A Neuro-Informatics Pipeline for Cerebrovascular Disease: Research Registry Development.

BACKGROUND: Although stroke is well recognized as a critical disease, treatment options are often limited. Inpatient stroke encounters carry critical information regarding the mechanisms of stroke and patient outcomes; however, these data are typically formatted to support administrative functions instead of research. To support improvements in the care of patients with stroke, a substantive research data platform is needed. OBJECTIVE: To advance a stroke-oriented learning health care system, we sought to establish a comprehensive research repository of stroke data using the Houston Methodist electronic health record (EHR) system. METHODS: Dedicated processes were developed to import EHR data of patients with primary acute ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack, and subarachnoid hemorrhage under a review board-approved protocol. Relevant patients were identified from discharge diagnosis codes and assigned registry patient identification numbers. For identified patients, extract, transform, and load processes imported EHR data of primary cerebrovascular disease admissions and available data from any previous or subsequent admissions. Data were loaded into patient-focused SQL objects to enable cross-sectional and longitudinal analyses. Primary data domains (admission details, comorbidities, laboratory data, medications, imaging data, and discharge characteristics) were loaded into separate relational tables unified by patient and encounter identification numbers. Computed tomography, magnetic resonance, and angiography images were retrieved. Imaging data from patients with ICH were assessed for hemorrhage characteristics and cerebral small vessel disease markers. Patient information needed to interface with other local and national databases was retained. Prospective patient outreach was established, with patients contacted via telephone to assess functional outcomes 30, 90, 180, and 365 days after discharge. Dashboards were constructed to provide investigators with data summaries to support access. RESULTS: The Registry of Neurological Endpoint Assessments among Patients with Ischemic and Hemorrhagic Stroke (REINAH) database was constructed as a series of relational category-specific SQL objects. Encounter summaries and dashboards were constructed to draw from these objects, providing visual data summaries for investigators seeking to build studies based on REINAH data. As of June 2022, the database contains 18,061 total patients, including 1809 (10.02%) with ICH, 13,444 (74.43%) with acute ischemic stroke, 1221 (6.76%) with subarachnoid hemorrhage, and 3165 (17.52%) with transient ischemic attack. Depending on the cohort, imaging data from computed tomography are available for 85.83% (1048/1221) to 98.4% (1780/1809) of patients, with magnetic resonance imaging available for 27.85% (340/1221) to 85.54% (11,500/13,444) of patients. Outcome assessment has successfully contacted 56.1% (240/428) of patients after ICH, with 71.3% (171/240) of responders providing consent for assessment. Responders reported a median modified Rankin Scale score of 3 at 90 days after discharge. CONCLUSIONS: A highly curated and clinically focused research platform for stroke data will establish a foundation for future research that may fundamentally improve poststroke patient care and outcomes.

Rapid Response to Drive COVID-19 Research in a Learning Health Care System: Rationale and Design of the Houston Methodist COVID-19 Surveillance and Outcomes Registry (CURATOR).

BACKGROUND: The COVID-19 pandemic has exacerbated the challenges of meaningful health care digitization. The need for rapid yet validated decision-making requires robust data infrastructure. Organizations with a focus on learning health care (LHC) systems tend to adapt better to rapidly evolving data needs. Few studies have demonstrated a successful implementation of data digitization principles in an LHC context across health care systems during the COVID-19 pandemic. OBJECTIVE: We share our experience and provide a framework for assembling and organizing multidisciplinary resources, structuring and regulating research needs, and developing a single source of truth (SSoT) for COVID-19 research by applying fundamental principles of health care digitization, in the context of LHC systems across a complex health care organization. METHODS: Houston Methodist (HM) comprises eight tertiary care hospitals and an expansive primary care network across Greater Houston, Texas. During the early phase of the pandemic, institutional leadership envisioned the need to streamline COVID-19 research and established the retrospective research task force (RRTF). We describe an account of the structure, functioning, and productivity of the RRTF. We further elucidate the technical and structural details of a comprehensive data repository-the HM COVID-19 Surveillance and Outcomes Registry (CURATOR). We particularly highlight how CURATOR conforms to standard health care digitization principles in the LHC context. RESULTS: The HM COVID-19 RRTF comprises expertise in epidemiology, health systems, clinical domains, data sciences, information technology, and research regulation. The RRTF initially convened in March 2020 to prioritize and streamline COVID-19 observational research; to date, it has reviewed over 60 protocols and made recommendations to the institutional review board (IRB). The RRTF also established the charter for CURATOR, which in itself was IRB-approved in April 2020. CURATOR is a relational structured query language database that is directly populated with data from electronic health records, via largely automated extract, transform, and load procedures. The CURATOR design enables longitudinal tracking of COVID-19 cases and controls before and after COVID-19 testing. CURATOR has been set up following the SSoT principle and is harmonized across other COVID-19 data sources. CURATOR eliminates data silos by leveraging unique and disparate big data sources for COVID-19 research and provides a platform to capitalize on institutional investment in cloud computing. It currently hosts deeply phenotyped sociodemographic, clinical, and outcomes data of approximately 200,000 individuals tested for COVID-19. It supports more than 30 IRB-approved protocols across several clinical domains and has generated numerous publications from its core and associated data sources. CONCLUSIONS: A data-driven decision-making strategy is paramount to the success of health care organizations. Investment in cross-disciplinary expertise, health care technology, and leadership commitment are key ingredients to foster an LHC system. Such systems can mitigate the effects of ongoing and future health care catastrophes by providing timely and validated decision support.

Racial and ethnic disparities in SARS-CoV-2 pandemic: analysis of a COVID-19 observational registry for a diverse US metropolitan population.

INTRODUCTION: Data on race and ethnic disparities for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. We analysed sociodemographic factors associated with higher likelihood of SARS-CoV-2 infection and explore mediating pathways for race and ethnic disparities in the SARS-CoV-2 pandemic. METHODS: This is a cross-sectional analysis of the COVID-19 Surveillance and Outcomes Registry, which captures data for a large healthcare system, comprising one central tertiary care hospital, seven large community hospitals and an expansive ambulatory/emergency care network in the Greater Houston area. Nasopharyngeal samples for individuals inclusive of all ages, races, ethnicities and sex were tested for SARS-CoV-2. We analysed sociodemographic (age, sex, race, ethnicity, household income, residence population density) and comorbidity (Charlson Comorbidity Index, hypertension, diabetes, obesity) factors. Multivariable logistic regression models were fitted to provide adjusted OR (aOR) and 95% CI for likelihood of a positive SARS-CoV-2 test. Structural equation modelling (SEM) framework was used to explore three mediation pathways (low income, high population density, high comorbidity burden) for the association between non-Hispanic black (NHB) race, Hispanic ethnicity and SARS-CoV-2 infection. RESULTS: Among 20 228 tested individuals, 1551 (7.7%) tested positive. The overall mean (SD) age was 51.1 (19.0) years, 62% were females, 22% were black and 18% were Hispanic. NHB and Hispanic ethnicity were associated with lower socioeconomic status and higher population density residence. In the fully adjusted model, NHB (vs non-Hispanic white; aOR, 2.23, CI 1.90 to 2.60) and Hispanic ethnicity (vs non-Hispanic; aOR, 1.95, CI 1.72 to 2.20) had a higher likelihood of infection. Older individuals and males were also at higher risk of infection. The SEM framework demonstrated a significant indirect effect of NHB and Hispanic ethnicity on SARS-CoV-2 infection mediated via a pathway including residence in densely populated zip code. CONCLUSIONS: There is strong evidence of race and ethnic disparities in the SARS-CoV-2 pandemic that are potentially mediated through unique social determinants of health.

Complejos inmunes IgM-ApoB100 modificadas / Immune complexes IgM-modified ApoB100 / Complexos Imunes IgM-ApoB100 modificadas

La aterosclerosis es la patología vascular de mayor prevalencia, lo cual motiva numerosas investigaciones sobre su fisiopatogenia. Las lipoproteínas pueden ser modificadas por mecanismos de oxidación y acetilación entre otros, a nivel de sus componentes lipídicos como proteicos, tornándose aterogénicas. Las Apolipoproteínas B100 modificadas (ApoB100m), desempeñan un rol activo en el desarrollo de las lesiones ateroscleróticas conjuntamente con otros factores de riesgo. Éstas tienen la capacidad de producir respuesta inmune llevando a la producción de anticuerpos y la subsecuente formación de complejos inmunes. La importancia de los anticuerpos contra las ApoB100m en la aterogénesis todavía no está clara, existiendo datos contradictorios respecto a si su rol es protectivo o aterogénico. Se establecieron dos objetivos: Determinar los niveles de complejos inmunes circulantes IgM-ApoB100m por enzimoinmunoanálisis, en sujetos normales (sin riesgo aterogénico) y pacientes con alto riesgo y establecer su correlación con los factores de riesgo aterogénico ya establecidos, mediante un estudio observacional transversal. Se obtuvieron valores medios más elevados de IgM-ApoB100m en el grupo de sujetos normales. Los complejos inmunes IgM-ApoB100m correlacionan negativamente con los factores de riesgo aterogénicos clásicos (sexo masculino, avanzada edad, dislipemia, LDL-C aumentado y HDL-C disminuido).

Atherosclerosis is the most prevalent vascular disease, which motivates extensive research on its pathogenesis. Lipoproteins can be modified by acetylation and oxidation mechanisms, at the level of lipid components as protein, becoming atherogenic. Modified Apolipoprotein B100 (ApoB100m), play an active role in the development of atherosclerotic lesions in conjunction with other risk factors. These have the ability to produce immune response leading to antibody production and subsequent formation of immune complexes. The importance of antibodies against ApoB100m in atherogenesis is still unclear since, contradictory data exist on whether their role is protective or atherogenic. Two objectives were established: to determine the levels of circulating immune complexes IgM-ApoB100m by enzyme immunoassay, in normal subjects (without atherogenic risk) and high-risk patients and to establish its correlation with atherogenic risk factors established by a cross-sectional study. Higher mean values of IgM-ApoB100m were obtained in the group of normal subjects. Immune complexes IgM-ApoB100 negatively correlated with classic atherogenic risk factors (male, older, dyslipidemia, increased LDL-C and decreased HDL-C).

A aterosclerose é a doença vascular mais prevalente, o que motiva numerosas pesquisas sobre sua patogênese. As lipoproteínas podem ser modificadas por meio de mecanismos de oxidação e de acetilação entre outros, em nível de seus componentes lipídicos como proteicos, tornando-se aterogênicas. As apolipoproteínas B100 modificadas (ApoB100m), desempenham um papel ativo no desenvolvimento de lesões ateroscleróticas em conjunto com outros fatores de risco. Elas têm a capacidade de produzir resposta imune que conduz à produção de anticorpos e subsequente formação de complexos imunes. A importância de anticorpos contra a ApoB100m na aterogênese ainda não é clara, existindo dados contraditórios sobre se seu papel é de proteção ou aterogênico. Foram estabelecidos dois objetivos. Determinar os níveis de complexos imunes circulantes IgM-ApoB100m por enzimoimunoanálise em indivíduos normais (sem risco aterogênico) e pacientes de alto risco e, estabelecer sua correlação com os fatores de risco aterogênico já estabelecidos por um estudo Observacional Transversal. Foram obtidos valores médios mais elevados de IgM-ApoB100m no grupo de indivíduos normais. Os complexos imunes IgM-ApoB100 correlacionam negativamente com os fatores de risco aterogênicos clássicos (sexo masculino, idosos, dislipidemia, LDL-C aumentado e HDL-C diminuído).

Efectividad de la metformina en pacientes con diabetes tipo II según variantes en el gen SLC22A1 / Effectiveness of Metformin in patients with type II diabetes related to variants in the SLC22A1 gene / Eficácia de Metformina em doentes com diabetes tipo II, relacionado com variantes do gene SLC22A1

La diabetes mellitus tipo II (DM II) es una enfermedad que afecta una gran cantidad de individuos. Un medicamento empleado en el tratamiento de los pacientes es la metformina. Este medicamento es transportado al interior de los hepatocitos por un transportador codificado por el gen SLC22A1. Variantes en el gen con actividad reducida pueden disminuir la cantidad de metformina disponible en el hígado y reducir la respuesta terapéutica. Se propuso evaluar diferentes parámetros bioquímicos en relación a la dosis de metformina y la presencia de variantes en el transportador. Se estudiaron 103 pacientes mayores de 18 años con diagnóstico de DM II, tratados con 1700 mg/día de metformina por más de 6 meses. Se analizaron 5 polimorfismos en el gen SLC22A1, glucemia, HbA1c, función hepática, perfil lipídico y renal. Los niveles de HbA1c y de glucemia fueron más elevados en los pacientes que presentaban los polimorfismos R61C, G401S, M420del y G465R aunque la diferencia fue estadísticamente significativa sólo para la HbA1c en los pacientes que presentaban las variantes M420del y G465R (p=0,0273 y 0,0018, respectivamente). La presencia de polimorfismos con actividad reducida en el gen SLC22A1 afecta los niveles de glucemia y de HbA1c en pacientes con DM II cuando son tratados con metformina.

Diabetes mellitus type II (DM II) is a disease that affects a large number of individuals. One of the drugs used for the treatment is metformin. Metformin is delivered into hepatocytes by a transporter encoded by the SLC22A1 gene. Gene variants with reduced activity may decrease the amount of metformin available in the liver and reduce the therapeutic response. Various biochemical parameters were evaluated in relation to the metformin dose and the presence of transporter variants. A total of 103 patients older than 18 diagnosed with DM II who were treated with 1700 mg/day of metformin for more than six months were studied. Five polymorphisms in the SLC22A1 gene were analyzed as well as glycemia, HbA1c level, liver function, and lipid and kidney profiles. HbA1c and glycemia levels were higher in patients with the R61C, G401S, M420del and G465R polymorphisms; although the difference was statistically significant only for HbA1c in patients with the M420del and G465R variants (p=0.0273 and 0.0018, respectively). Polymorphisms with reduced activity in the SLC22A1 gene affect blood glucose levels and HbA1c in patients with DM II when they are treated with metformin.

O diabetes mellitus tipo II (DM II) é uma doença que afeta uma grande quantidade de indivíduos. Um medicamento utilizado no tratamento dos doentes é a metformina. Esse medicamento é transportado no interior dos hepatócitos por um transportador codificado pelo gene SLC22A1. Variantes no gene com atividade reduzida podem diminuir a quantidade de Metformina disponível no fígado e reduzir a resposta terapêutica. Propôs-se avaliar diferentes parâmetros bioquímicos em relação à dose da metformina e à presença de variantes no transportador. Foram estudados 103 pacientes maiores de 18 anos com diagnóstico de DM II tratados com 1700 mg/dia de metformina por mais de 6 meses. Foram analisados 5 polimorfismos no gene SLC22A1; glicemia, HbA1c, função hepática, perfil lipídico e renal. Os níveis de HbA1c e de glicemia foram superiores em doentes que apresentavam os polimorfismos R61C, G401S, M420del e G465R; embora a diferença seja estatisticamente significativa apenas para o HbA1c nos doentes que apresentavam as variantes M420del e G465R (p=0,0273 e 0,0018; respectivamente). A presença de polimorfismos com atividade reduzida no gene SLC22A1 afeta os níveis da glicemia e do HbA1c em doentes com DM II quando são tratados com metformina.

Efectividad de la metformina en pacientes con diabetes tipo II según variantes en el gen SLC22A1 / Effectiveness of Metformin in patients with type II diabetes related to variants in the SLC22A1 gene / Eficácia de Metformina em doentes com diabetes tipo II, relacionado com variantes do gene SLC22A1

La diabetes mellitus tipo II (DM II) es una enfermedad que afecta una gran cantidad de individuos. Un medicamento empleado en el tratamiento de los pacientes es la metformina. Este medicamento es transportado al interior de los hepatocitos por un transportador codificado por el gen SLC22A1. Variantes en el gen con actividad reducida pueden disminuir la cantidad de metformina disponible en el hígado y reducir la respuesta terapéutica. Se propuso evaluar diferentes parámetros bioquímicos en relación a la dosis de metformina y la presencia de variantes en el transportador. Se estudiaron 103 pacientes mayores de 18 años con diagnóstico de DM II, tratados con 1700 mg/día de metformina por más de 6 meses. Se analizaron 5 polimorfismos en el gen SLC22A1, glucemia, HbA1c, función hepática, perfil lipídico y renal. Los niveles de HbA1c y de glucemia fueron más elevados en los pacientes que presentaban los polimorfismos R61C, G401S, M420del y G465R aunque la diferencia fue estadísticamente significativa sólo para la HbA1c en los pacientes que presentaban las variantes M420del y G465R (p=0,0273 y 0,0018, respectivamente). La presencia de polimorfismos con actividad reducida en el gen SLC22A1 afecta los niveles de glucemia y de HbA1c en pacientes con DM II cuando son tratados con metformina.(AU)

Diabetes mellitus type II (DM II) is a disease that affects a large number of individuals. One of the drugs used for the treatment is metformin. Metformin is delivered into hepatocytes by a transporter encoded by the SLC22A1 gene. Gene variants with reduced activity may decrease the amount of metformin available in the liver and reduce the therapeutic response. Various biochemical parameters were evaluated in relation to the metformin dose and the presence of transporter variants. A total of 103 patients older than 18 diagnosed with DM II who were treated with 1700 mg/day of metformin for more than six months were studied. Five polymorphisms in the SLC22A1 gene were analyzed as well as glycemia, HbA1c level, liver function, and lipid and kidney profiles. HbA1c and glycemia levels were higher in patients with the R61C, G401S, M420del and G465R polymorphisms; although the difference was statistically significant only for HbA1c in patients with the M420del and G465R variants (p=0.0273 and 0.0018, respectively). Polymorphisms with reduced activity in the SLC22A1 gene affect blood glucose levels and HbA1c in patients with DM II when they are treated with metformin.(AU)

O diabetes mellitus tipo II (DM II) é uma doenþa que afeta uma grande quantidade de indivíduos. Um medicamento utilizado no tratamento dos doentes é a metformina. Esse medicamento é transportado no interior dos hepatócitos por um transportador codificado pelo gene SLC22A1. Variantes no gene com atividade reduzida podem diminuir a quantidade de Metformina disponível no fígado e reduzir a resposta terapÛutica. Prop¶s-se avaliar diferentes parÔmetros bioquímicos em relaþÒo O dose da metformina e O presenþa de variantes no transportador. Foram estudados 103 pacientes maiores de 18 anos com diagnóstico de DM II tratados com 1700 mg/dia de metformina por mais de 6 meses. Foram analisados 5 polimorfismos no gene SLC22A1; glicemia, HbA1c, funþÒo hepática, perfil lipídico e renal. Os níveis de HbA1c e de glicemia foram superiores em doentes que apresentavam os polimorfismos R61C, G401S, M420del e G465R; embora a diferenþa seja estatisticamente significativa apenas para o HbA1c nos doentes que apresentavam as variantes M420del e G465R (p=0,0273 e 0,0018; respectivamente). A presenþa de polimorfismos com atividade reduzida no gene SLC22A1 afeta os níveis da glicemia e do HbA1c em doentes com DM II quando sÒo tratados com metformina.(AU)