often used as adjuvant therapy in cancer patients for symptom management, although limited evidence-based studies evaluating its efficacy or safety exist. Similar to over-the-counter medications, supplements, or herbal products, documentation of medical marijuana is important to monitor efficacy, potential adverse effects, or interactions. The objective of this quality improvement study was to improve the consistency of medical marijuana documentation in cancer patients by assessing current practices; educating healthcare team members about the importance of documentation and newly established documentation process; and evaluating the new documentation process. METHODS: This three-part quality improvement study was approved by the Institutional Review Board. In part I, a voluntary survey was sent via email to Cancer Center healthcare personnel to assess the current documentation process of medical marijuana. In part II, a best practice process for documenting medical marijuana in the electronic medical record was established. Medical marijuana was to be listed as a historical medication in the medication list. In-person and electronic education sessions were offered to Cancer Center clinical staff. The education emphasized the importance of documenting medical marijuana use and provided a detailed process for electronic medical record documentation. A pre- and post-test to assess understanding was also included. Part III was a retrospective chart review to evaluate documentation practices of certified medical marijuana users in the Cancer Center. Patients included in the study were greater than 18 years old and certified for medical marijuana use on or after 1 January 2018. Department of Corrections patients were excluded. Descriptive statistics were used for data analysis. RESULTS: The survey results in part I demonstrated a lack of consistency in the documentation of medical marijuana in the Cancer Center. The pre- and post-test scores measured in part II showed a significant improvement in understanding after education was provided. The average pre-test score was a 61 and post-test score was 88, indicating an average increase of 27 points. A larger increase in test scores was observed in those attending the in-person education than the online sessions (p < 0.002). The results of the retrospective chart review in part III revealed 56 patients who met inclusion criteria, but only 39 patients were alive and evaluated at the time of the retrospective chart review. Of the 39 patients, 22 never completed the patient registration process and therefore, would never have been able to obtain medical marijuana. Seven patients had medical marijuana properly documented in their medication list and 10 patients were missing documentation in the medication list, showing room for improvement in documentation practices. CONCLUSIONS: This quality improvement study led to the implementation of medical marijuana documentation in the medication list. Education increased healthcare team members understanding of medical marijuana utilization and the importance of documentation.

Association of low-frequency genetic variants in regulatory regions with nonsyndromic orofacial clefts.

Genome-wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low-frequency variants may account for some of the "missing" heritability. Therefore, we scanned low-frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP-Seq studies in craniofacial tissues or cell lines contained multiple low-frequency (0.01-1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low-frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p-value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p-value = .001). These findings suggest that low-frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs.

Strategies for academic nursing to advance global and planetary health: A call to action.

Nurses play a crucial role in addressing human health influenced by global forces such as pandemics, and political conflicts that displace millions; in leading efforts to promote planetary health; and in achieving the United Nations (UN) Sustainable Development Agenda. Academic nursing programs have a significant role in actualizing nursing's impact on global health (GH) and planetary health (PH). This paper describes how nursing programs can actualize their GH and PH nursing perspectives to benefit students and society, thereby increasing nursing's effectiveness and improving health outcomes in local and global settings. Numerous strategies to actualize GH and PH perspectives were derived from current literature and an assessment of eleven nursing program websites. Nursing programs may adopt program-wide strategies such as reflecting GH and PH in their mission statement; through education, in courses; and through faculty or student scholarship, policy endeavors, and/or partnerships. Now is the time to take such action, recommitting to GH and PH nursing and deepening nursing's impact. Academic nursing programs' leadership role in society, and their role in preparing nurses to lead, educate, discover, and advocate is essential for the health of populations and the planet long into the future.

Planetary Health Nursing.

ABSTRACT: Planetary health is focused on the interconnectedness of the health of humans, other species, and the physical environment. Disruption of the Earth's natural ecosystems due to human overconsumption; disregard for sustainable practices; and the domination of other humans, species, and natural systems has led to an urgent moment in which humans must act to preserve these ecosystems, which support life on this planet. Restoring planetary health requires new directions for nursing. The pragmatic implications for nursing research, education, advocacy, and practice are explored in this article.

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab.

INTRODUCTION/BACKGROUND: Durvalumab is a programmed cell death ligand 1 (PD-L1) inhibitor indicated for stage III, unresectable non-small cell lung cancer (NSCLC) consolidation therapy following concurrent platinum-based chemoradiation based on results of the PACIFIC trial. Safety data of durvalumab demonstrates an increased risk of immune-related adverse effects (irAEs), most notably pneumonitis. Pneumonitis is a serious and potentially fatal complication of immunotherapy. It is important to investigate the incidence of pneumonitis in clinical practice to evaluate the generalizability of published data. The objective of this study is to assess and characterize real-world incidence of pneumonitis in patients with NSCLC receiving durvalumab. MATERIALS AND METHODS: This retrospective study included patients who were initiated on durvalumab for unresectable stage III NSCLC from February 2018 through November 2019. The data analysis utilized descriptive statistics to determine the incidence of pneumonitis associated with durvalumab. RESULTS: Of the 83 patients who were evaluated, 21 patients (25.3%) experienced pneumonitis, with 5 cases (6%) being grade 3/4. Seven patients were re-challenged with durvalumab, while 14 patients permanently discontinued durvalumab. There were no clearly identifiable risk factors leading to an increased incidence of pneumonitis. CONCLUSION: The results of this study indicate that real-world incidence of pneumonitis in stage III NSCLC patients receiving durvalumab consolidation therapy is congruent with the incidence reported in the PACIFIC trial.

Geographic Barriers Affect Follow-Up Care in Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: Follow-up care in head and neck cancers (HNC) is critical in managing patient health. However, social determinants of health (SDOH) can create difficulties in maintaining follow-up care. The study goal is to explore how SDOH impacts maintenance of HNC follow-up care appointments. METHODS: A systematic retrospective chart review of 877 HNC patients diagnosed in the past 10 years a safety-net tertiary care hospital with systems to help reduce care disparities. Cohort groups were identified and compared against protocols for follow-up. Data were analyzed using analysis of variance, chi-square tests, Fisher's exact tests, two-sample t-tests, and simple linear regression. RESULTS: The average length of follow-up time in months and average total number of follow-ups over 5 years were 32.96 (34.60) and 9.24 (7.87), respectively. There was no significant difference in follow-up care between United States (US) versus non-US born and English versus non-English speaking patients. Race/ethnicity, county median household income, insurance status, and county educational attainment were not associated with differences in follow-up. However, living a greater distance from the hospital was associated with lower follow-up length and less frequency in follow-up (P < .0001). CONCLUSION: While income, primary language, country of birth, race/ethnicity, insurance status, and markers of educational attainment do not appear to impact HNC follow-up at our safety-net, tertiary care institution, and distance from hospital remains an important contributor to disparities in care. This study shows that many barriers to care can be addressed in a model that addresses SDOH, but there are barriers that still require additional systems and resources. Laryngoscope, 132:1022-1028, 2022.

Social determinants of health and treatment decisions in head and neck cancer.

BACKGROUND: This study compares select social determinants of health (SDOH) with treatment modality selection and treatment completion in head and neck cancer (HNC) patients, to better understand disparities in health outcomes. METHODS: A retrospective cohort study of HNC (n = 1428) patients was conducted. Demographic and disease-specific variables were recorded, including treatment modality selection and completion. Data were analyzed using two-sample t tests, chi-square, and Fisher's exact tests. RESULTS: Primary language was significantly associated with treatment choice, where non-English speakers were less likely to choose treatment as recommended by the Tumor Board. Lower mean distance from the hospital (37.38 [48.31] vs. 16.92 [19.10], p < 0.0001) and a county-based higher mean percentage of bachelor degree or higher education (42.16 [8.82] vs. 44.95 [6.19], p < 0.0003) were associated with treatment selection. CONCLUSION: Language, distance from the hospital, and education affected treatment selection in this study and may be useful in understanding how to counsel patients on treatment selection for HNC.

Type 2 Diabetes Partitioned Polygenic Scores Associate With Disease Outcomes in 454,193 Individuals Across 13 Cohorts.

OBJECTIVE: Type 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed ß-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed. RESEARCH DESIGN AND METHODS: Here we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) and tested for cross-sectional association with T2D-related outcomes, including blood pressure, renal function, insulin use, age at T2D diagnosis, and coronary artery disease (CAD). RESULTS: Despite all clusters containing T2D risk-increasing alleles, they had differential associations with metabolic outcomes. Increased obesity and lipodystrophy cluster pPS, which had opposite directions of association with measures of adiposity, were both significantly associated with increased blood pressure and hypertension. The lipodystrophy and liver/lipid cluster pPS were each associated with CAD, with increasing and decreasing effects, respectively. An increased liver/lipid cluster pPS was also significantly associated with reduced renal function. The liver/lipid cluster includes known loci linked to liver lipid metabolism (e.g., GCKR, PNPLA3, and TM6SF2), and these findings suggest that cardiovascular disease risk and renal function may be impacted by these loci through their shared disease pathway. CONCLUSIONS: Our findings support that genetically driven pathways leading to T2D also predispose differentially to clinical outcomes.