8577 Columbine Rd
Eden Prairie MN 55344
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National variation in coronary angiography rates and timing after an acute coronary syndrome in New Zealand (ANZACS-QI 6). - The New Zealand medical journal
The New Zealand Cardiac Clinical Network and the Ministry of Health recommend a "3-day door-tocatheter target" for acute coronary syndromes (ACS) admissions, requiring that at least 70% of ACS patients referred for invasive coronary angiography (ICA) undergo this within 3 days of hospital admission. We assessed the variability in use of ICA, timing of ICA, and duration of hospital admission across New Zealand District Health Boards (DHBs).All patients admitted to all New Zealand public hospitals with suspected ACS undergoing ICA over 1 year ending November 2014 had demographic, risk factor, and diagnostic data collected prospectively using the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Complete datasets were available in 7,988 (98.4%) patients. DHBs were categorised as those able to perform percutaneous coronary intervention on-site (intervention-capable) or not.There was a near two-fold variation between DHBs in the age standardised rate (ASR) of ICA ranging from 16.8 per 10,000 to 34.1 per 10,000 population (New Zealand rate; 27.9 per 10,000). Patients in intervention-capable DHBs had a 30% higher ASR of ICA. The proportion of ACS patients meeting the 3-day target ranged from 56.7% to 92.9% (New Zealand; 76.4%). Those in intervention-capable DHBs were more likely to meet the target (78.7% vs 68.0%, p<0.0001) and spent 0.84 days (p<.0001) less in hospital.There is a considerable variation in the rate and timing of ICA in New Zealand. Patients with ACS admitted to DHBs without interventional-capability are disadvantaged. New initiatives to correct this discrepancy are needed.
Changing causes of heart valve disease mortality in New Zealand from 1988 to 2007. - The New Zealand medical journal
We wished to determine the mortality burden of valvular heart disease (VHD) in New Zealand, and how it changed prior to the introduction of transcatheter aortic valve replacement.Patient-level cause of death data from 1988 to 2007 were used to examine trends in VHD mortality rates over time. Our outcome measure was death, where the primary cause of death was valvular heart disease.The annual number of VHD deaths increased 2.9% in New Zealand each year (p<0.001). The total VHD mortality rate increased with older age and male sex. There was little, if any, overall change in age- and sex-adjusted total VHD mortality rate over time (annual mortality rate ratio 0.998, p=0.21). The oldest age group, aged 85 years and above, which now contribute most to total VHD mortality, had an increase in mortality rate through the 1990s, which plateaued after the year 2000. The adjusted mortality rate for non-rheumatic aortic valve disease increased (p<0.001), while that for rheumatic heart disease and endocarditis decreased (p<0.001). Assuming VHD mortality rates remain stable, deaths due to VHD are projected to double over the next 25 years.Adjusted VHD mortality rates showed no change over the two decades examined. Without a substantial reduction in mortality rates, the ageing population is likely to lead to an increase in VHD deaths in the future.
Management of non ST-elevationacute coronary syndrome patients in New Zealand: a longitudinal analysis. Results from the New Zealand Acute Coronary Syndrome national audits of 2002, 2007 and 2012. - The New Zealand medical journal
The first New Zealand Acute Coronary Syndrome (ACS) national audit of 2002 was a collaborative effort between clinicians and nurses, and demonstrated important limitations to Non ST-elevation ACS patient (NSTEACS) care. A momentum for change was created. Subsequent audits in 2007 and 2012 allow assessment over time.Over 14 days in May 2002, 2007 and 2012, patients with suspected ACS admitted to a hospital in New Zealand were audited. 'Definite' ACS was determined at discharge, after in-hospital investigations; we reviewed NSTEACS patients.From 2002, more patients underwent assessment of left ventricular function (echocardiogram) and coronary angiography. Evidence-based in-hospital medical treatments and revascularisation have also increased over the decade.Over a ten-year period, evidence-based care for patients presenting with a NSTEACS event in New Zealand has improved. However, considerable room remains to optimise management, particularly with development of systems of care to facilitate prompt referral and delivery of angiography in these high-risk individuals.
Bayesian Techniques for Comparison of the Test Performance of PCR and Culture for the Identification of Campylobacter in Enriched Comminuted Chicken Samples. - Journal of applied microbiology
Using Bayesian methods that do not require the definition of a gold standard, the diagnostic sensitivity and specificity of a real-time polymerase chain reaction (PCR) assay are compared to those of an enriched culture assay for detection of Campylobacter in enriched comminuted chicken samples.Food Safety and Inspection Service comminuted chicken samples were collected from production facilities across the United States. Enriched samples were examined using a commercial real-time PCR kit and plated for culture. Allowing for conditional dependence between these approaches and defining relatively uninformed prior distributions, the "no gold standard" Bayesian methods generated estimates of the means (95% credible interval) of the posterior distributions for sensitivity and specificity of the PCR as 93% (79%, 100%) and 95% (87%, 100%), respectively. The estimated sensitivity implies a mean false negative frequency of 7%. The estimated means of the posterior distributions for sensitivity and specificity of the culture assay were 91% (76%, 100%) and 96% (88%, 100%), respectively. In this case, the mean false negative frequency is 9%. Graphical comparisons of the posterior distributions with their corresponding prior distributions suggested only subtle differences for the sensitivities of both tests, but the posterior distributions for specificities are substantially more certain than the prior distributions.The study suggests that the commercial real-time PCR assay is a more sensitive screening test that would provide timelier negative test results. The modest 1% reduction in specificity of this PCR assay, as compared to an enriched culture assay, is less of a concern for regulatory testing programs if a culture-based confirmatory assay is applied to all presumptive positive samples.The sensitivity and specificity of a PCR assay and a culture assay for Campylobacter in comminuted poultry produced in the United States were estimated. The PCR assay was shown to be an appropriate alternative screening test. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
A competitive and reversible deactivation approach to catalysis-based quantitative assays. - Nature communications
Catalysis-based signal amplification makes optical assays highly sensitive and widely useful in chemical and biochemical research. However, assays must be fine-tuned to avoid signal saturation, substrate depletion and nonlinear performance. Furthermore, once stopped, such assays cannot be restarted, limiting the dynamic range to two orders of magnitude with respect to analyte concentrations. In addition, abundant analytes are difficult to quantify under catalytic conditions due to rapid signal saturation. Herein, we report an approach in which a catalytic reaction competes with a concomitant inactivation of the catalyst or consumption of a reagent required for signal generation. As such, signal generation proceeds for a limited time, then autonomously and reversibly stalls. In two catalysis-based assays, we demonstrate restarting autonomously stalled reactions, enabling accurate measurement over five orders of magnitude, including analyte levels above substrate concentration. This indicates that the dynamic range of catalysis-based assays can be significantly broadened through competitive and reversible deactivation.
Venous thromboembolism occurring during adolescence. - Archives of disease in childhood
Risk assessment for venous thromboembolism (VTE) and thromboprophylaxis in those with risk factors is established in adult practice. Evidence to support efficacy and safety of this approach in adolescents is lacking. We aimed to describe thrombotic risk factors and to determine the proportion of potentially preventable events in a retrospective cohort study of adolescents with VTE.Data were collected between 2008 and 2014 from eight tertiary UK centres. Qualifying events were radiologically confirmed VTE in subjects aged 12-17â€…years. Central venous line-related upper venous system events were excluded.76 cases were identified, 41 males, median age 15â€…years. Frequent risk factors were: reduced mobility, 45%; thrombophilia, 24%; malignancy, 20%; surgery, 18%; combined oral contraceptive pill, 12%; congenital venous anomaly, 5%. 28 (37%) had no significant underlying diagnosis and no provoking event/hospitalisation, presenting as outpatients with VTE which was considered 'unpreventable'. Of 48 where there had been opportunity for risk assessment, chemical thromboprophylaxis was not indicated in 26 and was contraindicated in 8. 14/76 (18%) had an indication to consider thromboprophylaxis and no contraindication. Of these, four had cerebral palsy, five malignancy and two inflammatory bowel disease. All had reduced mobility with recent surgery in eight. Four received chemical thromboprophylaxis prior to presentation.Among a cohort of adolescents with VTE, a small proportion (13%) had an indication to consider chemical thromboprophylaxis but did not receive it. VTE risk assessment and prevention should focus on adolescents with immobility or surgery, particularly in those with malignancy.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Irreproducibility in Preclinical Biomedical Research: Perceptions, Uncertainties, and Knowledge Gaps. - Trends in pharmacological sciences
Concerns regarding the reliability of biomedical research outcomes were precipitated by two independent reports from the pharmaceutical industry that documented a lack of reproducibility in preclinical research in the areas of oncology, endocrinology, and hematology. Given their potential impact on public health, these concerns have been extensively covered in the media. Assessing the magnitude and scope of irreproducibility is limited by the anecdotal nature of the initial reports and a lack of quantitative data on specific failures to reproduce published research. Nevertheless, remediation activities have focused on needed enhancements in transparency and consistency in the reporting of experimental methodologies and results. While such initiatives can effectively bridge knowledge gaps and facilitate best practices across established and emerging research disciplines and therapeutic areas, concerns remain on how these improve on the historical process of independent replication in validating research findings and their potential to inhibit scientific innovation.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
Post-ibrutinib outcomes in patients with mantle cell lymphoma. - Blood
Despite unprecedented clinical activity in mantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients that experience ibrutinib failure are unclear. We performed a retrospective cohort study of all patients with MCL that experienced disease progression while receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological, and radiological data, and therapies used pre and post ibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range 0-10). The MIPI scores at start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23%, respectively. Of patients with available data prior to ibrutinib and post-ibrutinib, 34/47 and 11/12 had a Ki67>30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% CI 1.6-4.9 months). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% C.I. 3.7 to 10.4 months). Multivariate Cox regression analysis of MIPI prior to post-ibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment following ibrutinib.Copyright Â© 2016 American Society of Hematology.
The prehospital and hospital costs of emergency care for frequent ED patients. - The American journal of emergency medicine
Frequent emergency department (ED) use has been identified as a cause of ED overcrowding and increasing health care costs. Studies have examined the expense of frequent patients (FPs) to hospitals but have not added the cost Emergency Medical Services (EMS) to estimate the total cost of this pattern of care.Data on 2012 ED visits to a rural Level I Trauma Center and public safety net hospital were collected through a deidentified patient database. Transport data and 2012 Medicare Reimbursement Schedules were used to estimate the cost of EMS transport. Health information, outcomes, and costs were compared to find differences between the FP and non-FP group.This study identified 1242 FPs who visited the ED 5 or more times in 2012. Frequent patients comprised 3.25% of ED patients but accounted for 17% of ED visits and 13.7% of hospital costs. Frequent patients had higher rates of chronic disease, severity scores, and mortality. Frequent patients arrived more often via ambulance and accounted for 32% of total transports at an estimated cost of $2.5-$3.2 million. Hospital costs attributable to FPs were $29.1 million, bringing the total cost of emergency care to $31.6-$32.3 million, approximately $25,000 per patient.This study demonstrates that the inclusion a prehospital cost estimate adds approximately 10% to the cost of care for the FP population. In addition to improving care for a sick population of patients, programs that reduce frequent EMS and ED use have the potential to produce a favorable cost benefit to communities and health systems.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior. - Genetics
The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a large-scale genetical genomics analysis in the brains of chickens to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl. We identify 10 putative quantitative trait genes affecting anxiety behavior. These genes were tested for an association in the mouse Heterogeneous Stock anxiety (open field) data set and human GWAS data sets for bipolar disorder, major depressive disorder, and schizophrenia. Although comparisons between species are complex, associations were observed for four of the candidate genes in mice and three of the candidate genes in humans. Using a multimodel approach we have therefore identified a number of putative quantitative trait genes affecting anxiety behavior, principally in chickens but also with some potentially translational effects as well. This study demonstrates that chickens are an excellent model organism for the genetic dissection of behavior.Copyright Â© 2016 by the Genetics Society of America.
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