Multidimensional Perioperative Recovery Trajectories in a Mixed Surgical Cohort: A Longitudinal Cluster Analysis Utilizing National Institutes of Health Patient-Reported Outcome Measurement Information System Measures.

BACKGROUND: Pain trajectories have been described in numerous surgical settings where preoperative characteristics have been used to predict trajectory membership. Suboptimal pain intensity trajectories have been linked to poor longitudinal outcomes. However, numerous biopsychosocial modulators of postoperative pain may also have distinct longitudinal trajectories that may inform additional targets to improve postoperative recovery. METHODS: Patients undergoing total joint arthroplasty, thoracic surgery, spine surgery, major abdominal surgery, or mastectomy completed Patient Reported Outcome Measurement Information System (PROMIS) measures and additional scales preoperatively and at 1 week, 2 weeks, 1 month, 3 months, and 6 months postoperatively. A k-means clustering for longitudinal data was utilized to explore and describe distinct pain impact (PROMIS Pain Interference and Physical Function) trajectories and associated changes in additional biopsychosocial measures. Follow-up analyses examined participant demographics and clinical characteristics associated with trajectory memberships. RESULTS: Three postoperative biopsychosocial symptom clusters were identified across all patients (n = 402): low (35%), average (47%), and high (18%) performance cluster trajectories. Participants undergoing total knee arthroplasty (TKA), spinal surgery, reporting presurgical opioid use, and higher pain catastrophizing scale scores were found to be associated with the low performance trajectory. Patients within the low performance trajectory, while demonstrating small improvements by 6 months, remained mild to moderately impaired in both pain impact and physical health outcomes. Alternatively, participants in the average performance trajectory demonstrated improvement in pain impact to population norms compared to baseline and demonstrated continued improvement across physical and psychological outcomes. Patients within the high performance cluster started within population norms across all measures at baseline and returned to baseline or exceeded baseline values by 6 months postoperatively. Self-reported opioid utilization was significantly higher in the low performance cluster across all time points. While a larger proportion of average performance patients reported opioid utilization during the first postoperative month compared to the high performance cluster, no differences were detected at 6 months postoperatively between these 2 clusters. CONCLUSIONS: These pain impact trajectories build upon previous unidimensional pain intensity trajectories and suggest that additional distinct biopsychosocial measures may have unique trajectories related to cluster assignment. Additionally, these findings highlight the importance of continued pain impact surveillance through the perioperative recovery period to detect patients at risk of experiencing a poor trajectory and subsequently poor longitudinal health outcomes.

Longitudinal analysis of National Institutes of Health funding for academic thoracic surgeons.

OBJECTIVE: National Institutes of Health (NIH) funding for academic (noncardiac) thoracic surgeons at the top-140 NIH-funded institutes in the United States was assessed. We hypothesized that thoracic surgeons have difficulty in obtaining NIH funding in a difficult funding climate. METHODS: The top-140 NIH-funded institutes' faculty pages were searched for noncardiac thoracic surgeons. Surgeon data, including gender, academic rank, and postfellowship training were recorded. These surgeons were then queried in NIH Research Portfolio Online Reporting Tools Expenditures and Results for their funding history. Analysis of the resulting grants (1980-2019) included grant type, funding amount, project start/end dates, publications, and a citation-based Grant Impact Metric to evaluate productivity. RESULTS: A total of 395 general thoracic surgeons were evaluated with 63 (16%) receiving NIH funding. These 63 surgeons received 136 grants totaling $228 million, resulting in 1772 publications, and generating more than 50,000 citations. Thoracic surgeons have obtained NIH funding at an increasing rate (1980-2019); however, they have a low percentage of R01 renewal (17.3%). NIH-funded thoracic surgeons were more likely to have a higher professorship level. Thoracic surgeons perform similarly to other physician-scientists in converting K-Awards into R01 funding. CONCLUSIONS: Contrary to our hypothesis, thoracic surgeons have received more NIH funding over time. Thoracic surgeons are able to fill the roles of modern surgeon-scientists by obtaining NIH funding during an era of increasing clinical demands. The NIH should continue to support this mission.

Toward an Anti-Racist Approach to Biomedical and Neuroscience Research.

Racism is a threat to public health. Race is a sociopolitical construct that has been used for generations to create disparities in educational access, housing conditions, exposure to environmental contaminants, and access to health care. Collectively, these disparities have a negative impact on the health of non-white Americans. The National Institutes of Health (NIH) funds biomedical research, including basic neuroscience research, aimed at understanding the mechanisms and consequences of health and disease in Americans. NIH has recently acknowledged its own structural racism, the disadvantage this perpetuates in the biomedical research enterprise, and has announced its commitment to eliminating these disparities. Here, we discuss different rates of disease in U.S. citizens from different racial backgrounds. We next describe ways in which the biomedical research enterprise (1) has contributed to health disparities and (2) can contribute to the solving this problem. Based on our own scientific expertise, we use neuroscience in general and mental health/addiction disorders more specifically as examples of a broader issue. The NIH, including its neuroscience-focused Institutes, and NIH-funded scientists, including neuroscientists, should prioritize research topics that reflect the health conditions that affect all Americans, not just white Americans.

NIH Funding of Researchers in Surgery: Decreased Career Development Awards Over Time.

BACKGROUND: Over time, NIH funding has become increasingly competitive. In addition, academic surgeons' research competes with time required for patient care, operating, and administrative work. Due to these competing interests for surgeons, we hypothesize that the percentage of NIH grants awarded to researchers from departments of surgery is decreasing. METHODS: The NIH Research Portfolio Online Reporting Tool was queried for the number and value of new and renewal R01 grants, and career development awards noting which surgery departments received awards from 1998 to -2018. Statistical analysis was performed using univariate and multivariable logistic regression. RESULTS: The number of career development awards granted to researchers from departments of surgery decreased significantly over time (P = 0.007) while new R01's and R01 renewal awards were stable. The number of grants awarded to researchers from all procedural departments were compared to non-procedural departments and again, career development awards decreased significantly (P = 0.005) over time but new R01's and R01 renewals stayed stable. Looking at the difference in average dollar amount received for new R01, renewal R01, or career development awards between department of surgery awardees and non-surgery over time, there was no significant difference. CONCLUSIONS: NIH funding is becoming increasingly competitive and surgeons have many competing interests. Our study found that there has been a significant decrease in career development awards to department of surgery awardees and procedural specialists. The decrease in receipt of these awards is particularly concerning given that they are meant to provide protected time for developing researchers and thus have potential consequences for future research.

Predicting 90-Day Outcome After Thrombectomy: Baseline-Adjusted 24-Hour NIHSS Is More Powerful Than NIHSS Score Change.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established. METHODS: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ. RESULTS: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR2 0.368 and adjusted odds ratio 0.79 [0.75-0.84], P<0.001 for mRS score 0-2; aR2 0.444 and adjusted odds ratio 0.84 [0.8-0.86] for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14-20], P<0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 [2.85-7.69], P<0.001). CONCLUSIONS: Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

Associations of topic-specific peer review outcomes and institute and center award rates with funding disparities at the National Institutes of Health.

A previous report found an association of topic choice with race-based funding disparities among R01 applications submitted to the National Institutes of Health ('NIH') between 2011 and 2015. Applications submitted by African American or Black ('AAB') Principal Investigators ('PIs') skewed toward a small number of topics that were less likely to be funded (or 'awarded'). It was suggested that lower award rates may be related to topic-related biases of peer reviewers. However, the report did not account for differential funding ecologies among NIH Institutes and Centers ('ICs'). In a re-analysis, we find that 10% of 148 topics account for 50% of applications submitted by AAB PIs. These applications on 'AAB Preferred' topics were funded at lower rates, but peer review outcomes were similar. The lower rate of funding for these topics was primarily due to their assignment to ICs with lower award rates, not to peer-reviewer preferences.

NIH Funding for Surgeon-Scientists in the US: What Is the Current Status?

BACKGROUND: Recent literature suggests that the future of surgeon-scientists in the US has been threatened for the past several decades. However, we documented an overall increase in NIH funding for surgeon-scientists, as well as the number of NIH-funded surgeons, from 2010 to 2020. STUDY DESIGN: NIH-funded principal investigators (PIs) were identified for June 2010 and June 2020 using the NIH internal data platform iSearch Grants (version 2.4). Biographical sketches were searched for key terms to identify surgeon-scientists. Grant research types and total grant costs were collected. American Association of Medical Colleges data were used to determine total surgeon and physician populations. Bivariate chi-square analyses were performed using population totals and were corroborated using z-tests of population proportions using JMP (version 13.0.0). A 2-tailed p value <0.05 was considered significant. RESULTS: In June of 2020, a total of 1,031 surgeon-scientists held $872,456,710 in NIH funding. The percentage of funded surgeons significantly increased from 2010 (0.5%) to 2020 (0.7%) (p < 0.05), and the percentage of funded other physicians significantly decreased from 2.2% in 2010 to 1.6% in 2020 (p < 0.05). All surgeons sustained R grant funding at both time points (58% in 2020 and 60% in 2010), and specifically maintained basic science-focused R grants (73% in 2020 and 78% in 2010). CONCLUSIONS: Our study found surgeon-scientists are increasing in number and NIH funding and are becoming more diverse in their research efforts, while maintaining a focus on basic science.

Trends Over a Decade in NIH Funding for Autism Spectrum Disorder Services Research.

Investments in autism spectrum disorder (ASD) research, guided by the Interagency Autism Coordinating Committee (IACC), have focused disproportionately on etiology over a well-established stakeholder priority area: research to improve accessibility and quality of community-based services. This study analyzed National Institutes of Health ASD services research funding from 2008 to 2018 to examine funding patterns, evaluate the impact of IACC objectives, and identify future directions. Approximately 9% of total funds were allocated to services research. This investment remained relatively stable across time and lacked diversity across domains (e.g., area of focus, ages sampled, implementation strategies used). While advancements were observed, including increased prevalence of projects focused on adult samples and on dissemination/implementation and prevention areas, greater investment in service research is critically needed.

Contributors to Independent Research Funding Success from the Perspective of K12 BIRCWH Program Directors.

INTRODUCTION: Faculty training awards are an important means of advancing early career faculty in research. The National Institutes of Health (NIH) Building Interdisciplinary Research Careers in Women's Health (BIRCWH) is a long-running K12 career development program and has been integral in promoting the research success of faculty nationally. We surveyed BIRCWH program directors to understand factors likely to influence long-term research careers and funding success. MATERIALS AND METHODS: We developed an online survey containing open-ended questions about individual and programmatic attributes and activities that promote success in achieving independent research funding. Domains of interest included: 1) strategies for funding success; 2) traits for predicting success; 3) groups considered vulnerable to attrition; and 4) existing resources and means of support. RESULTS: Fifteen institutions (75%) were included in the final analysis. Passion for research, persistence, resilience, and strong mentorship relationships were identified by all directors as factors important to scholar success. Responses also revealed an important pattern: program directors attributed attrition either to individual or organizational characteristics. This distinction has meaningful consequences for framing efforts to diminish attrition. Faculty who were clinicians, women, parents and underrepresented minorities were identified as vulnerable to attrition from the research careers. Common perceived challenges in these groups included isolation/feeling alienated, juggling numerous priorities, inadequate research time, lack of role models, and work-life balance issues. CONCLUSION: K12 BIRCWH directors identified persistence and resilience and developing community, networks, and other support opportunities as elements of scholar success. Programs and mentors can help early career faculty by teaching skills and providing tools they can use to maximize the value of these opportunities and expand their mentees' research relationships. Our study also highlights the importance of social factors, particularly isolation, on clinicians, women, and minoritized scholars on career success.

Critical NIH Resources to Advance Therapies for Pain: Preclinical Screening Program and Phase II Human Clinical Trial Network.

Opioid-related death and overdose have now reached epidemic proportions. In response to this public health crisis, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-term InitiativeSM, or NIH HEAL InitiativeSM, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Herein, we describe two NIH HEAL Initiative programs to accelerate development of non-opioid, non-addictive pain treatments: The Preclinical Screening Platform for Pain (PSPP) and Early Phase Pain Investigation Clinical Network (EPPIC-Net). These resources are provided at no cost to investigators, whether in academia or industry and whether within the USA or internationally. Both programs consider small molecules, biologics, devices, and natural products for acute and chronic pain, including repurposed and combination drugs. Importantly, confidentiality and intellectual property are protected. The PSPP provides a rigorous platform to identify and profile non-opioid, non-addictive therapeutics for pain. Accepted assets are evaluated in in vitro functional assays to rule out opioid receptor activity and to assess abuse liability. In vivo pharmacokinetic studies measure plasma and brain exposure to guide the dose range and pretreatment times for the side effect profile, efficacy, and abuse liability. Studies are conducted in accordance with published rigor criteria. EPPIC-Net provides academic and industry investigators with expert infrastructure for phase II testing of pain therapeutics across populations and the lifespan. For assets accepted after a rigorous, objective scientific review process, EPPIC-Net provides clinical trial design, management, implementation, and analysis.

Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: challenges and opportunities.

Pain medication plays an important role in the treatment of acute and chronic pain conditions, but some drugs, opioids in particular, have been overprescribed or prescribed without adequate safeguards, leading to an alarming rise in medication-related overdose deaths. The NIH Helping to End Addiction Long-term (HEAL) Initiative is a trans-agency effort to provide scientific solutions to stem the opioid crisis. One component of the initiative is to support biomarker discovery and rigorous validation in collaboration with industry leaders to accelerate high-quality clinical research into neurotherapeutics and pain. The use of objective biomarkers and clinical trial end points throughout the drug discovery and development process is crucial to help define pathophysiological subsets of pain, evaluate target engagement of new drugs and predict the analgesic efficacy of new drugs. In 2018, the NIH-led Discovery and Validation of Biomarkers to Develop Non-Addictive Therapeutics for Pain workshop convened scientific leaders from academia, industry, government and patient advocacy groups to discuss progress, challenges, gaps and ideas to facilitate the development of biomarkers and end points for pain. The outcomes of this workshop are outlined in this Consensus Statement.

NIH funding trends to US medical schools from 2009 to 2018.

Total NIH funding dollars have increased from 2009-2018. We questioned whether this growth has occurred proportionately around the country and throughout allopathic medical schools. Therefore, we compared the trend in NIH grant funding from 2009 to 2018 for United States allopathic medical schools among historically top-funded schools, private and public schools, and by region of the country. Changes in both unadjusted and real funding dollars over time revealed a significant difference. Region was the only significant factor for mean percent change in funding from 2009-2018, with the Western region showing a 33.79% increase in purchasing power. The Northeastern region showed a -6.64% decrease in purchasing power while the Central and Southern regions reported changes of 2.46% and -6.08%, respectively. The mean percent increases were more proportional and nonsignificant in the public vs. private institutions comparison, at -3.41% and 4.75%, respectively. Likewise, the top-funded institutions vs. other institutions comparisons demonstrated modest, nonsignificant differences. However, although the relative changes might be proportional, the absolute increases evidence a pattern of growing cumulative advantage that favor the highest-funded institutions and private institutions. The potential consequences of this disproportionate increase include health science education, biomedical research, and patient access disparities in large parts of the country. The NIH and the scientific community should explore potential solutions in its funding models.

NIH funding and the pursuit of edge science.

The National Institutes of Health (NIH) plays a critical role in funding scientific endeavors in biomedicine. Funding innovative science is an essential element of the NIH's mission, but many have questioned the NIH's ability to fulfill this aim. Based on an analysis of a comprehensive corpus of published biomedical research articles, we measure whether the NIH succeeds in funding work with novel ideas, which we term edge science. We find that edge science is more often NIH funded than less novel science, but with a delay. Papers that build on very recent ideas are NIH funded less often than are papers that build on ideas that have had a chance to mature for at least 7 y. We have three further findings. First, the tendency to fund edge science is mostly limited to basic science. Papers that build on novel clinical ideas are not more often NIH funded than are papers that build on well-established clinical knowledge. Second, novel papers tend to be NIH funded more often because there are more NIH-funded papers in innovative areas of investigation, rather than because the NIH funds innovative papers within research areas. Third, the NIH's tendency to have funded papers that build on the most recent advances has declined over time. In this regard, NIH funding has become more conservative despite initiatives to increase funding for innovative projects. Given our focus on published papers, the results reflect both the funding preferences of the NIH and the composition of the applications it receives.