Using heterogeneous, longitudinal EHR data for risk assessment and early detection of cardiovascular disease

Cardiovascular disease (CVD) affects millions of people and is a leading cause of death worldwide. CVD consists of a broad set of conditions including structural heart disease, coronary artery disease and stroke. Risk for each of these conditions accumulates over long periods of time depending on several risk factors. In order to reduce morbidity and mortality due to CVD, preventative treatments administered prior to first CVD event are critical. According to clinical guidelines, such treatments should be guided by an individual’s total risk within a window of time. A related objective is secondary prevention, or early detection, wherein the aim is to identify and mitigate the impact of a disease that has already taken effect. With the widespread adoption of electronic health records (EHRs), there is tremendous opportunity to build better methods for risk assessment and early detection. However, existing methods which use EHRs are limited in several ways: (1) they do not leverage the full longitudinal history of patients, (2) they use a limited feature set or specific data modalities, and (3) they are rarely validated in broader populations and across different institutions. In this dissertation, I address each of these limitations. In Aim 1, I explore the challenge of handling longitudinal, irregularly sampled clinical data, proposing discriminative and generative approaches to model this data. In Aim 2, I develop a multimodal approach for the early detection of structural heart disease. Finally, in Aim 3, I study how different feature inclusion choices affect the transportability of deep risk assessment models of coronary artery disease across institutions. Collectively, this dissertation contributes important insights towards building better approaches for risk assessment and early detection of CVD using EHR data and systematically assessing their transportability across institutions and populations

Reversal agents for NOACs: Connecting the dots

Objective: The objective of this review is to provide an overview on the current development of the specific reversal agents for Non-vitamin K Oral Anticoagulants (NOACs). Methods: We conducted a systematic literature search strategy to identify potential studies on Medline, Embase, and the Cochrane register. Conclusions: These new reversal agents for NOACs, will help address the unmet need for the management of major or life threatening bleeds, and the management of emergency surgical procedures in patients taking NOACs. It will increase confidence in the use of NOACs; thereby extending treatment to a wider range of patients

Unusual immunophenotype of T-cell large granular lymphocytic leukemia: Report of two cases

Large granular lymphocytes (LGL) leukemias are commonly of the T-cell or NK-cell type. T-cell LGL leukemia is typically a disorder of mature CD3, CD8 and T-cell receptor TCR (TCR - T cell receptor)-αβ positive cytotoxic T-cells. Rare variants include TCRγδ+ variants and CD4 + TCRαβ+ cases. We report a case of each of these rare variants. An 83-year-old female presented with anemia and lymphocytosis with LGLs on peripheral smear. Six-color multiparametric flowcytometric analysis showed expression of CD3, heterogeneous CD7, dim CD2 and TCRγδ and lacked expression of CD5, TCRαβ, CD56, CD4 and CD8. A final diagnosis of TCRγδ+ T-cell LGL leukemia was made. Differentiation between TCRγδ+ T-cell LGL leukemia and other γδ+ T-cell malignancies is of utmost importance due to the indolent nature of the former as compared to the highly aggressive behavior of the latter. An 85-year-old male diagnosed with liposarcoma was identified to have lymphocytosis during preoperative evaluation. Peripheral smear showed presence of LGLs. Flowcytometric immunophenotyping showed expression of TCRαβ, CD3, CD2, CD5, CD4, dim CD8, CD56 with aberrant loss of CD7 expression. Vβ repertoire analysis by flowcytometry showed 97% cells with Vβ14 clonality. A final diagnosis of TCRαβ+ CD4 + T-cell LGL leukemia was made. CD4 + T-cell large granular lymphocytic leukemias have an indolent, less aggressive course when compared to their CD8 + counterparts and are not necessarily associated with cytopenias. However, their association with secondary neoplasia (29% of the cases) warrants a high degree of suspicion in the diagnosis as also noted in the index case. Use of a wide panel of antibodies and newer modalities such as Vβ repertoire analysis helps in accurate subtyping of LGL leukemia

The Indian consensus guidance on stroke prevention in atrial fibrillation: An emphasis on practical use of nonvitamin K oral anticoagulants

The last ten years have seen rapid strides in the evolution of nonvitamin K oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). For the preparation of this consensus, a comprehensive literature search was performed and data on available trials, subpopulation analyses, and case reports were analyzed. This Indian consensus document intends to provide guidance on selecting the right NOAC for the right patients by formulating expert opinions based on the available trials and Asian/Indian subpopulation analyses of these trials. A section has been dedicated to the current evidence of NOACs in the Asian population. Practical suggestions have been formulated in the following clinical situations: (i) Dose recommendations of the NOACs in different clinical scenarios; (ii) NOACs in patients with rheumatic heart disease (RHD); (iii) Monitoring anticoagulant effect of the NOACs; (iv) Overdose of NOACs; (v) Antidotes to NOACs; (vi) Treatment of hypertrophic cardiomyopathy (HCM) with AF using NOACs; (vii) NOACs dose in elderly, (viii) Switching between NOACs and vitamin K antagonists (VKA); (ix) Cardioversion or ablation in NOAC-treated patients; (x) Planned/emergency surgical interventions in patients currently on NOACs; (xi) Management of bleeding complications of NOACs; (xii) Management of acute coronary syndrome (ACS) in AF with NOACs; (xiii) Management of acute ischemic stroke while on NOACs