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Utility of device-derived daily activity, a novel digital biomarker, to predict ventricular arrhythmias-data from the CERTITUDE registry [Meeting Abstract]

Kutyifa, V; Rosero, S; Harrel, C; Singh, J; Hicks, J; Chinitz, L; Varma, N; Piccini, J; Turakhia, M
Background: While there have been prior studies showing an association between activity and outcomes, there have been no studies examining the temporal relationship between device-derived daily activity, a novel digital biomarker, and ventricular tachyarrhythmias (VT).
Purpose(s): In a big dataset with over 55,000 pacemaker, ICD, and CRT devices, we aimed to identify whether changes in activity predict VT, or else VT predict changes in activity.
Method(s): The CERTITUDE registry comprises a de-identified database of over 55,000 U.S. BIOTRONIK pacemaker, ICD, CRT devices, and loop recorders active on Home Monitoring. Daily data on leads, arrhythmias, and physiological parameters such as activity are captured. Patient activity is reported daily as percentage active during the day, assessed by a one-axis accelerometer at ~0.4 Hz frequency. Analysis to ascertain temporal changes in device-derived activity associated with treated VT was performed using the first event per device and 7-day activity windows (baseline, pre- and post-event). Baseline period was defined as 31-38 days prior to VT. VT events were categorized by heart rate (<=200 bpm,>200 bpm) and treatment (shock with or without ATP, ATP alone). Differences in activity between baseline, and pre- and post-VT were analyzed using the binomial proportion test.
Result(s): A total of 16,475 devices (9732 ICDs, 6743 CRT-Ds) had activity data available for analysis. The cumulative follow-up duration was 18,355 years (5.6 million days with transmission). Of the 2636 VT events analyzed, 1409 had a heart rate >200 bpm, and 593 were treated with shock. Patients with VT events >200 bpm treated with shock had a significant reduction in activity post-VT with a median -8.7% reduction (IQR -24.6%; 7.3%, p<0.001). However, there was no reduction in activity before the VT>200 bpm (p=0.690) (Figure). VT events >200 bpm treated with ATP alone were not associated with reduction in activity before or after the episode. Similarly, VT events <=200 bpm treated with shock were also associated with a reduction in activity following the event (-5.8%, IQR -29.5, 12.3%, p=0.003), but not prior to the VT event.
Conclusion(s): In this report from the CERTITUDE registry, we have shown a temporal decline in device-derived activity following ventricular arrhythmias>200 bpm and <=200 bpm treated with a shock, but not in patients treated with ATP. Monitoring device-derived activity post-VT events with a shock could provide relevant clinical information and potentially warrant intensified treatment
EMBASE:636529888
ISSN: 1522-9645
CID: 5083222

Single-Cell Applications of Next-Generation Sequencing

Anaparthy, Naishitha; Ho, Yu-Jui; Martelotto, Luciano; Hammell, Molly; Hicks, James
The single cell is considered the basic unit of biology, and the pursuit of understanding how heterogeneous populations of cells can functionally coexist in tissues, organisms, microbial ecosystems, and even cancer, makes them the subject of intense study. Next-generation sequencing (NGS) of RNA and DNA has opened a new frontier of (single)-cell biology. Hundreds to millions of cells now can be assayed in parallel, providing the molecular profile of each cell in its milieu inexpensively and in a manner that can be analyzed mathematically. The goal of this article is to provide a high-level overview of single-cell sequencing for the nonexpert and show how its applications are influencing both basic and applied clinical studies in embryology, developmental genetics, and cancer.
PMCID:6771363
PMID: 30617056
ISSN: 2157-1422
CID: 5428592

Single-cell RNA-seq analysis identifies markers of resistance to targeted BRAF inhibitors in melanoma cell populations

Ho, Yu-Jui; Anaparthy, Naishitha; Molik, David; Mathew, Grinu; Aicher, Toby; Patel, Ami; Hicks, James; Hammell, Molly Gale
Single-cell RNA-seq's (scRNA-seq) unprecedented cellular resolution at a genome-wide scale enables us to address questions about cellular heterogeneity that are inaccessible using methods that average over bulk tissue extracts. However, scRNA-seq data sets also present additional challenges such as high transcript dropout rates, stochastic transcription events, and complex population substructures. Here, we present a single-cell RNA-seq analysis and klustering evaluation (SAKE), a robust method for scRNA-seq analysis that provides quantitative statistical metrics at each step of the analysis pipeline. Comparing SAKE to multiple single-cell analysis methods shows that most methods perform similarly across a wide range of cellular contexts, with SAKE outperforming these methods in the case of large complex populations. We next applied the SAKE algorithms to identify drug-resistant cellular populations as human melanoma cells respond to targeted BRAF inhibitors (BRAFi). Single-cell RNA-seq data from both the Fluidigm C1 and 10x Genomics platforms were analyzed with SAKE to dissect this problem at multiple scales. Data from both platforms indicate that BRAF inhibitor-resistant cells can emerge from rare populations already present before drug application, with SAKE identifying both novel and known markers of resistance. These experimentally validated markers of BRAFi resistance share overlap with previous analyses in different melanoma cell lines, demonstrating the generality of these findings and highlighting the utility of single-cell analysis to elucidate mechanisms of BRAFi resistance.
PMCID:6120620
PMID: 30061114
ISSN: 1549-5469
CID: 5428462

Fifty signs of mental illness : a guide to understanding mental health

Hicks, James Whitney
New Haven : Yale University Press, c2005
Extent: xiii, 389 p. ; 24 cm.
ISBN: 9780300116946
CID: 2459

Ethnicity, race, and forensic psychiatry: are we color-blind?

Hicks, James W
Race, ethnicity, and culture have an effect on all aspects of mental illness. Forensic psychiatrists and psychologists should consider these issues when performing evaluations for legal purposes and when providing treatment to the special populations with whom they work. This article defines race and ethnicity and reviews the available literature on the impact of race and ethnicity on diagnosis, dangerousness assessment, involuntary commitment, competency, criminal matters, evaluation of children and matters related to them, and tort issues. Also discussed is the effect of ethnicity on the role of the forensic evaluator in his or her interactions with the subject and the justice system. Forensic evaluators are encouraged to develop specific skills related to competency in dealing with cultural matters
PMID: 15497624
ISSN: 1093-6793
CID: 147203

Legal regulation of psychiatry

Chapter by: Hicks, James W
in: Principles and practice of forensic psychiatry by Rosner, Richard [Eds]
London : Arnold ; New York : Distributed in the USA by Oxford University Press, c2003
pp. 850-876
ISBN: 9780340806647
CID: 5978