Introduction: The NHLBI supported Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) (NCT0... more Introduction: The NHLBI supported Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) (NCT01206062) aimed to identify an SBP target to reduce incidence of cardiovascular (CV) morbidity and mortality in hypertensive, non-diabetic patients of age ≥ 50 at increased CV risk. It found that intensive treatment (SBP target <120 mmHg) led to fewer major CV events and death but higher rates of adverse events. We reused publicly available patient-level SPRINT data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF), to identify age specific baseline (bl) predictors for all-cause mortality (ACM). Methods: RSF was performed on 30 bl variables from 9361 patients in age group specific cohorts (50-59, 60-69, 70-79, 80-90). The identified top 10 predictors from each cohort were included in a multivariate analysis using a Cox proportional hazards model. Results: The top 10 predictors of ACM for...
Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldoste... more Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) (NCT00094302) investigated whether treatment with spironolactone reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and a left ventricular ejection fraction over 45%. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) on the American TOPCAT cohort (n=1767) to identify gender and age groups specific baseline (bl) predictors of hHF. Methods: The subjects were stratified into subgroups based on gender (male and female) and age (50-59, 60-69, 70-79, 80-90). Random Survival Forest (RSF), a non-parametric ML approach, evaluated 172 bl variables as predictors of hHF. Top 10 predictors were subsequently included in a multivariate Cox proportional hazards model. Results: The top 10 predictors of hHF are s...
Background: Multiple reports have pointed towards involvement of community and socioeconomic char... more Background: Multiple reports have pointed towards involvement of community and socioeconomic characteristics of people in the United States may be associated with COVID-19 cases and deaths. Methods: In this study, zip-code level data from 5 major metropolitan areas, was utilized to study the effect of multiple demographic & socio-economic factors including race, age, income, chronic disease comorbidity, population density, number of people per household on number of positive cases and ensuing death. Adjusted linear regression analysis using 13 to 16 such variables was performed. Results: Overall, 442 zip codes reporting 93,170 positive COVID-19 cases and 138 zip codes reporting mortality ranging from 0 to 25 were included in this study. A multivariable linear regression model noted that 1% increase in the proportion of residents above the age of 65 years, proportion of African American residents, proportion of females, persons per household and population density of the zip code inc...
Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE).... more Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined. Transcriptomics and epigenetic assessment of lupus LDGs, autologous normal-density neutrophils, and healthy control neutrophils was performed by bulk and single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. Functional readouts were compared among neutrophil subsets. SLE LDGs display significant transcriptional and epigenetic heterogeneity and comprise 2 subpopulations of intermediate-mature and immature neutrophils, with different degrees of chromatin accessibility and differences in transcription factor motif analysis. Differences in neutrophil extracellular trap (NET) formation, oxidized mitochondrial DNA release, chemotaxis...
Introduction: The NHLBI supported Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) (NCT0... more Introduction: The NHLBI supported Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) (NCT01206062) aimed to identify an SBP target to reduce incidence of cardiovascular (CV) morbidity and mortality in hypertensive, non-diabetic patients of age ≥ 50 at increased CV risk. It found that intensive treatment (SBP target <120 mmHg) led to fewer major CV events and death but higher rates of adverse events. We reused publicly available patient-level SPRINT data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF), to identify age specific baseline (bl) predictors for all-cause mortality (ACM). Methods: RSF was performed on 30 bl variables from 9361 patients in age group specific cohorts (50-59, 60-69, 70-79, 80-90). The identified top 10 predictors from each cohort were included in a multivariate analysis using a Cox proportional hazards model. Results: The top 10 predictors of ACM for...
Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldoste... more Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) (NCT00094302) investigated whether treatment with spironolactone reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and a left ventricular ejection fraction over 45%. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) on the American TOPCAT cohort (n=1767) to identify gender and age groups specific baseline (bl) predictors of hHF. Methods: The subjects were stratified into subgroups based on gender (male and female) and age (50-59, 60-69, 70-79, 80-90). Random Survival Forest (RSF), a non-parametric ML approach, evaluated 172 bl variables as predictors of hHF. Top 10 predictors were subsequently included in a multivariate Cox proportional hazards model. Results: The top 10 predictors of hHF are s...
Background: Multiple reports have pointed towards involvement of community and socioeconomic char... more Background: Multiple reports have pointed towards involvement of community and socioeconomic characteristics of people in the United States may be associated with COVID-19 cases and deaths. Methods: In this study, zip-code level data from 5 major metropolitan areas, was utilized to study the effect of multiple demographic & socio-economic factors including race, age, income, chronic disease comorbidity, population density, number of people per household on number of positive cases and ensuing death. Adjusted linear regression analysis using 13 to 16 such variables was performed. Results: Overall, 442 zip codes reporting 93,170 positive COVID-19 cases and 138 zip codes reporting mortality ranging from 0 to 25 were included in this study. A multivariable linear regression model noted that 1% increase in the proportion of residents above the age of 65 years, proportion of African American residents, proportion of females, persons per household and population density of the zip code inc...
Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE).... more Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined. Transcriptomics and epigenetic assessment of lupus LDGs, autologous normal-density neutrophils, and healthy control neutrophils was performed by bulk and single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. Functional readouts were compared among neutrophil subsets. SLE LDGs display significant transcriptional and epigenetic heterogeneity and comprise 2 subpopulations of intermediate-mature and immature neutrophils, with different degrees of chromatin accessibility and differences in transcription factor motif analysis. Differences in neutrophil extracellular trap (NET) formation, oxidized mitochondrial DNA release, chemotaxis...
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Papers by Amit Dey