Palm Desert, CA, United States
Palm Desert, CA, United States

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Ghorbanian P.,Villanova University | Devilbiss D.M.,NexStep Biomarkers | Verma A.,Brain Computer Interface, LLC | Bernstein A.,Palm Drive Hospital | And 3 more authors.
Annals of Biomedical Engineering | Year: 2013

Alzheimer's disease (AD) is associated with deficits in a number of cognitive processes and executive functions. Moreover, abnormalities in the electroencephalogram (EEG) power spectrum develop with the progression of AD. These features have been traditionally characterized with montage recordings and conventional spectral analysis during resting eyes-closed and resting eyes-open (EO) conditions. In this study, we introduce a single lead dry electrode EEG device which was employed on AD and control subjects during resting and activated battery of cognitive and sensory tasks such as Paced Auditory Serial Addition Test (PASAT) and auditory stimulations. EEG signals were recorded over the left prefrontal cortex (Fp1) from each subject. EEG signals were decomposed into sub-bands approximately corresponding to the major brain frequency bands using several different discrete wavelet transforms and developed statistical features for each band. Decision tree algorithms along with univariate and multivariate statistical analysis were used to identify the most predictive features across resting and active states, separately and collectively. During resting state recordings, we found that the AD patients exhibited elevated D4 (~4-8 Hz) mean power in EO state as their most distinctive feature. During the active states, however, the majority of AD patients exhibited larger minimum D3 (~8-12 Hz) values during auditory stimulation (18 Hz) combined with increased kurtosis of D5 (~2-4 Hz) during PASAT with 2 s interval. When analyzed using EEG recording data across all tasks, the most predictive AD patient features were a combination of the first two feature sets. However, the dominant discriminating feature for the majority of AD patients were still the same features as the active state analysis. The results from this small sample size pilot study indicate that although EEG recordings during resting conditions are able to differentiate AD from control subjects, EEG activity recorded during active engagement in cognitive and auditory tasks provide important distinct features, some of which may be among the most predictive discriminating features. © 2013 Biomedical Engineering Society.


Winkler C.,Fairfield University | Funk M.,Yale University | Schindler D.M.,Palm Drive Hospital | Hemsey J.Z.,University of California at San Francisco | And 2 more authors.
Heart and Lung: Journal of Acute and Critical Care | Year: 2013

Objectives: In patients with acute coronary syndrome (ACS), we sought to: 1) describe arrhythmias during hospitalization, 2) explore the association between arrhythmias and patient outcomes, and 3) explore predictors of the occurrence of arrhythmias. Methods: In a prospective sub-study of the IMMEDIATE AIM study, we analyzed electrocardiographic (ECG) data from 278 patients with ACS. On emergency department admission, a Holter recorder was attached for continuous 12-lead ECG monitoring. Results: Approximately 22% of patients had more than 50 premature ventricular contractions (PVCs) per hour. Non-sustained ventricular tachycardia (VT) occurred in 15% of patients. Very few patients (≤1%) had a malignant arrhythmia (sustained VT, asystole, torsade de pointes, or ventricular fibrillation). Only more than 50PVCs/hour independently predicted an increased length of stay ( p<.0001). No arrhythmias predicted mortality. Age greater than 65 years and a final diagnosis of acute myocardial infarction independently predicted more than 50PVCs per hour ( p=.0004). Conclusions: Patients with ACS seem to have fewer serious arrhythmias today, which may have implications for the appropriate use of continuous ECG monitoring. © 2013 Elsevier Inc.


Gianfrancesco M.A.,University of California at Berkeley | Acuna B.,Kaiser Permanente | Shen L.,Kaiser Permanente | Briggs F.B.S.,University of California at Berkeley | And 11 more authors.
Obesity Research and Clinical Practice | Year: 2014

Objective: To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors.Methods: Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regres-sion models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied.Results: In analyses stratified by gender, being overweight at ages 10 and 20 wereassociated with MS in females( P < 0.01). Estimates trended in the same direction formales, but were not significant. BMI in 20s demonstrated a linear relationship withMS (p-trend = 9.60 10-4), and a twofold risk of MS for females with a BMI ≥30 kg/m2was observed (OR = 2.15, 95% CI 1.18, 3.92). Significant associations between BMI in20s and MS in males were not observed. Multivariate modelling demonstrated thatsignificant associations between BMI or body size with MS in females persisted afteradjusting for history of infectious mononucleosis and genetic risk factors, includingHLA-DRB1∗15:01 and established non-HLA risk alleles.Interpretation: Results show that childhood and adolescence obesity confer increasedrisk of MS in females beyond established heritable and environmental risk factors.Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitudeof BMI association with MS is as large as other known MS risk factors. © 2014 Asian Oceanian Association for the Study of Obesity.


Pittock S.J.,Mayo Medical School | Lennon V.A.,Mayo Medical School | Bakshi N.,Permanente Medical Group | Shen L.,Kaiser Permanente | And 7 more authors.
JAMA Neurology | Year: 2014

IMPORTANCE: Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay. OBSERVATIONS: Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transversemyelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive. CONCLUSIONS AND RELEVANCE: Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5%and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA. Copyright 2014 American Medical Association. All rights reserved.


Briggs F.B.S.,University of California at Berkeley | Acuna B.,Kaiser Permanente | Shen L.,Kaiser Permanente | Ramsay P.,University of California at Berkeley | And 10 more authors.
Epidemiology | Year: 2014

BACKGROUND: Tobacco smoke is an established risk factor for multiple sclerosis (MS). We hypothesized that variation in genes involved in metabolism of tobacco smoke constituents may modify MS risk in smokers. METHODS: A three-stage gene-environment investigation was conducted for NAT1, NAT2, and GSTP1 variants. The discovery analysis was conducted among 1588 white MS cases and controls from the Kaiser Permanente Northern California Region HealthPlan (Kaiser). The replication analysis was carried out in 988 white MS cases and controls from Sweden. RESULTS: Tobacco smoke exposure at the age of 20 years was associated with greater MS risk in both data sets (in Kaiser, odds ratio [OR] = 1.51 [95% confidence interval (CI) = 1.17-1.93]; in Sweden, OR = 1.35 [1.04-1.74]). A total of 42 NAT1 variants showed evidence for interaction with tobacco smoke exposure (Pcorrected < 0.05). Genotypes for 41 NAT1 single nucleotide polymorphisms (SNPs) were studied in the replication data set. A variant (rs7388368C>A) within a dense transcription factor-binding region showed evidence for interaction (Kaiser, OR for interaction = 1.75 [95% CI = 1.19-2.56]; Sweden, OR = 1.62 [1.05-2.49]). Tobacco smoke exposure was associated with MS risk among rs7388368A carriers only; homozygote individuals had the highest risk (A/A, OR = 5.17 [95% CI = 2.17-12.33]). CONCLUSIONS: We conducted a three-stage analysis using two population-based case-control datasets that consisted of a discovery population, a replication population, and a pooled analysis. NAT1 emerged as a genetic effect modifier of tobacco smoke exposure in MS susceptibility. Copyright © 2014 by Lippincott Williams & Wilkins.


Briggs F.B.S.,University of California at Berkeley | Acuna B.S.,Kaiser Permanente | Shen L.,Kaiser Permanente | Bellesis K.H.,Kaiser Permanente | And 6 more authors.
Journal of Epidemiology and Community Health | Year: 2014

Background: Adverse socioeconomic position (SEP) in childhood and adulthood is associated with a proinflammatory phenotype, and therefore an important exposure to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune disease. The objective was to determine whether SEP over the life course confers increased susceptibility to MS. Methods: 1643 white, non-Hispanic MS case and control members recruited from the Kaiser Permanente Medical Care Plan, Northern California Region, for which comprehensive genetic, clinical and environmental exposure data have been collected were studied. Logistic regression models investigated measures of childhood and adulthood SEP, and accounted for effects due to established MS risk factors, including HLA-DRB1*15:01 allele carrier status, smoking history, history of infectious mononucleosis, family history of MS and body size. Results: Multiple measures of childhood and adulthood SEP were significantly associated with risk of MS, including parents renting versus owning a home at age 10: OR=1.48, 95% CI 1.09 to 2.02, p=0.013; less than a college education versus at least a college education based on parental household: OR=1.28, 95% CI 1.01 to 1.63, p=0.041; low versus high life course SEP: OR=1.50, 95% CI 1.09 to 2.05, p=0.012; and low versus high social mobility: OR=1.74, 95% CI 1.27 to 2.39, p=5.7×10-4. Conclusions: Results derived from a populationrepresentative case-control study provide support for the role of adverse SEP in MS susceptibility and add to the growing evidence linking lower SEP to poorer health outcomes. Both genetic and environmental contributions to chronic conditions are important and must be characterised to fully understand MS aetiology.


PubMed | Kaiser Permanente, University of California at Berkeley and Palm Drive Hospital
Type: Journal Article | Journal: Journal of epidemiology and community health | Year: 2014

Adverse socioeconomic position (SEP) in childhood and adulthood is associated with a proinflammatory phenotype, and therefore an important exposure to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune disease. The objective was to determine whether SEP over the life course confers increased susceptibility to MS.1643 white, non-Hispanic MS case and control members recruited from the Kaiser Permanente Medical Care Plan, Northern California Region, for which comprehensive genetic, clinical and environmental exposure data have been collected were studied. Logistic regression models investigated measures of childhood and adulthood SEP, and accounted for effects due to established MS risk factors, including HLA-DRB1*15:01 allele carrier status, smoking history, history of infectious mononucleosis, family history of MS and body size.Multiple measures of childhood and adulthood SEP were significantly associated with risk of MS, including parents renting versus owning a home at age 10: OR=1.48, 95% CI 1.09 to 2.02, p=0.013; less than a college education versus at least a college education based on parental household: OR=1.28, 95% CI 1.01 to 1.63, p=0.041; low versus high life course SEP: OR=1.50, 95% CI 1.09 to 2.05, p=0.012; and low versus high social mobility: OR=1.74, 95% CI 1.27 to 2.39, p=5.710(-4).Results derived from a population-representative case-control study provide support for the role of adverse SEP in MS susceptibility and add to the growing evidence linking lower SEP to poorer health outcomes. Both genetic and environmental contributions to chronic conditions are important and must be characterised to fully understand MS aetiology.


PubMed | Kaiser Permanente, Karolinska Institutet, University of California at Berkeley and Palm Drive Hospital
Type: Journal Article | Journal: Obesity research & clinical practice | Year: 2014

To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors.Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied.In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.6010(-4)), and a twofold risk of MS for females with a BMI30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles.Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.


PubMed | Kaiser Permanente, Mayo Medical School, The Permanente Medical Group, University of California at Berkeley and Palm Drive Hospital
Type: Journal Article | Journal: JAMA neurology | Year: 2014

Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay.Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive.Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.


PubMed | Palm Drive Hospital, Villanova University, NexStep Biomarkers LLC and Cerora Inc.
Type: Journal Article | Journal: Medical & biological engineering & computing | Year: 2015

We have developed a novel approach to elucidate several discriminating EEG features of Alzheimers disease. The approach is based on the use of a variety of continuous wavelet transforms, pairwise statistical tests with multiple comparison correction, and several decision tree algorithms, in order to choose the most prominent EEG features from a single sensor. A pilot study was conducted to record EEG signals from Alzheimers disease (AD) patients and healthy age-matched control (CTL) subjects using a single dry electrode device during several eyes-closed (EC) and eyes-open (EO) resting conditions. We computed the power spectrum distribution properties and wavelet and sample entropy of the wavelet coefficients time series at scale ranges approximately corresponding to the major brain frequency bands. A predictive index was developed using the results from statistical tests and decision tree algorithms to identify the most reliable significant features of the AD patients when compared to healthy controls. The three most dominant features were identified as larger absolute mean power and larger standard deviation of the wavelet scales corresponding to 4-8 Hz () during EO and lower wavelet entropy of the wavelet scales corresponding to 8-12 Hz () during EC, respectively. The fourth reliable set of distinguishing features of AD patients was lower relative power of the wavelet scales corresponding to 12-30 Hz () followed by lower skewness of the wavelet scales corresponding to 2-4 Hz (upper ), both during EO. In general, the results indicate slowing and lower complexity of EEG signal in AD patients using a very easy-to-use and convenient single dry electrode device.

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