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HIV early detection (CD4 counts ≥350 cells/µL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors, including physical, cultural, structural, and financial barriers, may limit early detection of HIV. This is a first-of-its-kind study on population-level differences in early detection of HIV across time within Tajikistan and any country in the Central Asia region. Utilizing the Tajikistan Ministry of Health's national HIV data (N = 10,700) spanning 2010 to 2023, we developed median regression models with the median CD4 cell count as the outcome and with the following predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old were detected early for HIV, whereas those older than 39 years were detected late. Females were detected earlier compared to their male counterparts regardless of region of residence. Rural populations were detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. There were differences identified among different demographic and geographic groups which warrant further attention.
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Diagnóstico Precoz , Infecciones por VIH , Humanos , Tayikistán/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Femenino , Masculino , Adulto , Adulto Joven , Persona de Mediana Edad , Adolescente , Población Rural , Recuento de Linfocito CD4 , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Población UrbanaRESUMEN
Background Some internal medicine (IM) residents pursuing subspecialty training choose short-term hospitalist employment prior to fellowship, or "pre-fellowship hospitalist years." Residency and fellowship program directors (PDs) advise residents on this decision, but PD experience with fellows pursuing pre-fellowship hospitalist years and the impact on fellowship applications is unknown. Objective We aimed to explore perceptions of fellowship PDs regarding experience with fellows who pursued pre-fellowship hospitalist years, including perceived effects on how such years affect fellowship application candidacy. Methods A purposive sample of 20 fellowship PDs in the most highly competitive and commonly selected IM fellowships (cardiology, pulmonology/critical care medicine, hematology/oncology, gastroenterology) from 5 academic institutions were approached for participation in fall 2021. Interviews included semi-structured questions about pre-fellowship hospitalist employment. Utilizing rapid qualitative analysis, interview transcripts were summarized and reviewed to identify themes and subthemes describing fellowship PDs' perspectives of pre-fellowship hospitalist years. Results Sixteen fellowship PDs (80%) participated. PDs identified 4 major themes as important for trainees considering pre-fellowship hospitalist years: (1) Explain the "Why"-why the year was pursued; (2) Characteristics of the Hospitalist Position-what type of employment; (3) The Challenges-potential concerns faced with pre-fellowship hospitalist years; and (4) Describe the "What"-the experience's contribution to resident professional development. Conclusions Fellowship PDs in 4 competitive IM subspecialities placed a strong emphasis on explaining a clear, logical reason for seeking short-term hospitalist employment prior to fellowship, describing how it fits into the overall career trajectory, and selecting activities that demonstrate continued commitment to the subspecialty.
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Empleo , Becas , Médicos Hospitalarios , Medicina Interna , Internado y Residencia , Investigación Cualitativa , Humanos , Medicina Interna/educación , Educación de Postgrado en Medicina , Femenino , Masculino , Entrevistas como AsuntoRESUMEN
ABSTRACT: Working groups have tremendous potential to contribute to the academic career development of early-career clinician-educators. These individuals may find themselves engaged in many different working spaces, including working groups or committees such as those found within specialty societies or professional organizations. Such working groups may be underrecognized opportunities for academic skill building and professional growth because they are often characterized as primarily service-oriented, citizenship, or administrative work. Working groups can use their natural cross-institutional collaborations for mentorship and externalization-2 key building blocks for academic success that frequently represent challenges for early-career clinician-educators. In this article, the authors review common challenges that early-career clinician-educators may encounter during their academic development and propose a 3-step tactical framework, the academic catalyst group, that working group leaders can apply to groups to purposefully enhance professional development for clinician-educators. The framework urges working group leaders and members to conceptualize and develop academic catalyst groups as communities of practice by (1) assembling with intention, (2) mining the mission, and (3) finding an easy win. This framework can inspire working group leaders to align their work with academic career development and ultimately foster career growth for all group members.
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Importance: Patients with inequitable access to patient portals frequently present to emergency departments (EDs) for care. Little is known about portal use patterns among ED patients. Objectives: To describe real-time patient portal usage trends among ED patients and compare demographic and clinical characteristics between portal users and nonusers. Design, Setting, and Participants: In this cross-sectional study of 12 teaching and 24 academic-affiliated EDs from 8 health systems in California, Connecticut, Massachusetts, Ohio, Tennessee, Texas, and Washington, patient portal access and usage data were evaluated for all ED patients 18 years or older between April 5, 2021, and April 4, 2022. Exposure: Use of the patient portal during ED visit. Main Outcomes and Measures: The primary outcomes were the weekly proportions of ED patients who logged into the portal, viewed test results, and viewed clinical notes in real time. Pooled random-effects models were used to evaluate temporal trends and demographic and clinical characteristics associated with real-time portal use. Results: The study included 1â¯280â¯924 unique patient encounters (53.5% female; 0.6% American Indian or Alaska Native, 3.7% Asian, 18.0% Black, 10.7% Hispanic, 0.4% Native Hawaiian or Pacific Islander, 66.5% White, 10.0% other race, and 4.0% with missing race or ethnicity; 91.2% English-speaking patients; mean [SD] age, 51.9 [19.2] years). During the study, 17.4% of patients logged into the portal while in the ED, whereas 14.1% viewed test results and 2.5% viewed clinical notes. The odds of accessing the portal (odds ratio [OR], 1.36; 95% CI, 1.19-1.56), viewing test results (OR, 1.63; 95% CI, 1.30-2.04), and viewing clinical notes (OR, 1.60; 95% CI, 1.19-2.15) were higher at the end of the study vs the beginning. Patients with active portal accounts at ED arrival had a higher odds of logging into the portal (OR, 17.73; 95% CI, 9.37-33.56), viewing test results (OR, 18.50; 95% CI, 9.62-35.57), and viewing clinical notes (OR, 18.40; 95% CI, 10.31-32.86). Patients who were male, Black, or without commercial insurance had lower odds of logging into the portal, viewing results, and viewing clinical notes. Conclusions and Relevance: These findings suggest that real-time patient portal use during ED encounters has increased over time, but disparities exist in portal access that mirror trends in portal usage more generally. Given emergency medicine's role in caring for medically underserved patients, there are opportunities for EDs to enroll and train patients in using patient portals to promote engagement during and after their visits.
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Servicio de Urgencia en Hospital , Portales del Paciente , Humanos , Femenino , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Portales del Paciente/estadística & datos numéricos , Estudios Transversales , Persona de Mediana Edad , Adulto , Estados Unidos , Anciano , Adulto JovenRESUMEN
OBJECTIVE: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. DESIGN: Retrospective cohort study. SETTING: US administrative database. PATIENTS: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. INTERVENTION: Platinum-based chemotherapy. MAIN OUTCOME MEASURES: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). RESULTS: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively. CONCLUSIONS: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions.
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Supervivientes de Cáncer , Infertilidad Femenina , Nacimiento Vivo , Humanos , Femenino , Adolescente , Supervivientes de Cáncer/estadística & datos numéricos , Adulto Joven , Adulto , Estudios Retrospectivos , Infertilidad Femenina/epidemiología , Infertilidad Femenina/terapia , Infertilidad Femenina/inducido químicamente , Infertilidad Femenina/diagnóstico , Nacimiento Vivo/epidemiología , Embarazo , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Preservación de la Fertilidad/métodos , Factores de Riesgo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/tratamiento farmacológico , Estados Unidos/epidemiología , Resultado del Tratamiento , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias/epidemiología , Neoplasias/tratamiento farmacológico , Fertilidad/efectos de los fármacos , Medición de RiesgoRESUMEN
BACKGROUND: Artificial Intelligence (AI) is rapidly transforming healthcare, and there is a critical need for a nuanced understanding of how AI is reshaping teaching, learning, and educational practice in medical education. This review aimed to map the literature regarding AI applications in medical education, core areas of findings, potential candidates for formal systematic review and gaps for future research. METHODS: This rapid scoping review, conducted over 16 weeks, employed Arksey and O'Malley's framework and adhered to STORIES and BEME guidelines. A systematic and comprehensive search across PubMed/MEDLINE, EMBASE, and MedEdPublish was conducted without date or language restrictions. Publications included in the review spanned undergraduate, graduate, and continuing medical education, encompassing both original studies and perspective pieces. Data were charted by multiple author pairs and synthesized into various thematic maps and charts, ensuring a broad and detailed representation of the current landscape. RESULTS: The review synthesized 278 publications, with a majority (68%) from North American and European regions. The studies covered diverse AI applications in medical education, such as AI for admissions, teaching, assessment, and clinical reasoning. The review highlighted AI's varied roles, from augmenting traditional educational methods to introducing innovative practices, and underscores the urgent need for ethical guidelines in AI's application in medical education. CONCLUSION: The current literature has been charted. The findings underscore the need for ongoing research to explore uncharted areas and address potential risks associated with AI use in medical education. This work serves as a foundational resource for educators, policymakers, and researchers in navigating AI's evolving role in medical education. A framework to support future high utility reporting is proposed, the FACETS framework.
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Inteligencia Artificial , Educación Médica , Humanos , Educación Médica/métodos , Aprendizaje , EnseñanzaRESUMEN
Importance: Procedural proficiency is a core competency for graduate medical education; however, procedural reporting often relies on manual workflows that are duplicative and generate data whose validity and accuracy are difficult to assess. Failure to accurately gather these data can impede learner progression, delay procedures, and negatively impact patient safety. Objective: To examine accuracy and procedure logging completeness of a system that extracts procedural data from an electronic health record system and uploads these data securely to an application used by many residency programs for accreditation. Design, Setting, and Participants: This quality improvement study of all emergency medicine resident physicians at University of California, San Diego Health was performed from May 23, 2023, to June 25, 2023. Exposures: Automated system for procedure data extraction and upload to a residency management software application. Main Outcomes and Measures: The number of procedures captured by the automated system when running silently compared with manually logged procedures in the same timeframe, as well as accuracy of the data upload. Results: Forty-seven residents participated in the initial silent assessment of the extraction component of the system. During a 1-year period (May 23, 2022, to May 7, 2023), 4291 procedures were manually logged by residents, compared with 7617 procedures captured by the automated system during the same period, representing a 78% increase. During assessment of the upload component of the system (May 8, 2023, to June 25, 2023), a total of 1353 procedures and patient encounters were evaluated, with the system operating with a sensitivity of 97.4%, specificity of 100%, and overall accuracy of 99.5%. Conclusions and Relevance: In this quality improvement study of emergency medicine resident physicians, an automated system demonstrated that reliance on self-reported procedure logging resulted in significant procedural underreporting compared with the use of data obtained at the point of performance. Additionally, this system afforded a degree of reliability and validity heretofore absent from the usual after-the-fact procedure logging workflows while using a novel application programming interface-based approach. To our knowledge, this system constitutes the first generalizable implementation of an automated solution to a problem that has existed in graduate medical education for decades.
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Medicina de Emergencia , Médicos , Humanos , Registros Electrónicos de Salud , Reproducibilidad de los Resultados , Educación de Postgrado en MedicinaRESUMEN
OBJECTIVES: Effective communication amongst healthcare workers simultaneously promotes optimal patient outcomes when present and is deleterious to outcomes when absent. The advent of electronic health record (EHR)-embedded secure instantaneous messaging systems has provided a new conduit for provider communication. This manuscript describes the experience of one academic medical center with deployment of one such system (Secure Chat). METHODS: Data were collected on Secure Chat message volume from June 2017 to April 2023. Significant perideployment events were reviewed chronologically. RESULTS: After the first coronavirus disease 2019 lockdown in March 2020, messaging use increased by over 25â000 messages per month, with 1.2 million messages sent monthly by April 2023. Comparative features of current communication modalities in healthcare were summarized, highlighting the many advantages of Secure Chat. CONCLUSIONS: While EHR-embedded secure instantaneous messaging systems represent a novel and potentially valuable communication medium in healthcare, generally agreed-upon best practices for their implementation are, as of yet, undetermined.
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Registros Electrónicos de Salud , Envío de Mensajes de Texto , Humanos , Correo Electrónico , Atención a la Salud , Personal de Salud , ComunicaciónRESUMEN
AIMS: The HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions. METHODS AND RESULTS: The PREEMPT-HF study is a global, multicentre, prospective, observational, single-arm, post-market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in-clinic visit at 12 months was required for collection of all-cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no adjustment for multiple testing will be performed. A total of 2183 patients were enrolled at 103 sites between June 2018 and June 2020. A significant proportion of the patients were implanted with implantable defibrillator devices (39%) versus cardiac resynchronization therapy with defibrillator (61%); were female (27%); over 65 (61%); New York Heart Association class I (13%), II (53%), and III (33%); ejection fraction < 25% (21%); ischaemic (50%); and with a history of renal dysfunction (23%). CONCLUSIONS: The PREEMPT study will provide clinical data and blinded sensor trends for the characterization of sensor changes with HF readmission, tachyarrhythmias, and event subgroups. These data may help to refine the clinical use of HeartLogic and to improve patient outcomes.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Femenino , Humanos , Masculino , Terapia de Resincronización Cardíaca/métodos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Hospitalización , Estudios ProspectivosRESUMEN
OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic disrupted how educational conferences were delivered, leaving programs to choose between in-person and virtual morning report formats. The objective of our study was to describe morning reports during the COVID-19 pandemic, including the use of virtual formats, attendance, leadership, and content. METHODS: A prospective observational study of morning reports was conducted at 13 Internal Medicine residency programs between September 1, 2020 and March 30, 2021, including a follow-up survey of current morning report format in January 2023. RESULTS: In total, 257 reports were observed; 74% used virtual formats, including single hospital, multiple hospital, and a hybrid format with both in-person and virtual participants. Compared with in-person reports, virtual reports had more participants, with increased numbers of learners (median 21 vs 7; P < 0.001) and attendings (median 4 vs 2; P < 0.001), and they were more likely to involve medical students (83% vs 40%; P < 0.001), interns (99% vs 53%; P < 0.001), and program directors (68% vs 32%; P < 0.001). Attendings were less likely to lead virtual reports (3% vs 28%, P < 0.001). Virtual reports also were more likely to be case based (88% vs 69%; P < 0.001) and to use digital presentation slides (91% vs 36%; P < 0.001). There was a marked increase in the number of slides (median 20 vs 0; P < 0.001). As of January 2023, all 13 programs had returned to in-person reports, with only 1 program offering an option to participate virtually. CONCLUSIONS: During the COVID-19 pandemic, virtual morning report formats predominated. Compared with traditional in-person reports, virtual report increased attendance, favored resident leadership, and approached a similar range of patient diagnoses with a greater number of case-based presentations and slides. In spite of these characteristics, all programs returned to an in-person format for morning report as pandemic restrictions waned.
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COVID-19 , Rondas de Enseñanza , Humanos , COVID-19/epidemiología , Pandemias , Escolaridad , HospitalesRESUMEN
OBJECTIVES: Acknowledging that a successful career in hospital medicine (HM) requires specialized skills, residency programs have developed hospital medicine-focused education (HMFE) programs. Surveys of Internal Medicine residency leaders have described HMFE curricula but are limited to that specialty and lack perspectives from early career hospitalists (ECHs) who recently completed this training. As such, we surveyed multispecialty ECHs to evaluate their preferences for HMFE and to identify gaps in standard residency training and career development that HMFE can bridge. The objectives of our study were to describe multispecialty ECH needs and preferences for HMFE and to identify gaps in standard residency training and career development that HMFE can bridge. METHODS: From February to March 2021, ECHs (defined as hospitalists within 0-5 years from residency) were surveyed using the Society of Hospital Medicine's listserv. Respondents identified as having participated in HMFE or not during residency (defining them as HMFE participants or non-HMFE participants). RESULTS: From 257 respondents, 84 (33%) ECHs met inclusion criteria. Half (n = 42) were HMFE participants. ECHs ranked clinical hospitalist career preparation (86%) and mentorship from HM faculty (85%) as the most important gaps in standard residency training and career development that HMFE can bridge. Other key components of HMFE included exposure to quality improvement, patient safety, and high-value care (67%); provision of autonomy through independent rounding (54%); and preparation for the job application process (70%). CONCLUSIONS: Multispecialty ECHs describe HMFE as positively influencing their decision to pursue a hospitalist career and increasing their preparedness for practice. HMFE may be particularly well suited to foster advanced clinical skills such as independent rounding, critical thinking, and self-reflection. We propose an organizing framework for HMFE in residency that may assist in the implementation and innovation of HMFE programs nationwide and in the development of standardized HMFE competencies.
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Medicina Hospitalar , Médicos Hospitalarios , Medicina , Humanos , Escolaridad , Hospitales de EnseñanzaRESUMEN
Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Fallo Renal Crónico , Humanos , Animales , Ratones , Nefropatías Diabéticas/patología , Adenina , Diabetes Mellitus Experimental/complicaciones , Riñón/metabolismo , Biomarcadores , Serina-Treonina Quinasas TORRESUMEN
Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality, however, few mechanistic biomarkers are available for high risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from Chronic Renal Insufficiency Cohort (CRIC), Singapore Study of Macro-Angiopathy and Reactivity in Type 2 Diabetes (SMART2D), and the Pima Indian Study determined if urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in CRIC (HR 1.57, 1.18, 2.10) and SMART2D (HR 1.77, 1.00, 3.12). ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in CRIC (HR 2.36, 1.26, 4.39), SMART2D (HR 2.39, 1.08, 5.29), and Pima Indian study (HR 4.57, CI 1.37-13.34). Empagliflozin lowered UAdCR in non-macroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology and transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mammalian target of rapamycin (mTOR). Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.
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OBJECTIVE: To determine if a novel symptom-based alcohol withdrawal syndrome (AWS) protocol in a US Veterans cohort leads to significant clinical improvements in patient outcomes and safety. BACKGROUND: Prior studies of AWS management, oftentimes using the revised version of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) index, have demonstrated the effectiveness of symptom-triggered therapy for AWS. The Minnesota Detoxification Scale (MINDS) is an alternative to the CIWA-Ar index but remains unevaluated outside of the intensive care unit (ICU) setting. This study assesses outcomes in AWS management prior to and after the implementation of a novel MINDS-based AWS protocol (SDAWP) utilizing a revised MINDS index (MINDS-rev) in an inpatient medical ward setting. METHODS: Retrospective cohort study including encounters prior to (n = 342) and after (n = 338) the implementation of the protocol. Pre- and post-protocol encounters were selected by combinations of diagnostic codes and charting elements. Outcome measures of AWS management were obtained in both groups. The primary endpoint was median total benzodiazepine exposure. Secondary outcomes included median length of hospitalization, median duration of benzodiazepine administration, and the incidence of complications. RESULTS: The median total benzodiazepine exposure in the post-SDAWP group was significantly lower than the pre-SDAWP group (21.2 vs. 12.0 mg, p < 0.0001) and for a significantly shorter median duration of time (4.0 vs. 3.0 days, p < 0.0001). There was no significant difference in the median length of stay (4.0 vs. 4.0 days, p = 0.50). The incidence of delirium tremens (21 vs. 7, p = 0.01) and need for transfer to a higher level of care (33 vs. 12, p = 0.002) was significantly lower in the post-SDAWP group. CONCLUSION: The SDAWP has provided significant improvements in AWS management in our institution and may potentially serve as a template for wider use in other inpatient settings.
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Delirio por Abstinencia Alcohólica , Alcoholismo , Síndrome de Abstinencia a Sustancias , Humanos , Síndrome de Abstinencia a Sustancias/diagnóstico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Alcoholismo/complicaciones , Alcoholismo/tratamiento farmacológico , Delirio por Abstinencia Alcohólica/diagnóstico , Delirio por Abstinencia Alcohólica/tratamiento farmacológico , Estudios Retrospectivos , Pacientes Internos , Minnesota , Benzodiazepinas/efectos adversos , EtanolRESUMEN
BACKGROUND: The growing amount of high dimensional biomolecular data has spawned new statistical and computational models for risk prediction and disease classification. Yet, many of these methods do not yield biologically interpretable models, despite offering high classification accuracy. An exception, the top-scoring pair (TSP) algorithm derives parameter-free, biologically interpretable single pair decision rules that are accurate and robust in disease classification. However, standard TSP methods do not accommodate covariates that could heavily influence feature selection for the top-scoring pair. Herein, we propose a covariate-adjusted TSP method, which uses residuals from a regression of features on the covariates for identifying top scoring pairs. We conduct simulations and a data application to investigate our method, and compare it to existing classifiers, LASSO and random forests. RESULTS: Our simulations found that features that were highly correlated with clinical variables had high likelihood of being selected as top scoring pairs in the standard TSP setting. However, through residualization, our covariate-adjusted TSP was able to identify new top scoring pairs, that were largely uncorrelated with clinical variables. In the data application, using patients with diabetes (n = 977) selected for metabolomic profiling in the Chronic Renal Insufficiency Cohort (CRIC) study, the standard TSP algorithm identified (valine-betaine, dimethyl-arg) as the top-scoring metabolite pair for classifying diabetic kidney disease (DKD) severity, whereas the covariate-adjusted TSP method identified the pair (pipazethate, octaethylene glycol) as top-scoring. Valine-betaine and dimethyl-arg had, respectively, ≥ 0.4 absolute correlation with urine albumin and serum creatinine, known prognosticators of DKD. Thus without covariate-adjustment the top-scoring pair largely reflected known markers of disease severity, whereas covariate-adjusted TSP uncovered features liberated from confounding, and identified independent prognostic markers of DKD severity. Furthermore, TSP-based methods achieved competitive classification accuracy in DKD to LASSO and random forests, while providing more parsimonious models. CONCLUSIONS: We extended TSP-based methods to account for covariates, via a simple, easy to implement residualizing process. Our covariate-adjusted TSP method identified metabolite features, uncorrelated from clinical covariates, that discriminate DKD severity stage based on the relative ordering between two features, and thus provide insights into future studies on the order reversals in early vs advanced disease states.