29 results on '"Dworkis DA"'
Search Results
2. A genome-wide association study of total Bilirubin and Cholelithiasis risk in sickle cell anemia
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Milton, JN, Sebastiani, P, Solovieff, N, Hartley, SW, Bhatnagar, P, Arking, DE, Dworkis, DA, Casella, JF, Barron-Casella, E, Bean, CJ, Hooper, WC, DeBaun, MR, Garrett, ME, Soldano, K, Telen, MJ, Ashley-Koch, A, Gladwin, MT, Baldwin, CT, Steinberg, MH, Klings, ES, Milton, JN, Sebastiani, P, Solovieff, N, Hartley, SW, Bhatnagar, P, Arking, DE, Dworkis, DA, Casella, JF, Barron-Casella, E, Bean, CJ, Hooper, WC, DeBaun, MR, Garrett, ME, Soldano, K, Telen, MJ, Ashley-Koch, A, Gladwin, MT, Baldwin, CT, Steinberg, MH, and Klings, ES
- Abstract
Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10-8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10-25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10-4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities. © 2012 Milton et al.
- Published
- 2012
3. Characteristics and Outcomes of 360 Consecutive COVID-19 Patients Discharged From the Emergency Department With Supplemental Oxygen.
- Author
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Terp S, Reichert Z, Burner E, Randhawa J, Axeen S, Messina M, Dworkis DA, Menchine M, Lam CN, Banerjee J, Spellberg B, and Arora S
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- Humans, Hospitalization, Emergency Service, Hospital, Oxygen, Retrospective Studies, Patient Discharge, COVID-19 therapy
- Abstract
Study Objective: To describe characteristics and outcomes of coronavirus disease (COVID-19) patients with new supplemental oxygen requirements discharged from a large public urban emergency department (ED) with supplemental oxygen., Methods: This observational case series describes the characteristics and outcomes of 360 consecutive COVID-19 patients with new supplemental oxygen requirements discharged from a large urban public ED between April 2020 and March 2021 with supplemental oxygen. Primary outcomes included 30-day survival and 30-day survival without unscheduled inpatient admission. Demographic and clinical data were collected through a structured chart review., Results: Among 360 patients with COVID-19 discharged from the ED with supplemental oxygen, 30-day survival was 97.5% (95% confidence interval (CI) 95.3 to 98.9%; n=351), and 30-day survival without unscheduled admission was 81.1% (95% CI 76.7 to 85.0%; n=292). A sensitivity analysis incorporating worst-case-scenario for 12 patients without complete follow-up 30 days after index visit yields 30-day survival of 95.5% (95% CI 92.5 to 97.2%; n=343), and 30-day survival without unscheduled admission of 78.9% (95% CI 74.3 to 83.0%; n=284). Among study patients, 32.2% (n=116) had a nadir ED oxygen saturation of <90%, among these 30-day survival was 97.4% (95% CI 92.6 to 99.4%; n=113), and 30-day survival without unscheduled admission was 76.7% (95% CI 68.8 to 84.1%; n=89)., Conclusion: COVID-19 patients with new supplemental oxygen requirements discharged from the ED had survival comparable to COVID-19 ED patients with mild exertional hypoxia treated with supplemental oxygen in other settings, and this held true when the analysis was restricted to patients with nadir ED index visit oxygen saturations <90%. Discharge of select COVID-19 patients with supplemental oxygen from the ED may provide a viable alternative to hospitalization, particularly when inpatient capacity is limited., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)
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- 2023
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4. Cognitive load during training for out-of-department emergency responses.
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Dworkis DA, Jain A, Wolfe M, Sanko S, and Arora S
- Abstract
Background: Emergency medicine (EM) physicians sometimes respond to critical events outside the emergency department. To prepare for these complex cases-typically called "rapid responses" (RRs)-EM residents receive simulation-based training involving four practice tasks and three exam tasks during a 1-day session. Cognitive load (CL) theory describes how humans function with limited working memories to perform complex tasks. RRs are expected to generate high levels of CL, but the profile of CL across providers and RR cases is not well understood. In this study, we analyzed resident's CL during RR training. We hypothesized variations in CL across individual and case and that exam cases would cause higher CLs than practice cases., Methods: Residents anonymously self-reported CL levels after each case using the Paas scale, a single-item, 9-point scale from "very, very low CL" to "very, very high CL." To examine case-based differences in CL, data were rescaled by individual residents. "High CL" was defined as a score of 9/9., Results: Among 18 residents participating, CLs ranged from 4 to 9, with median of 7 and interquartile range of 7-8. While many cases showed bell curve-like distributions of CLs, one case-a bleeding tracheostomy-showed a rightward skew reflecting higher levels of CL. No significant difference was found in CL between practice and exam cases. There were 20 reports (16.5%) of "high" CL with variation across residents (0/7 [0%] to 5/6 [83.3%] cases) and across cases (1/18 [5.6%) to 8/18 [44.4%])., Conclusions: The CL that EM residents experienced did show considerable interpersonal and intercase variation, but there was no significant difference between practice and exam cases. These results highlight several questions about how to optimally design future training, including how best to balance low and high CL training cases and which cases may require further training., Competing Interests: The authors have no potential conflicts to disclose., (© 2022 The Authors. AEM Education and Training published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)
- Published
- 2022
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5. Blue light phones as potential locations for deploying public access naloxone kits on a college campus.
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Dworkis DA, Tang W, Ritcheson NC, Raviv O, Fowler A, Ellig K, Goley S, and Arora S
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- Adult, Humans, Naloxone therapeutic use, Narcotic Antagonists therapeutic use, Students, Universities, Young Adult, Drug Overdose drug therapy, Opiate Overdose
- Abstract
Objective Opioid use and the risk of opioid overdose are growing public health concerns for college-aged adults. Naloxone can temporarily reverse opioid overdoses, but only if easily accessible. On most college campuses, "blue light" phones (BLPs)-call boxes topped with a blue light-offer visible access to emergency services. We hypothesized that BLPs would provide potential naloxone access points. Participants: A major university campus in Los Angeles, CA. Methods: BLP locations were obtained using Google Maps, and the area of campus within a set distance to each BLP calculated. To model effects of loss or diversion, we simulated the random loss of various BLPs. Results: Placing naloxone kits at the 59 BLP locations could provide access within 100 m to 91.5% of the campus. With loss of half of the BLPs, campus access remained above 70%. Conclusions: Naloxone at BLP locations could be accessed from almost all campus areas.
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- 2022
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6. Who Stayed Home Under Safer-at-Home? Impacts of COVID-19 on Volume and Patient-Mix at an Emergency Department.
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Lam CN, Axeen S, Terp S, Burner E, Dworkis DA, Arora S, and Menchine M
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- Adult, Age Distribution, Communicable Disease Control, Female, Humans, Los Angeles epidemiology, Male, Medicaid statistics & numerical data, Medicare statistics & numerical data, Middle Aged, Pandemics, Patient Acuity, Patient Admission statistics & numerical data, Racial Groups statistics & numerical data, Retrospective Studies, Sex Distribution, United States epidemiology, Urban Population, COVID-19 epidemiology, Emergency Service, Hospital statistics & numerical data
- Abstract
Introduction: To describe the impact of COVID-19 on a large, urban emergency department (ED) in Los Angeles, California, we sought to estimate the effect of the novel coronavirus 2019 (COVID-19) and "safer-at-home" declaration on ED visits, patient demographics, and diagnosis-mix compared to prior years., Methods: We used descriptive statistics to compare ED volume and rates of admission for patients presenting to the ED between January and early May of 2018, 2019, and 2020., Results: Immediately after California's "safer-at-home" declaration, ED utilization dropped by 11,000 visits (37%) compared to the same nine weeks in prior years. The drop affected patients regardless of acuity, demographics, or diagnosis. Reductions were observed in the number of patients reporting symptoms often associated with COVID-19 and all other complaints. After the declaration, higher acuity, older, male, Black, uninsured or non-Medicaid, publicly insured, accounted for a disproportionate share of utilization., Conclusion: We show an abrupt, discontinuous impact of COVID-19 on ED utilization with a slow return as safer-at-home orders have lifted. It is imperative to determine how this reduction will impact patient outcomes, disease control, and the health of the community in the medium and long terms.
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- 2021
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7. Rubber Meeting the Road: Access to Comprehensive Stroke Care in the Face of Traffic.
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Dworkis DA, Axeen S, and Arora S
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- 2020
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8. Neighborhood-level stroke hot spots within major United States cities.
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Dworkis DA, Marvel J, Sanossian N, and Arora S
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- Cities epidemiology, Cities statistics & numerical data, Cohort Studies, Cross-Sectional Studies, Humans, Monte Carlo Method, Prevalence, Retrospective Studies, Risk Factors, Socioeconomic Factors, United States epidemiology, Geographic Mapping, Residence Characteristics statistics & numerical data, Stroke epidemiology
- Abstract
Objective: Identifying communities at high risk of stroke is an important step in improving systems of stroke care. Stroke is known to show spatial clustering at the state and county levels, but it is not known if clusters are present within city boundaries., Methods: We performed a geospatial analysis of the prevalence of stroke within 500 major cities in the United States using the Centers for Disease Control and Prevention 500 Cities Project. For each city, we calculated the Moran's I statistic, which looks for evidence of spatial clustering, and used Monte Carlo simulation to assess for clustering significance., Results: The mean overall crude prevalence of self-reported history of stroke at the city level was 2.8% (IQR 2.4-3.2%). Monte Carlo simulations of spatial patterns of stroke were successfully performed for 497 cities, of which 136 (27.3%) showed significant spatial clustering at the neighborhood level. All nine cities with more than one million inhabitants in 2010 showed significant spatial clustering., Conclusions: This is the first study to demonstrate that stroke shows clustering at the neighborhood level within many major cities in the United States and within all of the largest cities. Understanding where stroke clusters exist within cities can form the basis of optimizing emergency medical services deployment and improving systems of stroke care., Competing Interests: Declaration of Competing Interest DD, JM, NS, and SA declare they have no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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9. Impact of Urgent Care Openings on Emergency Department Visits to Two Academic Medical Centers Within an Integrated Health Care System.
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Carlson LC, Raja AS, Dworkis DA, Lee J, Brown DFM, Samuels-Kalow M, Wilson M, Shapiro M, Kim J, and Yun BJ
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- Academic Medical Centers organization & administration, Adult, Aged, Boston, Delivery of Health Care, Integrated organization & administration, Emergency Service, Hospital organization & administration, Female, Health Services Accessibility organization & administration, Health Services Accessibility statistics & numerical data, Humans, Male, Middle Aged, Spatial Analysis, Academic Medical Centers statistics & numerical data, Ambulatory Care Facilities statistics & numerical data, Delivery of Health Care, Integrated statistics & numerical data, Emergency Service, Hospital statistics & numerical data, Patient Acceptance of Health Care statistics & numerical data
- Abstract
Study Objective: The effect of urgent cares on local emergency department (ED) patient volumes is presently unknown. In this paper, we aimed to assess the change in low-acuity ED utilization at 2 academic medical centers in relation to patient proximity to an affiliated urgent care., Methods: We created a geospatial database of ED visits occurring between April 2016 and March 2018 to 2 academic medical centers in an integrated health care system, geocoded by patient home address. We used logistic regression to characterize the relationship between the likelihood of patients visiting the ED for a low-acuity condition, based on ED discharge diagnosis, and urgent care center proximity, defined as living within 1 mile of an open urgent care center, for each of the academic medical centers in the system, adjusting for spatial, temporal, and patient factors., Results: We identified a statistically significant reduction in the likelihood of ED visits for low-acuity conditions by patients living within 1 mile of an urgent care center at 1 of the 2 academic medical centers, with an adjusted odds ratio of 0.87 (95% confidence interval 0.78 to 0.98). There was, however, no statistically significant reduction at the other affiliated academic medical center. Further analysis showed a statistically significant temporal relationship between time since urgent care center opening and likelihood of a low-acuity ED visit, with approximately a 1% decrease in the odds of a low-acuity visit for every month that the proximal urgent care center was open (odds ratio 0.99; 95% confidence interval 0.985 to 0.997)., Conclusion: Although further research is needed to assess the factors driving urgent care centers' variable influence on low-acuity ED use, these findings suggest that in similar settings urgent care center development may be an effective strategy for health systems hoping to decrease ED utilization for low-acuity conditions at academic medical centers., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)
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- 2020
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10. Location of Violent Crime Relative to Trauma Resources in Detroit: Implications for Community Interventions.
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Clery MJ, Dworkis DA, Sonuyi T, Khaldun JS, and Abir M
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- Adult, Delivery of Health Care, Female, Health Services Accessibility, Humans, Male, Michigan, Retrospective Studies, United States, Crime, Homicide, Trauma Centers statistics & numerical data, Violence statistics & numerical data
- Abstract
Introduction: Detroit, Michigan, is among the leading United States cities for per-capita homicide and violent crime. Hospital- and community-based intervention programs could decrease the rate of violent-crime related injury but require a detailed understanding of the locations of violence in the community to be most effective., Methods: We performed a retrospective geospatial analysis of all violent crimes reported within the city of Detroit from 2009-2015 comparing locations of crimes to locations of major hospitals. We calculated distances between violent crimes and trauma centers, and applied summary spatial statistics., Results: Approximately 1.1 million crimes occurred in Detroit during the study period, including approximately 200,000 violent crimes. The distance between the majority of violent crimes and hospitals was less than five kilometers (3.1 miles). Among violent crimes, the closest hospital was an outlying Level II trauma center 60% of the time., Conclusion: Violent crimes in Detroit occur throughout the city, often closest to a Level II trauma center. Understanding geospatial components of violence relative to trauma center resources is important for effective implementation of hospital- and community-based interventions and targeted allocation of resources.
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- 2020
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11. Closing the gap: Improving access to trauma care in New Mexico (2007-2017).
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Anderson ES, Greenwood-Ericksen M, Wang NE, and Dworkis DA
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cross-Sectional Studies, Female, Health Services Accessibility statistics & numerical data, Healthcare Disparities ethnology, Hispanic or Latino, Humans, Indians, North American, Infant, Infant, Newborn, Logistic Models, Male, Middle Aged, New Mexico, Retrospective Studies, Rural Health Services organization & administration, Rural Health Services supply & distribution, Trauma Centers statistics & numerical data, Young Adult, Health Services Accessibility organization & administration, Healthcare Disparities statistics & numerical data, Trauma Centers organization & administration
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Background: Trauma is a major cause of death and disability in the United States, and significant disparities exist in access to care, especially in non-urban settings. From 2007 to 2017 New Mexico expanded its trauma system by focusing on building capacity at the hospital level., Methods: We conducted a geospatial analysis at the census block level of access to a trauma center in New Mexico within 1 h by ground or air transportation for the years 2007 and 2017. We then examined the characteristics of the population with access to care. A multiple logistic regression model assessed for remaining disparities in access to trauma centers in 2017., Results: The proportion of the population in New Mexico with access to a trauma center within 1 h increased from 73.8% in 2007 to 94.8% in 2017. The largest increases in access to trauma care within 1 h were found among American Indian/Alaska Native populations (AI/AN) (35.2%) and people living in suburban areas (62.9%). In 2017, the most rural communities (aOR 58.0), communities on an AI/AN reservation (aOR 25.6), communities with a high proportion of Hispanic/Latino persons (aOR 8.4), and a high proportion of elderly persons (aOR 3.2) were more likely to lack access to a trauma center within 1 h., Conclusion: The New Mexico trauma system expansion significantly increased access to trauma care within 1 h for most of New Mexico, but some notable disparities remain. Barriers persist for very rural parts of the state and for its sizable American Indian community., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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12. Nontargeted Diabetes Screening in a Navajo Nation Emergency Department.
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Anderson ES, Dworkis DA, DeFries T, Emery E, Deegala C, and Mohs K
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- Adult, Aged, Body Mass Index, Female, Glycated Hemoglobin analysis, Humans, Indians, North American statistics & numerical data, Male, Middle Aged, Public Health, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 epidemiology, Emergency Service, Hospital, Mass Screening methods
- Abstract
We developed a nontargeted diabetes screening program in a rural Indian Health Service emergency department in Shiprock, New Mexico to measure the proportion of previously undiagnosed diabetes and prediabetes, and to assess glycemic control among patients with known disease. Of 924 patients screened in the emergency department between May and July 2017, 28.8% screened positive for previously undiagnosed diabetes or prediabetes; among patients with known disease, the median hemoglobin A1c was 8.2%. Of the newly identified patients, 54.9% attended follow-up.
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- 2019
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13. Feasibility of Bystander Administration of Public-Access Naloxone for Opioid Overdose.
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Goldberg SA, Dworkis DA, Liao VT, Eyre AJ, Albert J, Fawcett MM, Narovec CM, DiClemente J, and Weiner SG
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- Adult, Aged, Emergency Medical Services, Feasibility Studies, Female, Helping Behavior, Humans, Male, Middle Aged, Young Adult, Analgesics, Opioid administration & dosage, Drug Overdose drug therapy, Health Services Accessibility, Naloxone administration & dosage, Naloxone therapeutic use, Narcotic Antagonists administration & dosage, Narcotic Antagonists therapeutic use, Public Facilities, Substance-Related Disorders drug therapy
- Abstract
Objective: Pre-stationing naloxone, a competitive antagonist that can reverse the effects of opioid overdose, in public spaces may expedite antidote delivery. Our study aimed to determine the feasibility of bystander-assisted overdose treatment using pre-stationed naloxone., Methods: Convenience sample of bystanders in Cambridge, Massachusetts in April 2017. Subjects assisted a simulated patient described as unconscious. Subjects interacted with simulated EMS dispatch to locate a nearby box, unlock it, and administer naloxone., Results: Fifty participants completed the simulation. Median time from simulated ambulance dispatch to naloxone administration was 189 seconds, and from arrival at patient side to administration 61 seconds. All but one participant (98.0%) correctly administered naloxone. Subjects' comfort with administration and willingness to provide medical care increased from before to after the trial. Comfort in administering naloxone varied significantly with level of previous training prior to, but not following, study participation., Conclusions: Bystanders are willing and able to access pre-stationed naloxone and administer it to a simulated patient in a public space. Public access naloxone stations may be a useful tool to reduce time to naloxone administration, particularly in areas where opioid overdoses are clustered.
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- 2018
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14. Geospatial Clustering of Opioid-Related Emergency Medical Services Runs for Public Deployment of Naloxone.
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Dworkis DA, Weiner SG, Liao VT, Rabickow D, and Goldberg SA
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- Drug Overdose mortality, Humans, Massachusetts, Retrospective Studies, Analgesics, Opioid toxicity, Drug Overdose drug therapy, Emergency Medical Services, Geographic Information Systems statistics & numerical data, Naloxone therapeutic use, Narcotic Antagonists therapeutic use, Opioid-Related Disorders drug therapy
- Abstract
Introduction: The epidemic of opioid use disorder and opioid overdose carries extensive morbidity and mortality and necessitates a multi-pronged, community-level response. Bystander administration of the opioid overdose antidote naloxone is effective, but it is not universally available and requires consistent effort on the part of citizens to proactively carry naloxone. An alternate approach would be to position naloxone kits where they are most needed in a community, in a manner analogous to automated external defibrillators. We hypothesized that opioid overdoses would show geospatial clustering within a community, leading to potential target sites for such publicly deployed naloxone (PDN)., Methods: We performed a retrospective chart review of 700 emergency medical service (EMS) runs that involved opioid overdose or naloxone administration in Cambridge, Massachusetts, between October 16, 2016 and May 10, 2017. We used geospatial analysis to examine for clustering in general, and to identify specific clusters amenable to PDN sites., Results: Opioid-related emergency medical services (EMS) runs in Cambridge, Massachusetts (MA), exhibit significant geospatial clustering, and we identified three clusters of opioid-related EMS runs in Cambridge, MA, with distinct characteristics. Models of PDN sites at these clusters show that approximately 40% of all opioid-related EMS runs in Cambridge, MA, would be accessible within 200 meters of PDN sites placed at cluster centroids., Conclusion: Identifying clusters of opioid-related EMS runs within a community may help to improve community coverage of naloxone, and strongly suggests that PDN could be a useful adjunct to bystander-administered naloxone in stemming the tide of opioid-related death., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. Scott Goldberg and Scott Weiner serve on the medical advisory board of General Emergency Medical Supplies, Inc. (GEMS), a manufacturer of public access naloxone boxes. Vincent Liao serves at the Chief Medical Officer for GEMS. GEMS provided no financial support for the study, and did not contribute to study design, data analysis or manuscript development.
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- 2018
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15. Geospatial analysis of emergency department visits for targeting community-based responses to the opioid epidemic.
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Dworkis DA, Taylor LA, Peak DA, and Bearnot B
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- Age Distribution, Female, Hospitals, General statistics & numerical data, Humans, Male, Sex Distribution, Emergency Service, Hospital statistics & numerical data, Epidemics statistics & numerical data, Opioid-Related Disorders epidemiology
- Abstract
The opioid epidemic in the United States carries significant morbidity and mortality and requires a coordinated response among emergency providers, outpatient providers, public health departments, and communities. Anecdotally, providers across the spectrum of care at Massachusetts General Hospital (MGH) in Boston, MA have noticed that Charlestown, a community in northeast Boston, has been particularly impacted by the opioid epidemic and needs both emergency and longer-term resources. We hypothesized that geospatial analysis of the home addresses of patients presenting to the MGH emergency department (ED) with opioid-related emergencies might identify "hot spots" of opioid-related healthcare needs within Charlestown that could then be targeted for further investigation and resource deployment. Here, we present a geospatial analysis at the United States census tract level of the home addresses of all patients who presented to the MGH ED for opioid-related emergency visits between 7/1/2012 and 6/30/2015, including 191 visits from 100 addresses in Charlestown, MA. Among the six census tracts that comprise Charlestown, we find a 9.5-fold difference in opioid-related ED visits, with 45% of all opioid-related visits from Charlestown originating in tract 040401. The signal from this census tract remains strong after adjusting for population differences between census tracts, and while this tract is one of the higher utilizing census tracts in Charlestown of the MGH ED for all cause visits, it also has a 2.9-fold higher rate of opioid-related visits than the remainder of Charlestown. Identifying this hot spot of opioid-related emergency needs within Charlestown may help re-distribute existing resources efficiently, empower community and ED-based physicians to advocate for their patients, and serve as a catalyst for partnerships between MGH and local community groups. More broadly, this analysis demonstrates that EDs can use geospatial analysis to address the emergency and longer-term health needs of the communities they are designed to serve.
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- 2017
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16. Reaching Out of the Box: Effective Emergency Care Requires Looking Outside the Emergency Department.
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Dworkis DA, Peak DA, Ahn J, Joseph TA, Bernstein E, and Nadel ES
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- Emergency Service, Hospital statistics & numerical data, Health Services Needs and Demand statistics & numerical data, Hospitalization, Humans, Insurance, Health, Socioeconomic Factors, Emergency Medical Services standards, Emergency Service, Hospital organization & administration, Health Services Needs and Demand organization & administration, Patient Acceptance of Health Care statistics & numerical data
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- 2016
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17. Accuracy of Inferior Vena Cava Ultrasound for Predicting Dehydration in Children with Acute Diarrhea in Resource-Limited Settings.
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Modi P, Glavis-Bloom J, Nasrin S, Guy A, Chowa EP, Dvor N, Dworkis DA, Oh M, Silvestri DM, Strasberg S, Rege S, Noble VE, Alam NH, and Levine AC
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- Acute Disease, Aorta diagnostic imaging, Child, Preschool, Diarrhea diagnosis, Female, Humans, Infant, Male, Point-of-Care Systems, Prognosis, Prospective Studies, ROC Curve, Reproducibility of Results, Risk Factors, Ultrasonography, Dehydration diagnostic imaging, Dehydration etiology, Diarrhea complications, Vena Cava, Inferior diagnostic imaging
- Abstract
Introduction: Although dehydration from diarrhea is a leading cause of morbidity and mortality in children under five, existing methods of assessing dehydration status in children have limited accuracy., Objective: To assess the accuracy of point-of-care ultrasound measurement of the aorta-to-IVC ratio as a predictor of dehydration in children., Methods: A prospective cohort study of children under five years with acute diarrhea was conducted in the rehydration unit of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Ultrasound measurements of aorta-to-IVC ratio and dehydrated weight were obtained on patient arrival. Percent weight change was monitored during rehydration to classify children as having "some dehydration" with weight change 3-9% or "severe dehydration" with weight change > 9%. Logistic regression analysis and Receiver-Operator Characteristic (ROC) curves were used to evaluate the accuracy of aorta-to-IVC ratio as a predictor of dehydration severity., Results: 850 children were enrolled, of which 771 were included in the final analysis. Aorta to IVC ratio was a significant predictor of the percent dehydration in children with acute diarrhea, with each 1-point increase in the aorta to IVC ratio predicting a 1.1% increase in the percent dehydration of the child. However, the area under the ROC curve (0.60), sensitivity (67%), and specificity (49%), for predicting severe dehydration were all poor., Conclusions: Point-of-care ultrasound of the aorta-to-IVC ratio was statistically associated with volume status, but was not accurate enough to be used as an independent screening tool for dehydration in children under five years presenting with acute diarrhea in a resource-limited setting.
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- 2016
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18. Empowering medical students to design and execute advocacy projects.
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Premkumar A, Haddad DN, and Dworkis DA
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- Humans, Consumer Advocacy, Education, Medical, Graduate, Education, Medical, Undergraduate, Physician's Role
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- 2013
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19. Barriers to outpatient respiratory therapy among adult residents of emergency shelters.
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Dworkis DA, Brown SS, Gaeta JM, Brown JW, and Gonzalez MH
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- Boston, Humans, Male, Middle Aged, Organizational Policy, Outpatients, Emergency Shelter organization & administration, Hypoxia therapy, Nebulizers and Vaporizers, Oxygen Inhalation Therapy instrumentation
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- 2012
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20. Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span.
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Andersen SL, Sebastiani P, Dworkis DA, Feldman L, and Perls TT
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- Aged, 80 and over, Cardiovascular Diseases epidemiology, Cognition Disorders epidemiology, Dementia epidemiology, Female, Humans, Male, Neoplasms epidemiology, Prevalence, Prospective Studies, Stroke epidemiology, Age of Onset, Longevity, Morbidity
- Abstract
We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.
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- 2012
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21. A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.
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Milton JN, Sebastiani P, Solovieff N, Hartley SW, Bhatnagar P, Arking DE, Dworkis DA, Casella JF, Barron-Casella E, Bean CJ, Hooper WC, DeBaun MR, Garrett ME, Soldano K, Telen MJ, Ashley-Koch A, Gladwin MT, Baldwin CT, Steinberg MH, and Klings ES
- Subjects
- Anemia, Sickle Cell blood, Bilirubin genetics, Cohort Studies, Genome-Wide Association Study, Genotype, Humans, Inheritance Patterns genetics, Isoenzymes genetics, Polymorphism, Single Nucleotide genetics, Principal Component Analysis, Risk Factors, Black or African American genetics, Anemia, Sickle Cell complications, Anemia, Sickle Cell genetics, Bilirubin blood, Cholelithiasis blood, Cholelithiasis etiology, Glucuronosyltransferase genetics
- Abstract
Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5 × 10(-8)). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08 × 10(-25)). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15 × 10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities.
- Published
- 2012
- Full Text
- View/download PDF
22. Genetic signatures of exceptional longevity in humans.
- Author
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Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, and Perls TT
- Subjects
- Aged, Aged, 80 and over, Alleles, Bayes Theorem, Cohort Studies, Female, Gene Frequency, Genetic Predisposition to Disease genetics, Genotype, Humans, Male, Models, Genetic, Models, Statistical, Aging genetics, Genome, Human genetics, Longevity genetics, Polymorphism, Single Nucleotide
- Abstract
Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different "genetic signatures" of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity.
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- 2012
- Full Text
- View/download PDF
23. Retraction.
- Author
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Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, and Perls TT
- Published
- 2011
- Full Text
- View/download PDF
24. Severe sickle cell anemia is associated with increased plasma levels of TNF-R1 and VCAM-1.
- Author
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Dworkis DA, Klings ES, Solovieff N, Li G, Milton JN, Hartley SW, Melista E, Parente J, Sebastiani P, Steinberg MH, and Baldwin CT
- Subjects
- Adult, Anemia, Sickle Cell genetics, Biomarkers blood, Female, Genome-Wide Association Study, Guanine Nucleotide Exchange Factors genetics, Humans, Introns, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Severity of Illness Index, United States, Vascular Cell Adhesion Molecule-1 genetics, Anemia, Sickle Cell blood, Anemia, Sickle Cell physiopathology, Receptors, Tumor Necrosis Factor, Type I blood, Vascular Cell Adhesion Molecule-1 blood
- Abstract
Sickle cell anemia (SCA, HBB glu6val) is characterized by multiple complications and a high degree of phenotypic variability: some subjects have only sporadic pain crises and few acute hospitalizations, while others experience multiple serious complications, high levels of morbidity, and accelerated mortality [1]. The tumor necrosis factor-α (TNF-α) signaling pathway plays important roles in inflammation and the immune response; variation in this pathway might be expected to modify the overall severity of SCA through the pathway's effects on the vascular endothelium [2,3]. We examined plasma biomarkers of TNF-α activity and endothelial cell activation for associations with SCA severity in 24 adults (12 mild, 12 severe). Two biomarkers, tumor necrosis factor-α receptor-1 (TNF-R1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in subjects with severe SCA. Along with these biomarker differences, we also examined data from a genome-wide association study (GWAS) using SCA severity as a disease phenotype, and found evidence of genetic association between disease severity and a single nucleotide polymorphism (SNP) in VCAM1, which codes for VCAM-1, and several SNPs in ARFGEF2, a gene involved in TNF-R1 release [4].
- Published
- 2011
- Full Text
- View/download PDF
25. A framework for designing training in medical advocacy.
- Author
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Dworkis DA, Wilbur MB, and Sandel MT
- Subjects
- Curriculum, Health Care Reform, Health Education, Health Policy, Humans, Leadership, Models, Educational, United States, Consumer Advocacy, Physician's Role, Politics
- Published
- 2010
- Full Text
- View/download PDF
26. Genetic signatures of exceptional longevity in humans.
- Author
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Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, and Perls TT
- Abstract
Healthy aging is thought to reflect the combined influence of environmental factors (lifestyle choices) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity (EL) in 1055 centenarians and 1267 controls. Using these data, we built a genetic model that includes 150 single-nucleotide polymorphisms (SNPs) and found that it could predict EL with 77% accuracy in an independent set of centenarians and controls. Further in silico analysis revealed that 90% of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes-or genetic signatures-of varying predictive value. The different signatures, which attest to the genetic complexity of EL, correlated with differences in the prevalence and age of onset of age-associated diseases (e.g., dementia, hypertension, and cardiovascular disease) and may help dissect this complex phenotype into subphenotypes of healthy aging.
- Published
- 2010
- Full Text
- View/download PDF
27. Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5' olfactory receptor gene cluster.
- Author
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Solovieff N, Milton JN, Hartley SW, Sherva R, Sebastiani P, Dworkis DA, Klings ES, Farrer LA, Garrett ME, Ashley-Koch A, Telen MJ, Fucharoen S, Ha SY, Li CK, Chui DH, Baldwin CT, and Steinberg MH
- Subjects
- Adolescent, Adult, Black or African American genetics, Carrier Proteins genetics, Child, Child, Preschool, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, X genetics, Female, Genome-Wide Association Study, Hemoglobin E genetics, Hong Kong, Humans, Male, Nuclear Proteins genetics, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Thailand, Young Adult, beta-Thalassemia genetics, Anemia, Sickle Cell blood, Anemia, Sickle Cell genetics, Fetal Hemoglobin genetics, Fetal Hemoglobin metabolism, Multigene Family, Polymorphism, Single Nucleotide, Receptors, Odorant genetics
- Abstract
In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or beta thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E-08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E-21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in gamma-globin gene expression.
- Published
- 2010
- Full Text
- View/download PDF
28. Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study.
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Sebastiani P, Solovieff N, Hartley SW, Milton JN, Riva A, Dworkis DA, Melista E, Klings ES, Garrett ME, Telen MJ, Ashley-Koch A, Baldwin CT, and Steinberg MH
- Subjects
- Adolescent, Adult, Anemia, Sickle Cell physiopathology, Child, Complement C8 genetics, Computational Biology, Genome-Wide Association Study, Humans, MAP Kinase Kinase Kinases genetics, Middle Aged, Potassium Channels, Tandem Pore Domain genetics, Severity of Illness Index, Tankyrases genetics, Young Adult, Anemia, Sickle Cell complications, Anemia, Sickle Cell genetics, Phenotype, Polymorphism, Single Nucleotide
- Abstract
We conducted a genome-wide association study (GWAS) to discover single nucleotide polymorphisms (SNPs) associated with the severity of sickle cell anemia in 1,265 patients with either "severe" or "mild" disease based on a network model of disease severity. We analyzed data using single SNP analysis and a novel SNP set enrichment analysis (SSEA) developed to discover clusters of associated SNPs. Single SNP analysis discovered 40 SNPs that were strongly associated with sickle cell severity (odds for association >1,000); of the 32 that we could analyze in an independent set of 163 patients, five replicated, eight showed consistent effects although failed to reach statistical significance, whereas 19 did not show any convincing association. Among the replicated associations are SNPs in KCNK6 a K(+) channel gene. SSEA identified 27 genes with a strong enrichment of significant SNPs (P < 10(-6)); 20 were replicated with varying degrees of confidence. Among the novel findings identified by SSEA is the telomere length regulator gene TNKS. These studies are the first to use GWAS to understand the genetic diversity that accounts the phenotypic heterogeneity sickle cell anemia as estimated by an integrated model of severity. Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work., ((c) 2009 Wiley-Liss, Inc.)
- Published
- 2010
- Full Text
- View/download PDF
29. Genome-wide association studies and the genetic dissection of complex traits.
- Author
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Sebastiani P, Timofeev N, Dworkis DA, Perls TT, and Steinberg MH
- Subjects
- Animals, Humans, Sequence Analysis, DNA, Anemia, Sickle Cell metabolism, Genome, Human, Genome-Wide Association Study, Quantitative Trait Loci genetics
- Abstract
The availability of affordable high throughput technology for parallel genotyping has opened the field of genetics to genome-wide association studies (GWAS), and in the last few years hundreds of articles reporting results of GWAS for a variety of heritable traits have been published. What do these results tell us? Although GWAS have discovered a few hundred reproducible associations, this number is underwhelming in relation to the huge amount of data produced, and challenges the conjecture that common variants may be the genetic causes of common diseases. We argue that the massive amount of genetic data that result from these studies remains largely unexplored and unexploited because of the challenge of mining and modeling enormous data sets, the difficulty of using nontraditional computational techniques and the focus of accepted statistical analyses on controlling the false positive rate rather than limiting the false negative rate. In this article, we will review the common approach to analysis of GWAS data and then discuss options to learn more from these data. We will use examples from our ongoing studies of sickle cell anemia and also GWAS in multigenic traits.
- Published
- 2009
- Full Text
- View/download PDF
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