Implementation of a "Health Equity Rounds" Curriculum in a Military Internal Medicine Residency Program: A Pilot Study.

INTRODUCTION: Health disparities in the Military Health System (MHS) have been consistently documented despite the system ensuring equal access to care for its beneficiaries. Research has shown that social, economic, and political factors (i.e., Social Determinants of Health) and health care-specific factors like provider bias and systemic discrimination are key drivers of health disparities in the general population. Medical education focused on introducing these concepts using case-based learning has led to effective learning of health equity terminology. However, a significant gap exists in identifying optimal teaching approaches to develop skills to recognize these factors in actual clinical cases. This begs the million-dollar question: can case-based learning help trainees acquire the skills needed to identify the main factors contributing to health disparities in the MHS? MATERIALS AND METHODS: A longitudinal case-based curriculum was developed in which clinical cases from the Internal Medicine Wards, Medical Intensive Care Unit, or General Internal Medicine Clinic at the National Capital Consortium were solicited from trainees and analyzed for evidence of health care provider bias and systemic forms of discrimination using small groups. The National Capital Consortium Internal Medicine Residency Program implemented this pilot study in November 2021. A retrospective pretest-posttest survey assessing trainee reactions to the curriculum and changes in self-reported confidence in skills was used for curriculum assessment. Survey data were analyzed using a paired samples t-test. RESULTS: The survey was administered during the last session of the 2022-2023 academic year, with 14 of the 23 available trainees completing it: a 60.8% response rate. Overall, 93% reported that the cases selected that academic year were engaging; the skills they were taught were practice-changing, and the educational value of the curriculum was good, very good, or excellent. Confidence ratings, assessed via a 5-point Likert Scale, demonstrated a statistically significant increase in self-reported confidence in the following skill domains with large effect sizes: identification of bias and systemic discrimination in clinical cases-change in mean: 1.07 (Pre: 3.29, Post: 4.36), P < .001, g = 1.38; recognizing and mitigating personal biases-change in mean: 0.71 (Pre: 3.50, Post: 4.21), P <.001, g = 1.10; participating in a discussion about health care provider bias and systemic discrimination-change in mean: 0.79 (Pre: 3.57, Post: 4.36), P = .001, g = 1.06; and leading a discussion about bias and systemic discrimination-change in mean: 1.00 (Pre: 2.93, Post: 3.93), P = .002, g = 0.98. CONCLUSIONS: As the need to address health disparities in the United States becomes more pressing, so does the need for military physicians to recognize the drivers of these disparities within the MHS. Results from this pilot study of Health Equity Rounds suggest that case-based learning may be an optimal teaching approach to improve the skills of military Internal Medicine trainees in identifying and recognizing the impact of health care provider bias and systemic discrimination on clinical cases from the MHS.

Delphi survey of intercontinental experts to identify areas of consensus on the use of indocyanine green angiography for tissue perfusion assessment during plastic and reconstructive surgery.

BACKGROUND: In recent years, indocyanine green angiography (ICG-A) has been used increasingly to assist tissue perfusion assessments during plastic and reconstructive surgery procedures, but no guidelines exist regarding its use. We sought to identify areas of consensus and non-consensus among international experts on the use of ICG-A for tissue-perfusion assessments during plastic and reconstructive surgery. METHODS: A two-round, online Delphi survey was conducted of 22 international experts from four continents asking them to vote on 79 statements divided into five modules: module 1 = patient preparation and contraindications (n = 11 statements); module 2 = ICG administration and camera settings (n = 17); module 3 = other factors impacting perfusion assessments (n = 10); module 4 = specific indications, including trauma debridement (n = 9), mastectomy skin flaps (n = 6), and free flap reconstruction (n = 8); and module 5 = general advantages and disadvantages, training, insurance coverage issues, and future directions (n = 18). Consensus was defined as ≥70% inter-voter agreement. RESULTS: Consensus was reached on 73/79 statements, including the overall value, advantages, and limitations of ICG-A in numerous surgical settings; also, on the dose (0.05 mg/kg) and timing of ICG administration (∼20-60 seconds preassessment) and best camera angle (61-90o) and target-to-tissue distance (20-30 cm). However, consensus also was reached that camera angle and distance can vary, depending on the make of camera, and that further research is necessary to technically optimize this imaging tool. The experts also agreed that ambient light, patient body temperature, and vasopressor use impact perfusion assessments. CONCLUSION: ICG-A aids perfusion assessments during plastic and reconstructive surgery and should no longer be considered experimental. It has become an important surgical tool.

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.

Assessment Framework for Recognizing Clinical Deterioration in Patients With ACS Undergoing PCI.

TOPIC: Patients with acute coronary syndrome undergoing primary percutaneous coronary intervention are at risk of clinical deterioration that results in similar general signs and symptoms regardless of its cause. However, specific causes and forms of clinical deterioration are associated with key differences in assessment findings. Focused clinical assessments using a modified primary survey enable nurses to rapidly identify the cause and form of clinical deterioration, facilitating targeted treatment. CLINICAL RELEVANCE: Clinical deterioration during percutaneous coronary intervention is associated with increased mortality and morbidity. Previous studies identified nursing inconsistencies when recognizing clinical deterioration, with inconsistent collection of cues and prioritization of cues related to cardiac performance over more sensitive indicators of clinical deterioration. PURPOSE OF PAPER: To describe a framework to help nurses optimize physiological cue collection to improve recognition of clinical deterioration during periprocedural care of patients undergoing percutaneous coronary intervention for unstable acute coronary syndrome. CONTENT COVERED: Literature analysis revealed 7 forms of clinical deterioration in patients undergoing percutaneous coronary intervention: coronary artery occlusion, stroke, ventricular rupture, valvular insufficiency, lethal cardiac arrhythmias, access-site and non-access-site bleeding, and anaphylaxis. Evidence for the pathophysiology, incidence, severity, and clinical features of each form of clinical deterioration is identified. A framework is proposed to help nurses conduct highly focused patient assessments, enabling prompt recognition of and response to the specific forms of clinical deterioration that occur in patients undergoing percutaneous coronary intervention.

Time to Surgery for Unstable Thoracolumbar Fractures in Latin America-A Multicentric Study.

OBJECTIVE: We sought to identify delays for surgery to stabilize unstable thoracolumbar fractures and the main reasons for them across Latin America. METHODS: We reviewed the charts of 547 patients with type B or C thoracolumbar fractures from 21 spine centers across 9 Latin American countries. Data were collected on demographics, mechanism of trauma, time between hospital arrival and surgery, type of hospital (public vs. private), fracture classification, spinal level of injury, neurologic status (American Spinal Injury Association impairment scale), number of levels instrumented, and reason for delay between hospital arrival and surgical treatment. RESULTS: The sample included 403 men (73.6%) and 144 women (26.3%), with a mean age of 40.6 years. The main mechanism of trauma was falls (44.4%), followed by car accidents (24.5%). The most frequent pattern of injury was B2 injuries (46.6%), and the most affected level was T12-L1 (42.2%). Neurologic status at admission was 60.5% intact and 22.9% American Spinal Injury Association impairment scale A. The time from admission to surgery was >72 hours in over half the patients and over a week in >25% of them. The most commonly reported reasons for surgical delay were clinical instability (22.9%), lack of operating room availability (22.7%), and lack of hardware for spinal instrumentation (e.g., screws/rods) (18.8%). CONCLUSIONS: Timing for surgery in this sample of unstable fractures was over 72 hours in more than half of the sample and longer than a week in about a quarter. The main reasons for this delay were clinical instability and lack of economic resources. There is an apparent need for increased funding for the treatment of spinal trauma patients in Latin America.

Functional assessment of human enhancer activities using whole-genome STARR-sequencing.

BACKGROUND: Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome. RESULTS:  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. CONCLUSION: WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation.

Assessment of copy number status of chromosomes 6 and 11 by FISH provides independent prognostic information in primary melanoma.

Melanoma incidence has been rising steadily for decades, whereas mortality rates have remained flat. This type of discordant pattern between incidence and mortality has been linked to diagnostic drift in cancers of the thyroid, breast, and prostate. Ancillary tests, such as fluorescent in situ hybridization (FISH), are now being used to help differentiate melanomas from melanocytic nevi. Multicolor FISH has been shown to distinguish between these 2 with 86.7% sensitivity and 95.4% specificity. To assess the ability of FISH to differentiate melanomas with metastatic or lethal potential from those with an indolent disease course, we performed FISH with probes targeting 6p25, centromere 6, 6q23, and 11q13 on 144 primary melanomas with a minimal tumor thickness of 2 mm and compared the development of metastatic disease and melanoma-specific mortality as well as relapse-free and disease-specific survival between FISH-positive and FISH-negative cases. Of the melanomas, 82% were positive by FISH according to previously defined criteria. The percentage was significantly higher (93%) in cases that developed systemic metastases (n=43) than in patients that did not (77%, n=101). FISH-positive primaries had a significantly increased risk of metastasis or melanoma-related death compared with FISH-negative cases odds ratio 4.11; confidence interval, 1.14-22.7 and odds ratio 7.0, confidence interval 1.03-300.4, respectively. FISH status remained an independent parameter when controlling for known prognostic factors. These data indicate that the group of melanomas diagnosed with routine histopathology that lack aberrations detected by FISH is enriched for melanomas with a more indolent disease course. This suggests that molecular techniques can assist in a more accurate identification of tumors with metastatic potential.

An integrated genomic approach to the assessment and treatment of acute myeloid leukemia.

Traditionally, new scientific advances have been applied quickly to the leukemias based on the ease with which relatively pure samples of malignant cells can be obtained. Currently, our arsenal of approaches used to characterize an individual's acute myeloid leukemia (AML) combines hematopathologic evaluation, flow cytometry, cytogenetic analysis, and molecular studies focused on a few key genes. The advent of high-throughput methods capable of full-genome evaluation presents new options for a revolutionary change in the way we diagnose, characterize, and treat AML. Next-generation DNA sequencing techniques allow full sequencing of a cancer genome or transcriptome, with the hope that this will be affordable for routine clinical care within the decade. Microarray-based testing will define gene and miRNA expression, DNA methylation patterns, chromosomal imbalances, and predisposition to disease and chemosensitivity. The vision for the future entails an integrated and automated approach to these analyses, bringing the possibility of formulating an individualized treatment plan within days of a patient's initial presentation. With these expectations comes the hope that such an approach will lead to decreased toxicities and prolonged survival for patients.

Spine adverse events severity system: content validation and interobserver reliability assessment.

STUDY DESIGN: A prospective validation study, preliminary single-center report. OBJECTIVE: The purpose of this study was to assess the content validity and interobserver reliability of a simple severity classification system for adverse events (AEs) associated with spinal surgery. SUMMARY OF BACKGROUND DATA: In the surgical literature what is defined as an AE, the severity of an AE, and the reporting of AEs are variable. Consequently, valid comparison of AEs within or among specialties or surgical centers for the same or different procedures is often impossible. METHODS: Since 2002, a Spine Adverse Events Severity system (SAVES) has been locally developed and prospectively used. AEs were graded as I (requires none/minimal treatment, minimal effect [<1-2 days] on length of stay [LOS]), II (requires treatment and/or increases LOS [3-7 days] with no long-term sequelae), III (requires treatment and/or increased LOS [>7 days] with long-term sequelae [>6 months]), and IV (death). Content validity of the grading system was assessed using the hospital chart abstraction (current defacto gold standard) compared with the SAVES from 200 randomly selected patients. Interobserver reliability was assessed in consecutive operative cases for 1 spine surgeon during a 1-year period (2006) using 3 raters (staff surgeon, fellow, and/or resident). RESULTS: The prospectively administered form reported a higher number of surgical AEs (n = 43 vs. n = 30) and a similar number of medical AEs (n = 31 vs. n = 27). Compared with the chart, the AE form displayed substantial agreement for number (70%; weighted Kappa [wK] = 0.60) and type (75%; wK = 0.67) of AE. The interobserver reliability was near perfect (kappa = 0.8) for the actual grade of AE and moderate (kappa = 0.5) for the criteria behind the grading (i.e., clinical effect of the AE or the effect of the AE on LOS or both). CONCLUSION: The result of this study demonstrates improved capture of surgical AEs using SAVES. Excellent interobserver reliability between surgeons at different level of training was demonstrated with minimal education or training regarding the use of SAVES.

Fibromyalgia syndrome in an Amish community: a controlled study to determine disease and symptom prevalence.

OBJECTIVES: To estimate the point prevalence of fibromyalgia syndrome (FM) in Amish adults and to compare the prevalence of chronic pain, chronic widespread pain, FM, chronic fatigue, and debilitating fatigue in the Amish versus non-Amish rural and urban controls. The a priori assumption was that, if litigation and/or compensation availability have major effects on FM prevalence, then FM prevalence in the Amish should approach zero. METHODS: We surveyed 242 Amish adults in a small rural community southeast of London, Ontario, Canada. Individuals were screened using a validated screening instrument. Those reporting chronic, widespread pain were examined for FM using published classification criteria. Amish results were compared to results collected in a random telephone survey of 492 non-Amish adults living in rural Southwestern Ontario and 3395 non-Amish adults previously surveyed in London. RESULTS: Pain lasting at least one week in the preceding 3 months was reported by 34.3% of the Amish; pain in the upper extremities by 25.4%, in the lower extremities by 22.5%, and in the trunk by 28.1%. Twenty-six (15 women, 11 men) reported chronic, widespread pain. Eleven FM cases were confirmed among women (age adjusted point prevalence, p = 10.4%) and 2 among men (p = 3.7%) for an overall age and sex adjusted prevalence of 7.3% (95% CI 5.3, 9.7); this was both statistically greater than zero (p < 0.0001) and greater than in either control population (both p < 0.05). CONCLUSION: FM is relatively common among the Amish.

Genotyping African haplotypes in ATM using a co-spotted single-base extension assay.

Human genetic analysis, including population genetic studies, increasingly calls for cost-effective, high-throughput methods for the rapid screening of single nucleotide polymorphisms (SNPs) across many individuals. The modified single-base extension assay described here (arrayed SBE) is a highly accurate and robust method for SNP genotyping that can deliver genotypes at 3.5 cents each, following PCR. Specifically, amino-modified probe/target pairs were prehybridized, then co-spotted in a microarray format prior to enzymatic addition of allele-specific nucleotides. Probe/target identity was determined solely by its physical location on the array rather than by hybridization to a complementary target, resulting in a call rate of 99-100%. These innovations result in an inexpensive, accurate assay with exceptional signal-to-noise ratios, depending on the glass surface employed. Comparison of glass slides from three different manufacturers indicated that aldehyde-based Zyomyx slides provided superior performance for this assay. Arrayed SBE was applied to study the geographic distribution of three African-specific haplotypes in the human ATM gene. Four selectively neutral markers, which define the haplotypes H5, H6, and H7, were screened in a total of 415 individuals. Region-specific haplotype frequencies were consistent with patterns of human migration across and outside of Africa, suggesting a possible haplotype origin in East Africa. Arrayed SBE was a robust tool for this analysis that could be applied to any situation requiring the genotyping of a few SNPs in many individuals.