Product Development within the National Institutes of Health Radiation and Nuclear Countermeasures Program.

The Radiation and Nuclear Countermeasures Program (RNCP) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) was established to facilitate the development of medical countermeasures (MCMs) and diagnostic approaches for use in a radiation public health emergency. Approvals for MCMs can be very challenging but are made possible under the United States Food and Drug Administration (FDA) Animal Rule, which is designed to enable licensure of drugs or biologics when clinical efficacy studies are unethical or unfeasible. The NIAID portfolio includes grants, contracts, and inter-agency agreements designed to span all aspects of drug development and encompasses basic research through FDA approval. In addition, NIAID manages an active portfolio of biodosimetry approaches to assess injuries and absorbed radiation levels to guide triage and treatment decisions. NIAID, together with grantees, contractors, and other stakeholders with promising products, works to advance candidate MCMs and biodosimetry tools through an established product development pipeline. In addition to managing grants and contracts, NIAID tests promising candidates in our established preclinical animal models, and the NIAID Program Officers work closely with sponsors as product managers to guide them through the process. In addition, a valuable benefit for stakeholders is working with the NIAID Office of Regulatory Affairs, where NIAID coordinates with the FDA to facilitate interactions between sponsors and the agency. Activities funded by NIAID include basic research (e.g., library screens to discover new products, determine early efficacy, and delineate mechanism of action) and the development of small and large animal models of radiation-induced hematopoietic, gastrointestinal, lung, kidney, and skin injury, radiation combined injury, and radionuclide decorporation. NIAID also sponsors Good Laboratory Practice product safety, pharmacokinetic, pharmacodynamic, and toxicology studies, as well as efficacy and dose-ranging studies to optimize product regimens. For later-stage candidates, NIAID funds large-scale manufacturing and formulation development of products. The program also supports Phase 1 human clinical studies to ensure human safety and to bridge pharmacokinetic, pharmacodynamic, and efficacy data from animals to humans. To date, NIAID has supported >900 animal studies and one clinical study, evaluating >500 new/repurposed radiation MCMs and biodosimetric approaches. NIAID sponsorship led to the approval of three of the six drugs for acute radiation syndrome under the FDA Animal Rule, five Investigational New Drug applications, and 18 additional submissions for Investigational Device Exemptions, while advancing 38 projects to the Biomedical Advanced Research and Development Authority for follow-on research and development.

National Institutes of Health Funding for Surgeon-Scientists in the US-An Update and an Expanded Landscape.

Importance: Current reports suggest that the surgeon-scientist phenotype is significantly threatened. However, a significant increase in the proportion of surgeons in the workforce funded by the National Institutes of Health (NIH) from 2010 (0.5%) to 2020 (0.7%) was recently reported and showed that surgeons primarily performed basic science research (78% in 2010; 73% in 2020) rather than clinical research. Objective: To provide an update on the status of surgeons funded by the NIH for fiscal year (FY) 2022. Evidence Review: NIH-funded surgeons were identified in FY2012 and FY2022, including those who were awarded grants with more than 1 principal investigator (PI) by querying the internal database at the NIH. The main outcome for this study was the total number of NIH-funded surgeons in FY2012 and FY2022, including total grant costs and number of grants. The secondary analysis included self-reported demographic characteristics of the surgeons in FY2022. The research type (basic science vs clinical) of R01 grants was also examined. Findings: Including multiple PI grants, 1324 surgeon-scientists were awarded $1.3 billion in FY2022. Women surgeons increased to 31.3% (339 of 1084) of the population of surgeon PIs in FY2022 compared with 21.0% (184 of 876) in FY2012. Among surgeon PIs awarded grants, a total of 200 (22.8%) were Asian, 35 (4.0%) were Black or African American, 18 (2.1%) were another race (including American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and more than 1 race), and 623 (71.1%) were White. A total of 513 of 689 R01 grants (74.5%) were for basic science, 131 (19.0%) were for clinical trials, and 45 (6.5%) were for outcomes research. Conclusions and Relevance: NIH-funded surgeons are increasing in number and grant costs, including the proportion of women surgeon PIs, and are representative of the diversity among US academic surgical faculty. The results of this study suggest that despite the many obstacles surgeon-scientists face, their research portfolio continues to grow, they perform a myriad of mostly basic scientific research as both independent PIs and on multidisciplinary teams.

Developing the next-generation cancer research workforce in the National Institutes of Health Intramural Research Program.

Although the National Institutes of Health is renowned for being the largest funder of biomedical research in the world, the research and associated career development programs on its own campuses are relatively unknown. These intramural programs provide many outstanding and programmatically unique opportunities for research-intensive careers and training in cancer biology, prevention, diagnosis, and therapeutics. Their complementary foci, structures, and review mechanisms make the extramural and intramural cancer research contributions of the National Institutes of Health the perfect partners in the quest to rid the world of cancer as we know it.

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

National Institutes of Health grant funding for cerebrovascular diseases.

BACKGROUND: Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types. OBJECTIVE: To examine the current scope of NIH grant funding for cerebrovascular conditions. METHODS: The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses. RESULTS: We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546). CONCLUSION: Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS.

The unfunded grant, now what? Advice, approach, and strategy.

BACKGROUND: Grant writing takes significant time and effort and often may be elusive, especially on a first attempt. After the rejection of a grant, many investigators face a dilemma regarding the best next steps. In this article, we discuss the options of revision versus resubmission and how to navigate these decisions. METHODS: The literature was surveyed, including review articles, personal perspectives, and editorial pieces regarding the grant writing and funding processes. The National Institute of Health database was reviewed, and data were extrapolated from the past 10 years of funding percentages and rates of both R01 initial applications and resubmissions. Recommendations were then generated based on pertinent literature and experience from the authors. RESULTS: The grant writing process involves many checkpoints between conception and funding. Only approximately 15% of R01 and R01-equivalent grants are accepted for funding on the initial submission. However, this statistic increases to >30% if the appropriate steps are taken to revise and resubmit the grant. These steps include consulting co-investigators, modifying hypotheses, drafting a succinct "Introduction" document, and many more. Knowing the options after the rejection of an original submission plays a huge role in the ultimate success of the grant. CONCLUSION: Although receiving funding for an original grant can be difficult, with appropriate guidance, it may seem more feasible than initially expected. Adequately responding to the critiques of the grant and revising the grant appropriately can make or break the outcome of the grant.

Therapeutic response of oral chronic graft-versus-host disease to topical corticosteroids according to the 2014 National Institutes of Health (USA) consensus criteria.

BACKGROUND: Chronic graft-versus-host-disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. The oral cavity is one of the most frequently affected anatomic sites and is affected in 70% of all patients who develop cGVHD. The objective of this study was to determine the therapeutic response to topical corticosteroids and clinical outcome of patients with oral cGVHD using the 2014 NIH consensus criteria. MATERIAL AND METHODS: The oral manifestations of cGVHD were collected at the first and the follow-up (FU) visits after the therapeutic treatment of oral GVHD. The FU intervals were: FU0, first visit; FU1, 0-1 month; FU2, 1-3 months; FU3, 3-6 months; FU4, 6-9 months; and FU5, 9-12 months. The oral cGVHD activity was assessed using the NIH modification of the Schubert Oral Mucosa Rating Scale (OMRS) and Thongprasom sign score. The functional impact was assessed by the organ-specific severity score. RESULTS: Fourteen patients (93.3%) at FU0 were being treated with at least one form of systemic immunosuppressive therapy, i.e., prednisolone, cyclosporin, and tacrolimus. The OMRS was reduced between FU0 and FU3 (p < 0.001), FU0 and FU4 (p < 0.001), and FU0 and FU5 (p = 0.004). The organ-specific severity scores were also reduced between FU0 and FU4 (p = 0.016), and FU0 and FU5 (p = 0.001). There was no significant difference in the highest Thongprasom sign score between all follow-up intervals (FU0-FU5) (p = 0.201). One patient (6.7%) at FU4 and three patients (20.0%) at FU5 did not receive topical corticosteroid therapy for oral cGVHD. CONCLUSIONS: The oral cGVHD lesions and functional impacts improved within 6 months and 9 months, respectively. However, most of the patients required topical corticosteroid therapy for more than 1 year to control their symptoms and lesions.

Using a Modern Linked Research Database to Examine Gender Disparities in Orthopaedic Grant Funding from 2010 to 2022.

BACKGROUND: Gender disparities in research grant funding persist in many disciplines. With use of the Dimensions database, we sought to examine the extent of gender disparities in U.S. orthopaedic grant funding from 2010 onward. Our aim was to provide insights into the extent of gender disparities in the field of orthopaedic research and to highlight the potential need for future action to address these disparities. METHODS: Using orthopaedic-related search terms, we queried all U.S. grants awarded for orthopaedic research from 2010 to 2022. A total of 22,326 results were then manually screened to exclude those without a direct focus on orthopaedic research. The amounts received per principal investigator were reported in U.S. dollars and adjusted for inflation. Author gender was predicted with use of the Genderize.io algorithm application programming interface. The iCite Relative Citation Ratio (RCR) was utilized to assess the impact of the publications linked to each grant. RESULTS: A total of 1,723 grants were included. Men principal investigators received significantly higher median funding per grant in 2011, 2012, and 2013; however, this trend reversed with women receiving nonsignificantly higher funding in 2015, 2017, 2018, 2021, and 2022. In 2020, women received significantly higher median funding per grant than men ($166,234 versus $121,384; p = 0.04). Throughout the 13-year period, men principal investigators accounted for approximately 71% of grants, with a very weak increasing trend in the percent of grants attributed to women (R 2 = 0.16; p < 0.001). Grants with men principal investigators resulted in more publications than those with women principal investigators (mean publications, 11.1 versus 6.6; p = 0.001). Publications resulting from grants awarded to men had a significantly higher mean RCR than those resulting from grants awarded to women (2.42 versus 2.09; p = 0.04). CONCLUSIONS: There was no significant difference in the median amounts of funding per grant awarded to men and to women in 7 of the past 8 years, despite significantly greater funding per grant having been awarded to men from 2011 to 2013. Men principal investigators accounted for the majority of grants received during the study period, although this proportion was lower than the proportion of men among orthopaedic surgeons in 2022. This study could inform initiatives aimed at promoting equity in grant funding for orthopaedic research.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

Current status of National Institutes of Health funding for thoracic surgeons in the United States: Beacon of hope or candle in the wind?

OBJECTIVE: Increasing forces threaten the viability of thoracic surgeon-initiated research, a core component of our academic mission. National Institutes of Health funding is a benchmark of research productivity and innovation. This study examined the current status of National Institutes of Health funding for thoracic surgeons. METHODS: Thoracic surgeon principal investigators on National Institutes of Health-funded grants during June 2010, June 2015, and June 2020 were identified using National Institutes of Health iSearchGrants (version 2.4). American Association of Medical Colleges data were used to identify all surgeons in the United States. Types and total costs of National Institutes of Health-funded grants were compared relative to other surgical specialties. RESULTS: A total of 61 of 4681 (1.3%), 63 of 4484 (1.4%), and 60 of 4497 (1.3%) thoracic surgeons were principal investigators on 79, 76, and 87 National Institutes of Health-funded grants in 2010, 2015, and 2020, respectively; these rates were higher than those for most other surgical specialties (P ≤ .0001). Total National Institutes of Health costs for Thoracic Surgeon-initiated grants increased 57% from 2010 to 2020, outpacing the 33% increase in total National Institutes of Health budget. Numbers and types of grants varied among cardiovascular, transplant, and oncology subgroups. Although the majority of grants and costs were cardiovascular related, increased National Institutes of Health expenditures primarily were due to funding for transplant and oncology grants. Per-capita costs were highest for transplant-related grants during both years. Percentages of R01-to-total costs were constant at 55%. Rates and levels of funding for female versus male thoracic surgeons were comparable. Awards to 5 surgeons accounted for 33% of National Institutes of Health costs for thoracic surgeon principal investigators in 2020; a similar phenomenon was observed for 2010 and 2015. CONCLUSIONS: Long-term structural changes must be implemented to more effectively nurture the next generation of thoracic surgeon scientists.

Developing research programs that align with the clinical mission.

Building a competitive research program within a department of surgery requires a significant commitment by the department and the institution to provide the necessary resources for faculty recruitment, retention of current faculty, and physical space/infrastructure to support research activities. We expanded the academic footprint of our department as demonstrated by the expansion of the department of surgery research funding by 13-fold over a period of 7 years, resulting in an increase in national ranking from 55th place to 10th place in the National Institutes of Health extramural funding. This required attention to multiple factors that affect the ability of faculty to establish and maintain competitive research programs. We executed a plan that established a leadership structure that coordinates resources and provides mentorship to faculty. The department invested heavily in the recruitment of new faculty, especially junior faculty, but also some mid-career and senior investigators to develop a critical mass in specific areas for competitive large grant and program project applications. The pipeline of new trainees interested in research was augmented by successful training grant applications that created a mechanism by which residents and fellows can pursue research for periods ranging from a few weeks to 2 years. Administrative infrastructure was created to assist faculty in grant submissions as well as post-award management. Finally, in partnership with institutional leadership, the department acquired the physical space necessary to support both dry-lab and wet-lab research activities. To achieve true excellence, an academic surgery department must maintain excellence in both the clinical and research areas, which, in the context of an academic medical center, are not separate goals.

Promoting Surgeon-Scientists in Otolaryngology-Head and Neck Surgery-From Bench to Bedside.

Importance: Surgeon-scientists (defined as principal investigators [PIs] with a Doctor of Medicine [MD] degree or a combined MD and Doctor of Philosophy [PhD] degree) in otolaryngology-head and neck surgery (OHNS) are imperative for achieving clinical translation in the OHNS field. Objective: To (1) raise awareness about the current state of surgeon-scientists in OHNS, (2) contextualize the landscape of surgeon-scientists in OHNS by comparing it to those of neurosurgery and ophthalmology, and (3) identify strategies for attracting and retaining surgeon-scientists in OHNS. Evidence Review: Research funding data from fiscal years 2015 to 2021 among surgeon-scientists in OHNS, neurosurgery, and ophthalmology were obtained from the National Institutes of Health (NIH) Research Portfolio Online Reporting Tools Expenditures and Results and the US Department of Defense (DOD) Congressionally Directed Medical Research Programs awards database. The Association of American Medical Colleges provided the total number of active physicians in each specialty per year and the number and percentage of residents with an MD-PhD degree in each specialty per year. Cohen d was used to express the standardized value of the magnitude of the mean difference between compared groups. Findings: From 2015 to 2021, on average, there were 9566 active physicians in OHNS, 5559.8 in neurosurgery, and 18908.8 in ophthalmology. In OHNS, a greater number of NIH K (research career development) grants were held by surgeon-scientists than by PIs with a PhD degree (21.4 vs 5.1; mean difference, 16.3; 95% CI, 14.3-18.3; Cohen d = 9.6), whereas most NIH R (research) and U (cooperative agreement) grants (144.1 vs 81.6; mean difference, 62.6; 95% CI, 46.3-78.9; Cohen d = 4.5) and DOD grants (9.9 vs 4.1; mean difference, 5.7; 95% CI, 1.0-10.4; Cohen d = 1.4) were held by PIs with a PhD degree. In a comparison of OHNS to neurosurgery and ophthalmology, after the number of R and U grants was scaled by the number of physicians in each field, neurosurgery had a much greater number of grants per surgeon than OHNS (0.02 vs 0.01; mean difference, 0.01; 95% CI, 0.01-0.02; Cohen d = 4.2). Additionally, neurosurgeons received a much larger R and U grant amount per physician than otolaryngologists ($10 630.20 vs $4511.80; mean difference, $6118.40; 95% CI, $2625.90-$9610.80; Cohen d = 2.0). For the R and U grant metrics, there were no meaningful differences between OHNS and ophthalmology. Conclusions and Relevance: Results of this database study showed that from 2015 to 2021, the number of governmental grants held by surgeon-scientists in OHNS increased, but there is room for improvement given the metrics of neurosurgeons, a population smaller than otolaryngologists. Possible strategies include intramural research grants, surgeon-scientist training programs, and partnerships between specialty societies and NIH administering institutes and centers.

Global oncology research and training at US National Cancer Institute-designated cancer centres: results of the 2021 Global Oncology Survey.

Global oncology research and training are crucial to address the growing global burden of cancer, which largely and increasingly occurs in low-income and middle-income countries. To better understand global oncology activities at the 71 National Cancer Institute (NCI)-designated cancer centres, the US NCI Centre for Global Health regularly surveys cancer centre directors, global oncology leads, and principal investigators in 36 US states and the District of Columbia. The survey results complement internal and publicly available data about global oncology research funded directly by the US National Institutes of Health to provide a comprehensive catalogue of global oncology research, training, and activities led by NCI-designated cancer centres. 91% (61 of 67) of responding cancer centres reported global oncology activities not directly funded by the National Institutes of Health. The survey results indicate that global oncology is an important priority at cancer centres and provide a valuable resource for these centres, researchers, collaborators, trainees, and the NCI and other funders.

The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health.

Comparative genomics is the comparison of genetic information within and across organisms to understand the evolution, structure, and function of genes, proteins, and non-coding regions (Sivashankari and Shanmughavel, Bioinformation 1:376-8, 2007). Advances in sequencing technology and assembly algorithms have resulted in the ability to sequence large genomes and provided a wealth of data that are being used in comparative genomic analyses. Comparative analysis can be leveraged to systematically explore and evaluate the biological relationships and evolution between species, aid in understanding the structure and function of genes, and gain a better understanding of disease and potential drug targets. As our knowledge of genetics expands, comparative genomics can help identify emerging model organisms among a broader span of the tree of life, positively impacting human health. This impact includes, but is not limited to, zoonotic disease research, therapeutics development, microbiome research, xenotransplantation, oncology, and toxicology. Despite advancements in comparative genomics, new challenges have arisen around the quantity, quality assurance, annotation, and interoperability of genomic data and metadata. New tools and approaches are required to meet these challenges and fulfill the needs of researchers. This paper focuses on how the National Institutes of Health (NIH) Comparative Genomics Resource (CGR) can address both the opportunities for comparative genomics to further impact human health and confront an increasingly complex set of challenges facing researchers.

Anthropometric, dietary, and lifestyle factors and risk of advanced thyroid cancer: The NIH-AARP diet and health cohort study.

BACKGROUND: Most patients diagnosed with thyroid cancer have low-risk disease, but some have a higher risk for persistent or recurrent disease and even death from thyroid cancer. Few studies have evaluated potential anthropometric, lifestyle, or dietary risk factors for advanced or aggressive types of thyroid cancer. METHODS: Using data from a large US cohort study, we examined associations for high-risk thyroid cancer (HRTC) and, separately, low-risk thyroid cancer (LRTC) in relation to anthropometric factors, diet, smoking, and alcohol consumption. The National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study included 304,122 participants (124,656 women and 179,466 men) without a history of cancer who completed a mailed questionnaire in 1996-1997 and were followed for cancer incidence through 2011 via linkages with state cancer registries. Hazard ratios (HRs) for anthropometric, dietary, and lifestyle factors in relation to HRTC or LRTC, defined using guidance from the American Thyroid Association initial risk of recurrence classification, were calculated using multivariable-adjusted Cox proportional hazards regression models. RESULTS: During follow-up (median = 10.1 years), 426 participants were diagnosed with HRTC (n = 95) or LRTC (n = 331). In models combining men and women, baseline waist circumference (per 5 cm, HR = 1.13, 95% confidence interval [CI] 1.01-1.27) and weight gain from age 18 years to baseline age (per 5 kg, HR = 1.14, 95% CI 1.02-1.28) were positively associated with risk of HRTC but not LRTC. In contrast, vegetable intake (per cup equivalents/day, HR = 1.15, 95% CI 1.01-1.30), cigarette smoking (current vs. never, HR = 0.39, 95% CI 0.23-0.68), and alcohol consumption (per drink/day, HR = 0.83, 95% CI 0.70-0.97) were associated with risk of LRTC but not HRTC. The association of LRTC risk with vegetable intake was limited to men, and that of current smoking was more pronounced in women. CONCLUSIONS: Our findings suggest that greater waist circumference and adulthood weight gain are associated with thyroid cancers at higher risk for recurrence. These results may have implications for the primary prevention of advanced thyroid cancer.

Readability Analysis of Online Breast Cancer Surgery Patient Education Materials from National Cancer Institute-Designated Cancer Centers Compared with Top Internet Search Results.

BACKGROUND: The National Institutes of Health (NIH) recommends patient education materials reflect the average reading grade level of the US population. Due to the importance of shared decision-making in breast cancer surgery, this study evaluates the reading level of patient education materials from National Cancer Institute-designated cancer centers (NCI-DCC) compared with top Internet search results. METHODS: Online materials from NCI-DCC and top Internet search results on breast cancer, staging, surgical options, and pre- and postoperative expectations were analyzed using three validated readability algorithms: Simplified Measure of Gobbledygook Readability Formula, Coleman-Liau index, and Flesch-Kincaid grade level. Mean readability was compared across source groups and information subcategories using an unpaired t-test with statistical significance set at p < 0.05. Mean readability was compared using a one-way analysis of variance. RESULTS: Mean readability scores from NCI-DCC and Internet groups ranged from a 9th-12th grade level, significantly above the NIH recommended reading level of 6th-7th grade. There was no significant difference between reading levels from the two sources. The discrepancy between actual and recommended reading level was most pronounced for "surgical options" at a 10th-12th grade level from both sources. CONCLUSIONS: Patient education materials on breast cancer from both NCI-DCC and top Internet search results were written several reading grade levels higher than the NIH recommendation. Materials should be revised to enhance patient comprehension of breast cancer surgical treatment and guide patients in this important decision-making process to ultimately improve health outcomes.

Limited number of spine surgeons among recipients of National Institutes of Health grants awarded for degenerative spine disease research.

OBJECTIVE: Surgeon scientists remain underrepresented among recipients of National Institutes of Health (NIH) grants despite their unique ability to perform translational research. This study elucidates the portfolio of NIH grants awarded for degenerative spine diseases and the role of spine surgeons in this portfolio. METHODS: The most common diagnoses and surgical procedures for degenerative spine diseases were queried on the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database (2011-2021). Total NIH funding was extracted for 20 additional clinical areas and compound annual growth rates (CAGRs) were calculated. A retrospective cohort study of principal investigators (PIs) was conducted. NIH grants and funding totals were extracted and compared to those from other clinical areas. RESULTS: The total NIH research budget increased from $31 to $43 billion over the 10-year period (CAGR 3.4%). A total of 273 unique grants equaling $91 million (CAGR 0%) were awarded for degenerative spine diseases. Diabetes ($11.8 billion, CAGR 0%), obesity ($10.6 billion, CAGR 3%), and chronic pain ($5.6 billion, CAGR 7%) received the most funding. Most NIH funding for degenerative spine disease research was awarded through the R01 (66%) and R44 (8%) grant mechanisms. The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the most NIH funding (64%). Departments of orthopedic surgery were awarded the most funding (32%). NIH funding supported clinical (28%), translational (37%), and basic science (35%) research. Disease mechanisms (58%), imaging modalities (20%), and emerging technologies (16%) received the most funding. Nineteen spine surgeons were identified as PIs (16%). There were no significant differences in NIH funding totals by PI demographic and academic characteristics (p > 0.05)-except for full professors, who had the most NIH funding (p = 0.007) and highest h-index values (p < 0.001). CONCLUSIONS: Few spine surgeons receive NIH grants for degenerative spine disease research. Future opportunities may exist for spine surgeons to collaborate in identified areas of clinical interest. Additional strategies are needed to increase NIH funding in spine surgery.