RocHealthData.org: Development and usage of a publicly available, geographic source of social determinants of health data.

Access to local, population specific, and timely data is vital in understanding factors that impact population health. The impact of place (neighborhood, census tract, and city) is particularly important in understanding the Social Determinants of Health. The University of Rochester Medical Center's Clinical and Translational Science Institute created the web-based tool RocHealthData.org to provide access to thousands of geographically displayed publicly available health-related datasets. The site has also hosted a variety of locally curated datasets (eg., COVID-19 vaccination rates and community-derived health indicators), helping set community priorities and impacting outcomes. Usage statistics (available through Google Analytics) show returning visitors with a lower bounce rate (leaving a site after a single page access) and spent longer at the site than new visitors. Of the currently registered 1033 users, 51.7% were from within our host university, 20.1% were from another educational institution, and 28.2% identified as community members. Our assessments indicate that these data are useful and valued across a variety of domains. Continuing site improvement depends on new sources of locally relevant data, as well as increased usage of data beyond our local region.

Implementation of a self-determination based clinical program to reduce cardiovascular disease risk.

Health behaviors are the cornerstone of cardiovascular risk reduction but change is challenging and maintenance is uncommon. The use of Self-Determination Theory (SDT) can promote long-term change however the pathway is uncertain related to cardiovascular risk reduction. A multi-disciplinary clinical team trained in SDT counseled 294 individuals with high cardiovascular risk. Our participants had a significant decrease in cholesterol as well as a significant increase healthy diet and motivation measures. Autonomous motivation was a critical element in the pathways. We demonstrated that a SDT team-based clinical intervention can promote cardiovascular risk reduction through autonomous motivation.

Implementation of PROMIS® in an Optometry Clinic.

PURPOSE: The full utility of general health Patient-Reported Outcomes Measurement Information System® (PROMIS) surveys in the eye care setting has not been previously demonstrated. This report demonstrates the feasibility of implementing PROMIS in an eye care clinic. PATIENTS AND METHODS: Over 2 months, general health and functioning PROMIS surveys were offered to all patients in an optometric clinic in Rochester, NY. Demographic and clinical variables were recorded along with percent completion and time to completion of the survey. RESULTS: Across 651 patients, 258 chose to attempt PROMIS. Patients with low visual acuity were less likely to attempt the survey (p=0.049), and younger patients were more likely to complete the survey (p=0.025); no other patient characteristics were found to differ between those who did and did not participate in, nor complete, PROMIS. A total of 193 patients completed the survey (74.8%) in a mean time of 6.36 minutes (range = [1.43, 51.92] minutes; standard deviation = 5.62 minutes). Time to completion did not vary significantly across any groups. CONCLUSION: Our relatively high completion rate among those who attempted PROMIS indicates that PROMIS surveys are feasible to implement in an optometry clinic. While most patients completed the survey in little time, the large range of time to completion may indicate that some patients had difficulty completing the survey. Furthermore, the significant difference in visual acuity between those who participated in the survey and those who did not highlights the need to address the way PROMIS is delivered in order to foster greater inclusion.

Methods Matter: Standard Production Platforms for Recombinant AAV Produce Chemically and Functionally Distinct Vectors.

Different approaches are used in the production of recombinant adeno-associated virus (rAAV). The two leading approaches are transiently transfected human HEK293 cells and live baculovirus infection of Spodoptera frugiperda (Sf9) insect cells. Unexplained differences in vector performance have been seen clinically and preclinically. Thus, we performed a controlled comparative production analysis varying only the host cell species but maintaining all other parameters. We characterized differences with multiple analytical approaches: proteomic profiling by mass spectrometry, isoelectric focusing, cryo-EM (transmission electron cryomicroscopy), denaturation assays, genomic and epigenomic sequencing of packaged genomes, human cytokine profiling, and functional transduction assessments in vitro and in vivo, including in humanized liver mice. Using these approaches, we have made two major discoveries: (1) rAAV capsids have post-translational modifications (PTMs), including glycosylation, acetylation, phosphorylation, and methylation, and these differ between platforms; and (2) rAAV genomes are methylated during production, and these are also differentially deposited between platforms. Our data show that host cell protein impurities differ between platforms and can have their own PTMs, including potentially immunogenic N-linked glycans. Human-produced rAAVs are more potent than baculovirus-Sf9 vectors in various cell types in vitro (p < 0.05-0.0001), in various mouse tissues in vivo (p < 0.03-0.0001), and in human liver in vivo (p < 0.005). These differences may have clinical implications for rAAV receptor binding, trafficking, expression kinetics, expression durability, vector immunogenicity, as well as cost considerations.

Functional Genomic Screening Independently Identifies CUL3 as a Mediator of Vemurafenib Resistance via Src-Rac1 Signaling Axis.

Patients with malignant melanoma have a 5-year survival rate of only 15-20% once the tumor has metastasized to distant tissues. While MAP kinase pathway inhibitors (MAPKi) are initially effective for the majority of patients with melanoma harboring BRAFV600E mutation, over 90% of patients relapse within 2 years. Thus, there is a critical need for understanding MAPKi resistance mechanisms. In this manuscript, we performed a forward genetic screen using a whole genome shRNA library to identify negative regulators of vemurafenib resistance. We identified loss of NF1 and CUL3 as drivers of vemurafenib resistance. NF1 is a known driver of vemurafenib resistance in melanoma through its action as a negative regulator of RAS. However, the mechanism by which CUL3, a key protein in E3 ubiquitin ligase complexes, is involved in vemurafenib resistance was unknown. We found that loss of CUL3 was associated with an increase in RAC1 activity and MEKS298 phosphorylation. However, the addition of the Src family inhibitor saracatinib prevented resistance to vemurafenib in CUL3KD cells and reversed RAC1 activation. This finding suggests that inhibition of the Src family suppresses MAPKi resistance in CUL3KD cells by inactivation of RAC1. Our results also indicated that the loss of CUL3 does not promote the activation of RAC1 through stabilization, suggesting that CUL3 is involved in the stability of upstream regulators of RAC1. Collectively, our study identifies the loss of CUL3 as a driver of MAPKi resistance through activation of RAC1 and demonstrates that inhibition of the Src family can suppress the MAPKi resistance phenotype in CUL3KD cells by inactivating RAC1 protein.

The Positive Effects of Accreditation on Graduate Medical Education Programs in Singapore.

BACKGROUND: There is worldwide interest in assessing the impact of accreditation systems to quantify their benefits to medical education and, through this, health care at the local and global levels. OBJECTIVE: We analyzed ACGME-I Resident Survey data from Singapore for 2011-2018 to assess the impact of accreditation on residents' evaluations of their programs. METHODS: We focused on 7 questions from the annual Resident Survey, which would be affected by accreditation compliance, along with a single global rating of respondents' overall perception of their program. We assessed for differences among specialty groupings (medical, surgical, and hospital-based) and Singapore's 3 health care systems. Repeated measures analysis of variance procedures was used to assess trends across time for the combined 8 items and each individual item. RESULTS: Analysis of the combined items showed significant improvement over the 7 years Singaporean programs had accreditation. There were no effects for specialty type or sponsoring institution. Analyses of individual questions showed 6 of 8 were significant for improvement. For the individual question related to duty hour compliance, there was a significant interaction between time and specialty, suggesting medical specialties showed greater improvement across time compared to surgical and hospital-based specialties. CONCLUSIONS: Implementation of accreditation in Singapore provided educational and clinical learning environment infrastructure not present prior to 2010, with the benefits of this reflected in residents' perceptions of their learning environment. Future assessments of the effects of accreditation might add stakeholder interviews to more fully describe its value and impact.

Relationships Between the ACGME Resident and Faculty Surveys and Program Pass Rates on the ABIM Internal Medicine Certification Examination.

PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) has surveyed residents since 2003, and faculty since 2012. Surveys are designed to assess program functioning and specify areas for improvement. The purpose of this study was to assess the association of the ACGME's resident and faculty surveys with residency-program-specific performance on the American Board of Internal Medicine (ABIM) certification exam. METHOD: Data were available from residents and faculty in 375 U.S. ACGME-accredited internal medicine programs from the 2012-2013, 2013-2014, and 2014-2015 academic years. Analysis of variance and correlations were used to examine the relationship between noncompliance with ACGME program requirements as assessed by the resident and faculty surveys, and ABIM program pass rates. RESULTS: Noncompliance reported on the resident and faculty surveys was highest for programs not meeting the ACGME program requirement of an 80% pass rate on the ABIM certification examination. This relationship was significant for overall noncompliance, both within the resident (P < .001) and faculty (P < .05) surveys, for many areas within the two surveys (correlations ranged between -.07 and -.25, and P values ranged between .20 and < .001), and for the highest levels of noncompliance across areas of the resident (P < .001) and faculty (P < .04) surveys. CONCLUSIONS: ACGME resident and faculty surveys were significantly associated with ABIM program pass rates, supporting the importance of these surveys within the ACGME's Next Accreditation System.

The Potential for Proactive Housing Inspections to Inform Public Health Interventions.

Municipal housing inspection data can inform planning, targeting, and evaluating interventions aimed at reducing housing hazards (lead paint, mold, pests, etc) that may affect residents' health. However, the potential of these data to inform public health initiatives is underexplored. We determined whether home health hazards identified by city inspectors during proactive inspections of single-family private rental housing are predicted by housing age, assessed value, or location in one of 26 geographic "inspector areas" in Rochester, New York. A comparison of linear mixed models, using housing inspector area as a random effect and assessment and construction year as fixed effects, shows that while a large proportion of variation (64%) in violations is due to housing stock, inspectors provide significant additional information about the presence of potential health hazards, particularly in the highest-risk housing stock. This suggests that inspector-generated housing hazard data may be valuable in designing public health interventions.

Risk factors for carbapenem-nonsusceptible Pseudomonas aeruginosa: Case-control study.

The objective of this case case-control study was to identify risk factors for carbapenem-nonsusceptible Pseudomonas aeruginosa in adult acute care hospitalized patient at 2 large academic medical centers. Risk factors were evaluated using logistic regression within a generalized estimating equations framework to account for clustering of patients within study site. Of 1161 total isolates, 271 (23.3%) were carbapenem-nonsusceptible of which respiratory was the most common source (54.3%). In the multivariable model, intra-abdominal (P < 0.0001) and respiratory (P = 0.0014) sources were associated with a higher odds for carbapenem nonsusceptibility when compared to urine source. Prior positive culture (P < 0.0001), use of an antipseudomonal carbapenem in the prior 30 days (P < 0.0001) and culture collection in the intensive care unit (P < 0.0001) were also associated with increased odds for carbapenem-nonsusceptibility. Further studies to validate these findings are warranted.

Lentiviral Vectors Pseudotyped with Filoviral Glycoproteins.

Pseudotyping lentivirus-based vectors is a strategy used to study conferred vector tropism and mechanisms of envelope glycoprotein function. Lentiviruses and filoviruses both assemble at the plasma membrane and have homotrimeric structural envelope glycoproteins that mediate both receptor binding and fusion. Such similarities help foster efficient pseudotyping. Importantly, filovirus glycoprotein pseudotyping of lentiviral vectors allows investigators to study virus entry at substantially less restrictive levels of biosafety containment than that required for wild-type filovirus work (biosafety level-2 vs. biosafety level-4, respectively). Standard lentiviral vector production involves transient transfection of viral component expression plasmids into producer cells, supernatant collection, and centrifuge concentration. Because the envelope glycoprotein expression plasmid is provided in trans, wild type or variant filoviral glycoproteins from marburgvirus or ebolavirus species may be used for pseudotyping and compared side-by-side. In this chapter we discuss the manufacture of pseudotyped lentiviral vector with an emphasis on small-scale laboratory grade production.

Patterns of Change in ACGME-Accredited Residency Programs and Positions: Implication for the Adequacy of GME Positions and Supply of Physicians in the United States.

BACKGROUND: Recent studies suggest that the supply of primary care physicians and generalist physicians in other specialties may be inadequate to meet the needs of the US population. Data on the numbers and types of physicians-in-training, such as those collected by the Accreditation Council for Graduate Medical Education (ACGME), can be used to help understand variables affecting this supply. OBJECTIVE: We assessed trends in the number and type of medical school graduates entering accredited residencies, and the impact those trends could have on the future physician workforce. METHODS: Since 2004, the ACGME has published annually its data on accredited institutions, programs, and residents to help the graduate medical education community understand major trends in residency education, and to help guide graduate medical education policy. We present key results and trends for the period between academic years 2003-2004 and 2012-2013. RESULTS: The data show that increases in trainees in accredited programs are not uniform across specialties, or the types of medical school from which trainees graduated. In the past 10 years, the growth in residents entering training that culminates in initial board certification ("pipeline" specialties) was 13.0%, the number of trainees entering subspecialty education increased 39.9%. In the past 5 years, there has been a 25.8% increase in the number of osteopathic physicians entering allopathic programs. CONCLUSIONS: These trends portend challenges in absorbing the increasing numbers of allopathic and osteopathic graduates, and US international graduates in accredited programs. The increasing trend in subspecialization appears at odds with the current understanding of the need for generalist physicians.

Effects of potential federal funding cuts on graduate medical education: results of a survey of designated institutional officials.

BACKGROUND: Proposed reductions in federal funding for physician education may affect the United States' ability to produce the number of physicians needed to provide care. OBJECTIVE: Using a survey similar to that used by the ACGME in 2011, we assessed designated institutional officials' (DIOs) perceptions of the impact of potential GME funding reductions. METHOD: In August 2013, we sent a survey link to all DIOs of ACGME-accredited institutions (N  =  678). A 9-item survey asked how future federal funding would affect the number of residency programs in their institutions under 4 different funding scenarios: stable funding, and reductions of 10%, 33%, and 50%. We also asked about changes in the number of residency positions during the last 2 years. RESULTS: The response rate was 47.9% (325 of 678 DIOs); respondents represent 58.9% of accredited institutions with more than 1 program. Most respondents reported no change or an increase under the stable funding scenario. Under a 33% funding reduction, an estimated 17 379 (14.8% of all current) positions would be lost, and a 50% reduction would result in a loss of 33 562 positions (28.6%). Primary care specialties (eg, family medicine, internal medicine) would be most affected under the greatest funding reductions. CONCLUSIONS: The findings of the 2013 survey are consistent with 2011 data, with DIOs projecting significant reductions in programs and positions under more severe budget cuts. DIO comments highlighted reduced optimism (compared to data obtained in 2011) about the effect of funding cuts and concerns about the impact of reductions on patient care and health care personnel at teaching institutions.

The Impact of ACGME Work-Hour Reforms on the Operative Experience of Fellows in Surgical Subspecialty Programs.

BACKGROUND: In July 2003, the Accreditation Council for Graduate Medical Education (ACGME) introduced a set of regulations that mandated a reduction in the number of hours that medical residents can work. These requirements have generated controversy among medical educators, with some expressing concern that reducing resident hours may limit clinical exposure and competency, particularly in surgical specialties. OBJECTIVE: This study examines the impact of duty hour restrictions on resident operative experience in residents in 2 surgical subspecialties since the implementation of the ACGME duty hour limits. METHOD: We examined operative log data for vascular surgery and pediatric surgery, using the academic year immediately preceding the duty hour restrictions, 2002 to 2003, as a baseline for comparison to subsequent academic years through 2006 to 2007 for vascular surgery and 2007 to 2008 for pediatric surgery. RESULTS: Graduating fellows in pediatric surgery showed no change in their total operative volume following duty hour restrictions. The pediatric-defined category of neonate procedures showed an increase following duty hour restrictions. Graduating fellows in vascular surgery showed an increase in total major procedures as surgeon. The vascular-defined categories of endovascular-diagnostic, endovascular-therapeutic, and endovascular-graft procedures also increased. CONCLUSIONS: The reduction of duty hours has not resulted in a decrease in operative volume as some have predicted. Operative volume in pediatric surgery remained mainly unchanged, whereas operative volume in vascular surgery increased. We explore possible explanations for the observed findings.

Resident operative experience in general surgery, plastic surgery, and urology 5 years after implementation of the ACGME duty hour policy.

OBJECTIVE: Resident duty hour restrictions were implemented in 2002-2003. This study examines changes in resident surgical experience since these restrictions were put into place. METHOD: Operative log data for 3 specialties were examined: general surgery, urology, and plastic surgery. The academic year immediately preceding the duty hour restrictions, 2002-2003, was used as a baseline for comparison to subsequent academic years. Operative log data for graduating residents through 2007-2008 were the primary focus of the analysis. Examination of associated variables that may moderate the relationship between fewer duty hours and surgical volume was also included. RESULTS: Plastic surgery showed no changes in operative volume following duty hour restrictions. Operative volume increased in urology programs. General surgery showed a decrease in volume in some operative categories but an increase in others. Specifically the procedures in vascular, plastic, and thoracic areas showed a consistent decrease. There was no increase in the percentage of programs' graduates falling below minimum requirements. Procedures in pancreas, endocrine, and laparoscopic areas demonstrated an increase in volume. Graduates in larger surgical programs performed fewer procedures than graduates in smaller programs; this was not the case for urology or plastic surgery programs. CONCLUSIONS: The reduction of duty hours has not resulted in an across the board decrease in operative volume. Factors other than duty hour reforms may be responsible for some of the observed findings.

A mouse knockout library for secreted and transmembrane proteins.

Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.

Residents' perspectives on the learning environment: data from the Accreditation Council for Graduate Medical Education resident survey.

PURPOSE: Residents' assessment of their learning environment is an important element of residency accreditation and a strong predictor of resident satisfaction. The authors examined the reliability and validity of a resident/fellow survey and explored the relationship between reported duty hours noncompliance and residents' perceptions of other aspects of their learning environments. METHOD: The Accreditation Council for Graduate Medical Education (ACGME) administered a 29-item Web-based survey in 2007 and 2008 to 91,073 residents in 5,610 programs. Aggregate data from the survey comprised indicators of substantial compliance or noncompliance. The authors examined relationships among duty hours and aspects of the educational environment, as well as the relationship of the survey results to citations from accreditation reviews. RESULTS: The survey demonstrated a high degree of internal reliability (Cronbach alpha, 0.84). Common factor analysis revealed two factors, educational environment and resident duty hours (eigenvalues of 5.49 and 2.42, respectively). Programs having resident-identified duty hours issues were more likely than those without such issues to have received duty hours citations from residency review committees (odds ratio: 2.04; 95% CI: 1.03, 3.05). CONCLUSIONS: The ACGME Resident/Fellow Survey is a reliable, valid, and useful tool for evaluating residency programs. There are strong relationships between duty hours noncompliance and noncompliance in other aspects of the program environment.

Tracking Residents Through Multiple Residency Programs: A Different Approach for Measuring Residents' Rates of Continuing Graduate Medical Education in ACGME-Accredited Programs.

BACKGROUND: Increased focus on the number and type of physicians delivering health care in the United States necessitates a better understanding of changes in graduate medical education (GME). Data collected by the Accreditation Council for Graduate Medical Education (ACGME) allow longitudinal tracking of residents, revealing the number and type of residents who continue GME following completion of an initial residency. We examined trends in the percent of graduates pursuing additional clinical education following graduation from ACGME-accredited pipeline specialty programs (specialties leading to initial board certification). METHODS: Using data collected annually by the ACGME, we tracked residents graduating from ACGME-accredited pipeline specialty programs between academic year (AY) 2002-2003 and AY 2006-2007 and those pursuing additional ACGME-accredited training within 2 years. We examined changes in the number of graduates and the percent of graduates continuing GME by specialty, by type of medical school, and overall. RESULTS: The number of pipeline specialty graduates increased by 1171 (5.3%) between AY 2002-2003 and AY 2006-2007. During the same period, the number of graduates pursuing additional GME increased by 1059 (16.7%). The overall rate of continuing GME increased each year, from 28.5% (6331/22229) in AY 2002-2003 to 31.6% (7390/23400) in AY 2006-2007. Rates differed by specialty and for US medical school graduates (26.4% [3896/14752] in AY 2002-2003 to 31.6% [4718/14941] in AY 2006-2007) versus international medical graduates (35.2% [2118/6023] to 33.8% [2246/6647]). CONCLUSION: The number of graduates and the rate of continuing GME increased from AY 2002-2003 to AY 2006-2007. Our findings show a recent increase in the rate of continued training for US medical school graduates compared to international medical graduates. Our results differ from previously reported rates of subspecialization in the literature. Tracking individual residents through residency and fellowship programs provides a better understanding of residents' pathways to practice.

Residency Programs' Evaluations of the Competencies: Data Provided to the ACGME About Types of Assessments Used by Programs.

BACKGROUND: In 1999, the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project began to focus on resident performance in the 6 competencies of patient care, medical knowledge, professionalism, practice-based learning and improvement, interpersonal communication skills, and professionalism. Beginning in 2007, the ACGME began collecting information on how programs assess these competencies. This report provides information on the nature and extent of those assessments. METHODS: Using data collected by the ACGME for site visits, we use descriptive statistics and percentages to describe the number and type of methods and assessors accredited programs (n  =  4417) report using to assess the competencies. Observed differences among specialties, methodologies, and assessors are tested with analysis of variance procedures. RESULTS: Almost all (>97%) of programs report assessing all of the competencies and using multiple methods and multiple assessors. Similar assessment methods and evaluator types were consistently used across the 6 competencies. However, there were some differences in the use of patient and family as assessors: Primary care and ambulatory specialties used these to a greater extent than other specialties. CONCLUSION: Residency programs are emphasizing the competencies in their evaluation of residents. Understanding the scope of evaluation methodologies that programs use in resident assessment is important for both the profession and the public, so that together we may monitor continuing improvement in US graduate medical education.