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BACKGROUND: Data collected via wearables may complement in-clinic assessments to monitor subclinical heart failure (HF). OBJECTIVES: Evaluate the association of sensor-based digital walking measures with HF stage and characterize their correlation with in-clinic measures of physical performance, cardiac function and participant reported outcomes (PROs) in individuals with early HF. METHODS: The analyzable cohort included participants from the Project Baseline Health Study (PBHS) with HF stage 0, A, or B, or adaptive remodeling phenotype (without risk factors but with mild echocardiographic change, termed RF-/ECHO+) (based on available first-visit in-clinic test and echocardiogram results) and with sufficient sensor data. We computed daily values per participant for 18 digital walking measures, comparing HF subgroups vs stage 0 using multinomial logistic regression and characterizing associations with in-clinic measures and PROs with Spearman's correlation coefficients, adjusting all analyses for confounders. RESULTS: In the analyzable cohort (N=1265; 50.6% of the PBHS cohort), one standard deviation decreases in 17/18 walking measures were associated with greater likelihood for stage-B HF (multivariable-adjusted odds ratios [ORs] vs stage 0 ranging from 1.18-2.10), or A (ORs vs stage 0, 1.07-1.45), and lower likelihood for RF-/ECHO+ (ORs vs stage 0, 0.80-0.93). Peak 30-minute pace demonstrated the strongest associations with stage B (OR vs stage 0=2.10; 95% CI:1.74-2.53) and A (OR vs stage 0=1.43; 95% CI:1.23-1.66). Decreases in 13/18 measures were associated with greater likelihood for stage-B HF vs stage A. Strength of correlation with physical performance tests, echocardiographic cardiac-remodeling and dysfunction indices and PROs was greatest in stage B, then A, and lowest for 0. CONCLUSIONS: Digital measures of walking captured by wearable sensors could complement clinic-based testing to identify and monitor pre-symptomatic HF.
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It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant-or target-populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose. However, generalizability and transportability studies present challenges, particularly around the strength of their conclusions. We review and summarize state-of-the-art methods for translating trial findings to target populations. We additionally provide a novel step-by-step guide to address these challenges, illustrating principles through a published case study. When conducted with rigor, generalizability and transportability studies can play an integral role in regulatory decisions by providing key real-world evidence.
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Proyectos de Investigación , Humanos , CausalidadRESUMEN
BACKGROUND: Hirschsprung's disease, or congenital aganglionosis, is a developmental disorder of the enteric nervous system and is the most common cause of intestinal obstruction in neonates and infants. The disease has more than 80% heritability, including significant associations with rare and common sequence variants in genes related to the enteric nervous system, as well as with monogenic and chromosomal syndromes. METHODS: We genotyped and exome-sequenced samples from 190 patients with Hirschsprung's disease to quantify the genetic burden in patients with this condition. DNA sequence variants, large copy-number variants, and karyotype variants in probands were considered to be pathogenic when they were significantly associated with Hirschsprung's disease or another neurodevelopmental disorder. Novel genes were confirmed by functional studies in the mouse and human embryonic gut and in zebrafish embryos. RESULTS: The presence of five or more variants in four noncoding elements defined a widespread risk of Hirschsprung's disease (48.4% of patients and 17.1% of controls; odds ratio, 4.54; 95% confidence interval [CI], 3.19 to 6.46). Rare coding variants in 24 genes that play roles in enteric neural-crest cell fate, 7 of which were novel, were also common (34.7% of patients and 5.0% of controls) and conferred a much greater risk than noncoding variants (odds ratio, 10.02; 95% CI, 6.45 to 15.58). Large copy-number variants, which were present in fewer patients (11.4%, as compared with 0.2% of controls), conferred the highest risk (odds ratio, 63.07; 95% CI, 36.75 to 108.25). At least one identifiable genetic risk factor was found in 72.1% of the patients, and at least 48.4% of patients had a structural or regulatory deficiency in the gene encoding receptor tyrosine kinase (RET). For individual patients, the estimated risk of Hirschsprung's disease ranged from 5.33 cases per 100,000 live births (approximately 1 per 18,800) to 8.38 per 1000 live births (approximately 1 per 120). CONCLUSIONS: Among the patients in our study, Hirschsprung's disease arose from common noncoding variants, rare coding variants, and copy-number variants affecting genes involved in enteric neural-crest cell fate that exacerbate the widespread genetic susceptibility associated with RET. For individual patients, the genotype-specific odds ratios varied by a factor of approximately 67, which provides a basis for risk stratification and genetic counseling. (Funded by the National Institutes of Health.).
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Variación Genética , Genotipo , Enfermedad de Hirschsprung/genética , Exoma , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Mutación , Oportunidad Relativa , Penetrancia , Análisis de Secuencia de ADN , Secuenciación del ExomaRESUMEN
PURPOSE: Exome sequencing (ES) is becoming increasingly important for diagnosing rare genetic disorders. Patients and clinicians face several barriers when attempting to obtain ES. This study is aimed to describe factors associated with a longer time interval between provider recommendation of testing and sample collection for ES. METHODS: A retrospective chart review was conducted for insurance-authorized, completed pediatric ES in which initial requests were reviewed by Stanford's Genetic Testing Optimization Service between November 2018 and December 2019. Regression analysis was used to determine the association between the geocoded median household income and 3 different time point intervals defined as time to test, insurance decision, and scheduling/consent. RESULTS: Of the 281 charts reviewed, 115 cases were included in the final cohort. The average time from provider preauthorization request to sample collection took 104.4 days, and income was negatively correlated with the length of the insurance decision interval. CONCLUSION: Pediatric patients undergo a lengthy, uncertain process when attempting to obtain ES, some of which is associated with income. More research and clinician interventions are required to clarify specific socioeconomic factors that influence the ability to obtain timely ES and develop optimal protocols.
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Exoma , Pruebas Genéticas , Niño , Exoma/genética , Humanos , Estudios Retrospectivos , Factores Socioeconómicos , Secuenciación del Exoma/métodosRESUMEN
OBJECTIVES: The objective of this study is to investigate the change in functional status in infants, children, and adolescents undergoing congenital heart surgery using the Functional Status Scale. DESIGN: A single-center retrospective study. SETTING: A 26-bed cardiac ICU in a free-standing university-affiliated tertiary children's hospital. PATIENTS: All patients 0-18 years who underwent congenital heart surgery from January 1, 2014, to December 31, 2017. INTERVENTIONS: None. MEASUREMENTS AND MIN RESULTS: The primary outcome variable was change in Functional Status Scale scores from admission to discharge. Additionally, two binary outcomes were derived from the primary outcome: new morbidity (change in Functional Status Scale ≥ 3) and unfavorable functional outcome (change in Functional Status Scale ≥ 5); their association with risk factors was assessed using modified Poisson regression. Out of 1,398 eligible surgical encounters, 65 (4.6%) and 15 (1.0%) had evidence of new morbidity and unfavorable functional outcomes, respectively. Higher Surgeons Society of Thoracic and the European Association for Cardio-Thoracic Surgery score, single-ventricle physiology, and longer cardiopulmonary bypass time were associated with new morbidity. Longer hospital length of stay was associated with both new morbidity and unfavorable outcome. CONCLUSIONS: This study demonstrates the novel application of the Functional Status Scale on patients undergoing congenital heart surgery. New morbidity was noted in 4.6%, whereas unfavorable outcome in 1%. There was a small change in the total Functional Status Scale score that was largely attributed to changes in the feeding domain. Higher Society of Thoracic and the European Association for Cardio-Thoracic Surgery score, single-ventricle physiology, and longer cardiopulmonary bypass times were associated with new morbidity, whereas longer hospital length of stay was associated with both new morbidity and unfavorable outcome. Further studies with larger sample size will need to be done to confirm our findings and to better ascertain the utility of Functional Status Scale on this patient population.
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Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Adolescente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Niño , Estado Funcional , Cardiopatías Congénitas/cirugía , Hospitales , Humanos , Lactante , Tiempo de Internación , Estudios RetrospectivosRESUMEN
BACKGROUND: Understanding factors that impact tissue oxygen extraction may guide red blood cell (RBC) transfusion decision making in preterm infants. Our objective was to assess the influence of enteral feeding and anemia on cerebral and mesenteric oxygen saturation (Csat and Msat) and fractional tissue oxygen extraction (cFTOE and mFTOE) over the entire time course of RBC transfusion. STUDY DESIGN AND METHODS: Preterm, very low-birth-weight infants receiving RBC transfusions at a single center were enrolled. Near-infrared spectroscopy sensors measured Csat and Msat levels from an hour before transfusion to 24 hours after. During this period, changes in Csat, Msat, cFTOE, and mFTOE were described, and their association with enteral feeding status and pretransfusion degree of anemia were assessed using generalized estimating equations. RESULTS: RBC transfusion data from 31 preterm infants were included. Infants receiving enteral feeds exhibited lower pretransfusion Msat. Infants with pretransfusion hematocrit greater than 30% exhibited higher pretransfusion Csat and lower pretransfusion cFTOE. Such differences in baseline measurements persisted through 24 hours after transfusion. However, no statistically significant differences in oxygenation measures over time by enteral feeding or anemia status were identified. CONCLUSION: Compared to NPO, enteral feeding was associated with lower Msat; anemia (hematocrit ≤30%) was associated with lower Csat and higher cFTOE. Over the time course of RBC transfusion, trajectories of Csat, Msat, cFTOE and mFTOE did not differ by enteral feeding or anemia status.
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Anemia/terapia , Transfusión de Eritrocitos , Peso al Nacer/fisiología , Nutrición Enteral , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Espectroscopía Infrarroja CortaRESUMEN
OBJECTIVE: To evaluate whether in vitro fertilization (IVF) has an effect on the cardiovascular health of offspring. STUDY DESIGN: This was a cross-sectional pilot study. We performed vascular health assessment for 17 children aged 10-14 years who were conceived via IVF with autologous oocytes at Stanford University. Carotid artery ultrasound evaluated intima-media thickness and stiffness, carotid-femoral pulse wave velocity determined segmental arterial stiffness, and endothelial pulse amplitude testing assessed endothelial function. We compared IVF offspring with control adolescents assessed in the same laboratory, with all comparisons adjusted for age, sex, and race/ethnicity. RESULTS: All participants had normal body mass index and blood pressure. Compared with controls, IVF children had thicker common carotid artery intima-media thickness (0.44 ± 0.03 mm vs 0.38 ± 0.03 mm; P < .01), higher elastic modulus (395.29 ± 185.33 mm Hg vs 242.79 ± 37.69 mm Hg; P = .01), higher ßstiffness (2.65 ± 0.38 vs 2.28 ± 0.23; P < .01), and higher peak velocity (142.29 ± 31.62 cm/s vs 117.71 ± 32.69 cm/s; P = .04). The mean endothelial pulse amplitude testing reactive hyperemia index was not significantly different between IVF and controls. The mean pulse wave velocity was 4.69 ± 0.51 m/s compared with the controls 4.60 ± 0.57 m/s (P = .11), with 8 (47%) having abnormal values. CONCLUSION: In an assessment of endothelial function and arterial properties of children conceived via IVF, we found that children conceived via IVF seem to have evidence of abnormal vascular health. Further studies with larger sample size and long-term follow-up are warranted.
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Enfermedades Cardiovasculares/etiología , Fertilización In Vitro/efectos adversos , Adolescente , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Proyectos Piloto , Análisis de la Onda del Pulso , Factores de Riesgo , Rigidez VascularRESUMEN
Innervation of the gut is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomous defects in enteric neuronal cell differentiation, proliferation, migration, or survival. Rare, high-penetrance coding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET). We used a genome-wide association (220 trios) and replication (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on chromosome 7 within the class 3 Semaphorin gene cluster. Analysis in Ret wild-type and Ret-null mice demonstrates specific expression of Sema3a, Sema3c, and Sema3d in the enteric nervous system (ENS). In zebrafish embryos, sema3 knockdowns show reduction of migratory ENS precursors with complete ablation under conjoint ret loss of function. Seven candidate receptors of Sema3 proteins are also expressed within the mouse ENS and their expression is also lost in the ENS of Ret-null embryos. Sequencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein structure modeling and functional analyses identified five disease-associated alleles with loss-of-function defects in semaphorin dimerization and binding to their cognate neuropilin and plexin receptors. Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis.
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Epistasis Genética/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética , Enfermedad de Hirschsprung/genética , Proteínas Proto-Oncogénicas c-ret/genética , Semaforinas/genética , Animales , Secuencia de Bases , Estudio de Asociación del Genoma Completo , Ratones , Datos de Secuencia Molecular , Semaforinas/deficiencia , Semaforinas/metabolismo , Análisis de Secuencia de ADNRESUMEN
OBJECTIVES: Detection of atrial fibrillation (AF) in post-cryptogenic stroke (CS) or transient ischemic attack (TIA) patients carries important therapeutic implications. METHODS: To risk stratify CS/TIA patients for later development of AF, we conducted a retrospective cohort study using data from 1995 to 2015 in the Stanford Translational Research Integrated Database Environment (STRIDE). RESULTS: Of the 9,589 adult patients (age ≥40 years) with CS/TIA included, 482 (5%) patients developed AF post CS/TIA. Of those patients, 28.4, 26.3, and 45.3% were diagnosed with AF 1-12 months, 1-3 years, and >3 years after the index CS/TIA, respectively. Age (≥75 years), obesity, congestive heart failure, hypertension, coronary artery disease, peripheral vascular disease, and valve disease are significant risk factors, with the following respective odds ratios (95% CI): 1.73 (1.39-2.16), 1.53 (1.05-2.18), 3.34 (2.61-4.28), 2.01 (1.53-2.68), 1.72 (1.35-2.19), 1.37 (1.02-1.84), and 2.05 (1.55-2.69). A risk-scoring system, i.e., the HAVOC score, was constructed using these 7 clinical variables that successfully stratify patients into 3 risk groups, with good model discrimination (area under the curve = 0.77). CONCLUSIONS: Findings from this study support the strategy of looking longer and harder for AF in post-CS/TIA patients. The HAVOC score identifies different levels of AF risk and may be used to select patients for extended rhythm monitoring.
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Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Ataque Isquémico Transitorio/complicaciones , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Anciano , Anciano de 80 o más Años , California/epidemiología , Enfermedad Coronaria/complicaciones , Bases de Datos Factuales , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertensión/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Denitrovibrio acetiphilus N2460(T) is one of the few members of the phylum Deferribacteres with a sequenced genome. N2460(T) was capable of growing with dimethyl sulfoxide, selenate, or arsenate provided as a terminal electron acceptor, and we identified 15 genes that could possibly encode respiratory reductases for these compounds. The protein encoded by one of these genes, YP_003504839, clustered with respiratory arsenate reductases on a phylogenetic tree. Transcription of the gene for YP_003504839, Dacet_2121, was highly induced when arsenate was provided as a terminal electron acceptor. Dacet_2121 exists in a possible operon that is distinct from the previously characterized respiratory arsenate reductase operon in Shewanella sp. ANA-3.
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Arseniato Reductasas/aislamiento & purificación , Bacterias/enzimología , Secuencia de Aminoácidos , Arseniato Reductasas/genética , Arseniato Reductasas/metabolismo , Bacterias/clasificación , Bacterias/genética , Operón , Filogenia , Alineación de Secuencia , Shewanella/enzimologíaRESUMEN
Background: According to recent census data, Hispanic and Latino populations comprise the largest minority group in the United States. Despite ongoing efforts for improved diversity, equity, and inclusion, Hispanics remain underrepresented in medicine (UIM). In addition to well-established benefits to patient care and health systems, physician diversity and increased representation in academic faculty positively impact the recruitment of trainees from UIM backgrounds. Disproportionate representation (as compared to increases of certain underrepresented groups in the US population) has direct implications for recruitment of UIM trainees to residency programs. Objective: To examine the number of full-time US medical school faculty physicians who self-identify as Hispanic in light of the increasing Hispanic population in the United States. Methods: We analyzed data from the Association of American Medical Colleges from 1990 to 2021, looking at those academic faculty who were classified as Hispanic, Latino, of Spanish Origin, or of Multiple Race-Hispanic. We used descriptive statistics and visualizations to illustrate the level of representation of Hispanic faculty by sex, rank, and clinical specialty over time. Results: Overall, the proportion of faculty studied who identified as Hispanic increased from 3.1% (1990) to 6.01% (2021). Moreover, while the proportion of female Hispanic academic faculty increased, there remains a lag between females versus males. Conclusions: Our analysis shows that the number of full-time US medical school faculty who self-identify as Hispanic has not increased, though the population of Hispanics in the United States has increased.
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Internado y Residencia , Facultades de Medicina , Masculino , Humanos , Femenino , Estados Unidos , Hispánicos o Latinos , Grupos Minoritarios , Docentes MédicosRESUMEN
BACKGROUND: An early HIV diagnosis improves patient outcomes, reduces the burden of undiagnosed HIV, and limits transmission. There is a need for an updated assessment of HIV testing rates in the emergency department (ED). SETTING: The National Hospital Ambulatory Medical Care Survey sampling ED visits were weighted to give an estimate of ED visits across all US states in 2018. METHODS: We analyzed patients aged 13-64 years without known HIV and estimated ED visits with HIV testing and then stratified by race, ethnicity, and region. Descriptive statistics and mapping were used to illustrate and compare patient, visit, and hospital characteristics for visits with HIV testing. RESULTS: Of 83.0 million weighted visits to EDs in 2018 by patients aged 13-64 years without a known HIV infection (based on 13,237 National Hospital Ambulatory Medical Care Survey sample visits), HIV testing was performed in 1.05% of visits. HIV testing was more frequent for patients aged 13-34 years compared with that for patients aged 35-64 years (1.32% vs. 0.82%, P = 0.056), Black patients compared with that for White and other patients (1.73% vs. 0.79% and 0.41%, P = 0.002), Hispanic or Latino patients compared with that for non-Hispanic or Latino patients (2.18% vs. 0.84%, P = 0.001), and patients insured by Medicaid compared with that for patients insured by private or other insurance (1.71% vs. 0.64% and 0.96%, P = 0.003). HIV testing rates were the highest in the Northeast (1.72%), followed by the South (1.05%). CONCLUSIONS: HIV testing occurred in a minority of ED visits. There are differences in rates of HIV testing by race, ethnicity, and location. Although rates of testing have increased, rates of ED-based HIV testing remain low.
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Infecciones por VIH , Servicio de Urgencia en Hospital , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH , Encuestas de Atención de la Salud , Humanos , Medicaid , Estados Unidos/epidemiologíaRESUMEN
Inverse odds of participation weighting (IOPW) has been proposed to transport clinical trial findings to target populations of interest when the distribution of treatment effect modifiers differs between trial and target populations. We set out to apply IOPW to transport results from an observational study to a target population of interest. We demonstrated the feasibility of this idea with a real-world example using a nationwide electronic health record derived de-identified database from Flatiron Health. First, we conducted an observational study that carefully adjusted for confounding to estimate the treatment effect of fulvestrant plus palbociclib relative to letrozole plus palbociclib as a second-line therapy among estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer patients. Second, we transported these findings to the broader cohort of patients who were eligible for a first-line therapy. The interpretation of the findings and validity of such studies, however, rely on the extent that causal inference assumptions are met.
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Neoplasias de la Mama , Receptor ErbB-2 , Humanos , Femenino , Receptor ErbB-2/metabolismo , Letrozol/uso terapéutico , Receptores de Estrógenos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Piperazinas/uso terapéutico , Piridinas/uso terapéutico , Neoplasias de la Mama/patologíaRESUMEN
OBJECTIVE: To address potential safety concerns of Janus Kinase Inhibitors (JAK-Is), we characterized their safety profile in the atopic dermatitis (AD) patient population. METHODS: In this retrospective observational study, we used propensity score-based methods and a Poisson modeling framework to estimate the incidence of health outcomes of interest (HOI) for the AD patient. To that end, two mutually exclusive cohorts were created using a real world data resource: a rheumatoid arthritis (RA) cohort, where we directly quantify the safety risk of JAK-Is on HOIs, and an AD cohort, that comprises the target population of interest and to whom we transport the results obtained from the RA cohort. The RA cohort included all adults who filled at least one prescription for a JAK-I (tofacitinib, baricitinib, or upadacitinib) between 1 January 2017 and 31 January 2020. The AD cohort consisted of all adults diagnosed with AD during the same period. We first estimated the incidence rate of each HOI in the RA cohort, and then transported the results to the AD population. RESULTS: The RA and AD cohorts included 5,296 and 261,855 patients, respectively. On average, patients in the AD cohort were younger, more often male, more likely to be Asian, and had higher household income. They also had a lower prevalence of several comorbid conditions including hypertension, chronic kidney disease, obesity, and depression. Overall, the transported incidence rates of the HOIs to the AD cohort were lower than those obtained in the RA cohort by 13-50%. CONCLUSION: We applied transportability methods to characterize the risk of the HOIs in the AD population and found absolute risks higher than that of the general population. Future work is needed to validate these conclusions in comparable populations.
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Artritis Reumatoide , Dermatitis Atópica , Inhibidores de las Cinasas Janus , Adulto , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , Humanos , Incidencia , Inhibidores de las Cinasas Janus/efectos adversos , Masculino , PrevalenciaRESUMEN
Background: The Society for Academic Emergency Medicine (SAEM) has a core value to promote a diverse workforce for patients, providers, and learners. Understanding the organization's membership demographics and how that compares to the academic emergency medicine (EM) workforce is prerequisite to the success of this core value. Methods: We obtained 2020 faculty membership data sets from the Association of American Medical Colleges (AAMC) and SAEM; data included self-reported sex, race and ethnicity, and academic rank (professor, associate professor, assistant professor, and instructor). We employed standardized mean difference (SMD) to quantify difference in proportions between data sets. Results: We identified 5874 (AAMC) and 2785 (SAEM) faculty. The AAMC (38.3%) and the SAEM (41.3%) had similar proportions of overall female faculty (SMD 0.063) although SAEM (compared to AAMC) had a higher proportion of female full (25.5% vs. 20.5%, SMD 0.121) and assistant (46.5% vs. 41.2%, SMD 0.106) professors. With the exception of Hispanic instructors, SAEM (compared to AAMC) also had higher proportions of Black and Hispanic female faculty at all ranks (SMD ranging from 0.109 to 0.777). Conclusion: SAEM faculty demographics generally reflect that of the academic EM workforce demographics reported in the AAMC database and that overall, the proportions of female, Black, and Hispanic faculty in SAEM are slightly larger than those in the AAMC database. However, faculty who identify as Black or Hispanic in both the AAMC and the SAEM databases (compared to the overall U.S. population) are dramatically underrepresented.
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Purpose: To describe trends in emergency medicine faculty demographics, examining changes in the proportion of historically underrepresented groups including female, Black, and Latinx faculty over time. Methods: Data from the Association of American Medical Colleges faculty roster (1990-2020) were used to assess the changing demographics of full-time emergency medicine faculty. Descriptive statistics, graphic visualizations, and logistic regression modeling were used to illustrate trends in the proportion of female, Black, and Latinx faculty. Odds ratios (OR) were used to describe the estimated annual rate of change of underrepresented demographic groups. Results: The number of full-time emergency medicine faculty increased from 214 in 1990 to 5874 in 2020. Female emergency medicine faculty demonstrated increases in representation overall, from 35 (16.36%) in 1990 to 2247 (38.25%) in 2020, suggesting a 3% estimated annual rate of increase (OR 1.03, 95% CI 1.03-1.04) and within each academic rank. A very small positive trend was noted among Latinx faculty (n = 3, 1.40% in 1990 to n = 326, 5.55% in 2020; OR 1.01, 95% CI 1.01-1.02), whereas an even smaller, statistically insignificant increase was observed among Black emergency medicine faculty during the 31-year study period (N = 9, 4.21% in 1990 and N = 266, 4.53% in 2020; OR 1.00, 95% CI 0.99-1.00). Conclusions: Although female physicians have progressed toward equitable representation among academic emergency medicine faculty, no meaningful progress has been made toward racial parity. The persistent underrepresentation of Black and Latinx physicians in the academic emergency medicine workforce underscores the need for urgent structural changes to address contemporary manifestations of racism in academic medicine and beyond.
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OBJECTIVES: Most population-based cancer databases lack information on metastatic recurrence. Electronic medical records (EMR) and cancer registries contain complementary information on cancer diagnosis, treatment and outcome, yet are rarely used synergistically. To construct a cohort of metastatic breast cancer (MBC) patients, we applied natural language processing techniques within a semisupervised machine learning framework to linked EMR-California Cancer Registry (CCR) data. MATERIALS AND METHODS: We studied all female patients treated at Stanford Health Care with an incident breast cancer diagnosis from 2000 to 2014. Our database consisted of structured fields and unstructured free-text clinical notes from EMR, linked to CCR, a component of the Surveillance, Epidemiology and End Results Program (SEER). We identified de novo MBC patients from CCR and extracted information on distant recurrences from patient notes in EMR. Furthermore, we trained a regularized logistic regression model for recurrent MBC classification and evaluated its performance on a gold standard set of 146 patients. RESULTS: There were 11 459 breast cancer patients in total and the median follow-up time was 96.3 months. We identified 1886 MBC patients, 512 (27.1%) of whom were de novo MBC patients and 1374 (72.9%) were recurrent MBC patients. Our final MBC classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.917, with sensitivity 0.861, specificity 0.878, and accuracy 0.870. DISCUSSION AND CONCLUSION: To enable population-based research on MBC, we developed a framework for retrospective case detection combining EMR and CCR data. Our classifier achieved good AUC, sensitivity, and specificity without expert-labeled examples.
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Over 75 million Americans have multiple concurrent chronic conditions and medical decision making for these patients is mostly based on retrospective cohort studies. Current methods to generate cohorts of patients with comorbidities are neither scalable nor generalizable. We propose a supervised machine learning algorithm for learning comorbidity phenotypes without requiring manually created training sets. First, we generated myocardial infarction (MI) and type-2 diabetes (T2DM) patient cohorts using ICD9-based imperfectly labeled samples upon which LASSO logistic regression models were trained. Second, we assessed the effects of training sample size, inclusion of physician input, and inclusion of clinical text features on model performance. Using ICD9 codes as our labeling heuristic, we achieved comparable performance to models created using keywords as labeling heuristic. We found that expert input and higher training sample sizes could compensate for the lack of clinical text derived features. However, our best performing model included clinical text as features with a large training sample size.
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Comorbilidad , Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Aprendizaje Automático Supervisado , Enfermedad Crónica , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Clasificación Internacional de Enfermedades , Modelos Logísticos , Infarto del Miocardio/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND: Hirschsprung disease (HSCR) is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract in neonates. Three polymorphisms, rs2435357, within a conserved transcriptional enhancer of RET, and, rs7835688 and rs16879552, within intron 1 of NRG1, have been shown to be associated with isolated forms of HSCR. We wished to replicate these findings, and study the interactions between these variants, in Indonesian HSCR patients. METHODS: Sixty isolated HSCR patients and 124 controls were ascertained for this study. The three genetic markers were examined using TaqMan Genotyping Assays in genomic DNA for association studies. RESULTS: RET rs2435357 showed the strongest association with HSCR both by case-control analysis (p=2.5 × 10(-8)) and transmission disequilibrium test (p=4.2 × 10(-6)). NRG1 rs7835688 was modestly associated with HSCR only by case-control analysis (p=4.3 × 10(-3)), whereas rs16879552 demonstrated no association (p>0.097). Two locus analyses of variants showed significant interactions with increased and decreased disease risks of HSCR at NRG1 but conditional on rs2435357 genotype. CONCLUSIONS: RET and NRG1 variants are common susceptibility factors for HSCR in Indonesia. These common variants demonstrate that development of HSCR requires joint effects of RET and NRG1 early in gut development.